Estimation of shedding time in laboratory-confirmed COVID-19 cases in South Africa: a population-based record linkage study, March-December 2020.

Introduction: in South Africa, COVID-19 cases are notifiable and hospitalized cases are reported on a dedicated platform. It is crucial to estimate the duration of SARS-CoV-2 shedding to inform public health interventions. We aimed to estimate viral shedding time among laboratory-confirmed COVID-19 cases in South Africa. Methods: we analyzed COVID-19 PCR results from 5 March to 31 December 2020. We included cases with at least 2 consecutive positive PCR tests and a subsequent negative test. We performed multiple linear regression to determine the association between shedding time and predictor variables (age, sex, admission status and province). We included 2752 cases that met the inclusion criteria. Results: about 39.9% (1099/2752) of participants were inpatients and 60.1% (1653/2752) were outpatients. The median shedding time was 17 days (range: 1-128). There was no difference in shedding time between males and females and between hospitalized patients and outpatients. Individuals aged 0-4 years had the lowest shedding time (median: 14 days, range: 1-72). After adjusting for age, sex and province, shedding time was shorter for hospitalized patients compared to outpatients (co-efficient: -0.14, CI: -0.24 - -0.03, P-value: 0.014). Six provinces (KwaZulu-Natal, Gauteng, Limpopo, North West, Mpumalanga, and Western Cape) had a significant association with shedding time. Conclusion: the duration of viral shedding within our population varies from 1-128 days. Although prolonged shedding might not necessarily indicate infectiousness, individual patient monitoring and management are needed for patients with prolonged shedding. Further studies are required to explore the association between comorbidities and SARS-CoV-2 shedding time.

Severity and outcomes of Omicron variant of SARS-CoV-2 compared to Delta variant and severity of Omicron sublineages: a systematic review and metanalysis.

OBJECTIVES: To compare severity and clinical outcomes from Omicron as compared with the Delta variant and to compare outcomes between Omicron sublineages. METHODS: We searched the WHO COVID-19 Research database for studies that compared clinical outcomes for patients with Omicron variant and the Delta variant, and separately Omicron sublineages BA.1 and BA.2. A random-effects meta-analysis was used to pool estimates of relative risk (RR) between variants and sublineages. Heterogeneity between studies was assessed using the I2 index. Risk of bias was assessed using the tool developed by the Clinical Advances through Research and Information Translation team. RESULTS: Our search identified 1494 studies and 42 met the inclusion criteria. Eleven studies were published as preprints. Of the 42 studies, 29 adjusted for vaccination status; 12 had no adjustment; and for 1, the adjustment was unclear. Three of the included studies compared the sublineages of Omicron BA.1 versus BA.2. As compared with Delta, individuals infected with Omicron had 61% lower risk of death (RR 0.39, 95% CI 0.33 to 0.46) and 56% lower risk of hospitalisation (RR 0.44, 95% CI 0.34 to 0.56). Omicron was similarly associated with lower risk of intensive care unit (ICU) admission, oxygen therapy, and non-invasive and invasive ventilation. The pooled risk ratio for the outcome of hospitalisation when comparing sublineages BA.1 versus BA.2 was 0.55 (95% 0.23 to 1.30). DISCUSSION: Omicron variant was associated with lower risk of hospitalisation, ICU admission, oxygen therapy, ventilation and death as compared with Delta. There was no difference in the risk of hospitalisation between Omicron sublineages BA.1 and BA.2. PROSPERO REGISTRATION NUMBER: CRD42022310880.

Evaluation of the rubella surveillance system in South Africa, 2016-2018: A cross-sectional study.

