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Adjuvant-boosted shingles vaccine earns FDA panel’s unanimous nod
A new vaccine for herpes zoster is both safe and effective in preventing herpes zoster, and in reducing the incidence of postherpetic neuralgia in older adults, according to a Food and Drug Administration advisory committee, which voted unanimously to recommend the vaccine.
The FDA generally follows the recommendations of its advisory committees.
The recombinant vaccine, dubbed HZ/su during the trial phase, showed efficacy of 97.2% against herpes zoster infection in adults aged 50 years and older, and 91.3% in adults aged 70 years and older. The effect persisted for up to the 4 years of study follow-up.
HZ/su had a generally favorable safety profile, though early constitutional symptoms and local site reactions were common, according to data presented by GlaxoSmithKline. HZ/su uses an adjuvant not found in any other U.S.-approved vaccine.
The incidence of postherpetic neuralgia, a common, persistent, and costly complication of herpes zoster, was 0.1 per 1,000 person-years in those receiving vaccine, compared with 0.9-1.2 per 1,000 person-years for those receiving placebo in the pivotal clinical trials for a median follow-up of 4 years.
In the vaccine’s pivotal clinical trials, efficacy was significantly higher than the levels seen for the only currently approved zoster live vaccine, Zostavax, especially for older populations. Zostavax’s efficacy for those aged 50-59 years is 69.8%, dropping to 18% for those aged 80 years or older.
The results of the two pivotal clinical trials were presented and analyzed by the sponsor and by FDA staff during a meeting of the Vaccines and Related Biological Products Advisory Committee of the FDA’s Center for Biologics Evaluation and Research (CBER).
During pre-vote discussions, committee members were unanimous in noting with favor the high and sustained efficacy seen for HZ/su in the trial data, especially for older populations. However, some participants wondered about the generalizability of both safety and efficacy data to all populations, given the very low trial enrollment numbers for Africans, African Americans, and individuals of Hispanic origin.
The two studies, Zoster-006 and Zoster-022, were similar in design and were conducted in parallel across 18 countries; data were able to be pooled for key efficacy and safety outcomes. Study Zoster-006 enrolled patients aged 50 years and older, while study Zoster-022 began enrollment at age 70. Patients were randomized to receive vaccine or placebo, and were followed for a median of 3.1 years for efficacy in Zoster-006 and a median of 3.9 years for Zoster-022. Safety data were obtained for a median 4.4 years for both studies.
The primary outcome measure for both studies in pooled analysis was the vaccine’s effectiveness against herpes zoster and postherpetic neuropathy in adults aged 70 and over. Safety was also assessed using pooled data.
The United States was represented by 3,934 of more than 29,000 patients enrolled globally. The remainder were primarily in Western Europe, with some sites in Australia and eastern Asia, Canada, and Latin America.
The vaccine consists of a recombinant, lyophilized truncated form of the varicella zoster virus (VZV) glycoprotein E (gE) antigen protein that, at the time of administration, is reconstituted with a novel adjuvant suspension. The antigen selection was based on the fact that gE is expressed on the surface of infected cells and is the target of both humoral and cellular immune responses in the host, said GSK’s Arnaud Didierlaurent, PhD, director and head of the adjuvant platform for GSK Vaccine’s Belgium research and development division.
The adjuvant, termed ASO1B, is not currently in use for any U.S.-approved vaccine, though it was developed more than 20 years ago, said Dr. Didierlaurent. Its combination with recombinant VZV gE was found to significantly boost the antigen’s immunogenicity during GSK’s vaccine development program. The adjuvant enhances a transient innate response in the first 3 days after administration that later helps maintain durably high levels of gE-specific antibodies and strengthens gE-specific cell-mediated immunity.
Mechanistically, the robust initial innate response is responsible for the constitutional symptoms and local site reactions seen in pooled data from the two pivotal clinical trials: 70%-85% of participants receiving HZ/su reported injection site pain, 38% of participants receiving HZ/su reported redness, and about a quarter reported swelling. By comparison, 9%-13% of those receiving placebo reported injection site pain, and about 1% reported redness and swelling.
Fatigue, headache, mild fever, myalgia, and shivering were all more common in those receiving HZ/su; both local and generalized symptoms were more common in younger recipients.
“I think this is a very good case for the first licensure of this adjuvant in the United States, because the efficacy seems pretty compelling, the disease is morbid, and there are a lot of people whose lives would be changed,” said committee member Sarah Long, MD, professor of pediatrics at Drexel University, Philadelphia.
Both the GSK and FDA presentations were in agreement that serious adverse events were in the range to be expected for an older population, and balanced across study arms. However, particular attention will be given to certain potential complications during the proposed pharmacovigilance plan.
“An imbalance toward vaccine versus placebo was observed” for gout, optic ischemic neuropathy, amyotrophic lateral sclerosis, osteonecrosis, convulsion-type reactions, and supraventricular tachycardias. “All are an adverse event of interest and will be included in planned targeted safety study,” said Dr. Didierlaurent.
Several committee members remarked on the difficulty of evaluating vaccine safety in an older population, where analysis takes place against the backdrop of more comorbidities and acute illnesses than in the younger population.
“There has been a thoughtful job both by the sponsor and by CBER in looking at complicated data,” said Melinda Wharton, MD, the director of the immunization services division of the National Center for Immunization and Respiratory Diseases at the Centers for Disease Control and Prevention, Atlanta.
The committee’s chair, Kathryn Edwards, MD, agreed. “I applaud the comprehensive analysis of all these safety signals. Both the sponsor and the FDA have done a wonderful job of drilling down and answering these questions,” she said. Dr. Edwards is the Sarah H. Sell and Cornelius Vanderbilt chair in pediatrics at Vanderbilt University, Nashville, Tenn.
Herpes zoster, a reactivation of the varicella virus that lies dormant in dorsal root or cranial nerve ganglia from earlier infection, is seen in about 1 million cases per year in the United States, with about 100,000 to 200,000 cases of postherpetic neuralgia occurring, said Jeffrey Cohen, MD, chief of the laboratory of infectious diseases at the National Institute of Allergy and Infectious Diseases, Bethesda, Md. The rates of herpes zoster are increasing in the United States for unknown reasons, and direct medical costs may currently exceed $1 billion annually, he said.
Each 0.5 mL dose of the HZ/su vaccine contains 50 mcg each of the recombinant VZV gE antigen and each of the two component parts of the ASO1B adjuvant. Two doses of the vaccine are administered intramuscularly 2-6 months apart. Dose-ranging studies were conducted before the pivotal clinical trials to ascertain the optimal dose of all of the vaccine components, the need for two doses, and the optimal spacing between doses.
All committee participants submitted conflict of interest statements to the FDA, and any potential conflicts were resolved before the hearing.
koakes@frontlinemedcom.com
On Twitter @karioakes
A new vaccine for herpes zoster is both safe and effective in preventing herpes zoster, and in reducing the incidence of postherpetic neuralgia in older adults, according to a Food and Drug Administration advisory committee, which voted unanimously to recommend the vaccine.
The FDA generally follows the recommendations of its advisory committees.
The recombinant vaccine, dubbed HZ/su during the trial phase, showed efficacy of 97.2% against herpes zoster infection in adults aged 50 years and older, and 91.3% in adults aged 70 years and older. The effect persisted for up to the 4 years of study follow-up.
HZ/su had a generally favorable safety profile, though early constitutional symptoms and local site reactions were common, according to data presented by GlaxoSmithKline. HZ/su uses an adjuvant not found in any other U.S.-approved vaccine.
The incidence of postherpetic neuralgia, a common, persistent, and costly complication of herpes zoster, was 0.1 per 1,000 person-years in those receiving vaccine, compared with 0.9-1.2 per 1,000 person-years for those receiving placebo in the pivotal clinical trials for a median follow-up of 4 years.
In the vaccine’s pivotal clinical trials, efficacy was significantly higher than the levels seen for the only currently approved zoster live vaccine, Zostavax, especially for older populations. Zostavax’s efficacy for those aged 50-59 years is 69.8%, dropping to 18% for those aged 80 years or older.
The results of the two pivotal clinical trials were presented and analyzed by the sponsor and by FDA staff during a meeting of the Vaccines and Related Biological Products Advisory Committee of the FDA’s Center for Biologics Evaluation and Research (CBER).
During pre-vote discussions, committee members were unanimous in noting with favor the high and sustained efficacy seen for HZ/su in the trial data, especially for older populations. However, some participants wondered about the generalizability of both safety and efficacy data to all populations, given the very low trial enrollment numbers for Africans, African Americans, and individuals of Hispanic origin.
The two studies, Zoster-006 and Zoster-022, were similar in design and were conducted in parallel across 18 countries; data were able to be pooled for key efficacy and safety outcomes. Study Zoster-006 enrolled patients aged 50 years and older, while study Zoster-022 began enrollment at age 70. Patients were randomized to receive vaccine or placebo, and were followed for a median of 3.1 years for efficacy in Zoster-006 and a median of 3.9 years for Zoster-022. Safety data were obtained for a median 4.4 years for both studies.
The primary outcome measure for both studies in pooled analysis was the vaccine’s effectiveness against herpes zoster and postherpetic neuropathy in adults aged 70 and over. Safety was also assessed using pooled data.
The United States was represented by 3,934 of more than 29,000 patients enrolled globally. The remainder were primarily in Western Europe, with some sites in Australia and eastern Asia, Canada, and Latin America.
The vaccine consists of a recombinant, lyophilized truncated form of the varicella zoster virus (VZV) glycoprotein E (gE) antigen protein that, at the time of administration, is reconstituted with a novel adjuvant suspension. The antigen selection was based on the fact that gE is expressed on the surface of infected cells and is the target of both humoral and cellular immune responses in the host, said GSK’s Arnaud Didierlaurent, PhD, director and head of the adjuvant platform for GSK Vaccine’s Belgium research and development division.
The adjuvant, termed ASO1B, is not currently in use for any U.S.-approved vaccine, though it was developed more than 20 years ago, said Dr. Didierlaurent. Its combination with recombinant VZV gE was found to significantly boost the antigen’s immunogenicity during GSK’s vaccine development program. The adjuvant enhances a transient innate response in the first 3 days after administration that later helps maintain durably high levels of gE-specific antibodies and strengthens gE-specific cell-mediated immunity.
Mechanistically, the robust initial innate response is responsible for the constitutional symptoms and local site reactions seen in pooled data from the two pivotal clinical trials: 70%-85% of participants receiving HZ/su reported injection site pain, 38% of participants receiving HZ/su reported redness, and about a quarter reported swelling. By comparison, 9%-13% of those receiving placebo reported injection site pain, and about 1% reported redness and swelling.
Fatigue, headache, mild fever, myalgia, and shivering were all more common in those receiving HZ/su; both local and generalized symptoms were more common in younger recipients.
“I think this is a very good case for the first licensure of this adjuvant in the United States, because the efficacy seems pretty compelling, the disease is morbid, and there are a lot of people whose lives would be changed,” said committee member Sarah Long, MD, professor of pediatrics at Drexel University, Philadelphia.
Both the GSK and FDA presentations were in agreement that serious adverse events were in the range to be expected for an older population, and balanced across study arms. However, particular attention will be given to certain potential complications during the proposed pharmacovigilance plan.
“An imbalance toward vaccine versus placebo was observed” for gout, optic ischemic neuropathy, amyotrophic lateral sclerosis, osteonecrosis, convulsion-type reactions, and supraventricular tachycardias. “All are an adverse event of interest and will be included in planned targeted safety study,” said Dr. Didierlaurent.
Several committee members remarked on the difficulty of evaluating vaccine safety in an older population, where analysis takes place against the backdrop of more comorbidities and acute illnesses than in the younger population.
“There has been a thoughtful job both by the sponsor and by CBER in looking at complicated data,” said Melinda Wharton, MD, the director of the immunization services division of the National Center for Immunization and Respiratory Diseases at the Centers for Disease Control and Prevention, Atlanta.
The committee’s chair, Kathryn Edwards, MD, agreed. “I applaud the comprehensive analysis of all these safety signals. Both the sponsor and the FDA have done a wonderful job of drilling down and answering these questions,” she said. Dr. Edwards is the Sarah H. Sell and Cornelius Vanderbilt chair in pediatrics at Vanderbilt University, Nashville, Tenn.
Herpes zoster, a reactivation of the varicella virus that lies dormant in dorsal root or cranial nerve ganglia from earlier infection, is seen in about 1 million cases per year in the United States, with about 100,000 to 200,000 cases of postherpetic neuralgia occurring, said Jeffrey Cohen, MD, chief of the laboratory of infectious diseases at the National Institute of Allergy and Infectious Diseases, Bethesda, Md. The rates of herpes zoster are increasing in the United States for unknown reasons, and direct medical costs may currently exceed $1 billion annually, he said.
Each 0.5 mL dose of the HZ/su vaccine contains 50 mcg each of the recombinant VZV gE antigen and each of the two component parts of the ASO1B adjuvant. Two doses of the vaccine are administered intramuscularly 2-6 months apart. Dose-ranging studies were conducted before the pivotal clinical trials to ascertain the optimal dose of all of the vaccine components, the need for two doses, and the optimal spacing between doses.
All committee participants submitted conflict of interest statements to the FDA, and any potential conflicts were resolved before the hearing.
koakes@frontlinemedcom.com
On Twitter @karioakes
A new vaccine for herpes zoster is both safe and effective in preventing herpes zoster, and in reducing the incidence of postherpetic neuralgia in older adults, according to a Food and Drug Administration advisory committee, which voted unanimously to recommend the vaccine.
The FDA generally follows the recommendations of its advisory committees.
The recombinant vaccine, dubbed HZ/su during the trial phase, showed efficacy of 97.2% against herpes zoster infection in adults aged 50 years and older, and 91.3% in adults aged 70 years and older. The effect persisted for up to the 4 years of study follow-up.
HZ/su had a generally favorable safety profile, though early constitutional symptoms and local site reactions were common, according to data presented by GlaxoSmithKline. HZ/su uses an adjuvant not found in any other U.S.-approved vaccine.
The incidence of postherpetic neuralgia, a common, persistent, and costly complication of herpes zoster, was 0.1 per 1,000 person-years in those receiving vaccine, compared with 0.9-1.2 per 1,000 person-years for those receiving placebo in the pivotal clinical trials for a median follow-up of 4 years.
In the vaccine’s pivotal clinical trials, efficacy was significantly higher than the levels seen for the only currently approved zoster live vaccine, Zostavax, especially for older populations. Zostavax’s efficacy for those aged 50-59 years is 69.8%, dropping to 18% for those aged 80 years or older.
The results of the two pivotal clinical trials were presented and analyzed by the sponsor and by FDA staff during a meeting of the Vaccines and Related Biological Products Advisory Committee of the FDA’s Center for Biologics Evaluation and Research (CBER).
During pre-vote discussions, committee members were unanimous in noting with favor the high and sustained efficacy seen for HZ/su in the trial data, especially for older populations. However, some participants wondered about the generalizability of both safety and efficacy data to all populations, given the very low trial enrollment numbers for Africans, African Americans, and individuals of Hispanic origin.
The two studies, Zoster-006 and Zoster-022, were similar in design and were conducted in parallel across 18 countries; data were able to be pooled for key efficacy and safety outcomes. Study Zoster-006 enrolled patients aged 50 years and older, while study Zoster-022 began enrollment at age 70. Patients were randomized to receive vaccine or placebo, and were followed for a median of 3.1 years for efficacy in Zoster-006 and a median of 3.9 years for Zoster-022. Safety data were obtained for a median 4.4 years for both studies.
The primary outcome measure for both studies in pooled analysis was the vaccine’s effectiveness against herpes zoster and postherpetic neuropathy in adults aged 70 and over. Safety was also assessed using pooled data.
The United States was represented by 3,934 of more than 29,000 patients enrolled globally. The remainder were primarily in Western Europe, with some sites in Australia and eastern Asia, Canada, and Latin America.
The vaccine consists of a recombinant, lyophilized truncated form of the varicella zoster virus (VZV) glycoprotein E (gE) antigen protein that, at the time of administration, is reconstituted with a novel adjuvant suspension. The antigen selection was based on the fact that gE is expressed on the surface of infected cells and is the target of both humoral and cellular immune responses in the host, said GSK’s Arnaud Didierlaurent, PhD, director and head of the adjuvant platform for GSK Vaccine’s Belgium research and development division.
The adjuvant, termed ASO1B, is not currently in use for any U.S.-approved vaccine, though it was developed more than 20 years ago, said Dr. Didierlaurent. Its combination with recombinant VZV gE was found to significantly boost the antigen’s immunogenicity during GSK’s vaccine development program. The adjuvant enhances a transient innate response in the first 3 days after administration that later helps maintain durably high levels of gE-specific antibodies and strengthens gE-specific cell-mediated immunity.
Mechanistically, the robust initial innate response is responsible for the constitutional symptoms and local site reactions seen in pooled data from the two pivotal clinical trials: 70%-85% of participants receiving HZ/su reported injection site pain, 38% of participants receiving HZ/su reported redness, and about a quarter reported swelling. By comparison, 9%-13% of those receiving placebo reported injection site pain, and about 1% reported redness and swelling.
Fatigue, headache, mild fever, myalgia, and shivering were all more common in those receiving HZ/su; both local and generalized symptoms were more common in younger recipients.
“I think this is a very good case for the first licensure of this adjuvant in the United States, because the efficacy seems pretty compelling, the disease is morbid, and there are a lot of people whose lives would be changed,” said committee member Sarah Long, MD, professor of pediatrics at Drexel University, Philadelphia.
Both the GSK and FDA presentations were in agreement that serious adverse events were in the range to be expected for an older population, and balanced across study arms. However, particular attention will be given to certain potential complications during the proposed pharmacovigilance plan.
“An imbalance toward vaccine versus placebo was observed” for gout, optic ischemic neuropathy, amyotrophic lateral sclerosis, osteonecrosis, convulsion-type reactions, and supraventricular tachycardias. “All are an adverse event of interest and will be included in planned targeted safety study,” said Dr. Didierlaurent.
Several committee members remarked on the difficulty of evaluating vaccine safety in an older population, where analysis takes place against the backdrop of more comorbidities and acute illnesses than in the younger population.
“There has been a thoughtful job both by the sponsor and by CBER in looking at complicated data,” said Melinda Wharton, MD, the director of the immunization services division of the National Center for Immunization and Respiratory Diseases at the Centers for Disease Control and Prevention, Atlanta.
The committee’s chair, Kathryn Edwards, MD, agreed. “I applaud the comprehensive analysis of all these safety signals. Both the sponsor and the FDA have done a wonderful job of drilling down and answering these questions,” she said. Dr. Edwards is the Sarah H. Sell and Cornelius Vanderbilt chair in pediatrics at Vanderbilt University, Nashville, Tenn.
Herpes zoster, a reactivation of the varicella virus that lies dormant in dorsal root or cranial nerve ganglia from earlier infection, is seen in about 1 million cases per year in the United States, with about 100,000 to 200,000 cases of postherpetic neuralgia occurring, said Jeffrey Cohen, MD, chief of the laboratory of infectious diseases at the National Institute of Allergy and Infectious Diseases, Bethesda, Md. The rates of herpes zoster are increasing in the United States for unknown reasons, and direct medical costs may currently exceed $1 billion annually, he said.
Each 0.5 mL dose of the HZ/su vaccine contains 50 mcg each of the recombinant VZV gE antigen and each of the two component parts of the ASO1B adjuvant. Two doses of the vaccine are administered intramuscularly 2-6 months apart. Dose-ranging studies were conducted before the pivotal clinical trials to ascertain the optimal dose of all of the vaccine components, the need for two doses, and the optimal spacing between doses.
All committee participants submitted conflict of interest statements to the FDA, and any potential conflicts were resolved before the hearing.
koakes@frontlinemedcom.com
On Twitter @karioakes
Meningitis B vaccine’s high price tag poses a health care conundrum
Four years ago, when meningitis B, an extremely rare but potentially lethal form of the infection, sickened a small number of college students at Princeton and the University of California–Santa Barbara, there was no vaccine against the disease sold in the U.S. Despite its availability abroad, it had never been licensed in the country due to its limited marketability.
Scientific evidence supporting an absolute need to immunize against meningitis B still falls short. The risk of contracting it is smaller than that of being involved in a car crash.
But the headlines prompted by those 13 campus cases – which resulted in one death and one double amputation – helped reshape the financial prospects for a vaccine.
Today, two brand-name vaccines, both with price tags of more than $300, are widely advertised on television and touted as a smart investment for parents who love their college-bound kids.
“As moms, we send our kids out into the world, full of hope,” says a mother in the ad for Bexsero, sold by pharmaceutical giant GlaxoSmithKline, as her son loads up the car to go off to college.
Says another voice, “And we don’t want something like meningitis B getting in their way.”
Analysts expect the two vaccines to generate annually at least hundreds of millions of dollars in global sales.
As new crops of students head to college, some physicians and other industry experts, though, are growing uneasy about the role of marketing in leveraging parental fears to sell the MenB vaccine – as well as ever more expensive vaccines that prevent quite rare illnesses. A complete Bexsero series costs $320; a competing vaccine, Trumenba, costs $345.
“Parents believe their children are susceptible to this terrible condition, and [drugmakers] use that fear to get parents to take action,” said Adrienne Faerber, a lecturer at the Dartmouth Institute for Health Policy and Clinical Practice who researches drug marketing.
The advertising, especially when coupled with news coverage, puts parents in a quandary left unresolved by federal vaccination guidelines and university requirements.
The Centers for Disease Control and Prevention recommends doctors consider the meningitis B vaccine for people ages 16-23 years on an individual basis. This recommendation – ranked as a category B – is not as universal as the approach applied to illnesses such as measles or human papillomavirus vaccines or even the “quadrivalent” vaccine for meningitis A, C, W, and Y, which all students must get.
Meanwhile, insurers generally cover it as part of preventive care. Still, most universities don’t require the vaccine but simply list it as an option for families to consider.
The resulting messages can confuse parents.
“There is perhaps, with all the marketing and advertising, some bending of the truth, and perhaps a little bit of creating fear – again recognizing that meningitis disease is a very severe disease,” said William Moss, a professor at Johns Hopkins Bloomberg School of Public Health who specializes in vaccines and global children’s health. “[The risk] is not a large enough problem to warrant routine vaccination.”
In recent years, drugmakers’ interests have begun to expand beyond the relatively cheap, broadly used immunizations – such as a tetanus shot or the children’s hepatitis A vaccine – to new, much pricier ones for less common infections.
These newer treatments have the potential to transform what’s long been a less lucrative side of drug production, manufacturing vaccines, into a major cash cow. But since the newer vaccines are regarded as less crucial than, say, preventing measles – and are often not required – marketing has become a big part of the sales equation.
Bexsero and its competitor, Trumenba, offer clues into how this scenario plays out.
Both vaccines got accelerated approval by the Food and Drug Administration in 2015 and 2014 respectively, following the Princeton and UCSB outbreaks.
