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There is an increasing global burden from chikungunya virus (CHIKV). Bangladesh reported a major epidemic in 2017, but it was unclear whether there had been prior widespread transmission. We conducted a nationally representative seroprevalence survey in 70 randomly selected communities immediately before the epidemic. We found that 69 of 2938 sampled individuals (2.4%) were seropositive to CHIKV. Seropositivity to dengue virus (adjusted odds ratio, 3.13 [95% confidence interval, 1.86-5.27]), male sex (0.59 [.36-.99]), and community presence of Aedes aegypti mosquitoes (1.80 [1.05-3.0]7) were significantly associated with CHIKV seropositivity. Using a spatial prediction model, we estimated that across the country, 4.99 (95% confidence interval, 4.89-5.08) million people had been previously infected. These findings highlight high population susceptibility before the major outbreak and that previous outbreaks must have been spatially isolated., Competing Interests: Potential conflicts of interest. All authors: No reported conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Background: The role of meningitis in causing deaths and in children under 5 is unclear, especially since widespread use of vaccines to prevent common causes of meningitis. Child Health and Mortality Prevention Surveillance (CHAMPS) uses post-mortem minimally invasive tissue sampling (MITS) and ante-mortem data to explore death causes. We aimed to assess meningitis's contribution to mortality and identify causative pathogens in children under 5 within CHAMPS Network sites., Method: In this observational study, we analyzed deaths in live-born children <5 years of age that occurred between December 16, 2016, and December 31, 2023, in CHAMPS catchments in six sub-Saharan African countries (Ethiopia, Kenya, Mali, Mozambique, Sierra Leone, South Africa) and Bangladesh. MITS was conducted within 24-72hours of death, including blood and cerebrospinal fluid (CSF) culture, multi-organism targeted nucleic acid amplification tests on blood, CSF and lung tissue, and histopathology of lung, liver and brain. Expert panels at each site reviewed data to attribute causes of death following ICD-10 standards., Result: Meningitis was in the causal pathway for 7.0% (270/3857) of deaths; in 4.8% (13/270) meningitis was considered the underlying condition. Neonates accounted for 65.9% (178/270) and infants or children 34.1% (92/270). Among neonatal meningitis deaths, 55.6% (99/178) occurred ≥72hours post-hospital admission; and common pathogens were Acinetobacter baumannii (49.5%, 49/99; mainly from South Africa) and Klebsiella pneumoniae (40.4%, 40/99). Forty-four percent (79/178) of neonatal meningitis deaths were community-associated, primarily due to K. pneumoniae (35.4%, 28/79) and Escherichia coli (13.9%, 11/79). Among infant and child meningitis deaths, 43.5% (40/92) occurred ≥72hours post-admission; and common pathogens were K. pneumoniae (42.5%,17/40) and A. baumannii (17.5%, 7/40). Among community-associated meningitis deaths in infants and children (56.5%, 52/92), Streptococcus pneumoniae (34.6%, 18/52) and K. pneumoniae (19.2%, 10/52) were common pathogens. Pathogen prevalence varied by region., Conclusion: Our study highlights meningitis as a significant contributor to under-5 mortality in low-middle-income countries. The prominent role of K. pneumoniae and A. baumannii, particularly in healthcare settings and specific regions, highlights the need for better infection control, targeted interventions, and more effective treatment strategies., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Nipah virus causes highly lethal disease, with case-fatality rates ranging from 40% to 100% in recognised outbreaks. No treatments or licensed vaccines are currently available for the prevention and control of Nipah virus infection. In 2019, WHO published an advanced draft of a research and development roadmap for accelerating development of medical countermeasures, including diagnostics, therapeutics, and vaccines, to enable effective and timely emergency response to Nipah virus outbreaks. This Personal View provides an update to the WHO roadmap by defining current research priorities for development of Nipah virus medical countermeasures, based primarily on literature published in the last 5 years and consensus opinion of 15 subject matter experts with broad experience in development of medical countermeasures for Nipah virus or experience in the epidemiology, ecology, or public health control of outbreaks of Nipah virus. The research priorities are organised into four main sections: cross-cutting issues (for those that apply to more than one category of medical countermeasures), diagnostics, therapeutics, and vaccines. The strategic goals and milestones identified in each section focus on key achievements that are needed over the next 6 years to ensure that the necessary tools are available for rapid response to future outbreaks of Nipah virus or related henipaviruses., Competing Interests: Declaration of interests CCB declares grant U19AI142764 from the National Institute of Allergy and Infectious Diseases (NIAID), the National Institutes of Health (NIH). CCB received royalties from the licensing of Hendra sG to Zoetis (Equivac HeV), Auro Vaccines (subsidiary of Aurobindo Pharma USA), and monoclonal antibodies to Henipaviruses, Absolute Antibody, UK, created and operating under the laws of the UK. CCB declares patents planned, issued, or pending for “Soluble forms of Hendra and Nipah virus G glycoprotein” (Australian patent number 2005327194; US patent numbers 8865171, 9045532, 9056902, 9533038, and 10053495); “Soluble forms of Hendra and Nipah virus F glycoprotein and uses thereof” (Australian patent numbers 2013276968; US patent numbers 10040825 and 10590172); “Human monoclonal antibodies against Hendra and Nipah viruses” (US patent numbers 7988971, 8313746, and 8858938); “Antibodies against F glycoprotein of Hendra and Nipah viruses” (US patent numbers 9982038 and 10738104); and “Cedar virus and methods of use” (US patent number 10227664). EdW received financial support from the Intramural Research Program, NIAID, NIH; and royalties related to the vesicular stomatitis virus Nipah vaccine mentioned in this manuscript. ESG received funding (through a grant to ESG's institution) from Stanford University (Coalition for Epidemic Preparedness Innovations [CEPI] was the primary donor) to work on two studies related to development of Nipah vaccines, including development of consent documents for future trials in Bangladesh. ESG is also the principal investigator of a U01 (cooperative agreement) from NIAID, NIH for the study of Nipah virus spillovers in Bangladesh. ESG also received funding (grant to institution) from the Defense Advanced Research Projects Agency to study the dynamics of Nipah virus transmission in bats in Bangladesh. ESG received a consultancy contract from Montana State University to provide technical guidance to a study collecting biological samples from bats in Bangladesh; and served as an unpaid elected board member for the American Society for Tropical Medicine and Hygiene. LTM received financial support as a science consultant at FIND; and received consulting fees as a science consultant at FIND. SPL received research funding from CEPI to support the development of two vaccine candidates against Nipah virus. SP received research funding from Public Health Vaccines through a subaward from Stanford University. CFS declares patents planned, issued, or pending for “Nipah Henipavirus virus replicon particles and their use” (US patent number WO2023/133077 A1). KAM, AJM, NMM, JTO, MTO, and AKU received financial support for the completion of this Personal View from the Wellcome Trust (grant number 226538/Z/22/Z; payments were made to the University of Minnesota). Wellcome supported travel to attend the workshop identified in this Personal View for CCB, EdW, ANF, ESG, KH, SPL, LTM, KAM, JTO, M-PP, MTO, SP, and MR. PCF, PJH, and JPG worked at the Wellcome Trust during the time that this Personal View was completed. No authors were paid by a pharmaceutical company or any other agency to write this Personal View. All other authors declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.)

SARS-CoV-2 superspreading occurs when transmission is highly efficient and/or an individual infects many others, contributing to rapid spread. To better quantify heterogeneity in SARS-CoV-2 transmission, particularly superspreading, we performed a systematic review of transmission events with data on secondary attack rates or contact tracing of individual index cases published before September 2021 prior to the emergence of variants of concern and widespread vaccination. We reviewed 592 distinct events and 9,883 index cases from 491 papers. A meta-analysis of secondary attack rates identified substantial heterogeneity across 12 chosen event types/settings, with the highest transmission (25-35%) in co-living situations including households, nursing homes, and other congregate housing. Among index cases, 67% reported zero secondary cases and only 3% (287) infected >5 secondary cases ("superspreaders"). Index case demographic data were limited, with only 55% of individuals reporting age, sex, symptoms, real-time polymerase chain reaction (PCR) cycle threshold values, or total contacts. With the data available, we identified a higher percentage of superspreaders among symptomatic individuals, individuals aged 49-64 years, and individuals with over 100 total contacts. Addressing gaps in the literature regarding transmission events and contact tracing is needed to properly explain the heterogeneity in transmission and facilitate control efforts for SARS-CoV-2 and other infections.

