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To determine whether gut permeability is associated with post-discharge growth and systemic inflammation among hospitalized children in low- and middle-income countries.Children aged 2-23 months being discharged from Civil Hospital Karachi (Pakistan) and Migori County Referral Hospital (Kenya) underwent lactulose-rhamnose ratio (LRR) permeability testing and were compared to age-matched children from their home communities. Linear mixed effect models estimated the associations between LRR among discharged children with change in length-for-age (LAZ) and weight-for-age z score (WAZ) at 45, 90, and 180 days after discharge. Linear regression tested if relationships between LRR, systemic inflammation [C-reative protein (CRP), Cluster of Differentiation 14 (CD14), Tumour Necrosis Factor Alpha (TNFα), Interleukin-6 (IL-6)], and enterocyte damage [Intestinal Fatty-Acid Binding protein (I-FABP)] differed between the hospitalized and community groups.One hundred thirty-seven hospitalized and 84 community participants were included. The hospitalized group had higher log-LRR [0.43, 95% confidence interval (CI): 0.15-0.71, P = 0.003] than the community children. Adjustment for weight-for-length z score at discharge attenuated this association (0.31, 95% CI: 0.00-0.62, P = 0.049). LRR was not associated with changes in WAZ or LAZ in the post-discharge period. Associations between LRR and CRP (interaction P = 0.036), TNFα ( P = 0.017), CD14 ( P = 0.078), and IL-6 ( P = 0.243) differed between community and hospitalized groups. LRR was associated with TNFα ( P = 0.004) and approached significance with CD14 ( P = 0.078) and IL-6 ( P = 0.062) in community children, but there was no evidence of these associations among hospitalized children.Although increased enteric permeability is more prevalent among children being discharged from hospital compared to children in the community, it does not appear to be an important determinant of systemic inflammation or post-discharge growth among hospitalized children.

BackgroundHospital-acquired infections (HAIs) represent the most prevalent adverse event among patients in hospital settings. Contamination with pathogenic bacteria that are highly resistant in the hospital environment increases the risk of HAIs.ObjectiveThe antimicrobial resistance (AMR) patterns of hospital contaminants isolated from highly frequented surfaces in a tertiary hospital in Kenya.MethodsA total of 62 swabs were collected from selected surfaces, equipment, and health workers’ palms in April 2020. They were cultured and bacterial contaminants were identified using standard microbiological procedures and their AMR patterns were determined using recommended laboratory assays.ResultsOf the 62 swabs collected, 61.3% (n=38) yielded bacterial growth, from which 46 bacteria were isolated. Swab positivity varied across the departments as follows: gynecology wards (78.6%), New Born Unit (NBU) (56.2%), Pediatric ward (61.9%), and Renal Unit (45.5%). Gram negative species comprised 86.96%(n=40) while Gram positive species comprised 13.04%(n=6). Of all the 46 isolates obtained, 36.96% (n=17) were positive for the resistance markers screened. Specifically, 10.9% (n=5) showed both extended-spectrum beta-lactamases (ESBL)and carbapenem-resistant (CR) resistance, while 23.9%(n=11) were positive for ESBL production. The rest were non-resistant strains as shown by negative ESBL at 47.8% (n=22), methicillin sensitivity at 13% (n=6) and vancomycin sensitivity at 2.2% (n=1).Acinetobacterspecies which were most reported, had the highest resistance (36.84% (7/19).ConclusionThere was a high prevalence of contamination with resistant pathogenic bacteria species.Acinetobacterspecies were the most common pathogen. Interventions are needed to mitigate the problem of resistant HAI.

Background: Poor maternal mental health during childhood hospitalization is associated with post-discharge child mortality. We aimed to establish if maternal PHQ-9 scores during hospitalization are associated with acute stressors or longer trends in mental health status. Method: Mothers of children admitted to nine hospitals in six countries completed a PHQ-9 assessment during hospitalization and 45-days post-discharge. Community participants were recruited from homes near the hospitalized children. The prevalence and correlates of high PHQ-9 scores among hospitalized and community mothers were compared. Outcomes: Among 2762 mothers of hospitalized children, 514 (19 %) had PHQ-9 scores ≥10, significantly more than the 116 (10 %, p < 0·001) of 1159 community participants. Recruitment site and food insecurity were PHQ-9 correlates in both groups. Correlates of higher mean PHQ-9 scores among the hospitalized cohort included maternal illness (mean difference [MD]: 1·27, 95%CI: 0·77, 1·77), pregnancy (MD: 0·77, 95%CI: 0·27, 1·28), child HIV-infection (MD: 2·51. 95%CI: 1·55, 3·52), and lower child weight-for-height (MD: 0·21, 95%CI: 0·32, 0·11). Marriage (MD −0·92, 95%CI: −1·36, −0·48) and a positive malaria test (MD: −0·63, 95%CI: −1·15, −0·10) were associated with lower PHQ-9 scores among mothers of hospitalized children. Among mothers with PHQ-9 ≥10 during admission, 410 had repeat assessments 45-days after their child's discharge, and 108 (26 %) continued to meet the high PHQ-9 criterion. Interpretation: Among mothers of hospitalized children, there are subgroups with transient and persistent depressive symptoms. Interventions tailored to address acute stressors may improve post-discharge pediatric and maternal health outcomes. Funding: Bill & Melinda Gates Foundation OPP1131320.

