Cascade Immune Mechanisms of Protection against Mycobacterium tuberculosis (IMPAc-TB): study protocol for the Household Contact Study in the Western Cape, South Africa.

BACKGROUND: Natural immunity against Mycobacterium tuberculosis exists, and > 90% of those infected remain disease-free. Innate and adaptive immune responses required to mediate such protection against tuberculosis (TB) are, however, poorly understood. METHODS: This is an analytical study exploring protective and non-protective pathways of immunity against Mycobacterium tuberculosis. Adults without HIV infection are recruited at community healthcare clinics in high TB incidence areas of the Western Cape Province, South Africa. Data regarding participants' medical, social and medication usage will be collected, and clinical examinations and point-of-care tests documented. Reference tests for TB (chest radiographs and sputum tests for GeneXpert MTB/RIF Ultra®, Auramine smear and liquid cultures) and investigations to classify infection states [interferon-gamma release assay (IGRA) and SARS-CoV-2 polymerase chain reaction (PCR) nasopharyngeal swab and IgG], are done on all participants who meet the inclusion criteria. 18F-Fluorodeoxyglucose positron emission tomography combined with computerized tomography will be done on all close contacts (contacts) and healthy control (controls) participants. Participants are divided into 12 study groups representing a spectrum of TB clinical phenotypes and prior SARS-CoV-2 infection based on their TB status, exposure history, results of IGRA test at baseline and 3 months, SARS-CoV-2 serology, and PCR results, and for contacts and controls, PET-CT imaging findings indicative of sub-clinical TB lesions. Samples for experimental assays include whole blood for isolation of peripheral blood mononuclear cells and blood in PAXgene® tubes for RNA isolation. All SARS-CoV-2 PCR negative study participants undergo bronchoscopy for collecting bronchoalveolar lavage samples. DISCUSSION: The paired blood and BAL samples will be used for comprehensive analyses of the tissue-specific and systemic immunity that will include e.g., cytometry by time-of-flight analyses, RNA-sequencing, multiplex immunoassays, epigenetic analysis, and mechanistic studies of control of infection by Mycobacterium tuberculosis. Results will be integrated with those from mice and non-human primate studies to provide a comprehensive analysis of protective pathways in natural and vaccine-induced immunity against Mycobacterium tuberculosis.

The invisibility of men in South African violence prevention policy: national prioritization, male vulnerability, and framing prevention.

BACKGROUND: South Africa has a significant violence problem. The exposure of girls and women to interpersonal violence is widespread, and the victimization of men, especially to severe and homicidal forms of aggression, is of considerable concern, with male homicide eight times the global rate. In the last two decades, there have been a plethora of South African policies to promote safety. However, indications suggest that the policy response to violence is not coherently formulated, comprehensive, or evenly implemented. OBJECTIVE: This study examines selected South African national legislative instruments in terms of their framing and definition of violence and its typology, vulnerable populations, and prevention. DESIGN: This study comprises a directed content analysis of selected legislative documents from South African ministries mandated to prevent violence and its consequences or tasked with the prevention of key contributors to violence. Documents were selected using an electronic keyword search method and analyzed independently by two researchers. RESULTS: The legislative documents recognized the high levels of violence, confirmed the prioritization of selected vulnerable groups, especially women, children, disabled persons, and rural populations, and above all drew on criminological perspectives to emphasize tertiary prevention interventions. There is a policy focus on the protection and support of victims and the prosecution of perpetrators, but near absent recognition of men as victims. CONCLUSIONS: There is a need to broaden the policy framework from primarily criminological and prosecutorial perspectives to include public health contributions. It is likewise important to enlarge the conceptions of vulnerability to include men alongside other vulnerable groups. These measures are important for shaping and resourcing prevention decisions and strengthening primary prevention approaches to violence.