Michael G. Bruce

Outbreak of Leptospirosis among Triathlon Participants and Community Residents in Springfield, Illinois, 1998

We investigated an outbreak of leptospirosis among athletes and community residents after a triathlon was held in Springfield, Illinois. A telephone survey was conducted to collect clinical information and data on possible risk factors, community surveillance was established, and animal specimens and lake water samples were collected to determine the source of the leptospiral contamination. A total of 834 of 876 triathletes were contacted; 98 (12%) reported being ill. Serum samples obtained from 474 athletes were tested; 52 of these samples (11%) tested positive for leptospirosis. Fourteen (6%) of 248 symptomatic community residents tested positive for leptospirosis. Heavy rains that preceded the triathlon are likely to have increased leptospiral contamination of Lake Springfield. Among athletes, ingestion of 1 or more swallows of lake water was a predominant risk factor for illness. This is the largest outbreak of leptospirosis that has been reported in the United States. Health care providers and occupational and recreational users of bodies of freshwater in the United States should be aware of the risk of contracting leptospirosis, particularly after heavy rains.

The relationship among previous antimicrobial use, antimicrobial resistance, and treatment outcomes for Helicobacter pylori infections

Context Adverse effects of previous antibiotic use in patients with Helicobacter pylori infections are unclear. Contribution This retrospective study examined relationships between resistant H. pylori infections and past antibiotic use in 125 Alaskan Native adults. Clarithromycin-resistant H. pylori isolates were common (prevalence, 30%) and were associated in a dose-response manner with previous use of macrolide antibiotics. Of patients with these resistant isolates, 77% had treatment failure with clarithromycin-based regimens. Implications Previous use of macrolide antibiotics is associated with increased risk for infection with clarithromycin-resistant H. pylori and increased risk for treatment failure with that antibiotic. The Editors Helicobacter pylori is a common pathogen of the gastric mucosa, infecting up to 40% of persons in developed countries and up to 90% of individuals living in developing nations (1, 2). Infection with H. pylori has been shown to be a major cause of gastric and duodenal ulcers and is also associated with chronic gastritis, mucosa-associated lymphoid tissue lymphoma, and adenocarcinoma of the stomach (3-6). Eradication of H. pylori has been reported in up to 95% of patients treated with a combination of antimicrobial agents (7-9). In the United States and elsewhere, antimicrobial resistance to metronidazole and clarithromycin is increasing; resistance to amoxicillin and tetracycline remains uncommon (10-12). Compared with persons with susceptible isolates, persons infected with clarithromycin- or metronidazole-resistant H. pylori have lower cure rates when treated with regimens containing these antimicrobial agents (12-15). In studies that have addressed risk factors associated with resistant H. pylori infection, none to our knowledge have evaluated prediagnosis antimicrobial use as a risk factor for resistance or treatment failure (16, 17). Alaska Nativespersons of Eskimo, Indian, and Aleut descenthave high rates of H. pylori infection, with an overall seroprevalence of 75% for specific antibodies (18). We are conducting a study in urban Alaska Native, rural Alaska Native, and urban non-Native adults to determine and compare reinfection rates after successful eradication of H. pylori. The study in urban Alaska Native adults is completed, and in this group, we sought to determine whether past antimicrobial use was associated with antimicrobial resistance among H. pylori isolates obtained through diagnostic endoscopy. We then determined whether H. pylori antimicrobial resistance affected the outcome of H. pylori treatment. Methods From September 1998 through June 2002, the Arctic Investigations Program of the U.S. Centers for Disease Control and Prevention and the Alaska Native Medical Center (ANMC) conducted a study to determine reinfection rates after successful eradication of H. pylori infection among Alaska Natives living in Anchorage. The ANMC is a 150-bed referral hospital that provides outpatient primary care services for Alaska Natives living in the Anchorage area. The institutional review boards of the Centers for Disease Control and Prevention, the Alaska Area Tribal Health Consortium, and the Indian Health Service approved the study, as did the Alaska Native Health Board. Written informed consent was obtained from all participants. Patients and Data Collection From September 1998 through June 2002, we attempted to recruit all Alaska Natives 18 years of age or older from the Anchorage area who had no history of an immunodeficiency condition or were not taking immunosuppressive medications (such as corticosteroids or cancer chemotherapeutic agents) and were scheduled for esophagogastroduodenoscopy. Alaska Natives who use ANMC for surgical procedures are very likely to receive most of their care from this facility, since no copayment is assessed to persons eligible for care at ANMC. A study nurse recruited 293 persons during the study period, 149 of whom had a positive culture for H. pylori. Since 27 September 1990, patient care information from all outpatient health care visits and outpatient pharmacy encounters at ANMC has been entered into a computerized records system. For this analysis, we recorded all antimicrobial prescriptions for 10 years before