Assessing the performance of clinical diagnostic models for dehydration among patients with cholera and undernutrition in Bangladesh.

OBJECTIVE: Accurately assessing dehydration severity is a critical step in reducing mortality from diarrhoea, but is complicated by cholera and undernutrition. This study seeks to assess the accuracy of two clinical diagnostic models for dehydration among patients over five years with cholera and undernutrition and compare their respective performance to the World Health Organization (WHO) algorithm. METHODS: In this secondary analysis of data collected from the NIRUDAK study, accuracy of the full and simplified NIRUDAK models for predicting severe and any dehydration was measured using the area under the Receiver Operator Characteristic curve (AUC) among patients over five with/without cholera and with/without wasting. Bootstrap with 1000 iterations was used to compare the m-index for each NIRUDAK model to that of the WHO algorithm. RESULTS: A total of 2,139 and 2,108 patients were included in the nutrition and cholera subgroups respectively with an overall median age of 35 years (IQR = 42) and 49.6% female. All subgroups had acceptable discrimination in diagnosing severe or any dehydration (AUC > 0.60); though the full NIRUDAK model performed best among patients without cholera, with an AUC of 0.82 (95%CI:0.79, 0.85) and among patients without wasting, with an AUC of 0.79 (95%CI:0.76, 0.81). Compared with the WHO's algorithm, both the full and simplified NIRUDAK models performed significantly better in terms of their m-index (p < 0.001) for all comparisons, except for the simplified NIRUDAK model in the wasting group. CONCLUSIONS: Both the full and simplified NIRUDAK models performed less well in patients over five years with cholera and/or wasting; however, both performed better than the WHO algorithm.

Ultrasound Adds No Benefit to Clinical Exam for Predicting Dehydration in Children With Acute Diarrhea in a Resource-Limited Setting.

OBJECTIVES: Diarrhea is one of the most common and deadly conditions affecting children, causing over 525,000 deaths annually, largely in resource-limited settings. Appropriate treatment depends on accurate determination of dehydration status. This study evaluated the accuracy of a new model using clinical and ultrasound measurements for predicting dehydration status in children with acute diarrhea. METHODS: The Dehydration: Assessing Kids Accurately (DHAKA) study was a prospective cohort study of children under 5 years of age with acute diarrhea presenting to the International Centre for Diarrhoeal Disease Research in Dhaka, Bangladesh. Clinical signs and sonographic measurements of the aorta-to-inferior vena cava ratio were recorded. Percent weight change with rehydration was used to classify dehydration severity. Logistic regression was used to create a combined DHAKA-US model based on clinical and sonographic measurements. Area under the curve and calibration slope were used to assess the model's accuracy and compare it to the original DHAKA score model. RESULTS: A total of 850 children were enrolled, with 736 included in the final analysis. The combined DHAKA-US model showed equivalent discrimination with the original DHAKA score, with an area under the curve of 0.79 for both models for severe dehydration (95% confidence interval, 0.74-0.84), as well as similar classification (48% versus 50% correctly classified) and calibration (calibration slopes of 0.900 versus 0.904 for presence of any dehydration). CONCLUSION: Adding sonographic measurements to the DHAKA score had no effect on discrimination, classification, or calibration when compared to the original DHAKA score. Clinical signs alone may be the most important predictors of dehydration status in children with diarrhea in limited resource settings.

Carotid Flow Time Test Performance for the Detection of Dehydration in Children With Diarrhea.

OBJECTIVES: Unstructured clinical assessments of dehydration in children are inaccurate. Point-of-care ultrasound is a noninvasive diagnostic tool that can help evaluate the volume status; the corrected carotid artery flow time has been shown to predict volume depletion in adults. We sought to determine the ability of the corrected carotid artery flow time to identify dehydration in a population of children presenting with acute diarrhea in Dhaka, Bangladesh. METHODS: Children presenting with acute diarrhea were recruited and rehydrated according to hospital protocols. The corrected carotid artery flow time was measured at the time of presentation. The percentage of weight change with rehydration was used to categorize each child's dehydration as severe (>9%), some (3%-9%), or none (<3%). A receiver operating characteristic curve was constructed to test the performance of the corrected carotid artery flow time for detecting severe dehydration. Linear regression was used to model the relationship between the corrected carotid artery flow time and percentage of dehydration. RESULTS: A total of 350 children (0-60 months) were enrolled. The mean corrected carotid artery flow time was 326 milliseconds (interquartile range, 295-351 milliseconds). The area under the receiver operating characteristic curve for the detection of severe dehydration was 0.51 (95% confidence interval, 0.42, 0.61). Linear regression modeling showed a weak association between the flow time and dehydration. CONCLUSIONS: The corrected carotid artery flow time was a poor predictor of severe dehydration in this population of children with diarrhea.

