'Bring us the female condom': HIV intervention, gender and political empowerment in two South African communities

The quotation which heads this paper encapsulates two important issues in AIDS research in South Africa: the one is substantive, the other methodological. The link between them is the rapid spread of HIV/AIDS in the country and the indication not only that women are more at risk of infection than men, but that, as in many other parts of the world, much of their vulnerability is gender based. ‘Bring us the female condom’ sums up the response of one particular group of black South African women to AIDS education. Their demand was a reflection of their relative domestic and gender empowerment - and also a high degree of political mobilization. However, their position is not necessarily shared by other black women. But the call for the female condom went further: it was a challenge to rethink our position as researchers and particularly to face the implications of commitment to a participatory model of community based intervention research

Teaching and assessing consultation skills: an evaluation of a South African workshop on using the Leicester Assessment Package

BackgroundThe consultation is at the very centre of clinical practice. It is in the meeting between doctor and patient that the story is told (and in good practice properly heeded) and decisions are made about the cause and treatment of the patient's problem. Following one year of supervised internship, South African doctors are required to do a year of community service and these doctors mostly work in understaffed peripheral hospitals. A substantial component of this work is unsupervised consultations with patients suffering from new or complex continuing diseases. On graduation, these doctors therefore require a high level of consultation competence. They must be able to make accurate diagnoses and manage patients' problems reliably and efficiently.The Leicester Assessment Package (LAP) was originally developed to assess the consultation competence of general practitioners in the UK. It was subsequently adapted for use in undergraduate teaching. In 2002, the LAP was presented at a medical education conference in South Africa. As a result, the Department of Family Medicine at Pretoria University began using the LAP in the teaching and formative assessment of the consultation skills of senior students in outpatient clinics. In 2003, the University of the Witwatersrand introduced a four-year graduate entry medical curriculum. The Centre for Health Care Education was interested in assessing whether the LAP would be suitable for the summative assessment of the consultation performance of students during their third and four years of the new curriculum.A workshop course was organised to train senior clinicians from the Universities of Pretoria and the Witwatersrand in the use of the LAP as a means of teaching and assessing the consultation performance of South African medical students.MethodTwenty-two experienced South African medical educators participated in a three-day workshop. Their attitudes to the LAP and the forms of teaching that its use promotes were analysed by responses to pre- and post-workshop questionnaires with Likert-scale and free-text questions.ResultsThe participants were positive about the LAP at the end of the workshop. They all believed that it was a useful instrument, and a majority would apply this method in their own departments. There were continuing reservations about the feasibility of the method and some respondents felt it would require some adaptation, particularly to the criteria for awarding grades.ConclusionsThe workshop participants learnt to use an instrument developed in the United Kingdom that encourages an analytical approach to the assessment and teaching of consultation skills. They believed it would be useful in the contexts in which they worked.For full text, click here:SA Fam Pract 2006;48(3):14-14

The 'causes' of teenage pregnancy: review of South African research - Part 2

This article forms the second of a two-part series in which South African research on teenage pregnancy is reviewed. Part 1 of the series dealt with the consequences of teenage pregnancy; this paper reviews the 'causes' thereof. International literature is incorporated in the discussion by way of comparison. Contributory factors which have been investigated by South African researchers include: reproductive ignorance; the earlier occurrence of menarche; risktaking behaviour; psychological problems; peer influence; co-ercive sexual relations; dysfunctional family patterns; poor health services; socio-economic status; the breakdown of cultural traditions; and the cultural value placed on children. Preston-Whyte and colleagues present a revisionist argument, stating that early pregnancy may represent a rational life choice for certain adolescent women. The article is concluded with comments on methodological problems encountered in the South African research, and a discussion on the implications in terms of policy formulation

The effects of high HIV prevalence on orphanhood and living arrangements of children in Malawi, Tanzania, and South Africa

