The indelible toll of enteric pathogens: Prevalence, clinical characterization, and seasonal trends in patients with acute community-acquired diarrhea in disenfranchised communities

PLOS ONE RESEARCH ARTICLE The indelible toll of enteric pathogens: Prevalence, clinical characterization, and seasonal trends in patients with acute community-acquired diarrhea in disenfranchised communities Marwan Osman ID1,2, Issmat I. Kassem ID3, Fouad Dabboussi4, Kevin J. Cummings2, Monzer Hamze ID4* a1111111111 a1111111111 a1111111111 a1111111111 a1111111111 1 Cornell Atkinson Center for Sustainability, Cornell University, Ithaca, NY, United States of America, 2 Department of Public and Ecosystem Health, College of Veterinary Medicine, Cornell University, Ithaca, NY, United States of America, 3 Center for Food Safety and Department of Food Science and Technology, University of Georgia, Griffin, GA, United States of America, 4 Laboratoire Microbiologie Santé et Environnement (LMSE), Doctoral School of Sciences and Technology, Faculty of Public Health, Lebanese University, Tripoli, Lebanon * OPEN ACCESS Citation: Osman M, Kassem II, Dabboussi F, Cummings KJ, Hamze M (2023) The indelible toll of enteric pathogens: Prevalence, clinical characterization, and seasonal trends in patients with acute community-acquired diarrhea in disenfranchised communities. PLoS ONE 18(3): e0282844. https://doi.org/10.1371/journal. pone.0282844 Editor: Fernando Navarro-Garcia, CINVESTAV-IPN, MEXICO Abstract Background There is little information on the epidemiology of enteric pathogens in Lebanon, a low- and middle-income country that suffers from a myriad of public health challenges. To address this knowledge gap, we aimed to assess the prevalence of enteric pathogens, identify risk factors and seasonal variations, and describe associations between pathogens among diarrheic patients in the Lebanese community. Received: November 4, 2022 Accepted: February 23, 2023 Methodology and principal findings Published: March 13, 2023 A multicenter cross-sectional community-based study was conducted in the north of Lebanon. Stool samples were collected from 360 outpatients suffering from acute diarrhea. Based on fecal examination using the BioFire® FilmArray® Gastrointestinal Panel assay, the overall prevalence of enteric infections was 86.1%. Enteroaggregative Escherichia coli (EAEC) was the most frequently identified (41.7%), followed by enteropathogenic E. coli (EPEC) (40.8%) and rotavirus A (27.5%). Notably, two cases of Vibrio cholerae were identified, while Cryptosporidium spp. (6.9%) was the most common parasitic agent. Overall, 27.7% (86/310) of the cases were single infections, and the majority, 73.3% (224/310), were mixed infections. Multivariable logistic regression models showed that enterotoxigenic E. coli (ETEC) and rotavirus A infections were significantly more likely to occur in the fall and winter compared to the summer. Rotavirus A infections significantly decreased with age but increased in patients living in rural areas or suffering from vomiting. We identified strong Peer Review History: PLOS recognizes the benefits of transparency in the peer review process; therefore, we enable the publication of all of the content of peer review and author responses alongside final, published articles. The editorial history of this article is available here: https://doi.org/10.1371/journal.pone.0282844 Copyright: © 2023 Osman et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. PLOS ONE | https://doi.org/10.1371/journal.pone.0282844 March 13, 2023 1 / 28 PLOS ONE Data Availability Statement: All code necessary to replicate the analysis is publicly available (DOI: 10. 6084/m9.figshare.22013054). Funding: This work was supported by a humanitarian donation from BioFire Diagnostics and Fondation Merieux USA. Marwan Osman is supported by the Atkinson Postdoctoral Fellowship (Cornell University). The donors and funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Enteric pathogens in patients with acute community-acquired diarrhea in disenfranchised communities associations in the co-occurrence of EAEC, EPEC, and ETEC infections and a higher percentage of rotavirus A and norovirus GI/GII infections among EAEC-positive cases. Conclusions Several of the enteric pathogens reported in this study are not routinely tested in Lebanese clinical laboratories. However, anecdotal evidence suggests that diarrheal diseases are on the rise due to widespread pollution and the deterioration of the economy. Therefore, this study is of paramount importance to identify circulating etiologic agents and prioritize dwindling resources to control them and limit outbreaks in the future. Competing interests: The authors have declared that no competing interests exist. 1. Introduction Enteric infections represent a significant public health problem worldwide, greatly impacting human health and the economy [1, 2]. These pathogens spread commonly via the fecal-oral route following direct and/or indirect contact with the infectious agents which include human-to-human, zoonotic, waterborne, and foodborne transmission [3, 4]. The typical clinical features of these infections include gastrointestinal symptoms such as diarrhea, abdominal pain, vomiting, fever, nausea, malaise, and dehydration [5]. Gastrointestinal infections are widespread among children and constitute a neglected public health threat in underprivileged and disenfranchised populations, particularly in countries affected by adverse socioeconomic factors [6]. Indeed, diarrhea is the second leading cause of death in children younger than 5 years old, with an estimated 500,000 cases annually, many of which occur in low- and middleincome countries (LMICs) [7]. A broad range of enteric bacterial, viral, or parasitic pathogens can cause diarrhea and associated short- and long-term complications. Host vulnerabilities associated with poor nutritional status, anemia, inadequate sanitation and hygiene, overcrowded living conditions, and gaps in health literacy could facilitate repeated infections with certain pathogens, leading to severe consequences, including enteric and systemic inflammation, increased risk of stunting, impaired cognitive development, and/or death [2, 8–12]. Recent data from the Global Enteric Multicenter Study (GEMS) on the burden and etiology of diarrhea among children residing in developing countries showed that rotavirus, Cryptosporidium spp., enterotoxigenic Escherichia coli (ETEC), and Shigella spp. are the major causes of diarrheal diseases and death [6]. Furthermore, norovirus infections are the principal cause of foodborne disease outbreaks and are associated with approximately 20% of diarrhea cases, with similar prevalence in both children and adults [13, 14]. Hundreds of millions of people across the globe are estimated to have clinically diagnosable campylobacterio (...truncated)