The cyclical cascade of HIV care: Temporal care engagement trends within a population-wide cohort.

BACKGROUND: The traditional HIV treatment cascade aims to visualise the journey of each person living with HIV from diagnosis, through initiation on antiretroviral therapy (ART) to treatment success, represented by virological suppression. This representation has been a pivotal tool in highlighting and quantifying sequential gaps along the care continuum. There is longstanding recognition, however, that this may oversimplify the complexity of real-world engagement with HIV services in settings with mature high-burden HIV epidemics. A complementary "cyclical" cascade has been proposed to represent the processes of disengagement at different points on the care continuum, with multiple pathways to re-engagement, although the feasibility of implementing this at scale has been uncertain. This study aimed to populate, refine, and explore the utility of a cyclical representation of the HIV cascade, using routine data from a high-burden HIV setting. METHODS AND FINDINGS: This observational cohort study leveraged person-level data on all people living with HIV in the Western Cape (WC), South Africa, who accessed public health services in the 2 years prior to 31 December 2023. Programme data from disease registers were complemented by data from pharmacy and laboratory systems. At study closure, 494 370 people were included, constituting 93% of those of those estimated to be living with HIV in the province, of whom 355 104 were on ART. Substantial disengagement from HIV care was evident at every point on the cascade. Early treatment emerged as a period of higher risk of disengagement, but it did not account for the majority of disengagement. Almost all those currently disengaged had prior experience of treatment. While re-engagement was also common, overall treatment coverage had increased slowly over 5 years. The transition to dolutegravir-based regimens was dramatic with good virological outcomes for those in care, notwithstanding a clearly discernible impact of the Coronavirus Disease 2019 (COVID-19) pandemic on viral load (VL) testing. People currently engaged and disengaged in care are similar with respect to age and gender. Those who died or disengaged recently were previously distributed across a range of cascade statuses, and a substantial proportion of those newly initiating and re-initiating treatment were no longer on treatment 6 months later. The main limitation of this study was incomplete evidence of HIV testing, linkage to HIV-specific services, and out-of-facility mortality. CONCLUSIONS: Using routine data, it was possible to populate and automate a cyclical cascade of HIV care that continuously captured the nonlinear care journeys of individuals living with HIV. In this generalised mature HIV epidemic, most people are treatment experienced. Disengagement is common and occurs at various points along the cascade, making it challenging to identify high-impact intervention opportunities. While historical HIV cascades remain valuable for target setting and service monitoring, they can be complemented with insights from more detailed cyclical cascades.

Outcomes of laboratory-confirmed SARS-CoV-2 infection in the Omicron-driven fourth wave compared with previous waves in the Western Cape Province, South Africa.

OBJECTIVES: The objective was to compare COVID-19 outcomes in the Omicron-driven fourth wave with prior waves in the Western Cape, assess the contribution of undiagnosed prior infection to differences in outcomes in a context of high seroprevalence due to prior infection and determine whether protection against severe disease conferred by prior infection and/or vaccination was maintained. METHODS: In this cohort study, we included public sector patients aged ≥20 years with a laboratory-confirmed COVID-19 diagnosis between 14 November and 11 December 2021 (wave four) and equivalent prior wave periods. We compared the risk between waves of the following outcomes using Cox regression: death, severe hospitalisation or death and any hospitalisation or death (all ≤14 days after diagnosis) adjusted for age, sex, comorbidities, geography, vaccination and prior infection. RESULTS: We included 5144 patients from wave four and 11,609 from prior waves. The risk of all outcomes was lower in wave four compared to the Delta-driven wave three (adjusted hazard ratio (aHR) [95% confidence interval (CI)] for death 0.27 [0.19; 0.38]. Risk reduction was lower when adjusting for vaccination and prior diagnosed infection (aHR: 0.41, 95% CI: 0.29; 0.59) and reduced further when accounting for unascertained prior infections (aHR: 0.72). Vaccine protection was maintained in wave four (aHR for outcome of death: 0.24; 95% CI: 0.10; 0.58). CONCLUSIONS: In the Omicron-driven wave, severe COVID-19 outcomes were reduced mostly due to protection conferred by prior infection and/or vaccination, but intrinsically reduced virulence may account for a modest reduction in risk of severe hospitalisation or death compared to the Delta-driven wave.

