Persistence of Severe Acute Respiratory Syndrome Coronavirus 2 Omicron Variant in Children and Utility of Rapid Antigen Testing as an Indicator of Culturable Virus.

We screened 65 longitudinally collected nasal swab samples from 31 children aged 0-16 years who were positive for severe acute respiratory syndrome coronavirus 2 Omicron BA.1. By day 7 after onset of symptoms, 48% of children remained positive by rapid antigen test. In a sample subset, we found 100% correlation between antigen test results and virus culture.

Ancestral Origin and Dissemination Dynamics of Reemerging Toxigenic Vibrio cholerae, Haiti.

The 2010 cholera epidemic in Haiti was thought to have ended in 2019, and the Prime Minister of Haiti declared the country cholera-free in February 2022. On September 25, 2022, cholera cases were again identified in Port-au-Prince. We compared genomic data from 42 clinical Vibrio cholerae strains from 2022 with data from 327 other strains from Haiti and 1,824 strains collected worldwide. The 2022 isolates were homogeneous and closely related to clinical and environmental strains circulating in Haiti during 2012-2019. Bayesian hypothesis testing indicated that the 2022 clinical isolates shared their most recent common ancestor with an environmental lineage circulating in Haiti in July 2018. Our findings strongly suggest that toxigenic V. cholerae O1 can persist for years in aquatic environmental reservoirs and ignite new outbreaks. These results highlight the urgent need for improved public health infrastructure and possible periodic vaccination campaigns to maintain population immunity against V. cholerae.

Population-Based Serologic Survey of Vibrio cholerae Antibody Titers before Cholera Outbreak, Haiti, 2022.

A Vibrio cholerae O1 outbreak emerged in Haiti in October 2022 after years of cholera absence. In samples from a 2021 serosurvey, we found lower circulating antibodies against V. cholerae lipopolysaccharide in children <5 years of age and no vibriocidal antibodies, suggesting high susceptibility to cholera, especially among young children.

Implementation of a Pediatric Telemedicine and Medication Delivery Service in a Resource-limited Setting: A Pilot Study for Clinical Safety and Feasibility.

OBJECTIVE: Determine the clinical safety and feasibility of implementing a telemedicine and medication delivery service (TMDS) to address gaps in nighttime access to health care for children in low-resource settings. STUDY DESIGN: We implemented a TMDS called 'MotoMeds' in Haiti as a prospective cohort study. A parent/guardian of a sick child ≤ 10 years contacted the call center (6 PM-5 AM). A nurse provider used decision support tools to triage cases (mild, moderate, or severe). Severe cases were referred to emergency care. For nonsevere cases, providers gathered clinical findings to generate an assessment and plan. For cases within the delivery zone, a provider and driver were dispatched and the provider performed a paired in-person exam as a reference standard for the virtual call center exam. Families received a follow-up call at 10 days. Data were analyzed for clinical safety and feasibility. RESULTS: A total of 391 cases were enrolled from September 9, 2019, to January 19, 2021. Most cases were nonsevere (92%; 361); household visits were completed for 89% (347) of these cases. Among the 30 severe cases, 67% (20) sought referred care. Among all cases, respiratory problems were the most common complaint (63%; 246). At 10 days, 95% (329) of parents reported their child had "improved" or "recovered". Overall, 99% (344) rated the TMDS as "good" or "great". The median phone consultation time was 20 minutes, time to household arrival was 73 minutes, and total case time was 114 minutes. CONCLUSION: The TMDS was a feasible health care delivery model. Although many cases were likely self-limiting, the TMDS was associated with high rates of reported improvement in clinical status at 10 days. TRIAL REGISTRATION: clinicaltrials.gov: NCT03943654.

Evaluating the prerequisites for adapting a paediatric nighttime telemedicine and medication delivery service to a setting with high malarial burden: A cross-sectional pre-implementation study.

