Paul V. Effler

Sporadic Campylobacter jejuni Infections in Hawaii: Associations with Prior Antibiotic Use and Commercially Prepared Chicken

Campylobacter is the most common cause of bacterial foodborne illness in the United States, and Hawaii has the highest rate of Campylobacter jejuni infections in the nation. A case-control study was conducted to determine indigenous exposures that contribute to the high incidence of sporadic C. jejuni infection in Hawaii. A total of 211 case patients with diarrhea and confirmed Campylobacter infection was enrolled, along with 1 age- and telephone exchange-matched control subject for each patient. Participants were interviewed about illness, medicines, food consumption, food-handling practices, and exposure to animals. In matched logistic regression analyses, eating chicken prepared by a commercial food establishment in the 7 days before case illness onset (adjusted odds ratio [AOR], 1.8; P=.03) and consuming antibiotics during the 28 days before illness onset (AOR, 3.3; P=.03) were significant independent predictors of illness. Further study of the association of Campylobacter illness with commercially prepared chicken and prior antibiotic use is needed.

Multidrug-Resistant Neisseria gonorrhoeae with Decreased Susceptibility to Cefixime—Hawaii, 2001

We report 4 urogenital Neisseria gonorrhoeae isolates recovered from 3 patients that demonstrated resistance to penicillin, tetracycline, and ciprofloxacin and reduced susceptibility to cefixime. This report of the first 3 patients in the United States identified with this multidrug-resistant strain may portend an emerging problem for clinicians and public health officials.

Evaluation of eight rapid screening tests for acute leptospirosis in Hawaii.

ABSTRACT Leptospirosis is a major public health problem throughout the world. Clinical recognition of leptospirosis is challenging, and the definitive serologic diagnostic assay, the microscopic agglutination test, is time-consuming and difficult to conduct. Various serologic screening tests have been developed, but their performance among ill persons in the United States has not been established. Eight screening tests were compared using 379 serum samples obtained in 1998 and 1999 from a series of 236 patients (33 with confirmed infection). The median number of days between illness onset and specimen collection was 9. The overall sensitivity, by specimen, for each test was as follows: indirect hemagglutination assay (MRL Diagnostics, Cypress, Calif.), 29%; INDX Leptospira Dip-S-Tick (PanBio InDx, Inc., Baltimore, Md.), 52%; Biognost IgM IFA test (Bios GmbH Labordiagnostik, Gräfelfing, Germany), 40%; Biolisa IgM ELISA (Bios GmbH, Labordiagnostik), 48%; Leptospira IgM ELISA (PanBio Pty Ltd., Brisbane, Australia), 36%; SERION ELISA classic Leptospira (Institut Virion•Serion GmbH, Würzburg, Germany), 48%; LEPTO Dipstick(Organon-Teknika, Ltd., Amsterdam, The Netherlands), 34%; Biosave latex agglutination test (LATEX; Bios GmbH Labordiagnostik), 86%. Test specificity ranged from 85 to 100% among all tests except LATEX, for which the specificity was significantly lower, at 10%. Test sensitivity was particularly low (<25%) for all tests (except LATEX) on specimens collected during the first week of illness. This is the most comprehensive field trial of leptospirosis screening tests reported to date. The data indicate that immunoglobulin M detection tests have limited utility for diagnosing leptospirosis during the initial evaluation of patients seen in Hawaii, a time when important therapeutic decisions are made. Improved leptospirosis screening tests are needed.

Epidemiological study of severe febrile reactions in young children in Western Australia caused by a 2010 trivalent inactivated influenza vaccine