Evaluation of a public COVID-19 dashboard in the Western Cape, South Africa: a tool for communication, trust, and transparency.

BACKGROUND: Public health dashboards have been used in the past to communicate and guide local responses to outbreaks, epidemics, and a host of various health conditions. During the first year of the COVID-19 pandemic, dashboards proliferated but the availability and quality differed across the world. This study aimed to evaluate the quality, access, and end-user experience of one such dashboard in the Western Cape province, South Africa. METHODS: We analysed retrospective aggregate data on viewership over time for the first year since launch of the dashboard (30 April 2020 - 29 April 2021) and conducted a cross-sectional survey targeting adult users of the dashboard at one year post the initial launch. The self-administered, anonymous questionnaire with a total of 13 questions was made available via an online digital survey tool for a 2-week period (6 May 2021 - 21 May 2021). RESULTS: After significant communication by senior provincial political leaders, adequate media coverage and two waves of COVID-19 the Western Cape public COVID-19 dashboard attracted a total of 2,248,456 views during its first year. The majority of these views came from Africa/South Africa with higher median daily views during COVID-19 wave periods. A total of 794 participants responded to the survey questionnaire. Reported devices used to access the dashboard differed statistically between occupational status groups with students tending toward using mobile devices whilst employed and retired participants tending toward using desktop computers/laptops. Frequency of use increases with increasing age with 65.1% of those > 70 years old viewing it daily. Overall, 76.4% of respondents reported that the dashboard influenced their personal planning and behaviour. High Likert score ratings were given for clarity, ease of use and overall end-user experience, with no differences seen across the various age groups surveyed. CONCLUSION: The study demonstrated that both the availability of data and an understanding of end-user need is critical when developing and delivering public health tools that may ultimately garner public trust and influence individual behaviour.

Effect of HIV Infection and Antiretroviral Treatment on Pregnancy Rates in the Western Cape Province of South Africa.

BACKGROUND: Previous studies suggest that untreated human immunodeficiency virus (HIV) infection is associated with a reduced incidence of pregnancy, but studies of the effect of antiretroviral treatment (ART) on pregnancy incidence have been inconsistent. METHODS: Routine data from health services in the Western Cape province of South Africa were linked to identify pregnancies during 2007-2017 and maternal HIV records. The time from the first (index) pregnancy outcome date to the next pregnancy was modeled using Cox proportional hazards models. RESULTS: During 2007-2017, 1 042 647 pregnancies were recorded. In all age groups, pregnancy incidence rates were highest in women who had started ART, lower in HIV-negative women, and lowest in ART-naive HIV-positive women. In multivariable analysis, after controlling for the most recent CD4+ T-cell count, pregnancy incidence rates in HIV-positive women receiving ART were higher than those in untreated HIV-positive women (adjusted hazard ratio, 1.63; 95% confidence interval, 1.59-1.67) and those in HIV-negative women. CONCLUSION: Among women who have recently been pregnant, receipt of ART is associated with high rates of second pregnancy. Better integration of family planning into HIV care services is needed.

Safety and Effectiveness of Isoniazid Preventive Therapy in Pregnant Women Living with Human Immunodeficiency Virus on Antiretroviral Therapy: An Observational Study Using Linked Population Data.

