Tenofovir versus Placebo to Prevent Perinatal Transmission of Hepatitis B.

BACKGROUND: Pregnant women with an elevated viral load of hepatitis B virus (HBV) have a risk of transmitting infection to their infants, despite the infants' receiving hepatitis B immune globulin. METHODS: In this multicenter, double-blind clinical trial performed in Thailand, we randomly assigned hepatitis B e antigen (HBeAg)-positive pregnant women with an alanine aminotransferase level of 60 IU or less per liter to receive tenofovir disoproxil fumarate (TDF) or placebo from 28 weeks of gestation to 2 months post partum. Infants received hepatitis B immune globulin at birth and hepatitis B vaccine at birth and at 1, 2, 4, and 6 months. The primary end point was a hepatitis B surface antigen (HBsAg)-positive status in the infant, confirmed by the HBV DNA level at 6 months of age. We calculated that a sample of 328 women would provide the trial with 90% power to detect a difference of at least 9 percentage points in the transmission rate (expected rate, 3% in the TDF group vs. 12% in the placebo group). RESULTS: From January 2013 to August 2015, we enrolled 331 women; 168 women were randomly assigned to the TDF group and 163 to the placebo group. At enrollment, the median gestational age was 28.3 weeks, and the median HBV DNA level was 8.0 log10 IU per milliliter. Among 322 deliveries (97% of the participants), there were 319 singleton births, two twin pairs, and one stillborn infant. The median time from birth to administration of hepatitis B immune globulin was 1.3 hours, and the median time from birth to administration of hepatitis B vaccine was 1.2 hours. In the primary analysis, none of the 147 infants (0%; 95% confidence interval [CI], 0 to 2) in the TDF group were infected, as compared with 3 of 147 (2%; 95% CI, 0 to 6) in the placebo group (P=0.12). The rate of adverse events did not differ significantly between groups. The incidence of a maternal alanine aminotransferase level of more than 300 IU per liter after discontinuation of the trial regimen was 6% in the TDF group and 3% in the placebo group (P=0.29). CONCLUSIONS: In a setting in which the rate of mother-to-child HBV transmission was low with the administration of hepatitis B immune globulin and hepatitis B vaccine in infants born to HBeAg-positive mothers, the additional maternal use of TDF did not result in a significantly lower rate of transmission. (Funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development; ClinicalTrials.gov number, NCT01745822 .).

Recent and occult hepatitis B virus infections among blood donors in the United States.

BACKGROUND: Characteristics of US blood donors with recent (RBI) or occult (OBI) hepatitis B virus (HBV) infection are not well defined. METHODS: Donors with RBI and OBI were identified by nucleic acid and serologic testing among 34.4 million donations during 2009-2015. Consenting donors were interviewed and their HBV S-gene sequenced. RESULTS: The overall rate of HBV-infected donors was 7.95 per 100,000; of these, 0.35 per 100,000 and 1.70 per 100,000 were RBI and OBI, respectively. RBI (n = 120) and OBI (n = 583) donors constituted 26% of all HBV-infected (n = 2735) donors. Detection of HBV DNA in 92% of OBI donors required individual donation nucleic acid testing. Donors with OBI compared to RBI were older (mean age, 48 vs 39 years; p < 0.0001) with lower median viral loads (9 vs. 529 IU/mL; p < 0.0001). A higher proportion of OBI than RBI donors were born or resided in an endemic country (39% vs. 5%; p = 0.0078). Seventy-seven percent of all RBI and OBI donors had multiple sex partners, an HBV-risk factor. Of 40 RBI and 10 OBI donors whose S gene was sequenced, 33 (83%) and 6 (60%), respectively, carried HBV subgenotype A2; 18 (55%) and 2 (33%), respectively, shared an identical sequence. Infection with 1 or more putative HBV-immune-escape mutants was identified in 5 (50%) of OBI but no RBI donors. CONCLUSION: RBI and OBI continue to be identified at low rates, confirming the importance of comprehensive HBV DNA screening of US blood donations. HBV-infected donors require referral for care and evaluation and contact tracing; their HBV strains may provide important information on emergent genotypes.

Tenofovir Exposure during Pregnancy and Postpartum in Women Receiving Tenofovir Disoproxil Fumarate for the Prevention of Mother-to-Child Transmission of Hepatitis B Virus.