Meningitis B does not spread readily from person to person. It requires close physical contact, like kissing or sharing utensils. It can be fatal but is treatable with antibiotics if caught early. Caused by the B serogroup of the meningococcal infection, it tends to appear in rare-scatter, slowed, self-limited outbreaks on college campuses. The standard meningitis vaccine doesn’t prevent it.
After new cases at Princeton and UC Santa Barbara kept appearing over many months, the CDC arranged for an emergency import of Bexsero. All students on those campuses got the shots, and there were no more cases.
Now the drugmakers are urging all parents to be proactive. Last year, Pfizer put more than $21 million into paid advertisements for the vaccine, according to figures kept by Kantar Media, a firm that tracks multimedia advertising. GlaxoSmithKline put in just about $79,000.
Those figures don’t account for other efforts such as meningitis awareness and ongoing social media campaigns done by GlaxoSmithKline, a “substantial effort” that “wasn’t cheap,” said Sriram Jambunathan, who heads GlaxoSmithKline’s meningococcal franchise in the United States. They also don’t include Pfizer’s investments in similar activities.
Already, industry analysts forecast Bexsero could bring in global revenue north of $1 billion per year by 2022. Trumenba is expected to earn Pfizer $880 million by that time.
But the industry’s gain may come at the expense of efficient health care spending and inflated consumer concern.
First, there’s the relative rarity of meningitis B. The CDC has estimated fewer than 300 cases occur in the United States per year, and some medical experts interviewed suggested the number may be closer to 50 or 60.
“As a mom, I would say, if my kid got this disease, and I had had the opportunity to prevent it, and I didn’t, I would kill myself,” said Martha Arden, a practicing physician and the medical director of Mount Sinai Adolescent Health Center’s school-based health program in New York City. “But the odds are small. It’s much more dangerous to send a kid out skiing than it is to not give the vaccine.”
Jambunathan said the price tag is warranted given the resources needed to bring Bexsero to market. Similar vaccines, he added, are comparably priced, and firms won’t necessarily want to develop these pharmaceuticals if they aren’t sure they can recoup their investment.
For parents who opt for the vaccines, there are caveats. Researchers don’t know, for instance, how long its immunity lasts. Many noted it also doesn’t cover all strains of the infection, so its efficacy in the United States is uncertain (there are different strains in different parts of the world).
And the cost of vaccination, while substantial, isn’t immediately felt by consumers because the treatment usually is covered without having to pay out-of-pocket. But the price tag may contribute to increasing premium costs.
In a world where there already aren’t enough health care dollars to address every possible harm, many experts noted, other health concerns might be a smarter investment.
Still, the price tag might not cause parents to blink. “When it’s your child or one case you know about, suddenly the health economic arguments feel difficult to have,” Jambunathan said.
Kaiser Health News is a national health policy news service that is part of the nonpartisan Henry J. Kaiser Family Foundation.
In October 2014 and January 2015, the Food and Drug Administration licensed two meningococcal serogroup B vaccines for administration in adolescents and young adults aged 10-25 years based on each vaccine's ability to elicit bactericidal antibody against the majority of invasive serogroup B strains and demonstrated safety. Each vaccine represented novel technology that overcame the challenge of both the poor immunogenicity of serogroup B polysaccharide protein conjugates and the potential cross reactivity with fetal brain tissue. In the United States, the vaccine was recommended (category A) for individuals in this age grouping with complement deficiency, anatomic or functional asplenia, outbreaks (when indicated), and for microbiologists. The Centers for Disease Control and Prevention also recommends that physicians consider the MenB vaccine for individuals aged 16-23 years who wish to obtain short-term protection against diverse strains of serogroup B meningococcal disease (category B). The American Academy of Pediatrics encouraged pediatricians to discuss the availability of the MenB vaccines with families.
The annual incidence of meningococcal disease varied between approximately 0.5-1.5 cases per 100,000 population between 1950 and 1990 - approximately 3,000 cases annually. Between 1990 and 2010, disease caused by the three common serogroups in the United States (B, C, and Y) declined to approximately 0.35 cases per 100,000. Subsequent to the introduction of a tetravalent meningococcal conjugate vaccine (MCV4) further declines - sustained over a longer time period than previously observed - have occurred, reaching a nadir of approximately 400 annual cases. Despite the absence of serogroup B component in MCV4, declines in serogroup B disease were reported in addition to vaccine serogroups C and Y. The biological explanations for the substantial decline in the overall rate of meningococcal disease are unknown. This decline in meningococcal serogroup B disease has created a controversy about implementation of Advisory Committee of Immunization Practices and the AAP and American Academy of Family Physician recommendations reflected in Shefali Luthra's writings.
There is widespread agreement about the severity of invasive meningococcal disease, the peaks of incidence in infancy and late adolescence, a 10% case fatality rate, an additional 10%-15% morbidity, and the limited number of cases (in the United States) to be prevented by adolescent immunization despite serogroup B being the most common. The effectiveness (greater than 80%) of at least one of these vaccines (MenB-4C) has been established in the United Kingdom, where it is recommended for all infants as part of a three-dose series at 2, 4, and 12 months. The value proposition (number of people immunized to prevent one death), however, is estimated at 1 million vaccinees for each death prevented.
Some experts believe the small burden of disease that might be prevented by these expensive vaccines requires thoughtful consideration in this era of increasingly limited resources. Others (as cited in the accompanying article) believe the marketing and advertising bend the truth and create fear in the public and conclude the risk is not great enough to warrant universal immunization (called category A by ACIP designation). In contrast, parent groups (especially those including parents of children who had meningococcal serogroup B disease) advocate strongly for a universal approach. For example, Alicia Stillman, director of the Emily Stillman Foundation, feels the current recommendation is "irresponsible" because it leaves so many teens and young adults vulnerable to the disease. The group believes that ACIP has made the menB vaccine to be an "optional item," but there is no requirement to provide the education to the parent and/or patient so they are aware of this option.
For me, the question is this: Who should decide how we use limited resources? I am reminded of an editorial in the New England Journal of Medicine titled, "The Meningococcal Vaccine - Public Policy and Individual Choices" by Paul Offit, MD, and Georges Peter, MD, that examined this question (N Engl J Med. 2003;349[24]:2353-6). They advocated that parents, if aware, may choose vaccination to protect adolescents and young adults from devastating infection, even if they were required to pay. I believe the CDC foresaw this as likely and moved to recommend individual choice. The wisdom of this was that category B status required MenB vaccine to be covered by insurers, thus preventing a potential divergent uptake, where families that could afford the price would recognize its value and those unable to pay for the vaccine would have no choice but to decline. This is especially relevant as there are not specific risk factors among healthy adolescents to warrant prioritizing one group over another.
MenB vaccines are valuable but costly tools for the prevention of life-threatening infectious disease. The use of increasingly limited resources, as raised by Dr. Moss and others, is a relevant and important question, and a call for a national dialogue.
As new medical breakthroughs increase, seemingly exponentially, how do we resolve the individual versus societal benefit of costly new treatments or preventions? How do we value prevention of life-threatening illness and death in mostly healthy adolescents, compared with treatment of end-stage diseases? These are important conversations that are only in their infancy.
Abraham Verghese wrote, in his book "Cutting for Stone," that American ambulance crews "salvaged people we'd never see in Missing [fictional hospital in Addis Ababa], because no one would have tried to bring them to a hospital [in Addis Ababa]. Judging someone to be beyond help never crossed the minds of police, firemen, or doctors here" in the United States. We need transparency and a national dialogue to develop consensus about priorities. We need to make sure the discussions are comprehensive and civil - not about pushing grandmothers over cliffs or death panels. Currently, ACIP and AAP have advocated for individual choice and to empower the parent and adolescent to choose after we (clinicians) communicate disease severity, the risk to the adolescent, and adverse events associated with MenB vaccine.
Stephen I. Pelton, MD, is chief of pediatric infectious disease and coordinator of the maternal-child HIV program at Boston Medical Center. Dr. Pelton disclosed that he has participated in advisory boards on meningitis B vaccines for GlaxoSmithKline and Pfizer, has research grants from Pfizer and Merck, and has spoken at CME events on meningitis B vaccines.
In October 2014 and January 2015, the Food and Drug Administration licensed two meningococcal serogroup B vaccines for administration in adolescents and young adults aged 10-25 years based on each vaccine's ability to elicit bactericidal antibody against the majority of invasive serogroup B strains and demonstrated safety. Each vaccine represented novel technology that overcame the challenge of both the poor immunogenicity of serogroup B polysaccharide protein conjugates and the potential cross reactivity with fetal brain tissue. In the United States, the vaccine was recommended (category A) for individuals in this age grouping with complement deficiency, anatomic or functional asplenia, outbreaks (when indicated), and for microbiologists. The Centers for Disease Control and Prevention also recommends that physicians consider the MenB vaccine for individuals aged 16-23 years who wish to obtain short-term protection against diverse strains of serogroup B meningococcal disease (category B). The American Academy of Pediatrics encouraged pediatricians to discuss the availability of the MenB vaccines with families.
The annual incidence of meningococcal disease varied between approximately 0.5-1.5 cases per 100,000 population between 1950 and 1990 - approximately 3,000 cases annually. Between 1990 and 2010, disease caused by the three common serogroups in the United States (B, C, and Y) declined to approximately 0.35 cases per 100,000. Subsequent to the introduction of a tetravalent meningococcal conjugate vaccine (MCV4) further declines - sustained over a longer time period than previously observed - have occurred, reaching a nadir of approximately 400 annual cases. Despite the absence of serogroup B component in MCV4, declines in serogroup B disease were reported in addition to vaccine serogroups C and Y. The biological explanations for the substantial decline in the overall rate of meningococcal disease are unknown. This decline in meningococcal serogroup B disease has created a controversy about implementation of Advisory Committee of Immunization Practices and the AAP and American Academy of Family Physician recommendations reflected in Shefali Luthra's writings.
There is widespread agreement about the severity of invasive meningococcal disease, the peaks of incidence in infancy and late adolescence, a 10% case fatality rate, an additional 10%-15% morbidity, and the limited number of cases (in the United States) to be prevented by adolescent immunization despite serogroup B being the most common. The effectiveness (greater than 80%) of at least one of these vaccines (MenB-4C) has been established in the United Kingdom, where it is recommended for all infants as part of a three-dose series at 2, 4, and 12 months. The value proposition (number of people immunized to prevent one death), however, is estimated at 1 million vaccinees for each death prevented.
Some experts believe the small burden of disease that might be prevented by these expensive vaccines requires thoughtful consideration in this era of increasingly limited resources. Others (as cited in the accompanying article) believe the marketing and advertising bend the truth and create fear in the public and conclude the risk is not great enough to warrant universal immunization (called category A by ACIP designation). In contrast, parent groups (especially those including parents of children who had meningococcal serogroup B disease) advocate strongly for a universal approach. For example, Alicia Stillman, director of the Emily Stillman Foundation, feels the current recommendation is "irresponsible" because it leaves so many teens and young adults vulnerable to the disease. The group believes that ACIP has made the menB vaccine to be an "optional item," but there is no requirement to provide the education to the parent and/or patient so they are aware of this option.
For me, the question is this: Who should decide how we use limited resources? I am reminded of an editorial in the New England Journal of Medicine titled, "The Meningococcal Vaccine - Public Policy and Individual Choices" by Paul Offit, MD, and Georges Peter, MD, that examined this question (N Engl J Med. 2003;349[24]:2353-6). They advocated that parents, if aware, may choose vaccination to protect adolescents and young adults from devastating infection, even if they were required to pay. I believe the CDC foresaw this as likely and moved to recommend individual choice. The wisdom of this was that category B status required MenB vaccine to be covered by insurers, thus preventing a potential divergent uptake, where families that could afford the price would recognize its value and those unable to pay for the vaccine would have no choice but to decline. This is especially relevant as there are not specific risk factors among healthy adolescents to warrant prioritizing one group over another.
MenB vaccines are valuable but costly tools for the prevention of life-threatening infectious disease. The use of increasingly limited resources, as raised by Dr. Moss and others, is a relevant and important question, and a call for a national dialogue.
As new medical breakthroughs increase, seemingly exponentially, how do we resolve the individual versus societal benefit of costly new treatments or preventions? How do we value prevention of life-threatening illness and death in mostly healthy adolescents, compared with treatment of end-stage diseases? These are important conversations that are only in their infancy.
Abraham Verghese wrote, in his book "Cutting for Stone," that American ambulance crews "salvaged people we'd never see in Missing [fictional hospital in Addis Ababa], because no one would have tried to bring them to a hospital [in Addis Ababa]. Judging someone to be beyond help never crossed the minds of police, firemen, or doctors here" in the United States. We need transparency and a national dialogue to develop consensus about priorities. We need to make sure the discussions are comprehensive and civil - not about pushing grandmothers over cliffs or death panels. Currently, ACIP and AAP have advocated for individual choice and to empower the parent and adolescent to choose after we (clinicians) communicate disease severity, the risk to the adolescent, and adverse events associated with MenB vaccine.
Stephen I. Pelton, MD, is chief of pediatric infectious disease and coordinator of the maternal-child HIV program at Boston Medical Center. Dr. Pelton disclosed that he has participated in advisory boards on meningitis B vaccines for GlaxoSmithKline and Pfizer, has research grants from Pfizer and Merck, and has spoken at CME events on meningitis B vaccines.
In October 2014 and January 2015, the Food and Drug Administration licensed two meningococcal serogroup B vaccines for administration in adolescents and young adults aged 10-25 years based on each vaccine's ability to elicit bactericidal antibody against the majority of invasive serogroup B strains and demonstrated safety. Each vaccine represented novel technology that overcame the challenge of both the poor immunogenicity of serogroup B polysaccharide protein conjugates and the potential cross reactivity with fetal brain tissue. In the United States, the vaccine was recommended (category A) for individuals in this age grouping with complement deficiency, anatomic or functional asplenia, outbreaks (when indicated), and for microbiologists. The Centers for Disease Control and Prevention also recommends that physicians consider the MenB vaccine for individuals aged 16-23 years who wish to obtain short-term protection against diverse strains of serogroup B meningococcal disease (category B). The American Academy of Pediatrics encouraged pediatricians to discuss the availability of the MenB vaccines with families.
The annual incidence of meningococcal disease varied between approximately 0.5-1.5 cases per 100,000 population between 1950 and 1990 - approximately 3,000 cases annually. Between 1990 and 2010, disease caused by the three common serogroups in the United States (B, C, and Y) declined to approximately 0.35 cases per 100,000. Subsequent to the introduction of a tetravalent meningococcal conjugate vaccine (MCV4) further declines - sustained over a longer time period than previously observed - have occurred, reaching a nadir of approximately 400 annual cases. Despite the absence of serogroup B component in MCV4, declines in serogroup B disease were reported in addition to vaccine serogroups C and Y. The biological explanations for the substantial decline in the overall rate of meningococcal disease are unknown. This decline in meningococcal serogroup B disease has created a controversy about implementation of Advisory Committee of Immunization Practices and the AAP and American Academy of Family Physician recommendations reflected in Shefali Luthra's writings.
There is widespread agreement about the severity of invasive meningococcal disease, the peaks of incidence in infancy and late adolescence, a 10% case fatality rate, an additional 10%-15% morbidity, and the limited number of cases (in the United States) to be prevented by adolescent immunization despite serogroup B being the most common. The effectiveness (greater than 80%) of at least one of these vaccines (MenB-4C) has been established in the United Kingdom, where it is recommended for all infants as part of a three-dose series at 2, 4, and 12 months. The value proposition (number of people immunized to prevent one death), however, is estimated at 1 million vaccinees for each death prevented.
Some experts believe the small burden of disease that might be prevented by these expensive vaccines requires thoughtful consideration in this era of increasingly limited resources. Others (as cited in the accompanying article) believe the marketing and advertising bend the truth and create fear in the public and conclude the risk is not great enough to warrant universal immunization (called category A by ACIP designation). In contrast, parent groups (especially those including parents of children who had meningococcal serogroup B disease) advocate strongly for a universal approach. For example, Alicia Stillman, director of the Emily Stillman Foundation, feels the current recommendation is "irresponsible" because it leaves so many teens and young adults vulnerable to the disease. The group believes that ACIP has made the menB vaccine to be an "optional item," but there is no requirement to provide the education to the parent and/or patient so they are aware of this option.
For me, the question is this: Who should decide how we use limited resources? I am reminded of an editorial in the New England Journal of Medicine titled, "The Meningococcal Vaccine - Public Policy and Individual Choices" by Paul Offit, MD, and Georges Peter, MD, that examined this question (N Engl J Med. 2003;349[24]:2353-6). They advocated that parents, if aware, may choose vaccination to protect adolescents and young adults from devastating infection, even if they were required to pay. I believe the CDC foresaw this as likely and moved to recommend individual choice. The wisdom of this was that category B status required MenB vaccine to be covered by insurers, thus preventing a potential divergent uptake, where families that could afford the price would recognize its value and those unable to pay for the vaccine would have no choice but to decline. This is especially relevant as there are not specific risk factors among healthy adolescents to warrant prioritizing one group over another.
MenB vaccines are valuable but costly tools for the prevention of life-threatening infectious disease. The use of increasingly limited resources, as raised by Dr. Moss and others, is a relevant and important question, and a call for a national dialogue.
As new medical breakthroughs increase, seemingly exponentially, how do we resolve the individual versus societal benefit of costly new treatments or preventions? How do we value prevention of life-threatening illness and death in mostly healthy adolescents, compared with treatment of end-stage diseases? These are important conversations that are only in their infancy.
Abraham Verghese wrote, in his book "Cutting for Stone," that American ambulance crews "salvaged people we'd never see in Missing [fictional hospital in Addis Ababa], because no one would have tried to bring them to a hospital [in Addis Ababa]. Judging someone to be beyond help never crossed the minds of police, firemen, or doctors here" in the United States. We need transparency and a national dialogue to develop consensus about priorities. We need to make sure the discussions are comprehensive and civil - not about pushing grandmothers over cliffs or death panels. Currently, ACIP and AAP have advocated for individual choice and to empower the parent and adolescent to choose after we (clinicians) communicate disease severity, the risk to the adolescent, and adverse events associated with MenB vaccine.
Stephen I. Pelton, MD, is chief of pediatric infectious disease and coordinator of the maternal-child HIV program at Boston Medical Center. Dr. Pelton disclosed that he has participated in advisory boards on meningitis B vaccines for GlaxoSmithKline and Pfizer, has research grants from Pfizer and Merck, and has spoken at CME events on meningitis B vaccines.
Four years ago, when meningitis B, an extremely rare but potentially lethal form of the infection, sickened a small number of college students at Princeton and the University of California–Santa Barbara, there was no vaccine against the disease sold in the U.S. Despite its availability abroad, it had never been licensed in the country due to its limited marketability.
Scientific evidence supporting an absolute need to immunize against meningitis B still falls short. The risk of contracting it is smaller than that of being involved in a car crash.
But the headlines prompted by those 13 campus cases – which resulted in one death and one double amputation – helped reshape the financial prospects for a vaccine.
Today, two brand-name vaccines, both with price tags of more than $300, are widely advertised on television and touted as a smart investment for parents who love their college-bound kids.
“As moms, we send our kids out into the world, full of hope,” says a mother in the ad for Bexsero, sold by pharmaceutical giant GlaxoSmithKline, as her son loads up the car to go off to college.
Says another voice, “And we don’t want something like meningitis B getting in their way.”
Analysts expect the two vaccines to generate annually at least hundreds of millions of dollars in global sales.
As new crops of students head to college, some physicians and other industry experts, though, are growing uneasy about the role of marketing in leveraging parental fears to sell the MenB vaccine – as well as ever more expensive vaccines that prevent quite rare illnesses. A complete Bexsero series costs $320; a competing vaccine, Trumenba, costs $345.
“Parents believe their children are susceptible to this terrible condition, and [drugmakers] use that fear to get parents to take action,” said Adrienne Faerber, a lecturer at the Dartmouth Institute for Health Policy and Clinical Practice who researches drug marketing.
The advertising, especially when coupled with news coverage, puts parents in a quandary left unresolved by federal vaccination guidelines and university requirements.
The Centers for Disease Control and Prevention recommends doctors consider the meningitis B vaccine for people ages 16-23 years on an individual basis. This recommendation – ranked as a category B – is not as universal as the approach applied to illnesses such as measles or human papillomavirus vaccines or even the “quadrivalent” vaccine for meningitis A, C, W, and Y, which all students must get.
Meanwhile, insurers generally cover it as part of preventive care. Still, most universities don’t require the vaccine but simply list it as an option for families to consider.
The resulting messages can confuse parents.
“There is perhaps, with all the marketing and advertising, some bending of the truth, and perhaps a little bit of creating fear – again recognizing that meningitis disease is a very severe disease,” said William Moss, a professor at Johns Hopkins Bloomberg School of Public Health who specializes in vaccines and global children’s health. “[The risk] is not a large enough problem to warrant routine vaccination.”
In recent years, drugmakers’ interests have begun to expand beyond the relatively cheap, broadly used immunizations – such as a tetanus shot or the children’s hepatitis A vaccine – to new, much pricier ones for less common infections.
These newer treatments have the potential to transform what’s long been a less lucrative side of drug production, manufacturing vaccines, into a major cash cow. But since the newer vaccines are regarded as less crucial than, say, preventing measles – and are often not required – marketing has become a big part of the sales equation.
Bexsero and its competitor, Trumenba, offer clues into how this scenario plays out.
Both vaccines got accelerated approval by the Food and Drug Administration in 2015 and 2014 respectively, following the Princeton and UCSB outbreaks.
Meningitis B does not spread readily from person to person. It requires close physical contact, like kissing or sharing utensils. It can be fatal but is treatable with antibiotics if caught early. Caused by the B serogroup of the meningococcal infection, it tends to appear in rare-scatter, slowed, self-limited outbreaks on college campuses. The standard meningitis vaccine doesn’t prevent it.
After new cases at Princeton and UC Santa Barbara kept appearing over many months, the CDC arranged for an emergency import of Bexsero. All students on those campuses got the shots, and there were no more cases.
Now the drugmakers are urging all parents to be proactive. Last year, Pfizer put more than $21 million into paid advertisements for the vaccine, according to figures kept by Kantar Media, a firm that tracks multimedia advertising. GlaxoSmithKline put in just about $79,000.
Those figures don’t account for other efforts such as meningitis awareness and ongoing social media campaigns done by GlaxoSmithKline, a “substantial effort” that “wasn’t cheap,” said Sriram Jambunathan, who heads GlaxoSmithKline’s meningococcal franchise in the United States. They also don’t include Pfizer’s investments in similar activities.
Already, industry analysts forecast Bexsero could bring in global revenue north of $1 billion per year by 2022. Trumenba is expected to earn Pfizer $880 million by that time.
But the industry’s gain may come at the expense of efficient health care spending and inflated consumer concern.
First, there’s the relative rarity of meningitis B. The CDC has estimated fewer than 300 cases occur in the United States per year, and some medical experts interviewed suggested the number may be closer to 50 or 60.