BACKGROUND: Isoniazid preventive therapy (IPT) is widely used to protect against tuberculosis (TB) in people living with human immunodeficiency virus (HIV). Data on the safety and efficacy of IPT in pregnant women living with HIV (PWLHIV) are mixed. We used an individual-level, population-wide health database to examine associations between antenatal IPT exposure and adverse pregnancy outcomes, maternal TB, all-cause mortality, and liver injury during pregnancy through 12 months postpartum. METHODS: We used linked routine electronic health data generated in the public sector of the Western Cape, South Africa, to define a cohort of PWLHIV on antiretroviral therapy. Pregnancy outcomes were assessed using logistic regression; for maternal outcomes we applied a proportional hazards model with time-updated IPT exposure. RESULTS: Of 43 971 PWLHIV, 16.6% received IPT. Women who received IPT were less likely to experience poor pregnancy outcomes (adjusted odds ratio [aOR], 0.83 [95% confidence interval {CI}, .78-.87]); this association strengthened with IPT started after the first trimester compared with none (aOR, 0.71 [95% CI, .65-.79]) or with first-trimester exposure (aOR, 0.64 [95% CI, .55-.75]). IPT reduced the risk of TB by approximately 30% (aHR, 0.71 [95% CI, .63-.81]; absolute risk difference, 1518/100 000 women). The effect was modified by CD4 cell count with protection conferred if CD4 count was ≤350 cells/µL (aHR, 0.51 [95% CI, .41-.63]) vs 0.93 [95% CI, .76-1.13] for CD4 count >350 cells/µL). CONCLUSIONS: This analysis of programmatic data is reassuring regarding the safety of antenatal IPT, with the greatest benefits against TB disease observed in women with CD4 count ≤350 cells/µL.

Consolidating strategic information to monitor progress against the UNAIDS 90-90-90 targets: evaluating the operational feasibility of an electronic HIV testing register in Cape Town, South Africa.

BACKGROUND: HIV diagnosis in South Africa is based on a point-of-care testing (PoCT) algorithm with paper-based record-keeping. Aggregated testing data are reported routinely. To facilitate improved HIV case-based surveillance, the Western Cape Province implemented a unique pilot intervention to digitise PoCT results, at an individual level, and generate an electronic register using the newly developed Provincial Health Data Centre (PHDC). We describe the intervention (phased) and present an evaluation of the operational feasibility of the intervention. We also offer implementation insights into establishing electronic capture of individual level testing data. METHODS: Cross-sectional analyses were conducted on records of all patients attending a local Community Health Centre who had an HIV-PoCT during the study period. Data from the intervention were linked to the PHDC using a unique identifier and compared with aggregate data from the paper-based register. Correlation coefficients were calculated to quantify the correlation between the two monthly datasets. To support an understanding of the findings, the Department of Health project management team generated reflections on the implementation process, which were then grouped thematically into implementation lessons. RESULTS: In total, 11,337 PoCT records were digitised (70% (7954) during Phase I; and 30% (3383) during Phase II). Linkage of forms to the PHDC was 96% in Phase I and 98% in Phase II. Comparison with aggregate data showed high correlation during Phase I, but notable divergence during Phase II. Divergence in Phase II was due to stringent data quality requirements and high clinical staff turnover. Factors supporting implementation success in Phase I included direct oversight of data capturing by a manager with clinical and operational insight. Implementation challenges included operational, health system, and high cost-related issues. CONCLUSIONS: We demonstrate that rapid digitisation of HIV PoCT data, without compromising currently collected aggregate data, is operationally feasible, and can contribute to person-level longitudinal HIV case-based surveillance. To take to scale, we will need to improve PoCT platforms and clerical and administrative systems. Although we highlight challenges, we demonstrate that electronic HIV testing registers can successfully replace manual registers and improve efforts to monitor and evaluate HIV testing strategies.

The Influence of HIV on the Evolution of Mycobacterium tuberculosis.

HIV significantly affects the immunological environment during tuberculosis coinfection, and therefore may influence the selective landscape upon which M. tuberculosis evolves. To test this hypothesis whole genome sequences were determined for 169 South African M. tuberculosis strains from HIV-1 coinfected and uninfected individuals and analyzed using two Bayesian codon-model based selection analysis approaches: FUBAR which was used to detect persistent positive and negative selection (selection respectively favoring and disfavoring nonsynonymous substitutions); and MEDS which was used to detect episodic directional selection specifically favoring nonsynonymous substitutions within HIV-1 infected individuals. Among the 25,251 polymorphic codon sites analyzed, FUBAR revealed that 189-fold more were detectably evolving under persistent negative selection than were evolving under persistent positive selection. Three specific codon sites within the genes celA2b, katG, and cyp138 were identified by MEDS as displaying significant evidence of evolving under directional selection influenced by HIV-1 coinfection. All three genes encode proteins that may indirectly interact with human proteins that, in turn, interact functionally with HIV proteins. Unexpectedly, epitope encoding regions were enriched for sites displaying weak evidence of directional selection influenced by HIV-1. Although the low degree of genetic diversity observed in our M. tuberculosis data set means that these results should be interpreted carefully, the effects of HIV-1 on epitope evolution in M. tuberculosis may have implications for the design of M. tuberculosis vaccines that are intended for use in populations with high HIV-1 infection rates.

