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

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

Causes of death identified in neonates enrolled through Child Health and Mortality Prevention Surveillance (CHAMPS), December 2016 -December 2021.

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

Immediate and antecedent causes of death when underlying cause was low birth weight and prematurity complications N9 (N = 404).

Immediate and antecedent causes of death when underlying cause was low birth weight and prematurity complications N9 (N = 404).</p

Number of other conditions in the causal chain for CHAMPS deaths that occurred in the neonatal period, by age group.

Number of other conditions in the causal chain for CHAMPS deaths that occurred in the neonatal period, by age group.</p

WHO ICD10 Perinatal Mortality underlying cause of death categories & specific underlying cause of death by age group.

WHO ICD10 Perinatal Mortality underlying cause of death categories & specific underlying cause of death by age group.</p

Neonatal deaths who had low birth weight in the causal pathway, by age at death.

Neonatal deaths who had low birth weight in the causal pathway, by age at death.</p

Immediate and antecedent causes of the death when the underlying cause of the death was: Congenital malformation (N1, Fig 3), complication of intrapartum event (N4, Fig 4), infection (N6, Fig 5), respiratory and cardiovascular disorder (N7, Fig 6), and low birth weight and prematurity (N9, Fig 7).

There may be multiple immediate and antecedent causes of death for any individual, so the total number of causes may be greater than is listed in the figure titles.</p

Pathogens identified in neonatal deaths in which infection was determined in the causal pathway, by age at death.

Pathogens identified in neonatal deaths in which infection was determined in the causal pathway, by age at death.</p

Immediate and antecedent causes of death when underlying cause was infection N6 (N = 254).

Immediate and antecedent causes of death when underlying cause was infection N6 (N = 254).</p

Flowchart of enrolled neonatal deaths from CHAMPS sites between December 2016 –December 2021, that had minimally invasive tissue samples (MITS) and consent only for verbal autopsy and clinical abstraction (Non-MITS) and included in the analysis.

Flowchart of enrolled neonatal deaths from CHAMPS sites between December 2016 –December 2021, that had minimally invasive tissue samples (MITS) and consent only for verbal autopsy and clinical abstraction (Non-MITS) and included in the analysis.</p