Denise O. Garrett

Waterborne toxoplasmosis, Brazil, from field to gene

Water was the suspected vehicle of Toxoplasma gondii dissemination in a toxoplasmosis outbreak in Brazil. A case-control study and geographic mapping of cases were performed. T. gondii was isolated directly from the implicated water and genotyped as SAG 2 type I.

Interferon-γ Release Assays and Tuberculin Skin Testing for Diagnosis of Latent Tuberculosis Infection in Healthcare Workers in the United States

RATIONALE IFN-γ release assays (IGRAs) are alternatives to tuberculin skin testing (TST) for diagnosis of latent tuberculosis infection. Limited data suggest IGRAs may not perform well for serial testing of healthcare workers (HCWs). OBJECTIVES Determine the performance characteristics of IGRAs versus TST for serial testing of HCWs. METHODS A longitudinal study involving 2,563 HCWs undergoing occupational tuberculosis screening at four healthcare institutions in the United States, where the average tuberculosis case rate ranged from 4 to 9 per 100,000 persons. QuantiFERON-TB Gold In-Tube (QFT-GIT), T-SPOT.TB (T-SPOT), and TST were performed at baseline and every 6 months for 18 months between February 2008 and March 2011. MEASUREMENTS AND MAIN RESULTS A total of 2,418 HCWs completed baseline testing, which was positive for 125 (5.2%) by TST, 118 (4.9%) by QFT-GIT, and 144 (6.0%) by T-SPOT. A baseline positive TST with negative IGRAs was associated with bacillus Calmette-Guérin (BCG) vaccination (odds ratio: 25.1 [95% confidence interval: 15.5, 40.5] vs. no BCG). Proportions of participants with test conversion during the study period were 138 of 2,263 (6.1%) for QFT-GIT, 177 of 2,137 (8.3%) for T-SPOT, and 21 of 2,293 (0.9%) for TST (P < 0.001 for QFT-GIT vs. TST and for T-SPOT vs. TST; P = 0.005 for QFT-GIT vs. T-SPOT). Of the QFT-GIT and T-SPOT converters, 81 of 106 (76.4%) and 91 of 118 (77.1%), respectively, were negative when retested 6 months later. There was negative/positive discordance for 15 of 170 (8.8%) participants by QFT-GIT and for 19 of 151 (12.6%) by T-SPOT when blood was drawn 2 weeks later. CONCLUSIONS Most conversions among HCWs in low TB incidence settings appear to be false positives, and these occurred six to nine times more frequently with IGRAs than TST; repeat testing of apparent converters is warranted.

The emergence of decreased susceptibility to vancomycin in Staphylococcus epidermidis.

BACKGROUND Coagulase-negative staphylococci (CNS) are the major cause of nosocomial bloodstream infection. Emergence of vancomycin resistance among CNS is a serious public health concern, because CNS usually are multidrug-resistant, and glycopeptide antibiotics, among which only vancomycin is available in the United States, are the only remaining effective therapy. In this report, we describe the first bloodstream infection in the United States associated with a Staphylococcus epidermidis strain with decreased susceptibility to vancomycin. METHODS We reviewed the hospitals microbiology records for all CNS strains, reviewed the patients medical and laboratory records, and obtained all available CNS isolates with decreased susceptibility to vancomycin. Blood cultures were processed and CNS isolates identified by using standard methods; antimicrobial susceptibility was determined by using minimum inhibitory concentration (MIC) and disk-diffusion methods. Nares cultures were obtained from exposed healthcare workers (HCWs) to identify possible colonization by CNS with decreased susceptibility to vancomycin. RESULTS The bloodstream infection by an S. epidermidis strain with decreased susceptibility to vancomycin occurred in a 49-year-old woman with carcinoma. She had two blood cultures positive for CNS; both isolates were S. epidermidis. Although susceptible to vancomycin by the disk-diffusion method (16-17 mm), the isolates were intermediate by MIC (8-6 microg/mL). The patient had received an extended course of vancomycin therapy; she died of her underlying disease. No HCW was colonized by CNS with decreased susceptibility to vancomycin. CONCLUSIONS This is the first report in the United States of bloodstream infection due to S. epidermidis with decreased susceptibility to vancomycin. Contact precautions likely played a role in preventing nosocomial transmission of this strain, and disk-diffusion methods may be inadequate to detect CNS with decreased susceptibility to vancomycin.

