Vaccines

Poor influenza vaccination rates in children with chronic diseases is primarily due to poor parental understanding of influenza risk and vaccination benefits, according to Janita Pak Chun Chau, PhD, of the Chinese University of Hong Kong, and associates.

Studies show that children with chronic conditions “are at a disproportionately higher risk for severe influenza-associated complications, causing increased visits to outpatient or emergency departments, longer hospital stays, and higher mortality,” the researchers said.

A total of 623 parents of children with chronic conditions in Hong Kong were included in the study. The most common chronic condition was asthma, followed by chronic respiratory disease and cardiomyopathy. Only 33% of children had received an influenza vaccination in the previous 12 months, and 57% of children had ever received one.

Just under 40% of parents indicated intent to have their children vaccinated in the next 12 months. Parents who had their children vaccinated were more aware of vaccination benefits and considered vaccination a social norm, compared with parents who had not had their children vaccinated. Television was by far the most common source of information about influenza, followed by health professionals, and newspapers and magazines.

“Development of community-based influenza vaccination programs by health care professionals targeted to promote awareness and communicate the benefits and effectiveness of the vaccines in children with chronic conditions, as well as clarifying safety issues concerning the vaccination, may be able to promote the uptake of influenza vaccination,” the investigators wrote.

Find the study in the Pediatric Infectious Disease Journal (doi: INF.0000000000001550).

lfranki@frontlinemedcom.com

Poor influenza vaccination rates in children with chronic diseases is primarily due to poor parental understanding of influenza risk and vaccination benefits, according to Janita Pak Chun Chau, PhD, of the Chinese University of Hong Kong, and associates.

Studies show that children with chronic conditions “are at a disproportionately higher risk for severe influenza-associated complications, causing increased visits to outpatient or emergency departments, longer hospital stays, and higher mortality,” the researchers said.

A total of 623 parents of children with chronic conditions in Hong Kong were included in the study. The most common chronic condition was asthma, followed by chronic respiratory disease and cardiomyopathy. Only 33% of children had received an influenza vaccination in the previous 12 months, and 57% of children had ever received one.

Just under 40% of parents indicated intent to have their children vaccinated in the next 12 months. Parents who had their children vaccinated were more aware of vaccination benefits and considered vaccination a social norm, compared with parents who had not had their children vaccinated. Television was by far the most common source of information about influenza, followed by health professionals, and newspapers and magazines.

“Development of community-based influenza vaccination programs by health care professionals targeted to promote awareness and communicate the benefits and effectiveness of the vaccines in children with chronic conditions, as well as clarifying safety issues concerning the vaccination, may be able to promote the uptake of influenza vaccination,” the investigators wrote.

Find the study in the Pediatric Infectious Disease Journal (doi: INF.0000000000001550).

lfranki@frontlinemedcom.com

Poor influenza vaccination rates in children with chronic diseases is primarily due to poor parental understanding of influenza risk and vaccination benefits, according to Janita Pak Chun Chau, PhD, of the Chinese University of Hong Kong, and associates.

Studies show that children with chronic conditions “are at a disproportionately higher risk for severe influenza-associated complications, causing increased visits to outpatient or emergency departments, longer hospital stays, and higher mortality,” the researchers said.

A total of 623 parents of children with chronic conditions in Hong Kong were included in the study. The most common chronic condition was asthma, followed by chronic respiratory disease and cardiomyopathy. Only 33% of children had received an influenza vaccination in the previous 12 months, and 57% of children had ever received one.

Just under 40% of parents indicated intent to have their children vaccinated in the next 12 months. Parents who had their children vaccinated were more aware of vaccination benefits and considered vaccination a social norm, compared with parents who had not had their children vaccinated. Television was by far the most common source of information about influenza, followed by health professionals, and newspapers and magazines.

“Development of community-based influenza vaccination programs by health care professionals targeted to promote awareness and communicate the benefits and effectiveness of the vaccines in children with chronic conditions, as well as clarifying safety issues concerning the vaccination, may be able to promote the uptake of influenza vaccination,” the investigators wrote.

Find the study in the Pediatric Infectious Disease Journal (doi: INF.0000000000001550).

lfranki@frontlinemedcom.com

Vaccination programs targeting rotavirus and pneumonia in children younger than 2 years both contributed to a “rapid and considerable” decline in the hospital burden of pediatric patients, both in relation to those diseases and overall, according to an observational study.

Three vaccines were added to the National Immunization Plan in Israel within a 1.5-year interval, between July 2009 and January 2011: rotavirus vaccine and the 7-valent and 13-valent pneumococcal conjugate vaccines (PCV). Researchers studied the population at the Soroka University Medical Center in Beer Sheva, Israel, which was split roughly 50/50 between Jewish children and Bedouin Muslim children.

©Rawpixel Ltd/Thinkstock

dwatson@frontlinemedcom.com

Vaccination programs targeting rotavirus and pneumonia in children younger than 2 years both contributed to a “rapid and considerable” decline in the hospital burden of pediatric patients, both in relation to those diseases and overall, according to an observational study.

Three vaccines were added to the National Immunization Plan in Israel within a 1.5-year interval, between July 2009 and January 2011: rotavirus vaccine and the 7-valent and 13-valent pneumococcal conjugate vaccines (PCV). Researchers studied the population at the Soroka University Medical Center in Beer Sheva, Israel, which was split roughly 50/50 between Jewish children and Bedouin Muslim children.

©Rawpixel Ltd/Thinkstock

dwatson@frontlinemedcom.com

Vaccination programs targeting rotavirus and pneumonia in children younger than 2 years both contributed to a “rapid and considerable” decline in the hospital burden of pediatric patients, both in relation to those diseases and overall, according to an observational study.

Three vaccines were added to the National Immunization Plan in Israel within a 1.5-year interval, between July 2009 and January 2011: rotavirus vaccine and the 7-valent and 13-valent pneumococcal conjugate vaccines (PCV). Researchers studied the population at the Soroka University Medical Center in Beer Sheva, Israel, which was split roughly 50/50 between Jewish children and Bedouin Muslim children.

©Rawpixel Ltd/Thinkstock

dwatson@frontlinemedcom.com

During a 2012 pertussis outbreak in Oregon, unvaccinated or poorly vaccinated children were affected significantly earlier than fully vaccinated children were, according to Steve G. Robison, MPH, and Juventila Liko, MD, MPH, from the Immunization Program, Oregon Health Authority, Portland.

A total of 351 pertussis cases in children aged 2 months to 10 years were reported in Portland and the upper Willamette Valley from Jan. 1 to Nov. 1, 2012. Children who were unvaccinated accounted for 76 (22%) of the reported cases, and children who were poorly vaccinated accounted for 50 of the 275 (18%) cases in vaccinated children.

designer491/Thinkstock

lfranki@frontlinemedcom.com

During a 2012 pertussis outbreak in Oregon, unvaccinated or poorly vaccinated children were affected significantly earlier than fully vaccinated children were, according to Steve G. Robison, MPH, and Juventila Liko, MD, MPH, from the Immunization Program, Oregon Health Authority, Portland.

A total of 351 pertussis cases in children aged 2 months to 10 years were reported in Portland and the upper Willamette Valley from Jan. 1 to Nov. 1, 2012. Children who were unvaccinated accounted for 76 (22%) of the reported cases, and children who were poorly vaccinated accounted for 50 of the 275 (18%) cases in vaccinated children.

designer491/Thinkstock

lfranki@frontlinemedcom.com

During a 2012 pertussis outbreak in Oregon, unvaccinated or poorly vaccinated children were affected significantly earlier than fully vaccinated children were, according to Steve G. Robison, MPH, and Juventila Liko, MD, MPH, from the Immunization Program, Oregon Health Authority, Portland.

A total of 351 pertussis cases in children aged 2 months to 10 years were reported in Portland and the upper Willamette Valley from Jan. 1 to Nov. 1, 2012. Children who were unvaccinated accounted for 76 (22%) of the reported cases, and children who were poorly vaccinated accounted for 50 of the 275 (18%) cases in vaccinated children.

designer491/Thinkstock

lfranki@frontlinemedcom.com

Viral hepatitis affects mother and child, and pregnancy can exacerbate the disease. Vertical transmission contributes significantly to the high prevalence of viral hepatitis and compromises the well-being and the prognosis in the newborn. The indications for therapy in pregnant women may differ from those in the general population, and new therapies are available.

HEPATITIS A

Hepatitis A virus (HAV) infection is associated with significant morbidity and death around the world, as 1.4 million cases are reported every year worldwide.¹ However, in the United States, the prevalence has declined by 95% since HAV vaccination was introduced in 1995, and in 2013, the prevalence was 0.6 per 100,000 population.² Acute HAV infection during pregnancy is rare. As a result, the incidence during pregnancy is difficult to ascertain.³

HAV is transmitted by the fecal-oral route from person to person contact and from contamination of food and water. Vertical transmission from pregnant mother to fetus has not been reported.⁴

Clinical outcomes of HAV in pregnancy

Acute HAV infection during pregnancy is rare, and teratogenicity associated with HAV has not been reported.³ The course of the disease during pregnancy is generally similar to that in nonpregnant patients, with excellent maternal and fetal outcomes in developed nations. There have been reports in developing nations of premature contractions and labor, placental separation, premature rupture of the membranes, and vaginal bleeding.^5,6

Diagnosis

Routine screening for HAV is not recommended, but serologic testing by detection of anti-HAV immunoglobulin M (IgM) antibodies is done in high-risk patients suspected of having acute HAV infection.

Prevention

Prevention includes adherence to sanitary practices and active and passive immunoprophylaxis.³ Universal vaccination for pregnant mothers is not recommended,^1,2,6 but vaccination is recommended for high-risk patients and mothers—those with chronic liver disease, those receiving clotting factors, those who use illegal drugs, and travelers to areas where HAV is endemic. Immune globulin is also available for postexposure prophylaxis. HAV vaccines and immune globulin are safe in pregnancy.^3,6,7

Treatment

Treatment of acute HAV in pregnancy is supportive because of its benign nature; few patients require hospitalization.³

Pregnant patients with HAV can deliver vaginally, and breastfeeding is not contraindicated.⁸

HEPATITIS B

Hepatitis B virus (HBV) infection is a major global health problem. About 240 million people worldwide have chronic HBV infection, and more than 780,000 die every year from acute and chronic consequences.⁹

Vertical transmission is responsible for about half of chronic HBV infections worldwide. Thus, interruption of mother-to-child transmission is important. Universal maternal screening and passive-active immunoprophylaxis of newborns have lowered the transmission rates to between 5% and 10%. The 10% failure rate is unacceptably high and has been attributed to seropositivity for hepatitis B e antigen and a high viral load in the mother (ie, HBV DNA > 10⁶ copies/mL). High viral load is an independent risk factor for failure of immunoprophylaxis.¹⁰ Therefore, antiviral therapy is suggested in pregnant women who have a high HBV viral load to further decrease the chance of mother-to-child transmission and to prevent failure of immunoprophylaxis.¹¹

Clinical outcomes of HBV in pregnancy

Acute HBV infection during pregnancy is usually benign and is not associated with increased risk of death or teratogenicity.¹² Symptomatic disease in the mother with acute hepatitis B includes nausea, vomiting, abdominal pain, fatigue, and jaundice.³ For the newborn, there is increased risk of low birth weight and prematurity.¹³

When acute HBV infection occurs early in pregnancy, the rate of perinatal transmission is about 10%, increasing to 60% if it occurs near delivery.^12,13

Chronic HBV infection does not usually affect the outcome of pregnancy, but it may if the woman has cirrhosis or advanced liver disease¹⁴; however, pregnancy is very rare in women with HBV cirrhosis due to anovulation, and acute HBV flares have been described during pregnancy and postpartum.¹⁵

Pregnant patients with cirrhosis and portal hypertension are at risk of hepatic decompensation, variceal bleeding, and death.¹⁶ Risk is high with a score of 10 or more on the Model for End-stage Liver Disease scale, and is low with a score of 6 or less.¹⁷ Like nonpregnant patients, pregnant patients with cirrhosis should be monitored, and upper endoscopy should be performed in the 2nd trimester to assess for varices. A beta-blocker should be given or banding of varices should be done to avoid rupture. Rates of fetal demise, premature labor, spontaneous abortion, and stillbirth are high with portal hypertension.¹⁶

Risk of mother-to-child HBV transmission

Vertical HBV transmission can occur during the antepartum, intrapartum, and postpartum periods,^18,19 but it most often occurs during the intrapartum period at the time of delivery. Without immunoprophylaxis of the newborn, the risk of mother-to-child transmission can be as high as 90% if the mother is hepatitis B e antigen-positive and has a viral load greater than 10⁶ copies/mL. With active and passive immunoprophylaxis, the risk decreases substantially.

