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.

Epidemiology and outcomes of SARS-CoV-2 infection associated with anti-nucleocapsid seropositivity in Cape Town, South Africa.

Background: In low- and middle-income countries where SARS-CoV-2 testing is limited, seroprevalence studies can characterise the scale and determinants of the pandemic, as well as elucidate protection conferred by prior exposure. Methods: We conducted repeated cross-sectional serosurveys (July 2020 - November 2021) using residual plasma from routine convenient blood samples from patients with non-COVID-19 conditions from Cape Town, South Africa. 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, to estimate variant disease severity. Findings: Among the subset sampled, seroprevalence of SARS-CoV-2 in Cape Town increased from 39.2% in July 2020 to 67.8% 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. 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). Interpretation: 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. Funding: Wellcome Trust, National Health Laboratory Service, the Division of Intramural Research, NIAID, NIH (ADR) and Western Cape Government Health.

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.

Objective: We aimed to compare 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 1-21 May 2022 (BA.4/BA.5 wave) and equivalent prior 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 prior infection. Results: Among 3,793 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 lower risk of severe outcomes than previous waves. Prior infection (aHR 0.29, 95% CI 0.24; 0.36) and vaccination (aHR 0.17; 95% CI 0.07; 0.40 for boosted vs. no vaccine) were protective. Conclusion: Disease severity was similar amongst 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 prior infection and vaccination, both of which were strongly protective.

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.

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: We aimed to compare COVID-19 outcomes in the Omicron-driven fourth wave with prior waves in the Western Cape, the contribution of undiagnosed prior infection to differences in outcomes in a context of high seroprevalence due to prior infection, and 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-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 hospitalization or death and any hospitalization or death (all ≤14 days after diagnosis) adjusted for age, sex, comorbidities, geography, vaccination and prior infection. RESULTS: We included 5,144 patients from wave four and 11,609 from prior waves. 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 an approximately 25% reduced risk of severe hospitalization or death compared to Delta.

An Evaluation of the Role of an Intermediate Care Facility in the Continuum of Care in Western Cape, South Africa.

BACKGROUND: A comprehensive primary healthcare (PHC) approach requires clear referral and continuity of care pathways. South Africa is a lower-middle income country (LMIC) that lacks data on the role of intermediate care (IC) services in the health system. This study described the model of service provision at one facility in Cape Town, including reason for admission, the mix of services and skills provided and needed, patient satisfaction, patient outcome and articulation with other services across the spectrum of care. METHODS: A multi-method design was used. Sixty-eight patients were recruited over one month in mid-2011 in a prospective cohort. Patient data were collected from clinical record review and an interviewer-administered questionnaire, administered shortly after admission to assess primary and secondary diagnosis, referring institution, knowledge of and previous use of home based care (HBC) services, reason for admission and demographics. A telephonic questionnaire at 9-weeks post-discharge recorded their vital status, use of HBC post-discharge and their satisfaction with care received. Staff members completed a self-administered questionnaire to describe demographics and skills. Cox regression was used to identify predictors of survival. RESULTS: Of the 68 participants, 38% and 24% were referred from a secondary and tertiary hospital, respectively. Stroke (35%) was the most common single reason for admission. The three most common reasons reported why care was better at the IC facility were staff attitude, the presence of physiotherapy and the wound care. Even though most patients reported admission to another health facility in the preceding year, only 13 patients (21%) had ever accessed HBC and only 25% (n=15) of discharged patients used HBC post-discharge. Of the 57 patients traced on follow-up, 21(37%) had died. The presence of a Care-plan was significantly associated with a 62% lower risk of death (hazard ratio: 0.38; CI 0.15-0.97). Notably, 46% of staff members reported performing roles that were outside their scope of practice and there was a mismatch between what staff reported doing and their actual tasks. CONCLUSION: Clients understood this service as a caring environment primarily responsible for rehabilitation services. A Care-plan beyond admission could significantly reduce mortality. There was poor referral to and poor articulation with HBC services. IC services should be recognised as an integral part of the health system and should be accessible.

Temporal trends in TB notification rates during ART scale-up in Cape Town: an ecological analysis.