Background The 2010 influenza vaccination program for children aged 6 months to 4 years in Western Australia (WA) was suspended following reports of severe febrile reactions, including febrile convulsions, following vaccination with trivalent inactivated influenza vaccine (TIV). Methods To investigate the association between severe febrile reactions and TIV, three studies were conducted: (i) rates of febrile convulsions within 72 h of receiving TIV in 2010 were estimated by vaccine formulation and batch; (ii) numbers of children presenting to hospital emergency departments with febrile convulsions from 2008 to 2010 were compared; and (iii) a retrospective cohort study of 360 children was conducted to compare the reactogenicity of available TIV formulations. Findings In 2010, an estimated maximum of 18 816 doses of TIV were administered and 63 febrile convulsions were recorded, giving an estimated rate of 3.3 (95% CI 2.6 to 4.2) per 1000 doses of TIV administered. The odds of a TIV-associated febrile convulsion was highly elevated in 2010 (p<0.001) and was associated with the vaccine formulations of one manufacturer—Fluvax and Fluvax Junior (CSL Biotherapies). The risk of both febrile convulsions (p<0.0001) and other febrile reactions (p<0.0001) was significantly greater for Fluvax formulations compared to the major alternate brand. The risk of febrile events was not associated with prior receipt of TIV or monovalent 2009 H1N1 pandemic vaccine. The biological cause of the febrile reactions is currently unknown. Interpretation One brand of influenza vaccine was responsible for the increase in febrile reactions, including febrile convulsions. Until the biological reason for this is determined and remediation undertaken, childhood influenza vaccination programs should not include Fluvax-type formulations and enhanced surveillance for febrile reactions in children receiving TIV should be undertaken.

Differential functional avidity of dengue virus-specific T-cell clones for variant peptides representing heterologous and previously encountered serotypes.

ABSTRACT Proinflammatory cytokines secreted by memory CD8+ and CD4+ T cells are thought to play a direct role in the pathogenesis of dengue virus infection by increasing vascular permeability and thereby inducing the pathophysiologic events associated with dengue hemorrhagic fever and dengue shock syndrome. Severe disease is frequently observed in the setting of secondary infection with heterologous dengue virus serotypes, suggesting a role for cross-reactive memory T cells in the immunopathogenesis of severe disease. We used a large panel of well-characterized dengue virus-specific CD8+ T-cell clones isolated from Pacific Islanders previously infected with dengue virus 1 to examine effector memory function, focusing on a novel dominant HLA-B*5502-restricted NS5329-337 epitope, and assessed T-cell responses to stimulation with variant peptides representing heterologous serotypes. Variant peptides were differentially recognized by dengue virus 1-specific effector CD8+ cytotoxic T lymphocytes (CTL) in a heterogeneous and clone-specific manner, in which cytolytic function and cytokine secretion could be enhanced, diminished, or abrogated compared with cognate peptide stimulation. Dengue virus-specific CTL stimulated with cognate and variant peptides demonstrated a cytokine response hierarchy of gamma IFN (IFN-γ) > tumor necrosis factor alpha (TNF-α) > interleukin-2 (IL-2), and a subset of clones also produced IL-4 and IL-6. Individual clones demonstrated greater avidity for variant peptides representing heterologous serotypes, including serotypes previously encountered by the subject, and IFN-γ and TNF-α secretion was enhanced by stimulation with these heterologous peptides. Altered antiviral T-cell responses in response to stimulation with heterologous dengue virus serotypes have implications for control of virus replication and for disease pathogenesis.

Statewide school-located influenza vaccination program for children 5-13 years of age, Hawaii, USA.

Nearly half of students in participating elementary and middle schools were vaccinated during 2007–2008.

Underrecognition of leptospirosis during a dengue fever outbreak in Hawaii, 2001-2002

During the 10-year period from 1997 through 2006, the reported mean annual incidence rate of leptospirosis in the state of Hawaii was 3.3/100,000 with a range of 22-60 infections reported each year. Because the clinical presentation is highly variable, however, leptospirosis illness is challenging to recognize and may be underdiagnosed. To assess whether the incidence may be substantially higher than reported figures indicate, we retrospectively studied the prevalence of anti-Leptospira IgM antibodies among specimens obtained over a 12-month period (May 2001 to April 2002) from patients presenting with febrile illness during a dengue fever outbreak in Hawaii. Of 1206 patients testing negative or indeterminate for dengue, 54 (4.5%; 95% confidence interval: 3.3%-5.7%) were positive for anti-Leptospira IgM antibodies using a commercially available dipstick enzyme-linked immunosorbent assay (ELISA). The most common clinical symptoms reported by laboratory-positive leptospirosis patients were fever (92%), headache (88%), and myalgia (83%). Three clinical symptoms were significantly less common among persons laboratory positive for leptospirosis when compared with the 122 patients who had been diagnosed with dengue fever during the outbreak: rash (p < 0.0001), chills (p = 0.05), and petechiae (p = 0.0005). Laboratory-positive leptospirosis infections were identified in persons exposed on each of the 5 most populous islands and illness onsets spanned a 10-month period, reflecting an endemic pattern of disease. If added to the figures obtained via routine passive surveillance, the number of leptospirosis infections identified through this study would more than double the annual incidence rate for Hawaii during 2001. These findings indicate that many leptospiral infections in Hawaii go undiagnosed. Physicians should maintain a high index of suspicion for leptospirosis when assessing patients presenting with acute febrile illness among residents and visitors to Hawaii.