Multiplex-based serological surveillance is a valuable but underutilized tool to understand gaps in population-level exposure, susceptibility, and immunity to infectious diseases. Assays for which blood samples can be tested for antibodies against several pathogens simultaneously, such as multiplex bead immunoassays, can more efficiently integrate public health surveillance in low- and middle-income countries. On March 7-8, 2023 a group of experts representing research institutions, multilateral organizations, private industry, and country partners met to discuss experiences, identify challenges and solutions, and create a community of practice for integrated, multi-pathogen serosurveillance using multiplex bead assay technologies. Participants were divided into six working groups: 1) supply chain; 2) laboratory assays; 3) seroepidemiology; 4) data analytics; 5) sustainable implementation; and 6) use case scenarios. These working groups discussed experiences, challenges, solutions, and research needs to facilitate integrated, multi-pathogen serosurveillance for public health. Several solutions were proposed to address challenges that cut across working groups.

Importance: The emergence of acute neurological symptoms in children necessitates immediate intervention. Although low- and middle-income countries (LMICs) bear the highest burden of neurological diseases, there is a scarcity of diagnostic and therapeutic resources. Therefore, current understanding of the etiology of neurological emergencies in LMICs relies mainly on clinical diagnoses and verbal autopsies., Objective: To characterize the association of premortem neurological symptoms and their management with postmortem-confirmed cause of death among children aged younger than 5 years in LMICs and to identify current gaps and improve strategies to enhance child survival., Design, Setting, and Participants: This cross-sectional study was conducted between December 3, 2016, and July 22, 2022, at the 7 participating sites in the Child Health and Mortality Prevention Surveillance (CHAMPS) network (Bangladesh, Ethiopia, Kenya, Mali, Mozambique, Sierra Leone, and South Africa). Minimally invasive tissue sampling was performed at the CHAMPS sites with specimens from deceased children aged younger than 5 years. This study included deceased children who underwent a premortem neurological evaluation and had a postmortem-confirmed cause of death. Data analysis was performed between July 22, 2022, and January 15, 2023., Main Outcomes and Measures: Descriptive analysis was performed using neurological evaluations from premortem clinical records and from postmortem determination of cause of death (based on histopathology, microbiological testing, clinical records, and verbal autopsies)., Results: Of the 2127 deaths of children codified during the study period, 1330 (62.5%) had neurological evaluations recorded and were included in this analysis. The 1330 children had a median age of 11 (IQR, 2-324) days; 745 (56.0%) were male and 727 (54.7%) presented with neurological symptoms during illness before death. The most common postmortem-confirmed neurological diagnoses related to death were hypoxic events (308 [23.2%]), meningoencephalitis (135 [10.2%]), and cerebral malaria (68 [5.1%]). There were 12 neonates with overlapping hypoxic events and meningoencephalitis, but there were no patients with overlapping meningoencephalitis and cerebral malaria. Neurological symptoms were similar among diagnoses, and no combination of symptoms was accurate in differentiating them without complementary tools. However, only 25 children (18.5%) with meningitis had a lumbar puncture performed before death. Nearly 90% of deaths (442 of 511 [86.5%]) with neurological diagnoses in the chain of events leading to death were considered preventable., Conclusions and Relevance: In this cross-sectional study of children aged younger than 5 years, neurological symptoms were frequent before death. However, clinical phenotypes were insufficient to differentiate the most common underlying neurological diagnoses. The low rate of lumbar punctures performed was especially worrying, suggesting a challenge in quality of care of children presenting with neurological symptoms. Improved diagnostic management of neurological emergencies is necessary to ultimately reduce mortality in this vulnerable population.

Japanese encephalitis virus (JEV) is a major threat to human health. Bangladesh is considering introducing a JEV vaccine; however, the investment case is hampered by a limited understanding of key aspects of JEV ecology. We conducted a seroprevalence study in a high-incidence region using an assay that limits cross-reactivity with dengue virus. We also trapped mosquitoes and collected information about potential host species. We used mathematical models to recover risk factors for infection and underlying probabilities of severe disease and death. We observed 19.0% [95% confidence interval (CI):17.1 to 21.1] of JEV antibodies. On average, 0.7% (95% CI: 0.2 to 2.0) of the susceptible population gets infected yearly, with pig proximity being the main human infection risk factor. Our traps captured 10 different mosquito species that have been linked with JEV transmission. We estimated that 1 in 1000 infections results in severe disease, 1 in 10,000 results in death, and 76% of severe cases are missed by surveillance.

Background: Hepatitis E virus (HEV) leads to high mortality in pregnant women in low-income countries. We aimed to evaluate the safety of a HEV vaccine and its effectiveness in preventing hepatitis E during pregnancy., Methods: In this phase 4, double-blind, cluster-randomised trial, 67 villages in Matlab, Bangladesh, were randomised 1:1 to receive HEV239 (a recombinant HEV vaccine) or a control vaccine (Hepa-B, a hepatitis B vaccine), using block randomisation with random number tables and blocks of size eight, stratified by cluster population size. Eligible non-pregnant women (aged 16-39 years) were vaccinated intramuscularly on day 0, at 1 month, and at 6 months, and followed up for 2 years after the last immunisation. The primary endpoint was hepatitis E in the pregnant, per-protocol population (those who received all three doses within 2 days of the scheduled dates), while safety was a secondary endpoint, assessed in the intention-to-treat (ITT) population (participants who received at least one dose). Solicited adverse events were recorded for the first 7 days after each dose, and unsolicited events until 2 years after a participant's final dose. Pregnancy-related safety outcomes were assessed in the pregnant ITT population. This study is registered with ClinicalTrials.gov (NCT02759991)., Findings: Between Oct 2, 2017, and Feb 28, 2019, 19 460 participants were enrolled and received either HEV239 (9478 [48·7%] participants, 33 clusters) or Hepa-B (9982 [51·3%] participants, 34 clusters), of whom 17 937 (92·2%) participants received three doses and 17 613 (90·5%) were vaccinated according to protocol (8524 [48·4%] in the HEV239 group and 9089 [51·6%] in the control group). No pregnant participants were confirmed to have hepatitis E in either treatment group. HEV239 showed a mild safety profile, similar to Hepa-B, with no difference in the proportion of solicited adverse events between groups and no severe solicited events. Pain was the most common local symptom (1215 [12·8%] HEV239 recipients and 1218 [12·2%] Hepa-B recipients) and fever the most common systemic symptom (141 [1·5%] HEV239 recipients and 145 [1·5%] Hepa-B recipients). None of the serious adverse events or deaths were vaccine related. Among pregnant participants, the HEV239 group had a higher risk of miscarriage (136 [5·7%] of 2407 pregnant participants) compared with the control group (102 [3·9%] of 2604; adjusted odds ratio 1·54 [95% CI 1·15-2·08])., Interpretation: The effectiveness of HEV239 in pregnant women remains uncertain. HEV239 was safe and well tolerated in non-pregnant women, but findings regarding miscarriage warrant further investigation., Funding: Research Council of Norway; Innovax., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

In resource-limited settings where vital registration and medical death certificates are unavailable or incomplete, verbal autopsy (VA) is often used to attribute causes of death (CoD) and prioritize resource allocation and interventions. We aimed to determine the CoD concordance between InterVA and CHAMPS's method. The causes of death (CoDs) of children <5 were determined by two methods using data from seven low- and middle-income countries (LMICs) enrolled in the Child Health and Mortality Prevention Surveillance (CHAMPS) network. The first CoD method was from the DeCoDe panel using data from Minimally Invasive Tissue Sampling (MITS), whereas the second method used Verbal Autopsy (VA), which utilizes the InterVA software. This analysis evaluated the agreement between the two using Lin's concordance correlation coefficient. The overall concordance of InterVA4 and DeCoDe in assigning causes of death across surveillance sites, age groups, and causes of death was poor (0.75 with 95% CI: 0.73-0.76) and lacked precision. We found substantial differences in agreement by surveillance site, with Mali showing the lowest and Mozambique and Ethiopia the highest concordance. The InterVA4 assigned CoD agrees poorly in assigning causes of death for U5s and stillbirths. Because VA methods are relatively easy to implement, such systems could be more useful if algorithms were improved to more accurately reflect causes of death, for example, by calibrating algorithms to information from programs that used detailed diagnostic testing to improve the accuracy of COD determination., Competing Interests: The authors have declared that no competing interests exist., (Copyright: This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.)