We assessed tenofovir exposure during pregnancy and postpartum in hepatitis B virus (HBV)-infected HIV-uninfected women receiving tenofovir disoproxil fumarate (TDF) to prevent mother-to-child transmission of HBV. Data from 154 women who received TDF within a randomized controlled trial were included. Individual plasma tenofovir exposures (area under the concentration-time curve from 0 to 24 h [AUC0-24]) were estimated using a population pharmacokinetic approach. The estimated geometric mean tenofovir AUC0-24 was 20% (95% confidence interval [95% CI], 19 to 21%) lower during pregnancy than during postpartum; this modest reduction in the absence of HBV transmission suggests that no dose adjustment is needed.

Cost-effectiveness of active-passive prophylaxis and antiviral prophylaxis during pregnancy to prevent perinatal hepatitis B virus infection.

UNLABELLED: In an era of antiviral treatment, reexamination of the cost-effectiveness of strategies to prevent perinatal hepatitis B virus (HBV) transmission in the United States is needed. We used a decision tree and Markov model to estimate the cost-effectiveness of the current U.S. strategy and two alternatives: (1) Universal hepatitis B vaccination (HepB) strategy: No pregnant women are screened for hepatitis B surface antigen (HBsAg). All infants receive HepB before hospital discharge; no infants receive hepatitis B immunoglobulin (HBIG). (2) Current strategy: All pregnant women are screened for HBsAg. Infants of HBsAg-positive women receive HepB and HBIG ≤12 hours of birth. All other infants receive HepB before hospital discharge. (3) Antiviral prophylaxis strategy: All pregnant women are screened for HBsAg. HBsAg-positive women have HBV-DNA load measured. Antiviral prophylaxis is offered for 4 months starting in the third trimester to women with DNA load ≥10(6) copies/mL. HepB and HBIG are administered at birth to infants of HBsAg-positive women, and HepB is administered before hospital discharge to infants of HBsAg-negative women. Effects were measured in quality-adjusted life years (QALYs) and incremental cost-effectiveness ratios (ICER). Compared to the universal HepB strategy, the current strategy prevented 1,006 chronic HBV infections and saved 13,600 QALYs (ICER: $6,957/QALY saved). Antiviral prophylaxis dominated the current strategy, preventing an additional 489 chronic infections, and saving 800 QALYs and $2.8 million. The results remained robust over a wide range of assumptions. CONCLUSION: The current U.S. strategy for preventing perinatal HBV remains cost-effective compared to the universal HepB strategy. An antiviral prophylaxis strategy was cost saving compared to the current strategy and should be considered to continue to decrease the burden of perinatal hepatitis B in the United States.

Prevention of mother-to-child transmission of hepatitis B virus: a phase III, placebo-controlled, double-blind, randomized clinical trial to assess the efficacy and safety of a short course of tenofovir disoproxil fumarate in women with hepatitis B virus e-antigen.

BACKGROUND: Chronic hepatitis B virus (HBV) infection is complicated by cirrhosis and liver cancer. In Thailand, 6-7 % of adults are chronically infected with HBV. The risk of mother-to-child transmission (MTCT) of HBV has been estimated to be about 12 % when mothers have a high hepatitis B viral load, even if infants receive passive-active prophylaxis with HBV immunoglobulin (HBIg) and initiate the hepatitis B vaccine series at birth. We designed a study to assess the efficacy and safety of a short course of maternal tenofovir disoproxil fumarate (TDF) among women with a marker of high viral load for the prevention of MTCT of HBV. METHODS: The study is a phase III, multicenter (17 sites in Thailand), placebo-controlled, double-blind, randomized 1:1, two-arm clinical trial of TDF 300 mg once daily versus placebo among pregnant women from 28 weeks' gestation through 2-month post-partum. All infants receive HBIg at birth, and a hepatitis B (HB) vaccination series according to Thai guidelines: birth, and age 1, 2, 4 and 6 months. Participant women at study entry must be age ≥18 years, hepatitis B surface antigen (HBsAg) and e-antigen (HBeAg) positive, have alanine aminotransferase (ALT) level < 30 IU/L at screening (confirmed < 60 IU/L pre-entry), negative hepatitis C serology, creatinine clearance >50 mL/min, and no history of anti-HBV antiviral treatment. The target sample size of 328 mother/infant pairs assumed 156 evaluable cases per arm to detect a ≥9 % difference in MTCT transmission (3 % experimental arm versus 12 % placebo arm) with 90 % power. Mothers and infants are followed until 12 months after delivery. The primary infant endpoint is detection of HBsAg, confirmed by detection of HBV DNA at six months of age. Secondary endpoints are maternal and infant adverse events, acute exacerbations of maternal hepatitis B disease (ALT >300 IU/L, defined as a "flare") following discontinuation of study treatment, infant HBV infection status and growth up to 12 months of age. DISCUSSION: The results of this randomized trial will clarify the efficacy and safety of a short course of antiviral treatment to prevent mother-to-child transmission of HBV and inform international guidelines. TRIAL REGISTRATION: ClinicalTrials.gov Identifier NCT01745822 .

