Introduction and methods Hepatitis B is a vaccine preventable disease and is notifiable in South Africa. Hepatitis B vaccination was incorporated into the Expanded Programme on Immunisation in South Africa in 1995. We used a convenience sample from community-based febrile rash surveillance in 2013 to estimate hepatitis B sero-prevalence. Of samples serologically negative for acute measles infection, 450 samples spanning nine provinces of South Africa were tested for hepatitis B surface antigen (HBsAg), hepatitis B surface antibody (anti-HBs) and hepatitis B core antibody (anti-HBc). Results Two children (2/450; 0.4%) tested positive for HBsAg. Three hundred and three children (67.3%) had evidence of vaccine induced immunity. Vaccine induced immunity was present in 80.2% of 1–5 year olds, but only 60.3% of 10–14 year olds. Natural immunity, indicating exposure to circulating hepatitis B, was present in 13/450 (2.9%) children. Conclusion Chronic hepatitis B in South African has decreased in prevalence from highly endemic levels prior to vaccine introduction to approximately 0.4% in this sample, demonstrating impact of a successful vaccination programme 18 years after introduction. Decreased vaccine-induced immunity with increasing age may reflect waning antibody titres over time.

The World Health Organization has identified the need for a non-sputum-based test capable of detecting active tuberculosis (TB) as a priority. The plasma kynurenine-to-tryptophan (K/T) ratio, largely mediated by activity of the enzyme indoleamine 2,3-dioxygenase, may have potential as a suitable biomarker for active TB. Method: We evaluated a commercial enzyme-linked immunosorbent assay (ELISA) in comparison to mass spectrometry for measuring the K/T ratio. We also used ELISA to determine the K/T ratio in plasma from patients with active TB compared to latently infected controls, with and without HIV. Results: The two methods showed good agreement, with a mean bias of 0.01 (limit of agreement from À0.06 to 0.10). Using ELISA, it was found that HIV-infected patients with active TB disease had higher K/T ratios than those without TB (median, 0.101 [interquartile range (IQR), 0.091-0.140] versus 0.061 [IQR, 0.034-0.077], P < 0.0001). At a cutoff of 0.080, the K/T ratio produced a sensitivity of 90%, a specificity of 80%, a positive predictive value (PPV) of 82%, and a negative predictive value (NPV) of 90%. In a receiver operating characteristics analysis, the K/T ratio had an area under the curve of 0.93. HIV-uninfected patients with active TB also had higher K/T ratios than those with latent TB infections (median, 0.064 [IQR, 0.040-0.088] versus 0.022 [IQR, 0.016-0.027], P < 0.0001). A cutoff of 0.040 gave a sensitivity of 85%, a specificity of 92%, a PPV of 91%, and an NPV of 84%. Conclusion:The plasma K/T ratio is a sensitive biomarker for active TB. The K/T ratio can be measured from blood using ELISA. The K/T ratio should be evaluated as an initial test for TB.

Background and Aims To enhance screening and diagnosis in those at‐risk of hepatitis C virus (HCV), efficient and improved sampling and testing is required. We investigated the performance of point‐of‐care (POC) tests and dried blood spots (DBS) for HCV antibody and HCV RNA quantification in individuals at higher risk for HCV (people who use and inject drugs, sex workers and men who have sex with men) in seven South African cities. Methods Samples were screened on the OraQuick HCV POC test (471 whole blood and 218 oral fluid); 218 whole blood and DBS paired samples were evaluated on the ARCHITECT HCV antibody (Abbott) and HCV viral load (COBAS Ampliprep/COBAS TaqMan version 2) assays. For HCV RNA quantification, 107 dB were analyzed with and without normalization coefficients. Results POC on either whole blood or oral fluid showed an overall sensitivity of 98.5% (95% CI 97.4‐99.5), specificity of 98.2% (95% CI 98.8‐100) and accuracy of 98.4% (95% CI 96.5‐99.3). On the antibody immunoassay, DBS showed a sensitivity of 96.0% (95% CI 93.4‐98.6), specificity of 97% (95% CI 94.8‐99.3) and accuracy of 96.3% (95% CI 93.8‐98.8). A strong correlation ( R 2 = 0.90) between viral load measurements for DBS and plasma samples was observed. After normalization, DBS viral load results showed an improved bias from 0.5 to 0.16 log10 IU/mL. Conclusion The POC test performed sufficiently well to be used for HCV screening in at‐risk populations. DBS for diagnosis and quantification was accurate and should be considered as an alternative sample to test. POC and DBS can help scale up hepatitis services in the country, in light of our elimination goals.

