Provision of HIV services by community health workers should be strengthened to achieve full programme potential: a cross-sectional analysis in rural South Africa.

OBJECTIVE: South Africa's community health workers (CHWs) provide a bridge between the primary healthcare (PHC) facility and its community. We conducted a cross-sectional analysis to determine the contribution of the community-based HIV programme (CBHP) to the overall HIV programme. METHODS: We collected service provision data from the daily activity register of CHWs attached to 12 PHC facilities in rural Mopani District, South Africa. Personal identifiers of individuals referred to the facility for HIV services were recorded and verified against facility routine patient registers to determine the effectiveness of referral. RESULTS: HIV services were provided on 18 927 occasions; 30% of the total activities performed by CHWs during the study period. CHWs assessed 12 159 individuals for HIV risk (13% coverage of the study population); only 290 (2%) were referred for HIV testing services. Referral was effective in 213 (73%) individuals; evidence of an HIV-positive status was found for 38 (18%) individuals. However, 30 (79%) of these individuals were referred by CHWs despite being on ART. Adherence support was provided during 5657 visits; only one individual was referred for complications. Finally, of the 864 individuals lost to the ART programme, CHWs managed to find 452 (52%) for referral back to the facility; only 241 (53%) of these were (re)initiated on ART. CONCLUSIONS: Provision of HIV services by CHWs should be strengthened to fully deliver on the programme's potential. Human resource investment, home-based HIV testing and improved tracing models constitute potential strategies to enhance CHWs impact on the HIV programme.

OBJECTIF: Les agents de santé communautaires (ASC) d'Afrique du Sud constituent un pont entre les établissements de soins de santé primaires et leur communauté. Nous avons effectué une analyse transversale pour déterminer la contribution du programme VIH basé sur la communauté (PVBC) au programme global de lutte contre le VIH. MÉTHODES: Nous avons collecté des données sur la prestation de services à partir du registre des activités quotidiennes des ASC rattachés à 12 établissements de soins de santé primaires dans le district rural de Mopani, en Afrique du Sud. Les identifiants individuels des personnes référées vers l'établissement pour des services VIH ont été enregistrés et vérifiés par rapport aux registres de routine des patients de l'établissement afin de déterminer l'efficacité de l'aiguillage. RÉSULTATS: Les services VIH ont été fournis dans 18.927 occasions; 30% du total des activités réalisées par les ASC au cours de la période d'étude. Les ASC ont évalué 12.159 personnes pour les risques du VIH (couverture de 13% de la population étudiée); seuls 290 (2%) ont été référés pour des services de dépistage du VIH. L'aiguillage a été efficace chez 213 personnes (73%). L'évidence de séropositivité a été trouvée chez 38 personnes (18%). Cependant, 30 (79%) de ces personnes ont été référées par des ASC alors qu'elles étaient sous ART. Un soutien à la compliance a été fourni au cours de 5.657 visites; un seul individu a été référé pour des complications. Enfin, sur 864 personnes perdues du programme ART, les ASC ont réussi à retrouver 452 (52%) pour les référer de nouveau à l'établissement; seuls 241 (53%) de celles-ci ont été (ré) initiées sous ART. CONCLUSIONS: La fourniture de services VIH par les ASC devrait être renforcée pour exploiter pleinement le potentiel du programme. Les investissements dans les ressources humaines, le dépistage du VIH à domicile et les modèles de traçage améliorés constituent des stratégies potentielles pour améliorer l'impact des ASC sur le programme VIH.

The impact of implementing a Xpert MTB/RIF algorithm on drug-sensitive pulmonary tuberculosis: a retrospective analysis.

Xpert MTB/RIF (Xpert) is the preferred first-line test for all persons with tuberculosis (TB) symptoms in South Africa in line with a diagnostic algorithm. This study evaluates pre- and post-implementation trends in diagnostic practices for drug-sensitive, pulmonary TB in adults in an operational setting, following the introduction of the Xpert-based algorithm. We retrospectively analysed data from the national TB database for Greater Tzaneen sub-district, Limpopo Province. Trends in a number of cases, diagnosis and outcome and characteristics associated with death are reported. A total of 8407 cases were treated from 2008 until 2015, with annual cases registered decreasing by 31·7% over that time period (from 1251 to 855 per year). After implementation of Xpert, 69·9% of cases were diagnosed by Xpert, 29·4% clinically, 0·6% by smear microscopy and 0·1% by culture. Cases with a recorded microbiological test increased from 76·2% to 96·4%. Cases started on treatment without confirmation, but with a negative microbiological test increased from 7·1% to 25·7%. Case fatality decreased from 15·0% to 9·8%, remaining consistently higher in empirically treated groups, regardless of HIV status. Implementation of the algorithm coincided with a reduced number of TB cases treated and improved coverage of microbiological testing; however, a substantial proportion of cases continued to start treatment empirically.

