Search

Background: Dual HIV/syphilis testing may be an acceptable intervention to identify men with sexually transmitted infections (STIs) and at risk of HIV acquisition., Objectives: We sought to determine the acceptability, and performance of dual HIV/syphilis testing among men attending voluntary medical male circumcision (VMMC) services at six public sector facilities in Gauteng., Method: This was a cross-sectional study at VMMC facilities. Men ≥ 18 years were enrolled. The men had (1) a questionnaire administered, (2) on-site dual HIV/syphilis testing with First Response HIV1+2/Syphilis Combo Card Test by routine lay counsellors, and (3) a blood specimen collected for centralised laboratory testing for HIV and syphilis serology. We evaluated pre-test and post-test acceptability and performance compared to serological testing., Results: Of the 679 men analysed (median age 32.1 years), 96.7% of HIV-negative men preferred testing for HIV and syphilis simultaneously. Of the 675 men tested for syphilis, 28 (4.7%) tested positive (past or recent). In the laboratory, 43/609 (7.1%) had syphilis infection detected, with 9/609 (1.5%) having recent syphilis. There was sub-optimal sensitivity for HIV detection (90.9%; 95% confidence interval [CI]: 88.5% - 93.3%), and for past/recent syphilis (55.8%; 95% CI: 51.9% - 59.8%), improving to 88.9% (95% CI: 86.4% - 91.4%) for recent syphilis. Specificities were > 99% for HIV and syphilis (past or recent). Post-test acceptability was 96.6% and willingness to pay for future testing was 86.1%., Conclusion: Dual HIV/syphilis testing was acceptable but had sub-optimal sensitivity for HIV and syphilis. Syphilis detection was adequate for recent infection., Competing Interests: The authors declare that they have no financial or personal relationships that may have inappropriately influenced them in writing this article., (© 2024. The Authors.)

Background: Syndromic management is widely used to treat symptomatic sexually transmitted infections in settings without aetiologic diagnostics. However, underlying aetiologies and consequent treatment suitability are uncertain without regular assessment. This systematic review estimated the distribution, trends, and determinants of aetiologies for vaginal discharge, urethral discharge, and genital ulcer in sub-Saharan Africa (SSA)., Methods and Findings: We searched Embase, MEDLINE, Global Health, Web of Science, and grey literature from inception until December 20, 2023, for observational studies reporting aetiologic diagnoses among symptomatic populations in SSA. We adjusted observations for diagnostic test performance, used generalised linear mixed-effects meta-regressions to generate estimates, and critically appraised studies using an adapted Joanna Briggs Institute checklist. Of 4,418 identified records, 206 reports were included from 190 studies in 32 countries conducted between 1969 and 2022. In 2015, estimated primary aetiologies for vaginal discharge were candidiasis (69.4% [95% confidence interval (CI): 44.3% to 86.6%], n = 50), bacterial vaginosis (50.0% [95% CI: 32.3% to 67.8%], n = 39), chlamydia (16.2% [95% CI: 8.6% to 28.5%], n = 50), and trichomoniasis (12.9% [95% CI: 7.7% to 20.7%], n = 80); for urethral discharge were gonorrhoea (77.1% [95% CI: 68.1% to 84.1%], n = 68) and chlamydia (21.9% [95% CI: 15.4% to 30.3%], n = 48); and for genital ulcer were herpes simplex virus type 2 (HSV-2) (48.3% [95% CI: 32.9% to 64.1%], n = 47) and syphilis (9.3% [95% CI: 6.4% to 13.4%], n = 117). Temporal variation was substantial, particularly for genital ulcer where HSV-2 replaced chancroid as the primary cause. Aetiologic distributions for each symptom were largely the same across regions and population strata, despite HIV status and age being significantly associated with several infection diagnoses. Limitations of the review include the absence of studies in 16 of 48 SSA countries, substantial heterogeneity in study observations, and impeded assessment of this variability due to incomplete or inconsistent reporting across studies., Conclusions: In our study, syndrome aetiologies in SSA aligned with World Health Organization guidelines without strong evidence of geographic or demographic variation, supporting broad guideline applicability. Temporal changes underscore the importance of regular aetiologic re-assessment for effective syndromic management., Prospero Number: CRD42022348045., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Michalow 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.)

Syphilis, 'the great imitator', caused by Treponema pallidum infection, remains a complex and multifaceted disease with a rich history of clinical diversity. This guideline aims to be a comprehensive guide for healthcare workers in Southern Africa, offering practical insights into the epidemiology, pathogenesis, clinical manifestations, diagnostic testing, therapeutic principles, and public health responses to syphilis. Although the syphilis burden has declined over the years, recent data indicate a troubling resurgence, particularly among pregnant women and neonates. This guideline highlights the diagnostic challenges posed by syphilis, stemming from the absence of a single high-sensitivity and -specificity test. While treatment with penicillin remains the cornerstone of treatment, alternative regimens may be used for specific scenarios. We highlight the importance of thorough patient follow-up and management of sex partners to ensure optimal care of syphilis cases. In the context of public health, we emphasise the need for concerted efforts to combat the increasing burden of syphilis, especially within high-risk populations, including people living with HIV., Competing Interests: The authors declare that they have no financial or personal relationships that may have inappropriately influenced them in writing this article., (© 2024. The Authors.)

Background: Accurate measurement of antenatal antiretroviral treatment (ART) coverage in pregnancy is imperative in tracking progress towards elimination of vertical HIV transmission. In the Western Cape, South Africa, public-sector individual-level routine data are consolidated from multiple sources, enabling the description of temporal changes in population-wide antenatal antiretroviral coverage. We evaluated the validity of different methods for measuring ART coverage among pregnant women., Methods: We compared self-reported ART data from a 2014 antenatal survey with laboratory assay data from a sub-sample within the survey population. Thereafter, we conducted a retrospective cohort analysis of all pregnancies consolidated in the Provincial Health Data Centre (PHDC) from January 2011 to December 2020. Evidence of antenatal and HIV care from electronic platforms were linked using a unique patient identifier. ART coverage estimates were triangulated with available antenatal survey estimates, aggregated programmatic data from registers recorded in the District Health Information System (DHIS) and Thembisa modelling estimates., Results: Self-reported ART in the 2014 sentinel antenatal survey (n = 1434) had high sensitivity (83.5%), specificity (94.5%) and agreement (k = 0.8) with the gold standard of laboratory analysis of ART. Based on linked routine data, ART coverage by the time of delivery in mothers of live births increased from 67.4% in 2011 to 94.7% by 2019. This pattern of increasing antenatal ART coverage was also seen in the DHIS data, and estimated by the Thembisa model, but was less consistent in the antenatal survey data., Conclusion: This study is the first in a high-burden HIV setting to compare sentinel ART surveillance data with consolidated individuated administrative data. Although self-report in survey conditions showed high validity, more recent data sources based on self-report and medical records may be uncertain with increasing ART coverage over time. Linked individuated data may offer a promising option for ART coverage estimation with greater granularity and efficiency., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Jacob 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.)