“As a mom, I would say, if my kid got this disease, and I had had the opportunity to prevent it, and I didn’t, I would kill myself,” said Martha Arden, a practicing physician and the medical director of Mount Sinai Adolescent Health Center’s school-based health program in New York City. “But the odds are small. It’s much more dangerous to send a kid out skiing than it is to not give the vaccine.”
Jambunathan said the price tag is warranted given the resources needed to bring Bexsero to market. Similar vaccines, he added, are comparably priced, and firms won’t necessarily want to develop these pharmaceuticals if they aren’t sure they can recoup their investment.
For parents who opt for the vaccines, there are caveats. Researchers don’t know, for instance, how long its immunity lasts. Many noted it also doesn’t cover all strains of the infection, so its efficacy in the United States is uncertain (there are different strains in different parts of the world).
And the cost of vaccination, while substantial, isn’t immediately felt by consumers because the treatment usually is covered without having to pay out-of-pocket. But the price tag may contribute to increasing premium costs.
In a world where there already aren’t enough health care dollars to address every possible harm, many experts noted, other health concerns might be a smarter investment.
Still, the price tag might not cause parents to blink. “When it’s your child or one case you know about, suddenly the health economic arguments feel difficult to have,” Jambunathan said.
Kaiser Health News is a national health policy news service that is part of the nonpartisan Henry J. Kaiser Family Foundation.
Four years ago, when meningitis B, an extremely rare but potentially lethal form of the infection, sickened a small number of college students at Princeton and the University of California–Santa Barbara, there was no vaccine against the disease sold in the U.S. Despite its availability abroad, it had never been licensed in the country due to its limited marketability.
Scientific evidence supporting an absolute need to immunize against meningitis B still falls short. The risk of contracting it is smaller than that of being involved in a car crash.
But the headlines prompted by those 13 campus cases – which resulted in one death and one double amputation – helped reshape the financial prospects for a vaccine.
Today, two brand-name vaccines, both with price tags of more than $300, are widely advertised on television and touted as a smart investment for parents who love their college-bound kids.
“As moms, we send our kids out into the world, full of hope,” says a mother in the ad for Bexsero, sold by pharmaceutical giant GlaxoSmithKline, as her son loads up the car to go off to college.
Says another voice, “And we don’t want something like meningitis B getting in their way.”
Analysts expect the two vaccines to generate annually at least hundreds of millions of dollars in global sales.
As new crops of students head to college, some physicians and other industry experts, though, are growing uneasy about the role of marketing in leveraging parental fears to sell the MenB vaccine – as well as ever more expensive vaccines that prevent quite rare illnesses. A complete Bexsero series costs $320; a competing vaccine, Trumenba, costs $345.
“Parents believe their children are susceptible to this terrible condition, and [drugmakers] use that fear to get parents to take action,” said Adrienne Faerber, a lecturer at the Dartmouth Institute for Health Policy and Clinical Practice who researches drug marketing.
The advertising, especially when coupled with news coverage, puts parents in a quandary left unresolved by federal vaccination guidelines and university requirements.
The Centers for Disease Control and Prevention recommends doctors consider the meningitis B vaccine for people ages 16-23 years on an individual basis. This recommendation – ranked as a category B – is not as universal as the approach applied to illnesses such as measles or human papillomavirus vaccines or even the “quadrivalent” vaccine for meningitis A, C, W, and Y, which all students must get.
Meanwhile, insurers generally cover it as part of preventive care. Still, most universities don’t require the vaccine but simply list it as an option for families to consider.
The resulting messages can confuse parents.
“There is perhaps, with all the marketing and advertising, some bending of the truth, and perhaps a little bit of creating fear – again recognizing that meningitis disease is a very severe disease,” said William Moss, a professor at Johns Hopkins Bloomberg School of Public Health who specializes in vaccines and global children’s health. “[The risk] is not a large enough problem to warrant routine vaccination.”
In recent years, drugmakers’ interests have begun to expand beyond the relatively cheap, broadly used immunizations – such as a tetanus shot or the children’s hepatitis A vaccine – to new, much pricier ones for less common infections.
These newer treatments have the potential to transform what’s long been a less lucrative side of drug production, manufacturing vaccines, into a major cash cow. But since the newer vaccines are regarded as less crucial than, say, preventing measles – and are often not required – marketing has become a big part of the sales equation.
Bexsero and its competitor, Trumenba, offer clues into how this scenario plays out.
Both vaccines got accelerated approval by the Food and Drug Administration in 2015 and 2014 respectively, following the Princeton and UCSB outbreaks.
Meningitis B does not spread readily from person to person. It requires close physical contact, like kissing or sharing utensils. It can be fatal but is treatable with antibiotics if caught early. Caused by the B serogroup of the meningococcal infection, it tends to appear in rare-scatter, slowed, self-limited outbreaks on college campuses. The standard meningitis vaccine doesn’t prevent it.
After new cases at Princeton and UC Santa Barbara kept appearing over many months, the CDC arranged for an emergency import of Bexsero. All students on those campuses got the shots, and there were no more cases.
Now the drugmakers are urging all parents to be proactive. Last year, Pfizer put more than $21 million into paid advertisements for the vaccine, according to figures kept by Kantar Media, a firm that tracks multimedia advertising. GlaxoSmithKline put in just about $79,000.
Those figures don’t account for other efforts such as meningitis awareness and ongoing social media campaigns done by GlaxoSmithKline, a “substantial effort” that “wasn’t cheap,” said Sriram Jambunathan, who heads GlaxoSmithKline’s meningococcal franchise in the United States. They also don’t include Pfizer’s investments in similar activities.
Already, industry analysts forecast Bexsero could bring in global revenue north of $1 billion per year by 2022. Trumenba is expected to earn Pfizer $880 million by that time.
But the industry’s gain may come at the expense of efficient health care spending and inflated consumer concern.
First, there’s the relative rarity of meningitis B. The CDC has estimated fewer than 300 cases occur in the United States per year, and some medical experts interviewed suggested the number may be closer to 50 or 60.
“As a mom, I would say, if my kid got this disease, and I had had the opportunity to prevent it, and I didn’t, I would kill myself,” said Martha Arden, a practicing physician and the medical director of Mount Sinai Adolescent Health Center’s school-based health program in New York City. “But the odds are small. It’s much more dangerous to send a kid out skiing than it is to not give the vaccine.”
Jambunathan said the price tag is warranted given the resources needed to bring Bexsero to market. Similar vaccines, he added, are comparably priced, and firms won’t necessarily want to develop these pharmaceuticals if they aren’t sure they can recoup their investment.
For parents who opt for the vaccines, there are caveats. Researchers don’t know, for instance, how long its immunity lasts. Many noted it also doesn’t cover all strains of the infection, so its efficacy in the United States is uncertain (there are different strains in different parts of the world).
And the cost of vaccination, while substantial, isn’t immediately felt by consumers because the treatment usually is covered without having to pay out-of-pocket. But the price tag may contribute to increasing premium costs.
In a world where there already aren’t enough health care dollars to address every possible harm, many experts noted, other health concerns might be a smarter investment.
Still, the price tag might not cause parents to blink. “When it’s your child or one case you know about, suddenly the health economic arguments feel difficult to have,” Jambunathan said.
Kaiser Health News is a national health policy news service that is part of the nonpartisan Henry J. Kaiser Family Foundation.
Vaccinate and consider tofacitinib monotherapy to prevent herpes zoster in RA
The results of two studies of tofacitinib treatment for rheumatoid arthritis offer evidence to support the use of the drug without concomitant conventional synthetic disease-modifying antirheumatic drugs in order to reduce the risk of risk of herpes zoster infection and the safety of starting the drug 2-3 weeks after administering live zoster vaccine.
The risk of herpes zoster infection was elevated among rheumatoid arthritis (RA) patients receiving tofacitinib (Xeljanz) with glucocorticoids, compared with those receiving tofacitinib monotherapy, according to an analysis of data from 19 phase 2, phase 3, and long-term extension studies of tofacitinib.
“Further, physicians should continue to consider shingles vaccination prior to starting tofacitinib or biologic therapy,” they wrote.
Dr. Winthrop is the first author of a separate phase 2 study that also appears in Arthritis & Rheumatology, which suggests that live zoster vaccine (LZV) is safe in RA patients who start tofacitinib 2-3 weeks after vaccination. The study also showed that varicella-zoster virus (VZV)-specific humoral and cell-mediated immune responses to LZV are similar in tofacitinib- and placebo-treated patients.
“Our study provides the first data with this vaccine in the RA setting and suggests that these patients, even while using nonbiologic DMARDs at the time of vaccination, are capable of mounting adequate immune responses to this vaccine. Further, our data suggest that the use of tofacitinib following VZV vaccination in the RA setting did not impact negatively the vaccine immunogenicity or the time course of the immune response to the vaccine,” he and his colleagues wrote (Arthritis Rheumatol. 2017 Aug 28. doi: 10.1002/art.40187).
Increased herpes zoster risk in combination therapy
In the first study, herpes zoster (HZ) was reported in 636 of 6,192 patients over a median follow-up of 3 years of tofacitinib exposure, for an incident rate (IR) of 4.0 per 100 patient-years. However, IRs varied by region, ranging from 2.4 in Eastern Europe to 8.0 and 8.4 in Japan and Korea, respectively.
Further, in phase 3 studies, the IRs varied by tofacitinib dose, background use of conventional csDMARDs, and baseline glucocorticoid use; the rates were lowest among patients on tofacitinib monotherapy at a dose of 5 mg twice daily (IR, 0.6), and highest in those on tofacitinib at 10 mg twice daily with csDMARDs and glucocorticoids (IR, 5.4), the investigators found.
Independent risk factors for HZ included age, glucocorticoid use, tofacitinib dose, and enrollment within Asia, they said.
“Shingles, or reactivation of varicella virus, is a common and potentially debilitating illness. Around one-third of the general population will develop HZ in their lifetime, and approximately 10% of these patients develop postherpetic neuralgia which can last months to years and cause significant pain and morbidity,” the investigators wrote, adding that RA patients are at 1.5- to 2-fold greater risk vs. similarly aged individuals in the general population.
RA itself and treatment with glucocorticoids are known to increase HZ risk, but recent data have suggested that Janus kinase inhibitors, such as tofacitinib, and tumor necrosis factor antagonists are also associated with a higher rate of HZ. Additionally, a theoretical risk exists with various csDMARDs, they said.
“Given the increased risk of HZ observed among patients with RA versus the general population and the risk associated with RA therapies, it is possible that risk of HZ may be further increased when such therapies are combined,” they wrote.
Indeed, the findings of the study demonstrate an increased risk of HZ with tofacitinib in combination with glucocorticoids vs. tofacitinib monotherapy.
Further research is necessary to understand why Japanese and Korean patients are at elevated risk, and to understand the mechanism for the effects of combination therapy on VZV reactivation, they concluded.
LZV immunogenicity holds up during tofacitinib treatment
In the second study, 112 patients aged 50 years and older with active RA on background methotrexate received LZV and were then randomized to receive 5 mg tofacitinib twice daily or placebo 2-3 weeks after vaccination.
At 6 weeks after vaccination, VZV-specific IgG geometric mean fold rise (GMFR) was 2.11 and 1.74 in the tofacitinib and placebo patients, respectively; at all postvaccination time points at which VZV-specific IgG levels were evaluated, there was a trend toward numerically higher GMFR in tofacitinib patients, but the differences were not statistically significant. Also, the proportion of patients developing a 1.5-fold or greater postvaccination rise in IgG levels at 6 weeks trended higher for tofacitinib (57.4% vs. 43.4% with placebo).
VZV-specific T-cell GMFR at 6 weeks increased similarly in the groups (1.50 with tofacitinib and 1.29 with placebo).
Serious adverse events occurred in three patients in the tofacitinib group (5.5%) and in none of the placebo patients.
“The three SAEs included one case each of cholangitis and bronchitis, and once case of disseminated primary varicella,” the investigators said, noting that the onset of the latter was 16 days postvaccination, 2 days after starting tofacitinib. The rash resolved with discontinuation of tofacitinib and treatment with valacyclovir for 7 days.
The findings suggest that patients with active RA develop robust immune responses to HZ vaccine, and that starting tofacitinib 2-3 weeks after vaccination has no negative impact on the established immune response.
“Importantly, while our results suggest the vaccine is safe for patients with RA with prior VZV exposure, they also indicate the potential need to either screen for prior exposure before giving this vaccine or waiting longer than 2-3 weeks before starting immunosuppression with tofacitinib,” they said, noting that the current data suggest 4 weeks might be preferable.
Alternatively, testing patients who don’t recollect a history of chickenpox to ensure prior VZV exposure prior to vaccination could also mitigate the risk, they said.
“Further research is necessary to understand the risk of this complication, as well as the long-term effectiveness of this vaccine to prevent HZ in this high-risk population,” they concluded.
Both studies were sponsored by Pfizer. Dr. Winthrop has received research grants from and served as a scientific consultant to Pfizer. Other authors also reported financial relationships with Pfizer.
At a symposium during the 2015 annual meeting of the American College of Rheumatology, William Schaffner, MD, highlighted the connection between the seriousness of an infection, and the respect one has for the solution.
Dr. Schaffner said that “if you don’t fear the infection, you won’t value the solution.” Herpes zoster (HZ) should be feared, and the solution – the live zoster vaccine – valued.
Live zoster vaccine (LZV) was approved in 2006 on the basis of a trial involving more than 38,500 adults over age 60 years, which showed a 51% HZ prevention rate (64% protection in the 60-69 year age group) and a two-thirds reduction in postherpetic neuralgia. Complications and disseminated infection were rare.
HZ vaccination should be offered regardless of a history of varicella infection or prior shingles, as HZ may recur.
There is an imperative need to know who is at risk, when and how they should be vaccinated, and what other risk reduction measures should be considered.
John J. Cush, MD, is director of clinical rheumatology at Baylor Scott & White Research Institute and professor of medicine and rheumatology at Baylor University Medical Center, both in Dallas. His comments are taken from his editorial accompanying the two studies by Winthrop et al. (Arthritis Rheumatol. 2017 Aug 28. doi: 10.1002/art.40188).
At a symposium during the 2015 annual meeting of the American College of Rheumatology, William Schaffner, MD, highlighted the connection between the seriousness of an infection, and the respect one has for the solution.
Dr. Schaffner said that “if you don’t fear the infection, you won’t value the solution.” Herpes zoster (HZ) should be feared, and the solution – the live zoster vaccine – valued.
Live zoster vaccine (LZV) was approved in 2006 on the basis of a trial involving more than 38,500 adults over age 60 years, which showed a 51% HZ prevention rate (64% protection in the 60-69 year age group) and a two-thirds reduction in postherpetic neuralgia. Complications and disseminated infection were rare.
HZ vaccination should be offered regardless of a history of varicella infection or prior shingles, as HZ may recur.
There is an imperative need to know who is at risk, when and how they should be vaccinated, and what other risk reduction measures should be considered.
John J. Cush, MD, is director of clinical rheumatology at Baylor Scott & White Research Institute and professor of medicine and rheumatology at Baylor University Medical Center, both in Dallas. His comments are taken from his editorial accompanying the two studies by Winthrop et al. (Arthritis Rheumatol. 2017 Aug 28. doi: 10.1002/art.40188).
At a symposium during the 2015 annual meeting of the American College of Rheumatology, William Schaffner, MD, highlighted the connection between the seriousness of an infection, and the respect one has for the solution.
Dr. Schaffner said that “if you don’t fear the infection, you won’t value the solution.” Herpes zoster (HZ) should be feared, and the solution – the live zoster vaccine – valued.
Live zoster vaccine (LZV) was approved in 2006 on the basis of a trial involving more than 38,500 adults over age 60 years, which showed a 51% HZ prevention rate (64% protection in the 60-69 year age group) and a two-thirds reduction in postherpetic neuralgia. Complications and disseminated infection were rare.
HZ vaccination should be offered regardless of a history of varicella infection or prior shingles, as HZ may recur.
There is an imperative need to know who is at risk, when and how they should be vaccinated, and what other risk reduction measures should be considered.
John J. Cush, MD, is director of clinical rheumatology at Baylor Scott & White Research Institute and professor of medicine and rheumatology at Baylor University Medical Center, both in Dallas. His comments are taken from his editorial accompanying the two studies by Winthrop et al. (Arthritis Rheumatol. 2017 Aug 28. doi: 10.1002/art.40188).
The results of two studies of tofacitinib treatment for rheumatoid arthritis offer evidence to support the use of the drug without concomitant conventional synthetic disease-modifying antirheumatic drugs in order to reduce the risk of risk of herpes zoster infection and the safety of starting the drug 2-3 weeks after administering live zoster vaccine.
The risk of herpes zoster infection was elevated among rheumatoid arthritis (RA) patients receiving tofacitinib (Xeljanz) with glucocorticoids, compared with those receiving tofacitinib monotherapy, according to an analysis of data from 19 phase 2, phase 3, and long-term extension studies of tofacitinib.
“Further, physicians should continue to consider shingles vaccination prior to starting tofacitinib or biologic therapy,” they wrote.
Dr. Winthrop is the first author of a separate phase 2 study that also appears in Arthritis & Rheumatology, which suggests that live zoster vaccine (LZV) is safe in RA patients who start tofacitinib 2-3 weeks after vaccination. The study also showed that varicella-zoster virus (VZV)-specific humoral and cell-mediated immune responses to LZV are similar in tofacitinib- and placebo-treated patients.
“Our study provides the first data with this vaccine in the RA setting and suggests that these patients, even while using nonbiologic DMARDs at the time of vaccination, are capable of mounting adequate immune responses to this vaccine. Further, our data suggest that the use of tofacitinib following VZV vaccination in the RA setting did not impact negatively the vaccine immunogenicity or the time course of the immune response to the vaccine,” he and his colleagues wrote (Arthritis Rheumatol. 2017 Aug 28. doi: 10.1002/art.40187).
Increased herpes zoster risk in combination therapy
In the first study, herpes zoster (HZ) was reported in 636 of 6,192 patients over a median follow-up of 3 years of tofacitinib exposure, for an incident rate (IR) of 4.0 per 100 patient-years. However, IRs varied by region, ranging from 2.4 in Eastern Europe to 8.0 and 8.4 in Japan and Korea, respectively.
Further, in phase 3 studies, the IRs varied by tofacitinib dose, background use of conventional csDMARDs, and baseline glucocorticoid use; the rates were lowest among patients on tofacitinib monotherapy at a dose of 5 mg twice daily (IR, 0.6), and highest in those on tofacitinib at 10 mg twice daily with csDMARDs and glucocorticoids (IR, 5.4), the investigators found.
Independent risk factors for HZ included age, glucocorticoid use, tofacitinib dose, and enrollment within Asia, they said.
“Shingles, or reactivation of varicella virus, is a common and potentially debilitating illness. Around one-third of the general population will develop HZ in their lifetime, and approximately 10% of these patients develop postherpetic neuralgia which can last months to years and cause significant pain and morbidity,” the investigators wrote, adding that RA patients are at 1.5- to 2-fold greater risk vs. similarly aged individuals in the general population.
RA itself and treatment with glucocorticoids are known to increase HZ risk, but recent data have suggested that Janus kinase inhibitors, such as tofacitinib, and tumor necrosis factor antagonists are also associated with a higher rate of HZ. Additionally, a theoretical risk exists with various csDMARDs, they said.
“Given the increased risk of HZ observed among patients with RA versus the general population and the risk associated with RA therapies, it is possible that risk of HZ may be further increased when such therapies are combined,” they wrote.
Indeed, the findings of the study demonstrate an increased risk of HZ with tofacitinib in combination with glucocorticoids vs. tofacitinib monotherapy.
Further research is necessary to understand why Japanese and Korean patients are at elevated risk, and to understand the mechanism for the effects of combination therapy on VZV reactivation, they concluded.
LZV immunogenicity holds up during tofacitinib treatment
In the second study, 112 patients aged 50 years and older with active RA on background methotrexate received LZV and were then randomized to receive 5 mg tofacitinib twice daily or placebo 2-3 weeks after vaccination.
At 6 weeks after vaccination, VZV-specific IgG geometric mean fold rise (GMFR) was 2.11 and 1.74 in the tofacitinib and placebo patients, respectively; at all postvaccination time points at which VZV-specific IgG levels were evaluated, there was a trend toward numerically higher GMFR in tofacitinib patients, but the differences were not statistically significant. Also, the proportion of patients developing a 1.5-fold or greater postvaccination rise in IgG levels at 6 weeks trended higher for tofacitinib (57.4% vs. 43.4% with placebo).
VZV-specific T-cell GMFR at 6 weeks increased similarly in the groups (1.50 with tofacitinib and 1.29 with placebo).
Serious adverse events occurred in three patients in the tofacitinib group (5.5%) and in none of the placebo patients.
“The three SAEs included one case each of cholangitis and bronchitis, and once case of disseminated primary varicella,” the investigators said, noting that the onset of the latter was 16 days postvaccination, 2 days after starting tofacitinib. The rash resolved with discontinuation of tofacitinib and treatment with valacyclovir for 7 days.
The findings suggest that patients with active RA develop robust immune responses to HZ vaccine, and that starting tofacitinib 2-3 weeks after vaccination has no negative impact on the established immune response.
“Importantly, while our results suggest the vaccine is safe for patients with RA with prior VZV exposure, they also indicate the potential need to either screen for prior exposure before giving this vaccine or waiting longer than 2-3 weeks before starting immunosuppression with tofacitinib,” they said, noting that the current data suggest 4 weeks might be preferable.
Alternatively, testing patients who don’t recollect a history of chickenpox to ensure prior VZV exposure prior to vaccination could also mitigate the risk, they said.
“Further research is necessary to understand the risk of this complication, as well as the long-term effectiveness of this vaccine to prevent HZ in this high-risk population,” they concluded.
Both studies were sponsored by Pfizer. Dr. Winthrop has received research grants from and served as a scientific consultant to Pfizer. Other authors also reported financial relationships with Pfizer.
The results of two studies of tofacitinib treatment for rheumatoid arthritis offer evidence to support the use of the drug without concomitant conventional synthetic disease-modifying antirheumatic drugs in order to reduce the risk of risk of herpes zoster infection and the safety of starting the drug 2-3 weeks after administering live zoster vaccine.
The risk of herpes zoster infection was elevated among rheumatoid arthritis (RA) patients receiving tofacitinib (Xeljanz) with glucocorticoids, compared with those receiving tofacitinib monotherapy, according to an analysis of data from 19 phase 2, phase 3, and long-term extension studies of tofacitinib.
“Further, physicians should continue to consider shingles vaccination prior to starting tofacitinib or biologic therapy,” they wrote.
Dr. Winthrop is the first author of a separate phase 2 study that also appears in Arthritis & Rheumatology, which suggests that live zoster vaccine (LZV) is safe in RA patients who start tofacitinib 2-3 weeks after vaccination. The study also showed that varicella-zoster virus (VZV)-specific humoral and cell-mediated immune responses to LZV are similar in tofacitinib- and placebo-treated patients.
