Persistence of antibody to Hepatitis A virus 20 years after receipt of Hepatitis A vaccine in Alaska.

Hepatitis A vaccine is recommended for children ≥1 year old to prevent hepatitis A virus (HAV) infection. However, the duration of vaccine-induced immunity is unknown. We evaluated a cohort of Alaska Native persons 20 years after HAV vaccination. Children aged 3-6 years had been previously randomized to receive three doses of HAV vaccine (360 ELISA units/dose) at: (i) 0,1,2 months; (ii) 0,1,6 months; and (iii) 0,1,12 months. We measured anti-HAV antibody concentrations every 2-3 years; described geometric mean concentrations (GMC) and the proportion with protective antibody (≥20 mIU mL-1 ) over time; and modelled the change in GMC using fractional polynomial regression. Of the 144 participants, after 20 years 52 (36.1%) were available for the follow-up (17, 18, 17 children in Groups A, B and C, respectively). Overall, 46 (88.5%) of 52 available participants had anti-HAV antibody concentrations ≥20 mIU mL-1 , and overall GMC was 107 mIU mL-1 . Although GMC levels were lower in Group A (60; CI 34-104) than in Group B (110; CI 68-177) or Group C (184; CI 98-345) (B vs C: P=.168; A vs B/C: P=.011), there was no difference between groups after adjusting for peak antibody levels post-vaccination (P=.579). Models predicted geometric mean concentrations of 124 mIU mL-1 after 25 years, and 106 mIU mL-1 after 30 years. HAV vaccine provides protective antibody levels 20 years after childhood vaccination. Lower antibody levels in Group A may be explained by a lower initial peak response. Our results suggest a booster vaccine dose is unnecessary for at least 25-30 years.

The diagnosis and treatment of Helicobacter pylori infection in Arctic regions with a high prevalence of infection: Expert Commentary.

Helicobacter pylori infection is a major cause of peptic ulcer and is also associated with chronic gastritis, mucosa-associated lymphoid tissue (MALT) lymphoma, and adenocarcinoma of the stomach. Guidelines have been developed in the United States and Europe (areas with low prevalence) for the diagnosis and management of this infection, including the recommendation to 'test and treat' those with dyspepsia. A group of international experts performed a targeted literature review and formulated an expert opinion for evidenced-based benefits and harms for screening and treatment of H. pylori in high-prevalence countries. They concluded that in Arctic countries where H. pylori prevalence exceeds 60%, treatment of persons with H. pylori infection should be limited only to instances where there is strong evidence of direct benefit in reduction of morbidity and mortality, associated peptic ulcer disease and MALT lymphoma and that the test-and-treat strategy may not be beneficial for those with dyspepsia.

Reinfection after successful eradication of Helicobacter pylori in three different populations in Alaska.

We performed a study to determine rates of reinfection in three groups followed for 2 years after successful treatment: American Indian/Alaska Native (AI/AN) persons living in urban (group 1) and rural (group 2) communities, and urban Alaska non-Native persons (group 3). We enrolled adults diagnosed with H. pylori infection based on a positive urea breath test (13C-UBT). After successful treatment was documented at 2 months, we tested each patient by 13C-UBT at 4, 6, 12 and 24 months. At each visit, participants were asked about medication use, illnesses and risk factors for reinfection. We followed 229 persons for 2 years or until they became reinfected. H. pylori reinfection occurred in 36 persons; cumulative reinfection rates were 14·5%, 22·1%, and 12·0% for groups 1, 2, and 3, respectively. Study participants who became reinfected were more likely to have peptic ulcer disease (P = 0·02), low education level (P = 0·04), or have a higher proportion of household members infected with H. pylori compared to participants who did not become reinfected (P = 0·03). Among all three groups, reinfection occurred at rates higher than those reported for other US populations (<5% at 2 years); rural AI/AN individuals appear to be at highest risk for reinfection.

Incidence of diabetes mellitus in a population-based cohort of persons with chronic hepatitis B virus infection.

To investigate the effect of hepatitis B virus (HBV) infection on the development of diabetes mellitus (DM), we compared DM incidence and characteristics of Alaska Native persons with and without HBV infection. From 1990 to 2010, there were 52 incident DM cases among 1309 persons with infection vs 4557 DM cases among 85 698 persons without infection (log-rank test, P = 0.20). Compared to infected persons without DM, those with DM were significantly older (57.0 vs 47.4 years, P < 0.001) and had higher body mass index (34.5 vs 28.4 kg/m(2) , P < 0.001). Genotype, immune active disease and the presence of cirrhosis were not associated with DM. In this population-based cohort with over 20 years of follow-up, there was no effect of HBV infection on DM development.