Update: Shortened Interval for Postvaccination Serologic Testing of Infants Born to Hepatitis B-Infected Mothers.

Infants born to hepatitis B-infected mothers receive postexposure prophylaxis to reduce their risk for perinatal hepatitis B virus (HBV) infection. Postexposure prophylaxis consists of hepatitis B (HepB) vaccine and hepatitis B immune globulin administered within 12 hours of birth, followed by completion of the 3-dose or 4-dose HepB vaccine series. Postvaccination serologic testing (PVST) assesses an infant's response to HepB vaccination and has typically occurred at age 9-18 months. This report provides a CDC update recommending shortening the interval for PVST from age 9-18 months to age 9-12 months. Providers should order PVST (consisting of hepatitis B surface antigen [HBsAg] and antibody to HBsAg [anti-HBs]) for infants born to HBsAg-positive mothers at age 9-12 months (or 1-2 months after the final dose of the vaccine series, if the series is delayed). This recommendation was prompted by the discontinuation of production of Hib/HepB vaccine (Comvax) and new data from the Enhanced Perinatal Hepatitis B Prevention Program supporting PVST 1・2 months after receipt of the last HepB vaccine dose, and at age ≥9 months.

Discrepant hepatitis B surface antigen results in pregnant women screened to identify hepatitis B virus infection.

OBJECTIVE: To resolve discrepant hepatitis B surface antigen (HBsAg) results for pregnant women screened for hepatitis B virus (HBV) infection. STUDY DESIGN: A case was defined as discrepant HBsAg (reactive followed by non-reactive) result during the same pregnancy. The Centers for Disease Control and Prevention examined a convenience sample of cases passively reported by US Perinatal Hepatitis B Prevention Programs. Using a standard form, available results were obtained for hepatitis B tests and vaccination histories. Results were independently reviewed by 3 viral hepatitis experts and a clinical virologist to resolve discrepancies. The initial HBsAg result was classified as probable true positive, probable false positive, or unresolved. RESULTS: From April 2009-December 2011, 142 (75.9%) of 187 reported discrepant cases met the case definition. Of the 142 initial reactive HBsAg results, 113 (79.5%) were laboratory-confirmed, and 89 (62.7%) were resolved. Among these 89 cases, the initial test was a probable true positive in 14 (15.7%), and a false positive in 75 (84.3%). Total antibody to hepatitis B core antigen was positive for 11 (78.6%) of the true positive cases and negative for 67 (89.3%) of the false positive cases. True positives included 2 cases of resolving acute HBV infection and one case recently given hepatitis B vaccination. CONCLUSIONS: In this retrospective analysis of discrepant HBsAg-reactive screening results from pregnant women, the majority were false positives, but true positives occurred. Testing for total hepatitis B core antibody, an indicator of past or current HBV infection, was useful for resolving discrepancies.

CDC guidance for evaluating health-care personnel for hepatitis B virus protection and for administering postexposure management.

This report contains CDC guidance that augments the 2011 recommendations of the Advisory Committee on Immunization Practices (ACIP) for evaluating hepatitis B protection among health-care personnel (HCP) and administering post-exposure prophylaxis. Explicit guidance is provided for persons working, training, or volunteering in health-care settings who have documented hepatitis B (HepB) vaccination years before hire or matriculation (e.g., when HepB vaccination was received as part of routine infant [recommended since 1991] or catch-up adolescent [recommended since 1995] vaccination). In the United States, 2,890 cases of acute hepatitis B were reported to CDC in 2011, and an estimated 18,800 new cases of hepatitis B occurred after accounting for underreporting of cases and asymptomatic infection. Although the rate of acute hepatitis B virus (HBV) infections have declined approximately 89% during 1990-2011, from 8.5 to 0.9 cases per 100,000 population in the United States, the risk for occupationally acquired HBV among HCP persists, largely from exposures to patients with chronic HBV infection. ACIP recommends HepB vaccination for unvaccinated or incompletely vaccinated HCP with reasonably anticipated risk for blood or body fluid exposure. ACIP also recommends that vaccinated HCP receive postvaccination serologic testing (antibody to hepatitis B surface antigen [anti-HBs]) 1-2 months after the final dose of vaccine is administered (CDC. Immunization of health-care personnel: recommendations of the Advisory Committee on Immunization Practices [ACIP]. MMWR 2011;60 [No. RR-7]). Increasing numbers of HCP have received routine HepB vaccination either as infants (recommended since 1991) or as catch-up vaccination (recommended since 1995) in adolescence. HepB vaccination results in protective anti-HBs responses among approximately 95% of healthy-term infants. Certain institutions test vaccinated HCP by measuring anti-HBs upon hire or matriculation, even when anti-HBs testing occurs greater than 2 months after vaccination. This guidance can assist clinicians, occupational health and student health providers, infection-control specialists, hospital and health-care training program administrators, and others in selection of an approach for assessing HBV protection for vaccinated HCP. This report emphasizes the importance of administering HepB vaccination for all HCP, provides explicit guidance for evaluating hepatitis B protection among previously vaccinated HCP (particularly those who were vaccinated in infancy or adolescence), and clarifies recommendations for postexposure management of HCP exposed to blood or body fluids.