Maternal hypertension may be an underrecognized but important risk factor for perinatal death in low resource settings. We investigated the association of maternal hypertension and perinatal mortality in rural Bangladesh. This nested, matched case-control study used data from a 2019 cross-sectional survey and demographic surveillance database in Baliakandi, Bangladesh. We randomly matched each pregnancy ending in perinatal death with five pregnancies in which the neonate survived beyond seven days based on maternal age, education, and wealth quintile. We estimated associations of antenatal care-seeking and self-reported hypertension with perinatal mortality using conditional logistic regression and used median and interquartile ranges to assess the mediation of antenatal care by timing or frequency. Among 191 cases and 934 matched controls, hypertension prevalence was 14.1% among cases and 7.7% among controls. Compared with no diagnosis, the probability of perinatal death was significantly higher among women with a pre-gestational hypertension diagnosis (OR 2.90, 95% CI 1.29, 6.57), but not among women with diagnosis during pregnancy (OR 1.68, 95% CI 0.98, 2.98). We found no association between the number of antenatal care contacts and perinatal death (p = 0.66). Among women with pre-gestational hypertension who experienced a perinatal death, 78% had their first antenatal contact in the sixth or seventh month of gestation. Hypertension was more common among rural women who experience a perinatal death. Greater effort to prevent hypertension prior to conception and provide early maternity care to women with hypertension could improve perinatal outcomes in rural Bangladesh., Competing Interests: The authors declare that they have no competing interests., (Copyright: © 2024 Bear et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Introduction: Determining aetiology of severe illness can be difficult, especially in settings with limited diagnostic resources, yet critical for providing life-saving care. Our objective was to describe the accuracy of antemortem clinical diagnoses in young children in high-mortality settings, compared with results of specific postmortem diagnoses obtained from Child Health and Mortality Prevention Surveillance (CHAMPS)., Methods: We analysed data collected during 2016-2022 from seven sites in Africa and South Asia. We compared antemortem clinical diagnoses from clinical records to a reference standard of postmortem diagnoses determined by expert panels at each site who reviewed the results of histopathological and microbiological testing of tissue, blood, and cerebrospinal fluid. We calculated test characteristics and 95% CIs of antemortem clinical diagnostic accuracy for the 10 most common causes of death. We classified diagnostic discrepancies as major and minor, per Goldman criteria later modified by Battle., Results: CHAMPS enrolled 1454 deceased young children aged 1-59 months during the study period; 881 had available clinical records and were analysed. The median age at death was 11 months (IQR 4-21 months) and 47.3% (n=417) were female. We identified a clinicopathological discrepancy in 39.5% (n=348) of deaths; 82.3% of diagnostic errors were major. The sensitivity of clinician antemortem diagnosis ranged from 26% (95% CI 14.6% to 40.3%) for non-infectious respiratory diseases (eg, aspiration pneumonia, interstitial lung disease, etc) to 82.2% (95% CI 72.7% to 89.5%) for diarrhoeal diseases. Antemortem clinical diagnostic specificity ranged from 75.2% (95% CI 72.1% to 78.2%) for diarrhoeal diseases to 99.0% (95% CI 98.1% to 99.6%) for HIV., Conclusions: Antemortem clinical diagnostic errors were common for young children who died in areas with high childhood mortality rates. To further reduce childhood mortality in resource-limited settings, there is an urgent need to improve antemortem diagnostic capability through advances in the availability of diagnostic testing and clinical skills., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)

Background: Nipah virus (NiV), a highly lethal virus in humans, circulates in Pteropus bats throughout South and Southeast Asia. Difficulty in obtaining viral genomes from bats means we have a poor understanding of NiV diversity., Methods: We develop phylogenetic approaches applied to the most comprehensive collection of genomes to date (N=257, 175 from bats, 73 from humans) from six countries over 22 years (1999-2020). We divide the four major NiV sublineages into 15 genetic clusters. Using Approximate Bayesian Computation fit to a spatial signature of viral diversity, we estimate the presence and the average size of genetic clusters per area., Results: We find that, within any bat roost, there are an average of 2.4 co-circulating genetic clusters, rising to 5.5 clusters at areas of 1500-2000km2. We estimate that each genetic cluster occupies an average area of 1.3million km2 (95%CI: 0.6-2.3 million), with 14 clusters in an area of 100,000km2 (95%CI: 6-24). In the few sites in Bangladesh and Cambodia where genomic surveillance has been concentrated, we estimate that most clusters have been identified, but only ∼15% of overall NiV diversity has been uncovered., Conclusion: Our findings are consistent with entrenched co-circulation of distinct lineages, even within roosts, coupled with slow migration over larger spatial scales., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Hepatitis E virus (HEV) is a major cause of acute jaundice in South Asia. Gaps in our understanding of transmission are driven by non-specific symptoms and scarcity of diagnostics, impeding rational control strategies. In this context, serological data can provide important proxy measures of infection. We enrolled a population-representative serological cohort of 2,337 individuals in Sitakunda, Bangladesh. We estimated the annual risks of HEV infection and seroreversion both using serostatus changes between paired serum samples collected 9 months apart, and by fitting catalytic models to the age-stratified cross-sectional seroprevalence. At baseline, 15% (95 CI: 14-17%) of people were seropositive, with seroprevalence highest in the relatively urban south. During the study, 27 individuals seroreverted (annual seroreversion risk: 15%, 95 CI: 10-21%), and 38 seroconverted (annual infection risk: 3%, 95CI: 2-5%). Relying on cross-sectional seroprevalence data alone, and ignoring seroreversion, underestimated the annual infection risk five-fold (0.6%, 95 CrI: 0.5-0.6%). When we accounted for the observed seroreversion in a reversible catalytic model, infection risk was more consistent with measured seroincidence. Our results quantify HEV infection risk in Sitakunda and highlight the importance of accounting for seroreversion when estimating infection incidence from cross-sectional seroprevalence data.

