PCV7-induced changes in pneumococcal carriage and invasive disease burden in Alaskan children.

BACKGROUND: Changes in pneumococcal serotype-specific carriage and invasive pneumococcal disease (IPD) after the introduction of pneumococcal conjugate vaccine (PCV7) could inform serotype epidemiology patterns following the introduction of newer conjugate vaccines. METHODS: We used data from statewide IPD surveillance and annual pneumococcal carriage studies in four regions of Alaska to calculate serotype-specific invasiveness ratios (IR; odds ratio of a carried serotype's likelihood to cause invasive disease compared to other serotypes) in children <5 years of age. We describe changes in carriage, disease burden, and invasiveness between two time periods, the pre-PCV7 period (1996-2000) and the late post-PCV7 period (2006-2009). RESULTS: Incidence of IPD decreased from the pre- to post-vaccine period (95.7 vs. 57.2 cases per 100,000 children, P<0.001), with a 99% reduction in PCV7 disease. Carriage prevalence did not change between the two periods (49% vs. 50%), although PCV7 serotype carriage declined by 97%, and non-vaccine serotypes increased in prevalence. Alaska pre-vaccine IRs corresponded to pooled results from eight pre-vaccine comparator studies (Spearman's rho=0.44, P=0.002) and to the Alaska post-vaccine period (Spearman's rho=0.28, P=0.029). Relatively invasive serotypes (IR>1) caused 66% of IPD in both periods, although fewer serotypes with IR>1 remained in the post-vaccine (n=9) than the pre-vaccine period (n=13). CONCLUSIONS: After PCV7 introduction, serotype IRs changed little, and four of the most invasive serotypes were nearly eliminated. If PCV13 use leads to a reduction of carriage and IPD for the 13 vaccine serotypes, the overall IPD rate should further decline. NOTE: The findings and conclusions in this report are those of the author(s) and do not necessarily represent the official position of the Centers for Disease Control and Prevention.

Treatment eligibility in Alaska Native and American Indian persons with hepatitis C virus infection.

OBJECTIVES: Treatment with pegylated interferon and ribavirin may prevent progression of liver disease among patients with chronic hepatitis C virus infection (HCV). Treatment initiation is based on published clinical eligibility criteria, patients' willingness to undergo treatment and likelihood of success. We examined treatment eligibility in a cohort of Alaska Native and American Indian persons with chronic HCV infection. STUDY DESIGN: Retrospective cohort study. METHODS: Medical records of all treatment naïve HCV RNA positive patients given an appointment by hepatology specialty clinic staff in 2003 and 2007 were evaluated by a hepatology provider to investigate documented reasons for treatment deferral. RESULTS: Treatment was initiated in 4 of 94 patients (4%) in 2003 and 14 of 146 patients (10%) in 2007. Major reasons for treatment deferral in 2003 versus 2007 included inconsistent appointment attendance (36% of deferrals vs. 18%), active substance abuse (17% vs. 22%), patient decision (17% vs. 27%), liver biopsy without fibrosis or normal ALT (8% vs. 3%), uncontrolled psychiatric condition (7% vs. 7%) and concurrent medical condition (6% vs. 9%). There was significant improvement in proportion of appointments attended in 2007 versus 2003 (76% vs. 67%, p = 0.04) and the percentage of patients attending at least 1 appointment (84% vs. 66%, p = 0.002). CONCLUSIONS: Multiple reasons for treatment deferral were documented. Despite a significant improvement in hepatology clinic attendance and an increase in the number of patients started on treatment in 2007 compared to 2003, the overall percentage of those treated remained low.

Diagnostic accuracy of tests for Helicobacter pylori in an Alaska Native population.

AIM: To evaluate the accuracy of two non-invasive tests in a population of Alaska Native persons. High rates of Helicobacter pylori (H. pylori) infection, H. pylori treatment failure, and gastric cancer in this population necessitate documentation of infection status at multiple time points over a patient's life. METHODS: In 280 patients undergoing endoscopy, H. pylori was diagnosed by culture, histology, rapid urease test, (13)C urea breath test (UBT), and immunoglobulin G antibodies to H. pylori in serum. The performances of (13)C-UBT and antibody test were compared to a gold standard defined by a positive H. pylori test by culture or, in case of a negative culture result, by positive histology and a positive rapid urease test. RESULTS: The sensitivity and specificity of the (13)C-UBT were 93% and 88%, respectively, relative to the gold standard. The antibody test had an equivalent sensitivity of 93% with a reduced specificity of 68%. The false positive results for the antibody test were associated with previous treatment for an H. pylori infection [relative risk (RR) = 2.8]. High levels of antibodies to H. pylori were associated with chronic gastritis and male gender, while high scores in the (13)C-UBT test were associated with older age and with the H. pylori bacteria load on histological examination (RR = 4.4). CONCLUSION: The (13)C-UBT outperformed the antibody test for H. pylori and could be used when a non-invasive test is clinically necessary to document treatment outcome or when monitoring for reinfection.