INTRODUCTION: Although antiretroviral therapy (ART) reduces individual tuberculosis (TB) risk by two-thirds, the population-level impact remains uncertain. Cape Town reports high TB notification rates associated with endemic HIV. We examined population trends in TB notification rates during a 10-year period of expanding ART. METHODS: Annual Cape Town TB notifications were used as numerators and mid-year Cape Town populations as denominators. HIV-stratified population was calculated using overall HIV prevalence estimates from the Actuarial Society of South Africa AIDS and Demographic model. ART provision numbers from Western Cape government reports were used to calculate overall ART coverage. We calculated rates per 100,000 population over time, overall and stratified by HIV status. Rates per 100,000 total population were also calculated by ART use at treatment initiation. Absolute numbers of notifications were compared by age and sub-district. Changes over time were described related to ART provision in the city as a whole (ART coverage) and by sub-district (numbers on ART). RESULTS: From 2003 to 2013, Cape Town's population grew from 3.1 to 3.7 million inhabitants, and estimated HIV prevalence increased from 3.6 to 5.2%. ART coverage increased from 0 to 63% in 2013. TB notification rates declined by 16% (95% confidence interval (CI), 14-17%) from a 2008 peak (851/100,000) to a 2013 nadir (713/100,000). Decreases were higher among the HIV-positive (21% (95% CI, 19-23%)) than the HIV-negative (9% (95% CI, 7-11%)) population. The number of HIV-positive TB notifications decreased mainly among 0- to 4- and 20- to 34-year-olds. Total population rates on ART at TB treatment initiation increased over time but levelled off in 2013. Overall median CD4 counts increased from 146 cells/µl (interquartile range (IQR), 66, 264) to 178 cells/µl (IQR 75, 330; p<0.001). Sub-district antenatal HIV seroprevalence differed (10-33%) as did numbers on ART (9-29 thousand). Across sub-districts, infant HIV-positive TB decreased consistently whereas adult decreases varied. CONCLUSIONS: HIV-positive TB notification rates declined during a period of rapid scale-up of ART. Nevertheless, both HIV-positive and HIV-negative TB notification rates remained very high. Decreases among HIV positives were likely blunted by TB remaining a major entry to the ART programme and occurring after delayed ART initiation.

Restricting or banning alcohol advertising to reduce alcohol consumption in adults and adolescents.