Midupper Arm Circumference Outperforms Weight-Based Measures of Nutritional Status in Children with Diarrhea.

BACKGROUND: Undernutrition contributes to 45% of all deaths in children <5 y of age worldwide, with a large proportion of those deaths caused by diarrhea. However, no validated tools exist for assessing undernutrition in children with diarrhea and possible dehydration. OBJECTIVE: This study assessed the validity of different measures of undernutrition in children with diarrhea. METHODS: A prospective cohort study was conducted at an urban hospital in Bangladesh. Children <60 mo of age presenting to the hospital rehydration unit with acute diarrhea were eligible for enrollment. Study staff randomly selected 1196 children for screening, of which 1025 were eligible, 850 were enrolled, and 721 had complete data for analysis. Anthropometric measurements, including weight-for-age z score (WAZ), weight-for-length z score (WLZ), midupper arm circumference (MUAC), and midupper arm circumference z score (MUACZ), were calculated pre- and posthydration in all patients. Measurements were evaluated for their ability to correctly identify undernutrition in children with varying degrees of dehydration. RESULTS: Of the 721 patients with full data for analysis, the median percent dehydration was 4%. Of the 4 measures evaluated, MUAC and MUACZ demonstrated 92-94% agreement pre- and posthydration compared with 69-76% for WAZ and WLZ. Although each 1% change in hydration status was found to change weight-for-age by 0.0895 z scores and weight-for-length by 0.1304 z scores, MUAC and MUACZ were not significantly affected by dehydration status. Weight-based measures misclassified 12% of children with severe underweight and 14% with severe acute malnutrition (SAM) compared with only 1-2% for MUAC and MUACZ. CONCLUSIONS: MUAC and MUACZ were the most accurate predictors of undernutrition in children with diarrhea. WAZ and WLZ were significantly affected by dehydration status, leading to the misdiagnosis of many patients on arrival with severe underweight and SAM. This trial was registered at clinicaltrials.gov as NCT02007733.

Understanding variations in diarrhea management across healthcare facilities in Bangladesh: a formative qualitative study.

INTRODUCTION: Acute diarrhea remains a leading cause of morbidity and mortality with over 6.3 billion cases and 1.3 million deaths annually. Despite the existence of standardized guidelines for diarrhea management, wide variability in clinical practice exists, particularly in resource-limited settings. The goal of this study was to qualitatively explore how diarrhea management in Bangladesh varies according to resource availability, clinical setting, and provider roles. METHODOLOGY: This was a secondary analysis of a cross-sectional qualitative study conducted in three diverse hospital settings (district hospital, subdistrict hospital, and specialty diarrhea research hospital) in Bangladesh. A total of eight focus group discussions with nurses and physicians were conducted. Applied thematic analysis was used to identify themes regarding variations in diarrhea management. RESULTS: Of the 27 focus group participants, 14 were nurses and 13 doctors; 15 worked in a private diarrhea specialty hospital and 12 worked in government district or subdistrict hospitals. Several key themes emerged from the qualitative data analysis: 1) priorities in the clinical assessment of diarrhea 2) use of guidelines versus clinical judgment; 3) variability in clinician roles and between clinical settings influences care delivery; 4) impact of resource availability on diarrhea management; and 5) perceptions of community health workers' role in diarrhea management. CONCLUSIONS: Findings from this study may aid in informing interventions to improve and standardize diarrhea management in resource-constrained settings. Resource availability, practices regarding diarrhea assessment and treatment, provider experience, and variability in provider roles are essential considerations when developing clinical tools in low- and middle- income countries.

Site-Specific Analysis of the Incidence Rate of Enterotoxigenic Escherichia coli Infection Elucidates an Association with Childhood Stunting, Wasting, and Being Underweight: A Secondary Analysis of the MAL-ED Birth Cohort.

Asymptomatic infection by fecal enteropathogens is a major contributor to childhood malnutrition. Here, we investigated the incidence rate of asymptomatic infection by enterotoxigenic Escherichia coli (ETEC) and assessed its association with childhood stunting, wasting, and being underweight among children under 2 years of age. The Malnutrition and Enteric Disease birth cohort study included 1,715 children who were followed from birth to 24 months of age from eight distinct geographic locations including Bangladesh, Brazil, India, Peru, Tanzania, Pakistan, Nepal, and South Africa. The TaqMan array card assay was used to determine the presence of ETEC in the nondiarrheal stool samples collected from these children. Poisson regression was used to estimate the incidence rate, and multiple generalized estimating equations with binomial family, logit link function, and exchangeable correlation were used to analyze the association between asymptomatic ETEC infection and anthropometric indicators such as stunting, wasting, and being underweight. The site-specific incidence rates of asymptomatic ETEC infections per 100 child-months were also higher at the study locations in Tanzania (54.81 [95% CI: 52.64, 57.07]) and Bangladesh (46.75 [95% CI: 44.75, 48.83]). In the Bangladesh, India, and Tanzania sites, the composite indicator of anthropometric failure was significantly associated with asymptomatic ETEC infection. Furthermore, a significant association between asymptomatic heat-stable toxin ETEC infections and childhood stunting, wasting, and being underweight was found in only the Bangladesh and Tanzania sites.

