The 2024 Pediatric Sepsis Challenge: Predicting In-Hospital Mortality in Children With Suspected Sepsis in Uganda.

The aim of this "Technical Note" is to inform the pediatric critical care data research community about the "2024 Pediatric Sepsis Data Challenge." This competition aims to facilitate the development of open-source algorithms to predict in-hospital mortality in Ugandan children with sepsis. The challenge is to first develop an algorithm using a synthetic training dataset, which will then be scored according to standard diagnostic testing criteria, and then be evaluated against a nonsynthetic test dataset. The datasets originate from admissions to six hospitals in Uganda (2017-2020) and include 3837 children, 6 to 60 months old, who were confirmed or suspected to have a diagnosis of sepsis. The synthetic dataset was created from a random subset of the original data. The test validation dataset closely resembles the synthetic dataset. The challenge should generate an optimal model for predicting in-hospital mortality. Following external validation, this model could be used to improve the outcomes for children with proven or suspected sepsis in low- and middle-income settings.

Neonatal Paenibacilliosis: Paenibacillus Infection as a Novel Cause of Sepsis in Term Neonates With High Risk of Sequelae in Uganda.

BACKGROUND: Paenibacillus thiaminolyticus may be an underdiagnosed cause of neonatal sepsis. METHODS: We prospectively enrolled a cohort of 800 full-term neonates presenting with a clinical diagnosis of sepsis at 2 Ugandan hospitals. Quantitative polymerase chain reaction specific to P. thiaminolyticus and to the Paenibacillus genus were performed on the blood and cerebrospinal fluid (CSF) of 631 neonates who had both specimen types available. Neonates with Paenibacillus genus or species detected in either specimen type were considered to potentially have paenibacilliosis, (37/631, 6%). We described antenatal, perinatal, and neonatal characteristics, presenting signs, and 12-month developmental outcomes for neonates with paenibacilliosis versus clinical sepsis due to other causes. RESULTS: Median age at presentation was 3 days (interquartile range 1, 7). Fever (92%), irritability (84%), and clinical signs of seizures (51%) were common. Eleven (30%) had an adverse outcome: 5 (14%) neonates died during the first year of life; 5 of 32 (16%) survivors developed postinfectious hydrocephalus (PIH) and 1 (3%) additional survivor had neurodevelopmental impairment without hydrocephalus. CONCLUSIONS: Paenibacillus species was identified in 6% of neonates with signs of sepsis who presented to 2 Ugandan referral hospitals; 70% were P. thiaminolyticus. Improved diagnostics for neonatal sepsis are urgently needed. Optimal antibiotic treatment for this infection is unknown but ampicillin and vancomycin will be ineffective in many cases. These results highlight the need to consider local pathogen prevalence and the possibility of unusual pathogens when determining antibiotic choice for neonatal sepsis.

Xpert MTB/RIF diagnosis of childhood tuberculosis from sputum and stool samples in a high TB-HIV-prevalent setting.

The Xpert MTB/RIF assay is a major advance for diagnosis of tuberculosis (TB) in high-burden countries but is limited in children by their difficulty to produce sputum. We investigated TB in sputum and stool from children with the aim of improving paediatric TB diagnosis. A prospective cohort of children with presumptive TB, provided two sputum or induced sputum at enrolment in a regional referral hospital in Uganda. Stool was collected from those started on TB treatment. All specimen were tested for Xpert MTB/RIF, mycobacteria growth indicator tube (MGIT), Lowenstein Jensen cultures and microscopy (except stool). We compared TB detection between age categories and assessed the performance of Xpert MTB/RIF in sputum and stool. Of the 392 children enrolled, 357 (91.1%) produced at least one sputum sample. Sputum culture yield was 13/357 (3.6%): 3/109 (2.6%), 3/89 (3.2%), 3/101 (2.6%) and 4/44 (8.2%) among children of < 2, 2-5, ≥ 5-10 and > 10 years, respectively (p = 0.599). Xpert MTB/RIF yield was 14/350 (4.0%): 3/104 (2.9%), 4/92 (4.3%), 3/88 (2.9%) and 4/50 (.0%), respectively (p = 0.283). Sensitivity and specificity of Xpert MTB/RIF in sputum against sputum culture were 90.9% (95% CI 58.7-99.8) and 99.1% (99.1-99.8). In stool, it was 55.6% (21.2-86.3) and 98.2% (98.2-100) against Xpert MTB/RIF and culture in sputum. Only a minority of children had microbiologically confirmed TB with a higher proportion in children above 10 years. Although sensitivity of Xpert MTB/RIF in stool was low, with good optimization, it might be a good alternative to sputum in children.

