Case-Control Study of the Etiology of Infant Diarrheal Disease in 14 Districts in Madagascar

Randremanana, Rindra Vatosoa; Randrianirina, Frédérique; Gousseff, Marie; Dubois, Natasha; Razafindratsimandresy, Richter; Hariniana, Elisoa Ratsima; Garin, Benoît; Randriamanantena, Arthur; Rakotonirina, Hanitra Clara; Ramparany, Lovasoa; Ramarokoto, Charles Emile; Rakotomanana, Fanjasoa; Ratsitorahina, Maherisoa; Rajatonirina, Soatiana; Talarmin, Antoine; Richard, Vincent

doi:10.1371/journal.pone.0044533

Cited by 45 publications

(51 citation statements)

References 15 publications

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“…The detection rate of at least one enteric pathogen was significantly higher in diarrhea cases than in healthy controls, which showed a wide range of pathogens involving bacteria, and similar results have also been obtained from other countries [29, 30]. Although bacteria and parasites were the prominent enteropathogen in acute diarrheal cases aged more than 5 years in some developing countries [31], to our surprise, viral pathogens (RVA and NoV) were the most common pathogen in present study.…”

Section: Discussionsupporting

confidence: 83%

Case–control study of diarrheal disease etiology in individuals over 5 years in southwest China

Zhang

Yang

et al. 2016

Gut Pathog

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BackgroundAcute diarrhea is one of the major public health problems worldwide. Most of studies on acute diarrhea have been made on infants aged below 5 years and few efforts have been made to identify the etiological agents of acute diarrhea in people over five, especially in China.Methods271 diarrhea cases and 149 healthy controls over 5 years were recruited from four participating hospitals between June 2014 and July 2015. Each stool specimen was collected to detect a series of enteric pathogens, involving five viruses (Rotavirus group A, RVA; Norovirus, NoV; Sapovirus, SaV; Astrovirus, As; and Adenovirus, Ad), seven bacteria (diarrheagenic Escherichia coli, DEC; non-typhoidal Salmonella, NTS; Shigella spp.; Vibrio cholera; Vibrio parahaemolyticus; Aeromonas spp.; and Plesiomonas spp.) and three protozoa (Cryptosporidium spp., Giardia lamblia, G. lamblia, and Blastocystis hominis, B. hominis). Standard microbiological and molecular methods were applied to detect these pathogens. Data was analyzed using Chi square, Fisher-exact tests and logistic regressions.ResultsThe prevalence of at least one enteric pathogen was detected in 29.2% (79/271) acute diarrhea cases and in 12.1% (18/149) in healthy controls (p < 0.0001). Enteric viral infections (14.4%) were the most common in patients suffering from acute diarrhea, followed by bacteria (13.7%) and intestinal protozoa (4.8%). DEC (12.5%) was the most common causative agent in diarrhea cases, followed by NoV GII (10.0%), RVA (7.4%) and B. hominis (4.8%). The prevalence of co-infection was statistically higher (p = 0.0059) in the case group (7.7%) than in the healthy control (1.3%). RVA–NoV GII (3.0%) was the most common co-infection in symptomatic cases.ConclusionsDEC was the most predominant pathogen in diarrhea cases, but it was largely overlooked because the lack of laboratory capacities. Because of the high prevalence of co-infections, it is recommended the urgent development of alternative laboratory methods to assess polymicrobial infections. Such methodological improvements will result in a better prevention and treatment strategies to control diarrhea illness in China.Electronic supplementary materialThe online version of this article (doi:10.1186/s13099-016-0141-1) contains supplementary material, which is available to authorized users.

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Section: Discussionsupporting

confidence: 83%

Case–control study of diarrheal disease etiology in individuals over 5 years in southwest China

Zhang

Yang

et al. 2016

Gut Pathog

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“…There was a weak association between C T values and disease (P ϭ 0.03), but an independent association could not be confirmed in the multivariate analysis. Previous studies in sub-Saharan Africa also reported similar detection rates for children with and without diarrhea, but in general the rates were lower than we observed (37,38,49), a difference that might be explained by the lower sensitivity of culture versus PCR (11).…”

Section: Discussioncontrasting

confidence: 48%

“…Whereas some agents (norovirus GII and rotavirus) were found mainly among patients, others were found at high rates also among asymptomatic controls. The latter group included ETEC, Shigella, and Campylobacter, which previously have been found at significant rates among children without diarrhea (3,10,16,(36)(37)(38). These findings suggest substantial exposure to enteric pathogens in the study population, probably due to poor sanitation.…”

