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: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: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:In recent years children and adolescents have emerged as a priority for HIV prevention and care services. We conducted a systematic review to investigate the acceptability, yield and prevalence of HIV testing and counselling (HTC) strategies in children and adolescents (5 to 19 years) in sub-Saharan Africa.An electronic search was conducted in MEDLINE, EMBASE, Global Health and conference abstract databases. Studies reporting on HTC acceptability, yield and prevalence and published between January 2004 and September 2014 were included. Pooled proportions for these three outcomes were estimated using a random effects model. A quality assessment was conducted on included studies.A total of 16,380 potential citations were identified, of which 21 studies (23 entries) were included. Most studies were conducted in Kenya (n=5) and Uganda (n=5) and judged to provide moderate (n=15) to low quality (n=7) evidence, with data not disaggregated by age. Seven studies reported on provider-initiated testing and counselling (PITC), with the remainder reporting on family-centred (n=5), home-based (n=5), outreach (n=5) and school-linked HTC among primary schoolchildren (n=1). PITC among inpatients had the highest acceptability (86.3%; 95% confidence interval [CI]: 65.5 to 100%), yield (12.2%; 95% CI: 6.1 to 18.3%) and prevalence (15.4%; 95% CI: 5.0 to 25.7%). Family-centred HTC had lower acceptance compared to home-based HTC (51.7%; 95% CI: 10.4 to 92.9% vs. 84.9%; 95% CI: 74.4 to 95.4%) yet higher prevalence (8.4%; 95% CI: 3.4 to 13.5% vs. 3.0%; 95% CI: 1.0 to 4.9%). School-linked HTC showed poor acceptance and low prevalence.While PITC may have high test acceptability priority should be given to evaluating strategies beyond healthcare settings (e.g. home-based HTC among families) to identify individuals earlier in their disease progression. Data on linkage to care and cost-effectiveness of HTC strategies are needed to strengthen policies.
Project description:BACKGROUND:Tuberculosis (TB) is the deadliest infectious disease globally, with 10.4 million people infected and more than 1.8 million deaths in 2015. TB is a preventable, treatable, and curable disease, yet there are numerous barriers to initiating treatment. These barriers to treatment are exacerbated in low-resource settings and may be compounded by factors related to childhood. OBJECTIVE:Timely initiation of tuberculosis (TB) treatment is critical to reducing disease transmission and improving patient outcomes. The aim of this paper is to describe patient- and system-level barriers to TB treatment initiation specifically for children and youth in sub-Saharan Africa through systematic review of the literature. DESIGN:This review was conducted in October 2015 in accordance with preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines. Six databases were searched to identify studies where primary or secondary objectives were related to barriers to TB treatment initiation and which included children or youth 0-24 years of age. RESULTS:A total of 1490 manuscripts met screening criteria; 152 met criteria for full-text review and 47 for analysis. Patient-level barriers included limited knowledge, attitudes and beliefs regarding TB, and economic burdens. System-level barriers included centralization of services, health system delays, and geographical access to healthcare. Of the 47 studies included, 7 evaluated cost, 19 health-seeking behaviors, and 29 health system infrastructure. Only 4 studies primarily assessed pediatric cohorts yet all 47 studies were inclusive of children. CONCLUSIONS:Recognizing and removing barriers to treatment initiation for pediatric TB in sub-Saharan Africa are critical. Both patient- and system-level barriers must be better researched in order to improve patient outcomes.
Project description:Mortality rates are high in antiretroviral therapy (ART) programmes in sub-Saharan Africa, especially during the first few months of treatment. Tuberculosis (TB) has been identified as a major underlying cause. Under routine programme conditions, between 5 and 40% of adult patients enrolling in ART services have a baseline diagnosis of TB. There is also a high TB incidence during the first few months of ART (much of which is prevalent disease missed by baseline screening) and long-term rates remain several-folds higher than background. We identify three groups of patients entering ART programmes for which different interventions are required to reduce TB-related deaths. First, diagnostic screening is needed in patients who have undiagnosed active TB so that timely anti-TB treatment can be started. This may be greatly facilitated by new diagnostic assays such as the Xpert MTB/RIF assay. Second, patients with a diagnosis of active TB need optimized case management, which includes early initiation of ART (with timing now defined by randomized controlled trials), trimethoprim-sulphamethoxazole prophylaxis and treatment of comorbidity. Third, all remaining patients who are TB-free at enrolment have high ongoing risk of developing TB and require preventive interventions, including optimized immune recovery (with ART ideally started early in the course of HIV infection), isoniazid preventive therapy and infection control to reduce infection risk. Further specific measures are needed to address multidrug-resistant TB (MDR-TB). Finally, scale-up of all these interventions requires nationally and locally tailored models of care that are patient-centred and provide integrated healthcare delivery for TB, HIV and other comorbidities.
Project description:Mass spectrometry-based proteomics was carried out on Naso- and oropharyngeal swabs collected from infants and children presenting to hospital with both mild and severe respiratory illnesses as well as age-matched control children who were well and sampled from home.
