Global Respiratory Syncytial Virus-Related Infant Community Deaths.

BACKGROUND: Respiratory syncytial virus (RSV) is a leading cause of pediatric death, with >99% of mortality occurring in low- and lower middle-income countries. At least half of RSV-related deaths are estimated to occur in the community, but clinical characteristics of this group of children remain poorly characterized. METHODS: The RSV Global Online Mortality Database (RSV GOLD), a global registry of under-5 children who have died with RSV-related illness, describes clinical characteristics of children dying of RSV through global data sharing. RSV GOLD acts as a collaborative platform for global deaths, including community mortality studies described in this supplement. We aimed to compare the age distribution of infant deaths <6 months occurring in the community with in-hospital. RESULTS: We studied 829 RSV-related deaths <1 year of age from 38 developing countries, including 166 community deaths from 12 countries. There were 629 deaths that occurred <6 months, of which 156 (25%) occurred in the community. Among infants who died before 6 months of age, median age at death in the community (1.5 months; IQR: 0.8-3.3) was lower than in-hospital (2.4 months; IQR: 1.5-4.0; P < .0001). The proportion of neonatal deaths was higher in the community (29%, 46/156) than in-hospital (12%, 57/473, P < 0.0001). CONCLUSIONS: We observed that children in the community die at a younger age. We expect that maternal vaccination or immunoprophylaxis against RSV will have a larger impact on RSV-related mortality in the community than in-hospital. This case series of RSV-related community deaths, made possible through global data sharing, allowed us to assess the potential impact of future RSV vaccines.

Deaths Attributed to Respiratory Syncytial Virus in Young Children in High-Mortality Rate Settings: Report from Child Health and Mortality Prevention Surveillance (CHAMPS).

BACKGROUND: Lower respiratory tract infections are a leading cause of death in young children, but few studies have collected the specimens needed to define the role of specific causes. The Child Health and Mortality Prevention Surveillance (CHAMPS) platform aims to investigate causes of death in children aged <5 years in high-mortality rate settings, using postmortem minimally invasive tissue sampling and other advanced diagnostic techniques. We examined findings for deaths identified in CHAMPS sites in 7 countries in sub-Saharan Africa and south Asia to evaluate the role of respiratory syncytial virus (RSV). METHODS: We included deaths that occurred between December 2016 and December 2019. Panels determined causes of deaths by reviewing all available data including pathological results from minimally invasive tissue sampling, polymerase chain reaction screening for multiple infectious pathogens in lung tissue, nasopharyngeal swab, blood, and cerebrospinal fluid samples, clinical information from medical records, and verbal autopsies. RESULTS: We evaluated 1213 deaths, including 695 in neonates (aged <28 days), 283 in infants (28 days to <12 months), and 235 in children (12-59 months). RSV was detected in postmortem specimens in 67 of 1213 deaths (5.5%); in 24 deaths (2.0% of total), RSV was determined to be a cause of death, and it contributed to 5 other deaths. Younger infants (28 days to <6 months of age) accounted for half of all deaths attributed to RSV; 6.5% of all deaths in younger infants were attributed to RSV. RSV was the underlying and only cause in 4 deaths; the remainder (n = 20) had a median of 2 (range, 1-5) other conditions in the causal chain. Birth defects (n = 8) and infections with other pathogens (n = 17) were common comorbid conditions. CONCLUSIONS: RSV is an important cause of child deaths, particularly in young infants. These findings add to the substantial body of literature calling for better treatment and prevention options for RSV in high-mortality rate settings.

Postmortem investigations and identification of multiple causes of child deaths: An analysis of findings from the Child Health and Mortality Prevention Surveillance (CHAMPS) network.