Using longitudinal data from three demographic surveillance systems (DSS) and a retrospective cohort study, we estimate levels and trends in the prevalence and incidence of orphanhood in South Africa, Tanzania, and Malawi in the period 1988–2004. The prevalence of maternal, paternal, and double orphans rose in all three populations. In South Africa—where the HIV epidemic started later, has been very severe, and has not yet stabilized—the incidence of orphanhood among children is double that of the other populations. The living arrangements of children vary considerably between the populations, particularly in relation to fathers. Patterns of marriage, migration, and adult mortality influence the living and care arrangements of orphans and non-orphans. DSS data provide new insights into the impact of adult mortality on children, challenging several widely held assumptions. For example, we find no evidence that the prevalence of child-headed households is significant or has increased in the three study areas

Impaired Mitochondrial Microbicidal Responses in Chronic Obstructive Pulmonary Disease Macrophages

RATIONALE: Chronic obstructive pulmonary disease (COPD) is characterized by impaired clearance of pulmonary bacteria. OBJECTIVES: The effect of COPD on alveolar macrophage (AM) microbicidal responses was investigated. METHODS: Alveolar macrophages (AMs) were obtained from bronchoalveolar lavage from healthy donors or COPD patients and challenged with opsonized serotype 14 Streptococcus pneumoniae. Cells were assessed for apoptosis, bactericidal activity and mitochondrial reactive oxygen species (mROS) production. A transgenic mouse line, in which the CD68 promoter ensures macrophage specific expression of human Mcl-1 (CD68.hMcl-1), was used to model the molecular aspects of COPD. MEASUREMENTS AND MAIN RESULTS: COPD AM had elevated levels of Mcl-1, an anti-apoptotic Bcl-2 family member, with selective reduction of delayed intracellular bacterial killing. CD68.hMcl-1 AM phenocopied the microbicidal defect since transgenic mice demonstrated impaired clearance of pulmonary bacteria and increased neutrophilic inflammation. Murine bone marrow-derived macrophages (BMDM) and human monocyte-derived macrophages (MDM) generated mitochondrial reactive oxygen species (mROS) in response to pneumococci, which co-localized with bacteria and phagolysosomes to enhance bacterial killing. The Mcl-1 transgene increased oxygen consumption rates and mROS expression in mock-infected BMDM but reduced caspase-dependent mROS production after pneumococcal challenge. COPD AM also increased basal mROS expression, but failed to increase production after pneumococcal challenge, in keeping with reduced intracellular bacterial killing. The defect in COPD AM intracellular killing was associated with a reduced ratio of mROS /superoxide dismutase 2. CONCLUSIONS: Upregulation of Mcl-1 and chronic adaption to oxidative stress alters mitochondrial metabolism and microbicidal function, reducing the delayed phase of intracellular bacterial clearance in COPD

Obligation to family during times of transition: care, support and the response to HIV and AIDS in rural South Africa

In rural South Africa, high HIV prevalence has the potential to affect the care and support that kin are able to provide to those living with HIV. Despite this, families seem to be largely resilient and a key source of care and support to family affected by HIV. In this article, we explore the motivations for the provision of care and support by kin. We use the results of a small-scale in-depth qualitative study conducted in 10 households over 6 months in rural KwaZulu-Natal, South Africa, to show that family obligation and conditional reciprocity operate in varying degrees and build social capital. We highlight the complexity of kin relations where obligation is not guaranteed or is limited, requiring the consideration of policy measures that provide means of social support that are not reliant on the family

The isimodeni style: traditional beadwork, Zulu trinket or, South African sartorial tradition on Durban’s Golden Mile?

Beadwork is a well-documented aspect of the socio-political culture of isiZulu-speaking groupings in Southern Africa. Whilst scholarship on beadwork deals largely with the denotative and connotative value it offers wearers, this article’s contribution relates both to its commodification and apolitical value by confronting a general assumption that a beadwork style known as isimodeni (modern beadwork), produced as a trinket for tourists along Durban’s racially stratified Golden Mile since the 1960s, is an authentic representation of a Zulu material culture. The paper probes how traditional beadwork and rickshaw rides (with both highly decorated carts and pullers) were earmarked by tourism officials of the time as commodities that could serve a demand for colourful exoticism and accessible “Zulu” culture. Methodologically, the article draws on the visual analysis of beaded artefacts and photographs, in addition to ethnographic data derived from unstructured interviews with beadworkers on the Durban beachfront, to examine how a beadwork tradition transformed into a “Zulu” tourism commodity, and then transmuted into a nationalised form of ethnic identity and sartorial tradition

Hypoxia determines survival outcomes of bacterial infection through HIF-1alpha dependent re-programming of leukocyte metabolism.