Application of Sepsis Definitions to Pediatric Patients Admitted With Suspected Infections in Uganda.

OBJECTIVES: Acute infectious diseases are the most common cause of under-5 mortality. However, the hospital burden of nonneonatal pediatric sepsis has not previously been described in the resource poor setting. The objective of this study was to determine the prevalence of sepsis among children 6 months to 5 years old admitted with proven or suspected infection and to evaluate the presence of sepsis as a predictive tool for mortality during admission. DESIGN: In this prospective cohort study, we used the pediatric International Consensus Conference definition of sepsis to determine the prevalence of sepsis among children admitted to the pediatric ward with a proven or suspected infection. The diagnosis of sepsis, as well as each individual component of the sepsis definition, was evaluated for capturing in-hospital mortality. SETTING: The pediatric ward of two hospitals in Mbarara, Uganda. PATIENTS: Admitted children between 6 months and 5 years with a confirmed or suspected infection. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: One thousand three hundred seven (1,307) subjects with a confirmed or suspected infection were enrolled, and 65 children died (5.0%) during their admission. One thousand one hundred twenty-one (85.9%) met the systemic inflammatory response syndrome criteria, and therefore, they were defined as having sepsis. The sepsis criteria captured 61 deaths, demonstrating a sensitivity and a specificity of 95% (95% CI, 90-100%) and 15% (95% CI, 13-17%), respectively. The most discriminatory individual component of the systemic inflammatory response syndrome criteria was the leukocyte count, which alone had a sensitivity of 72% and a specificity of 56% for the identification of mortality in hospital. CONCLUSIONS: This study is among the first to quantify the burden of nonneonatal pediatric sepsis in children with suspected infection, using the international consensus sepsis definition, in a typical resource-constrained setting in Africa. This definition was found to be highly sensitive in identifying those who died but had very low specificity as most children who were admitted with infections had sepsis. The systemic inflammatory response syndrome-based sepsis definition offers little value in identification of children at high risk of in-hospital mortality in this setting.

The dynamic relationship between social support and HIV-related stigma in rural Uganda.

BACKGROUND: Cross-sectional studies show that human immunodeficiency virus (HIV) stigma is negatively correlated with social support. PURPOSE: The purpose of this study is to examine the bidirectional relationship between social support and HIV stigma. METHODS: We collected quarterly data from a cohort of 422 people living with HIV in Uganda, followed for a median of 2.1 years. We used multilevel regression to model the contemporaneous and 3-month-lagged associations between social support and both enacted and internalized stigma. RESULTS: Lagged enacted stigma was negatively correlated with emotional and instrumental social support, and lagged instrumental social support was negatively correlated with enacted stigma. Internalized stigma and emotional social support had reciprocal lagged associations. CONCLUSIONS: Interventions to reduce enacted stigma may strengthen social support for people living with HIV. Improved social support may in turn have a protective influence against future enacted and internalized stigma.

Primary Healthcare Workers' Awareness of Acute Rheumatic Fever & Rheumatic Heart Disease: A Study in Public Health Facilities in South Western Uganda.

Introduction: Timely identification and treatment of a streptococcal throat infection prevents acute rheumatic fever (ARF) and its progression to Rheumatic Heart Disease (RHD). However, children in developing countries still present with established RHD, due to either missed, untreated or sub-optimally treated sore throats and ARF. We aimed to determine the level of knowledge, skills, and practices of primary health workers in South Western Uganda in providing care such children. Methods: We conducted a comparative quantitative cross-sectional study to assess knowledge, practices, and skills regarding the care of a child with a sore throat, ARF, and RHD. The responses were scored against a structured guide. The Fisher's exact test and the chi-squared test with level of significance set at 0.05 were utilized to compare differences in knowledge, skills, and practices among health workers in private and public health facilities about ARF and RHD. Results: Eighty health workers from health facilities were interviewed in Mbarara district with a median age of 29.5 years (IQR 27.34) and median duration in practice of 5 years (IQR: 2, 10). On average, there were at least 3 children with sore throats weekly. At least 95% (CI: 87.25%-98.80%) of the health worker had awareness about ARF and RHD. Only 43.75% (95% CI: 33.18%-54.91%) had good knowledge about ARF and RHD. Majority, 61.25% (95% CI: 50.03%-71.39%) did not know the proper prophylaxis and investigations for a child with ARF. There were no statistically significant differences but a clinically meaningful differentials in the level of knowledge among health workers in public and private facilities. Conclusion: The knowledge and skill level of health workers in primary healthcare facilities about ARF and RHD in South Western Uganda remains low, with no difference between practitioners in public and private facilities.

Newborn care knowledge and practices among care givers of newborns and young infants attending a regional referral hospital in Southwestern Uganda.