BACKGROUND: The current burden of >5 million deaths yearly is the focus of the Sustainable Development Goal (SDG) to end preventable deaths of newborns and children under 5 years old by 2030. To accelerate progression toward this goal, data are needed that accurately quantify the leading causes of death, so that interventions can target the common causes. By adding postmortem pathology and microbiology studies to other available data, the Child Health and Mortality Prevention Surveillance (CHAMPS) network provides comprehensive evaluations of conditions leading to death, in contrast to standard methods that rely on data from medical records and verbal autopsy and report only a single underlying condition. We analyzed CHAMPS data to characterize the value of considering multiple causes of death. METHODS AND FINDINGS: We examined deaths identified from December 2016 through November 2020 from 7 CHAMPS sites (in Bangladesh, Ethiopia, Kenya, Mali, Mozambique, Sierra Leone, and South Africa), including 741 neonatal, 278 infant, and 241 child <5 years deaths for which results from Determination of Cause of Death (DeCoDe) panels were complete. DeCoDe panelists included all conditions in the causal chain according to the ICD-10 guidelines and assessed if prevention or effective management of the condition would have prevented the death. We analyzed the distribution of all conditions listed as causal, including underlying, antecedent, and immediate causes of death. Among 1,232 deaths with an underlying condition determined, we found a range of 0 to 6 (mean 1.5, IQR 0 to 2) additional conditions in the causal chain leading to death. While pathology provides very helpful clues, we cannot always be certain that conditions identified led to death or occurred in an agonal stage of death. For neonates, preterm birth complications (most commonly respiratory distress syndrome) were the most common underlying condition (n = 282, 38%); among those with preterm birth complications, 256 (91%) had additional conditions in causal chains, including 184 (65%) with a different preterm birth complication, 128 (45%) with neonatal sepsis, 69 (24%) with lower respiratory infection (LRI), 60 (21%) with meningitis, and 25 (9%) with perinatal asphyxia/hypoxia. Of the 278 infant deaths, 212 (79%) had ≥1 additional cause of death (CoD) beyond the underlying cause. The 2 most common underlying conditions in infants were malnutrition and congenital birth defects; LRI and sepsis were the most common additional conditions in causal chains, each accounting for approximately half of deaths with either underlying condition. Of the 241 child deaths, 178 (75%) had ≥1 additional condition. Among 46 child deaths with malnutrition as the underlying condition, all had ≥1 other condition in the causal chain, most commonly sepsis, followed by LRI, malaria, and diarrheal disease. Including all positions in the causal chain for neonatal deaths resulted in 19-fold and 11-fold increases in attributable roles for meningitis and LRI, respectively. For infant deaths, the proportion caused by meningitis and sepsis increased by 16-fold and 11-fold, respectively; for child deaths, sepsis and LRI are increased 12-fold and 10-fold, respectively. While comprehensive CoD determinations were done for a substantial number of deaths, there is potential for bias regarding which deaths in surveillance areas underwent minimally invasive tissue sampling (MITS), potentially reducing representativeness of findings. CONCLUSIONS: Including conditions that appear anywhere in the causal chain, rather than considering underlying condition alone, markedly changed the proportion of deaths attributed to various diagnoses, especially LRI, sepsis, and meningitis. While CHAMPS methods cannot determine when 2 conditions cause death independently or may be synergistic, our findings suggest that considering the chain of events leading to death can better guide research and prevention priorities aimed at reducing child deaths.

The Changing Global Epidemiology of Measles, 2013-2018.

BACKGROUND: Measles incidence and mortality rates have significantly decreased since vaccine introduction. Despite this progress, however, there has been a global resurgence of measles. To understand the current global epidemiology, we analyzed measles surveillance data. METHODS: We analyzed data on measles cases from 2013-2018 reported to the World Health Organization. Univariate analysis was undertaken based on age, vaccination history, onset year, World Health Organization region, and World Bank income status for the country where the case was reported, and a surrogate indicator of the historical strength of the country's immunization program. Annual incidence and a 2013-2018 mean country incidence per million were calculated. RESULTS: From 2013 through 2018, there were 899 800 reported measles cases, of which 57% occurred unvaccinated or undervaccinated persons, with an unknown vaccination history in another 30%. Lower-middle-income countries accounted for 66% of cases, 23% occurred in persons ≥15 years of age. In countries with stronger historical vaccination programs and higher country income, case patients had higher median ages. CONCLUSIONS: Although most measles case patients are <15 years of age, an age shift is seen in countries with a higher income or a stronger historical vaccination program. Countries must strengthen immunization programs to achieve high vaccination coverage; some must undertake strategies to reach persons ≥15 years of age and close immunity gaps.

Oral rehydration therapies in Senegal, Mali, and Sierra Leone: a spatial analysis of changes over time and implications for policy.

BACKGROUND: Oral rehydration solution (ORS) is a simple intervention that can prevent childhood deaths from severe diarrhea and dehydration. In a previous study, we mapped the use of ORS treatment subnationally and found that ORS coverage increased over time, while the use of home-made alternatives or recommended home fluids (RHF) decreased, in many countries. These patterns were particularly striking within Senegal, Mali, and Sierra Leone. It was unclear, however, whether ORS replaced RHF in these locations or if children were left untreated, and if these patterns were associated with health policy changes. METHODS: We used a Bayesian geostatistical model and data from household surveys to map the percentage of children with diarrhea that received (1) any ORS, (2) only RHF, or (3) no oral rehydration treatment between 2000 and 2018. This approach allowed examination of whether RHF was replaced with ORS before and after interventions, policies, and external events that may have impacted healthcare access. RESULTS: We found that RHF was replaced with ORS in most Sierra Leone districts, except those most impacted by the Ebola outbreak. In addition, RHF was replaced in northern but not in southern Mali, and RHF was not replaced anywhere in Senegal. In Senegal, there was no statistical evidence that a national policy promoting ORS use was associated with increases in coverage. In Sierra Leone, ORS coverage increased following a national policy change that abolished health costs for children. CONCLUSIONS: Children in parts of Mali and Senegal have been left behind during ORS scale-up. Improved messaging on effective diarrhea treatment and/or increased ORS access such as through reducing treatment costs may be needed to prevent child deaths in these areas.

