Global Causes of Diarrheal Disease Mortality in Children <5 Years of Age: A Systematic Review

School of Medicine, Universidad Peruana de Ciencias Aplicadas, Lima, Peru.
PLoS ONE (Impact Factor: 3.23). 09/2013; 8(9):72788-. DOI: 10.1371/journal.pone.0072788


Estimation of pathogen-specific causes of child diarrhea deaths is needed to guide vaccine development and other prevention strategies. We did a systematic review of articles published between 1990 and 2011 reporting at least one of 13 pathogens in children <5 years of age hospitalized with diarrhea. We included 2011 rotavirus data from the Rotavirus Surveillance Network coordinated by WHO. We excluded studies conducted during diarrhea outbreaks that did not discriminate between inpatient and outpatient cases, reporting nosocomial infections, those conducted in special populations, not done with adequate methods, and rotavirus studies in countries where the rotavirus vaccine was used. Age-adjusted median proportions for each pathogen were calculated and applied to 712 000 deaths due to diarrhea in children under 5 years for 2011, assuming that those observed among children hospitalized for diarrhea represent those causing child diarrhea deaths. 163 articles and WHO studies done in 31 countries were selected representing 286 inpatient studies. Studies seeking only one pathogen found higher proportions for some pathogens than studies seeking multiple pathogens (e.g. 39% rotavirus in 180 single-pathogen studies vs. 20% in 24 studies with 5-13 pathogens, p<0·0001). The percentage of episodes for which no pathogen could be identified was estimated to be 34%; the total of all age-adjusted percentages for pathogens and no-pathogen cases was 138%. Adjusting all proportions, including unknowns, to add to 100%, we estimated that rotavirus caused 197 000 [Uncertainty range (UR) 110 000-295 000], enteropathogenic E. coli 79 000 (UR 31 000-146 000), calicivirus 71 000 (UR 39 000-113 000), and enterotoxigenic E. coli 42 000 (UR 20 000-76 000) deaths. Rotavirus, calicivirus, enteropathogenic and enterotoxigenic E. coli cause more than half of all diarrheal deaths in children <5 years in the world.

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    • "Rotavirus (RV) is an important pathogen of severe diarrhoea in infants and young children globally [1]. A major reduction of severe RV diarrhoea has been observed in countries with high RV vaccine coverage, but several clinical trials have shown the vaccine efficacy to be lower in countries with high RV mortality [2]. "
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    ABSTRACT: Rotaviruses (RVs) are a major cause of severe diarrhea in young children. Nicaragua introduced routine immunization with the pentavalent rotavirus vaccine (RV5) in 2006; which greatly reduced the incidence of diarrhea. A remaining concern has been the possible emergence of new RV strains to which the vaccination has less effect. In this study, 837 children with diarrhea in hospital settings were investigated for RV between May 2011 and July 2013. RVs were subsequently typed by multiplex PCR and/or sequencing. Fecal anti-RV IgA titers for a subset of RV-infected (n = 137) and non-infected children (n = 52), were determined with an in-house ELISA assay. The RV detection rate was 8% in 2011, followed by a sharp increase to 29% in 2012 and 19% in 2013. This was associated with emergence and predominance of genotype G12 RV, from 0% in 2011 to 66% in 2012 and 82% in 2013, infecting children from 1 month to 10 years of age. Two sequenced G12 strains, showed a Wa-like genome with genotype G12-P[8]-I1-R1-C1-M1-A1-N1-T1-E1-H1, similar to the globally emerging G12 strains. Fecal anti-RV IgA analysis showed that most G12-infected and non-infected children had been in contact with either vaccine or wild RV strains, but such antibodies did not prevent symptomatic G12 infection. To conclude, in this study we have shown a marked increase of RV in the hospital setting associated with a nationwide emergence and predominance of RV G12 genotype in a population with high RV5 vaccine coverage. Copyright © 2015. Published by Elsevier Ltd.
    Clinical Microbiology and Infection 02/2015; 21(6). DOI:10.1016/j.cmi.2015.01.022 · 5.77 Impact Factor
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    • "E. coli is a constituent of the intestinal microbiota of several vertebrates characterizing relevant reservoirs, epidemiologically connected or not, and is released into the environment through fecal material (Torres et al., 2010; Williams et al., 2010; Lanata et al., 2013). In our study, E. coli was found to occur at every aquatic ecosystem that we sampled; however, the percentages of bacterial isolation in each sampling site differed according to the location. "
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    ABSTRACT: Escherichia coli contamination in aquatic ecosystems has emerged as a relevant concern of public health impact, especially in developing areas. In this study, E. coli isolates were recovered from residential, industrial, agricultural, hospital wastewaters and recreational waters and, further characterized according to diarrheagenic potential, phylotyping and antimicrobial resistance phenotype. Among the total 178 E. coli isolates, antimicrobial resistance was detected in 37% to at least one of the 11 antimicrobials tested. The highest percentage of resistant E. coli was recovered from agricultural wastewaters (57.7%) followed by recreational waters (56.4%), hospital (34.5%), residential (22.7%) and industrial wastewaters (22.2%). Twenty-three resistance profiles (I-XXIII) were detected and 17 isolates exhibited the MDR phenotype. 11.2% of the total E. coli isolates carried diarrheagenic markers: astA (7.3%, 13/178), stx1 (2.8%, 05/178), escV (2.2%, 04/178) and estIa (0.6%, 01/178). All isolates harbored the uidA gene. E. coli isolates were mostly found in phylogenetic groups A (91.6%, 163/178) followed by groups D (5%, 09/178) and B2 (3.4%, 06/178). Specific gene combinations characterized E. coli pathotypes as ETEC (01/20), ATEC (04/20) and STEC (05/20) which belonged to A (75%, 15/20), D (15%, 03/20) and B2 (10%, 02/20) phylogroups. Our results revealed the widespread distribution of E. coli in aquatic systems in Rio de Janeiro. The circulation of pathogenic E. coli and antimicrobial resistance within bacterial population represents high risk to ecosystem and human health and highlights epidemiological surveillance and sanitary improvement.
    Science of The Total Environment 05/2014; 490C:19-27. DOI:10.1016/j.scitotenv.2014.04.040 · 4.10 Impact Factor

  • BMJ (online) 12/2013; 347(dec30 1):f7204. DOI:10.1136/bmj.f7204 · 17.45 Impact Factor
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Nov 2, 2015