Nipah virus Bangladesh (NiVB) is a bat-borne zoonosis transmitted between people through the respiratory route. The risk posed by related henipaviruses, including Hendra virus (HeV) and Nipah virus Malaysia (NiVM), is less clear. We conducted a broad search of the literature encompassing both human infections and animal models to synthesize evidence about potential for person-to-person spread. More than 600 human infections have been reported in the literature, but information on viral shedding was only available for 40 case-patients. There is substantial evidence demonstrating person-to-person transmission of NiVB, and some evidence for NiVM. Less direct evidence is available about the risk for person-to-person transmission of HeV, but animals infected with HeV shed more virus in the respiratory tract than those infected with NiVM, suggesting potential for transmission. As the group of known henipaviruses continues to grow, shared protocols for conducting and reporting from human investigations and animal experiments are urgently needed., Competing Interests: Potential conflicts of interest. The authors: No reported conflicts of interest. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Background: The Child Health and Mortality Prevention Surveillance (CHAMPS) Network programme undertakes post-mortem minimally invasive tissue sampling (MITS), together with collection of ante-mortem clinical information, to investigate causes of childhood deaths across multiple countries. We aimed to evaluate the overall contribution of pneumonia in the causal pathway to death and the causative pathogens of fatal pneumonia in children aged 1-59 months enrolled in the CHAMPS Network., Methods: In this observational study we analysed deaths occurring between Dec 16, 2016, and Dec 31, 2022, in the CHAMPS Network across six countries in sub-Saharan Africa (Ethiopia, Kenya, Mali, Mozambique, Sierra Leone, and South Africa) and one in South Asia (Bangladesh). A standardised approach of MITS was undertaken on decedents within 24-72 h of death. Diagnostic tests included blood culture, multi-organism targeted nucleic acid amplifications tests (NAATs) of blood and lung tissue, and histopathology examination of various organ tissue samples. An interdisciplinary expert panel at each site reviewed case data to attribute the cause of death and pathogenesis thereof on the basis of WHO-recommended reporting standards., Findings: Pneumonia was attributed in the causal pathway of death in 455 (40·6%) of 1120 decedents, with a median age at death of 9 (IQR 4-19) months. Causative pathogens were identified in 377 (82·9%) of 455 pneumonia deaths, and multiple pathogens were implicated in 218 (57·8%) of 377 deaths. 306 (67·3%) of 455 deaths occurred in the community or within 72 h of hospital admission (presumed to be community-acquired pneumonia), with the leading bacterial pathogens being Streptococcus pneumoniae (108 [35·3%]), Klebsiella pneumoniae (78 [25·5%]), and non-typeable Haemophilus influenzae (37 [12·1%]). 149 (32·7%) deaths occurred 72 h or more after hospital admission (presumed to be hospital-acquired pneumonia), with the most common pathogens being K pneumoniae (64 [43·0%]), Acinetobacter baumannii (19 [12·8%]), S pneumoniae (15 [10·1%]), and Pseudomonas aeruginosa (15 [10·1%]). Overall, viruses were implicated in 145 (31·9%) of 455 pneumonia-related deaths, including 54 (11·9%) of 455 attributed to cytomegalovirus and 29 (6·4%) of 455 attributed to respiratory syncytial virus., Interpretation: Pneumonia contributed to 40·6% of all childhood deaths in this analysis. The use of post-mortem MITS enabled biological ascertainment of the cause of death in the majority (82·9%) of childhood deaths attributed to pneumonia, with more than one pathogen being commonly implicated in the same case. The prominent role of K pneumoniae, non-typable H influenzae, and S pneumoniae highlight the need to review empirical management guidelines for management of very severe pneumonia in low-income and middle-income settings, and the need for research into new or improved vaccines against these pathogens., Funding: Bill & Melinda Gates Foundation., Competing Interests: Declaration of interests CGW received honoraria from the University of St Andrews for speaking to alumni about CHAMPS and global health work. SAM has received grants from the Bill & Melinda Gates Foundation, GSK, Pfizer, Minervax, Novavax, Merck, Providence, Gritstone, and ImmunityBio. SAM has received honoraria from GSK for lecturing. GR has received grants from Fleming Fund Kenya Country, Deutsche Forschungsgemeinschaft, and bioMerieux. SA and JAGS have received support for attending meetings or travels, or both, for WHO, Bill & Melinda Gates Foundation (SA) and the International Society of Pneumonia & Pneumococcal Diseases (JAGS). CGW, JAGS, and SAM report serving on data safety monitoring boards for Safety Platform for Emergency VACcines (SPEAC; CGW), PATH (SAM), Centre for the AIDS Programme of Research in South Africa (CAPRISA; SAM), MRC The Gambia (JAGS) and ILiAD Biotechnologies (JAGS). All other authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Background: Malaria is a leading cause of childhood mortality worldwide. However, accurate estimates of malaria prevalence and causality among patients who die at the country level are lacking due to the limited specificity of diagnostic tools used to attribute etiologies. Accurate estimates are crucial for prioritizing interventions and resources aimed at reducing malaria-related mortality., Methods: Seven Child Health and Mortality Prevention Surveillance (CHAMPS) Network sites collected comprehensive data on stillbirths and children <5 years, using minimally invasive tissue sampling (MITS). A DeCoDe (Determination of Cause of Death) panel employed standardized protocols for assigning underlying, intermediate, and immediate causes of death, integrating sociodemographic, clinical, laboratory (including extensive microbiology, histopathology, and malaria testing), and verbal autopsy data. Analyses were conducted to ascertain the strength of evidence for cause of death (CoD), describe factors associated with malaria-related deaths, estimate malaria-specific mortality, and assess the proportion of preventable deaths., Findings: Between December 3, 2016, and December 31, 2022, 2673 deaths underwent MITS and had a CoD attributed from four CHAMPS sites with at least 1 malaria-attributed death. No malaria-attributable deaths were documented among 891 stillbirths or 924 neonatal deaths, therefore this analysis concentrates on the remaining 858 deaths among children aged 1-59 months. Malaria was in the causal chain for 42.9% (126/294) of deaths from Sierra Leone, 31.4% (96/306) in Kenya, 18.2% (36/198) in Mozambique, 6.7% (4/60) in Mali, and 0.3% (1/292) in South Africa. Compared to non-malaria related deaths, malaria-related deaths skewed towards older infants and children (p < 0.001), with 71.0% among ages 12-59 months. Malaria was the sole infecting pathogen in 184 (70.2%) of malaria-attributed deaths, whereas bacterial and viral co-infections were identified in the causal pathway in 24·0% and 12.2% of cases, respectively. Malnutrition was found at a similar level in the causal pathway of both malaria (26.7%) and non-malaria (30.7%, p = 0.256) deaths. Less than two-thirds (164/262; 62.6%) of malaria deaths had received antimalarials prior to death. Nearly all (98·9%) malaria-related deaths were deemed preventable., Interpretation: Malaria remains a significant cause of childhood mortality in the CHAMPS malaria-endemic sites. The high bacterial co-infection prevalence among malaria deaths underscores the potential benefits of antibiotics for severe malaria patients. Compared to non-malaria deaths, many of malaria-attributed deaths are preventable through accessible malaria control measures., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Our understanding of cholera transmission and burden largely relies on clinic-based surveillance, which can obscure trends, bias burden estimates and limit the impact of targeted cholera-prevention measures. Serological surveillance provides a complementary approach to monitoring infections, although the link between serologically derived infections and medically attended disease incidence-shaped by immunological, behavioral and clinical factors-remains poorly understood. We unravel this cascade in a cholera-endemic Bangladeshi community by integrating clinic-based surveillance, healthcare-seeking and longitudinal serological data through statistical modeling. Combining the serological trajectories with a reconstructed incidence timeline of symptomatic cholera, we estimated an annual Vibrio cholerae O1 infection incidence rate of 535 per 1,000 population (95% credible interval 514-556), with incidence increasing by age group. Clinic-based surveillance alone underestimated the number of infections and reported cases were not consistently correlated with infection timing. Of the infections, 4 in 3,280 resulted in symptoms, only 1 of which was reported through the surveillance system. These results impart insights into cholera transmission dynamics and burden in the epicenter of the seventh cholera pandemic, where >50% of our study population had an annual V. cholerae O1 infection, and emphasize the potential for a biased view of disease burden and infection risk when depending solely on clinical surveillance data., (© 2024. The Author(s).)

Delays in illness recognition, healthcare seeking, and in the provision of appropriate clinical care are common in resource-limited settings. Our objective was to determine the frequency of delays in the "Three Delays-in-Healthcare", and factors associated with delays, among deceased infants and children in seven countries with high childhood mortality. We conducted a retrospective, descriptive study using data from verbal autopsies and medical records for infants and children aged 1-59 months who died between December 2016 and February 2022 in six sites in sub-Saharan Africa and one in South Asia (Bangladesh) and were enrolled in Child Health and Mortality Prevention Surveillance (CHAMPS). Delays in 1) illness recognition in the home/decision to seek care, 2) transportation to healthcare facilities, and 3) the receipt of clinical care in healthcare facilities were categorized according to the "Three Delays-in-Healthcare". Comparisons in factors associated with delays were made using Chi-square testing. Information was available for 1,326 deaths among infants and under 5 children. The majority had at least one identified delay (n = 854, 64%). Waiting >72 hours after illness recognition to seek health care (n = 422, 32%) was the most common delay. Challenges in obtaining transportation occurred infrequently when seeking care (n = 51, 4%). In healthcare facilities, prescribed medications were sometimes unavailable (n = 102, 8%). Deceased children aged 12-59 months experienced more delay than infants aged 1-11 months (68% vs. 61%, P = 0.018). Delays in seeking clinical care were common among deceased infants and children. Additional study to assess the frequency of delays in seeking clinical care and its provision among children who survive is warranted., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: CGW received honoraria from the University of St. Andrews for speaking to alumni about CHAMPS and global health work. JAGS reports receiving funding from the Wellcome Trust, UK FCDO, European Union, and the National Institute for Health Research. SM has received grants from the Bill & Melinda Gates Foundation, GSK, Pfizer, Minervax, Novavax, Providence, Gritstone, and ImmunityBio. SM has received honoraria from GSK for lecturing. CGW and SM report serving on data safety monitoring boards for SPEAC (CGW) and PATH and CAPRISA (SM). DT-F reports having received the support of a fellowship from “La Caixa” Foundation (ID 100010434, “LCF/BQ/DR21/11880018”). All other investigators declare no competing interests., (Copyright: This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.)