Screening and diagnosis

All pregnant women should be tested for hepatitis B surface antigen during the 1st trimester,²⁰ or any time thereafter if early testing was not done, even if they were vaccinated before becoming pregnant.²¹

Prevention

HBV infection is best prevented before pregnancy by vaccinating the mother or, after delivery, by vaccinating the newborn. Universal vaccination of newborns has been the standard of care since the 1990s. Pregnant women should be tested early in the pregnancy; unvaccinated, uninfected women at high risk of acquiring HBV (eg, because of sexual contacts or intravenous drug use) should be vaccinated.^2,3

HBV vaccine and immune globulin are both approved by the US Food and Drug Administration (FDA) for prevention of HBV infection and can be given during pregnancy and breastfeeding.³ All infants should be vaccinated for HBV at birth, and all infants born to mothers who test positive for hepatitis B s antigen should receive the HBV vaccine and the immune globulin within 12 to 24 hours after delivery. The vaccine series should be completed within 6 months.^20,21 This will decrease the rate of neonatal infection.

Treatment of HBV infection in pregnancy

The main objectives of treating chronic HBV infection in pregnancy are to maintain stable liver function in the mother and to prevent neonatal infection, which may cause cirrhosis and hepatocellular carcinoma and contribute to the global burden of the disease.²² Therefore, maternal HBV DNA and liver aminotransferase levels should be tested regularly during gestation.

The current guidelines of the American Association for the Study of Liver Diseases suggest antiviral therapy to reduce the risk of perinatal transmission of HBV in pregnant women with an HBV DNA level greater than 200,000 IU/mL or greater than 10⁶ copies/mL.^23,24

In a meta-analysis,²⁵ antiviral therapy with lamivudine, telbivudine, or tenofovir showed no apparent teratogenicity or safety concerns for maternal and fetal outcomes²⁶ and significantly reduced the rate of mother-to-child transmission. Of these 3 drugs, telbivudine was associated with a higher rate of normalization of liver enzymes, HBV suppression, and e-antigen seroconversion.²⁵ Lamivudine has proven the test of time in mothers co-infected with HBV and human immunodeficiency virus (HIV). However, tenofovir is considered the preferred treatment in pregnancy, owing to concerns about drug resistance to telbivudine and lamivudine and a high genetic barrier to resistance with tenofovir.²⁶ In mothers with HBV and HIV treated with tenofovir, treatment was associated with lower bone mineral density in the newborns, with a propensity for renal injury in the mothers. No safety concerns for maternal or fetal outcomes were identified in pregnant women infected only with HBV.²⁵

Many pregnant mothers choose to stop therapy around the time of conception because of safety concerns for the baby. In such situations, close monitoring is necessary to detect flares of HBV infection.

When the decision to treat is made, treatment should begin at 28 to 30 weeks of gestation, when organogenesis is complete and to allow enough time for HBV DNA levels to decline.

Breastfeeding is not contraindicated because antiviral drugs are minimally excreted in breast milk and are unlikely to cause toxicity. However, data are insufficient as to the long-term safety for the newborn when the mother took these drugs during pregancy and while breastfeeding.^23,27

Alanine aminotransferase and HBV DNA levels should be monitored postpartum because of the possibility of a hepatitis flare. In this setting, any of the three drugs can be used.²⁸ For mothers on therapy because of cirrhosis or an advanced histologic feature, antiviral therapy should be continued throughout pregnancy to prevent disease progression and decompensation.^19,22,27

No drug therapy is necessary for pregnant carriers of HBV.

Delivery and breastfeeding

The mode of delivery does not appear to have a significant effect on the interruption of vertical transmission of HBV.²⁹ Cesarean delivery is not recommended by the US Centers for Disease Control and Prevention (CDC)² or the American College of Obstetricians and Gynecologists.⁶ Breastfeeding is encouraged if the infant has received appropriate immunoprophylaxis.⁶

Coinfection with hepatitis D

Coinfection with hepatitis D virus (HDV) and HBV is associated with severe acute hepatitis^30,31 and increases the risk of death by a factor of 10. The World Health Organization recommends testing for HDV in pregnant women who are HBV-positive.⁸

Prevention of HDV infection requires prevention of HBV. The treatment of HDV in pregnancy is supportive. Pegylated interferon is successful outside pregnancy but is contraindicated during pregnancy.³² In patients with fulminant hepatic failure and end-stage liver disease, liver transplant can be lifesaving.

Take-home points

• HBV infection during pregnancy is usually benign and not severe but can be associated with an increased risk of mother-to-child transmission and progression of liver disease in the pregnant mother.
• Prevention of vertical transmission of HBV is important to reduce the burden of chronic HBV infection. Universal maternal screening early in pregnancy and passive-active immunoprophylaxis of newborns are usually sufficient to prevent vertical transmission of HBV, but antiviral therapy is needed for highly viremic mothers to further reduce the risk.
• Antiviral therapy is also indicated for pregnant women with moderate to severe hepatitis or cirrhosis to prevent disease progression and liver failure.
• Telbivudine, tenofovir, or lamivudine can be used during pregnancy, but more data are needed on the long-term safety of fetal exposure to these agents.

HEPATITIS C

The global prevalence of hepatitis C virus (HCV) infection is 2% to 3%, with 130 to 170 million HCV-positive people, most of whom are chronically infected.³³ The incidence of HCV during pregnancy is 1% to 2.4%, but 3% to 5% of infected mothers transmit HCV to their child at the time of birth.^6,34 Women coinfected with HIV and HCV have twice the risk of perinatal HCV transmission compared with women who have HCV infection alone.^6,34

HCV infection is usually asymptomatic and is discovered either by screening high-risk patients or during evaluation of persistently elevated aminotransferase levels. Acute HCV infection during pregnancy has been reported only rarely, and most pregnant women who are infected have chronic disease with no effect on the pregnancy or the infant.^6,34

Treatment

The CDC recommends that all adults (including pregnant women) born between 1945 and 1965 undergo 1-time testing for HCV without prior ascertainment of HCV risk (strong recommendation, with moderate quality of evidence).³⁵ The most important risk factor for HCV infection is past or current injection drug use.³³ Additional risk factors are similar to those for nonpregnant patients.

Because of the benign effect of HCV on the pregnancy, treatment is not recommended. To decrease the risk of maternal-child transmission, it is prudent to avoid amniocentesis, scalp instrumentation, and prolonged rupture of membranes.⁶

There is no vaccine or immune globulin for prevention. HCV infection should not influence the mode of delivery, and it is not a contraindication to breastfeeding.^34,36,37

HEPATITIS E

Every year, 20 million cases of hepatitis E virus (HEV) infection are recorded worldwide. These numbers include 3.3 million symptomatic cases and 56,600 deaths.³⁸ HEV infection is most common in developing countries, and pregnant women traveling to these areas are at high risk of acquiring this infection, of developing fulminant hepatitis, and of death.³⁹ Sporadic cases not associated with travel are increasingly reported in developed countries and are attributed to immunocompromised status (due to HIV or solid-organ transplant).^38,40

Modes of transmission of HEV are mainly via fecal-oral contamination and by vertical transmission.⁴¹  

Diagnosis

HEV infection can be diagnosed either by detecting IgM antibody with an enzyme-linked immunosorbent assay or by detecting HEV RNA in the blood using reverse transcription polymerase chain reaction testing.⁴²

Treatment and prevention

Hospitalization should be considered for pregnant women. Ribavirin or pegylated interferon alpha or both are effective but are contraindicated in pregnancy because of the risk of teratogenicity.^41,42 Urgent liver transplant can be a successful option in acute liver failure.

Prevention relies primarily on good sanitation, clean drinking water, and avoiding raw pork and venison. Boiling and chlorination of water inactivate HEV.^39,40 Pregnant women should be advised to avoid travel to highly endemic areas.

Viral hepatitis affects mother and child, and pregnancy can exacerbate the disease. Vertical transmission contributes significantly to the high prevalence of viral hepatitis and compromises the well-being and the prognosis in the newborn. The indications for therapy in pregnant women may differ from those in the general population, and new therapies are available.

HEPATITIS A

Hepatitis A virus (HAV) infection is associated with significant morbidity and death around the world, as 1.4 million cases are reported every year worldwide.¹ However, in the United States, the prevalence has declined by 95% since HAV vaccination was introduced in 1995, and in 2013, the prevalence was 0.6 per 100,000 population.² Acute HAV infection during pregnancy is rare. As a result, the incidence during pregnancy is difficult to ascertain.³

HAV is transmitted by the fecal-oral route from person to person contact and from contamination of food and water. Vertical transmission from pregnant mother to fetus has not been reported.⁴

Clinical outcomes of HAV in pregnancy

Acute HAV infection during pregnancy is rare, and teratogenicity associated with HAV has not been reported.³ The course of the disease during pregnancy is generally similar to that in nonpregnant patients, with excellent maternal and fetal outcomes in developed nations. There have been reports in developing nations of premature contractions and labor, placental separation, premature rupture of the membranes, and vaginal bleeding.^5,6

Diagnosis

Routine screening for HAV is not recommended, but serologic testing by detection of anti-HAV immunoglobulin M (IgM) antibodies is done in high-risk patients suspected of having acute HAV infection.