Genetic diversity of hepatitis B virus genotypes B6, D and F among circumpolar indigenous individuals.

Hepatitis B virus (HBV) infection is highly prevalent in circumpolar indigenous peoples. However, the clinical outcome is extremely variable, such that while hepatocellular carcinoma (HCC) is uncommon in Canadian Inuit, the incidence of HCC is slightly higher in Greenlanders than in Danes, and it is especially high in Alaskan Native people infected with HBV genotypes F (HBV/F) and C (HBV/C). These differences may be associated with the genomic variability of the predominant HBV genotype in each group. The purpose of this study was to determine the rate, nature and regional susceptibility of HBV genomic mutations among circumpolar indigenous individuals. Paired serum samples, separated by 5-6 years, were analysed from Canadian and Greenlandic Inuit infected with HBV genotype B6 (HBV/B6) and HBV/D, respectively, and from Alaskan Native people infected with HBV/F, each having subsequently developed HCC. Phylogenetic and mutational analyses were performed on full-genome sequences, and the dynamic evolution within the quasispecies population of each patient group was determined by clonal analysis of the non-overlapping core coding region. Mutations associated with severe outcomes predominated in HBV/F, mostly within the precore/core and PreS1 region. HBV/B6 genomes exhibited higher diversity compared to HBV/D and HBV/F, particularly within the core coding region. Thus, differing mutational profiles and genetic variability were observed among different HBV genotypes predominating in circumpolar indigenous patients. The unusual observation of persistently high genetic variability with HBV/B6 despite clinical inactivity could be due to the evolution of a host-pathogen balance, but other possible factors also need to be explored.

Is chronic hepatitis B being undertreated in the United States?

Chronic infection with the hepatitis B virus (HBV) is a major risk factor for development of end-stage liver disease, including cirrhosis, liver failure and primary liver cancer. There are now seven antiviral agents approved by the United States Food and Drug Administration (FDA) for the management of chronic HBV infection. Despite the fact that there are between 1.4 and 2 million chronic HBV infections in the United States, fewer than 50,000 people per year receive prescriptions for HBV antiviral medications. This report discusses possible explanations for the disparity between the number of people who are chronically infected and the number of people who receive treatment. Explanations for this incongruence include the potentially large number of infected persons who are unscreened and thus remain undiagnosed, and lack of access, including insurance, education and referral to appropriate medical care, particularly for disproportionately infected populations.

Hepatitis D outbreak among children in a hepatitis B hyper-endemic settlement in Greenland.

Hepatitis B virus (HBV) infection is endemic in Greenland with 5-10% of the population being HBsAg-positive (chronic carriers). Surprisingly, despite of the high prevalence of HBV infection, acute and chronic hepatitis B, liver cirrhosis and primary hepatocellular carcinoma appear much less frequently than expected. The reasons for the low frequencies are unknown, but as a consequence implementation of a childhood HBV vaccination programme, though debated for years, has never been instituted. We describe an outbreak of hepatitis D (HDV) infection among children in a hepatitis B hyper-endemic settlement of 133 inhabitants on the west coast of Greenland. In 2006 a total of 27% of the inhabitants were HBsAg-positive (chronic carriers) and 83% were HBcAb-positive (previously exposed). Forty-six percent of the HBsAg-positive persons were below 20 years of age. On follow-up 1 year later a total of 68% of the HBsAg-positive persons were HDV-IgG positive. Five children, who were HBsAg-positive in 2006, had HDV-seroconverted from 2006 to 2007, indicating a HDV-super-infection. Most of the HDV-IgG positive children had markedly elevated liver enzymes. In the multivariate analysis, among the HBV and HDV markers, presence of HDV-IgG was most strongly associated with elevation of liver enzymes. In conclusion, the HBV-HDV super-infection and presumed HDV outbreak in this settlement challenges the notion that HBV infection may not be as harmless in Greenland as previously anticipated. The findings strongly suggest that HBV vaccination should be included in the child-immunization program in Greenland.

Hepatitis B virus precore mutation and fulminant hepatitis in the United States. A polymerase chain reaction-based assay for the detection of specific mutation.