Alaska sentinel surveillance study of Helicobacter pylori isolates from Alaska Native persons from 2000 to 2008.

Helicobacter pylori infection is more common in Alaska Native persons than in the general U.S. population, with seroprevalence to H. pylori approaching 75%. Previous studies in Alaska have demonstrated elevated proportions of antimicrobial resistance among H. pylori isolates. We analyzed H. pylori data from the Centers for Disease Control and Prevention's sentinel surveillance in Alaska from January 2000 to December 2008 to determine the proportion of culture-positive biopsy specimens with antimicrobial resistance from Alaska Native persons undergoing endoscopy. The aim of the present study was to monitor antimicrobial resistance of H. pylori isolates over time and by region in Alaska Native persons. Susceptibility testing of H. pylori isolates to metronidazole, clarithromycin, amoxicillin, and tetracycline was performed using agar dilution. Susceptibility testing for levofloxacin was performed by Etest. Overall, 45% (532/1,181) of persons undergoing upper endoscopy were culture positive for H. pylori. Metronidazole resistance was demonstrated in isolates from 222/531 (42%) persons, clarithromycin resistance in 159/531 (30%) persons, amoxicillin resistance in 10/531 (2%) persons, and levofloxacin resistance in 30/155 (19%) persons; no tetracycline resistance was documented. The prevalence of metronidazole, clarithromycin, and levofloxacin resistance varied by region. Female patients were more likely than male patients to demonstrate metronidazole (P < 0.05) and clarithromycin (P < 0.05) resistance. No substantial change in the proportion of persons with resistant isolates was observed over time. Resistance to metronidazole, clarithromycin, and levofloxacin is more common among H. pylori isolates from Alaska Native persons than those from elsewhere in the United States.

2009 Pandemic influenza A H1N1 in Alaska: temporal and geographic characteristics of spread and increased risk of hospitalization among Alaska Native and Asian/Pacific Islander people.

Alaska Native people have suffered disproportionately from previous influenza pandemics. We evaluated 3 separate syndromic data sources to determine temporal and geographic patterns of spread of 2009 pandemic influenza A H1N1 (pH1N1) in Alaska, and reviewed records from persons hospitalized with pH1N1 disease in 3 areas in Alaska to characterize clinical and epidemiologic features of disease in Alaskans. A wave of pH1N1 disease swept through Alaska beginning in most areas in August or early September. In rural regions, where Alaska Native people comprise a substantial proportion of the population, disease occurred earlier than in other regions. Alaska Native people and Asian/Pacific Islanders (A/PI) were 2-4 times more likely to be hospitalized than whites. Alaska Native people and other minorities remain at high risk for early and substantial morbidity from pandemic influenza episodes. These findings should be integrated into plans for distribution and use of vaccine and antiviral agents.

Factors associated with the progression of fibrosis on liver biopsy in Alaska Native and American Indian persons with chronic hepatitis C.