Prevention

Prevention includes adherence to sanitary practices and active and passive immunoprophylaxis.³ Universal vaccination for pregnant mothers is not recommended,^1,2,6 but vaccination is recommended for high-risk patients and mothers—those with chronic liver disease, those receiving clotting factors, those who use illegal drugs, and travelers to areas where HAV is endemic. Immune globulin is also available for postexposure prophylaxis. HAV vaccines and immune globulin are safe in pregnancy.^3,6,7

Treatment

Treatment of acute HAV in pregnancy is supportive because of its benign nature; few patients require hospitalization.³

Pregnant patients with HAV can deliver vaginally, and breastfeeding is not contraindicated.⁸

HEPATITIS B

Hepatitis B virus (HBV) infection is a major global health problem. About 240 million people worldwide have chronic HBV infection, and more than 780,000 die every year from acute and chronic consequences.⁹

Vertical transmission is responsible for about half of chronic HBV infections worldwide. Thus, interruption of mother-to-child transmission is important. Universal maternal screening and passive-active immunoprophylaxis of newborns have lowered the transmission rates to between 5% and 10%. The 10% failure rate is unacceptably high and has been attributed to seropositivity for hepatitis B e antigen and a high viral load in the mother (ie, HBV DNA > 10⁶ copies/mL). High viral load is an independent risk factor for failure of immunoprophylaxis.¹⁰ Therefore, antiviral therapy is suggested in pregnant women who have a high HBV viral load to further decrease the chance of mother-to-child transmission and to prevent failure of immunoprophylaxis.¹¹

Clinical outcomes of HBV in pregnancy

Acute HBV infection during pregnancy is usually benign and is not associated with increased risk of death or teratogenicity.¹² Symptomatic disease in the mother with acute hepatitis B includes nausea, vomiting, abdominal pain, fatigue, and jaundice.³ For the newborn, there is increased risk of low birth weight and prematurity.¹³

When acute HBV infection occurs early in pregnancy, the rate of perinatal transmission is about 10%, increasing to 60% if it occurs near delivery.^12,13

Chronic HBV infection does not usually affect the outcome of pregnancy, but it may if the woman has cirrhosis or advanced liver disease¹⁴; however, pregnancy is very rare in women with HBV cirrhosis due to anovulation, and acute HBV flares have been described during pregnancy and postpartum.¹⁵

Pregnant patients with cirrhosis and portal hypertension are at risk of hepatic decompensation, variceal bleeding, and death.¹⁶ Risk is high with a score of 10 or more on the Model for End-stage Liver Disease scale, and is low with a score of 6 or less.¹⁷ Like nonpregnant patients, pregnant patients with cirrhosis should be monitored, and upper endoscopy should be performed in the 2nd trimester to assess for varices. A beta-blocker should be given or banding of varices should be done to avoid rupture. Rates of fetal demise, premature labor, spontaneous abortion, and stillbirth are high with portal hypertension.¹⁶

Risk of mother-to-child HBV transmission

Vertical HBV transmission can occur during the antepartum, intrapartum, and postpartum periods,^18,19 but it most often occurs during the intrapartum period at the time of delivery. Without immunoprophylaxis of the newborn, the risk of mother-to-child transmission can be as high as 90% if the mother is hepatitis B e antigen-positive and has a viral load greater than 10⁶ copies/mL. With active and passive immunoprophylaxis, the risk decreases substantially.

Screening and diagnosis

All pregnant women should be tested for hepatitis B surface antigen during the 1st trimester,²⁰ or any time thereafter if early testing was not done, even if they were vaccinated before becoming pregnant.²¹

Prevention

HBV infection is best prevented before pregnancy by vaccinating the mother or, after delivery, by vaccinating the newborn. Universal vaccination of newborns has been the standard of care since the 1990s. Pregnant women should be tested early in the pregnancy; unvaccinated, uninfected women at high risk of acquiring HBV (eg, because of sexual contacts or intravenous drug use) should be vaccinated.^2,3

HBV vaccine and immune globulin are both approved by the US Food and Drug Administration (FDA) for prevention of HBV infection and can be given during pregnancy and breastfeeding.³ All infants should be vaccinated for HBV at birth, and all infants born to mothers who test positive for hepatitis B s antigen should receive the HBV vaccine and the immune globulin within 12 to 24 hours after delivery. The vaccine series should be completed within 6 months.^20,21 This will decrease the rate of neonatal infection.

Treatment of HBV infection in pregnancy

The main objectives of treating chronic HBV infection in pregnancy are to maintain stable liver function in the mother and to prevent neonatal infection, which may cause cirrhosis and hepatocellular carcinoma and contribute to the global burden of the disease.²² Therefore, maternal HBV DNA and liver aminotransferase levels should be tested regularly during gestation.

The current guidelines of the American Association for the Study of Liver Diseases suggest antiviral therapy to reduce the risk of perinatal transmission of HBV in pregnant women with an HBV DNA level greater than 200,000 IU/mL or greater than 10⁶ copies/mL.^23,24

In a meta-analysis,²⁵ antiviral therapy with lamivudine, telbivudine, or tenofovir showed no apparent teratogenicity or safety concerns for maternal and fetal outcomes²⁶ and significantly reduced the rate of mother-to-child transmission. Of these 3 drugs, telbivudine was associated with a higher rate of normalization of liver enzymes, HBV suppression, and e-antigen seroconversion.²⁵ Lamivudine has proven the test of time in mothers co-infected with HBV and human immunodeficiency virus (HIV). However, tenofovir is considered the preferred treatment in pregnancy, owing to concerns about drug resistance to telbivudine and lamivudine and a high genetic barrier to resistance with tenofovir.²⁶ In mothers with HBV and HIV treated with tenofovir, treatment was associated with lower bone mineral density in the newborns, with a propensity for renal injury in the mothers. No safety concerns for maternal or fetal outcomes were identified in pregnant women infected only with HBV.²⁵

Many pregnant mothers choose to stop therapy around the time of conception because of safety concerns for the baby. In such situations, close monitoring is necessary to detect flares of HBV infection.

When the decision to treat is made, treatment should begin at 28 to 30 weeks of gestation, when organogenesis is complete and to allow enough time for HBV DNA levels to decline.

Breastfeeding is not contraindicated because antiviral drugs are minimally excreted in breast milk and are unlikely to cause toxicity. However, data are insufficient as to the long-term safety for the newborn when the mother took these drugs during pregancy and while breastfeeding.^23,27

Alanine aminotransferase and HBV DNA levels should be monitored postpartum because of the possibility of a hepatitis flare. In this setting, any of the three drugs can be used.²⁸ For mothers on therapy because of cirrhosis or an advanced histologic feature, antiviral therapy should be continued throughout pregnancy to prevent disease progression and decompensation.^19,22,27

No drug therapy is necessary for pregnant carriers of HBV.

Delivery and breastfeeding

The mode of delivery does not appear to have a significant effect on the interruption of vertical transmission of HBV.²⁹ Cesarean delivery is not recommended by the US Centers for Disease Control and Prevention (CDC)² or the American College of Obstetricians and Gynecologists.⁶ Breastfeeding is encouraged if the infant has received appropriate immunoprophylaxis.⁶

Coinfection with hepatitis D

Coinfection with hepatitis D virus (HDV) and HBV is associated with severe acute hepatitis^30,31 and increases the risk of death by a factor of 10. The World Health Organization recommends testing for HDV in pregnant women who are HBV-positive.⁸

Prevention of HDV infection requires prevention of HBV. The treatment of HDV in pregnancy is supportive. Pegylated interferon is successful outside pregnancy but is contraindicated during pregnancy.³² In patients with fulminant hepatic failure and end-stage liver disease, liver transplant can be lifesaving.

Take-home points

• HBV infection during pregnancy is usually benign and not severe but can be associated with an increased risk of mother-to-child transmission and progression of liver disease in the pregnant mother.
• Prevention of vertical transmission of HBV is important to reduce the burden of chronic HBV infection. Universal maternal screening early in pregnancy and passive-active immunoprophylaxis of newborns are usually sufficient to prevent vertical transmission of HBV, but antiviral therapy is needed for highly viremic mothers to further reduce the risk.
• Antiviral therapy is also indicated for pregnant women with moderate to severe hepatitis or cirrhosis to prevent disease progression and liver failure.
• Telbivudine, tenofovir, or lamivudine can be used during pregnancy, but more data are needed on the long-term safety of fetal exposure to these agents.

HEPATITIS C

The global prevalence of hepatitis C virus (HCV) infection is 2% to 3%, with 130 to 170 million HCV-positive people, most of whom are chronically infected.³³ The incidence of HCV during pregnancy is 1% to 2.4%, but 3% to 5% of infected mothers transmit HCV to their child at the time of birth.^6,34 Women coinfected with HIV and HCV have twice the risk of perinatal HCV transmission compared with women who have HCV infection alone.^6,34

HCV infection is usually asymptomatic and is discovered either by screening high-risk patients or during evaluation of persistently elevated aminotransferase levels. Acute HCV infection during pregnancy has been reported only rarely, and most pregnant women who are infected have chronic disease with no effect on the pregnancy or the infant.^6,34

Treatment

The CDC recommends that all adults (including pregnant women) born between 1945 and 1965 undergo 1-time testing for HCV without prior ascertainment of HCV risk (strong recommendation, with moderate quality of evidence).³⁵ The most important risk factor for HCV infection is past or current injection drug use.³³ Additional risk factors are similar to those for nonpregnant patients.

Because of the benign effect of HCV on the pregnancy, treatment is not recommended. To decrease the risk of maternal-child transmission, it is prudent to avoid amniocentesis, scalp instrumentation, and prolonged rupture of membranes.⁶

There is no vaccine or immune globulin for prevention. HCV infection should not influence the mode of delivery, and it is not a contraindication to breastfeeding.^34,36,37

HEPATITIS E

Every year, 20 million cases of hepatitis E virus (HEV) infection are recorded worldwide. These numbers include 3.3 million symptomatic cases and 56,600 deaths.³⁸ HEV infection is most common in developing countries, and pregnant women traveling to these areas are at high risk of acquiring this infection, of developing fulminant hepatitis, and of death.³⁹ Sporadic cases not associated with travel are increasingly reported in developed countries and are attributed to immunocompromised status (due to HIV or solid-organ transplant).^38,40

Modes of transmission of HEV are mainly via fecal-oral contamination and by vertical transmission.⁴¹  

Diagnosis

HEV infection can be diagnosed either by detecting IgM antibody with an enzyme-linked immunosorbent assay or by detecting HEV RNA in the blood using reverse transcription polymerase chain reaction testing.⁴²

Treatment and prevention

Hospitalization should be considered for pregnant women. Ribavirin or pegylated interferon alpha or both are effective but are contraindicated in pregnancy because of the risk of teratogenicity.^41,42 Urgent liver transplant can be a successful option in acute liver failure.

Prevention relies primarily on good sanitation, clean drinking water, and avoiding raw pork and venison. Boiling and chlorination of water inactivate HEV.^39,40 Pregnant women should be advised to avoid travel to highly endemic areas.

Viral hepatitis affects mother and child, and pregnancy can exacerbate the disease. Vertical transmission contributes significantly to the high prevalence of viral hepatitis and compromises the well-being and the prognosis in the newborn. The indications for therapy in pregnant women may differ from those in the general population, and new therapies are available.

HEPATITIS A

Hepatitis A virus (HAV) infection is associated with significant morbidity and death around the world, as 1.4 million cases are reported every year worldwide.¹ However, in the United States, the prevalence has declined by 95% since HAV vaccination was introduced in 1995, and in 2013, the prevalence was 0.6 per 100,000 population.² Acute HAV infection during pregnancy is rare. As a result, the incidence during pregnancy is difficult to ascertain.³

HAV is transmitted by the fecal-oral route from person to person contact and from contamination of food and water. Vertical transmission from pregnant mother to fetus has not been reported.⁴

Clinical outcomes of HAV in pregnancy

Acute HAV infection during pregnancy is rare, and teratogenicity associated with HAV has not been reported.³ The course of the disease during pregnancy is generally similar to that in nonpregnant patients, with excellent maternal and fetal outcomes in developed nations. There have been reports in developing nations of premature contractions and labor, placental separation, premature rupture of the membranes, and vaginal bleeding.^5,6

Diagnosis

Routine screening for HAV is not recommended, but serologic testing by detection of anti-HAV immunoglobulin M (IgM) antibodies is done in high-risk patients suspected of having acute HAV infection.