Introduction: Congenital syphilis (CS) is preventable through timely antenatal care (ANC), syphilis screening and treatment among pregnant women. Robust CS surveillance can identify gaps in this prevention cascade. We reviewed CS cases reported to the South African notifiable medical conditions surveillance system (NMCSS) from January 2020 to June 2022., Methods: CS cases are reported using a case notification form (CNF) containing limited infant demographic and clinical characteristics. During January 2020-June 2022, healthcare workers supplemented CNFs with a case investigation form (CIF) containing maternal and infant testing and treatment information. We describe CS cases with/without a matching CIF and gaps in the CS prevention cascade among those with clinical information., Findings: During January 2020-June 2022, 938 CS cases were reported to the NMCSS with a median age of 1 day (interquartile range: 0-5). Nine percent were diagnosed based on clinical signs and symptoms only. During January 2020-June 2022, 667 CIFs were reported with 51% (343) successfully matched to a CNF. Only 57% of mothers of infants with a matching CIF had an ANC booking visit (entry into ANC). Overall, 87% of mothers were tested for syphilis increasing to 98% among mothers with an ANC booking visit. Median time between first syphilis test and delivery was 16 days overall increasing to 82 days among mothers with an ANC booking visit., Discussion: Only 37% of CS cases had accompanying clinical information to support evaluation of the prevention cascade. Mothers with an ANC booking visit had increased syphilis screening and time before delivery to allow for adequate treatment., (© The Author(s) [2024]. Published by Oxford University Press.)

Background: In South Africa, extragenital etiological sexually transmitted infection (STI) screening among men who have sex with men (MSM) is not routinely available. We aimed to determine the prevalence of STI pathogens at rectal and pharyngeal sites, syphilis seroprevalence, and associated risk factors among a selection of high-risk MSM without symptomatic urethritis attending a men's health clinic in Johannesburg, South Africa., Methods: A cross-sectional study was conducted in 2022. Enrolled clients self-reported demographic, sexual behavioral risks, and clinical information. Client or clinician-collected rectal and pharyngeal swabs were tested for Neisseria gonorrhoeae, Chlamydia trachomatis, Mycoplasma genitalium, and Trichomonas vaginalis. C. trachomatis-positive rectal samples were reflex tested for lymphogranuloma venereum. Blood specimens were screened for syphilis. Univariate and multivariate regression models were used to determine factors independently associated with the presence of an extragenital STI or syphilis., Results: Among the 97 participants (median age, 29 years), 24.7% had an extragenital STI and 9.4% had high nontreponemal antibody titers (rapid plasma reagin ≥1:16). Rectal STIs were detected in 26.4% participants: N. gonorrhoeae (14.3%), C. trachomatis (9.9%), and M. genitalium (5.5%). Pharyngeal STIs were less prevalent (4.1%). Overall, the prevalence of any STI was 41%. Sex under the influence of drugs (adjusted odds ratio, 4.94; 95% confidence interval, 1.56-15.69) and engaging in condomless receptive anal intercourse with a casual partner (adjusted odds ratio, 8.36; 95% confidence interval, 1.73-40.28) were independent risk factors for having an extragenital STI., Conclusions: The high burden of extragenital STIs and active syphilis in asymptomatic MSM underscores the importance of routine etiological screening in this key population, as the syndromic approach would not enable detection or treatment of these infections., Competing Interests: Conflict of Interest and Sources of Funding: The authors have no conflicts of interest to declare. This work was internally funded by the Centre of HIV & STIs at the National Institute for Communicable Diseases, a division of the National Health Laboratory Service, South Africa., (Copyright © 2024 American Sexually Transmitted Diseases Association. All rights reserved.)

Human immunodeficiency virus (HIV) viral load (VL) monitoring was likely interrupted during the Coronavirus disease 2019 (COVID-19) pandemic. We used routine data on repeat VL testing among 667 prevention of vertical HIV transmission (PVT) clients in Ehlanzeni district, to determine compliance to VL testing recommendations and associated factors during different time periods: pre-COVID-19, transition, and COVID-19. Descriptive and multivariable Poisson regression analyses were conducted, with and without including revised PVT-guidelines rolled out in January-2020. Among 405 women with ≥ 2 VL tests, the overall median age was 30 years (interquartile range: 26-35 years). Compliance to recommended VL testing guidelines ranged between 81.5% (172/211) and 92.3% (191/207) at different time periods. Across all three periods and when revised PVT-guidelines were used, being compliant was significantly reduced among those with earliest VL = 50-999 copies/ml (incidence rate ratio (IRR) = 0.71 [95% confidence interval (CI) 0.61-0.82], p value < 0.001) and VL ≥ 1000 copies/ml (IRR = 0.18 [95% CI 0.09-0.36], p value < 0.001). When guideline revisions were excluded, compliance was only significantly reduced among those with VL ≥ 1000 copies/ml (IRR = 0.14 [95% CI 0.06-0.32], p value < 0.001) and increased during the COVID-19 period versus pre-COVID-19 (IRR = 1.10 [95% CI 1.05-1.15], p value < 0.001). Similar significant associations between compliance and VL level were observed when the COVID-19 period was analyzed separately. Significantly increased compliance to VL testing among the 25-34 years age-group versus younger women was also observed across all periods. These results highlight the importance of strengthening strategies such as short message service reminders and educational messaging, reaching all age-groups, to fast-track implementation targets for VL monitoring., (© 2023. The Author(s).)

Background: In 2021, the HIV prevalence among South African adults was 18% and more than 2 million people had uncontrolled HIV and, therefore, had increased risk of poor outcomes with SARS-CoV-2 infection. We investigated trends in COVID-19 admissions and factors associated with in-hospital COVID-19 mortality among people living with HIV and people without HIV., Methods: In this analysis of national surveillance data, we linked and analysed data collected between March 5, 2020, and May 28, 2022, from the DATCOV South African national COVID-19 hospital surveillance system, the SARS-CoV-2 case line list, and the Electronic Vaccination Data System. All analyses included patients hospitalised with SARS-CoV-2 with known in-hospital outcomes (ie, who were discharged alive or had died) at the time of data extraction. We used descriptive statistics for admissions and mortality trends. Using post-imputation random-effect multivariable logistic regression models, we compared characteristics and the case fatality ratio of people with HIV and people without HIV. Using modified Poisson regression models, we compared factors associated with mortality among all people with COVID-19 admitted to hospital and factors associated with mortality among people with HIV., Findings: Among 397 082 people with COVID-19 admitted to hospital, 301 407 (75·9%) were discharged alive, 89 565 (22·6%) died, and 6110 (1·5%) had no recorded outcome. 270 737 (68·2%) people with COVID-19 had documented HIV status (22 858 with HIV and 247 879 without). Comparing characteristics of people without HIV and people with HIV in each COVID-19 wave, people with HIV had increased odds of mortality in the D614G (adjusted odds ratio 1·19, 95% CI 1·09-1·29), beta (1·08, 1·01-1·16), delta (1·10, 1·03-1·18), omicron BA.1 and BA.2 (1·71, 1·54-1·90), and omicron BA.4 and BA.5 (1·81, 1·41-2·33) waves. Among all COVID-19 admissions, mortality was lower among people with previous SARS-CoV-2 infection (adjusted incident rate ratio 0·32, 95% CI 0·29-0·34) and with partial (0·93, 0·90-0·96), full (0·70, 0·67-0·73), or boosted (0·50, 0·41-0·62) COVID-19 vaccination. Compared with people without HIV who were unvaccinated, people without HIV who were vaccinated had lower risk of mortality (0·68, 0·65-0·71) but people with HIV who were vaccinated did not have any difference in mortality risk (1·08, 0·96-1·23). In-hospital mortality was higher for people with HIV with CD4 counts less than 200 cells per μL, irrespective of viral load and vaccination status., Interpretation: HIV and immunosuppression might be important risk factors for mortality as COVID-19 becomes endemic., Funding: South African National Institute for Communicable Diseases, the South African National Government, and the United States Agency for International Development., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Competing Interests: We declare no competing interests.