Background: A better understanding of which children are likely to die during acute illness will help clinicians and policy makers target resources at the most vulnerable children. We used machine learning to characterise mortality in the 30-days following admission and the 180-days after discharge from nine hospitals in low and middle-income countries (LMIC). Methods: A cohort of 3101 children aged 2–24 months were recruited at admission to hospital for any acute illness in Bangladesh (Dhaka and Matlab Hospitals), Pakistan (Civil Hospital Karachi), Kenya (Kilifi, Mbagathi, and Migori Hospitals), Uganda (Mulago Hospital), Malawi (Queen Elizabeth Central Hospital), and Burkina Faso (Banfora Hospital) from November 2016 to January 2019. To record mortality, children were observed during their hospitalisation and for 180 days post-discharge. Extreme gradient boosted models of death within 30 days of admission and mortality in the 180 days following discharge were built. Clusters of mortality sharing similar characteristics were identified from the models using Shapley additive values with spectral clustering. Findings: Anthropometric and laboratory parameters were the most influential predictors of both 30-day and post-discharge mortality. No WHO/IMCI syndromes were among the 25 most influential mortality predictors of mortality. For 30-day mortality, two lower-risk clusters (N = 1915, 61%) included children with higher-than-average anthropometry (1% died, 95% CI: 0–2), and children without signs of severe illness (3% died, 95% CI: 2–4%). The two highest risk 30-day mortality clusters (N = 118, 4%) were characterised by high urea and creatinine (70% died, 95% CI: 62–82%); and nutritional oedema with low platelets and reduced consciousness (97% died, 95% CI: 92–100%). For post-discharge mortality risk, two low-risk clusters (N = 1753, 61%) were defined by higher-than-average anthropometry (0% died, 95% CI: 0–1%), and gastroenteritis with lower-than-average anthropometry and without major laboratory abnormalities (0% died, 95% CI: 0–1%). Two highest risk post-discharge clusters (N = 267, 9%) included children leaving against medical advice (30% died, 95% CI: 25–37%), and severely-low anthropometry with signs of illness at discharge (46% died, 95% CI: 34–62%). Interpretation: WHO clinical syndromes are not sufficient at predicting risk. Integrating basic laboratory features such as urea, creatinine, red blood cell, lymphocyte and platelet counts into guidelines may strengthen efforts to identify high-risk children during paediatric hospitalisations. Funding: Bill & Melinda Gates Foundation OPP1131320.

Background Mortality among children with acute illness in low-income and middle-income settings remains unacceptably high and the importance of post-discharge mortality is increasingly recognised. We aimed to explore the epidemiology of deaths among young children with acute illness across sub-Saharan Africa and south Asia to inform the development of interventions and improved guidelines. Methods In this prospective cohort study, we enrolled children aged 2–23 months with acute illness, stratified by nutritional status defined by anthropometry (ie, no wasting, moderate wasting, or severe wasting or kwashiorkor), who were admitted to one of nine hospitals in six countries across sub-Saharan Africa and south Asia between Nov 20, 2016, and Jan 31, 2019. We assisted sites to comply with national guidelines. Co-primary outcomes were mortality within 30 days of hospital admission and post-discharge mortality within 180 days of hospital discharge. A priori exposure domains, including demographic, clinical, and anthropometric characteristics at hospital admission and discharge, as well as child, caregiver, and household-level characteristics, were examined in regression and survival structural equation models. Findings Of 3101 children (median age 11 months [IQR 7–16]), 1120 (36·1%) had no wasting, 763 (24·6%) had moderate wasting, and 1218 (39·3%) had severe wasting or kwashiorkor. Of 350 (11·3%) deaths overall, 234 (66·9%) occurred within 30 days of hospital admission and 168 (48·0%) within 180 days of hospital discharge. 90 (53·6%) post-discharge deaths occurred at home. The proportion of children who died following discharge was relatively preserved across nutritional strata. Numerically large high-risk and low-risk groups could be disaggregated for early mortality and post-discharge mortality. Structural equation models identified direct pathways to mortality and multiple socioeconomic, clinical, and nutritional domains acting indirectly through anthropometric status. Interpretation Among diverse sites in Africa and south Asia, almost half of mortality occurs following hospital discharge. Despite being highly predictable, these deaths are not addressed in current guidelines. A fundamental shift to a child-centred, risk-based approach to inpatient and post-discharge management is needed to further reduce childhood mortality, and clinical trials of these approaches with outcomes of mortality, readmission, and cost are warranted.

Background: The increasing spread of fluoroquinolone resistant enteric bacteria is a global public health concern. Children recently discharged from the hospital are at high risk of carriage of antimicrobial resistance (AMR) due to frequent exposure to antimicrobials during inpatient stays. This study aimed to determine the prevalence, correlates of ciprofloxacin non-susceptibility, and distribution of plasmid-mediated quinolone resistance (PMQR) genes in Escherichia coli (E. coli) and Klebsiella spp isolated from children under five years being discharged from two Kenyan Hospitals. Methods: E. coli and Klebsiella spp were isolated from fecal samples from children discharged from hospital and subjected to antimicrobial susceptibility testing by disc diffusion and E-test. Ciprofloxacin non-susceptible isolates were screened for seven PMQR genes using multiplex PCR. Poisson regression was used to determine the association between carriage of ciprofloxacin non-susceptible isolates and patient characteristics. Results: Of the 280 ciprofloxacin non-susceptible isolates: 188 E. coli and 92 Klebsiella spp isolates identified among 266 discharged children, 195 (68%) were ciprofloxacin-resistant (MIC ≥ 1µg/mL). Among these 195 isolates, 130 (67%) had high level ciprofloxacin minimum inhibitory concentrations (MICs) (≥32 µg/mL). Over 80% of the isolates had at least one PMQR gene identified: aac(6’)lb-cr (60%), qnrB (24%), oqxAB (22%), qnrS (16%), and qepA (6%), howeverqnrA was not identified in any isolates tested. Co-carriage of qnrB with acc(6’)-lb-cr was the most predominant accounting for 20% of all the isolates. Ceftriaxone use during hospital admission and the presence of ESBL production were significantly associated with the carriage of ciprofloxacin non-susceptible E. coli and Klebsiella spp. Conclusion: Ciprofloxacin non-susceptibility is common among E. coli and Klebsiella spp isolated from hospital discharged children in Kenya. Carriage and co-carriage of PMQR, including the newly identified qepA gene, were frequently observed. These findings suggest that children leaving the hospital may serve as an important reservoir for transmission of resistant E. coli and Klebsiella spp to the community. Enhanced surveillance for AMR determinants is critical to inform interventions to control antimicrobial-resistant bacteria.

