Summary Background Diarrhoea is the second leading cause of mortality in children worldwide, but establishing the cause can be complicated by diverse diagnostic approaches and varying test ...characteristics. We used quantitative molecular diagnostic methods to reassess causes of diarrhoea in the Global Enteric Multicenter Study (GEMS). Methods GEMS was a study of moderate to severe diarrhoea in children younger than 5 years in Africa and Asia. We used quantitative real-time PCR (qPCR) to test for 32 enteropathogens in stool samples from cases and matched asymptomatic controls from GEMS, and compared pathogen-specific attributable incidences with those found with the original GEMS microbiological methods, including culture, EIA, and reverse-transcriptase PCR. We calculated revised pathogen-specific burdens of disease and assessed causes in individual children. Findings We analysed 5304 sample pairs. For most pathogens, incidence was greater with qPCR than with the original methods, particularly for adenovirus 40/41 (around five times), Shigella spp or enteroinvasive Escherichia coli (EIEC) and Campylobactor jejuni o C coli (around two times), and heat-stable enterotoxin-producing E coli (ST-ETEC around 1·5 times). The six most attributable pathogens became, in descending order, Shigella spp, rotavirus, adenovirus 40/41, ST-ETEC, Cryptosporidium spp, and Campylobacter spp. Pathogen-attributable diarrhoeal burden was 89·3% (95% CI 83·2–96·0) at the population level, compared with 51·5% (48·0–55·0) in the original GEMS analysis. The top six pathogens accounted for 77·8% (74·6–80·9) of all attributable diarrhoea. With use of model-derived quantitative cutoffs to assess individual diarrhoeal cases, 2254 (42·5%) of 5304 cases had one diarrhoea-associated pathogen detected and 2063 (38·9%) had two or more, with Shigella spp and rotavirus being the pathogens most strongly associated with diarrhoea in children with mixed infections. Interpretation A quantitative molecular diagnostic approach improved population-level and case-level characterisation of the causes of diarrhoea and indicated a high burden of disease associated with six pathogens, for which targeted treatment should be prioritised. Funding Bill & Melinda Gates Foundation.
Background A long-term care facility (LTCF) reported an outbreak of Legionnaires' disease (LD) in September 2004. Methods We conducted case finding through enhanced surveillance, medical record ...review (n = 131), and community surveys (n = 258). We cultured water samples from the LTCF and assayed their outdoor air-intake filters for Legionella DNA. We also investigated a cooling tower, the only nearby outdoor aerosol source. Results Among 7 confirmed cases, 2 LTCF residents never exited, and 2 community residents never entered the LTCF during the incubation period. Among 63 water and biofilm samples collected from throughout the LTCF, we found no evidence of Legionella colonization, either in the potable water or air-handling systems. Conversely, we isolated a common outbreak-causing strain of Legionella pneumophila serogroup 1 from an industrial cooling tower located 0.4 km from the LTCF and recovered L pneumophila DNA from the LTCF's outdoor air-intake filters, suggesting that aerosolized Legionella from the cooling tower most likely entered the LTCF through the air-intake system or, possibly, through open windows. Conclusion Residents of LTCFs can acquire LD from community sources. A cluster of LD cases among LTCF residents does not necessarily indicate transmission from within the LTCF.
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