In this review, we aimed to evaluate the level of South Africa’s readiness to eliminate measles. We reviewed six years’ retrospective data from the national surveillance programme for febrile rash illness. Between the years 2015 to 2020, a total of 285 confirmed measles cases (excluding rubella infections) were detected in South Africa, with the highest incidence rate of 6.1 cases per million detected in 2017 in Gauteng province, while the lowest incidence rate of infection was zero detected in many provinces in multiple years (Table 2).
Younger children aged from 0–4 years were the most affected age group. Stratified by population figures, the highest incidence rate was in the age group of 0–4 years at 7.8 per million in 2017, 3.0 per million in 2018, and 1.9 per million in 2019, however in 2017 all age groups had had high incidence rates, with many adult cases, due to the outbreak that affected the country (Table 1). In 2017, one death was reported but outcome data for most cases was not available.
In the past six years, South Africa had a good surveillance system in place, evidenced by the adequate non-measles rash surveillance rate of more than 2.0 per 100,000 population in all provinces from 2015 to 2020, except in 2020 in KwaZulu-Natal and Limpopo, which had a rate of 1.4 and 1.0 per 100,000 respectively. This reduction of the rate of non-measles rash surveillance was probably due to the lockdown from March to August imposed because of the COVID-19 pandemic, resulting in reduced health-seeking behavior but also lowering the transmission of respiratory-borne viruses. The non-measles rash surveillance in South Africa in 2020 was 2.1 per 100,000, still above the recommended threshold.
On the other hand, certain indicators were poorly performed such as the completion of CIF, assignment of unique EPID number, and completion of vaccination information of confirmed and discarded measles cases. In addition, vaccination coverage in all provinces did not reach 95% coverage [22]. Low vaccine coverage explains the viral transmission of measles.
Over the period of 2015—2020, South Africa failed to meet the WHO recommendation for immunization coverage target of children under one-year-old. South Africa had less than 95% coverage in all provinces over the period 2015–2019 except Gauteng in 2015. Vaccination coverage was below 90% in three districts in South Africa between November 2020 and January 2021 [23]. Of note, vaccination coverage was the lowest in 2017, corresponding with the 2017 measles outbreak [22].
Interestingly, choice of the measles case definition plays an important role in evaluating the status of South Africa’s measles elimination goals. Using the standard case definition, South Africa only achieved the elimination target of an incidence rate of less than one case per one million nationally in the years 2015, 2016 and 2020. The years 2017 to 2019 had incidence rates greater than one per million nationally. Conversely, using a narrow case definition that excluded positive rubella cases from the analysis improved the indicators. Only the year 2017 had an incidence rate of more than one per million. In years 2018 and 2019 South Africa kept the incidence rate below one, which means the country is approaching achieving the measles elimination goals. In the year 2020, all provinces had a rate below one per million population, which could be explained by COVID-19 restrictions and interruption of the spread of respiratory illnesses generally due to social distancing, increased hygiene measures and lockdowns, or by hesitation in seeking medical services during lockdown periods.
While we cannot definitively conclude that all dual positive measles and rubella samples were due to rubella rather than measles, rubella is more common in the South African setting, and therefore the positive predictive value of a positive rubella IgM result is higher than the positive predictive value of a positive measles IgM result. With relatively few measles cases diagnosed, additional confirmatory tests are required to confirm measles positive results, thus our results excluding the dual positive cases is likely the more accurate estimate. Because almost all of specimens received were serum, we were limited in our ability to perform molecular epidemiology.
Conducting measles and rubella serology on all samples is a strength of our study and allowed us to differentiate between samples positive only for measles and those positive for both measles and rubella. Cross-reactive serology occurs reasonably uncommonly using the ELISA methodology, however, the influence of false-positive serology can form a large proportion of cases when overall measles numbers are low and rubella numbers high [18,19,20]. Of note, cross-reactive measles and rubella serology has been reported with most commercial assays [18,19,20] and likely represents biological increases in polyclonal antibody titres in patients in vivo, rather than in vitro flaws of the diagnostic kits.. Such challenges indicate the need for improved molecular diagnostics for routine measles surveillance in South Africa, necessitating future collection of throat swabs, urine samples or other suitable samples for confirmatory measles molecular testing. Throat swabs have become more readily available in small health clinics following the COVID-19 pandemic. Rubella vaccine introduction to South Africa is likely within the next few years and may alleviate testing ambiguities.
Using the narrow case definition, which excluded the rubella positive cases, measles vaccine effectiveness in South Africa was determined as 80% among children aged between 1–4 years old. This is low compared to other studies that reported vaccine effectiveness of 95%, using large datasets [24, 25]. Our results also showed that the odds of being vaccinated and having measles was lower prior to 2016, when children received vaccine at 9 months and 18 months, compared to post 2016 when children receive the vaccine at 6 months and 12 months. Early vaccination might blunt the immune response to subsequent measles vaccine doses [26]. Ongoing evaluation of vaccine effectiveness with the new schedule is warranted. A confounder of these results may be that the measles cases in our dataset occurred mostly during the 2017 outbreaks, resulting in most measles cases in our dataset occurring after 2017. Our work is also limited by missing information in our programmatic data, particularly the number of respondents with available information on measles vaccination status and of doses. Nevertheless, our program data provides a good reflection of the impact of the vaccine program in a routine setting.
In conclusion, the results of this study suggested that more effort is needed to increase the completion of surveillance indicators including clinical investigation form, unique EPID number and information on vaccination status in febrile rash cases. Improvements in laboratory confirmatory measles diagnostic assays will also be required to meet the goals for measles elimination. Logistics of obtaining throat swabs on suspected measles cases was a barrier to effective molecular surveillance, however, following the COVID-19 pandemic throat swabs have become readily available which should facilitate improved molecular epidemiology. Moreover, catch-up vaccinations will be needed to fill the gaps particularly following the COVID-19 pandemic in which many children missed their routine immunizations.