A child born in developing countries has a 10 times higher mortality risk compared to one born in developed countries. Uganda still struggles with a high neonatal mortality rate at 27/1000 live births. Majority of these death occur in the community when children are under the sole care of their parents and guardian. Lack of knowledge in new born care, inappropriate new born care practices are some of the contributors to neonatal mortality in Uganda. Little is known about parent/caregivers' knowledge, practices and what influences these practices while caring for the newborns. We systematically studied and documented newborn care knowledge, practices and associated factors among parents and care givers. To assess new born care knowledge, practices and associated factors among parents and care givers attending MRRH. We carried out a quantitative cross section methods study among caregivers of children from birth to six weeks of life attending a regional referral hospital in south western Uganda. Using pretested structured questionnaires, data was collected about care givers' new born care knowledge, practices and the associated factors. Data analysis was done using Stata version 17.0. We interviewed 370 caregivers, majority of whom were the biological mothers at 86%. Mean age was 26 years, 14% were unemployed and 74% had monthly earning below the poverty line. Mothers had a high antenatal care attendance of 97.6% and 96.2% of the deliveries were at a health facility Care givers had variant knowledge of essential newborn care with associated incorrect practices. Majority (84.6%) of the respondents reported obliviousness to putting anything in the babies' eyes at birth, however, breastmilk, water and saliva were reportedly put in the babies' eyes at birth by some caregivers. Hand washing was not practiced at all in 16.2% of the caregivers before handling the newborn. About 7.4% of the new borns received a bath within 24 hours of delivery and 19% reported use of herbs. Caregivers practiced adequate thermal care 87%. Cord care practices were inappropriate in 36.5%. Only 21% of the respondents reported initiation of breast feeding within 1 hour of birth, Prelacteal feeds were given by 37.6% of the care givers, water being the commonest prelacteal feed followed by cow's milk at 40.4 and 18.4% respectively. Majority of the respondents had below average knowledge about danger signs in the newborn where 63% and mean score for knowledge about danger signs was 44%. Caretaker's age and relationship with the newborn were found to have a statistically significant associated to knowledge of danger signs in the newborn baby. There are variable incorrect practices in the essential new born care and low knowledge and awareness of danger signs among caregivers of newborn babies. There is high health center deliveries and antenatal care attendance among the respondents could be used as an opportunity to increase caregiver awareness about the inappropriate practices in essential newborn care and the danger signs in a newborn.

Pediatric post-discharge mortality in resource-poor countries: a systematic review and meta-analysis.

Background: Under-five mortality remains concentrated in resource-poor countries. Post-discharge mortality is becoming increasingly recognized as a significant contributor to overall child mortality. With a substantial recent expansion of research and novel data synthesis methods, this study aims to update the current evidence base by providing a more nuanced understanding of the burden and associated risk factors of pediatric post-discharge mortality after acute illness. Methods: Eligible studies published between January 1, 2017 and January 31, 2023, were retrieved using MEDLINE, Embase, and CINAHL databases. Studies published before 2017 were identified in a previous review and added to the total pool of studies. Only studies from countries with low or low-middle Socio-Demographic Index with a post-discharge observation period greater than seven days were included. Risk of bias was assessed using a modified version of the Joanna Briggs Institute critical appraisal tool for prevalence studies. Studies were grouped by patient population, and 6-month post-discharge mortality rates were quantified by random-effects meta-analysis. Secondary outcomes included post-discharge mortality relative to in-hospital mortality, pooled risk factor estimates, and pooled post-discharge Kaplan-Meier survival curves. PROSPERO study registration: #CRD42022350975. Findings: Of 1963 articles screened, 42 eligible articles were identified and combined with 22 articles identified in the previous review, resulting in 64 total articles. These articles represented 46 unique patient cohorts and included a total of 105,560 children. For children admitted with a general acute illness, the pooled risk of mortality six months post-discharge was 4.4% (95% CI: 3.5%-5.4%, I2 = 94.2%, n = 11 studies, 34,457 children), and the pooled in-hospital mortality rate was 5.9% (95% CI: 4.2%-7.7%, I2 = 98.7%, n = 12 studies, 63,307 children). Among disease subgroups, severe malnutrition (12.2%, 95% CI: 6.2%-19.7%, I2 = 98.2%, n = 10 studies, 7760 children) and severe anemia (6.4%, 95% CI: 4.2%-9.1%, I2 = 93.3%, n = 9 studies, 7806 children) demonstrated the highest 6-month post-discharge mortality estimates. Diarrhea demonstrated the shortest median time to death (3.3 weeks) and anemia the longest (8.9 weeks). Most significant risk factors for post-discharge mortality included unplanned discharges, severe malnutrition, and HIV seropositivity. Interpretation: Pediatric post-discharge mortality rates remain high in resource-poor settings, especially among children admitted with malnutrition or anemia. Global health strategies must prioritize this health issue by dedicating resources to research and policy innovation. Funding: No specific funding was received.