Symptomatic and Asymptomatic Campylobacter Infections and Child Growth in South Asia: Analyzing Data from the Global Enteric Multicenter Study.

Campylobacter is a major cause of food-borne gastrointestinal illnesses worldwide, predominantly affecting children under 5 years of age. This study examined potential associations of symptomatic (with diarrhea) and asymptomatic (without diarrhea) Campylobacter infections with child growth among children under 5 years of age in South Asia. The Global Enteric Multicenter Study was conducted from 2007 to 2011 with a case-control design. Children were followed for 60 days after enrollment. Stool culture was performed to isolate Campylobacter spp. Among the 22,567 enrolled children, 9,439 were symptomatic, with 786 (8.28%) testing positive for Campylobacter. Conversely, 13,128 asymptomatic healthy controls were included, with 1,057 (8.05%) testing positive for Campylobacter. Growth faltering was observed in the symptomatic group, particularly among children aged 0-11 months (-0.19 height-for-age z score [HAZ]; 95% CI: -0.36, -0.03; P = 0.018) and 24-59 months (-0.16 HAZ; 95% CI: -0.28, -0.04; P = 0.010). However, in the asymptomatic group, growth faltering was observed only in the 24- to 59-month age group, in terms of HAZ (-0.15 HAZ; 95% CI: -0.24, -0.05; P = 0.002) and weight-for-height z score (-0.16; 95% CI: -0.26, -0.06; P = 0.001). These findings underscore the importance of immediate and enhanced introduction of preventive modalities to reduce the burden of Campylobacter infections and reduce their long-term sequelae.

Vibrio cholerae in rural and urban Bangladesh, findings from hospital-based surveillance, 2000-2021.

With more than 100,000 cases estimated each year, Bangladesh is one of the countries with the highest number of people at risk for cholera. Moreover, Bangladesh is formulating a countrywide cholera-control plan to satisfy the GTFCC (The Global Task Force on Cholera Control) Roadmap's goals. With a particular focus on cholera trends, variance in baseline and clinical characteristics of cholera cases, and trends in antibiotic susceptibility among clinical isolates of Vibrio cholerae, we used data from facility-based surveillance systems from icddr,b's Dhaka, and Matlab Hospitals from years 2000 to 2021. Female patients comprised 3,553 (43%) in urban and 1,099 (51.6%) in rural sites. Of the cases and most patients 5,236 (63.7%) in urban and 1,208 (56.7%) in the rural site were aged 15 years and more. More than 50% of the families belonged to the poor and lower-middle-class; in 2009 (24.4%) were in urban and in 1,791 (84.2%) were in rural sites. In the urban site, 2,446 (30%) of households used untreated drinking water, and 702 (9%) of families disposed of waste in their courtyard. In the multiple logistic regression analysis, the risk of cholera has significantly increased due to waste disposal in the courtyard and the boiling of water has a protective effect against cholera. Rotavirus (9.7%) was the most prevalent co-pathogen among the under-5 children in both sites. In urban sites, the percentage of V. cholerae along with co-existing ETEC and Campylobacter is changing in the last 20 years; Campylobacter (8.36%) and Enterotoxigenic Escherichia coli (ETEC) (7.15%) were the second and third most prevalent co-pathogens. Shigella (1.64%) was the second most common co-pathogen in the rural site. Azithromycin susceptibility increased slowly from 265 (8%) in 2006-2010 to 1485 (47.8%) in 2016-2021, and erythromycin susceptibility dropped substantially over 20 years period from 2,155 (98.4%) to 21 (0.9%). Tetracycline susceptibility decreased in the urban site from 2051 (45.9%) to 186 (4.2%) and ciprofloxacin susceptibility decreased from 2,581 (31.6%) to 1,360 (16.6%) until 2015, then increased 1,009 (22.6%) and 1,490 (18.2%) in 2016-2021, respectively. Since 2016, doxycycline showed 902 (100%) susceptibility. Clinicians need access to up-to-date information on antimicrobial susceptibility for treating hospitalized patients. To achieve the WHO-backed objective of eliminating cholera by 2030, the health systems need to be put under a proper surveillance system that may help to improve water and sanitation practices and deploy oral cholera vaccines strategically.

A comparison of the NIRUDAK models and WHO algorithm for dehydration assessment in older children and adults with acute diarrhoea: a prospective, observational study.