Vaccination to prevent human papillomavirus infections: From promise to practice.

In an essay, Paul Bloem and Ikechukwu Ogbuanu discuss the public health implications of HPV vaccination.

An assessment of the reasons for oral poliovirus vaccine refusals in northern Nigeria.

BACKGROUND: Accumulation of susceptible children whose caregivers refuse to accept oral poliovirus vaccine (OPV) contributes to the spread of poliovirus in Nigeria. METHODS: During and immediately following the OPV campaign in October 2012, polio eradication partners conducted a study among households in which the vaccine was refused, using semistructured questionnaires. The selected study districts had a history of persistent OPV refusals in previous campaigns. RESULTS: Polio risk perception was low among study participants. The majority (59%) of participants believed that vaccination was either not necessary or would not be helpful, and 30% thought it might be harmful. Religious beliefs were an important driver in the way people understood disease. Fifty-two percent of 48 respondents reported that illnesses were due to God's will and/or destiny and that only God could protect them against illnesses. Only a minority (14%) of respondents indicated that polio was a significant problem in their community. CONCLUSIONS: Caregivers refuse OPV largely because of poor polio risk perception and religious beliefs. Communication strategies should, therefore, aim to increase awareness of polio as a real health threat and educate communities about the safety of the vaccine. In addition, polio eradication partners should collaborate with other agencies and ministries to improve total primary healthcare packages to address identified unmet health and social needs.

Outreach to underserved communities in northern Nigeria, 2012-2013.

BACKGROUND: Persistent wild poliovirus transmission in Nigeria constitutes a major obstacle to global polio eradication. In August 2012, the Nigerian national polio program implemented a strategy to conduct outreach to underserved communities within the context of the country's polio emergency action plans. METHODS: A standard operating procedure (SOP) for outreach to underserved communities was developed and included in the national guidelines for management of supplemental immunization activities (SIAs). The SOP included the following key elements: (1) community engagement meetings, (2) training of field teams, (3) field work, and (4) acute flaccid paralysis surveillance. RESULTS: Of the 46,437 settlements visited and enumerated during the outreach activities, 8607 (19%) reported that vaccination teams did not visit their settlements during prior SIAs, and 5112 (11.0%) reported never having been visited by polio vaccination teams. Fifty-two percent of enumerated settlements (23,944) were not found in the existing microplan used for the immediate past SIAs. CONCLUSIONS: During a year of outreach to >45,000 scattered, nomadic, and border settlements, approximately 1 in 5 identified were missed in the immediately preceding SIAs. These missed settlements housed a large number of previously unvaccinated children and potentially served as reservoirs for persistent wild poliovirus transmission in Nigeria.

An evaluation of community perspectives and contributing factors to missed children during an oral polio vaccination campaign--Katsina State, Nigeria.

BACKGROUND: Unvaccinated children contribute to accumulation of susceptible persons and the continued transmission of wild poliovirus in Nigeria. In September 2012, the Expert Review Committee (ERC) on Polio Eradication and Routine Immunization in Nigeria recommended that social research be conducted to better understand why children are missed during supplementary immunization activities (SIAs), also known as "immunization plus days (IPDs)" in Nigeria. METHODS: Immediately following the SIA in October 2012, polio eradication partners and the government of Nigeria conducted a study to assess why children are missed. We used semistructured questionnaires and focus group discussions in 1 rural and 1 urban local government area (LGA) of Katsina State. RESULTS: Participants reported that 61% of the children were not vaccinated because of poor vaccination team performance: either the teams did not visit the homes (25%) or the children were reported absent and not revisited (36%). This lack of access to vaccine was more frequently reported by respondents from scattered/nomadic communities (85%). In 1 out of 4 respondents (25%), refusal was the main reason their child was not vaccinated. The majority of respondents reported they would have consented to their children being vaccinated if the vaccine had been offered. CONCLUSIONS: Poor vaccination team performance is a major contributor to missed children during IPD campaigns. Addressing such operational deficiencies will help close the polio immunity gap and eradicate polio from Nigeria.