Hypoxia and bacterial infection frequently co-exist, in both acute and chronic clinical settings, and typically result in adverse clinical outcomes. To ameliorate this morbidity, we investigated the interaction between hypoxia and the host response. In the context of acute hypoxia, both S. aureus and S. pneumoniae infections rapidly induced progressive neutrophil mediated morbidity and mortality, with associated hypothermia and cardiovascular compromise. Preconditioning animals through longer exposures to hypoxia, prior to infection, prevented these pathophysiological responses and profoundly dampened the transcriptome of circulating leukocytes. Specifically, perturbation of HIF pathway and glycolysis genes by hypoxic preconditioning was associated with reduced leukocyte glucose utilisation, resulting in systemic rescue from a global negative energy state and myocardial protection. Thus we demonstrate that hypoxia preconditions the innate immune response and determines survival outcomes following bacterial infection through suppression of HIF-1α and neutrophil metabolism. The therapeutic implications of this work are that in the context of systemic or tissue hypoxia therapies that target the host response could improve infection associated morbidity and mortality.This work was supported by the Medical Research Council (MRC) Clinical Training Fellowship (awards G0802255 and MR/K023845/1 to A.A.R.T. and R.S.D., respectively), a National Institute for Health Research (NIHR) Clinical Lectureship and an Academy of Medical Sciences starter grant (to A.A.R.T.), a Wellcome Trust postdoctoral clinical fellowship (110086 to A.M.), a Wellcome Trust Senior Clinical Fellowship award (098516 to S.R.W.), a Wellcome Trust Senior Clinical Fellowship award (076945 to D.H.D.), a British Lung Foundation Fellowship (F05/7 to H.M.M.), a Wellcome Trust New Investigator Award (WT100981MA to N.M.M.), and a British Heart Foundation Senior Basic Science Research Fellowship (FS/13/48/30453 to A.L.). E.R.C. and A.S.C. are supported by the NIHR Cambridge Biomedical Research Centre. R.H.S. is supported by the MRC. R.R.M. is supported by MRC (MC_PC_U127574433), Biotechnology and Biological Sciences Research Council, and European Chemical Industry Council grants. M.M. is supported by the European Research Council (OxyMO). The MRC/University of Edinburgh Centre for Inflammation Research is supported by an MRC Centre Grant

Whole-genome sequencing reveals host factors underlying critical COVID-19

Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2–4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease

Genetic mechanisms of critical illness in COVID-19.

Host-mediated lung inflammation is present1, and drives mortality2, in the critical illness caused by coronavirus disease 2019 (COVID-19). Host genetic variants associated with critical illness may identify mechanistic targets for therapeutic development3. Here we report the results of the GenOMICC (Genetics Of Mortality In Critical Care) genome-wide association study in 2,244 critically ill patients with COVID-19 from 208 UK intensive care units. We have identified and replicated the following new genome-wide significant associations: on chromosome 12q24.13 (rs10735079, P = 1.65 × 10-8) in a gene cluster that encodes antiviral restriction enzyme activators (OAS1, OAS2 and OAS3); on chromosome 19p13.2 (rs74956615, P = 2.3 × 10-8) near the gene that encodes tyrosine kinase 2 (TYK2); on chromosome 19p13.3 (rs2109069, P = 3.98 ×  10-12) within the gene that encodes dipeptidyl peptidase 9 (DPP9); and on chromosome 21q22.1 (rs2236757, P = 4.99 × 10-8) in the interferon receptor gene IFNAR2. We identified potential targets for repurposing of licensed medications: using Mendelian randomization, we found evidence that low expression of IFNAR2, or high expression of TYK2, are associated with life-threatening disease; and transcriptome-wide association in lung tissue revealed that high expression of the monocyte-macrophage chemotactic receptor CCR2 is associated with severe COVID-19. Our results identify robust genetic signals relating to key host antiviral defence mechanisms and mediators of inflammatory organ damage in COVID-19. Both mechanisms may be amenable to targeted treatment with existing drugs. However, large-scale randomized clinical trials will be essential before any change to clinical practice