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Model: Quadrivalent vaccine could cost effectively cut MSM’s HPV-related cancers
Use of a quadrivalent HPV vaccine in men who have sex with men, administered in genitourinary specialty clinics, would cost effectively provide herd immunity against the ill effects of the virus, particularly anogenital warts and male HPV-related cancers, according to an English mathematical model.
Mark Jit, PhD, a professor of vaccine epidemiology at the London School of Hygiene & Tropical Medicine, and his colleagues considered in which settings HPV vaccination delivery would have the greatest effect size; the patterns of sexual behavior in MSM leading to the transmission of HPV 6, 11, 16, and 18; and the costs and quality adjusted life year (QALY) implications of disease outcomes (Clin Infect Dis. 2016 Dec 23. doi: 10.1093/cid/ciw845).
Clinic attendance rates were based on genitourinary clinic returns in England recorded in public health surveillance data recorded between 2009 and 2012, stratified according to diagnosed HIV-positive status. Also modeled were the effects of vaccination in MSM between the ages of 16 and 40 years, according to groups aged 16-25 years, 16-30 years, 16-35 years, and 16-40 years. Models for ages on either side of 16 or 40 years were not considered because of confidentiality constraints in the former and limited specialty clinic use in the latter.
Herd protection likely would be notable in the first year, because of the breadth of the age ranges modeled, Dr. Jit and his colleagues determined. Specifically, the models predicted a 35% decline in incidence rates of anogenital warts within 5 years of initiating the vaccine across all MSM men seen in specialty clinics. If only HIV-positive MSM across the age groups were vaccinated, the models predicted a 5-year decline of 15%.
Declines predicted in HPV-related cancers would happen more slowly, because progression from infection to malignancies tends to occur over years. For example, there would be a 55% reduction over 100 years for anal cancer if all 16- to 40-year-old MSM attending specialty clinics are offered vaccination. However, the reduction rate would drop to 40% in that same time period if only HIV-positive men across the age groups were vaccinated.
Using a cost-effectiveness threshold of 20,000 British pounds (about $24,500) per QALY, with no more than a 10% probability that the incremental cost-effectiveness ratio would exceed 30,000 pounds per QALY ($36,710), Dr. Jit and his colleagues determined that using a quadrivalent HPV vaccination in MSM between ages 16 and 40 years in the specialty clinic setting would be cost effective if delivery cost an average of 63 pounds ($77) per dose.
By offering vaccination only to HIV-positive MSM between 16 and 40 years, even if the quadrivalent vaccine were to cost as much as 96.50 pounds ($118), it would still be cost effective. A nonavalent vaccine at the same price would also be cost effective, because nearly all HPV-related cancers are linked to HPV 16 and 18. However, a bivalent vaccine was not shown by the models to be cost effective in such a limited program.
The investigators theorized that HIV infection is associated with the rate of HPV-related disease progression. To simplify computation, however, their models only considered the overall cost effectiveness of offering HPV vaccination to either HIV-positive MSM or to MSM regardless of current HIV status. That could mean “the cost effectiveness of MSM vaccination may be even better than reported,” the researchers noted.
This study was funded primarily by the National Institute for Health Research and Public Health England in the United Kingdom. The authors had no relevant disclosures.
Use of a quadrivalent HPV vaccine in men who have sex with men, administered in genitourinary specialty clinics, would cost effectively provide herd immunity against the ill effects of the virus, particularly anogenital warts and male HPV-related cancers, according to an English mathematical model.
Mark Jit, PhD, a professor of vaccine epidemiology at the London School of Hygiene & Tropical Medicine, and his colleagues considered in which settings HPV vaccination delivery would have the greatest effect size; the patterns of sexual behavior in MSM leading to the transmission of HPV 6, 11, 16, and 18; and the costs and quality adjusted life year (QALY) implications of disease outcomes (Clin Infect Dis. 2016 Dec 23. doi: 10.1093/cid/ciw845).
Clinic attendance rates were based on genitourinary clinic returns in England recorded in public health surveillance data recorded between 2009 and 2012, stratified according to diagnosed HIV-positive status. Also modeled were the effects of vaccination in MSM between the ages of 16 and 40 years, according to groups aged 16-25 years, 16-30 years, 16-35 years, and 16-40 years. Models for ages on either side of 16 or 40 years were not considered because of confidentiality constraints in the former and limited specialty clinic use in the latter.
Herd protection likely would be notable in the first year, because of the breadth of the age ranges modeled, Dr. Jit and his colleagues determined. Specifically, the models predicted a 35% decline in incidence rates of anogenital warts within 5 years of initiating the vaccine across all MSM men seen in specialty clinics. If only HIV-positive MSM across the age groups were vaccinated, the models predicted a 5-year decline of 15%.
Declines predicted in HPV-related cancers would happen more slowly, because progression from infection to malignancies tends to occur over years. For example, there would be a 55% reduction over 100 years for anal cancer if all 16- to 40-year-old MSM attending specialty clinics are offered vaccination. However, the reduction rate would drop to 40% in that same time period if only HIV-positive men across the age groups were vaccinated.
Using a cost-effectiveness threshold of 20,000 British pounds (about $24,500) per QALY, with no more than a 10% probability that the incremental cost-effectiveness ratio would exceed 30,000 pounds per QALY ($36,710), Dr. Jit and his colleagues determined that using a quadrivalent HPV vaccination in MSM between ages 16 and 40 years in the specialty clinic setting would be cost effective if delivery cost an average of 63 pounds ($77) per dose.
By offering vaccination only to HIV-positive MSM between 16 and 40 years, even if the quadrivalent vaccine were to cost as much as 96.50 pounds ($118), it would still be cost effective. A nonavalent vaccine at the same price would also be cost effective, because nearly all HPV-related cancers are linked to HPV 16 and 18. However, a bivalent vaccine was not shown by the models to be cost effective in such a limited program.
The investigators theorized that HIV infection is associated with the rate of HPV-related disease progression. To simplify computation, however, their models only considered the overall cost effectiveness of offering HPV vaccination to either HIV-positive MSM or to MSM regardless of current HIV status. That could mean “the cost effectiveness of MSM vaccination may be even better than reported,” the researchers noted.
This study was funded primarily by the National Institute for Health Research and Public Health England in the United Kingdom. The authors had no relevant disclosures.
Use of a quadrivalent HPV vaccine in men who have sex with men, administered in genitourinary specialty clinics, would cost effectively provide herd immunity against the ill effects of the virus, particularly anogenital warts and male HPV-related cancers, according to an English mathematical model.
Mark Jit, PhD, a professor of vaccine epidemiology at the London School of Hygiene & Tropical Medicine, and his colleagues considered in which settings HPV vaccination delivery would have the greatest effect size; the patterns of sexual behavior in MSM leading to the transmission of HPV 6, 11, 16, and 18; and the costs and quality adjusted life year (QALY) implications of disease outcomes (Clin Infect Dis. 2016 Dec 23. doi: 10.1093/cid/ciw845).
Clinic attendance rates were based on genitourinary clinic returns in England recorded in public health surveillance data recorded between 2009 and 2012, stratified according to diagnosed HIV-positive status. Also modeled were the effects of vaccination in MSM between the ages of 16 and 40 years, according to groups aged 16-25 years, 16-30 years, 16-35 years, and 16-40 years. Models for ages on either side of 16 or 40 years were not considered because of confidentiality constraints in the former and limited specialty clinic use in the latter.
Herd protection likely would be notable in the first year, because of the breadth of the age ranges modeled, Dr. Jit and his colleagues determined. Specifically, the models predicted a 35% decline in incidence rates of anogenital warts within 5 years of initiating the vaccine across all MSM men seen in specialty clinics. If only HIV-positive MSM across the age groups were vaccinated, the models predicted a 5-year decline of 15%.
Declines predicted in HPV-related cancers would happen more slowly, because progression from infection to malignancies tends to occur over years. For example, there would be a 55% reduction over 100 years for anal cancer if all 16- to 40-year-old MSM attending specialty clinics are offered vaccination. However, the reduction rate would drop to 40% in that same time period if only HIV-positive men across the age groups were vaccinated.
Using a cost-effectiveness threshold of 20,000 British pounds (about $24,500) per QALY, with no more than a 10% probability that the incremental cost-effectiveness ratio would exceed 30,000 pounds per QALY ($36,710), Dr. Jit and his colleagues determined that using a quadrivalent HPV vaccination in MSM between ages 16 and 40 years in the specialty clinic setting would be cost effective if delivery cost an average of 63 pounds ($77) per dose.
By offering vaccination only to HIV-positive MSM between 16 and 40 years, even if the quadrivalent vaccine were to cost as much as 96.50 pounds ($118), it would still be cost effective. A nonavalent vaccine at the same price would also be cost effective, because nearly all HPV-related cancers are linked to HPV 16 and 18. However, a bivalent vaccine was not shown by the models to be cost effective in such a limited program.
The investigators theorized that HIV infection is associated with the rate of HPV-related disease progression. To simplify computation, however, their models only considered the overall cost effectiveness of offering HPV vaccination to either HIV-positive MSM or to MSM regardless of current HIV status. That could mean “the cost effectiveness of MSM vaccination may be even better than reported,” the researchers noted.
This study was funded primarily by the National Institute for Health Research and Public Health England in the United Kingdom. The authors had no relevant disclosures.
Key clinical point:
Major finding: Substantial declines in HPV-related events in MSM were projected within 5 years of vaccination between ages 16 and 40 years in this cohort.
Data source: Mathematical modeling of HPV 6, 11, 16, and 18 sexual transmission in the MSM population of England.
Disclosures: This study was funded primarily by the National Institute for Health Research and Public Health England in the United Kingdom. The authors had no relevant disclosures.
It isn’t over until it’s over
Pediatricians take heart.
Yes, I know it is discouraging when families occasionally ignore our advice and refuse vaccines for their children. It is even worse when political leaders who ought to know better question the safety and value of vaccines.
But let’s not lose perspective. Let me share a quick reminder of why vaccines are (almost) universally considered one of the greatest public health achievements of the 20th century.
Not long ago, I reviewed a clinical case with students as part of a medical microbiology course. A 6-year-old girl presented with fever, headache, and flaccid paralysis of the right arm with areflexia. With little prompting, the students generated a short differential diagnosis. Enterovirus. West Nile virus. “I guess we should include polio,” one student offered. “But who gets that anymore?”
A mere 120 years changes everything. At the dawn of the 20th century, we didn’t even know with certainty what caused polio, although infection was suspected.
On Sept. 9, 1954, the Courier-Journal, a newspaper in my hometown of Louisville, Ky., carried a story about the annual number of polio cases in Jefferson County, noting that they had reached 198 and General Hospital had opened a polio ward usually reserved for epidemics. Concerns about the infection were rippling throughout the state, and the paper reported that at least one high school marching band had elected to withdraw from annual Kentucky State Fair competition because of concerns about infection.
My mom was 10 years old in the summer of 1954, and she recalls that it was a “scary” time. Swimming pools closed. Parents refused to allow their children to go to movie theaters or the local amusement park because of fear that they might come into contact with the virus. My mom said, “Then one of my friends was diagnosed with polio. We had played together the week before she got sick. We worried that we were going to get sick, too. And once you got sick, you didn’t necessarily get better.”
I probably don’t need to remind you that both Dr. Sabin and Dr. Salk did develop successful poliovirus vaccines. Dr. Enders, along with junior colleagues Fred C. Robbins, MD, and Thomas H. Weller, MD, developed the techniques to grow poliovirus and other viruses in culture, making the work of Dr. Sabin and Dr. Salk possible. For this, Dr. Enders, Dr. Robbins, and Dr. Weller received the Nobel Prize in 1954.