Acceptability and Feasibility of Integrating Point-of-Care Diagnostic Testing of Sexually Transmitted Infections into a South African Antenatal Care Program for HIV-Infected Pregnant Women.

Background: Chlamydia trachomatis (CT), Neisseria gonorrhoeae (NG), and Trichomonas vaginalis (TV) infections may increase the risk of vertical transmission of the human immunodeficiency virus (HIV). In resource-limited settings, symptomatic screening, and syndromic management of sexually transmitted infections (STIs) during pregnancy continue to be the standard of care. In the absence of diagnostic testing, asymptomatic infections in pregnant women go untreated. Objective: To describe the acceptability and feasibility of integrating diagnostic STI screening into first antenatal care visits for HIV-infected pregnant women. Methods: HIV-infected pregnant women were recruited during their first antenatal care visit from three antenatal care clinics in Tshwane District, South Africa, between June 2016 and October 2017. Self-collected vaginal swabs were used to screen for CT, NG, and TV with a diagnostic point-of-care (POC) nucleic acid amplification test. Those with STIs were provided treatment per South African national guidelines. Results: Of 442 eligible women, 430 (97.3%) agreed to participate and were tested. Of those with a positive STI test result (n = 173; 40.2%), 159 (91.9%) received same-day results and treatment; 100% of STI-infected women were treated within seven days. Conclusions: Integration of POC diagnostic STI screening into first-visit antenatal care services was feasible and highly acceptable for HIV-infected pregnant women.

HIV viraemia and mother-to-child transmission risk after antiretroviral therapy initiation in pregnancy in Cape Town, South Africa.

OBJECTIVES: Maternal HIV viral load (VL) drives mother-to-child HIV transmission (MTCT) risk but there are few data from sub-Saharan Africa, where most MTCT occurs. We investigated VL changes during pregnancy and MTCT following antiretroviral therapy (ART) initiation in Cape Town, South Africa. METHODS: We conducted a prospective study of HIV-infected women initiating ART within routine antenatal services in a primary care setting. VL measurements were taken before ART initiation and up to three more times within 7 days postpartum. Analyses examined VL changes over time, viral suppression (VS) at delivery, and early MTCT based on polymerase chain reaction (PCR) testing up to 8 weeks of age. RESULTS: A total of 620 ART-eligible HIV-infected pregnant women initiated ART, with 2425 VL measurements by delivery (median gestation at initiation, 20 weeks; median pre-ART VL, 4.0 log10 HIV-1 RNA copies/mL; median time on ART before delivery, 118 days). At delivery, 91% and 73% of women had VL ≤ 1000 and ≤ 50 copies/mL, respectively. VS was strongly predicted by time on therapy and pre-ART VL. The risk of early MTCT was strongly associated with delivery VL, with risks of 0.25, 2.0 and 8.5% among women with VL < 50, 50-1000 and > 1000 copies/mL at delivery, respectively (P < 0.001). CONCLUSIONS: High rates of VS at delivery and low rates of MTCT can be achieved in a routine care setting in sub-Saharan Africa, indicating the effectiveness of currently recommended ART regimens. Women initiating ART late in pregnancy and with high VL appear substantially less likely to achieve VS and require targeted research and programmatic attention.

A 10-year cohort analysis of routine paediatric ART data in a rural South African setting.

South Africa's paediatric antiretroviral therapy (ART) programme is managed using a monitoring and evaluation tool known as TIER.Net. This electronic system has several advantages over paper-based systems, allowing profiling of the paediatric ART programme over time. We analysed anonymized TIER.Net data for HIV-infected children aged <15 years who had initiated ART in a rural district of South Africa between 2005 and 2014. We performed Kaplan-Meier survival analysis to assess outcomes over time. Records of 5461 children were available for analysis; 3593 (66%) children were retained in care. Losses from the programme were higher in children initiated on treatment in more recent years (P < 0·0001) and in children aged ≤1 year at treatment initiation (P < 0·0001). For children aged <3 years, abacavir was associated with a significantly higher rate of loss from the programme compared to stavudine (hazard ratio 1·9, P < 0·001). Viral load was suppressed in 48-52% of the cohort, with no significant change over the years (P = 0·398). Analysis of TIER.Net data over time provides enhanced insights into the performance of the paediatric ART programme and highlights interventions to improve programme performance.