Estimates of excess mortality can provide insight into direct and indirect impacts of the coronavirus disease 2019 (COVID-19) pandemic beyond deaths specifically attributed to COVID-19. We analyzed death certificate data from Baltimore City, Maryland, from March 1, 2020, to March 31, 2021, and found that 1,725 individuals (95% confidence interval: 1,495, 1,954) died in excess of what was expected from all-cause mortality trends in 2016-2019; 1,050 (61%) excess deaths were attributed to COVID-19. Observed mortality was 23%-32% higher than expected among individuals aged 50 years and older. Non-White residents of Baltimore City also experienced 2 to 3 times higher rates of excess mortality than White residents (e.g., 37.4 vs. 10.7 excess deaths per 10,000 population among Black residents vs. White residents). There was little to no observed excess mortality among residents of hospice, long-term care, and nursing home facilities, despite accounting for nearly 30% (312/1,050) of recorded COVID-19 deaths. There was significant geographic variation in excess mortality within the city, largely following racial population distributions. These results demonstrate the substantial and unequal impact of the COVID-19 pandemic on Baltimore City residents and the importance of building robust, timely surveillance systems to track disparities and inform targeted strategies to remediate the impact of future epidemics., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Klebsiella pneumoniae is an important cause of nosocomial and community-acquired pneumonia and sepsis in children, and antibiotic-resistant K pneumoniae is a growing public health threat. We aimed to characterise child mortality associated with this pathogen in seven high-mortality settings., Methods: We analysed Child Health and Mortality Prevention Surveillance (CHAMPS) data on the causes of deaths in children younger than 5 years and stillbirths in sites located in seven countries across sub-Saharan Africa (Ethiopia, Kenya, Mali, Mozambique, Sierra Leone, and South Africa) and south Asia (Bangladesh) from Dec 9, 2016, to Dec 31, 2021. CHAMPS sites conduct active surveillance for deaths in catchment populations and following reporting of an eligible death or stillbirth seek consent for minimally invasive tissue sampling followed by extensive aetiological testing (microbiological, molecular, and pathological); cases are reviewed by expert panels to assign immediate, intermediate, and underlying causes of death. We reported on susceptibility to antibiotics for which at least 30 isolates had been tested, and excluded data on antibiotics for which susceptibility testing is not recommended for Klebsiella spp due to lack of clinical activity (eg, penicillin and ampicillin)., Findings: Among 2352 child deaths with cause of death assigned, 497 (21%, 95% CI 20-23) had K pneumoniae in the causal chain of death; 100 (20%, 17-24) had K pneumoniae as the underlying cause. The frequency of K pneumoniae in the causal chain was highest in children aged 1-11 months (30%, 95% CI 26-34; 144 of 485 deaths) and 12-23 months (28%, 22-34; 63 of 225 deaths); frequency by site ranged from 6% (95% CI 3-11; 11 of 184 deaths) in Bangladesh to 52% (44-61; 71 of 136 deaths) in Ethiopia. K pneumoniae was in the causal chain for 450 (22%, 95% CI 20-24) of 2023 deaths that occurred in health facilities and 47 (14%, 11-19) of 329 deaths in the community. The most common clinical syndromes among deaths with K pneumoniae in the causal chain were sepsis (44%, 95% CI 40-49; 221 of 2352 deaths), sepsis in conjunction with pneumonia (19%, 16-23; 94 of 2352 deaths), and pneumonia (16%, 13-20; 80 of 2352 deaths). Among K pneumoniae isolates tested, 121 (84%) of 144 were resistant to ceftriaxone and 80 (75%) of 106 to gentamicin., Interpretation: K pneumoniae substantially contributed to deaths in the first 2 years of life across multiple high-mortality settings, and resistance to antibiotics used for sepsis treatment was common. Improved strategies are needed to rapidly identify and appropriately treat children who might be infected with this pathogen. These data suggest a potential impact of developing and using effective K pneumoniae vaccines in reducing neonatal, infant, and child deaths globally., Funding: Bill & Melinda Gates Foundation., Competing Interests: Declaration of interests SEA, KLK, and MT report receiving funding from Emory University. JAGS reports receiving funding from Emory University, the Bill & Melinda Gates Foundation, Wellcome Trust, UK Foreign Commonwealth & Development Office, European Union, and National Institute for Health Research. SMad reports receiving funds from the Bill & Melinda Gates Foundation, Pfizer, Minervax, GSK, South African Medical Research Council, Merck, PATH, and Center for the AIDS Programme of Research in South Africa. All other authors declare no competing interests., (Published by Elsevier Ltd.)

Background: Antimicrobial resistance (AMR) is a growing global health threat that contributes to substantial neonatal mortality. Bangladesh has reported some of the highest rates of AMR among bacteria causing neonatal sepsis. As AMR colonization among newborns can predispose to infection with these bacteria, we aimed to characterize the frequency of and risk factors for colonization of mothers and newborns during hospitalization for delivery., Methods: We enrolled pregnant women presenting for delivery to a tertiary care hospital in Faridpur, Bangladesh. We collected vaginal and rectal swabs from mothers pre- and post-delivery, rectal swabs from newborns, and swabs from the hospital environment. Swabs were plated on agars selective for extended-spectrum-beta-lactamase producing bacteria (ESBL-PB) and carbapenem-resistant bacteria (CRB). We performed logistic regression to determine factors associated with ESBL-PB/CRB colonization., Results: We enrolled 177 women and their newborns during February-October 2020. Prior to delivery, 77% of mothers were colonized with ESBL-PB and 15% with CRB. 79% of women underwent cesarean deliveries (C-section). 98% of women received antibiotics. Following delivery, 98% of mothers and 89% of newborns were colonized with ESBL-PB and 89% of mothers and 72% of newborns with CRB. Of 290 environmental samples, 77% were positive for ESBL-PB and 69% for CRB. Maternal pre-delivery colonization was associated with hospitalization during pregnancy (RR for ESBL-PB 1.24, 95% CI 1.10-1.40; CRB 2.46, 95% CI 1.39-4.37). Maternal post-delivery and newborn colonization were associated with C-section (RR for maternal CRB 1.31, 95% CI 1.08-1.59; newborn ESBL-PB 1.34, 95% CI 1.09-1.64; newborn CRB 1.73, 95% CI 1.20-2.47)., Conclusions: In this study, we observed high rates of colonization with ESBL-PB/CRB among mothers and newborns, with pre-delivery colonization linked to prior healthcare exposure. Our results demonstrate this trend may be driven by intense use of antibiotics, frequent C-sections, and a contaminated hospital environment. These findings highlight that greater attention should be given to the use of perinatal antibiotics, improved surgical stewardship for C-sections, and infection prevention practices in healthcare settings to reduce the high prevalence of colonization with AMR organisms., (© 2024. The Author(s).)