Regarding the prediction of long-term protection, I’d say we’re there. According to the Centers for Disease Control and Prevention, wild poliovirus cases have declined more than 99.9% since 1988. According to the Global Polio Eradication Initiative, that means that there are approximately 10 million people walking today who would have otherwise been paralyzed by the disease.
In 2015, there were only 74 cases identified in the world, and these were localized to two countries. Even better, a global commission announced that wild poliovirus type 2 had been eradicated from the world. Eradicated. The last known transmission occurred in India in 1999.
Type 3 poliovirus may not be far behind. The last known case of wildtype poliovirus 3 was detected in 2012.
The complete story of poliovirus eradication efforts could read like a suspense novel: There have been twists and turns, some missed deadlines, and now a bit of irony. Success, in large part, has hinged on the use of trivalent, live attenuated oral poliovirus vaccine (tOPV) throughout much of the world. Now eradication of all polio disease is going to require withdrawal of OPV in countries that still use it.
Rarely, the live attenuated vaccine viruses contained in OPV can cause polio, and since 2012, vaccine-derived cases have exceeded wild poliovirus cases. Vaccine-derived cases include vaccine-associated paralytic polio (VAPP) – paralysis occurs in a vaccine recipient or a close contact – as well as cases of circulating vaccine-derived polioviruses (cVDPVs). Remember that vaccine viruses are shed in the stool, and in communities with low immunization rates, they circulate and acquire mutations that confer the transmissibility and neurovirulence properties of wild viruses. Ultimately, cVDPVs lead to outbreaks.
In 2013, the Global Polio Eradication Initiative published a new “endgame plan” for polio that outlined a stepwise approach for removing OPV from immunization programs. First, it called on all countries to introduce at least one dose of inactivated poliovirus vaccine by the third quarter of 2015, immunizing infants at 14 weeks or at first contact thereafter. Second, it called for all countries to replace tOPV with a bivalent vaccine containing only types 1 and 3 by 2016. Given the eradication of wild poliovirus type 2, keeping type 2 in the oral vaccine just creates risk. An estimated 40% of VAPP cases and 98% of cVDPVs detected since 2012 were caused by poliovirus type 2. The type 2 component of tOPV also interferes with the immune response to the other types. Once poliovirus eradication has been achieved and certified, hopefully no later than 2019, all OPV will be withdrawn.
What’s the role of pediatricians in the United States in polio eradication? For now, our job is to continue to protect all children in the United States against all three types of poliovirus. Current Advisory Committee on Immunization Practices (ACIP) recommendations specify 4 doses of trivalent inactivated poliovirus vaccine (IPV) at ages 2 months, 4 months, 6-18 months, and 4-6 years. Children vaccinated outside the United States with bivalent vaccine, including immigrants and refugees, will need to be revaccinated. Those without appropriate documentation of vaccine (written, dated records that specify trivalent vaccine) also should be revaccinated.
Serologic testing for immunity is no longer recommended. In the past, children without documentation of vaccines could be tested for neutralizing antibodies to poliovirus types 1, 2, and 3. Moving forward, serologic testing for antibodies to poliovirus type 2 won’t be available because it requires live virus, and in accordance with World Health Organization recommendations, laboratories have been destroying supplies of poliovirus type 2.
We also need to make sure that our patients who are traveling internationally receive all recommended vaccines, including a dose of IPV when appropriate. Specific recommendations can be found on the CDC’s pages for travelers.
A 2015 statement from the American Academy of Pediatrics called on pediatricians to consider polio as a potential diagnosis of any child presenting with fever and acute flaccid paralysis (Pediatrics. 2015 Jan;135[1]:196-202). When polio is suspected, public health authorities should be notified and two stool samples collected 24 hours apart, and within 14 days of the onset of paralysis, sent for testing. According to lead author Walter A. Orenstein, MD, “because most polio infections are silent, a case of paralytic polio in the United States may have been acquired from an asymptomatic individual, so a history of travel to a polio-infected area may be absent in the case of paralysis.”
I’ll second what my mom said. Scary.
Dr. Bryant is a pediatrician specializing in infectious diseases at the University of Louisville (Ky.) and Kosair Children’s Hospital, also in Louisville. She said she had no relevant financial disclosures. Email her at pdnews@frontlinemedcom.com.
Pediatricians take heart.
Yes, I know it is discouraging when families occasionally ignore our advice and refuse vaccines for their children. It is even worse when political leaders who ought to know better question the safety and value of vaccines.
But let’s not lose perspective. Let me share a quick reminder of why vaccines are (almost) universally considered one of the greatest public health achievements of the 20th century.
Not long ago, I reviewed a clinical case with students as part of a medical microbiology course. A 6-year-old girl presented with fever, headache, and flaccid paralysis of the right arm with areflexia. With little prompting, the students generated a short differential diagnosis. Enterovirus. West Nile virus. “I guess we should include polio,” one student offered. “But who gets that anymore?”
A mere 120 years changes everything. At the dawn of the 20th century, we didn’t even know with certainty what caused polio, although infection was suspected.
On Sept. 9, 1954, the Courier-Journal, a newspaper in my hometown of Louisville, Ky., carried a story about the annual number of polio cases in Jefferson County, noting that they had reached 198 and General Hospital had opened a polio ward usually reserved for epidemics. Concerns about the infection were rippling throughout the state, and the paper reported that at least one high school marching band had elected to withdraw from annual Kentucky State Fair competition because of concerns about infection.
My mom was 10 years old in the summer of 1954, and she recalls that it was a “scary” time. Swimming pools closed. Parents refused to allow their children to go to movie theaters or the local amusement park because of fear that they might come into contact with the virus. My mom said, “Then one of my friends was diagnosed with polio. We had played together the week before she got sick. We worried that we were going to get sick, too. And once you got sick, you didn’t necessarily get better.”
I probably don’t need to remind you that both Dr. Sabin and Dr. Salk did develop successful poliovirus vaccines. Dr. Enders, along with junior colleagues Fred C. Robbins, MD, and Thomas H. Weller, MD, developed the techniques to grow poliovirus and other viruses in culture, making the work of Dr. Sabin and Dr. Salk possible. For this, Dr. Enders, Dr. Robbins, and Dr. Weller received the Nobel Prize in 1954.
Regarding the prediction of long-term protection, I’d say we’re there. According to the Centers for Disease Control and Prevention, wild poliovirus cases have declined more than 99.9% since 1988. According to the Global Polio Eradication Initiative, that means that there are approximately 10 million people walking today who would have otherwise been paralyzed by the disease.
In 2015, there were only 74 cases identified in the world, and these were localized to two countries. Even better, a global commission announced that wild poliovirus type 2 had been eradicated from the world. Eradicated. The last known transmission occurred in India in 1999.
Type 3 poliovirus may not be far behind. The last known case of wildtype poliovirus 3 was detected in 2012.
The complete story of poliovirus eradication efforts could read like a suspense novel: There have been twists and turns, some missed deadlines, and now a bit of irony. Success, in large part, has hinged on the use of trivalent, live attenuated oral poliovirus vaccine (tOPV) throughout much of the world. Now eradication of all polio disease is going to require withdrawal of OPV in countries that still use it.
Rarely, the live attenuated vaccine viruses contained in OPV can cause polio, and since 2012, vaccine-derived cases have exceeded wild poliovirus cases. Vaccine-derived cases include vaccine-associated paralytic polio (VAPP) – paralysis occurs in a vaccine recipient or a close contact – as well as cases of circulating vaccine-derived polioviruses (cVDPVs). Remember that vaccine viruses are shed in the stool, and in communities with low immunization rates, they circulate and acquire mutations that confer the transmissibility and neurovirulence properties of wild viruses. Ultimately, cVDPVs lead to outbreaks.
In 2013, the Global Polio Eradication Initiative published a new “endgame plan” for polio that outlined a stepwise approach for removing OPV from immunization programs. First, it called on all countries to introduce at least one dose of inactivated poliovirus vaccine by the third quarter of 2015, immunizing infants at 14 weeks or at first contact thereafter. Second, it called for all countries to replace tOPV with a bivalent vaccine containing only types 1 and 3 by 2016. Given the eradication of wild poliovirus type 2, keeping type 2 in the oral vaccine just creates risk. An estimated 40% of VAPP cases and 98% of cVDPVs detected since 2012 were caused by poliovirus type 2. The type 2 component of tOPV also interferes with the immune response to the other types. Once poliovirus eradication has been achieved and certified, hopefully no later than 2019, all OPV will be withdrawn.
What’s the role of pediatricians in the United States in polio eradication? For now, our job is to continue to protect all children in the United States against all three types of poliovirus. Current Advisory Committee on Immunization Practices (ACIP) recommendations specify 4 doses of trivalent inactivated poliovirus vaccine (IPV) at ages 2 months, 4 months, 6-18 months, and 4-6 years. Children vaccinated outside the United States with bivalent vaccine, including immigrants and refugees, will need to be revaccinated. Those without appropriate documentation of vaccine (written, dated records that specify trivalent vaccine) also should be revaccinated.
Serologic testing for immunity is no longer recommended. In the past, children without documentation of vaccines could be tested for neutralizing antibodies to poliovirus types 1, 2, and 3. Moving forward, serologic testing for antibodies to poliovirus type 2 won’t be available because it requires live virus, and in accordance with World Health Organization recommendations, laboratories have been destroying supplies of poliovirus type 2.
We also need to make sure that our patients who are traveling internationally receive all recommended vaccines, including a dose of IPV when appropriate. Specific recommendations can be found on the CDC’s pages for travelers.
A 2015 statement from the American Academy of Pediatrics called on pediatricians to consider polio as a potential diagnosis of any child presenting with fever and acute flaccid paralysis (Pediatrics. 2015 Jan;135[1]:196-202). When polio is suspected, public health authorities should be notified and two stool samples collected 24 hours apart, and within 14 days of the onset of paralysis, sent for testing. According to lead author Walter A. Orenstein, MD, “because most polio infections are silent, a case of paralytic polio in the United States may have been acquired from an asymptomatic individual, so a history of travel to a polio-infected area may be absent in the case of paralysis.”
I’ll second what my mom said. Scary.
Dr. Bryant is a pediatrician specializing in infectious diseases at the University of Louisville (Ky.) and Kosair Children’s Hospital, also in Louisville. She said she had no relevant financial disclosures. Email her at pdnews@frontlinemedcom.com.
Pediatricians take heart.
Yes, I know it is discouraging when families occasionally ignore our advice and refuse vaccines for their children. It is even worse when political leaders who ought to know better question the safety and value of vaccines.
But let’s not lose perspective. Let me share a quick reminder of why vaccines are (almost) universally considered one of the greatest public health achievements of the 20th century.
Not long ago, I reviewed a clinical case with students as part of a medical microbiology course. A 6-year-old girl presented with fever, headache, and flaccid paralysis of the right arm with areflexia. With little prompting, the students generated a short differential diagnosis. Enterovirus. West Nile virus. “I guess we should include polio,” one student offered. “But who gets that anymore?”
A mere 120 years changes everything. At the dawn of the 20th century, we didn’t even know with certainty what caused polio, although infection was suspected.
On Sept. 9, 1954, the Courier-Journal, a newspaper in my hometown of Louisville, Ky., carried a story about the annual number of polio cases in Jefferson County, noting that they had reached 198 and General Hospital had opened a polio ward usually reserved for epidemics. Concerns about the infection were rippling throughout the state, and the paper reported that at least one high school marching band had elected to withdraw from annual Kentucky State Fair competition because of concerns about infection.
My mom was 10 years old in the summer of 1954, and she recalls that it was a “scary” time. Swimming pools closed. Parents refused to allow their children to go to movie theaters or the local amusement park because of fear that they might come into contact with the virus. My mom said, “Then one of my friends was diagnosed with polio. We had played together the week before she got sick. We worried that we were going to get sick, too. And once you got sick, you didn’t necessarily get better.”
