Project description:Sub-Saharan Africa represents 69% of the total number of individuals living with HIV infection worldwide and 72% of AIDS deaths globally. Pulmonary infection is a common and frequently fatal complication, though little is known regarding the lower airway microbiome composition of this population. Our objectives were to characterize the lower airway microbiome of Ugandan HIV-infected patients with pneumonia, to determine relationships with demographic, clinical, immunological, and microbiological variables and to compare the composition and predicted metagenome of these communities to a comparable cohort of patients in the US (San Francisco). Bronchoalveolar lavage samples from a cohort of 60 Ugandan HIV-infected patients with acute pneumonia were collected. Amplified 16S ribosomal RNA was profiled and aforementioned relationships examined. Ugandan airway microbiome composition and predicted metagenomic function were compared to US HIV-infected pneumonia patients. Among the most common bacterial pulmonary pathogens, Pseudomonas aeruginosa was most prevalent in the Ugandan cohort. Patients with a richer and more diverse airway microbiome exhibited lower bacterial burden, enrichment of members of the Lachnospiraceae and sulfur-reducing bacteria and reduced expression of TNF-alpha and matrix metalloproteinase-9. Compared to San Franciscan patients, Ugandan airway microbiome were significantly richer, and compositionally distinct with predicted metagenomes that encoded a multitude of distinct pathogenic pathways e.g secretion systems. Ugandan pneumonia-associated airway microbiome is compositionally and functionally distinct from those detected in comparable patients in developed countries, a feature which may contribute to adverse outcomes in this population. Please note that the data from the comparable cohort of patients in the USUS data was published as supplemental material of PMID: 22760045 but not submitted to GEO The 'patient_info.txt' contains 12 clinical, 7 immunological and 3 microbiological variables for each patient.

Project description:Sub-Saharan Africa represents 69% of the total number of individuals living with HIV infection worldwide and 72% of AIDS deaths globally. Pulmonary infection is a common and frequently fatal complication, though little is known regarding the lower airway microbiome composition of this population. Our objectives were to characterize the lower airway microbiome of Ugandan HIV-infected patients with pneumonia, to determine relationships with demographic, clinical, immunological, and microbiological variables and to compare the composition and predicted metagenome of these communities to a comparable cohort of patients in the US (San Francisco). Bronchoalveolar lavage samples from a cohort of 60 Ugandan HIV-infected patients with acute pneumonia were collected. Amplified 16S ribosomal RNA was profiled and aforementioned relationships examined. Ugandan airway microbiome composition and predicted metagenomic function were compared to US HIV-infected pneumonia patients. Among the most common bacterial pulmonary pathogens, Pseudomonas aeruginosa was most prevalent in the Ugandan cohort. Patients with a richer and more diverse airway microbiome exhibited lower bacterial burden, enrichment of members of the Lachnospiraceae and sulfur-reducing bacteria and reduced expression of TNF-alpha and matrix metalloproteinase-9. Compared to San Franciscan patients, Ugandan airway microbiome were significantly richer, and compositionally distinct with predicted metagenomes that encoded a multitude of distinct pathogenic pathways e.g secretion systems. Ugandan pneumonia-associated airway microbiome is compositionally and functionally distinct from those detected in comparable patients in developed countries, a feature which may contribute to adverse outcomes in this population. Please note that the data from the comparable cohort of patients in the USUS data was published as supplemental material of PMID: 22760045 but not submitted to GEO The 'patient_info.txt' contains 12 clinical, 7 immunological and 3 microbiological variables for each patient. The G2 PhyloChip microarray platform (commercially available from Second Genome, Inc.) was used to profile bacteria in lower airway samples from 60 subjects