Polio eradication in Nigeria and the role of the National Stop Transmission of Polio program, 2012-2013.

To strengthen the Nigeria polio eradication program at the operational level, the National Stop Transmission of Polio (N-STOP) program was established in July 2012 as a collaborative effort of the National Primary Health Care Development Agency, the Nigerian Field Epidemiology and Laboratory Training Program, and the US Centers for Disease Control and Prevention. Since its inception, N-STOP has recruited and trained 125 full-time staff, 50 residents in training, and 50 ad hoc officers. N-STOP officers, working at national, state, and district levels, have conducted enumeration outreaches in 46,437 nomadic and hard-to-reach settlements in 253 districts of 19 states, supported supplementary immunization activities in 236 districts, and strengthened routine immunization in 100 districts. Officers have also conducted surveillance assessments, outbreak response, and applied research as needs evolved. The N-STOP program has successfully enhanced Global Polio Eradication Initiative partnerships and outreach in Nigeria, providing an accessible, flexible, and culturally competent technical workforce at the front lines of public health. N-STOP will continue to respond to polio eradication program needs and remain a model for other healthcare initiatives in Nigeria and elsewhere.

Progress toward poliomyelitis eradication in Nigeria.

BACKGROUND: Transmission of wild poliovirus (WPV) has never been interrupted in Afghanistan, Pakistan, and Nigeria. Since 2003, infections with WPV of Nigerian origin have been detected in 25 polio-free countries. In 2012, the Nigerian government created an emergency operations center and implemented a national emergency action plan to eradicate polio. The 2013 revision of this plan prioritized (1) improving the quality of supplemental immunization activities (SIAs), (2) implementing strategies to reach underserved populations, (3) adopting special approaches in security-compromised areas, (4) improving outbreak response, (5) enhancing routine immunization and activities implemented between SIAs, and (6) strengthening surveillance. This report summarizes implementation of these activities during a period of unprecedented insecurity and violence, including the killing of health workers and the onset of a state of emergency in the northeast zone. METHODS: This report reviews management strategies, innovations, trends in case counts, vaccination and social mobilization activities, and surveillance and monitoring data to assess progress in polio eradication in Nigeria. RESULTS: Nigeria has made significant improvements in the management of polio eradication initiative (pei) activities with marked improvement in the quality of SIAs, as measured by lot quality assurance sampling (LQAS). Comparing results from February 2012 with results from December 2013, the proportion of local government areas (LGAs) conducting LQAS in the 11 high-risk states at the ≥90% pass/fail threshold increased from 7% to 42%, and the proportion at the 80%-89% threshold increased from 9% to 30%. During January-December 2013, 53 polio cases were reported from 26 LGAs in 9 states in Nigeria, compared with 122 cases reported from 13 states in 2012. No cases of WPV type 3 infection have been reported since November 2012. In 2013, no polio cases due to any poliovirus type were detected in the northwest sanctuaries of Nigeria. In the second half of 2013, WPV transmission was restricted to Kano, Borno, Bauchi, and Taraba states. Despite considerable progress, 24 LGAs in 2012 and 7 LGAs in 2013 reported ≥2 cases, and WPV continued to circulate in 8 LGAs that had cases in 2012. Campaign activities were negatively impacted by insecurity and violence in Borno and Kano states. CONCLUSIONS: Efforts to interrupt transmission remain impeded by poor SIA implementation in localized areas, anti-polio vaccine sentiment, and limited access to vaccinate children because of insecurity. Sustained improvement in SIA quality, surveillance, and outbreak response and special strategies in security-compromised areas are needed to interrupt WPV transmission in 2014.

Maternal, fetal, and neonatal outcomes associated with measles during pregnancy: Namibia, 2009-2010.