Summary Background Mass drug administration of azithromycin to children in sub-Saharan Africa has been shown to improve survival in high-mortality settings. The period after hospital discharge is a time of elevated risk unaddressed by current interventions and might provide an opportunity for targeting empirical azithromycin administration. We aimed to assess the efficacy of azithromycin administered at hospital discharge on risk of death and rehospitalisation in Kenyan children younger than 5 years. Methods In this double-blind, placebo-controlled randomised trial, children were randomly assigned (1:1) to receive a 5-day course of azithromycin (oral suspension 10 mg/kg on day 1, followed by 5mg/kg per day on days 2–5) or identically appearing and tasting placebo at discharge from four hospitals in western Kenya. Children were eligible if they were aged 1–59 months at hospital discharge, weighed at least 2 kg, and had been admitted to hospital for any medical reason other than trauma, poisoning, or congenital anomaly. The primary outcome was death or rehospitalisation in the subsequent 6-month period in a modified intention-to-treat population, compared by randomisation group with Cox proportional hazards regression and Kaplan-Meier. Azithromycin resistance in Escherichia coli isolates from a random subset of children was compared by randomisation group with generalised estimating equations. This trial is registered with ClinicalTrials.gov , NCT02414399 . Findings Between June 28, 2016, and Nov 4, 2019, 1400 children were enrolled in the trial at discharge from hospital, with 703 (50·2%) randomly assigned to azithromycin and 697 (49·8%) to placebo. Among the 1398 children included in the modified intention-to-treat analysis (702 in the azithromycin group and 696 in the placebo group), the incidence of death or rehospitalisation was 20·4 per 100 child-years in the azithromycin group and 22·5 per 100 child-years in the placebo group (adjusted hazard ratio 0·91, 95·5% CI 0·64–1·29, p=0·58). Azithromycin resistance was common in commensal E coli isolates from enrolled children before randomisation (37·7% of 406 isolates) despite only 3·7% of children having received a macrolide antibiotic during the hospitalisation. Azithromycin resistance was slightly higher at 3 months after randomisation in the azithromycin group (26·9%) than in the placebo group (19·1%; adjusted prevalence ratio 1·41, 95% CI 0·95–2·09, p=0·088), with no difference observed at 6 months (1·17, 0·78–1·76, p=0·44). Interpretation We did not observe a significant benefit of a 5-day course of azithromycin delivered to children younger than 5 years at hospital discharge despite the overall high risk of mortality and rehospitalisation. These findings highlight the need for more research into mechanisms and interventions for prevention of morbidity and mortality in the post-discharge period. Funding Eunice Kennedy Shriver National Institute of Child Health & Human Development.

Background: Current guidelines for the management of childhood wasting primarily focus on the provision of therapeutic foods and the treatment of medical complications. However, many children with wasting live in food-secure households, and multiple studies have demonstrated that the etiology of wasting is complex, including social, nutritional, and biological causes. We evaluated the contribution of household food insecurity, dietary diversity, and the consumption of specific food groups to the time to recovery from wasting after hospital discharge. Methods: We conducted a secondary analysis of the Childhood Acute Illness Network (CHAIN) cohort, a multicenter prospective study conducted in six low- or lower-middle-income countries. We included children aged 6–23 months with wasting (mid-upper arm circumference [MUAC] ≤ 12.5 cm) or kwashiorkor (bipedal edema) at the time of hospital discharge. The primary outcome was time to nutritional recovery, defined as a MUAC > 12.5 cm without edema. Using Cox proportional hazards models adjusted for age, sex, study site, HIV status, duration of hospitalization, enrollment MUAC, referral to a nutritional program, caregiver education, caregiver depression, the season of enrollment, residence, and household wealth status, we evaluated the role of reported food insecurity, dietary diversity, and specific food groups prior to hospitalization on time to recovery from wasting during the 6 months of posthospital discharge. Findings: Of 1286 included children, most participants (806, 63%) came from food-insecure households, including 170 (13%) with severe food insecurity, and 664 (52%) participants had insufficient dietary diversity. The median time to recovery was 96 days (18/100 child-months (95% CI: 17.0, 19.0)). Moderate (aHR 1.17 [0.96, 1.43]) and severe food insecurity (aHR 1.14 [0.88, 1.48]), and insufficient dietary diversity (aHR 1.07 [0.91, 1.25]) were not significantly associated with time to recovery. Children who had consumed legumes and nuts prior to diagnosis had a quicker recovery than those who did not (adjusted hazard ratio (aHR): 1.21 [1.01,1.44]). Consumption of dairy products (aHR 1.13 [0.96, 1.34], p = 0.14) and meat (aHR 1.11 [0.93, 1.33]), p = 0.23) were not statistically significantly associated with time to recovery. Consumption of fruits and vegetables (aHR 0.78 [0.65,0.94]) and breastfeeding (aHR 0.84 [0.71, 0.99]) before diagnosis were associated with longer time to recovery. Conclusion: Among wasted children discharged from hospital and managed in compliance with wasting guidelines, food insecurity and dietary diversity were not major determinants of recovery.

