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: 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.

Evaluation of the response to a booster dose of hepatitis B vaccine in previously immunized healthcare workers.

INTRODUCTION: Hepatitis B vaccination is recommended for all healthcare workers (HCW) at risk of exposure to infectious body fluids. However, the absolute duration of protection from immunization is unknown. The purpose of this randomized comparison trial was to determine how previously immunized HCW respond to different booster doses of hepatitis B vaccine. METHOD: Adult HCW (n=59) were classified by level of hepatitis B surface antigen (anti-HBs), either <10 milli-International Units per milliliter (mIU/ml) or 10-50 mIU/ml. Participants were then randomized to receive a 2.5 or 10 microg dose of hepatitis B vaccine. Evaluation of anti-HBs levels were conducted 10 to 14 days, one month and one year postbooster. RESULTS AND DISCUSSION: All participants responded to the booster dose with increased anti-HBs levels. At 14 days, mean anti-HBs levels were significantly higher for those with higher levels at baseline (P=0.004) and those receiving the 10 microg dose (P=0.016). At one month, those with higher anti-HBs levels at baseline and those receiving the 10 microg dose were significantly higher (P<0.01 for both). At one year, the increase for the higher dose was no longer statistically significant when examined by itself (P=0.081); statistical significance (P=0.021) was achieved after adjusting for anti-HBs level at baseline. For all participants, the geometric mean anti-HBs level was 2618 mIU/ml at 14 days, 2175 mIU/ml at one month and 88.9 mIU/ml at one year. At all time points the increase in anti-HBs levels represented an increase over the geometric mean baseline level of anti-HBs (7.4 mIU/ml). Hepatitis B immunized adults responded to a booster dose of hepatitis B vaccine from 3 to 13 yr postvaccination series. Data support current recommendations that immunized HCW do not require periodic antibody testing or vaccine boosters.

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.

Sequential inactivation of rdxA (HP0954) and frxA (HP0642) nitroreductase genes causes moderate and high-level metronidazole resistance in Helicobacter pylori.

Helicobacter pylori is a human-pathogenic bacterial species that is subdivided geographically, with different genotypes predominating in different parts of the world. Here we test and extend an earlier conclusion that metronidazole (Mtz) resistance is due to mutation in rdxA (HP0954), which encodes a nitroreductase that converts Mtz from prodrug to bactericidal agent. We found that (i) rdxA genes PCR amplified from 50 representative Mtz(r) strains from previously unstudied populations in Asia, South Africa, Europe, and the Americas could, in each case, transform Mtz(s) H. pylori to Mtz(r); (ii) Mtz(r) mutant derivatives of a cultured Mtz(s) strain resulted from mutation in rdxA; and (iii) transformation of Mtz(s) strains with rdxA-null alleles usually resulted in moderate level Mtz resistance (16 microg/ml). However, resistance to higher Mtz levels was common among clinical isolates, a result that implicates at least one additional gene. Expression in Escherichia coli of frxA (HP0642; flavin oxidoreductase), an rdxA paralog, made this normally resistant species Mtz(s), and frxA inactivation enhanced Mtz resistance in rdxA-deficient cells but had little effect on the Mtz susceptibility of rdxA(+) cells. Strains carrying frxA-null and rdxA-null alleles could mutate to even higher resistance, a result implicating one or more additional genes in residual Mtz susceptibility and hyperresistance. We conclude that most Mtz resistance in H. pylori depends on rdxA inactivation, that mutations in frxA can enhance resistance, and that genes that confer Mtz resistance without rdxA inactivation are rare or nonexistent in H. pylori populations.

Serotype distribution and antimicrobial resistance patterns of invasive isolates of Streptococcus pneumoniae: Alaska, 1991-1998.

