Cytomegalovirus Infections in Ugandan Infants:Newborns, Neonates with Sepsis and Infants with Hydrocephalus

Abstract

Background: Congenital and postnatal cytomegalovirus (CMV) infections in Uganda is prevalent and may compromise the health of Ugandan children. The objective of this study is to estimate the prevalence of CMV infections in newborns, neonates with sepsis, and infants with hydrocephalus in Uganda. Methods: Three populations: (1) newborn-mother pairs, (2) neonates with sepsis, and (3) infants (≤ 3 months) with non-postinfectious (NPIH) or postinfectious (PIH) hydrocephalus, were evaluated over four years (2016-2019) for CMV infection at three medical centers – two in the Eastern (Mbale) and one in Western (Mbarara) Uganda. To characterize the prevalence of CMV we used quantitative PCR (qPCR) analysis. In newborn-mother pairs maternal blood (n=99) and a subset of matching cord blood (n=92), placental tissue (n=99), and vaginal specimens (n=99) were tested for CMV. In neonates and infants aged 3 months or less, peripheral blood (751 with sepsis, 399 with hydrocephalus) and cerebrospinal fluid samples (560 with sepsis, 399 with hydrocephalus (205 PIH, 194 NPIH) were also tested for CMV. Findings: The overall CMV prevalence across all groups was 9%. In newborn-mother pairs, a 3% (n=3/92; 95% CI, 1-9%) prevalence of cord blood positivity and 33% (n=33/99; 95% CI, 24-44%) prevalence of maternal vaginal shedding of CMV was estimated. In neonates with clinical sepsis, a 2% (n=17/751; 95% CI, 1-4%) CMV prevalence was estimated. Maternal HIV seropositivity (adjusted odds ratio [aOR], 21.09; 95% CI, 4-109; p= 0.0002), residence in Eastern Uganda (aOR, 11.10; 95% CI, 3-77; p=0 .003), maternal age < 25 years (aOR, 4.91; 95% CI, 2-20; p=0.012), and older neonatal age (9 days vs. 5 days; p= 0.006) were associated with CMV in neonates with clinical sepsis. In infants with PIH, the prevalence in blood was 24% (n=50/205; 95% CI, 19-31%) and in infants with NPIH it was 20% (n=39/194; 95% CI, 15-26%; p=0.34). CMV was present in the CSF of 13% (n=26/205; 95% CI, 8-18%) of infants with PIH compared to 0.5% of infants with NPIH (n=1/194; 95% CI, 0-3%, p<0.0001). Interpretation: Our findings highlight that congenital and postnatal CMV prevalence is high in this African setting and the associated complications may be significant. Universal testing and longitudinal studies are critical to understand the burden infant CMV has in sub-Saharan African countries. Funding Statement: U.S. National Institutes of Health (N.I.H) Director’s Pioneer Award 5DP1HD086071 and NIH Director’s Transformative Award 1R01AI145057. Declaration of Interests: No conflict of interest reported. Ethics Approval Statement: For all participants, mothers had to be at least 18 years of age and able to give informed written consent in either English, Lumasaba, Lugwere, Luganda, Ateso or Runyankole. The study was performed with approval from the CCHU Institutional Review Board, the Mbarara University of Science and Technology Research Ethics Committee, the Pennsylvania State University Institutional Review Board, and with oversight from the Ugandan National Council on Science and Technology. Material Transfer Agreements and a US Centers for Disease Control permit were obtained for the proper transfer and importation of samples to the Pennsylvania State University.