The effectiveness of contact investigation among contacts of tuberculosis patients: a systematic review and meta-analysis.

Background: We aimed to evaluate the effectiveness of contact investigation in comparison with passive case detection alone, and estimate the yield of co-prevalent and incident tuberculosis (TB) and latent TB infection (LTBI) among contacts of patients with TB.

Methods: A systematic search was undertaken of studies published between 1 January 2011 and 1 October 2019 in the English language. The proportion of contacts diagnosed with co-prevalent TB, incident TB and/or LTBI was estimated.

Intersectional Stigma Among People Transitioning From Incarceration to Community-Based HIV Care in Gauteng Province, South Africa.

People transitioning from incarceration to community-based HIV care experience HIV stigma, incarceration stigma, and the convergence of these stigmas with social inequities. The objective of this study is to understand intersectional stigma among people returning from incarceration with HIV in Gauteng Province, South Africa. Qualitative interviews were conducted with 42 study participants.

Strengthening health systems to improve the value of tuberculosis diagnostics in South Africa: A cost and cost-effectiveness analysis.

Background: In South Africa, replacing smear microscopy with Xpert-MTB/RIF (Xpert) for tuberculosis diagnosis did not reduce mortality and was cost-neutral. The unchanged mortality has been attributed to suboptimal Xpert implementation. We developed a mathematical model to explore how complementary investments may improve cost-effectiveness of the tuberculosis diagnostic algorithm.

Efficacy of NVX-CoV2373 Covid-19 Vaccine against the B.1.351 Variant.

Background: The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants threatens progress toward control of the coronavirus disease 2019 (Covid-19) pandemic. In a phase 1-2 trial involving healthy adults, the NVX-CoV2373 nanoparticle vaccine had an acceptable safety profile and was associated with strong neutralizing-antibody and antigen-specific polyfunctional CD4+ T-cell responses. Evaluation of vaccine efficacy was needed in a setting of ongoing SARS-CoV-2 transmission.

Melting the : Nondetection of Kanamycin Resistance Markers by Routine Diagnostic Tests and Identification of New Promoter Variants.

promoter mutations can confer reduced Mycobacterium tuberculosis kanamycin susceptibility. GenoType MTBDR a widely used assay evaluating this region, wrongly classified 17/410 isolates as promoter wild type. Six out of seventeen isolates harbored mutations known to confer kanamycin resistance, and the remainder harbored either novel promoter mutations (7/11) or disputed mutations (4/11).

Performance of GeneXpert MTB/RIF for Diagnosing Tuberculosis Among Symptomatic Household Contacts of Index Patients in South Africa.

Background: We describe the performance of GeneXpert MTB/RIF (Xpert) for diagnosing tuberculosis (TB) among symptomatic household contacts (HHCs) of rifampicin-resistant and drug-sensitive index cases.

Methods: We conducted a cross-sectional study among HHCs of recently diagnosed (<2 weeks) smear-positive and Xpert-positive index cases in the Bojanala District, South Africa. The HHCs were screened for TB symptoms; persons with ≥1 TB symptom provided 1 sputum for smear microscopy, Xpert, and mycobacterial growth indicator tube (MGIT) culture.

Systems Analysis to Increase HIV Testing Delivery and HIV Diagnosis in Primary Care Clinics in South Africa.

Background: Provider-initiated testing and counseling remains highly underused in many South African health facilities. We implemented a systems analysis to investigate whether simple adjustments to HIV testing services (HTS) delivery can increase HTS provision.

Setting: Ten primary care facilities in the Ekurhuleni District in South Africa.

Validation of a host blood transcriptomic biomarker for pulmonary tuberculosis in people living with HIV: a prospective diagnostic and prognostic accuracy study.

Background: A rapid, blood-based triage test that allows targeted investigation for tuberculosis at the point of care could shorten the time to tuberculosis treatment and reduce mortality. We aimed to test the performance of a host blood transcriptomic signature (RISK11) in diagnosing tuberculosis and predicting progression to active pulmonary disease (prognosis) in people with HIV in a community setting.

Methods: In this prospective diagnostic and prognostic accuracy study, adults (aged 18-59 years) with HIV were recruited from five communities in South Africa.

Meta-analysis of HIV-1 vaccine elicited mucosal antibodies in humans.

We studied mucosal immune responses in six HIV-1 vaccine trials investigating different envelope (Env)-containing immunogens. Regimens were classified into four categories: DNA/vector, DNA/vector plus protein, protein alone, and vector alone. We measured HIV-1-specific IgG and IgA in secretions from cervical (n = 111) and rectal swabs (n = 154), saliva (n = 141), and seminal plasma (n = 124) and compared to corresponding blood levels.

Data quality assessment of a South African electronic registry for drug-resistant TB, 2015-2016.

Setting: Assessment of bedaquiline roll-out in South Africa requires accurate patient data in EDRWeb, a national case-based rifampicin-resistant TB (RR-TB) surveillance register.

Objective: To ensure EDRWeb data reflect programmatic DR-TB source data, we implemented a data quality improvement initiative.

Design: We conducted data quality assessments of EDRWeb data compared to paper patient folders at two South African RR-TB treatment facilities in 2015 and 2016.

Resistance to Mycobacterium tuberculosis Infection Among Household Contacts: A Multinational Study.

Background: Some contacts of patients with tuberculosis remain negative on tests for tuberculosis infection, despite prolonged exposure, suggesting they might be resistant to Mycobacterium tuberculosis infection. The objective of this multinational study was to estimate the proportion of household contacts resistant to M. tuberculosis (resisters).