“Our study provides the first data with this vaccine in the RA setting and suggests that these patients, even while using nonbiologic DMARDs at the time of vaccination, are capable of mounting adequate immune responses to this vaccine. Further, our data suggest that the use of tofacitinib following VZV vaccination in the RA setting did not impact negatively the vaccine immunogenicity or the time course of the immune response to the vaccine,” he and his colleagues wrote (Arthritis Rheumatol. 2017 Aug 28. doi: 10.1002/art.40187).
Increased herpes zoster risk in combination therapy
In the first study, herpes zoster (HZ) was reported in 636 of 6,192 patients over a median follow-up of 3 years of tofacitinib exposure, for an incident rate (IR) of 4.0 per 100 patient-years. However, IRs varied by region, ranging from 2.4 in Eastern Europe to 8.0 and 8.4 in Japan and Korea, respectively.
Further, in phase 3 studies, the IRs varied by tofacitinib dose, background use of conventional csDMARDs, and baseline glucocorticoid use; the rates were lowest among patients on tofacitinib monotherapy at a dose of 5 mg twice daily (IR, 0.6), and highest in those on tofacitinib at 10 mg twice daily with csDMARDs and glucocorticoids (IR, 5.4), the investigators found.
Independent risk factors for HZ included age, glucocorticoid use, tofacitinib dose, and enrollment within Asia, they said.
“Shingles, or reactivation of varicella virus, is a common and potentially debilitating illness. Around one-third of the general population will develop HZ in their lifetime, and approximately 10% of these patients develop postherpetic neuralgia which can last months to years and cause significant pain and morbidity,” the investigators wrote, adding that RA patients are at 1.5- to 2-fold greater risk vs. similarly aged individuals in the general population.
RA itself and treatment with glucocorticoids are known to increase HZ risk, but recent data have suggested that Janus kinase inhibitors, such as tofacitinib, and tumor necrosis factor antagonists are also associated with a higher rate of HZ. Additionally, a theoretical risk exists with various csDMARDs, they said.
“Given the increased risk of HZ observed among patients with RA versus the general population and the risk associated with RA therapies, it is possible that risk of HZ may be further increased when such therapies are combined,” they wrote.
Indeed, the findings of the study demonstrate an increased risk of HZ with tofacitinib in combination with glucocorticoids vs. tofacitinib monotherapy.
Further research is necessary to understand why Japanese and Korean patients are at elevated risk, and to understand the mechanism for the effects of combination therapy on VZV reactivation, they concluded.
LZV immunogenicity holds up during tofacitinib treatment
In the second study, 112 patients aged 50 years and older with active RA on background methotrexate received LZV and were then randomized to receive 5 mg tofacitinib twice daily or placebo 2-3 weeks after vaccination.
At 6 weeks after vaccination, VZV-specific IgG geometric mean fold rise (GMFR) was 2.11 and 1.74 in the tofacitinib and placebo patients, respectively; at all postvaccination time points at which VZV-specific IgG levels were evaluated, there was a trend toward numerically higher GMFR in tofacitinib patients, but the differences were not statistically significant. Also, the proportion of patients developing a 1.5-fold or greater postvaccination rise in IgG levels at 6 weeks trended higher for tofacitinib (57.4% vs. 43.4% with placebo).
VZV-specific T-cell GMFR at 6 weeks increased similarly in the groups (1.50 with tofacitinib and 1.29 with placebo).
Serious adverse events occurred in three patients in the tofacitinib group (5.5%) and in none of the placebo patients.
“The three SAEs included one case each of cholangitis and bronchitis, and once case of disseminated primary varicella,” the investigators said, noting that the onset of the latter was 16 days postvaccination, 2 days after starting tofacitinib. The rash resolved with discontinuation of tofacitinib and treatment with valacyclovir for 7 days.
The findings suggest that patients with active RA develop robust immune responses to HZ vaccine, and that starting tofacitinib 2-3 weeks after vaccination has no negative impact on the established immune response.
“Importantly, while our results suggest the vaccine is safe for patients with RA with prior VZV exposure, they also indicate the potential need to either screen for prior exposure before giving this vaccine or waiting longer than 2-3 weeks before starting immunosuppression with tofacitinib,” they said, noting that the current data suggest 4 weeks might be preferable.
Alternatively, testing patients who don’t recollect a history of chickenpox to ensure prior VZV exposure prior to vaccination could also mitigate the risk, they said.
“Further research is necessary to understand the risk of this complication, as well as the long-term effectiveness of this vaccine to prevent HZ in this high-risk population,” they concluded.
Both studies were sponsored by Pfizer. Dr. Winthrop has received research grants from and served as a scientific consultant to Pfizer. Other authors also reported financial relationships with Pfizer.
FROM ARTHRITIS & RHEUMATOLOGY
Key clinical point:
Major finding: HZ rates were lowest among patients on tofacitinib monotherapy at a dose of 5 mg twice daily (IR, 0.6).
Data source: A phase 2 trial of 112 patients, and a review of 19 studies involving 6,192 patients.
Disclosures: Both studies were sponsored by Pfizer. Dr. Winthrop has received research grants from and served as a scientific consultant to Pfizer. Other authors also reported financial relationships with Pfizer.
In California, medical vaccine exemptions tripled after personal belief exemption ban
The proportion of California kindergartners with medical exemptions from vaccination tripled after the state eliminated personal belief exemptions, a study has shown.
Furthermore, California counties that previously had the highest rates of personal belief exemptions now have the highest rates of medical exemptions, Paul L. Delamater, PhD, of the University of North Carolina at Chapel Hill, and his associates reported in a research letter in JAMA. Such trends undermine California Senate Bill 277, will “limit [the law’s] long-term benefits, if sustained,” and could lead to outbreaks of vaccine-preventable diseases in the near future, the researchers warned.
Beginning in fall 2016, SB 277 prohibited unvaccinated kindergartners from matriculating at a public or private school in California without a medical exemption from vaccination, having eliminated the personal belief exemption from the state’s school-entry vaccine requirements. But the new law also gave physicians broader discretion to grant the medical exemptions, prompting concerns that “vaccine-hesitant” parents might successfully obtain medical exemptions in lieu of personal belief exemptions. To explore that possibility, the researchers analyzed data from the California state health department on kindergarten enrollment, vaccination, and vaccination exemptions. These data covered about 95% of California kindergartners, Dr. Delamater and his associates noted (JAMA. 2017;318[9]:863-4).
At the county level, rates of medical exemptions strongly correlated with historic rates of personal belief exemptions (P less than .001). Thus, counties with the highest historic rates of personal belief exemptions had the largest increases in rates of medical exemptions in 2016, that is, a change of between –1.00% and 3.38% of kindergartners. Furthermore, vaccination rates among all elementary school-aged children in California are even lower because SB 277 permitted children who previously entered kindergarten with personal belief exemptions to continue attending school without receiving vaccines until seventh grade. “Because the largest increases in [medical exemption] percentage occurred in regions with high past–[personal belief exemption] use, portions of California may remain susceptible to vaccine-preventable disease outbreaks in the near future,” Dr. Delamater and his associates concluded.
The investigators reported having no conflicts of interest.
The proportion of California kindergartners with medical exemptions from vaccination tripled after the state eliminated personal belief exemptions, a study has shown.
Furthermore, California counties that previously had the highest rates of personal belief exemptions now have the highest rates of medical exemptions, Paul L. Delamater, PhD, of the University of North Carolina at Chapel Hill, and his associates reported in a research letter in JAMA. Such trends undermine California Senate Bill 277, will “limit [the law’s] long-term benefits, if sustained,” and could lead to outbreaks of vaccine-preventable diseases in the near future, the researchers warned.
Beginning in fall 2016, SB 277 prohibited unvaccinated kindergartners from matriculating at a public or private school in California without a medical exemption from vaccination, having eliminated the personal belief exemption from the state’s school-entry vaccine requirements. But the new law also gave physicians broader discretion to grant the medical exemptions, prompting concerns that “vaccine-hesitant” parents might successfully obtain medical exemptions in lieu of personal belief exemptions. To explore that possibility, the researchers analyzed data from the California state health department on kindergarten enrollment, vaccination, and vaccination exemptions. These data covered about 95% of California kindergartners, Dr. Delamater and his associates noted (JAMA. 2017;318[9]:863-4).
At the county level, rates of medical exemptions strongly correlated with historic rates of personal belief exemptions (P less than .001). Thus, counties with the highest historic rates of personal belief exemptions had the largest increases in rates of medical exemptions in 2016, that is, a change of between –1.00% and 3.38% of kindergartners. Furthermore, vaccination rates among all elementary school-aged children in California are even lower because SB 277 permitted children who previously entered kindergarten with personal belief exemptions to continue attending school without receiving vaccines until seventh grade. “Because the largest increases in [medical exemption] percentage occurred in regions with high past–[personal belief exemption] use, portions of California may remain susceptible to vaccine-preventable disease outbreaks in the near future,” Dr. Delamater and his associates concluded.
The investigators reported having no conflicts of interest.
The proportion of California kindergartners with medical exemptions from vaccination tripled after the state eliminated personal belief exemptions, a study has shown.
Furthermore, California counties that previously had the highest rates of personal belief exemptions now have the highest rates of medical exemptions, Paul L. Delamater, PhD, of the University of North Carolina at Chapel Hill, and his associates reported in a research letter in JAMA. Such trends undermine California Senate Bill 277, will “limit [the law’s] long-term benefits, if sustained,” and could lead to outbreaks of vaccine-preventable diseases in the near future, the researchers warned.
Beginning in fall 2016, SB 277 prohibited unvaccinated kindergartners from matriculating at a public or private school in California without a medical exemption from vaccination, having eliminated the personal belief exemption from the state’s school-entry vaccine requirements. But the new law also gave physicians broader discretion to grant the medical exemptions, prompting concerns that “vaccine-hesitant” parents might successfully obtain medical exemptions in lieu of personal belief exemptions. To explore that possibility, the researchers analyzed data from the California state health department on kindergarten enrollment, vaccination, and vaccination exemptions. These data covered about 95% of California kindergartners, Dr. Delamater and his associates noted (JAMA. 2017;318[9]:863-4).
At the county level, rates of medical exemptions strongly correlated with historic rates of personal belief exemptions (P less than .001). Thus, counties with the highest historic rates of personal belief exemptions had the largest increases in rates of medical exemptions in 2016, that is, a change of between –1.00% and 3.38% of kindergartners. Furthermore, vaccination rates among all elementary school-aged children in California are even lower because SB 277 permitted children who previously entered kindergarten with personal belief exemptions to continue attending school without receiving vaccines until seventh grade. “Because the largest increases in [medical exemption] percentage occurred in regions with high past–[personal belief exemption] use, portions of California may remain susceptible to vaccine-preventable disease outbreaks in the near future,” Dr. Delamater and his associates concluded.
The investigators reported having no conflicts of interest.
FROM JAMA
Key clinical point:
Major finding: In 2016, 0.51% of California kindergartners had medical exemptions, a threefold rise from 2015.
Data source: An analysis of reportable state health department data from 2001 to 2016.
Disclosures: The investigators reported having no conflicts of interest.
Latest recommendations for the 2017-2018 flu season
The Centers for Disease Control and Prevention (CDC) recently reported details of the 2016-2017 influenza season in Morbidity and Mortality Weekly Report1 and at the June meeting of the Advisory Committee on Immunization Practices. The CDC monitors influenza activity using several systems, and last flu season was shown to be moderately severe, starting in December in the Western United States, moving east, and peaking in February.
During the peak, 5.1% of outpatient visits were attributed to influenza-like illnesses, and 8.2% of reported deaths were due to pneumonia and influenza. For the whole influenza season, there were more than 18,000 confirmed influenza-related hospitalizations, with 60% of these occurring among those ≥65 years.1 Confirmed influenza-associated pediatric deaths totaled 98.1
The predominant influenza strain last year was type A (H3N2), accounting for about 76% of positive tests in public health laboratories (FIGURE).1 This was followed by influenza B (all lineages) at 22%, and influenza A (H1N1), accounting for only 2%. However, in early April, the predominant strain changed from A (H3N2) to influenza B. Importantly, all viruses tested last year were sensitive to oseltamivir, zanamivir, and peramivir. No antiviral resistance was detected to these neuraminidase inhibitors.
Good news and bad news on vaccine effectiveness. The good news: Circulating viruses were a close match to those contained in the vaccine. The bad news: Vaccine effectiveness at preventing illness was estimated to be just 34% against A (H3N2) and 56% against influenza B viruses.1 There has been no analysis of the relative effectiveness of different vaccines and vaccine types.
The past 6 influenza seasons have revealed a pattern of lower vaccine effectiveness against A (H3N2) compared with effectiveness against A (H1N1) and influenza B viruses. While vaccine effectiveness is not optimal, routine universal use still prevents a great deal of mortality and morbidity. It’s estimated that in 2012-2013, vaccine effectiveness (comparable to that in 2016-2017) prevented 5.6 million illnesses, 2.7 million medical visits, 61,500 hospitalizations, and 1800 deaths.1
More good news: Vaccine safety studies are reassuring
The CDC monitors influenza vaccine safety by using several sources, including the Vaccine Adverse Event Reporting System and the Vaccine Safety Datalink.2
Changes for the 2017-2018 influenza season
The composition of influenza vaccine products for the 2017-2018 season will differ slightly from last year’s formulation in the H1N1 component. Viral antigens to be included in the trivalent products are A/Michigan (H1N1), A/Hong Kong (H3N2), and B/Brisbane.3 Quadrivalent products will add B/Phuket to the other 3 antigens.3 A wide array of influenza vaccine products is available. Each one is described on the CDC Web site.4
Two minor changes in the recommendations were made at the June ACIP meeting.5 Afluria is approved by the FDA for use in children starting at age 5 years. ACIP had recommended that its use be reserved for children 9 years and older because previous influenza seasons had raised concerns about increased rates of febrile seizures in children younger than age 9. These concerns have been resolved, however, and the ACIP recommendations are now in concert with those of the FDA for this product.
Influenza immunization with an inactivated influenza vaccine product has been recommended for all pregnant women. Safety data are increasingly available for other product options as well, and ACIP now recommends vaccination in pregnancy with any age-appropriate product except for live attenuated influenza vaccine. 5
Antivirals: Give as needed, even before lab confirmation
The CDC recommends antiviral medication for individuals with confirmed or suspected influenza who have severe, complicated, or progressive illness, who require hospitalization, or who are at high risk of complications from influenza (TABLE6). Start treatment without waiting for laboratory confirmation for those with suspected influenza who are seriously ill. Outcomes are best when antivirals are started within 48 hours of illness onset, but they can be started even after this “window” has passed.
Once antiviral treatment has begun, make sure the full 5-day course is completed regardless of culture or rapid-test results.6 Use only neuraminidase inhibitors, as there is widespread resistance to adamantanes among influenza A viruses.
Influenza can occur year round
Rates of influenza infection are low in the summer, but cases do occur. Be especially alert if patients with influenza-like illness have been exposed to swine or poultry; they may have contracted a novel influenza A virus. Report such cases to the state or local health department so that staff can facilitate laboratory testing of viral subtypes. Follow the same protocol for patients with influenza symptoms who have traveled to areas where avian influenza viruses have been detected. The CDC is interested in detecting novel influenza viruses, which can start a pandemic.
Prepare for the 2017-2018 influenza season
Family physicians can help prevent influenza and its associated morbidity and mortality in several ways. Offer immunization to all patients, and immunize all health care personnel in your offices and clinics. Treat with antivirals those for whom they are recommended. Prepare office triage policies that prevent patients with flu symptoms from mixing with other patients, ensure that clinic infection control practices are enforced, and advise ill patients to avoid exposing others.7 Finally, stay current on influenza epidemiology and changes in recommendations for treatment and vaccination.
1. Blanton L, Alabi N, Mustaquim D, et al. Update: Influenza activity in the United States during the 2016-2017 season and composition of the 2017-2018 influenza vaccine. MMWR Morb Mortal Wkly Rep. 2017;66:668-676.
2. Shimabukuro T. End-of-season update: 2016-2017 influenza vaccine safety monitoring. Presented at: meeting of the Advisory Committee on Immunization Practices; June 21, 2017; Atlanta, Ga. Available at: https://www.cdc.gov/vaccines/acip/meetings/downloads/slides-2017-06/flu-04-shimabukuro.pdf. Accessed August 1, 2017.
3. CDC. Frequently asked flu questions 2017-2018 influenza season. Available at: https://www.cdc.gov/flu/about/season/flu-season-2017-2018.htm. Accessed July 17, 2017.
4. CDC. Influenza vaccines — United States, 2016-17 influenza season. Available at: https://www.cdc.gov/flu/protect/vaccine/vaccines.htm. Accessed July 17, 2017.
5. Grohskopf L. Influenza WG considerations and proposed recommendations. Presented at: meeting of the Advisory Committee on Immunization Practices; June 21, 2017; Atlanta, Ga. Available at: https://www.cdc.gov/vaccines/acip/meetings/downloads/slides-2017-06/flu-06-grohskopf.pdf. Accessed August 1, 2017.
6. CDC. Use of antivirals. Available at: https://www.cdc.gov/flu/professionals/antivirals/antiviral-use-influenza.htm#Box. Accessed July 17, 2017.
7. CDC. Prevention strategies for seasonal influenza in healthcare settings. Available at: https://www.cdc.gov/flu/professionals/infectioncontrol/healthcaresettings.htm. Accessed July 17, 2017.
The Centers for Disease Control and Prevention (CDC) recently reported details of the 2016-2017 influenza season in Morbidity and Mortality Weekly Report1 and at the June meeting of the Advisory Committee on Immunization Practices. The CDC monitors influenza activity using several systems, and last flu season was shown to be moderately severe, starting in December in the Western United States, moving east, and peaking in February.
During the peak, 5.1% of outpatient visits were attributed to influenza-like illnesses, and 8.2% of reported deaths were due to pneumonia and influenza. For the whole influenza season, there were more than 18,000 confirmed influenza-related hospitalizations, with 60% of these occurring among those ≥65 years.1 Confirmed influenza-associated pediatric deaths totaled 98.1
The predominant influenza strain last year was type A (H3N2), accounting for about 76% of positive tests in public health laboratories (FIGURE).1 This was followed by influenza B (all lineages) at 22%, and influenza A (H1N1), accounting for only 2%. However, in early April, the predominant strain changed from A (H3N2) to influenza B. Importantly, all viruses tested last year were sensitive to oseltamivir, zanamivir, and peramivir. No antiviral resistance was detected to these neuraminidase inhibitors.
Good news and bad news on vaccine effectiveness. The good news: Circulating viruses were a close match to those contained in the vaccine. The bad news: Vaccine effectiveness at preventing illness was estimated to be just 34% against A (H3N2) and 56% against influenza B viruses.1 There has been no analysis of the relative effectiveness of different vaccines and vaccine types.
The past 6 influenza seasons have revealed a pattern of lower vaccine effectiveness against A (H3N2) compared with effectiveness against A (H1N1) and influenza B viruses. While vaccine effectiveness is not optimal, routine universal use still prevents a great deal of mortality and morbidity. It’s estimated that in 2012-2013, vaccine effectiveness (comparable to that in 2016-2017) prevented 5.6 million illnesses, 2.7 million medical visits, 61,500 hospitalizations, and 1800 deaths.1
More good news: Vaccine safety studies are reassuring
The CDC monitors influenza vaccine safety by using several sources, including the Vaccine Adverse Event Reporting System and the Vaccine Safety Datalink.2
Changes for the 2017-2018 influenza season
The composition of influenza vaccine products for the 2017-2018 season will differ slightly from last year’s formulation in the H1N1 component. Viral antigens to be included in the trivalent products are A/Michigan (H1N1), A/Hong Kong (H3N2), and B/Brisbane.3 Quadrivalent products will add B/Phuket to the other 3 antigens.3 A wide array of influenza vaccine products is available. Each one is described on the CDC Web site.4
Two minor changes in the recommendations were made at the June ACIP meeting.5 Afluria is approved by the FDA for use in children starting at age 5 years. ACIP had recommended that its use be reserved for children 9 years and older because previous influenza seasons had raised concerns about increased rates of febrile seizures in children younger than age 9. These concerns have been resolved, however, and the ACIP recommendations are now in concert with those of the FDA for this product.
Influenza immunization with an inactivated influenza vaccine product has been recommended for all pregnant women. Safety data are increasingly available for other product options as well, and ACIP now recommends vaccination in pregnancy with any age-appropriate product except for live attenuated influenza vaccine. 5
Antivirals: Give as needed, even before lab confirmation
The CDC recommends antiviral medication for individuals with confirmed or suspected influenza who have severe, complicated, or progressive illness, who require hospitalization, or who are at high risk of complications from influenza (TABLE6). Start treatment without waiting for laboratory confirmation for those with suspected influenza who are seriously ill. Outcomes are best when antivirals are started within 48 hours of illness onset, but they can be started even after this “window” has passed.
Once antiviral treatment has begun, make sure the full 5-day course is completed regardless of culture or rapid-test results.6 Use only neuraminidase inhibitors, as there is widespread resistance to adamantanes among influenza A viruses.
Influenza can occur year round
Rates of influenza infection are low in the summer, but cases do occur. Be especially alert if patients with influenza-like illness have been exposed to swine or poultry; they may have contracted a novel influenza A virus. Report such cases to the state or local health department so that staff can facilitate laboratory testing of viral subtypes. Follow the same protocol for patients with influenza symptoms who have traveled to areas where avian influenza viruses have been detected. The CDC is interested in detecting novel influenza viruses, which can start a pandemic.
Prepare for the 2017-2018 influenza season
Family physicians can help prevent influenza and its associated morbidity and mortality in several ways. Offer immunization to all patients, and immunize all health care personnel in your offices and clinics. Treat with antivirals those for whom they are recommended. Prepare office triage policies that prevent patients with flu symptoms from mixing with other patients, ensure that clinic infection control practices are enforced, and advise ill patients to avoid exposing others.7 Finally, stay current on influenza epidemiology and changes in recommendations for treatment and vaccination.
The Centers for Disease Control and Prevention (CDC) recently reported details of the 2016-2017 influenza season in Morbidity and Mortality Weekly Report1 and at the June meeting of the Advisory Committee on Immunization Practices. The CDC monitors influenza activity using several systems, and last flu season was shown to be moderately severe, starting in December in the Western United States, moving east, and peaking in February.
During the peak, 5.1% of outpatient visits were attributed to influenza-like illnesses, and 8.2% of reported deaths were due to pneumonia and influenza. For the whole influenza season, there were more than 18,000 confirmed influenza-related hospitalizations, with 60% of these occurring among those ≥65 years.1 Confirmed influenza-associated pediatric deaths totaled 98.1
The predominant influenza strain last year was type A (H3N2), accounting for about 76% of positive tests in public health laboratories (FIGURE).1 This was followed by influenza B (all lineages) at 22%, and influenza A (H1N1), accounting for only 2%. However, in early April, the predominant strain changed from A (H3N2) to influenza B. Importantly, all viruses tested last year were sensitive to oseltamivir, zanamivir, and peramivir. No antiviral resistance was detected to these neuraminidase inhibitors.