BACKGROUND: Alcohol is estimated to be the fifth leading risk factor for global disability-adjusted life years. Restricting or banning alcohol advertising may reduce exposure to the risk posed by alcohol at the individual and general population level. To date, no systematic review has evaluated the effectiveness, possible harms and cost-effectiveness of this intervention. OBJECTIVES: To evaluate the benefits, harms and costs of restricting or banning the advertising of alcohol, via any format, compared with no restrictions or counter-advertising, on alcohol consumption in adults and adolescents. SEARCH METHODS: We searched the Cochrane Drugs and Alcohol Group Specialised Register (May 2014); CENTRAL (Issue 5, 2014); MEDLINE (1966 to 28 May 2014); EMBASE (1974 to 28 May 2014); PsychINFO (June 2013); and five alcohol and marketing databases in October 2013. We also searched seven conference databases and www.clinicaltrials.gov and http://apps.who.int/trialsearch/ in October 2013. We checked the reference lists of all studies identified and those of relevant systematic reviews or guidelines, and contacted researchers, policymakers and other experts in the field for published or unpublished data, regardless of language. SELECTION CRITERIA: We included randomised controlled trials (RCTs), controlled clinical trials, prospective and retrospective cohort studies, controlled before-and-after studies and interrupted time series (ITS) studies that evaluated the restriction or banning of alcohol advertising via any format including advertising in the press, on the television, radio, or internet, via billboards, social media or product placement in films. The data could be at the individual (adults or adolescent) or population level. DATA COLLECTION AND ANALYSIS: We used the standard methodological procedures expected by The Cochrane Collaboration. MAIN RESULTS: We included one small RCT (80 male student participants conducted in the Netherlands and published in 2009) and three ITS studies (general population studies in Canadian provinces conducted in the 1970s and 80s).The RCT found that young men exposed to movies with a low-alcohol content drank less than men exposed to movies with a high-alcohol content (mean difference (MD) -0.65 drinks; 95% CI -1.2, -0.07; p value = 0.03, very-low-quality evidence). Young men exposed to commercials with a neutral content compared with those exposed to commercials for alcohol drank less (MD -0.73 drinks; 95% CI -1.30, -0.16; p value = 0.01, very-low-quality evidence). Outcomes were assessed immediately after the end of the intervention (lasting 1.5 hours), so no follow-up data were available. Using the Grading of Recommendations Assessment, Development and Evaluation approach, the quality of the evidence was rated as very low due to a serious risk of bias, serious indirectness of the included population and serious level of imprecision.Two of the ITS studies evaluated the implementation of an advertising ban and one study evaluated the lifting of such a ban. Each of the three ITS studies evaluated a different type of ban (partial or full) compared with different degrees of restrictions or no restrictions during the control period. The results from the three ITS studies were inconsistent. A meta-analysis of the two studies that evaluated the implementation of a ban showed an overall mean non-significant increase in beer consumption in the general population of 1.10% following the ban (95% CI -5.26, 7.47; p value = 0.43; I(2) = 83%, very-low-quality evidence). This finding is consistent with an increase, no difference, or a decrease in alcohol consumption. In the study evaluating the lifting of a total ban on all forms of alcohol advertising to a partial ban on spirits advertising only, which utilised an Abrupt Auto-regressive Integrated Moving Average model, the volume of all forms of alcohol sales decreased by 11.11 kilolitres (95% CI -27.56, 5.34; p value = 0.19) per month after the ban was lifted. In this model, beer and wine sales increased per month by 14.89 kilolitres (95% CI 0.39, 29.39; p value = 0.04) and 1.15 kilolitres (95% CI -0.91, 3.21; p value = 0.27), respectively, and spirits sales decreased statistically significantly by 22.49 kilolitres (95% CI -36.83, -8.15; p value = 0.002). Using the GRADE approach, the evidence from the ITS studies was rated as very low due to a high risk of bias arising from a lack of randomisation and imprecision in the results.No other prespecified outcomes (including economic loss or hardship due to decreased alcohol sales) were addressed in the included studies and no adverse effects were reported in any of the studies. None of the studies were funded by the alcohol or advertising industries. AUTHORS' CONCLUSIONS: There is a lack of robust evidence for or against recommending the implementation of alcohol advertising restrictions. Advertising restrictions should be implemented within a high-quality, well-monitored research programme to ensure the evaluation over time of all relevant outcomes in order to build the evidence base.

Safety, feasibility and efficacy of a rapid ART initiation in pregnancy pilot programme in Cape Town, South Africa.

BACKGROUND: Antiretroviral therapy (ART) in pregnancy is a crucial intervention in the prevention of mother-to-child transmission (PMTCT) of HIV. It is recognised that mother-to-child transmission is reduced with each week on ART. However, in most South African settings, ART initiation is delayed owing to slow determination of treatment eligibility and separation of HIV and antenatal care services. OBJECTIVE: The rapid initiation of an ART in pregnancy programme is a model of care designed to expedite treatment initiation in ART- eligible pregnant women. This study evaluated the performance of the programme. METHODS: Participants enrolled in the ART programme in the same week as their first ANC visit throughout 2011, and had outcome data available by March 2012. Treatment eligibility was determined or confirmed via point-of-care CD4+ testing. Eligible women were offered ART immediately, with concurrent counselling and safety laboratory blood testing. Women attended until 6 - 8 weeks after delivery. Data were collected from clinical records with infant polymerase chain reaction (PCR) results at 6 weeks. RESULTS: Of 134 ART-eligible (CD4+ count <350 cells/µl or WHO stage III/IV) pregnant women, 130 (97.0%) started ART, 118 (90.8%) initiating treatment the same day that treatment eligibility was determined. There were no abnormal laboratory blood results or adverse events that required medical intervention. Pre-delivery retention in care and infant mortality were comparable to those in similar settings. Of the 107 pregnancies with PCR outcomes available, there was 1 positive HIV result in an infant (0.9%). Maternal viral load suppression in this mother was not achieved by the time of delivery. CONCLUSIONS: This pilot programme provides evidence that rapid ART initiation in pregnancy is safe, feasible and effective in reducing PMTCT. Further follow-up is required to monitor long-term outcomes.

