Vaginal microbicides for preventing mother-to-child transmission of HIV infection - no evidence of an effect or evidence of no effect?

Background. Vaginal disinfection is a simple, potentially effective strategy for reducing mother-to-child transmission (MTCT) of HIV that can be implemented in combination with antiretroviraltherapy or even in the absence of prenatal HfV testing. We systematically reviewed currently available randomised controlled trials to estimate the benefits and risks of this intervention.Methods. We conducted an exhaustive search for published and. unpublished trials assessing the effect of vaginal microbicides on MTCT of HIV, extracted data in triplicate, assesed statistical heterogeneity between trial results, and conducted meta-analysis using Mantel-Haenszel's method.Findings. Five potentially eligible studies were iclentified, two of which met eligibility criteria. Pooling the data shows that the effect of vaginal disinfection on the risk of MTCT of HIV relative risk (RR) 0.94, 95% confidence interval (CI) 0.71 1.25) and neonatal death (RR 1.36, 95% CI 0.32- 5.79) is uncertain. The combined data (two trials with 708 participants) had less than 80% power to detect a 30% reduction in the risk of MTCT of HIV from a baseline risk of 30%, and are compatible with a widerange of effects; from a 29% reduction to a 25% increase in risk. One trial with 108 participants, showed no evidence that adverse effects increased inmothers (RR L02, 95% CI 0.87- 1.20) and found that adverse effects decreased in neonates (RR 0.45, 95% CI 0.32 - 0.64).Interpretation. At present there is insufficient and inconclusive evidence on the effect of vaginal microbicides on the risk of MTCT of HIV. This review identifies the need and provides the impetus for an adequately powered randomised controlled trial to assess the effect(s) of this inexpensive intervention

The impact of mass media interventions on tuberculosis awareness, health-seeking behaviour and health service utilisation : a systematic review protocol

Introduction: Tuberculosis (TB) is a serious public health problem in many parts of the world. Strategies to curb the spread of TB must match the multifaceted nature of the epidemic. The use of mass media is one of the important strategies in communicating behavioural change in relation to TB prevention and the treatment. However, the benefits of this intervention are unclear. We, therefore, plan to conduct a systematic review on the effects of mass media interventions on TB awareness, health-seeking behaviour and health service utilisation. Methods and analysis: We will preferably include randomised controlled trials (RCTs) in this systematic review. However, non-randomised studies will be included if there is an inadequate number of RCTs. We will perform electronic searches in PubMed, Scopus and other databases, along with manual searches. Articles written (or translated) in English and French and published between 1 January 1980 and 31 October 2013 will be eligible for inclusion in this review. The primary outcomes will be TB knowledge, attitudes and awareness, healthcare-seeking behaviour and service utilisation. The secondary outcomes will include stigma and discrimination against people with TB and the costs of the interventions. We will investigate clinical and statistical heterogeneity and pool studies judged to be clinically and statistically homogeneous. Relative risks will be calculated for dichotomous outcomes and mean differences for continuous outcomes, both with their corresponding 95% CIs. Ethics and dissemination: The systematic review will use data that is not linked to individuals. The review findings may have implications for clinical practice and future research, and will be disseminated electronically and in print through peer-reviewed publications

Co-formulated abacavir-lamivudine-zidovudine for initial treatment of HIV infection and AIDS.

The primary objective of this review was to evaluate the antiviral efficacy of co-formulated abacavir-lamivudine-zidovudine for initial treatment of HIV infection. The secondary objectives were to evaluate the safety and tolerability of the triple drug combination. We identified 15 potentially eligible studies, four of which met our inclusion criteria. Our findings indicate that co-formulated abacavirlamivudine-zidovudine remains a viable option for initiating antiretroviral therapy, especially in HIV-infected patients with pre-existing hyperlipidaemia and those who do not tolerate ritonavir

Advances in childhood immunisation in South Africa: where to now? Programme managers’ views and evidence from systematic reviews.