Prevention

Prevention includes adherence to sanitary practices and active and passive immunoprophylaxis.³ Universal vaccination for pregnant mothers is not recommended,^1,2,6 but vaccination is recommended for high-risk patients and mothers—those with chronic liver disease, those receiving clotting factors, those who use illegal drugs, and travelers to areas where HAV is endemic. Immune globulin is also available for postexposure prophylaxis. HAV vaccines and immune globulin are safe in pregnancy.^3,6,7

Treatment

Treatment of acute HAV in pregnancy is supportive because of its benign nature; few patients require hospitalization.³

Pregnant patients with HAV can deliver vaginally, and breastfeeding is not contraindicated.⁸

HEPATITIS B

Hepatitis B virus (HBV) infection is a major global health problem. About 240 million people worldwide have chronic HBV infection, and more than 780,000 die every year from acute and chronic consequences.⁹

Vertical transmission is responsible for about half of chronic HBV infections worldwide. Thus, interruption of mother-to-child transmission is important. Universal maternal screening and passive-active immunoprophylaxis of newborns have lowered the transmission rates to between 5% and 10%. The 10% failure rate is unacceptably high and has been attributed to seropositivity for hepatitis B e antigen and a high viral load in the mother (ie, HBV DNA > 10⁶ copies/mL). High viral load is an independent risk factor for failure of immunoprophylaxis.¹⁰ Therefore, antiviral therapy is suggested in pregnant women who have a high HBV viral load to further decrease the chance of mother-to-child transmission and to prevent failure of immunoprophylaxis.¹¹

Clinical outcomes of HBV in pregnancy

Acute HBV infection during pregnancy is usually benign and is not associated with increased risk of death or teratogenicity.¹² Symptomatic disease in the mother with acute hepatitis B includes nausea, vomiting, abdominal pain, fatigue, and jaundice.³ For the newborn, there is increased risk of low birth weight and prematurity.¹³

When acute HBV infection occurs early in pregnancy, the rate of perinatal transmission is about 10%, increasing to 60% if it occurs near delivery.^12,13

Chronic HBV infection does not usually affect the outcome of pregnancy, but it may if the woman has cirrhosis or advanced liver disease¹⁴; however, pregnancy is very rare in women with HBV cirrhosis due to anovulation, and acute HBV flares have been described during pregnancy and postpartum.¹⁵

Pregnant patients with cirrhosis and portal hypertension are at risk of hepatic decompensation, variceal bleeding, and death.¹⁶ Risk is high with a score of 10 or more on the Model for End-stage Liver Disease scale, and is low with a score of 6 or less.¹⁷ Like nonpregnant patients, pregnant patients with cirrhosis should be monitored, and upper endoscopy should be performed in the 2nd trimester to assess for varices. A beta-blocker should be given or banding of varices should be done to avoid rupture. Rates of fetal demise, premature labor, spontaneous abortion, and stillbirth are high with portal hypertension.¹⁶

Risk of mother-to-child HBV transmission

Vertical HBV transmission can occur during the antepartum, intrapartum, and postpartum periods,^18,19 but it most often occurs during the intrapartum period at the time of delivery. Without immunoprophylaxis of the newborn, the risk of mother-to-child transmission can be as high as 90% if the mother is hepatitis B e antigen-positive and has a viral load greater than 10⁶ copies/mL. With active and passive immunoprophylaxis, the risk decreases substantially.

Screening and diagnosis

All pregnant women should be tested for hepatitis B surface antigen during the 1st trimester,²⁰ or any time thereafter if early testing was not done, even if they were vaccinated before becoming pregnant.²¹

Prevention

HBV infection is best prevented before pregnancy by vaccinating the mother or, after delivery, by vaccinating the newborn. Universal vaccination of newborns has been the standard of care since the 1990s. Pregnant women should be tested early in the pregnancy; unvaccinated, uninfected women at high risk of acquiring HBV (eg, because of sexual contacts or intravenous drug use) should be vaccinated.^2,3

HBV vaccine and immune globulin are both approved by the US Food and Drug Administration (FDA) for prevention of HBV infection and can be given during pregnancy and breastfeeding.³ All infants should be vaccinated for HBV at birth, and all infants born to mothers who test positive for hepatitis B s antigen should receive the HBV vaccine and the immune globulin within 12 to 24 hours after delivery. The vaccine series should be completed within 6 months.^20,21 This will decrease the rate of neonatal infection.

Treatment of HBV infection in pregnancy

The main objectives of treating chronic HBV infection in pregnancy are to maintain stable liver function in the mother and to prevent neonatal infection, which may cause cirrhosis and hepatocellular carcinoma and contribute to the global burden of the disease.²² Therefore, maternal HBV DNA and liver aminotransferase levels should be tested regularly during gestation.

The current guidelines of the American Association for the Study of Liver Diseases suggest antiviral therapy to reduce the risk of perinatal transmission of HBV in pregnant women with an HBV DNA level greater than 200,000 IU/mL or greater than 10⁶ copies/mL.^23,24

In a meta-analysis,²⁵ antiviral therapy with lamivudine, telbivudine, or tenofovir showed no apparent teratogenicity or safety concerns for maternal and fetal outcomes²⁶ and significantly reduced the rate of mother-to-child transmission. Of these 3 drugs, telbivudine was associated with a higher rate of normalization of liver enzymes, HBV suppression, and e-antigen seroconversion.²⁵ Lamivudine has proven the test of time in mothers co-infected with HBV and human immunodeficiency virus (HIV). However, tenofovir is considered the preferred treatment in pregnancy, owing to concerns about drug resistance to telbivudine and lamivudine and a high genetic barrier to resistance with tenofovir.²⁶ In mothers with HBV and HIV treated with tenofovir, treatment was associated with lower bone mineral density in the newborns, with a propensity for renal injury in the mothers. No safety concerns for maternal or fetal outcomes were identified in pregnant women infected only with HBV.²⁵

Many pregnant mothers choose to stop therapy around the time of conception because of safety concerns for the baby. In such situations, close monitoring is necessary to detect flares of HBV infection.

When the decision to treat is made, treatment should begin at 28 to 30 weeks of gestation, when organogenesis is complete and to allow enough time for HBV DNA levels to decline.

Breastfeeding is not contraindicated because antiviral drugs are minimally excreted in breast milk and are unlikely to cause toxicity. However, data are insufficient as to the long-term safety for the newborn when the mother took these drugs during pregancy and while breastfeeding.^23,27

Alanine aminotransferase and HBV DNA levels should be monitored postpartum because of the possibility of a hepatitis flare. In this setting, any of the three drugs can be used.²⁸ For mothers on therapy because of cirrhosis or an advanced histologic feature, antiviral therapy should be continued throughout pregnancy to prevent disease progression and decompensation.^19,22,27

No drug therapy is necessary for pregnant carriers of HBV.

Delivery and breastfeeding

The mode of delivery does not appear to have a significant effect on the interruption of vertical transmission of HBV.²⁹ Cesarean delivery is not recommended by the US Centers for Disease Control and Prevention (CDC)² or the American College of Obstetricians and Gynecologists.⁶ Breastfeeding is encouraged if the infant has received appropriate immunoprophylaxis.⁶

Coinfection with hepatitis D

Coinfection with hepatitis D virus (HDV) and HBV is associated with severe acute hepatitis^30,31 and increases the risk of death by a factor of 10. The World Health Organization recommends testing for HDV in pregnant women who are HBV-positive.⁸

Prevention of HDV infection requires prevention of HBV. The treatment of HDV in pregnancy is supportive. Pegylated interferon is successful outside pregnancy but is contraindicated during pregnancy.³² In patients with fulminant hepatic failure and end-stage liver disease, liver transplant can be lifesaving.

Take-home points

• HBV infection during pregnancy is usually benign and not severe but can be associated with an increased risk of mother-to-child transmission and progression of liver disease in the pregnant mother.
• Prevention of vertical transmission of HBV is important to reduce the burden of chronic HBV infection. Universal maternal screening early in pregnancy and passive-active immunoprophylaxis of newborns are usually sufficient to prevent vertical transmission of HBV, but antiviral therapy is needed for highly viremic mothers to further reduce the risk.
• Antiviral therapy is also indicated for pregnant women with moderate to severe hepatitis or cirrhosis to prevent disease progression and liver failure.
• Telbivudine, tenofovir, or lamivudine can be used during pregnancy, but more data are needed on the long-term safety of fetal exposure to these agents.

HEPATITIS C

The global prevalence of hepatitis C virus (HCV) infection is 2% to 3%, with 130 to 170 million HCV-positive people, most of whom are chronically infected.³³ The incidence of HCV during pregnancy is 1% to 2.4%, but 3% to 5% of infected mothers transmit HCV to their child at the time of birth.^6,34 Women coinfected with HIV and HCV have twice the risk of perinatal HCV transmission compared with women who have HCV infection alone.^6,34

HCV infection is usually asymptomatic and is discovered either by screening high-risk patients or during evaluation of persistently elevated aminotransferase levels. Acute HCV infection during pregnancy has been reported only rarely, and most pregnant women who are infected have chronic disease with no effect on the pregnancy or the infant.^6,34

Treatment

The CDC recommends that all adults (including pregnant women) born between 1945 and 1965 undergo 1-time testing for HCV without prior ascertainment of HCV risk (strong recommendation, with moderate quality of evidence).³⁵ The most important risk factor for HCV infection is past or current injection drug use.³³ Additional risk factors are similar to those for nonpregnant patients.

Because of the benign effect of HCV on the pregnancy, treatment is not recommended. To decrease the risk of maternal-child transmission, it is prudent to avoid amniocentesis, scalp instrumentation, and prolonged rupture of membranes.⁶

There is no vaccine or immune globulin for prevention. HCV infection should not influence the mode of delivery, and it is not a contraindication to breastfeeding.^34,36,37

HEPATITIS E

Every year, 20 million cases of hepatitis E virus (HEV) infection are recorded worldwide. These numbers include 3.3 million symptomatic cases and 56,600 deaths.³⁸ HEV infection is most common in developing countries, and pregnant women traveling to these areas are at high risk of acquiring this infection, of developing fulminant hepatitis, and of death.³⁹ Sporadic cases not associated with travel are increasingly reported in developed countries and are attributed to immunocompromised status (due to HIV or solid-organ transplant).^38,40

Modes of transmission of HEV are mainly via fecal-oral contamination and by vertical transmission.⁴¹  

Diagnosis

HEV infection can be diagnosed either by detecting IgM antibody with an enzyme-linked immunosorbent assay or by detecting HEV RNA in the blood using reverse transcription polymerase chain reaction testing.⁴²

Treatment and prevention

Hospitalization should be considered for pregnant women. Ribavirin or pegylated interferon alpha or both are effective but are contraindicated in pregnancy because of the risk of teratogenicity.^41,42 Urgent liver transplant can be a successful option in acute liver failure.

Prevention relies primarily on good sanitation, clean drinking water, and avoiding raw pork and venison. Boiling and chlorination of water inactivate HEV.^39,40 Pregnant women should be advised to avoid travel to highly endemic areas.

Because of a spate of mumps outbreaks over the last decade, adding a third dose of the mumps vaccine to the currently standard two-dose series was debated during a meeting of the Center for Disease Control and Prevention’s Advisory Committee on Immunization Practices (ACIP).

“Data [on recent outbreaks] were presented to ACIP in 2012, and ACIP determined that the data were insufficient to recommend for or against the use of a third dose of MMR vaccine for mumps outbreak control,” explained Mona Marin, MD, of the CDC’s National Center for Immunization and Respiratory Diseases. “Subsequently, CDC issued guidance for consideration for use of a third dose in specifically identified target populations, along with criteria for public health departments to consider for decision-making. That includes settings with high two-dose coverage, intense exposure, and ongoing transmission.”