Background Shigella is a leading cause of childhood diarrhea and target for vaccine development. Microbiologic and clinical case definitions are needed for pediatric field vaccine efficacy trials. Methods We compared characteristics of moderate to severe diarrhea (MSD) cases in the Global Enteric Multicenter Study (GEMS) between children with culture positive Shigella to those with culture-negative, quantitative polymerase chain reaction (qPCR)-attributable Shigella (defined by an ipaH gene cycle threshold, Molecular methods identified Shigella more commonly than microbiologic culture in younger and stunted children. A simplified clinical score containing dehydration, hospitalization, and diarrhea duration could be used to stratify vaccine trial endpoints by severity based on its ability to predict death.

Summary: Background: Host vulnerabilities associated with acute malnutrition could facilitate the ability of specific enteric pathogens to cause diarrhoea and associated mortality. Using data from the Global Enteric Multicenter Study, we assessed whether acute malnutrition modifies the association between common enteric pathogens and moderate-to-severe diarrhoea, and whether associations between enteric pathogens and death were modified by acute malnutrition. Methods: Children with moderate-to-severe diarrhoea and age-matched and community-matched controls were included in this post-hoc analysis if their mid-upper arm circumference had been measured and if they were older than 6 months of age. Acute malnutrition was defined as mid-upper arm circumference below 12·5 cm, capturing both severe acute malnutrition (

Background Cytomegalovirus (CMV) viremia is associated with mortality in severely ill immunocompetent adults and hospitalized children with HIV (CWH). We measured CMV viremia in HIV-exposed and -unexposed Kenyan children aged 1–59 months discharged from hospital and determined its relationship with postdischarge mortality. Methods CMV DNA levels were measured in plasma from 1024 children (97 of which were HIV exposed uninfected [HEU], and 15 CWH). Poisson and Cox proportional hazards regression models were used to identify correlates of CMV viremia ≥ 1000 IU/mL and estimate associations with 6-month mortality, respectively. Results CMV viremia was detected in 31% of children, with levels ≥ 1000 IU/mL in 5.8%. HIV infection, age < 2 years, breastfeeding, and midupper arm circumference < 12.5 cm were associated with CMV viremia ≥ 1000 IU/mL. Among HEU children, CMV ≥ 1000 IU/mL (hazard ratio [HR] = 32.0; 95% confidence interval [CI], 2.9–354.0; P = .005) and each 1-log increase in CMV viral load (HR = 5.04; 95% CI, 1.7–14.6; P = .003) were associated with increased risk of mortality. CMV viremia was not significantly associated with mortality in HIV-unexposed children. Conclusions CMV levels at hospital postdischarge predict increased risk of 6-month mortality in Kenyan HEU children. CMV suppression may be a novel target to reduce mortality in HEU children. Clinical Trial Registration NCT02414399.

Human subjects research protections have historically focused on mitigating risk of harm and promoting benefits for research participants. In many low-resource settings (LRS), complex and often severe challenges in daily living, poverty, geopolitical uprisings, sociopolitical, economic, and climate crises increase the burdens of even minimal risk research. While there has been important work to explore the scope of ethical responsibilities of researchers and research teams to respond to these wider challenges and hidden burdens in global health research, less attention has been given to the ethical dilemmas and risk experienced by frontline researcher staff as they perform research-related activities in LRS. Risks such as job insecurity, moral distress, infection, or physical harm can be exacerbated during public health crises, as recently highlighted by the COVID-19 pandemic. We highlight the layers of risk research staff face in LRS and present a conceptual model to characterize drivers of this risk, with particular attention to public health crises. A framework by which funders, institutions, principal investigators, and/or research team leaders can systematically consider these additional layers of risk to researchers and frontline staff is an important and needed addition to routine research proposals and protocol review.

ObjectivesMortality during acute illness among children in low- and middle-income settings remain unacceptably high and there is increasing recognition of the importance of post-discharge mortality. A comprehensive understanding of pathways underlying mortality among acutely ill children is needed to develop interventions and improve guidelines. We aimed to determine the incidence, timing and contributions of proximal and underlying exposures for mortality among acutely ill young children from admission to hospital until 6 months after discharge in sub-Saharan Africa and South Asia in the context of guideline-based care.DesignA prospective stratified cohort study recruiting acutely ill children at admission to hospital with follow up until 180 days after discharge from hospital (November 2016-July 2019).SettingNine urban and rural hospitals in sub-Saharan Africa and South Asia across a range of facility levels, and local prevalences of HIV and malaria.ParticipantsInclusion criteria were age 2-23 months, admission to hospital with acute, non-traumatic medical illness and stratified into three groups by anthropometry. Children were excluded if currently receiving pulmonary resuscitation, had a known condition requiring surgery within 6 months or known terminal illness with death expected within 6 months.Main outcome measuresAcute mortality occurring within 30-days from admission; post-discharge mortality within 180-days from discharge; characteristics with direct and indirect associations with mortality within a multi-level a priori framework including demographic, clinical, anthropometric characteristics at admission and discharge from hospital, and pre-existing child-, caregiver- and household-level characteristics.ResultsOf 3101 participants (median age 11 months), 1218 were severely wasted/kwashiorkor, 763 moderately wasted and 1120 were not wasted. Of 350 deaths, 182 (52%) occurred during index admission, 234 (67%) within 30-days of admission and 168 (48%) within 180-days post-discharge. Ninety (54%) post-discharge deaths occurred at home. The ratio of inpatient to post-discharge mortality was consistent across anthropometric strata and sites. Large high and low risk groups could be disaggregated for both early and post-discharge mortality. Structural equation models identified direct pathways to mortality and multiple socioeconomic, clinical and nutritional domains acting indirectly through anthropometric status.ConclusionsAmong diverse sites in Africa and South Asia, almost half of mortality occurs post-discharge. Despite being highly predictable, these deaths are not addressed in current guidelines. A fundamental shift to a risk-based approach to inpatient and post-discharge management is needed to further reduce childhood mortality and clinical trials of these approaches with outcomes of mortality, readmission and cost are warranted.Trial RegistrationClinicalTrials.gov: NCT03208725

