High prevalence of Helicobacter pylori in the Alaska native population and association with low serum ferritin levels in young adults.

Iron deficiency anemia is a common public health problem in the Alaska Native population. Yet, a clear etiology has eluded researchers for decades. Previous studies suggested a link between Helicobacter pylori infection, gastrointestinal blood loss due to hemorrhagic gastritis, and generalized iron deficiency anemia in adult Alaska Natives. Therefore, we examined the association between the prevalence of H. pylori-specific immunoglobulin G (IgG) and serum ferritin levels, a marker of iron deficiency. A random sample of 2,080 serum samples from Alaska Native residents drawn between 1980 and 1986 from residents in 13 regions was selected, and the samples were stratified by age, sex, and region. Overall, 75% were positive for H. pylori-specific IgG. The rate of H. pylori seropositivity increased with age; by age 14 years, 78% of the residents were positive. There were no gender differences in H. pylori seropositivity. However, marked regional differences were observed. Serum ferritin levels of <12 ng/ml were found most commonly among persons <20 years of age and among women of childbearing age. A significant association between low serum ferritin levels and prevalence of H. pylori-specific IgG was found, particularly for people aged less than 20 years. H. pylori may be a factor contributing to the iron deficiency anemia in the Alaska Native population.

Malaria, intestinal parasites, and schistosomiasis among Barawan Somali refugees resettling to the United States: a strategy to reduce morbidity and decrease the risk of imported infections.

In 1997, enhanced health assessments were performed for 390 (10%) of approximately 4,000 Barawan refugees resettling to the United States. Of the refugees who received enhanced assessments, 26 (7%) had malaria parasitemia and 128 (38%) had intestinal parasites, while only 2 (2%) had Schistosoma haematobium eggs in the urine. Mass therapy for malaria (a single oral dose of 25 mg/kg of sulfadoxine-pyrimethamine) was given to all Barawan refugees 1-2 days before resettlement. Refugees >2 years of age and nonpregnant women received a single oral dose of 600 mg albendazole for intestinal parasite therapy. If mass therapy had not been provided, upon arrival in the United States an estimated 280 (7%) refugees would have had malaria infections and 1,500 (38%) would have had intestinal parasites. We conclude that enhanced health assessments provided rapid on-site assessment of parasite prevalence and helped decrease morbidity among Barawan refugees, as well as, the risk of imported infections.

Elimination of new chronic hepatitis B virus infections: results of the Alaska immunization program.

An immunization assessment and a serologic survey were conducted to evaluate the effectiveness of a hepatitis B immunization program in eliminating hepatitis B virus (HBV) transmission among Alaska Natives in a region in which HBV infection is endemic. Hepatitis B vaccine coverage was 93% among 567 children

Increases in levels of antibody to hepatitis B surface antigen in an immunized population.

Hepatitis B vaccine is effective in preventing infection with hepatitis B virus (HBV), but its duration of protection is unknown. To examine the effect of exposure to HBV on an immunized population, data were analyzed from a cohort of Alaska Natives who were immunized and then followed up annually for 10 years. A boost in antibody to hepatitis B surface antigen (anti-HBs) was defined as a fourfold rise in levels to > or = 20 mIU/mL that was not accompanied by the presence of antibody to hepatitis B core antigen or attributable to interim vaccination. During 10 years of follow-up, 8.2% of 1,595 vaccines had boosts in anti-HBs. Persons with boosts did not differ significantly from those without boosts in terms of age, gender, village, initial level of anti-HBs, or level of anti-HBs before the boost. These results underscore the continued exposure to HBV among vaccinees and the continued protection against disease that the vaccine provides.

Hepatitis B and hepatocellular carcinoma in Eskimo/Inuit population.