Hepatitis B virus (HBV) variants with precore mutation(s) resulting in the absence of HBeAg production have been associated with the occurrence of fulminant hepatitis in Japan, Israel, and southern Europe, where the prevalence of this HBV strain appears common. In areas such as United States, where HBV infection is not endemic, the role of this mutant virus in fulminant hepatitis is unknown. We developed an amplification refractory mutation detection system to detect specifically the presence of the G to A mutation at nucleotide position 1898, which is the most frequently observed mutation resulting in a precore stop codon. In addition, this method provided a quantitative measurement of the relative ratio of one strain to the other. Using this system, we tested HBV strains for the presence of the stop codon mutation in sera from 40 cases of fulminant hepatitis B occurring in the United States. Serum HBV DNAs from 28 patients were analyzed successfully. A mixture of wild-type and mutant strains in various ratios were observed in 15 patients, wild type exclusively in 11, and mutant exclusively in 2. Four of these patients had undergone liver transplantation for HBV-associated cirrhosis and developed fulminant HBV-associated hepatitis after transplantation. Pre- and posttransplant serum samples from one patient were analyzed: a mixture of wild-type and mutant HBV strains was detected in both samples. Our study demonstrated that both wild-type and mutant HBV strains are associated with fulminant hepatitis, and that in some patients in the United States, factors other than precore mutations contribute to the development of fulminant hepatitis.

Reinfection after successful eradication of Helicobacter pylori: a 2-year prospective study in Alaska Natives.

BACKGROUND: Limited information exists regarding risk factors for reinfection after cure of Helicobacter pylori infection. AIM: To determine the 2-year reinfection rate of H. pylori in a cohort of urban Alaska Natives. METHODS: Participants over 18 years of age undergoing oesophagogastroduodenoscopy had (13)C urea breath test, culture, CLOtest and histology performed. Those diagnosed with H. pylori who tested urea breath test-negative at 8 weeks after treatment were followed prospectively at 4 months, 6 months, 1 year and 2 years. Subjects experiencing H. pylori reinfection as defined by a positive urea breath test were compared with those who did not become reinfected using univariable and multivariable analysis. Risk of reinfection over time was estimated by the Kaplan-Meier method. RESULTS: Helicobacter pylori reinfection occurred in 14 of 98 subjects successfully treated. The cumulative reinfection rate was 5.1% (95% CI: 0.7%-9.5%) at 4 months, 7.2% (2.0-12.3%) at 6 months, 10.3% (4.2-16.3%) at 1-year and 14.5% (7.5-21.6%) at 2 years. In multivariable analysis, a history of previous peptic ulcer disease or presence of ulcer at time of study oesophagogastroduodenoscopy were the only risk factors associated with reinfection (P = 0.01). CONCLUSIONS: Based on the findings from our study, subjects with a history of or current peptic ulcer disease should be followed, after successful treatment for H. pylori, with periodic urea breath test to detect reinfection, as reinfection would put them at high risk for ulcer recurrence.

Nested case-control study: hepatocellular carcinoma risk after hepatitis B surface antigen seroclearance.

BACKGROUND: Hepatocellular carcinoma (HCC) risk after resolving chronic hepatitis B virus (HBV) infection is unclear. AIM: To compare HCC risk between Alaska Native (AN) patients with and without hepatitis B surface antigen (HBsAg) seroclearance. METHODS: We selected persons with (case-patients) and without (control-patients) HBsAg seroclearance from a cohort of 1346 chronically HBV-infected AN patients followed during 1982-2013. We attempted to match two control-patients/case-patient on sex, HBV genotype, and age. Person-years of follow-up for case-patients began on the date of HBsAg resolution and for control-patients began on the date equivalent to the cohort entry date plus the years of HBsAg duration for their corresponding case-patient. We compared HCC risk using a Cox proportional hazards model. RESULTS: The 238 case-patients (4 with HCC) and 435 control-patients (9 with HCC) were similar in age [P-value (P) = 0.30], sex (P = 0.53) and HBV genotype (P = 0.99). Case-patients had longer person-years of follow-up than control-patients (11.7 vs. 10.1 years; P = 0.04). The HCC rate/100 000 persons was similar between case- (132) and control-patients (178; P = 0.65). The adjusted hazard ratio comparing case- and control-patients was similar for HCC [0.7; 95% confidence interval (CI): 0.2-2.4], increased for each 1-year increment for age (1.1; CI: 1.0-1.1; P < 0.01), and was greater if the initial HBeAg was positive (3.5; CI: 1.1-11.0; P = 0.03). CONCLUSIONS: Hepatitis B surface antigen seroclearance was not associated with reduced HCC risk; the HCC risk estimates are limited by wide 95% confidence intervals. Persons meeting HCC surveillance indications prior to HBsAg seroclearance could benefit from continued surveillance after seroclearance.

