Protection and antibody levels 35 years after primary series with hepatitis B vaccine and response to a booster dose.

BACKGROUND AND AIMS: The duration of protection from hepatitis B vaccination in children and adults is not known. In 1981, we used three doses of plasma-derived hepatitis B vaccine to immunize a cohort of 1578 Alaska Native adults and children from 15 Alaska communities who were ≥6 months old. APPROACH AND RESULTS: We tested persons for antibody to hepatitis B surface antigen (anti-HBs) levels 35 years after receiving the primary series. Those with levels <10 mIU/ml received one booster dose of recombinant hepatitis B vaccine 2-4 weeks later and were then evaluated on the basis of anti-HBs measurements 30 days postbooster. Among the 320 recruited, 112 persons had not participated in the 22- or 30-year follow-up study (group 1), and 208 persons had participated but were not given an HBV booster dose (group 2). Among the 112 persons in group 1 who responded to the original primary series, 53 (47.3%) had an anti-HBs level ≥10 mIU/ml. Among group 1, 73.7% (28 of 38) of persons available for a booster dose responded to it with an anti-HBs level ≥10 mIU/ml at 30 days. Initial anti-HBs level after the primary series was correlated with higher anti-HBs levels at 35 years. Among 8 persons who tested positive for antibody to hepatitis B core antigen, none tested positive for HBsAg or HBV DNA. CONCLUSIONS: Based on anti-HBs level ≥10 mIU/ml at 35 years and a 73.7% booster dose response, we estimate that 86% of participants had evidence of protection 35 years later. Booster doses are not needed in the general population at this time.

Hepatitis A vaccine immune response 22 years after vaccination.

In the United States, the incidence of hepatitis A virus (HAV) infection has been reduced through universal childhood vaccination. However, the duration of immunogenicity for the hepatitis A vaccine is not known. We report on the 22 year follow-up time point of a cohort of Alaska children who were randomized to three different vaccine schedules: A) 0, 1, and 2 months; B) 0, 1, and 6 months; and C) 0, 1, and 12 months. Among 46 participant available for follow-up, 40 (87%) maintained protective levels of anti-hepatitis A antibody. These results indicate that a supplemental booster dose is not yet necessary at or before the 22-year time point.

Prevalence of Helicobacter pylori among Alaskans: Factors associated with infection and comparison of urea breath test and anti-Helicobacter pylori IgG antibodies.

BACKGROUND: Helicobacter pylori is one of the most common human infections in the world, and studies in Alaska Native people, as well as other Indigenous peoples, have shown a high prevalence of this gastric infection. This study was undertaken to determine the prevalence of H. pylori infection by urea breath test (UBT) and anti- H. pylori IgG among Alaskans living in four regions of the state and to identify factors associated with infection. METHODS: A convenience sample of persons > 6 months old living in five rural and one urban Alaskan community were recruited from 1996 to 1997. Participants were asked about factors possibly associated with infection. Sera were collected and tested for anti- H. pylori IgG antibodies; a UBT was administered to participants > 5 years old. RESULTS: We recruited 710 people of whom 571 (80%) were Alaska Native and 467 (66%) were from rural communities. Rural residents were more likely to be Alaska Native compared with urban residents (P < .001). Of the 710 people, 699 (98%) had a serum sample analyzed, and 634 (97%) persons > 5 years old had a UBT performed. H. pylori prevalence was 69% by UBT and 68% by anti- H. pylori IgG. Among those with a result for both tests, there was 94% concordance. Factors associated with H. pylori positivity were Alaska Native racial status, age ≥ 20 years, rural region of residence, living in a crowded home, and drinking water that was not piped or delivered. CONCLUSIONS: Helicobacter pylori prevalence is high in Alaska, especially in Alaska Native persons and rural residents. Concordance between UBT and serology was also high in this group. Two socioeconomic factors, crowding and drinking water that was not piped or delivered, were found to be associated with H. pylori positivity.

Persistence of seropositivity among persons vaccinated for hepatitis A during infancy by maternal antibody status: 15-year follow-up.