Background: Sexually transmitted infections (STIs), particularly in the absence of viral suppression, increase the risk of HIV transmission to uninfected partners. We determined factors associated with having an unsuppressed VL among HIV-positive individuals attending STI services in South Africa (SA)., Methods: We analysed secondary cross-sectional data collected on HIV-positive individuals presenting with STI symptoms s at sentinel sites in Western Cape and Gauteng provinces between January-December 2019 in SA. We compared demographic characteristics of individuals on ART or not on ART, and a Poisson regression model to identify factors associated with having an unsuppressed VL (≥ 50 copies/ml) was used., Results: Among 93 HIV-positive individuals attending STI services with VL data, the median age was 32 years (IQR 27-37). Thirty-two (34.41%) individuals were on ART compared to 61 (65.59%) not on ART. Most of those on ART (56.25%) had an unsuppressed VL, while 86.89% of those not on ART had an unsuppressed VL. ART use was associated with a 33% lower prevalence of having unsuppressed VL. In a model adjusting for age, age at first sex and oral sex, none of the factors were significant. Among those on ART, individuals < 25 years were more likely to have an unsuppressed VL (aPRR = 1.94: 95% CI = 1.27-2.97) compared to those ≥ 25 years., Conclusion: ART use among HIV-positive individuals was low and VL suppression among those on ART was sub-optimal. Intensified ART initiation and adherence support to HIV-positive individuals seeking STI services could improve VL suppression., (© 2024. The Author(s).)

Bacterial vaginosis (BV) is a dysbiosis of vaginal microbiota characterized by a shift from Lactobacillus species predomination to a heterogeneous mixture of anaerobes. We compared the performance characteristics of the Allplex ™ BV molecular assay with the reference test, Nugent score microscopy, for vaginal swab specimens from symptomatic South African women. A total of 213 patients were enrolled, of whom 99 (46.5%) and 132 (62.0%) were diagnosed with BV by Nugent and Allplex™, respectively. The Allplex™ BV assay displayed a sensitivity of 94.9% (95% CI, 88.7%-97.8%) and a specificity of 66.7% (95% CI, 57.6%-74.6%), with an agreement of 79.8% (95% CI, 73.9%-84.7%) (κ = 0.60). Assay design may be enhanced for improved specificity by accounting for differences in healthy and BV-associated vaginal microbiomes among women of different ethnicities., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Minimal data exist on HIV drug resistance patterns and prevalence among paediatric patients failing ART in resource-limited settings. We assessed levels of HIV drug resistance in children with virological failure., Methods: This cross-sectional study, performed from March 2017 to March 2019 in South Africa, enrolled HIV-positive children aged ≤19 years, receiving ART through public health facilities with recent evidence suggestive of virological failure (at least one viral load ≥1000 copies/mL), across 45 randomly selected high-volume clinics from all nine provinces. Resistance genotyping was performed using next-generation sequencing technologies. Descriptive analysis taking into account survey design was used to determine outcomes., Results: Among 899 participants enrolled, the adjusted proportion of HIV drug resistance among children with virological failure was 87.5% (95% CI 83.0%-90.9%). Resistance to NNRTIs was detected in 77.4% (95% CI 72.5%-81.7%) of participants, and resistance to NRTIs in 69.5% (95% CI 62.9%-75.4%) of participants. Overall, resistance to PIs was detected in 7.7% (95% CI 4.4%-13.0%) of children., Conclusions: HIV drug resistance was highly prevalent in paediatric patients failing ART in South Africa, with 9 in 10 patients harbouring resistance to NNRTIs and/or NRTIs. PI-based regimens are predicted to be highly efficacious in achieving virological suppression amongst patients failing NNRTI-based regimens. Scaling up resistance testing amongst patients would facilitate access to second- and third-line regimens in South Africa., (Published by Oxford University Press on behalf of British Society for Antimicrobial Chemotherapy 2023.)

Background: South Africa experienced four waves of SARS-CoV-2 infection, dominated by Wuhan-Hu, Beta, Delta, and Omicron (BA.1/BA.2). We describe the trends in SARS-CoV-2 testing, cases, admissions, and deaths among children and adolescents in South Africa over successive waves., Methods: We analyzed national SARS-CoV-2 testing, case, and admissions data from March 2020 to February 2022 and estimated cumulative rates by age group for each endpoint. The severity in the third versus the fourth wave was assessed using multivariable logistic regression., Results: Individuals ≤18 years comprised 35% (21,008,060/60,142,978) of the population but only 12% (424,394/3,593,644) of cases and 6% (26,176/451,753) of admissions. Among individuals ≤18 years, infants had the highest admission (505/100,000) rates. Testing, case, and admission rates generally increased successively in the second (Beta) and third (Delta) waves among all age groups. In the fourth (Omicron BA.1/BA.2) wave, the case rate dropped among individuals ≥1 year but increased among those <1 year. Weekly admission rates for children <1 year (169/100,000) exceeded rates in adults (124/100,000) in the fourth wave. The odds of severe COVID-19 in all admitted cases were lower in the fourth wave versus the third wave in each age group, but they were twice as high in admitted cases with at least one comorbidity than those without., Conclusions: The admission rate for children <5 years was higher in the fourth wave than in previous waves, but the overall outcomes were less severe. However, children with at least one comorbidity had increased odds of severe disease, warranting consideration of prioritizing this group for vaccination., (© The Author(s) 2023. Published by Oxford University Press on behalf of The Journal of the Pediatric Infectious Diseases Society.)

