Effect of Delays in Maternal Access to Healthcare on Neonatal Mortality in Sierra Leone: A Social Autopsy Case-Control Study at a Child Health and Mortality Prevention Surveillance (CHAMPS) Site.

INTRODUCTION: In low-resource settings, a social autopsy tool has been proposed to measure the effect of delays in access to healthcare on deaths, complementing verbal autopsy questionnaires routinely used to determine cause of death. This study estimates the contribution of various delays in maternal healthcare to subsequent neonatal mortality using a social autopsy case-control design. METHODS: This study was conducted at the Child Health and Mortality Prevention Surveillance (CHAMPS) Sierra Leone site (Makeni City and surrounding rural areas). Cases were neonatal deaths in the catchment area, and controls were sex- and area-matched living neonates. Odds ratios for maternal barriers to care and neonatal death were estimated, and stratified models examined this association by neonatal age and medical complications. RESULTS: Of 53 neonatal deaths, 26.4% of mothers experienced at least one delay during pregnancy or delivery compared to 46.9% of mothers of stillbirths and 18.6% of control mothers. The most commonly reported delay among neonatal deaths was receiving care at the facility (18.9%). Experiencing any barrier was weakly associated (OR 1.68, CI 0.77, 3.67) and a delay in receiving care at the facility was strongly associated (OR 19.15, CI 3.90, 94.19) with neonatal death. DISCUSSION: Delays in healthcare are associated with neonatal death, particularly delays experienced at the healthcare facility. Heterogeneity exists in the prevalence of specific delays, which has implications for local public health policy. The findings and conclusions in this report are those of the author(s) and do not necessarily represent the official position of the Centers for Disease Control and Prevention.

Initial findings from a novel population-based child mortality surveillance approach: a descriptive study.

BACKGROUND: Sub-Saharan Africa and south Asia contributed 81% of 5·9 million under-5 deaths and 77% of 2·6 million stillbirths worldwide in 2015. Vital registration and verbal autopsy data are mainstays for the estimation of leading causes of death, but both are non-specific and focus on a single underlying cause. We aimed to provide granular data on the contributory causes of death in stillborn fetuses and in deceased neonates and children younger than 5 years, to inform child mortality prevention efforts. METHODS: The Child Health and Mortality Prevention Surveillance (CHAMPS) Network was established at sites in seven countries (Baliakandi, Bangladesh; Harar and Kersa, Ethiopia; Siaya and Kisumu, Kenya; Bamako, Mali; Manhiça, Mozambique; Bombali, Sierra Leone; and Soweto, South Africa) to collect standardised, population-based, longitudinal data on under-5 mortality and stillbirths in sub-Saharan Africa and south Asia, to improve the accuracy of determining causes of death. Here, we analysed data obtained in the first 2 years after the implementation of CHAMPS at the first five operational sites, during which surveillance and post-mortem diagnostics, including minimally invasive tissue sampling (MITS), were used. Data were abstracted from all available clinical records of deceased children, and relevant maternal health records were also extracted for stillbirths and neonatal deaths, to incorporate reported pregnancy or delivery complications. Expert panels followed standardised procedures to characterise causal chains leading to death, including underlying, intermediate (comorbid or antecedent causes), and immediate causes of death for stillbirths, neonatal deaths, and child (age 1-59 months) deaths. FINDINGS: Between Dec 10, 2016, and Dec 31, 2018, MITS procedures were implemented at five sites in Mozambique, South Africa, Kenya, Mali, and Bangladesh. We screened 2385 death notifications for inclusion eligibility, following which 1295 families were approached for consent; consent was provided for MITS by 963 (74%) of 1295 eligible cases approached. At least one cause of death was identified in 912 (98%) of 933 cases (180 stillbirths, 449 neonatal deaths, and 304 child deaths); two or more conditions were identified in the causal chain for 585 (63%) of 933 cases. The most common underlying causes of stillbirth were perinatal asphyxia or hypoxia (130 [72%] of 180 stillbirths) and congenital infection or sepsis (27 [15%]). The most common underlying causes of neonatal death were preterm birth complications (187 [42%] of 449 neonatal deaths), perinatal asphyxia or hypoxia (98 [22%]), and neonatal sepsis (50 [11%]). The most common underlying causes of child deaths were congenital birth defects (39 [13%] of 304 deaths), lower respiratory infection (37 [12%]), and HIV (35 [12%]). In 503 (54%) of 933 cases, at least one contributory pathogen was identified. Cytomegalovirus, Escherichia coli, group B Streptococcus, and other infections contributed to 30 (17%) of 180 stillbirths. Among neonatal deaths with underlying prematurity, 60% were precipitated by other infectious causes. Of the 275 child deaths with infectious causes, the most common contributory pathogens were Klebsiella pneumoniae (86 [31%]), Streptococcus pneumoniae (54 [20%]), HIV (40 [15%]), and cytomegalovirus (34 [12%]), and multiple infections were common. Lower respiratory tract infection contributed to 174 (57%) of 304 child deaths. INTERPRETATION: Cause of death determination using MITS enabled detailed characterisation of contributing conditions. Global estimates of child mortality aetiologies, which are currently based on a single syndromic cause for each death, will be strengthened by findings from CHAMPS. This approach adds specificity and provides a more complete overview of the chain of events leading to death, highlighting multiple potential interventions to prevent under-5 mortality and stillbirths. FUNDING: Bill & Melinda Gates Foundation.