BACKGROUND: Rubella is a leading vaccine-preventable cause of birth defects. We conducted this study to evaluate the rubella surveillance system in South Africa from 2016 to 2018. The rubella surveillance system had not been evaluated since its inception; therefore, a formal evaluation is necessary to assess key attributes and to ascertain the extent to which the system achieves its objectives. METHODS: We conducted a cross-sectional study to assess the usefulness, simplicity, positive predictive value, timeliness, and data quality of the rubella surveillance system from 2016 to 2018. We reviewed retrospective rubella surveillance data and conducted a survey with key stakeholders of the system. We compiled a summary report from the survey and calculated the annualized detection rate of rubella and non-rubella febrile rash, positive predictive value, the proportion of complete records, and timeliness between the surveillance steps. We compared our results with recommended performance indicators from the 2015 revised World Health Organization African regional guidelines for measles and rubella surveillance. RESULTS: The rubella surveillance system was useful but weak in terms of simplicity. The annualized detection rate of rubella febrile rash was 1.5 per 100,000 populations in 2016, 4.4 in 2017, and 2.1 in 2018. The positive predictive value was 29.1% in 2016, 40.9% in 2017, and 32.9% in 2018. The system did not meet the timeliness goal in the health facility component but met this goal in the laboratory component. The system had poor data quality, particularly in the health facility component. CONCLUSIONS: The rubella surveillance system was useful, although it was not simple to use and had low PPV, poor timeliness, and poor data quality. Efforts should be made to improve the system's simplicity, PPV, timeliness, and data quality at the facility level.

Hepatitis A virus seroprevalence among children and adolescents in a high-burden HIV setting in urban South Africa.

Hepatitis A virus (HAV) infection is one of the most important global causes of viral hepatitis. Recent reviews suggested that HAV endemicity in South Africa could shift from high to intermediate. A hospital-based HAV seroprevalence study was conducted between February 2018 and December 2019 in Pretoria, South Africa. Systematic sampling was performed on children and adolescents (1-15 years) who attended outpatient services. Participants with a known HIV status and valid HAV serology results were included. Of the 1220 participants, the median age was 7 years (IQR: 4-11), with 648 (53.11%) males and 572 (46.89%) females. Of 628 (51.48%) HIV-infected participants, most (329, 71.83%) were both immunologically and virologically controlled or had low-level viremia (74, 16.16%). Almost three-quarters (894, 73.28%) were living in formal dwellings, and just over half (688, 56.39%) had access to clean water sources inside the house. Increasing age was associated with testing HAV IgG-positive (OR 1.25; 95% CI 1.20-1.30, p < 0.001), with 19.8% of participants one year of age compared with 86.7% of participants 15 years of age. This study suggests that South Africa has an intermediate HAV seroprevalence, with rates < 90% by 10 years of age (68.6%). Increased age and informal dwellings are statistically associated with HAV seropositivity, while HIV status does not significantly influence HAV seropositivity.

Association between preeclampsia and HIV: a case-control study in urban South Africa.

