Burden of congenital rubella syndrome and potential impact of rubella vaccine introduction in South Africa

Thesis (PhD)--Stellenbosch University, 2021.ENGLISH SUMMARY : Background: Introduction of rubella vaccines into public vaccination schedules of all countries is necessary if global rubella elimination is to be achieved. Rubella is targeted for elimination in five World Health Organization (WHO) regions and several international organizations, under the stewardship of the WHO, are working towards this goal. Although there is no rubella elimination or control target for the WHO Africa region, there has been accelerated introduction of rubella vaccination on the continent. South African government is planning to introduce rubella vaccination in its Expanded Programme on Immunization (EPI) schedule and several epidemiological studies have been conducted to aid preparation of this public health intervention. In the absence of vaccination, rubella is mainly a mild endemic childhood viral illness that is asymptomatic in up to 50% of cases. The most severe consequences of rubella occur when infection occurs during pregnancy. These include miscarriages, stillbirths, intra-uterine growth restriction and congenital rubella syndrome. Rubella vaccines are therefore intended to prevent rubella and associated complications. In South Africa, rubella vaccines are not part of the EPI schedule and there is limited information on the epidemiology of rubella and its complications. In addition, the South African government has to cover the cost of introducing rubella vaccination. Therefore, the aim of this research project was to characterize the epidemiology of rubella and congenital rubella syndrome in South Africa, to assess the potential impact of introducing rubella vaccination in the EPI schedule. Methods: Four different studies were carried out as part of this PhD project: a cross-sectional descriptive study, a sero-survey, a mathematical modelling study and a systematic review. Results: The findings of a newly established CRS surveillance system to provide data on disease trends in the absence of rubella vaccination are presented in the first research component. We provided baseline data on laboratory-confirmed CRS that will enable planning and monitoring of RCV implementation in the South African EPI program. Ninety-eight percent of mothers of infants with CRS were young women 14 to 30 years old, indicating a potential immunity gap in this age group for consideration during introduction of RCV. In the second research component, we present results of testing on residual samples collected from public health facilities to identify immunity gaps in various age groups and genders. The bulk of individuals susceptible to rubella are children under sixteen years old and about 20% of individuals 16 to 49 years old are susceptible to rubella. In multivariable logistic regression, age and province of residence were found to be associated with rubella susceptibility.Webuilt on a previously published mathematical model adapted to the South African context in the third research component and provide insights into optimal scenarios for RCV introduction into the South African public immunization schedule. We simulated a number of scenarios that combined infant vaccination with vaccination of older individuals. Routine vaccination at 12 months of age coupled with vaccination of nine-year-old children was associated with the lowest RCV cost per CRS case averted for a similar percentage CRS reduction. Interestingly, at 80% RCV coverage, all vaccine introduction scenarios could achieve rubella and CRS elimination in South Africa.In the final research component, we systematically reviewed mathematical modelling studies to identify the most effective approach for countries introducing RCV into their public immunization schedules. There were variations in the manner in which individual studies reported outcomes. However, we found that better outcomes are obtained when rubella vaccination is introduced into public vaccination schedules at coverage figures of 80%, as recommended by WHO, or higher. Conclusion: The results from these different studies support the implementation of a strategy involving infant vaccination in combination with vaccination of older individuals. Further research projects are required to provide more detail on