Objectives: Interpreting real-time reverse transcription-polymerase chain reaction (rRT-PCR) results for human avian influenza A virus (AIV) detection in contaminated settings like live bird markets (LBMs) without serology or viral culture poses a challenge., Methods: During February-March 2012 and November 2012-February 2013, we screened workers at nine LBMs in Dhaka, Bangladesh, to confirm molecular detections of AIV RNA in respiratory specimens with serology. We tested nasopharyngeal (NP) and throat swabs from workers with influenza-like illness (ILI) and NP, throat, and arm swabs from asymptomatic workers for influenza virus by rRT-PCR and sera for seroconversion and antibodies against HPAI A(H5N1) and A(H9N2) viruses., Results: Among 1273 ILI cases, 34 (2.6%) had A(H5), 56 (4%) had A(H9), and six (0.4%) had both A(H5) and A(H9) detected by rRT-PCR. Of 192 asymptomatic workers, A(H5) was detected in eight (4%) NP and 38 (20%) arm swabs. Of 28 ILI cases with A(H5) or A(H9) detected, none had evidence of seroconversion, but one (3.5%) and 12 (43%) were seropositive for A(H5) and A(H9), respectively., Conclusion: Detection of AIV RNA in respiratory specimens from symptomatic and asymptomatic LBM workers without evidence of seroconversion or virus isolation suggests environmental contamination, emphasizing caution in interpreting rRT-PCR results in high viral load settings., Competing Interests: Declarations of Competing Interest The authors have no competing interests to declare., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Bats harbor diverse intracellular Bartonella bacteria, but there is limited understanding of the factors that influence transmission over time. Investigation of Bartonella dynamics in bats could reveal general factors that control transmission of multiple bat-borne pathogens, including viruses. We used molecular methods to detect Bartonella DNA in paired bat (Pteropus medius) blood and bat flies in the family Nycteribiidae collected from a roost in Faridpur, Bangladesh between September 2020 and January 2021. We detected high prevalence of Bartonella DNA in bat blood (35/55, 64%) and bat flies (59/60, 98%), with sequences grouping into three phylogenetic clades. Prevalence in bat blood increased over the study period (33% to 90%), reflecting an influx of juvenile bats in the population and an increase in the prevalence of bat flies. Discordance between infection status and the clade/genotype of detected Bartonella was also observed in pairs of bats and their flies, providing evidence that bat flies take blood meals from multiple bat hosts. This evidence of bat fly transfer between hosts and the changes in Bartonella prevalence during a period of increasing nycteribiid density support the role of bat flies as vectors of bartonellae. The study provides novel information on comparative prevalence and genetic diversity of Bartonella in pteropodid bats and their ectoparasites, as well as demographic factors that affect Bartonella transmission and potentially other bat-borne pathogens., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Healthcare workers (HCWs) are at increased risk of tuberculosis infection (TBI). We estimated the prevalence and incidence of TBI and risk factors among HCWs in Bangladeshi hospitals to target TB infection prevention and control (IPC) interventions., Methods: During 2013-2016, we conducted a longitudinal study among HCWs in four chest disease hospitals. At baseline, we administered a questionnaire on sociodemographic and occupational factors for TB, tuberculin skin tests (TST) in all hospitals, and QuantiFERON ®-TB Gold in-Tube (QFT-GIT) tests in one hospital. We assessed factors associated with baseline TST positivity (induration ≥10mm), TST conversion (induration increase ≥10mm from baseline), baseline QFT-GIT positivity (interferon-gamma ≥0.35 IU/mL), and QFT-GIT conversion (interferon-gamma <0.35 IU/mL to ≥0.35 IU/mL). We included factors with a biologically plausible relationship with TBI identified in prior studies or having an association (p = <0.20) in the bivariate analyses with TST positivity or QFT-GIT positivity in multivariable generalized linear models. The Kaplan-Meier was used to estimate the cumulative TBI incidence rate per 100 person-years., Results: Of the 758 HCWs invited, 732 (97%) consented to participate and 731 completed the one-step TST, 40% had a positive TST result, and 48% had a positive QFT-GIT result. In multivariable models, HCWs years of service 11-20 years had 2.1 (95% CI: 1.5-3.0) times higher odds of being TST-positive and 1.6 (95% CI 1.1-2.5) times higher odds of QFT-GIT-positivity at baseline compared with those working ≤10 years. HCWs working 11-20 years in pulmonary TB ward had 2.0 (95% CI: 1.4-2.9) times higher odds of TST positivity, and those >20 years had 2.5 (95% CI: 1.3-4.9) times higher odds of QFT-GIT-positivity at baseline compared with those working <10 years. TBI incidence was 4.8/100 person-years by TST and 4.2/100 person-years by QFT-GIT. Females had 8.5 (95% CI: 1.5-49.5) times higher odds of TST conversion than males., Conclusions: Prevalent TST and QFT-GIT positivity was associated with an increased number of years working as a healthcare worker and in pulmonary TB wards. The incidence of TBI among HCWs suggests ongoing TB exposure in these facilities and an urgent need for improved TB IPC in chest disease hospitals in Bangladesh., Competing Interests: The authors have declared that no competing interests exist., (Copyright: This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.)

Health care systems in low- and middle-income countries may not meet the needs of pregnant women where the burden of diabetes and hypertension is rapidly increasing. We asked recently pregnant women about ever having been screened for or diagnosed with hypertension or diabetes and their ANC-seeking experiences in a cross-sectional survey. We used chi-squared tests and logistic regression to test the associations between self-reported coverage of hypertension and diabetes screening, diagnoses, and elements of ANC by age, wealth, educational attainment, and gravidity. Among 4,692 respondents, for hypertension, 97% reported having been screened and 10% of screened women reported a diagnosis. Women 30-39 years of age (aOR 3.02, 95% CI 2.00, 4.56) or in the top wealth quintile (aOR 1.70, 95% CI 1.18, 2.44) were more likely to be diagnosed with hypertension compared to reference groups. Any hypertension diagnosis was associated with reporting four or more antenatal care contacts (44% vs. 35%, p < 0.01), blood pressure measurements (85% vs. 79%, p < 0.01), and urine tests (71% vs. 61%, p < 0.01) conducted during ANC visits. For diabetes, 46% of respondents reported having been screened and 3% of screened women reported a diagnosis. Women 30-39 years of age were more likely to be diagnosed with diabetes (aOR 8.19, 95% CI 1.74, 38.48) compared to the reference group. Any diabetes diagnosis was associated with reporting four or more ANC contacts (48% vs. 36%, p = 0.04) and having blood testing during pregnancy (83% vs. 66%, p < 0.01). However, the frequency and quality of ANC was below the national guidelines among all groups. Focused efforts to ensure that women receive the recommended number of ANC contacts, coupled with improved compliance with ANC guidelines, would improve awareness of hypertension and diabetes among women in Bangladesh., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Bear et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Most childhood deaths globally are considered preventable through high-quality clinical care, which includes adherence to clinical care recommendations. Our objective was to describe adherence to World Health Organization recommendations for the management of leading causes of death among children., Methods: We conducted a retrospective, descriptive study examining clinical data for children aged 1-59 months who were hospitalized and died in a Child Health and Mortality Prevention Surveillance (CHAMPS) catchment, December 2016-June 2021. Catchment areas included: Baliakandi and Faridpur, Bangladesh; Kersa, Haramaya, and Harar, Ethiopia; Kisumu and Siaya, Kenya; Bamako, Mali; Manhiça and Quelimane, Mozambique; Makeni, Sierra Leone; Soweto, South Africa. We reviewed medical records of those who died from lower respiratory tract infections, sepsis, malnutrition, malaria, and diarrheal diseases to determine the proportion who received recommended treatments and compared adherence by hospitalization duration., Findings: CHAMPS enrolled 460 hospitalized children who died from the leading causes (median age 12 months, 53.0% male). Median hospital admission was 31 h. There were 51.0% (n = 127/249) of children who died from lower respiratory tract infections received supplemental oxygen. Administration of intravenous fluids for sepsis (15.9%, n = 36/226) and supplemental feeds for malnutrition (14.0%, n = 18/129) were uncommon. There were 51.4% (n = 55/107) of those who died from malaria received antimalarials. Of the 80 children who died from diarrheal diseases, 76.2% received intravenous fluids. Those admitted for ≥24 h more commonly received antibiotics for lower respiratory tract infections and sepsis, supplemental feeds for malnutrition, and intravenous fluids for sepsis than those admitted <24 h., Interpretation: Provision of recommended clinical care for leading causes of death among young children was suboptimal. Further studies are needed to understand the reasons for deficits in clinical care recommendation adherence., Funding: Bill & Melinda Gates Foundation., Competing Interests: CGW received honoraria from the University of St. Andrews for speaking to alumni about CHAMPS and global health work. JAGS reports receiving funding from the Wellcome Trust, UK FCDO, European Union, and the National Institute for Health Research. SM has received grants from the Bill & Melinda Gates Foundation, GSK, Pfizer, Minervax, Novavax, Providence, Gritstone, and ImmunityBio. SM has received honoraria from GSK for lecturing. CGW and SM report serving on data safety monitoring boards for SPEAC (CGW) and PATH and CAPRISA (SM). All other investigators declare no competing interests., (© 2023 The Author(s).)

