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.

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.

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.

Investigating the Feasibility of Child Mortality Surveillance With Postmortem Tissue Sampling: Generating Constructs and Variables to Strengthen Validity and Reliability in Qualitative Research.

BACKGROUND: The Child Health and Mortality Prevention Surveillance (CHAMPS) network aims to generate reliable data on the causes of death among children aged <5 years using all available information, including minimally invasive tissue sampling (MITS). The sensitive nature of MITS inevitably evokes religious, cultural, and ethical questions influencing the feasibility and sustainability of CHAMPS. METHODS: Due to limited behavioral studies related to child MITS, we developed an innovative qualitative methodology to determine the barriers, facilitators, and other factors that affect the implementation and sustainability of CHAMPS surveillance across 7 diverse locations in sub-Saharan Africa and South Asia. We employed a multimethod grounded theory approach and analytical structure based on culturally specific conceptual frameworks. The methodology guided data interpretation and collective analyses confirming how to define dimensions of CHAMPS feasibility within the cultural context of each site while reducing subjectivity and bias in the process of interpretation and reporting. RESULTS: Findings showed that the approach to gain consent to conduct the MITS procedure involves religious factors associated with timing of burial, use of certain terminology, and methods of transporting the body. Community misperceptions and uncertainties resulted in rumor surveillance and consistency in information sharing. Religious pronouncements, recognition of health priorities, attention to pregnancy, and advancement of child health facilitated community acceptability. CONCLUSIONS: These findings helped formulate program priorities, guided site-specific adaptations in surveillance procedures, and verified inferences drawn from CHAMPS epidemiological and formative research data. Results informed appropriate community sensitization and engagement activities for introducing and sustaining mortality surveillance, including MITS.

Using Participatory Workshops to Assess Alignment or Tension in the Community for Minimally Invasive Tissue Sampling Prior to Start of Child Mortality Surveillance: Lessons From 5 Sites Across the CHAMPS Network.

The Child Health and Mortality Prevention Surveillance (CHAMPS) program is a 7-country network (as of December 2018) established by the Bill & Melinda Gates Foundation to identify the causes of death in children in communities with high rates of under-5 mortality. The program carries out both mortality and pregnancy surveillance, and mortality surveillance employs minimally invasive tissue sampling (MITS) to gather small samples of body fluids and tissue from the bodies of children who have died. While this method will lead to greater knowledge of the specific causes of childhood mortality, the procedure is in tension with cultural and religious norms in many of the countries where CHAMPS works-Bangladesh, Ethiopia, Kenya, Mali, Mozambique, Sierra Leone, and South Africa. Participatory Inquiry Into Community Knowledge of Child Health and Mortality Prevention (PICK-CHAMP) is a community entry activity designed to introduce CHAMPS to communities and gather initial perspectives on alignments and tensions between CHAMPS activities and community perceptions and priorities. Participants' responses revealed medium levels of overall alignment in all sites (with the exception of South Africa, where alignment was high) and medium levels of tension (with the exception of Ethiopia, where tension was high). Alignment was high and tension was low for pregnancy surveillance across all sites, whereas Ethiopia reflected low alignment and high tension for MITS. Participants across all sites indicated that support for MITS was possible only if the procedure did not interfere with burial practices and rituals.

Development and Implementation of Multiplex TaqMan Array Cards for Specimen Testing at Child Health and Mortality Prevention Surveillance Site Laboratories.

Child Health and Mortality Prevention Surveillance (CHAMPS) laboratories are employing a variety of laboratory methods to identify infectious agents contributing to deaths of children <5 years old and stillbirths in sub-Saharan Africa and South Asia. In support of this long-term objective, our team developed TaqMan Array Cards (TACs) for testing postmortem specimens (blood, cerebrospinal fluid, lung tissue, respiratory tract swabs, and rectal swabs) for >100 real-time polymerase chain reaction (PCR) targets in total (30-45 per card depending on configuration). Multipathogen panels were configured by syndrome and customized to include pathogens of significance in young children within the regions where CHAMPS is conducted, including bacteria (57 targets covering 30 genera), viruses (48 targets covering 40 viruses), parasites (8 targets covering 8 organisms), and fungi (3 targets covering 3 organisms). The development and application of multiplex real-time PCR reactions to the TAC microfluidic platform increased the number of targets in each panel while maintaining assay efficiency and replicates for heightened sensitivity. These advances represent a substantial improvement in the utility of this technology for infectious disease diagnostics and surveillance. We optimized all aspects of the CHAMPS molecular laboratory testing workflow including nucleic acid extraction, quality assurance, and data management to ensure comprehensive molecular testing of specimens and high-quality data. Here we describe the development and implementation of multiplex TACs and associated laboratory protocols for specimen processing, testing, and data management at CHAMPS site laboratories.

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.

