11 research outputs found
Comparative genomics revealed adaptive admixture in Cryptosporidium hominis in Africa
Cryptosporidiosis is a major cause of diarrhoeal illness among African children, and is associated with childhood mortality, malnutrition, cognitive development and growth retardation. Cryptosporidium hominis is the dominant pathogen in Africa, and genotyping at the glycoprotein 60 (gp60) gene has revealed a complex distribution of different subtypes across this continent. However, a comprehensive exploration of the metapopulation structure and evolution based on whole-genome data has yet to be performed. Here, we sequenced and analysed the genomes of 26 C. hominis isolates, representing different gp60 subtypes, collected at rural sites in Gabon, Ghana, Madagascar and Tanzania. Phylogenetic and cluster analyses based on single-nucleotide polymorphisms showed that isolates predominantly clustered by their country of origin, irrespective of their gp60 subtype. We found a significant isolation-by-distance signature that shows the importance of local transmission, but we also detected evidence of hybridization between isolates of different geographical regions. We identified 37 outlier genes with exceptionally high nucleotide diversity, and this group is significantly enriched for genes encoding extracellular proteins and signal peptides. Furthermore, these genes are found more often than expected in recombinant regions, and they show a distinct signature of positive or balancing selection. We conclude that: (1) the metapopulation structure of C. hominis can only be accurately captured by whole-genome analyses; (2) local anthroponotic transmission underpins the spread of this pathogen in Africa; (3) hybridization occurs between distinct geographical lineages; and (4) genetic introgression provides novel substrate for positive or balancing selection in genes involved in host–parasite coevolution
A genomic appraisal of invasive Salmonella Typhimurium and associated antibiotic resistance in sub-Saharan Africa
Invasive non-typhoidal Salmonella (iNTS) disease manifesting as bloodstream infection with high mortality is responsible for a huge public health burden in sub-Saharan Africa. Salmonella enterica serovar Typhimurium (S. Typhimurium) is the main cause of iNTS disease in Africa. By analysing whole genome sequence data from 1303 S. Typhimurium isolates originating from 19 African countries and isolated between 1979 and 2017, here we show a thorough scaled appraisal of the population structure of iNTS disease caused by S. Typhimurium across many of Africa’s most impacted countries. At least six invasive S. Typhimurium clades have already emerged, with ST313 lineage 2 or ST313-L2 driving the current pandemic. ST313-L2 likely emerged in the Democratic Republic of Congo around 1980 and further spread in the mid 1990s. We observed plasmid-borne as well as chromosomally encoded fluoroquinolone resistance underlying emergences of extensive-drug and pan-drug resistance. Our work provides an overview of the evolution of invasive S. Typhimurium disease, and can be exploited to target control measures
A genomic appraisal of invasive Salmonella Typhimurium and associated antibiotic resistance in sub-Saharan Africa
Invasive non-typhoidal Salmonella (iNTS) disease manifesting as bloodstream infection with high mortality is responsible for a huge public health burden in sub-Saharan Africa. Salmonella enterica serovar Typhimurium (S. Typhimurium) is the main cause of iNTS disease in Africa. By analysing whole genome sequence data from 1303 S. Typhimurium isolates originating from 19 African countries and isolated between 1979 and 2017, here we show a thorough scaled appraisal of the population structure of iNTS disease caused by S. Typhimurium across many of Africa’s most impacted countries. At least six invasive S. Typhimurium clades have already emerged, with ST313 lineage 2 or ST313-L2 driving the current pandemic. ST313-L2 likely emerged in the Democratic Republic of Congo around 1980 and further spread in the mid 1990s. We observed plasmid-borne as well as chromosomally encoded fluoroquinolone resistance underlying emergences of extensive-drug and pan-drug resistance. Our work provides an overview of the evolution of invasive S. Typhimurium disease, and can be exploited to target control measures
Determinants of household dietary practices in rural Tanzania: Implications for nutrition interventions
A household cross-sectional survey of a sample of 120 households to analyze consumption practices and determinants of household dietary diversity in rural areas of differing agro-climatic conditions in Tanzania was conducted in four villages of Morogoro and Dodoma regions. The respondent was the mother/woman or any other person responsible for food preparation and serving in the household. The inclusion criteria were those women who had given consent to participate, those from a rural area and in the age bracket 15 to 49Â years. Data were collected using the Food and Agriculture Organization dietary diversity questionnaire with twelve food groups. Two independent multinomial logistic regression models were used to establish relationships between dietary diversity and categorical variables in Morogoro and Dodoma regions. The mean dietary diversity scores were 4.7 and 4.1 for Morogoro and Dodoma, respectively. The Cereals were highly consumed by all households that participated in the study during the past 24Â h preceding the survey and that the consumption of animal based protein foods was below 40%. Determinants of household dietary diversity in Morogoro included literacy status of the mother and prior nutrition training/knowledge. In Dodoma, cultivated land size, literacy status of the mother and distance to a water source determined household dietary diversity. It is therefore recommended that nutrition and food security interventions should not only empower rural women but also pay special attention to differences in agro-ecological environments of the areas in determining interventions to address malnutrition and for effective successful implementation and outcomes
Performance of a rapid diagnostic test for the detection of Cryptosporidium spp. in African children admitted to hospital with diarrhea.