Case Definitions Used During the First 6 Months of the 10th Ebola Virus Disease Outbreak in the Democratic Republic of the Congo - Four Neighboring Countries, August 2018-February 2019.

On August 1, 2018, the Democratic Republic of the Congo (DRC) declared its 10th Ebola virus disease (Ebola) outbreak in an area with a high volume of cross-border population movement to and from neighboring countries. The World Health Organization (WHO) designated Rwanda, South Sudan, and Uganda as the highest priority countries for Ebola preparedness because of the high risk for cross-border spread from DRC (1). Countries might base their disease case definitions on global standards; however, historical context and perceived risk often affect why countries modify and adapt definitions over time, moving toward or away from regional harmonization. Discordance in case definitions among countries might reduce the effectiveness of cross-border initiatives during outbreaks with high risk for regional spread. CDC worked with the ministries of health (MOHs) in DRC, Rwanda, South Sudan, and Uganda to collect MOH-approved Ebola case definitions used during the first 6 months of the outbreak to assess concordance (i.e., commonality in category case definitions) among countries. Changes in MOH-approved Ebola case definitions were analyzed, referencing the WHO standard case definition, and concordance among the four countries for Ebola case categories (i.e., community alert, suspected, probable, confirmed, and case contact) was assessed at three dates (2). The number of country-level revisions ranged from two to four, with all countries revising Ebola definitions by February 2019 after a December 2018 peak in incidence in DRC. Case definition complexity increased over time; all countries included more criteria per category than the WHO standard definition did, except for the "case contact" and "confirmed" categories. Low case definition concordance and lack of awareness of regional differences by national-level health officials could reduce effectiveness of cross-border communication and collaboration. Working toward regional harmonization or considering systematic approaches to addressing country-level differences might increase efficiency in cross-border information sharing.

Illuminating Child Mortality: Discovering Why Children Die.

Current understanding of the causes of under-5 childhood deaths in low- and middle-income countries relies heavily on country-level vital registration data and verbal autopsies. Reliable data on specific causes of deaths are crucial to target interventions more effectively and achieve rapid reductions in under-5 mortality. The Child Health and Mortality Prevention Surveillance (CHAMPS) network aims to systematically describe causes of child death and stillbirth in low- and middle-income countries using minimally invasive tissue sampling. The articles in this supplement introduce the set of foundational epidemiologic, demographic surveillance, social behavioral science, and laboratory methods. Undergirding the CHAMPS surveillance system designed to determine causes of child mortality.

Potential of Minimally Invasive Tissue Sampling for Attributing Specific Causes of Childhood Deaths in South Africa: A Pilot, Epidemiological Study.

BACKGROUND: Current estimates for causes of childhood deaths are mainly premised on modeling of vital registration and limited verbal autopsy data and generally only characterize the underlying cause of death (CoD). We investigated the potential of minimally invasive tissue sampling (MITS) for ascertaining the underlying and immediate CoD in children 1 month to 14 years of age. METHODS: MITS included postmortem tissue biopsies of brain, liver, and lung for histopathology examination; microbial culture of blood, cerebrospinal fluid (CSF), liver, and lung samples; and molecular microbial testing on blood, CSF, lung, and rectal swabs. Each case was individually adjudicated for underlying, antecedent, and immediate CoD by an international multidisciplinary team of medical experts and coded using the International Classification of Diseases, Tenth Revision (ICD-10). RESULTS: An underlying CoD was determined for 99% of 127 cases, leading causes being congenital malformations (18.9%), complications of prematurity (14.2%), human immunodeficiency virus/AIDS (12.6%), diarrheal disease (8.7%), acute respiratory infections (7.9%), injuries (7.9%), and malignancies (7.1%). The main immediate CoD was pneumonia, sepsis, and diarrhea in 33.9%, 19.7%, and 10.2% of cases, respectively. Infection-related deaths were either an underlying or immediate CoD in 78.0% of cases. Community-acquired pneumonia deaths (n = 32) were attributed to respiratory syncytial virus (21.9%), Pneumocystis jirovecii (18.8%), cytomegalovirus (15.6%), Klebsiella pneumoniae (15.6%), and Streptococcus pneumoniae (12.5%). Seventy-one percent of 24 sepsis deaths were hospital-acquired, mainly due to Acinetobacter baumannii (47.1%) and K. pneumoniae (35.3%). Sixty-two percent of cases were malnourished. CONCLUSIONS: MITS, coupled with antemortem clinical information, provides detailed insight into causes of childhood deaths that could be informative for prioritization of strategies aimed at reducing under-5 mortality.