Objective The purpose of this study was to assess the distribution of HIV-program staff and the extent to which their availability influences HIV programmatic and patient outcomes. Methods The study was a facility level cross-sectional survey. Data from October 2018 to September 2019 were abstracted from HIV program reports conducted in 18 districts of Côte d’Ivoire. The distribution of staff in clinical, laboratory, pharmacy, management, lay, and support cadres were described across high and low antiretroviral therapy (ART) volume facilities. Non-parametric regression was used to estimate the effects of cadre categories on the number of new HIV cases identified, the number of cases initiated on ART, and the proportion of patients achieving viral load suppression. Results Data from 49,871 patients treated at 216 health facilities were included. Low ART volume facilities had a median of 8.1 staff-per-100 ART patients, significantly higher than the 4.4 staff-per-100 ART patients at high-ART volume facilities. One additional laboratory staff member was associated with 4.30 (IQR: 2.00–7.48, p p p p Conclusions HCWs in the laboratory and lay cadre categories were associated with an increase in HIV-positive case identification and initiation on ART. Our findings suggest that allocation of HCWs across health facilities should take into consideration the ART patient volume. Overall, increasing investment in health workforce is critical to achieve national HIV goals and reaching HIV epidemic control.

Background Environmental enteric dysfunction (EED) is an acquired enteropathy of the small intestine, characterized by enteric inflammation, villus blunting and decreased crypt-to-villus ratio. EED has been associated with poor outcomes, including chronic malnutrition (stunting), wasting and reduced vaccine efficacy among children living in low-resource settings. As a result, EED may be a valuable interventional target for programs aiming to reduce childhood morbidity in low and middle-income countries. Main text Several highly plausible mechanisms link the proposed pathophysiology underlying EED to adverse outcomes, but causal attribution of these pathways has proved challenging. We provide an overview of recent studies evaluating the causes and consequences of EED. These include studies of the role of subclinical enteric infection as a primary cause of EED, and efforts to understand how EED-associated systemic inflammation and malabsorption may result in long-term morbidity. Finally, we outline recently completed and upcoming clinical trials that test novel interventions to prevent or treat this highly prevalent condition. Conclusions Significant strides have been made in linking environmental exposure to enteric pathogens and toxins with EED, and in understanding the multifactorial mechanisms underlying this complex condition. Further insights may come from several ongoing and upcoming interventional studies trialing a variety of novel management strategies.

Background Intestinal disorders such as environmental enteric dysfunction (EED) are prevalent in low- and middle-income countries (LMICs) and important contributors to childhood undernutrition and mortality. Autopsies are rarely performed in LMICs but minimally invasive tissue sampling is increasingly deployed as a more feasible and acceptable procedure, although protocols have been devoid of intestinal sampling to date. We sought to determine (1) the feasibility of postmortem intestinal sampling, (2) whether autolysis precludes enteric biopsies’ utility, and (3) histopathologic features among children who died during hospitalization with acute illness or undernutrition. Methods Transabdominal needle and endoscopic forceps upper and lower intestinal sampling were conducted among children aged 1 week to 59 months who died while hospitalized in Blantyre, Malawi. Autolysis ratings were determined for each hematoxylin and eosin slide, and upper and lower intestinal scoring systems were adapted to assess histopathologic features and their severity. Results Endoscopic and transabdominal sampling procedures were attempted in 28 and 14 cases, respectively, with >90% success obtaining targeted tissue. Varying degrees of autolysis were present in all samples and precluded histopathologic scoring of 6% of 122 biopsies. Greater autolysis in duodenal samples was seen with longer postmortem interval (Beta = 0.06, 95% confidence interval, 0.02–0.11). Histopathologic features identified included duodenal Paneth and goblet cell depletion. Acute inflammation was absent but chronic inflammation was prevalent in both upper and lower enteric samples. Severe chronic rectal inflammation was identified in children as young as 5.5 weeks. Conclusions Minimally invasive postmortem intestinal sampling is feasible and identifies histopathology that can inform mortality contributors.

Objective To assess attitudes, perceptions, and practices of healthcare workers regarding hospital discharge and follow-up care for children under age five in Migori and Homa Bay, Kenya. Methods This mixed-methods study included surveys and semi-structured telephone interviews with healthcare workers delivering inpatient pediatric care at eight hospitals between November 2017 and December 2018. Results The survey was completed by 111 (85%) eligible HCWs. Ninety-seven of the surveyed HCWs were invited for interviews and 39 (40%) participated. Discharge tasks were reported to be “very important” to patient outcomes by over 80% of respondents, but only 37 (33%) perceived their hospital to deliver this care “very well” and 23 (21%) believed their facility provides sufficient resources for its provision. The vast majority (97%) of participants underestimated the risk of pediatric post-discharge mortality. Inadequate training, understaffing, stock-outs of take-home therapeutics, and user fees were commonly reported health systems barriers to adequate discharge care while poverty was seen as limiting caregiver adherence to discharge and follow-up care. Respondents endorsed the importance of follow-up care, but reported supportive mechanisms to be lacking. They requested enhanced guidelines on discharge and follow-up care. Conclusion Kenyan healthcare workers substantially underestimated the risk of pediatric post-discharge mortality. Pre- and in-service training should incorporate instruction on discharge and follow-up care. Improved post-discharge deaths tracking–e.g., through vital registry systems, child mortality surveillance studies, and community health worker feedback loops–is needed, alongside dissemination which could leverage platforms such as routine hospital-based mortality reports. Finally, further interventional trials are needed to assess the efficacy and cost-effectiveness of novel packages to improve discharge and follow-up care.