We describe coverage of maternal syphilis screening, syphilis positivity, coverage of treatment and their association with maternal HIV infection and antiretroviral treatment (ART) status among pregnant women attending South African antenatal clinics. The 2019 antenatal care sentinel survey was a cross-sectional survey conducted from 1 October to 15 November 2019 at 1589 sentinel sites in all nine provinces of the country and aimed to enrol 36,000 pregnant women ages 15-49 years regardless of HIV, ART or syphilis status. Data collection procedures included obtaining written informed consent, a brief interview, medical record review and blood specimen collection. Completed data collection forms and specimens were sent to designated regional laboratories for data capture and HIV serology testing. Data analysis determined four outcomes i) syphilis screening coverage ii) syphilis positivity iii) coverage of any treatment and iv) with Benzathine penicillin G (BPG). Multivariable logistic regression models with or without interaction between HIV infection and ART status with province were used to determine factors associated with syphilis positivity. Of the 41 598 women enrolled, 35 900 were included in the analysis for syphilis screening coverage. The weighted syphilis screening coverage was 96.4% [95% Confidence Interval (CI) 95.9-96.7%] nationally and was lowest among HIV positive women not on ART at 93.5% (95% CI 92.2-94.5%). Syphilis positivity was 2.6% (95% CI 2.4-2.9%) nationally. Among those who were syphilis positive, 91.9% (95% CI 89.8-93.7%) had documentation of syphilis treatment status, of whom 92.0% (95% CI 89.8-93.9%) were treated, with the majority treated with one or more doses of BPG [92.2% (95% CI 89.8-94.3%)]. HIV-positive women, not on ART [adjusted odd ratio (aOR) 2.24 (95% 1.71-2.93)] and those on ART [aOR 2.25 (95% CI 1.91-2.64)] were more likely to be syphilis positive compared to those who were HIV negative. The national syphilis screening coverage met the global screening target of 95%. Syphilis positivity was higher among HIV positive women compared to negative women. Introduction of rapid syphilis testing and ensuring a universal supply of appropriate treatment for syphilis will reduce the likelihood of mother-to-child transmission of syphilis., (© 2023. The Author(s).)

Globally, high viral load (VL) suppression rates are indicators of successful HIV treatment programs. Evaluation of these programmes at lower levels is likely to highlight variations that are masked at the provincial or national levels. This ecological study used routinely collected clinical and surveillance data on the HIV programme from 88 sampled Ekurhuleni wards. Between January 2012 and December 2016, 26 222 HIV VL tests for 2817 patients were conducted. We conducted a secondary analysis to determine the predictors of high VL suppression accounting for space and time random effects and estimate the impact of the national universal test-and-treat roll-out in 2016 and forecast VL suppression rates for five years post-2016.The proportion of VL suppression increased over the years: 2012 (47.8%: 95% confidence interval (CI): 36.7%-67.4%); 2013 (58.2%: 95%CI: 41.4%-79.6%); 2014 (62.7%: 95%CI: 45.2%-84.7%); 2015 (67.2%: 95%CI: 49.0%-89.9%) and 2016 (61.2%: 95%CI: 43.9%-83.0%). For every percentage increase in ART initiation, high VL suppression rates increased by 35% (RR: 1.345; 95% credible interval (Crl) 1.221-1.492) and for every percentage increase in women in the ward, high VL suppression increased by 44% (RR: 1.442; 95%CrI: 1.056-1.962). There was evidence of high and low clusters of viral load suppression observed at ward-level. The VL suppression rates in Ekurhuleni were lower than the 90% UNAIDS target. There was heterogeneity of high VL suppression across wards and study period. Targeted interventions strengthening ART initiation and retention in care are critical to achieving optimal VL suppression in Ekurhuleni and districts with similar profiles., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests. Lucy Chimoyi is an academic Editor for the Plos Global Public Health Journal., (Copyright: © 2023 Chimoyi 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.)

Monitoring HIV prevalence using antenatal HIV sentinel surveillance is important for efficient epidemic tracking, programme planning and resource allocation. HIV sentinel surveillance usually employs unlinked anonymous HIV testing which raises ethical, epidemiological and public health challenges in the current era of universal test and treat. The World Health Organization (WHO) recommends that countries should consider using routine prevention of mother-to-child transmission of HIV (PMTCT) data for surveillance. We audited antenatal care clinics to assess the quality of HIV rapid testing practices as the first step to assess whether South Africa is ready to utilize PMTCT programme data for antenatal HIV surveillance. In 2017, we conducted a cross-sectional survey in 360 randomly sampled antenatal care clinics using the adapted WHO Stepwise-Process-for-Improving-the-Quality-of-HIV-Rapid-Testing (SPI-RT) checklist. We calculated median percentage scores within a domain (domain-specific median score), and across all domains (overall median percentage scores). The latter was used to classify sites according to five implementation levels; (from 0:<40% to 4: 90% or higher). Of 346 (96.1%) facilities assessed, an overall median percentage score of 62.1% (inter-quartile range (IQR): 50.8-71.9%) was obtained. The lowest domain-specific median percentage scores were obtained under training/certification (35% IQR: 10.0-50.0%) and external quality assurance (12.5% IQR: 0.0-50.0%), respectively. The majority (89%) of sites had an overall median score at level 2 or below; of these, 37% required improvement in specific areas and 6.4% in all areas. Facilities in districts implementing the HIV Rapid Test Quality Improvement Initiative and supported by the President's Emergency Plan for AIDS Relief (PEPFAR) had significantly higher median overall scores (65.6% IQR: 53.9-74.2%) (P-value from rank sum test: <0.001) compared with non-PEPFAR-supported facilities (56.6% IQR:47.7-66.0%). We found sub-optimal implementation of HIV rapid testing practices. We recommend the expansion of the PEPFAR-funded Rapid Test Continuous Quality Improvement (RTCQI) support to all antenatal care testing sites., Competing Interests: The authors have declared that no competing interests exist.

Competing Interests: I declare no competing interests.

Background: Herpes simplex virus (HSV) has been the leading cause of genital ulcer syndrome (GUS) in South Africa for more than a decade, and acyclovir therapy is incorporated into syndromic management guidelines. We conducted surveillance at 3 sentinel sites to define the common sexually transmitted etiologies of GUS and to determine whether current syndromic management is appropriate. Secondary objectives of surveillance were to determine the seroprevalence of coinfections (HIV, syphilis, HSV-2) in persons presenting with GUS., Methods: Consecutive, consenting adult men and women presenting with visible genital ulceration were enrolled between January 1, 2019, and December 31, 2020. Genital ulcer swab and blood specimens were collected and transported to a central sexually transmitted infection reference laboratory in Johannesburg., Results: Among 190 participants with GUS, HSV-2 was the most frequently detected ulcer pathogen (49.0%; 95% confidence interval [CI], 41.9%-56.1%). The relative prevalence of the second most common ulcer-derived pathogen, Treponema pallidum, was 26.3% (95% CI, 20.5%-33.1%), with 90% of primary syphilis cases having a positive rapid plasma reagin (RPR) titer. Male sex was independently associated with primary syphilis compared with herpetic ulcers, after adjusting for the effect of casual sex partners and other exposures (adjusted odds ratio, 3.53; 95% CI, 1.35-9.21; P = 0.010). The overall HIV prevalence among participants was 41.3% (78 of 189; 95% CI, 34.2%-48.6%)., Conclusions: Herpes simplex virus 2 remains the predominant cause of GUS, justifying the continued use of acyclovir in syndromic guidelines. Adequate supplies of benzathine penicillin G for syphilis treatment are essential at primary health care level, in addition to the provision of syphilis and HIV risk reduction services., Competing Interests: Conflict of Interest and Source of Funding: All authors have no conflicts of interest to declare. Funding for this work was obtained from the operational cost center of the Centre for HIV & STI at the National Institute for Communicable Diseases, Johannesburg, South Africa., (Copyright © 2022 American Sexually Transmitted Diseases Association. All rights reserved.)

