Etiology of travellers’ diarrhea

Journal of Travel Medicine, 2017, Vol 24, Suppl 1, S13–S16 doi: 10.1093/jtm/tax003 Review Review Etiology of travellers’ diarrhea Z.D. Jiang1,* and H.L. DuPont2 1 *To whom correspondence should be addressed. Email: Editorial decision 10 January 2017; Accepted 11 January 2017 Abstract Eleven published studies of the etiology of travellers’ diarrhea (TD) were reviewed define the etiology of TD and to exam newly developed technology such as Real-Time multiplex polymerase chain reaction (PCR) to identify multiple pathogens in one assay to define the cause of TD. Using PCR methods bacterial pathogens were found in 72% of patients acquiring diarrhea in Latin America and in 80% in travellers with illness acquired in Southeast Asia). In these studies, enterotoxigenic Escherichia coli as the predominant pathogen (42% in Latin America and 28% in Southeast Asia). Ciprofloxacin-resistant Campylobacter was commonly associated with TD in Southeast Asia. Multiplex PCR has improved the detection of enteropathogens and allowed better assessment returning travellers hospitalized with TD and those with persistent diarrhea. Introduction Methods The first thorough description of the epidemiology and clinical features of travellers’ diarrhea (TD) was by Kean in 1963.1 The topic has been updated by Steffen, Hill and DuPont more recently in their systematic review in 2015.2 It is obvious from these two papers that the rates of TD remain essentially the same over the past 50 years. An infectious agent can be identified in 60–80% of individual with TD using research techniques which include DNA probe, PCR and conventional methods.3 The important causes of TD are diarrhea-producing Escherichia coli including strains of enterotoxigenic (ETEC) and enteroaggregative (EAEC) E. coli, Campylobacter, Salmonella and Shigella, norovirus, astrovirus, Giardia and Cryptosporidium. The diagnosis of TD is usually obtained through a combination of several tests.2–4 Current methods in detection of enteric pathogens are microbiological culture, immunoassays and standard polymerase chain reaction (PCR) and real-time PCR. Conventional laboratory-based culture tests are time consuming and have a low yield. Quantitative real time PCR approaches detect bacterial, viral and parasitic pathogens across multiple laboratories with high sensitivity and excellent reproducibility and quantification.5 The aims of the review were to look at recent data on the etiology of TD and to exam newly developed technology such as multiplex PCR to identify the cause of TD. We searched the PubMed, Refworks and Ovid Medline for publications on etiology of TD from 2010 through 2016. Search terms included were etiology of TD, multiplex PCR, and diagnosis of TD. Studies were included if they are published in English. Data extracted from published studies including enteric pathogens identified, identification methods and condition of samples collection. TD was defined as the occurrence of three or more episodes of unformed stools within 24 h after more than 2 days arrivals the country visited with at least one of the following symptoms: vomiting, nausea, abdominal pain or fever. Results Eleven published studies between 2010 and 2016 reported data on the etiology of TD and met the criteria of the study (Table 1). The total population with TD in this review included the studies of 4838 diarrhea samples for detection of a broad range of enteric pathogens by multiplex PCR. A total 1389 samples were collected from patients developed in Latin America and 990 were collected from South or Southeast Asia. One of the studies had unspecified regions included 2459 diarrhea stool specimens. Most common pathogens identified from patients with TD were enteric diarrhea-producing E. coli, especially ETEC and C International Society of Travel Medicine, 2017. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: V School of Medicine, University of Texas, Houston, TX, USA and 2Houston School of Public Health, The University of Texas, and Medical School, Center for Infectious Diseases, Houston, TX, USA S14 Journal of Travel Medicine, 2017, Vol. 24, Suppl 1 Table 1. Etiology of TD, data obtained from 11 published literatures between 2010 and 2016 Year of study 2011–12 2012 2011 2009–14 2013 2011 2014 2016 2011 2010 Total sample size Methods used in the study References 185 312 233 479 245 381 93 2459 353 98/75 Conventional Culture vs Multiplex PCR Direct Antigen Detection vs Multiplex PCR Standard vs Multiplex PCR Conventional Culture or Molecular Detection vs Multiplex PCR Quantitative PCR Direct antigen detection and conventional PCR Conventional PCR and quantitative PCR Multiplex PCR Seroconversion Reverse transcription-PCR 6 Enteric pathogens No bacterial pathogens Bacterial pathogens Single pathogens EAEC ETEC Shigella Campylobacter Salmonella Norovirus Giardia Cryptospridium Latin America Southeast Asia 28% 72% 34% 38% 42% 4% 2% 2% 10% 3% 4% 35% 80% 41% 17% 28% 13% 16% 5% 3% 9% 2% EAEC (Table 2). Campylobacter, Shigella, Salmonella, Norovirus, Giardia and Cryptosporidium. ETEC was the most frequently identified in travellers to Latin American found in 42% of subjects to the location. In contrast, Campylobacter was more often in identified in Asia compared with Latin America, 16 and 2%, respectively. Norovirus was the most common viral cause of TD15 when travellers visited Latin America. Mixed infections in patients with TD were common, found in 34% in cases studied from Latin America and 41% from Southeast Asia. To detect intestinal pathogens, conventional culture and antigen-direct detection methods were compared with several automated molecular detection assays, including Luminex xTAG GPP, BioFire FilmArray GI Panel and BD Max EPP. Individual targets on each panel were presented in Table 3). Sensitivity and specificity were calculated with respect to the comparator methods. All three panels had high sensitivities, 90% for Shigella, Salmonella, Campylobacter, rotavirus, adenovirus and norovirus in comparison to both a positive microbiological culture and real-time PCR positive gold standard to identify the cause of TD. Luminex xTAG GPP had low specificity for Salmonella identification (61%, Table 3) using culture as a gold standard. Using conventional PCR as a reference method, BioFire FilmArray GI panel yielded sensitivity and specificity of 100% for Giardia and Cryptosporidium. BD Max EPP had sensitivity of 93% for Cryptosporidium, 99% for Giardia, 100% for Entamoeba histolytica. Multiplex PCR was 8 9 3 10 11 12 13 14,15 found to have a higher level of sensitivity than the routine culture methods for common enteric pathogens. Evaluation of sensitivity is unreliable for Shigella spp., Y. enterocolitica and Aeromonas spp., due to the lack of positive results by culture methods and the few or no positive results by multiplex PCR. The use of multiplex PCR in published studies did not alw (...truncated)