South Africa has yet to introduce a rubella-containing vaccine (RCV) into its Expanded Programme on Immunisation (EPI). Here we evaluated the incidence of laboratory-confirmed rubella and congenital rubella syndrome (CRS) cases over the years 2015 to 2019, to document the epidemiology of rubella and CRS within South Africa prior to a RCV introduction. This retrospective study evaluated the number of laboratory-confirmed rubella cases reported through the national febrile rash surveillance system. A positive test for rubella immunoglobulin M (IgM) antibodies was considered a confirmed rubella case. For CRS cases, we reported laboratory-confirmed CRS cases collected from 28 sentinel-sites from all nine provinces of South Africa. From 2015–2019, 19 773 serum samples were tested for rubella IgM antibodies, 6 643 (33.6%) were confirmed rubella cases. Rubella was seasonal, with peaks in spring (September to November). Case numbers were similar between males (n = 3 239; 50.1%) and females (n = 3 232; 49.9%). The highest burden of cases occurred in 2017 (n = 2 526; 38%). The median age was 5 years (IQR: 3–7 years). Importantly, of females with rubella, 5.0% (161 of 3 232) of the cases were among women of reproductive age (15–44 years). A total of 62 CRS cases were reported, the mortality rate was 12.9% (n = 8), and the most common birth defect was congenital heart disease. In conclusion, rubella is endemic in South Africa. Children below the age of 10 years were the most affected, however, rubella was also reported among women of reproductive age. The baseline data represented here provides insight into the burden of rubella and CRS in South Africa prior to the introduction of a RCV, and can enable planning of RCV introduction into the South African EPI.

Introduction: South Africa is yet to introduce rubella-containing vaccines (RCV) into its routine immunization schedule. Selecting the target population when introducing RCV should take into account the ages of susceptible individuals in the population. We aimed to determine the seroprevalence of antibodies to rubella and characterize immunity gaps among individuals of all ages in South Africa. Methods: We tested for rubella immunoglobulin G (IgG) antibodies with a commercial enzyme-linked immunosorbent assay. We used residual samples collected from 2016 through 2018 as part of the national measles surveillance program. We only tested samples that were negative for measles and rubella immunoglobulin M (IgM) and explored the association between rubella susceptibility (IgG negative) and predictor variables (year of sample collection, age, sex, and province of residence) using logistic regression analysis. Results: We obtained results for 6057 records. Rubella susceptibility was highest among Individuals aged zero to 11 months (81.9%), followed by children 1 to 5 years old (71.5%), 6 to 10 y old (40.9%) and 11 to 15 y old (31.25) while the smallest proportion of susceptible individuals was among those 16 to 49 y old (19.9%). Females were less likely to be susceptible to rubella compared to males (OR = 0.79 (95%CI: 0.71-0.87), P < .001) in unadjusted analysis but this effect was not observed after adjusting for age and province. In multivariable logistic regression, age (OR = 6.24 (4.52-8.63), P < .001) and province of residence (OR = 0.97 (95%CI: 0.95-0.99), P = .01) were associated with rubella susceptibility. Conclusion: In the absence of rubella vaccination in the Expanded Program on Immunization in South Africa, the bulk of individuals susceptible to rubella are children under 16 y old. About 20% of individuals 16 to 49 y old are susceptible to rubella. This susceptibility gap must be born in mind during RCV introduction.

In 2012 the World Health Organization (WHO) aimed to eliminate measles in five regions by 2020. This retrospective descriptive study reviewed measles surveillance data in South Africa for the period 2015—2020 to document the epidemiology of measles and the progress made towards meeting the 2020 measles elimination goal.A total of 22,578 specimens were tested over the period 2015—2020 yielding 401 (1.8%) confirmed measles cases, 321 (1.4%) compatible and 21,856 (96.8%) discarded cases. The most affected age group was 0–4 year olds. At the provincial level, South Africa achieved adequate surveillance, defined as more than two cases of febrile rash notified annually per 100 000 popoulation, except for KwaZulu-Natal and Limpopo in 2020, probably due to COVID-19 lockdown restrictions. Of confirmed cases, only 26% were vaccinated, 3% were too young to receive vaccines, 5% were not vaccinated, and 65% had unknown vaccination status. Measles vaccine effectiveness amongst 1–4 year olds was 80%. Using the standard case definition, South Africa achieved the measles elimination target of less than one case per one million nationally in years 2015, 2016 and 2020. The years 2017 to 2019 had incidence rates exceeding one per million nationally. Using a narrow case definition, that excluded positive rubella cases, improved the indicators with only the year 2017 having an incidence rate of more than one per million.South Africa displays intermittent measles outbreaks approximately six-yearly interspersed by inter-epidemic periods in which the country meets measles elimination targets. Intense effort is needed to increase the vaccine coverage to avoid periodic outbreaks. Enhanced molecular testing of each case will be required as measles incidence declines regionally.