BACKGROUND: Various factors influence the development and rate of fibrosis progression in chronic hepatitis C virus (HCV) infection. OBJECTIVES: To examine factors associated with fibrosis in a longterm outcomes study of Alaska Native/American Indian persons who underwent liver biopsy, and to examine the rate of fibrosis progression in persons with subsequent biopsies. METHODS: A cross-sectional analysis of the demographic, inflammatory and viral characteristics of persons undergoing liver biopsy compared individuals with early (Ishak fibrosis score of lower than 3) with those with advanced (Ishak score of 3 or greater) fibrosis. Persons who underwent two or more biopsies were analyzed for factors associated with fibrosis progression. RESULTS: Of 253 HCV RNA-positive persons who underwent at least one liver biopsy, 76 (30%) had advanced fibrosis. On multivariate analysis, a Knodell histological activity index score of 10 to 14 and an alpha-fetoprotein level of 8 ng/mL or higher were found to be independent predictors of advanced liver fibrosis (P<0.0001 for each). When surrogate markers of liver inflammation (alanine aminotransferase, aspartate aminotransferase/alanine aminotransferase ratio and alpha-fetoprotein) were removed from the model, type 2 diabetes mellitus (P=0.001), steatosis (P=0.03) and duration of HCV infection by 10-year intervals (P=0.02) were associated with advanced fibrosis. Among 52 persons who underwent two or more biopsies a mean of 6.2 years apart, the mean Ishak fibrosis score increased between biopsies (P=0.002), with progression associated with older age at initial biopsy and HCV risk factors. CONCLUSIONS: The presence of type 2 diabetes mellitus, steatosis and duration of HCV infection were independent predictors of advanced fibrosis in the present cohort, with significant fibrosis progression demonstrated in persons who underwent serial biopsies.

Methicillin-resistant Staphylococcus aureus-associated hospitalizations among the American Indian and Alaska native population.

BACKGROUND: American Indians and Alaska Natives (AI/ANs) have had documented outbreaks of methicillin-resistant Staphylococcus aureus (MRSA) infection but, to our knowledge, no studies have examined MRSA infection among this population nationally. We describe MRSA-associated hospitalizations among the approximately 1.6 million AI/ANs who receive care at Indian Health Service health care facilities nationwide. METHODS: We used hospital discharge data from the Indian Health Service National Patient Information Reporting System to determine the rate of MRSA-associated hospitalizations among AI/ANs who used Indian Health Service health care in 1996-2005 and in the comparison periods 1996-1998 and 2003-2005. Hospitalization rates among AI/ANs were examined by year, age group, sex, and region. MRSA-associated diagnoses were also examined. Rate comparisons were performed using Poisson regression analysis. Comparison of rates to those of the general United States population was made for 2003-2005 by means of the Nationwide Inpatient Sample. RESULTS: Between comparison periods, the rate of MRSA-associated hospitalization increased from 4.6 to 50.6 hospitalizations per 100,000 AI/ANs (P<.01), with increases in both sexes, all age groups, and all regions. By 2005, MRSA was the causative organism for the majority (52%) of all S. aureus-associated hospitalizations. The most common associated diagnosis was skin and soft-tissue infection, which accounted for 59% of MRSA-associated diagnoses. In 2003-2005, the age-adjusted rate among AI/ANs was 58.8 hospitalizations per 100,000 persons, compared with 84.7 hospitalizations per 100,000 persons in the general US population. CONCLUSIONS: MRSA-associated hospitalizations have increased significantly among AI/ANs served by Indian Health Service health care facilities. Clinicians should have a high index of suspicion for MRSA infection in AI/ANs, especially in those with a diagnosis of skin and soft-tissue infection.

Controlled, household-randomized, open-label trial of the effect of treatment of Helicobacter pylori infection on iron deficiency among children in rural Alaska: results at 40 months.

BACKGROUND: Helicobacter pylori infection treatment was found not to reduce the prevalence of iron deficiency or anemia among Alaska Native children at 14 months after treatment initiation. We hypothesized that 14 months was to early to resolve H. pylori-induced gastric damage. Consequently, we conducted a 40-month follow-up. METHODS: We enrolled 219 children 7-11 years old who had H. pylori infection (as diagnosed by (13)C-labeled urea breath test) and iron deficiency (serum ferritin level, <22.47 pmol/L) in a controlled, household-randomized trial of the effect of treatment of H. pylori on iron deficiency and anemia (hemoglobin level, <115 g/L). At 40 months, 176 children were evaluated. RESULTS: Forty-four (52%) of 85 children in the intervention group and 53 (58%) of 91 in the control group had iron deficiency (adjusted relative risk [ARR], 0.92 [95% confidence interval {CI}, 0.68-1.26]), versus 4 (5%) and 17(19%), respectively, with both iron deficiency and anemia (ARR, 0.25 [95% CI, 0.09-0.73]). Reinfection occurred among 33 (52%) of 64 children who had cleared their infection. H. pylori-negative children had lower prevalences of iron deficiency (ARR, 0.62 [95% CI, 0.38-1.01]) and iron deficiency and anemia (ARR, 0.22 [95% CI, 0.03-1.50]), compared with H. pylori -positive children. CONCLUSIONS: The resolution of H. pylori infection for >14 months modestly reduced the prevalence of iron deficiency and substantially reduced the prevalence of iron deficiency and anemia. H. pylori likely plays a casual role in hematological outcomes for some children.

