Achieving the Sustainable Development Goal of reducing child mortality to <25 deaths per 1000 live births by 2030 requires strategies to prevent diarrheal disease-related morbidity and mortality. Accurate etiological diagnosis is essential. This study used postmortem diagnostics to investigate the contribution of diarrhea to under-5 mortality and examine co-morbidities and co-infections in Africa and South Asia. Child Health and Mortality Prevention Surveillance (CHAMPS) generates data on child deaths through minimally invasive tissue sampling, clinical record review, and verbal autopsies. Multidisciplinary panels assign cause(s) of death using WHO International Classification of Diseases. This analysis included deaths among children aged 1-59 months enrolled from 18 December 2016-31 December 2023 across six African sites (Ethiopia, Mali, Kenya, Sierra Leone, Mozambique, South Africa) and Bangladesh. Of 1517 deaths assessed, diarrhea was in the causal pathway in 240 (15.8%). The proportion of diarrhea-related deaths was highest in Ethiopia (41.0%, 34/83), followed by Bangladesh, (30.0%, 3/10), Mozambique (21.7%, 56/258), Mali (17.5%, 18/103), Kenya (13.9%, 51/366), Sierra Leone (12.8%, 46/358), and South Africa (9.4%, 32/339). Diarrhea was underlying cause in 44.2% (106/240) of cases and immediate/antecedent cause in 58.3% (140/240), with some deaths involving multiple roles in the causal chain. When diarrhea was underlying cause, sepsis (33.0%) and lower respiratory infections (25.5%) were common downstream conditions; when an antecedent/immediate cause, leading underlying causes were malnutrition (64.3%) and HIV (13.6%). No pathogen was identified in 49.6% (119/240) of diarrhea-related deaths; among these, diarrhea was underlying cause in 42.9%. Among the 121 pathogen-attributed deaths, the most frequent were EAEC (34.7%), typical EPEC (15.7%), Shigella/EIEC (14.0%), ST-ETEC (12.4%), rotavirus (26.4%), and adenovirus (non-40/41: 19.0%; 40/41: 5.0%). These pathogens were frequently identified as co-infections. Diarrheal disease accounted for a substantial share of child deaths across CHAMPS sites. Reducing mortality will require preventing diarrhea and addressing key contributors such as malnutrition and HIV.

IMPORTANCE: Most of the 2.3 million annual neonatal deaths occur in sub-Saharan Africa and South Asia, with perinatal asphyxia and neonatal sepsis being the leading causes of neonatal mortality. Most neonatal deaths are considered preventable through high-quality clinical care, which includes adherence to clinical care guidelines. OBJECTIVE: To assess adherence to World Health Organization clinical care guidelines for management of perinatal asphyxia and neonatal sepsis and to identify patient-level factors in adherence among neonates who died from these conditions. DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study obtained data from December 2015 through October 2023 from the Child Health and Mortality Prevention Surveillance (CHAMPS) catchment areas in 7 low- and middle-income countries in sub-Saharan Africa (Ethiopia, Kenya, Mali, Mozambique, Sierra Leone, and South Africa) and South Asia (Bangladesh). Participants were neonates who were born alive and were aged 0 to 28 days at the time of death and had either perinatal asphyxia or neonatal sepsis. EXPOSURE: Medical records of neonates who died from perinatal asphyxia or neonatal sepsis determined by postmortem diagnostics. MAIN OUTCOMES AND MEASURES: The main outcome was the proportion of deceased neonates who received guideline-adherent treatments before they died. Mixed-effect multivariable logistic regression analyses were performed to identify factors associated with administration of at least bag-valve-mask (BVM) ventilation for perinatal asphyxia. RESULTS: Of the 1194 neonates (median [IQR] age at the time of death, 2 [1-6] days; 692 males [58.0%]) who died and were enrolled in CHAMPS with available clinical data, 476 (39.9%) died from perinatal asphyxia, 562 (47.0%) died from neonatal sepsis, and 156 (13.1%) from both conditions. These neonates had a median (IQR) birth weight of 2130 (1266-2988) g. For cases with perinatal asphyxia, guideline adherence ranged from 12.2% (n = 77) for adrenaline administration to 85.4% (540) for supplemental oxygen administration. Only 4.4% of neonates (28) with perinatal asphyxia received all recommended treatments. Among cases with neonatal sepsis, antibiotics were administered to 86.8% (623), although the recommended treatment was administered to only 61.0% (438). In multivariable analyses, neonates in whom clinicians accurately identified perinatal asphyxia were more likely to receive BVM ventilation than those who had received discordant antemortem and postmortem diagnoses (adjusted odds ratio, 2.00; 95% CI, 1.29-3.12). CONCLUSIONS AND RELEVANCE: In this cross-sectional study, clinical care guideline adherence was suboptimal among neonates who died from perinatal asphyxia or neonatal sepsis. This finding underscores the critical need to increase adherence in regions with high rates of neonatal mortality and may inform strategies for strengthening health systems to support compliance with clinical care guidelines.

