Drug-resistant TB (DR-TB) remains a significant challenge in TB treatment and control programmes worldwide. Advances in sequencing technology have significantly increased our understanding of the mechanisms of resistance to anti-TB drugs. This review provides an update on advances in our understanding of drug resistance mechanisms to new, existing drugs and repurposed agents. Recent advances in WGS technology hold promise as a tool for rapid diagnosis and clinical management of TB. Although the standard approach to WGS of Mycobacterium tuberculosis is slow due to the requirement for organism culture, recent attempts to sequence directly from clinical specimens have improved the potential to diagnose and detect resistance within days. The introduction of new databases may be helpful, such as the Relational Sequencing TB Data Platform, which contains a collection of whole-genome sequences highlighting key drug resistance mutations and clinical outcomes. Taken together, these advances will help devise better molecular diagnostics for more effective DR-TB management enabling personalized treatment, and will facilitate the development of new drugs aimed at improving outcomes of patients with this disease.

Passive immunisation with broadly neutralizing antibodies (bnAbs) is a promising approach to reduce the 1.7 million annual HIV infections globally. Early studies on bnAbs showed safety in humans, but short elimination half-lives and low potency and breadth. Since 2010, several new highly potent bnAbs have been assessed in clinical trials alone or in combination for HIV prevention. Published data indicate that these bnAbs are safe and have a half-life ranging from 15 to 71 days. Only intravenous VRC01 has advanced to an efficacy trial, with results expected in late 2020. If bnAbs are shown to be effective in preventing HIV infection, they could fast-track vaccine development as correlates of protection, and contribute as passive immunisation to achieving the goal of epidemic control. The purpose of this review is to describe the current status and provide a synopsis of the available data on bnAbs in clinical trials for HIV prevention.

BackgroundImproved research ability is a core competency to achieve in health professionals. The Selectives is a three-year, longitudinal, community-based programme within the undergraduate curriculum which aims to develop research capacity in all medical students during the prescribed curriculum. In relation to the programme, the authors describe the types of studies conducted by students, conditions that facilitated their learning, how the experience improved students’ knowledge of research and public health and their development of reflective learning practices.MethodsA cohort of 212 students completed the Selectives Programme in 2014, and 69 (32 %) completed an anonymous online evaluation thereafter. Data collected include students’ perceptions of the research component of Selectives; its impact on their knowledge of research and a documentary analysis of their research protocols and posters. Ethical approval for the ongoing evaluation of the Selectives was sought and obtained from the institutional Biomedical Research Ethics Committee.ResultsDuring Selectives, 75 groups of 2–4 students conducted research studies of primary health care problems in community settings. Each group is assessed on their presentation of research findings as a scientific poster. The Selectives facilitated learning for the majority of the cohort. Students reported positive learning experiences about the research process, including ethics; protocol writing; data processing; dissemination of findings and results; and their use in informing a health promotion intervention. Students reported having gained a better understanding of their strengths and weaknesses through reflective learning from this academic activity. The Selectives is scheduled adjacent to the students’ mid-year vacation. This scheduling together with the placement in the students’ home community minimizes travel and accommodation costs associated with working outside the academic teaching platform and therefore makes it a cost-effective model in a low resource context.ConclusionsThe Selectives has proven beneficial to develop a range of generic and practical research competencies for a full cohort of students enrolled in the undergraduate medical curriculum. The Selectives research process is integrated with learning about population health and the social determinants of health in a primary health care setting.Electronic supplementary materialThe online version of this article (doi:10.1186/s12909-016-0567-7) contains supplementary material, which is available to authorized users.

SettingThe dual epidemics of HIV-TB including MDR-TB are major contributors to high morbidity and mortality rates in South Africa. Rifampicin (RIF) resistance is regarded as a proxy for MDR-TB. Currently available molecular assays have the advantage of rapidly detecting resistant strains of MTB, but the GeneXpert does not detect isoniazid (INH) resistance and the GenoTypeMTBDRplus(LPA) assay may underestimate resistance to INH. Increasing proportions of rifampicin mono-resistance resistance (RMR) have recently been reported from South Africa and other countries.ObjectiveThis laboratory based study was conducted at NHLS TB Laboratory, Durban, which is the reference laboratory for culture and susceptibility testing in KwaZulu-Natal. We retrospectively determined, for the period 2007 to 2009, the proportion of RMR amongst Mycobacterium tuberculosis (MTB) isolates, that were tested for both RIF and INH, using the gold standard of culture based phenotypic drug susceptibility testing (DST). Gender and age were also analysed to identify possible risk factors for RMR.DesignMTB culture positive sputum samples from 16,748 patients were analysed for susceptibility to RIF and INH during the period 2007 to 2009. RMR was defined as MTB resistant to RIF and susceptible to INH. For the purposes of this study, only the first specimen from each patient was included in the analysis.ResultsRMR was observed throughout the study period. The proportion of RMR varied from a low of 7.3% to a high of 10.0% [overall 8.8%]. Overall, males had a 42% increased odds of being RMR as compared to females. In comparison to the 50 plus age group, RMR was 37% more likely to occur in the 25–29 year age category.ConclusionWe report higher proportions of RMR ranging from 7.3% to 10% [overall 8.8%] than previously reported in the literature. To avoid misclassification of RMR, detected by the GeneXpert, as MDR-TB, culture based phenotypic DST must be performed on a second specimen, as recommended by the SA NDOH TB guidelines as well as WHO. We suggest that two sputum samples should be obtained at the first visit. The second sputum sample should be stored at 4°C. The latter sample is then readily available for performing additional DST (phenotypic or genotypic) for 2nd lines drugs, resulting in a decreased waiting period for DST results to become available.