Evaluation of QuantiFERON-TB gold in-tube and tuberculin skin tests among immigrant children being screened for latent tuberculosis infection

Background: Centers for Disease Control and Prevention requirements for pre-immigration tuberculosis (TB) screening of children 2- to 14-years old permit a tuberculin skin test (TST) or an interferon-gamma release assay (IGRA). Few data are available on the performance of IGRAs versus TSTs in foreign-born children. Methods: We compared the performance of TST and QuantiFERON-TB (QFT) Gold In-Tube in children 2- to 14-years old applying to immigrate to the United States from Mexico, the Philippines and Vietnam, using diagnosis of TB in immigrating family members as a measure of potential exposure. Results: We enrolled 2520 children: 664 (26%) were TST+ and 142 (5.6%) were QFT+. One hundred and eleven (4.4%) were TST+/QFT+, 553 (21.9%) were TST+/QFT− and 31 (1.2%) were TST−/QFT+. Agreement between tests was poor (&kgr; = 0.20). Although positive results of both tests were significantly associated with older age (relative risks [RR] TST+, 1.64; 95% confidence interval [CI]: 1.36–1.97; RR QFT+, 3.05; 95% CI: 1.72–5.38) and with the presence of TB in at least 1 immigrating family member (RR TST+, 1.40; 95% CI: 1.12–1.75; RR QFT+ 2.24; 95% CI: 1.18–4.28), QFT+ results were more strongly associated with both predictive variables. Conclusions: The findings support the preferential use of QFT over TST for pre-immigration screening of foreign-born children 2 years of age and older and lend support to the preferential use of IGRAs in testing foreign-born children for latent TB infection.

An Outbreak of Neonatal Deaths in Brazil Associated with Contaminated Intravenous Fluids

A nursery outbreak of fever and clinical sepsis resulted in the deaths of 36 neonates in Roraima, Brazil. To determine the cause, epidemiologic studies were performed, along with culture and endotoxin analysis of intravenous (iv) fluids. Affected neonates were more likely to have lower birth weight (2.1 vs. 3.2 kg; P<.01), lower APGAR (activity, pulse, grimace, appearance, and respiration) score at 1 (7 vs. 8; P=.1) or 5 min (8 vs. 9; P=.03), lower gestational age (32 vs. 39 weeks; P=.001), or to receive iv medications (20/20 vs. 2/40; P<.0001). Fever occurred only after iv medication administration. Although culture results of unopened iv medications were negative, endotoxin levels of glucose and distilled water for injection were elevated (3.3 and 1.2 U/mL, respectively). Endotoxin-contaminated iv medications were distributed nationally and may have caused other outbreaks of unexplained death. These results highlight the importance of monitoring both pharmaceutical quality and postmarketing surveillance for adverse events.

Avaliação do sistema de vigilância de hantavírus no Brasil

Resumo A sindrome cardiopulmonar por hantavirus (SCPH), uma forma grave de infeccao por hantavirus, foi identificada no continente americano em 1993, nos Estados Unidos da America (EUA). No mesmo ano, um surto de SCPH ocorreu no Brasil, no Municipio paulista de Juquitiba. Com os objetivos de descrever os componentes e analisar os atributos, a utilidade e os recursos necessarios para operacao do Sistema de Vigilância de Hantavirus no Brasil (SVH), uma avaliacao foi realizada. A metodologia utilizada foi baseada nas Diretrizes para a Avaliacao de Sistemas de Vigilância, dos Centers for Disease Control and Prevention (CDC, EUA). Os resultados evidenciaram que o SVH e complexo, pouco flexivel, instavel, com baixa aceita bilidade, sensibilidade, valor preditivo positivo e representatividade, alem da insatisfatoria qualidade dos dados. Ademais, o sistema carece de grandes quantidades de recursos. Entretanto, mostrou ser de grande utilidade para detectar casos de SCPH e identificar surtos, orientar medidas de prevencao e controle e gerar mudancas nas praticas clinicas e de vigilância. Com base nesses resultados, recomenda-se aos Estados e Municipios que: implementem, de forma plena, acoes de vigilância da doenca e de capacitacao dos profissionais de saude; definam servicos de referencia para notificacao, diagnostico e tratamento; e que promovam o uso dos dados da vigilância, a divulgacao das informacoes para profissionais de saude e a informacao a populacao sobre como prevenir a sindrome. Palavras-chaves: avaliacao de sistema de vigilância; hantavirose; sindrome cardiopulmonar por hantavirus. Summary Hantavirus pulmonary syndrome (HPS), a serious complication of hantavirus infection, was first identified on the American continent in 1993, in the United States of America (USA). During the same year, HPS was also identified

Efficacy of artemether–lumefantrine, artesunate–amodiaquine, and dihydroartemisinin–piperaquine for treatment of uncomplicated Plasmodium falciparum malaria in Angola, 2015