Pandemic (H1N1) 2009 Influenza Community Transmission Was Established in One Australian State When the Virus Was First Identified in North America

Background In mid-June 2009 the State of Victoria in Australia appeared to have the highest notification rate of pandemic (H1N1) 2009 influenza in the world. We hypothesise that this was because community transmission of pandemic influenza was already well established in Victoria at the time testing for the novel virus commenced. In contrast, this was not true for the pandemic in other parts of Australia, including Western Australia (WA). Methods We used data from detailed case follow-up of patients with confirmed infection in Victoria and WA to demonstrate the difference in the pandemic curve in two Australian states on opposite sides of the continent. We modelled the pandemic in both states, using a susceptible-infected-removed model with Bayesian inference accounting for imported cases. Results Epidemic transmission occurred earlier in Victoria and later in WA. Only 5% of the first 100 Victorian cases were not locally acquired and three of these were brothers in one family. By contrast, 53% of the first 102 cases in WA were associated with importation from Victoria. Using plausible model input data, estimation of the effective reproductive number for the Victorian epidemic required us to invoke an earlier date for commencement of transmission to explain the observed data. This was not required in modelling the epidemic in WA. Conclusion Strong circumstantial evidence, supported by modelling, suggests community transmission of pandemic influenza was well established in Victoria, but not in WA, at the time testing for the novel virus commenced in Australia. The virus is likely to have entered Victoria and already become established around the time it was first identified in the US and Mexico.

Effectiveness of Trivalent Flu Vaccine in Healthy Young Children

BACKGROUND: There are few studies evaluating the effectiveness of trivalent influenza vaccination (TIV) in young children, particularly in children <2 years. The Western Australian Influenza Vaccine Effectiveness Study commenced in 2008 to evaluate a program providing TIV to children aged 6 to 59 months. METHODS: An observational study enrolling children with influenza-like illness presenting to a tertiary pediatric hospital was conducted (2008–2012). Vaccination status was determined by parental questionnaire and confirmed via the national immunization register and/or vaccine providers. Respiratory virus polymerase chain reaction and culture were performed on nasopharyngeal samples. The test-negative design was used to estimate vaccine effectiveness (VE) by using 2 control groups: all influenza test-negative subjects and other-virus-detected (OVD) subjects. Adjusted odds ratios were estimated from models with season, month of disease onset, age, gender, indigenous status, prematurity, and comorbidities as covariates. Subjects enrolled in 2009 were excluded from VE calculations. RESULTS: Of 2001 children enrolled, influenza was identified in 389 (20.4%) children. Another respiratory virus was identified in 1134 (59.6%) children. Overall, 295 of 1903 (15.5%) children were fully vaccinated and 161 of 1903 (8.4%) children were partially vaccinated. Vaccine uptake was significantly lower in 2010–2012 after increased febrile adverse events observed in 2010. Using test-negative controls, VE was 64.7% (95% confidence interval [CI]: 33.7%–81.2%). No difference in VE was observed with OVD controls (65.8%; 95% CI: 32.1%–82.8%). The VE for children <2 years was 85.8% (95% CI: 37.9%–96.7%). CONCLUSIONS: This study reveals the effectiveness of TIV in young children over 4 seasons by using test-negative and OVD controls. TIV was effective in children aged <2 years. Despite demonstrated vaccine effectiveness, uptake of TIV remains suboptimal.

Comparison of pandemic (H1N1) 2009 and seasonal influenza, Western Australia, 2009.

TOC summary: Infections were similar in terms of symptoms, risk factors, and proportion of patients hospitalized.