BACKGROUND: There is paucity of information on the role of cytomegalovirus (CMV) infection as a cause of stillbirths or childhood deaths in low-and middle-income countries (LMICs). We investigated attribution of CMV-disease in the causal pathway to stillbirths and deaths in children <5 years of age in seven LMICs participating in the Child Health and Mortality Prevention Surveillance (CHAMPS) network. METHODS: We analyzed stillbirths and decedents enrolled between December 2016 and July 2023. Deaths were investigated using post-mortem minimally invasive tissue sampling with histopathology and molecular diagnostic investigations of tissues and body fluids, along with review of clinical records. Multi-disciplinary expert panels reviewed findings and reported on the causal pathway to death. RESULTS: CMV was detected in 19.5%(1140/5841) of all evaluated deaths, including 5.0% (111/2204), 6.2% (139/2229), 41.2% (107/260), 68.1%(323/474) and 68.2%(460/674) of stillbirths, neonates (deaths 0-<28 days postnatal), young infants (28-<90 days), older infants (90-<365 days) and children (12-<60 months), respectively. CMV-disease was attributed in the causal pathway to death in 0.9%(20/2204) of stillbirths, 0.8%(17/2229) of neonates, 13.1% (34/260) of young infants, 9.7%(46/474) of older infants and 3.3%(22/674) of children. Decedents with CMV-disease compared with those without CMV-disease in the causal pathway, were more likely to have severe microcephaly (38.2% vs. 21.1%; aOR 2.2, 95%CI: 1.3-3.6) and HIV-infected (36.9% vs. 6.2%; aOR: 10.9, 95%CI: 6.5-18.5). CONCLUSIONS: CMV-disease is an important contributor to deaths during infancy and childhood and is often associated with severe microcephaly and HIV-infection. Improving management of CMV in HIV-infected children and a vaccine to prevent CMV are needed interventions.

INTRODUCTION: Malnutrition contributes to 45% of all childhood deaths globally, but these modelled estimates lack direct measurements in countries with high malnutrition and under-5 mortality rates. We investigated malnutrition's role in infant and child deaths in the Child Health and Mortality Prevention Surveillance (CHAMPS) network. METHODS: We analysed CHAMPS data from seven sites (Bangladesh, Ethiopia, Kenya, Mali, Mozambique, Sierra Leone and South Africa) collected between 2016 and 2023. An expert panel assessed each death to determine whether malnutrition was an underlying, antecedent or immediate cause or other significant condition. Malnutrition was further classified based on postmortem anthropometry using WHO growth standards for underweight (z-scores for weight-for-age <-2), stunting (length-for-age <-2), and wasting (weight-for-length or MUAC Z-scores <-2). RESULTS: Of 1601 infant and child deaths, malnutrition was considered a causal or significant condition in 632 (39.5%) cases, including 85 (13.4%) with HIV infection. Postmortem measurements indicated 90.1%, 61.2% and 94.1% of these cases were underweight, stunted and wasted, respectively. Most malnutrition-related deaths (n=632) had an infectious cause (89.1%). The adjusted odds of having malnutrition as causal or significant condition were 2.4 (95% CI 1.7 to 3.2) times higher for deaths involving infectious diseases compared with other causes. Common pathogens in the causal pathway for malnutrition-related deaths included Klebsiella pneumoniae (30.4%), Streptococcus pneumoniae (21.5%), Plasmodium falciparum (18.7%) and Escherichia coli/Shigella (17.2%). CONCLUSION: Malnutrition was identified as a causal or significant factor in 39.5% of under-5 deaths in the CHAMPS network, often in combination with infectious diseases. These findings highlight the need for integrated interventions addressing both malnutrition and infectious diseases to effectively reduce under-5 mortality.