Hepatitis B virus (HBV) is major risk factor for the development of hepatocellular carcinoma (HCC) worldwide. Serologic surveys performed in the 1970s and 1980s have demonstrated that Alaskan Eskimos, Canadian Inuit, and Greenland Inuit have very high prevalence rates of HBV. In Alaska, a high incidence of HCC in Eskimos, especially males, has been reported. Alaska Natives chronically infected with HBV have a relative risk of HCC of 148 compared to Alaska Natives who are not chronically infected. In Canada the incidence of HCC is six times more frequent in elderly Inuit than in Canadians in general. However, an elevated rate of HCC has not been found in Greenland. Primary prevention programs to prevent HCC by vaccination against HBV are being conducted in Alaska, Canada, and Greenland. In addition, in Alaska a program to detect HCC earlier by screening persons chronically infected with HBV, using semiannual alpha-fetoprotein testing, has resulted in detecting over 60% of HCC early enough for surgical resection.

Protection provided by hepatitis B vaccine in a Yupik Eskimo population--results of a 10-year study.

A hepatitis B virus vaccine demonstration project was conducted in southwest Alaska in 1981-1982 to determine the immunogenicity and efficacy of the vaccine. A total of 1630 susceptible persons in the Alaskan Native population were vaccinated with the recommended three-dose regimen of plasma-derived hepatitis B vaccine, and 94% demonstrated antibody to hepatitis B surface antigen (anti-HBs) at levels > or = 10 mIU/mL. After 10 years of follow-up, 76% of those immunized had anti-HBs levels > or = 10 mIU. During the 10 years following the first dose of vaccine, 13 study participants developed antibody to hepatitis B core antigen (10 vaccine responders, 3 nonresponders), and none developed sustained HBs positivity or had clinical hepatitis. These data suggest that immunization with hepatitis B vaccine continues to provide high levels of protection from clinical disease for at least 10 years.

Detection of alpha-fetoprotein and hepatitis-B surface antigen in blood spotted on filter paper: use as a screen for hepatocellular carcinoma in Alaska Natives.

A program of twice yearly testing of Alaska Native carriers of hepatitis-B surface antigen (HBsAg), for alpha-fetoprotein elevations as an indicator of early hepatocellular carcinoma has been established in Alaska. Because many HBsAg carriers live in remote regions of Alaska, logistical and cost considerations complicate the efficiency of this program. We evaluated the feasibility of using blood spotted onto mail-in cards as a system of blood collection and commercial assays for alpha-fetoprotein and HBsAg testing. We compared alpha-fetoprotein levels and the detection of HBsAg in both plasma and blood spots from HBsAg-positive carriers, normal volunteers, and pregnant females. There was good correlation between serum and blood spot AFP levels (r = 0.94, p < 0.001) over a wide range of serum alpha-fetoprotein levels. alpha-fetoprotein and HBsAg remained detectable in blood spots stored at room temperature for more than 8 weeks. The sensitivity of detection of HBsAg in blood spots was not as great in blood spots when compared to plasma levels. This system has been incorporated into the hepatocellular carcinoma screening program in Alaska. It should also prove feasible and economical for such screening to be undertaken in developed countries and possibly make alpha-fetoprotein screening affordable in those developing countries where the prevalence of hepatitis-B virus infection is high.

Decline of Haemophilus influenzae type b disease in a region of high risk: impact of passive and active immunization.

Haemophilus influenzae type b (Hib) is a major cause of serious childhood bacterial infections. Before 1989 Alaska Native infants in the Yukon Kuskokwim Delta (YKD) had the highest recorded Hib disease rate, 2960:100,000 in children less than 1 year of age with 6 to 35 (mean, 13) cases/year between 1980 and 1988. In July, 1989, Alaska Area Native Health Service initiated a passive immunization project in the YKD using bacterial polysaccharide immunoglobulin (BPIG) administered at 3-month intervals to prevent Hib infections in infants less than 13 months of age. On January 1, 1991, after licensure of Hib conjugate vaccines for infants, the program was modified to a passive-active strategy using BPIG at birth and PedvaxHIB at 2, 4 and 12 months of age. Between July 1, 1989, and December 31, 1990, 80% of YKD children less than 1 year of age received at least 1 dose of BPIG. During this period there were 7 Hib cases in this age group, but only 1 of the cases had received any BPIG. Between January 1, 1991, and December 31, 1992, 4 Hib cases occurred in 2 YKD children. During the combined period, July 1, 1989, to December 31, 1992, the incidence of Hib disease for infants less than 1 year of age was 302:100,000. A dramatic decrease in Hib disease was observed in this high incidence region concurrent with implementation of passive and passive-active immunization strategies.