Integrations of the hepatitis B virus (HBV) and human papillomavirus (HPV) into the human telomerase reverse transcriptase (hTERT) gene in liver and cervical cancers.

Chronic infections with the hepatitis B virus (HBV) and high-risk human papillomaviruses (HPVs) are important risk factors for hepatocellular carcinoma (HCC) and cervical cancer (CC), respectively. HBV and HPV are DNA viruses that almost invariably integrate into the host genome in invasive tumors. The viral integration sites occur throughout the genome, leading to the presumption that there are no preferred sites of integration. A number of viral integrations have been shown to occur within the vicinity of important cancer-related genes. In studies of HBV-induced HCC and HPV-induced CC, we have identified two HBV and three HPV integrations into the human telomerase reverse transcriptase (hTERT) gene. Detailed characterization of the integrations revealed that four integrations occurred within the hTERT promoter and upstream region and the fifth integration occurred in intron 3 of the hTERT gene. None of the integrations altered the hTERT coding sequence and all resulted in juxtaposition of viral enhancers near hTERT, with potential activation of hTERT expression. Our work supports the hypothesis that the sites of oncogenic viral integration are nonrandom and that genes at the sites of viral integration may play important roles in carcinogenesis.

Hepatitis B-related sequelae. Prospective study in 1400 hepatitis B surface antigen-positive Alaska native carriers.

A total 1400 hepatitis B surface antigen-positive Alaska natives, 824 men and 576 women of all ages, were followed up prospectively over a period of 7815 carrier years for the development of sequelae related to chronic hepatitis B virus infection. During the observation period, 20 cases of hepatocellular carcinoma, 14 cases of chronic active hepatitis, 8 cases of cirrhosis, and 1 case of glomerulonephritis developed in this cohort. The annual incidence of hepatocellular carcinoma was 387 per 100,000 for men and 63 per 100,000 for women. The incidence of chronic active hepatitis and cirrhosis was 193 and 107 per 100,000 in men and 158 and 95 per 100,000 in women, respectively. No cases of either essential mixed cryoglobulinemia or necrotizing vasculitis were seen. Sixty of the hepatitis B surface antigen-positive carriers died, with 13 (21.7%) of the deaths due to hepatocellular carcinoma. The leading cause of death in this group was malignant neoplasms compared with accidents in the general Alaska native population.

Protection provided by hepatitis B vaccine in a Yupik Eskimo population. Seven-year results.

The long-term immunogenicity and protection provided by a plasma-derived hepatitis B vaccine (Heptavax B) was determined in a cohort of susceptible persons immunized in 1981. In this study 1581 susceptible persons were immunized with the recommended three-dose regimen of hepatitis B vaccine. After 7 years, 74% of vaccinees retained antibody to hepatitis B surface antigen (anti-HBs) levels of 10 mIU/mL or more. Anti-HBs levels at 7 years varied inversely with age and directly with the level of anti-HBs attained 1 year after the first dose. During the 7 years after the first dose of vaccine, five vaccine responders and three other persons developed antibody to hepatitis B core antigen and their level of anti-HBs increased. None developed detectable hepatitis B surface antigen or clinical hepatitis. This update of an ongoing study continues to suggest that the risk of hepatitis B virus infection to most persons with an initial anti-HBs response to hepatitis B virus vaccine of 10 mIU/mL or greater is low, regardless of the initial antibody level.

Antimicrobial Resistance in Wildlife: Implications for Public Health.