Distinct cytokine profiles in late pregnancy in Ugandan people with HIV.

During pregnancy, multiple immune regulatory mechanisms establish an immune-tolerant environment for the allogeneic fetus, including cellular signals called cytokines that modify immune responses. However, the impact of maternal HIV infection on these responses is incompletely characterized. We analyzed paired maternal and umbilical cord plasma collected during labor from 147 people with HIV taking antiretroviral therapy and 142 HIV-uninfected comparators. Though cytokine concentrations were overall similar between groups, using Partial Least Squares Discriminant Analysis we identified distinct cytokine profiles in each group, driven by higher IL-5 and lower IL-8 and MIP-1α levels in pregnant people with HIV and higher RANTES and E-selectin in HIV-unexposed umbilical cord plasma (P-value < 0.01). Furthermore, maternal RANTES, SDF-α, gro α -KC, IL-6, and IP-10 levels differed significantly by HIV serostatus (P < 0.01). Although global maternal and umbilical cord cytokine profiles differed significantly (P < 0.01), umbilical cord plasma profiles were similar by maternal HIV serostatus. We demonstrate that HIV infection is associated with a distinct maternal plasma cytokine profile which is not transferred across the placenta, indicating a placental role in coordinating local inflammatory response. Furthermore, maternal cytokine profiles in people with HIV suggest an incomplete shift from Th2 to Th1 immune phenotype at the end of pregnancy.

Prediction models for post-discharge mortality among under-five children with suspected sepsis in Uganda: A multicohort analysis.

In many low-income countries, over five percent of hospitalized children die following hospital discharge. The lack of available tools to identify those at risk of post-discharge mortality has limited the ability to make progress towards improving outcomes. We aimed to develop algorithms designed to predict post-discharge mortality among children admitted with suspected sepsis. Four prospective cohort studies of children in two age groups (0-6 and 6-60 months) were conducted between 2012-2021 in six Ugandan hospitals. Prediction models were derived for six-months post-discharge mortality, based on candidate predictors collected at admission, each with a maximum of eight variables, and internally validated using 10-fold cross-validation. 8,810 children were enrolled: 470 (5.3%) died in hospital; 257 (7.7%) and 233 (4.8%) post-discharge deaths occurred in the 0-6-month and 6-60-month age groups, respectively. The primary models had an area under the receiver operating characteristic curve (AUROC) of 0.77 (95%CI 0.74-0.80) for 0-6-month-olds and 0.75 (95%CI 0.72-0.79) for 6-60-month-olds; mean AUROCs among the 10 cross-validation folds were 0.75 and 0.73, respectively. Calibration across risk strata was good: Brier scores were 0.07 and 0.04, respectively. The most important variables included anthropometry and oxygen saturation. Additional variables included: illness duration, jaundice-age interaction, and a bulging fontanelle among 0-6-month-olds; and prior admissions, coma score, temperature, age-respiratory rate interaction, and HIV status among 6-60-month-olds. Simple prediction models at admission with suspected sepsis can identify children at risk of post-discharge mortality. Further external validation is recommended for different contexts. Models can be digitally integrated into existing processes to improve peri-discharge care as children transition from the hospital to the community.

Internalized stigma, social distance, and disclosure of HIV seropositivity in rural Uganda.

BACKGROUND: HIV is highly stigmatized, compromising both treatment and prevention in resource-limited settings. PURPOSE: We sought to study the relationship between internalized HIV-related stigma and serostatus disclosure and to determine the extent to which this association varies with the degree of social distance. METHODS: We fit multivariable Poisson regression models, with cluster-correlated robust estimates of variance, to data from 259 persons with HIV enrolled in an ongoing cohort study in rural Uganda. RESULTS: Persons with more internalized stigma were less likely to disclose their seropositivity. The magnitude of association increased with social distance such that the largest association was observed for public disclosures and the smallest association was observed for disclosures to sexual partners. CONCLUSIONS: Among persons with HIV in rural Uganda, internalized stigma was negatively associated with serostatus disclosure. The inhibiting effect of stigma was greatest for the most socially distant ties.

How does antiretroviral treatment attenuate the stigma of HIV? Evidence from a cohort study in rural Uganda.