Reduction in extrapulmonary tuberculosis in context of antiretroviral therapy scale-up in rural South Africa.

Scale-up of antiretroviral therapy (ART) for human immunodeficiency virus (HIV) infection has reduced the incidence of pulmonary tuberculosis (PTB) in South Africa. Despite the strong association of HIV infection with extrapulmonary tuberculosis (EPTB), the effect of ART on the epidemiology of EPTB remains undocumented. We conducted a retrospective record review of patients initiated on treatment for EPTB in 2009 (ART coverage <5%) and 2013 (ART coverage 41%) at four public hospitals in rural Mopani District, South Africa. Data were obtained from TB registers and patients' clinical records. There was a 13% decrease in overall number of TB cases, which was similar for cases registered as EPTB (n = 399 in 2009 vs. 336 in 2013; P < 0·01) and for PTB (1031 vs. 896; P < 0·01). Among EPTB cases, the proportion of miliary TB and disseminated TB decreased significantly (both P < 0·01), TB meningitis and TB of bones increased significantly (P < 0·01 and P = 0·02, respectively) and TB pleural effusion and lymphadenopathy remained the same. This study shows a reduction of EPTB cases that is similar to that of PTB in the context of the ART scale-up. The changing profile of EPTB warrants attention of healthcare workers.

HIV-infected individuals on long-term antiretroviral therapy are at higher risk for ocular disease.

Introduction of antiretroviral therapy (ART) has dramatically reduced the incidence of infectious ocular diseases in human immunodeficiency virus (HIV)-infected individuals. However, the effects of long-term ART and chronic HIV infection on the eye are ill-defined. This study determined the occurrence and severity of ocular diseases among 342 participants in a rural South African setting: HIV-naïve (n = 105), HIV-infected ART-naïve (n = 16), HIV-infected on ART for 36 months (long-term ART; n = 165). More HIV-infected participants presented with an external eye condition, in particular blepharitis, than HIV-naïve individuals (18% vs. 7%; age-adjusted odds ratio (aOR) = 2·8, P < 0·05). Anterior segment conditions (particularly keratoconjunctivitis sicca and pterygium) were also more common (50% vs. 27%; aOR = 2·4; P < 0·01). Compared with individuals on short-term ART, participants receiving long-term ART were more likely to have clinically detectable cataract (57% vs. 38%; aOR = 2·2, P = 0·01) and posterior segment diseases, especially HIV retinopathy (30% vs. 11%; aOR = 3·4, P < 0·05). Finally, long-term ART was significantly associated with presence of HIV retinopathy (P < 0·01). These data implicate that ocular disease is more common and of more diverse etiology among HIV-infected individuals, especially those on long-term ART and suggest that regular ophthalmological monitoring of HIV-infected individuals on ART is warranted.

Clinical and corneal microbial profile of infectious keratitis in a high HIV prevalence setting in rural South Africa.

The purpose of this investigation was to determine the clinical and corneal microbial profile of infectious keratitis in a high human immunodeficiency virus (HIV) prevalence setting in rural South Africa. Data in this cross-sectional study were collected from patients presenting with symptoms of infectious keratitis (n = 46) at the ophthalmology outpatient department of three hospitals in rural South Africa. Corneal swabs were tested for herpes simplex virus type 1 (HSV-1) and 2 (HSV-2), varicella zoster virus (VZV) and adenovirus DNA by real-time polymerase chain reaction (PCR) and for bacteria and fungi by culture. Based on clinical history, disease characteristics and laboratory results, 29 (63 %) patients were diagnosed as viral keratitis, including 14 (48 %) viral keratitis cases complicated by bacterial superinfection, and 17 (37 %) as bacterial keratitis. VZV and HSV-1 DNA was detected in 11 (24 %) and 5 (11 %) corneal swabs, respectively. Among clinically defined viral keratitis cases, a negative viral swab was predominantly (93 %) observed in cases with subepithelial inflammation and was significantly associated with an increased duration of symptoms (p = 0.003). The majority of bacteria cultured were Gram-positive (24/35), including Staphylococcus epidermidis and S. aureus. Viral aetiology was significantly associated with a history of herpes zoster ophthalmicus (p < 0.001) and a trend was observed between viral aetiology and HIV infection (p = 0.06). Twenty-one (47 %) keratitis cases were complicated by anterior uveitis, of which 18 (86 %) were HIV-infected cases with viral keratitis. The data implicate a high prevalence of herpetic keratitis, in part complicated by bacterial superinfection and/or uveitis, in HIV-infected individuals presenting with infectious keratitis in rural South Africa.