OBJECTIVE: We sought to evaluate the prerequisites (demand, interest, feasibility) for adapting a paediatric nighttime telemedicine and medication delivery service (TMDS) to Ghana. METHODS: A cross-sectional survey of households and associated healthcare providers was conducted in urban and rural Ghana. Households were identified through randomised geospatial sampling; households with at least one child <10 years were enrolled. Household surveys collected information relating to demographics, household resources, standardised case scenarios, recent paediatric health events, satisfaction with healthcare access, and interest in TMDS intervention models. Providers were identified by households and enrolled. Provider surveys collected provider type, hours of operation, services, and opinions of a TMDS model. RESULTS: A total of 511 (263 urban, 248 rural) households and 18 providers (10 urban, 8 rural) were surveyed. A total of 262 health events involving children <10 years were reported, of which 47% occurred at night. Care was sought for >70% of health events presenting at night; however, care-seeking was delayed until morning or later for >75% of these events; 54% of households expressed dissatisfaction with their current access to paediatric care at night; 99% of households expressed that a nighttime TMDS service for children would be directly useful to their families. Correspondingly, 17 of 18 providers stated that a TMDS was needed in their community; >99% of households had access to a cellular phone. All households expressed willingness to use their phones to call a TMDS and allow a TMDS provider into their homes at night. Willingness to pay and provider-recommended price points varied by setting. CONCLUSIONS: Prerequisites for adapting a TMDS to Ghana were met. A nighttime paediatric TMDS service was found to be needed, appealing, and feasible in Ghana. These data motivate the adaptation of a TMDS to urban and rural Ghana.

Toxigenic Vibrio cholerae evolution and establishment of reservoirs in aquatic ecosystems.

The spread of cholera in the midst of an epidemic is largely driven by direct transmission from person to person, although it is well-recognized that Vibrio cholerae is also capable of growth and long-term survival in aquatic ecosystems. While prior studies have shown that aquatic reservoirs are important in the persistence of the disease on the Indian subcontinent, an epidemiological view postulating that locally evolving environmental V. cholerae contributes to outbreaks outside Asia remains debated. The single-source introduction of toxigenic V. cholerae O1 in Haiti, one of the largest outbreaks occurring this century, with 812,586 suspected cases and 9,606 deaths reported through July 2018, provided a unique opportunity to evaluate the role of aquatic reservoirs and assess bacterial transmission dynamics across environmental boundaries. To this end, we investigated the phylogeography of both clinical and aquatic toxigenic V. cholerae O1 isolates and show robust evidence of the establishment of aquatic reservoirs as well as ongoing evolution of V. cholerae isolates from aquatic sites. Novel environmental lineages emerged from sequential population bottlenecks, carrying mutations potentially involved in adaptation to the aquatic ecosystem. Based on such empirical data, we developed a mixed-transmission dynamic model of V. cholerae, where aquatic reservoirs actively contribute to genetic diversification and epidemic emergence, which underscores the complexity of transmission pathways in epidemics and endemic settings and the need for long-term investments in cholera control at both human and environmental levels.

Development of a Monoclonal Antibody to a Vibriophage as a Proxy for Vibrio cholerae Detection.

Cholera is an acute watery, diarrheal disease that causes high rates of morbidity and mortality without treatment. Early detection of the etiologic agent of toxigenic Vibrio cholerae is important to mobilize treatment and mitigate outbreaks. Monoclonal antibody (mAb) based rapid diagnostic tests (RDTs) enable early detection in settings without laboratory capacity. However, the odds of an RDT testing positive are reduced by nearly 90% when the common virulent bacteriophage ICP1 is present. We hypothesize that adding a mAb for the common, and specific, virulent bacteriophage ICP1 as a proxy for V. cholerae to an RDT will increase diagnostic sensitivity when virulent ICP1 phage is present. In this study, we used an in-silico approach to identify immunogenic ICP1 protein targets that were conserved across disparate time periods and locations. Specificity of targets to cholera patients with known ICP1 was determined, and specific targets were used to produce mAbs in a murine model. Candidate mAbs to the head protein demonstrated specificity to ICP1 by Enzyme linked immunosorbent assay (ELISA) and an ICP1 phage neutralization assay. The limit of detection of the final mAb candidate for ICP1 phage particles spiked into cholera stool matrix was 8 × 105 PFU by Western blotting analysis. This mAb will be incorporated into a RDT prototype for evaluation in a future diagnostic study to test the guiding hypothesis behind this study.