Antiviral treatment among pregnant women with chronic hepatitis B.

OBJECTIVE: To describe the antiviral treatment patterns for chronic hepatitis B (CHB) among pregnant and nonpregnant women. METHODS: Using 2011 MarketScan claims, we calculated the rates of antiviral treatment among women (aged 10-50 years) with CHB. We described the pattern of antiviral treatment during pregnancy and ≥1 month after delivery. RESULTS: We identified 6274 women with CHB during 2011. Among these, 64 of 507 (12.6%) pregnant women and 1151 of 5767 (20.0%) nonpregnant women received antiviral treatment (P < 0.01). Pregnant women were most commonly prescribed tenofovir (73.4%) and lamivudine (21.9%); nonpregnant women were most commonly prescribed tenofovir (50.2%) and entecavir (41.3%) (P < 0.01). Among 48 treated pregnant women with an identifiable delivery date, 16 (33.3%) were prescribed an antiviral before pregnancy and continued treatment for at least one month after delivery; 14 (29.2%) started treatment during the third trimester and continued at least one month after delivery. CONCLUSION: Among this insured population, pregnant women with CHB received an antiviral significantly less often than nonpregnant women. The most common antiviral prescribed for pregnant women was tenofovir. These data provide a baseline for assessing changes in treatment patterns with anticipated increased use of antivirals to prevent breakthrough perinatal hepatitis B virus infection.

Which newborns missed the hepatitis B birth dose vaccination among U.S. children?

OBJECTIVES: Hepatitis B birth dose vaccination is a critical step in preventing perinatal hepatitis B virus infection. This study assesses the prevalence of children who missed the birth dose of hepatitis B vaccination and identifies socio-demographic factors associated with non-receipt of the birth dose among children in the United States. METHODS: A survey observation study was conducted with the national representative sample of 17,053 U.S. children aged 19-35 months obtained from the 2009 National Immunization Survey. Categorical data analysis and multivariable logistic regression in the context of complex sample survey were applied to evaluate the prevalence and determine the independent risk factors. RESULTS: 39.2% of children missed the birth dose of hepatitis B vaccination. Children who reside in states without a universal hepatitis B vaccine supply policy, are not covered by health insurance, and have only 1 vaccination provider are significantly associated with non-receipt of the birth dose hepatitis B vaccination. CONCLUSIONS: Children who reside in states without a universal hepatitis B vaccine supply policy, and who are not covered by health insurance are two important modifiable risk factors for not receiving the birth dose hepatitis B vaccination. Future intervention studies could be needed to help control those modifiable risk factors.

Factors associated with bowel resection among infants with intussusception in the United States.

BACKGROUND: Intussusception is the most common cause of infant bowel obstruction. Because delays in diagnosis can lead to severe outcomes, differentiating milder cases from those with potentially serious outcomes is important. OBJECTIVE: The objective of this study was to identify factors associated with bowel resection among intussusception cases using data from a large nationwide study, which investigated the association between intussusception and Rotashield. METHODS: We examined characteristics of 376 intussusception cases not associated with Rotashield use. Cases were confirmed by a radiologic procedure, surgery, or autopsy. Clinical characteristics of infants with and without bowel resection were compared. RESULTS: During the week before hospitalization, 93% of the 376 infants with intussusception had vomiting, 72% reported bloody stool, 63% had hemoccult positive stool, 51% had diarrhea, 43% reported fever, and 14% had documented fever. Surgery was performed on 209 cases (56%). Of these 209 cases, 33% (67/209) required bowel resection. Documented fever on admission significantly increased the risk of bowel resection (odds ratio, adjusted for race and sex, 2.7; 95% confidence interval, 1.2-6.0). Among infants with intussusception, the presence of a reported symptom for at least 2 days before hospital admission was also an independent predictor of bowel resection (adjusted odds ratio, 2.7; 95% confidence interval, 1.5-4.8). CONCLUSIONS: Bowel resection appears to be more likely among intussusception patients with documented fever and symptoms for at least 2 days. However, because resection also occurred among those without fever or prolonged symptoms, severe disease must also be considered in absence of these symptoms.

