UNASSIGNED: The coronavirus disease 2019 (COVID-19) pandemic led to disruptions of health service delivery in many countries; some were more resilient in either limiting or rapidly responding to the disruption than others. We used mixed methods implementation research to understand factors and strategies associated with resiliency in Rwanda and Bangladesh, focussing on how evidence-based interventions targeting amenable under-five mortality that had been used during the Millennium Development Goal (MDG) period (2000-15) were maintained during the early period of COVID-19.
UNASSIGNED: We triangulated data from three sources - a desk review of available documents, existing quantitative data on evidence-based intervention coverage, and key informant interviews - to perform a comparative analysis using multiple case studies methodology, comparing contextual factors (barriers or facilitators), implementation strategies (existing from 2000-15, new, or adapted), and implementation outcomes across the two countries. We also analysed which health system resiliency capabilities were present in the two countries.
UNASSIGNED: Both countries experienced many of the same facilitators for resiliency of evidence-based interventions for children under five, as well as new, pandemic-specific barriers during the early COVID-19 period (March to December 2020) that required targeted implementation strategies in response. Common facilitators included leadership and governance and a culture of accountability, while common barriers included movement restrictions, workload, and staff shortages. We saw a continuity of implementation strategies that had been associated with success in care delivery during the MDG period, including data use for monitoring and decision-making, as well as building on community health worker programmes for community-based health care delivery. New or adapted strategies used in responding to new barriers included the expanded use of digital platforms. We found implementation outcomes and strong resilience capabilities, including awareness and adaptiveness, which were related to pre-existing facilitators and implementation strategies (continued and new).
UNASSIGNED: The strategies and contextual factors Rwanda and Bangladesh leveraged to build \'everyday resilience\' before COVID-19, i.e. during the MDG period, likely supported the maintained delivery of the evidence-based interventions targeting under-five mortality during the early stages of the pandemic. Expanding our understanding of pre-existing factors and strategies that contributed to resilience before and during the pandemic is important to support other countries\' efforts to incorporate \'everyday resilience\' into their health systems.

BACKGROUND: Previous studies have shown that an elevated triglyceride-glucose (TyG) index was associated with all-cause mortality in both general adult individuals and critically ill adult patients. However, the relationship between the TyG index and clinical prognosis in pediatric patients admitted to the intensive care unit (ICU) remains unknown. We aimed to investigate the association of the TyG index with in-hospital all-cause mortality in critically ill pediatric patients.
METHODS: A total of 5706 patients in the Pediatric Intensive Care database were enrolled in this study. The primary outcome was 30-day in-hospital all-cause mortality, and secondary outcome was 30-day in-ICU all-cause mortality. The restricted cubic spline (RCS) curves and two-piecewise multivariate Cox hazard regression models were performed to explore the relationship between the TyG index and outcomes.
RESULTS: The median age of the study population was 20.5 [interquartile range (IQR): 4.8, 63.0] months, and 3269 (57.3%) of the patients were male. The mean TyG index level was 8.6 ± 0.7. A total of 244 (4.3%) patients died within 30 days of hospitalization during a median follow-up of 11 [7, 18] days, and 236 (4.1%) patients died in ICU within 30 days of hospitalization during a median follow-up of 6 [3, 11] days. The RCS curves indicated a U-shape association between the TyG index and 30-day in-hospital and in-ICU all-cause mortality (both P values for non-linear < 0.001). The risk of 30-day in-hospital all-cause mortality was negatively correlated with the TyG index until it bottoms out at 8.6 (adjusted hazard ratio [HR], 0.72, 95% confidence interval [CI] 0.55-0.93). However, when the TyG index was higher than 8.6, the risk of primary outcome increased significantly (adjusted HR, 1.51, 95% CI 1.16-1.96]). For 30-day in-ICU all-cause mortality, we also found a similar relationship (TyG < 8.6: adjusted HR, 0.75, 95% CI 0.57-0.98; TyG ≥ 8.6: adjusted HR, 1.42, 95% CI 1.08-1.85). Those results were consistent in subgroups and various sensitivity analysis.
CONCLUSIONS: Our study showed that the association between the TyG index and 30-day in-hospital and in-ICU all-cause mortality was nonlinear U-shaped, with a cutoff point at the TyG index of 8.6 in critically ill pediatric patients. Our findings suggest that the TyG index may be a novel and important factor for the short-term clinical prognosis in pediatric patients.