Program implementers and qualitative researchers have described how increasing availability of HIV antiretroviral therapy (ART) is associated with improvements in psychosocial health and internalized stigma. To determine whether, and through what channels, ART reduces internalized stigma, we analyzed data from 262 HIV-infected, treatment-naïve persons in rural Uganda followed from ART initiation over a median of 3.4 years. We fitted Poisson regression models with cluster-correlated robust estimates of variance, specifying internalized stigma as the dependent variable, adjusting for time on treatment as well as socio-demographic, clinical, and psychosocial variables. Over time on treatment, internalized stigma declined steadily, with the largest decline observed during the first 2 years of treatment. This trend remained statistically significant after multivariable adjustment (χ(2) = 28.3; P = 0.03), and appeared to be driven by ART-induced improvements in HIV symptom burden, physical and psychological wellbeing, and depression symptom severity.

Pediatric post-discharge mortality in resource-poor countries: A protocol for an updated systematic review and meta-analysis.

BACKGROUND: More than 50 countries, mainly in Sub-Saharan Africa and South Asia, are not on course to meet the neonatal and under-five mortality target set by the Sustainable Development Goals (SDGs) for the year 2030. One important, yet neglected, aspect of child mortality rates is deaths occurring during the post-discharge period. For children living in resource-poor countries, the rate of post-discharge mortality within the first several months after discharge is often as high as the rates observed during the initial admission period. This has generally been observed within the context of acute illness and has been closely linked to underlying conditions such as malnutrition, HIV, and anemia. These post-discharge mortality rates tend to be underreported and present a major oversight in the efforts to reduce overall child mortality. This review will explore recurrent illness following discharge through determination of rates of, and risk factors for, pediatric post-discharge mortality in resource-poor settings. METHODS: Eligible studies will be retrieved using MEDLINE, EMBASE, and CINAHL databases. Only studies with a post-discharge observation period of more than 7 days following discharge will be eligible for inclusion. Secondary outcomes will include post-discharge mortality relative to in-hospital mortality, overall readmission rates, pooled estimates of risk factors (e.g. admission details vs discharge factors, clinical vs social factors), pooled post-discharge mortality Kaplan-Meier survival curves, and outcomes by disease subgroups (e.g. malnutrition, anemia, general admissions). A narrative description of the included studies will be synthesized to categorize commonly affected patient population categories and a random-effects meta-analysis will be conducted to quantify overall post-discharge mortality rates at the 6-month time point. DISCUSSION: Post-discharge mortality contributes to global child mortality rates with a greater burden of deaths occurring in resource-poor settings. Literature concentrated on child mortality published over the last decade has expanded to focus on the fatal outcomes of children post-discharge and associated risk factors. The results from this systematic review will inform current policy and interventions on the epidemiological burden of post-discharge mortality and morbidity following acute illness among children living in resource-poor settings. SYSTEMATIC REVIEW REGISTRATION: PROSPERO Registration ID: CRD42022350975.

Mortality after hospital discharge among children younger than 5 years admitted with suspected sepsis in Uganda: a prospective, multisite, observational cohort study.

BACKGROUND: Substantial mortality occurs after hospital discharge in children younger than 5 years with suspected sepsis, especially in low-income countries. A better understanding of its epidemiology is needed for effective interventions to reduce child mortality in these countries. We evaluated risk factors for death after discharge in children admitted to hospital for suspected sepsis in Uganda, and assessed how these differed by age, time of death, and location of death. METHODS: In this prospective, multisite, observational cohort study, we recruited and consecutively enrolled children aged 0-60 months admitted with suspected sepsis from the community to the paediatric wards of six Ugandan hospitals. Suspected sepsis was defined as the need for admission due to a suspected or proven infectious illness. At admission, trained study nurses systematically collected data on clinical variables, sociodemographic variables, and baseline characteristics with encrypted study tablets. Participants were followed up for 6 months after discharge by field officers who contacted caregivers at 2 months and 4 months after discharge by telephone and at 6 months after discharge in person to measure vital status, health-care seeking after discharge, and readmission details. We assessed 6-month mortality after hospital discharge among those discharged alive, with verbal autopsies conducted for children who had died after hospital discharge. FINDINGS: Between July 13, 2017, and March 30, 2020, 16 991 children were screened for eligibility. 6545 children (2927 [44·72%] female children and 3618 [55·28%] male children) were enrolled and 6191 were discharged from hospital alive. 6073 children (2687 [44·2%] female children and 3386 [55·8%] male children) completed follow-up. 366 children died in the 6-month period after discharge (weighted mortality rate 5·5%). Median time from discharge to death was 28 days (IQR 9-74). For the 360 children for whom location of death was documented, deaths occurred at home (162 [45·0%]), in transit to care (66 [18·3%]), or in hospital (132 [36·7%]) during a subsequent readmission. Death after hospital discharge was strongly associated with weight-for-age Z scores less than -3 (adjusted risk ratio [aRR] 4·7, 95% CI 3·7-5·8 vs a Z score of >-2), discharge or referral to a higher level of care (7·3, 5·6-9·5), and unplanned discharge (3·2, 2·5-4·0). Hazard ratios (HRs) for severe anaemia (<7g/dL) increased with time since discharge, from 1·7 (95% CI 0·9-3·0) for death occurring in the first time tertile to 5·2 (3·1-8·5) in the third time tertile. HRs for some discharge vulnerabilities decreased significantly with increasing time since discharge, including unplanned discharge (from 4.5 [2·9-6·9] in the first tertile to 2·0 [1·3-3·2] in the third tertile) and poor feeding status (from 7·7 [5·4-11·0] to 1·84 [1·0-3·3]). Age interacted with several variables, including reduced weight-for-age Z score, severe anaemia, and reduced admission temperature. INTERPRETATION: Paediatric mortality following hospital discharge after suspected sepsis is common, with diminishing, although persistent, risk during the first 6 months after discharge. Efforts to improve outcomes after hospital discharge are crucial to achieving Sustainable Development Goal 3.2 (ending preventable childhood deaths under age 5 years). FUNDING: Grand Challenges Canada, Thrasher Research Fund, BC Children's Hospital Foundation, and Mining4Life.