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.

Psychosocial health of school-aged children during the initial COVID-19 safer-at-home school mandates in Florida: a cross-sectional study.

BACKGROUND: Given the emerging literature regarding the impacts of lockdown measures on mental health, this study aims to describe the psychosocial health of school-aged children and adolescents during the COVID-19 Safer-at-Home School mandates. METHODS: A cross-sectional study was conducted in April 2020 (n = 280) among K-12 students at a research school in North Central Florida. Bivariate analysis and logistic and multinomial logistic regression models were used to examine socio-demographic and knowledge, attitude, and practice (KAP) predictors of indicators of anxiety-related, depressive, and obsessive-compulsive disorder(OCD)-related symptoms. Outcomes (anxiety, OCD, and depressive related symptoms) were measured by indices generated based on reported symptoms associated with each psychosocial outcome. RESULTS: Loss of household income was associated with increased risk for all three index-based outcomes: depressive symptoms [aOR = 3.130, 95% CI = (1.41-6.97)], anxiety-related symptoms [aOR = 2.531, 95%CI = (1.154-5.551)], and OCD-related symptoms [aOR = 2.90, 95%CI = (1.32-6.36)]. Being female was associated with being at higher risk for depressive symptoms [aOR = 1.72, 95% CI = (1.02-2.93)], anxiety-related symptoms [aOR = 1.75, 95% CI = (1.04-2.97)], and OCD-related symptoms [aOR = 1.764, 95%CI = (1.027-3.028)]. Parental practices protective against COVID-19 were associated with children being at higher risk of depressive symptoms [aOR = 1.55, 95% CI = (1.04-2.31)]. Lower school level was associated with children being at higher risk of anxiety-related and OCD-related symptoms. CONCLUSIONS: As the COVID-19 pandemic continues, schools should prioritize mental health interventions that target younger, female students, and children of families with income loss. Limiting the spread of COVID-19 through school closure may exacerbate negative psychosocial health outcomes in children, thus school administrators should move quickly to target those at greatest risk.

Identification of Widespread Antibiotic Exposure in Patients With Cholera Correlates With Clinically Relevant Microbiota Changes.

BACKGROUND: A first step to combating antimicrobial resistance in enteric pathogens is to establish an objective assessment of antibiotic exposure. Our goal was to develop and evaluate a liquid chromatography-ion trap mass spectrometry (LC/MS) method to determine antibiotic exposure in patients with cholera. METHODS: A priority list for targeted LC/MS was generated from medication-vendor surveys in Bangladesh. A study of patients with and those without cholera was conducted to collect and analyze paired urine and stool samples. RESULTS: Among 845 patients, 11% (90) were Vibrio cholerae positive; among these 90 patients, analysis of stool specimens revealed ≥1 antibiotic in 86% and ≥2 antibiotics in 52%. Among 44 patients with cholera and paired urine and stool specimens, ≥1 antibiotic was detected in 98% and ≥2 antibiotics were detected in 84%, despite 55% self-reporting medication use. Compared with LC/MS, a low-cost antimicrobial detection bioassay lacked a sufficient negative predictive value (10%; 95% confidence interval, 6%-16%). Detection of guideline-recommended antibiotics in stool specimens did (for azithromycin; P = .040) and did not (for ciprofloxacin) correlate with V. cholerae suppression. A nonrecommended antibiotic (metronidazole) was associated with decreases in anaerobes (ie, Prevotella organisms; P < .001). CONCLUSION: These findings suggest that there may be no true negative control group when attempting to account for antibiotic exposure in settings like those in this study.

Qualitative Assessment of a Smartphone-Based Mobile Health Tool to Guide Diarrhea Management in Bangladesh.