Exploring the validity of routine individuated service data for antenatal HIV surveillance in the Western Cape.

Background: In the Western Cape, South Africa, public-sector individual-level routine data are consolidated from multiple sources through the Provincial Health Data Centre (PHDC). This enables the description of temporal changes in population-wide antenatal HIV seroprevalence. We evaluated the validity of these data compared to aggregated program data and population-wide sentinel antenatal HIV seroprevalence surveys for the Western Cape province. Methods: We conducted a retrospective cohort analysis of all pregnancies identified in the PHDC from January 2011 to December 2020. Evidence of antenatal and HIV care from electronic platforms were linked using a unique patient identifier. HIV prevalence estimates were triangulated and compared with available survey estimates and aggregated programmatic data from registers as recorded in the District Health Information System. Provincial, district-level and age-group HIV prevalence estimates were compared between data systems using correlation coefficients, absolute differences and trend analysis. Results: Of the 977800 pregnancies ascertained, PHDC HIV prevalence estimates from 2011-2013 were widely disparate from aggregate and survey data (due to incomplete electronic data), whereas from 2014 onwards, estimates were within the 95% confidence interval of survey estimates, and closely correlated to aggregate data estimates (r = 0.8; p = 0.01), with an average prevalence difference of 0.4%. PHDC data show a slow but steady increase in provincial HIV prevalence from 16.7% in 2015 to 18.6% in 2020. The highest HIV prevalence was in the Cape Metro district (20.3%) Prevalence estimates by age group were comparable between sentinel surveys and PHDC from 2015 onwards, with prevalence estimates stable over time among younger age-groups (15-24 years) but increased among older age-groups (> 34 years). Conclusions: This study compares sentinel seroprevalence surveys with both register-based aggregate data and consolidated individuated administrative data. We show that in this setting linked individuated data may be reliably used for HIV surveillance and provide more granular estimates with greater efficiency than seroprevalence surveys and register-based aggregate data.

Can routine antenatal data be used to assess HIV antiretroviral therapy coverage among pregnant women? Evaluating the validity of different data sources in the Western Cape, South Africa.

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.

Factors associated with vertical transmission of HIV in the Western Cape, South Africa: a retrospective cohort analysis.

INTRODUCTION: Monitoring mother-infant pairs with HIV exposure is needed to assess the effectiveness of vertical transmission (VT) prevention programmes and progress towards VT elimination. METHODS: We used routinely collected data on infants with HIV exposure, born May 2018-April 2021 in the Western Cape, South Africa, with follow-up through mid-2022. We assessed the proportion of infants diagnosed with HIV at birth (≤7 days), 10 weeks (>1 to 14 weeks) and >14 weeks as proxies for intrauterine, intrapartum/early breastfeeding and late breastfeeding transmission, respectively. We used mixed-effects Poisson regression to assess factors associated with VT in mothers known with HIV by delivery. RESULTS: We included 50,461 infants born to mothers known with HIV by delivery. HIV was diagnosed in 894 (1.8%) infants. Among mothers, 51% started antiretroviral treatment (ART) before and 27% during pregnancy; 17% restarted during pregnancy after ≥6 months interruption; and 6% had no recorded ART during pregnancy. Most pregnancy ART regimens included non-nucleoside reverse transcriptase inhibitors (83%). Of mothers with available results (90% with viral load [VL]; 70% with CD4), VL nearest delivery was <100 copies/ml in 78% and CD4 count ≥350 cells/µl in 62%. HIV-PCR results were available for 86%, 67% and 48% of eligible infants at birth, 10 weeks and >14 weeks. Among these infants, 0.9%, 0.4% and 1.5% were diagnosed positive at birth, 10 weeks and >14 weeks, respectively. Among infants diagnosed with HIV, 43%, 16% and 41% were diagnosed at these respective time periods. Among mothers with VL<100, 100-999, 1000-99,000 and ≥100,000 copies/ml nearest delivery, infant HIV diagnosis incidence was 0.4%, 2.3%, 6.6% and 18.4%, respectively. Increased VT was strongly associated with recent elevated maternal VL with a seven-fold increased rate with even modestly elevated VL (100-999 vs. <100 copies/ml). VT was also associated with unknown/low maternal CD4, maternal age <20 years, no antenatal ART, later maternal ART start/restart in pregnancy and ART gaps. CONCLUSIONS: Despite high maternal ART coverage and routine postnatal prophylaxis, ongoing VT remains a concern. Timing of infant HIV diagnoses suggests intrapartum and/or breastfeeding transmission in nearly 60%. Interventions to ensure retention on ART and sustained maternal viral suppression are needed to reduce VT.