From January 1991 through December 1998, a total of 1046 pneumococcal isolates were received from 23 laboratories participating in the statewide surveillance system. Of these, 1037 were recovered from normally sterile sites (blood and cerebrospinal and pleural fluid) and were available for serotyping and susceptibility testing. Ninety-two percent of these isolates were serotypes represented in the 23-valent pneumococcal polysaccharide vaccine. Serotypes in the 7-valent pneumococcal conjugate vaccine (4, 6B, 9V, 14, 18C, 19F, and 23F) were recovered from 72% of Alaska Natives and 84% of non-Native children <5 years old with invasive disease. Statewide, 7.3% and 3.2% of isolates had intermediate and high levels of resistance to penicillin, respectively; 9.2% were resistant to erythromycin (minimal inhibitory concentration, >/=1 microg/mL) and 19% to trimethoprim/sulfamethoxazole (minimal inhibitory concentration, >/=4/76 microg/mL). Twelve percent of invasive isolates were resistant to >/=2 classes of antibiotics; of these, serotype 6B accounted for 33%, and 63% were recovered from children <5 years old.

Immunogenicity of a heptavalent pneumococcal conjugate vaccine in Apache and Navajo Indian, Alaska native, and non-native American children aged <2 years.

High rates of invasive pneumococcal disease have been described among infants living in various Native American communities. In this study, we evaluated the immunogenicity of a 7-valent pneumococcal vaccine consisting of serotypes 4, 6B, 9V, 14, 18C, 19F, and 23F covalently linked to the outer membrane protein complex of Neisseria meningitidis in Apache and Navajo Indian, Alaska Native, and non-Native American children. The vaccine was administered at ages 2, 4, and 6 months; a booster dose was given at age 15 months. Levels of serotype-specific immunoglobulin G (IgG) were measured by a standardized enzyme-linked immunosorbent assay. The responses after 3 primary doses of vaccine were similar in all 3 groups of children, except for those to serotypes 14 and 23F. One month after the booster dose, geometric mean concentrations (GMCs) of serotype-specific IgG antibodies increased significantly in all 3 groups of children, compared with GMCs of IgG antibodies to pneumococcal serotypes before the booster dose.

Invasive Haemophilus influenzae disease in Alaskan residents aged 10 years and older before and after infant vaccination programs.

CONTEXT: The introduction of Haemophilus influenzae type b (Hib) vaccination of children has led to a decline in incidence of Hib disease in young Alaskan children. However, the impact of vaccination on unimmunized Alaskan adolescents and adults has not been studied. OBJECTIVE: To characterize trends in incidence of and mortality due to invasive H influenzae disease in Alaskan residents aged 10 years and older prior to and after the introduction of a statewide Hib infant vaccination program. DESIGN AND SETTING: Population-based, descriptive correlational study conducted 1980-1996 in Alaska. SUBJECTS: One hundred twenty-nine individuals (31 Alaska Natives and 98 nonnative Alaska residents) aged 10 years and older in whom H influenzae was cultured from a normally sterile site. MAIN OUTCOME MEASURES: Incidence of H influenzae infection before (1980-1990) vs after (1991-1996) vaccination program initiation; serotype, biotype, and beta-lactamase production of isolates. RESULTS: The overall annual incidence of invasive H influenzae in those aged 10 years and older declined 33%, from 2.1 per 100,000 persons per year to 1.4 per 100,000 persons per year (P=. 03) after initiation of statewide infant Hib vaccination programs in 1991. This reduction appeared to be the result of a decrease in serotype b disease (82%; P<.001). Infection with other H influenzae serotypes and nontypeable strains increased from 0.5 per 100,000 persons per year to 1.1 per 100,000 persons per year (P=.01). Incidence declined from 4.2 per 100,000 persons per year to 1.2 per 100,000 persons per year in Alaska Natives (P=.005) and from 1.7 per 100,000 persons per year to 1.4 per 100,000 persons per year in nonnative Alaska residents (P=.37). Pneumonia (43%), sepsis (26%), and meningitis (16%) were the most common clinical presentations. Alcohol/drug abuse was comorbid in 15% of patients, while 13% of patients were pregnant women. beta-Lactamase production occurred in 35% of isolates and was stable throughout the surveillance. The overall case-fatality rate was 15%. CONCLUSION: The overall statewide incidence of invasive H influenzae infections in unimmunized persons aged 10 years and older decreased after the initiation of an infant Hib vaccine program, perhaps by decreasing Hib carriage in child reservoirs. An increase in non-serotype b strains was observed. This trend justifies the need for continued surveillance of invasive disease caused by H influenzae. JAMA. 2000.

