The global tuberculosis burden remains substantial, with more than 10 million people newly ill per year. Nevertheless, tuberculosis incidence has slowly declined over the past decade, and mortality ...has decreased by almost a third in tandem. This positive trend was abruptly reversed by the COVID-19 pandemic, which in many parts of the world has resulted in a substantial reduction in tuberculosis testing and case notifications, with an associated increase in mortality, taking global tuberculosis control back by roughly 10 years. Here, we consider points of intersection between the tuberculosis and COVID-19 pandemics, identifying wide-ranging approaches that could be taken to reverse the devastating effects of COVID-19 on tuberculosis control. We review the impact of COVID-19 at the population level on tuberculosis case detection, morbidity and mortality, and the patient-level impact, including susceptibility to disease, clinical presentation, diagnosis, management, and prognosis. We propose strategies to reverse or mitigate the deleterious effects of COVID-19 and restore tuberculosis services. Finally, we highlight research priorities and major challenges and controversies that need to be addressed to restore and advance the global response to tuberculosis.
Innovative approaches are needed to increase lay health workers in HIV programs. The Youth Health Africa (YHA) program is a novel approach that places young adults seeking work experience in one-year ...internships in health facilities to support HIV-related programming (e.g., HIV testing) or administration (e.g., filing).
We implemented a pragmatic, randomized trial among 20 facilities in Ngaka Modiri Molema district in North West province from October 2020-August 2021 to assess impact of YHA interns on HIV testing, treatment initiation, and retention in care. The primary outcome was proportion of patients tested for HIV. Secondary outcomes assessed HIV positivity, initiation in care, retention in care, and HIV testing among males and adolescents/young adults. We conducted an intention-to-treat analysis accounting for variations in baseline outcomes between control and intervention facilities using difference-in-difference and controlled time series approaches. We repeated this using as-treated groupings for sensitivity analyses.
Fifty interns were placed in 20 facilities; thirty-four interns remained at 18 facilities through August 2021. Compared to control facilities, intervention facilities had a greater improvement in HIV testing (ΔΔ+5.7%, 95% Confidence Interval (CI): -3.7%-15.1%) and treatment initiation (ΔΔ+10.3%, 95% CI: -27.8-48.5%), but these differences were not statistically significant. There was an immediate increase in HIV testing in intervention facilities after program interns were placed, which was not observed in control facilities; this difference was significant (ΔΔ+8.4%, 95% CI: 0.5-16.4%, p = 0.036). There were no other differences in outcomes observed between intervention and control facilities.
This was largely a null trial, but there were signals that program interns may have positive impact on HIV testing and treatment initiation. As implemented in this study, addition of YHA program interns had little impact on facility-based HIV service delivery. A higher number of interns placed per facility may be necessary to affect HIV services.
Registration: This trial was registered with the ISRCTN (Registration number: ISRCTN67031403) in October 2022.
HIV treatment has reduced morbidity and mortality. By 2012, it was estimated that 60.4% of eligible South Africans accessed antiretroviral treatment; however, treatment adherence and retention remain ...the greatest challenges. There is a growing belief that social capital, seen as "the features of social organization that facilitate cooperation for mutual benefit", is important in promoting HIV treatment retention. The aim of this study was to establish whether social capital is associated with HIV treatment outcomes.
This was a cross-sectional analysis of data from a cohort study that investigated how patient outcomes were linked to clinical characteristics, and included exploratory factor and logistic regression analysis. Data from 943 patients were analyzed. Outcomes for the analysis were visit non-adherence, unsuppressed viral load, and treatment failure. Sixteen percent of patients (n = 118) had unsuppressed viral loads; 19% (n = 179) were non-adherent; and 32% (n = 302) experienced treatment failure. Social capital had two dimensions that were described by two factors. There was no association between either factor and visit non-adherence. Social capital factor 1 was marginally associated with lower risks of unsuppressed viral load and treatment failure at 12 months (OR = 0.78; 95% CI = 0.58-1.03 and OR = 0.76; 95% CI = 0.62-0.93, respectively); but not with visit non-adherence (OR = 0.93; 95% CI = 0.71-1.22). After controlling for confounders, the odds of both unsuppressed viral load and treatment failure decreased with an increase in social capital factor 1.