Good news and bad news on vaccine effectiveness. The good news: Circulating viruses were a close match to those contained in the vaccine. The bad news: Vaccine effectiveness at preventing illness was estimated to be just 34% against A (H3N2) and 56% against influenza B viruses.1 There has been no analysis of the relative effectiveness of different vaccines and vaccine types.
The past 6 influenza seasons have revealed a pattern of lower vaccine effectiveness against A (H3N2) compared with effectiveness against A (H1N1) and influenza B viruses. While vaccine effectiveness is not optimal, routine universal use still prevents a great deal of mortality and morbidity. It’s estimated that in 2012-2013, vaccine effectiveness (comparable to that in 2016-2017) prevented 5.6 million illnesses, 2.7 million medical visits, 61,500 hospitalizations, and 1800 deaths.1
More good news: Vaccine safety studies are reassuring
The CDC monitors influenza vaccine safety by using several sources, including the Vaccine Adverse Event Reporting System and the Vaccine Safety Datalink.2
Changes for the 2017-2018 influenza season
The composition of influenza vaccine products for the 2017-2018 season will differ slightly from last year’s formulation in the H1N1 component. Viral antigens to be included in the trivalent products are A/Michigan (H1N1), A/Hong Kong (H3N2), and B/Brisbane.3 Quadrivalent products will add B/Phuket to the other 3 antigens.3 A wide array of influenza vaccine products is available. Each one is described on the CDC Web site.4
Two minor changes in the recommendations were made at the June ACIP meeting.5 Afluria is approved by the FDA for use in children starting at age 5 years. ACIP had recommended that its use be reserved for children 9 years and older because previous influenza seasons had raised concerns about increased rates of febrile seizures in children younger than age 9. These concerns have been resolved, however, and the ACIP recommendations are now in concert with those of the FDA for this product.
Influenza immunization with an inactivated influenza vaccine product has been recommended for all pregnant women. Safety data are increasingly available for other product options as well, and ACIP now recommends vaccination in pregnancy with any age-appropriate product except for live attenuated influenza vaccine. 5
Antivirals: Give as needed, even before lab confirmation
The CDC recommends antiviral medication for individuals with confirmed or suspected influenza who have severe, complicated, or progressive illness, who require hospitalization, or who are at high risk of complications from influenza (TABLE6). Start treatment without waiting for laboratory confirmation for those with suspected influenza who are seriously ill. Outcomes are best when antivirals are started within 48 hours of illness onset, but they can be started even after this “window” has passed.
Once antiviral treatment has begun, make sure the full 5-day course is completed regardless of culture or rapid-test results.6 Use only neuraminidase inhibitors, as there is widespread resistance to adamantanes among influenza A viruses.
Influenza can occur year round
Rates of influenza infection are low in the summer, but cases do occur. Be especially alert if patients with influenza-like illness have been exposed to swine or poultry; they may have contracted a novel influenza A virus. Report such cases to the state or local health department so that staff can facilitate laboratory testing of viral subtypes. Follow the same protocol for patients with influenza symptoms who have traveled to areas where avian influenza viruses have been detected. The CDC is interested in detecting novel influenza viruses, which can start a pandemic.
Prepare for the 2017-2018 influenza season
Family physicians can help prevent influenza and its associated morbidity and mortality in several ways. Offer immunization to all patients, and immunize all health care personnel in your offices and clinics. Treat with antivirals those for whom they are recommended. Prepare office triage policies that prevent patients with flu symptoms from mixing with other patients, ensure that clinic infection control practices are enforced, and advise ill patients to avoid exposing others.7 Finally, stay current on influenza epidemiology and changes in recommendations for treatment and vaccination.
1. Blanton L, Alabi N, Mustaquim D, et al. Update: Influenza activity in the United States during the 2016-2017 season and composition of the 2017-2018 influenza vaccine. MMWR Morb Mortal Wkly Rep. 2017;66:668-676.
2. Shimabukuro T. End-of-season update: 2016-2017 influenza vaccine safety monitoring. Presented at: meeting of the Advisory Committee on Immunization Practices; June 21, 2017; Atlanta, Ga. Available at: https://www.cdc.gov/vaccines/acip/meetings/downloads/slides-2017-06/flu-04-shimabukuro.pdf. Accessed August 1, 2017.
3. CDC. Frequently asked flu questions 2017-2018 influenza season. Available at: https://www.cdc.gov/flu/about/season/flu-season-2017-2018.htm. Accessed July 17, 2017.
4. CDC. Influenza vaccines — United States, 2016-17 influenza season. Available at: https://www.cdc.gov/flu/protect/vaccine/vaccines.htm. Accessed July 17, 2017.
5. Grohskopf L. Influenza WG considerations and proposed recommendations. Presented at: meeting of the Advisory Committee on Immunization Practices; June 21, 2017; Atlanta, Ga. Available at: https://www.cdc.gov/vaccines/acip/meetings/downloads/slides-2017-06/flu-06-grohskopf.pdf. Accessed August 1, 2017.
6. CDC. Use of antivirals. Available at: https://www.cdc.gov/flu/professionals/antivirals/antiviral-use-influenza.htm#Box. Accessed July 17, 2017.
7. CDC. Prevention strategies for seasonal influenza in healthcare settings. Available at: https://www.cdc.gov/flu/professionals/infectioncontrol/healthcaresettings.htm. Accessed July 17, 2017.
1. Blanton L, Alabi N, Mustaquim D, et al. Update: Influenza activity in the United States during the 2016-2017 season and composition of the 2017-2018 influenza vaccine. MMWR Morb Mortal Wkly Rep. 2017;66:668-676.
2. Shimabukuro T. End-of-season update: 2016-2017 influenza vaccine safety monitoring. Presented at: meeting of the Advisory Committee on Immunization Practices; June 21, 2017; Atlanta, Ga. Available at: https://www.cdc.gov/vaccines/acip/meetings/downloads/slides-2017-06/flu-04-shimabukuro.pdf. Accessed August 1, 2017.
3. CDC. Frequently asked flu questions 2017-2018 influenza season. Available at: https://www.cdc.gov/flu/about/season/flu-season-2017-2018.htm. Accessed July 17, 2017.
4. CDC. Influenza vaccines — United States, 2016-17 influenza season. Available at: https://www.cdc.gov/flu/protect/vaccine/vaccines.htm. Accessed July 17, 2017.
5. Grohskopf L. Influenza WG considerations and proposed recommendations. Presented at: meeting of the Advisory Committee on Immunization Practices; June 21, 2017; Atlanta, Ga. Available at: https://www.cdc.gov/vaccines/acip/meetings/downloads/slides-2017-06/flu-06-grohskopf.pdf. Accessed August 1, 2017.
6. CDC. Use of antivirals. Available at: https://www.cdc.gov/flu/professionals/antivirals/antiviral-use-influenza.htm#Box. Accessed July 17, 2017.
7. CDC. Prevention strategies for seasonal influenza in healthcare settings. Available at: https://www.cdc.gov/flu/professionals/infectioncontrol/healthcaresettings.htm. Accessed July 17, 2017.
Individualizing immunization for international travelers
International travel, whether for business, pleasure, child adoption, medical tourism, or adventure, continues to grow. In 2015, more than 70 million US citizens traveled internationally.1 Many individuals contact family physicians first about their plans for travel and questions about travel-related health advice. This article provides an overview of the vaccines recommended for travelers headed to international destinations. Because country-specific vaccination recommendations and requirements for entry and departure change over time, check the Centers for Disease Control and Prevention (CDC) Web site for up-to-date requirements and recommendations (www.cdc.gov/travel).
Vaccine schedules vary according to destination and individual risks
There is no single vaccination schedule that applies to all travelers. Each schedule should be individualized based on the traveler’s destination, risk assessment, previous immunizations, health status, and time available before departure.2,3 Pregnant or immunocompromised travelers should seek advice from an experienced travel medicine consultant on the immunization recommendations specifically meant for them.4,5
Travel vaccines (TABLE6) are generally categorized as routine, required, or recommended.
- Routine vaccines are the standard child and adult immunizations recommended by the Advisory Committee on Immunization Practices (ACIP). These include such vaccines as diphtheria-tetanus toxoids-acellular pertussis (DTaP), inactivated polio vaccine (IPV), Haemophilus influenzae type b (Hib), hepatitis B, rotavirus and pneumococcal vaccines, and human papillomavirus (HPV).
- Required vaccines—eg, yellow fever and meningococcal vaccines—must be documented on the International Certificate of Vaccination before entry into certain countries.
- Recommended vaccines are advised based on the travel destination and anticipated activities. These would include vaccines for typhoid, rabies, Japanese encephalitis, and polio (adult booster).
Routine vaccinations may need to be accelerated
Pre-travel patient encounters are an opportunity to update routine vaccinations.7,8 Immunization against childhood diseases remains suboptimal in developing countries, where vaccine-preventable illnesses occur more frequently.9
Routine vaccines may be administered on an accelerated basis depending on geographic destination, seasonal disease variations, anticipated exposures, and known outbreaks at the time of travel.
MMR vaccine. Measles is still common in many parts of the world, and unvaccinated or incompletely vaccinated travelers are at risk of acquiring the disease and importing it to the United States (see “Measles: Why it’s still a threat,” 2017;66:446-449.) In 2015, a large, widespread measles outbreak occurred in the United States, linked to an amusement park in California, likely originating with an infected traveler who visited the park.10
All children older than 12 months should receive 2 doses of measles-mumps-rubella (MMR) vaccine separated by at least 28 days before departure (regardless of their destination). Infants between 6 and 11 months are at risk for high morbidity and may therefore receive a single dose of MMR earlier than the routinely recommended age of 12 to 15 months. Adolescents and adults without evidence of immunity against measles should get 2 doses of MMR separated by at least 28 days.11 Acceptable presumptive evidence of immunity against measles includes written documentation of adequate vaccination, laboratory evidence of immunity, laboratory confirmation of measles, or birth before 1957.
Varicella vaccine. Children, adolescents, and young adults who have received only one dose of varicella should get a second dose prior to departure. For children 7 to 12 years, the recommended minimum interval between doses is 3 months. For individuals 13 years or older, the minimum interval is 4 weeks.7,8
Influenza vaccine is routinely recommended for all travelers 6 months of age or older, as flu season varies geographically. Flu season in the Northern Hemisphere may begin as early as October and can extend until May. In the Southern Hemisphere, it may begin in April and last through September. Travelers should be vaccinated at least 2 weeks before travel in order to develop adequate immunity.12,13
Required vaccinations: Proof is needed before traveling
Yellow fever (YF) is a mosquito-borne viral illness characterized by fever, chills, headache, myalgia, and vomiting. The disease can progress to coagulopathy, shock, and multisystem organ failure.14 YF vaccine is recommended for individuals 9 months or older who are traveling to or living in areas of South America or Africa where YF virus transmission is common (map: http://www.cdc.gov/yellowfever/maps/).
YF vaccine is a live-attenuated virus formulation and, therefore, should not be given to individuals with primary immunodeficiencies, transplant recipients or patients on immunosuppressive and immunomodulatory therapies, or patients with human immunodeficiency virus (HIV) whose CD4 count is below 200/mL. Other contraindications to YF vaccine are age younger than 6 months, allergy to a vaccine component, and thymic disorders. Serious adverse reactions to the vaccine are rare, but include 2 syndromes: YF-associated neurotropic disease and YF vaccine-associated viscerotropic disease.15
In many YF-endemic countries, vaccination is legally required for entry, and proof of vaccination must be documented on an International Certificate of Vaccination or Prophylaxis (ICVP). Additionally, some countries may require proof of vaccination before allowing travel through an endemic region, to prevent introduction of the disease elsewhere. Travelers with a specific contraindication to YF vaccine should obtain a waiver from a physician before traveling to a country requiring vaccination.16
The vaccination certificate is valid beginning 10 days after administration of YF vaccine. Immunity after a single dose is long lasting and may provide lifetime protection. Previously, re-vaccination was required every 10 years; however, in February 2015, ACIP approved a new recommendation stating a single dose of YF vaccine is adequate for most travelers.1
Although ACIP no longer recommends booster doses of YF vaccine for most travelers, clinicians and travelers should review the entry requirements for destination countries because changes to the International Health Regulations have not yet been fully implemented. Once this change is instituted, a completed ICVP will be valid for the lifetime of the vaccine.18,19 Country-specific requirements for YF can be found at http://www.cdc.gov/yellowfever/maps/. (Click on the link below the appropriate map.) In the United States, the YF vaccine is distributed only through approved vaccination centers. These designated clinics are listed in a registry on the CDC travel Web site at https://wwwnc.cdc.gov/travel/yellow-fever-vaccination-clinics/search.
Meningococcal disease. ACIP recommends routine vaccination against meningococcal disease for people 11 to 18 years of age and for individuals with persistent complement component deficiency, functional or anatomic asplenia, and HIV. Vaccination is recommended for travelers who visit or reside in areas where meningococcal disease is hyperendemic or epidemic, such as the meningitis belt of sub-Saharan Africa during the dry season of December to June (map: http://wwwnc.cdc.gov/travel/yellowbook/2016/infectious-diseases-related-to-travel/meningococcal-disease). Travelers to Saudi Arabia during the annual Hajj and Umrah pilgrimages are required to have a certificate of vaccination with quadrivalent (serogroups A, C, Y, W-135) meningococcal vaccine issued within 3 years (and not less than 10 days) before entry.
Several meningococcal vaccines are available in the United States. The quadrivalent vaccines are Menactra (MenACWY-D, Sanofi Pasteur) and Menveo (MenACWY-CRM, GSK). A bivalent (serogroups C and Y) conjugate vaccine MenHibrix (Hib-MenCY-TT, GSK) is also licensed for use in the United States, but infants traveling to areas with high endemic rates of meningococcal disease who received this vaccine are not protected against serogroups A and W and should receive quadrivalent meningococcal conjugate vaccine. Serogroup B vaccination is not routinely recommended for travelers. Approximately 7 to 10 days are required after vaccination for the development of protective antibody levels.7,8,20,21
Polio. Although polio has been nearly eradicated, as of the time this article was written, the disease has not been eliminated in Afghanistan, Guinea, Laos, Nigeria, or Pakistan. Other countries, such as Cameroon, Chad, and Ukraine remain vulnerable to international transmission.22 The CDC recommends that adults who are traveling to areas where wild polio virus (WPV) has circulated in the last 12 months and who are unvaccinated, incompletely vaccinated, or whose vaccination status is unknown should receive a series of 3 doses of IPV to prevent ongoing spread.23 Adults who completed the polio vaccine series as children and are traveling to areas where WPV has circulated in the last 12 months should receive a one-time booster dose of IPV.23
Infants and children in the United States should be vaccinated against polio as part of a routine age-appropriate series. If a child cannot complete the routine series before departure and is traveling to an area where WPV has circulated in the last 12 months, an accelerated schedule is recommended. Vaccination should be documented on the ICVP, as countries with active spread of poliovirus may require proof of polio vaccination upon exit. A list of the countries where the polio virus is currently circulating is available at http://polioeradication.org/polio-today/polio-now/wild-poliovirus-list/.
Both routine and accelerated vaccination schedules for children and adults are published annually by the CDC and are available at http://www.cdc.gov/vaccines/schedules/hcp/index.html.
Recommended vaccines
Japanese encephalitis (JE) is endemic throughout most of Asia and parts of the Western Pacific region (map: http://www.cdc.gov/japaneseencephalitis/maps/). JE vaccine is recommended for travelers who plan to spend more than a month in endemic areas during the JE virus transmission season. (In temperate areas of Asia, JE virus transmission is seasonal and usually peaks in the summer and fall. In the subtropics and tropics, transmission can occur year-round, often with a peak during the rainy season.)
This recommendation includes recurrent travelers or expatriates who are likely to visit endemic rural or agricultural areas during a high-risk period of JE virus transmission. Risk is low for travelers who spend less than a month in endemic areas and for those who confine their travel to urban centers. Nevertheless, vaccination should be considered if travel is planned for outside an urban area and includes such activities as camping, hiking, trekking, biking, fishing, hunting, or farming. Inactivated Vero cell culture-derived vaccine (Ixiaro) is the only JE vaccine licensed and available in the United States. Ixiaro is given as a 2-dose series, with the doses spaced 28 days apart. The last dose should be given at least one week before travel.24
Typhoid fever. Vaccination against typhoid fever is recommended for travelers to highly endemic areas such as the Indian subcontinent, Africa, and Central and South America. Two typhoid vaccines are available: Vi capsular polysaccharide vaccine (ViCPS) administered intramuscularly (IM), and oral live attenuated vaccine (Ty21a). Ty21a is a live vaccine and should not be given to immunocompromised people or those taking antibiotics, as it may reduce immunogenicity. Ty21a must be kept refrigerated at 35.6° F to 46.4° F (2° C - 8° C) and administered with cool liquid no warmer than 98.6° F (37° C). Both vaccines are only 50% to 80% efficacious, making access to clean food and water essential.3,5,25
Hepatitis A vaccine should be given to all children older than one year traveling to areas where there is an intermediate or high risk of the disease. Children younger than one year who are traveling to high-risk areas can receive a single dose of immunoglobulin (IG) 0.02 mL/kg IM, which provides protection for up to 3 months. One 0.06 mL/kg-dose IM provides protection for 3 to 5 months.
If travel continues, children should receive a second dose after 5 months. IG does not interfere with the response to YF vaccine, but can interfere with the response to other live injected vaccines (such as MMR and varicella).26
Hepatitis B vaccination should be administered to all unvaccinated travelers who plan to visit an area with intermediate to high prevalence of chronic hepatitis B (HBV surface antigen prevalence ≥2%). Unvaccinated travelers who may engage in high-risk sexual activity or injection drug use should receive hepatitis B vaccine regardless of destination. Additionally, travelers who access medical care for injury or illness while abroad may also be at risk of acquiring hepatitis B via contaminated blood products or medical equipment.27
Serologic testing and booster vaccination are not recommended before travel for immunocompetent adults who have been previously vaccinated. The combined hepatitis A and B vaccine provides effective and convenient dual protection for travelers and can be administered with an accelerated 0-, 7-, and 21-day schedule for last-minute travelers.7,8
Rabies remains endemic in developing countries of Africa and Asia, where appropriate post-exposure prophylaxis is limited or non-existent.28 Consider pre-exposure rabies prophylaxis for traveling patients based on the availability of rabies vaccine and immunoglobulin in their destination area, planned duration of stay, and the likelihood of animal exposure (eg, veterinarians, animal handlers, cavers, missionaries). Advise travelers who decline vaccination to avoid or minimize animal contact during travel. In the event the traveler sustains an animal bite or scratch, immediate cleansing of the wound substantially reduces the risk of infection, especially when followed by timely administration of post-exposure prophylaxis.
Post-exposure prophylaxis for unvaccinated individuals consists of local infiltration of rabies immunoglobulin at the site of the bite and a series of 4 injections of rabies vaccine over 14 days, or 5 doses over one month for immunosuppressed patients. The first dose of the 4-dose course should be administered as soon as possible after exposure. Two vaccines are licensed for use in the United States: human diploid cell vaccine (HDCV, Imovax Rabies, Sanofi Pasteur) and purified chick embryo cell vaccine (PCECV, RabAvert, Novartis Vaccines and Diagnostics). The vaccine should never be administered in the gluteal area, as this may result in lower antibody titers.29
Additionally, promising new vaccines against malaria and dengue fever are under clinical development and may be available in the near future.
CORRESPONDENCE
Vini Vijayan, MD, Division of Infectious Diseases, Arkansas Children's Hospital, 1 Children's Way, Slot 512-11, Little Rock, AR 72202; vvijayan@uams.edu.
1. U.S. Department of Commerce, International Trade Administration, National Travel and Tourism Office (NTTO). 2015. Available at: http://travel.trade.gov/view/m-2015-O-001/index.html. Accessed July 12, 2017.
2. Hill DR, Ericsson CD, Pearson RD, et al. The practice of travel medicine: guidelines by the Infectious Diseases Society of America. Clin Infect Dis. 2006;43:1499-1539.
3. Centers for Disease Control and Prevention. The pre-travel consultation. Available at: https://wwwnc.cdc.gov/travel/yellowbook/2018/the-pre-travel-consultation/the-pre-travel-consultation. Accessed June 20, 2017.
4. Hochberg NS, Barnett ED, Chen LH, et al. International travel by persons with medical comorbidities: understanding risks and providing advice. Mayo Clin Proc. 2013;88:1231-1240.
5. Rubin LG, Levin MJ, Ljungman P, et al. 2013 IDSA clinical practice guideline for vaccination of the immunocompromised host. Clin Infect Dis. 2014;58:e44-e100.
6. Centers for Disease Control and Prevention. Yellow Book table of contents: Chapter 3. Available at: https://wwwnc.cdc.gov/travel/yellowbook/2018/table-of-contents. Accessed July 21, 2017.
7. Centers for Disease Control and Prevention. Advisory Committee on Immunization Practices (ACIP) recommended immunization schedules for persons aged 0 through 18 years—United States, 2016. MMWR Morb Mortal Wkly Rep. 2016;65;86-87.
8. Centers for Disease Control and Prevention. Advisory Committee on Immunization Practices recommended immunization schedule for adults aged 19 years or older - United States, 2016. MMWR Morb Mortal Wkly Rep. 2016;65:88-90.
9. Boggild AK, Castelli F, Gautret P, et al. Vaccine preventable diseases in returned international travelers: results from the GeoSentinel Surveillance Network. Vaccine. 2010;28:7389-7395.
10. Sotir MJ, Esposito DH, Barnett ED, et al. Measles in the 21st century, a continuing preventable risk to travelers: data from the GeoSentinel Global Network. Clin Infect Dis. 2016;62:210-212.
11. Measles. In: Kimberlin DW, Brady MT, Jackson MA, Long SS, eds. Red Book: 2015 Report of the Committee on Infectious Diseases. 30th ed. Elk Grove Village, IL: American Academy of Pediatrics; 2015:535-546.
12. Centers for Disease Control and Prevention. Prevention and control of influenza with vaccines. Recommendations of the Advisory Committee on Immunization Practices—United States, 2015-16 Influenza Season. MMWR Morb Mortal Wkly Rep. 2015;64:818-825.
13. Marti F, Steffen R, Mutsch M. Influenza vaccine: a travelers’ vaccine? Expert Rev Vaccines. 2008;7:679-687.
14. Monath T, Gershman MD, Staples JE, et al. Yellow fever vaccine. In: Plotkin SA, Orenstein WA, Offit PA, eds. Vaccines. 6th ed. London, England: W.B. Saunders; 2013:870-968.
15. Staples JE, Gershman M, Fischer M. Yellow fever vaccine: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep. 2010;59:1-27.