Maternal and birth outcomes in pregnant people with and without HIV in the Western Cape, South Africa.

INTRODUCTION: We evaluated associations of HIV and antiretroviral therapy (ART) with birth and maternal outcomes at a province-wide-level in the Western Cape, South Africa, in a recent cohort before dolutegravir-based first-line ART implementation. METHODS: This retrospective cohort study included pregnant people delivering in 2018-2019 with data in the Western Cape Provincial Health Data Centre which integrates individual-level data on all public sector patients from multiple electronic platforms using unique identifiers. Adverse birth outcomes (stillbirth, low birth weight (LBW), very LBW (VLBW)) and maternal outcomes (early and late pregnancy-related deaths, early and late hospitalizations) were compared by HIV/ART status and adjusted prevalence ratios (aPRs) calculated using log-binomial regression. RESULTS: Overall 171,960 pregnant people and their singleton newborns were included, 19% (N = 32 015) identified with HIV. Amongst pregnant people with HIV (PPHIV), 60% (N = 19 157) were on ART preconception, 29% (N = 9276) initiated ART during pregnancy and 11% (N = 3582) had no ART. Adjusted for maternal age, multiparity, hypertensive disorders and residential district, stillbirths were higher only for PPHIV not on ART [aPR 1.31 (95%CI 1.04-1.66)] compared to those without HIV. However, LBW and VLBW were higher among all PPHIV, with aPRs of 1.11-1.22 for LBW and 1.14-1.54 for VLBW. Pregnancy-initiated ART was associated with early pregnancy-related death (aPR 3.21; 95%CI 1.55-6.65), and HIV with or without ART was associated with late pregnancy-related death (aPRs 7.89-9.01). CONCLUSIONS: Even in the universal ART era, PPHIV experienced higher rates of LBW and VLBW newborns, and higher late pregnancy-related death regardless of ART status than pregnant people without HIV.

Population-based prevalence of congenital defects in a routine sentinel site-based surveillance system in the Western Cape, South Africa.

BACKGROUND: Lack of data on the burden and scope of congenital disorders (CDs) in South Africa undermines resource allocation and limits the ability to detect signals from potentially teratogenic pregnancy exposures. METHODS: We used routine electronic data in the Western Cape Pregnancy Exposure Registry (PER) to determine the overall and individual prevalence of CD identified on neonatal surface examination at birth in the Western Cape, South Africa, 2016-2022. CD was confirmed by record review. The contribution of late (≤24 months) and antenatal diagnoses was assessed. We compared demographic and obstetric characteristics between women with/without pregnancies affected by CD. RESULTS: Women with a viable pregnancy (>22 weeks gestation; birth weight ≥ 500 g) (n = 32,494) were included. Of 1106 potential CD identified, 56.1% were confirmed on folder review. When internal and minor CD were excluded the prevalence of major CD identified on surface examination at birth was 7.2/1000 births. When missed/late diagnoses on examination (16.8%) and ultrasound (6.8%) were included, the prevalence was 9.2/1000 births: 8.9/1000 livebirths and 21.5/1000 stillbirths. The PER did not detect 21.5% of major CD visible at birth. Older maternal age and diabetes mellitus were associated with an increased prevalence of CD. Women living with/without HIV (or the timing of antiretroviral therapy, before/after conception), hypertension or obesity did not significantly affect prevalence of CD. CONCLUSIONS: A surveillance system based on routine data successfully determined the prevalence of major CD identified on surface examination at birth at rates slightly higher than in equivalent studies. Overall rates, modeled at ~2%, are likely underestimated. Strengthening routine neonatal examination and clinical record-keeping could improve CD ascertainment.