BACKGROUND: Randomized controlled trials found that twice-yearly mass azithromycin administration (MDA) reduces childhood mortality, presumably by reducing infection burden. World Health Organization (WHO) issued conditional guidelines for mass azithromycin administration in high-mortality settings in sub-Saharan Africa given concerns for antibiotic resistance. While prolonged twice-yearly MDA has been shown to increase antibiotic resistance in small randomized controlled trials, the objective of this study was to determine if macrolide and non-macrolide resistance in the gut increases with the duration of azithromycin MDA in a larger setting.
RESULTS: The Macrolide Oraux pour Réduire les Décès avec un Oeil sur la Résistance (MORDOR) study was conducted in Niger from December 2014 to June 2020. It was a cluster-randomized trial of azithromycin (A) versus placebo (P) aimed at evaluating childhood mortality. This is a sub-study in the MORDOR trial to track changes in antibiotic resistance after prolonged azithromycin MDA. A total of 594 communities were eligible. Children 1 to 59 months in 163 randomly chosen communities were eligible to receive treatment and included in resistance monitoring. Participants, staff, and investigators were masked to treatment allocation. At the conclusion of MORDOR Phase I, by design, all communities received an additional year of twice-yearly azithromycin treatments (Phase II). Thus, at the conclusion of Phase II, the treatment history (1 letter per 6-month period) for the participating communities was either (PP-PP-AA) or (AA-AA-AA). In Phase III, participating communities were then re-randomized to receive either another 3 rounds of azithromycin or placebo, thus resulting in 4 treatment histories: Group 1 (AA-AA-AA-AA-A, N = 51), Group 2 (PP-PP-AA-AA-A, N = 40), Group 3 (AA-AA-AA-PP-P, N = 27), and Group 4 (PP-PP-AA-PP-P, N = 32). Rectal swabs from each child (N = 5,340) were obtained 6 months after the last treatment. Each child contributed 1 rectal swab and these were pooled at the community level, processed for DNA-seq, and analyzed for genetic resistance determinants. The primary prespecified outcome was macrolide resistance determinants in the gut. Secondary outcomes were resistance to beta-lactams and other antibiotic classes. Communities recently randomized to azithromycin (groups 1 and 2) had significantly more macrolide resistance determinants than those recently randomized to placebo (groups 3 and 4) (fold change 2.18, 95% CI 1.5 to 3.51, Punadj < 0.001). However, there was no significant increase in macrolide resistance in communities treated 4.5 years (group 1) compared to just the most recent 2.5 years (group 2) (fold change 0.80, 95% CI 0.50 to 1.00, Padj = 0.010), or between communities that had been treated for 3 years in the past (group 3) versus just 1 year in the past (group 4) (fold change 1.00, 95% CI 0.78 to 2.35, Padj = 0.52). We also found no significant differences for beta-lactams or other antibiotic classes. The main limitations of our study were the absence of phenotypic characterization of resistance, no complete placebo arm, and no monitoring outside of Niger limiting generalizability.
CONCLUSIONS: In this study, we observed that mass azithromycin distribution for childhood mortality among preschool children in Niger increased macrolide resistance determinants in the gut but that resistance may plateau after 2 to 3 years of treatment. Co-selection to other classes needs to be monitored.
BACKGROUND: NCT02047981 https://classic.clinicaltrials.gov/ct2/show/NCT02047981.

BACKGROUND: Respiratory ailments, encompassing a spectrum of disorders, are a leading cause of mortality and morbidity in children, with pneumonia being particularly significant, accounting for 16% of child mortality. To ensure timely engagement with healthcare services, it is imperative to instill awareness through Information, Education, and Communication (IEC) initiatives targeting mothers of children under five. The primary objective of this pilot study is to assess the feasibility of a community-based intervention on health-seeking behaviour, knowledge, and practice measures concerning the management and prevention of pneumonia in children.
METHODS: The pilot study mirrored the main study\'s procedures in two villages, Bhuvanahalli and Gavanahalli, each randomly assigned as either an experimental or a control group. We selected 12 mothers with children under the age of five who had community-acquired pneumonia, employing a straightforward random technique, with six mothers from each group. These mothers were interviewed using a structured questionnaire focusing on health-seeking behaviour, knowledge, and practices related to the management and prevention of pneumonia. Mothers in the experimental group received a community-based intervention, specifically an educational set focusing on health-seeking behaviour, knowledge, and practice measures concerning the management and prevention of pneumonia in children, while those in the control group continued with their routine practices. We collected post-test data from the mothers in both groups at the 2nd, 4th, and 6th months of the intervention. The data analysis was conducted using the IBM SPSS Statistics for Windows, Version 28 (Released 2021; IBM Corp., Armonk, New York) software. The Mann-Whitney test and Kruskal-Wallis analyses indicated a notable and statistically significant shift in health-seeking behaviour, knowledge, and practices pertaining to the management and prevention of pneumonia in children as a result of the community-based educational intervention implemented in the experimental group (P<0.05).
CONCLUSIONS: Community-based intervention is crucial to preventing mortality and morbidity in children. The findings of the pilot study affirm its feasibility and lay a strong foundation for further investigation and implementation.