BACKGROUND: Preeclampsia is a considerable cause of maternal and infant morbidity and mortality. Although its etiology is unknown, preeclampsia has been described as a state of exaggerated maternal inflammatory response. Therefore, it has been hypothesized that preeclampsia would occur less commonly in states of immune deficiency. OBJECTIVE: This study aimed to compare the prevalence of treated and untreated HIV infections among preeclamptic cases and controls, determine infant outcomes, and evaluate the association between HIV and preeclampsia after adjusting for known predictor variables, including maternal age, gravidity, body mass index, and smoking. STUDY DESIGN: This case-control study investigated the association between preeclampsia and HIV infection using secondary data from an unrelated study. We defined preeclamptic cases as pregnant women who were normotensive until 20 weeks of gestation and thereafter had at least 1 high blood pressure measurement either before or at delivery and proteinuria, defined as protein excretion of ≥300 mg within 24 hours or >2 protein on dipstick urinalysis. The prevalence of HIV infection was compared between cases and controls. Multivariate logistic regression analysis was used to assess the association between preeclampsia and potential confounding variables and reported using odds ratios and 95% confidence intervals. RESULTS: There were 571 cases with preeclampsia and 596 normotensive controls included in this study. The median age was 27 years for cases and 26 years for controls (P=.008). Most participants (69%) had ≥2 previous pregnancies with no difference between the cases and controls (P=.176). Overall, 43% of the participants were obese, with a mean body mass index of 29 (interquartile range, 24.5-34.2), with higher proportions of women who were overweight and obese in the group with preeclampsia (P=.031). The prevalence of HIV was significantly lower in cases than in controls (24% vs 30%, respectively; P=.014). Compared with 16% of infants born preterm to normotensive controls, 48% of infants were born preterm born to women with preeclampsia (P<.001). Compared with 14% of infants born with low birthweight to normotensive controls, 53% of infants were born with low birthweight to women with preeclampsia (P<.0001). Untreated HIV infection was negatively associated with preeclampsia (unadjusted odds ratio, 0.330; 95% confidence interval, 0.197-0.552; P<.0001), whereas factors associated with preeclampsia were advanced maternal age (odds ratio, 1.673; 95% confidence interval, 1.209-2.316; P=.002) and obesity (odds ratio, 1.611; 95% confidence interval, 1.023-2.537; P=.040). After adjusting for maternal age, gravidity, smoking, and body mass index in the multivariate regression, only obesity remained significantly associated with preeclampsia (adjusted odds ratio, 1.624; 95% confidence interval, 1.024-2.575; P=.039). CONCLUSION: Before the large-scale rollout of antiretroviral therapy in a setting with a high burden of HIV and preeclampsia, untreated HIV infection was found to have a protective effect against preeclampsia. The protective effect against preeclampsia was not apparent for HIV infection treated with antiretroviral therapy.

A retrospective 5-year review of rubella in South Africa prior to the introduction of a rubella-containing vaccine.

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.

Variation in SARS-CoV-2 outbreaks across sub-Saharan Africa.

A surprising feature of the SARS-CoV-2 pandemic to date is the low burdens reported in sub-Saharan Africa (SSA) countries relative to other global regions. Potential explanations (for example, warmer environments1, younger populations2-4) have yet to be framed within a comprehensive analysis. We synthesized factors hypothesized to drive the pace and burden of this pandemic in SSA during the period from 25 February to 20 December 2020, encompassing demographic, comorbidity, climatic, healthcare capacity, intervention efforts and human mobility dimensions. Large diversity in the probable drivers indicates a need for caution in interpreting analyses that aggregate data across low- and middle-income settings. Our simulation shows that climatic variation between SSA population centers has little effect on early outbreak trajectories; however, heterogeneity in connectivity, although rarely considered, is likely an important contributor to variance in the pace of viral spread across SSA. Our synthesis points to the potential benefits of context-specific adaptation of surveillance systems during the ongoing pandemic. In particular, characterizing patterns of severity over age will be a priority in settings with high comorbidity burdens and poor access to care. Understanding the spatial extent of outbreaks warrants emphasis in settings where low connectivity could drive prolonged, asynchronous outbreaks resulting in extended stress to health systems.

Government regulation of private health insurance.