Seroprevalence of hepatitis B viral markers in 52,000 Alaska Natives.

As a part of a program to screen and immunize as many Alaska Natives as possible against hepatitis B infection, hepatitis B virus seromarkers were measured in 52,022 Alaska Natives between 1983 and 1987. Hepatitis B surface antigen (HBsAg) was found in 1,603 persons (3.1%), and 7,155 persons (13.8%) exhibited hepatitis B virus seropositivity. While the prevalence of total seropositivity increased with increasing age (p < 0.001), the proportion of seropositive persons who were also positive for HBsAg was significantly higher in children under age 5 years than in persons over age 60 (p < 0.001). The total hepatitis B virus seropositivity was significantly higher in males than in females (p < 0.001), and a greater proportion of seropositive males than seropositive females had HBsAg (p < 0.001). The prevalence of HBsAg and total seropositivity differed significantly by geographic region (p < 0.001), ranging from 0.5% to 8.2% for presence of HBsAg and from 5.4% to 29% for total seropositivity. Of persons who were HBsAg positive, hepatitis B e antigen was found in 35.4%, and antibody to hepatitis e antigen was found in 49.6%. The prevalence of hepatitis B e antigen significantly decreased with age, while that of antibody to hepatitis e antigen significantly increased. The prevalence of hepatitis B virus seropositivity is high in Alaska Natives, and there are significant differences in both the prevalence of HBsAg and total hepatitis B virus seromarkers by age, sex, and geographic region.

Secular trends in hepatitis A virus infection among Alaska Natives.

To assess the epidemiologic characteristics of the population susceptible to hepatitis A virus (HAV) infection and determine the natural history of infection, a retrospective survey was done using banked serum specimens. A random sample of 4030 Alaska Natives statewide was selected, stratified by year of birth and community of residence. Overall, 1988 serum samples (49.3%) tested positive for antibody to HAV (anti-HAV). Past HAV infection was strongly age-related, increasing from 7% in persons born since 1975 to 85% among persons born before 1945. Prevalence of infection also varied between regions. In small communities, a clear demarcation typically existed between previously infected older persons and younger anti-HAV-negative persons. This indicated that village-wide outbreaks of HAV infection have been the norm and appear to be dependent on the presence of a young susceptible population. Widespread vaccination with hepatitis A vaccine to maintain a high proportion of young anti-HAV-positive persons may be successful in preventing future epidemics.

Safety and immunogenicity of a combined hepatitis B virus-Haemophilus influenzae type B vaccine formulation in healthy adults.

We administered a combined preparation of hepatitis B virus (HBV) vaccine and Haemophilus influenzae type b (Hib) conjugate vaccine (meningococcal protein conjugate) to 20 healthy adult volunteers. Participants received two doses of vaccine one month apart, and had serum samples drawn each time they received the vaccine and 1 month after the second dose. In 18 of 19 persons who were positive for antibody to hepatitis B surface antigen (anti-HBs), these levels had a median fold increase of 23.4 (range 0.69 to 270) 1 month after the first dose of vaccine. Anti-HBs levels generally fell slightly one month after the second dose was given. All of the study participants initially had detectable levels of antibody to Hib capsular polysaccharide (anti-PRP), and 19 of the 20 exhibited a median fold increase of 11.2 (range 0.81 to 740) in anti-PRP 1 month after vaccination. Over half (65%) continued to demonstrate increased levels of anti-PRP with the second dose of vaccine. Most participants experienced some slight to moderate discomfort at the injection site. The results indicate that the combined Hib/HBV vaccine produces increased antibody levels in healthy adults who have previously been exposed to these two antigens.

Comparative immunogenicity of four Haemophilus influenzae type b conjugate vaccines in Alaska Native infants.