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.

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.

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.

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.

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.

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.

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. FUNDING: This work was supported by the Bill & Melinda Gates Foundation [OPP1126780].

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.

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.

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.

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.

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.

IMPORTANCE: Although child mortality trends have decreased worldwide, deaths among children younger than 5 years of age remain high and disproportionately circumscribed to sub-Saharan Africa and Southern Asia. Tailored and innovative approaches are needed to increase access, coverage, and quality of child health care services to reduce mortality, but an understanding of health system deficiencies that may have the greatest impact on mortality among children younger than 5 years is lacking. OBJECTIVE: To investigate which health care and public health improvements could have prevented the most stillbirths and deaths in children younger than 5 years using data from the Child Health and Mortality Prevention Surveillance (CHAMPS) network. DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study used longitudinal, population-based, and mortality surveillance data collected by CHAMPS to understand preventable causes of death. Overall, 3390 eligible deaths across all 7 CHAMPS sites (Bangladesh, Ethiopia, Kenya, Mali, Mozambique, Sierra Leone, and South Africa) between December 9, 2016, and December 31, 2021 (1190 stillbirths, 1340 neonatal deaths, 860 infant and child deaths), were included. Deaths were investigated using minimally invasive tissue sampling (MITS), a postmortem approach using biopsy needles for sampling key organs and fluids. MAIN OUTCOMES AND MEASURES: For each death, an expert multidisciplinary panel reviewed case data to determine the plausible pathway and causes of death. If the death was deemed preventable, the panel identified which of 10 predetermined health system gaps could have prevented the death. The health system improvements that could have prevented the most deaths were evaluated for each age group: stillbirths, neonatal deaths (aged <28 days), and infant and child deaths (aged 1 month to <5 years). RESULTS: Of 3390 deaths, 1505 (44.4%) were female and 1880 (55.5%) were male; sex was not recorded for 5 deaths. Of all deaths, 3045 (89.8%) occurred in a healthcare facility and 344 (11.9%) in the community. Overall, 2607 (76.9%) were deemed potentially preventable: 883 of 1190 stillbirths (74.2%), 1010 of 1340 neonatal deaths (75.4%), and 714 of 860 infant and child deaths (83.0%). Recommended measures to prevent deaths were improvements in antenatal and obstetric care (recommended for 588 of 1190 stillbirths [49.4%], 496 of 1340 neonatal deaths [37.0%]), clinical management and quality of care (stillbirths, 280 [23.5%]; neonates, 498 [37.2%]; infants and children, 393 of 860 [45.7%]), health-seeking behavior (infants and children, 237 [27.6%]), and health education (infants and children, 262 [30.5%]). CONCLUSIONS AND RELEVANCE: In this cross-sectional study, interventions prioritizing antenatal, intrapartum, and postnatal care could have prevented the most deaths among children younger than 5 years because 75% of deaths among children younger than 5 were stillbirths and neonatal deaths. Measures to reduce mortality in this population should prioritize improving existing systems, such as better access to antenatal care, implementation of standardized clinical protocols, and public education campaigns.