BACKGROUND: The decline in global child mortality is an important public health achievement, yet child mortality remains disproportionally high in many low-income countries like Guinea-Bissau. The persisting high mortality rates necessitate targeted research to identify vulnerable subgroups of children and formulate effective interventions.
OBJECTIVE: This study aimed to discover subgroups of children at an elevated risk of mortality in the urban setting of Bissau, Guinea-Bissau, West Africa. By identifying these groups, we intend to provide a foundation for developing targeted health interventions and inform public health policy.
METHODS: We used data from the health and demographic surveillance site, Bandim Health Project, covering 2003 to 2019. We identified baseline variables recorded before children reached the age of 6 weeks. The focus was on determining factors consistently linked with increased mortality up to the age of 3 years. Our multifaceted methodological approach incorporated spatial analysis for visualizing geographical variations in mortality risk, causally adjusted regression analysis to single out specific risk factors, and machine learning techniques for identifying clusters of multifactorial risk factors. To ensure robustness and validity, we divided the data set temporally, assessing the persistence of identified subgroups over different periods. The reassessment of mortality risk used the targeted maximum likelihood estimation (TMLE) method to achieve more robust causal modeling.
RESULTS: We analyzed data from 21,005 children. The mortality risk (6 weeks to 3 years of age) was 5.2% (95% CI 4.8%-5.6%) for children born between 2003 and 2011, and 2.9% (95% CI 2.5%-3.3%) for children born between 2012 and 2016. Our findings revealed 3 distinct high-risk subgroups with notably higher mortality rates, children residing in a specific urban area (adjusted mortality risk difference of 3.4%, 95% CI 0.3%-6.5%), children born to mothers with no prenatal consultations (adjusted mortality risk difference of 5.8%, 95% CI 2.6%-8.9%), and children from polygamous families born during the dry season (adjusted mortality risk difference of 1.7%, 95% CI 0.4%-2.9%). These subgroups, though small, showed a consistent pattern of higher mortality risk over time. Common social and economic factors were linked to a larger share of the total child deaths.
CONCLUSIONS: The study\'s results underscore the need for targeted interventions to address the specific risks faced by these identified high-risk subgroups. These interventions should be designed to work to complement broader public health strategies, creating a comprehensive approach to reducing child mortality. We suggest future research that focuses on developing, testing, and comparing targeted intervention strategies unraveling the proposed hypotheses found in this study. The ultimate aim is to optimize health outcomes for all children in high-mortality settings, leveraging a strategic mix of targeted and general health interventions to address the varied needs of different child subgroups.

Between 2018 and 2022 the Liberian Government implemented the National Community Health Assistant (NCHA) program to improve provision of maternal and child health care to underserved rural areas of the country. Whereas the contributions of this and similar community health worker (CHW) based healthcare programs have been associated with improved process measures, the impact of a governmental CHW program at scale on child mortality has not been fully established. We will conduct a cluster sampled, community-based survey with landmark event calendars to retrospectively assess child births and deaths among all children born to women in the Grand Bassa District of Liberia. We will use a mixed effects Cox proportional hazards model, taking advantage of the staggered program implementation in Grand Bassa districts over a period of 4 years to compare rates of under-5 child mortality between the pre- and post-NCHA program implementation periods. This study will be the first to estimate the impact of the Liberian NCHA program on under-5 mortality.

BACKGROUND: The Ethiopian government implemented a national community health program, the Health Extension Program (HEP), to provide community-based health services to address persisting access-related barriers to care using health extension workers (HEWs). We used implementation research to understand how Ethiopia leveraged the HEP to widely implement evidence-based interventions (EBIs) known to reduce under-5 mortality (U5M) and address health inequities.
METHODS: This study was part of a six-country case study series using implementation research to understand how countries implemented EBIs between 2000-2015. Our mixed-methods research was informed by a hybrid implementation science framework using desk review of published and gray literature, analysis of existing data sources, and 11 key informant interviews. We used implementation of pneumococcal conjugate vaccine (PCV-10) and integrated community case management (iCCM) to illustrate Ethiopia\'s ability to rapidly integrate interventions into existing systems at a national level through leveraging the HEP and other implementation strategies and contextual factors which influenced implementation outcomes.
RESULTS: Ethiopia implemented numerous EBIs known to address leading causes of U5M, leveraging the HEP as a platform for delivery to successfully introduce and scale new EBIs nationally. By 2014/15, estimated coverage of three doses of PCV-10 was at 76%, with high acceptability (nearly 100%) of vaccines in the community. Between 2000 and 2015, we found evidence of improved care-seeking; coverage of oral rehydration solution for treatment of diarrhea, a service included in iCCM, doubled over this period. HEWs made health services more accessible to rural and pastoralist communities, which account for over 80% of the population, with previously low access, a contextual factor that had been a barrier to high coverage of interventions.
CONCLUSIONS: Leveraging the HEP as a platform for service delivery allowed Ethiopia to successfully introduce and scale existing and new EBIs nationally, improving feasibility and reach of introduction and scale-up of interventions. Additional efforts are required to reduce the equity gap in coverage of EBIs including PCV-10 and iCCM among pastoralist and rural communities. As other countries continue to work towards reducing U5M, Ethiopia\'s experience provides important lessons in effectively delivering key EBIs in the presence of challenging contextual factors.