Steve Mann/thinkstock

dchitnis@frontlinemedcom.com

Because of a spate of mumps outbreaks over the last decade, adding a third dose of the mumps vaccine to the currently standard two-dose series was debated during a meeting of the Center for Disease Control and Prevention’s Advisory Committee on Immunization Practices (ACIP).

“Data [on recent outbreaks] were presented to ACIP in 2012, and ACIP determined that the data were insufficient to recommend for or against the use of a third dose of MMR vaccine for mumps outbreak control,” explained Mona Marin, MD, of the CDC’s National Center for Immunization and Respiratory Diseases. “Subsequently, CDC issued guidance for consideration for use of a third dose in specifically identified target populations, along with criteria for public health departments to consider for decision-making. That includes settings with high two-dose coverage, intense exposure, and ongoing transmission.”

Steve Mann/thinkstock

dchitnis@frontlinemedcom.com

Because of a spate of mumps outbreaks over the last decade, adding a third dose of the mumps vaccine to the currently standard two-dose series was debated during a meeting of the Center for Disease Control and Prevention’s Advisory Committee on Immunization Practices (ACIP).

“Data [on recent outbreaks] were presented to ACIP in 2012, and ACIP determined that the data were insufficient to recommend for or against the use of a third dose of MMR vaccine for mumps outbreak control,” explained Mona Marin, MD, of the CDC’s National Center for Immunization and Respiratory Diseases. “Subsequently, CDC issued guidance for consideration for use of a third dose in specifically identified target populations, along with criteria for public health departments to consider for decision-making. That includes settings with high two-dose coverage, intense exposure, and ongoing transmission.”

Steve Mann/thinkstock

dchitnis@frontlinemedcom.com

EVIDENCE SUMMARY

A 2010 meta-analysis evaluated 14 RCTs investigating the effectiveness of giving sweet solutions before immunization in 1707 healthy term infants from beyond the neonatal period to 12 months of age.¹ Intervention groups received 0.25 to 10 mL (median, 2 mL) of 12% to 75% sucrose or 30% to 40% glucose orally 2 minutes before one to 4 injections (one study used 3 oral doses every 30 seconds, and one study added topical EMLA cream). Control groups received water or nothing (plus topical placebo in one study).

Pooled outcome data for crying duration from 6 studies (5 sucrose, one glucose; 716 injections) showed no significant difference between groups. When 2 studies with widely differing results using 12% sucrose were removed, however, a statistically significant weighted mean difference of 12 seconds less crying favored sweet solutions (3 sucrose, one glucose; 568 injections; 95% confidence interval, −23 to −0.78).

Differences among studies in volumes and concentrations of sweet solutions used prevented investigators from ascertaining optimal dosing.

Sucrose solution significantly reduces crying time compared with placebo

A 2014 double-blind RCT evaluated sucrose solutions compared with sterile water in older infants.² One nurse gave 2 mL of a 75% sucrose solution, a 25% sucrose solution, or sterile water orally over 15 seconds immediately before administering diphtheria, tetanus, acellular pertussis/Haemophilus influenzae type b/inactivated poliovirus (DTaP/Hib/IPV), pneumococcal, and hepatitis A vaccines to 537 healthy 16- to 19-month-old infants simultaneously in the right and left deltoids. Parents cuddled the infant over one shoulder while a distracting noise was made. Pacifiers (5 infants) and pretreatment paracetamol (8 infants) were permitted.

Infants receiving sucrose solutions showed significantly reduced total crying times compared with controls (75% sucrose, 43 seconds; 25% sucrose, 62 seconds; placebo, 120 seconds; P<.001 for 75% sucrose compared with other solutions; P<.001 for 25% sucrose compared with placebo).

Glucose also shortens crying

A 2012 double-blind RCT compared glucose solution with sterile water before vaccination in 120 healthy infants 2 months of age.³ Parents used a syringe to apply 2 mL of a 25% glucose solution or sterile water over 30 seconds to the lateral side of the infant’s tongue immediately before injection of DTaP/Hib/IPV vaccine into the right thigh followed by injection of hepatitis B vaccine into the left thigh.

Infants lay on the examination table in the supine position with the head elevated. Parents weren’t permitted to use a pacifier or bottle, or swaddle, cuddle, or restrain the infant during the procedure, but they were allowed to lift and calm the infant 15 seconds after the injections. Mean full-lung crying time and mean total crying time were significantly shorter in the treatment group (TABLE³).

EVIDENCE SUMMARY

A 2010 meta-analysis evaluated 14 RCTs investigating the effectiveness of giving sweet solutions before immunization in 1707 healthy term infants from beyond the neonatal period to 12 months of age.¹ Intervention groups received 0.25 to 10 mL (median, 2 mL) of 12% to 75% sucrose or 30% to 40% glucose orally 2 minutes before one to 4 injections (one study used 3 oral doses every 30 seconds, and one study added topical EMLA cream). Control groups received water or nothing (plus topical placebo in one study).

Pooled outcome data for crying duration from 6 studies (5 sucrose, one glucose; 716 injections) showed no significant difference between groups. When 2 studies with widely differing results using 12% sucrose were removed, however, a statistically significant weighted mean difference of 12 seconds less crying favored sweet solutions (3 sucrose, one glucose; 568 injections; 95% confidence interval, −23 to −0.78).

Differences among studies in volumes and concentrations of sweet solutions used prevented investigators from ascertaining optimal dosing.

Sucrose solution significantly reduces crying time compared with placebo

A 2014 double-blind RCT evaluated sucrose solutions compared with sterile water in older infants.² One nurse gave 2 mL of a 75% sucrose solution, a 25% sucrose solution, or sterile water orally over 15 seconds immediately before administering diphtheria, tetanus, acellular pertussis/Haemophilus influenzae type b/inactivated poliovirus (DTaP/Hib/IPV), pneumococcal, and hepatitis A vaccines to 537 healthy 16- to 19-month-old infants simultaneously in the right and left deltoids. Parents cuddled the infant over one shoulder while a distracting noise was made. Pacifiers (5 infants) and pretreatment paracetamol (8 infants) were permitted.

Infants receiving sucrose solutions showed significantly reduced total crying times compared with controls (75% sucrose, 43 seconds; 25% sucrose, 62 seconds; placebo, 120 seconds; P<.001 for 75% sucrose compared with other solutions; P<.001 for 25% sucrose compared with placebo).

Glucose also shortens crying

A 2012 double-blind RCT compared glucose solution with sterile water before vaccination in 120 healthy infants 2 months of age.³ Parents used a syringe to apply 2 mL of a 25% glucose solution or sterile water over 30 seconds to the lateral side of the infant’s tongue immediately before injection of DTaP/Hib/IPV vaccine into the right thigh followed by injection of hepatitis B vaccine into the left thigh.

Infants lay on the examination table in the supine position with the head elevated. Parents weren’t permitted to use a pacifier or bottle, or swaddle, cuddle, or restrain the infant during the procedure, but they were allowed to lift and calm the infant 15 seconds after the injections. Mean full-lung crying time and mean total crying time were significantly shorter in the treatment group (TABLE³).

EVIDENCE SUMMARY

A 2010 meta-analysis evaluated 14 RCTs investigating the effectiveness of giving sweet solutions before immunization in 1707 healthy term infants from beyond the neonatal period to 12 months of age.¹ Intervention groups received 0.25 to 10 mL (median, 2 mL) of 12% to 75% sucrose or 30% to 40% glucose orally 2 minutes before one to 4 injections (one study used 3 oral doses every 30 seconds, and one study added topical EMLA cream). Control groups received water or nothing (plus topical placebo in one study).

Pooled outcome data for crying duration from 6 studies (5 sucrose, one glucose; 716 injections) showed no significant difference between groups. When 2 studies with widely differing results using 12% sucrose were removed, however, a statistically significant weighted mean difference of 12 seconds less crying favored sweet solutions (3 sucrose, one glucose; 568 injections; 95% confidence interval, −23 to −0.78).

Differences among studies in volumes and concentrations of sweet solutions used prevented investigators from ascertaining optimal dosing.

Sucrose solution significantly reduces crying time compared with placebo

A 2014 double-blind RCT evaluated sucrose solutions compared with sterile water in older infants.² One nurse gave 2 mL of a 75% sucrose solution, a 25% sucrose solution, or sterile water orally over 15 seconds immediately before administering diphtheria, tetanus, acellular pertussis/Haemophilus influenzae type b/inactivated poliovirus (DTaP/Hib/IPV), pneumococcal, and hepatitis A vaccines to 537 healthy 16- to 19-month-old infants simultaneously in the right and left deltoids. Parents cuddled the infant over one shoulder while a distracting noise was made. Pacifiers (5 infants) and pretreatment paracetamol (8 infants) were permitted.

Infants receiving sucrose solutions showed significantly reduced total crying times compared with controls (75% sucrose, 43 seconds; 25% sucrose, 62 seconds; placebo, 120 seconds; P<.001 for 75% sucrose compared with other solutions; P<.001 for 25% sucrose compared with placebo).

Glucose also shortens crying

A 2012 double-blind RCT compared glucose solution with sterile water before vaccination in 120 healthy infants 2 months of age.³ Parents used a syringe to apply 2 mL of a 25% glucose solution or sterile water over 30 seconds to the lateral side of the infant’s tongue immediately before injection of DTaP/Hib/IPV vaccine into the right thigh followed by injection of hepatitis B vaccine into the left thigh.

Infants lay on the examination table in the supine position with the head elevated. Parents weren’t permitted to use a pacifier or bottle, or swaddle, cuddle, or restrain the infant during the procedure, but they were allowed to lift and calm the infant 15 seconds after the injections. Mean full-lung crying time and mean total crying time were significantly shorter in the treatment group (TABLE³).

The Advisory Committee on Immunization Practices (ACIP) met 3 times in 2016 and introduced or revised recommendations on influenza, meningococcal, human papillomavirus (HPV), cholera, and hepatitis B vaccines. This Practice Alert highlights the most important new recommendations, except those for influenza vaccines, which were described in a previous Practice Alert.¹ (See the summary of how this year’s flu season compares to last year’s.)

Meningococcal vaccine: Now recommended for HIV-positive patients

Meningococcal conjugate vaccine (serogroups A, C, W, and Y) is recommended for all adolescents ages 11 to 12 as a single dose with a booster at age 16.² It is also recommended for adults and for children (starting at age 2 months) who have high-risk conditions such as functional or anatomic asplenia or complement deficiencies. Others at high risk include microbiologists routinely exposed to isolates of Neisseria meningitidis and those traveling to areas of high meningococcal incidence. ACIP recently added human immunodeficiency virus (HIV) infection to the list of high-risk conditions.³

Two meningococcal conjugate vaccines are available in the United States: Menactra, (Sanofi Pasteur), licensed for use in individuals ages 9 months to 55 years; and Menveo (GlaxoSmithKline), licensed for use in individuals ages 2 months to 55 years. Menveo is the preferred vaccine for children younger than 2 years infected with HIV. However, if Menactra is used, give it at least 4 weeks after completing all pneumococcal conjugate vaccine doses and either before or concomitantly with diphtheria and tetanus toxoid and acellular pertussis vaccine (DTaP). All individuals who are HIV positive should receive a multi-dose primary series and booster doses. The number of primary doses and timing of boosters depends on the product used and the ages of those vaccinated (TABLE³).