The emergence and spread of antimicrobial-resistant (AMR) bacteria in natural environments is a major concern with serious implications for human and animal health. The aim of this study was to determine the prevalence of AMR Escherichia coli (E. coli) in wild birds and mammalian species. Thirty faecal samples were collected from each of the following wildlife species: herring gulls (Larus argentatus), black-headed gulls (Larus ridibundus), lesser black-back gulls (Larus fuscus), hybrid deer species (Cervus elaphus x Cervus nippon) and twenty-six from starlings (Sturnus vulgaris). A total of 115 E. coli isolates were isolated from 81 of 146 samples. Confirmed E. coli isolates were tested for their susceptibility to seven antimicrobial agents by disc diffusion. In total, 5.4% (8/146) of samples exhibited multidrug-resistant phenotypes. The phylogenetic group and AMR-encoding genes of all multidrug resistance isolates were determined by PCR. Tetracycline-, ampicillin- and streptomycin-resistant isolates were the most common resistant phenotypes. The following genes were identified in E. coli: bla(TEM), strA, tet(A) and tet(B). Plasmids were identified in all samples that exhibited multidrug-resistant phenotypes. This study indicates that wild birds and mammals may function as important host reservoirs and potential vectors for the spread of resistant bacteria and genetic determinants of AMR.

p53 is not mutated in hepatocellular carcinomas from Alaska Natives.

Hepatocellular carcinoma is common among Alaska Natives. The known risk factor in this population is hepatitis B viral infection; fungal toxins, including aflatoxin B1, have not been detected in foodstuffs. In this series of 14 patients (including 4 siblings and 2 second cousins), 3 patients were less than 12 years old at diagnosis of hepatocellular carcinoma, 8 patients were 13-24 years old, and 3 patients were more than 60 years old. Since p53 mutations occur in 29% of hepatocellular carcinomas worldwide, we tested the tumors for p53 mutations and serum samples for anti-p53 antibodies. Serum samples from these 14 patients did not contain detectable levels of anti-p53 antibodies. Loss of heterozygosity within the p53 locus was not detected in any of 9 informative cases. Immunohistochemical analysis for p53 protein accumulation was negative in all of 11 tumors. DNA sequence analysis of 12 tumor samples showed no evidence of p53 mutation in the highly conserved regions included in exons 5-8. These data, combined with one case from a previous report, indicate a mutation frequency of 0 of 13, which differs significantly from the worldwide frequency of 29% (chi 2 3.9; P = 0.048). These results indicate that liver carcinogenesis among Alaska Natives occurs independently of a traditional p53 pathway. The familial clustering and early onset in this population strongly suggest an inherited genetic predisposition to develop liver cancer. Germline mutations in a tumor suppressor or a cancer susceptibility gene are likely. Future studies of these samples should include investigations of candidate suppressor or susceptibility genes which map to chromosomal regions commonly deleted in liver cancers.

Frequency of adverse reactions to hepatitis B vaccine in 43,618 persons.

PURPOSE: To determine the incidence of adverse reactions to hepatitis B plasma-derived vaccine. PATIENTS: Alaska natives (43,618) who received 101,360 doses of hepatitis B vaccine. METHODS: All adverse reactions, excluding transient fever, myalgia, or soreness lasting less than 3 days, were reported. An intradermal skin test was developed to test purported adverse reactions. Records of the entire population were reviewed for Guillain-Barré syndrome (GBS). SETTING: A statewide hepatitis B control program for Alaska natives. RESULTS: Possible adverse reactions occurred in 39 persons. The most frequent adverse reactions were myalgia/arthralgia lasting longer than 3 days (14), followed by skin rashes (eight) and dizziness (seven). Skin tests were performed on 13 persons and were positive in five. Six of the persons with negative skin tests and eight persons who did not undergo skin testing received additional doses of vaccine without any adverse reactions. No increased incidence of GBS was found in the vaccinees. CONCLUSION: Hepatitis B vaccine is safe and most adverse reactions are coincidental.

Response to hepatitis B vaccine in Alaska natives with chronic alcoholism compared with non-alcoholic control subjects.