INTRODUCTION: The high burden of stillbirths and neonatal deaths is driving global initiatives to improve birth outcomes. Discerning stillbirths from neonatal deaths can be difficult in some settings, yet this distinction is critical for understanding causes of perinatal deaths and improving resuscitation practices for live born babies. METHODS: We evaluated data from the Child Health and Mortality Prevention Surveillance (CHAMPS) network to compare the accuracy of determining stillbirths versus neonatal deaths from different data sources and to evaluate evidence of resuscitation at delivery in accordance with World Health Organization (WHO) guidelines. CHAMPS works to identify causes of stillbirth and death in children <5 years of age in Bangladesh and 6 countries in sub-Saharan Africa. Using CHAMPS data, we compared the final classification of a case as a stillbirth or neonatal death as certified by the CHAMPS Determining Cause of Death (DeCoDe) panel to both the initial report of the case by the family member or healthcare worker at CHAMPS enrollment and the birth outcome as stillbirth or livebirth documented in the maternal health record. RESULTS: Of 1967 deaths ultimately classified as stillbirth, only 28 (1.4%) were initially reported as livebirths. Of 845 cases classified as very early neonatal death, 33 (4%) were initially reported as stillbirth. Of 367 cases with post-mortem examination showing delivery weight >1000g and no maceration, the maternal clinical record documented that resuscitation was not performed in 161 cases (44%), performed in 14 (3%), and unknown or data missing for 192 (52%). CONCLUSION: This analysis found that CHAMPS cases assigned as stillbirth or neonatal death after DeCoDe expert panel review were generally consistent with the initial report of the case as a stillbirth or neonatal death. Our findings suggest that more frequent use of resuscitation at delivery and improvements in documentation around events at birth could help improve perinatal outcomes.

BACKGROUND: Globally, mortality in children younger than 5 years has been decreasing over the past few decades, but high under-5 mortality persists across regions of sub-Saharan Africa and southern Asia. Interventions-such as improved quality of clinical and antenatal care, better access to emergency obstetrical procedures, better triage and risk stratification, better immunisation coverage, or infection control measures-could substantially reduce deaths, but it is unclear which strategies could save the most lives. We aimed to use data from the Child Health and Mortality Prevention Surveillance (CHAMPS) network to examine which health-care and public health improvements could have prevented the most deaths. METHODS: We used standardised, population-based, mortality surveillance data collected by CHAMPS from seven sites (Bangladesh, Ethiopia, Kenya, Mali, Mozambique, Sierra Leone, and South Africa) to understand preventable causes of death in children younger than 5 years. Deaths were investigated with minimally invasive tissue sampling, a post-mortem approach using biopsy needles for sampling key organs and body fluids. For each death, an expert panel reviewed case data to determine whether the death was preventable and (if preventable) provided recommendations as to how the death could have been avoided. We evaluated which health system improvements could have prevented the most deaths among those who underwent minimally invasive tissue sampling for each age group: stillbirths, neonatal deaths (aged <28 days), and infant or child deaths (aged 1 month to <5 years). FINDINGS: We included 1982 eligible deaths (with minimally invasive tissue sampling performed) that occurred between Dec 9, 2016, and Feb 29, 2020, including 556 stillbirths, 828 neonatal deaths, and 598 child deaths. Of these 1982 deaths across all seven CHAMPS sites, 393 (71%) stillbirths, 583 (70%) neonatal deaths, and 487 (81%) child deaths were deemed preventable. The most recommended measures to prevent deaths were improvements in antenatal or obstetric care (recommended for 44% of stillbirths and 31% of neonatal deaths), clinical management and quality of care (stillbirths 26%, neonates 32%, children 46%), health-seeking behaviour (children 24%), and health education (children 22%). Given that 70% of under-5 deaths are stillbirths and neonatal deaths, an intervention that focuses on these age groups (eg, improved antenatal care) could prevent the most under-5 deaths. INTERPRETATION: These data indicate areas in which greater focus on improving existing systems could prevent the most deaths. Investments in interventions such as better access to antenatal care, improvements in clinical practice, and public education campaigns could substantially reduce child mortality. FUNDING: Bill & Melinda Gates Foundation (OPP1126780).