UNLABELLED: The effect of passively transferred maternal antibody to hepatitis A virus (anti-HAV) on the duration of seropositivity after hepatitis A vaccination during infancy and early childhood is unclear. We obtained levels of anti-HAV at intervals through age 15-16 years among three groups of Alaskan Native children who initiated a two-dose inactivated hepatitis A vaccination series at ages 6 months (group 1), 12 months (group 2), and 15 months (group 3), each group randomized according to maternal anti-HAV status. Seropositivity (anti-HAV ≥20 mIU/mL) 30 years after the second vaccine dose among the three groups was predicted using a random effects model. One hundred eighty-three children participated in the study; follow-up did not differ significantly by vaccine group or maternal anti-HAV status. Although the frequency of seropositivity among all participants through age 10 years was high (100% among groups 2 and 3 and >90% among group 1), there was a decrease thereafter through age 15-16 years among group 1 children, who initiated vaccination at age 6 months (50%-75%), and among maternal anti-HAV-positive children in groups 2 and 3 (67%-87%), who initiated vaccination at ages 12 months and 15 months, respectively. Nonetheless, the model indicated that anti-HAV seropositivity should persist for ≥30 years after vaccination in 64% of all participants; among those seropositive at age 15-16 years, 84% were predicted to remain so for ≥30 years. CONCLUSION: Most children vaccinated during early childhood available for sampling maintained seropositivity through age 15-16 years; however, seropositivity was less frequent among those starting vaccination at age 6 months and among maternal antibody-positive participants who started vaccination at age 12 months or 15 months; overall, our findings support current vaccine recommendations and continued follow-up of this cohort.

Declines in traditional marine food intake and vitamin D levels from the 1960s to present in young Alaska Native women.

OBJECTIVE: To measure the trends in traditional marine food intake and serum vitamin D levels in Alaska Native women of childbearing age (20-29 years old) from the 1960s to the present. DESIGN: We measured a biomarker of traditional food intake, the δ15N value, and vitamin D level, as 25-hydroxycholecalciferol (25(OH)D3) concentration, in 100 serum samples from 20-29-year-old women archived in the Alaska Area Specimen Bank, selecting twenty-five per decade from the 1960s to the 1990s. We compared these with measurements of red-blood-cell δ15N values and serum 25(OH)D3 concentrations from 20-29-year-old women from the same region collected during the 2000s and 2010s in a Center for Alaska Native Health Research study. SETTING: The Yukon Kuskokwim Delta region of south-west Alaska. SUBJECTS: Alaska Native women (n 319) aged 20-29 years at the time of specimen collection. RESULTS: Intake of traditional marine foods, as measured by serum δ15N values, decreased significantly each decade from the 1960s through the 1990s, then remained constant from the 1990s through the present (F 5,306=77·4, P<0·0001). Serum vitamin D concentrations also decreased from the 1960s to the present (F 4,162=26·1, P<0·0001). CONCLUSIONS: Consumption of traditional marine foods by young Alaska Native women dropped significantly between the 1960s and the 1990s and was associated with a significant decline in serum vitamin D concentrations. Studies are needed to evaluate the promotion of traditional marine foods and routine vitamin D supplementation during pregnancy for this population.

Ascertainment of Alaska Native Stroke Incidence, 2005-2009: Lessons for Assessing the Global Burden of Stroke.

BACKGROUND: Stroke is a critical public health issue in the United States and globally. System models to optimally capture stroke incidence in rural and culturally diverse communities are needed. The epidemiological transition to a western lifestyle has been associated with an increased burden of vascular risk factors among Alaska Native (AN) people. The burden of stroke in AN communities remains understudied. METHODS: The Alaska Native Stroke Registry (ANSR) was designed to screen and capture all stroke cases between 2005 and 2009 through its integration into the existing single-payer Alaska Tribal Health System infrastructure. Registry staff received notification each time stroke International Classification of Diseases, Ninth Revision codes (430-436) were initiated anywhere in the system. Trained chart abstractors reviewed medical records to document incident strokes among AN patients, which were adjudicated. RESULTS: Between October 2005 and October 2009, over 2100 alerts were screened identifying 514 unique stroke cases, of which 372 were incident strokes. The average annual incidence of stroke (per 100,000) among AN adults was 190.6: 219.2 in men and 164.7 in women. Overall, the ischemic stroke incidence rate was 148.5 per 100,000 with men (184.6) having higher ischemic rates per 100,000 than women (118.3). Men have higher rates of ischemic stroke at all ages, whereas older women experienced higher rates of hemorrhagic strokes over the age of 75 years. CONCLUSIONS: We report a high rate of overall stroke, 190.6 per 100,000. The ANSR methods and findings have implications for other indigenous populations and for global health populations currently undergoing similar epidemiological transitions.