This study suggests that social capital, in terms of the number of groups to which an HIV-infected person belongs, the diversity of the groups, availability of child support, and time available for community projects, is protective against poor HIV treatment outcomes. Implementers and policy makers in the areas of HIV treatment and prevention need to consider the inclusion of social capital in the design of HIV/AIDS treatment program.
Tuberculosis regimens that are shorter and simpler than the current 6-month daily regimen are needed.
We randomly assigned patients with newly diagnosed, smear-positive, drug-sensitive tuberculosis ...to one of three regimens: a control regimen that included 2 months of ethambutol, isoniazid, rifampicin, and pyrazinamide administered daily followed by 4 months of daily isoniazid and rifampicin; a 4-month regimen in which the isoniazid in the control regimen was replaced by moxifloxacin administered daily for 2 months followed by moxifloxacin and 900 mg of rifapentine administered twice weekly for 2 months; or a 6-month regimen in which isoniazid was replaced by daily moxifloxacin for 2 months followed by one weekly dose of both moxifloxacin and 1200 mg of rifapentine for 4 months. Sputum specimens were examined on microscopy and after culture at regular intervals. The primary end point was a composite treatment failure and relapse, with noninferiority based on a margin of 6 percentage points and 90% confidence intervals.
We enrolled a total of 827 patients from South Africa, Zimbabwe, Botswana, and Zambia; 28% of patients were coinfected with the human immunodefiency virus. In the per-protocol analysis, the proportion of patients with an unfavorable response was 4.9% in the control group, 3.2% in the 6-month group (adjusted difference from control, -1.8 percentage points; 90% confidence interval CI, -6.1 to 2.4), and 18.2% in the 4-month group (adjusted difference from control, 13.6 percentage points; 90% CI, 8.1 to 19.1). In the modified intention-to-treat analysis these proportions were 14.4% in the control group, 13.7% in the 6-month group (adjusted difference from control, 0.4 percentage points; 90% CI, -4.7 to 5.6), and 26.9% in the 4-month group (adjusted difference from control, 13.1 percentage points; 90% CI, 6.8 to 19.4).
The 6-month regimen that included weekly administration of high-dose rifapentine and moxifloxacin was as effective as the control regimen. The 4-month regimen was not noninferior to the control regimen. (Funded by the European and Developing Countries Clinical Trials Partnership and the Wellcome Trust; RIFAQUIN Current Controlled Trials number, ISRCTN44153044.).
Summary Background Tuberculosis is the world's leading infectious disease killer. We aimed to identify shorter, safer drug regimens for the treatment of tuberculosis. Methods We did a randomised ...controlled, open-label trial with a multi-arm, multi-stage design. The trial was done in seven sites in South Africa and Tanzania, including hospitals, health centres, and clinical trial centres. Patients with newly diagnosed, rifampicin-sensitive, previously untreated pulmonary tuberculosis were randomly assigned in a 1:1:1:1:2 ratio to receive (all orally) either 35 mg/kg rifampicin per day with 15–20 mg/kg ethambutol, 20 mg/kg rifampicin per day with 400 mg moxifloxacin, 20 mg/kg rifampicin per day with 300 mg SQ109, 10 mg/kg rifampicin per day with 300 mg SQ109, or a daily standard control regimen (10 mg/kg rifampicin, 5 mg/kg isoniazid, 25 mg/kg pyrazinamide, and 15–20 mg/kg ethambutol). Experimental treatments were given with oral 5 mg/kg isoniazid and 25 mg/kg pyrazinamide per day for 12 weeks, followed by 14 weeks of 5 mg/kg isoniazid and 10 mg/kg rifampicin per day. Because of the orange discoloration of body fluids with higher doses of rifampicin it was not possible to mask patients and clinicians to treatment allocation. The primary endpoint was time to culture conversion in liquid media within 12 weeks. Patients without evidence of rifampicin resistance on phenotypic test who took at least one dose of study treatment and had one positive culture on liquid or solid media before or within the first 2 weeks of treatment were included in the primary analysis (modified intention to treat). Time-to-event data were analysed using a Cox proportional-hazards regression model and adjusted for minimisation variables. The proportional hazard assumption was tested using Schoelfeld residuals, with threshold p<0·05 for non-proportionality. The trial is registered with ClinicalTrials.gov ( NCT01785186 ). Findings Between May 7, 2013, and March 25, 2014, we enrolled and randomly assigned 365 patients to different treatment arms (63 to rifampicin 35 mg/kg, isoniazid, pyrazinamide, and ethambutol; 59 to rifampicin 10 mg/kg, isoniazid, pyrazinamide, SQ109; 57 to rifampicin 20 mg/kg, isoniazid, pyrazinamide, and SQ109; 63 to rifampicin 10 mg/kg, isoniazid, pyrazinamide, and moxifloxacin; and 123 to the control arm). Recruitment was stopped early in the arms containing SQ109 since prespecified efficacy thresholds were not met at the planned interim analysis. Time to stable culture conversion in liquid media was faster in the 35 mg/kg rifampicin group than in the control group (median 48 days vs 62 days, adjusted hazard ratio 1·78; 95% CI 1·22–2·58, p=0·003), but not in other experimental arms. There was no difference in any of the groups in time to culture conversion on solid media. 11 patients had treatment failure or recurrent disease during post-treatment follow-up: one in the 35 mg/kg rifampicin arm and none in the moxifloxacin arm. 45 (12%) of 365 patients reported grade 3–5 adverse events, with similar proportions in each arm. Interpretation A dose of 35 mg/kg rifampicin was safe, reduced the time to culture conversion in liquid media, and could be a promising component of future, shorter regimens. Our adaptive trial design was successfully implemented in a multi-centre, high tuberculosis burden setting, and could speed regimen development at reduced cost. Funding The study was funded by the European and Developing Countries Clinical Trials partnership (EDCTP), the German Ministry for Education and Research (BmBF), and the Medical Research Council UK (MRC).
We sought to assess mental health at the time of antiretroviral therapy (ART) initiation and subsequent retention in care over a six-month follow-up period. A total of 136 people living with HIV in ...South Africa were administered surveys measuring demographic information and mental health indicators at the time of ART initiation. Follow-up was completed via chart abstraction to assess for six-month outcomes of retention in care and viral suppression. At enrollment, 45/136 (33%), 67/136 (49%), and 45/136 (33%) participants screened positive for depression, anxiety, and alcohol use disorder, respectively. After six months of follow-up, 96/136 (71%) participants remained in care; 35/87 (40.2%) participants who remained in care had a level <50 copies/mL. Those with depression (49% vs. 77% retained; p < 0.01) and those with alcohol use disorder (52% vs. 76% retained; p < 0.01) were less likely to be retained in care. In multivariable logistic regression, depression OR 3.46 (95% CI: 1.33, 7.97; p < 0.01) and alcohol abuse OR 3.89 (95% CI: 1.70, 8.97; p < 0.01) were independently associated with loss from care. These results emphasize the importance of mental health on early ART outcomes and the HIV care continuum.
As the SARS-CoV2 pandemic has progressed, there have been marked geographical differences in the pace and extent of its spread. We evaluated the association of BCG vaccination on morbidity and ...mortality of SARS-CoV2, adjusted for country-specific responses to the epidemic, demographics and health. SARS-CoV2 cases and deaths as reported by 31 May 2020 in the World Health Organization situation reports were used. Countries with at least 28 days following the first 100 cases, and available information on BCG were included. We used log-linear regression models to explore associations of cases and deaths with the BCG vaccination policy in each country, adjusted for population size, gross domestic product, proportion aged over 65 years, stringency level measures, testing levels, smoking proportion, and the time difference from date of reporting the 100th case to 31 May 2020. We further looked at the association that might have been found if the analyses were done at earlier time points. The study included 97 countries with 73 having a policy of current BCG vaccination, 13 having previously had BCG vaccination, and 11 having never had BCG vaccination. In a log-linear regression model there was no effect of country-level BCG status on SARS-CoV2 cases or deaths. Univariable log-linear regression models showed a trend towards a weakening of the association over time. We found no statistical evidence for an association between BCG vaccination policy and either SARS-CoV2 morbidity or mortality. We urge countries to rather consider alternative tools with evidence supporting their effectiveness for controlling SARS-CoV2 morbidity and mortality.