16. World Health Organization. International Health Regulations. 2nd ed. Geneva, Switzerland: World Health Organization; 2005. Available at: http://whqlibdoc.who.int/publications/2008/9789241580410_eng.pdf. Accessed June 20, 2017.
17. Centers for Disease Control and Prevention. Advisory Committee on Immunization Practices: summary report. February 26, 2015. Available at: https://www.cdc.gov/vaccines/acip/meetings/downloads/min-archive/min-2015-02.pdf. Accessed July 20, 2017.
18. Staples JE, Bocchini JA Jr, Rubin L, et al. Yellow fever vaccine booster doses: recommendations of the Advisory Committee on Immunization Practices, 2015. MMWR Morb Mortal Wkly Rep. 2015;64:647-650.
19. World Health Organization. International travel and health: World–yellow fever vaccination booster. Geneva, Switzerland: World Health Organization; 2014. Available at: http://www.who.int/ith/updates/20140605/en. Accessed June 20, 2017.
20. Centers for Disease Control and Prevention. Prevention and control of meningococcal disease: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep. 2013;62:1-28.
21. Memish ZA, Stephens GM, Steffen R, et al. Emergence of medicine for mass gatherings: lessons from the Hajj. Lancet Infect Dis. 2012;12:56-65.
22. World Health Organization. Twelfth meeting of the Emergency Committee under the International Health Regulations (2015) regarding the international spread of poliovirus. Available at: http://www.who.int/mediacentre/news/statements/2017/poliovirus-twelfth-ec/en/. Accessed June 21, 2017.
23. Centers for Disease Control and Prevention. Interim CDC Guidance for Travel to and from Countries Affected by the New Polio Vaccine Requirements. Available at http://wwwnc.cdc.gov/travel/news-announcements/polio-guidance-new-requirements. Accessed August 1, 2017.
24. Centers for Disease Control and Prevention. Use of Japanese encephalitis vaccine in children: recommendations of the advisory committee on immunization practices, 2013. MMWR Morb Mortal Wkly Rep. 2013;62:898-900.
25. Mahon BE, Newton AE, Mintz ED. Effectiveness of typhoid vaccination in US travelers. Vaccine. 2014;32:3577-3579.
26. Fiore AE, Wasley A, Bell BP. Prevention of hepatitis A through active or passive immunization: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Morb Mortal Wkly Rep. 2006;55:1-23.
27. Vivancos R, Abubakar I, Hunter PR. Foreign travel, casual sex, and sexually transmitted infections: systematic review and meta-analysis. Int J Infect Dis. 2010;14:e842-e851.
28. Gautret P, Harvey K, Pandey P, et al for the GeoSentinel Surveillance Network. Animal-associated exposure to rabies virus among travelers, 1997-2012. Emerg Infect Dis. 2015;21:569-577.
29. Rupprecht CE, Briggs D, Brown CM, et al; Centers for Disease Control and Prevention. Use of a reduced (4-dose) vaccine schedule for postexposure prophylaxis to prevent human rabies: recommendations of the Advisory Committee on Immunization Practices. MMWR Recomm Rep. 2010;59:1-9.
International travel, whether for business, pleasure, child adoption, medical tourism, or adventure, continues to grow. In 2015, more than 70 million US citizens traveled internationally.1 Many individuals contact family physicians first about their plans for travel and questions about travel-related health advice. This article provides an overview of the vaccines recommended for travelers headed to international destinations. Because country-specific vaccination recommendations and requirements for entry and departure change over time, check the Centers for Disease Control and Prevention (CDC) Web site for up-to-date requirements and recommendations (www.cdc.gov/travel).
Vaccine schedules vary according to destination and individual risks
There is no single vaccination schedule that applies to all travelers. Each schedule should be individualized based on the traveler’s destination, risk assessment, previous immunizations, health status, and time available before departure.2,3 Pregnant or immunocompromised travelers should seek advice from an experienced travel medicine consultant on the immunization recommendations specifically meant for them.4,5
Travel vaccines (TABLE6) are generally categorized as routine, required, or recommended.
- Routine vaccines are the standard child and adult immunizations recommended by the Advisory Committee on Immunization Practices (ACIP). These include such vaccines as diphtheria-tetanus toxoids-acellular pertussis (DTaP), inactivated polio vaccine (IPV), Haemophilus influenzae type b (Hib), hepatitis B, rotavirus and pneumococcal vaccines, and human papillomavirus (HPV).
- Required vaccines—eg, yellow fever and meningococcal vaccines—must be documented on the International Certificate of Vaccination before entry into certain countries.
- Recommended vaccines are advised based on the travel destination and anticipated activities. These would include vaccines for typhoid, rabies, Japanese encephalitis, and polio (adult booster).
Routine vaccinations may need to be accelerated
Pre-travel patient encounters are an opportunity to update routine vaccinations.7,8 Immunization against childhood diseases remains suboptimal in developing countries, where vaccine-preventable illnesses occur more frequently.9
Routine vaccines may be administered on an accelerated basis depending on geographic destination, seasonal disease variations, anticipated exposures, and known outbreaks at the time of travel.
MMR vaccine. Measles is still common in many parts of the world, and unvaccinated or incompletely vaccinated travelers are at risk of acquiring the disease and importing it to the United States (see “Measles: Why it’s still a threat,” 2017;66:446-449.) In 2015, a large, widespread measles outbreak occurred in the United States, linked to an amusement park in California, likely originating with an infected traveler who visited the park.10
All children older than 12 months should receive 2 doses of measles-mumps-rubella (MMR) vaccine separated by at least 28 days before departure (regardless of their destination). Infants between 6 and 11 months are at risk for high morbidity and may therefore receive a single dose of MMR earlier than the routinely recommended age of 12 to 15 months. Adolescents and adults without evidence of immunity against measles should get 2 doses of MMR separated by at least 28 days.11 Acceptable presumptive evidence of immunity against measles includes written documentation of adequate vaccination, laboratory evidence of immunity, laboratory confirmation of measles, or birth before 1957.
Varicella vaccine. Children, adolescents, and young adults who have received only one dose of varicella should get a second dose prior to departure. For children 7 to 12 years, the recommended minimum interval between doses is 3 months. For individuals 13 years or older, the minimum interval is 4 weeks.7,8
Influenza vaccine is routinely recommended for all travelers 6 months of age or older, as flu season varies geographically. Flu season in the Northern Hemisphere may begin as early as October and can extend until May. In the Southern Hemisphere, it may begin in April and last through September. Travelers should be vaccinated at least 2 weeks before travel in order to develop adequate immunity.12,13
Required vaccinations: Proof is needed before traveling
Yellow fever (YF) is a mosquito-borne viral illness characterized by fever, chills, headache, myalgia, and vomiting. The disease can progress to coagulopathy, shock, and multisystem organ failure.14 YF vaccine is recommended for individuals 9 months or older who are traveling to or living in areas of South America or Africa where YF virus transmission is common (map: http://www.cdc.gov/yellowfever/maps/).
YF vaccine is a live-attenuated virus formulation and, therefore, should not be given to individuals with primary immunodeficiencies, transplant recipients or patients on immunosuppressive and immunomodulatory therapies, or patients with human immunodeficiency virus (HIV) whose CD4 count is below 200/mL. Other contraindications to YF vaccine are age younger than 6 months, allergy to a vaccine component, and thymic disorders. Serious adverse reactions to the vaccine are rare, but include 2 syndromes: YF-associated neurotropic disease and YF vaccine-associated viscerotropic disease.15
In many YF-endemic countries, vaccination is legally required for entry, and proof of vaccination must be documented on an International Certificate of Vaccination or Prophylaxis (ICVP). Additionally, some countries may require proof of vaccination before allowing travel through an endemic region, to prevent introduction of the disease elsewhere. Travelers with a specific contraindication to YF vaccine should obtain a waiver from a physician before traveling to a country requiring vaccination.16
The vaccination certificate is valid beginning 10 days after administration of YF vaccine. Immunity after a single dose is long lasting and may provide lifetime protection. Previously, re-vaccination was required every 10 years; however, in February 2015, ACIP approved a new recommendation stating a single dose of YF vaccine is adequate for most travelers.1
Although ACIP no longer recommends booster doses of YF vaccine for most travelers, clinicians and travelers should review the entry requirements for destination countries because changes to the International Health Regulations have not yet been fully implemented. Once this change is instituted, a completed ICVP will be valid for the lifetime of the vaccine.18,19 Country-specific requirements for YF can be found at http://www.cdc.gov/yellowfever/maps/. (Click on the link below the appropriate map.) In the United States, the YF vaccine is distributed only through approved vaccination centers. These designated clinics are listed in a registry on the CDC travel Web site at https://wwwnc.cdc.gov/travel/yellow-fever-vaccination-clinics/search.
Meningococcal disease. ACIP recommends routine vaccination against meningococcal disease for people 11 to 18 years of age and for individuals with persistent complement component deficiency, functional or anatomic asplenia, and HIV. Vaccination is recommended for travelers who visit or reside in areas where meningococcal disease is hyperendemic or epidemic, such as the meningitis belt of sub-Saharan Africa during the dry season of December to June (map: http://wwwnc.cdc.gov/travel/yellowbook/2016/infectious-diseases-related-to-travel/meningococcal-disease). Travelers to Saudi Arabia during the annual Hajj and Umrah pilgrimages are required to have a certificate of vaccination with quadrivalent (serogroups A, C, Y, W-135) meningococcal vaccine issued within 3 years (and not less than 10 days) before entry.
Several meningococcal vaccines are available in the United States. The quadrivalent vaccines are Menactra (MenACWY-D, Sanofi Pasteur) and Menveo (MenACWY-CRM, GSK). A bivalent (serogroups C and Y) conjugate vaccine MenHibrix (Hib-MenCY-TT, GSK) is also licensed for use in the United States, but infants traveling to areas with high endemic rates of meningococcal disease who received this vaccine are not protected against serogroups A and W and should receive quadrivalent meningococcal conjugate vaccine. Serogroup B vaccination is not routinely recommended for travelers. Approximately 7 to 10 days are required after vaccination for the development of protective antibody levels.7,8,20,21
Polio. Although polio has been nearly eradicated, as of the time this article was written, the disease has not been eliminated in Afghanistan, Guinea, Laos, Nigeria, or Pakistan. Other countries, such as Cameroon, Chad, and Ukraine remain vulnerable to international transmission.22 The CDC recommends that adults who are traveling to areas where wild polio virus (WPV) has circulated in the last 12 months and who are unvaccinated, incompletely vaccinated, or whose vaccination status is unknown should receive a series of 3 doses of IPV to prevent ongoing spread.23 Adults who completed the polio vaccine series as children and are traveling to areas where WPV has circulated in the last 12 months should receive a one-time booster dose of IPV.23
Infants and children in the United States should be vaccinated against polio as part of a routine age-appropriate series. If a child cannot complete the routine series before departure and is traveling to an area where WPV has circulated in the last 12 months, an accelerated schedule is recommended. Vaccination should be documented on the ICVP, as countries with active spread of poliovirus may require proof of polio vaccination upon exit. A list of the countries where the polio virus is currently circulating is available at http://polioeradication.org/polio-today/polio-now/wild-poliovirus-list/.
Both routine and accelerated vaccination schedules for children and adults are published annually by the CDC and are available at http://www.cdc.gov/vaccines/schedules/hcp/index.html.
Recommended vaccines
Japanese encephalitis (JE) is endemic throughout most of Asia and parts of the Western Pacific region (map: http://www.cdc.gov/japaneseencephalitis/maps/). JE vaccine is recommended for travelers who plan to spend more than a month in endemic areas during the JE virus transmission season. (In temperate areas of Asia, JE virus transmission is seasonal and usually peaks in the summer and fall. In the subtropics and tropics, transmission can occur year-round, often with a peak during the rainy season.)
This recommendation includes recurrent travelers or expatriates who are likely to visit endemic rural or agricultural areas during a high-risk period of JE virus transmission. Risk is low for travelers who spend less than a month in endemic areas and for those who confine their travel to urban centers. Nevertheless, vaccination should be considered if travel is planned for outside an urban area and includes such activities as camping, hiking, trekking, biking, fishing, hunting, or farming. Inactivated Vero cell culture-derived vaccine (Ixiaro) is the only JE vaccine licensed and available in the United States. Ixiaro is given as a 2-dose series, with the doses spaced 28 days apart. The last dose should be given at least one week before travel.24
Typhoid fever. Vaccination against typhoid fever is recommended for travelers to highly endemic areas such as the Indian subcontinent, Africa, and Central and South America. Two typhoid vaccines are available: Vi capsular polysaccharide vaccine (ViCPS) administered intramuscularly (IM), and oral live attenuated vaccine (Ty21a). Ty21a is a live vaccine and should not be given to immunocompromised people or those taking antibiotics, as it may reduce immunogenicity. Ty21a must be kept refrigerated at 35.6° F to 46.4° F (2° C - 8° C) and administered with cool liquid no warmer than 98.6° F (37° C). Both vaccines are only 50% to 80% efficacious, making access to clean food and water essential.3,5,25
Hepatitis A vaccine should be given to all children older than one year traveling to areas where there is an intermediate or high risk of the disease. Children younger than one year who are traveling to high-risk areas can receive a single dose of immunoglobulin (IG) 0.02 mL/kg IM, which provides protection for up to 3 months. One 0.06 mL/kg-dose IM provides protection for 3 to 5 months.
If travel continues, children should receive a second dose after 5 months. IG does not interfere with the response to YF vaccine, but can interfere with the response to other live injected vaccines (such as MMR and varicella).26
Hepatitis B vaccination should be administered to all unvaccinated travelers who plan to visit an area with intermediate to high prevalence of chronic hepatitis B (HBV surface antigen prevalence ≥2%). Unvaccinated travelers who may engage in high-risk sexual activity or injection drug use should receive hepatitis B vaccine regardless of destination. Additionally, travelers who access medical care for injury or illness while abroad may also be at risk of acquiring hepatitis B via contaminated blood products or medical equipment.27
Serologic testing and booster vaccination are not recommended before travel for immunocompetent adults who have been previously vaccinated. The combined hepatitis A and B vaccine provides effective and convenient dual protection for travelers and can be administered with an accelerated 0-, 7-, and 21-day schedule for last-minute travelers.7,8
Rabies remains endemic in developing countries of Africa and Asia, where appropriate post-exposure prophylaxis is limited or non-existent.28 Consider pre-exposure rabies prophylaxis for traveling patients based on the availability of rabies vaccine and immunoglobulin in their destination area, planned duration of stay, and the likelihood of animal exposure (eg, veterinarians, animal handlers, cavers, missionaries). Advise travelers who decline vaccination to avoid or minimize animal contact during travel. In the event the traveler sustains an animal bite or scratch, immediate cleansing of the wound substantially reduces the risk of infection, especially when followed by timely administration of post-exposure prophylaxis.
Post-exposure prophylaxis for unvaccinated individuals consists of local infiltration of rabies immunoglobulin at the site of the bite and a series of 4 injections of rabies vaccine over 14 days, or 5 doses over one month for immunosuppressed patients. The first dose of the 4-dose course should be administered as soon as possible after exposure. Two vaccines are licensed for use in the United States: human diploid cell vaccine (HDCV, Imovax Rabies, Sanofi Pasteur) and purified chick embryo cell vaccine (PCECV, RabAvert, Novartis Vaccines and Diagnostics). The vaccine should never be administered in the gluteal area, as this may result in lower antibody titers.29
Additionally, promising new vaccines against malaria and dengue fever are under clinical development and may be available in the near future.
CORRESPONDENCE
Vini Vijayan, MD, Division of Infectious Diseases, Arkansas Children's Hospital, 1 Children's Way, Slot 512-11, Little Rock, AR 72202; vvijayan@uams.edu.
International travel, whether for business, pleasure, child adoption, medical tourism, or adventure, continues to grow. In 2015, more than 70 million US citizens traveled internationally.1 Many individuals contact family physicians first about their plans for travel and questions about travel-related health advice. This article provides an overview of the vaccines recommended for travelers headed to international destinations. Because country-specific vaccination recommendations and requirements for entry and departure change over time, check the Centers for Disease Control and Prevention (CDC) Web site for up-to-date requirements and recommendations (www.cdc.gov/travel).
Vaccine schedules vary according to destination and individual risks
There is no single vaccination schedule that applies to all travelers. Each schedule should be individualized based on the traveler’s destination, risk assessment, previous immunizations, health status, and time available before departure.2,3 Pregnant or immunocompromised travelers should seek advice from an experienced travel medicine consultant on the immunization recommendations specifically meant for them.4,5
Travel vaccines (TABLE6) are generally categorized as routine, required, or recommended.
- Routine vaccines are the standard child and adult immunizations recommended by the Advisory Committee on Immunization Practices (ACIP). These include such vaccines as diphtheria-tetanus toxoids-acellular pertussis (DTaP), inactivated polio vaccine (IPV), Haemophilus influenzae type b (Hib), hepatitis B, rotavirus and pneumococcal vaccines, and human papillomavirus (HPV).
- Required vaccines—eg, yellow fever and meningococcal vaccines—must be documented on the International Certificate of Vaccination before entry into certain countries.
- Recommended vaccines are advised based on the travel destination and anticipated activities. These would include vaccines for typhoid, rabies, Japanese encephalitis, and polio (adult booster).
Routine vaccinations may need to be accelerated
Pre-travel patient encounters are an opportunity to update routine vaccinations.7,8 Immunization against childhood diseases remains suboptimal in developing countries, where vaccine-preventable illnesses occur more frequently.9
Routine vaccines may be administered on an accelerated basis depending on geographic destination, seasonal disease variations, anticipated exposures, and known outbreaks at the time of travel.
MMR vaccine. Measles is still common in many parts of the world, and unvaccinated or incompletely vaccinated travelers are at risk of acquiring the disease and importing it to the United States (see “Measles: Why it’s still a threat,” 2017;66:446-449.) In 2015, a large, widespread measles outbreak occurred in the United States, linked to an amusement park in California, likely originating with an infected traveler who visited the park.10
All children older than 12 months should receive 2 doses of measles-mumps-rubella (MMR) vaccine separated by at least 28 days before departure (regardless of their destination). Infants between 6 and 11 months are at risk for high morbidity and may therefore receive a single dose of MMR earlier than the routinely recommended age of 12 to 15 months. Adolescents and adults without evidence of immunity against measles should get 2 doses of MMR separated by at least 28 days.11 Acceptable presumptive evidence of immunity against measles includes written documentation of adequate vaccination, laboratory evidence of immunity, laboratory confirmation of measles, or birth before 1957.
Varicella vaccine. Children, adolescents, and young adults who have received only one dose of varicella should get a second dose prior to departure. For children 7 to 12 years, the recommended minimum interval between doses is 3 months. For individuals 13 years or older, the minimum interval is 4 weeks.7,8
Influenza vaccine is routinely recommended for all travelers 6 months of age or older, as flu season varies geographically. Flu season in the Northern Hemisphere may begin as early as October and can extend until May. In the Southern Hemisphere, it may begin in April and last through September. Travelers should be vaccinated at least 2 weeks before travel in order to develop adequate immunity.12,13
Required vaccinations: Proof is needed before traveling
Yellow fever (YF) is a mosquito-borne viral illness characterized by fever, chills, headache, myalgia, and vomiting. The disease can progress to coagulopathy, shock, and multisystem organ failure.14 YF vaccine is recommended for individuals 9 months or older who are traveling to or living in areas of South America or Africa where YF virus transmission is common (map: http://www.cdc.gov/yellowfever/maps/).
YF vaccine is a live-attenuated virus formulation and, therefore, should not be given to individuals with primary immunodeficiencies, transplant recipients or patients on immunosuppressive and immunomodulatory therapies, or patients with human immunodeficiency virus (HIV) whose CD4 count is below 200/mL. Other contraindications to YF vaccine are age younger than 6 months, allergy to a vaccine component, and thymic disorders. Serious adverse reactions to the vaccine are rare, but include 2 syndromes: YF-associated neurotropic disease and YF vaccine-associated viscerotropic disease.15
In many YF-endemic countries, vaccination is legally required for entry, and proof of vaccination must be documented on an International Certificate of Vaccination or Prophylaxis (ICVP). Additionally, some countries may require proof of vaccination before allowing travel through an endemic region, to prevent introduction of the disease elsewhere. Travelers with a specific contraindication to YF vaccine should obtain a waiver from a physician before traveling to a country requiring vaccination.16
The vaccination certificate is valid beginning 10 days after administration of YF vaccine. Immunity after a single dose is long lasting and may provide lifetime protection. Previously, re-vaccination was required every 10 years; however, in February 2015, ACIP approved a new recommendation stating a single dose of YF vaccine is adequate for most travelers.1
Although ACIP no longer recommends booster doses of YF vaccine for most travelers, clinicians and travelers should review the entry requirements for destination countries because changes to the International Health Regulations have not yet been fully implemented. Once this change is instituted, a completed ICVP will be valid for the lifetime of the vaccine.18,19 Country-specific requirements for YF can be found at http://www.cdc.gov/yellowfever/maps/. (Click on the link below the appropriate map.) In the United States, the YF vaccine is distributed only through approved vaccination centers. These designated clinics are listed in a registry on the CDC travel Web site at https://wwwnc.cdc.gov/travel/yellow-fever-vaccination-clinics/search.
Meningococcal disease. ACIP recommends routine vaccination against meningococcal disease for people 11 to 18 years of age and for individuals with persistent complement component deficiency, functional or anatomic asplenia, and HIV. Vaccination is recommended for travelers who visit or reside in areas where meningococcal disease is hyperendemic or epidemic, such as the meningitis belt of sub-Saharan Africa during the dry season of December to June (map: http://wwwnc.cdc.gov/travel/yellowbook/2016/infectious-diseases-related-to-travel/meningococcal-disease). Travelers to Saudi Arabia during the annual Hajj and Umrah pilgrimages are required to have a certificate of vaccination with quadrivalent (serogroups A, C, Y, W-135) meningococcal vaccine issued within 3 years (and not less than 10 days) before entry.
Several meningococcal vaccines are available in the United States. The quadrivalent vaccines are Menactra (MenACWY-D, Sanofi Pasteur) and Menveo (MenACWY-CRM, GSK). A bivalent (serogroups C and Y) conjugate vaccine MenHibrix (Hib-MenCY-TT, GSK) is also licensed for use in the United States, but infants traveling to areas with high endemic rates of meningococcal disease who received this vaccine are not protected against serogroups A and W and should receive quadrivalent meningococcal conjugate vaccine. Serogroup B vaccination is not routinely recommended for travelers. Approximately 7 to 10 days are required after vaccination for the development of protective antibody levels.7,8,20,21
Polio. Although polio has been nearly eradicated, as of the time this article was written, the disease has not been eliminated in Afghanistan, Guinea, Laos, Nigeria, or Pakistan. Other countries, such as Cameroon, Chad, and Ukraine remain vulnerable to international transmission.22 The CDC recommends that adults who are traveling to areas where wild polio virus (WPV) has circulated in the last 12 months and who are unvaccinated, incompletely vaccinated, or whose vaccination status is unknown should receive a series of 3 doses of IPV to prevent ongoing spread.23 Adults who completed the polio vaccine series as children and are traveling to areas where WPV has circulated in the last 12 months should receive a one-time booster dose of IPV.23
Infants and children in the United States should be vaccinated against polio as part of a routine age-appropriate series. If a child cannot complete the routine series before departure and is traveling to an area where WPV has circulated in the last 12 months, an accelerated schedule is recommended. Vaccination should be documented on the ICVP, as countries with active spread of poliovirus may require proof of polio vaccination upon exit. A list of the countries where the polio virus is currently circulating is available at http://polioeradication.org/polio-today/polio-now/wild-poliovirus-list/.