Sociodemographic and dietary risk factors for natural infant intussusception in the United States.

BACKGROUND: In 1999, a US case-control study demonstrated a strong association between intussusception and a rotavirus vaccine (Rotashield). However, because most (87%) cases were not temporally associated with vaccination, we reanalyzed these data to assess risk factors for intussusception cases unrelated to Rotashield. PATIENTS AND METHODS: Case-patients were infants with intussusception between November 1998 and June 1999. Controls were matched by age and hospital of birth. Sociodemographic and feeding practice data were collected through parent and provider interviews. Conditional logistic regression was used to identify risk factors for intussusception, controlling for exposure to Rotashield <21 days before intussusception. RESULTS: Four hundred twenty-nine cases and 1763 controls were enrolled. Among case-patients, 372 (87%) had not received Rotashield within 21 days before intussusception. After adjusting for recent Rotashield administration, factors associated with intussusception included male sex (odds ratio [OR] 1.7; 95% confidence interval [CI] 1.3-2.2), Hispanic (OR 2.1; 95% CI 1.4-3.2) or black (OR 1.8; 95% CI 1.2-2.7) race/ethnicity, and Medicaid enrollment (OR 1.5; 95% CI 1.1-2.0). Feeding practices modified the risk of intussusception. Interaction was found between introduction of solid food (ISF) and type of formula consumption. Using breast milk as the referent group, infants with ISF for at least 5 weeks who consumed soy milk-based formula had a lower risk (OR 0.26; 95% CI 0.1-0.7) and infants without ISF who consumed cow's-milk formula had an increased risk (OR 2.33; 95% CI 1.4-3.9). CONCLUSIONS: Risk of intussusception among US infants varies based on sociodemographic characteristics and feeding patterns.

Prevention of pertussis, tetanus, and diphtheria among pregnant and postpartum women and their infants recommendations of the Advisory Committee on Immunization Practices (ACIP).

In 2005, two tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis (Tdap) vaccines were licensed and recommended for use in adults and adolescents in the United States: ADACEL (sanofi pasteur, Swiftwater, Pennsylvania), which is licensed for use in persons aged 11--64 years, and BOOSTRIX (GlaxoSmithKline Biologicals, Rixensart, Belgium), which is licensed for use in persons aged 10-18 years. Both Tdap vaccines are licensed for single-dose use to add protection against pertussis and to replace the next dose of tetanus and diphtheria toxoids vaccine (Td). Available evidence does not address the safety of Tdap for pregnant women, their fetuses, or pregnancy outcomes sufficiently. Available data also do not indicate whether Tdap-induced transplacental maternal antibodies provide early protection against pertussis to infants or interfere with an infant's immune responses to routinely administered pediatric vaccines. Until additional information is available, CDC's Advisory Committee on Immunization Practices recommends that pregnant women who were not vaccinated previously with Tdap: 1) receive Tdap in the immediate postpartum period before discharge from hospital or birthing center, 2) may receive Tdap at an interval as short as 2 years since the most recent Td vaccine, 3) receive Td during pregnancy for tetanus and diphtheria protection when indicated, or 4) defer the Td vaccine indicated during pregnancy to substitute Tdap vaccine in the immediate postpartum period if the woman is likely to have sufficient protection against tetanus and diphtheria. Although pregnancy is not a contraindication for receiving Tdap vaccine, health-care providers should weigh the theoretical risks and benefits before choosing to administer Tdap vaccine to a pregnant woman. This report 1) describes the clinical features of pertussis, tetanus, and diphtheria among pregnant and postpartum women and their infants, 2) reviews available evidence of pertussis vaccination during pregnancy as a strategy to prevent infant pertussis, 3) summarizes Tdap vaccination policy in the United States, and 4) presents recommendations for use of Td and Tdap vaccines among pregnant and postpartum women.

Infant and maternal risk factors for pertussis-related infant mortality in the United States, 1999 to 2004.