I probably don’t need to remind you that both Dr. Sabin and Dr. Salk did develop successful poliovirus vaccines. Dr. Enders, along with junior colleagues Fred C. Robbins, MD, and Thomas H. Weller, MD, developed the techniques to grow poliovirus and other viruses in culture, making the work of Dr. Sabin and Dr. Salk possible. For this, Dr. Enders, Dr. Robbins, and Dr. Weller received the Nobel Prize in 1954.
Regarding the prediction of long-term protection, I’d say we’re there. According to the Centers for Disease Control and Prevention, wild poliovirus cases have declined more than 99.9% since 1988. According to the Global Polio Eradication Initiative, that means that there are approximately 10 million people walking today who would have otherwise been paralyzed by the disease.
In 2015, there were only 74 cases identified in the world, and these were localized to two countries. Even better, a global commission announced that wild poliovirus type 2 had been eradicated from the world. Eradicated. The last known transmission occurred in India in 1999.
Type 3 poliovirus may not be far behind. The last known case of wildtype poliovirus 3 was detected in 2012.
The complete story of poliovirus eradication efforts could read like a suspense novel: There have been twists and turns, some missed deadlines, and now a bit of irony. Success, in large part, has hinged on the use of trivalent, live attenuated oral poliovirus vaccine (tOPV) throughout much of the world. Now eradication of all polio disease is going to require withdrawal of OPV in countries that still use it.
Rarely, the live attenuated vaccine viruses contained in OPV can cause polio, and since 2012, vaccine-derived cases have exceeded wild poliovirus cases. Vaccine-derived cases include vaccine-associated paralytic polio (VAPP) – paralysis occurs in a vaccine recipient or a close contact – as well as cases of circulating vaccine-derived polioviruses (cVDPVs). Remember that vaccine viruses are shed in the stool, and in communities with low immunization rates, they circulate and acquire mutations that confer the transmissibility and neurovirulence properties of wild viruses. Ultimately, cVDPVs lead to outbreaks.
In 2013, the Global Polio Eradication Initiative published a new “endgame plan” for polio that outlined a stepwise approach for removing OPV from immunization programs. First, it called on all countries to introduce at least one dose of inactivated poliovirus vaccine by the third quarter of 2015, immunizing infants at 14 weeks or at first contact thereafter. Second, it called for all countries to replace tOPV with a bivalent vaccine containing only types 1 and 3 by 2016. Given the eradication of wild poliovirus type 2, keeping type 2 in the oral vaccine just creates risk. An estimated 40% of VAPP cases and 98% of cVDPVs detected since 2012 were caused by poliovirus type 2. The type 2 component of tOPV also interferes with the immune response to the other types. Once poliovirus eradication has been achieved and certified, hopefully no later than 2019, all OPV will be withdrawn.
What’s the role of pediatricians in the United States in polio eradication? For now, our job is to continue to protect all children in the United States against all three types of poliovirus. Current Advisory Committee on Immunization Practices (ACIP) recommendations specify 4 doses of trivalent inactivated poliovirus vaccine (IPV) at ages 2 months, 4 months, 6-18 months, and 4-6 years. Children vaccinated outside the United States with bivalent vaccine, including immigrants and refugees, will need to be revaccinated. Those without appropriate documentation of vaccine (written, dated records that specify trivalent vaccine) also should be revaccinated.
Serologic testing for immunity is no longer recommended. In the past, children without documentation of vaccines could be tested for neutralizing antibodies to poliovirus types 1, 2, and 3. Moving forward, serologic testing for antibodies to poliovirus type 2 won’t be available because it requires live virus, and in accordance with World Health Organization recommendations, laboratories have been destroying supplies of poliovirus type 2.
We also need to make sure that our patients who are traveling internationally receive all recommended vaccines, including a dose of IPV when appropriate. Specific recommendations can be found on the CDC’s pages for travelers.
A 2015 statement from the American Academy of Pediatrics called on pediatricians to consider polio as a potential diagnosis of any child presenting with fever and acute flaccid paralysis (Pediatrics. 2015 Jan;135[1]:196-202). When polio is suspected, public health authorities should be notified and two stool samples collected 24 hours apart, and within 14 days of the onset of paralysis, sent for testing. According to lead author Walter A. Orenstein, MD, “because most polio infections are silent, a case of paralytic polio in the United States may have been acquired from an asymptomatic individual, so a history of travel to a polio-infected area may be absent in the case of paralysis.”
I’ll second what my mom said. Scary.
Dr. Bryant is a pediatrician specializing in infectious diseases at the University of Louisville (Ky.) and Kosair Children’s Hospital, also in Louisville. She said she had no relevant financial disclosures. Email her at pdnews@frontlinemedcom.com.
Don’t delay pneumococcal conjugate vaccine for preterm infants
There should be no hesitation in administering the routine vaccination schedule for 13-valent pneumococcal conjugate vaccine (PCV13) on account of gestational age or birth weight in preterm infants, researchers concluded.
In a phase IV study, researchers compared 100 term with 100 preterm infants; both groups were vaccinated on the routine schedule at ages 2, 3, 4, and 12 months. After the 12-month (toddler) dose of the PCV13, the infants were evaluated for serum antibody persistence at 12 and 24 months. “To date, no studies have examined the long-term persistence of immune responses to PCV13 in formerly preterm infants,” noted Federico Martinón-Torres, MD, PhD, of Hospital Clínico Universitario de Santiago de Compostela, Spain, and his coauthors. 
In the study, at six sites in Spain and five sites in Poland between October 2010 and January 2014, both groups were checked for geometric mean concentrations of serotype-specific anticapsular immunoglobulin G binding antibodies and for opsonophagocytic activity. All 200 subjects were white and were generally healthy; the preterm infants were grouped by gestational age at birth of less than 29 weeks (n = 25), 29 weeks to less than 32 weeks (n = 50), or 32 weeks to less than 37 weeks (n = 25). Twelve subjects dropped out of the study by the first year’s evaluation, and another eight of the term subjects and seven of preterm subjects dropped out by the second year’s evaluation (Ped Infect Dis J. 2017. doi: 10.1097/INF.0000000000001428).
At both follow-up time points, no discernible patterns were observed in IgG GMCs for any serotype or in opsonophagocytic activity geometric mean titers across preterm subgroups based on gestational age.
“The vaccination phase of the study demonstrated that preterm infants are able to generate an immune response to PCV13 that is likely to protect against invasive pneumococcal disease. However, IgG GMCs were lower in preterm than term infants for nearly half of the serotypes at all time points. Antipneumococcal IgG levels in preterm infants were generally lower than in term infants, but fewer differences in opsonophagocytic activity were seen between the groups,” Dr. Martinón-Torres and his associates reported.
Pfizer funded the study. Dr. Martinón-Torres reported receiving research grants and/or honoraria as a consultant/adviser and/or speaker and for conducting vaccine trials for GlaxoSmithKline, MedImmune, Merck, Novartis, Pfizer/Wyeth, Sanofi Pasteur, and the Carlos III Health Institute. Several coauthors disclosed ties with pharmaceutical companies; four are stock-holding employees of Pfizer and another is an employee of a company contracted by Pfizer.
There should be no hesitation in administering the routine vaccination schedule for 13-valent pneumococcal conjugate vaccine (PCV13) on account of gestational age or birth weight in preterm infants, researchers concluded.
In a phase IV study, researchers compared 100 term with 100 preterm infants; both groups were vaccinated on the routine schedule at ages 2, 3, 4, and 12 months. After the 12-month (toddler) dose of the PCV13, the infants were evaluated for serum antibody persistence at 12 and 24 months. “To date, no studies have examined the long-term persistence of immune responses to PCV13 in formerly preterm infants,” noted Federico Martinón-Torres, MD, PhD, of Hospital Clínico Universitario de Santiago de Compostela, Spain, and his coauthors.
In the study, at six sites in Spain and five sites in Poland between October 2010 and January 2014, both groups were checked for geometric mean concentrations of serotype-specific anticapsular immunoglobulin G binding antibodies and for opsonophagocytic activity. All 200 subjects were white and were generally healthy; the preterm infants were grouped by gestational age at birth of less than 29 weeks (n = 25), 29 weeks to less than 32 weeks (n = 50), or 32 weeks to less than 37 weeks (n = 25). Twelve subjects dropped out of the study by the first year’s evaluation, and another eight of the term subjects and seven of preterm subjects dropped out by the second year’s evaluation (Ped Infect Dis J. 2017. doi: 10.1097/INF.0000000000001428).
At both follow-up time points, no discernible patterns were observed in IgG GMCs for any serotype or in opsonophagocytic activity geometric mean titers across preterm subgroups based on gestational age.
“The vaccination phase of the study demonstrated that preterm infants are able to generate an immune response to PCV13 that is likely to protect against invasive pneumococcal disease. However, IgG GMCs were lower in preterm than term infants for nearly half of the serotypes at all time points. Antipneumococcal IgG levels in preterm infants were generally lower than in term infants, but fewer differences in opsonophagocytic activity were seen between the groups,” Dr. Martinón-Torres and his associates reported.
Pfizer funded the study. Dr. Martinón-Torres reported receiving research grants and/or honoraria as a consultant/adviser and/or speaker and for conducting vaccine trials for GlaxoSmithKline, MedImmune, Merck, Novartis, Pfizer/Wyeth, Sanofi Pasteur, and the Carlos III Health Institute. Several coauthors disclosed ties with pharmaceutical companies; four are stock-holding employees of Pfizer and another is an employee of a company contracted by Pfizer.
There should be no hesitation in administering the routine vaccination schedule for 13-valent pneumococcal conjugate vaccine (PCV13) on account of gestational age or birth weight in preterm infants, researchers concluded.
In a phase IV study, researchers compared 100 term with 100 preterm infants; both groups were vaccinated on the routine schedule at ages 2, 3, 4, and 12 months. After the 12-month (toddler) dose of the PCV13, the infants were evaluated for serum antibody persistence at 12 and 24 months. “To date, no studies have examined the long-term persistence of immune responses to PCV13 in formerly preterm infants,” noted Federico Martinón-Torres, MD, PhD, of Hospital Clínico Universitario de Santiago de Compostela, Spain, and his coauthors.
In the study, at six sites in Spain and five sites in Poland between October 2010 and January 2014, both groups were checked for geometric mean concentrations of serotype-specific anticapsular immunoglobulin G binding antibodies and for opsonophagocytic activity. All 200 subjects were white and were generally healthy; the preterm infants were grouped by gestational age at birth of less than 29 weeks (n = 25), 29 weeks to less than 32 weeks (n = 50), or 32 weeks to less than 37 weeks (n = 25). Twelve subjects dropped out of the study by the first year’s evaluation, and another eight of the term subjects and seven of preterm subjects dropped out by the second year’s evaluation (Ped Infect Dis J. 2017. doi: 10.1097/INF.0000000000001428).
At both follow-up time points, no discernible patterns were observed in IgG GMCs for any serotype or in opsonophagocytic activity geometric mean titers across preterm subgroups based on gestational age.
“The vaccination phase of the study demonstrated that preterm infants are able to generate an immune response to PCV13 that is likely to protect against invasive pneumococcal disease. However, IgG GMCs were lower in preterm than term infants for nearly half of the serotypes at all time points. Antipneumococcal IgG levels in preterm infants were generally lower than in term infants, but fewer differences in opsonophagocytic activity were seen between the groups,” Dr. Martinón-Torres and his associates reported.
Pfizer funded the study. Dr. Martinón-Torres reported receiving research grants and/or honoraria as a consultant/adviser and/or speaker and for conducting vaccine trials for GlaxoSmithKline, MedImmune, Merck, Novartis, Pfizer/Wyeth, Sanofi Pasteur, and the Carlos III Health Institute. Several coauthors disclosed ties with pharmaceutical companies; four are stock-holding employees of Pfizer and another is an employee of a company contracted by Pfizer.