IntroductionOver 52 million children under 5 years of age become wasted each year, but only 17% of these children receive treatment. Novel methods to identify and deliver treatment to malnourished children are necessary to achieve the sustainable development goals target for child health. Mobile health (mHealth) programmes may provide an opportunity to rapidly identify malnourished children in the community and link them to care.Methods and analysisThis randomised controlled trial will recruit 1200 children aged 6–12 months at routine vaccine appointments in Migori and Homa Bay Counties, Kenya. Caregiver–infant dyads will be randomised to either a maternally administered malnutrition monitoring system (MAMMS) or standard of care (SOC). Study staff will train all caregivers to measure their child’s mid-upper arm circumference (MUAC). Caregivers in the MAMMS arm will be given two colour coded and graduated insertion MUAC tapes and be enrolled in a mHealth system that sends weekly short message service (SMS) messages prompting caregivers to measure and report their child’s MUAC by SMS. Caregivers in the SOC arm will receive routine monitoring by community health volunteers coupled with a quarterly visit from study staff to ensure adequate screening coverage. The primary outcome is identification of childhood malnutrition, defined as MUAC Ethics and disseminationThe study was approved by review boards at the University of Washington and the Kenya Medical Research Institute. A data and safety monitoring board has been convened, and the results of the trial will be published in peer-reviewed scientific journals, presented at appropriate conferences and to key stakeholders.Trial registration numberNCT03967015.

