Investigating the role of cytomegalovirus as a cause of stillbirths and child deaths in low and middle-income countries through postmortem minimally invasive tissue sampling.
Velaphi S., Madewell ZJ., Tippett-Barr B., Blau DM., Rogena EA., Lala SG., Mahtab S., Swart PJ., Akelo V., Onyango D., Otieno K., Rogena EA., Were JA., Bassat Q., Carrilho C., Mandomando I., Torres-Fernandez D., Varo R., Luke R., Moses F., Nwajiobi-Princewill P., Ogbuanu IU., Ojulong J., El Arifeen S., Gurley ES., Assefa N., Gedefa L., Madrid L., Scott JAG., Wale H., Juma J., Keita AM., Kotloff KL., Sow SO., Tapia MD., Mutevedzi P., Whitney CG., Madhi SA.
BackgroundThere is paucity of information on the role of cytomegalovirus (CMV) infection as a cause of stillbirths or childhood deaths in low-and middle-income countries (LMICs). We investigated attribution of CMV-disease in the causal pathway to stillbirths and deaths in children <5 years of age in seven LMICs participating in the Child Health and Mortality Prevention Surveillance (CHAMPS) network.MethodsWe analyzed stillbirths and decedents enrolled between December 2016 and July 2023. Deaths were investigated using post-mortem minimally invasive tissue sampling with histopathology and molecular diagnostic investigations of tissues and body fluids, along with review of clinical records. Multi-disciplinary expert panels reviewed findings and reported on the causal pathway to death.ResultsCMV was detected in 19.5%(1140/5841) of all evaluated deaths, including 5.0% (111/2204), 6.2% (139/2229), 41.2% (107/260), 68.1%(323/474) and 68.2%(460/674) of stillbirths, neonates (deaths 0-<28 days postnatal), young infants (28-<90 days), older infants (90-<365 days) and children (12-<60 months), respectively. CMV-disease was attributed in the causal pathway to death in 0.9%(20/2204) of stillbirths, 0.8%(17/2229) of neonates, 13.1% (34/260) of young infants, 9.7%(46/474) of older infants and 3.3%(22/674) of children. Decedents with CMV-disease compared with those without CMV-disease in the causal pathway, were more likely to have severe microcephaly (38.2% vs. 21.1%; aOR 2.2, 95%CI: 1.3-3.6) and HIV-infected (36.9% vs. 6.2%; aOR: 10.9, 95%CI: 6.5-18.5).ConclusionsCMV-disease is an important contributor to deaths during infancy and childhood and is often associated with severe microcephaly and HIV-infection. Improving management of CMV in HIV-infected children and a vaccine to prevent CMV are needed interventions.