Training Site: Kenema Government Hospital
Country: Sierra Leone
Mentors: John Schieffelin, MD, MSPH; Donald Grant, MD, MPH; Soren Gantt, MD, PhD
Title: “Cytomegalovirus (CMV) Reinfection of Pregnant Women in a High Sero-prevalence Population”
Aim 1. Determine the frequency of CMV non-primary infection in a prospective cohort of pregnant and postpartum women in Kenema, Sierra Leone. Boucoiran et al. demonstrated oral shedding of virus in 50% of postpartum mothers in Uganda over a 12-month period. A longitudinal study over a mean 30 months in seropositive women in the US, where there is less viral burden, demonstrated 83% shed in urine at least once, with evidence of reinfection in about one third of women. Thus, in our population, where we expect exposures to reinfection may be higher than in low sero-prevalence settings, we hypothesize that non-primary infection will occur in about 50% of these women.
Aim 2. Characterize the genotypes of CMV shed by children and transmitted to seropositive mothers. The high genomic variability of CMV allows differentiation of isolates between individuals as well as between different anatomic sites (ie saliva, breast milk, urine) within an individual. We hypothesize that CMV transmitted by children (≤3yoa) to mothers will be closely related to virus isolated from pregnant and postpartum mothers prior to evidence of reinfection, indicating that antigenically distinct strains are not required for reinfection.
Aim 3. Identify the determinants of maternal non-primary infection. We will measure the viral load in children’s saliva and urine to evaluate temporal and dose-response associations between the viral load shed by children and risk of non-primary infection in their mothers. We hypothesize that exposure to high CMV viral (>7 log10 genome copies/mL) shedding by children is strongly associated with the risk of maternal non-primary infection.
NIH Support: Fogarty fellow postdoctoral training award