To understand how the World Health Organization's (WHO's) guidelines on the inpatient care of children with complicated severe acute malnutrition may be strengthened to improve outcomes.In December 2015, we searched Google scholar and WHO's website for WHO recommendations on severe acute malnutrition management and evaluated the history and cited evidence behind these recommendations. We systematically searched WHO International Clinical Trials Registry Platform, clinicaltrials.gov and the Controlled Trials metaRegister until 10 August 2015 for recently completed, ongoing, or pending trials.WHO's guidelines provide 33 recommendations on the topic. However, 16 (48.5%) of these recommendations were based solely on expert opinion - unsupported by published evidence. Another 11 (33.3%) of the recommendations were supported by the results of directly relevant research - i.e. either randomized trials (8) or observational studies (3). The other six recommendations (18.2%) were based on studies that were not conducted among children with complicated severe malnutrition or studies of treatment that were not identical to the recommended intervention. Trials registries included 20 studies related to the topic, including nine trials of alternative feeding regimens. Acute medical management and follow-up care studies were minimally represented.WHO's guidelines on the topic have a weak evidence base and have undergone limited substantive adjustments over the past decades. More trials are needed to make that evidence base more robust. If the mortality associated with severe malnutrition is to be reduced, inpatient and post-discharge management trials, supported by studies on the causes of mortality, are needed.Comprendre comment renforcer les lignes directrices de l'Organisation mondiale de la Santé (OMS) relatives à la prise en charge des enfants hospitalisés pour malnutrition aiguë sévère avec complications en vue d’améliorer les résultats.En décembre 2015, nous avons recherché les recommandations de l'OMS concernant la prise en charge de la malnutrition aiguë sévère dans Google Scholar et sur le site Internet de l'OMS, puis évalué l'historique et les éléments invoqués à l'appui de ces recommandations. Nous avons systématiquement recherché les essais récemment effectués, en cours ou en attente, jusqu'au 10 août 2015, dans le Système d'enregistrement international des essais cliniques de l'OMS, sur ClinicalTrials.gov et dans le metaRegister of Controlled Trials.Les lignes directrices de l'OMS contiennent 33 recommandations à ce sujet. Cependant, 16 (48,5%) d'entre elles s'appuyaient uniquement sur une opinion d'expert non étayée par des données publiées. Onze (33,3%) autres étaient corroborées par les résultats de recherches présentant un intérêt direct, c'est-à-dire des essais randomisés (8) ou des études observationnelles (3). Les six dernières (18,2%) reposaient quant à elles sur des études n'ayant pas été menées auprès d'enfants atteints de malnutrition sévère avec complications ou sur des études de traitement non conforme à l'intervention recommandée. Les essais enregistrés incluaient 20 études en lien avec le sujet, dont neuf essais de régimes alimentaires alternatifs. Les études sur la prise en charge médicale urgente et les soins de suivi n'étaient que très peu représentées.Les lignes directrices de l'OMS sur le sujet s'appuient sur des données insuffisantes et n'ont fait l'objet que d'ajustements substantiels limités au cours des dernières décennies. Il est nécessaire de réaliser davantage d’essais afin de rendre cet ensemble de données plus fiable. Pour réduire la mortalité associée à la malnutrition sévère, il est nécessaire de réaliser des essais sur la prise en charge des enfants pendant et après leur hospitalisation, et de les étayer par des études sur les causes de la mortalité.Comprender cómo deben fortalecerse las directrices de la Organización Mundial de la Salud (OMS) sobre la atención hospitalaria de niños con malnutrición aguda grave complicada con el fin de mejorar los resultados.En diciembre de 2015, se realizaron búsquedas de recomendaciones eruditas en Google y en el sitio web de la OMS en relación con la gestión de la malnutrición aguda grave y se evaluó el historial y se citaron las pruebas detrás de estas recomendaciones. De forma sistemática, se realizaron búsquedas de ensayos completados, en proceso o pendientes hasta el 10 de agosto de 2015 en la Plataforma Internacional de Registros de Ensayos Clínicos (International Clinical Trials Registry Platform) de la OMS, en clinicaltrials.gov y en el Metarregistro de Ensayos Clínicos Controlados (Controlled Trials metaRegister).Las directrices de la OMS ofrecen 33 recomendaciones sobre el tema. No obstante, 16 (48,5%) de estas recomendaciones se basaron únicamente en opiniones de expertos, sin el respaldo de pruebas publicadas. Otras 11 (33,3%) recomendaciones estaban respaldadas por los resultados de investigaciones directamente relevantes, es decir, ensayos aleatorizados (8) o estudios de observación (3). Las otras 6 recomendaciones (18,2%) se basaban en estudios que no se realizaron en niños con malnutrición grave complicada o en estudios de tratamientos que no eran idénticos a la intervención recomendada. Los registros de los ensayos incluían 20 estudios relacionados con el tema, incluyendo 9 ensayos de regímenes de alimentación alternativos. La gestión médica aguda y los estudios de casos de seguimiento obtuvieron una representación mínima.Las directrices de la OMS sobre el tema tienen una base de pruebas deficiente y han sufrido pocos ajustes importantes durante las últimas décadas. Es preciso realizar más ensayos para que esta base de pruebas sea mucho más firme. Si se pretende reducir la mortalidad asociada a la malnutrición grave, se necesitan ensayos de gestión hospitalaria y tras el alta, con el apoyo de estudios basados en las causas de la mortalidad.فهم كيف يمكن تعزيز المبادئ التوجيهية الخاصة بمنظمة الصحة العالمية حول رعاية المرضى من الأطفال المصابين بحالات معقدة من سوء التغذية الحاد والشديد داخل المستشفى من أجل تحسين المحصّلات.في شهر ديسمبر من عام 2015، قمنا بالبحث في الباحث العلمي من Google scholar والموقع الإلكتروني الخاص بمنظمة الصحة العالمية لمعرفة توصيات منظمة الصحة العالمية بشأن إدارة حالات الإصابة بسوء التغذية الحاد والشديد وقمنا بتقييم التاريخ والأدلة الواردة نتيجة لهذه التوصيات. وبحثنا بشكل منهجي في منبر منظمة الصحة العالمية للسجلات الدولية للتجارب السريرية، وهو clinicaltrials.gov والسجل العام "metaRegister" للتجارب المضبطة بالشواهد حتى 10 أغسطس 2015 للتجارب المكتملة مؤخرًا أو الجارية أو المعلّقة.توفر المبادئ التوجيهية الخاصة بمنظمة الصحة العالمية 33 توصية بشأن الموضوع. ومع ذلك، استندت 16 توصية من هذه التوصيات (بنسبة ‏48.5%) على آراء الخبراء وحدها، غير مدعومة من جانب الأدلة المنشورة. وتم دعم 11 توصية أخرى من التوصيات بنسبة (33.3‏%) من جانب نتائج البحوث ذات الصلة المباشرة، أي إما التجارب المعشاة (8) أو الدراسات الرصدية (3). استندت التوصيات الست الأخرى (بنسبة 18.2‏%) على دراسات لم يتم إجراؤها بين الأطفال المصابين بحالات معقدة من سوء التغذية الشديد أو دراسات العلاج التي لم تكن مماثلة للتدخل المُوصى به. اشتملت سجلات التجارب على 20 دراسة متعلقة بالموضوع، من بينها تسع تجارب لأنظمة التغذية البديلة. كانت الدراسات الخاصة بإدارة الحالات الطبية الحادة والرعاية اللاحقة للمرضى ممثلة بالحد الأدنى.يوجد لدى المبادئ التوجيهية الخاصة بمنظمة الصحة العالمية قاعدة ضعيفة من الأدلة وخضعت لبعض التعديلات الموضوعية المحدودة على مدار العقود الماضية. وهناك حاجة لإجراء المزيد من التجارب لتعزيز قاعدة الأدلة. إذا كان معدل الوفيات المرتبط بسوء التغذية الحاد في طريقه للانخفاض، فهناك حاجة إلى إجراء تجارب إدارة المرضى داخل المستشفى وبعد الخروج من المستشفى، مدعومة بدراسات حول أسباب الوفيات.了解如何加强世界卫生组织 (WHO) 严重营养不良儿童住院治疗指南，以改善治疗结果。.2015 年 12 月，我们在谷歌学术和 WHO 网站上搜索了关于严重急性营养不良管理的 WHO 建议，并且评估了这些建议背后的历史和引用的证据。 我们在 2015 年 8 月 10 日之前在 WHO 国际临床试验注册平台 (clinicaltrials.gov) 和临床对照试验 (mRCT) 上进行了系统性搜索，以查找最近完成的、正在进行的或即将进行的试验。.WHO 指南针对这一课题提出 33 条建议。 然而，这些建议中，有 16 条 (48.5%) 仅基于专家意见——无公开发表的证据支持。 另外 11 条建议 (33.3%) 基于直接相关研究的结果——即随机试验 (8) 或观察性研究 (3)。 还有 6 条建议 (18.2%) 基于未在复杂严重营养不良儿童身上进行的研究或不同于所建议干预措施的治疗研究。 试验注册平台上包含 20 项与本课题相关的研究，包括 9 项替代性供餐计划试验。 关于急性医疗管理和后续护理的研究数量很少。.WHO 指南在该课题证据基础薄弱，并且在过去数十年仅进行了有限的实质性调整。 需要进行更多试验以增强证据基础。 要想降低与严重营养不良相关的死亡率，我们需要进行由死亡原因研究支持的住院和出院后管理试验.Определить возможные способы усовершенствования руководящих принципов Всемирной организации здравоохранения (ВОЗ) по ведению детей, страдающих тяжелой острой недостаточностью питания с осложнениями, в условиях стационара для улучшения конечных результатов.В декабре 2015 года авторы статьи провели поиск в системе Google Scholar и на веб-сайте ВОЗ на предмет рекомендаций ВОЗ по ведению тяжелой острой недостаточности и проанализировали историю изменений этих рекомендаций и цитируемые факты, лежащие в их основе. До 10 августа 2015 года также выполнялся систематический поиск на Международной платформе для регистрации клинических испытаний (International Clinical Trials Registry Platform) ВОЗ, clinicaltrials.gov, а также в Метарегистре контролируемых исследований (Controlled Trials metaRegister) на предмет недавно завершенных, текущих или еще не завершенных исследований.Руководящие принципы ВОЗ содержат 33 рекомендации по данной теме. Однако 16 (48,5%) из этих рекомендаций основывались исключительно на экспертном мнении, не подтвержденном опубликованными фактическими данными. Еще 11 (33,3%) из этих рекомендаций были подкреплены результатами непосредственно относящегося к ним исследования, рандомизированного (8) или наблюдательного (3). Остальные шесть рекомендаций (18,2%) основывались на исследованиях, которые проводились не среди детей с осложненной тяжелой недостаточностью питания, или на исследованиях лечения, которое не было идентично рекомендуемому вмешательству. Реестры исследований включали 20 исследований, относящихся к данной теме, в том числе девять исследований альтернативных рационов. Исследования неотложной медицинской помощи и последующего ухода были практически не представлены.Руководящие принципы ВОЗ по данной теме имеют слабо подкрепленную доказательную базу, и их содержание незначительно изменялось в течение последних десятилетий. Необходимо выполнить больше исследований для того, чтобы укрепить соответствующую доказательную базу. Для снижения смертности, связанной с тяжелой недостаточностью питания, потребуются исследования ведения пациентов в условиях стационара и наблюдения после выписки, подкрепленные изучением причин смертности.