Knowledge, Attitudes and Beliefs regarding Post Exposure Prophylaxis among South African Men who have Sex with Men.

The Soweto Men's Study (2008), demonstrated an overall HIV prevalence rate of 13.2 %, with 10.1 % among straight-identified Men-who-have-sex-with-men (MSM), 6.4 % among bisexual-identified MSM and 33.9 % among gay-identified MSM. Behavioral interventions are imperative, but insufficient to prevent new HIV infections. Biomedical prevention of HIV offers a variety of combination prevention tools, including Post-exposure prophylaxis (PEP). PEP studies amongst MSM have been conducted in Amsterdam, Brazil and San Francisco, but never before in Africa. A cross-sectional, Internet-based survey was initiated to measure knowledge, attitudes and beliefs regarding PEP among South African MSM. Recruitment commenced in June 2014 and ran until October 2015. Participants were recruited through banner advertisements on Facebook.com and mambaonline.com, advertisements in the local gay media and at Health4Men (H4M) MSM-targeted clinics. Outreach workers distributed flyers advertising the study in their local communities. The survey was also made available on a computer at the H4M clinics in Cape Town and Johannesburg to reach MSM who may not have Internet access. A total of 408 men completed the survey. The majority of these men were under the age of 40, identified as gay/homosexual and were employed; 51 % (208/408) self-identified as black or of mixed race. In multivariate analysis participants who identified as gay had greater odds of having previously heard of PEP (AOR 1.91, 95 % CI 1.04, 3.51; p = 0.036), as did those who reported their HIV status as positive (AOR 2.59, 95 % CI 1.47, 4.45; p = 0.001). Participants with medical insurance had greater odds of having used PEP previously (AOR 2.67, 95 % CI 1.11, 6.43; p = 0.029). Bivariate analysis showed that condomless sex in the past 6 months was not significantly associated with PEP knowledge (p = 0.75) or uptake (p = 0.56) of PEP. Our findings suggest a lack of PEP knowledge and uptake among non-gay identified, HIV negative and un-insured MSM. Focusing PEP programs on these men may potentially increase uptake. Increased knowledge needs to be provided to MSM who engage in risky sexual behaviors.

Anti-retroviral Therapy Based HIV Prevention Among a Sample of Men Who Have Sex with Men in Cape Town, South Africa: Use of Post-exposure Prophylaxis and Knowledge on Pre-exposure Prophylaxis.

Men who have Sex with Men (MSM) have been affected disproportionately by the global HIV pandemic. Rates of consistent condom-use are low and there is a need for further biomedical prevention interventions to prevent new HIV infections. Post exposure prophylaxis (PEP) can reduce the risk of HIV, but uptake among MSM is low. Pre-exposure prophylaxis (PrEP), an innovative anti-retroviral-based HIV prevention tool might be an appropriate intervention for MSM who have recently accessed PEP that involves HIV negative individuals taking daily tenofovir+emtricitabine for HIV prevention. 44 MSM, attending a primary health-care level MSM-focused sexual health clinic in Cape Town, South Africa, who had initiated PEP were enrolled in this study. Participants were followed up after 2, 4 and 12 weeks. Self-administered electronic surveys were completed at the initial, 4 and 12 week visit. Barriers and facilitators to accessing PEP and remaining adherent were examined, as was knowledge about PrEP. Thirty-two participants (80 %) were <40 years of age (range 20-65 years). 35 % of the participants reported their reason for requiring PEP as condomless receptive anal intercourse. A further 20 % required PEP following condomless penetrative anal intercourse; 27.5 % required PEP due to a broken condom during receptive anal sex and 2 participants during insertive anal sex. Three participants did not complete 28 days of PEP or were lost to follow up. Over half (58.5 %) of the participants reported being completely adherent to their regime; under a third (31.7 %) reported missing one PEP dose; and 9.8 % reported missing more than one dose. 36/40 (90 %) had heard of PrEP and 30/40 (75 %) indicated that they would use PrEP if it were accessible to them. That we enrolled 44 MSM who accessed PEP from a Department of Health affiliated clinic over 12 months, speaks to the low uptake by MSM of PEP services in South Africa. Adherence was high and demonstrates that adherence support is feasible from a state health clinic. Reported risk behaviors in some high-risk participants did not change over time, demonstrating the need for additional longer-term HIV preventions such as PrEP. PEP users could conceivably be transitioned from PEP to PrEP.