BACKGROUND: The strain on public resources to meet the healthcare needs of populations through publicly-provided health insurance programmes is increasing and many governments turn to private health insurance (PHI) to ease the pressure on government budgets. With the goal of improving access to basic health care for citizens through PHI programmes, several high-income countries have developed strong regulations for PHI schemes. Low- and middle-income countries have the opportunity to learn from this experience to optimise PHI. If poorly regulated, PHI can hardly achieve an adequate quantity or quality of population coverage, as can be seen in the USA where a third of adults younger than 65 years of age have no insurance, sporadic coverage or coverage that exposes them to high out-of-pocket healthcare costs. OBJECTIVES: To assess the effects of policies that regulate private health insurance on utilisation, quality, and cost of health care provided. SEARCH METHODS: In November 2019 we searched CENTRAL; MEDLINE; Embase; Sociological Abstracts and Social Services Abstracts; ICTRP; ClinicalTrials.gov; and Web of Science Core Collection for papers that have cited the included studies. This complemented the search conducted in February 2017 in IBSS; EconLit; and Global Health. We also searched selected grey literature databases and web-sites.  SELECTION CRITERIA: Randomised trials, non-randomised trials, interrupted time series (ITS) studies, and controlled before-after (CBA) studies conducted in any population or setting that assessed one or more of the following interventions that governments use to regulate private health insurance: legislation and licensing, monitoring, auditing, and intelligence. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed study eligibility, extracted data, and assessed risk of bias and certainty of the evidence resolving discrepancies by consensus. We planned to summarise the results (using random-effects or fixed-effect meta-analysis) to produce an overall summary if an average intervention effect across studies was considered meaningful, and we would have discussed the implications of any differences in intervention effects across studies. However, due to the nature of the data obtained, we have provided a narrative synthesis of the findings. MAIN RESULTS: We included seven CBA studies, conducted in the USA, and that directly assessed state laws on cancer screening. Only for-profit PHI schemes were addressed in the included studies and no study addressed other types of PHI (community and not for-profit). The seven studies were assessed as having 'unclear risk' of bias. All seven studies reported on utilisation of healthcare services, and one study reported on costs. None of the included studies reported on quality of health care and patient health outcomes. We assessed the certainty of evidence for patient health outcomes, and utilisation and costs of healthcare services as very low. Therefore, we are uncertain of the effects of government mandates on for-profit PHI schemes. AUTHORS' CONCLUSIONS: Our review suggests that, from currently available evidence, it is uncertain whether policies that regulate private health insurance have an effect on utilisation of healthcare services, costs, quality of care, or patient health outcomes. The findings come from studies conducted in the USA and might therefore not be applicable to other countries; since the regulatory environment could be different. Studies are required in countries at different income levels because the effects of government regulation of PHI are likely to differ across these income and health system settings. Further studies should assess the different types of regulation (including regulation and licensing, monitoring, auditing, and intelligence). While regulatory research on PHI remains relatively scanty, future research can draw on the rich body of research on the regulation of other health financing interventions such as user fees and results-based provider payments.

The Impact of Rubella Vaccine Introduction on Rubella Infection and Congenital Rubella Syndrome: A Systematic Review of Mathematical Modelling Studies.

INTRODUCTION: Rubella vaccines have been used to prevent rubella and congenital rubella syndrome (CRS) in several World Health Organization (WHO) regions. Mathematical modelling studies have simulated introduction of rubella-containing vaccines (RCVs), and their results have been used to inform rubella introduction strategies in several countries. This systematic review aimed to synthesize the evidence from mathematical models regarding the impact of introducing RCVs. METHODS: We registered the review in the international prospective register of systematic reviews (PROSPERO) with registration number CRD42020192638. Systematic review methods for classical epidemiological studies and reporting guidelines were followed as far as possible. A comprehensive search strategy was used to identify published and unpublished studies with no language restrictions. We included deterministic and stochastic models that simulated RCV introduction into the public sector vaccination schedule, with a time horizon of at least five years. Models focused only on estimating epidemiological parameters were excluded. Outcomes of interest were time to rubella and CRS elimination, trends in incidence of rubella and CRS, number of vaccinated individuals per CRS case averted, and cost-effectiveness of vaccine introduction strategies. The methodological quality of included studies was assessed using a modified risk of bias tool, and a qualitative narrative was provided, given that data synthesis was not feasible. RESULTS: Seven studies were included from a total of 1393 records retrieved. The methodological quality was scored high for six studies and very high for one study. Quantitative data synthesis was not possible, because only one study reported point estimates and uncertainty intervals for the outcomes. All seven included studies presented trends in rubella incidence, six studies reported trends in CRS incidence, two studies reported the number vaccinated individuals per CRS case averted, and two studies reported an economic evaluation measure. Time to CRS elimination and time to rubella elimination were not reported by any of the included studies. Reported trends in CRS incidence showed elimination within five years of RCV introduction with scenarios involving mass vaccination of older children in addition to routine infant vaccination. CRS incidence was higher with RCV introduction than without RCV when public vaccine coverage was lower than 50% or only private sector vaccination was implemented. Although vaccination of children at a given age achieved slower declines in CRS incidence compared to mass campaigns targeting a wide age range, this approach resulted in the lowest number of vaccinated individuals per CRS case averted. CONCLUSION AND RECOMMENDATIONS: We were unable to conduct data synthesis of included studies due to discrepancies in outcome reporting. However, qualitative assessment of results of individual studies suggests that vaccination of infants should be combined with vaccination of older children to achieve rapid elimination of CRS. Better outcomes are obtained when rubella vaccination is introduced into public vaccination schedules at coverage figures of 80%, as recommended by WHO, or higher. Guidelines for reporting of outcomes in mathematical modelling studies and the conduct of systematic reviews of mathematical modelling studies are required.

