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

Respiratory Syncytial Virus-related Death in Children with down Syndrome: The RSV GOLD Study

Background: Respiratory syncytial virus (RSV) is a major cause of mortality in children younger than 5 years worldwide. Systematic reviews have shown that Down syndrome (DS) is an independent risk factor for severe RSV infection. We aimed to describe demographic and clinical characteristics of children with DS who died with RSV infection. Methods: We performed a retrospective case series in which data were shared by individual researchers, research networks and physicians worldwide as part of the RSV Global Online Database study. We included children with DS who died when younger than 5 years of age with laboratory-confirmed RSV infection. Results: We included 53 children with DS and RSV-related mortality from 20 countries in 5 continents. Five (9.4%) children were from low-income or lower-middle-income countries. Median age at time of death was 6.0 months [interquartile range (IQR): 3.00-12.0]. Thirteen (24.5%) children were born term and had no other risk factors for severe RSV disease. In total, 36 (67.9%) children had congenital heart disease, 8 (15.1%) had chronic lung disease and 1 (1.9%) had congenital immunodeficiency. Duration of hospitalization was significantly longer for children with DS compared with children without DS [median length of stay, 13 days (IQR: 6.8-21.0) vs. 8 days (IQR: 3.0-18.5), P=0.005]. Conclusions: One-fourth of children with DS and RSV-confirmed death did not have risk factors for severe RSV disease, indicating that DS is an important risk factor for RSV-related mortality. Age distribution at time of death demonstrates that maternal vaccination would not be sufficient to protect children with DS against RSV-related mortality

Nosocomial RSV-related In-hospital Mortality in Children:A Global Case Series

Background: According to the World Health Organization, the global burden of nosocomial infections is poorly characterized as surveillance systems are lacking. Nosocomial infections occur at higher rates in low- and lower-middle-income countries (LMICs) than in high-income countries (HICs). Current global RSV burden estimates are largely based on community-acquired infection. We aimed to characterize children with nosocomial RSV-related mortality and to understand the potential impact of RSV immunization strategies. Materials: RSV GOLD is a global registry of children younger than 5 years who died with laboratory-confirmed RSV infection. We compared clinical and demographic characteristics of children with nosocomial and community-acquired RSV in-hospital mortality. Results: We included 231 nosocomial and 931 community-acquired RSVrelated in-hospital from deaths from 65 countries. Age at death was similar for both groups (5.4 vs. 6 months). A higher proportion of nosocomial deaths had comorbidities (87% vs. 57%; P < 0.001) or was born preterm (46% vs. 24%; P < 0.001) than community-acquired deaths. The proportion of nosocomial deaths among all RSV deaths was lower in LMICs than in upper-middle-income countries (UMICs) and HICs (12% vs. 18% and 26%, respectively). Conclusions: This is the first global case series of children dying with nosocomial RSV infection. Future infant-targeted immunization strategies could prevent the majority of nosocomial RSV-related deaths. Although nosocomial RSV deaths are expected to occur at highest rates in LMICs, the number of reported nosocomial RSV deaths was low in these countries. Hospital-based surveillance is needed to capture the full burden of nosocomial RSV mortality in LMICs.Fil: Löwensteyn, Yvette N.. University Medical Center Utrecht; Países BajosFil: Willemsen, Joukje E.. University Medical Center Utrecht; Países BajosFil: Mazur, Natalie I.. University Medical Center Utrecht; Países BajosFil: Scheltema, Nienke M.. University Medical Center Utrecht; Países BajosFil: Van Haastregt, Nynke C. J.. University Medical Center Utrecht; Países BajosFil: Ten Buuren, Amber A. A.. University Medical Center Utrecht; Países BajosFil: Van Roessel, Ichelle. University Medical Center Utrecht; Países BajosFil: Scheepmaker, Dunja. University Medical Center Utrecht; Países BajosFil: Nair, Harish. Respiratory Syncytial Virus Network Foundation; Países Bajos. University of Edinburgh; Reino UnidoFil: Van De Ven, Peter M.. University Medical Center Utrecht; Países BajosFil: Bont, Louis J.. University Medical Center Utrecht; Países Bajos. Respiratory Syncytial Virus Network Foundation; Países BajosFil: Caballero, Mauricio Tomás. Fundación Infant; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin

Global respiratory syncytial virus–related infant community deaths

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

Estimated impact of maternal vaccination on global paediatric influenza-related in-hospital mortality: A retrospective case series