Both routine and accelerated vaccination schedules for children and adults are published annually by the CDC and are available at http://www.cdc.gov/vaccines/schedules/hcp/index.html.
Recommended vaccines
Japanese encephalitis (JE) is endemic throughout most of Asia and parts of the Western Pacific region (map: http://www.cdc.gov/japaneseencephalitis/maps/). JE vaccine is recommended for travelers who plan to spend more than a month in endemic areas during the JE virus transmission season. (In temperate areas of Asia, JE virus transmission is seasonal and usually peaks in the summer and fall. In the subtropics and tropics, transmission can occur year-round, often with a peak during the rainy season.)
This recommendation includes recurrent travelers or expatriates who are likely to visit endemic rural or agricultural areas during a high-risk period of JE virus transmission. Risk is low for travelers who spend less than a month in endemic areas and for those who confine their travel to urban centers. Nevertheless, vaccination should be considered if travel is planned for outside an urban area and includes such activities as camping, hiking, trekking, biking, fishing, hunting, or farming. Inactivated Vero cell culture-derived vaccine (Ixiaro) is the only JE vaccine licensed and available in the United States. Ixiaro is given as a 2-dose series, with the doses spaced 28 days apart. The last dose should be given at least one week before travel.24
Typhoid fever. Vaccination against typhoid fever is recommended for travelers to highly endemic areas such as the Indian subcontinent, Africa, and Central and South America. Two typhoid vaccines are available: Vi capsular polysaccharide vaccine (ViCPS) administered intramuscularly (IM), and oral live attenuated vaccine (Ty21a). Ty21a is a live vaccine and should not be given to immunocompromised people or those taking antibiotics, as it may reduce immunogenicity. Ty21a must be kept refrigerated at 35.6° F to 46.4° F (2° C - 8° C) and administered with cool liquid no warmer than 98.6° F (37° C). Both vaccines are only 50% to 80% efficacious, making access to clean food and water essential.3,5,25
Hepatitis A vaccine should be given to all children older than one year traveling to areas where there is an intermediate or high risk of the disease. Children younger than one year who are traveling to high-risk areas can receive a single dose of immunoglobulin (IG) 0.02 mL/kg IM, which provides protection for up to 3 months. One 0.06 mL/kg-dose IM provides protection for 3 to 5 months.
If travel continues, children should receive a second dose after 5 months. IG does not interfere with the response to YF vaccine, but can interfere with the response to other live injected vaccines (such as MMR and varicella).26
Hepatitis B vaccination should be administered to all unvaccinated travelers who plan to visit an area with intermediate to high prevalence of chronic hepatitis B (HBV surface antigen prevalence ≥2%). Unvaccinated travelers who may engage in high-risk sexual activity or injection drug use should receive hepatitis B vaccine regardless of destination. Additionally, travelers who access medical care for injury or illness while abroad may also be at risk of acquiring hepatitis B via contaminated blood products or medical equipment.27
Serologic testing and booster vaccination are not recommended before travel for immunocompetent adults who have been previously vaccinated. The combined hepatitis A and B vaccine provides effective and convenient dual protection for travelers and can be administered with an accelerated 0-, 7-, and 21-day schedule for last-minute travelers.7,8
Rabies remains endemic in developing countries of Africa and Asia, where appropriate post-exposure prophylaxis is limited or non-existent.28 Consider pre-exposure rabies prophylaxis for traveling patients based on the availability of rabies vaccine and immunoglobulin in their destination area, planned duration of stay, and the likelihood of animal exposure (eg, veterinarians, animal handlers, cavers, missionaries). Advise travelers who decline vaccination to avoid or minimize animal contact during travel. In the event the traveler sustains an animal bite or scratch, immediate cleansing of the wound substantially reduces the risk of infection, especially when followed by timely administration of post-exposure prophylaxis.
Post-exposure prophylaxis for unvaccinated individuals consists of local infiltration of rabies immunoglobulin at the site of the bite and a series of 4 injections of rabies vaccine over 14 days, or 5 doses over one month for immunosuppressed patients. The first dose of the 4-dose course should be administered as soon as possible after exposure. Two vaccines are licensed for use in the United States: human diploid cell vaccine (HDCV, Imovax Rabies, Sanofi Pasteur) and purified chick embryo cell vaccine (PCECV, RabAvert, Novartis Vaccines and Diagnostics). The vaccine should never be administered in the gluteal area, as this may result in lower antibody titers.29
Additionally, promising new vaccines against malaria and dengue fever are under clinical development and may be available in the near future.
CORRESPONDENCE
Vini Vijayan, MD, Division of Infectious Diseases, Arkansas Children's Hospital, 1 Children's Way, Slot 512-11, Little Rock, AR 72202; vvijayan@uams.edu.
1. U.S. Department of Commerce, International Trade Administration, National Travel and Tourism Office (NTTO). 2015. Available at: http://travel.trade.gov/view/m-2015-O-001/index.html. Accessed July 12, 2017.
2. Hill DR, Ericsson CD, Pearson RD, et al. The practice of travel medicine: guidelines by the Infectious Diseases Society of America. Clin Infect Dis. 2006;43:1499-1539.
3. Centers for Disease Control and Prevention. The pre-travel consultation. Available at: https://wwwnc.cdc.gov/travel/yellowbook/2018/the-pre-travel-consultation/the-pre-travel-consultation. Accessed June 20, 2017.
4. Hochberg NS, Barnett ED, Chen LH, et al. International travel by persons with medical comorbidities: understanding risks and providing advice. Mayo Clin Proc. 2013;88:1231-1240.
5. Rubin LG, Levin MJ, Ljungman P, et al. 2013 IDSA clinical practice guideline for vaccination of the immunocompromised host. Clin Infect Dis. 2014;58:e44-e100.
6. Centers for Disease Control and Prevention. Yellow Book table of contents: Chapter 3. Available at: https://wwwnc.cdc.gov/travel/yellowbook/2018/table-of-contents. Accessed July 21, 2017.
7. Centers for Disease Control and Prevention. Advisory Committee on Immunization Practices (ACIP) recommended immunization schedules for persons aged 0 through 18 years—United States, 2016. MMWR Morb Mortal Wkly Rep. 2016;65;86-87.
8. Centers for Disease Control and Prevention. Advisory Committee on Immunization Practices recommended immunization schedule for adults aged 19 years or older - United States, 2016. MMWR Morb Mortal Wkly Rep. 2016;65:88-90.
9. Boggild AK, Castelli F, Gautret P, et al. Vaccine preventable diseases in returned international travelers: results from the GeoSentinel Surveillance Network. Vaccine. 2010;28:7389-7395.
10. Sotir MJ, Esposito DH, Barnett ED, et al. Measles in the 21st century, a continuing preventable risk to travelers: data from the GeoSentinel Global Network. Clin Infect Dis. 2016;62:210-212.
11. Measles. In: Kimberlin DW, Brady MT, Jackson MA, Long SS, eds. Red Book: 2015 Report of the Committee on Infectious Diseases. 30th ed. Elk Grove Village, IL: American Academy of Pediatrics; 2015:535-546.
12. Centers for Disease Control and Prevention. Prevention and control of influenza with vaccines. Recommendations of the Advisory Committee on Immunization Practices—United States, 2015-16 Influenza Season. MMWR Morb Mortal Wkly Rep. 2015;64:818-825.
13. Marti F, Steffen R, Mutsch M. Influenza vaccine: a travelers’ vaccine? Expert Rev Vaccines. 2008;7:679-687.
14. Monath T, Gershman MD, Staples JE, et al. Yellow fever vaccine. In: Plotkin SA, Orenstein WA, Offit PA, eds. Vaccines. 6th ed. London, England: W.B. Saunders; 2013:870-968.
15. Staples JE, Gershman M, Fischer M. Yellow fever vaccine: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep. 2010;59:1-27.
16. World Health Organization. International Health Regulations. 2nd ed. Geneva, Switzerland: World Health Organization; 2005. Available at: http://whqlibdoc.who.int/publications/2008/9789241580410_eng.pdf. Accessed June 20, 2017.
17. Centers for Disease Control and Prevention. Advisory Committee on Immunization Practices: summary report. February 26, 2015. Available at: https://www.cdc.gov/vaccines/acip/meetings/downloads/min-archive/min-2015-02.pdf. Accessed July 20, 2017.
18. Staples JE, Bocchini JA Jr, Rubin L, et al. Yellow fever vaccine booster doses: recommendations of the Advisory Committee on Immunization Practices, 2015. MMWR Morb Mortal Wkly Rep. 2015;64:647-650.
19. World Health Organization. International travel and health: World–yellow fever vaccination booster. Geneva, Switzerland: World Health Organization; 2014. Available at: http://www.who.int/ith/updates/20140605/en. Accessed June 20, 2017.
20. Centers for Disease Control and Prevention. Prevention and control of meningococcal disease: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep. 2013;62:1-28.
21. Memish ZA, Stephens GM, Steffen R, et al. Emergence of medicine for mass gatherings: lessons from the Hajj. Lancet Infect Dis. 2012;12:56-65.
22. World Health Organization. Twelfth meeting of the Emergency Committee under the International Health Regulations (2015) regarding the international spread of poliovirus. Available at: http://www.who.int/mediacentre/news/statements/2017/poliovirus-twelfth-ec/en/. Accessed June 21, 2017.
23. Centers for Disease Control and Prevention. Interim CDC Guidance for Travel to and from Countries Affected by the New Polio Vaccine Requirements. Available at http://wwwnc.cdc.gov/travel/news-announcements/polio-guidance-new-requirements. Accessed August 1, 2017.
24. Centers for Disease Control and Prevention. Use of Japanese encephalitis vaccine in children: recommendations of the advisory committee on immunization practices, 2013. MMWR Morb Mortal Wkly Rep. 2013;62:898-900.
25. Mahon BE, Newton AE, Mintz ED. Effectiveness of typhoid vaccination in US travelers. Vaccine. 2014;32:3577-3579.
26. Fiore AE, Wasley A, Bell BP. Prevention of hepatitis A through active or passive immunization: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Morb Mortal Wkly Rep. 2006;55:1-23.
27. Vivancos R, Abubakar I, Hunter PR. Foreign travel, casual sex, and sexually transmitted infections: systematic review and meta-analysis. Int J Infect Dis. 2010;14:e842-e851.
28. Gautret P, Harvey K, Pandey P, et al for the GeoSentinel Surveillance Network. Animal-associated exposure to rabies virus among travelers, 1997-2012. Emerg Infect Dis. 2015;21:569-577.
29. Rupprecht CE, Briggs D, Brown CM, et al; Centers for Disease Control and Prevention. Use of a reduced (4-dose) vaccine schedule for postexposure prophylaxis to prevent human rabies: recommendations of the Advisory Committee on Immunization Practices. MMWR Recomm Rep. 2010;59:1-9.
1. U.S. Department of Commerce, International Trade Administration, National Travel and Tourism Office (NTTO). 2015. Available at: http://travel.trade.gov/view/m-2015-O-001/index.html. Accessed July 12, 2017.
2. Hill DR, Ericsson CD, Pearson RD, et al. The practice of travel medicine: guidelines by the Infectious Diseases Society of America. Clin Infect Dis. 2006;43:1499-1539.
3. Centers for Disease Control and Prevention. The pre-travel consultation. Available at: https://wwwnc.cdc.gov/travel/yellowbook/2018/the-pre-travel-consultation/the-pre-travel-consultation. Accessed June 20, 2017.
4. Hochberg NS, Barnett ED, Chen LH, et al. International travel by persons with medical comorbidities: understanding risks and providing advice. Mayo Clin Proc. 2013;88:1231-1240.
5. Rubin LG, Levin MJ, Ljungman P, et al. 2013 IDSA clinical practice guideline for vaccination of the immunocompromised host. Clin Infect Dis. 2014;58:e44-e100.
6. Centers for Disease Control and Prevention. Yellow Book table of contents: Chapter 3. Available at: https://wwwnc.cdc.gov/travel/yellowbook/2018/table-of-contents. Accessed July 21, 2017.
7. Centers for Disease Control and Prevention. Advisory Committee on Immunization Practices (ACIP) recommended immunization schedules for persons aged 0 through 18 years—United States, 2016. MMWR Morb Mortal Wkly Rep. 2016;65;86-87.
8. Centers for Disease Control and Prevention. Advisory Committee on Immunization Practices recommended immunization schedule for adults aged 19 years or older - United States, 2016. MMWR Morb Mortal Wkly Rep. 2016;65:88-90.
9. Boggild AK, Castelli F, Gautret P, et al. Vaccine preventable diseases in returned international travelers: results from the GeoSentinel Surveillance Network. Vaccine. 2010;28:7389-7395.
10. Sotir MJ, Esposito DH, Barnett ED, et al. Measles in the 21st century, a continuing preventable risk to travelers: data from the GeoSentinel Global Network. Clin Infect Dis. 2016;62:210-212.
11. Measles. In: Kimberlin DW, Brady MT, Jackson MA, Long SS, eds. Red Book: 2015 Report of the Committee on Infectious Diseases. 30th ed. Elk Grove Village, IL: American Academy of Pediatrics; 2015:535-546.
12. Centers for Disease Control and Prevention. Prevention and control of influenza with vaccines. Recommendations of the Advisory Committee on Immunization Practices—United States, 2015-16 Influenza Season. MMWR Morb Mortal Wkly Rep. 2015;64:818-825.
13. Marti F, Steffen R, Mutsch M. Influenza vaccine: a travelers’ vaccine? Expert Rev Vaccines. 2008;7:679-687.
14. Monath T, Gershman MD, Staples JE, et al. Yellow fever vaccine. In: Plotkin SA, Orenstein WA, Offit PA, eds. Vaccines. 6th ed. London, England: W.B. Saunders; 2013:870-968.
15. Staples JE, Gershman M, Fischer M. Yellow fever vaccine: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep. 2010;59:1-27.
16. World Health Organization. International Health Regulations. 2nd ed. Geneva, Switzerland: World Health Organization; 2005. Available at: http://whqlibdoc.who.int/publications/2008/9789241580410_eng.pdf. Accessed June 20, 2017.
17. Centers for Disease Control and Prevention. Advisory Committee on Immunization Practices: summary report. February 26, 2015. Available at: https://www.cdc.gov/vaccines/acip/meetings/downloads/min-archive/min-2015-02.pdf. Accessed July 20, 2017.
18. Staples JE, Bocchini JA Jr, Rubin L, et al. Yellow fever vaccine booster doses: recommendations of the Advisory Committee on Immunization Practices, 2015. MMWR Morb Mortal Wkly Rep. 2015;64:647-650.
19. World Health Organization. International travel and health: World–yellow fever vaccination booster. Geneva, Switzerland: World Health Organization; 2014. Available at: http://www.who.int/ith/updates/20140605/en. Accessed June 20, 2017.
20. Centers for Disease Control and Prevention. Prevention and control of meningococcal disease: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep. 2013;62:1-28.
21. Memish ZA, Stephens GM, Steffen R, et al. Emergence of medicine for mass gatherings: lessons from the Hajj. Lancet Infect Dis. 2012;12:56-65.
22. World Health Organization. Twelfth meeting of the Emergency Committee under the International Health Regulations (2015) regarding the international spread of poliovirus. Available at: http://www.who.int/mediacentre/news/statements/2017/poliovirus-twelfth-ec/en/. Accessed June 21, 2017.
23. Centers for Disease Control and Prevention. Interim CDC Guidance for Travel to and from Countries Affected by the New Polio Vaccine Requirements. Available at http://wwwnc.cdc.gov/travel/news-announcements/polio-guidance-new-requirements. Accessed August 1, 2017.
24. Centers for Disease Control and Prevention. Use of Japanese encephalitis vaccine in children: recommendations of the advisory committee on immunization practices, 2013. MMWR Morb Mortal Wkly Rep. 2013;62:898-900.
25. Mahon BE, Newton AE, Mintz ED. Effectiveness of typhoid vaccination in US travelers. Vaccine. 2014;32:3577-3579.
26. Fiore AE, Wasley A, Bell BP. Prevention of hepatitis A through active or passive immunization: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Morb Mortal Wkly Rep. 2006;55:1-23.
27. Vivancos R, Abubakar I, Hunter PR. Foreign travel, casual sex, and sexually transmitted infections: systematic review and meta-analysis. Int J Infect Dis. 2010;14:e842-e851.
28. Gautret P, Harvey K, Pandey P, et al for the GeoSentinel Surveillance Network. Animal-associated exposure to rabies virus among travelers, 1997-2012. Emerg Infect Dis. 2015;21:569-577.
29. Rupprecht CE, Briggs D, Brown CM, et al; Centers for Disease Control and Prevention. Use of a reduced (4-dose) vaccine schedule for postexposure prophylaxis to prevent human rabies: recommendations of the Advisory Committee on Immunization Practices. MMWR Recomm Rep. 2010;59:1-9.
PRACTICE RECOMMENDATIONS
› Recommend immunizations and safety precautions to international travelers based on their destinations, previous immunizations, health status and anticipated activities, and time available before departure. C
› Consider accelerating routine immunizations for children who may be traveling abroad. C
› Refer immunocompromised or pregnant patients to a travel medicine clinic for consultation before departure. C
Strength of recommendation (SOR)
A Good-quality patient-oriented evidence
B Inconsistent or limited-quality patient-oriented evidence
C Consensus, usual practice, opinion, disease-oriented evidence, case series
Developing vaccines against enterovirus-A71 called a priority
MADRID – Is there a need for an enterovirus-A71 vaccine?
This is a new question for North American and European physicians, but not so new in Asia.
“China says yes, with more than 15 million cases of hand, foot, and mouth disease resulting in 3,500 deaths since surveillance started in 2009,” Heli Harvala, MD, said at the annual meeting of the European Society for Paediatric Infectious Diseases.
Seroconversion rates 28 days after the second dose of these vaccines, both directed specifically against viral subgenotype C-4, are 92%-100%. Vaccine efficacy is 91%-97%, according to Dr. Harvala, a consultant medical virologist at University College London.
It remains a mystery why major outbreaks of severe EV-A71 disease have mostly occurred in Asia, with the notable exception of a Spanish outbreak of EV-A71 encephalitis in 2016. The possibility of much wider spread is concerning.
The Chinese monovalent EV-A71 vaccines, however, are seen as a stopgap. For one thing, recent evidence suggests that it’s probably not the specific EV-A71 C-4 viral subgenotype that accounts for all severe disease.
“I think we have to aim for a multivalent vaccine,” Dr. Harvala said.
Now in clinical trials, investigational bivalent vaccines are directed against other EV-A71 subgenotypes in addition to C-4, and also against another enterovirus, coxsackievirus serotype A16, the most common cause of classic hand, foot, and mouth disease in the United States. But that’s probably not enough, according to Dr. Harvala. She noted that coxsackievirus A6, which was first identified more than 50 years ago, abruptly became the main cause of mild hand, foot, and mouth disease in China in 2013 and again in 2015. Moreover, its role in severe cases is growing, and there have been important outbreaks in the United States in recent years. These severe cases come in three main presentations, resembling either erythema multiforme, chicken pox, or eczema herpeticum.
Dr. Harvala added that a next-generation vaccine probably also should offer protection against enterovirus-D68. In 2014, there were 1,153 laboratory-confirmed EV-D68 infections and 14 deaths in the United States and Canada. This infection poses a diagnostic challenge: while the virus is readily detectable on throat swabs, it’s only rarely present in stool or cerebrospinal fluid samples.
“It’s important to keep in mind that this infection is still underdiagnosed. We are not really looking for it,” she said.
No specific treatment for enterovirus infections is available. Three capsid-binding antiviral agents now are in clinical trials: pleconaril, vapendavir, and pocapavir. In addition, translational studies have demonstrated that the SSRI fluoxetine inhibits enterovirus replication, but there have been no clinical trials as yet.
Although development of antivirals effective against enterovirus is an active area of research, Dr. Harvala thinks drug resistance will be an issue, underscoring the importance of vaccine development.
She reported having no financial conflicts of interest regarding her presentation.
MADRID – Is there a need for an enterovirus-A71 vaccine?
This is a new question for North American and European physicians, but not so new in Asia.
“China says yes, with more than 15 million cases of hand, foot, and mouth disease resulting in 3,500 deaths since surveillance started in 2009,” Heli Harvala, MD, said at the annual meeting of the European Society for Paediatric Infectious Diseases.
Seroconversion rates 28 days after the second dose of these vaccines, both directed specifically against viral subgenotype C-4, are 92%-100%. Vaccine efficacy is 91%-97%, according to Dr. Harvala, a consultant medical virologist at University College London.
It remains a mystery why major outbreaks of severe EV-A71 disease have mostly occurred in Asia, with the notable exception of a Spanish outbreak of EV-A71 encephalitis in 2016. The possibility of much wider spread is concerning.
The Chinese monovalent EV-A71 vaccines, however, are seen as a stopgap. For one thing, recent evidence suggests that it’s probably not the specific EV-A71 C-4 viral subgenotype that accounts for all severe disease.
“I think we have to aim for a multivalent vaccine,” Dr. Harvala said.
Now in clinical trials, investigational bivalent vaccines are directed against other EV-A71 subgenotypes in addition to C-4, and also against another enterovirus, coxsackievirus serotype A16, the most common cause of classic hand, foot, and mouth disease in the United States. But that’s probably not enough, according to Dr. Harvala. She noted that coxsackievirus A6, which was first identified more than 50 years ago, abruptly became the main cause of mild hand, foot, and mouth disease in China in 2013 and again in 2015. Moreover, its role in severe cases is growing, and there have been important outbreaks in the United States in recent years. These severe cases come in three main presentations, resembling either erythema multiforme, chicken pox, or eczema herpeticum.
Dr. Harvala added that a next-generation vaccine probably also should offer protection against enterovirus-D68. In 2014, there were 1,153 laboratory-confirmed EV-D68 infections and 14 deaths in the United States and Canada. This infection poses a diagnostic challenge: while the virus is readily detectable on throat swabs, it’s only rarely present in stool or cerebrospinal fluid samples.
“It’s important to keep in mind that this infection is still underdiagnosed. We are not really looking for it,” she said.
No specific treatment for enterovirus infections is available. Three capsid-binding antiviral agents now are in clinical trials: pleconaril, vapendavir, and pocapavir. In addition, translational studies have demonstrated that the SSRI fluoxetine inhibits enterovirus replication, but there have been no clinical trials as yet.