BACKGROUND: Infants aged <12 months have the highest rates of complications and death from pertussis of any age group. Factors that increase the risk of pertussis-related death in infants are not well defined. METHODS: The US Multiple Cause-of-Death and Linked Birth/Infant Death databases were used for 1999 to 2004 to examine pertussis-related infant mortality rates and to obtain anonymous records of infants with pertussis listed as a cause of death and of surviving infants. Infant and maternal characteristics present at the time of birth for infants who died with pertussis were compared with those of surviving infants. RESULTS: During 1999 to 2004, 91 infant deaths were reported with pertussis as a cause of death. All infants were 7 months or younger; 58% were age <2 months. The average annual infant mortality rate attributed to pertussis was 3.8 (95% CI: 3.0-4.6) per 1,000,000 live births, and 13.1 (95% CI: 9.8-17.1) per 1,000,000 live births for infants aged <2 months. Infant pertussis deaths showed an independent association with birth weight <2500 g, female sex, Apgar score <8, and mother with <12 years education. The mortality rate among Hispanic infants aged <2 months was 2.6 times greater than among non-Hispanic infants of similar age. CONCLUSIONS: Ensuring pertussis booster vaccination of adults and adolescents in close contact with an infant is warranted to prevent transmission of pertussis to vulnerable infants, particularly infants too young to be immunized. Special emphasis should be given to women and infant settings in which the risk of infant pertussis death might be increased.

Estimating Annual Births to Hepatitis B Surface Antigen-Positive Women in the United States by Using Data on Maternal Country of Birth.

OBJECTIVE: A national estimate of births to hepatitis B surface antigen (HBsAg)-positive women can help public health programs plan surveillance, educational, and outreach activities to improve identification and management of at-risk women and infants. Stratifying mothers by country of birth allows for the application of region-specific HBsAg prevalence estimates, which can more precisely estimate the number of at-risk infants. The objective of our study was to estimate the number of births to HBsAg-positive women in the United States with more granularity than previous models. METHODS: We developed a model that incorporated maternal country of birth (MCOB) and updated HBsAg prevalence estimates. We assessed birth certificate data by MCOB, and we stratified US-born mothers by race/ethnicity, US territory-born mothers by territory, and non-US-born mothers by region. We multiplied and summed data in each subcategory by using HBsAg prevalence estimates calculated from the 2009-2014 National Health and Nutrition Examination Surveys or Perinatal Hepatitis B Prevention Program. We compared the findings of our MCOB model with a race/ethnicity model. RESULTS: In 2015, an estimated 20 678 infants were born to HBsAg-positive women in the United States, representing 0.5% of all births. Births to US-born and non-US-born women comprised 77.2% and 21.5% of all births, respectively, and 40.1% and 57.9% of estimated births to HBsAg-positive women, respectively. The estimated contribution of births to HBsAg-positive women varied by MCOB region, from 4 (0.03%) infants born to women from Australia/Oceania to 5795 (28.0%) infants born to women from East Asia. Our MCOB model estimated 5666 fewer births to HBsAg-positive women than did the race/ethnicity model. CONCLUSIONS: As global vaccine programs reduce HBsAg prevalence, the MCOB model can incorporate evolving HBsAg prevalence estimates for women from various regions of the world.

Pertussis-associated hospitalizations in American Indian and Alaska Native infants.

OBJECTIVE: To investigate the burden of pertussis in American Indian and Alaska Native (AI/AN) infants. STUDY DESIGN: AI/AN pertussis-associated hospitalizations between 1980 and 2004 were evaluated using Indian Health Service (IHS)/tribal inpatient data, which include all reported hospitalizations within the IHS/tribal health care system. RESULTS: Between 1980 and 2004, 483 pertussis-associated hospitalizations in AI/AN infants were documented; 88% of cases involved infants age < 6 months. For this entire period, the average annual hospitalization rate was 132.7 per 100,000 AI/AN infants (95% confidence interval [CI] = 121.3 to 145.2), and 234.5 per 100,000 AI/AN infants age < 6 months (95% CI = 213.1 to 258.1). Between 2000 and 2004, the annual hospitalization rate was 100.5 per 100,000 AI/AN infants (95% CI = 81.6 to 123.7), which exceeds the estimated 2003 pertussis hospitalization rate of 67.7 per 100,000 in the general US infant population (95% CI = 61.9 to 73.5). The highest pertussis hospitalization rates in 2000 to 2004 were in AI/AN infants in the Alaska and Southwestern IHS regions of the United States. CONCLUSIONS: The burden of pertussis in AI/AN infants is high, particularly so in infants age < 6 months in the Alaska and the Southwestern IHS regions of the United States. Ensuring implementation of vaccination strategies to reduce the incidence of pertussis in AI/AN, infants, adolescents, and adults alike is warranted to reduce the burden of pertussis in AI/AN infants.