Background: In South Africa, male urethritis syndrome (MUS) is the most common sexually transmitted infection (STI) syndrome in men. We determined the distribution of STI etiologies and the susceptibility profiles of Neisseria gonorrhoeae isolates from men presenting with MUS to 3 sentinel surveillance health care facilities. Secondary objectives were to determine the seroprevalence of coinfections (HIV, syphilis, herpes simplex virus 2)., Methods: Consecutive, consenting men with symptomatic urethral discharge were enrolled between January 1, 2019, and December 31, 2020. Genital discharge swab and blood specimens were collected and transported to a central STI reference laboratory in Johannesburg, South Africa., Results: Among 769 men enrolled, N. gonorrhoeae was the commonest cause of MUS (674 [87.8%]; 95% confidence interval [CI], 85.2%-89.9%), followed by Chlamydia trachomatis (161 [21.0%]; 95% CI, 18.2%-24.0%). Of 542 cultivable N. gonorrhoeae isolates, all were susceptible to ceftriaxone (modal minimum inhibitory concentration, 0.004 mg/L) and azithromycin (modal minimum inhibitory concentration, 0.128 mg/L). Seroprevalence rates of HIV, syphilis, and HSV-2 were 21.4% (95% CI, 18.5%-24.5%), 2.3%, and 50.1%, respectively. Condom use at last sexual encounter was reported by only 7%, less than 50% had been medically circumcised, and only 66.7% (58 of 87) who self-reported an HIV-positive status were adherent on antiretroviral drugs., Conclusions: Neisseria gonorrhoeae and C. trachomatis were the predominant causes of MUS. Currently recommended dual ceftriaxone and azithromycin therapy are appropriate for MUS syndromic management; however, surveillance must be maintained to timeously detect emerging and increasing gonococcal resistance. Clinic-based interventions must be intensified in men seeing sexual health care to reduce the community transmission and burden of STI and HIV., Competing Interests: Conflict of Interest and Source of Funding: All authors have no conflicts of interest to declare. Funding for this work was obtained from the operational cost center of the Centre for HIV & STI at the National Institute for Communicable Diseases, Johannesburg, South Africa., (Copyright © 2022 American Sexually Transmitted Diseases Association. All rights reserved.)

Background: The syndromic management of vaginal discharge syndrome (VDS) is challenging because of the prevalence of mixed infection with sexually transmitted infection (STI) pathogens and non-STI causes, such as bacterial vaginosis and candidiasis (CA). We aimed to determine the relative prevalence of VDS etiologies in women presenting to sentinel primary health care clinics in South Africa. Secondary objectives were to ascertain the predictive value of speculum findings for the presence of STI pathogens and the proportion of women presenting with clinical features of CA who had identifiable yeast on vaginal smear microscopy., Methods: Consecutive, consenting women with complaints of abnormal vaginal discharge were enrolled between January 1, 2019, and December 31, 2020. Genital discharge swab and blood specimens were collected and transported to a central STI reference laboratory in Johannesburg., Results: A total of 364 women were enrolled at 3 sentinel sites. Bacterial vaginosis was the most common cause of VDS (163 of 361 [45.2%]; 95% confidence interval [CI], 40.1%-50.3%); however, a significant proportion had STI coinfection (71 of 163 [43.6%]; 95% CI, 35.8%-51.5%). The predominant STI etiology was Chlamydia trachomatis (73 [20.2%]; 95% CI, 16.4%-24.7%). An abnormal speculum finding had poor predictive value for STIs, and Gram stain microscopy showed yeast in only 37.2% of vaginal smears from women with CA symptoms., Conclusions: Bacterial vaginosis is the predominant cause of VDS in South Africa; however, STI coinfection is common. Clinical findings are poorly predictive of STI etiologies or candidiasis; therefore, a rapid and accurate STI point-of-care test would be useful in optimizing VDS management., Competing Interests: Conflict of Interest and Source of Funding: All authors have no conflicts of interest to declare. Funding for this work was obtained from the operational cost center of the Centre for HIV & STI at the National Institute for Communicable Diseases, South Africa., (Copyright © 2022 American Sexually Transmitted Diseases Association. All rights reserved.)

Objectives: The UNAIDS 95-95-95 global targets for epidemic control aim to ensure by 2030 that 95% of HIV-positive people know their HIV status, 95% of people diagnosed with HIV receive sustained antiretroviral therapy (ART), and 95% of people on ART have viral suppression. While data on the first and second 95 targets are routinely reported nationally, data on the third 95 target are not available for pregnant women in South Africa. The lack of data on the third 95 target limits the inclusion of low viral suppression as one of the contributing factors in MTCT root cause analyses. This study assessed progress towards the 95-95-95 targets among pregnant women between the ages of 15-49 years attending public health facilities in South Africa., Method: Data were obtained from two consecutive national cross-sectional antenatal HIV sentinel surveys conducted between 1 October and 15 November in both 2017 and 2019. In each survey, data on age, knowledge of HIV status, ART initiation, and geographical location (province) were extracted from medical records. A blood specimen was collected from each woman and tested for HIV. Viral load tests were performed on HIV-positive specimens. Descriptive and multiple logistic regression analyses were performed to examine association between province and viral suppression (defined as viral load <50 copies/mL) using the combined dataset (i.e., both 2017 and 2019 data combined). All analyses considered the survey design., Results: Of 10 065 and 11 321 HIV-positive women included in the 2017 and 2019 surveys, respectively, 96.0% (95% confidence interval (CI): 95.6-96.4%) and 97.6% (95% CI: 97.3-97.8%) knew their HIV-positive status; 86.6% (95% CI: 85.9-87.3%) and 96.0% (95% CI: 95.6-96.4%) of those who knew their HIV status were receiving ART; while 64.2% (95% CI: 63.2-65.2%) and 66.0% (95% CI: 65.1-66.8%) of those receiving ART were virally suppressed. Achievement of the third 95 target significantly varied by province ranging from 33.9-72.6% in 2017 and 43.4-77.3% in 2019. Knowledge of HIV-positive status, ART initiation, and viral suppression increased in both 15-24 and 25-49 year age groups between 2017 and 2019. In a multivariable analysis adjusting for survey year, gravidity, and education, the odds of viral suppression significantly varied by province (except KwaZulu-Natal and Western Cape, other provinces were less likely to attain viral suppression compared to Gauteng), age (adjusted odds ratio (AOR) for 15-24 years vs 25-49 years: 0.7, 95% CI: 0.6-0.8), and timing of ART initiation (AOR for ART initiation during pregnancy vs before pregnancy: 0.4, 95% CI: 0.5-0.6)., Conclusion: Although in 2019 the first and second 95 targets were achieved among pregnant women, meeting the third 95 target remains a challenge. This study highlighted the importance of promoting early ART initiation and the need to target young women in efforts to improve progress towards the third 95 target. Additionally, the provincial variation in viral suppression could be further investigated in future studies to identify and address the root causes underlying these differences., Competing Interests: The authors have declared that no competing interests exist.