Project description:BACKGROUND:We hypothesized that mass distribution of a broad-spectrum antibiotic agent to preschool children would reduce mortality in areas of sub-Saharan Africa that are currently far from meeting the Sustainable Development Goals of the United Nations. METHODS:In this cluster-randomized trial, we assigned communities in Malawi, Niger, and Tanzania to four twice-yearly mass distributions of either oral azithromycin (approximately 20 mg per kilogram of body weight) or placebo. Children 1 to 59 months of age were identified in twice-yearly censuses and were offered participation in the trial. Vital status was determined at subsequent censuses. The primary outcome was aggregate all-cause mortality; country-specific rates were assessed in prespecified subgroup analyses. RESULTS:A total of 1533 communities underwent randomization, 190,238 children were identified in the census at baseline, and 323,302 person-years were monitored. The mean (±SD) azithromycin and placebo coverage over the four twice-yearly distributions was 90.4±10.4%. The overall annual mortality rate was 14.6 deaths per 1000 person-years in communities that received azithromycin (9.1 in Malawi, 22.5 in Niger, and 5.4 in Tanzania) and 16.5 deaths per 1000 person-years in communities that received placebo (9.6 in Malawi, 27.5 in Niger, and 5.5 in Tanzania). Mortality was 13.5% lower overall (95% confidence interval [CI], 6.7 to 19.8) in communities that received azithromycin than in communities that received placebo (P<0.001); the rate was 5.7% lower in Malawi (95% CI, -9.7 to 18.9), 18.1% lower in Niger (95% CI, 10.0 to 25.5), and 3.4% lower in Tanzania (95% CI, -21.2 to 23.0). Children in the age group of 1 to 5 months had the greatest effect from azithromycin (24.9% lower mortality than that with placebo; 95% CI, 10.6 to 37.0). Serious adverse events occurring within a week after administration of the trial drug or placebo were uncommon, and the rate did not differ significantly between the groups. Evaluation of selection for antibiotic resistance is ongoing. CONCLUSIONS:Among postneonatal, preschool children in sub-Saharan Africa, childhood mortality was lower in communities randomly assigned to mass distribution of azithromycin than in those assigned to placebo, with the largest effect seen in Niger. Any implementation of a policy of mass distribution would need to strongly consider the potential effect of such a strategy on antibiotic resistance. (Funded by the Bill and Melinda Gates Foundation; MORDOR ClinicalTrials.gov number, NCT02047981 .).

Project description:Given the dual epidemics of HIV and tuberculosis in sub-Saharan Africa and evidence suggesting a disproportionate burden of these diseases among detainees in the region, we aimed to investigate the epidemiology of HIV and tuberculosis in prison populations, describe services available and challenges to service delivery, and identify priority areas for programmatically relevant research in sub-Saharan African prisons. To this end, we reviewed literature on HIV and tuberculosis in sub-Saharan African prisons published between 2011 and 2015, and identified data from only 24 of the 49 countries in the region. Where data were available, they were frequently of poor quality and rarely nationally representative. Prevalence of HIV infection ranged from 2·3% to 34·9%, and of tuberculosis from 0·4 to 16·3%; detainees nearly always had a higher prevalence of both diseases than did the non-incarcerated population in the same country. We identified barriers to prevention, treatment, and care services in published work and through five case studies of prison health policies and services in Zambia, South Africa, Malawi, Nigeria, and Benin. These barriers included severe financial and human-resource limitations and fragmented referral systems that prevent continuity of care when detainees cycle into and out of prison, or move between prisons. These challenges are set against the backdrop of weak health and criminal-justice systems, high rates of pre-trial detention, and overcrowding. A few examples of promising practices exist, including routine voluntary testing for HIV and screening for tuberculosis upon entry to South African and the largest Zambian prisons, reforms to pre-trial detention in South Africa, integration of mental health services into a health package in selected Malawian prisons, and task sharing to include detainees in care provision through peer-educator programmes in Rwanda, Zimbabwe, Zambia, and South Africa. However, substantial additional investments are required throughout sub-Saharan Africa to develop country-level policy guidance, build human-resource capacity, and strengthen prison health systems to ensure universal access to HIV and tuberculsosis prevention, treatment, and care of a standard that meets international goals and human rights obligations.