Preventing tetanus, diphtheria, and pertussis among adults: use of tetanus toxoid, reduced diphtheria toxoid and acellular pertussis vaccine recommendations of the Advisory Committee on Immunization Practices (ACIP) and recommendation of ACIP, supported by the Healthcare Infection Control Practices Advisory Committee (HICPAC), for use of Tdap among health-care personnel.

On June 10, 2005, a tetanus toxoid, reduced diphtheria toxoid and acellular pertussis vaccine (Tdap) formulated for use in adults and adolescents was licensed in the United States for persons aged 11-64 years (ADACEL, manufactured by sanofi pasteur, Toronto, Ontario, Canada). Prelicensure studies demonstrated safety and efficacy, inferred through immunogenicity, against tetanus, diphtheria, and pertussis when Tdap was administered as a single booster dose to adults. To reduce pertussis morbidity among adults and maintain the standard of care for tetanus and diphtheria prevention and to reduce the transmission of pertussis to infants and in health-care settings, the Advisory Committee on Immunization Practices (ACIP) recommends that: 1) adults aged 19-64 years should receive a single dose of Tdap to replace tetanus and diphtheria toxoids vaccine (Td) for booster immunization against tetanus, diphtheria, and pertussis if they received their last dose of Td >or=10 years earlier and they have not previously received Tdap; 2) intervals shorter than 10 years since the last Td may be used for booster protection against pertussis; 3) adults who have or who anticipate having close contact with an infant aged <12 months (e.g., parents, grandparents aged <65 years, child-care providers, and health-care personnel) should receive a single dose of Tdap to reduce the risk for transmitting pertussis. An interval as short as 2 years from the last Td is suggested; shorter intervals can be used. When possible, women should receive Tdap before becoming pregnant. Women who have not previously received Tdap should receive a dose of Tdap in the immediate postpartum period; 4) health-care personnel who work in hospitals or ambulatory care settings and have direct patient contact should receive a single dose of Tdap as soon as feasible if they have not previously received Tdap. An interval as short as 2 years from the last dose of Td is recommended; shorter intervals may be used. These recommendations for use of Tdap in health-care personnel are supported by the Healthcare Infection Control Practices Advisory Committee (HICPAC). This statement 1) reviews pertussis, tetanus and diphtheria vaccination policy in the United States; 2) describes the clinical features and epidemiology of pertussis among adults; 3) summarizes the immunogenicity, efficacy, and safety data of Tdap; and 4) presents recommendations for the use of Tdap among adults aged 19-64 years.

Preventing tetanus, diphtheria, and pertussis among adolescents: use of tetanus toxoid, reduced diphtheria toxoid and acellular pertussis vaccines recommendations of the Advisory Committee on Immunization Practices (ACIP).

During spring 2005, two tetanus toxoid, reduced diphtheria toxoid and acellular pertussis vaccine (Tdap) products formulated for use in adolescents (and, for one product, use in adults) were licensed in the United States (BOOSTRIX, GlaxoSmithKline Biologicals, Rixensart, Belgium [licensed May 3, 2005, for use in persons aged 10-18 years], and ADACEL, sanofi pasteur, Toronto, Ontario, Canada [licensed June 10, 2005, for use in persons aged 11-64 years]). Prelicensure studies demonstrated safety and efficacy against tetanus, diphtheria, and pertussis when Tdap was administered as a single booster dose to adolescents. To reduce pertussis morbidity in adolescents and maintain the standard of care for tetanus and diphtheria protection, the Advisory Committee on Immunization Practices (ACIP) recommends that: 1) adolescents aged 11-18 years should receive a single dose of Tdap instead of tetanus and diphtheria toxoids vaccine (Td) for booster immunization against tetanus, diphtheria, and pertussis if they have completed the recommended childhood diphtheria and tetanus toxoids and whole cell pertussis vaccine (DTP)/ diphtheria and tetanus toxoids and acellular pertussis vaccine (DTaP) vaccination series (five doses of pediatric DTP/DTaP before the seventh birthday; if the fourth dose was administered on or after the fourth birthday, the fifth dose is not needed) and have not received Td or Tdap. The preferred age for Tdap vaccination is 11-12 years; 2) adolescents aged 11-18 years who received Td, but not Tdap, are encouraged to receive a single dose of Tdap to provide protection against pertussis if they have completed the recommended childhood DTP/DTaP vaccination series. An interval of at least 5 years between Td and Tdap is encouraged to reduce the risk for local and systemic reactions after Tdap vaccination. However, an interval less than 5 years between Td and Tdap can be used; and 3) vaccine providers should administer Tdap and tetravalent meningococcal conjugate vaccine (Menactra, sanofi pasteur, Swiftwater, Pennsylvania) to adolescents aged 11-18 years during the same visit if both vaccines are indicated and available. This statement 1) reviews tetanus, diphtheria and pertussis vaccination policy in the United States, with emphasis on adolescents; 2) describes the clinical features and epidemiology of pertussis among adolescents; 3) summarizes the immunogenicity, efficacy, and safety data of the two Tdap vaccines licensed for use among adolescents; and 4) presents recommendations for tetanus, diphtheria, and pertussis vaccination among adolescents aged 11-18 years.