Background Influenza virus infection is an important cause of under-five mortality. Maternal vaccination protects children younger than 3 months of age from influenza infection. However, it is unknown to what extent paediatric influenza-related mortality may be prevented by a maternal vaccine since global age-stratified mortality data are lacking. Methods We invited clinicians and researchers to share clinical and demographic characteristics from children younger than 5 years who died with laboratory-confirmed influenza infection between January 1, 1995 and March 31, 2020. We evaluated the potential impact of maternal vaccination by estimating the number of children younger than 3 months with in-hospital influenza-related death using published global mortality estimates. Findings We included 314 children from 31 countries. Comorbidities were present in 166 (53%) children and 41 (13%) children were born prematurely. Median age at death was 8·6 (IQR 4·5–16·6), 11·5 (IQR 4·3–24·0), and 15·5 (IQR 7·4–27·0) months for children from low- and lower-middle-income countries (LMICs), upper-middle-income countries (UMICs), and high-income countries (HICs), respectively. The proportion of children younger than 3 months at time of death was 17% in LMICs, 12% in UMICs, and 7% in HICs. We estimated that 3339 annual influenza-related in-hospital deaths occur in the first 3 months of life globally. Interpretation In our study, less than 20% of children is younger than 3 months at time of influenza-related death. Although maternal influenza vaccination may impact maternal and infant influenza disease burden, additional immunisation strategies are needed to prevent global influenza-related childhood mortality. The missing data, global coverage, and data quality in this study should be taken into consideration for further interpretation of the results. Funding Bill & Melinda Gates Foundation

Estimated impact of maternal vaccination on global paediatric influenza-related in-hospital mortality: A retrospective case series

Background Influenza virus infection is an important cause of under-five mortality. Maternal vaccination protects children younger than 3 months of age from influenza infection. However, it is unknown to what extent paediatric influenza-related mortality may be prevented by a maternal vaccine since global age-stratified mortality data are lacking. Methods We invited clinicians and researchers to share clinical and demographic characteristics from children younger than 5 years who died with laboratory-confirmed influenza infection between January 1, 1995 and March 31, 2020. We evaluated the potential impact of maternal vaccination by estimating the number of children younger than 3 months with in-hospital influenza-related death using published global mortality estimates. Findings We included 314 children from 31 countries. Comorbidities were present in 166 (53%) children and 41 (13%) children were born prematurely. Median age at death was 8·6 (IQR 4·5–16·6), 11·5 (IQR 4·3–24·0), and 15·5 (IQR 7·4–27·0) months for children from low- and lower-middle-income countries (LMICs), upper-middle-income countries (UMICs), and high-income countries (HICs), respectively. The proportion of children younger than 3 months at time of death was 17% in LMICs, 12% in UMICs, and 7% in HICs. We estimated that 3339 annual influenza-related in-hospital deaths occur in the first 3 months of life globally. Interpretation In our study, less than 20% of children is younger than 3 months at time of influenza-related death. Although maternal influenza vaccination may impact maternal and infant influenza disease burden, additional immunisation strategies are needed to prevent global influenza-related childhood mortality. The missing data, global coverage, and data quality in this study should be taken into consideration for further interpretation of the results. Funding Bill & Melinda Gates Foundation

Global Respiratory Syncytial Virus-Related Infant Community Deaths

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. © 2021 The Author(s). Published by Oxford University Press for the Infectious Diseases Society of America.Bill and Melinda Gates Foundation, BMGF: OPP1148988.8; Johnson and Johnson, J&J; Merck; Roche; AbbVieThis publication is based on research funded in part by the Bill & Melinda Gates Foundation (grant number OPP1148988.8). ES reports grants from Bill and Melinda Gates Foundation, during the conduct of the study; grants, personal fees and non-financial support from Astra Zeneca Inc, grants, personal fees and non-financial support from Merck & Co., grants, personal fees and non-financial support from Regeneron Inc, grants, personal fees and non-financial support from Pfizer Inc, personal fees, non-financial support and other from Abbvie Inc, personal fees from Alere Inc, grants, personal fees and non-financial support from Roche Inc, other from GSK Inc, grants from Johnson and Johnson, grants and nonfinancial support from Novavax Inc, outside the submitted work; FP reports grants and personal fees from JANSSEN, grants and personal fees from NOVAVAX, INC, personal fees from BAVARIAN NORDIC A/S, personal fees from PFIZER, personal fees from SANOFI, personal fees from REGENERON, personal fees from MERCK, outside the submitted work

Birth asphyxia following delayed recognition and response to abnormal labour progress and fetal distress in a 31-year-old multiparous Malawian woman

Reducing neonatal mortality is one of the targets of Sustainable Development Goal 3 on good health and well-being. The highest rates of neonatal death occur in sub-Saharan Africa. Birth asphyxia is one of the major preventable causes. Early detection and timely management of abnormal labour progress and fetal compromise are critical to reduce the global burden of birth asphyxia. Labour progress, maternal and fetal well-being are assessed using the WHO partograph and intermittent fetal heart rate monitoring. However, in low-resource settings adherence to labour guidelines and timely response to arising labour complications is generally poor. Reasons for this are multifactorial and include lack of resources and skilled health care staff. This case study in a Malawian hospital illustrates how delayed recognition of abnormal labour and prolonged decision-to-delivery interval contributed to birth asphyxia, as an example of many delivery rooms in low-income country settings