Repeated mass distribution of azithromycin has been shown to reduce childhood mortality by 14% in sub-Saharan Africa. However, the estimated effect varied by location, suggesting that the intervention may not be effective in different geographical areas, time periods, or conditions.
To evaluate the efficacy of twice-yearly azithromycin to reduce mortality in children in the presence of seasonal malaria chemoprevention.
This cluster randomized placebo-controlled trial evaluating the efficacy of single-dose azithromycin for prevention of all-cause childhood mortality included 341 communities in the Nouna district in rural northwestern Burkina Faso. Participants were children aged 1 to 59 months living in the study communities.
Communities were randomized in a 1:1 ratio to receive oral azithromycin or placebo distribution. Children aged 1 to 59 months were offered single-dose treatment twice yearly for 3 years (6 distributions) from August 2019 to February 2023.
The primary outcome was all-cause childhood mortality, measured during a twice-yearly enumerative census.
A total of 34 399 children (mean [SD] age, 25.2 [18] months) in the azithromycin group and 33 847 children (mean [SD] age, 25.6 [18] months) in the placebo group were included. A mean (SD) of 90.1% (16.0%) of the censused children received the scheduled study drug in the azithromycin group and 89.8% (17.1%) received the scheduled study drug in the placebo group. In the azithromycin group, 498 deaths were recorded over 60 592 person-years (8.2 deaths/1000 person-years). In the placebo group, 588 deaths were recorded over 58 547 person-years (10.0 deaths/1000 person-years). The incidence rate ratio for mortality was 0.82 (95% CI, 0.67-1.02; P = .07) in the azithromycin group compared with the placebo group. The incidence rate ratio was 0.99 (95% CI, 0.72-1.36) in those aged 1 to 11 months, 0.92 (95% CI, 0.67-1.27) in those aged 12 to 23 months, and 0.73 (95% CI, 0.57-0.94) in those aged 24 to 59 months.
Mortality in children (aged 1-59 months) was lower with biannual mass azithromycin distribution in a setting in which seasonal malaria chemoprevention was also being distributed, but the difference was not statistically significant. The study may have been underpowered to detect a clinically relevant difference.
ClinicalTrials.gov Identifier: NCT03676764.

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.
RESULTS: 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.
CONCLUSIONS: 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.
BACKGROUND: Bill & Melinda Gates Foundation.

As the largest profession within the healthcare industry, nursing and midwifery workforce (NMW) provides comprehensive healthcare to children and their families. This study quantified the independent role of NMW in reducing under-5 mortality rate (U5MR) worldwide.
A retrospective, observational and correlational study to examine the independent role of NMW in protecting against U5MR.
Within 266 \"countries\", the cross-sectional correlations between NMW and U5MR were examined with scatter plots, Pearson\'s r, nonparametric, partial correlation and multiple regression. The affluence, education and urban advantages were considered as the potential competing factors for the NMW-U5MR relationship. The NMW-U5MR correlations in both developing and developed countries were explored and compared.
Bivariate correlations revealed that NMW negatively and significantly correlated to U5MR worldwide. When the contributing effects of economic affluence, urbanization and education were removed, the independent NMW role in reducing U5MR remained significant. NMW independently explained 9.36% U5MR variance. Multilinear regression selected NMW as a significant factor contributing an extra 3% of explanation to U5MR variance when NMW, affluence, education and urban advantage were incorporated as the predicting variables. NMW correlated with U5MR significantly more strongly in developing countries than in developed countries.
NMW, indexing nursing and midwifery service, was a significant factor for reducing U5MR worldwide. This beneficial effect explained 9.36% of U5MR variance which was independent of economic affluence, urbanization and education. The NMW may be a more significant risk factor for protecting children from dying under 5 years old in developing countries. As a strategic response to the advocacy of the United Nations to reduce child mortality, it is worthy for health authorities to consider a further extension of nurses and midwives\' practice scope to enable communities to have more access to NMW healthcare services.