High variation expected in the pace and burden of SARS-CoV-2 outbreaks across sub-Saharan Africa.

A surprising feature of the SARS-CoV-2 pandemic to date is the low burdens reported in sub-Saharan Africa (SSA) countries relative to other global regions. Potential explanations (e.g., warmer environments1, younger populations2-4) have yet to be framed within a comprehensive analysis accounting for factors that may offset the effects of climate and demography. Here, we synthesize factors hypothesized to shape the pace of this pandemic and its burden as it moves across SSA, encompassing demographic, comorbidity, climatic, healthcare and intervention capacity, and human mobility dimensions of risk. We find large scale diversity in probable drivers, such that outcomes are likely to be highly variable among SSA countries. While simulation shows that extensive climatic variation among SSA population centers has little effect on early outbreak trajectories, heterogeneity in connectivity is likely to play a large role in shaping the pace of viral spread. The prolonged, asynchronous outbreaks expected in weakly connected settings may result in extended stress to health systems. In addition, the observed variability in comorbidities and access to care will likely modulate the severity of infection: We show that even small shifts in the infection fatality ratio towards younger ages, which are likely in high risk settings, can eliminate the protective effect of younger populations. We highlight countries with elevated risk of 'slow pace', high burden outbreaks. Empirical data on the spatial extent of outbreaks within SSA countries, their patterns in severity over age, and the relationship between epidemic pace and health system disruptions are urgently needed to guide efforts to mitigate the high burden scenarios explored here.

Rubella Vaccine Introduction in the South African Public Vaccination Schedule: Mathematical Modelling for Decision Making.

Background: age structured mathematical models have been used to evaluate the impact of rubella-containing vaccine (RCV) introduction into existing measles vaccination programs in several countries. South Africa has a well-established measles vaccination program and is considering RCV introduction. This study aimed to provide a comparison of different scenarios and their relative costs within the context of congenital rubella syndrome (CRS) reduction or elimination. Methods: we used a previously published age-structured deterministic discrete time rubella transmission model. We obtained estimates of vaccine costs from the South African medicines price registry and the World Health Organization. We simulated RCV introduction and extracted estimates of rubella incidence, CRS incidence and effective reproductive number over 30 years. Results: compared to scenarios without mass campaigns, scenarios including mass campaigns resulted in more rapid elimination of rubella and congenital rubella syndrome (CRS). 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. Conclusion: At 80% RCV coverage, all vaccine introduction scenarios would achieve rubella and CRS elimination in South Africa. Any RCV introduction strategy should consider a combination of routine vaccination in the primary immunization series and additional vaccination of older children.

Epidemiology of laboratory-confirmed mumps infections in South Africa, 2012-2017: a cross-sectional study.