Adolescent pregnancies, a risk factor for obstetric complications and perinatal mortality, are driven by child marriage in many regions of South Asia. We used data collected between 2017-2019 from 56,155 married adolescents and women in a health and demographic surveillance system to present a population-level description of historical trends in child marriage from 1990-2019 as well as epidemiologic associations between maternal age and pregnancy outcomes in Baliakandi, a rural sub-district of Bangladesh. For pregnancies identified between 2017-2019, we used Kaplan-Meier estimates to examine timing of first pregnancies after first marriage and multinomial logistic regression to estimate associations between maternal age and perinatal death. We described the frequency of self-reported obstetric complications at labor and delivery by maternal age. In 1990, 71% of all marriages were to female residents under 18 years of age. This decreased to 57% in 2010, with the largest reduction among females aged 10-12 years (22% to 3%), and to 53% in 2019. Half of all newly married females were pregnant within a year of marriage, including adolescent brides. Although we observed a decline in child marriages since 1990, over half of all marriages in 2019 were to child brides in Baliakandi. In this same population, adolescent pregnancies were more likely to result in obstetric complications (13-15 years: 36%, 16-17 years: 32%, 18-34 years: 23%; χ2 test, p<0.001) and perinatal deaths (13-15 years: stillbirth OR 2.23, 95% CI 1.01-2.42; 16-17 years: early neonatal death OR 1.57, 95% CI: 1.01-2.42) compared to adult pregnancies. Preventing child marriage can improve the health of girls and contribute to Bangladesh's commitment to reducing child mortality., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Lee et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Invasive Group B Streptococcus (GBS) is a common cause of early-onset neonatal sepsis and is also associated with stillbirth. This study aimed to determine the proportion of stillborn infants and infants who died between 0 and 90 days attributable to GBS using postmortem minimally invasive tissue sampling (MITS) in 7 low- and middle-income countries (LMICs) participating in Child Health and Mortality Prevention Surveillance (CHAMPS)., Methods: Deaths that occurred between December 2016 and December 2021 were investigated with MITS, including culture for bacteria of blood and cerebrospinal fluid (CSF), multipathogen polymerase chain reaction on blood, CSF, and lung tissue and histopathology of lung, liver, and brain. Data collection included clinical record review and verbal autopsy. Expert panels reviewed all information and assigned causes of death., Results: We evaluated 2966 deaths, including stillborn infants ( n = 1322), infants who died during first day of life (0 to <24 hours, n = 597), early neonatal deaths (END) (1 day to <7 days; END; n = 593), and deaths from 7 to 90 days ( n = 454). Group B Streptococcus was determined to be in the causal pathway of death for 2.7% of infants (79 of 2, 966; range, 0.3% in Sierra Leone to 7.2% in South Africa), including 2.3% (31 of 1322) of stillbirths, 4.7% (28 of 597) 0 to <24 hours, 1.9% (11 of 593) END, and 2.0% (9 of 454) of deaths from 7 to 90 days of age. Among deaths attributed to GBS with birth weight data available, 61.9% (39 of 63) of decedents weighed <2500 grams at birth. Group B Streptococcus sepsis was the postmortem diagnosis for 100% (31 of 31) of stillbirths. For deaths <90 days, postmortem diagnoses included GBS sepsis (83.3%, 40 of 48), GBS meningitis (4.2%, 2 of 48), and GBS pneumonia (2.1%, 1 of 48)., Conclusions: Our study reveals significant heterogeneity in the contribution of invasive GBS disease to infant mortality across different countries, emphasizing the need for tailored prevention strategies. Moreover, our findings highlight the substantial impact of GBS on stillbirths, shedding light on a previously underestimated aspect in LMICs., Competing Interests: Potential conflicts of interest. The authors have declared that no competing interests exist., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Importance: The number of deaths of children younger than 5 years has been steadily decreasing worldwide, from more than 17 million annual deaths in the 1970s to an estimated 5.3 million in 2019 (with 2.8 million deaths occurring in those aged 1-59 months [53% of all deaths in children aged <5 years]). More detailed characterization of childhood deaths could inform interventions to improve child survival., Objective: To describe causes of postneonatal child deaths across 7 mortality surveillance sentinel sites in Africa and Asia., Design, Setting, and Participants: The Child Health and Mortality Prevention Surveillance (CHAMPS) Network conducts childhood mortality surveillance in sub-Saharan Africa and South Asia using innovative postmortem minimally invasive tissue sampling (MITS). In this cross-sectional study, MITS was conducted in deceased children aged 1 to 59 months at 7 sites in sub-Saharan Africa and South Asia from December 3, 2016, to December 3, 2020. Data analysis was conducted between October and November 2021., Main Outcomes and Measures: The expert panel attributed underlying, intermediate, and immediate conditions in the chain of events leading to death, based on histopathologic analysis, microbiological diagnostics, clinical data, and verbal autopsies., Results: In this study, MITS was performed in 632 deceased children (mean [SD] age at death, 1.3 [0.3] years; 342 [54.1%] male). The 6 most common underlying causes of death were malnutrition (104 [16.5%]), HIV (75 [11.9%]), malaria (71 [11.2%]), congenital birth defects (64 [10.1%]), lower respiratory tract infections (LRTIs; 53 [8.4%]), and diarrheal diseases (46 [7.2%]). When considering immediate causes only, sepsis (191 [36.7%]) and LRTI (129 [24.8%]) were the 2 dominant causes. An infection was present in the causal chain in 549 of 632 deaths (86.9%); pathogens most frequently contributing to infectious deaths included Klebsiella pneumoniae (155 of 549 infectious deaths [28.2%]; 127 [81.9%] considered nosocomial), Plasmodium falciparum (122 of 549 [22.2%]), and Streptococcus pneumoniae (109 of 549 [19.9%]). Other organisms, such as cytomegalovirus (57 [10.4%]) and Acinetobacter baumannii (39 [7.1%]; 35 of 39 [89.7%] considered nosocomial), also played important roles. For the top underlying causes of death, the median number of conditions in the chain of events leading to death was 3 for malnutrition, 3 for HIV, 1 for malaria, 3 for congenital birth defects, and 1 for LRTI. Expert panels considered 494 of 632 deaths (78.2%) preventable and 26 of 632 deaths (4.1%) preventable under certain conditions., Conclusions and Relevance: In this cross-sectional study investigating causes of child mortality in the CHAMPS Network, results indicate that, in these high-mortality settings, infectious diseases continue to cause most deaths in infants and children, often in conjunction with malnutrition. These results also highlight opportunities for action to prevent deaths and reveal common interaction of various causes in the path toward death.