Antibody Levels and Protection After Hepatitis B Vaccine: Results of a 30-Year Follow-up Study and Response to a Booster Dose.

BACKGROUND: The duration of protection in children and adults resulting from hepatitis B vaccination is unknown. In 1981, we immunized a cohort of 1578 Alaska Native adults and children from 15 Alaska communities aged ≥6 months using 3 doses of plasma-derived hepatitis B vaccine. METHODS: Persons were tested for antibody to hepatitis B surface antigen (anti-HBs) levels 30 years after receiving the primary series. Those with levels <10 mIU/mL received 1 booster dose of recombinant hepatitis B vaccine 2-4 weeks later and were then evaluated on the basis of anti-HBs measurements 30 days after the booster. RESULTS: Among 243 persons (56%) who responded to the original primary series but received no subsequent doses during the 30-year period, 125 (51%) had an anti-HBs level ≥10 mIU/mL. Among participants with anti-HBs levels <10 mIU/mL who were available for follow-up, 75 of 85 (88%) responded to a booster dose with an anti-HBs level ≥10 mIU/mL at 30 days. Initial anti-HBs level after the primary series was correlated with higher anti-HBs levels at 30 years. CONCLUSIONS: Based on anti-HBs level ≥10 mIU/mL at 30 years and an 88% booster dose response, we estimate that ≥90% of participants had evidence of protection 30 years later. Booster doses are not needed.

Hepatocellular Carcinoma Risk in Alaska Native Children and Young Adults with Hepatitis B Virus: Retrospective Cohort Analysis.

OBJECTIVES: To evaluate the hepatocellular carcinoma (HCC) risk in Alaska Native children and young adults with hepatitis B virus (HBV). STUDY DESIGN: Retrospective analysis of a population-based cohort of Alaska Native persons with HBV followed during 1982-2012. All individuals with HBV were offered HCC screening regardless of age using alpha-fetoprotein every 6 months; persons with an elevated alpha-fetoprotein or persons at high-risk for HCC, such as cirrhosis, family history of HCC, were offered ultrasound. We calculated the HCC incidence/1000 person-years from date of cohort entry until death, diagnosis of HCC, or attaining the age of 40 years (males) or 50 years (females). RESULTS: We followed 1083 subjects with HBV (56% male) comprising 5 genotypes (A2 [12.5%], B6 [1.7%], C [5.3%], D [49.7%], F1 [18.6%], unknown [12.4%]) for a median of 23.4 years/person. We observed 22 HCC cases (incidence/1000 person-years follow-up: 1.0); 19 HCC cases among persons with genotype F1. There was no significant difference in HCC incidence between males (1.4) and females (0.6). The HCC incidence was significantly higher for persons with genotype F1 (4.4) compared with genotype A2 (0.4) and D (0.2) and remained higher among persons with HBV genotype F1 excluding persons with HCC family history/cirrhosis (1.9). CONCLUSIONS: Alaska Native children and young adults with HBV genotype F1 are at high risk for HCC and should receive HCC surveillance. For males <40 years of age and females <50 years of age with HBV in regions of the world with a high genotype F prevalence, testing/confirming genotype F can identify persons who could benefit from HCC surveillance.

The changing epidemiology and aetiology of hepatocellular carcinoma from 1969 through 2013 in Alaska Native people.