Verbal Autopsy to Assess Postdischarge Mortality in Children With Suspected Sepsis in Uganda.

BACKGROUND: Reducing child mortality in low-income countries is constrained by a lack of vital statistics. In the absence of such data, verbal autopsies provide an acceptable method to determining attributable causes of death. The objective was to assess potential causes of pediatric postdischarge mortality in children younger than age 5 years (under-5) originally admitted for suspected sepsis using verbal autopsies. METHODS: Secondary analysis of verbal autopsy data from children admitted to 6 hospitals across Uganda from July 2017 to March 2020. Structured verbal autopsy interviews were conducted for all deaths within 6 months after discharge. Two physicians independently classified a primary cause of death, up to 4 alternative causes, and up to 5 contributing conditions using the Start-Up Mortality List, with discordance resolved by consensus. RESULTS: Verbal autopsies were completed for 361 (98.6%) of the 366 (5.9%) children who died among 6191 discharges (median admission age: 5.4 months [interquartile range, 1.8-16.7]; median time to mortality: 28 days [interquartile range, 9-74]). Most deaths (62.3%) occurred in the community. Leading primary causes of death, assigned in 356 (98.6%) of cases, were pneumonia (26.2%), sepsis (22.1%), malaria (8.5%), and diarrhea (7.9%). Common contributors to death were malnutrition (50.5%) and anemia (25.7%). Reviewers were less confident in their causes of death for neonates than older children (P < .05). CONCLUSIONS: Postdischarge mortality frequently occurred in the community in children admitted for suspected sepsis in Uganda. Analyses of the probable causes for these deaths using verbal autopsies suggest potential areas for interventions, focused on early detection of infections, as well as prevention and treatment of underlying contributors such as malnutrition and anemia.

Paenibacillus spp infection among infants with postinfectious hydrocephalus in Uganda: an observational case-control study.

BACKGROUND: Paenibacillus thiaminolyticus is a cause of postinfectious hydrocephalus among Ugandan infants. To determine whether Paenibacillus spp is a pathogen in neonatal sepsis, meningitis, and postinfectious hydrocephalus, we aimed to complete three separate studies of Ugandan infants. The first study was on peripartum prevalence of Paenibacillus in mother-newborn pairs. The second study assessed Paenibacillus in blood and cerebrospinal fluid (CSF) from neonates with sepsis. The third study assessed Paenibacillus in CSF from infants with hydrocephalus. METHODS: In this observational study, we recruited mother-newborn pairs with and without maternal fever (mother-newborn cohort), neonates (aged ≤28 days) with sepsis (sepsis cohort), and infants (aged ≤90 days) with hydrocephalus with and without a history of neonatal sepsis and meningitis (hydrocephalus cohort) from three hospitals in Uganda between Jan 13, 2016 and Oct 2, 2019. We collected maternal blood, vaginal swabs, and placental samples and the cord from the mother-newborn pairs, and blood and CSF from neonates and infants. Bacterial content of infant CSF was characterised by 16S rDNA sequencing. We analysed all samples using quantitative PCR (qPCR) targeting either the Paenibacillus genus or Paenibacillus thiaminolyticus spp. We collected cranial ultrasound and computed tomography images in the subset of participants represented in more than one cohort. FINDINGS: No Paenibacillus spp were detected in vaginal, maternal blood, placental, or cord blood specimens from the mother-newborn cohort by qPCR. Paenibacillus spp was detected in 6% (37 of 631 neonates) in the sepsis cohort and, of these, 14% (5 of 37 neonates) developed postinfectious hydrocephalus. Paenibacillus was the most enriched bacterial genera in postinfectious hydrocephalus CSF (91 [44%] of 209 patients) from the hydrocephalus cohort, with 16S showing 94% accuracy when validated by qPCR. Imaging showed progression from Paenibacillus spp-related meningitis to postinfectious hydrocephalus over 1-3 months. Patients with postinfectious hydrocephalus with Paenibacillus spp infections were geographically clustered. INTERPRETATION: Paenibacillus spp causes neonatal sepsis and meningitis in Uganda and is the dominant cause of subsequent postinfectious hydrocephalus. There was no evidence of transplacental transmission, and geographical evidence was consistent with an environmental source of neonatal infection. Further work is needed to identify routes of infection and optimise treatment of neonatal Paenibacillus spp infection to lessen the burden of morbidity and mortality. FUNDING: National Institutes of Health and Boston Children's Hospital Office of Faculty Development.