Although neither meningococcal conjugate vaccine product is licensed for use in individuals 56 years or older, ACIP recommends using one of the products for HIV-infected individuals in this age group because the only meningococcal vaccine licensed for use in adults 56 or older, meningococcal polysaccharide vaccine (MPSV4, Menomune, Sanofi Pasteur), has not been studied in patients with HIV infection.

Serogroup B. Two vaccine products provide short-term protection against meningococcal serogroup B: MenB-FHbp (Trumenba, Wyeth Pharmaceuticals, Inc.) and MenB-4C (Bexsero, GlaxoSmithKline). In 2015, ACIP made a “B” recommendation for the use of these vaccines in individuals 16 to 23 years of age, with the preferred age range being 16 to 18.⁴ A “B” recommendation means that while ACIP does not advise routine use of the vaccines in this age group, the vaccines can be administered to those who desire them. ACIP has recommended routine use of these products only for individuals 10 years and older who are at high risk for meningococcal disease.⁵

Trumenba was approved as a 3-dose vaccine, administered at 0, 2, and 6 months. Bexsero requires 2 doses given at least one month apart. At its October 2016 meeting, ACIP approved a 2-dose Trumenba schedule, at 0 and 6 months, when administered to those not at risk for meningococcal disease.⁶ However, during an outbreak, and for those at high risk for meningococcal disease, adhere to the original 3-dose schedule.

HPV vaccine: Now a 2-dose schedule for younger patients

The only HPV vaccine available in the United States is the 9-valent HPV vaccine (9vHPV), Gardasil 9. It is approved for both males and females ages 9 to 26 years. ACIP recommends it for both sexes at ages 11 or 12, and advises catch-up doses for men through age 21 and women through age 26. It also recommends vaccination through age 26 for men who have sex with men and men with HIV/acquired immunodeficiency syndrome (AIDS). Children with a history of being sexually abused or assaulted should begin vaccination at age 9 years.

The HPV vaccine is approved for a 3-dose schedule at 0, 1 to 2, and 6 months. At its October 2016 meeting, ACIP approved a 2-dose schedule (0, 6-12 months) for those starting the vaccine before their 15th birthday.⁷ Those starting the vaccine after their 15th birthday, and individuals at any age with an immune-compromising condition, should receive 3 doses. It is hoped that a 2-dose schedule will help to increase the uptake of this safe, effective, and underused vaccine.

Cholera: A new vaccine is available

In June 2016, the FDA approved a live, attenuated, single-dose, oral vaccine (Vaxchora, PaxVax, Inc.) for the prevention of cholera in adults ages 18 to 64 years. It is the only cholera vaccine approved in the United States.

Cholera occurs at low rates among travelers to areas where the disease is endemic. The key to prevention is food and water precautions, and thus the vaccine is not recommended for most travelers—only for those who are at increased risk of exposure to cholera or who have a medical condition that predisposes them to a poor response to medical care if cholera is contracted.⁸ Risk increases with long-term or frequent travel to endemic areas where safe food and water is not always available. Examples of compromising medical conditions include a blood type O, low gastric acidity, and heart or kidney disease.

Duration of the vaccine’s effectiveness is unknown, given a lack of data beyond 6 months. No recommendation for revaccination has been made, and this issue will be assessed as more data are collected. Other unknowns about the vaccine include its effectiveness among immune-suppressed individuals and pregnant women, as well as for those who live in cholera endemic areas or were previously vaccinated with another cholera vaccine.

Hepatitis B: Vaccinate newborns sooner

The incidence of hepatitis B virus (HBV) infection has declined by more than 90% since the introduction of a vaccine in 1982.⁹ However, about 19,000 new cases still arise each year,¹⁰ and about 950 of these are acquired by babies born to HBV-infected mothers.¹¹ About 90% of these infected newborns will develop chronic HBV infection¹² and, if untreated, incur its long-term risks of cirrhosis and liver failure. Hepatitis B vaccine given soon after birth is 75% effective in preventing perinatal HBV infection, and hepatitis B immune globulin (HBIG) is 71% effective.¹³ Used together, the 2 are 94% effective.¹³

Current recommendations for the prevention of HBV include:⁹

• Screen all pregnant women for hepatitis B surface antigen (HBsAg), and use HBIG and hepatitis B vaccines within 12 hours of birth for all newborns whose mothers are HBsAg positive or have an unknown HBsAg status.
• Administer the 3-dose hepatitis B vaccine to all other infants.
• Routinely vaccinate previously unvaccinated children and adolescents.
• Routinely vaccinate adults who are non-immune and at risk for HBV infection.

At its October 2016 meeting, ACIP adopted a comprehensive update of all HBV prevention recommendations. (This will be the subject of a future Practice Alert.) Included was a revision of a previously permissive recommendation that allowed the first dose of hepatitis B vaccine for newborns to be given within 2 months of hospital discharge. The new recommendation⁹ states that newborns of mothers known to be HBsAg negative should be vaccinated within 24 hours (if weight is ≥2000 g) or at age one month or at hospital discharge (if weight is <2000 g).

The first dose should be given within 12 hours of birth to all newborns whose mothers are HBsAg positive or have an unknown HBsAg status.⁹

Immunization schedules

Every year ACIP updates the adult and child immunization schedules to incorporate the changes from the previous year. These can be found on the ACIP Web site at https://www.cdc.gov/vaccines/schedules/hcp/index.html. This Web site remains the most authoritative and accurate source of information on vaccines and immunizations for both professionals and the public.

The Advisory Committee on Immunization Practices (ACIP) met 3 times in 2016 and introduced or revised recommendations on influenza, meningococcal, human papillomavirus (HPV), cholera, and hepatitis B vaccines. This Practice Alert highlights the most important new recommendations, except those for influenza vaccines, which were described in a previous Practice Alert.¹ (See the summary of how this year’s flu season compares to last year’s.)

Meningococcal vaccine: Now recommended for HIV-positive patients

Meningococcal conjugate vaccine (serogroups A, C, W, and Y) is recommended for all adolescents ages 11 to 12 as a single dose with a booster at age 16.² It is also recommended for adults and for children (starting at age 2 months) who have high-risk conditions such as functional or anatomic asplenia or complement deficiencies. Others at high risk include microbiologists routinely exposed to isolates of Neisseria meningitidis and those traveling to areas of high meningococcal incidence. ACIP recently added human immunodeficiency virus (HIV) infection to the list of high-risk conditions.³

Two meningococcal conjugate vaccines are available in the United States: Menactra, (Sanofi Pasteur), licensed for use in individuals ages 9 months to 55 years; and Menveo (GlaxoSmithKline), licensed for use in individuals ages 2 months to 55 years. Menveo is the preferred vaccine for children younger than 2 years infected with HIV. However, if Menactra is used, give it at least 4 weeks after completing all pneumococcal conjugate vaccine doses and either before or concomitantly with diphtheria and tetanus toxoid and acellular pertussis vaccine (DTaP). All individuals who are HIV positive should receive a multi-dose primary series and booster doses. The number of primary doses and timing of boosters depends on the product used and the ages of those vaccinated (TABLE³).

Although neither meningococcal conjugate vaccine product is licensed for use in individuals 56 years or older, ACIP recommends using one of the products for HIV-infected individuals in this age group because the only meningococcal vaccine licensed for use in adults 56 or older, meningococcal polysaccharide vaccine (MPSV4, Menomune, Sanofi Pasteur), has not been studied in patients with HIV infection.

Serogroup B. Two vaccine products provide short-term protection against meningococcal serogroup B: MenB-FHbp (Trumenba, Wyeth Pharmaceuticals, Inc.) and MenB-4C (Bexsero, GlaxoSmithKline). In 2015, ACIP made a “B” recommendation for the use of these vaccines in individuals 16 to 23 years of age, with the preferred age range being 16 to 18.⁴ A “B” recommendation means that while ACIP does not advise routine use of the vaccines in this age group, the vaccines can be administered to those who desire them. ACIP has recommended routine use of these products only for individuals 10 years and older who are at high risk for meningococcal disease.⁵

Trumenba was approved as a 3-dose vaccine, administered at 0, 2, and 6 months. Bexsero requires 2 doses given at least one month apart. At its October 2016 meeting, ACIP approved a 2-dose Trumenba schedule, at 0 and 6 months, when administered to those not at risk for meningococcal disease.⁶ However, during an outbreak, and for those at high risk for meningococcal disease, adhere to the original 3-dose schedule.

HPV vaccine: Now a 2-dose schedule for younger patients

The only HPV vaccine available in the United States is the 9-valent HPV vaccine (9vHPV), Gardasil 9. It is approved for both males and females ages 9 to 26 years. ACIP recommends it for both sexes at ages 11 or 12, and advises catch-up doses for men through age 21 and women through age 26. It also recommends vaccination through age 26 for men who have sex with men and men with HIV/acquired immunodeficiency syndrome (AIDS). Children with a history of being sexually abused or assaulted should begin vaccination at age 9 years.

The HPV vaccine is approved for a 3-dose schedule at 0, 1 to 2, and 6 months. At its October 2016 meeting, ACIP approved a 2-dose schedule (0, 6-12 months) for those starting the vaccine before their 15th birthday.⁷ Those starting the vaccine after their 15th birthday, and individuals at any age with an immune-compromising condition, should receive 3 doses. It is hoped that a 2-dose schedule will help to increase the uptake of this safe, effective, and underused vaccine.

Cholera: A new vaccine is available

In June 2016, the FDA approved a live, attenuated, single-dose, oral vaccine (Vaxchora, PaxVax, Inc.) for the prevention of cholera in adults ages 18 to 64 years. It is the only cholera vaccine approved in the United States.

Cholera occurs at low rates among travelers to areas where the disease is endemic. The key to prevention is food and water precautions, and thus the vaccine is not recommended for most travelers—only for those who are at increased risk of exposure to cholera or who have a medical condition that predisposes them to a poor response to medical care if cholera is contracted.⁸ Risk increases with long-term or frequent travel to endemic areas where safe food and water is not always available. Examples of compromising medical conditions include a blood type O, low gastric acidity, and heart or kidney disease.

Duration of the vaccine’s effectiveness is unknown, given a lack of data beyond 6 months. No recommendation for revaccination has been made, and this issue will be assessed as more data are collected. Other unknowns about the vaccine include its effectiveness among immune-suppressed individuals and pregnant women, as well as for those who live in cholera endemic areas or were previously vaccinated with another cholera vaccine.

Hepatitis B: Vaccinate newborns sooner

The incidence of hepatitis B virus (HBV) infection has declined by more than 90% since the introduction of a vaccine in 1982.⁹ However, about 19,000 new cases still arise each year,¹⁰ and about 950 of these are acquired by babies born to HBV-infected mothers.¹¹ About 90% of these infected newborns will develop chronic HBV infection¹² and, if untreated, incur its long-term risks of cirrhosis and liver failure. Hepatitis B vaccine given soon after birth is 75% effective in preventing perinatal HBV infection, and hepatitis B immune globulin (HBIG) is 71% effective.¹³ Used together, the 2 are 94% effective.¹³

Current recommendations for the prevention of HBV include:⁹

• Screen all pregnant women for hepatitis B surface antigen (HBsAg), and use HBIG and hepatitis B vaccines within 12 hours of birth for all newborns whose mothers are HBsAg positive or have an unknown HBsAg status.
• Administer the 3-dose hepatitis B vaccine to all other infants.
• Routinely vaccinate previously unvaccinated children and adolescents.
• Routinely vaccinate adults who are non-immune and at risk for HBV infection.