The relationship between in-home water service and the risk of respiratory tract, skin, and gastrointestinal tract infections among rural Alaska natives.

OBJECTIVES: We investigated the relationship between the presence of in-home piped water and wastewater services and hospitalization rates for respiratory tract, skin, and gastrointestinal tract infections in rural Alaska. METHODS: We determined in-home water service and hospitalizations for selected infectious diseases among Alaska Natives by region during 2000 to 2004. Within 1 region, infant respiratory hospitalizations and skin infections for all ages were compared by village-level water services. RESULTS: Regions with a lower proportion of home water service had significantly higher hospitalization rates for pneumonia and influenza (rate ratio [RR] = 2.5), skin or soft tissue infection (RR = 1.9), and respiratory syncytial virus (RR = 3.4 among those younger than 5 years) than did higher-service regions. Within 1 region, infants from villages with less than 10% of homes served had higher hospitalization rates for pneumonia (RR = 1.3) and respiratory syncytial virus (RR = 1.2) than did infants from villages with more than 80% served. Outpatient Staphylococcus aureus infections (RR = 5.1, all ages) and skin infection hospitalizations (RR = 2.7, all ages) were higher in low-service than in high-service villages. CONCLUSIONS: Higher respiratory and skin infection rates were associated with a lack of in-home water service. This disparity should be addressed through sanitation infrastructure improvements.

Impact of conjugate vaccine on transmission of antimicrobial-resistant Streptococcus pneumoniae among Alaskan children.

BACKGROUND: The impact of heptavalent pneumococcal conjugate vaccine (PCV7) on transmission of antimicrobial-resistant Streptococcus pneumoniae is an important concern for countries considering PCV7 introduction. METHODS: Every winter from 2000 to 2004, as PCV7 was routinely introduced, we obtained nasopharyngeal swabs for pneumococcal culture, serotyping, and susceptibility testing from 150 children aged 3-59 months at each of 3 Anchorage, Alaska clinics. We assessed risk factors for pneumococcal carriage, including vaccination status and antimicrobial use. RESULTS: Between 2000 and 2004, 2250 nasopharyngeal swabs from 2061 infants and children were collected. The proportion of children receiving > or = 1 PCV7 vaccination increased from 0 to 89%, whereas overall pneumococcal carriage remained stable (38% versus 41%, respectively). Among S. pneumoniae carriers, we observed declines in carriage of PCV7 serotypes (from 54% to 10%, P < 0.01) and trimethoprim-sulfamethoxazole nonsusceptible strains (44% to 16%, P < 0.01), but not in PCN-nonsusceptible strains (36% versus 37%). Among PCN-nonsusceptible types, the proportion of serotype 19A strains increased from 10% to 32% (P = 0.0002). Recent beta-lactam use was stable throughout the period (29% overall), whereas trimethoprim-sulfamethoxazole use declined from 6% to 2% (P = 0.02). CONCLUSIONS: PCV7 vaccination in the first 5 years did not affect overall pneumococcal carriage, but was associated with a shift in serotype distribution from PCV7 types to non-PCV7 types. With persistent pressure of some antimicrobials, reductions in carriage of antimicrobial nonsusceptible PCV7 types may be offset by increases in carriage of nonsusceptible non-PCV7 types.

Dynamics of Helicobacter pylori-specific immunoglobulin G for 2 years after successful eradication of Helicobacter pylori infection in an American Indian and Alaska Native population.

Helicobacter pylori antibodies were measured over 24 months in American Indian and Alaska Native persons who cleared their infections. Two months after treatment, 82% of H. pylori-negative persons remained seropositive. While there were declines in H. pylori antibodies for 12 months, after 24 months 71% of persons remained seropositive.

Alaska sentinel surveillance for antimicrobial resistance in Helicobacter pylori isolates from Alaska native persons, 1999-2003.