the burden of CRS and the economic impact of RCV introduction into the EPI schedule.AFRIKAANSE OPSOMMING : Agtergrond: Om rubella-entstowwe in openbare inentingsskedules van alle lande in te stel, is nodig om wêreldwye eliminasie van rubella te bereik. Rubella word geteiken vir uitskakeling in vyf streke van die Wêreldgesondheidsorganisasie (WGO) en verskeie internasionale organisasies, onder toesig van die WGO, werk daaraan. Alhoewel daar geen eliminasie- of beheerdoelwit vir rubella vir die WGO-Afrika bestaan nie, is daar 'n vinnige instelling van inenting teen rubella op die vasteland. Die Suid-Afrikaanse regering is van plan om rubella-inenting in te stel in sy program vir uitgebreide immunisering (EPI), en verskeie epidemiologiese studies is gedoen om die voorbereiding van hierdie ingryping in die gesondheid te help. In die afwesigheid van inenting, is rubella hoofsaaklik 'n ligte endemiese virussiekte by kinders wat in tot 50% van die gevalle asimptomaties is. Die ernstigste gevolge van rubella kom voor wanneer infeksie tydens swangerskap voorkom. Dit sluit miskrame, doodgeboortes, groeibeperking binne die baarmoeder en aangebore rubella-sindroom in. Inenting teen rubella is dus bedoel om rubella en gepaardgaande komplikasies te voorkom. In Suid-Afrika maak rubella-entstowwe nie deel uit van die EPI-skedule nie en is daar beperkte inligting oor die epidemiologie van rubella en die komplikasies daarvan. Daarbenewens moet die Suid-Afrikaanse regering die koste dek vir die instelling van rubella-inenting. Daarom was die doel van hierdie navorsingsprojek om die epidemiologie van rubella en aangebore rubella-sindroom in Suid-Afrika te karakteriseer, om die potensiële impak van die instelling van rubella-inenting in die EPI-skedule te bepaal. Metodes: Vier verskillende studies is uitgevoer as deel van hierdie PhD-projek; 'n beskrywende deursnee-studie, 'n sero-opname, 'n wiskundige modelleringstudie en 'n sistematiese oorsig. Resultate: Die bevindinge van 'n nuutgestigte CRS-bewakingstelsel om inligting oor siektetendense te verskaf in die afwesigheid van inenting teen rubella word in die eerste navorsingskomponent aangebied. Ons het basisdata gegee oor CRS wat deur laboratorium bevestig is, wat die beplanning en monitering van RCV-implementering in die Suid-Afrikaanse EPI-program moontlik maak. Agt-en-negentig persent van moeders van babas met CRS was jong vroue van 14 tot 30 jaar oud, wat dui op 'n moontlike immuniteitsgaping in hierdie ouderdomsgroep vir oorweging tydens die bekendstelling van RCV. In die tweede navorsingskomponent bied ons die resultate aan van die toetsing van residuele monsters wat van openbare gesondheidsinstellings versamel is om immuniteitsgapings in verskillende ouderdomsgroepe en geslagte te identifiseer. Die grootste deel van die individue wat vatbaar is vir rubella is kinders jonger as sestien jaar en ongeveer 20% van individue tussen 16 en 49 jaar oud is vatbaar vir rubella. In meerveranderlikke logistieke regressie is gevind dat ouderdom en provinsie geassosieer word met rubella vatbaarheid. Gebou op 'n voorheen gepubliseerde wiskundige model wat aangepas is vir die Suid-Afrikaanse konteks in die derde navorsingskomponent en bied insigte in optimale scenario's vir RCV-bekendstelling in die Suid-Afrikaanse openbare inentingskedule. Ons het 'n aantal scenario's gesimuleer wat baba-inenting kombineer met inenting van ouer persone. Roetine-inenting op 12-maande-ouderdom, tesame met die inenting van nege-jarige kinders, is geassosieer met die laagste RCV-koste per CRS-geval wat afgeweer is vir 'n soortgelyke persentasie CRS-vermindering. Interessant genoeg, met 80% RCV-dekking, kan alle inenting-inleidingscenario's rubella en CRS-uitskakeling in Suid-Afrika bereik. Daar was variasies in die wyse waarop individuele studies die uitkomste gerapporteer het. Ons het egter gevind dat beter resultate behaal word wanneer rubella-inenting in openbare inentingsskedules bekendgestel word teen 'n dekkingsyfer van 80%, soos aanbeveel deur die WGO, of hoër. Afsluiting: Die resultate van hierdie verskillende studies ondersteun die implementering van 'n strategie rakende baba-inenting in kombinasie met inenting van ouer individue. Verdere navorsingsprojekte is nodig om meer besonderhede te gee oor die las van CRS en die ekonomiese impak van die bekendstelling van RCV in die EPI-skedule.Doctora