Diarrheal diseases are a major cause of morbidity and mortality in children worldwide and a significant contributor to antimicrobial resistance. In the absence of laboratory diagnostics to establish diarrhea etiology, electronic clinical decision support tools can help physicians make informed treatment decisions for children with diarrhea. In Bangladesh, we assessed the feasibility and acceptability of an electronic Diarrhea Etiology Prediction algorithm (DEP tool) embedded into a rehydration calculator, which was designed to help physicians manage children with diarrhea, including decisions on antibiotic use. A team of Bangladeshi anthropologists conducted in-depth interviews with physicians (N = 13) in three public hospitals in Bangladesh about their experience using the tool in the context of a pilot trial. Physicians expressed positive opinions of the DEP tool. Participants perceived the tool to be simple and easy to use, with structured guidance on collecting and entering clinical data from patients. Significant strengths of the tool were as follows: standardization of protocol, efficiency of clinical decision-making, and improved clinical practice. Participants also noted barriers that might restrict the widespread impact of the tool, including physicians' reluctance to use an electronic tool for clinical decision-making, increasing work in overburdened healthcare settings, unavailability of a smartphone, and patients' preferences for antibiotics. We conclude that an electronic clinical decision support tool is a promising method for improving diarrheal management and antibiotic stewardship. Future directions include developing and implementing such a tool for informal healthcare physicians in low-resource settings, where families may first seek care for pediatric diarrhea.

Development and evaluation of a clinical guideline for a paediatric telemedicine service in a low-resource setting.

OBJECTIVE: To develop and evaluate a guideline for a paediatric telemedicine and medication delivery service (TMDS). METHODS: A clinical guideline for paediatric telemedicine was derived from the World Health (WHO) Organization Integrated Management of Childhood Illness (IMCI) Handbook. The guideline was deployed at a TMDS in Haiti and evaluated through a prospective cohort study; children ≤10 years were enrolled. For non-severe cases, paired virtual and in-person examinations were conducted at the call centre and household; severe cases were referred to the hospital. The performance of virtual examination components were evaluated by comparison with the paired in-person examination findings (reference). RESULTS: A total of 391 cases were enrolled. Among the 320 cases with paired examinations, no general WHO danger signs were identified during in-person examinations; 5 cases (2%) required hospital referral due to problem-specific danger signs or other reasons for escalation. Cohen's kappa for the virtual designation of mild cases was 0.78 (95% CI: 0.69 to 0.87). The sensitivity and specificity of a virtually reported fever were 91% (95% CI: 87% to 96%) and 69% (95% CI: 62% to 76%), respectively; the sensitivity and specificity of virtually reported 'fast breathing' were 47% (95% CI: 21% to 72%) and 89% (95% CI: 85% to 94%), respectively. Kappa for 'no' and 'some' dehydration indicated moderate congruence between virtual and in-person examinations (0.69; 95% CI: 0.41 to 0.98). At 10 days, 273 (95%) of the 287 cases reached by phone were better/recovered. CONCLUSION: Critical components of the virtual examination (triage, danger signs and dehydration assessment) performed well despite varied performance among the problem-specific components. The study and associated resources represents formative steps towards an evidence-based paediatric telemedicine guideline built on WHO clinical principles. In-person examinations for select cases were important to address limitations with virtual examinations and identify cases for escalation. TRIAL REGISTRATION NUMBER: NCT03943654.

Phage predation, disease severity and pathogen genetic diversity in cholera patients.

Despite an increasingly detailed picture of the molecular mechanisms of phage-bacterial interactions, we lack an understanding of how these interactions evolve and impact disease within patients. Here we report a year-long, nation-wide study of diarrheal disease patients in Bangladesh. Among cholera patients, we quantified Vibrio cholerae (prey) and its virulent phages (predators) using metagenomics and quantitative PCR, while accounting for antibiotic exposure using quantitative mass spectrometry. Virulent phage (ICP1) and antibiotics suppressed V. cholerae to varying degrees and were inversely associated with severe dehydration depending on resistance mechanisms. In the absence of anti-phage defenses, predation was 'effective,' with a high predator:prey ratio that correlated with increased genetic diversity among the prey. In the presence of anti-phage defenses, predation was 'ineffective,' with a lower predator:prey ratio that correlated with increased genetic diversity among the predators. Phage-bacteria coevolution within patients should therefore be considered in the deployment of phage-based therapies and diagnostics.

