Abstract

Globally, diarrhoeal diseases are the second leading cause of death among children under 5 years old. Few case–control studies on the aetiology of diarrhoea have been conducted in China. A case–control study on 922 children under 5 years old who presented with diarrhoea and individually matched controls was conducted in China between May 2011 and January 2013. Quantitative PCR was used to analyze stool samples for 10 diarrhoeal pathogens. Potential enteric pathogens were detected in 377 (81.8%) of 461 children with diarrhoea and 215 controls (46.6%, p <0.001). Rotavirus, norovirus GII, Shigella and adenovirus were qualitatively associated with diarrhoea. Using receiver operating characteristic curves, the optimal cutoff threshold for defining a symptomatic individual was 72, 5840, and 104 copies per reaction for rotavirus (odds ratio 259), norovirus GII (odds ratio 10.6) and Shigella (odds ratio 5.1). The attributable fractions were 0.18 for rotavirus, 0.08 for norovirus GII, 0.01 for Shigella and 0.04 for adenovirus. Coinfections between pathogens were common. Two pairs, rotavirus and adenovirus, and norovirus GII and Salmonella were positively associated. The co-occurrence of rotavirus and sapovirus, astrovirus, enterotoxigenic Escherichia coli or Campylobacter jejuni only occurred in children with disease. Coinfection was not correlated with clinical symptoms. Quantitative data are critical. Our results indicate that increased pathogen loads increase the OR between diarrhoea and rotavirus, norovirus GII and Shigella. Coinfections with rotavirus and norovirus GII are common and occur in a nonrandom distribution. Despite testing for ten diarrhoeal pathogens, over two-thirds of cases do not have a recognized attributable cause.

Highlights

  • Diarrhoeal disease accounts for the deaths of one in nine children worldwide; it is responsible for 0.75 million deaths every year [1]

  • When the pathogen load was considered, we found that the odds ratios (ORs) of diarrhoea increased for rotavirus, norovirus GII and Shigella spp., indicating that these pathogens have an effective concentration above which they are likely to cause diarrhoeal symptoms

  • The populationattributable fraction was highest for rotavirus and norovirus GII

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Summary

Introduction

Diarrhoeal disease accounts for the deaths of one in nine children worldwide; it is responsible for 0.75 million deaths every year [1]. The possible pathogenic culprits include rotavirus A, norovirus GI and GII, adenovirus, sapovirus, astrovirus, Salmonella, Campylobacter jejuni, Shigella spp. and enterotoxigenic Escherichia coli (ETEC) [3,4] A number of previous epidemiologic studies have described the distribution of a variety of enteropathogens in south Asia, Africa, Europe, the Middle East, South America and the United States [5,6,7,8,9,10,11,12]. None of these studies included China, and enteropathogen estimates in China are limited. Most of the previous studies focused on only a small number of diarrhoea-causing pathogens, and many did not include healthy controls

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