Background: The WHO-recommended tuberculosis screening and diagnostic algorithm in ambulatory people living with HIV is a four-symptom screen (known as the WHO-recommended four symptom screen [W4SS]) followed by a WHO-recommended molecular rapid diagnostic test (eg Xpert MTB/RIF [hereafter referred to as Xpert]) if W4SS is positive. To inform updated WHO guidelines, we aimed to assess the diagnostic accuracy of alternative screening tests and strategies for tuberculosis in this population., Methods: In this systematic review and individual participant data meta-analysis, we updated a search of PubMed (MEDLINE), Embase, the Cochrane Library, and conference abstracts for publications from Jan 1, 2011, to March 12, 2018, done in a previous systematic review to include the period up to Aug 2, 2019. We screened the reference lists of identified pieces and contacted experts in the field. We included prospective cross-sectional, observational studies and randomised trials among adult and adolescent (age ≥10 years) ambulatory people living with HIV, irrespective of signs and symptoms of tuberculosis. We extracted study-level data using a standardised data extraction form, and we requested individual participant data from study authors. We aimed to compare the W4SS with alternative screening tests and strategies and the WHO-recommended algorithm (ie, W4SS followed by Xpert) with Xpert for all in terms of diagnostic accuracy (sensitivity and specificity), overall and in key subgroups (eg, by antiretroviral therapy [ART] status). The reference standard was culture. This study is registered with PROSPERO, CRD42020155895., Findings: We identified 25 studies, and obtained data from 22 studies (including 15 666 participants; 4347 [27·7%] of 15 663 participants with data were on ART). W4SS sensitivity was 82% (95% CI 72-89) and specificity was 42% (29-57). C-reactive protein (≥10 mg/L) had similar sensitivity to (77% [61-88]), but higher specificity (74% [61-83]; n=3571) than, W4SS. Cough (lasting ≥2 weeks), haemoglobin (<10 g/dL), body-mass index (<18·5 kg/m 2 ), and lymphadenopathy had high specificities (80-90%) but low sensitivities (29-43%). The WHO-recommended algorithm had a sensitivity of 58% (50-66) and a specificity of 99% (98-100); Xpert for all had a sensitivity of 68% (57-76) and a specificity of 99% (98-99). In the one study that assessed both, the sensitivity of sputum Xpert Ultra was higher than sputum Xpert (73% [62-81] vs 57% [47-67]) and specificities were similar (98% [96-98] vs 99% [98-100]). Among outpatients on ART (4309 [99·1%] of 4347 people on ART), W4SS sensitivity was 53% (35-71) and specificity was 71% (51-85). In this population, a parallel strategy (two tests done at the same time) of W4SS with any chest x-ray abnormality had higher sensitivity (89% [70-97]) and lower specificity (33% [17-54]; n=2670) than W4SS alone; at a tuberculosis prevalence of 5%, this strategy would require 379 more rapid diagnostic tests per 1000 people living with HIV than W4SS but detect 18 more tuberculosis cases. Among outpatients not on ART (11 160 [71·8%] of 15 541 outpatients), W4SS sensitivity was 85% (76-91) and specificity was 37% (25-51). C-reactive protein (≥10 mg/L) alone had a similar sensitivity to (83% [79-86]), but higher specificity (67% [60-73]; n=3187) than, W4SS and a sequential strategy (both test positive) of W4SS then C-reactive protein (≥5 mg/L) had a similar sensitivity to (84% [75-90]), but higher specificity than (64% [57-71]; n=3187), W4SS alone; at 10% tuberculosis prevalence, these strategies would require 272 and 244 fewer rapid diagnostic tests per 1000 people living with HIV than W4SS but miss two and one more tuberculosis cases, respectively., Interpretation: C-reactive protein reduces the need for further rapid diagnostic tests without compromising sensitivity and has been included in the updated WHO tuberculosis screening guidelines. However, C-reactive protein data were scarce for outpatients on ART, necessitating future research regarding the utility of C-reactive protein in this group. Chest x-ray can be useful in outpatients on ART when combined with W4SS. The WHO-recommended algorithm has suboptimal sensitivity; Xpert for all offers slight sensitivity gains and would have major resource implications., Funding: World Health Organization., Competing Interests: Declaration of interests AC reports grants from National Institutes of Health (NIH), Global Health Labs, and Stop TB Partnership, and consulting fees from the US Centers for Disease Control and Prevention (CDC). AK reports grants from Sanofi. FAK reports grants from WHO, Canadian Institutes of Health Research, Fonds de Recherche Quebec, and McGill Interdisciplinary Initiative on Infection and Immunity. GT reports receipt of consumables and equipment from Boditech and Cepheid. NM reports grants from Pfizer and Roche. REC reports grants from NIH, CDC, and Unitaid, and consulting fees from Sanofi. SML reports grants from NIH and CDC. SSk reports grants from Swedish Heart-Lung Foundation. TKr reports consulting fees from WHO. All other authors declare no competing interests., (© 2022 World Health Organization; licensee Elsevier. This is an Open Access article published under the CC BY 3·0 IGO license which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. In any use of this article, there should be no suggestion that WHO endorses any specific organisation, products or services. The use of the WHO logo is not permitted. This notice should be preserved along with the article's original URL.)

Objectives: About half of the pregnancies among women living with HIV (WLWH) receiving antiretroviral therapy (ART) in sub-Saharan African countries are reported to be unintended. Unintended pregnancy is associated with late initiation of antenatal care (ANC), and may delay provision of viral load monitoring services, antenatal adherence counselling and support, and other services that promote sustained viral suppression throughout pregnancy. This study examines the association between unsuppressed viral load during the third trimester of pregnancy and unintended pregnancy among women who initiated ART before pregnancy., Methods: This was an analysis of data from a national antenatal survey conducted at 1 589 public health facilities in South Africa between 1 October and 15 November 2019. Consenting pregnant women aged 15-49 years attending ANC during the survey period were enrolled. Demographic and clinical data were collected through interview and medical record review. Pregnancy intention was assessed using two questions from the London Measure of Unplanned Pregnancy, and responses were categorized as "unintended," "undecided," and "intended." Blood specimens were collected from all women and tested for HIV; and if positive, a viral load test was performed. A survey domain-based poisson regression model examined the association between unsuppressed viral load during the third trimester of pregnancy and unintended pregnancy among women who initiated ART before pregnancy. Viral suppression was defined as viral load <50 copies/mL., Results: Of 10 901 WLWH with viral load data available, 63.3% (95% confidence interval (CI): 62.4%-64.1%) were virally suppressed. Among the 2 681 women (representing 24.1% of all WLWH with viral load data) who initiated ART before pregnancy and were in their third trimester at the time of enrolment, 74.4% (95% CI: 73.0%-75.8%) were virally suppressed. In the same population, the proportion virally suppressed was lower among women whose current pregnancies were unintended (72.1%, 95% CI: 70.1%-74.1%) compared to women whose pregnancies were intended (78.3%, 95% CI: 75.9%-80.5%). In multivariable analyses adjusted for age, gravity, marital status, education, location of facility and syphilis status, unintended pregnancy was associated with unsuppressed viral load during the third trimester (adjusted relative risk: 1.3, 95% CI: 1.1-1.4) among women who initiated ART before pregnancy., Conclusion: The identified association between unsuppressed viral load and unintended pregnancy among pregnant women who initiated ART before pregnancy highlights the need to strengthen routine assessment of fertility preferences and provision of contraceptive services to reproductive age WLWH receiving ART., Competing Interests: The authors have declared that no competing interests exist.

