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WHAT CAUSES DIARRHEA IN THE UNITED STATES? Risk Factors for and Causes of Diarrhea in Selected Jurisdictions in the United StatesBackground: In the United States, an estimated 9.4 million foodborne related illnesses from known pathogens and 38.4 million foodborne related illnesses from unknown causes occur annually. It is critically important to improve our ability to identify enteric pathogens and to characterize risk factors associated with potentially distinct diarrheal illnesses. Objectives: Risk factors for hospital admission among patients with diarrhea are not well characterized. In this study, we analyzed risk factors for hospitalization among outpatients with complaints of diarrhea, focusing on patients with multiple enteric pathogens. Additionally, we investigated the most commonly recognized infectious cause of diarrhea among hospitalized individuals, Clostridium difficile, in order to better understand its increasing frequency in community-onset diarrhea. Methods: Through the use of core epidemiologic methodology in combination with state-of-the-art laboratory techniques, known and putative pathogens were identified in patients with diarrhea presenting to selected emergency departments and ambulatory care clinics in Baltimore, Maryland, and New Haven, Connecticut from 2002-2007. Results: Of 1197 outpatients with diarrhea, 405 (35.0%) had definitive enteric pathogens, 527 (45.8%) had definitive or possible pathogens, 62 (5.4%) had multiple definitive pathogens, and 142 (12.3%) had multiple definitive or possible pathogens. At presentation, 233 patients (19.5%) were admitted to the hospital and 919 (76.8%) were not. When forced into a multivariable logistic regression model, multiple enteric pathogens (odds ratio (OR)=0.86, 95% confidence interval (CI)=0.61-1.21) lacked significance; however, age >65 (OR=7.2, 95% CI=4.16-12.46), history of prior gastrointestinal (OR=3.65, 95% CI=2.12-6.29) or immunocompromising co-morbid conditions (OR=2.67, 95% CI=1.69-4.21), hospitalization in the previous month (OR=3.24, 95% CI=2.07-5.07), and presentation at an emergency department (OR=2.53, 95% CI=1.72-3.73) were significantly associated with hospitalization. Of 1,091 outpatients tested for C. difficile toxin, 43 (3.9%) had positive results. Seven had no recognized risk factors, and three of these had neither risk factors nor co-infection with another enteric pathogen. Conclusions: A significant portion of outpatients with diarrhea were hospitalized. Identification of enteric pathogens or multiple pathogens was not associated with increased likelihood for hospitalization after adjustment for age and past medical conditions. Additionally, most outpatients with C. difficile infection had either recognized risk factors or co-infection.
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Clinical, environmental, and behavioral characteristics associated with Cryptosporidium infection among children with moderate-to-severe diarrhea in rural western Kenya, 2008-2012: The Global Enteric Multicenter Study (GEMS)Background Cryptosporidium is a leading cause of moderate-to-severe diarrhea (MSD) in young children in Africa. We examined factors associated with Cryptosporidium infection in MSD cases enrolled at the rural western Kenya Global Enteric Multicenter Study (GEMS) site from 2008-2012. Methodology/Principal findings At health facility enrollment, stool samples were tested for enteric pathogens and data on clinical, environmental, and behavioral characteristics collected. Each child’s health status was recorded at 60-day follow-up. Data were analyzed using logistic regression. Of the 1,778 children with MSD enrolled as cases in the GEMS-Kenya case-control study, 11% had Cryptosporidium detected in stool by enzyme immunoassay; in a genotyped subset, 81% were C. hominis. Among MSD cases, being an infant, having mucus in stool, and having prolonged/persistent duration diarrhea were associated with being Cryptosporidium-positive. Both boiling drinking water and using rainwater as the main drinking water source were protective factors for being Cryptosporidium-positive. At follow-up, Cryptosporidium-positive cases had increased odds of being stunted (adjusted odds ratio [aOR] = 1.65, 95% CI: 1.06–2.57), underweight (aOR = 2.08, 95% CI: 1.34–3.22), or wasted (aOR = 2.04, 95% CI: 1.21–3.43), and had significantly larger negative changes in height- and weight-for-age z-scores from enrollment. Conclusions/Significance Cryptosporidium contributes significantly to diarrheal illness in young children in western Kenya. Advances in point of care detection, prevention/control approaches, effective water treatment technologies, and clinical management options for children with cryptosporidiosis are needed. Copyright 2018, Public Library of Science. All rights reserved. https://creativecommons.org/publicdomain/zero/1.0/.
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Risk factors for death among children 0-59 months of age with moderate-to-severe diarrhea in Manhiça district, southern MozambiqueBackground: Despite major improvements in child survival rates, the number of deaths due to diarrhea remains unacceptably high. We aimed to describe diarrhea-associated mortality and evaluate risk factors for death among Mozambican children with moderate-to-severe diarrhea (MSD). Methods: Between December 2007 and November 2012, children under-five with MSD were enrolled in Manhiça district, as part of the Global Enteric Multicenter study (GEMS). Clinical, epidemiological, and socio-demographic characteristics were collected. Anthropometric measurements were performed and stool samples collected upon recruitment. A follow-up visit ~ 60 days post-enrolment was conducted and verbal autopsies performed in all death cases. Results: Of the 916 MSD-cases analyzed; 90% (821/916) completed 60 days follow-up and 69 patients died. The case fatality rate at follow-up was 8% (69/821), and the mortality rate 10.2 (95%CI: 7.75-13.59) deaths per 1000 persons-week at risk. Nearly half of the deaths 48% (33/69) among study participants clustered within 2 weeks of the onset of diarrhea. Typical enteropathogenic Escherichia coli (typical EPEC) and Cryptosporidium were the two pathogens associated to an increased risk of death in the univariate analysis with (HR = 4.16, p = 0.0461) and (H = 2.84, p = 0.0001) respectively. Conversely, Rotavirus infection was associated to a decreased risk of death (HR = 0.52, p = 0.0198). According to the multivariate analysis, risk factors for death included co-morbidities such as malnutrition (HR = 4.13, p < 0.0001), pneumonia/lower respiratory infection (HR = 3.51, p < 0.0001) or invasive bacterial disease (IBD) (HR = 6.80, p = 0.0009), presenting on arrival with lethargy or overt unconsciousness (HR = 1.73, p = 0.0302) or wrinkled skin (HR = 1.71, p = 0.0393), and cryptosporidium infection (HR = 2.14, p = 0.0038). When restricting the analysis to those with available HIV results (n = 191, 22% of the total study sample), HIV was shown to be a significant risk factor for death (HR = 5.05, p = 0.0009). Verbal autopsies were conducted in 100% of study deaths, and highlighted diarrhea as the main underlying cause of death 39%, (27/69); followed by HIV/AIDS related deaths 29.0% (20/69) and sepsis 11.6% (8/69). Conclusion: Preventive strategies targeting Cryptosporidium, malnutrition and early identification and treatment of associated co-morbidities could contribute to the prevention of the majority of diarrhea associated deaths in Mozambican children. © 2019 The Author(s).