At its October 2016 meeting, ACIP adopted a comprehensive update of all HBV prevention recommendations. (This will be the subject of a future Practice Alert.) Included was a revision of a previously permissive recommendation that allowed the first dose of hepatitis B vaccine for newborns to be given within 2 months of hospital discharge. The new recommendation⁹ states that newborns of mothers known to be HBsAg negative should be vaccinated within 24 hours (if weight is ≥2000 g) or at age one month or at hospital discharge (if weight is <2000 g).

The first dose should be given within 12 hours of birth to all newborns whose mothers are HBsAg positive or have an unknown HBsAg status.⁹

Immunization schedules

Every year ACIP updates the adult and child immunization schedules to incorporate the changes from the previous year. These can be found on the ACIP Web site at https://www.cdc.gov/vaccines/schedules/hcp/index.html. This Web site remains the most authoritative and accurate source of information on vaccines and immunizations for both professionals and the public.

The Advisory Committee on Immunization Practices (ACIP) met 3 times in 2016 and introduced or revised recommendations on influenza, meningococcal, human papillomavirus (HPV), cholera, and hepatitis B vaccines. This Practice Alert highlights the most important new recommendations, except those for influenza vaccines, which were described in a previous Practice Alert.¹ (See the summary of how this year’s flu season compares to last year’s.)

Meningococcal vaccine: Now recommended for HIV-positive patients

Meningococcal conjugate vaccine (serogroups A, C, W, and Y) is recommended for all adolescents ages 11 to 12 as a single dose with a booster at age 16.² It is also recommended for adults and for children (starting at age 2 months) who have high-risk conditions such as functional or anatomic asplenia or complement deficiencies. Others at high risk include microbiologists routinely exposed to isolates of Neisseria meningitidis and those traveling to areas of high meningococcal incidence. ACIP recently added human immunodeficiency virus (HIV) infection to the list of high-risk conditions.³

Two meningococcal conjugate vaccines are available in the United States: Menactra, (Sanofi Pasteur), licensed for use in individuals ages 9 months to 55 years; and Menveo (GlaxoSmithKline), licensed for use in individuals ages 2 months to 55 years. Menveo is the preferred vaccine for children younger than 2 years infected with HIV. However, if Menactra is used, give it at least 4 weeks after completing all pneumococcal conjugate vaccine doses and either before or concomitantly with diphtheria and tetanus toxoid and acellular pertussis vaccine (DTaP). All individuals who are HIV positive should receive a multi-dose primary series and booster doses. The number of primary doses and timing of boosters depends on the product used and the ages of those vaccinated (TABLE³).

Although neither meningococcal conjugate vaccine product is licensed for use in individuals 56 years or older, ACIP recommends using one of the products for HIV-infected individuals in this age group because the only meningococcal vaccine licensed for use in adults 56 or older, meningococcal polysaccharide vaccine (MPSV4, Menomune, Sanofi Pasteur), has not been studied in patients with HIV infection.

Serogroup B. Two vaccine products provide short-term protection against meningococcal serogroup B: MenB-FHbp (Trumenba, Wyeth Pharmaceuticals, Inc.) and MenB-4C (Bexsero, GlaxoSmithKline). In 2015, ACIP made a “B” recommendation for the use of these vaccines in individuals 16 to 23 years of age, with the preferred age range being 16 to 18.⁴ A “B” recommendation means that while ACIP does not advise routine use of the vaccines in this age group, the vaccines can be administered to those who desire them. ACIP has recommended routine use of these products only for individuals 10 years and older who are at high risk for meningococcal disease.⁵

Trumenba was approved as a 3-dose vaccine, administered at 0, 2, and 6 months. Bexsero requires 2 doses given at least one month apart. At its October 2016 meeting, ACIP approved a 2-dose Trumenba schedule, at 0 and 6 months, when administered to those not at risk for meningococcal disease.⁶ However, during an outbreak, and for those at high risk for meningococcal disease, adhere to the original 3-dose schedule.

HPV vaccine: Now a 2-dose schedule for younger patients

The only HPV vaccine available in the United States is the 9-valent HPV vaccine (9vHPV), Gardasil 9. It is approved for both males and females ages 9 to 26 years. ACIP recommends it for both sexes at ages 11 or 12, and advises catch-up doses for men through age 21 and women through age 26. It also recommends vaccination through age 26 for men who have sex with men and men with HIV/acquired immunodeficiency syndrome (AIDS). Children with a history of being sexually abused or assaulted should begin vaccination at age 9 years.

The HPV vaccine is approved for a 3-dose schedule at 0, 1 to 2, and 6 months. At its October 2016 meeting, ACIP approved a 2-dose schedule (0, 6-12 months) for those starting the vaccine before their 15th birthday.⁷ Those starting the vaccine after their 15th birthday, and individuals at any age with an immune-compromising condition, should receive 3 doses. It is hoped that a 2-dose schedule will help to increase the uptake of this safe, effective, and underused vaccine.

Cholera: A new vaccine is available

In June 2016, the FDA approved a live, attenuated, single-dose, oral vaccine (Vaxchora, PaxVax, Inc.) for the prevention of cholera in adults ages 18 to 64 years. It is the only cholera vaccine approved in the United States.

Cholera occurs at low rates among travelers to areas where the disease is endemic. The key to prevention is food and water precautions, and thus the vaccine is not recommended for most travelers—only for those who are at increased risk of exposure to cholera or who have a medical condition that predisposes them to a poor response to medical care if cholera is contracted.⁸ Risk increases with long-term or frequent travel to endemic areas where safe food and water is not always available. Examples of compromising medical conditions include a blood type O, low gastric acidity, and heart or kidney disease.

Duration of the vaccine’s effectiveness is unknown, given a lack of data beyond 6 months. No recommendation for revaccination has been made, and this issue will be assessed as more data are collected. Other unknowns about the vaccine include its effectiveness among immune-suppressed individuals and pregnant women, as well as for those who live in cholera endemic areas or were previously vaccinated with another cholera vaccine.

Hepatitis B: Vaccinate newborns sooner

The incidence of hepatitis B virus (HBV) infection has declined by more than 90% since the introduction of a vaccine in 1982.⁹ However, about 19,000 new cases still arise each year,¹⁰ and about 950 of these are acquired by babies born to HBV-infected mothers.¹¹ About 90% of these infected newborns will develop chronic HBV infection¹² and, if untreated, incur its long-term risks of cirrhosis and liver failure. Hepatitis B vaccine given soon after birth is 75% effective in preventing perinatal HBV infection, and hepatitis B immune globulin (HBIG) is 71% effective.¹³ Used together, the 2 are 94% effective.¹³

Current recommendations for the prevention of HBV include:⁹

• Screen all pregnant women for hepatitis B surface antigen (HBsAg), and use HBIG and hepatitis B vaccines within 12 hours of birth for all newborns whose mothers are HBsAg positive or have an unknown HBsAg status.
• Administer the 3-dose hepatitis B vaccine to all other infants.
• Routinely vaccinate previously unvaccinated children and adolescents.
• Routinely vaccinate adults who are non-immune and at risk for HBV infection.

At its October 2016 meeting, ACIP adopted a comprehensive update of all HBV prevention recommendations. (This will be the subject of a future Practice Alert.) Included was a revision of a previously permissive recommendation that allowed the first dose of hepatitis B vaccine for newborns to be given within 2 months of hospital discharge. The new recommendation⁹ states that newborns of mothers known to be HBsAg negative should be vaccinated within 24 hours (if weight is ≥2000 g) or at age one month or at hospital discharge (if weight is <2000 g).

The first dose should be given within 12 hours of birth to all newborns whose mothers are HBsAg positive or have an unknown HBsAg status.⁹

Immunization schedules

Every year ACIP updates the adult and child immunization schedules to incorporate the changes from the previous year. These can be found on the ACIP Web site at https://www.cdc.gov/vaccines/schedules/hcp/index.html. This Web site remains the most authoritative and accurate source of information on vaccines and immunizations for both professionals and the public.

ORLANDO – An inactivated varicella zoster virus vaccine currently in development for adult patients undergoing autologous hematopoietic stem cell transplantation is efficacious and well tolerated, according to findings from a randomized, placebo-controlled, phase III trial.

During the course of the 2 1/2-year pivotal multicenter trial, confirmed herpes zoster infections occurred in 42 of 560 patients who were randomized to receive inactivated varicella zoster virus vaccine (ZV_IN) consistency lot (overall incidence of 32.8 cases/1,000 patient-years), compared with 113 of 564 patients who received placebo (overall incidence of 91.8/1,000 patient-years). The estimated vaccine efficacy was 63.8% after adjusting for age and duration of antiviral prophylaxis, Drew J. Winston, MD, reported at the combined annual meetings of the Center for International Blood & Marrow Transplant Research and the American Society for Blood and Marrow Transplantation.

The vaccine also was effective for reducing moderate and severe herpes zoster pain (estimated vaccine efficacy, 69.5%), for preventing postherpetic neuralgia (estimated vaccine efficacy, 83.7%), and for prevention of herpes zoster–related complications (estimated vaccine efficacy, 73.5%), he noted.

Study subjects were adults aged 18 years or older who were undergoing autologous hematopoietic stem cell transplantation (auto-HCT) for a malignancy or other indication. The most common underlying diseases were lymphoma and multiple myeloma. All patients had a history of varicella infection or were seropositive for varicella zoster virus (VZV) antibody, and had no history of VZV vaccine or herpes zoster infection within the prior year.

They were randomized to receive a four-dose regimen of either ZV_IN consistency lot, ZV_IN high-antigen lot, or placebo. A group of 106 patients who received the ZV_IN high-antigen lot were included in the safety analysis only. The first ZV_IN dose was administered about a month before transplantation, and doses two through four were administered about 30, 60, and 90 days after transplantation. About 90% in each group received antiviral agents after transplantation, and the duration of the use of antivirals also was similar in the groups. All patients were followed for the duration of the study, and those who developed herpes zoster were followed for 6 months after onset.

Herpes zoster cases were confirmed by polymerase chain reaction or by blinded endpoint committee adjudication.

Serious adverse events and vaccine-related serious adverse events occurred in a similar proportion of patients in the treatment and placebo groups (32.9% and 32.7%, and 0.8% and 0.9%, respectively). Vaccine-related events were primarily injection-site reactions. Systemic adverse events that occurred up to 28 days after vaccination were mainly gastrointestinal side effects, such as diarrhea, nausea, and vomiting. Pyrexia, oral mucositis, thrombocytopenia, and febrile neutropenia also were reported.

The most common serious adverse events were infectious complications, such as febrile neutropenia and relapse of underlying disease.

The findings are notable, as patients undergoing auto-HCT have an increased risk of developing herpes zoster infection and its complications, including postherpetic neuralgia, secondary bacterial infections, and disseminated VZV infection, as well as an increased risk of hospitalization and mortality, Dr. Winston explained.

Herpes zoster infections are associated primarily with cell-mediated immunity, and in older studies done prior to the routine use of antiviral prophylaxis, the reported incidence in auto-HCT patients was between 16% and 25%. Because of this high risk, current guidelines call for antiviral prophylaxis during auto-HCT, but even in this current era of acyclovir or valacyclovir prophylaxis, infections occur at relatively high rates after auto-HCT, he noted.

“Now another approach to prevention of herpes zoster infection is vaccination,” he said.

The live attenuated vaccine currently on the market is generally contraindicated in immunocompromised patients – at least in early period after transplantation, but ZV_IN showed promise with respect to safety in earlier studies, which led to the current trial.