HIV Drug Resistance in Newly Diagnosed Young Children in the Western Cape, South Africa.

BACKGROUND: Pretreatment of HIV drug resistance among children living with HIV (CLHIV) can compromise antiretroviral therapy (ART) effectiveness. Resistance may be transmitted directly from mothers or acquired following exposure to antiretrovirals consumed through breastfeeding or administered as prophylaxis. METHODS: We performed resistance testing in children aged <3 years, newly diagnosed with HIV in Western Cape, South Africa (2021-2022), who either (1) acquired HIV via possible breastfeeding transmission from mothers who received ART (any regimen) during pregnancy/postpartum and/or (2) were exposed to protease inhibitors or integrase strand transfer inhibitors (INSTIs) in utero. Possible breastfeeding transmission was defined as testing HIV-polymerase chain reaction positive at age >28 days, after previously testing negative. We used surveillance drug-resistance mutation lists to define mutations. RESULTS: We included 135 CLHIV. Most mothers started ART prepregnancy (73%). Overall, 57% (77/135) of children had resistance mutations detected. Nonnucleoside reverse transcriptase inhibitor-associated, nucleoside reverse transcriptase inhibitor-associated, protease inhibitor-associated and INSTI-associated mutations were found in 55% (74/135), 10% (13/135), <1% (1/135) and <1% (1/122) of children tested, respectively. One child with breastfeeding transmission had high-level INSTI resistance detected at HIV diagnosis, aged 18 months (E138K and G118R mutations). CONCLUSIONS: Although not clinically relevant, nonnucleoside reverse transcriptase inhibitor-associated mutations were common. Dolutegravir is currently the preferred first-line treatment for adults and CLHIV age ≥4 weeks, and although very low INSTI resistance levels have been observed in adults, limited data exist on genotyping the integrase region in children. Pretreatment INSTI resistance in children is likely to be unusual, but future surveillance, including longitudinal studies with paired mother-child resistance testing, is needed.

The Retrospective Implementation of Standardized In Utero HIV Exposure Definitions Using Routinely Collected Public Sector Data Across the Western Cape Province, South Africa.

Using the Data Evaluation and Preparation for HIV-Exposed Uninfected Child Cohorts project's standardized child HIV exposure definitions, 64%, 64% and 90% of children exposed to HIV in utero could be classified as HIV-uninfected with moderate or high certainty at the ages of 1 and 3 years and at the time of first infectious disease hospitalization, respectively. These definitions can be applied retrospectively to routine datasets with linked mother-child data.

COVID-19 Vaccine Uptake and Effectiveness by Time since Vaccination in the Western Cape Province, South Africa: An Observational Cohort Study during 2020-2022.

There are few data on the real-world effectiveness of COVID-19 vaccines and boosting in Africa, which experienced widespread SARS-CoV-2 infection before vaccine availability. We assessed the association between vaccination and severe COVID-19 in the Western Cape, South Africa, in an observational cohort study of >2 million adults during 2020-2022. We described SARS-CoV-2 testing, COVID-19 outcomes, and vaccine uptake over time. We used multivariable cox models to estimate the association of BNT162b2 and Ad26.COV2.S vaccination with COVID-19-related hospitalization and death, adjusting for demographic characteristics, underlying health conditions, socioeconomic status proxies, and healthcare utilization. We found that by the end of 2022, 41% of surviving adults had completed vaccination and 8% had received a booster dose. Recent vaccination was associated with notable reductions in severe COVID-19 during periods dominated by Delta, and Omicron BA.1/2 and BA.4/5 (sub)lineages. During the latest Omicron BA.4/5 wave, within 3 months of vaccination or boosting, BNT162b2 and Ad26.COV2.S were each 84% effective against death (95% CIs: 57-94 and 49-95, respectively). However, distinct reductions of effectiveness occurred at longer times post completing or boosting vaccination. Results highlight the importance of continued emphasis on COVID-19 vaccination and boosting for those at high risk of severe COVID-19, even in settings with widespread infection-induced immunity.