BACKGROUND: Despite the importance of accurate and rapid assessment of hydration status in patients with acute diarrhoea, no validated tools exist to help clinicians assess dehydration severity in older children and adults. The aim of this study is to validate a clinical decision support tool (CDST) and a simplified score for dehydration severity in older children and adults with acute diarrhoea (both developed during the NIRUDAK study) and compare their accuracy and reliability with current WHO guidelines. METHODS: A random sample of patients aged 5 years or older presenting with diarrhoea to the icddr,b Dhaka Hospital in Bangladesh between Jan 30 and Dec 13, 2022 were included in this prospective cohort study. Patients with fewer than three loose stools per day, more than 7 days of symptoms, previous enrolment in the study, or a diagnosis other than acute gastroenteritis were excluded. Patients were weighed on arrival and assessed separately by two nurses using both our novel clinical tools and WHO guidelines. Patients were weighed every 4 h to determine their percent weight change with rehydration, our criterion standard for dehydration. Accuracy for the diagnosis of dehydration category (none, some, or severe) was assessed using the ordinal c-index (ORC). Reliability was assessed by comparing the prediction of severe dehydration from each nurse's independent assessment using the intraclass correlation coefficient (ICC). FINDINGS: 1580 patients were included in our primary analysis, of whom 921 (58·3%) were female and 659 (41·7%) male. The ORC was 0·74 (95% CI 0·71-0·77) for the CDST, 0·75 (0·71-0·78) for the simplified score, and 0·64 (0·61-0·67) for the WHO guidelines. The ICC was 0·98 (95% CI 0·97-0·98) for the CDST, 0·94 (0·93-0·95) for the simplified score, and 0·56 (0·52-0·60) for the WHO guidelines. INTERPRETATION: Use of our CDST or simplified score by clinicians could reduce undertreatment and overtreatment of older children and adults with acute diarrhoea, potentially reducing morbidity and mortality for this common disease. FUNDING: US National Institutes of Health. TRANSLATION: For the Bangla translation of the abstract see Supplementary Materials section.

Use of Framework Matrix and Thematic Coding Methods in Qualitative Analysis for mHealth: NIRUDAK Study Data.

Objective: Framework Matrix Analysis (FMA) and Applied Thematic Analysis (ATA) are qualitative methods that have not been as widely used/cited compared to content analysis or grounded theory. This paper compares methods of FMA with ATA for mobile health (mHealth) research. The same qualitative data were analyzed separately, using each methodology. The methods, utility, and results of each are compared, and recommendations made for their effective use. Methods: Formative qualitative data were collected in eight focus group discussions with physicians and nurses from three hospitals in Bangladesh. Focus groups were conducted via video conference in the local language, Bangla, and audio recorded. Audio recordings were used to complete a FMA of participants' opinions about key features of a novel mHealth application (app) designed to support clinical management in patients with acute diarrhea. The resulting framework matrix was shared with the app design team and used to guide iterative development of the product for a validation study of the app. Subsequently, focus group audio recordings were transcribed in Bangla then translated into English for ATA; transcripts and codes were entered into NVivo qualitative analysis software. Code summaries and thematic memos explored the clinical utility of the mHealth app including clinicians' attitudes about using this decision support tool. Results: Each of the two methods contributes differently to the research goal and have different implications for an mHealth research timeline. Recommendations for the effective use of each method in app development include: using FMA for data reduction where specific outcomes are needed to make programming and design decisions and using ATA to capture the more nuanced issues that guide use, product implementation, training, and workflow. Conclusions: By describing how both analytical methods were used in this context, this paper provides guidance and an illustration for use of these two methods, specifically in mHealth design.

Effectiveness, safety and economic viability of daycare versus usual hospital care management of severe pneumonia with or without malnutrition in children using the existing health system of Bangladesh: a cluster randomised controlled trial.