Overview and Development of the Child Health and Mortality Prevention Surveillance Determination of Cause of Death (DeCoDe) Process and DeCoDe Diagnosis Standards.

Mortality surveillance and cause of death data are instrumental in improving health, identifying diseases and conditions that cause a high burden of preventable deaths, and allocating resources to prevent these deaths. The Child Health and Mortality Prevention Surveillance (CHAMPS) network uses a standardized process to define, assign, and code causes of stillbirth and child death (<5 years of age) across the CHAMPS network. A Determination of Cause of Death (DeCoDe) panel composed of experts from a local CHAMPS site analyzes all available individual information, including laboratory, histopathology, abstracted clinical records, and verbal autopsy findings for each case and, if applicable, also for the mother. Using this information, the site panel ascertains the underlying cause (event that precipitated the fatal sequence of events) and other antecedent, immediate, and maternal causes of death in accordance with the International Classification of Diseases, Tenth Revision and the World Health Organization death certificate. Development and use of the CHAMPS diagnosis standards-a framework of required evidence to support cause of death determination-assures a homogenized procedure leading to a more consistent interpretation of complex data across the CHAMPS network. This and other standardizations ensures future comparability with other sources of mortality data produced externally to this project. Early lessons learned from implementation of DeCoDe in 5 CHAMPS sites in sub-Saharan Africa and Bangladesh have been incorporated into the DeCoDe process, and the implementation of DeCoDe has the potential to spur health systems improvements and local public health action.

Health and Demographic Surveillance Systems Within the Child Health and Mortality Prevention Surveillance Network.

Health and demographic surveillance systems (HDSSs) provide a foundation for characterizing and defining priorities and strategies for improving population health. The Child Health and Mortality Prevention Surveillance (CHAMPS) project aims to inform policy to prevent child deaths through generating causes of death from surveillance data combined with innovative diagnostic and laboratory methods. Six of the 7 sites that constitute the CHAMPS network have active HDSSs: Mozambique, Mali, Ethiopia, Kenya, Bangladesh, and South Africa; the seventh, in Sierra Leone, is in the early planning stages. This article describes the network of CHAMPS HDSSs and their role in the CHAMPS project. To generate actionable health and demographic data to prevent child deaths, the network depends on reliable demographic surveillance, and the HDSSs play this crucial role.

Mortality Surveillance Methods to Identify and Characterize Deaths in Child Health and Mortality Prevention Surveillance Network Sites.

Despite reductions over the past 2 decades, childhood mortality remains high in low- and middle-income countries in sub-Saharan Africa and South Asia. In these settings, children often die at home, without contact with the health system, and are neither accounted for, nor attributed with a cause of death. In addition, when cause of death determinations occur, they often use nonspecific methods. Consequently, findings from models currently utilized to build national and global estimates of causes of death are associated with substantial uncertainty. Higher-quality data would enable stakeholders to effectively target interventions for the leading causes of childhood mortality, a critical component to achieving the Sustainable Development Goals by eliminating preventable perinatal and childhood deaths. The Child Health and Mortality Prevention Surveillance (CHAMPS) Network tracks the causes of under-5 mortality and stillbirths at sites in sub-Saharan Africa and South Asia through comprehensive mortality surveillance, utilizing minimally invasive tissue sampling (MITS), postmortem laboratory and pathology testing, verbal autopsy, and clinical and demographic data. CHAMPS sites have established facility- and community-based mortality notification systems, which aim to report potentially eligible deaths, defined as under-5 deaths and stillbirths within a defined catchment area, within 24-36 hours so that MITS can be conducted quickly after death. Where MITS has been conducted, a final cause of death is determined by an expert review panel. Data on cause of death will be provided to local, national, and global stakeholders to inform strategies to reduce perinatal and childhood mortality in sub-Saharan Africa and South Asia.

Integrating HIV and hypertension management in low-resource settings: Lessons from Malawi.

Pragna Patel and colleagues describe the implementation of a hypertension management model for HIV-infected people in Malawi.

Reporting Deaths Among Children Aged <5 Years After the Ebola Virus Disease Epidemic - Bombali District, Sierra Leone, 2015-2016.

Mortality surveillance and vital registration are limited in Sierra Leone, a country with one of the highest mortality rates among children aged <5 years worldwide, approximately 120 deaths per 1,000 live births (1,2). To inform efforts to strengthen surveillance, stillbirths and deaths in children aged <5 years from multiple surveillance streams in Bombali Sebora chiefdom were retrospectively reviewed. In total, during January 2015-November 2016, 930 deaths in children aged <5 years were identified, representing 73.3% of the 1,269 deaths that were expected based on modeled estimates. The "117" telephone alert system established during the Ebola virus disease (Ebola) epidemic captured 683 (73.4%) of all reported deaths in children aged <5 years, and was the predominant reporting source for stillbirths (n = 172). In the absence of complete vital events registration, 117 call alerts markedly improved the completeness of reporting of stillbirths and deaths in children aged <5 years.