SARS-CoV-2 seroepidemiology in Cape Town, South Africa, and implications for future outbreaks in low-income communities.

In low- and middle-income countries where SARS-CoV-2 testing is limited, seroprevalence studies can help describe and characterise the extent of the pandemic, as well as elucidate protection conferred by prior exposure. We conducted repeated cross-sectional serosurveys (July 2020 -November 2021) using residual samples from patients from Cape Town, South Africa, sent for routine laboratory studies for non-COVID-19 conditions. SARS-CoV-2 anti-nucleocapsid antibodies and linked clinical information were used to investigate: (1) seroprevalence over time and risk factors associated with seropositivity, (2) ecological comparison of seroprevalence between subdistricts, (3) case ascertainment rates, and (4) the relative protection against COVID-19 associated with seropositivity and vaccination statuses. Among the subset sampled, seroprevalence of SARS-CoV-2 in Cape Town increased from 39.19% (95% confidence interval [CI] 37.23-41.19) in July 2020 to 67.8% (95%CI 66.31-69.25) in November 2021. Poorer communities had both higher seroprevalence and COVID-19 mortality. Only 10% of seropositive individuals had a recorded positive SARS-CoV-2 test. Using COVID-19 hospital admission and death data at the Provincial Health Data Centre, antibody positivity before the start of the Omicron BA.1 wave (28 November 2021) was strongly protective for severe disease (adjusted odds ratio [aOR] 0.15; 95%CI 0.05-0.46), with additional benefit in those who were also vaccinated (aOR 0.07, 95%CI 0.01-0.35). The high population seroprevalence in Cape Town was attained at the cost of substantial COVID-19 mortality. At the individual level, seropositivity was highly protective against subsequent infections and severe COVID-19 disease. In low-income communities, where diagnostic testing capacity is often limited, surveillance systems dependent on them will underestimate the true extent of an outbreak. Rapidly conducted seroprevalence studies can play an important role in addressing this.

COVID-19 vaccine uptake and effectiveness by time since vaccination in the Western Cape province, South Africa: An observational cohort study during 2020-2022.

Background: There are few data on the real-world effectiveness of COVID-19 vaccines and boosting in Africa, which experienced high levels of SARS-CoV-2 infection in a mostly vaccine-naïve population, and has limited vaccine coverage and competing health service priorities. We assessed the association between vaccination and severe COVID-19 in the Western Cape, South Africa. Methods: We performed an observational cohort study of >2 million adults during 2020-2022. We described SARS-CoV-2 testing, COVID-19 outcomes, and vaccine uptake over time. We used multivariable cox models to estimate the association of BNT162b2 and Ad26.COV2.S vaccination with COVID-19-related hospitalisation and death, adjusting for demographic characteristics, underlying health conditions, socioeconomic status proxies and healthcare utilisation. Results: By end 2022, only 41% of surviving adults had completed vaccination and 8% a booster dose, despite several waves of severe COVID-19. Recent vaccination was associated with notable reductions in severe COVID-19 during distinct analysis periods dominated by Delta, Omicron BA.1/2 and BA.4/5 (sub)lineages: within 6 months of completing vaccination or boosting, vaccine effectiveness was 46-92% for death (range across periods), 45-92% for admission with severe disease or death, and 25-90% for any admission or death. During the Omicron BA.4/5 wave, within 3 months of vaccination or boosting, BNT162b2 and Ad26.COV2.S were each 84% effective against death (95% CIs: 57-94 and 49-95, respectively). However, there were distinct reductions of VE at larger times post completing or boosting vaccination. Conclusions: Continued emphasis on regular COVID-19 vaccination including boosting is important for those at high risk of severe COVID-19 even in settings with widespread infection-induced immunity.

Record linkage for routinely collected health data in an African health information exchange.