We compared the immunogenicity of the four available Haemophilus influenzae type b (Hib) conjugate vaccines in Alaska Native infants. Three of the vaccines, Hib oligosaccharide-CRM197 (HbOC), polyribosylribitol phosphate-diphtheria toxoid (PRP-D) and polyribosylribitol phosphate-tetanus toxoid (PRP-T), were given at 2, 4 and 6 months of age, and the PRP Neisseria meningitidis outer membrane protein (PRP-OMP) conjugate vaccine was given at 2 and 4 months of age. Enrollment was largely sequential by vaccine availability beginning with HbOC and ending with PRP-T. A total of 225 infants completed the full vaccination series. Groups of infants receiving the different vaccines did not differ significantly by sex, ethnicity, degree Alaska Native or age at vaccination. The only vaccine that induced a response with the first 2-month dose was PRP-OMP; 91% of infants had > or = 0.15 micrograms/ml and 57% had > or = 1.0 microgram/ml of anti-PRP antibody by 4 months of age. After two doses it also remained the most immunogenic. After the full three vaccine series, trials that requires cough of 21 days is excessively restrictive.

Clinical and laboratory comparison of botulism from toxin types A, B, and E in the United States, 1975-1988.

Cases of adult botulism (n = 309) were studied to identify clinical differences between toxin types and to evaluate the sensitivity of diagnostic laboratory testing. Patients with illness from type E toxin had the shortest incubation periods. Sporadic case-patients were more severely ill: 85% required intubation compared with only 42% in multiperson outbreaks. Of patients with type A botulism, 67% required intubation compared with 52% with type B and 39% with type E. Toxin testing was positive for 40%-44% of serum and stool specimens obtained within 3 days of toxin ingestion and for 15%-23% of specimens obtained thereafter, while 37% of stool specimens obtained > 3 days after toxin ingestion were positive by culture. Patients with type A botulism have more severe illness. In general, specimens obtained early are more likely to be positive by toxin assay, and stool cultures are more sensitive than toxin detection for specimens obtained later in the illness.

Response to hepatitis B vaccine of persons positive for antibody to hepatitis B core antigen.

The significance of antibody to hepatitis B core antigen (anti-HBc) present in a person's serum without hepatitis B surface antigen (HBsAg) or its antibody (anti-HBs) is unknown. Serum specimens from 281 persons initially positive only for anti-HBc by enzyme immunoassay (EIA) were retested by radioimmunoassay (RIA), and of these, 177 (63%) remained positive for anti-HBc by both assays. Of these 177 persons, 3 were positive for HBsAg, and 72 possessed low levels of anti-HBs [less than 10 sample ratio units; (SRU's)]. When persons positive for anti-HBc by EIA and RIA were given one 20-micrograms dose of plasma-derived hepatitis B vaccine and tested for anti-HBs 1 month later, a booster response was observed in 14 of 41 (34%) persons with low level anti-HBs and 3 of 50 (6%) persons negative for anti-HBs. Of those positive only for anti-HBc by EIA but negative by RIA, only 3 of 37 (8.1%) showed a booster response. Of those who completed the three-dose immunization series and did not show a booster response, 63 of 80 (78.8%) developed anti-HBs levels greater than 10 standard ratio unit. The majority of persons with isolated anti-HBc will have a primary rather than a booster response to hepatitis B vaccine.

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.

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.

Botulism among Alaska Natives. The role of changing food preparation and consumption practices.

Alaska Natives have one of the highest rates of food-borne botulism worldwide. All outbreaks have been associated with the consumption of native foods, but in recent years outbreaks have occurred in previously unaffected areas and have involved new food items. Five botulism outbreaks occurred between 1975 and 1985 in an area of southwestern Alaska without previous confirmed outbreaks and among one ethnic group, the Yupik Eskimo. Of the 5 outbreaks, 3 were associated with fermented beaver tail, a nontraditional native food recently introduced into the region. Preparation techniques vary widely within villages and among ethnic groups. Traditional fermentation techniques have changed over the past 50 years; current preparation methods used by some families and ethnic groups may be more favorable for Clostridium botulinum growth. Prevention efforts should be targeted at high-risk subgroups of Alaska Natives who appear to have modified traditional practices and increased their risk of food-borne botulism.

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.