diagnosis of H. pylori infection by consulting outpatient records of study participants for whom at least 8 years of pharmacy records were available. We also recorded antimicrobial use during all hospitalizations and emergency department visits at ANMC for each participant in the same 10-year period. An antimicrobial course was defined as a prescription for an antimicrobial drug regardless of dose, duration, and frequency. Biopsy and Culture All participants had up to 3 gastric biopsy specimens taken for culture, antimicrobial susceptibility testing, and histologic examination for H. pylori. Gastric biopsy specimens stored in cysteine freeze medium at 80 C were ground in a sterile tissue grinder with heat-inactivated fetal bovine serum and inoculated to 3 types of solid media: blood agar (tryptic soy agar with 5% sheep blood); chocolate agar; and brucella agar containing 10% horse blood, trimethoprim, vancomycin, and polymyxin B. All cultures were incubated at 37 C under microaerophilic conditions and high humidity (12% CO2, 98% humidity) for up to 10 days. Positive cultures were usually identified after 3 to 5 days of incubation. Isolates were identified as H. pylori on the basis of positive catalase, oxidase, and urease reactions; typical uniform, small, translucent colonies; curved gram-negative bacilli on Gram-stained smears; susceptibility to cephalothin (30 g); and resistance to nalidixic acid (30 g). Minimum inhibitory concentrations (MICs) for clarithromycin, amoxicillin, metronidazole, and tetracycline were determined by using agar dilution. Helicobacter pylori isolates were defined as susceptible if the MIC was within the following limits: less than or equal to 0.25 g/mL for clarithromycin, less than or equal to 0.25 g/mL for amoxicillin, less than 8 g/mL for metronidazole, and less than 2 g/mL for tetracycline. Helicobacter pylori isolates with MICs above these limits were classified as resistant (19). In participants who had many cultures of their H. pylori isolates, the highest MIC determined from all of the cultures was used for analysis. Culture results were not available to providers before initiation of treatment. Treatment and Follow-up Each participants attending physician decided whether to initiate treatment and selected the treatment regimen. Patients who were treated received a 2-week course of a combination of 2 or 3 antibiotics plus lansoprazole. A study nurse called each patient approximately every 3 days to document adherence. Successful eradication of H. pylori was defined as negative results on a urea breath test (BreathTek UBT, Meretek Diagnostics, Inc., Nashville, Tennessee) 8 weeks after initiation of treatment. Statistical Analysis Statistical analysis was performed by using StatXact 5 (Cytel Software Corp., Cambridge, Massachusetts) and SAS software (SAS Institute, Inc., Cary, North Carolina). Confidence intervals for binomial proportions were computed by using the Casella procedure (20). Bivariate associations were examined by using the chi-square test or the Fisher exact test for dichotomous variables. The Wilcoxon rank-sum test was used for comparisons of continuous variables. Logistic regression was used to test univariable dose-response relationships and multivariable associations with antimicrobial resistance. Variables were considered for the multivariable models if their univariable P value was less than 0.25, with the exception of sex, which was included in all models. The numbers of courses of macrolides, clarithromycin, erythromycin, azithromycin, and metronidazole were entered into the multivariable models as indicator variables ( 1 course or 0 courses), while the number of all other courses of antibiotics was entered as an interval variable. Variables were considered confounders and remained in the model if their exclusion changed the value of the coefficients of interest by more than 15%. All P values are two-sided, and confidence intervals are exact when appropriate. Results One hundred forty-nine persons with culture-confirmed H. pylori infection were enrolled in the study. Of these, 125 who had documented health encounters for at least 8 years before enrollment (84%) were included for analysis. The median age of participants was 46.5 years (range, 22.2 to 88.7 years). Eighty-two (66%) were women, and all were Alaska Natives. Pharmacy records were available for a median of 8.6 years (range, 8.0 to 9.6 years). A median of 11 (range, 0 to 68) antimicrobial courses was prescribed during the 8 to 10 years before enrollment (mean, 1.52 courses per year). For -lactam antimicrobial agents and macrolide antimicrobial agents, the median number of courses prescribed was 5 (range, 0 to 31) and 1 (range, 0 to 11), respectively. The median number of courses for all other classes of antimicrobial agents prescribed (including metronidazole) was 3 (range, 0 to 30). Thirteen patients (10%) had received previous treatment for H. pylori infection in the 10 years before enrollment. Clinical symptoms included heartburn (75%), nausea (72%), vomiting (40%), and hematemesis (11%). Endoscopic findings included hemorrhagic or superficial ulcerations of the gastric mucosa in 56 patients (45%), duodenal ulcers in 4 (3%), and gastric ulcers in 8 (6%). Two specimens of the gastric mucosa were obtained for culture from 105 participants (84%) at the time of diagnosis. Seventeen patients (14%) had a single specimen submitted for culture, and 3 (2%) had 3 or more specimens. Among the 125 participants, 83 (66%) were found to have H. pylori isolates resistant to metronidazole, 37 (30%) were found to have H. pylori isolates resistant to clarithromycin, 7 (6%) were found to have H. pylori isolates resistant t