Background: We aimed to define clinical and cost-effectiveness of a Day Care Approach (DCA) alternative to Usual Care (UC, comparison group) within the Bangladesh health system to manage severe childhood pneumonia. Methods: This was a cluster randomised controlled trial in urban Dhaka and rural Bangladesh between November 1, 2015 and March 23, 2019. Children aged 2-59 months with severe pneumonia with or without malnutrition received DCA or UC. The DCA treatment settings comprised of urban primary health care clinics run by NGO under Dhaka South City Corporation and in rural Union health and family welfare centres under the Ministry of Health and Family welfare Services. The UC treatment settings were hospitals in these respective areas. Primary outcome was treatment failure (persistence of pneumonia symptoms, referral or death). We performed both intention-to-treat and per-protocol analysis for treatment failure. Registered at www.ClinicalTrials.gov, NCT02669654. Findings: In total 3211 children were enrolled, 1739 in DCA and 1472 in UC; primary outcome data were available in 1682 and 1357 in DCA and UC, respectively. Treatment failure rate was 9.6% among children in DCA (167 of 1739) and 13.5% in the UC (198 of 1472) (group difference, -3.9 percentage point; 95% confidence interval (CI), -4.8 to -1.5, p = 0.165). Treatment success within the health care systems [DCA plus referral vs. UC plus referral, 1587/1739 (91.3%) vs. 1283/1472 (87.2%), group difference 4.1 percentage point, 95% CI, 3.7 to 4.1, p = 0.160)] was better in DCA. One child each in UC of both urban and rural sites died within day 6 after admission. Average cost of treatment per child was US$94.2 (95% CI, 92.2 to 96.3) and US$184.8 (95% CI, 178.6 to 190.9) for DCA and UC, respectively. Interpretation: In our population of children with severe pneumonia with or without malnutrition, >90% were successfully treated at Day care Clinics at 50% lower cost. A modest investment to upgrade Day care facilities may provide a cost-effective, accessible alternative to hospital management. Funding: UNICEF, Botnar Foundation, UBS Optimus Foundation, and EAGLE Foundation, Switzerland.

Incidence of Asymptomatic Shigella Infection and Association with the Composite Index of Anthropometric Failure among Children Aged 1-24 Months in Low-Resource Settings.

Asymptomatic or subclinical infection by diarrheal enteropathogens during childhood has been linked to poor health and nutritional outcomes. In this study, we aimed to assess the impact of asymptomatic Shigella infection on different forms of childhood malnutrition including the composite index of anthropometric failure (CIAF). We used data from 1715 children enrolled in the multi-country birth cohort study, MAL-ED, from November 2009 to February 2012. Monthly non-diarrheal stools were collected and assessed using TaqMan Array Cards (TAC). Poisson regression was used to calculate incidence rates of asymptomatic Shigella infection. Generalized estimating equations (GEE) were used to assess the association between asymptomatic Shigella infection and nutritional indicators after adjusting for relevant covariates. Incidence rates per 100 child-months were higher in Tanzania, Bangladesh and Peru. Overall, after adjusting for relevant covariates, asymptomatic Shigella infection was significantly associated with stunting (aOR 1.60; 95% CI: 1.50, 1.70), wasting (aOR 1.26; 95% CI: 1.09, 1.46), underweight (aOR 1.45; 95% CI: 1.35, 1.56), and CIAF (aOR 1.55; 95% CI: 1.46, 1.65) in all the study sites except for Brazil. The high incidence rates of asymptomatic Shigella infection underscore the immediate need for Shigella vaccines to avert the long-term sequelae involving childhood growth.

Factors associated with community acquired severe pneumonia among under five children in Dhaka, Bangladesh: A case control analysis.

BACKGROUND: Pneumonia is the leading cause of death in children globally with the majority of these deaths observed in resource-limited settings. Globally, the annual incidence of clinical pneumonia in under-five children is approximately 152 million, mostly in the low- and middle-income countries. Of these, 8.7% progressed to severe pneumonia requiring hospitalization. However, data to predict children at the greatest risk to develop severe pneumonia from pneumonia are limited. METHOD: Secondary data analysis was performed after extracting relevant data from a prospective cluster randomized controlled clinical trial; children of either sex, aged two months to five years with pneumonia or severe pneumonia acquired in the community were enrolled over a period of three years in 16 clusters in urban Dhaka city. RESULTS: The analysis comprised of 2,597 children aged 2-59 months. Of these, 904 and 1693 were categorized as pneumonia (controls) and severe pneumonia (cases), respectively based on WHO criteria. The median age of children was 9.2 months (inter quartile range, 5.1-17.1) and 1,576 (60%) were male. After adjustment for covariates, children with temperature ≥38°C, duration of illness ≥3 days, male sex, received prior medical care and severe stunting showed a significantly increased likelihood of developing severe pneumonia compared to those with pneumonia. Severe pneumonia in children occurred more often in older children who presented commonly from wealthy quintile families, and who often sought care from private facilities in urban settings. CONCLUSION AND RECOMMENDATION: Male sex, longer duration of illness, fever, received prior medical care, and severe stunting were significantly associated with development of WHO-defined severe childhood pneumonia in our population. The results of this study may help to develop interventions target to reduce childhood morbidity and mortality of children suffering from severe pneumonia.

Designing a Novel Clinician Decision Support Tool for the Management of Acute Diarrhea in Bangladesh: Formative Qualitative Study.

