Rubella virus IgM and IgG antibodies with avidity in pregnant women and outcomes at a tertiary facility in Ghana

PLOS ONE RESEARCH ARTICLE Rubella virus IgM and IgG antibodies with avidity in pregnant women and outcomes at a tertiary facility in Ghana Naa Baake Armah1*, Kwamena W. Sagoe ID2*, Mercy Nuamah1, Alfred E. Yawson3, Edmund T. Nartey4, Vera A. Essuman5, Nana-Akyaa Yao6, Kenneth K. Baidoo5, Jemima Anowa Fynn5, Derrick Tetteh2, Eva Gyamaa-Yeboah1, Makafui Seshie2, Isaac Boamah2, Kobina Nkyekyer1 a1111111111 a1111111111 a1111111111 a1111111111 a1111111111 1 Department of Obstetrics and Gynaecology, Korle Bu Teaching Hospital, Accra, Ghana, 2 Department of Medical Microbiology, University of Ghana Medical School, College of Health Sciences, University of Ghana, Legon, Ghana, 3 Department of Community Health, University of Ghana Medical School, College of Health Sciences, University of Ghana, Legon, Ghana, 4 Center for Tropical Clinical Pharmacology and Therapeutics, University of Ghana Medical School, College of Health Sciences, University of Ghana, Legon, Ghana, 5 Department of Surgery, University of Ghana Medical School, University of Ghana, Accra, Ghana, 6 Cardiothoracic Centre, Korle Bu Teaching Hospital, Accra, Ghana * (NBA); (KWS) OPEN ACCESS Citation: Armah NB, Sagoe KW, Nuamah M, Yawson AE, Nartey ET, Essuman VA, et al. (2022) Rubella virus IgM and IgG antibodies with avidity in pregnant women and outcomes at a tertiary facility in Ghana. PLoS ONE 17(12): e0279733. https://doi. org/10.1371/journal.pone.0279733 Editor: Ray Borrow, Public Health England, UNITED KINGDOM Received: February 11, 2022 Accepted: December 14, 2022 Abstract Background Congenital rubella syndrome (CRS) is a recognised cause of childhood deafness and blindness caused by the transplacental transmission of rubella virus during pregnancy. Women in the reproductive age group, and by extension their unborn babies may therefore be at increased risk. The prevalence of Rubella virus specific IgM and IgG antibodies, including IgG avidity, was determined in pregnant women attending the antenatal clinic at a Teaching Hospital in Ghana. Published: December 30, 2022 Peer Review History: PLOS recognizes the benefits of transparency in the peer review process; therefore, we enable the publication of all of the content of peer review and author responses alongside final, published articles. The editorial history of this article is available here: https://doi.org/10.1371/journal.pone.0279733 Copyright: © 2022 Armah et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Data Availability Statement: All relevant data are within the paper. Funding: The authors received no specific funding for this work. Methods One hundred and forty-five women in their second and third trimesters of pregnancy from the outpatient clinic were recruited over a period of 2 months after written informed consent was obtained. Study participants completed a questionnaire and venous blood drawn for IgM, IgG, and avidity testing using SERION ELISA (SERION® Immunologics, Würzburg, Germany). Babies of mothers with positive or indeterminate IgM and low avidity IgG antibodies were offered specialist cardiological, ophthalmological or hearing assessment during follow up. Results One hundred and twenty-eight (88.3%) had only IgG antibodies, 5 (3.4%) had IgM and IgG antibodies, while 12 (8.3%) had no antibodies. No patient had IgM antibodies alone. Ten women (6.9%) had indeterminate levels of IgM antibodies. Majority of the women had high avidity IgG antibodies, while 5 (3.4%) had low avidity antibodies. No patient had IgM with PLOS ONE | https://doi.org/10.1371/journal.pone.0279733 December 30, 2022 1 / 15 PLOS ONE Competing interests: The authors have declared that no competing interests exist. Rubella infections in pregnant women and congenital rubella syndrome low avidity antibodies. There was no statistical association between socio-demographic factors and the presence of IgM, IgG (low or high avidity) antibodies. Of all the children followed, none had the clinical definition of CRS. Conclusions Consistent with the World Health Organization elimination strategy for measles and rubella viruses, non-immune women in the reproductive age group should be vaccinated. The immunization programme should be expanded to include teenagers and adults. Though Congenital Rubella Syndrome was not detected, the risk still remains. Introduction Mathematical models estimate the number of congenital rubella syndrome (CRS) cases in developing countries to be more than 110,000 per annum with majority of the disease burden in Asia (48%) and Africa (38%) [1], and majority of these are in developing countries without rubella vaccination programmes. The highest incidence of these defects have been associated with the first trimester and subsequently reduce as gestational age advances [2]. The World Health Organization (WHO) has therefore suggested the antenatal screening of pregnant women as one of the arms for rubella surveillance [3]. The burden of CRS in Ghana has been previously described [4]. Global rubella virus seropositivity estimates varies with WHO regions in pregnant women and women of child bearing age, with susceptible rates of > 5% [5]. Several studies from West Africa using ELISAs from different companies have recorded varying prevalence rates of rubella virus (RV) specific IgM (1.36–38.8%) and IgG (53.0%–95.7%) [6–14]. There are always varying percentages of non-immune pregnant women, and most of these studies did not identify specific risk factors. Avidity testing provides information on the recency of RV specific IgG. Long standing infections have higher avidities as compared with recent infections [15]. In all the aforementioned studies, none performed avidity testing. The avidity testing seems to enhance the detection of recent infections as compared to re-infections [15]. To our knowledge, there is little data on the use of avidity testing for RV IgG [16]. The Ghana Health Service states that there are over 700 cases of CRS in Ghana every year, with a stated IgG seroprevalence in pregnant women of 92.6% (Personal Communication). In 2013 the Ghana Health Service through GAVI and WHO introduced the combined measles and rubella vaccine as part of its expanded programme of immunization. The vaccine was introduced throughout the country with special mass vaccination campaigns targeting children between the ages of 9–14 years as well in a successful start in the three northern regions (http://www.gov.gh/). However, vaccination strategies that focused on women and children in Brazil were associated with a 5.5-fold increase in rubella in men and an increase in the incidence of CRS [17]. More recent data in Ghana suggests that the non-immune status of pregnant women may be >5% [18, 19]. There is therefore likely to be a significant risk for CRS in Gha (...truncated)