Introduction: The Patient Master Index (PMI) plays an important role in management of patient information and epidemiological research, and the availability of unique patient identifiers improves the accuracy when linking patient records across disparate datasets. In our environment, however, a unique identifier is seldom present in all datasets containing patient information. Quasi identifiers are used to attempt to link patient records but sometimes present higher risk of over-linking. Data quality and completeness thus affect the ability to make correct linkages. Aim: This paper describes the record linkage system that is currently implemented at the Provincial Health Data Centre (PHDC) in the Western Cape, South Africa, and assesses its output to date. Methods: We apply a stepwise deterministic record linkage approach to link patient data that are routinely collected from health information systems in the Western Cape province of South Africa. Variables used in the linkage process include South African National Identity number (RSA ID), date of birth, year of birth, month of birth, day of birth, residential address and contact information. Descriptive analyses are used to estimate the level and extent of duplication in the provincial PMI. Results: The percentage of duplicates in the provincial PMI lies between 10% and 20%. Duplicates mainly arise from spelling errors, and surname and first names carry most of the errors, with the first names and surname being different for the same individual in approximately 22% of duplicates. The RSA ID is the variable mostly affected by poor completeness with less than 30% of the records having an RSA ID.The current linkage algorithm requires refinement as it makes use of algorithms that have been developed and validated on anglicised names which might not work well for local names. Linkage is also affected by data quality-related issues that are associated with the routine nature of the data which often make it difficult to validate and enforce integrity at the point of data capture.

Outcomes of laboratory-confirmed SARS-CoV-2 infection during resurgence driven by Omicron lineages BA.4 and BA.5 compared with previous waves in the Western Cape Province, South Africa.

OBJECTIVES: We aimed to compare the clinical severity of Omicron BA.4/BA.5 infection with BA.1 and earlier variant infections among laboratory-confirmed SARS-CoV-2 cases in the Western Cape, South Africa, using timing of infection to infer the lineage/variant causing infection. METHODS: We included public sector patients aged ≥20 years with laboratory-confirmed COVID-19 between May 01-May 21, 2022 (BA.4/BA.5 wave) and equivalent previous wave periods. We compared the risk between waves of (i) death and (ii) severe hospitalization/death (all within 21 days of diagnosis) using Cox regression adjusted for demographics, comorbidities, admission pressure, vaccination, and previous infection. RESULTS: Among 3793 patients from the BA.4/BA.5 wave and 190,836 patients from previous waves, the risk of severe hospitalization/death was similar in the BA.4/BA.5 and BA.1 waves (adjusted hazard ratio [aHR] 1.12; 95% confidence interval [CI] 0.93; 1.34). Both Omicron waves had a lower risk of severe outcomes than previous waves. Previous infection (aHR 0.29, 95% CI 0.24; 0.36) and vaccination (aHR 0.17; 95% CI 0.07; 0.40 for at least three doses vs no vaccine) were protective. CONCLUSION: Disease severity was similar among diagnosed COVID-19 cases in the BA.4/BA.5 and BA.1 periods in the context of growing immunity against SARS-CoV-2 due to previous infection and vaccination, both of which were strongly protective.

Cohort profile: the Western Cape Pregnancy Exposure Registry (WCPER).

PURPOSE: The Western Cape Pregnancy Exposure Registry (PER) was established at two public sector healthcare sentinel sites in the Western Cape province, South Africa, to provide ongoing surveillance of drug exposures in pregnancy and associations with pregnancy outcomes. PARTICIPANTS: Established in 2016, all women attending their first antenatal visit at primary care obstetric facilities were enrolled and followed to pregnancy outcome regardless of the site (ie, primary, secondary, tertiary facility). Routine operational obstetric and medical data are digitised from the clinical stationery at the healthcare facilities. Data collection has been integrated into existing services and information platforms and supports routine operations. The PER is situated within the Provincial Health Data Centre, an information exchange that harmonises and consolidates all health-related electronic data in the province. Data are contributed via linkage across a unique identifier. This relationship limits the missing data in the PER, allows validation and avoids misclassification in the population-level data set. FINDINGS TO DATE: Approximately 5000 and 3500 pregnant women enter the data set annually at the urban and rural sites, respectively. As of August 2021, >30 000 pregnancies have been recorded and outcomes have been determined for 93%. Analysis of key obstetric and neonatal health indicators derived from the PER are consistent with the aggregate data in the District Health Information System. FUTURE PLANS: This represents significant infrastructure, able to address clinical and epidemiological concerns in a low/middle-income setting.