Declining maternal mortality in the face of persistently high HIV prevalence in a middle-income country.

OBJECTIVE: To estimate maternal mortality ratio (MMR) and determine maternal death causes and trends in Greater Soweto, Johannesburg, South Africa. DESIGN: Cross-sectional study. SETTING: Chris Hani Baragwanath Maternity Hospital (CHBMH) in Greater Soweto. POPULATION: Maternal deaths at CHBMH. METHODS: Record review of maternal deaths from 1997 to 2012, using hospital death records, with denominator data from the district health information system and the hospital. MAIN OUTCOME MEASURES: Maternal mortality ratio per 100,000 live births, and causes of death classified as in the South African confidential enquiries. RESULTS: There were 479 deaths, with a peak MMR of 139 in 2004 and a decline to 86 in 2012. Of 332 women tested, 245 (74%) were HIV-infected. Nonpregnancy-related infection (40%) was the most frequent cause of death, followed by hypertension (16%) and obstetric haemorrhage (13%). HIV infection rates in these groups were 92%, 30% and 61%, respectively. Previous caesarean section was associated with obstetric haemorrhage death (odds ratio [OR] 3.2, 95% confidence interval [95% CI] 1.7-6.0), maternal age ≥35 years with hypertension death (OR 2.2, 95% CI 1.2-3.7) and antenatal anaemia with nonpregnancy-related infection death (OR 4.0, 95% CI 2.3-6.9), compared with other causes of death. CONCLUSION: There is evidence of a decline in MMR since HIV treatment for pregnant women was introduced in 2004. Previous caesarean section, advanced maternal age, and anaemia were associated with death from obstetric haemorrhage, hypertensive disorders of pregnancy and nonpregnancy-related infections, respectively. MMR may be further reduced with accelerated initiation of HIV treatment during pregnancy.

Acyclovir and transmission of HIV-1 from persons infected with HIV-1 and HSV-2.

BACKGROUND: Most persons who are infected with human immunodeficiency virus type 1 (HIV-1) are also infected with herpes simplex virus type 2 (HSV-2), which is frequently reactivated and is associated with increased plasma and genital levels of HIV-1. Therapy to suppress HSV-2 reduces the frequency of reactivation of HSV-2 as well as HIV-1 levels, suggesting that suppression of HSV-2 may reduce the risk of transmission of HIV-1. METHODS: We conducted a randomized, placebo-controlled trial of suppressive therapy for HSV-2 (acyclovir at a dose of 400 mg orally twice daily) in couples in which only one of the partners was seropositive for HIV-1 (CD4 count, > or = 250 cells per cubic millimeter) and that partner was also infected with HSV-2 and was not taking antiretroviral therapy at the time of enrollment. The primary end point was transmission of HIV-1 to the partner who was not initially infected with HIV-1; linkage of transmissions was assessed by means of genetic sequencing of viruses. RESULTS: A total of 3408 couples were enrolled at 14 sites in Africa. Of the partners who were infected with HIV-1, 68% were women, and the baseline median CD4 count was 462 cells per cubic millimeter. Of 132 HIV-1 seroconversions that occurred after randomization (an incidence of 2.7 per 100 person-years), 84 were linked within couples by viral sequencing: 41 in the acyclovir group and 43 in the placebo group (hazard ratio with acyclovir, 0.92, 95% confidence interval [CI], 0.60 to 1.41; P=0.69). Suppression with acyclovir reduced the mean plasma concentration of HIV-1 by 0.25 log(10) copies per milliliter (95% CI, 0.22 to 0.29; P<0.001) and the occurrence of HSV-2-positive genital ulcers by 73% (risk ratio, 0.27; 95% CI, 0.20 to 0.36; P<0.001). A total of 92% of the partners infected with HIV-1 and 84% of the partners not infected with HIV-1 remained in the study for 24 months. The level of adherence to the dispensed study drug was 96%. No serious adverse events related to acyclovir were observed. CONCLUSIONS: Daily acyclovir therapy did not reduce the risk of transmission of HIV-1, despite a reduction in plasma HIV-1 RNA of 0.25 log(10) copies per milliliter and a 73% reduction in the occurrence of genital ulcers due to HSV-2. (ClinicalTrials.gov number, NCT00194519.)