Epidemiology ofHelicobacter pyloriInfection

This review summarizes studies on the epidemiology of Helicobacter pylori published in peer‐reviewed journals between April 2007 and March 2008. Infection with H. pylori often occurs in childhood, and once established, can persist lifelong if untreated. Prevalence of H. pylori infection is higher in developing countries when compared to developed countries, and can vary by ethnicity, place of birth, and socioeconomic factors even among persons living in the same country. Prevalence of infection is decreasing in many countries due to improvements in sanitation and living standards and the relatively recent movement of populations from rural to urban settings; however, post‐treatment recurrence rates of H. pylori infection remain high in developing countries, and in given populations within developed countries. In addition, a number of recent studies have begun to explore the possible link between childhood infection with H. pylori and protection against asthma and allergy.

Invasive Pneumococcal Disease in Alaskan Children: Impact of the Seven-Valent Pneumococcal Conjugate Vaccine and the Role of Water Supply

Background: Alaska Native (AN) children, especially those in the Yukon-Kuskokwim region (YK-AN children), suffer some of the highest rates of invasive pneumococcal disease (IPD) in the world. Rates of IPD declined after statewide introduction of the 7-valent pneumococcal conjugate vaccine (PCV7) in 2001, but increased in subsequent years. Methods: Population-based laboratory surveillance data (1986–2007) for invasive Streptococcus pneumoniae infection in Alaskan children <5 years old were used to evaluate the association of IPD rates and serotype distribution with immunization, socioeconomic status, and in-home water service. Results: Introduction of PCV7 vaccine resulted in elimination of IPD caused by vaccine serotypes, but was followed by increasing rates of IPD caused by nonvaccine serotypes. Among YK-AN children IPD rates dropped by 60%, but then rose due to non-PCV7 serotypes to levels 5- to 10-fold higher than rates in non-YK-AN children and non-AN children. IPD rates in YK-AN children were twice as high in villages where <10% of houses had in-home piped water compared with villages where more than 80% of houses had in-home piped water (390 cases/100,000 vs. 146 cases/100,000, P = 0.008). Conclusions: High IPD rates in Alaska are associated with lack of in-home piped water (controlling for household crowding and per capita income). The effect of in-home piped water is most likely mediated through reduced water supply leading to limitations on handwashing.

Epidemiology of Haemophilus influenzae serotype a, North American Arctic, 2000-2005.

Serotype a is now the most common seen in the North American Arctic; highest rates occur in indigenous children.

The Relationship between Previous Fluoroquinolone Use and Levofloxacin Resistance in Helicobacter pylori Infection

The relationship between prior fluoroquinolone use and levofloxacin resistance in Helicobacter pylori infection is unknown. Among 125 enrolled patients, 8.8% had H. pylori isolates that were resistant to levofloxacin. Levofloxacin resistance was associated with any prior fluoroquinolone use over the previous 10 years and with the total number of fluoroquinolone courses prescribed (P<.001).

Epidemiology and risk factors for hepatitis C in Alaska Natives

Large cohorts of persons infected with hepatitis C virus (HCV) that include patients with multiple risk exposures and behaviors have been rarely reported. We herein describe a population‐based cohort of 759 Alaska Natives (AN) with HCV who were recruited into a long‐term follow‐up study. History of injection drug use (IDU) was reported by 60.1% and blood transfusion by 14.0%. The most common genotype was 1a (42.0%), followed by 1b (20.3%), 2b (14.7%), 3a (14.3%), and 2a (7.8%). By multivariable analysis, risk exposures (blood transfusion vs. other; P < 0.01; odds ratio [OR], 2.87; 95% confidence interval [CI], 1.51–5.45) and year of infection (P < 0.01; OR, 3.47; 95% CI, 1.34–8.96) were significantly associated with HCV RNA‐positivity. Having an RNA concentration ≥2 million copies/mL was associated with male gender (OR, 1.94) and genotype (P < 0.01 overall; 1a vs. 3a: OR, 1.92; 2b vs. 3a: OR, 3.17) by multivariable analysis. In conclusion, the two principal risk exposures for AN infected with HCV (IDU and blood transfusion) are the same as the overall U.S. population. Persons with a history of blood transfusion were more likely to be HCV RNA positive than those without such history. Higher RNA levels found in males may explain the more severe disease previously reported in this group. (HEPATOLOGY 2004;39:325–332.)

International circumpolar surveillance system for invasive pneumococcal disease, 1999-2005

Disease rates are high among indigenous persons in Arctic countries, and PCV7 has resulted in decreased rates in North American children.

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.

International Circumpolar Surveillance, An Arctic Network for the Surveillance of Infectious Diseases

Hospitals, public health agencies, and reference laboratories work together to detect and control infectious disease in Arctic regions.