Comparison of human papillomavirus genotypes in archival cervical cancer specimens from Alaska natives, Greenland natives and Danish Caucasians.

Archival, formalin-fixed, paraffin-embedded cervical cancer specimens from 53 Alaska natives, 32 Greenland natives and 34 Danish Caucasians were analyzed for human papillomavirus (HPV) genotypes 16, 18, 31, 33, 35 and 45 and unidentified genotypes (HPV X) using PCR. The specimens were from the time period 1980-1989. No significant differences were observed in the overall HPV detection rates among cases from Alaska (98.1%), Greenland (84.4%) and Denmark (85.3%). HPV genotype 16 was the most prevalent type: 78.8% in Alaska natives, 96.3% in Greenland natives and 82.8% in Danish Caucasians. A prevalence of 21.2% HPV 31 and 30.8% HPV 33 was found in Alaska natives, of which most were coinfections with HPV 16. Only 3.7% HPV 31 and 3.7% HPV 33 were found in Greenland natives and no HPV 31 and 6.9% HPV 33 were found in Danish Caucasians. HPV 18 was only detected in Alaska natives and HPV 35 and 45 were not detected in any of the three populations. Infections with multiple genotypes were prevalent in Alaskan (36.5%) but not in Greenland natives (3. 7%) and Danish Caucasians (6.9%). The Eskimo subgroup of the Alaska native population has a significantly higher prevalence of HPV genotypes 31 and 33 associated with mixed infections in invasive cancer than the two other native subgroups (P = 0.04) and Greenland and Danish populations, reflecting genotype distributions in dysplasia and normal cervical cytology. The reason for HPV genotype diversity, although unknown, may be relevant to the current development of HPV vaccines.

The challenge of ongoing Haemophilus influenzae type B carriage and transmission in Alaska.

Cases of invasive Haemophilus influenzae type b disease in Alaskan children quickly dropped 10-fold after widespread vaccination with a conjugate vaccine (PRP-OMP) began in 1991. However, reemergence of invasive disease in 1996-97 soon followed a change to a combination diphtheria-tetanus toxoid-pertussis/H. influenzae type b vaccine which incorporates a different conjugate vaccine (HbOC). Previously unrecognized persistence of H. influenzae type b carriage in rural Alaska, coupled with characteristics of the immune response to HbOC, are the likely explanations for disease reemergence. The current vaccine recommendation--PRP-OMP for the first dose, followed by HbOC to complete the vaccination series--appears to protect Alaskan infants even in the face of continuing carriage and transmission. Successful control of invasive H. influenzae type b disease in Alaskan children will require not only appropriate immunization, but also continuing surveillance for both disease and carriage, identification of factors associated with carriage, and investigation into the feasibility of using vaccination plus antimicrobial drugs to eliminate this pathogen.

Hepatocellular carcinoma not related to hepatitis B virus infection among Alaska natives.

Chronic infection with hepatitis B or C viruses is a common underlying condition in patients with hepatocellular carcinoma worldwide. We studied serum and liver tissue from a cohort of Alaska natives with hepatocellular carcinoma (HCC) for evidence of hepatitis B, C and G viral infection using conventional serological tests as well as the sensitive polymerase chain reaction. Evidence of HBV infection was found in 25 and possible HCV infection in two cases. Among the remaining 11 patients, four had a history of recent or remote alcoholism while seven had no recognizable risk factors for HCC. Only one was seropositive for HGV RNA and that was an individual with a history of alcoholism. Non-tumorous liver tissue was available for study in six of these seven cases. Histological features of chronic hepatitis were present in five. Thus, at least five of 38 (13%) Alaska natives with HCC appeared to have chronic hepatitis not related to HBV or HCV infection, suggesting the possibility of some form of previously unrecognized chronic liver disease predisposing to HCC.

Characterization of a multidrug-resistant clone of invasive Streptococcus pneumoniae serotype 6B in Alaska by using pulsed-field gel electrophoresis and PspA serotyping.

