Project description:The African continent continues to bear the greatest burden of malaria and the greatest diversity of parasites, mosquito vectors, and human victims. The evolutionary plasticity of malaria parasites and their vectors is a major obstacle to eliminating the disease. Of current concern is the recently reported emergence of resistance to the front-line drug, artemisinin, in South-East Asia in Plasmodium falciparum, which calls for preemptive surveillance of the African parasite population for genetic markers of emerging drug resistance. Here we describe the Plasmodium Diversity Network Africa (PDNA), which has been established across 11 countries in sub-Saharan Africa to ensure that African scientists are enabled to work together and to play a key role in the global effort for tracking and responding to this public health threat.
Project description:Konzo, a disease characterized by sudden, irreversible spastic paraparesis, affecting up to 10% of the population in some regions of Sub-Saharan Africa during outbreaks and is strongly associated with dietary exposure to cyanogenic bitter cassava. The molecular mechanisms underlying the development of konzo, remain largely unknown. Here, through an analysis of 16 individuals with konzo and matched healthy controls from the same outbreak zones, we identified 117 differentially methylated loci involved in numerous biological processes that may identify cyanogenic- sensitive regions of the genome, providing the first study of epigenomic alterations associated with sub-lethal cyanide exposure and a clinical phenotype.
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:A characteristic of Plasmodium falciparum infections is the gradual acquisition of clinical immunity resulting from repeated exposures to the parasite. While the molecular basis of protection against clinical malaria remains unresolved, its effects on epidemiological patterns are well recognized. Accumulating epidemiological data constitute a valuable resource that must be intensively explored and interpreted as to effectively inform control planning.Here we apply a mathematical model to clinical data from eight endemic regions in sub-Saharan Africa. The model provides a quantitative framework within which differences in age distribution of clinical disease are assessed in terms of the parameters underlying transmission. The shorter infectious periods estimated for clinical infections induce a regime of bistability of endemic and malaria-free states in regions of mesoendemic transmission. The two epidemiological states are separated by a threshold that provides a convenient measure for intervention design. Scenarios of eradication and resurgence are simulated.In regions that support mesoendemic transmission, intervention success depends critically on reducing prevalence below a threshold which separates endemic and malaria-free regimes.
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:There are already 40 cities in Africa with over 1 million inhabitants and the United Nations Environmental Programme estimates that by 2025 over 800 million people will live in urban areas. Recognizing that malaria control can improve the health of the vulnerable and remove a major obstacle to their economic development, the Malaria Knowledge Programme of the Liverpool School of Tropical Medicine and the Systemwide Initiative on Malaria and Agriculture convened a multi-sectoral technical consultation on urban malaria in Pretoria, South Africa from 2nd to 4th December, 2004. The aim of the meeting was to identify strategies for the assessment and control of urban malaria. This commentary reflects the discussions held during the meeting and aims to inform researchers and policy makers of the potential for containing and reversing the emerging problem of urban malaria.
Project description:Venomous snakes are important parts of the ecosystem, and their behavior and evolution have been shaped by their surrounding environments over the eons. This is reflected in their venoms, which are typically highly adapted for their biological niche, including their diet and defense mechanisms for deterring predators. Sub-Saharan Africa is rich in venomous snake species, of which many are dangerous to humans due to the high toxicity of their venoms and their ability to effectively deliver large amounts of venom into their victims via their bite. In this study, the venoms of 26 of sub-Saharan Africa’s medically most relevant elapid and viper species were subjected to parallelized toxicovenomics analysis. The analysis included venom proteomics and enables a robust comparison of venom profiles between species. Moreover, two new venom proteomes (N. anchietae and E. leucogaster) are presented here for the first time.
Project description:BackgroundThe rapid urban malaria appraisal (RUMA) methodology aims to provide a cost-effective tool to conduct rapid assessments of the malaria situation in urban sub-Saharan Africa and to improve the understanding of urban malaria epidemiology.MethodsThis work was done in Yopougon municipality (Abidjan), Cotonou, Dar es Salaam and Ouagadougou. The study design consists of six components: 1) a literature review, 2) the collection of available health statistics, 3) a risk mapping, 4) school parasitaemia surveys, 5) health facility-based surveys and 6) a brief description of the health care system. These formed the basis of a multi-country evaluation of RUMA's feasibility, consistency and usefulness.ResultsA substantial amount of literature (including unpublished theses and statistics) was found at each site, providing a good overview of the malaria situation. School and health facility-based surveys provided an overview of local endemicity and the overall malaria burden in different city areas. This helped to identify important problems for in-depth assessment, especially the extent to which malaria is over-diagnosed in health facilities. Mapping health facilities and breeding sites allowed the visualization of the complex interplay between population characteristics, health services and malaria risk. However, the latter task was very time-consuming and required special expertise. RUMA is inexpensive, costing around 8,500-13,000 USD for a six to ten-week period.ConclusionRUMA was successfully implemented in four urban areas with different endemicity and proved to be a cost-effective first approach to study the features of urban malaria and provide an evidence basis for planning control measures.
Project description:BACKGROUND: In malarious areas of the world, a higher proportion of the population has blood group O than in non-malarious areas. This is probably due to a survival advantage conferred either by an attenuating effect on the course of or reduction in the risk of infection by plasmodial parasites. Here, the association between ABO blood group and incidence of placental malaria was assessed in order to determine the possible influence of the former on the latter. METHODS: Data from a study in Lambaréné, Gabon, and data from three previously published reports of studies in The Gambia, Malawi and Sudan, were compiled and compared. ABO blood groups were cross-tabulated with placental malaria stratified by parity. Odds ratios (OR), stratified by parity, were calculated for the outcome, placental parasitaemia, and compared between blood group O vs. non-O mothers in all four studies. Random effects meta-analysis of data from individual studies from areas with perennial hyper/holoendemic transmission was performed. RESULTS: In Gabon, the odds ratio (OR) for active placental parasitaemia in mothers with group O was 0.3 (95% CI 0.05-1.8) for primiparae and 0.7 (95% CI 0.3-1.8) for multiparae. The OR for primiparae in the published study from The Gambia was 3.0 (95% CI 1.2-7.3) and, in Malawi, 2.2 (95% CI 1.1-4.3). In the Sudanese study, no OR for primiparae could be calculated. The OR for placental parasitaemia in group O multiparae was 0.8 (95% CI 0.3-1.7) in the Gambia, 0.6 (95% CI 0.4-1.0) in Malawi and 0.4 (95% CI 0.1-1.8) in Sudan. Combining data from the three studies conducted in hyper-/holo-endemic settings (Gambia, Malawi, Gabon) the OR for placental malaria in blood group O multiparae was 0.65 (95% CI 0.44-0.96) and for primiparae 1.70 (95% CI 0.67-4.33). CONCLUSION: Studies conducted in The Gambia and Malawi suggest that blood group O confers a higher risk of active placental infection in primiparae, but a significantly lower risk in multiparae. These findings were not confirmed by the study from Gabon, in which statistically non-significant trends for reduced risk of placental parasitaemia in those with blood group O, regardless of parity, were observed.
Project description:Choline analogs represent a novel class of antimalarial compounds with strong potency against drug-sensitive and resistant P. falciparum. Although, these drugs are presumed to target proteins within lipid biosynthesis pathways; their complete mechanism of action and the parasite’s compensatory response remain to be elucidated. We have applied transcriptional profiling to characterize the global response to the choline analog T4 during the P. falciparum intraerythrocytic life cycle Keywords: Trascriptome analysis of Plasmodium falciparum in response to external stimuli using the affymetrix platform GPL3575