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.

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.

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.

BACKGROUND: To inform the introduction of pneumococcal conjugate vaccine (PCV) and rotavirus vaccine, the World Health Organization (WHO) established the Global Invasive Bacterial Vaccine-Preventable Disease Surveillance Network (GISN) and the Global Rotavirus Surveillance Network (GRSN) in 2008. We investigated whether participation in these networks or other surveillance was associated with vaccine introduction. METHODS: Between 2006 and 2018, among all WHO member states, we used multivariable models adjusting for economic status to assess (1) the association between surveillance for pneumococcal disease or rotavirus disease, including participation in GISN or GRSN and the introduction of the PCV or the rotavirus vaccine, respectively, and (2) the association between the rotavirus disease burden and the rotavirus vaccine introduction among 56 countries participating in GRSN from 2008 to 2018. RESULTS: Countries that participated in or conducted surveillance for invasive pneumococcal disease or rotavirus disease were 3.5 (95% confidence interval [CI], 1.7-7.1) and 4.2 (95% CI, 2.1-8.6) times more likely to introduce PCV or rotavirus respectively, compared to those without surveillance. Among countries participating in GRSN, there was insufficient evidence to demonstrate an association between countries with higher rotavirus positivity and vaccine introduction. CONCLUSIONS: Surveillance should be incorporated into advocacy strategies to encourage the introduction of vaccines, with countries benefiting from data from, support for, and coordination of international disease surveillance networks.

BACKGROUND: In November 2016, the Kenya National Vaccines and Immunization Programme conducted an assessment of missed opportunities for vaccination (MOV) using the World Health Organization (WHO) MOV methodology. A MOV includes any contact with health services during which an eligible individual does not receive all the vaccine doses for which he or she is eligible. METHODS: The MOV assessment in Kenya was conducted in 10 geographically diverse counties, comprising exit interviews with caregivers and knowledge, attitudes, and practices (KAP) surveys with health workers. On the survey dates, which covered a 4-day period in November 2016, all health workers and caregivers visiting the selected health facilities with children <24 months of age were eligible to participate. Health facilities (n = 4 per county) were purposively selected by size, location, ownership, and performance. We calculated the proportion of MOV among children eligible for vaccination and with documented vaccination histories (i.e., from a home-based record or health facility register), and stratified MOV by age and reason for visit. Timeliness of vaccine doses was also calculated. RESULTS: We conducted 677 age-eligible children exit interviews and 376 health worker KAP surveys. Of the 558 children with documented vaccination histories, 33% were visiting the health facility for a vaccination visit and 67% were for other reasons. A MOV was seen in 75% (244/324) of children eligible for vaccination with documented vaccination histories, with 57% (186/324) receiving no vaccinations. This included 55% of children visiting for a vaccination visit and 93% visiting for non-vaccination visits. Timeliness for multi-dose vaccine series doses decreased with subsequent doses. Among health workers, 25% (74/291) were unable to correctly identify the national vaccination schedule for vaccines administered during the first year of life. Among health workers who reported administering vaccines as part of their daily work, 39% (55/142) reported that they did not always have the materials they needed for patients seeking immunization services, such as vaccines, syringes, and vaccination recording documents. CONCLUSIONS: The MOV assessment in Kenya highlighted areas of improvement that could reduce MOV. The results suggest several interventions including standardizing health worker practices, implementing an orientation package for all health workers, and developing a stock management module to reduce stock-outs of vaccines and vaccination-related supplies. To improve vaccination coverage and equity in all counties in Kenya, interventions to reduce MOV should be considered as part of an overall immunization service improvement plan.