Factors Associated with 30-Day in-Hospital Mortality Among Patients Admitted with Severe Covid-19 in Mbarara Regional Referral Hospital.

Background: COVID-19 has created a burden on the healthcare system globally. Severe COVID-19 is linked with high hospital mortality. Data regarding 30-day in-hospital mortality and its factors has not been explored in southwestern Uganda. Methods: We carried out a retrospective, single-center cohort study, and included all in-patients with laboratory-confirmed, radiological, or clinical severe COVID-19 admitted between April 2020 and September 2021 at Mbarara Regional Referral Hospital (MRRH). Demographic, laboratory, treatment, and clinical outcome data were extracted from patients' files. These data were described comparing survivors and non-survivors. We used logistic regression to explore the factors associated with 30-day in-hospital mortality. Results: Of the 283 patients with severe COVID-19 admitted at MRRH COVID-19 unit, 58.1% were male. The mean age ± standard deviation (SD) was 61±17.4 years; there were no differences in mean age between survivors and non-survivors (59 ± 17.2 versus 64.4 ±17.3, respectively, p=0.24) The median length of hospital stay was 7 (IQR 3-10) days (non-survivors had a shorter median length of stay 5 (IQR 2-9) days compared to the survivors; 8 (IQR 5-11) days, p<0.001. The most frequent comorbidities were hypertension (30.5%) and diabetes mellitus (30%). The overall 30-day in-hospital mortality was 134 of 279 (48%) mortality rate of 47,350×105 with a standard error of 2.99%. The factors associated with 30-day in-hospital mortality were age: 65 years and above (aOR, 3.88; 95% CI, 1.24-11.70; P =0.020) a neutrophil to lymphocyte ratio above 5 (aOR, 4.83; 95% CI, 1.53-15.28; P =0.007) and oxygen requirement ≥15L/min (aOR, 15.80; 95% CI, 5.17-48.25; P <0.001). Conclusion: We found a high 30-day in-hospital mortality among patients with severe forms of COVID-19. The identified factors could help clinicians to identify patients with poor prognosis at an early stage of admission.

Cytomegalovirus infections in infants in Uganda: Newborn-mother pairs, neonates with sepsis, and infants with hydrocephalus.

OBJECTIVES: To estimate the prevalence of cytomegalovirus (CMV) infections among newborn-mother pairs, neonates with sepsis, and infants with hydrocephalus in Uganda. DESIGN AND METHODS: Three populations-newborn-mother pairs, neonates with sepsis, and infants (≤3 months) with nonpostinfectious (NPIH) or postinfectious (PIH) hydrocephalus-were evaluated for CMV infection at 3 medical centers in Uganda. Quantitative PCR (qPCR) was used to characterize the prevalence of CMV. RESULTS: The overall CMV prevalence in 2498 samples across all groups was 9%. In newborn-mother pairs, there was a 3% prevalence of cord blood CMV positivity and 33% prevalence of maternal vaginal shedding. In neonates with clinical sepsis, there was a 2% CMV prevalence. Maternal HIV seropositivity (adjusted odds ratio [aOR] 25.20; 95% confidence interval [CI] 4.43-134.26; p = 0.0001), residence in eastern Uganda (aOR 11.06; 95% CI 2.30-76.18; p = 0.003), maternal age <25 years (aOR 4.54; 95% CI 1.40-19.29; p = 0.02), and increasing neonatal age (aOR 1.08 for each day older; 95% CI 1.00-1.16; p = 0.05), were associated risk factors for CMV in neonates with clinical sepsis. We found a 2-fold higher maternal vaginal shedding in eastern (45%) vs western (22%) Uganda during parturition (n = 22/49 vs 11/50, the Fisher exact test; p = 0.02). In infants with PIH, the prevalence in blood was 24% and in infants with NPIH, it was 20%. CMV was present in the cerebrospinal fluid (CSF) of 13% of infants with PIH compared with 0.5% of infants with NPIH (n = 26/205 vs 1/194, p < 0.0001). CONCLUSIONS: Our findings highlight that congenital and postnatal CMV prevalence is substantial in this African setting, and the long-term consequences are uncharacterized.