BACKGROUND: The availability of mobile clinical decision support (CDS) tools has grown substantially with the increased prevalence of smartphone devices and apps. Although health care providers express interest in integrating mobile health (mHealth) technologies into their clinical settings, concerns have been raised, including perceived disagreements between information provided by mobile CDS tools and standard guidelines. Despite their potential to transform health care delivery, there remains limited literature on the provider's perspective on the clinical utility of mobile CDS tools for improving patient outcomes, especially in low- and middle-income countries. OBJECTIVE: This study aims to describe providers' perceptions about the utility of a mobile CDS tool accessed via a smartphone app for diarrhea management in Bangladesh. In addition, feedback was collected on the preliminary components of the mobile CDS tool to address clinicians' concerns and incorporate their preferences. METHODS: From November to December 2020, qualitative data were gathered through 8 web-based focus group discussions with physicians and nurses from 3 Bangladeshi hospitals. Each discussion was conducted in the local language-Bangla-and audio recorded for transcription and translation by the local research team. Transcripts and codes were entered into NVivo (version 12; QSR International), and applied thematic analysis was used to identify themes that explore the clinical utility of an mHealth app for assessing dehydration severity in patients with acute diarrhea. Summaries of concepts and themes were generated from reviews of the aggregated coded data; thematic memos were written and used for the final analysis. RESULTS: Of the 27 focus group participants, 14 (52%) were nurses and 13 (48%) were physicians; 15 (56%) worked at a diarrhea specialty hospital and 12 (44%) worked in government district or subdistrict hospitals. Participants' experience in their current position ranged from 2 to 14 years, with an average of 10.3 (SD 9.0) years. Key themes from the qualitative data analysis included current experience with CDS, overall perception of the app's utility and its potential role in clinical care, barriers to and facilitators of app use, considerations of overtreatment and undertreatment, and guidelines for the app's clinical recommendations. Participants felt that the tool would initially take time to use, but once learned, it could be useful during epidemic cholera. Some felt that clinical experience remains an important part of treatment that can be supplemented, but not replaced, by a CDS tool. In addition, diagnostic information, including mid-upper arm circumference and blood pressure, might not be available to directly inform programming decisions. CONCLUSIONS: Participants were positive about the mHealth app and its potential to inform diarrhea management. They provided detailed feedback, which developers used to revise the mobile CDS tool. These formative qualitative data provided timely and relevant feedback to improve the utility of a CDS tool for diarrhea treatment in Bangladesh.

Correction: Derivation of the first clinical diagnostic models for dehydration severity in patients over five years with acute diarrhea.

[This corrects the article DOI: 10.1371/journal.pntd.0009266.].

External validation of a mobile clinical decision support system for diarrhea etiology prediction in children: A multicenter study in Bangladesh and Mali.

Background: Diarrheal illness is a leading cause of antibiotic use for children in low- and middle-income countries. Determination of diarrhea etiology at the point-of-care without reliance on laboratory testing has the potential to reduce inappropriate antibiotic use. Methods: This prospective observational study aimed to develop and externally validate the accuracy of a mobile software application ('App') for the prediction of viral-only etiology of acute diarrhea in children 0-59 months in Bangladesh and Mali. The App used a previously derived and internally validated model consisting of patient-specific ('present patient') clinical variables (age, blood in stool, vomiting, breastfeeding status, and mid-upper arm circumference) as well as location-specific viral diarrhea seasonality curves. The performance of additional models using the 'present patient' data combined with other external data sources including location-specific climate, data, recent patient data, and historical population-based prevalence were also evaluated in secondary analysis. Diarrhea etiology was determined with TaqMan Array Card using episode-specific attributable fraction (AFe) >0.5. Results: Of 302 children with acute diarrhea enrolled, 199 had etiologies above the AFe threshold. Viral-only pathogens were detected in 22% of patients in Mali and 63% in Bangladesh. Rotavirus was the most common pathogen detected (16% Mali; 60% Bangladesh). The present patient+ viral seasonality model had an AUC of 0.754 (0.665-0.843) for the sites combined, with calibration-in-the-large α = -0.393 (-0.455--0.331) and calibration slope ß = 1.287 (1.207-1.367). By site, the present patient+ recent patient model performed best in Mali with an AUC of 0.783 (0.705-0.86); the present patient+ viral seasonality model performed best in Bangladesh with AUC 0.710 (0.595-0.825). Conclusions: The App accurately identified children with high likelihood of viral-only diarrhea etiology. Further studies to evaluate the App's potential use in diagnostic and antimicrobial stewardship are underway. Funding: Funding for this study was provided through grants from the Bill and Melinda GatesFoundation (OPP1198876) and the National Institute of Allergy and Infectious Diseases (R01AI135114). Several investigators were also partially supported by a grant from the National Institute of Diabetes and Digestive and Kidney Diseases (R01DK116163). This investigation was also supported by the University of Utah Population Health Research (PHR) Foundation, with funding in part from the National Center for Advancing Translational Sciences of the National Institutes of Health under Award Number UL1TR002538. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. The funders had no role in the study design, data collection, data analysis, interpretation of data, or in the writing or decision to submit the manuscript for publication.

