Coinfection with Enteric Pathogens in East African Children with Acute Gastroenteritis—Associations and Interpretations

Maria Andersson Department of Infectious Diseases, University of Gothenburg, Gothenburg, Sweden;

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Jean-Claude Kabayiza Department of Pediatrics, University of Rwanda, Kigali, Rwanda;

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Kristina Elfving Department of Infectious Diseases, University of Gothenburg, Gothenburg, Sweden;

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Staffan Nilsson Chalmers University of Technology, Gothenburg, Sweden;

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Mwinyi I. Msellem Zanzibar Malaria Elimination Programme (ZAMEP), Ministry of Health, Zanzibar, Tanzania;

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Andreas Mårtensson Department of Women’s and Children’s Health, International Maternal and Child Health (IMCH), Uppsala University, Uppsala, Sweden;

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Anders Björkman Malaria Research, Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden

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Tomas Bergström Department of Infectious Diseases, University of Gothenburg, Gothenburg, Sweden;

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Magnus Lindh Department of Infectious Diseases, University of Gothenburg, Gothenburg, Sweden;

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Enteric coinfections among children in low-income countries are very common, but it is not well known if specific pathogen combinations are associated or have clinical importance. In this analysis, feces samples from children in Rwanda and Zanzibar less than 5 years of age, with (N = 994) or without (N = 324) acute diarrhea, were analyzed by real-time polymerase chain reaction targeting a wide range of pathogens. Associations were investigated by comparing co-detection and mono-detection frequencies for all pairwise pathogen combinations. More than one pathogen was detected in 840 samples (65%). A negative association (coinfections being less common than expected from probability) was observed for rotavirus in combination with Shigella, Campylobacter, or norovirus genogroup II, but only in patients, which is statistically expected for agents that independently cause diarrhea. A positive correlation was observed, in both patients and controls, between Ct (threshold cycle) values for certain virulence factor genes in enteropathogenic Escherichia coli (EPEC) (eae and bfpA) and toxin genes in enterotoxigenic E. coli (eltB and estA), allowing estimation of how often these genes were present in the same bacteria. A significant positive association in patients only was observed for Shigella and EPEC-eae, suggesting that this coinfection might interact in a manner that enhances symptoms. Although interaction between pathogens that affect symptoms is rare, this work emphasizes the importance and difference in interpretation of coinfections depending on whether they are positively or negatively associated.

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Author Notes

Address correspondence to Maria Andersson, Department of Infectious Diseases, University of Gothenburg, Guldhedsgatan 10B, Gothenburg 413 46, Sweden. E-mail: maria.andersson.3@gu.se

Authors’ addresses: Maria Andersson, Kristina Elfving, Tomas Bergström, and Magnus Lindh, Department of Infectious Diseases, University of Gothenburg, Guldhedsgatan, Gothenburg, Sweden, E-mails: maria.andersson.3@gu.se, kristinaelfving@hotmail.com, tomas.bergstrom@microbio.gu.se, and magnus.lindh@microbio.gu.se. Jean-Claude Kabayiza, Department of Pediatrics, University of Rwanda, Kigali, Rwanda, E-mail: jckaba@yahoo.fr. Staffan Nilsson, Chalmers University of Technology, Gothenburg, Sweden, E-mail: staffan.nilsson@chalmers.se. Mwinyi I. Msellem, Zanzibar Malaria Elimination Programme (ZAMEP), Ministry of Health, Zanzibar, Tanzania, E-mail: mmwinyi@hotmail.com. Andreas Mårtensson, Department of Women’s and Children’s Health, International Maternal and Child Health (IMCH), Uppsala University, Uppsala, Sweden, E-mail: andreas.martensson@kbh.uu.se, Anders Björkman, Malaria Research, Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden, E-mail: anders.bjorkman@ki.se.

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