BACKGROUND & AIMS: Alaska Native people have an increased rate of hepatocellular carcinoma compared to the United States population. Viral hepatitis is a risk factor for malignancy and the leading cause of hepatocellular carcinoma in Alaska. With the introduction of hepatitis B immunization in 1982, as well as the emergence of hepatitis C virus in this population, the epidemiology and aetiology of hepatocellular carcinoma in Alaska have changed. METHODS: Using the Alaska Native Tumor Registry, all cases of viral and non-viral hepatocellular carcinoma occurring from 1969 through 2013 were identified and reviewed. Incidence rates per 100 000 population were calculated for hepatocellular carcinoma overall and by aetiological category. RESULTS: One hundred and fifty-two cases of hepatocellular carcinoma were identified in 148 Alaska Native persons. Overall tumour rate was 3.82 per 100 000 and did not change significantly over the study period. Hepatitis B-associated cases decreased significantly over the study period (P = 0.048) and were eliminated in persons under the age of 20. Hepatitis C-associated cases increased significantly (P < 0.001). Undetermined hepatocellular carcinoma rates also decreased (P = 0.034). CONCLUSIONS: Overall hepatocellular carcinoma rates in Alaska Native people remained stable over the study period, but the epidemiology and aetiology are changing. Two decades after routine hepatitis B immunization, the hepatocellular carcinoma age distribution has shifted to cases presenting later in life. This is consistent with an ageing hepatitis B-infected population with no new infected young persons' coming into the population, as well as the emergence of hepatitis C in adults.

Incidence of hepatocellular carcinoma according to hepatitis B virus genotype in Alaska Native people.

BACKGROUND & AIMS: Most regions of the world have ≤3 co-circulating hepatitis B virus (HBV) genotypes, which limits direct comparisons of hepatocellular carcinoma (HCC) risk among HBV-infected persons by genotype. We evaluated HCC incidence by HBV genotype in a cohort of Alaska Native (AN) persons where five HBV genotypes (A, B, C, D, F) have been identified. METHODS: Our cohort comprised AN persons with chronic HBV infection identified during 1983-2012 who consented to participate in this study. Cohort persons were offered annual hepatitis B e antigen (HBeAg) testing and semi-annual HCC screening. We developed a logistic regression model to compare HCC risk by genotype, adjusting for age, sex, region and HBeAg status. RESULTS: Among the 1235 consenting study participants, 711 (57.6%) were male, 510 (41.3%) were HBeAg positive at cohort entry and 43 (3.5%) developed HCC. The HBV genotype was known for 1142 (92.5%) persons (13.5% A, 3.9% B, 6.7% C, 56.9% D, 19.0% F). The HCC incidence/1000 person-years of follow-up for genotypes A, B, C, D and F was 1.3, 0, 5.5, 0.4 and 4.2 respectively. Compared with persons with HBV genotype B/D infection, the HCC risk was higher for persons with genotypes A [adjusted odds ratio (aOR): 3.9, 95% confidence interval (CI): 1.14-13.74], C (aOR: 16.3, 95% CI: 5.20-51.11) and F (aOR: 13.9, 95% CI: 5.30-36.69). CONCLUSION: HBV genotype is independently associated with HCC risk. AN persons with genotypes A, C and F are at higher risk compared with genotypes B or D.

Prevalence and causes of elevated serum aminotransferase levels in a population-based cohort of persons with chronic hepatitis B virus infection.

BACKGROUND & AIMS: Information delineating the possible causes for elevated serum aminotransferase activity among persons with chronic hepatitis B virus (HBV) infection is limited. METHODS: We analysed data collected from a population-based cohort of persons with chronic HBV infection followed from 2001 to 2010 to determine the frequency and causes of elevated aminotransferase activity. Any elevation concurrent with an HBV DNA level ⩾2000 IU/ml was attributed to immune active hepatitis B. Participant medical charts were reviewed by expert clinical staff to determine the presence of additional or alternative attributable causes. For each participant, a serum aminotransferase elevation could be attributed to more than one cause. RESULTS: Among 1090 persons with chronic HBV infection, the mean follow-up was 7.7 years and the median age in 2001 was 39 (range 19-96) years; 634 (58.2%) had ⩾1 elevated aminotransferase level during follow-up and 438 (69.1%) of persons with ⩾1 elevation had at least one cause assigned for the elevation. The most common causes of aminotransferase elevations were immune active hepatitis B (48.4%), alcohol consumption (30.8%), and non-alcoholic fatty liver disease (NAFLD) (24.7%). Among participants with HBV DNA levels persistently less than 2000 IU/ml, the most common causes were NAFLD or alcohol consumption. CONCLUSIONS: In this population-based cohort of persons with chronic HBV infection, the prevalence of elevated aminotransferase activity was high and attributable to immune active chronic hepatitis B in approximately half of the cases; however, NAFLD or alcohol consumption were also common causes for enzyme elevations. These findings underscore the importance of monitoring HBV DNA levels, in addition to aminotransferase activity, among persons with chronic HBV infection so that appropriate interventions, including antiviral therapy, are utilised.

