151 research outputs found
Global respiratory syncytial virus-related infant community deaths
Background: Respiratory syncytial virus (RSV) is a leading cause of pediatric death, with \u3e99% 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 \u3c6 months occurring in the community with in-hospital.Results: We studied 829 RSV-related deaths \u3c1 year of age from 38 developing countries, including 166 community deaths from 12 countries. There were 629 deaths that occurred \u3c6 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 \u3c .0001). The proportion of neonatal deaths was higher in the community (29%, 46/156) than in-hospital (12%, 57/473, P \u3c 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
Sneathia amnii and Maternal Chorioamnionitis and Stillbirth, Mozambique
We report a case of Sneathia amnii as the causative agent
of maternal chorioamnionitis and congenital pneumonia resulting
in a late fetal death in Mozambique, with strong supportive
postmortem molecular and histopathologic confirmation. This
rare, fastidious gram-negative coccobacillus has been reported
to infrequently cause abortions, stillbirths, and neonatal
infections
Pathology and Telepathology Methods in the Child Health and Mortality Prevention Surveillance Network
This manuscript describes the Child Health and Mortality
Prevention Surveillance (CHAMPS) network approach to pathologic
evaluation of minimally invasive tissue sampling (MITS)
specimens, including guidelines for histopathologic examination
and further diagnostics with special stains,
immunohistochemistry, and molecular testing, as performed at the
CHAMPS Central Pathology Laboratory (CPL) at the Centers for
Disease Control and Prevention, as well as techniques for
virtual discussion of these cases (telepathology) with CHAMPS
surveillance locations. Based on review of MITS from the early
phase of CHAMPS, the CPL has developed standardized
histopathology-based algorithms for achieving diagnoses from
MITS and telepathology procedures in conjunction with the CHAMPS
sites, with the use of whole slide scanners and digital image
archives, for maximizing concurrence and knowledge sharing
between site and CPL pathologists. These algorithms and
procedures, along with lessons learned from initial
implementation of these approaches, guide pathologists at the
CPL and CHAMPS sites through standardized diagnostics of MITS
cases, and allow for productive, real-time case discussions and
consultations
Prioritising health-care strategies to reduce childhood mortality, insights from Child Health and Mortality Prevention Surveillance (CHAMPS): a longitudinal study.
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)
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
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 âunderlyingâ and âimmediateâ causes of death (CoD) were determined for each case by an international panel of 12â15 medical specialists.
Results. We enrolled 153 neonatal deaths, 106 aged 3â28 days. Leading underlying CoD included âcomplications of prematurityâ
(52.9%), âcomplications of intrapartum eventsâ (15.0%), âcongenital malformationsâ (13.1%), and âinfection relatedâ (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 âcomplications of prematurityâ 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 âinfectionsâ 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
Initial findings from a novel population-based child mortality surveillance approach: a descriptive study.
--- - Label: BACKGROUND NlmCategory: BACKGROUND content:
"Sub-Saharan Africa and south Asia contributed 81% of 5\xC2\xB79
million under-5 deaths and 77% of 2\xC2\xB76 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." - Label: METHODS NlmCategory: METHODS content: "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; Manhi\xC3\xA7a, 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." - Label: FINDINGS NlmCategory:
RESULTS content: 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. - Label: INTERPRETATION NlmCategory:
CONCLUSIONS content: 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. -
Label: FUNDING NlmCategory: BACKGROUND content: Bill &
Melinda Gates Foundation
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 standardsâa framework of required evidence to support cause of death determinationâassures 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
Causes of stillbirth and death among children younger than 5 years in eastern Hararghe, Ethiopia: a population-based post-mortem study
BACKGROUND: Child mortality is high in Ethiopia, but reliable data on the causes of death are scarce. We aimed to gather data for the contributory causes of stillbirth and child deaths in eastern Ethiopia. METHODS: In this population-based post-mortem study, we established a death-notification system in health facilities and in the community in Kersa (rural), Haramaya (rural) and Harar (urban) in eastern Ethiopia, at a new site of the Child Health and Mortality Prevention Surveillance (CHAMPS) network. We collected ante-mortem data, did verbal autopsies, and collected post-mortem samples via minimally invasive tissue sampling from stillbirths (weighing at least 1000 g or with an estimated gestational age of at least 28 weeks) and children who died younger than 5 years. Children-or their mothers, in the case of stillbirths and deaths in children younger than 6 months-had to have lived in the catchment area for the past 6 months to be included. Molecular, microbiological, and histopathological analyses were done in collected samples. Cause of death was established by an expert panel on the basis of these data and classified as underlying, comorbid, or immediate separately for stillbirths, neonatal deaths (deaths aged 0-27 days), and child deaths (aged 28 days to <5 years). FINDINGS: Between Feb 4, 2019, and Feb 3, 2021, 312 deaths were eligible for inclusion, and the families gave consent in 195 (63%) cases. Cause of death was established in 193 (99%) cases. Among 114 stillbirths, the underlying cause of death was perinatal asphyxia or hypoxia in 60 (53%) and birth defects in 24 (21%). Among 59 neonatal deaths, the most common underlying cause was perinatal asphyxia or hypoxia (17 [29%]) and the most common immediate cause of death was neonatal sepsis, which occurred in 27 (60%). Among 20 deaths in children aged 28 days to 59 months, malnutrition was the leading underlying cause (15 [75%]) and infections were common immediate and comorbid causes. Pathogens were identified in 19 (95%) child deaths, most commonly Klebsiella pneumoniae and Streptococcus pneumoniae. INTERPRETATION: Perinatal asphyxia or hypoxia, infections, and birth defects accounted for most stillbirths and child deaths. Most deaths could have been prevented with feasible interventions, such as improved maternity services, folate supplementation, and improved vaccine uptake. FUNDING: Bill & Melinda Gates Foundation
Ebola virus epidemiology, transmission, and evolution during seven months in Sierra Leone
The 2013-2015 Ebola virus disease (EVD) epidemic is caused by the Makona variant of Ebola virus (EBOV). Early in the epidemic, genome sequencing provided insights into virus evolution and transmission and offered important information for outbreak response. Here, we analyze sequences from 232 patients sampled over 7 months in Sierra Leone, along with 86 previously released genomes from earlier in the epidemic. We confirm sustained human-to-human transmission within Sierra Leone and find no evidence for import or export of EBOV across national borders after its initial introduction. Using high-depth replicate sequencing, we observe both host-to-host transmission and recurrent emergence of intrahost genetic variants. We trace the increasing impact of purifying selection in suppressing the accumulation of nonsynonymous mutations over time. Finally, we note changes in the mucin-like domain of EBOV glycoprotein that merit further investigation. These findings clarify the movement of EBOV within the region and describe viral evolution during prolonged human-to-human transmission
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