Introduction: We describe epidemiology and outcomes of confirmed SARS-CoV-2 infection and positive admissions among children <18 years in South Africa, an upper-middle income setting with high inequality., Methods: Laboratory and hospital COVID-19 surveillance data, 28 January - 19 September 2020 was used. Testing rates were calculated as number of tested for SARS-CoV-2 divided by population at risk; test positivity rates were calculated as positive tests divided by total number of tests. In-hospital case fatality ratio (CFR) was calculated based on hospitalized positive admissions with outcome data who died in-hospital and whose death was judged SARS-CoV-2 related by attending physician., Findings: 315 570 children aged <18 years were tested for SARS-CoV-2; representing 8.9% of all 3 548 738 tests and 1.6% of all children in the country. Of children tested, 46 137 (14.6%) were positive. Children made up 2.9% (n = 2007) of all SARS-CoV-2 positive admissions to sentinel hospitals. Among children, 47 died (2.6% case-fatality). In-hospital deaths were associated with male sex [adjusted odds ratio (aOR) 2.18 (95% confidence intervals [CI] 1.08-4.40)] vs female; age <1 year [aOR 4.11 (95% CI 1.08-15.54)], age 10-14 years [aOR 4.20 (95% CI1.07-16.44)], age 15-17 years [aOR 4.86 (95% 1.28-18.51)] vs age 1-4 years; admission to a public hospital [aOR 5.07(95% 2.01-12.76)] vs private hospital and ≥1 underlying conditions [aOR 12.09 (95% CI 4.19-34.89)] vs none., Conclusions: Children with underlying conditions were at greater risk of severe SARS-CoV-2 outcomes. Children > 10 years, those in certain provinces and those with underlying conditions should be considered for increased testing and vaccination., (© 2021 The Authors. Influenza and Other Respiratory Viruses published by John Wiley & Sons Ltd.)

To describe the prevalence of unintended pregnancy and its association with HIV status among pregnant women in South Africa. A cross-sectional survey was conducted between October and mid-November 2019 among pregnant women aged 15-49 years in 1589 selected public antenatal care facilities. Pregnancy intention was assessed using two questions from the London Measure of Unplanned Pregnancy. Survey logistic regression examined factors associated with unintended pregnancy. Among 34,946 participants, 51.6% had an unintended pregnancy. On multivariable analysis, the odds of unintended pregnancy was higher among women who knew their HIV-positive status before pregnancy but initiated treatment after the first antenatal visit (adjusted odds ratio [aOR], 1.5 [95% confidence interval (CI):1.2-1.8]), women who initiated treatment before pregnancy (aOR, 1.3 [95% CI:1.2-1.3]), and women with a new HIV diagnosis during pregnancy (aOR, 1.2 [95% CI:1.1-1.3]) compared to HIV-negative women. Women who were single, in a non-cohabiting or a cohabiting relationship, and young women (15-24 years) had significantly higher risk of unintended pregnancy compared to married women and women aged 30-49 years, respectively. A comprehensive approach, including regular assessment of HIV clients' pregnancy intention, and adolescent and youth-friendly reproductive health services could help prevent unintended pregnancy., (© 2021. The Author(s).)

The increased coverage of antiretroviral therapy has resulted in a decrease in the positive predictive value (PPV) and diagnostic sensitivity of early infant diagnosis assays. To evaluate the diagnostic performance of the Aptima HIV-1 Quant DX assay (Aptima) in detecting HIV infection at birth. The study was a cross-sectional laboratory based evaluation using whole blood DBS specimens. Samples were collected from HIV-exposed neonates at birth at two paediatric facilities in Gauteng between 1st March 2018 - 31st January 2020. Performance of the Aptima compared to the Cobas® AmpliPrep/Cobas® TaqMan HIV-1 Qualitative Test v2.0 was calculated using a two-by-two table and reported as proportions with 95% confidence intervals. A total of 363 infants met the inclusion criteria of which 4 (1.1%) had an Aptima result discordant with CAP/CTM HIV status: two (50%) negative and two (50%) positive. The Aptima assay had a sensitivity of 93.75% (95% CI: 79.19%-99.23%), specificity of 99.4% (95% CI: 97.83%-99.93%), PPV of 93.75% (95% CI: 78.98%-98.36%), negative predictive value of 99.4% (95% CI: 97.73%-99.84%), and overall accuracy of 98.9% (95% CI: 97.2%-99.7%). The Aptima yielded an error code on 37 (10.19%) results, of which 35 (94.59%) were resolved on repeat testing. Of the 32 HIV-detected specimens, 20 had a plasma VL result available (18 on Abbott and 2 on Cobas). The absolute median difference was 0.66 log10 (IQR: 0.36-1.71). The Aptima demonstrated good EID performance and can be considered as a qualitative EID assay., Competing Interests: Competing interests The authors declare that they have no financial or personal relationships that may have inappropriately influenced them in writing this article., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Neisseria gonorrhoeae is the predominant cause of male urethral discharge in South Africa, and escalating prevalence of gonococcal antimicrobial resistance (AMR) is a major health concern both in-country and globally. We analyzed the demographic, behavioral, and clinical characteristics of 685 men presenting with gonococcal urethral discharge to sentinel surveillance clinics over a 3-year period (2017 to 2019) to determine the burden of factors that are known to be associated with N. gonorrhoeae AMR to first-line therapy (defined as group 1 isolates exhibiting resistance or reduced susceptibility to extended-spectrum cephalosporins or azithromycin). Among 685 men with gonococcal urethral discharge, median age was 28 years (interquartile range [IQR], 24 to 32). Only two men (2/632; 0.3%) self-identified as homosexual; however, on further enquiry, another 16 (2%) confirmed that they had sex with men only. Almost 30% practiced oral sex and were at risk for pharyngeal gonococcal infection. In univariate analysis, male circumcision (odds ratio [OR], 0.69; 95% confidence interval [CI], 0.49 to 0.99) and recent sex outside the country (OR, 1.83; 95% CI, 1.21 to 2.76) were significantly associated with having a category 1 N. gonorrhoeae isolate. In a multivariable model, only sex outside South Africa increased the odds of being infected with a decreased susceptible/resistant N. gonorrhoeae isolate (adjusted odds ratio [aOR], 1.64; 95% CI, 1.05 to 2.55). These findings warrant the intensification of N. gonorrhoeae AMR surveillance among recently arrived migrant and overseas traveler populations, as well as the inclusion of extragenital specimens for N. gonorrhoeae AMR surveillance purposes.