Incidence and predictors of preterm neonatal mortality at Mbarara Regional Referral Hospital in South Western Uganda.

INTRODUCTION: Preterm neonatal mortality contributes substantially to the high neonatal mortality globally. In Uganda, preterm neonatal mortality accounts for 31% of all neonatal deaths. Previous studies have shown variability in mortality rates by healthcare setting. Also, different predictors influence the risk of neonatal mortality in different populations. Understanding the predictors of preterm neonatal mortality in the low-resource setting where we conducted our study could guide the development of interventions to improve outcomes for preterm neonates. We thus aimed to determine the incidence and predictors of mortality among preterm neonates born at Mbarara Regional Referral Hospital (MRRH) in South Western Uganda. METHODS: We prospectively enrolled 538 live preterm neonates born at MRRH from October 2019 to September 2020. The neonates were followed up until death or 28 days, whichever occurred first. We used Kaplan Meier survival analysis to describe preterm neonatal mortality and Cox proportional hazards regression to assess predictors of preterm neonatal mortality over a maximum of 28 days of follow up. RESULTS: The cumulative incidence of preterm neonatal mortality was 19.8% (95% C.I: 16.7-23.5) at 28 days from birth. Birth asphyxia (adjusted hazard ratio [aHR], 14.80; 95% CI: 5.21 to 42.02), not receiving kangaroo mother care (aHR, 9.50; 95% CI: 5.37 to 16.78), delayed initiation of breastfeeding (aHR, 9.49; 95% CI: 2.84 to 31.68), late antenatal care (ANC) booking (aHR, 1.81 to 2.52; 95% CI: 1.11 to 7.11) and no ANC attendance (aHR, 3.56; 95% CI: 1.51 to 8.43), vaginal breech delivery (aHR, 3.04; 95% CI: 1.37 to 5.18), very preterm births (aHR, 3.17; 95% CI: 1.24 to 8.13), respiratory distress syndrome (RDS) (aHR, 2.50; 95% CI: 1.11 to 5.64) and hypothermia at the time of admission to the neonatal unit (aHR, 1.98; 95% CI: 1.18 to 3.33) increased the risk of preterm neonatal mortality. Attending more than 4 ANC visits (aHR, 0.35; 95% CI: 0.12 to 0.96) reduced the risk of preterm neonatal mortality. CONCLUSIONS: We observed a high cumulative incidence of mortality among preterm neonates born at a low-resource regional referral hospital in Uganda. The predictors of mortality among preterm neonates were largely modifiable factors occurring in the prenatal, natal and postnatal period (lack of ANC attendance, late ANC booking, vaginal breech delivery, birth asphyxia, respiratory distress syndrome, and hypothermia at the time of admission to the neonatal unit, not receiving kangaroo mother care and delayed initiation of breastfeeding). These findings suggest that investment in and enhancement of ANC attendance, intrapartum care, and the feasible essential newborn care interventions by providing the warm chain through kangaroo mother care, encouraging early initiation of breastfeeding, timely resuscitation for neonates when indicated and therapies reducing the incidence and severity of RDS could improve outcomes among preterm neonates in this setting.

Technical results from a trial of the FREO2 Low-Pressure Oxygen Storage system, Mbarara Regional Referral Hospital, Uganda.

Increased access to reliable medical oxygen would reduce the global burden of pneumonia. Oxygen concentrators have been shown to be an effective solution, however they have significant drawbacks when used in low-resource environments where pneumonia burden is the heaviest. Low quality grid power can damage oxygen concentrators and blackouts can prevent at-risk patients from receiving continual oxygen therapy. Gaps in prescribed oxygen flow can result in acquired brain injuries, extended hypoxemia and death. The FREO2 Low-Pressure Oxygen Storage (LPOS) system consists of a suite of improvements to a standard oxygen concentrator which address these limitations. This study reports the technical results of a field trial of the system in Mbarara, Uganda. During this trial, oxygen supplied from the LPOS system was distributed to four beds in the paediatric ward of Mbarara Regional Referral Hospital. Over a three-month period, medical-grade oxygen was made available to patients 100% of the time. This period was sufficient to quantify the ability of the LPOS system to deal with blackouts, maintenance, and an unscheduled repair to the LPOS store.