“This study demonstrated that the inactivated varicella vaccine is very effective for preventing herpes zoster after autologous stem cell transplantation,” Dr. Winston said, noting that efficacy was observed both in those younger than age 50 years and in those aged 50 and older, and also in those who received prophylaxis for less than 3 months and for 3-6 months.

“Finally!” said one audience member, who noted during a discussion of the findings that there has long been a need for a vaccine to prevent herpes zoster in auto-HCT patients.

Dr. Winston reported receiving research funding from Oxford, and serving as a consultant to Merck and Chimerix.

sworcester@frontlinemedcom.com

ORLANDO – An inactivated varicella zoster virus vaccine currently in development for adult patients undergoing autologous hematopoietic stem cell transplantation is efficacious and well tolerated, according to findings from a randomized, placebo-controlled, phase III trial.

During the course of the 2 1/2-year pivotal multicenter trial, confirmed herpes zoster infections occurred in 42 of 560 patients who were randomized to receive inactivated varicella zoster virus vaccine (ZV_IN) consistency lot (overall incidence of 32.8 cases/1,000 patient-years), compared with 113 of 564 patients who received placebo (overall incidence of 91.8/1,000 patient-years). The estimated vaccine efficacy was 63.8% after adjusting for age and duration of antiviral prophylaxis, Drew J. Winston, MD, reported at the combined annual meetings of the Center for International Blood & Marrow Transplant Research and the American Society for Blood and Marrow Transplantation.

The vaccine also was effective for reducing moderate and severe herpes zoster pain (estimated vaccine efficacy, 69.5%), for preventing postherpetic neuralgia (estimated vaccine efficacy, 83.7%), and for prevention of herpes zoster–related complications (estimated vaccine efficacy, 73.5%), he noted.

Study subjects were adults aged 18 years or older who were undergoing autologous hematopoietic stem cell transplantation (auto-HCT) for a malignancy or other indication. The most common underlying diseases were lymphoma and multiple myeloma. All patients had a history of varicella infection or were seropositive for varicella zoster virus (VZV) antibody, and had no history of VZV vaccine or herpes zoster infection within the prior year.

They were randomized to receive a four-dose regimen of either ZV_IN consistency lot, ZV_IN high-antigen lot, or placebo. A group of 106 patients who received the ZV_IN high-antigen lot were included in the safety analysis only. The first ZV_IN dose was administered about a month before transplantation, and doses two through four were administered about 30, 60, and 90 days after transplantation. About 90% in each group received antiviral agents after transplantation, and the duration of the use of antivirals also was similar in the groups. All patients were followed for the duration of the study, and those who developed herpes zoster were followed for 6 months after onset.

Herpes zoster cases were confirmed by polymerase chain reaction or by blinded endpoint committee adjudication.

Serious adverse events and vaccine-related serious adverse events occurred in a similar proportion of patients in the treatment and placebo groups (32.9% and 32.7%, and 0.8% and 0.9%, respectively). Vaccine-related events were primarily injection-site reactions. Systemic adverse events that occurred up to 28 days after vaccination were mainly gastrointestinal side effects, such as diarrhea, nausea, and vomiting. Pyrexia, oral mucositis, thrombocytopenia, and febrile neutropenia also were reported.

The most common serious adverse events were infectious complications, such as febrile neutropenia and relapse of underlying disease.

The findings are notable, as patients undergoing auto-HCT have an increased risk of developing herpes zoster infection and its complications, including postherpetic neuralgia, secondary bacterial infections, and disseminated VZV infection, as well as an increased risk of hospitalization and mortality, Dr. Winston explained.

Herpes zoster infections are associated primarily with cell-mediated immunity, and in older studies done prior to the routine use of antiviral prophylaxis, the reported incidence in auto-HCT patients was between 16% and 25%. Because of this high risk, current guidelines call for antiviral prophylaxis during auto-HCT, but even in this current era of acyclovir or valacyclovir prophylaxis, infections occur at relatively high rates after auto-HCT, he noted.

“Now another approach to prevention of herpes zoster infection is vaccination,” he said.

The live attenuated vaccine currently on the market is generally contraindicated in immunocompromised patients – at least in early period after transplantation, but ZV_IN showed promise with respect to safety in earlier studies, which led to the current trial.

“This study demonstrated that the inactivated varicella vaccine is very effective for preventing herpes zoster after autologous stem cell transplantation,” Dr. Winston said, noting that efficacy was observed both in those younger than age 50 years and in those aged 50 and older, and also in those who received prophylaxis for less than 3 months and for 3-6 months.

“Finally!” said one audience member, who noted during a discussion of the findings that there has long been a need for a vaccine to prevent herpes zoster in auto-HCT patients.

Dr. Winston reported receiving research funding from Oxford, and serving as a consultant to Merck and Chimerix.

sworcester@frontlinemedcom.com

ORLANDO – An inactivated varicella zoster virus vaccine currently in development for adult patients undergoing autologous hematopoietic stem cell transplantation is efficacious and well tolerated, according to findings from a randomized, placebo-controlled, phase III trial.

During the course of the 2 1/2-year pivotal multicenter trial, confirmed herpes zoster infections occurred in 42 of 560 patients who were randomized to receive inactivated varicella zoster virus vaccine (ZV_IN) consistency lot (overall incidence of 32.8 cases/1,000 patient-years), compared with 113 of 564 patients who received placebo (overall incidence of 91.8/1,000 patient-years). The estimated vaccine efficacy was 63.8% after adjusting for age and duration of antiviral prophylaxis, Drew J. Winston, MD, reported at the combined annual meetings of the Center for International Blood & Marrow Transplant Research and the American Society for Blood and Marrow Transplantation.

The vaccine also was effective for reducing moderate and severe herpes zoster pain (estimated vaccine efficacy, 69.5%), for preventing postherpetic neuralgia (estimated vaccine efficacy, 83.7%), and for prevention of herpes zoster–related complications (estimated vaccine efficacy, 73.5%), he noted.

Study subjects were adults aged 18 years or older who were undergoing autologous hematopoietic stem cell transplantation (auto-HCT) for a malignancy or other indication. The most common underlying diseases were lymphoma and multiple myeloma. All patients had a history of varicella infection or were seropositive for varicella zoster virus (VZV) antibody, and had no history of VZV vaccine or herpes zoster infection within the prior year.

They were randomized to receive a four-dose regimen of either ZV_IN consistency lot, ZV_IN high-antigen lot, or placebo. A group of 106 patients who received the ZV_IN high-antigen lot were included in the safety analysis only. The first ZV_IN dose was administered about a month before transplantation, and doses two through four were administered about 30, 60, and 90 days after transplantation. About 90% in each group received antiviral agents after transplantation, and the duration of the use of antivirals also was similar in the groups. All patients were followed for the duration of the study, and those who developed herpes zoster were followed for 6 months after onset.

Herpes zoster cases were confirmed by polymerase chain reaction or by blinded endpoint committee adjudication.

Serious adverse events and vaccine-related serious adverse events occurred in a similar proportion of patients in the treatment and placebo groups (32.9% and 32.7%, and 0.8% and 0.9%, respectively). Vaccine-related events were primarily injection-site reactions. Systemic adverse events that occurred up to 28 days after vaccination were mainly gastrointestinal side effects, such as diarrhea, nausea, and vomiting. Pyrexia, oral mucositis, thrombocytopenia, and febrile neutropenia also were reported.

The most common serious adverse events were infectious complications, such as febrile neutropenia and relapse of underlying disease.

The findings are notable, as patients undergoing auto-HCT have an increased risk of developing herpes zoster infection and its complications, including postherpetic neuralgia, secondary bacterial infections, and disseminated VZV infection, as well as an increased risk of hospitalization and mortality, Dr. Winston explained.

Herpes zoster infections are associated primarily with cell-mediated immunity, and in older studies done prior to the routine use of antiviral prophylaxis, the reported incidence in auto-HCT patients was between 16% and 25%. Because of this high risk, current guidelines call for antiviral prophylaxis during auto-HCT, but even in this current era of acyclovir or valacyclovir prophylaxis, infections occur at relatively high rates after auto-HCT, he noted.

“Now another approach to prevention of herpes zoster infection is vaccination,” he said.

The live attenuated vaccine currently on the market is generally contraindicated in immunocompromised patients – at least in early period after transplantation, but ZV_IN showed promise with respect to safety in earlier studies, which led to the current trial.

“This study demonstrated that the inactivated varicella vaccine is very effective for preventing herpes zoster after autologous stem cell transplantation,” Dr. Winston said, noting that efficacy was observed both in those younger than age 50 years and in those aged 50 and older, and also in those who received prophylaxis for less than 3 months and for 3-6 months.

“Finally!” said one audience member, who noted during a discussion of the findings that there has long been a need for a vaccine to prevent herpes zoster in auto-HCT patients.

Dr. Winston reported receiving research funding from Oxford, and serving as a consultant to Merck and Chimerix.

sworcester@frontlinemedcom.com

Progress continues to be made on creating a Zika vaccine, but taking any of the current candidates all the way through clinical trials and into production could take another few years, according to the latest information presented at a meeting of the Centers for Disease Control and Prevention’s Advisory Committee on Immunization Practices.

“As we all know, there is no vaccine for Zika, but there are a number of vaccines that have been developed over the last century or so for other flaviviruses, [such as] dengue, yellow fever, Japanese encephalitis, [West Nile], and we know a great deal about flaviviruses in general and the pathology that they have,” explained Gerald R. Kovacs, PhD, of the Biomedical Advanced Research and Development Authority (BARDA). “What we’re doing is using our lessons learned and working with the epidemiologists, with the clinicians, with the nonclinical development people, and using those lessons to develop new vaccines for Zika.”

Aunt_Spray/Thinkstock

dchitnis@frontlinemedcom.com

Progress continues to be made on creating a Zika vaccine, but taking any of the current candidates all the way through clinical trials and into production could take another few years, according to the latest information presented at a meeting of the Centers for Disease Control and Prevention’s Advisory Committee on Immunization Practices.

“As we all know, there is no vaccine for Zika, but there are a number of vaccines that have been developed over the last century or so for other flaviviruses, [such as] dengue, yellow fever, Japanese encephalitis, [West Nile], and we know a great deal about flaviviruses in general and the pathology that they have,” explained Gerald R. Kovacs, PhD, of the Biomedical Advanced Research and Development Authority (BARDA). “What we’re doing is using our lessons learned and working with the epidemiologists, with the clinicians, with the nonclinical development people, and using those lessons to develop new vaccines for Zika.”

Aunt_Spray/Thinkstock

dchitnis@frontlinemedcom.com

Progress continues to be made on creating a Zika vaccine, but taking any of the current candidates all the way through clinical trials and into production could take another few years, according to the latest information presented at a meeting of the Centers for Disease Control and Prevention’s Advisory Committee on Immunization Practices.

“As we all know, there is no vaccine for Zika, but there are a number of vaccines that have been developed over the last century or so for other flaviviruses, [such as] dengue, yellow fever, Japanese encephalitis, [West Nile], and we know a great deal about flaviviruses in general and the pathology that they have,” explained Gerald R. Kovacs, PhD, of the Biomedical Advanced Research and Development Authority (BARDA). “What we’re doing is using our lessons learned and working with the epidemiologists, with the clinicians, with the nonclinical development people, and using those lessons to develop new vaccines for Zika.”

Aunt_Spray/Thinkstock

dchitnis@frontlinemedcom.com