BACKGROUND: Previous studies in Alaska have demonstrated elevated proportions of antimicrobial resistance among Helicobacter pylori isolates. MATERIALS AND METHODS: We analyzed H. pylori data from the Centers for Disease Control and Prevention (CDC)'s sentinel surveillance in Alaska from July 1999 to June 2003 to determine the proportion of culture-positive biopsies from Alaska Native persons undergoing routine upper-endoscopy, and the susceptibility of H. pylori isolates to metronidazole [minimum inhibitory concentration (MIC) of > 8 g metronidazole/mL), clarithromycin (MIC > or = 1), tetracycline (MIC > or = 2) and amoxicillin (MIC > or = 1)] using agar dilution. RESULTS: Nine-hundred sixty-four biopsy specimens were obtained from 687 participants; 352 (51%) patients tested culture positive. Mean age of both culture-positive and culture-negative patients was 51 years. Metronidazole resistance was demonstrated in isolates from 155 (44%) persons, clarithromycin resistance from 108 (31%) persons, amoxicillin resistance from 8 (2%) persons, and 0 for tetracycline resistance. Metronidazole and clarithromycin resistance varied by geographic region. Female patients were more likely than male subjects to show metronidazole resistance (p < .01) and clarithromycin resistance (p = .05). CONCLUSIONS: Resistance to metronidazole and clarithromycin is more common among H. pylori isolates from Alaska Native persons when compared with those from elsewhere in the USA.

Indirect effect of conjugate vaccine on adult carriage of Streptococcus pneumoniae: an explanation of trends in invasive pneumococcal disease.

BACKGROUND: Use of heptavalent protein-polysaccharide pneumococcal conjugate vaccine (PCV7) has been associated with decreases in PCV7-type invasive pneumococcal disease and nasopharyngeal (NP) carriage in children. Vaccine use has also indirectly decreased the rate of invasive disease in adults, presumably through decreased transmission of pneumococci from vaccinated children to adults. METHODS: We conducted NP carriage surveys in 8 villages in Alaska in 1998-2004. Streptococcus pneumoniae isolates were characterized by serotype and antimicrobial susceptibility. We analyzed trends in serotype distribution, antibiotic resistance, and factors associated with adult carriage of PCV7-serotype pneumococci before and after the introduction of PCV7 in 2001. RESULTS: We collected 15,598 NP swabs; overall, 52% of adults living in the villages surveyed participated in the colonization study. The proportion of adult carriers with PCV7-type pneumococcal carriage decreased from 28% of carriers in 1998-2000 to 4.5% of carriers in 2004 (P<.0001). Among adults, the proportion of colonizing isolates that were resistant to penicillin decreased from 13% in 1998-2000 to 6% in 2004 (P=.05), whereas the percentage of isolates with intermediate susceptibility to penicillin increased from 12% in 1998-2000 to 19% in 2004 (P<.01). Adults were more likely to carry PCV7-type pneumococci if they lived with a child <5 years old or if they lived with a child who had not been age-appropriately vaccinated with PCV7. CONCLUSIONS: Pediatric vaccination with PCV7 has resulted in decreased PCV7-type pneumococcal carriage among adults and helps to explain recent decreases in the rate of PCV7-type invasive pneumococcal disease among adults.

Persistence of antibody to hepatitis B and protection from disease among Alaska natives immunized at birth.

BACKGROUND: Alaska Native (AN) children were at high risk of acquiring hepatitis B virus (HBV) infection before vaccination began in 1983. We evaluated the long-term protection from hepatitis B (HB) vaccination among AN children immunized when infants. METHODS: During 1984-1995, we recruited a convenience sample of AN children who had received a three dose series of HB vaccine starting at birth and had serum antibody to hepatitis B (anti-HBs) concentrations of >/= 10 mIU/mL at 7-26 months of age. We evaluated anti-HBs concentrations and the presence of anti-HBc in participants' sera every other year up to age 16 years. Anti-HB core antigen (anti-HBc)-positive specimens were tested for hepatitis B surface antigen and for HBV DNA. RESULTS: We followed 334 children for 3151 person-years (median, 10 years per child) with 1610 specimens collected. Anti-HBs concentrations dropped rapidly among all participants. Among children 2, 5 and 10 years of age, 37 of 79 (47%), 33 of 176 (19%) and 8 of 95 (8%), respectively, had anti-HBs concentrations of >/= 10 mIU/mL. Receipt of recombinant vaccine was significantly associated with a more rapid antibody decline (P < 0.001). Six (1.8%) children acquired anti-HBc, 3 of whom had definite breakthrough infections (at least 2 consecutive anti-HBc-positive specimens or at least 1 anti-HBc-positive specimen and HBV DNA detection by PCR). None of these children had detectable hepatitis B surface antigen, and none had symptoms of hepatitis. CONCLUSIONS: Anti-HBs concentrations declined over time among AN infants successfully immunized with HB vaccine starting at birth. Transient anti-HBc appeared in a small percentage of children; however, none developed clinical signs of hepatitis or chronic HBV infection.