BACKGROUND: Data on the burden of mumps in South Africa are limited and the epidemiology of mumps in this setting is not well understood. We present an analysis of mumps data in South Africa from 2012 to 2017. METHODS: This cross-sectional study included secondary data on laboratory-confirmed mumps infections from 2012 to 2017, archived at the South African National Health Laboratory Services' data repository as well as from four private laboratories. Mumps-specific immunoglobulin M (IgM) and/or viral nucleic acid positive results represented acute infections. We used age-specific mid-year population estimates for each study year as denominators when calculating annual cumulative incidence. Seasonality was based on the season that showed a peak in infections. RESULTS: Out of 48,580 records obtained from the public and private sectors, 46,713 (96.2%) were from the private sector. Over the study period, there were 7494 acute infections, 7085 (94.5%) of which were recorded in the private sector. Of these 7494 infections, 3924 (52.4%) occurred in males. The proportion of samples tested that were IgM positive was 18.6% (1058/5682) in 2012, 15% (1016/6790) in 2013, 15.8% (1280/8093) in 2014, 15.5% (1384/8944) in 2015, 13.1% (1260/9629) in 2016 and 15.8% (1496/9442) in 2017. The cumulative incidence rate per 100,000 was highest in children between one and 9 years throughout the study period. The cumulative incidence of infections was highest in the Western Cape, Gauteng and the Northern Cape. Infections peaked in June and November. CONCLUSION: Laboratory-confirmed mumps infections predominantly occurred in spring, affecting children below 10 years of age and individuals who were male. There were fewer tests performed in the public sector compared to the private sector. Since only laboratory data was analysed our results represent and underestimate of disease burden. Further studies that include clinical data are required to provide better estimates of disease burden in South Africa.

Factors associated with mortality in children under five years old hospitalized for Severe Acute Malnutrition in Limpopo province, South Africa, 2014-2018: A cross-sectional analytic study.

BACKGROUND: In South Africa, 30.9% of children under five years with Severe Acute Malnutrition (SAM) died in 2018. We aimed to identify factors associated with mortality among children under five years hospitalized with SAM in Limpopo province, South Africa. METHODS: We conducted a cross-sectional study including children under five years admitted with SAM from 2014 to 2018 in public hospitals of Limpopo province. We extracted socio-demographic and clinical data from hospital records. We used logistic regression to identify factors associated with mortality. FINDINGS: We included 956 children, 50.2% (480/956) male and 49.8% (476/956) female. The median age was 13 months (inter quartile range: 9-19 months). The overall SAM mortality over the study period was 25.9% (248/956). The most common complications were diarrhea, 63.8% (610/956), and lower respiratory tract infections (LRTIs), 42.4% (405/956). Factors associated with mortality included herbal medication use (adjusted Odds Ratio (aOR): 2.2, 95% Confidence Interval (CI): 1.4-3.5, p = 0.001), poor appetite (aOR: 2.7, 95% CI: 1.4-5.2, p = 0.003), Mid-upper circumference (MUAC) <11.5 cm (aOR: 3.0, 95% CI: 1.9-4.7, p<0.001), lower respiratory tract infections (LRTIs) (aOR: 1.6, 95% CI: 1.2-2.0, p<0.001), anemia (aOR: 2.5, 95% CI: 1.1-5.3, p = 0.021), hypoglycemia (aOR: 12.4, 95% CI: 7.1-21.8, p<0.001) and human immunodeficiency virus (HIV) infection (aOR: 2.3, 95% CI: 1.6-3.3, p<0.001). INTERPRETATION: Herbal medication use, poor appetite, LRTIs, anemia, hypoglycemia, and HIV infection were associated with mortality among children with SAM. These factors should guide management of children with SAM.

Hepatitis A virus seroprevalence in South Africa - Estimates using routine laboratory data, 2005-2015.