PURPOSE: This study was designed to determine if (1) alcoholics have a higher prevalence of hepatitis B virus (HBV) serologic markers than do non-alcoholic controls and (2) if they respond to hepatitis B vaccination in a manner similar to that of non-alcoholic controls. PATIENTS AND METHODS: The study was designed as a case-control study, and 129 Alaska Natives were recruited. Alcoholics were recruited from inpatient wards, outpatient clinics, a soup kitchen serving the homeless, and several alcohol rehabilitation centers; control subjects were recruited primarily from among Alaska Native Hospital employees. A standardized questionnaire, the Alcohol Dependency Scale (ADS), was administered to all participants. Each participant was screened for hepatitis B serologic markers, had liver function studies performed, and was examined for evidence of liver disease. Participants seronegative for HBV markers received three doses of hepatitis B vaccine. Linear regression analysis was performed to compare the amount of alcohol intake and variables associated with liver disease with the response to hepatitis B vaccination and antibody levels achieved. Using an ADS score of greater than 13, 64 participants were classified as chronic alcoholics, and 60 were classified as controls. RESULTS: HBV seropositivity was found in 22 alcoholics (34.4%) and seven controls (11.7%). After adjusting for age and sex, this difference was significant (chi 2 MH = 6.57, df = 1; p = 0.012). Abnormal levels of liver transaminase occurred significantly more often in alcoholic participants than in control subjects (chi 2 MH = 4.91, df = 1; p = 0.026). Of 95 seronegative persons, 72 received three doses of hepatitis B plasma-derived vaccine. Alcoholic subjects and control subjects did not differ significantly in their response to vaccination. Only four alcoholics and two controls did not develop antibody to hepatitis B surface antigen (anti-HBs) after hepatitis B vaccination, and two alcoholics and three controls had anti-HBs levels less than 10 SRU by radioimmunoassay. Mean anti-HBs levels measured in milli-international units (mIU) for the 62 responders showed a decrease in the anti-HBs level with increasing age (p less than 0.001). There was no difference in the mean anti-HBs log10 mIU between alcoholics and controls younger than 45 years of age, but in persons greater than 45 years of age, alcoholics had a lower mean anti-HBs log10 mIU level than did controls; this difference, however, was not significant (p greater than 0.10). CONCLUSION: Chronic alcoholics have a higher prevalence of HBV seromarkers than do age-matched controls. Seronegative alcoholics, especially those under age 45, respond well to hepatitis B vaccination, and such vaccination should be considered in all chronic alcoholic persons.

Immunogenicity of the 23-valent pneumococcal polysaccharide vaccine in Alaska Native chronic alcoholics compared with nonalcoholic Native and non-Native controls.

PURPOSE: This study was designed to evaluate the immunogenicity of the 23-valent pneumococcal polysaccharide vaccine in Alaska Native chronic alcoholics and compare these responses with those in age- and sex-matched nonalcoholic, Native and non-Native control subjects. PATIENTS AND METHODS: Native alcoholic patients were recruited from the inpatient medical service and outpatient clinics. Healthy age- and sex-matched Alaska Native and non-Native nonalcoholics were recruited from hospital employees. At the initial visit, a standardized questionnaire, the Alcohol Dependency Scale, was administered to all participants. Participants were examined for liver diseases; blood was drawn for liver function tests and prevaccination pneumococcal antibody levels. Charts of all Native participants were reviewed for alcohol-related diseases. Participants received one dose of the 23-valent pneumococcal vaccine at the time of the initial visit and returned 20 to 55 days after immunization for liver function tests and pneumococcal antibody level measurement. Serotype-specific pneumococcal antibody levels were measured by radioimmunoassay. Logistic regression analysis was used to examine the proportion of persons whose serotype-specific antibody level doubled following vaccination. A model including adjustments for age, sex, and initial antibody level was used to examine the effect of alcohol status and ethnicity on response to the vaccine. Eighty-five persons completed the study. Of these, 41 were chronic alcoholics and 44 were nonalcoholic. Of these, 21 were Alaska Natives and 23 were non-Natives. RESULTS: Before vaccination, the geometric mean titers (GMTs) were similar in all 3 groups but were slightly higher in Native alcoholic participants for 11 of 12 serotypes tested. For 11 or more serotypes tested, 46% of alcoholics and 27% of nonalcoholics had total antibody levels at or above 500 nanograms of antibody nitrogen per milliliter (p = 0.11). After vaccination, the GMTs were higher in nonalcoholic than in alcoholic participants for serotypes 3, 7F, and 19F (p < 0.05). When Natives and non-Natives were compared, non-Natives had higher antibody levels than Native participants for 10 of 12 serotypes. After vaccination, 83% of alcoholics and 91% of nonalcoholics had pneumococcal antibody levels of more than 500 nanograms of antibody nitrogen per milliliter for at least 11 serotypes. When responses consisting of a twofold or greater increase in antibody level were compared, a greater proportion of nonalcoholics than alcoholics responded to serotypes 3, 4, 7F, 8, and 19F. This difference was significant for types 3 and 19F only (p < 0.05). In alcoholics there was a direct correlation between pneumococcal antibody level and age both before and after vaccination. This was significant before vaccination for serotypes 4, 6B, 18C, and 23F, and after vaccination for these types and for types 1 and 19F. In nonalcoholics there was a correlation between age and antibody response, following vaccination, for serotype 9N and 18C. Alcoholic males had antibody levels higher than that in females for most serotypes, but significantly so only for serotype 12F before vaccination, and for type 14 after vaccination. There were no sex differences seen among nonalcoholics, and no differences in response to vaccine could be detected in patients with or without liver dysfunction. CONCLUSION: In this study of Alaska Natives with chronic alcoholism, Native and non-Native participants responded adequately to immunization with the 23-valent pneumococcal vaccine, although significant differences in some serotypes were evident.