Relationship between level of hepatitis B virus DNA and liver disease: a population-based study of hepatitis B e antigen-negative persons with hepatitis B.

BACKGROUND & AIMS: There is little information on the proportion of persons with chronic hepatitis B virus (HBV) infection with active hepatitis. We aimed to determine the proportion of persons with hepatitis B e antigen-negative chronic HBV infection who develop immune-active HBV infection over time and the relationship between demographic and viral factors on severity of disease on liver biopsy. METHODS: We performed a longitudinal population-based cohort study of 754 Alaska Native patients with chronic HBV infection. Levels of alanine aminotransferase (ALT) were measured every 6 months, and levels of HBV DNA were measured at study entry and whenever ALT levels exceeded the upper limit of normal (ULN). Immune-active chronic HBV infection was defined as levels of ALT ≥ 30 U/L in men and >20 U/L in women and levels of HBV DNA >2000 IU/mL at 1 or more time points from 2001-2008. Liver biopsies were scored by using the modified histology activity index score of Knodell and the Ishak fibrosis score. RESULTS: Of the study participants, 186 (25%) met the criteria for immune-active HBV, 56% of these initially and 44% later during follow up. Of the 38 patients with liver biopsy results, only 1 of 16 with ALT levels consistently below twice the ULN and 1 of 19 with HBV DNA between 2000 and 20,000 IU/mL, vs 12 of 22 (55%) with ALT > twice ULN (P = .002) and 11 of 18 (61%) with 1 or more measurements of HBV DNA >20,000 IU/mL (P < .001), had moderate or severe hepatitis or fibrosis. CONCLUSIONS: In a cohort of Alaska Natives with chronic HBV infection, 25% met criteria for immune-active HBV. There is a low probability of advanced fibrosis if levels of HBV DNA never exceed 20,000 IU/mL.

Long-term immunogenicity of hepatitis A virus vaccine in Alaska 17 years after initial childhood series.

The Centers for Disease Control and Prevention recommends hepatitis A virus (HAV) vaccination for all children at age 1 year and for high-risk adults. The vaccine is highly effective; however, protection duration is unknown. We report HAV antibody concentrations 17 years after childhood immunization, demonstrating that protective antibody levels remain and have stabilized over the past 7 years.

Application of COVIDTracer to Inform Public Health Workforce Planning in Alaska During the COVID-19 Pandemic.

The COVID-19 pandemic has caused social and economic disruption worldwide and spurred numerous mitigation strategies, including state investments in training a large contact tracing and case investigation workforce. A team at the University of Alaska Anchorage evaluated implementation of the COVID-19 contact tracing and case investigation program of the State of Alaska Department of Health and Social Services, Division of Public Health, Section of Public Health Nursing. As part of that evaluation, the team used COVIDTracer, a spreadsheet modeling tool. COVIDTracer generated projections of COVID-19 case counts that informed estimates of workforce needs and case prioritization strategies. Case count projections approximated the reported epidemiologic curve with a median 7% difference in the first month. The accuracy of case count predictions declined after 1 month with a median difference of 80% in the second month. COVIDTracer inputs included previous case counts, the average length of time for telephone calls to cases and outreach to identified contacts, and the average number of contacts per case. As each variable increased, so too did estimated workforce needs. Decreasing the average time from exposure to outreach from 10 to 5 days reduced case counts estimated by COVIDTracer by approximately 93% during a 5-month period. COVIDTracer estimates informed Alaska's workforce planning and decisions about prioritizing case investigation during the pandemic. Lessons learned included the importance of being able to rapidly scale up and scale down workforce to adjust to a dynamic crisis and the limitations of prediction modeling (eg, that COVIDTracer was accurate for only about 1 month into the future). These findings may be useful for future pandemic preparedness planning and other public health emergency response activities.