Key clinical point:
Major finding: IgG GMCs were lower in preterm than term infants for nearly half of the serotypes at all time points. Antipneumococcal IgG levels in preterm infants were generally lower than in term infants, but fewer differences in opsonophagocytic activity were seen between the groups.
Data source: In a phase IV study, 100 term and 100 preterm infants were evaluated for serum antibody persistence at 12 and 24 months.
Disclosures: Pfizer funded the study. Dr. Martinón-Torres reported receiving research grants and/or honoraria as a consultant/adviser and/or speaker and for conducting vaccine trials for GlaxoSmithKline, MedImmune, Merck, Novartis, Pfizer/Wyeth, Sanofi Pasteur, and the Carlos III Health Institute. Several coauthors disclosed ties with pharmaceutical companies; four are stock-holding employees of Pfizer and another is an employee of a company contracted by Pfizer.
Childhood PCV program produces overall protection
Childhood pneumococcal conjugate vaccines continue to indirectly produce widespread societal protection against invasive pneumococcal disease, a review and meta-analysis showed.
In fact, the reviewed studies suggest that the use of these vaccines in children can lead to an overall 90% drop in invasive pneumococcal disease within fewer than 10 years.
Herd immunity appears to be at work, the review authors said. The effect is so powerful that the findings raise questions about “the merit of offering [the 13-valent pneumococcal vaccine] in older groups” in places that have a children’s pneumococcal conjugate vaccine (PCV) program, the investigators said.
U.S. guidelines recommend vaccinations for older people, although the recommendations are up for review in 2018.
According to the review, childhood PCVs have had a tremendous impact since a seven-valent version (PCV7) was first released in 2000. “In vaccinated young children, disease due to serotypes included in the vaccines has been reduced to negligible levels,” the authors wrote.
But unvaccinated people, especially the elderly, remain susceptible.
The review authors, led by Tinevimbo Shiri, PhD, of the University of Warwick, Coventry, England, updated a 2013 systemic review (Vaccine. 2013 Dec 17;32[1]:133-45). They focused on studies from 1994 to 2016 that examined the effects of introducing PCV in children.
A total of 242 studies were included in the meta-analysis, published in the January issue of Lancet Global Health (2017 Jan;5[1]:e51-e9), including 70 from the previous review. Of these, only 9 (4%) were performed in poor or middle-income countries, with most of the rest having been done in North America (42%) and Europe (38%).
The researchers found that “[herd] immunity effects continued to accumulate over time and reduced disease due to PCV7 serotypes, for which follow-up data have generally been available for the longest period, with a 90% average reduction after about 9 years.”
Specifically, the review estimated it would take 8.9 years for a 90% reduction in invasive pneumococcal disease for grouped serotypes in the PCV7 and 9.5 years for the extra six grouped serotypes in the 13-valent PCV. The latter vaccine was introduced in 2010.
The researchers found evidence of a similar annual reduction in disease linked to grouped serotypes in the 23-valent pneumococcal polysaccharide vaccine in adults aged 19 and up. They noted that the 11 serotypes contained in PPV23 but not in PCV13 “did not change invasive pneumococcal disease at any age.”
The investigators added: “In countries with mature pediatric PCV programmes such as Canada, Germany, the Netherlands, the U.K., and the U.S.A., invasive pneumococcal disease due to PCV7 serotypes has been nearly eliminated through indirect protection - i.e., the average incidence of PCV7-invasive pneumococcal disease after nearly a decade of PCV7 use is less than 10 per 100,000 people. In these countries, consistent decreases in vaccine-type adult community-acquired pneumonia (CAP) or meningitis, and nonbacteraemic CAP, have been observed, indicating substantial indirect protection effects against noninvasive disease from childhood vaccination.”
The review authors noted that a major “evidence gap” in the effectiveness of childhood PCV programs in low-income countries exists. “Because these countries are increasingly undertaking childhood vaccination programs, research to assess the indirect effects in these settings is particularly relevant,” they wrote.
The review’s limitations include the possibility that the results could be thrown off by variations across nations in areas like diagnostic protocols, surveillance, and outcome measures.
The authors of the review, funded by the Policy Research Program of England’s Department of Health, reported no relevant financial disclosures.
The impact of pneumococcal conjugate vaccines has been hampered by serotypes that they don’t address, said David Goldblatt, PhD, MBChB, of the Great Ormond Street Institute of Child Health and University College London, in a commentary accompanying this review and meta-analysis (Lancet Glob Health. 2017 Jan;5[1]:e6-e7).
“Data from this meta-analysis have shown an overall reduction of invasive pneumococcal disease in all unvaccinated age groups of just 1%. … New extended-valency vaccines will be required to halt this erosion of PCV impact,” he wrote.
Dr. Goldblatt reported receiving grants and personal fees from GlaxoSmithKline, Merck, Sharpe, and Dohme and a publication with Pfizer.
The impact of pneumococcal conjugate vaccines has been hampered by serotypes that they don’t address, said David Goldblatt, PhD, MBChB, of the Great Ormond Street Institute of Child Health and University College London, in a commentary accompanying this review and meta-analysis (Lancet Glob Health. 2017 Jan;5[1]:e6-e7).
“Data from this meta-analysis have shown an overall reduction of invasive pneumococcal disease in all unvaccinated age groups of just 1%. … New extended-valency vaccines will be required to halt this erosion of PCV impact,” he wrote.
Dr. Goldblatt reported receiving grants and personal fees from GlaxoSmithKline, Merck, Sharpe, and Dohme and a publication with Pfizer.
The impact of pneumococcal conjugate vaccines has been hampered by serotypes that they don’t address, said David Goldblatt, PhD, MBChB, of the Great Ormond Street Institute of Child Health and University College London, in a commentary accompanying this review and meta-analysis (Lancet Glob Health. 2017 Jan;5[1]:e6-e7).
“Data from this meta-analysis have shown an overall reduction of invasive pneumococcal disease in all unvaccinated age groups of just 1%. … New extended-valency vaccines will be required to halt this erosion of PCV impact,” he wrote.
Dr. Goldblatt reported receiving grants and personal fees from GlaxoSmithKline, Merck, Sharpe, and Dohme and a publication with Pfizer.
Childhood pneumococcal conjugate vaccines continue to indirectly produce widespread societal protection against invasive pneumococcal disease, a review and meta-analysis showed.
In fact, the reviewed studies suggest that the use of these vaccines in children can lead to an overall 90% drop in invasive pneumococcal disease within fewer than 10 years.
Herd immunity appears to be at work, the review authors said. The effect is so powerful that the findings raise questions about “the merit of offering [the 13-valent pneumococcal vaccine] in older groups” in places that have a children’s pneumococcal conjugate vaccine (PCV) program, the investigators said.
U.S. guidelines recommend vaccinations for older people, although the recommendations are up for review in 2018.
According to the review, childhood PCVs have had a tremendous impact since a seven-valent version (PCV7) was first released in 2000. “In vaccinated young children, disease due to serotypes included in the vaccines has been reduced to negligible levels,” the authors wrote.
But unvaccinated people, especially the elderly, remain susceptible.
The review authors, led by Tinevimbo Shiri, PhD, of the University of Warwick, Coventry, England, updated a 2013 systemic review (Vaccine. 2013 Dec 17;32[1]:133-45). They focused on studies from 1994 to 2016 that examined the effects of introducing PCV in children.
A total of 242 studies were included in the meta-analysis, published in the January issue of Lancet Global Health (2017 Jan;5[1]:e51-e9), including 70 from the previous review. Of these, only 9 (4%) were performed in poor or middle-income countries, with most of the rest having been done in North America (42%) and Europe (38%).
The researchers found that “[herd] immunity effects continued to accumulate over time and reduced disease due to PCV7 serotypes, for which follow-up data have generally been available for the longest period, with a 90% average reduction after about 9 years.”
Specifically, the review estimated it would take 8.9 years for a 90% reduction in invasive pneumococcal disease for grouped serotypes in the PCV7 and 9.5 years for the extra six grouped serotypes in the 13-valent PCV. The latter vaccine was introduced in 2010.
The researchers found evidence of a similar annual reduction in disease linked to grouped serotypes in the 23-valent pneumococcal polysaccharide vaccine in adults aged 19 and up. They noted that the 11 serotypes contained in PPV23 but not in PCV13 “did not change invasive pneumococcal disease at any age.”
The investigators added: “In countries with mature pediatric PCV programmes such as Canada, Germany, the Netherlands, the U.K., and the U.S.A., invasive pneumococcal disease due to PCV7 serotypes has been nearly eliminated through indirect protection - i.e., the average incidence of PCV7-invasive pneumococcal disease after nearly a decade of PCV7 use is less than 10 per 100,000 people. In these countries, consistent decreases in vaccine-type adult community-acquired pneumonia (CAP) or meningitis, and nonbacteraemic CAP, have been observed, indicating substantial indirect protection effects against noninvasive disease from childhood vaccination.”
The review authors noted that a major “evidence gap” in the effectiveness of childhood PCV programs in low-income countries exists. “Because these countries are increasingly undertaking childhood vaccination programs, research to assess the indirect effects in these settings is particularly relevant,” they wrote.
The review’s limitations include the possibility that the results could be thrown off by variations across nations in areas like diagnostic protocols, surveillance, and outcome measures.
The authors of the review, funded by the Policy Research Program of England’s Department of Health, reported no relevant financial disclosures.
Childhood pneumococcal conjugate vaccines continue to indirectly produce widespread societal protection against invasive pneumococcal disease, a review and meta-analysis showed.
In fact, the reviewed studies suggest that the use of these vaccines in children can lead to an overall 90% drop in invasive pneumococcal disease within fewer than 10 years.
Herd immunity appears to be at work, the review authors said. The effect is so powerful that the findings raise questions about “the merit of offering [the 13-valent pneumococcal vaccine] in older groups” in places that have a children’s pneumococcal conjugate vaccine (PCV) program, the investigators said.
U.S. guidelines recommend vaccinations for older people, although the recommendations are up for review in 2018.
According to the review, childhood PCVs have had a tremendous impact since a seven-valent version (PCV7) was first released in 2000. “In vaccinated young children, disease due to serotypes included in the vaccines has been reduced to negligible levels,” the authors wrote.
But unvaccinated people, especially the elderly, remain susceptible.
The review authors, led by Tinevimbo Shiri, PhD, of the University of Warwick, Coventry, England, updated a 2013 systemic review (Vaccine. 2013 Dec 17;32[1]:133-45). They focused on studies from 1994 to 2016 that examined the effects of introducing PCV in children.
A total of 242 studies were included in the meta-analysis, published in the January issue of Lancet Global Health (2017 Jan;5[1]:e51-e9), including 70 from the previous review. Of these, only 9 (4%) were performed in poor or middle-income countries, with most of the rest having been done in North America (42%) and Europe (38%).
The researchers found that “[herd] immunity effects continued to accumulate over time and reduced disease due to PCV7 serotypes, for which follow-up data have generally been available for the longest period, with a 90% average reduction after about 9 years.”
Specifically, the review estimated it would take 8.9 years for a 90% reduction in invasive pneumococcal disease for grouped serotypes in the PCV7 and 9.5 years for the extra six grouped serotypes in the 13-valent PCV. The latter vaccine was introduced in 2010.
The researchers found evidence of a similar annual reduction in disease linked to grouped serotypes in the 23-valent pneumococcal polysaccharide vaccine in adults aged 19 and up. They noted that the 11 serotypes contained in PPV23 but not in PCV13 “did not change invasive pneumococcal disease at any age.”