Prevalence of hepatitis B virus infection in Tonga: identifying high risk groups for immunization with hepatitis B vaccine.

A serological survey for evidence of hepatitis B virus (HBV) infection was conducted in the Kingdom of Tonga as the first step in developing a strategy for an immunization programme. There were 414 individuals from the general population plus 137 pregnant women included in the survey. HBsAg was found in 20% of the general population and 88% had one or more serologic markers of HBV infection. In the 5-9 year age group, 80% of the children had one or more markers of HBV, and in the 10-19 year age group, the prevalence was 96.4%, indicating that most transmission of HBV in the Tongans studied occurs in the young. Of the pregnant women studied, 15% were positive for HBsAg, and 57% of those positive for HBsAg were also positive for HBeAg. Evidence of delta virus infection was not found in any of 82 HBsAg positive sera tested. Surveillance data suggested that significant serious sequelae to HBV infection (cirrhosis and primary hepatocellular carcinoma) also occur in Tonga. Immunization of infants and children is the most effective strategy for reducing or eliminating HBV infection and its sequelae in developing countries like Tonga.

A program to control an outbreak of hepatitis A in Alaska by using an inactivated hepatitis A vaccine.

OBJECTIVE: To stop an epidemic of hepatitis A in rural Alaska by mass immunization of susceptible persons with 1 dose of an inactivated hepatitis A vaccine. DESIGN: Nonrandomized, uncontrolled trial. Hepatitis A vaccine was offered to all persons in susceptible age groups in villages with documented cases of hepatitis A. Immune globulin was not offered at the time of vaccination. SETTING: Twenty-five rural communities located in interior Alaska and along the northwest coast of the Bering Sea and Arctic Ocean. PARTICIPANTS: Persons without a history of acute hepatitis A in age groups selected by applying results of a previous serosurvey conducted on serum collected before the epidemic. INTERVENTION: One dose of a formalin-inactivated hepatitis A vaccine was given to each participant. Adults 20 years of age and older received 1440 enzyme-linked immunosorbent assay units and persons younger than 20 years received 720 enzyme-linked immunosorbent assay units. Prevaccination and postvaccination levels of antibody to hepatitis A IgG were obtained from 136 participants. MAIN OUTCOME MEASURES: An active surveillance system was established to detect persons with symptomatic illnesses compatible with hepatitis A; persons who met the illness criteria were tested for antibody to hepatitis A IgM. One area (the Kotzebue region), where all communities were offered vaccine, was selected for intensive surveillance and analysis. RESULTS: During the 12-month period before the vaccine trial, 529 cases of icteric hepatitis A were reported, and 443 were confirmed to be positive for antibody to hepatitis A IgM. Hepatitis A vaccine was administered to 4930 persons, 3517 of whom were younger than 20 years. After vaccination began, 237 persons positive for antibody to hepatitis A IgM were identified during a 60-week surveillance period; 46 were vaccines and 191 were unvaccinated susceptible persons. In the Kotzebue region, in communities in which more than 80% of persons considered susceptible were vaccinated, the outbreak ceased in 4 to 8 weeks, whereas in 1 large community in which less than 50% of susceptible persons were vaccinated, the outbreak continued for more than 50 weeks. More than 90% of seronegative persons developed antibody to hepatitis A IgG 3 to 4 weeks after vaccination. CONCLUSION: This trial suggested that by providing both short-term and long-term protection, hepatitis A vaccine used without immune globulin halted an established epidemic of hepatitis A in rural Alaska.