Where have we come from and where are we going? The paediatric HIV programme in Johannesburg, South Africa, from 2004 to 2018: A retrospective analysis of programme trends.

BACKGROUND: The paediatric HIV treatment programme in South Africa (SA) has grown since its inception in 2004. Despite this impressive scale-up of antiretroviral therapy (ART) in children, the proportion of children started on ART and retained in care remains unacceptably low, with only 47% of the 340 000 HIV-positive children in SA on ART in 2020. Johannesburg is one of the districts in SA with the largest number of children living with HIV who are not on ART, and is a priority district for paediatric case finding and retention. OBJECTIVES: To describe the dynamics of the paediatric HIV programme in Johannesburg, SA. METHODS: A secondary analysis was conducted on patient-level HIV treatment data from TIER.Net, the nationally mandated HIV/ART database. Children aged <15 years who received ART between January 2004 and June 2019 at public health facilities in Johannesburg were included. We reported the number of children on ART and the number who entered and exited the programme by age group over time, and analysed the trends of these indicators. RESULTS: By December 2018, 7 630 children aged <15 years remained in Johannesburg's paediatric ART programme: 82.5% were aged 5 - <15 years, with 54.1% of these being 10 - <15 years old. During the study period, 19 850 children were newly initiated on ART. New initiations slowed from 2013, to range from 1 172 to 1 373 yearly. In 2018, 34.2% of initiators were aged <1 year, 24.2% 1 - <5 years and 41.6% 5 - <15 years. Despite these initiations, the number of children on ART only grew by 97 in 2018, owing to programme losses. In 2018, 924  children (12.1%) aged out, 35 (0.5%) died and 983 (12.9%) were lost to follow-up (LTFU), the latter having increased from 10.7% in 2017. Of children who aged out of the paediatric ART programme, 56.3% remained in care at the same facility. CONCLUSION: Early in the SA ART roll-out, many children were found to be HIV infected and started on ART. This number started to slow in 2013, after which the growth rate of the paediatric HIV programme also began to slow. Scale-up of methods for identifying older children with HIV is needed. While ageing out of the paediatric programme is a consideration, the number of children LTFU remains unacceptably high. Further interrogation of barriers to paediatric retention is needed to help realise the Joint United Nations Programme on HIV and AIDS (UNAIDS) 90:90:90 goals for children in SA.

Tuberculosis in pregnancy.

Tuberculosis (TB) remains an important infection in women globally. It is responsible for 700 000 deaths annually and is a major contributor to maternal mortality. Mycobacterium tuberculosis/HIV co-infection is common in areas of high HIV prevalence, and may be associated with significant perinatal and maternal morbidity. Improved diagnosis and treatment of TB in pregnant women are important interventions for both maternal and child health. Controlling TB in pregnancy in high-prevalence areas requires a range of interventions, including active TB screening in pregnant women, TB preventative therapy for HIV-infected pregnant women, treatment of active TB and linking mothers and children to TB care services.

Primary healthcare workers at risk during COVID-19: An analysis of infections in HIV service providers in five districts of South Africa.