Background: The Expanded Programme on Immunisation (EPI) is one of the most powerful and cost-effective public health programmes to improve child survival. We assessed challenges and enablers for the programme in South Africa, as we approach the 2015 deadline for the Millennium Development Goals. Methods: Between September 2009 and September 2010 we requested national and provincial EPI managers in South Africa to identify key challenges facing EPI, and to propose appropriate solutions. We collated their responses and searched for systematic reviews on the effectiveness of the proposed solutions; in the Health Systems Evidence, Cochrane Library, and PubMed electronic databases. We screened the search outputs, selected systematic reviews, extracted data, and assessed the quality of included reviews (using AMSTAR) and the quality of the evidence (using GRADE) in duplicate; resolving disagreements by discussion and consensus. Results: Challenges identified by EPI managers were linked to healthcare workers (insufficient knowledge of vaccines and immunisation), the public (anti-immunisation rumours and reluctance from parents), and health system (insufficient financial and human resources). Strategies proposed by managers to overcome the challenges include training, supervision, and audit and feedback; strengthening advocacy and social mobilisation; and sustainable EPI funding schemes, respectively. The findings from reliable systematic reviews indicate that interactive educational meetings, audit and feedback, and supportive supervision improve healthcare worker performance. Structured and interactive communication tools probably increase parents’ understanding of immunisation; and reminders and recall, use of community health workers, conditional cash transfers, and mass media interventions probably increase immunisation coverage. Finally, a national social health insurance scheme is a potential EPI financing mechanism; however, given the absence of high-quality evidence of effects, its implementation should be pilot-tested and the impacts and costs rigorously monitored. Conclusion: In line with the Millennium Development Goals, we have to ensure that our children’s right to health, development and survival is respected, protected and promoted. EPI is central to this vision. We found numerous promising strategies for improving EPI performance in South Africa. However, their implementation would need to be tailored to local circumstances and accompanied by high-quality monitoring and evaluation. The strength of our approach comes from having a strong framework for interventions before looking for systematic reviews. Without a framework, we would have been driven by what reviews have been done and what is easily researchable; rather than the values and preferences of key immunisation stakeholders

Early antituberculosis drug exposure in hospitalized patients with human immunodeficiency virus-associated tuberculosis

Aims: Patients hospitalized at the time of human immunodeficiency virus-associated tuberculosis (HIV-TB) diagnosis have high early mortality. We hypothesized that compared to outpatients, there would be lower anti-TB drug exposure in hospitalized HIV-TB patients, and amongst hospitalized patients exposure would be lower in patients who die or have high lactate (a sepsis marker). Methods: We performed pharmacokinetic sampling in hospitalized HIV-TB patients and outpatients. Plasma rifampicin, isoniazid and pyrazinamide concentrations were measured in samples collected predose and at 1, 2.5, 4, 6 and 8 hours on the third day of standard anti-TB therapy. Twelve-week mortality was ascertained for inpatients. Noncompartmental pharmacokinetic analysis was performed. Results: Pharmacokinetic data were collected in 59 hospitalized HIV-TB patients and 48 outpatients. Inpatient 12-week mortality was 11/59 (19%). Rifampicin, isoniazid and pyrazinamide exposure was similar between hospitalized and outpatients (maximum concentration [Cmax]: 7.4 vs 8.3 μg mL–1, P =.223; 3.6 vs 3.5 μg mL–1, P =.569; 50.1 vs 46.8 μg mL–1, P =.081; area under the concentration–time curve from 0 to 8 hours: 41.0 vs 43.8 mg h L–1, P = 0.290; 13.5 vs 12.4 mg h L–1, P =.630; 316.5 vs 292.2 mg h L–1, P =.164, respectively) and not lower in inpatients who died. Rifampicin and isoniazid Cmax were below recommended ranges in 61% and 39% of inpatients and 44% and 35% of outpatients. Rifampicin exposure was higher in patients with lactate >2.2 mmol L–1. Conclusion: Mortality in hospitalized HIV-TB patients was high. Early anti-TB drug exposure was similar to outpatients and not lower in inpatients who died. Rifampicin and isoniazid Cmax were suboptimal in 61% and 39% of inpatients and rifampicin exposure was higher in patients with high lactate. Treatment strategies need to be optimized to improve survival

Modulation of female genital tract-derived dendritic cell migration and activation in response to inflammatory cytokines and toll-like receptor agonists.