Diversity of patient preparation activities before initiation of antiretroviral therapy in Cape Town, South Africa.

OBJECTIVE: To investigate patient education and counseling activities prior to the initiation of antiretroviral therapy (ART) at public sector services across Cape Town, South Africa. METHODS: Key informant interviews and programme reviews were conducted with government bodies and non-governmental organisations involved in patient preparation activities. RESULTS: All 11 organisations in Cape Town involved in training and managing personnel to prepare patients for ART during 2010 participated. Each organisation reported a different approach to patient preparation within public sector clinics and in each aspect of patient preparation activities. The number of patient education sessions ranged from 3 to 7, and the delays to ART initiation introduced by patient preparation ranged from 3 to 6 weeks. Different patient education materials (pamphlets, posters and flipcharts) were used by various programmes, and all programmes reported that shortages in materials meant that patient preparation often took place without any educational materials. Each programme also reported attention to mental illness and alcohol/substance use disorders, but none employed formal screening tools consistently, and the handling of patients with potential mental health- or substance-related problems varied. CONCLUSION: Approaches to prepare patients before ART initiation are wide ranging in one part of South Africa. Their relative value requires investigation, as there is little evidence for the impact of varying approaches. Moreover, the risks associated with delayed ART initiation may outweigh any benefits of patient education before the start of treatment.

Pilot programme for the rapid initiation of antiretroviral therapy in pregnancy in Cape Town, South Africa.

Initiation of antiretroviral therapy (ART) in pregnancy is an important intervention to prevent the mother-to-child transmission (MTCT) of HIV and to promote maternal health. Early initiation of ART is particularly important to achieve viral suppression rapidly before delivery. However, current approaches to start ART in pregnancy may be problematic in many settings, with referrals between antenatal care (ANC) and ART services, and delays for patient preparation before ART initiation. These steps contribute to a sizable proportion of women failing to receive adequate duration of ART before delivery, increasing the risk of MTCT. To address these limitations, we developed the rapid initiation of antiretroviral therapy in pregnancy (RAP) programme. The programme featured the use of point-of-care CD4 testing to identify ART-eligible women with CD4 cell counts ≤ 350 cells/µl; immediate ART initiation in women on the same day that eligibility was determined, if possible; and intensive counselling and support for ART initiation during the first few weeks on ART. We implemented RAP in an antenatal clinic setting in Cape Town South Africa. Between February and August 2011, a total of 221 HIV-infected women were referred to the programme for CD4 cell count testing and 101 (46%) were eligible for ART. Of these, 98 women (97%) started therapy during pregnancy, 89 (91%) on the day of referral to the service. In-depth interviews suggested that although there were substantial challenges facing HIV-infected women initiating ART in pregnancy, the availability of immediate services and counselling support played an important role in addressing these. While further research is needed, this evaluation demonstrates that a novel service delivery approach may facilitate rapid ART initiation in pregnancy.

Enhanced anti-mycobacterial immunity in children with erythema nodosum and a positive tuberculin skin test.

Erythema nodosum (EN) may follow a variety of infections, but in regions with a high prevalence of tuberculosis, is frequently associated with a positive tuberculin skin test (TST) and tuberculosis infection. We aimed to investigate the immunological differences between patients with EN as a manifestation of primary tuberculosis, and those with progressive pulmonary tuberculosis (PTB) or asymptomatic infection. We studied the inflammatory response to both mycobacterial and non-mycobacterial antigens in 11 children with EN associated with a positive TST, 22 children with culture-confirmed tuberculosis, and 53 healthy skin test-positive children. In addition, we evaluated functional anti-mycobacterial immunity using an ex vivo assay of mycobacterial growth restriction in five children with EN and 15 with PTB. Patients with EN were distinguished by enhanced mycobacterial growth restriction on the functional assay, which was associated with a markedly increased production of IFNgamma in response to stimulation with purified protein derivative of Mycobacterium tuberculosis. Children presenting with EN and a positive TST show evidence of responses associated with enhanced anti-mycobacterial immunity.