OBJECTIVES: Globally, only 17% of children with wasting receive treatment. In Kenya, 4% of the 7 million children under-5 years of age are wasted and 26% are stunted. The Mama Aweza trial will test whether a two-way short message service (SMS) mobile health system, the Maternal Administered Malnutrition Monitoring System (MAMMS), can increase the coverage of malnutrition management programs in low-and-middle income countries. METHODS: Five formative focus group discussions (FGDs) were conducted with caregivers at an immunization clinic in Migori County, Kenya to inform feasibility and content of SMS messages in the MAMMS system. Caregivers were asked to explain anticipated facilitators and barriers to participation in a SMS program to facilitate home-based mid upper-arm circumference (MUAC) monitoring. FGDs also reviewed educational messages that accompany weekly SMS reminders to measure and report their child's MUAC. The feedback from these FGDs was included in the clinical trial, which begun in August 2019. RESULTS: The most anticipated challenge to responding to weekly messages was the use of a shared phone particularly that the SMS would be deleted or the caregiver would not be informed of the message. The greatest anticipated challenge for sending messages was and not knowing how to send a SMS. Overall, 52 messages were written on the following topics: developmental milestones, encouragement, fever, diarrhea, malaria, ear infections, sanitation and hygiene, vaccinations, respiratory illness, and kitchen gardening. To date, 144 mother-infant dyads have been enrolled and 77 randomly assigned to the MAMMS arm. Sixty-nine (90%) caregivers have responded to ≥1 message and 503 (68%) of 742 automated messages have received a response. At enrollment, 21 (27%) of caregivers in the MAMMS arm reported a shared phone, with no current evidence that caregivers sharing a phone respond less than those with their own phone. CONCLUSIONS: Caregivers found SMS-based malnutrition screening to be acceptable and engaging. In regions with high literacy and high mobile phone ownership, such as Kenya, SMS supported home MUAC monitoring may improve malnutrition screening coverage and lead to earlier identification and treatment. FUNDING SOURCES: Thrasher Research Foundation 14,656.

Objective: We evaluated the hypothesis that elective early-term delivery increases the risk of childhood lower respiratory tract disorder hospitalization. Methods: Children born via early-term elective inductions were compared to full- or late-term elective inductions in a retrospective cohort study using Washington State birth certificate and hospital discharge data. Outcomes were the odds of lower respiratory disorder hospitalization before age five and cause specific odds ratios for asthma, bronchiolitis, bronchitis, and pneumonia. In addition, a subgroup analysis excluding infants with perinatal complications was conducted. Results: Electively induced early-term children were at significantly increased risk of hospitalization before age five for lower respiratory disorders compared to similar full- or late-term children (adjusted OR: 1.31, 95% CI: 1.11–1.55). Bronchiolitis was the only cause-specific outcome with a statistically significant increase in odds of hospitalization, though comparable increases were found for the less common diagnoses of asthma (adjusted OR: 1.39, 95% CI: 0.93–2.08) and pneumonia (adjusted OR: 1.27, 95% CI: 0.99–1.64). Excluding infants with perinatal complications did not alter the results. Conclusions: There was an association between electively induced early-term delivery and hospitalization for lower respiratory tract disorders before age five. This reinforces policies discouraging elective early-term delivery.

Chronic malnutrition, defined by linear growth failure, or stunting, affects over 165 million children globally [1]. In many areas of the world with a high prevalence of stunting, children experience frequent and recurrent exposure to pathogens, including neglected tropical diseases (NTDs). These infections appear to have detrimental effects on linear growth [2–6], but interventions to promote linear growth have demonstrated limited benefit. Difficulty in establishing effective growth-promoting interventions is not unique to NTDs; even the optimal delivery of all interventions known to improve nutritional status is estimated to be able to reverse less than a quarter of all stunting [7]. The failure to identify effective interventions to reverse stunting offers the opportunity to develop a new conceptual model of chronic malnutrition that furthers our understanding of the mechanism linking pathogen and environmental exposures to linear growth failure. Such a conceptual model may guide the identification of new targets for intervention to reduce the substantial morbidity and mortality associated with chronic malnutrition [1].