An Investigation of Pediatric Case-patients With Invasive Haemophilus influenzae in Alaska, 2005-2011.

BACKGROUND: Haemophilus influenzae (Hi) can cause severe disease in children. This study aimed to identify risk factors related to invasive Hi disease in Alaska children and evaluate carriage in people around them. METHODS: From 2005 to 2011, we investigated episodes of invasive, typeable Hi disease in Alaska children <10 years old. Three age-matched control children were enrolled for each case-patient. We evaluated oropharyngeal Hi carriage in people in close contact with Hi case-patients (contacts) as well as control children and their household members. Individual and household risk factors for illness and carriage were evaluated using questionnaires and chart reviews. RESULTS: Thirty-eight of 44 (86%) children with invasive, typeable Hi disease were recruited: 20 Hi serotype a (53%), 13 serotype b (Hib) (34%) and 5 serotype f (13%). Children with the invasive Hi disease were more likely than controls to have underlying health problems (67% vs. 24%, P = 0.001), other carriers of any Hi in their household (61% vs. 15%, P < 0.001), and inadequate Hib vaccination (26% vs. 9%, P = 0.005). People who carried Hi were younger than noncarriers (mean 12.7 vs. 18.0 years, P = 0.008). The carriage was clustered within case-patient households, with carriage in 19% of household contacts, while only 6.3% of nonhousehold contacts and 5.5% of noncontacts carried the Hi serotype of interest ( P < 0.001). CONCLUSIONS: Factors associated with invasive Hi disease in children included underlying health problems, household carriage and inadequate Hib vaccination. The high level of carriage in case-patient households is important to consider when evaluating treatment and prophylaxis strategies.

Molecular resistance mechanisms of macrolide-resistant invasive Streptococcus pneumoniae isolates from Alaska, 1986 to 2010.

The rapid emergence of antibiotic-resistant pneumococcal strains has reduced treatment options. The aim of this study was to determine antimicrobial susceptibilities, serotype distributions, and molecular resistance mechanisms among macrolide-resistant invasive pneumococcal isolates in Alaska from 1986 to 2010. We identified cases of invasive pneumococcal disease in Alaska from 1986 to 2010 through statewide population-based laboratory surveillance. All invasive pneumococcal isolates submitted to the Arctic Investigations Program laboratory were confirmed by standard microbiological methods and serotyped by slide agglutination and the Quellung reaction. MICs were determined by the broth microdilution method, and macrolide-resistant genotypes were determined by multiplex PCR. Among 2,923 invasive pneumococcal isolates recovered from 1986 to 2010, 270 (9.2%) were nonsusceptible to erythromycin; 177 (66%) erythromycin-nonsusceptible isolates demonstrated coresistance to penicillin, and 167 (62%) were multidrug resistant. The most frequent serotypes among the macrolide-resistant isolates were serotypes 6B (23.3%), 14 (20.7%), 19A (16.7%), 9V (8.9%), 19F (6.3%), 6A (5.6%), and 23F (4.8%). mef and erm(B) genes were detected in 207 (77%) and 32 (12%) of the isolates, respectively. Nineteen (7%) of the erythromycin-nonsusceptible isolates contained both mef and erm(B) genotypes; 15 were of serotype 19A. There was significant year-to-year variation in the proportion of isolates that were nonsusceptible to erythromycin (P < 0.001). Macrolide resistance among pneumococcal isolates from Alaska is mediated predominantly by mef genes, and this has not changed significantly over time. However, there was a statistically significant increase in the proportion of isolates that possess both erm(B) and mef, primarily due to serotype 19A isolates.