Summary Given the dual epidemics of HIV and tuberculosis in sub-Saharan Africa and evidence suggesting a disproportionate burden of these diseases among detainees in the region, we aimed to ...investigate the epidemiology of HIV and tuberculosis in prison populations, describe services available and challenges to service delivery, and identify priority areas for programmatically relevant research in sub-Saharan African prisons. To this end, we reviewed literature on HIV and tuberculosis in sub-Saharan African prisons published between 2011 and 2015, and identified data from only 24 of the 49 countries in the region. Where data were available, they were frequently of poor quality and rarely nationally representative. Prevalence of HIV infection ranged from 2·3% to 34·9%, and of tuberculosis from 0·4 to 16·3%; detainees nearly always had a higher prevalence of both diseases than did the non-incarcerated population in the same country. We identified barriers to prevention, treatment, and care services in published work and through five case studies of prison health policies and services in Zambia, South Africa, Malawi, Nigeria, and Benin. These barriers included severe financial and human-resource limitations and fragmented referral systems that prevent continuity of care when detainees cycle into and out of prison, or move between prisons. These challenges are set against the backdrop of weak health and criminal-justice systems, high rates of pre-trial detention, and overcrowding. A few examples of promising practices exist, including routine voluntary testing for HIV and screening for tuberculosis upon entry to South African and the largest Zambian prisons, reforms to pre-trial detention in South Africa, integration of mental health services into a health package in selected Malawian prisons, and task sharing to include detainees in care provision through peer-educator programmes in Rwanda, Zimbabwe, Zambia, and South Africa. However, substantial additional investments are required throughout sub-Saharan Africa to develop country-level policy guidance, build human-resource capacity, and strengthen prison health systems to ensure universal access to HIV and tuberculsosis prevention, treatment, and care of a standard that meets international goals and human rights obligations.
ObjectiveTo explore the syndemic interaction between social, environmental, and structural contexts and HIV infection in peri-mining areas in South Africa.DesignMixed qualitative methods consisting ...of in-depth interviews (IDIs) and focus group discussions (FGDs) exploring the interaction between HIV infection and the social, environmental and structural factors affecting people living in the peri-mining areas of South Africa. Themes were analysed following the syndemic theoretical framework.SettingParticipants were recruited from three mining companies and locations in the peri-mining communities surrounding the mining companies in Limpopo, Mpumalanga, and Northern Cape provinces.ParticipantsInclusion criteria included mineworkers, healthcare workers, female sex workers (FSWs), injection drug users (IDUs), and other community members, ≥18 years, living in the peri-mining area at the time of participation. Three FGDs were conducted (n=30): 13 men and 17 women aged 18–55 years. IDIs were conducted with 45 participants: mineworkers (n=10), healthcare workers (n=11), FSWs (n=15), truck drivers (n=4) and IDUs (n=5).ResultsThe findings from this study indicate that a syndemic of four socio-behavioural factors is associated with HIV acquisition in peri-mining areas. These are migrancy, accessibility to alcohol and substance use, commercial and transactional sex, and uptake of HIV prevention services.ConclusionsOur findings have implications for HIV prevention programmes in mining companies, which rely on male condom usage promotion. More emphasis on better education about HIV prevalence, transmission and up-to-date prevention alternatives, such as pre-exposure prophylaxis for mineworkers is recommended. Furthermore, collaboration with community-based organisations is recommended to wholly address the syndemic factors influencing HIV transmission in peri-mining communities.
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