Estimating the burden of rubella virus infection and congenital rubella syndrome through a rubella immunity assessment among pregnant women in the Democratic Republic of the Congo: Potential impact on vaccination policy

Abstract

A rubella antibody seroprevalence assessment was conducted using serum collected during 2008-2009 from 1,605 pregnant women aged 15-46 years attending 7 antenatal care sites in 3 of DRC's provinces. Estimates of age-and site-specific rubella antibody seroprevalence, population, and fertility rates were used in catalytic models to estimate the incidence of CRS per 100,000 live births and the number of CRS cases born in 2013 in DRC.Overall 84% (95% CI 82, 86) of the women tested were estimated to be rubella antibody seropositive. The association between age and estimated antibody seroprevalence, adjusting for study site, was not significant (p=0.10). Differences in overall estimated seroprevalence by study site were observed indicating variation by geographical area (p<=0.03 for all). Estimated seroprevalence was similar for women declaring residence in urban (84%) versus rural (83%) settings (p=0.67). In 2013 for DRC nationally, the estimated incidence of CRS was 69/100,000 live births (95% CI 0, 186), corresponding to 2886 infants (95% CI 342, 6395) born with CRS.In the 3 provinces, rubella virus transmission is endemic, and most viral exposure and seroconversion occurs before age 15 years. However, approximately 10%-20% of the women were susceptible to rubella virus infection and thus at risk for having an infant with CRS. Per World Health Organization recommendations, introduction of RCV should be accompanied by a campaign targeting children 9 months to 14 years and vaccination of women of child bearing age through routine services. Please find below our responses (in italics in blue below each reviewer's comments) to the comments and the details describing how the manuscript was revised to address each.Reviewer #1: This manuscript provides estimates of Congenital Rubella Syndrome (CRS) for the Democratic Republic of Congo (DRC) using seroprevalence data obtained from existing blood specimens from antenatal clinics. It provides an idea of the occurrence of CRS in a country with little rubella data and that has not yet introduced a rubella-containing vaccine, thus shedding light on an issue that is relevant when discussing vaccine introduction and vaccination strategies. The paper is well written and the supplemental material useful to understand the models used.Specific comments: Abstract 1. What % of the population live in the selected provinces 193-199, lines 206-211, and lines 252-257). Additional details regarding a number of elements of DRC's population have been incorporated into the Methods section of the manuscript (Please see lines Clarify that the estimated CRS incidence and cases in 2013 is for all of DRCThe abstract has been revised to read "In 2013 for DRC nationally, the estimated incidence of CRS was 69/100,000 live births (95% CI 0, 186), corresponding to 2886 infants (95% CI 342, 6395) born with CRS."

Epidemiology of rubella infection and genotyping of rubella virus in Cote d’Ivoire, 2012‐2016

“…Epidemiologic data showed that an increase in the number of rubella cases was found in 2012 and again in 2016. The age distribution of rubella cases indicated that 4% of rubella cases occurred in women of reproductive age (>15 years old); therefore, the risk of CRS births in CIV is expected to be similar to the 5% previously reported in the African region . The seasonality of rubella cases is consistent with the pattern previously reported in the West African region with a sharp increase in rubella cases seen starting in January and peaks in March to April …”

Evaluation of nationwide supplementary immunization in Lao People's Democratic Republic: Population-based seroprevalence survey of anti-measles and anti-rubella IgG in children and adults, mathematical modelling and a stability testing of the vaccine

“…Adapting methods used previously [ 7 , 15 – 17 ], we first fitted four age-structured catalytic models to the observed weighted age-stratified serological data for those aged >21 years using maximum likelihood to estimate the average force of infection (the rate at which susceptibles are infected) that children (< 15 years) and adults (≥ 15 years) experienced before the 2011 SIA was introduced. The fitting just used data for those aged > 21 years in 2014 because they were outside the age groups targeted by the 2011 SIA and so their seroprevalence would not have been directly affected by vaccination.…”

“…The Supplementary Information provides further details about the models and the equations. The force of infection used in subsequent calculations (see below) was the one obtained from the model selected according to biological plausibility, as described elsewhere [ 17 ].…”

Use of FTA Cards To Transport Throat Swabs and Oral Fluid Samples for Molecular Detection and Genotyping of Measles and Rubella Viruses

“…The accumulation of rubella cases in the provinces of Kasai Occidental (Dibaya) and Sud Kivu (Kabare) indicates that there were rubella outbreaks during the sample collection period. As there is no rubella vaccination program in the Democratic Republic of the Congo (42,43), rubella remains endemic (44). Sequence information suggested that the 2BL2c lineage of RuV has circulated in the Democratic Republic of the Congo since at least 2012 (32).…”