Knowledge, Attitudes, and Practices Related to Ebola Virus Disease at the End of a National Epidemic - Guinea, August 2015.

Health communication and social mobilization efforts to improve the public's knowledge, attitudes, and practices (KAP) regarding Ebola virus disease (Ebola) were important in controlling the 2014-2016 Ebola epidemic in Guinea (1), which resulted in 3,814 reported Ebola cases and 2,544 deaths.* Most Ebola cases in Guinea resulted from the washing and touching of persons and corpses infected with Ebola without adequate infection control precautions at home, at funerals, and in health facilities (2,3). As the 18-month epidemic waned in August 2015, Ebola KAP were assessed in a survey among residents of Guinea recruited through multistage cluster sampling procedures in the nation's eight administrative regions (Boké, Conakry, Faranah, Kankan, Kindia, Labé, Mamou, and Nzérékoré). Nearly all participants (92%) were aware of Ebola prevention measures, but 27% believed that Ebola could be transmitted by ambient air, and 49% believed they could protect themselves from Ebola by avoiding mosquito bites. Of the participants, 95% reported taking actions to avoid getting Ebola, especially more frequent handwashing (93%). Nearly all participants (91%) indicated they would send relatives with suspected Ebola to Ebola treatment centers, and 89% said they would engage special Ebola burial teams to remove corpses with suspected Ebola from homes. Of the participants, 66% said they would prefer to observe an Ebola-affected corpse from a safe distance at burials rather than practice traditional funeral rites involving corpse contact. The findings were used to guide the ongoing epidemic response and recovery efforts, including health communication, social mobilization, and planning, to prevent and respond to future outbreaks or sporadic cases of Ebola.

Secondary Infections with Ebola Virus in Rural Communities, Liberia and Guinea, 2014-2015.

Persons who died of Ebola virus disease at home in rural communities in Liberia and Guinea resulted in more secondary infections than persons admitted to Ebola treatment units. Intensified monitoring of contacts of persons who died of this disease in the community is an evidence-based approach to reduce virus transmission in rural communities.

Transitioning to Country Ownership of HIV Programs in Rwanda.

Agnes Binagwaho and colleagues describe how Rwanda achieved country ownership of its HIV programs.

Ebola Virus Disease in Health Care Workers--Guinea, 2014.

An outbreak of Ebola virus disease (Ebola) began in Guinea in December 2013 and has continued through September 2015. Health care workers (HCWs) in West Africa are at high risk for Ebola infection owing to lack of appropriate triage procedures, insufficient equipment, and inadequate infection control practices. To characterize recent epidemiology of Ebola infections among HCWs in Guinea, national Viral Hemorrhagic Fever (VHF) surveillance data were analyzed for HCW cases reported during January 1­December 31, 2014. During 2014, a total of 162 (7.9%) of 2,210 laboratory-confirmed or probable Ebola cases among Guinean adults aged ≥15 years occurred among HCWs, resulting in an incidence of Ebola infection among HCWs 42.2 times higher than among non-HCWs. The disproportionate burden of Ebola infection among HCWs taxes an already stressed health infrastructure, underscoring the need for increased understanding of transmission among HCWs and improved infection prevention and control measures to prevent Ebola infection among HCWs.

Influenza sentinel surveillance in Rwanda, 2008-2010.

BACKGROUND: In 2008, Rwanda established an influenza sentinel surveillance (ISS) system to describe the epidemiology of influenza and monitor for the emergence of novel influenza A viruses. We report surveillance results from August 2008 to July 2010. METHODS: We conducted ISS by monitoring patients with influenza-like illness (ILI) and severe acute respiratory infection (SARI) at 6 hospitals. For each case, demographic and clinical data, 1 nasopharyngeal specimen, and 1 oropharyngeal specimen were collected. Specimens were tested by real-time reverse-transcription polymerase chain reaction for influenza A and B viruses at the National Reference Laboratory in Rwanda. RESULTS: A total of 1916 cases (945 ILI and 971 SARI) were identified. Of these, 29.2% (n = 276) of ILI and 10.4% (n = 101) of SARI cases tested positive for influenza. Of the total influenza-positive cases (n = 377), 71.8% (n = 271) were A(H1N1) pdm09, 5.6% (n = 21) influenza A(H1), 7.7% (n = 29) influenza A(H3), 1.6% (n = 6) influenza A (unsubtyped), and 13.3% (n = 50) influenza B. The percentage of positivity for influenza viruses was highest in October-November and February-March, during peaks in rainfall. CONCLUSIONS: The implementation of ISS enabled characterization of the epidemiology and seasonality of influenza in Rwanda for the first time. Future efforts should determine the population-based influenza burden to inform interventions such as targeted vaccination.