Identification, mapping, and self-reported practice patterns of village doctors in Sitakunda subdistrict, Bangladesh.

Background: Informally trained health care providers, such as village doctors in Bangladesh, are crucial in providing health care services to the rural poor in low- and middle-income countries. Despite being one of the primary vendors of antibiotics in rural Bangladesh, village doctors often have limited knowledge about appropriate antibiotic use, leading to varied and potentially inappropriate dispensing and treatment practices. In this study, we aimed to identify, map, and survey village doctors in the Sitakunda subdistrict of Bangladesh to understand their distribution, practice characteristics, clinical behaviours, access to technologies, and use of these technologies for clinical decision-making. Methods: Using a 'snowball' sampling method, we identified and mapped 411 village doctors, with 371 agreeing to complete a structured survey. Results: The median distance between a residential household and the closest village doctor practice was 0.37 km, and over half of the practices (51.2%) were within 100 m of the major highway. Village doctors were predominately male (98.7%), with a median age of 39. After completing village doctor training, 39.4% had completed an internship, with a median of 15 years of practice experience. Village doctors reported seeing a median of 84 patients per week, including a median of five paediatric diarrhoea cases per week. They stocked a range of antibiotics, with ciprofloxacin and metronidazole being the most prescribed for diarrhoea. Most had access to phones with an internet connection and used online resources for clinical decision-making and guidance. Conclusions: The findings provide insights into the characteristics and practices of village doctors and point to the potential for internet and phone-based interventions to improve patient care and reduce inappropriate antibiotic use in this health care provider group.

Phage predation, disease severity, and pathogen genetic diversity in cholera patients.

Despite an increasingly detailed picture of the molecular mechanisms of bacteriophage (phage)-bacterial interactions, we lack an understanding of how these interactions evolve and impact disease within patients. In this work, we report a year-long, nationwide study of diarrheal disease patients in Bangladesh. Among cholera patients, we quantified Vibrio cholerae (prey) and its virulent phages (predators) using metagenomics and quantitative polymerase chain reaction while accounting for antibiotic exposure using quantitative mass spectrometry. Virulent phage (ICP1) and antibiotics suppressed V. cholerae to varying degrees and were inversely associated with severe dehydration depending on resistance mechanisms. In the absence of antiphage defenses, predation was "effective," with a high predator:prey ratio that correlated with increased genetic diversity among the prey. In the presence of antiphage defenses, predation was "ineffective," with a lower predator:prey ratio that correlated with increased genetic diversity among the predators. Phage-bacteria coevolution within patients should therefore be considered in the deployment of phage-based therapies and diagnostics.

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.

Derivation and external validation of clinical prediction rules identifying children at risk of linear growth faltering.

Background: Nearly 150 million children under-5 years of age were stunted in 2020. We aimed to develop a clinical prediction rule (CPR) to identify children likely to experience additional stunting following acute diarrhea, to enable targeted approaches to prevent this irreversible outcome. Methods: We used clinical and demographic data from the Global Enteric Multicenter Study (GEMS) to build predictive models of linear growth faltering (decrease of ≥0.5 or ≥1.0 in height-for-age z-score [HAZ] at 60-day follow-up) in children ≤59 months presenting with moderate-to-severe diarrhea, and community controls, in Africa and Asia. We screened variables using random forests, and assessed predictive performance with random forest regression and logistic regression using fivefold cross-validation. We used the Etiology, Risk Factors, and Interactions of Enteric Infections and Malnutrition and the Consequences for Child Health and Development (MAL-ED) study to (1) re-derive, and (2) externally validate our GEMS-derived CPR. Results: Of 7639 children in GEMS, 1744 (22.8%) experienced severe growth faltering (≥0.5 decrease in HAZ). In MAL-ED, we analyzed 5683 diarrhea episodes from 1322 children, of which 961 (16.9%) episodes experienced severe growth faltering. Top predictors of growth faltering in GEMS were: age, HAZ at enrollment, respiratory rate, temperature, and number of people living in the household. The maximum area under the curve (AUC) was 0.75 (95% confidence interval [CI]: 0.75, 0.75) with 20 predictors, while 2 predictors yielded an AUC of 0.71 (95% CI: 0.71, 0.72). Results were similar in the MAL-ED re-derivation. A 2-variable CPR derived from children 0-23 months in GEMS had an AUC = 0.63 (95% CI: 0.62, 0.65), and AUC = 0.68 (95% CI: 0.63, 0.74) when externally validated in MAL-ED. Conclusions: Our findings indicate that use of prediction rules could help identify children at risk of poor outcomes after an episode of diarrheal illness. They may also be generalizable to all children, regardless of diarrhea status. Funding: This work was supported by the National Institutes of Health under Ruth L. Kirschstein National Research Service Award NIH T32AI055434 and by the National Institute of Allergy and Infectious Diseases (R01AI135114).