Impact of heptavalent pneumococcal conjugate vaccine on invasive disease, antimicrobial resistance and colonization in Alaska Natives: progress towards elimination of a health disparity.

We evaluated invasive pneumococcal disease (IPD), antimicrobial resistance and nasopharyngeal colonization before and after introduction of pneumococcal conjugate vaccine (PCV7) in Alaska Natives (AN), a population with high IPD rates. We obtained IPD rates from population-based surveillance. Colonization was determined from annual surveys among rural AN of all ages and from urban children. After vaccine introduction, vaccine-type IPD rates declined by 91% among AN children <2 years, by 80% among non-Natives <2 years, and by 40% for adults of all races (P<0.001 each). IPD decreased for isolates resistant to penicillin, erythromycin and cotrimoxazole (P<0.001 each). Vaccine-type colonization decreased among rural and urban children <5 years and among rural adults (P<0.001 each). PCV7 vaccine has eliminated a longstanding disparity of vaccine-type IPD for AN children. Decreased vaccine-type colonization and IPD in adults demonstrate indirect vaccine effects.

Evaluation of seaFAST, a rapid fluorescent in situ hybridization test, for detection of Helicobacter pylori and resistance to clarithromycin in paraffin-embedded biopsy sections.

A commercially available rapid fluorescent in situ hybridization (FISH) test, (seaFAST H. pylori Combi-Kit; SeaPro Theranostics International, Lelystad, The Netherlands) was used to simultaneously detect the presence of Helicobacter pylori and determine clarithromycin susceptibility in paraffin-embedded biopsy sections. The FISH method was found to be 97% sensitive, 94% specific for the detection of H. pylori and comparable to agar dilution for the detection of resistance to clarithromycin.

Evaluation of a volunteer sample in nasopharyngeal colonization surveys for Streptococcus pneumoniae in rural Alaska.

OBJECTIVE: To compare characteristics of persons in rural northern communities who participated in a study on antimicrobial use and drug-resistant Streptococcus pneumoniae (SP) to those who did not participate. STUDY DESIGN: The original study (1998--2000) was a community-based, controlled intervention trial designed to determine the penicillin susceptibility of nasopharyngeal SP isolates in relation to community-wide use of antibiotics. The study continued after 2000, in a subset of the original communities, to prospectively evaluate the impact of the heptavalent pneumococcal conjugate vaccine on the carriage of SP. The results presented here are an analysis of the first five years of data. METHODS: We conducted annual surveys (1998--2002) for nasopharyngeal colonization of SP using a volunteer sample of residents in rural communities. Medical chart reviews for health clinic visitation and antibiotic use were completed for all village residents. RESULTS: Participants were younger (22.8 vs. 28.4 years), had more health clinic utilization (3.3 vs. 2.4 visits) and received more antibiotics (1.0 vs. 0.6 courses) than non-participants. Differences between participants and non-participants were similar across all years of the study. CONCLUSIONS: Our study provides further empirical evidence that selection bias should be considered when designing studies. However, a volunteer sample provided internal consistency for comparison of our main study outcomes across time.

Antibody levels and protection after hepatitis B vaccination: results of a 15-year follow-up.