Background: We describe the epidemiology of COVID-19 in South Africa following importation and during implementation of stringent lockdown measures., Methods: Using national surveillance data including demographics, laboratory test data, clinical presentation, risk exposures (travel history, contacts and occupation) and outcomes of persons undergoing COVID-19 testing or hospitalised with COVID-19 at sentinel surveillance sites, we generated and interpreted descriptive statistics, epidemic curves, and initial reproductive numbers (Rt)., Findings: From 4 March to 30 April 2020, 271,670 SARS-CoV-2 PCR tests were performed (462 tests/100,000 persons). Of these, 7,892 (2.9%) persons tested positive (median age 37 years (interquartile range 28-49 years), 4,568 (58%) male, cumulative incidence of 13.4 cases/100,000 persons). Hospitalization records were found for 1,271 patients (692 females (54%)) of whom 186 (14.6%) died. Amongst 2,819 cases with data, 489/2819 (17.3%) travelled internationally within 14 days prior to diagnosis, mostly during March 2020 (466 (95%)). Cases diagnosed in April compared with March were younger (median age, 37 vs. 40 years), less likely female (38% vs. 53%) and resident in a more populous province (98% vs. 91%). The national initial R t was 2.08 (95% confidence interval (CI): 1.71-2.51)., Interpretation: The first eight weeks following COVID-19 importation were characterised by early predominance of imported cases and relatively low mortality and transmission rates. Despite stringent lockdown measures, the second month following importation was characterised by community transmission and increasing disease burden in more populous provinces., Competing Interests: KMM, PNN, JE, GN, YP, LE, DM, AMS, KS, MM, KM, NW, TM, JK, TK, WJ, LHB, SM, ST, SW declare no competing interests. AvG reports receipt of funding and equipment to the NICD to support surveillance for SARS-CoV-2 from the South African Medical Research Committee (funding), Wellcome Trust (funding), European Union, Germany (equipment), the Jack Ma Foundation (Allibaba) (testing equipment and reagents), the Centres for Disease Control, Atlanta (funding), the EDCTP (funding), the Africa CDC (funding) and the Fleming Fund (funding). CC reports grants from US CDC, grants from Wellcome Trust, grants from South Africa MRC during the conduct of the study and grants from Sanofi Pasteur outside the submitted work; NPG reports grants from NIH, grants from US CDC, grants from CDC Foundation, grants from Bill and Melinda Gates Foundation, grants from NHLS Research Trust, grants from UK MRC (JGHT scheme) all outside the submitted work. The findings and conclusions in this manuscript are those of the authors and do not necessarily represent the official position of the authors’ affiliated institutions or funding agencies., (© 2021 The Authors.)

Background: The interaction between COVID-19, non-communicable diseases, and chronic infectious diseases such as HIV and tuberculosis is unclear, particularly in low-income and middle-income countries in Africa. South Africa has a national HIV prevalence of 19% among people aged 15-49 years and a tuberculosis prevalence of 0·7% in people of all ages. Using a nationally representative hospital surveillance system in South Africa, we aimed to investigate the factors associated with in-hospital mortality among patients with COVID-19., Methods: In this cohort study, we used data submitted to DATCOV, a national active hospital surveillance system for COVID-19 hospital admissions, for patients admitted to hospital with laboratory-confirmed SARS-CoV-2 infection between March 5, 2020, and March 27, 2021. Age, sex, race or ethnicity, and comorbidities (hypertension, diabetes, chronic cardiac disease, chronic pulmonary disease and asthma, chronic renal disease, malignancy in the past 5 years, HIV, and past and current tuberculosis) were considered as risk factors for COVID-19-related in-hospital mortality. COVID-19 in-hospital mortality, the main outcome, was defined as a death related to COVID-19 that occurred during the hospital stay and excluded deaths that occurred because of other causes or after discharge from hospital; therefore, only patients with a known in-hospital outcome (died or discharged alive) were included. Chained equation multiple imputation was used to account for missing data and random-effects multivariable logistic regression models were used to assess the role of HIV status and underlying comorbidities on COVID-19 in-hospital mortality., Findings: Among the 219 265 individuals admitted to hospital with laboratory-confirmed SARS-CoV-2 infection and known in-hospital outcome data, 51 037 (23·3%) died. Most commonly observed comorbidities among individuals with available data were hypertension in 61 098 (37·4%) of 163 350, diabetes in 43 885 (27·4%) of 159 932, and HIV in 13 793 (9·1%) of 151 779. Tuberculosis was reported in 5282 (3·6%) of 146 381 individuals. Increasing age was the strongest predictor of COVID-19 in-hospital mortality. Other factors associated were HIV infection (adjusted odds ratio 1·34, 95% CI 1·27-1·43), past tuberculosis (1·26, 1·15-1·38), current tuberculosis (1·42, 1·22-1·64), and both past and current tuberculosis (1·48, 1·32-1·67) compared with never tuberculosis, as well as other described risk factors for COVID-19, such as male sex; non-White race; underlying hypertension, diabetes, chronic cardiac disease, chronic renal disease, and malignancy in the past 5 years; and treatment in the public health sector. After adjusting for other factors, people with HIV not on antiretroviral therapy (ART; adjusted odds ratio 1·45, 95% CI 1·22-1·72) were more likely to die in hospital than were people with HIV on ART. Among people with HIV, the prevalence of other comorbidities was 29·2% compared with 30·8% among HIV-uninfected individuals. Increasing number of comorbidities was associated with increased COVID-19 in-hospital mortality risk in both people with HIV and HIV-uninfected individuals., Interpretation: Individuals identified as being at high risk of COVID-19 in-hospital mortality (older individuals and those with chronic comorbidities and people with HIV, particularly those not on ART) would benefit from COVID-19 prevention programmes such as vaccine prioritisation as well as early referral and treatment., Funding: South African National Government., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: Untreated or inadequately treated maternal syphilis infection may be transmitted from mother to child resulting in congenital syphilis (CS) infection. In South Africa (SA), CS is a notifiable medical condition (NMC). The NMC surveillance system (NMCSS) was improved by introducing an electronic notification application, a new case notification form and training resources in July 2017. We describe CS surveillance in SA and report on experiences from implementing an improved NMCSS from August 2017 to December 2019., Methods: We present the CS case definition, data collected by the CS case investigation and notification forms and data flow through the NMCSS. Descriptive statistics were used to analyse CS notifications received from August 2017 to December 2019. Qualitative inductive analysis of the stakeholder communications diary was conducted to identify CS surveillance challenges., Results: There were 418 CS notifications submitted from 80 facilities in 35 out of 52 districts. Of the notified cases, 194 (46.8%) were male and the median age at notification was 7 days (interquartile range: 3-16 days). The majority were diagnosed in hospital (98.6%). KwaZulu-Natal Province notified the most cases (52.9%) followed by Gauteng (28.0%). Challenges in CS surveillance included the lack of awareness of the CS case definition, completed paper-based notifications not reaching the NMCSS and the limited ability of the system to distinguish improved notifications from increase in disease burden., Conclusion: Improved CS surveillance through NMCSS was implemented in SA. Training, support and mentoring on CS and the notification system will be needed to inform elimination efforts., (© The Author(s) [2021]. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)