BackgroundRecent anti-malarial resistance monitoring in Angola has shown efficacy of artemether–lumefantrine (AL) in certain sites approaching the key 90% lower limit of efficacy recommended for artemisinin-based combination therapy. In addition, a controversial case of malaria unresponsive to artemisinins was reported in a patient infected in Lunda Sul Province in 2013.MethodsDuring January–June 2015, investigators monitored the clinical and parasitological response of children with uncomplicated Plasmodium falciparum infection treated with AL, artesunate–amodiaquine (ASAQ), or dihydroartemisinin–piperaquine (DP). The study comprised two treatment arms in each of three provinces: Benguela (AL, ASAQ), Zaire (AL, DP), and Lunda Sul (ASAQ, DP). Samples from treatment failures were analysed for molecular markers of resistance for artemisinin (K13) and lumefantrine (pfmdr1).ResultsA total of 467 children reached a study endpoint. Fifty-four treatment failures were observed: four early treatment failures, 40 re-infections and ten recrudescences. Excluding re-infections, the 28-day microsatellite-corrected efficacy was 96.3% (95% CI 91–100) for AL in Benguela, 99.9% (95–100) for ASAQ in Benguela, 88.1% (81–95) for AL in Zaire, and 100% for ASAQ in Lunda Sul. For DP, the 42-day corrected efficacy was 98.8% (96–100) in Zaire and 100% in Lunda Sul. All treatment failures were wild type for K13, but all AL treatment failures had pfmdr1 haplotypes associated with decreased lumefantrine susceptibility.ConclusionsNo evidence was found to corroborate the specific allegation of artemisinin resistance in Lunda Sul. The efficacy below 90% of AL in Zaire matches findings from 2013 from the same site. Further monitoring, particularly including measurement of lumefantrine blood levels, is recommended.

Comparison of Strategies and Incidence Thresholds for Vi Conjugate Vaccines Against Typhoid Fever: A Cost-effectiveness Modeling Study

Abstract Background Typhoid fever remains a major public health problem globally. While new Vi conjugate vaccines hold promise for averting disease, the optimal programmatic delivery remains unclear. We aimed to identify the strategies and associated epidemiologic conditions under which Vi conjugate vaccines would be cost-effective. Methods We developed a dynamic, age-structured transmission and cost-effectiveness model that simulated multiple vaccination strategies with a typhoid Vi conjugate vaccine from a societal perspective. We simulated 10-year vaccination programs with (1) routine immunization of infants (aged <1 year) through the Expanded Program on Immunization (EPI) and (2) routine immunization of infants through the EPI plus a 1-time catch-up campaign in school-aged children (aged 5–14 years). In the base case analysis, we assumed a 0.5% case-fatality rate for all cases of clinically symptomatic typhoid fever and defined strategies as highly cost-effective by using the definition of a low-income country (defined as a country with a gross domestic product of

Social and Economic Burden Associated With Typhoid Fever in Kathmandu and Surrounding Areas: A Qualitative Study

1045 per capita). We defined incidence as the true number of clinically symptomatic people in the population per year. Results Vi conjugate typhoid vaccines were highly cost-effective when administered by routine immunization activities through the EPI in settings with an annual incidence of >50 cases/100000 (95% uncertainty interval, 40–75 cases) and when administered through the EPI plus a catch-up campaign in settings with an annual incidence of >130 cases/100000 (95% uncertainty interval, 50–395 cases). The incidence threshold was sensitive to the typhoid-related case-fatality rate, carrier contribution to transmission, vaccine characteristics, and country-specific economic threshold for cost-effectiveness. Conclusions Typhoid Vi conjugate vaccines would be highly cost-effective in low-income countries in settings of moderate typhoid incidence (50 cases/100000 annually). These results were sensitive to case-fatality rates, underscoring the need to consider factors contributing to typhoid mortality (eg, healthcare access and antimicrobial resistance) in the global vaccination strategy.

Tuberculosis Mortality in the United States: Epidemiology and Prevention Opportunities

Abstract Typhoid fever is a significant contributor to infectious disease mortality and morbidity in low- and middle-income countries, particularly in South Asia. With increasing antimicrobial resistance, commonly used treatments are less effective and risks increase for complications and hospitalizations. During an episode of typhoid fever, households experience multiple social and economic costs that are often undocumented. In the current study, qualitative interview data from Kathmandu and surrounding areas provide important insights into the challenges that affect those who contract typhoid fever and their caregivers, families, and communities, as well as insight into prevention and treatment options for health providers and outreach workers. When considering typhoid fever cases confirmed by blood culture, our data reveal delays in healthcare access, financial and time costs burden on households, and the need to increase health literacy. These data also illustrate the impact of limited laboratory diagnostic equipment and tools on healthcare providers’ abilities to distinguish typhoid fever from other febrile conditions and treatment challenges associated with antimicrobial resistance. In light of these findings, there is an urgent need to identify and implement effective preventive measures including vaccination policies and programs focused on at-risk populations and endemic regions such as Nepal.