Antimicrobial susceptibility, pneumococcal surface protein A (PspA) serotyping, and pulsed-field gel electrophoresis (PFGE) were used to evaluate clonal relatedness among 66 invasive isolates of Streptococcus pneumoniae serotype 6B collected during 1982-1996 from patients in Alaska. Thirty-seven (56%) of the isolates had penicillin minimal inhibitory concentration values >/=0.125 microgram/mL and were resistant to at least 1 other antibiotic. Fourteen PspA serotypes were observed; PspA 16 was the most common (35%). Forty-five (68%) of the 66 isolates shared common and highly related PFGE patterns using 3 enzymes. Twenty-six (58%) of the isolates with common PFGE patterns were from Native Alaskan children

Bacterial pathogens in chronic otitis media with effusion in Alaska Native children.

This study examined the bacterial pathogens and the presence of possible risk factors for the development of chronic otitis media with effusion (OME) in a group of Alaska Native children. Middle ear aspirates were collected from 128 children < 6 years of age requiring tympanocentesis between 1987 and 1989. Bacterial pathogens were cultured from 40% of 209 fluids. Predominant isolates, after contamination of the outer ear was controlled for, were Haemophilus influenzae (21%; 84% of these were nontypeable), Streptococcus pneumoniae (8.1%; serotypes 6B, 10A, 11A, 14, 18B, 18C, 19A, and 23F), Staphylococcus epidermidis (3.8%), and Moraxella (Brahmanella) catarrhalis (2.9%). Pneumococcal-C-polysaccharide (PnC) was detectable in 3 of 135 (2.2%) aspirates that did not grow Streptococcus pneumoniae. Combining culture and PnC assay results evidence of pneumococcal infection was found in almost 10% of aspirates tested. There was not a significant difference in the number of episodes of acute otitis media after the first year of life based on the age at the first episode (< 6 mo, > or = 6 mo). However, 88% of infants in the study had their first acute otitis media episode before 1 year of age.

Emerging infectious diseases in Alaska and the Arctic: a review and a strategy for the 21st century.

Emergence of new, previously unknown, and drug-resistant infectious diseases pose a major threat to global health. The emergence of infectious diseases in Alaska and the Arctic parallels the resurgence of infectious diseases worldwide. The Centers for Disease Control and Prevention has developed a strategy to revitalize the capacity to protect the public from emerging infectious diseases by improving four major public health activities: surveillance and response, applied research, infrastructure and training, and prevention and control. The plan targets high-priority emerging infectious disease problems and particular groups of people at increased risk. These target areas encompass a number of diseases of special concern in Alaska, such as drug-resistant Streptococcus pneumoniae infections, foodborne botulism, alveolar hydatid disease, viral hepatitis, Helicobacter pylori infections, Haemophilus influenzae type b bacteremia and meningitis, and infections of immunocompromised persons, pregnant women and newborns, and tourists. To address these and other emerging infectious disease issues, including the threat of bioterrorism in Alaska and the Arctic, future issues of Alaska Medicine will include updates on specific emerging infectious diseases for health care providers, clinical laboratory workers, and community public health professionals who form the front lines for recognizing, treating, and preventing emerging infectious diseases.

Molecular characterization of a globally distributed lineage of serotype 12F Streptococcus pneumoniae causing invasive disease.

These studies have identified a major genetic lineage of capsule serotype 12F Streptococcus pneumoniae, which has maintained two different types of the pneumococcal surface protein A (PspA) virulence factor and caused invasive disease in geographically disjoint locations. Twenty outbreak strains from a Texas jail and Maryland day care center and 16 reference strains from Texas, Maryland, Washington, Michigan, Oklahoma, Missouri, Alaska, and Australia were examined. Although the Texas and Maryland outbreak strains were indistinguishable by IS1167 and boxA genotyping procedures, all strains examined were members of a genetically similar lineage. The microevolutionary history of pspA differed from that of the overall genetic background of the strains. Taken together, these findings suggested that the Texas and Maryland outbreaks were caused by different clones of a major genetic lineage of serotype 12F pneumococci, within which at least one PspA has been acquired via localized genetic recombination.