Project description:BackgroundIn 2015 around 15 million people living with HIV were receiving antiretroviral treatment (ART) in sub-Saharan Africa. Sustained provision of ART, though both prudent and necessary, creates substantial long-term fiscal obligations for countries affected by HIV/AIDS. As donor assistance for health remains constrained, novel financing mechanisms are needed to augment funding domestic sources. We explore how Innovative Financing has been used to co-finance domestic HIV/AIDS responses. Based on analysis of non-health sectors, we identify innovative financing instruments that could be used in the HIV response.MethodsWe undertook a systematic review to identify innovative financing instruments used for (1) domestic HIV/AIDS financing in sub-Saharan Africa (2) international health financing and (3) financing in non-health sectors. We analyzed peer-reviewed and grey literature published between 2002 and 2014. We examined the nature and volume of funds mobilized with innovative financing, then in consultation with leading experts, identified instruments that held potential for financing the HIV response.ResultsOur analysis revealed three innovative financing instruments in use: Zimbabwe's AIDS Trust Fund (a tax/levy-based instrument), Botswana's National HIV/AIDS Prevention Support (BNAPS) International Bank for Reconstruction and Development (IBRD) Buy-Down (a debt conversion instrument), and Côte d'Ivoire's Debt2Health Debt Swap Agreement (a debt conversion instrument). Zimbabwe's AIDS Trust Fund generated US$ 52.7 million between 2008 and 2011, Botswana's IBRD Buy-Down generated US$ 20 million, and Côte d'Ivoire's Debt2Health Debt Swap Agreement generated US$ 27 million, at least half of which was to be invested in HIV/AIDS programs. Four additional categories of innovative financing instruments met our criteria for future use: (1) remittances and diaspora bonds (2) social and development impact bonds (3) sovereign wealth funds (4) risk and credit guarantees.ConclusionA limited number of innovative financing instruments contributed a very modest share of funding toward domestic HIV/AIDS programs. Several innovative financing instruments successfully applied in other sectors could be used to augment domestic financing toward HIV/AIDS programmes.

Project description:BackgroundTuberculosis (TB) is known to disproportionately affect the most economically disadvantaged strata of society. Many studies have assessed the association between poverty and TB, but only a few have assessed the direct financial burden TB treatment and care can place on households. Patient costs can be particularly burdensome for TB-affected households in sub-Saharan Africa where poverty levels are high; these costs include the direct costs of medical and non-medical expenditures and the indirect costs of time utilizing healthcare or lost wages. In order to comprehensively assess the existing evidence on the costs that TB patients incur, we undertook a systematic review of the literature.MethodsPubMed, EMBASE, Science Citation Index, Social Science Citation Index, EconLit, Dissertation Abstracts, CINAHL, and Sociological Abstracts databases were searched, and 5,114 articles were identified. Articles were included in the final review if they contained a quantitative measure of direct or indirect patient costs for treatment or care for pulmonary TB in sub-Saharan Africa and were published from January 1, 1994 to Dec 31, 2010. Cost data were extracted from each study and converted to 2010 international dollars (I$).ResultsThirty articles met all of the inclusion criteria. Twenty-one studies reported both direct and indirect costs; eight studies reported only direct costs; and one study reported only indirect costs. Depending on type of costs, costs varied from less than I$1 to almost I$600 or from a small fraction of mean monthly income for average annual income earners to over 10 times average annual income for income earners in the income-poorest 20% of the population. Out of the eleven types of TB patient costs identified in this review, the costs for hospitalization, medication, transportation, and care in the private sector were largest.ConclusionTB patients and households in sub-Saharan Africa often incurred high costs when utilizing TB treatment and care, both within and outside of Directly Observed Therapy Short-course (DOTS) programs. For many households, TB treatment and care-related costs were considered to be catastrophic because the patient costs incurred commonly amounted to 10% or more of per capita incomes in the countries where the primary studies included in this review were conducted. Our results suggest that policies to decrease direct and indirect TB patient costs are urgently needed to prevent poverty due to TB treatment and care for those affected by the disease.

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Harnessing poverty alleviation to reduce the stigma of HIV in Sub-Saharan Africa.

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Harnessing poverty alleviation to reduce the stigma of HIV in Sub-Saharan Africa.

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