Although development of antivirals effective against enterovirus is an active area of research, Dr. Harvala thinks drug resistance will be an issue, underscoring the importance of vaccine development.
She reported having no financial conflicts of interest regarding her presentation.
MADRID – Is there a need for an enterovirus-A71 vaccine?
This is a new question for North American and European physicians, but not so new in Asia.
“China says yes, with more than 15 million cases of hand, foot, and mouth disease resulting in 3,500 deaths since surveillance started in 2009,” Heli Harvala, MD, said at the annual meeting of the European Society for Paediatric Infectious Diseases.
Seroconversion rates 28 days after the second dose of these vaccines, both directed specifically against viral subgenotype C-4, are 92%-100%. Vaccine efficacy is 91%-97%, according to Dr. Harvala, a consultant medical virologist at University College London.
It remains a mystery why major outbreaks of severe EV-A71 disease have mostly occurred in Asia, with the notable exception of a Spanish outbreak of EV-A71 encephalitis in 2016. The possibility of much wider spread is concerning.
The Chinese monovalent EV-A71 vaccines, however, are seen as a stopgap. For one thing, recent evidence suggests that it’s probably not the specific EV-A71 C-4 viral subgenotype that accounts for all severe disease.
“I think we have to aim for a multivalent vaccine,” Dr. Harvala said.
Now in clinical trials, investigational bivalent vaccines are directed against other EV-A71 subgenotypes in addition to C-4, and also against another enterovirus, coxsackievirus serotype A16, the most common cause of classic hand, foot, and mouth disease in the United States. But that’s probably not enough, according to Dr. Harvala. She noted that coxsackievirus A6, which was first identified more than 50 years ago, abruptly became the main cause of mild hand, foot, and mouth disease in China in 2013 and again in 2015. Moreover, its role in severe cases is growing, and there have been important outbreaks in the United States in recent years. These severe cases come in three main presentations, resembling either erythema multiforme, chicken pox, or eczema herpeticum.
Dr. Harvala added that a next-generation vaccine probably also should offer protection against enterovirus-D68. In 2014, there were 1,153 laboratory-confirmed EV-D68 infections and 14 deaths in the United States and Canada. This infection poses a diagnostic challenge: while the virus is readily detectable on throat swabs, it’s only rarely present in stool or cerebrospinal fluid samples.
“It’s important to keep in mind that this infection is still underdiagnosed. We are not really looking for it,” she said.
No specific treatment for enterovirus infections is available. Three capsid-binding antiviral agents now are in clinical trials: pleconaril, vapendavir, and pocapavir. In addition, translational studies have demonstrated that the SSRI fluoxetine inhibits enterovirus replication, but there have been no clinical trials as yet.
Although development of antivirals effective against enterovirus is an active area of research, Dr. Harvala thinks drug resistance will be an issue, underscoring the importance of vaccine development.
She reported having no financial conflicts of interest regarding her presentation.
EXPERT ANALYSIS FROM ESPID 2017
CDC: Flu vaccine recommendations broaden for pregnant women and children
, according to new recommendations from the Centers for Disease Control and Prevention.
This change from the CDC’s previous guidance that pregnant women receive a seasonal inactivated influenza vaccine (IIV) was recommended by the Advisory Committee on Immunization Practices after some heated debate among committee members over evidence presented to support the change in wording (MMWR. 2017 Aug 25;66[(RR-2]:1-20). 
The new update gives women the ability to choose between receiving an IIV and FluBlok, a recombinant influenza vaccine (RIV) that is not egg based and can be manufactured more quickly, making it ideal in cases of pandemic or supply shortages, according to the CDC.
Although pregnant women may choose to receive a vaccination during the first trimester, the CDC warns there may be some risk involved.
“Although experience with the use of IIVs is substantial, and data from observational studies are available to support the safety of these vaccines in pregnancy, data are more limited for vaccination during the first trimester,” according to the CDC. “Moreover, there is substantially less experience with more recently licensed IIV products (e.g., quadrivalent, cell culture-based, and adjuvanted vaccines) during pregnancy in general.”
Data also are limited regarding RIVs, the CDC said, with the data used to determine safety among pregnant women “limited to reports of pregnancies occurring incidentally during clinical trials, Vaccine Adverse Event Reporting System (VAERS) reports, and pregnancy registry reports.”
Changes for children
The CDC chose to accept ACIP recommendations regarding Afluria (IIV3), expanding the age of children who can receive the vaccine from 9 years and older to 5 years and older.
Similar labeling changes were accepted for FluLaval Quadrivalent (IIV4), which had previously been given to children 3 years and older but now but will be available for children starting at 6 months of age.
New products
Recent product licensures included in the MMWR report are Afluria Quadrivalent (IIV4) and Flublok Quadrivalent (RIV4), both for persons over 18 years.
According to the CDC, Flublok Quadrivalent (an RIV) met noninferiority measures, compared with a similar IIV quadrivalent vaccine, for the A(H3H2) and B/Yamagata viruses but not for A(H1N1) or B/Victoria viruses.
Vaccine composition for 2017-2018
Approved viruses for the 2017-2018 season trivalent vaccines are an A/Michigan/45/2015 (H1N1) pdm09–like virus, an A/Hong Kong/4801/2014 (H3N2)-like virus, and a B/Brisbane/60/2008–like virus (Victoria lineage), according to the MMWR. Quadrivalent vaccines will include those viruses, with the addition of an B/Phuket/3073/2013–like virus (Yamagata lineage).
The CDC continues to recommend that the quadrivalent live attenuated influenza vaccine FluMist not be used by anyone for the 2017-2018 season, a decision that was made after evidence showed poor effectiveness against influenza A(H1N1)pdm09 viruses in the 2013-2014 and 2015-2016 seasons.
Vaccine updates published in this report were recommended by ACIP during meetings held in October 2016 and February and June 2017.
ezimmerman@frontlinemedcom.com
On Twitter @eaztweets
, according to new recommendations from the Centers for Disease Control and Prevention.
This change from the CDC’s previous guidance that pregnant women receive a seasonal inactivated influenza vaccine (IIV) was recommended by the Advisory Committee on Immunization Practices after some heated debate among committee members over evidence presented to support the change in wording (MMWR. 2017 Aug 25;66[(RR-2]:1-20).
The new update gives women the ability to choose between receiving an IIV and FluBlok, a recombinant influenza vaccine (RIV) that is not egg based and can be manufactured more quickly, making it ideal in cases of pandemic or supply shortages, according to the CDC.
Although pregnant women may choose to receive a vaccination during the first trimester, the CDC warns there may be some risk involved.
“Although experience with the use of IIVs is substantial, and data from observational studies are available to support the safety of these vaccines in pregnancy, data are more limited for vaccination during the first trimester,” according to the CDC. “Moreover, there is substantially less experience with more recently licensed IIV products (e.g., quadrivalent, cell culture-based, and adjuvanted vaccines) during pregnancy in general.”
Data also are limited regarding RIVs, the CDC said, with the data used to determine safety among pregnant women “limited to reports of pregnancies occurring incidentally during clinical trials, Vaccine Adverse Event Reporting System (VAERS) reports, and pregnancy registry reports.”
Changes for children
The CDC chose to accept ACIP recommendations regarding Afluria (IIV3), expanding the age of children who can receive the vaccine from 9 years and older to 5 years and older.
Similar labeling changes were accepted for FluLaval Quadrivalent (IIV4), which had previously been given to children 3 years and older but now but will be available for children starting at 6 months of age.
New products
Recent product licensures included in the MMWR report are Afluria Quadrivalent (IIV4) and Flublok Quadrivalent (RIV4), both for persons over 18 years.
According to the CDC, Flublok Quadrivalent (an RIV) met noninferiority measures, compared with a similar IIV quadrivalent vaccine, for the A(H3H2) and B/Yamagata viruses but not for A(H1N1) or B/Victoria viruses.
Vaccine composition for 2017-2018
Approved viruses for the 2017-2018 season trivalent vaccines are an A/Michigan/45/2015 (H1N1) pdm09–like virus, an A/Hong Kong/4801/2014 (H3N2)-like virus, and a B/Brisbane/60/2008–like virus (Victoria lineage), according to the MMWR. Quadrivalent vaccines will include those viruses, with the addition of an B/Phuket/3073/2013–like virus (Yamagata lineage).
The CDC continues to recommend that the quadrivalent live attenuated influenza vaccine FluMist not be used by anyone for the 2017-2018 season, a decision that was made after evidence showed poor effectiveness against influenza A(H1N1)pdm09 viruses in the 2013-2014 and 2015-2016 seasons.
Vaccine updates published in this report were recommended by ACIP during meetings held in October 2016 and February and June 2017.
ezimmerman@frontlinemedcom.com
On Twitter @eaztweets
, according to new recommendations from the Centers for Disease Control and Prevention.
This change from the CDC’s previous guidance that pregnant women receive a seasonal inactivated influenza vaccine (IIV) was recommended by the Advisory Committee on Immunization Practices after some heated debate among committee members over evidence presented to support the change in wording (MMWR. 2017 Aug 25;66[(RR-2]:1-20).
The new update gives women the ability to choose between receiving an IIV and FluBlok, a recombinant influenza vaccine (RIV) that is not egg based and can be manufactured more quickly, making it ideal in cases of pandemic or supply shortages, according to the CDC.
Although pregnant women may choose to receive a vaccination during the first trimester, the CDC warns there may be some risk involved.
“Although experience with the use of IIVs is substantial, and data from observational studies are available to support the safety of these vaccines in pregnancy, data are more limited for vaccination during the first trimester,” according to the CDC. “Moreover, there is substantially less experience with more recently licensed IIV products (e.g., quadrivalent, cell culture-based, and adjuvanted vaccines) during pregnancy in general.”
Data also are limited regarding RIVs, the CDC said, with the data used to determine safety among pregnant women “limited to reports of pregnancies occurring incidentally during clinical trials, Vaccine Adverse Event Reporting System (VAERS) reports, and pregnancy registry reports.”
Changes for children
The CDC chose to accept ACIP recommendations regarding Afluria (IIV3), expanding the age of children who can receive the vaccine from 9 years and older to 5 years and older.
Similar labeling changes were accepted for FluLaval Quadrivalent (IIV4), which had previously been given to children 3 years and older but now but will be available for children starting at 6 months of age.
New products
Recent product licensures included in the MMWR report are Afluria Quadrivalent (IIV4) and Flublok Quadrivalent (RIV4), both for persons over 18 years.
According to the CDC, Flublok Quadrivalent (an RIV) met noninferiority measures, compared with a similar IIV quadrivalent vaccine, for the A(H3H2) and B/Yamagata viruses but not for A(H1N1) or B/Victoria viruses.
Vaccine composition for 2017-2018
Approved viruses for the 2017-2018 season trivalent vaccines are an A/Michigan/45/2015 (H1N1) pdm09–like virus, an A/Hong Kong/4801/2014 (H3N2)-like virus, and a B/Brisbane/60/2008–like virus (Victoria lineage), according to the MMWR. Quadrivalent vaccines will include those viruses, with the addition of an B/Phuket/3073/2013–like virus (Yamagata lineage).
The CDC continues to recommend that the quadrivalent live attenuated influenza vaccine FluMist not be used by anyone for the 2017-2018 season, a decision that was made after evidence showed poor effectiveness against influenza A(H1N1)pdm09 viruses in the 2013-2014 and 2015-2016 seasons.
Vaccine updates published in this report were recommended by ACIP during meetings held in October 2016 and February and June 2017.
ezimmerman@frontlinemedcom.com
On Twitter @eaztweets
FROM MMWR
AAP recommends hepatitis B vaccine within 24 hours of birth for all infants
All newborns with a birth weight of at least 2,000 grams (4.4 pounds) should receive the hepatitis B vaccine within 24 hours of birth, according to a new policy statement by the American Academy of Pediatrics that brings its recommendations in line with those of the Advisory Committee on Immunization Practices at the Centers for Disease Control and Prevention.
“The birth dose can prevent infection of infants born to infected mothers in situations in which the mother’s results are never obtained, are misinterpreted, are falsely negative, are transcribed or reported to the infant care team inaccurately, or simply not communicated to the nursery,” announced the new statement from the AAP Committee on Infectious Diseases and the Committee on Fetus and Newborn (Pediatrics. 2017 Aug 28. doi: 10.1542/peds.2017-1870).
A dose of the hepatitis B vaccine within 24 hours of birth is 75%-95% effective at preventing perinatal hepatitis B transmission. “When postexposure prophylaxis with both hepatitis B vaccine and hepatitis B immune globulin (HBIG) is given, is timed appropriately, and is followed by completion of the infant hepatitis B immunization series, perinatal infection rates range from 0.7% to 1.1%,” according to the statement.
Approximately 1,000 newborns still contract perinatal hepatitis B infections every year. Of these, 90% will develop chronic hepatitis B infections, and a quarter of those who don’t receive treatment will die from liver cirrhosis or cancer. There has been an increase in the incidence of new hepatitis B infections in some states because of opioid epidemic in the United States, according to MMWR reports.
The cost effectiveness of preventing hepatitis B with the vaccine and, when necessary, HBIG, is estimated at $2,600 per quality-adjusted year of life. The most common side effects reported after hepatitis B administration are pain (3%-29%), erythema (3%), swelling (3%), fever (1%-6%) and headache (3%).
There has been extensive analysis of the safety of hepatitis B vaccines, the policy statement indicated. Analysis of Vaccine Safety Datalink data has found no causal link between administration of the hepatitis B vaccine and the following: neonatal sepsis or death, rheumatoid arthritis, Bell’s palsy, autoimmune thyroid disease, hemolytic anemia in children, anaphylaxis, optic neuritis, Guillain-Barré syndrome, sudden-onset sensorineural hearing loss, or other chronic illnesses.
Specific recommendations
• Infants born to mothers who test positive for hepatitis B surface antigen (HBsAg): Administer the hepatitis B vaccine and HBIG within 12 hours of birth.
• Infants weighing at least 2,000 g and born to mothers who are HBsAg negative: Administer the hepatitis B vaccine within 24 hours of birth.
• Infants weighing less than 2,000 g and born to mothers who are HBsAg negative: Administer the hepatitis B vaccine at hospital discharge or at age 1 month (whichever is first).
• Infants weighing at least 2,000 g and born to mothers with an unknown HBsAg status: Administer the hepatitis B vaccine within 12 hours of birth and HBIG by hospital discharge or age 7 days (whichever is first) if HBsAg status remains unknown or is confirmed positive.
• Infants weighing less than 2,000 g and born to mothers with an unknown HBsAg status: Administer the hepatitis B vaccine within 12 hours of birth and then HBIG within 12 hours unless the mother tests negative for HBsAg by then.
All newborns with a birth weight of at least 2,000 grams (4.4 pounds) should receive the hepatitis B vaccine within 24 hours of birth, according to a new policy statement by the American Academy of Pediatrics that brings its recommendations in line with those of the Advisory Committee on Immunization Practices at the Centers for Disease Control and Prevention.
“The birth dose can prevent infection of infants born to infected mothers in situations in which the mother’s results are never obtained, are misinterpreted, are falsely negative, are transcribed or reported to the infant care team inaccurately, or simply not communicated to the nursery,” announced the new statement from the AAP Committee on Infectious Diseases and the Committee on Fetus and Newborn (Pediatrics. 2017 Aug 28. doi: 10.1542/peds.2017-1870).
A dose of the hepatitis B vaccine within 24 hours of birth is 75%-95% effective at preventing perinatal hepatitis B transmission. “When postexposure prophylaxis with both hepatitis B vaccine and hepatitis B immune globulin (HBIG) is given, is timed appropriately, and is followed by completion of the infant hepatitis B immunization series, perinatal infection rates range from 0.7% to 1.1%,” according to the statement.
Approximately 1,000 newborns still contract perinatal hepatitis B infections every year. Of these, 90% will develop chronic hepatitis B infections, and a quarter of those who don’t receive treatment will die from liver cirrhosis or cancer. There has been an increase in the incidence of new hepatitis B infections in some states because of opioid epidemic in the United States, according to MMWR reports.
The cost effectiveness of preventing hepatitis B with the vaccine and, when necessary, HBIG, is estimated at $2,600 per quality-adjusted year of life. The most common side effects reported after hepatitis B administration are pain (3%-29%), erythema (3%), swelling (3%), fever (1%-6%) and headache (3%).
There has been extensive analysis of the safety of hepatitis B vaccines, the policy statement indicated. Analysis of Vaccine Safety Datalink data has found no causal link between administration of the hepatitis B vaccine and the following: neonatal sepsis or death, rheumatoid arthritis, Bell’s palsy, autoimmune thyroid disease, hemolytic anemia in children, anaphylaxis, optic neuritis, Guillain-Barré syndrome, sudden-onset sensorineural hearing loss, or other chronic illnesses.
Specific recommendations
• Infants born to mothers who test positive for hepatitis B surface antigen (HBsAg): Administer the hepatitis B vaccine and HBIG within 12 hours of birth.
• Infants weighing at least 2,000 g and born to mothers who are HBsAg negative: Administer the hepatitis B vaccine within 24 hours of birth.
• Infants weighing less than 2,000 g and born to mothers who are HBsAg negative: Administer the hepatitis B vaccine at hospital discharge or at age 1 month (whichever is first).
• Infants weighing at least 2,000 g and born to mothers with an unknown HBsAg status: Administer the hepatitis B vaccine within 12 hours of birth and HBIG by hospital discharge or age 7 days (whichever is first) if HBsAg status remains unknown or is confirmed positive.
• Infants weighing less than 2,000 g and born to mothers with an unknown HBsAg status: Administer the hepatitis B vaccine within 12 hours of birth and then HBIG within 12 hours unless the mother tests negative for HBsAg by then.
All newborns with a birth weight of at least 2,000 grams (4.4 pounds) should receive the hepatitis B vaccine within 24 hours of birth, according to a new policy statement by the American Academy of Pediatrics that brings its recommendations in line with those of the Advisory Committee on Immunization Practices at the Centers for Disease Control and Prevention.
“The birth dose can prevent infection of infants born to infected mothers in situations in which the mother’s results are never obtained, are misinterpreted, are falsely negative, are transcribed or reported to the infant care team inaccurately, or simply not communicated to the nursery,” announced the new statement from the AAP Committee on Infectious Diseases and the Committee on Fetus and Newborn (Pediatrics. 2017 Aug 28. doi: 10.1542/peds.2017-1870).
A dose of the hepatitis B vaccine within 24 hours of birth is 75%-95% effective at preventing perinatal hepatitis B transmission. “When postexposure prophylaxis with both hepatitis B vaccine and hepatitis B immune globulin (HBIG) is given, is timed appropriately, and is followed by completion of the infant hepatitis B immunization series, perinatal infection rates range from 0.7% to 1.1%,” according to the statement.
Approximately 1,000 newborns still contract perinatal hepatitis B infections every year. Of these, 90% will develop chronic hepatitis B infections, and a quarter of those who don’t receive treatment will die from liver cirrhosis or cancer. There has been an increase in the incidence of new hepatitis B infections in some states because of opioid epidemic in the United States, according to MMWR reports.
The cost effectiveness of preventing hepatitis B with the vaccine and, when necessary, HBIG, is estimated at $2,600 per quality-adjusted year of life. The most common side effects reported after hepatitis B administration are pain (3%-29%), erythema (3%), swelling (3%), fever (1%-6%) and headache (3%).
There has been extensive analysis of the safety of hepatitis B vaccines, the policy statement indicated. Analysis of Vaccine Safety Datalink data has found no causal link between administration of the hepatitis B vaccine and the following: neonatal sepsis or death, rheumatoid arthritis, Bell’s palsy, autoimmune thyroid disease, hemolytic anemia in children, anaphylaxis, optic neuritis, Guillain-Barré syndrome, sudden-onset sensorineural hearing loss, or other chronic illnesses.
Specific recommendations
• Infants born to mothers who test positive for hepatitis B surface antigen (HBsAg): Administer the hepatitis B vaccine and HBIG within 12 hours of birth.
• Infants weighing at least 2,000 g and born to mothers who are HBsAg negative: Administer the hepatitis B vaccine within 24 hours of birth.
• Infants weighing less than 2,000 g and born to mothers who are HBsAg negative: Administer the hepatitis B vaccine at hospital discharge or at age 1 month (whichever is first).
• Infants weighing at least 2,000 g and born to mothers with an unknown HBsAg status: Administer the hepatitis B vaccine within 12 hours of birth and HBIG by hospital discharge or age 7 days (whichever is first) if HBsAg status remains unknown or is confirmed positive.
• Infants weighing less than 2,000 g and born to mothers with an unknown HBsAg status: Administer the hepatitis B vaccine within 12 hours of birth and then HBIG within 12 hours unless the mother tests negative for HBsAg by then.
FROM PEDIATRICS
Key clinical point: All infants should receive hepatitis B vaccine within 24 hours of birth.
Major finding: Hepatitis B vaccine prevents 75%-95% of perinatal hepatitis B infections.
Data source: A literature review of data on hepatitis B epidemiology in the United States.
Disclosures: The statement did not receive external funding, and the authors stated that they have no conflicts of interest.
PD3 G1 SNA found to correlate with pentavalent rotavirus vaccine efficacy
(RV5), reported G. Frank Liu, PhD, and his associates at Merck in Kenilworth, N.J.
The researchers discovered this by analyzing data from five clinical trials of RV5 at both the individual and aggregated population level. Also, by looking at immunogenicity measures and case status of individuals from phase 2 and 3 trials of RV5, they found that “higher PD3 G1 SNA titers are associated with lower odds of contracting any [rotavirus gastroenteritis].”
Read more at (Hum Vaccin Immunother. 2017. doi: 10.1080/21645515.2017.1356522).
cnellist@frontlinemedcom.com
(RV5), reported G. Frank Liu, PhD, and his associates at Merck in Kenilworth, N.J.
The researchers discovered this by analyzing data from five clinical trials of RV5 at both the individual and aggregated population level. Also, by looking at immunogenicity measures and case status of individuals from phase 2 and 3 trials of RV5, they found that “higher PD3 G1 SNA titers are associated with lower odds of contracting any [rotavirus gastroenteritis].”
Read more at (Hum Vaccin Immunother. 2017. doi: 10.1080/21645515.2017.1356522).
cnellist@frontlinemedcom.com
(RV5), reported G. Frank Liu, PhD, and his associates at Merck in Kenilworth, N.J.
The researchers discovered this by analyzing data from five clinical trials of RV5 at both the individual and aggregated population level. Also, by looking at immunogenicity measures and case status of individuals from phase 2 and 3 trials of RV5, they found that “higher PD3 G1 SNA titers are associated with lower odds of contracting any [rotavirus gastroenteritis].”
Read more at (Hum Vaccin Immunother. 2017. doi: 10.1080/21645515.2017.1356522).
cnellist@frontlinemedcom.com
FROM HUMAN VACCINES & IMMUNOTHERAPEUTICS