Section: Discussionmentioning

confidence: 52%

Real-Time PCR Threshold Cycle Cutoffs Help To Identify Agents Causing Acute Childhood Diarrhea in Zanzibar

et al. 2014

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f Molecular assays might improve the identification of causes of acute diarrheal disease but might lead to more frequent detection of asymptomatic infections. In the present study, real-time PCR targeting 14 pathogens was applied to rectal swabs from 330 children aged 2 to 59 months in Zanzibar, including 165 patients with acute diarrhea and 165 asymptomatic control subjects. At least one pathogen was detected for 94% of the patients and 84% of the controls, with higher rates among patients for norovirus genogroup II (20% versus 2.4%; P < 0.0001), rotavirus (10% versus 1.8%; P ‫؍‬ 0.003), and Cryptosporidium (30% versus 11%; P < 0.0001). Detection rates did not differ significantly for enterotoxigenic Escherichia coli (ETEC)-estA (33% versus 24%), ETEC-eltB (44% versus 46%), Shigella (35% versus 33%), and Campylobacter (35% versus 33%), but for these agents threshold cycle (C T ) values were lower (pathogen loads were higher) in sick children than in controls. In a multivariate analysis, C T values for norovirus genogroup II, rotavirus, Cryptosporidium, ETEC-estA, and Shigella were independently associated with diarrhea. We conclude that this real-time PCR allows convenient detection of essentially all diarrheagenic agents and provides C T values that may be critical for the interpretation of results for pathogens with similar detection rates in patients and controls. The results indicate that the assessment of pathogen loads may improve the identification of agents causing gastroenteritis in children.

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“…Co-infections in children under five in Madagascar were assessed in a recent report; however, they only documented co-infections between bacteria and parasites or viruses [17]. Given the paucity of data on rates of co-infection with multiple enterobacteria, it is difficult to say whether our data are within the expected range, and certainly this is an area needing further investigation.…”

Section: Discussionmentioning

confidence: 91%

Epidemiology of Pathogenic Enterobacteria in Humans, Livestock, and Peridomestic Rodents in Rural Madagascar

et al. 2014

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BackgroundAmong the families of enteric bacteria are globally important diarrheal agents. Despite their potential for zoonotic and environmental transmission, few studies have examined the epidemiology of these pathogens in rural systems characterized by extensive overlap among humans, domesticated and peridomestic animals. We investigated patterns of infection with Enterotoxigenic Escherichia coli, Shigella spp., Salmonella enterica, Vibrio cholerae, and Yersinia spp. (enterocolitica, and pseudotuberculosis) in Southeastern Madagascar where the potential for the aforementioned interactions is high. In this pilot project we conducted surveys to examine behaviors potentially associated with risk of infection and if infection with specific enterobacteria species was associated with diarrheal disease.Methodology/Principal FindingsPCR was conducted on DNA from human, livestock, and rodent fecal samples from three villages. Overall, human prevalence was highest (77%), followed by rodents (51%) and livestock (18%). Rodents were ∼2.8 times more likely than livestock to carry one of the bacteria. The incidence of individual species varied between villages, with the observation that, E. coli and Shigella spp. were consistently associated with co-infections. As an aggregate, there was a significant risk of infection linked to a water source in one village. Individually, different pathogens were associated with certain behaviors, including: those who had used medication, experienced diarrhea in the past four weeks, or do not use toilets.Conclusions/SignificanceDifferent bacteria were associated with an elevated risk of infection for various human activities or characteristics. Certain bacteria may also predispose people to co-infections. These data suggest that a high potential for transmission among these groups, either directly or via contaminated water sources. As these bacteria were most prevalent in humans, it is possible that they are maintained in humans and that transmission to other species is infrequent. Further studies are needed to understand bacterial persistence, transmission dynamics, and associated consequences in this and similar systems.

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Case-Control Study of the Etiology of Infant Diarrheal Disease in 14 Districts in Madagascar

Cited by 45 publications

References 15 publications

Case–control study of diarrheal disease etiology in individuals over 5 years in southwest China

Case–control study of diarrheal disease etiology in individuals over 5 years in southwest China

Real-Time PCR Threshold Cycle Cutoffs Help To Identify Agents Causing Acute Childhood Diarrhea in Zanzibar

Epidemiology of Pathogenic Enterobacteria in Humans, Livestock, and Peridomestic Rodents in Rural Madagascar

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