Diarrhea is one of the most common illnesses among children worldwide. In low- and middle-income countries with limited health care resources, it can be deadly. Diarrhea can be caused by infections with viruses or bacteria. Antibiotics can treat bacterial infections, but they are not effective against viral infections. It can often be difficult to determine the cause of diarrhea. As a result, many clinicians just prescribe antibiotics. However, since diarrhea in young children is often due to viral infections, prescribing unnecessary antibiotics can cause children to have side effects without any benefit. Excessive use of antibiotics also contributes to the development of bacteria that are resistant to antibiotics, making infections harder to treat. Scientists are working to develop mobile health tools or 'apps' that may help clinicians identify the cause of diarrhea. Using computer algorithms to analyze information about the patient and seasonal infection patterns, the apps predict whether a bacterial or viral infection is the likely culprit. These tools may be particularly useful in low- or middle-income country settings, where clinicians have limited access to testing for bacteria or viruses. Garbern, Nelson et al. previously built an app to help distinguish cases of viral diarrhea in children in Mali and Bangladesh. Now, the researchers have put their app to the test in the real-world in a new group of patients to verify it works. In the experiments, nurses in Mali and Bangladesh used the app to predict whether a child with diarrhea had a viral or non-viral infection. The children's stool was then tested for viral or bacterial DNA to confirm whether the prediction was correct. The experiments showed the app accurately identified viral cases of diarrhea. The experiments also showed that customizing the app to local conditions may further improve its accuracy. For example, a version of the app that factored in seasonal virus transmission performed the best in Bangladesh, while a version that factored in data from recent patients in the past few weeks performed the best in Mali. Garbern and Nelson et al. are now testing whether their app could help reduce unnecessary use of antibiotics in children with diarrhea. If it does, it may help minimize antibiotic resistance and ensure more children get appropriate diarrhea care.

Clinical, Sociodemographic and Environmental Risk Factors for Acute Bacterial Diarrhea among Adults and Children over Five Years in Bangladesh.

In 2016, diarrheal disease was the eighth leading cause of mortality globally accounting for over 1.6 million deaths with the majority of deaths in adults and children over 5 years. This study aims to investigate the clinical, sociodemographic, and environmental risk factors associated with common bacterial acute diarrhea among adults and children over 5. Data were collected from March 2019 to March 2020 in patients over 5 years presenting with acute gastroenteritis at icddr,b. Stool samples were collected from each patient for culture and polymerase chain reaction (PCR) testing. Bivariate associations between independent variables and stool-testing indicating bacterial etiology were calculated. This analysis included 2,133 diarrheal patients of whom a bacterial enteropathogen was identified in 1,537 (72%). Detection of bacteria was associated with: younger age (OR 0.92; 95% CI: 0.88-0.96), lower mean arterial pressure (OR 0.84; 95% CI: 0.79-0.89), heart rate (OR 1.06; 95% CI: 1.01-1.10), percentage dehydration (OR 1.33; 95% CI: 1.13-1.55), respiration rate (OR 1.23; 95% CI: 1.04-1.46), lower mid-upper arm circumference (OR 0.97; 95% CI: 0.94-0.99), confused/lethargic mental status (OR 1.85; 95% CI: 1.11-3.25), rice watery stool (OR 1.92; 95% CI: 1.54-2.41), and vomiting more than three times in the past 24 hours (OR 1.30; 95% CI: 1.06-1.58). Higher monthly income (OR 0.92; 95% CI: 0.86-0.98), > 8 years of education (OR 0.79; 95% CI: 0.63-1.00), and having more than five people living at home (OR 0.80; 95% CI: 0.66-0.98) were associated with lower odds of bacterial diarrhea. These findings may help guide the development of predictive tools to aid in identifying patients with bacterial diarrhea for timely and appropriate use of antibiotics.

Continuous diagnostic models for volume deficit in patients with acute diarrhea.