BACKGROUND: The duration of protection afforded by hepatitis B vaccination is unknown. OBJECTIVE: To determine antibody persistence and protection from hepatitis B virus (HBV) infection. DESIGN: Prospective cohort study. SETTING: 15 villages in southwest Alaska. PARTICIPANTS: 1578 Alaska Natives vaccinated at age 6 months or older. INTERVENTION: During 1981-1982, participants received 3 doses of plasma-derived hepatitis B vaccine. This cohort was followed annually over the first 11 years, and 841 (53%) persons were tested at 15 years. MEASUREMENTS: Antibody to hepatitis B surface antigen (anti-HBs), markers of HBV infection, and testing to identify HBV variants. RESULTS: Levels of anti-HBs in the cohort decreased from a geometric mean concentration of 822 mIU/mL after vaccination to 27 mIU/mL at 15 years. Initial anti-HBs level, older age at vaccination, and male sex were associated with persistence of higher anti-HBs levels at 15 years when analyzed by a longitudinal linear mixed model. After adjustment for initial anti-HBs level and sex, those vaccinated at age 6 months to 4 years had the lowest anti-HBs level at 15 years. Asymptomatic breakthrough infections were detected in 16 participants and occurred more frequently in persons who did not respond to vaccination than those who responded (P = 0.01). Among infected persons with viremia, 2 were infected with wild-type HBV and 4 had HBV surface glycoprotein variants, generally accompanied by wild-type HBV. LIMITATIONS: The loss of participants to follow-up at 15 years was 47%. However, characteristics of persons tested were similar to those of persons lost to follow-up. CONCLUSIONS: Hepatitis B vaccination strongly protected against infection for at least 15 years in all age groups. Antibody levels decreased the most among persons immunized at 4 years of age or younger.

Impact of a conjugate vaccine on community-wide carriage of nonsusceptible Streptococcus pneumoniae in Alaska.

BACKGROUND: Streptococcus pneumoniae is a leading cause of invasive bacterial disease and pneumonia among children. Antimicrobial resistance among pneumococci has increased in recent years and complicates treatment. The introduction of heptavalent pneumococcal conjugate vaccine (PCV7) could reduce acquisition of antimicrobial-resistant pneumococci. METHODS: We obtained 1350 nasopharyngeal swabs for culture from 1275 children aged 3-59 months presenting at 3 clinics in Anchorage, Alaska, during the winters of 2000, 2001, and 2002, as PCV7 was being introduced into the routine immunization schedule. We recorded the frequency of use of antibiotics as well as the dates of doses of PCV7 for enrolled children. We used multivariate logistic regression modeling to identify independent risk factors for overall carriage of pneumococci and carriage of PCV7-type pneumococci, cotrimoxazole-nonsusceptible (COT-NS) pneumococci, or penicillin-nonsusceptible (PCN-NS) pneumococci. RESULTS: The proportion of children who were up-to-date for age, with respect to PCV7 vaccination, increased from 0% in 2000 to 55% in 2002. Carriage of PCV7-type pneumococci decreased by 43% (P<.0001). Risk of carriage of PCV7-type pneumococci was lower in 2002 than in 2000, independent of vaccination status, suggesting an indirect effect of vaccination. Carriage of COT-NS, but not PCN-NS, pneumococci also decreased (38%; P=.02), not only among vaccinated children but also among unvaccinated children without recent use of antibiotics. CONCLUSIONS: Introduction of PCV7 into the routine infant immunization schedule in a community with a high prevalence of antimicrobial-resistant pneumococci appears to reduce transmission of PCV7 vaccine serotypes and COT-NS pneumococci but has no impact on overall carriage of pneumococci or carriage of PCN-NS pneumococci.

Estimating the date of hepatitis C virus infection from patient interviews and antibody tests on stored sera.

OBJECTIVES: Studies on the natural history and outcome of chronic hepatitis C virus (HCV) infection differ regarding the proportion of persons who develop serious sequelae over time. Most of these studies use an estimated date of HCV infection based on risk factor data obtained from patient interviews. The date of HCV infection is often estimated using the year of a pre-1992 blood transfusion (BT), or the first year of injecting drug use (IDU). We sought to determine the accuracy of these dates obtained by interview. METHODS: We compared BT dates reported by patients in a long-term HCV outcome study to dates confirmed in a BT-Lookback project, and also compared the reported first year of IDU to seroconversion dates estimated from HCV tests on historical sera. RESULTS: Of 28 BT recipients who were interviewed in the HCV outcome study and identified in the Lookback project, 14 (50%; 95% CI: 31-69%) were unaware they had received a BT. Of 25 persons identified in the BT-Lookback project with historical sera available, 9 (36%; 95% CI: 19-57%) had anti-HCV results that did not correlate with their confirmed BT date. Of 216 persons with a history of IDU and historical serum samples available, 66 (31%; 95% CI: 25-37%) had anti-HCV results that did not correlate with their reported first year of IDU. CONCLUSIONS: Inaccuracies in the length of HCV could occur in outcome studies that rely on patient recall of risk-factor history. Statistical methods that incorporate the uncertainty in assigning infection date are needed.