Derivation and external validation of a clinical prognostic model identifying children at risk of death following presentation for diarrheal care.

Diarrhea continues to be a leading cause of death for children under-five. Amongst children treated for acute diarrhea, mortality risk remains elevated during and after acute medical management. Identification of those at highest risk would enable better targeting of interventions, but available prognostic tools lack validation. We used clinical and demographic data from the Global Enteric Multicenter Study (GEMS) to build predictive models for death (in-treatment, after discharge, or either) in children aged ≤59 months presenting with moderate-to-severe diarrhea (MSD), in Africa and Asia. We screened variables using random forests, and assessed predictive performance with random forest regression and logistic regression using repeated cross-validation. We used data from the Kilifi Health and Demographic Surveillance System (KHDSS) and Kilifi County Hospital (KCH) in Kenya to externally validate our GEMS-derived clinical prognostic model (CPM). Of 8060 MSD cases, 43 (0.5%) children died in treatment and 122 (1.5% of remaining) died after discharge. MUAC at presentation, respiratory rate, age, temperature, number of days with diarrhea at presentation, number of people living in household, number of children <60 months old living in household, and how much the child had been offered to drink since diarrhea started were predictive of death both in treatment and after discharge. Using a parsimonious 2-variable prediction model, we achieve an AUC=0.84 (95% CI: 0.82, 0.86) in the derivation dataset, and an AUC=0.74 (95% CI 0.71, 0.77) in the external dataset. Our findings suggest it is possible to identify children most likely to die after presenting to care for acute diarrhea. This could represent a novel and cost-effective way to target resources for the prevention of childhood mortality.

Derivation and external validation of a clinical prognostic model identifying children at risk of death following presentation for diarrheal care.

Diarrhea continues to be a leading cause of death for children under-five. Amongst children treated for acute diarrhea, mortality risk remains elevated during and after acute medical management. Identification of those at highest risk would enable better targeting of interventions, but available prognostic tools lack validation. We used clinical and demographic data from the Global Enteric Multicenter Study (GEMS) to build clinical prognostic models (CPMs) to predict death (in-treatment, after discharge, or either) in children aged ≤59 months presenting with moderate-to-severe diarrhea (MSD), in Africa and Asia. We screened variables using random forests, and assessed predictive performance with random forest regression and logistic regression using repeated cross-validation. We used data from the Kilifi Health and Demographic Surveillance System (KHDSS) and Kilifi County Hospital (KCH) in Kenya to externally validate our GEMS-derived CPM. Of 8060 MSD cases, 43 (0.5%) children died in treatment and 122 (1.5% of remaining) died after discharge. MUAC at presentation, respiratory rate, age, temperature, number of days with diarrhea at presentation, number of people living in household, number of children <60 months old living in household, and how much the child had been offered to drink since diarrhea started were predictive of death both in treatment and after discharge. Using a parsimonious 2-variable prediction model, we achieved an area under the ROC curve (AUC) of 0.84 (95% CI: 0.82, 0.86) in the derivation dataset, and an AUC = 0.74 (95% CI 0.71, 0.77) in the external dataset. Our findings suggest it is possible to identify children most likely to die after presenting to care for acute diarrhea. This could represent a novel and cost-effective way to target resources for the prevention of childhood mortality.