The investigators added: “In countries with mature pediatric PCV programmes such as Canada, Germany, the Netherlands, the U.K., and the U.S.A., invasive pneumococcal disease due to PCV7 serotypes has been nearly eliminated through indirect protection - i.e., the average incidence of PCV7-invasive pneumococcal disease after nearly a decade of PCV7 use is less than 10 per 100,000 people. In these countries, consistent decreases in vaccine-type adult community-acquired pneumonia (CAP) or meningitis, and nonbacteraemic CAP, have been observed, indicating substantial indirect protection effects against noninvasive disease from childhood vaccination.”
The review authors noted that a major “evidence gap” in the effectiveness of childhood PCV programs in low-income countries exists. “Because these countries are increasingly undertaking childhood vaccination programs, research to assess the indirect effects in these settings is particularly relevant,” they wrote.
The review’s limitations include the possibility that the results could be thrown off by variations across nations in areas like diagnostic protocols, surveillance, and outcome measures.
The authors of the review, funded by the Policy Research Program of England’s Department of Health, reported no relevant financial disclosures.
FROM THE LANCET GLOBAL HEALTH
Key clinical point: Through apparent herd immunity, childhood pneumococcal conjugate vaccines produce societywide reductions in invasive pneumococcal disease in less than a decade.
Major finding: When a seven-valent PCV is given to children, it would take an estimated 8.9 years for a 90% reduction in invasive pneumococcal disease to be seen among the grouped serotypes. It would take an estimated 9.5 years for an identical reduction in the extra six grouped serotypes in the 13-valent PCV.
Data source: A review and meta-analysis of 242 studies from 1994 to 2016 that examined the effects of introducing PCVs in children.
Disclosures: The review authors reported no relevant financial disclosures.
Double-dose influenza vaccine effective against type B strains
A double-dose inactivated quadrivalent influenza vaccine (IIV4) could be administered to all children aged 6-35 months, as it not only offers the best protection against influenza type B, but it also allows for simplifying the current vaccination schedule considerably.
“The introduction of IIV4 provides an opportunity to review long-accepted practices in administration of influenza vaccines,” explained Varsha K. Jain, MD, formerly employed by GlaxoSmithKline Vaccines, King of Prussia, Pa., and associates.
Giving a lower dose to young children was planned to reduce reactogenicity and febrile convulsions observed with the whole virus vaccines that were in use in the 1970s. But young children have a variable immune response to lower doses, especially against vaccine B strains, they noted (J Ped Infect Dis. 2017 Jan 6. doi: 10.1093/jpids/piw068).
Dr. Jain and coauthors enrolled 2,430 children aged 6-35 months during the 2014-2015 influenza season in the United States and Mexico in this phase III study. Children were randomized into one of two cohorts: one cohort received a standard-doze IIV4 vaccination, while the other received a double-dose. Data on age (6-17 months, 18-35 months), health care center, and influenza primer status also were taken into consideration.
The standard-dose vaccine contained 7.5 mcg of A/California/7/2009 (A/H1N1), A/Texas/50/2012 (A/H3N2), B/Brisbane/60/2008 (B/Victoria), and B/Massachusetts/2/2012 (B/Yamagata), while the double-dose vaccine contained 15 mcg, or twice the amount each, of the same strains. The former was developed by Sanofi Pasteur and the latter by GSK Vaccines.
Primed children who completed the study numbered 1,173; 586 received the standard-dose and 587 received the double-dose. On the unprimed side, 868 completed the study: 442 standard-dose and 426 double-dose. Each dose’s immunogenic noninferiority was quantified by calculating the geometric mean titer (GMT) ratio.
“Immunogenicity was higher in the double-dose group compared with the standard-dose group, particularly against vaccine B strains in children 6-17 months of age and unprimed children,” Dr. Vain and associates said. Both vaccines performed well against the influenza B strain, with the double-dose yielding a GMT of 1.89 against the B/Yamagata strain and 2.13 against the B/Victoria in children aged 6-17 months. Across the entire age spectrum of the study population, unprimed children registered a GMT of 1.85 and 2.04 against the same strains, respectively. For comparison, none of the A strains in any cohort based on age or primed/unprimed registered a GMT above 1.5.
“Increased protection against influenza B [would] be a beneficial clinical outcome [and] use of the same vaccine dose for all eligible ages would also simplify the annual influenza vaccine campaign and reduce cost and logistic complexity,” the authors concluded. “This study provides evidence to support a change in clinical practice to use [double-dose IIV4] in all children 6 months of age and older, once that dosing for a vaccine product has been approved.”
Dr. Jain now is employed by the Bill and Melinda Gates Foundation.
Dr. Jain and several coauthors disclosed ties to GlaxoSmithKline, which funded the study.
A double-dose inactivated quadrivalent influenza vaccine (IIV4) could be administered to all children aged 6-35 months, as it not only offers the best protection against influenza type B, but it also allows for simplifying the current vaccination schedule considerably.
“The introduction of IIV4 provides an opportunity to review long-accepted practices in administration of influenza vaccines,” explained Varsha K. Jain, MD, formerly employed by GlaxoSmithKline Vaccines, King of Prussia, Pa., and associates.
Giving a lower dose to young children was planned to reduce reactogenicity and febrile convulsions observed with the whole virus vaccines that were in use in the 1970s. But young children have a variable immune response to lower doses, especially against vaccine B strains, they noted (J Ped Infect Dis. 2017 Jan 6. doi: 10.1093/jpids/piw068).
Dr. Jain and coauthors enrolled 2,430 children aged 6-35 months during the 2014-2015 influenza season in the United States and Mexico in this phase III study. Children were randomized into one of two cohorts: one cohort received a standard-doze IIV4 vaccination, while the other received a double-dose. Data on age (6-17 months, 18-35 months), health care center, and influenza primer status also were taken into consideration.
The standard-dose vaccine contained 7.5 mcg of A/California/7/2009 (A/H1N1), A/Texas/50/2012 (A/H3N2), B/Brisbane/60/2008 (B/Victoria), and B/Massachusetts/2/2012 (B/Yamagata), while the double-dose vaccine contained 15 mcg, or twice the amount each, of the same strains. The former was developed by Sanofi Pasteur and the latter by GSK Vaccines.
Primed children who completed the study numbered 1,173; 586 received the standard-dose and 587 received the double-dose. On the unprimed side, 868 completed the study: 442 standard-dose and 426 double-dose. Each dose’s immunogenic noninferiority was quantified by calculating the geometric mean titer (GMT) ratio.
“Immunogenicity was higher in the double-dose group compared with the standard-dose group, particularly against vaccine B strains in children 6-17 months of age and unprimed children,” Dr. Vain and associates said. Both vaccines performed well against the influenza B strain, with the double-dose yielding a GMT of 1.89 against the B/Yamagata strain and 2.13 against the B/Victoria in children aged 6-17 months. Across the entire age spectrum of the study population, unprimed children registered a GMT of 1.85 and 2.04 against the same strains, respectively. For comparison, none of the A strains in any cohort based on age or primed/unprimed registered a GMT above 1.5.
“Increased protection against influenza B [would] be a beneficial clinical outcome [and] use of the same vaccine dose for all eligible ages would also simplify the annual influenza vaccine campaign and reduce cost and logistic complexity,” the authors concluded. “This study provides evidence to support a change in clinical practice to use [double-dose IIV4] in all children 6 months of age and older, once that dosing for a vaccine product has been approved.”
Dr. Jain now is employed by the Bill and Melinda Gates Foundation.
Dr. Jain and several coauthors disclosed ties to GlaxoSmithKline, which funded the study.
A double-dose inactivated quadrivalent influenza vaccine (IIV4) could be administered to all children aged 6-35 months, as it not only offers the best protection against influenza type B, but it also allows for simplifying the current vaccination schedule considerably.
“The introduction of IIV4 provides an opportunity to review long-accepted practices in administration of influenza vaccines,” explained Varsha K. Jain, MD, formerly employed by GlaxoSmithKline Vaccines, King of Prussia, Pa., and associates.
Giving a lower dose to young children was planned to reduce reactogenicity and febrile convulsions observed with the whole virus vaccines that were in use in the 1970s. But young children have a variable immune response to lower doses, especially against vaccine B strains, they noted (J Ped Infect Dis. 2017 Jan 6. doi: 10.1093/jpids/piw068).
Dr. Jain and coauthors enrolled 2,430 children aged 6-35 months during the 2014-2015 influenza season in the United States and Mexico in this phase III study. Children were randomized into one of two cohorts: one cohort received a standard-doze IIV4 vaccination, while the other received a double-dose. Data on age (6-17 months, 18-35 months), health care center, and influenza primer status also were taken into consideration.
The standard-dose vaccine contained 7.5 mcg of A/California/7/2009 (A/H1N1), A/Texas/50/2012 (A/H3N2), B/Brisbane/60/2008 (B/Victoria), and B/Massachusetts/2/2012 (B/Yamagata), while the double-dose vaccine contained 15 mcg, or twice the amount each, of the same strains. The former was developed by Sanofi Pasteur and the latter by GSK Vaccines.
Primed children who completed the study numbered 1,173; 586 received the standard-dose and 587 received the double-dose. On the unprimed side, 868 completed the study: 442 standard-dose and 426 double-dose. Each dose’s immunogenic noninferiority was quantified by calculating the geometric mean titer (GMT) ratio.
“Immunogenicity was higher in the double-dose group compared with the standard-dose group, particularly against vaccine B strains in children 6-17 months of age and unprimed children,” Dr. Vain and associates said. Both vaccines performed well against the influenza B strain, with the double-dose yielding a GMT of 1.89 against the B/Yamagata strain and 2.13 against the B/Victoria in children aged 6-17 months. Across the entire age spectrum of the study population, unprimed children registered a GMT of 1.85 and 2.04 against the same strains, respectively. For comparison, none of the A strains in any cohort based on age or primed/unprimed registered a GMT above 1.5.
“Increased protection against influenza B [would] be a beneficial clinical outcome [and] use of the same vaccine dose for all eligible ages would also simplify the annual influenza vaccine campaign and reduce cost and logistic complexity,” the authors concluded. “This study provides evidence to support a change in clinical practice to use [double-dose IIV4] in all children 6 months of age and older, once that dosing for a vaccine product has been approved.”
Dr. Jain now is employed by the Bill and Melinda Gates Foundation.
Dr. Jain and several coauthors disclosed ties to GlaxoSmithKline, which funded the study.
FROM THE JOURNAL OF THE PEDIATRIC INFECTIOUS DISEASES SOCIETY
Key clinical point:
Major finding: Geometric mean titer (GMT) ratios showed that the double-dose IIV4 vaccine was the most effective against influenza type B in children aged 6-17 months (GMT = 1.89) and in unprimed children aged 6-35 months (GMT = 1.85).
Data source: Phase III, randomized trial of 2,041 children aged 6-35 months.
Disclosures: Dr. Jain and several coauthors disclosed ties to GlaxoSmithKline, which funded the study.
Children in United States vaccinated for polio elsewhere may require revaccination
Poliovirus vaccinations for children in the United States who may have been vaccinated elsewhere must meet Advisory Committee on Immunization Practices recommendations to ensure protection against all three poliovirus types, according to guidance published in the Centers for Disease Control and Prevention’s Morbidity and Mortality Weekly Report.
Although the United States continues to use an inactivated polio vaccine (IPV) that contains all three types, other countries using an oral polio vaccine (OPV) switched from a trivalent oral poliovirus vaccine (tOPV) to a bivalent version (bOPV) after the World Health Organization declared type 2 polio virus eradicated in September 2015.
The researchers note that only written, dated records are acceptable evidence of complete vaccination, and documentation of polio vaccination outside of the United States should specify that the child has been vaccinated against all three types. “If both tOPV and IPV were administered as part of a series, the total number of doses needed to complete the series is the same as that recommended for the U.S. IPV schedule,” they wrote. That is, all infants and children should receive four doses of IPV at ages 2 months, 4 months, 6-18 months, and at 4-6 years. The minimum interval between the third and fourth doses should be 6 months.