BackgroundCryptosporidium is a protozoan parasite that causes mild to severe diarrhoeal disease in humans. To date, several commercial companies have developed rapid immunoassays for the detection of Cryptosporidium infection. However, the challenge is to identify an accurate, simple and rapid diagnostic tool for the estimation of cryptosporidiosis burden. This study aims at evaluating the accuracy of CerTest Crypto, a commercialized rapid diagnostic test (RDT) for the detection of Cryptosporidium antigens in the stool of children presenting with diarrhoea.MethodsA cross-sectional study was conducted in four study sites in Sub-Saharan Africa (Gabon, Ghana, Madagascar, and Tanzania), from May 2017 to April 2018. Stool samples were collected from children under 5 years with diarrhoea or a history of diarrhoea within the last 24 hours. All specimens were processed and analyzed using CerTest Crypto RDT against a composite diagnostic panel involving two polymerase chain reaction (PCR) tests (qPCR and RFLP-PCR,) as the gold standard.ResultsA total of 596 stool samples were collected. Evaluation of the RDT yielded a very low overall sensitivity of 49.6% (confidence interval (CI) 40.1-59.0), a specificity of 92.5% (CI 89.8-94.7), positive predictive value of 61.3% (CI 50.6-71.2), and negative predictive value of 88.5% (85.3-91.1) when compared to the composite reference standard of qPCR and RFLP-PCR for the detection of Cryptosporidium species. Moreover, the performance of this test varied across different sites.ConclusionThe weak performance of the studied RDT suggests the need to carefully evaluate available commercial RDTs before their use as standard tools in clinical trials and community survey of Cryptosporidium infections in pediatric cohorts
Transmission of Cryptosporidium Species Among Human and Animal Local Contact Networks in Sub-Saharan Africa: A Multicountry Study
Abstract
Background
Cryptosporidiosis has been identified as one of the major causes of diarrhea and diarrhea-associated deaths in young children in sub-Saharan Africa. This study traces back Cryptosporidium-positive children to their human and animal contacts to identify transmission networks.
Methods
Stool samples were collected from children < 5 years of age with diarrhea in Gabon, Ghana, Madagascar, and Tanzania. Cryptosporidium-positive and -negative initial cases (ICs) were followed to the community, where stool samples from households, neighbors, and animal contacts were obtained. Samples were screened for Cryptosporidium species by immunochromatographic tests and by sequencing the 18S ribosomal RNA gene and further subtyped at the 60 kDa glycoprotein gene (gp60). Transmission clusters were identified and risk ratios (RRs) calculated.