INTRODUCTION: South Africa is considered highly endemic for hepatitis A virus (HAV) although few seroprevalence studies have been conducted over the past two decades. The World Health Organization recommends integrating HAV vaccination into national childhood immunization schedules where there is transition from high to intermediate endemicity. As a means of gauging age-specific rates of infection, we report HAV seroprevalence rates among specimens tested for HAV serology within South Africa's public health sector from 2005-2015. MATERIALS AND METHODS: Hepatitis A serology results (Anti-HAV IgM, IgG and total antibody) from 2005-2015 were extracted from South Africa's National Health Laboratory Service's Corporate Data Warehouse (NHLS CDW), the central data repository of all laboratory test-sets within the public health sector. Results were extracted according to test-set, result, date of testing, health facility, name, surname, age, and sex. Anti-HAV IgG results were merged with total antibody results to reflect anti-HAV seroprevalence. Testing volume, positivity rates and age-specific anti-HAV seroprevalence rates by year and geographic distribution are described. RESULTS AND DISCUSSION: A total of 501 083 HAV IgM results were retrieved, of which 16 423 (3.3%) were positive, 484 259 (96.6%) negative and 401 (0.1%) equivocal; and 34 710 HAV total antibody/IgG tests of which 30 675 (88.4%) were positive, 4 020 (11.6%) negative and 15 equivocal. Whereas IgM positivity was highest among the 1-4 year age group (33.5%) and lowest among patients >45 years (<0.5%), total antibody positivity ranged from its lowest level of 52.7% in the 1-4 year age group increasing to levels of >90% only after 25 years of age. CONCLUSION: Anti-HAV total antibody testing within the South African public health sector demonstrates seroprevalence rates reach levels >90% only in adulthood, suggesting South Africa could be in transition from high to intermediate endemicity. Prospective studies with geographically representative sampling are required to confirm these findings and evaluate provincial and urban/rural heterogeneity.

Hepatitis B sero-prevalence in children under 15 years of age in South Africa using residual samples from community-based febrile rash surveillance.

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.

Congenital Rubella Syndrome Surveillance in South Africa Using a Sentinel Site Approach: A Cross-sectional Study.

BACKGROUND: Congenital rubella syndrome (CRS) includes disorders associated with intrauterine rubella infection. Incidence of CRS is higher in countries with no rubella-containing vaccines (RCV) in their immunization schedules. In the World Health Organization African region, RCVs are being introduced as part of the 2012-2020 global measles and rubella strategic plan. This study aimed to describe the epidemiology of confirmed CRS in South Africa prior to introduction of RCVs in the immunization schedule. METHODS: This was a descriptive study with 28 sentinel sites reporting laboratory-confirmed CRS cases in all 9 provinces of South Africa. In the retrospective phase (2010 to 2014), CRS cases were retrieved from medical records, and in the prospective phase (2015 to 2017) clinicians at study sites reported CRS cases monthly. RESULTS: There were 42 confirmed CRS cases in the retrospective phase and 53 confirmed CRS cases in the prospective phase. Most frequently reported birth defects were congenital heart disease and cataracts. The median age of mothers of CRS cases was 21 years in the retrospective phase (range: 11 to 38 years) and 22 years in the prospective phase (range: 15 to 38 years). CONCLUSION: Baseline data on laboratory-confirmed CRS will enable planning and monitoring of RCV implementation in the South African Expanded Programme on Immunization program. Ninety-eight percent of mothers of infants with CRS were young women 14-30 years old, indicating a potential immunity gap in this age group for consideration during introduction of RCV.

Treatment interventions for diarrhoea in HIV-infected and HIV-exposed children: a systematic review.

INTRODUCTION: Seventy percent of an estimated 10 million children less than five years of age in developing countries die each year of acute respiratory infections, diarrhoea, measles, malaria, malnutrition or a combination of these conditions. Children living with Human immunodeficiency virus (HIV) are at risk of diarrhoea because of drug interactions with antiretroviral therapy and bottle feeding. This may be aggravated by malnutrition and other infectious diseases which are frequent in children living with HIV. Objective: to evaluate treatment interventions for diarrhoea in HIV infected and exposed children. METHODS: A comprehensive search was conducted on 02 June 2016 to identify relevant studies for inclusion. We included randomised controlled trials of HIV infected or exposed children under 15 years of age with diarrhoea. Two authors independently selected studies for inclusion, assessed risk of bias (RoB) and extracted data using a pre-designed data extraction form. RESULTS: We included two studies (Amadi 2002 and Mda 2010) that each enrolled 50 participants. The RoB was assessed as low-risk for both included studies. There was no difference in clinical cure and all-cause mortality between nitazoxanide and placebo for cryptosporidial diarrhoea in Amadi 2002. In Mda 2010, there was a reduction in duration of hospitalisation in the micronutrient supplement group (P < 0.005) although there was no difference in all-cause mortality. CONCLUSION: There is low certainty evidence on the effectiveness of nitazoxanide for treating cryptosporidial diarrhoea and micronutrient supplementation in children with diarrhoea. Adequately powered trials are needed to assess micronutrients and nitazoxanide, as well as other interventions, for diarrhoea in HIV-infected and-exposed children.