BACKGROUND: Protecting healthcare workers (HCWs) from COVID-19 is a global priority. Anova Health Institute (Anova) is the PEPFAR (US President's Emergency Plan for AIDS Relief) District Support Partner for the Johannesburg, Cape Town, Sedibeng, Capricorn and Mopani districts in South Africa, operating in public sector primary healthcare facilities. At the time of the emergence of COVID-19, Anova employed close to 4 000 people: 41% community health workers (CHWs), 23% data staff, 20% nurses and doctors, 12% management/support and 5% allied HCWs. OBJECTIVES: To describe rates of COVID-19 diagnosis in Anova-employed HCWs in five districts. METHODS: Employees exposed to, tested for or diagnosed with COVID-19 were required to report the event. These reports were compiled into a database to monitor the impact of COVID-19 on the workforce. We kept a timeline of key events occurring at national and district level, including Anova's policies and their implementation, that was used to describe organisational response. We described the number of confirmed cases, cumulative incidence rates and testing rates, broken down by district and job category. We estimated expected deaths and the effect on time off work. RESULTS: Of Anova employees, 14% (n=562) were diagnosed with COVID-19 by the end of September 2020. Cumulative incidence was highest in Sedibeng (29%) and lowest in Mopani (5%). All HCWs experienced high incidences: data staff 17%, allied HCWs 16%, CHWs 14%, nurses and doctors 13%, and management/support 11%. At the peak of the epidemic, for 5 weeks, >5% of employees were unable to work owing to exposure or infection, significantly disrupting service delivery. The additional administrative burden on managers was substantial. CONCLUSIONS: It is critical that all cadres of HCWs are protected in the workplace, including in primary care settings, where better structuresare needed to perform risk assessments and conduct outbreak investigations. CHWs and data staff may be at higher risk owing to poor infrastructure, limited power to negotiate working conditions, and limited experience of infection prevention and control. Their working conditions must be improved to reduce their risk.

Effect of COVID-19 on HIV, tuberculosis, and prevention of mother-to-child transmission of HIV indicators in Mopani district, South Africa.

BACKGROUND: To prevent the spread of SARS-CoV-2, many countries instituted lockdown measures. As the virus was initially slow to spread to rural areas in South Africa, Mopani district in Limpopo Province did not experience a high incidence of COVID-19 until the second wave in December 2020. Until then, lockdown measures were more likely than SARS-CoV-2 infections to have an adverse impact on health services. OBJECTIVES: To analyse HIV, tuberculosis (TB) and prevention of mother-to-child transmission of HIV (PMTCT) indicator trends in Mopani during the COVID-19 lockdown and two COVID-19 waves. METHODS: Using monthly data from the District Health Information System from February 2019 to December 2020, we conducted a retrospective review of data elements and indicators that fall into the following domains: primary healthcare head count (HC), HIV, antiretroviral treatment (ART), PMTCT and TB. Aggregated data were analysed, and an interrupted time series analysis was conducted. We assessed percentage changes between the January - March 2020 and April - June 2020 periods, and differences in means for the period April - December 2019 v. the period April - December 2020 were assessed for statistical significance. RESULTS: At the start of the first wave in April 2020, a statistically significant decline of 10% was recorded for total HC utilisation rates (p=0.1). We also found declines of 665 HIV tests (from 1 608 to 942) and 22 positive HIV tests (from 27 to 4) for children between the ages of 18 months and 14 years (p=0.05), with no recovery. Significant declines were also recorded for children aged <15 years starting (change from 35 to 21) and remaining (change from 4 032 to 3 986) on ART, as well as for adults starting ART (change from 855 to 610) at the onset of the first wave (p=0.01). No significant change was detected in PMTCT and TB indicators during the first wave. Pronounced decreases in HC were recorded in December, during the country's second wave (change from 237 965 to 227 834). CONCLUSION: Declines were recorded for most indicators in Mopani, with HC being affected the most at the start of the first wave and not showing any significant recovery between waves. Strategies are required to mitigate the effects of future COVID-19 waves and encourage positive health-seeking behaviour.

Antigens of human trophoblast. Effects of heterologous anti-trophoblast sera on lymphocyte responses in vitro.

This report describes the inhibition of human mixed lymphocyte culture (MLC) reactions by rabbit antisera to intact and detergent solubilized, fractionated, human trophoblast membranes. Heat-inactivated antisera were passed through solid-phase immunoabsorption columns of normal human serum and extensively absorbed with human erythrocytes, lymphocytes and liver powder. Immunohistological experiments with these absorbed antisera showed that they reacted brilliantly with syncytiotrophoblast in cryostat sections of human but not baboon or monkey placentae, and not with other normal adult tissues including peripheral blood lymphocytes (PBL). Addition of these antisera to MLC reactions produced significant and reproducible suppression of responses without affecting cell viability. Absorption studies demonstrated complete removal of MLC inhibition and trophoblast membranes but not with PBL or suspensions of HEp-2 cells. Timed experiments showed that optimal inhibition occurred when the antisera were added between 2 and 6 h after culture initiation, and that little suppression was achieved after 18 h. Lymphocytes harvested from MLC reactions after 2 h showed that 3--5% of the cells reacted with PBL/liver-absorbed anti-trophoblast sera, and that unstimulated PBL were negative. Cultures of subhuman primate lymphocytes in the presence of heterologous antisera to human trophoblast membranes showed total inhibition of rhesus:human and human:rhesus MLC, and no suppression of baboon:human or human:baboon reactions, whereas human lymphocytes responded in an exagerated manner when stimulated by baboon cells. Modulated MLC responses to human, rhesus, or baboon lymphocytes, in the presence of anti-trophoblast sera indicate that the antisera recognize trophoblast cross-reactive lymphocytes antigens. We propose that these antigens are reaction products of cell-cell interactions, and that the nature of the antigens is determined by the specificity of the recognition signals which initiate the reaction.