CAPRISA, 2016.Abstract available in pdf

The global inequity of COVID-19 diagnostics : challenges and opportunities

Diagnostics for COVID-19 have advanced at an unprecedented pace over the last two years. Testing is a critical pillar of pandemic control, and is required for epidemiological tracking, treatment, and surveillance. Despite high quality SARS-CoV-2 viral diagnostic capability, there are vast global inequities in access. The Virology, Immunology, and Diagnostics Working Group(WG) of the COVID-19 Clinical Research Coalition (CRC) brings together experts in immunology, infectious diseases, and microbiology to advocate for equity-based COVID-19 research, prioritising solutions driven by communities in low-income and lower middle-income countries (LMICs).1 This commentary shares the unique perspective of the WG on the asymmetry in COVID-19 diagnostic access between low-income and high-income settings, the barriers to these disparities, and highlights opportunities to remedy these inequities.PostprintPeer reviewe

Genetic variation in TLR genes in Ugandan and South African populations and comparison with HapMap data

Genetic epidemiological studies of complex diseases often rely on data from the International HapMap Consortium for identification of single nucleotide polymorphisms (SNPs), particularly those that tag haplotypes. However, little is known about the relevance of the African populations used to collect HapMap data for study populations conducted elsewhere in Africa. Toll-like receptor (TLR) genes play a key role in susceptibility to various infectious diseases, including tuberculosis. We conducted full-exon sequencing in samples obtained from Uganda (n = 48) and South Africa (n = 48), in four genes in the TLR pathway: TLR2, TLR4, TLR6, and TIRAP. We identified one novel TIRAP SNP (with minor allele frequency [MAF] 3.2%) and a novel TLR6 SNP (MAF 8%) in the Ugandan population, and a TLR6 SNP that is unique to the South African population (MAF 14%). These SNPs were also not present in the 1000 Genomes data. Genotype and haplotype frequencies and linkage disequilibrium patterns in Uganda and South Africa were similar to African populations in the HapMap datasets. Multidimensional scaling analysis of polymorphisms in all four genes suggested broad overlap of all of the examined African populations. Based on these data, we propose that there is enough similarity among African populations represented in the HapMap database to justify initial SNP selection for genetic epidemiological studies in Uganda and South Africa. We also discovered three novel polymorphisms that appear to be population-specific and would only be detected by sequencing efforts

Clinical characteristics and initial management of patients with tuberculous pericarditis in the HIV era: the Investigation of the Management of Pericarditis in Africa (IMPI Africa) registry

BACKGROUND: The incidence of tuberculous pericarditis has increased in Africa as a result of the human immunodeficiency virus (HIV) epidemic. However, the effect of HIV co-infection on clinical features and prognosis in tuberculous pericarditis is not well characterised. We have used baseline data of the Investigation of the Management of Pericarditis in Africa (IMPI Africa) registry to assess the impact of HIV co-infection on clinical presentation, diagnostic evaluation, and treatment of patients with suspected tuberculous pericarditis in sub-Saharan Africa. METHODS: Consecutive adult patients in 15 hospitals in three countries in sub-Saharan Africa were recruited on commencement of treatment for tuberculous pericarditis, following informed consent. We recorded demographic, clinical, diagnostic and therapeutic information at baseline, and have used the chi-square test and analysis of variance to assess probabilities of significant differences (in these variables) between groups defined by HIV status. RESULTS: A total of 185 patients were enrolled from 01 March 2004 to 31 October 2004, 147 (79.5%) of whom had effusive, 28 (15.1%) effusive-constrictive, and 10 (5.4%) constrictive or acute dry pericarditis. Seventy-four (40%) had clinical features of HIV infection. Patients with clinical HIV disease were more likely to present with dyspnoea (odds ratio [OR] 3.2, 95% confidence interval [CI] 1.4 to 7.4, P = 0.005) and electrocardiographic features of myopericarditis (OR 2.8, 95% CI 1.1 to 6.9, P = 0.03). In addition to electrocardiographic features of myopericarditis, a positive HIV serological status was associated with greater cardiomegaly (OR 3.89, 95% CI 1.34 to 11.32, P = 0.01) and haemodynamic instability (OR 9.68, 95% CI 2.09 to 44.80, P = 0.0008). However, stage of pericardial disease at diagnosis and use of diagnostic tests were not related to clinical HIV status. Similar results were obtained for serological HIV status. Most patients were treated on clinical grounds, with microbiological evidence of tuberculosis obtained in only 13 (7.0%) patients. Adjunctive corticosteroids were used in 109 (58.9%) patients, with patients having clinical HIV disease less likely to be put on them (OR 0.37, 95% CI 0.20 to 0.68). Seven patients were on antiretroviral drugs. CONCLUSION: Patients with suspected tuberculous pericarditis and HIV infection in Africa have greater evidence of myopericarditis, dyspnoea, and haemodynamic instability. These findings, if confirmed in other studies, may suggest more intensive management of the cardiac disease is warranted in patients with HIV-associated pericardial disease