Cost effectiveness of pertussis vaccination in adults.

BACKGROUND: Prior economic analyses have reached disparate conclusions about whether vaccinating adults against pertussis would be cost effective. Newly available data on pertussis incidence were used to evaluate the cost effectiveness of one-time adult vaccination and adult vaccination with decennial boosters. METHODS: A Markov model was used to calculate the health benefits, risks, costs, and cost effectiveness of the following strategies: (1) no adult pertussis vaccination, (2) one-time adult vaccination at 20-64 years, and (3) adult vaccination with decennial boosters. The impact of the severity of pertussis illness, vaccine adverse events, and herd immunity on model outcomes were also examined. RESULTS: At a disease incidence of 360 per 100,000, the one-time adult vaccination strategy would prevent 2.8 million cases, and the decennial vaccination strategy would prevent 8.3 million cases. As disease incidence varied from 10 to 500 per 100,000, the one-time adult vaccination strategy was projected to prevent 79,000 to 3.8 million adult pertussis cases, while the decennial vaccination program would prevent 239,000 to 11.4 million cases. A one-time adult vaccination strategy would result in 106 million people vaccinated, or approximately 64% of the adult cohort, for a total program cost of $2.1 billion, while a decennial vaccination strategy would cost $6.7 billion. The one-time and decennial booster vaccination strategies result in cost-effectiveness ratios of <$50,000 per quality-adjusted life year saved if disease incidence in adults were greater than 120 cases per 100,000 population. CONCLUSIONS: Routine vaccination of adults aged 20 to 64 years with combined tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis is cost effective if pertussis incidence in this age group is greater than 120 per 100,000 population.

Historical comparisons of morbidity and mortality for vaccine-preventable diseases in the United States.

CONTEXT: National vaccine recommendations in the United States target an increasing number of vaccine-preventable diseases for reduction, elimination, or eradication. OBJECTIVE: To compare morbidity and mortality before and after widespread implementation of national vaccine recommendations for 13 vaccine-preventable diseases for which recommendations were in place prior to 2005. DESIGN, SETTING, AND PARTICIPANTS: For the United States, prevaccine baselines were assessed based on representative historical data from primary sources and were compared to the most recent morbidity (2006) and mortality (2004) data for diphtheria, pertussis, tetanus, poliomyelitis, measles, mumps, rubella (including congenital rubella syndrome), invasive Haemophilus influenzae type b (Hib), acute hepatitis B, hepatitis A, varicella, Streptococcus pneumoniae, and smallpox. MAIN OUTCOME MEASURES: Number of cases, deaths, and hospitalizations for 13 vaccine-preventable diseases. Estimates of the percent reductions from baseline to recent were made without adjustment for factors that could affect vaccine-preventable disease morbidity, mortality, or reporting. RESULTS: A greater than 92% decline in cases and a 99% or greater decline in deaths due to diseases prevented by vaccines recommended before 1980 were shown for diphtheria, mumps, pertussis, and tetanus. Endemic transmission of poliovirus and measles and rubella viruses has been eliminated in the United States; smallpox has been eradicated worldwide. Declines were 80% or greater for cases and deaths of most vaccine-preventable diseases targeted since 1980 including hepatitis A, acute hepatitis B, Hib, and varicella. Declines in cases and deaths of invasive S pneumoniae were 34% and 25%, respectively. CONCLUSIONS: The number of cases of most vaccine-preventable diseases is at an all-time low; hospitalizations and deaths have also shown striking decreases.