BACKGROUND: Episodes of acute diarrhea lead to dehydration, and existing care algorithms base treatment around categorical estimates for fluid resuscitation. This study aims to develop models for the percentage dehydration (fluid deficit) in individuals with acute diarrhea, to better target treatment and avoid the potential sequelae of over or under resuscitation. METHODS: This study utilizes data from two prospective cohort studies of patients with acute diarrhea in Dhaka, Bangladesh. Data were collected on patient arrival, including weight, clinical signs and symptoms, and demographic information. Consecutive weights were obtained to determine the true volume deficit of each patient. Data were entered into two distinct forward stepwise regression logistic models (DHAKA for under 5 years and NIRUDAK for 5 years and over). RESULTS: A total of 782 patients were included in the final analysis of the DHAKA data set, and 2139 were included in the final analysis of the NIRUDAK data set. The best model for the DHAKA data achieved an R2 of 0.27 and a root mean square error (RMSE) of 3.7 (compared to R2 of 0.06 and RMSE of 5.5 with the World Health Organization child care algorithm) and selected 6 predictors. The best performance model for the NIRUDAK data achieved an R2 of 0.28 and a RMSE of 2.6 (compared to R2 of 0.08 and RMSE of 4.3 with the World Health Organization adolescent/adult care algorithm) and selected 7 predictors with 2 interactions. CONCLUSIONS: These are the first mathematical models for patients with acute diarrhea that allow for the calculation of a patient's percentage dehydration (fluid deficit) and subsequent targeted treatment with fluid resuscitation. These findings are an improvement on existing World Health Organization care algorithms.

Derivation and Internal Validation of a Score to Predict Dehydration Severity in Patients over 5 Years with Acute Diarrhea.

Diarrheal disease accounts for more than one million deaths annually in patients over 5 years of age. Although most patients can be managed with oral rehydration solution, patients with severe dehydration require resuscitation with intravenous fluids. Scoring systems to assess dehydration have been empirically derived and validated in children under 5 years, but none have been validated for patients over 5 years. In this study, a prospective cohort of 2,172 patients over 5 years presenting with acute diarrhea to International Centre for Diarrhoeal Disease Research, Dhaka Hospital, Bangladesh, were assessed for clinical signs of dehydration. The percent difference between presentation and posthydration stable weight determined severe (≥ 9%), some (3-9%), or no (< 3%) dehydration. An ordinal regression model was derived using clinical signs and demographics and was then converted to a 13-point score to predict none (score of 0-3), some (4-6), or severe (7-13) dehydration. The Novel, Innovative Research for Understanding Dehydration in Adults and Kids (NIRUDAK) Score developed by our team included age, sex, sunken eyes, radial pulse, respiration depth, skin turgor, and vomiting episodes in 24 hours. Accuracy of the NIRUDAK Score for predicting severe dehydration, as measured by the area under the receiver operating characteristic curve, was 0.76 (95% confidence interval = 0.73-0.78), with a sensitivity of 0.78 and a specificity of 0.61. Reliability was also robust, with an Inter-Class Correlation Coefficient of 0.88 (95% confidence interval = 0.84-0.91). This study represents the first empirically derived and internally validated scoring system for assessing dehydration in children ≥ 5 years and adults with acute diarrhea in a resource-limited setting.

Multidrug-resistant enteric pathogens in older children and adults with diarrhea in Bangladesh: epidemiology and risk factors.

BACKGROUND: Antimicrobial resistance (AMR) is a global public health threat and is increasingly prevalent among enteric pathogens in low- and middle-income countries (LMICs). However, the burden of multidrug-resistant organisms (MDROs) in older children, adults, and elderly patients with acute diarrhea in LMICs is poorly understood. This study's aim was to characterize the prevalence of MDR enteric pathogens isolated from patients with acute diarrhea in Dhaka, Bangladesh, and assess a wide range of risk factors associated with MDR. METHODS: This study was a secondary analysis of data collected from children over 5 years, adults, and elderly patients with acute diarrhea at the International Centre for Diarrhoeal Disease Research, Bangladesh Dhaka Hospital between March 2019 and March 2020. Clinical, historical, socio-environmental information, and a stool sample for culture and antimicrobial susceptibility testing were collected from each patient. Univariate statistics and multiple logistic regression were used to assess the prevalence of MDR among enteric pathogens and the association between independent variables and presence of MRDOs among culture-positive patients. RESULTS: A total of 1198 patients had pathogens isolated by stool culture with antimicrobial susceptibility results. Among culture-positive patients, the prevalence of MDR was 54.3%. The prevalence of MDR was highest in Aeromonas spp. (81.5%), followed by Campylobacter spp. (72.1%), Vibrio cholerae (28.1%), Shigella spp. (26.2%), and Salmonella spp. (5.2%). Factors associated with having MDRO in multiple logistic regression included longer transport time to hospital (>90 min), greater stool frequency, prior antibiotic use prior to hospital presentation, and non-flush toilet use. However, pseudo-R2 was low 0.086, indicating that other unmeasured variables need to be considered to build a more robust predictive model of MDR. CONCLUSIONS: MDR enteric pathogens were common in this study population with clinical, historical, and socio-environmental risk factors associated with MDROs. These findings may help guide clinical decision-making regarding antibiotic use and selection in patients at greatest risk of complications due to MDROs. Further prospective research is urgently needed to determine what additional factors place patients at greatest risk of MDRO, and the best strategies to mitigate the spread of MDR in enteric pathogens.