Project description:BACKGROUND:Malaria is a leading cause of morbidity and mortality among HIV-infected pregnant women in sub-Saharan Africa: at least 1 million pregnancies among HIV-infected women are complicated by co-infection with malaria annually, leading to increased risk of premature delivery, severe anaemia, delivery of low birth weight infants, and maternal death. Current guidelines recommend either daily cotrimoxazole (CTX) or intermittent preventive treatment with sulfadoxine-pyrimethamine (IPTp-SP) for HIV-infected pregnant women to prevent malaria and its complications. The cost-effectiveness of CTX compared to IPTp-SP among HIV-infected pregnant women was assessed. METHODS:A microsimulation model of malaria and HIV among pregnant women in five malaria-endemic countries in sub-Saharan Africa was constructed. Four strategies were compared: (1) 2-dose IPTp-SP at current IPTp-SP coverage of the country ("2-IPT Low"); (2) 3-dose IPTp-SP at current coverage ("3-IPT Low"); (3) 3-dose IPTp-SP at the same coverage as antiretroviral therapy (ART) in the country ("3-IPT High"); and (4) daily CTX at ART coverage. Outcomes measured include maternal malaria, anaemia, low birth weight (LBW), and disability-adjusted life years (DALYs). Sensitivity analyses assessed the effect of adherence to CTX. RESULTS:Compared with the 2-IPT Low Strategy, women receiving CTX had 22.5% fewer LBW infants (95% CI 22.3-22.7), 13.5% fewer anaemia cases (95% CI 13.4-13.5), and 13.6% fewer maternal malaria cases (95% CI 13.6-13.7). In all simulated countries, CTX was the preferred strategy, with incremental cost-effectiveness ratios ranging from cost-saving to $3.9 per DALY averted from a societal perspective. CTX was less effective than the 3-IPT High Strategy when more than 18% of women stopped taking CTX during the pregnancy. CONCLUSION:In malarious regions of sub-Saharan Africa, daily CTX for HIV-infected pregnant women regardless of CD4 cell count is cost-effective compared with 3-dose IPTp-SP as long as more than 82% of women adhere to daily dosing.
Project description:BackgroundThe burden of Kaposi sarcoma (KS) in human immunodeficiency virus (HIV)-infected children and adolescents on combination antiretroviral therapy (cART) has not been compared globally.MethodsWe analyzed cohort data from the International Epidemiologic Databases to Evaluate AIDS and the Collaboration of Observational HIV Epidemiological Research in Europe. We included HIV-infected children aged <16 years at cART initiation from 1996 onward. We used Cox models to calculate hazard ratios (HRs), adjusted for region and origin, sex, cART start year, age, and HIV/AIDS stage at cART initiation.ResultsWe included 24 991 children from eastern Africa, southern Africa, Europe and Asia; 26 developed KS after starting cART. Incidence rates per 100 000 person-years (PYs) were 86 in eastern Africa (95% confidence interval [CI], 55-133), 11 in southern Africa (95% CI, 4-35), and 81 (95% CI, 26-252) in children of sub-Saharan African (SSA) origin in Europe. The KS incidence rates were 0/100 000 PYs in children of non-SSA origin in Europe (95% CI, 0-50) and in Asia (95% CI, 0-27). KS risk was lower in girls than in boys (adjusted HR [aHR], 0.3; 95% CI, .1-.9) and increased with age (10-15 vs 0-4 years; aHR, 3.4; 95% CI, 1.2-10.1) and advanced HIV/AIDS stage (CDC stage C vs A/B; aHR, 2.4; 95% CI, .8-7.3) at cART initiation.ConclusionsHIV-infected children from SSA but not those from other regions, have a high risk of developing KS after cART initiation. Early cART initiation in these children might reduce KS risk.
Project description:Noroviruses are a leading cause of acute sporadic gastroenteritis worldwide. In Sub-Saharan Africa, information regarding norovirus infections in children is scarce. A systematic review of studies performed between 1993 and June 2015 was conducted to establish the genotypic distribution and prevalence of norovirus infections in children (?17) in Sub-Saharan Africa. Analysis of data from 19 studies involving 8,399 samples from children with symptomatic and nonsymptomatic gastroenteritis revealed prevalence of 12.6% (range 4.6% to 32.4%). The prevalence of norovirus infections was higher in symptomatic children (14.2%) than asymptomatic children (9.2%). Genogroup II (GII) was the most prevalent genogroup accounting for 76.4% of all the reported norovirus infections. The rest of the infections were GI (21.7%) and GI/GII (1.9%). The most common genotypes were GII.4 (65.2%), GI.7 (33.3%), and GI.3 (21.3%). These statistics were calculated from studies carried out in 12 out of 48 Sub-Saharan African countries. Therefore, more studies involving several countries are required to determine fully the epidemiology of noroviruses and their contribution to childhood diarrhoea in Sub-Saharan Africa.