Children younger than 18 years lacking written, dated documentation of poliovirus vaccination should be vaccinated or revaccinated according to the U.S. IPV schedule for their age, according to the guidelines.
Serologic testing, once used to confirm immunity to polio, is not recommended as a measure of immunity in the United States because antibody testing against type 2 poliovirus often is not available, the researchers added.
The full guidelines are available at MMWR. 2017 Jan 13. doi: 10.15585/mmwr.mm6601a6.
Poliovirus vaccinations for children in the United States who may have been vaccinated elsewhere must meet Advisory Committee on Immunization Practices recommendations to ensure protection against all three poliovirus types, according to guidance published in the Centers for Disease Control and Prevention’s Morbidity and Mortality Weekly Report.
Although the United States continues to use an inactivated polio vaccine (IPV) that contains all three types, other countries using an oral polio vaccine (OPV) switched from a trivalent oral poliovirus vaccine (tOPV) to a bivalent version (bOPV) after the World Health Organization declared type 2 polio virus eradicated in September 2015.
The researchers note that only written, dated records are acceptable evidence of complete vaccination, and documentation of polio vaccination outside of the United States should specify that the child has been vaccinated against all three types. “If both tOPV and IPV were administered as part of a series, the total number of doses needed to complete the series is the same as that recommended for the U.S. IPV schedule,” they wrote. That is, all infants and children should receive four doses of IPV at ages 2 months, 4 months, 6-18 months, and at 4-6 years. The minimum interval between the third and fourth doses should be 6 months.
Children younger than 18 years lacking written, dated documentation of poliovirus vaccination should be vaccinated or revaccinated according to the U.S. IPV schedule for their age, according to the guidelines.
Serologic testing, once used to confirm immunity to polio, is not recommended as a measure of immunity in the United States because antibody testing against type 2 poliovirus often is not available, the researchers added.
The full guidelines are available at MMWR. 2017 Jan 13. doi: 10.15585/mmwr.mm6601a6.
Poliovirus vaccinations for children in the United States who may have been vaccinated elsewhere must meet Advisory Committee on Immunization Practices recommendations to ensure protection against all three poliovirus types, according to guidance published in the Centers for Disease Control and Prevention’s Morbidity and Mortality Weekly Report.
Although the United States continues to use an inactivated polio vaccine (IPV) that contains all three types, other countries using an oral polio vaccine (OPV) switched from a trivalent oral poliovirus vaccine (tOPV) to a bivalent version (bOPV) after the World Health Organization declared type 2 polio virus eradicated in September 2015.
The researchers note that only written, dated records are acceptable evidence of complete vaccination, and documentation of polio vaccination outside of the United States should specify that the child has been vaccinated against all three types. “If both tOPV and IPV were administered as part of a series, the total number of doses needed to complete the series is the same as that recommended for the U.S. IPV schedule,” they wrote. That is, all infants and children should receive four doses of IPV at ages 2 months, 4 months, 6-18 months, and at 4-6 years. The minimum interval between the third and fourth doses should be 6 months.
Children younger than 18 years lacking written, dated documentation of poliovirus vaccination should be vaccinated or revaccinated according to the U.S. IPV schedule for their age, according to the guidelines.
Serologic testing, once used to confirm immunity to polio, is not recommended as a measure of immunity in the United States because antibody testing against type 2 poliovirus often is not available, the researchers added.
The full guidelines are available at MMWR. 2017 Jan 13. doi: 10.15585/mmwr.mm6601a6.
FROM MMWR
PCV effective against HNIs, pHNIs that require hospitalization in immunized children
Pneumococcal conjugate vaccines (PCV) in immunized children show effectiveness against head and neck infections (HNIs), especially against pneumococcal HNIs (pHNIs) that require hospitalization, according to Tal Marom, MD, of Tel Aviv University, Zerifin, Israel, and associates.
In a retrospective study, researchers identified children aged 0-16 years who were hospitalized with HNIs between Jan. 1, 2007 and Dec. 31, 2014. HNIs accounted for 2.5%-4.7% of admissions to the pediatric department, and there was a downward trend in the incidence in the post-PCV years, compared with previous years. Of the 820 children admitted with HNIs, 11% children were identified with pHNIs, 5% with acute otitis media, 4% with acute mastoiditis, and 2% with meningitis; there were no cases of pneumococcal acute bacterial sinusitis or pneumococcal head and neck abscesses. In 2009-2010 (considered as the “transition years,” in which both PCV7 and PCV13 were implemented in Israel), pHNIs incidence sharply decreased, from 7/1,000 to 1.74/1,000 hospitalized children per year, because of a 55% reduction of pneumococcal acute otitis media episodes. There also was an additional decrease observed in the post-PCV years of 2012-2014 (1.62/1,000 hospitalized children per year).
It was noted that unimmunized children were more likely to suffer from pneumococcal infections than immunized children (P = .001). There were no significant differences in the clinical presentation of these two groups, except for the need for surgery, which was significantly greater in immunized children (P = .042).
“The findings of the current study provide further evidence of PCV effectiveness against HNIs in PCV immunized children, and particularly against pHNI which required hospitalization,” Dr. Marom and associates concluded. “A substantial reduction in the all-cause HNIs incidence, and more specifically in pHNIs, in PCV immunized children who required hospitalization, was evident in the present study. This was also followed by a significant reduction in [acute otitis media] rates and to a much lesser extent, in [acute mastoiditis] and meningitis rates.”
Find the full study in the Pediatric Infectious Disease Journal (2016. doi: 10.1097/INF.0000000000001425).
Pneumococcal conjugate vaccines (PCV) in immunized children show effectiveness against head and neck infections (HNIs), especially against pneumococcal HNIs (pHNIs) that require hospitalization, according to Tal Marom, MD, of Tel Aviv University, Zerifin, Israel, and associates.
In a retrospective study, researchers identified children aged 0-16 years who were hospitalized with HNIs between Jan. 1, 2007 and Dec. 31, 2014. HNIs accounted for 2.5%-4.7% of admissions to the pediatric department, and there was a downward trend in the incidence in the post-PCV years, compared with previous years. Of the 820 children admitted with HNIs, 11% children were identified with pHNIs, 5% with acute otitis media, 4% with acute mastoiditis, and 2% with meningitis; there were no cases of pneumococcal acute bacterial sinusitis or pneumococcal head and neck abscesses. In 2009-2010 (considered as the “transition years,” in which both PCV7 and PCV13 were implemented in Israel), pHNIs incidence sharply decreased, from 7/1,000 to 1.74/1,000 hospitalized children per year, because of a 55% reduction of pneumococcal acute otitis media episodes. There also was an additional decrease observed in the post-PCV years of 2012-2014 (1.62/1,000 hospitalized children per year).
It was noted that unimmunized children were more likely to suffer from pneumococcal infections than immunized children (P = .001). There were no significant differences in the clinical presentation of these two groups, except for the need for surgery, which was significantly greater in immunized children (P = .042).
“The findings of the current study provide further evidence of PCV effectiveness against HNIs in PCV immunized children, and particularly against pHNI which required hospitalization,” Dr. Marom and associates concluded. “A substantial reduction in the all-cause HNIs incidence, and more specifically in pHNIs, in PCV immunized children who required hospitalization, was evident in the present study. This was also followed by a significant reduction in [acute otitis media] rates and to a much lesser extent, in [acute mastoiditis] and meningitis rates.”
Find the full study in the Pediatric Infectious Disease Journal (2016. doi: 10.1097/INF.0000000000001425).
Pneumococcal conjugate vaccines (PCV) in immunized children show effectiveness against head and neck infections (HNIs), especially against pneumococcal HNIs (pHNIs) that require hospitalization, according to Tal Marom, MD, of Tel Aviv University, Zerifin, Israel, and associates.
In a retrospective study, researchers identified children aged 0-16 years who were hospitalized with HNIs between Jan. 1, 2007 and Dec. 31, 2014. HNIs accounted for 2.5%-4.7% of admissions to the pediatric department, and there was a downward trend in the incidence in the post-PCV years, compared with previous years. Of the 820 children admitted with HNIs, 11% children were identified with pHNIs, 5% with acute otitis media, 4% with acute mastoiditis, and 2% with meningitis; there were no cases of pneumococcal acute bacterial sinusitis or pneumococcal head and neck abscesses. In 2009-2010 (considered as the “transition years,” in which both PCV7 and PCV13 were implemented in Israel), pHNIs incidence sharply decreased, from 7/1,000 to 1.74/1,000 hospitalized children per year, because of a 55% reduction of pneumococcal acute otitis media episodes. There also was an additional decrease observed in the post-PCV years of 2012-2014 (1.62/1,000 hospitalized children per year).
It was noted that unimmunized children were more likely to suffer from pneumococcal infections than immunized children (P = .001). There were no significant differences in the clinical presentation of these two groups, except for the need for surgery, which was significantly greater in immunized children (P = .042).
“The findings of the current study provide further evidence of PCV effectiveness against HNIs in PCV immunized children, and particularly against pHNI which required hospitalization,” Dr. Marom and associates concluded. “A substantial reduction in the all-cause HNIs incidence, and more specifically in pHNIs, in PCV immunized children who required hospitalization, was evident in the present study. This was also followed by a significant reduction in [acute otitis media] rates and to a much lesser extent, in [acute mastoiditis] and meningitis rates.”
Find the full study in the Pediatric Infectious Disease Journal (2016. doi: 10.1097/INF.0000000000001425).
FROM THE PEDIATRIC INFECTIOUS DISEASE JOURNAL
Statin use increases risk of herpes zoster
Exposure to statins can significantly increase the odds of developing herpes zoster (HZ), according to a study published in the British Journal of Dermatology.
“The mechanisms by which statins may increase the risk of HZ are not established. As statins are commonly prescribed worldwide, any adverse effects may have substantial public health implications,” wrote Anthony Matthews of the London School of Hygiene and Tropical Medicine, and his colleagues. “An increased risk of HZ would not only have an impact on the quality of life of affected patients, but could also add to the burden on health services, given the high cost of treatment for PHN [postherpetic neuralgia].”
Each subject was matched with no more than four control patients – all of whom had no prior history of HZ or PHN – selected from the same databases. Matching was based on the following criteria: subject’s general practitioner (GP) practice, age (within 1 year of the HZ patient), sex, and lack of prior statin exposure. Ultimately 144,959 subjects were matched with 549,336 controls (Br J Dermatol. 2016 Dec;175[6]:1183-94).
The primary outcome was defined as incident diagnoses of HZ, which was measured via odds ratios (ORs) calculated from conditional logistic regression models and adjusted for any potential confounding factors. In addition, ORs were calculated to “explore the association between the risk of HZ and the dosage of the latest prescription (low, medium, high), stratified by time since last exposure,” the investigators noted.
Results showed an adjusted OR of 1.13 for HZ after any kind of statin treatment, indicating a significant increase in risk. There was also a higher adjusted OR for those who had stopped using statins 12-36 months prior to the study than those whose last exposure was greater than 36 months prior: 1.11 and 1.06, respectively (P less than .001). Those whose current statin usage was “high” had an adjusted OR of 1.27 versus 1.16 for those whose usage was “medium,” and 1.14 for those whose usage was “low” (P less than .001).
“It is clear that the preventive benefits of statin therapy are likely to outweigh the limited increase in HZ risk in many cases [but] this evidence should be taken into account by GPs when prescribing statins to those at high risk of HZ,” Mr. Matthews and his associates concluded. “We would also suggest that there may be an extra motivation to maximize HZ vaccine uptake among eligible patients who are also receiving a statin.”
