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Background: Diarrheal disease is a leading cause of morbidity and mortality globally, especially in low- and middle-income countries. High-throughput and low-cost approaches to identify etiologic agents are needed to guide public health mitigation. Nanoliter-qPCR (nl-qPCR) is an attractive alternative to more expensive methods yet is nascent in application and without a proof-of-concept among hospitalized patients., Methods: A census-based study was conducted among diarrheal patients admitted at two government hospitals in rural Bangladesh during a diarrheal outbreak period. DNA was extracted from stool samples and assayed by nl-qPCR for common bacterial, protozoan, and helminth enteropathogens as the primary outcome., Results: A total of 961 patients were enrolled; stool samples were collected from 827 patients. Enteropathogens were detected in 69% of patient samples; More than one enteropathogen was detected in 32%. Enteropathogens most commonly detected were enteroaggregative Escherichia coli (26.0%), Shiga toxin-producing E.coli (18.3%), enterotoxigenic E. coli (15.5% heat stable toxin positive, 2.2% heat labile toxin positive), Shigella spp. (14.8%), and Vibrio cholerae (9.0%). Geospatial analysis revealed that the median number of pathogens per patient and the proportion of cases presenting with severe dehydration were greatest amongst patients residing closest to the study hospitals.", Conclusions: This study demonstrates a proof-of-concept for nl-qPCR as a high-throughput low-cost method for enteropathogen detection among hospitalized patients., Competing Interests: The authors have read the journal’s policy and have the following competing interests: EJN is associated with a patent on data collection software (Outbreak Responder, A Method, Apparatus and Computer Program Product for Personal Identification and Electronic Data Management) used in this study (Patent Publication Number 2020/0082921). The software development was funded by the National Institutes of Health (DP5OD019893), the University of Florida and Stanford University. EJN has no financial interest in the development and deployment of the software. This does not alter our adherence to PLOS ONE policies on sharing data and materials. There are no other patents, products in development or marketed products associated with this research to declare. Development or marketed products associated with this research to declare.

Background: Acute diarrhoeal disease management often requires rehydration alone without antibiotics. However, non-indicated antibiotics are frequently ordered and this is an important driver of antimicrobial resistance. The mHealth Diarrhoea Management (mHDM) trial aimed to establish whether electronic decision support improves rehydration and antibiotic guideline adherence in resource-limited settings., Methods: A cluster randomised controlled trial was done at ten district hospitals in Bangladesh. Inclusion criteria were patients aged 2 months or older with uncomplicated acute diarrhoea. Admission orders were observed without intervention in the pre-intervention period, followed by randomisation to electronic (rehydration calculator) or paper formatted WHO guidelines for the intervention period. The primary outcome was rate of intravenous fluid ordered as a binary variable. Generalised linear mixed-effect models, accounting for hospital clustering, served as the analytical framework; the analysis was intention to treat. The trial is registered with ClinicalTrials.gov (NCT03154229) and is completed., Findings: From March 11 to Sept 10, 2018, 4975 patients (75·6%) of 6577 screened patients were enrolled. The intervention effect for the primary outcome showed no significant differences in rates of intravenous fluids ordered as a function of decision-support type. Intravenous fluid orders decreased by 0·9 percentage points for paper electronic decision support and 4·2 percentage points for electronic decision support, with a 4·2-point difference between decision-support types in the intervention period (paper 98·7% [95% CI 91·8-99·8] vs electronic 94·5% [72·2-99·1]; p interaction =0·31). Adverse events such as complications and mortality events were uncommon and could not be statistically estimated., Interpretation: Although intravenous fluid orders did not change, electronic decision support was associated with increases in the volume of intravenous fluid ordered and decreases in antibiotics ordered, which are consistent with WHO guidelines., Funding: US National Institutes of Health., (Copyright © 2020 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0. license. Published by Elsevier Ltd.. All rights reserved.)

The emergence of mobile technology offers new opportunities to improve clinical guideline adherence in resource-limited settings. We conducted a clinical pilot study in rural Bangladesh to evaluate the impact of a smartphone adaptation of the World Health Organization (WHO) diarrheal disease management guidelines, including a modality for age-based weight estimation. Software development was guided by end-user input and evaluated in a resource-limited district and sub-district hospital during the fall 2015 cholera season; both hospitals lacked scales which necessitated weight estimation. The study consisted of a 6 week pre-intervention and 6 week intervention period with a 10-day post-discharge follow-up. Standard of care was maintained throughout the study with the exception that admitting clinicians used the tool during the intervention. Inclusion criteria were patients two months of age and older with uncomplicated diarrheal disease. The primary outcome was adherence to guidelines for prescriptions of intravenous (IV) fluids, antibiotics and zinc. A total of 841 patients were enrolled (325 pre-intervention; 516 intervention). During the intervention, the proportion of prescriptions for IV fluids decreased at the district and sub-district hospitals (both p < 0.001) with risk ratios (RRs) of 0.5 and 0.2, respectively. However, when IV fluids were prescribed, the volume better adhered to recommendations. The proportion of prescriptions for the recommended antibiotic azithromycin increased (p < 0.001 district; p = 0.035 sub-district) with RRs of 6.9 (district) and 1.6 (sub-district) while prescriptions for other antibiotics decreased; zinc adherence increased. Limitations included an absence of a concurrent control group and no independent dehydration assessment during the pre-intervention. Despite limitations, opportunities were identified to improve clinical care, including better assessment, weight estimation, and fluid/ antibiotic selection. These findings demonstrate that a smartphone-based tool can improve guideline adherence. This study should serve as a catalyst for a randomized controlled trial to expand on the findings and address limitations., Competing Interests: The authors have declared that no competing interests exist.