Background: Neural tube defects are common birth defects resulting in severe morbidity and mortality; they can largely be prevented with periconceptional maternal intake of folic acid. Understanding the occurrence of neural tube defects and their contribution to mortality in settings where their burden is highest could inform prevention and health-care policy. We aimed to estimate the mortality attributed to neural tube defects in seven countries in sub-Saharan Africa and southeast Asia., Methods: This analysis used data from the Child Health and Mortality Prevention Surveillance (CHAMPS) network and health and demographic surveillance systems from South Africa, Mozambique, Bangladesh, Kenya, Mali, Ethiopia, and Sierra Leone. All stillbirths and infants and children younger than 5 years who died, who were enrolled in CHAMPS, whose families consented to post-mortem minimally invasive tissue sampling (MITS) between Jan 1, 2017, and Dec 31, 2021, and who were assigned a cause of death by a determination of cause of death panel as of May 24, 2022, were included in this analysis, regardless the cause of death. MITS and advanced diagnostic methods were used to describe the frequency and characteristics of neural tube defects among eligible deaths, identify risk factors, and estimate the mortality fraction and mortality rate (per 10 000 births) by CHAMPS site., Findings: Causes of death were determined for 3232 stillbirths, infants, and children younger than 5 years, of whom 69 (2%) died with a neural tube defect. Most deaths with a neural tube defect were stillbirths (51 [74%]); 46 (67%) were neural tube defects incompatible with life (ie, anencephaly, craniorachischisis, or iniencephaly) and 22 (32%) were spina bifida. Deaths with a neural tube defect were more common in Ethiopia (adjusted odds ratio 8·09 [95% CI 2·84-23·02]), among female individuals (4·40 [2·44-7·93]), and among those whose mothers had no antenatal care (2·48 [1·12-5·51]). Ethiopia had the highest adjusted mortality fraction of deaths with neural tube defects (7·5% [6·7-8·4]) and the highest adjusted mortality rate attributed to neural tube defects (104·0 per 10 000 births [92·9-116·4]), 4-23 times greater than in any other site., Interpretation: CHAMPS identified neural tube defects, a largely preventable condition, as a common cause of death among stillbirths and neonatal deaths, especially in Ethiopia. Implementing interventions such as mandatory folic acid fortification could reduce mortality due to neural tube defects., Funding: Bill & Melinda Gates Foundation., Competing Interests: Declaration of interests SEA reports grants from Emory University, during the conduct of the study. JAGS reports grants from the Wellcome Trust, the National Institute for Health and Care Research, Gavi, the Foreign Commonwealth and Development Office (UK), the European and Developing Countries Clinical Trials Partnership, the Medical Research Council, and the Bill & Melinda Gates Foundation whose payments were direct to his institution. LM reports grants from the Bill & Melinda Gates Foundation via Emory, whose payments were made direct to her institution. KLK reports grants from the Bill & Melinda Gates Foundation, whose payments were made direct to her institution and support attending meetings. KLK, SOS, and AMK report the provision of study materials and funding to their institution for this study from the Bill & Melinda Gates Foundation. AW reports a stipend for participating in the CHAMPS research and payment for travel to the High Horizons meeting in Belgium from the University of Witwatersrand; honoraria for lectures from Sanofi; and being a council member of The South African Society of Obstetricians and Gynaecologists. All other authors declare no competing interests., (Copyright © 2023 The Author(s). Published by Elsevier Ltd. This is an open access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Background: The potential benefits of using rapid influenza diagnostic tests (RIDTs) in urgent care facilities for clinical care and prescribing practices are understudied. We compared antiviral and antibiotic prescribing, imaging, and laboratory ordering in clinical encounters with and without RIDT results., Methods: We compared patients with acute respiratory infection (ARI) symptoms who received an RIDT and patients who did not at 2 urgent care facilities. Primary analysis using 1-to-1 exact matching resulted in 1145 matched pairs to which McNemar 2 × 2 tests were used to assess the association between the likelihood of prescribing, imaging/laboratory ordering, and RIDT use. Secondary analysis compared the same outcomes using logistic regression among the RIDT-tested population between participants who tested negative (RIDT(-)) and positive (RIDT(+))., Results: Primary analysis revealed that compared to the non-RIDT-tested population, RIDT(+) patients were more likely to be prescribed antivirals (OR, 10.23; 95% CI, 5.78-19.72) and less likely to be prescribed antibiotics (OR, 0.15; 95% CI, .08-.27). Comparing RIDT-tested to non-RIDT-tested participants, RIDT use increased antiviral prescribing odds (OR, 3.07; 95% CI, 2.25-4.26) and reduced antibiotic prescribing odds (OR, 0.52; 95% CI, .43-.63). Secondary analysis identified increased odds of prescribing antivirals (OR, 28.21; 95% CI, 18.15-43.86) and decreased odds of prescribing antibiotics (OR, 0.20; 95% CI, .13-.30) for RIDT(+) participants compared with RIDT(-)., Conclusions: Use of RIDTs in patients presenting with ARI symptoms influences clinician diagnostic and treatment decision-making, which could lead to improved patient outcomes, population-level reductions in influenza burden, and a decreased threat of antibiotic resistance., Competing Interests: Potential conflicts of interest. J. T. and S. R. are employed by the Quidel Corporation. J. L. T. received research support from the Quidel Corporation. G. C. reports grants or contracts from the National Institutes of Health, Patient-Centered Outcomes Research Institute, and the American Cancer Society. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

In 2015, human influenza surveillance identified a human infection with A/H9N2 in Dhaka, Bangladesh with evidence of exposure to a sick quail. We conducted in-depth interviews with household quail caregivers, pet bird retail shop owners, and mobile vendors, key informant interviews with pet bird wholesale shop owners, one group discussion with pet bird retail shop workers and unstructured observations in households, pet bird wholesale and retail markets, and mobile bird vendor's travelling areas to explore quail rearing and selling practices among households, mobile vendors, and retail pet bird and wholesale bird markets in Dhaka. Every day, quail were supplied from 23 districts to two wholesale markets, and then sold to households and restaurants directly, or through bird shops and mobile vendors. All respondents (67) reported keeping quail with other birds in cages, feeding quail, cleaning feeding pots, removing quail faeces, slaughtering sick quail, and discarding dead quail. Children played with quail and assisted in slaughtering of quail. Most respondents (94%) reported rinsing hands with water only after slaughtering and disposing of wastes and dead quail. No personal protective equipment was used during any activities. Frequent unprotected contact with quail and their by-products potentially increased the risk of cross-species avian influenza virus transmission. Avian influenza surveillance in retail pet bird and wholesale bird markets, mobile vendors, and households may identify cases promptly and reduce the risk of virus transmission., (© 2023. EcoHealth Alliance.)

Each year, 2.4 million children die within their first month of life. Child Health and Mortality Prevention Surveillance (CHAMPS) established in 7 countries aims to generate accurate data on why such deaths occur and inform prevention strategies. Neonatal deaths that occurred between December 2016 and December 2021 were investigated with MITS within 24-72 hours of death. Testing included blood, cerebrospinal fluid and lung cultures, multi-pathogen PCR on blood, CSF, nasopharyngeal swabs and lung tissue, and histopathology examination of lung, liver and brain. Data collection included clinical record review and family interview using standardized verbal autopsy. The full set of data was reviewed by local experts using a standardized process (Determination of Cause of Death) to identify all relevant conditions leading to death (causal chain), per WHO recommendations. For analysis we stratified neonatal death into 24-hours of birth, early (1-<7 days) and late (7-<28 days) neonatal deaths. We analyzed 1458 deaths, 41% occurring within 24-hours, 41% early and 18% late neonatal deaths. Leading underlying causes of death were complications of intrapartum events (31%), complications of prematurity (28%), infections (17%), respiratory disorders (11%), and congenital malformations (8%). In addition to the underlying cause, 62% of deaths had additional conditions and 14% had ≥3 other conditions in the causal chain. The most common causes considering the whole causal chain were infection (40%), prematurity (32%) and respiratory distress syndrome (28%). Common maternal conditions linked to neonatal death were maternal hypertension (10%), labour and delivery complications (8%), multiple gestation (7%), placental complications (6%) obstructed labour and chorioamnionitis (5%, each). CHAMPS' findings showing the full causal chain of events that lead to death, in addition to maternal factors, highlights the complexities involved in each death along with the multiple opportunities for prevention. Highlighting improvements to prenatal and obstetric care and infection prevention are urgently needed in high-mortality settings., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Mahtab et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)