BACKGROUND: Previous studies of maternal, fetal, and neonatal complications of measles during pregnancy suggest the possibility of increased risk for morbidity and mortality. In 2009-2011, a nationwide laboratory-confirmed measles outbreak occurred in Namibia, with 38% of reported cases among adults. This outbreak provided an opportunity to describe clinical features of measles in pregnant women and assess the relative risk for adverse maternal, fetal, and neonatal outcomes. METHODS: A cohort of pregnant women with clinical measles was identified retrospectively from 6 district hospitals and clinics over a 12-month period. Each pregnant woman with measles was matched with 3 pregnant women without measles, randomly selected from antenatal clinic registers at the same hospital during the same time interval. We reviewed hospital and clinic records and conducted in-person interviews to collect demographic and clinical information on the pregnant women and their infants. RESULTS: Of 55 pregnant women with measles, 53 (96%) were hospitalized; measles-related complications included diarrhea (60%), pneumonia (40%), and encephalitis (5%). Among pregnant women with known human immunodeficiency virus (HIV) status, 15% of those without measles and 19% of those with measles were HIV positive. Of 42 measles-related pregnancies with known outcomes, 25 (60%) had ≥1 adverse maternal, fetal, or neonatal outcome and 5 women (12%) died. Compared with 172 pregnancies without measles, after adjusting for age, pregnancies with measles carried significantly increased risks for neonatal low birth weight (adjusted relative risk [aRR] = 3.5; 95% confidence interval [CI], 1.5-8.2), spontaneous abortion (aRR = 5.9; 95% CI, 1.8-19.7), intrauterine fetal death (aRR = 9.0; 95% CI, 1.2-65.5), and maternal death (aRR = 9.6; 95% CI, 1.3-70.0). CONCLUSIONS: Our findings suggest that measles virus infection during pregnancy confers a high risk of adverse maternal, fetal, and neonatal outcomes, including maternal death. Maximizing measles immunity among women of childbearing age would decrease the incidence of gestational measles and the attendant maternal, fetal, and neonatal morbidity and mortality.

Post-mortem investigation of deaths due to pneumonia in children aged 1-59 months in sub-Saharan Africa and South Asia from 2016 to 2022: an observational study.

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.

Burden of child mortality from malaria in high endemic areas: Results from the CHAMPS network using minimally invasive tissue sampling.

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.

Child deaths caused by Klebsiella pneumoniae in sub-Saharan Africa and south Asia: a secondary analysis of Child Health and Mortality Prevention Surveillance (CHAMPS) data.

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.

Identifying delays in healthcare seeking and provision: The Three Delays-in-Healthcare and mortality among infants and children aged 1-59 months.

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.

Has Authorship in the Decolonizing Global Health Movement Been Colonized?

Background: Decolonization in global health is a recent movement aimed at relinquishing remnants of supremacist mindsets, inequitable structures, and power differentials in global health. Objective: To determine the author demographics of publications on decolonizing global health and global health partnerships between low- and middle-income countries (LMICs) and high-income countries (HICs). Methods: We conducted a cross-sectional analysis of publications related to decolonizing global health and global health partnerships from the inception of the selected journal databases (i.e., Medline, CAB Global Health, EMBASE, CINAHL, and Web of Science) to November 14, 2022. Author country affiliations were assigned as listed in each publication. Author gender was assigned using author first name and the software genderize.io. Descriptive statistics were used for author country income bracket, gender, and distribution. Findings: Among 197 publications on decolonizing global health and global health partnerships, there were 691 total authors (median 2 authors per publication, interquartile range 1, 4). Publications with author bylines comprised exclusively of authors affiliated with HICs were most common (70.0%, n = 138) followed by those with authors affiliated both with HICs and LMICs (22.3%, n = 44). Only 7.6% (n = 15) of publications had author bylines comprised exclusively of authors affiliated with LMICs. Over half (54.0%, n = 373) of the included authors had names that were female and female authors affiliated with HICs most commonly occupied first author positions (51.8%, n = 102). Conclusions: Authors in publications on decolonizing global health and global health partnerships have largely been comprised of individuals affiliated with HICs. There was a marked paucity of publications with authors affiliated with LMICs, whose voices provide context and crucial insight into the needs of the decolonizing global health movement.

A Practical Guide to Pilot Testing Community-Based Vaccination Coverage Surveys.

Pilot testing is crucial when preparing any community-based vaccination coverage survey. In this paper, we use the term pilot test to mean informative work conducted before a survey protocol has been finalized for the purpose of guiding decisions about how the work will be conducted. We summarize findings from seven pilot tests and provide practical guidance for piloting similar studies. We selected these particular pilots because they are excellent models of preliminary efforts that informed the refinement of data collection protocols and instruments. We recommend survey coordinators devote time and budget to identify aspects of the protocol where testing could mitigate project risk and ensure timely assessment yields, credible estimates of vaccination coverage and related indicators. We list specific items that may benefit from pilot work and provide guidance on how to prioritize what to pilot test when resources are limited.

Stillbirths and Neonatal Deaths Caused by Group B Streptococcus in Africa and South Asia Identified Through Child Health and Mortality Prevention Surveillance (CHAMPS).

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.

Neural tube defects as a cause of death among stillbirths, infants, and children younger than 5 years in sub-Saharan Africa and southeast Asia: an analysis of the CHAMPS network.

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.