Results
Among 1363 pediatric ICs, 184 (13%) were diagnosed with Cryptosporidium species. One hundred eight contact networks were sampled from Cryptosporidium-positive and 68 from negative ICs. Identical gp60 subtypes were detected among 2 or more contacts in 39 (36%) of the networks from positive ICs and in 1 contact (1%) from negative ICs. In comparison to Cryptosporidium-negative ICs, positive ICs had an increased risk of having Cryptosporidium-positive household members (RR, 3.6 [95% confidence interval {CI}, 1.7–7.5]) or positive neighboring children (RR, 2.9 [95% CI, 1.6–5.1]), but no increased risk of having positive animals (RR, 1.2 [95% CI, .8–1.9]) in their contact network.
Conclusions
Cryptosporidiosis in rural sub-Saharan Africa is characterized by infection clusters among human contacts, to which zoonotic transmission appears to contribute only marginally
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A genomic appraisal of invasive Salmonella Typhimurium and associated antibiotic resistance in sub-Saharan Africa
Acknowledgements: We are grateful to Jacqueline Keane, Christoph Puethe and the Pathogen Informatics team (Wellcome Sanger Institute, Hinxton, Cambridge, United Kingdom) for the support. The work by S.V.P. and G.D. is funded in part by a grant from the Bill & Melinda Gates Foundation (OPP1151153). R.K. and M.B. were supported by research grants BB/N007964/1 and BB/M025489/1, and by the BBSRC Institute Strategic Programme Microbes in the Food Chain BB/R012504/1 and its constituent projects BBS/E/F/000PR10348 and BBS/E/F/000PR10349. W.L.C. was supported by the Research Foundation—Flanders (FWO SB PhD fellowship 1S40018N); J.P.R. was financially supported by the Belgian Directorate General for Development Cooperation (DGD). M.A.B. and N.R.T. were supported by Wellcome funding to the Sanger Institute (#206194). The work done in Benin, Burkina Faso and DRC by B.B., L.M.-K., M.-F.P., D.F., D.A., J.J. and O.L. was funded by the Belgian Directorate of Development Cooperation (DGD) through the Multi-Year Programme (2012–2016) between the Belgian DGD and the Institute of Tropical Medicine, Belgium and (for DRC) by the Baillet-Latour find and the Flemish Interuniversity Council (VLIR-UOS). The isolates from Malawi were generated by Malawi Liverpool Wellcome Research Programme bacteraemia service, supported by Asia and Africa Programme Grant 206545/Z/17/Z to NF. The work in The Gambia was supported by the Bill & Melinda Gates Foundation (OPP1020327); GAVI The Vaccine Alliance’s Accelerated Development and Introduction Plan (PneumoADIP), Medical Research Council (UK) to GM. Salmonella isolates obtained through the RTS,S study was funded by the Bill & Melinda Gates Foundation to CAM. Salmonella isolates obtained through the TSAP study were funded by the Bill & Melinda Gates Foundation to IVI (OPPGH5231) to F.M., H.J.J. and S.E.P. This research by S.V.P., S.S. and G.D. was funded by the National Institute for Health Research [Cambridge Biomedical Research Centre at the Cambridge University Hospitals NHS Foundation Trust]. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health and Social Care. This research was funded in whole, or in part, by the Wellcome Trust (#206194).Funder: DH | National Institute for Health Research (NIHR); doi: https://doi.org/10.13039/501100000272Invasive non-typhoidal Salmonella (iNTS) disease manifesting as bloodstream infection with high mortality is responsible for a huge public health burden in sub-Saharan Africa. Salmonella enterica serovar Typhimurium (S. Typhimurium) is the main cause of iNTS disease in Africa. By analysing whole genome sequence data from 1303 S. Typhimurium isolates originating from 19 African countries and isolated between 1979 and 2017, here we show a thorough scaled appraisal of the population structure of iNTS disease caused by S. Typhimurium across many of Africa’s most impacted countries. At least six invasive S. Typhimurium clades have already emerged, with ST313 lineage 2 or ST313-L2 driving the current pandemic. ST313-L2 likely emerged in the Democratic Republic of Congo around 1980 and further spread in the mid 1990s. We observed plasmid-borne as well as chromosomally encoded fluoroquinolone resistance underlying emergences of extensive-drug and pan-drug resistance. Our work provides an overview of the evolution of invasive S. Typhimurium disease, and can be exploited to target control measures