BACKGROUND: In 2016, Kenya conducted a study of missed opportunities for vaccination (MOV)-when eligible children have contact with the health system but are not fully vaccinated-to explore some of the reasons for persistent low vaccination coverage. This paper details the qualitative findings from that assessment. METHODS: Using the World Health Organization MOV methodology, teams conducted focus group discussions among caregivers and health workers and in-depth interviews of key informants in 10 counties in Kenya. Caregivers of children <24 months of age visiting the selected health facilities on the day of the assessment were requested to participate in focus group discussions. Health workers were purposively sampled to capture a broad range of perspectives. Key informants were selected based on their perceived insight on immunization services at the county, sub-county, or health facility level. RESULTS: Six focus group discussions with caregivers, eight focus group discussions with health workers, and 35 in-depth interviews with key informants were completed. In general, caregivers had positive attitudes toward healthcare and vaccination services, but expressed a desire for increased education surrounding vaccination. In order to standardize vaccination checks at all health facility visits, health workers and key informants emphasized the need for additional trainings for all staff members on immunization. Health workers and key informants also highlighted the negative impact of significant understaffing in health facilities, and the persistent challenge of stock-outs of vaccines and vaccination-related supplies. CONCLUSIONS: Identified factors that could contribute to MOV include a lack of knowledge surrounding vaccination among caregivers and health workers, inadequate number of health workers, and stock-outs of vaccines or vaccination-related materials. In addition, vaccination checks outside of vaccination visits lacked consistency, leading to MOV in non-vaccinating departments. Qualitative assessments could provide a starting point for understanding and developing interventions to address MOV in other countries.

INTRODUCTION: Since its independence in 2002, Timor Leste has made significant strides in improving childhood vaccination coverage. However, coverage is still below national targets, and children continue to have missed opportunities for vaccination (MOV), when eligible children have contact with the health system but are not vaccinated. Timor Leste implemented the updated World Health Organization methodology for assessing MOV in 2016. METHODS: The MOV data collection included quantitative (caregiver exit interviews and health worker knowledge, attitudes, practices surveys (KAP)) and qualitative arms (focus group discussions (FGDs) with caregivers and health workers and in-depth interviews (IDIs) with health administrators). During a four-day period, health workers and caregivers with children <24months of age attending the selected eight facilities in Dili Municipality were invited to participate. The researchers calculated the proportion of MOV and timeliness of vaccine doses among children with documented vaccination histories (i.e., from a home-based record or facility register) and thematically analyzed the qualitative data. RESULTS: Researchers conducted 365 caregiver exit interviews, 169 health worker KAP surveys, 4 FGDs with caregivers, 2 FGDs with health workers, and 2 IDIs with health administrators. Among eligible children with documented vaccination histories (n=199), 41% missed an opportunity for vaccination. One-third of health workers (33%) believed their knowledge of immunization practices to be insufficient. Qualitative results showed vaccines were not available at all selected health facilities, and some facilities reported problems with their cold chain equipment. CONCLUSION: This study demonstrates that many children in Timor Leste miss opportunities for vaccination during health service encounters. Potential interventions to reduce MOV include training of health workers, improving availability of vaccines at more health facilities, and replacing unusable cold chain equipment. Timor Leste should continue to scale up successful MOV interventions beyond Dili Municipality to improve vaccination coverage nationally and strengthen the health system overall.

BACKGROUND: In 2015, the World Health Organization (WHO) updated the global methodology for assessing and reducing missed opportunities for vaccination (MOV), when eligible children have contact with the health system but are not vaccinated. This paper presents the results of two pilot assessments conducted in Chad and Malawi. METHODS: Using the ten-step global WHO MOV strategy, we purposively selected districts and health facilities, with non-probabilistic sampling of <24 month old children for exit interviews of caregivers and self-administered knowledge, attitudes, and practices (KAP) surveys of health workers. MOV were calculated based on a child's documented vaccination history (i.e., from a home-based record (HBR) or a health facility vaccination register), including selected vaccines in the national schedule. RESULTS: Respondents included caregivers of 353 children in Chad and of 580 children in Malawi. Among those with documented vaccination history, 82% (195/238) were eligible for vaccination in Chad and 47% (225/483) in Malawi. Among eligible children, 51% (99/195) in Chad, and 66% (149/225) in Malawi had one or more MOV on the survey date. During non-vaccination visits, 77% (24/31) of children eligible for vaccination in Chad and 92% (119/129) in Malawi had a MOV compared to 46% (75/164) and 31% (30/96) during vaccination visits, respectively. Among health workers, 92% in Chad and 88% in Malawi were unable to correctly identify valid contraindications for vaccination. CONCLUSION: The new MOV tool was able to characterize the type and potential causes of MOV. In both countries, the findings of the assessments point to two major barriers to full vaccination of eligible children-a lack of coordination between vaccination and curative health services and incomplete vaccination during vaccination visits. National immunization programs should explore tailored efforts to improve health worker practices and to increase vaccine delivery by making better use of existing health service contacts.