Three coauthors disclosed individual funding sources: the Wellcome Trust/Royal Society Sir Henry Dale fellowship, the Senior Wellcome Fellowship in Clinical Science, and the National Institute for Health Research Clinician Scientist fellowship. The authors did not report any relevant financial disclosures.
“The present study by Matthews et al. observed a dose-response relationship between statin exposure and zoster risk. [It] is the first to explore the association between time since last statin use and the occurrence of zoster. As the time since last statin exposure increased, the risk of zoster decreased, suggesting that the risk for zoster is reduced after termination of statin treatment.
“Zoster is a significant contributor to morbidity, disability, and chronic pain, and constitutes a major public health concern. Zoster vaccination is recommended in most persons who are 50 years of age or older. Vaccination reduces the risk of zoster and postherpetic neuralgia. However, the price of zoster vaccine limits its use worldwide.
“The ‘take home’ message from the article is that in the setting of older age or immune suppression, dermatologists should consider recommending to their patients the use of a zoster vaccine, particularly in patients who receive statin therapy.”
Guy Shalom, MD, is a member of the department of dermatology and venereology, Soroka Medical Center in Beer-Sheva, Israel, and reported no relevant financial conflicts. Arnon D. Cohen, MD, is a member of the Siaal Research Center for Family Medicine and Primary Care at Ben-Gurion University of the Negev, Beer-Sheva, and reported financial ties to AbbVie, Dexcel Pharma, Janssen, Novartis, Perrigo, Pfizer, and Rafa as a consultant, adviser, or speaker. These comments were excerpted from their commentary accompanying Mr. Matthews’ article ( Br J Dermatol. 2017;175:1137-8 ).
“The present study by Matthews et al. observed a dose-response relationship between statin exposure and zoster risk. [It] is the first to explore the association between time since last statin use and the occurrence of zoster. As the time since last statin exposure increased, the risk of zoster decreased, suggesting that the risk for zoster is reduced after termination of statin treatment.
“Zoster is a significant contributor to morbidity, disability, and chronic pain, and constitutes a major public health concern. Zoster vaccination is recommended in most persons who are 50 years of age or older. Vaccination reduces the risk of zoster and postherpetic neuralgia. However, the price of zoster vaccine limits its use worldwide.
“The ‘take home’ message from the article is that in the setting of older age or immune suppression, dermatologists should consider recommending to their patients the use of a zoster vaccine, particularly in patients who receive statin therapy.”
Guy Shalom, MD, is a member of the department of dermatology and venereology, Soroka Medical Center in Beer-Sheva, Israel, and reported no relevant financial conflicts. Arnon D. Cohen, MD, is a member of the Siaal Research Center for Family Medicine and Primary Care at Ben-Gurion University of the Negev, Beer-Sheva, and reported financial ties to AbbVie, Dexcel Pharma, Janssen, Novartis, Perrigo, Pfizer, and Rafa as a consultant, adviser, or speaker. These comments were excerpted from their commentary accompanying Mr. Matthews’ article ( Br J Dermatol. 2017;175:1137-8 ).
“The present study by Matthews et al. observed a dose-response relationship between statin exposure and zoster risk. [It] is the first to explore the association between time since last statin use and the occurrence of zoster. As the time since last statin exposure increased, the risk of zoster decreased, suggesting that the risk for zoster is reduced after termination of statin treatment.
“Zoster is a significant contributor to morbidity, disability, and chronic pain, and constitutes a major public health concern. Zoster vaccination is recommended in most persons who are 50 years of age or older. Vaccination reduces the risk of zoster and postherpetic neuralgia. However, the price of zoster vaccine limits its use worldwide.
“The ‘take home’ message from the article is that in the setting of older age or immune suppression, dermatologists should consider recommending to their patients the use of a zoster vaccine, particularly in patients who receive statin therapy.”
Guy Shalom, MD, is a member of the department of dermatology and venereology, Soroka Medical Center in Beer-Sheva, Israel, and reported no relevant financial conflicts. Arnon D. Cohen, MD, is a member of the Siaal Research Center for Family Medicine and Primary Care at Ben-Gurion University of the Negev, Beer-Sheva, and reported financial ties to AbbVie, Dexcel Pharma, Janssen, Novartis, Perrigo, Pfizer, and Rafa as a consultant, adviser, or speaker. These comments were excerpted from their commentary accompanying Mr. Matthews’ article ( Br J Dermatol. 2017;175:1137-8 ).
Exposure to statins can significantly increase the odds of developing herpes zoster (HZ), according to a study published in the British Journal of Dermatology.
“The mechanisms by which statins may increase the risk of HZ are not established. As statins are commonly prescribed worldwide, any adverse effects may have substantial public health implications,” wrote Anthony Matthews of the London School of Hygiene and Tropical Medicine, and his colleagues. “An increased risk of HZ would not only have an impact on the quality of life of affected patients, but could also add to the burden on health services, given the high cost of treatment for PHN [postherpetic neuralgia].”
Each subject was matched with no more than four control patients – all of whom had no prior history of HZ or PHN – selected from the same databases. Matching was based on the following criteria: subject’s general practitioner (GP) practice, age (within 1 year of the HZ patient), sex, and lack of prior statin exposure. Ultimately 144,959 subjects were matched with 549,336 controls (Br J Dermatol. 2016 Dec;175[6]:1183-94).
The primary outcome was defined as incident diagnoses of HZ, which was measured via odds ratios (ORs) calculated from conditional logistic regression models and adjusted for any potential confounding factors. In addition, ORs were calculated to “explore the association between the risk of HZ and the dosage of the latest prescription (low, medium, high), stratified by time since last exposure,” the investigators noted.
Results showed an adjusted OR of 1.13 for HZ after any kind of statin treatment, indicating a significant increase in risk. There was also a higher adjusted OR for those who had stopped using statins 12-36 months prior to the study than those whose last exposure was greater than 36 months prior: 1.11 and 1.06, respectively (P less than .001). Those whose current statin usage was “high” had an adjusted OR of 1.27 versus 1.16 for those whose usage was “medium,” and 1.14 for those whose usage was “low” (P less than .001).
“It is clear that the preventive benefits of statin therapy are likely to outweigh the limited increase in HZ risk in many cases [but] this evidence should be taken into account by GPs when prescribing statins to those at high risk of HZ,” Mr. Matthews and his associates concluded. “We would also suggest that there may be an extra motivation to maximize HZ vaccine uptake among eligible patients who are also receiving a statin.”
Three coauthors disclosed individual funding sources: the Wellcome Trust/Royal Society Sir Henry Dale fellowship, the Senior Wellcome Fellowship in Clinical Science, and the National Institute for Health Research Clinician Scientist fellowship. The authors did not report any relevant financial disclosures.
Exposure to statins can significantly increase the odds of developing herpes zoster (HZ), according to a study published in the British Journal of Dermatology.
“The mechanisms by which statins may increase the risk of HZ are not established. As statins are commonly prescribed worldwide, any adverse effects may have substantial public health implications,” wrote Anthony Matthews of the London School of Hygiene and Tropical Medicine, and his colleagues. “An increased risk of HZ would not only have an impact on the quality of life of affected patients, but could also add to the burden on health services, given the high cost of treatment for PHN [postherpetic neuralgia].”
Each subject was matched with no more than four control patients – all of whom had no prior history of HZ or PHN – selected from the same databases. Matching was based on the following criteria: subject’s general practitioner (GP) practice, age (within 1 year of the HZ patient), sex, and lack of prior statin exposure. Ultimately 144,959 subjects were matched with 549,336 controls (Br J Dermatol. 2016 Dec;175[6]:1183-94).
The primary outcome was defined as incident diagnoses of HZ, which was measured via odds ratios (ORs) calculated from conditional logistic regression models and adjusted for any potential confounding factors. In addition, ORs were calculated to “explore the association between the risk of HZ and the dosage of the latest prescription (low, medium, high), stratified by time since last exposure,” the investigators noted.
Results showed an adjusted OR of 1.13 for HZ after any kind of statin treatment, indicating a significant increase in risk. There was also a higher adjusted OR for those who had stopped using statins 12-36 months prior to the study than those whose last exposure was greater than 36 months prior: 1.11 and 1.06, respectively (P less than .001). Those whose current statin usage was “high” had an adjusted OR of 1.27 versus 1.16 for those whose usage was “medium,” and 1.14 for those whose usage was “low” (P less than .001).
“It is clear that the preventive benefits of statin therapy are likely to outweigh the limited increase in HZ risk in many cases [but] this evidence should be taken into account by GPs when prescribing statins to those at high risk of HZ,” Mr. Matthews and his associates concluded. “We would also suggest that there may be an extra motivation to maximize HZ vaccine uptake among eligible patients who are also receiving a statin.”
Three coauthors disclosed individual funding sources: the Wellcome Trust/Royal Society Sir Henry Dale fellowship, the Senior Wellcome Fellowship in Clinical Science, and the National Institute for Health Research Clinician Scientist fellowship. The authors did not report any relevant financial disclosures.
FROM THE BRITISH JOURNAL OF DERMATOLOGY
Key clinical point:
Major finding: There is an odds ratio of 1.13 of contracting HZ if given a statin previously, with a significant increase (P less than .001) in risk in patients who used statins more recently.
Data source: Matched case-control study of 144,959 adults with HZ from 2000 through 2011.
Disclosures: Dr. Matthews and colleagues reported no relevant financial disclosures.
Historic HIV vaccine efficacy study underway in South Africa
.
According to an announcement by the National Institute of Allergy and Infectious Diseases, a cofunder of the trial and part of the U.S. National Institutes of Health, the study (called HVTN 702) involves a new version of the only HIV vaccine candidate ever shown to provide some protection against the virus. HVTN 702 intends to enroll 5,400 men and women, which would make it the largest and most advanced HIV vaccine clinical trial to take place in South Africa.
“If deployed alongside our current armory of proven HIV prevention tools, a safe and effective vaccine could be the final nail in the coffin for HIV,” Anthony S. Fauci, MD, director of NIAID, said in a statement. “Even a moderately effective vaccine would significantly decrease the burden of HIV disease over time in countries and populations with high rates of HIV infection, such as South Africa.”
The experimental vaccine regimen tested in the Thai trial was found to be 31.2 % effective at preventing HIV infection over the 3.5-year follow-up after vaccination. In the HVTN 702 study, the design, schedule, and components of the RV144 vaccine regimen have been modified in an attempt to increase the magnitude and duration of vaccine-elicited protective immune responses.
NIAID is responsible for all operational aspects of this phase IIb/III trial, which is enrolling HIV-uninfected, sexually active men and women aged 18-35 years. The NIAID-funded HIV Vaccine Trials Network is conducting the trial at 15 sites across South Africa, and expects results in late 2020. The study volunteers are being randomized to receive either the investigational vaccine regimen or a placebo. All study participants will receive a total of five injections over 1 year.
“If an HIV vaccine were found to work in South Africa, it could dramatically alter the course of the pandemic,” said HVTN 702 protocol chair Glenda Gray, MBBCH, president and CEO of the South African Medical Research Council and research professor of pediatrics at the University of the Witwatersrand, Johannesburg.
The HVTN 702 study begins just months after interim results were reported for HVTN 100, a predecessor clinical trial that found that the new vaccine regimen was safe for the 252 study participants and induced comparable immune responses to those reported in RV144, according to NIAID.
Both HVTN 100 and HVTN 702 are part of a larger HIV vaccine research endeavor led by the Pox-Protein Public-Private Partnership (P5), which includes NIAID, the Bill & Melinda Gates Foundation, the South African Medical Research Council, HVTN, Sanofi Pasteur, GSK, and the U.S. Military HIV Research Program.
NIAID said the HVTN 702 vaccine regimen consists of two experimental vaccines: a canarypox vector–based vaccine called ALVAC-HIV and a two-component gp120 protein subunit vaccine with an adjuvant to enhance the body’s immune response to the vaccine. Both ALVAC-HIV and the protein vaccine have been modified from the versions used in RV144 to be specific to HIV subtype C, the predominant HIV subtype in southern Africa.