Persistence of hepatitis A vaccine induced seropositivity in infants and young children by maternal antibody status: 10-year follow-up.

UNLABELLED: Persistence of seropositivity conferred by hepatitis A vaccine administered to children <2 years of age is unknown and passively transferred maternal antibodies to hepatitis A virus (maternal anti-HAV) may lower the infant's immune response to the vaccine. One hundred ninety-seven infants and young children were randomized into three groups to receive a two-dose hepatitis A vaccine: group 1 at 6 and 12 months, group 2 at 12 and 18 months, and group 3 at 15 and 21 months of age. Within each group, infants were randomized by maternal anti-HAV status. Anti-HAV levels were measured at 1 and 6 months and at 3, 5, 7, and 10 years after the second dose of hepatitis A vaccination. Children in all groups had evidence of seroprotection (>10 mIU/mL) at 1 month after the second dose. At 10 years, all children retained seroprotective anti-HAV levels except for only 7% and 11% of children in group 1 born to anti-HAV-negative and anti-HAV-positive mothers, respectively, and 4% of group 3 children born to anti-HAV-negative mothers. At 10 years, children born to anti-HAV-negative mothers in group 3 had the highest geometric mean concentration (GMC) (97 mIU/mL; 95% confidence interval, 71-133 mIU/mL) and children born to anti-HAV-positive mothers in group 1 had the lowest GMC (29 mIU/mL; 95% confidence interval, 20-40 mIU/mL). Anti-HAV levels through 10 years of age correlated with initial peak anti-HAV levels (tested at 1 month after the second dose). CONCLUSION: The seropositivity induced by hepatitis A vaccine given to children <2 years of age persists for at least 10 years regardless of presence of maternal anti-HAV.

Modeling insights into Haemophilus influenzae type b disease, transmission, and vaccine programs.

In response to the 2007-2009 Haemophilus influenzae type b (Hib) vaccine shortage in the United States, we developed a flexible model of Hib transmission and disease for optimizing Hib vaccine programs in diverse populations and situations. The model classifies population members by age, colonization/disease status, and antibody levels, with movement across categories defined by differential equations. We implemented the model for the United States as a whole, England and Wales, and the Alaska Native population. This model accurately simulated Hib incidence in all 3 populations, including the increased incidence in England/Wales beginning in 1999 and the change in Hib incidence in Alaska Natives after switching Hib vaccines in 1996. The model suggests that a vaccine shortage requiring deferral of the booster dose could last 3 years in the United States before loss of herd immunity would result in increasing rates of invasive Hib disease in children <5 years of age.

Elimination of hepatocellular carcinoma and acute hepatitis B in children 25 years after a hepatitis B newborn and catch-up immunization program.

UNLABELLED: Alaska Native people experience the highest rates of acute and chronic hepatitis B virus (HBV) infection and hepatocellular carcinoma (HCC) in the United States. We examined the effect of a universal newborn immunization with hepatitis B vaccine and mass population screening immunization program initiated in 1984 on rates of HBV and HCC in children 25 years later. During this time, the population of Alaska Native people grew from an estimated 75,000 to 130,000 persons. A surveillance system to detect acute HBV infection in Alaska Native facilities was established in 1981. Cases of HCC in children under 20 years of age were identified using a National Cancer Institute (NCI)-funded Cancer Registry established in 1969 coupled with an active surveillance program of screening persons with chronic HBV semiannually for alpha-fetoprotein since 1982. The incidence of acute symptomatic HBV infection in persons <20 years of age fell from cases 19/100,000 in 1981-1982 to 0/100,000 in 1993-1994. No cases of acute HBV have occurred in children since 1992. The incidence of HCC in persons <20 years decreased from 3/100,000 in 1984-1988 to zero in 1995-1999 and no cases have occurred since 1999. The number of identified hepatitis B surface antigen-positive children <20 years in the Alaska Native population declined from 657 in 1987 to two in 2008. CONCLUSION: Universal newborn vaccination coupled with mass screening and immunization of susceptible Alaska Natives has eliminated HCC and acute symptomatic HBV infection among Alaska Native children and this approach is the best way to prevent HBV-related disease in children.