BACKGROUND: Despite recent success towards controlling poliovirus transmission, Nigeria has struggled to achieve uniformly high routine vaccination coverage. A lack of reliable vaccination coverage data at the operational level makes it challenging to target program improvement. To reliably estimate vaccination coverage, we conducted district-level vaccine coverage surveys using a pre-existing infrastructure of polio technical staff in northern Nigeria. METHODS: Household-level cluster surveys were conducted in 40 polio high risk districts of Nigeria during 2014-2015. Global positioning system technology and intensive supervision by a pool of qualified technical staff were used to ensure high survey quality. Vaccination status of children aged 12-23 months was documented based on vaccination card or caretaker's recall. District-level coverage estimates were calculated using survey methods. RESULTS: Data from 7,815 children across 40 districts were analyzed. District-level coverage with the third dose of diphtheria-pertussis-tetanus vaccine (DPT3) ranged widely from 1-63%, with all districts having DPT3 coverage below the target of 80%. Median coverage across all districts for each of eight vaccine doses (1 Bacille Calmette-Guerin dose, 3 DPT doses, 3 oral poliovirus vaccine doses, and 1 measles vaccine dose) was <50%. DPT3 coverage by survey was substantially lower (range: 28%-139%) than the 2013 administrative coverage reported among children aged <12 months. Common reported reasons for non-vaccination included lack of knowledge about vaccines and vaccination services (50%) and factors related to access to routine immunization services (15%). CONCLUSIONS: Survey results highlighted vaccine coverage gaps that were systematically underestimated by administrative reporting across 40 polio high risk districts in northern Nigeria. Given the limitations of administrative coverage data, our approach to conducting quality district-level coverage surveys and providing data to assess and remediate issues contributing to poor vaccination coverage could serve as an example in countries with sub-optimal vaccination coverage, similar to Nigeria.

BACKGROUND: The World Health Organization, African Region, set the goal of achieving measles elimination by 2020. Namibia was one of seven African countries to implement an accelerated measles control strategy beginning in 1996. Following implementation of this strategy, measles incidence decreased; however, between 2009 and 2011 a major outbreak occurred in Namibia. METHODS: Measles vaccination coverage data were analysed and a descriptive epidemiological analysis of the measles outbreak was conducted using measles case-based surveillance and laboratory data. RESULTS: During 1989 - 2008, MCV1 (the first routine dose of measles vaccine) coverage increased from 56% to 73% and five supplementary immunisation activities were implemented. During the outbreak (August 2009 - February 2011), 4 605 suspected measles cases were reported; of these, 3 256 were confirmed by laboratory testing or epidemiological linkage. Opuwo, a largely rural district in north-western Namibia with nomadic populations, had the highest confirmed measles incidence (16 427 cases per million). Infants aged ≤11 months had the highest cumulative age-specific incidence (9 252 cases per million) and comprised 22% of all confirmed cases; however, cases occurred across a wide age range, including adults aged ≥30 years. Among confirmed cases, 85% were unvaccinated or had unknown vaccination history. The predominantly detected measles virus genotype was B3, circulating in concurrent outbreaks in southern Africa, and B2, previously detected in Angola. CONCLUSION: A large-scale measles outbreak with sustained transmission over 18 months occurred in Namibia, probably caused by importation. The wide age distribution of cases indicated measles-susceptible individuals accumulated over several decades prior to the start of the outbreak.