A comparative evaluation of PDQ-Evidence.

BACKGROUND: A strategy for minimising the time and obstacles to accessing systematic reviews of health system evidence is to collect them in a freely available database and make them easy to find through a simple 'Google-style' search interface. PDQ-Evidence was developed in this way. The objective of this study was to compare PDQ-Evidence to six other databases, namely Cochrane Library, EVIPNet VHL, Google Scholar, Health Systems Evidence, PubMed and Trip. METHODS: We recruited healthcare policy-makers, managers and health researchers in low-, middle- and high-income countries. Participants selected one of six pre-determined questions. They searched for a systematic review that addressed the chosen question and one question of their own in PDQ-Evidence and in two of the other six databases which they would normally have searched. We randomly allocated participants to search PDQ-Evidence first or to search the two other databases first. The primary outcomes were whether a systematic review was found and the time taken to find it. Secondary outcomes were perceived ease of use and perceived time spent searching. We asked open-ended questions about PDQ-Evidence, including likes, dislikes, challenges and suggestions for improvements. RESULTS: A total of 89 people from 21 countries completed the study; 83 were included in the primary analyses and 6 were excluded because of data errors that could not be corrected. Most participants chose PubMed and Cochrane Library as the other two databases. Participants were more likely to find a systematic review using PDQ-Evidence than using Cochrane Library or PubMed for the pre-defined questions. For their own questions, this difference was not found. Overall, it took slightly less time to find a systematic review using PDQ-Evidence. Participants perceived that it took less time, and most participants perceived PDQ-Evidence to be slightly easier to use than the two other databases. However, there were conflicting views about the design of PDQ-Evidence. CONCLUSIONS: PDQ-Evidence is at least as efficient as other databases for finding health system evidence. However, using PDQ-Evidence is not intuitive for some people. TRIAL REGISTRATION: The trial was prospectively registered in the ISRCTN registry 17 April 2015. Registration number: ISRCTN12742235 .

Equity issues were not fully addressed in Cochrane human immunodeficiency virus systematic reviews.

OBJECTIVE: To describe and summarize equity reporting in human immunodeficiency virus (HIV) systematic reviews and explore the extent to which equity issues are addressed and reported in HIV reviews using the PROGRESS Plus framework. STUDY DESIGN AND SETTING: Application of the PROGRESS Plus framework to a bibliometric analysis of HIV reviews in the Cochrane Database of Systematic Reviews. RESULTS: The analysis included 103 reviews published as of March 2014, with a median of five studies per review (first quartile; Q1 = 2; third quartile; Q3 = 11). Reporting of PROGRESS Plus factors was as follows: Place of residence (low, middle, and high income; 55.3%), place of residence (urban or rural; 24.3%), race or ethnicity (20.4%), occupation (10.7%), gender (65.0%), religion (1.9%), education (7.8%), socioeconomic position (10.7%), social networks and capital (1.0%), age (1.9%), and sexual orientation (3.8%). CONCLUSION: Gaps in the reporting of relevant equity indicators were identified within Cochrane HIV systematic review indicating that research is not consistently conducted through an equity lens. There is a need to incorporate PROGRESS Plus factors into both primary and secondary studies.