A partially randomised trial of pretomanid, moxifloxacin and pyrazinamide for pulmonary TB.

Treatment for TB is lengthy and toxic, and new regimens are needed. Participants with pulmonary drug-susceptible TB (DS-TB) were randomised to receive: 200 mg pretomanid (Pa, PMD) daily, 400 mg moxifloxacin (M) and 1500 mg pyrazinamide (Z) for 6 months (6PaMZ) or 4 months (4PaMZ); 100 mg pretomanid daily for 4 months in the same combination (4PaMZ); or standard DS-TB treatment for 6 months. The primary outcome was treatment failure or relapse at 12 months post-randomisation.

Vaccine Efficacy of ALVAC-HIV and Bivalent Subtype C gp120-MF59 in Adults.

Background: A safe, effective vaccine is essential to eradicating human immunodeficiency virus (HIV) infection. A canarypox-protein HIV vaccine regimen (ALVAC-HIV plus AIDSVAX B/E) showed modest efficacy in reducing infection in Thailand. An analogous regimen using HIV-1 subtype C virus showed potent humoral and cellular responses in a phase 1-2a trial in South Africa.

Adjunctive host-directed therapies for pulmonary tuberculosis: a prospective, open-label, phase 2, randomised controlled trial.

Background: Current tuberculosis treatments leave patients with clinically significant lung injury and increased all-cause mortality post-cure. Adjunctive host-directed therapies could protect the lungs, improve long-term survival, and shorten treatment duration; however, few have been tested clinically. Therefore, we aimed to assess the safety and preliminary efficacy of four host-directed therapies for tuberculosis.

Innate immune signatures to a partially-efficacious HIV vaccine predict correlates of HIV-1 infection risk.

The pox-protein regimen tested in the RV144 trial is the only vaccine strategy demonstrated to prevent HIV-1 infection. Subsequent analyses identified antibody and cellular immune responses as correlates of risk (CoRs) for HIV infection. Early predictors of these CoRs could provide insight into vaccine-induced protection and guide efforts to enhance vaccine efficacy.

Determining the value of TB active case-finding: current evidence and methodological considerations.

Active case-finding (ACF) is an important component of the End TB Strategy. However, ACF is resource-intensive, and the economics of ACF are not well-understood. Data on the costs of ACF are limited, with little consistency in the units and methods used to estimate and report costs.

Drug susceptibility patterns of Mycobacterium tuberculosis from adults with multidrug-resistant tuberculosis and implications for a household contact preventive therapy trial.

Background: Drug susceptibility testing (DST) patterns of Mycobacterium tuberculosis (MTB) from patients with rifampicin-resistant tuberculosis (RR-TB) or multidrug-resistant TB (MDR-TB; or resistant to rifampicin and isoniazid (INH)), are important to guide preventive therapy for their household contacts (HHCs).

Methods: As part of a feasibility study done in preparation for an MDR-TB preventive therapy trial in HHCs, smear, Xpert MTB/RIF, Hain MTBDRplus, culture and DST results of index MDR-TB patients were obtained from routine TB programs. A sputum sample was collected at study entry and evaluated by the same tests.

Cost-effectiveness of scaling up short course preventive therapy for tuberculosis among children across 12 countries.

Background: While household contact investigation is widely recommended as a means to reduce the burden of tuberculosis (TB) among children, only 27% of eligible pediatric household contacts globally received preventive treatment in 2018. We assessed the cost-effectiveness of household contact investigation for TB treatment and short-course preventive therapy provision for children under 15 years old across 12 high TB burden countries.

Methods: We used decision analysis to compare the costs and estimated effectiveness of three intervention scenarios: (a) status quo (existing levels of coverage with isoniazid preventive therapy), (b) contact investigation with treatment of active TB but no additional preventive therapy, and (c) contact investigation with TB treatment and provision of short-course preventive therapy.

Safety, uptake, and use of a dapivirine vaginal ring for HIV-1 prevention in African women (HOPE): an open-label, extension study.

Background: Two phase 3 clinical trials showed that use of a monthly vaginal ring containing 25 mg dapivirine was well tolerated and reduced HIV-1 incidence in women by approximately 30% compared with placebo. We aimed to evaluate use and safety of the dapivirine vaginal ring (DVR) in open-label settings with high background rates of HIV-1 infection, an important step for future implementation.

Methods: We did a phase 3B open-label extension trial of the DVR (MTN-025/HIV Open-label Prevention Extension [HOPE]).

Biomarker-guided tuberculosis preventive therapy (CORTIS): a randomised controlled trial.

Background: Targeted preventive therapy for individuals at highest risk of incident tuberculosis might impact the epidemic by interrupting transmission. We tested performance of a transcriptomic signature of tuberculosis (RISK11) and efficacy of signature-guided preventive therapy in parallel, using a hybrid three-group study design.

Methods: Adult volunteers aged 18-59 years were recruited at five geographically distinct communities in South Africa.

Adaptation of WHO's generic tuberculosis patient cost instrument for a longitudinal study in Africa.

The WHO developed a generic 'TB patient cost survey' tool and a standardized approach to assess the direct and indirect costs of TB incurred by patients and their households, estimate the proportion of patients experiencing catastrophic costs, and measure the impact of interventions to reduce patient costs. While the generic tool is a facility-based cross-sectional survey, this standardized approach needs to be adapted for longitudinal studies. A longitudinal approach may overcome some of the limitations of a cross-sectional design and estimate the economic burden of TB more precisely.