Cryoprotectant-induced redistribution of intramembranous particles in mouse lymphocytes.

This study demonstrates, by freeze fracture, clustering of intramembranous particles caused by cryoprotectant treatment of intact unfixed mouse lymphoid cells. Both T and B cells react in a similar fashion, while similar clustering of particles is not observed in some other cell types. The intramembranous particles can be aggregated by incubating unfixed cells in glycerol or dimethylsulfoxide (DMSO) before freezing. The aggregation phenomenon is dependent on the length of time of exposure and the concentration of the cryoprotectants. Further, the cells remain viable and the cryoprotectant-induced clustering is completely reversible. Prefixation of glycerol-treated cells with glutaraldehyde prevents the formation of these particle clusters, and unfixed nonglycerinated cells show no clusters. Thin sections of cells exposed to glycerol or DMSO without previous fixation exhibit bizarre membrane alterations and numerous other degenerative changes. These observations stress the importance of prefixation of lymphoid cells before exposure to glycerol or DMSO, as well as indicate that the membrane characteristics of certain cell types may be probed by glycerol treatment of unfixed cells.

Human trophoblast-lymphocyte cross-reactive (TLX) antigens define a new alloantigen system.

Antisera to human syncytiotrophoblast microvillous cell surface membranes from different placentas are cytotoxic for lymphocytes from some people but not others, demonstrating the presence of allotypic trophoblast-lymphocyte cross-reactive (TLX) antigens. Exploratory principal components factor analysis, performed on limited data consisting of 300 cytotoxic reactions produced by ten separate trophoblast antisera on a panel of lymphocytes from 30 random donors, suggested the presence of three distinct TLX antigen groupings. It is proposed that such TLX alloantigens are central in establishing maternal recognition and protection of the blastocyst, and that lack of recognition results in implantation failure and spontaneous abortion. These findings are compatible with contemporary results of immunotherapy to prevent recurrent spontaneous abortions, and their implications extend to other conditions of allogeneic coexistence, such as organ transplantation and the tumor-host relationship.

HAART and risk of tuberculosis in HIV-infected South African children: a multi-site retrospective cohort.

SETTING: Four human immunodeficiency virus (HIV) clinics located at South African tertiary hospitals. OBJECTIVE: To assess the effectiveness of highly active antiretroviral therapy (HAART) in reducing incident tuberculosis (TB) in HIV-infected children. DESIGN: Retrospective cohort. RESULTS: A total of 1132 children's records were included in the study. At entry to the cohort, the median (interquartile range [IQR]) age, CD4%, CD4 count and viral load of all children was respectively 6.3 years (4.1-8.8), 15% (9.0-22.2), 576 cells/mm(3) (287-960) and 160 000 copies/ml (54 941.5-449 683); 75.9% were started on HAART. The male:female ratio was 1:1, and median follow-up time was 1.7 years. In children whose follow-up included both pre-HAART and on-HAART periods, the incidence of clinically diagnosed TB was respectively 21.1 per 100 person-years (py; 95%CI 18.2-24.4) and 6.4/100 py (95%CI 4.8-8.1), and when restricted to confirmed cases, respectively 3.1/100 py (95%CI 2.2-4.2) and 0.8/100 py (95%CI 0.5-1.4). Only 23% of all cases of TB were microbiologically confirmed. Multivariate analyses showed that HAART reduced incident TB by approximately 70%, both for confirmed and all TB cases. CONCLUSIONS: In this high TB burden country, the incidence of diagnosis of TB in HIV-infected children is at least as high as that of adults. HAART reduces incident TB, but further prospective TB preventive and diagnostic studies are urgently needed in children.