In addition, NIAID said the protein subunit vaccine in HVTN 702 is combined with MF59, a different adjuvant than the one used in RV144, in the hope of generating a more robust immune response. The HVTN 702 vaccine regimen includes booster shots at the 1-year mark in an effort to prolong the early protective effect observed in RV144.
rpizzi@frontlinemedcom.com
On Twitter @richpizzi
.
According to an announcement by the National Institute of Allergy and Infectious Diseases, a cofunder of the trial and part of the U.S. National Institutes of Health, the study (called HVTN 702) involves a new version of the only HIV vaccine candidate ever shown to provide some protection against the virus. HVTN 702 intends to enroll 5,400 men and women, which would make it the largest and most advanced HIV vaccine clinical trial to take place in South Africa.
“If deployed alongside our current armory of proven HIV prevention tools, a safe and effective vaccine could be the final nail in the coffin for HIV,” Anthony S. Fauci, MD, director of NIAID, said in a statement. “Even a moderately effective vaccine would significantly decrease the burden of HIV disease over time in countries and populations with high rates of HIV infection, such as South Africa.”
The experimental vaccine regimen tested in the Thai trial was found to be 31.2 % effective at preventing HIV infection over the 3.5-year follow-up after vaccination. In the HVTN 702 study, the design, schedule, and components of the RV144 vaccine regimen have been modified in an attempt to increase the magnitude and duration of vaccine-elicited protective immune responses.
NIAID is responsible for all operational aspects of this phase IIb/III trial, which is enrolling HIV-uninfected, sexually active men and women aged 18-35 years. The NIAID-funded HIV Vaccine Trials Network is conducting the trial at 15 sites across South Africa, and expects results in late 2020. The study volunteers are being randomized to receive either the investigational vaccine regimen or a placebo. All study participants will receive a total of five injections over 1 year.
“If an HIV vaccine were found to work in South Africa, it could dramatically alter the course of the pandemic,” said HVTN 702 protocol chair Glenda Gray, MBBCH, president and CEO of the South African Medical Research Council and research professor of pediatrics at the University of the Witwatersrand, Johannesburg.
The HVTN 702 study begins just months after interim results were reported for HVTN 100, a predecessor clinical trial that found that the new vaccine regimen was safe for the 252 study participants and induced comparable immune responses to those reported in RV144, according to NIAID.
Both HVTN 100 and HVTN 702 are part of a larger HIV vaccine research endeavor led by the Pox-Protein Public-Private Partnership (P5), which includes NIAID, the Bill & Melinda Gates Foundation, the South African Medical Research Council, HVTN, Sanofi Pasteur, GSK, and the U.S. Military HIV Research Program.
NIAID said the HVTN 702 vaccine regimen consists of two experimental vaccines: a canarypox vector–based vaccine called ALVAC-HIV and a two-component gp120 protein subunit vaccine with an adjuvant to enhance the body’s immune response to the vaccine. Both ALVAC-HIV and the protein vaccine have been modified from the versions used in RV144 to be specific to HIV subtype C, the predominant HIV subtype in southern Africa.
In addition, NIAID said the protein subunit vaccine in HVTN 702 is combined with MF59, a different adjuvant than the one used in RV144, in the hope of generating a more robust immune response. The HVTN 702 vaccine regimen includes booster shots at the 1-year mark in an effort to prolong the early protective effect observed in RV144.
rpizzi@frontlinemedcom.com
On Twitter @richpizzi
.
According to an announcement by the National Institute of Allergy and Infectious Diseases, a cofunder of the trial and part of the U.S. National Institutes of Health, the study (called HVTN 702) involves a new version of the only HIV vaccine candidate ever shown to provide some protection against the virus. HVTN 702 intends to enroll 5,400 men and women, which would make it the largest and most advanced HIV vaccine clinical trial to take place in South Africa.
“If deployed alongside our current armory of proven HIV prevention tools, a safe and effective vaccine could be the final nail in the coffin for HIV,” Anthony S. Fauci, MD, director of NIAID, said in a statement. “Even a moderately effective vaccine would significantly decrease the burden of HIV disease over time in countries and populations with high rates of HIV infection, such as South Africa.”
The experimental vaccine regimen tested in the Thai trial was found to be 31.2 % effective at preventing HIV infection over the 3.5-year follow-up after vaccination. In the HVTN 702 study, the design, schedule, and components of the RV144 vaccine regimen have been modified in an attempt to increase the magnitude and duration of vaccine-elicited protective immune responses.
NIAID is responsible for all operational aspects of this phase IIb/III trial, which is enrolling HIV-uninfected, sexually active men and women aged 18-35 years. The NIAID-funded HIV Vaccine Trials Network is conducting the trial at 15 sites across South Africa, and expects results in late 2020. The study volunteers are being randomized to receive either the investigational vaccine regimen or a placebo. All study participants will receive a total of five injections over 1 year.
“If an HIV vaccine were found to work in South Africa, it could dramatically alter the course of the pandemic,” said HVTN 702 protocol chair Glenda Gray, MBBCH, president and CEO of the South African Medical Research Council and research professor of pediatrics at the University of the Witwatersrand, Johannesburg.
The HVTN 702 study begins just months after interim results were reported for HVTN 100, a predecessor clinical trial that found that the new vaccine regimen was safe for the 252 study participants and induced comparable immune responses to those reported in RV144, according to NIAID.
Both HVTN 100 and HVTN 702 are part of a larger HIV vaccine research endeavor led by the Pox-Protein Public-Private Partnership (P5), which includes NIAID, the Bill & Melinda Gates Foundation, the South African Medical Research Council, HVTN, Sanofi Pasteur, GSK, and the U.S. Military HIV Research Program.
NIAID said the HVTN 702 vaccine regimen consists of two experimental vaccines: a canarypox vector–based vaccine called ALVAC-HIV and a two-component gp120 protein subunit vaccine with an adjuvant to enhance the body’s immune response to the vaccine. Both ALVAC-HIV and the protein vaccine have been modified from the versions used in RV144 to be specific to HIV subtype C, the predominant HIV subtype in southern Africa.
In addition, NIAID said the protein subunit vaccine in HVTN 702 is combined with MF59, a different adjuvant than the one used in RV144, in the hope of generating a more robust immune response. The HVTN 702 vaccine regimen includes booster shots at the 1-year mark in an effort to prolong the early protective effect observed in RV144.
rpizzi@frontlinemedcom.com
On Twitter @richpizzi
IPV boost after initial OPV offers sustained protection to at least 11 months
Protection against the poliovirus is lower at 1 month but remains sustained at 6 and 11 months after an inactivated poliovirus vaccine (IPV) boost following initial oral poliovirus vaccination (OPV), according to Jacob John, MD, of Christian Medical College, Vellore, Tamil Nadu, India, and his associates.
In a randomized controlled trial from Nov. 4 and Dec. 17, 2014, 900 healthy children from ages 1 to 4 years were randomly assigned between three study groups. The groups had the children receive IPV boost at 5 months (arm A), at enrollment (arm B), or no vaccine (arm C). Poliovirus shedding in stool 7 days after challenge, determined by Fisher’s exact test, was significantly lower in arms A and B, compared with C (risk ratio, 0.68; P = .003, RR, 0.70; P = .006 for arm A vs. C and B vs. C, respectively). The reduction in shedding was more marked for serotype 3 (RR, 0.60; P = .004, RR, 0.54; P = .001 respectively) than for serotype 1 (RR, 0.72; P = .057, RR, 0.80; P = .215, respectively).
It was noted that 41 serious adverse events (11 in arm A, 17 in arm B, and 13 in arm C), including 2 deaths in arm A, were reported during the trial. However, the reported adverse events were classified as unrelated, and the deaths were from leukemia and from viral hemorrhagic fever.
“The boost to intestinal immunity against poliovirus that results from administration of IPV to OPV-vaccinated children is sustained at 6 and 11 months. It is clear that IPV is playing an increasingly important role in the polio endgame as the world transitions away from the use of OPV,” the researchers concluded. “Every effort needs to be made to ensure supply of this vaccine to meet this expanding role.”
Find the full study in the Journal of Infectious Diseases 2016. doi: 10.1093/infdis/jiw595.
Protection against the poliovirus is lower at 1 month but remains sustained at 6 and 11 months after an inactivated poliovirus vaccine (IPV) boost following initial oral poliovirus vaccination (OPV), according to Jacob John, MD, of Christian Medical College, Vellore, Tamil Nadu, India, and his associates.
In a randomized controlled trial from Nov. 4 and Dec. 17, 2014, 900 healthy children from ages 1 to 4 years were randomly assigned between three study groups. The groups had the children receive IPV boost at 5 months (arm A), at enrollment (arm B), or no vaccine (arm C). Poliovirus shedding in stool 7 days after challenge, determined by Fisher’s exact test, was significantly lower in arms A and B, compared with C (risk ratio, 0.68; P = .003, RR, 0.70; P = .006 for arm A vs. C and B vs. C, respectively). The reduction in shedding was more marked for serotype 3 (RR, 0.60; P = .004, RR, 0.54; P = .001 respectively) than for serotype 1 (RR, 0.72; P = .057, RR, 0.80; P = .215, respectively).
It was noted that 41 serious adverse events (11 in arm A, 17 in arm B, and 13 in arm C), including 2 deaths in arm A, were reported during the trial. However, the reported adverse events were classified as unrelated, and the deaths were from leukemia and from viral hemorrhagic fever.
“The boost to intestinal immunity against poliovirus that results from administration of IPV to OPV-vaccinated children is sustained at 6 and 11 months. It is clear that IPV is playing an increasingly important role in the polio endgame as the world transitions away from the use of OPV,” the researchers concluded. “Every effort needs to be made to ensure supply of this vaccine to meet this expanding role.”
Find the full study in the Journal of Infectious Diseases 2016. doi: 10.1093/infdis/jiw595.
Protection against the poliovirus is lower at 1 month but remains sustained at 6 and 11 months after an inactivated poliovirus vaccine (IPV) boost following initial oral poliovirus vaccination (OPV), according to Jacob John, MD, of Christian Medical College, Vellore, Tamil Nadu, India, and his associates.
In a randomized controlled trial from Nov. 4 and Dec. 17, 2014, 900 healthy children from ages 1 to 4 years were randomly assigned between three study groups. The groups had the children receive IPV boost at 5 months (arm A), at enrollment (arm B), or no vaccine (arm C). Poliovirus shedding in stool 7 days after challenge, determined by Fisher’s exact test, was significantly lower in arms A and B, compared with C (risk ratio, 0.68; P = .003, RR, 0.70; P = .006 for arm A vs. C and B vs. C, respectively). The reduction in shedding was more marked for serotype 3 (RR, 0.60; P = .004, RR, 0.54; P = .001 respectively) than for serotype 1 (RR, 0.72; P = .057, RR, 0.80; P = .215, respectively).
It was noted that 41 serious adverse events (11 in arm A, 17 in arm B, and 13 in arm C), including 2 deaths in arm A, were reported during the trial. However, the reported adverse events were classified as unrelated, and the deaths were from leukemia and from viral hemorrhagic fever.
“The boost to intestinal immunity against poliovirus that results from administration of IPV to OPV-vaccinated children is sustained at 6 and 11 months. It is clear that IPV is playing an increasingly important role in the polio endgame as the world transitions away from the use of OPV,” the researchers concluded. “Every effort needs to be made to ensure supply of this vaccine to meet this expanding role.”
Find the full study in the Journal of Infectious Diseases 2016. doi: 10.1093/infdis/jiw595.
FROM THE JOURNAL OF INFECTIOUS DISEASES