An Observational Pilot Study Evaluating the Utility of Minimally Invasive Tissue Sampling to Determine the Cause of Stillbirths in South African Women.

BACKGROUND: Despite approximately 2.6 million stillbirths occurring annually, there is a paucity of systematic biological investigation and consequently knowledge on the causes of these deaths in low- and middle-income countries (LMICs). We investigated the utility of minimally invasive tissue sampling (MITS), placental examination, and clinical history, in attributing the causes of stillbirth in a South African LMIC setting. METHODS: This prospective, observational pilot study undertook sampling of brain, lung, and liver tissue using core biopsy needles, blood and cerebrospinal fluid collection, and placental examination. Testing included microbial culture and/or molecular testing and tissue histological examination. The cause of death was determined for each case by an international panel of medical specialists and categorized using the World Health Organization's International Classification of Diseases, Tenth Revision application to perinatal deaths. RESULTS: A cause of stillbirth was identifiable for 117 of 129 (90.7%) stillbirths, including an underlying maternal cause in 63.4% (n = 83) and an immediate fetal cause in 79.1% (n = 102) of cases. The leading underlying causes of stillbirth were maternal hypertensive disorders (16.3%), placental separation and hemorrhage (14.0%), and chorioamnionitis (10.9%). The leading immediate causes of fetal death were antepartum hypoxia (35.7%) and fetal infection (37.2%), including due to Escherichia coli (16.3%), Enterococcus species (3.9%), and group B Streptococcus (3.1%). CONCLUSIONS: In this pilot, proof-of-concept study, focused investigation of stillbirth provided granular detail on the causes thereof in an LMIC setting, including provisionally highlighting the largely underrecognized role of fetal sepsis as a dominant cause.

Unraveling Specific Causes of Neonatal Mortality Using Minimally Invasive Tissue Sampling: An Observational Study.

BACKGROUND: Postmortem minimally invasive tissue sampling (MITS) is a potential alternative to the gold standard complete diagnostic autopsy for identifying specific causes of childhood deaths. We investigated the utility of MITS, interpreted with available clinical data, for attributing underlying and immediate causes of neonatal deaths. METHODS: This prospective, observational pilot study enrolled neonatal deaths at Chris Hani Baragwanath Academic Hospital in Soweto, South Africa. The MITS included needle core-biopsy sampling for histopathology of brain, lung, and liver tissue. Microbiological culture and/or molecular tests were performed on lung, liver, blood, cerebrospinal fluid, and stool samples. The "underlying" and "immediate" causes of death (CoD) were determined for each case by an international panel of 12-15 medical specialists. RESULTS: We enrolled 153 neonatal deaths, 106 aged 3-28 days. Leading underlying CoD included "complications of prematurity" (52.9%), "complications of intrapartum events" (15.0%), "congenital malformations" (13.1%), and "infection related" (9.8%). Overall, infections were the immediate or underlying CoD in 57.5% (n = 88) of all neonatal deaths, including the immediate CoD in 70.4% (58/81) of neonates with "complications of prematurity" as the underlying cause. Overall, 74.4% of 90 infection-related deaths were hospital acquired, mainly due to multidrug-resistant Acinetobacter baumannii (52.2%), Klebsiella pneumoniae (22.4%), and Staphylococcus aureus (20.9%). Streptococcus agalactiae was the most common pathogen (5/15 [33.3%]) among deaths with "infections" as the underlying cause. CONCLUSIONS: MITS has potential to address the knowledge gap on specific causes of neonatal mortality. In our setting, this included the hitherto underrecognized dominant role of hospital-acquired multidrug-resistant bacterial infections as the leading immediate cause of neonatal deaths.