Over 290 million people are infected by schistosomes worldwide. Schistosomiasis control efforts f... more Over 290 million people are infected by schistosomes worldwide. Schistosomiasis control efforts focus on mass drug treatment with praziquantel (PZQ), a drug that kills the adult worm of allSchistosomaspecies. Nonetheless, re-infections have continued to be detected in endemic areas with individuals living in the same area presenting with varying infection intensities. Our objective was to characterize the transcriptome profiles in peripheral blood of children between 10 - 15 years with varying intensities ofSchistosoma mansoniinfection living along the Albert Nile in Uganda. RNA extracted from peripheral blood collected from 44S. mansoniinfected (34 high and 10 low by circulating anodic antigen [CAA] level) and 20 uninfected children was sequenced using Illumina NovaSeq S4 and the reads aligned to the GRCh38 human genome. Differential gene expression analysis was done using DESeq2 and enriched pathways in differentially expressed genes (DEGs) were identified using REACTOME. Principa...
Human genetic factors confer protection or susceptibility to malaria. Classical examples include ... more Human genetic factors confer protection or susceptibility to malaria. Classical examples include sickle cell trait, which confers up to 90% protection from severe <i>Plasmodium falciparum</i> malaria and Duffy antigen negativity, which offers almost complete resistance to <i>Plasmodium vivax</i> infection. Unfortunately, such genetic factors are insufficiently understood to design interventions. I conducted the current study in Asembo, western Kenya by recruiting a paediatric cohort, characterizing malaria epidemiology, genotyping for single nucleotide polymorphisms (SNPs) to identify genetic factors affecting malaria incidence and investigating their possible relationships with naturally acquired immunity. In addition, I investigated the effect of co-inheritance of genetic factors on malaria incidence. Children under 12 years were followed up over a 6 year period (2008-2013) to calculate malaria incidence. Odds ratios for malaria were also calculated for cat...
Warnings about the expected increase of the global public health burden of malaria-related red ce... more Warnings about the expected increase of the global public health burden of malaria-related red cell disorders are accruing. Past and present epidemiological data are necessary to track spatial and temporal changes in the frequencies of these genetic disorders. A number of open access biomedical databases including data on malaria-related red cell disorders have been launched over the last two decades. Here, we review the content of these databases, most of which focus on genetic diversity, and we describe a new epidemiological resource developed by the Malaria Atlas Project. To tackle upcoming public health challenges, the integration of epidemiological and genetic data is important. As many countries are considering implementing national screening programs, strategies to make such data more accessible are also needed.
geographic patterns. Interest in the global prevalence of the Duffy blood group variants is multi... more geographic patterns. Interest in the global prevalence of the Duffy blood group variants is multidisciplinary, but of particular importance to malariologists due to the resistance generally conferred by the Duffy-negative phenotype against Plasmodium vivax infection. Here we collate an extensive geo-database of surveys, forming the evidence-base for a multi-locus Bayesian geostatistical model to generate global frequency maps of the common Duffy alleles to refine the global cartography of the common Duffy variants. We show that the most prevalent allele globally was FY*A, while across sub-Saharan Africa the predominant allele was the silent FY*BES variant, commonly reaching fixation across stretches of the continent. The maps presented not only represent the first spatially and genetically comprehensive description of variation at this locus, but also constitute an advance towards understanding the transmission patterns of the neglected P. vivax malaria parasite.
T. b. rhodesienseis the causative agent of rhodesian Human African trypanosomiasis (r-HAT) in Mal... more T. b. rhodesienseis the causative agent of rhodesian Human African trypanosomiasis (r-HAT) in Malawi. Clinical presentation of r-HAT in Malawi varies between the different foci and differs from East African HAT clinical phenotypes. The purpose of this study was to gain more insights into the transcriptomic profiles of patients with early stage 1 and late stage 2 HAT disease in Malawi. Whole blood from individuals infected withT. b. rhodesiensewas used for RNA-Seq. Control samples were from healthy trypanosome negative individuals matched on sex, age range, and disease focus. Illumina sequence FASTQ reads were aligned to the GRCh38 release 84 human genome sequence using HiSat2 and differential analysis was done in R using the DESeq2 package. XGR, ExpressAnalyst and InnateDB algorithms were used for functional annotation and gene enrichment analysis of significant differentially expressed genes. RNA-seq was done on 25 healthy controls and 23 r-HAT case samples of which 3 case samples ...
BackgroundSleeping sickness caused byT.b. rhodesienseis a fatal disease and endemic in Southern a... more BackgroundSleeping sickness caused byT.b. rhodesienseis a fatal disease and endemic in Southern and Eastern Africa. There is an urgent need to develop novel diagnostic and control tools in order to achieve elimination of rhodesiense sleeping sickness which might be achieved through a better understanding of trypanosome gene expression and genetics using endemic isolates. Here, we describe transcriptome profiles and population structure of endemicT. b. rhodesienseisolates in human blood in Malawi.MethodologyBlood samples of r-HAT cases from Nkhotakota and Rumphi foci were collected in PaxGene tubes for RNA extraction before initiation of r-HAT treatment. 100 million reads were obtained per sample, reads were initially mapped to the human genome reference GRCh38 using HiSat2 and then the unmapped reads were mapped againstTrypanosoma bruceireference transcriptome (TriTrypDB54_TbruceiTREU927) using HiSat2. Differential gene expression analysis was done using the DeSeq2 package in R. SNP...
Background Knowing the prevalence of schistosomiasis is key to informing programmes to control an... more Background Knowing the prevalence of schistosomiasis is key to informing programmes to control and eliminate the disease as a public health problem. It is also important to understand the impact of infection on child growth and development in order to allocate appropriate resources and effort to the control of the disease. Methods We conducted a survey to estimate the prevalence of schistosomiasis among school aged children in villages along the Albert-Nile shore line in the district of Pakwach, North Western Uganda. A total of 914 children aged between 10–15 years were screened for Schistosoma mansoni using the POC-CCA and Kato Katz (KK) techniques. The infection intensities were assessed by POC-CCA and KK as well as CAA tests. The KK intensities were also correlated with POC-CCA and with CAA intensity. Anthropometric measurements were also taken and multivariate analysis was carried out to investigate their association with infection status. Results The prevalence of schistosomias...
Schistosomiasis affects over 250 million people worldwide with an estimated mortality of more tha... more Schistosomiasis affects over 250 million people worldwide with an estimated mortality of more than 200,000 deaths per year in sub-Saharan Africa. Efforts to control schistosomiasis in the affected areas have mainly relied on mass administration of praziquantel, which kills adult but not immature worms of all Schistosoma species. Mammalian hosts respond differently to Schistosoma infection with some being more susceptible than others, which is associated with risk factors such as sociodemographic, epidemiological, immunological and/or genetic. Host genetic factors play a major role in influencing molecular processes in response to schistosomiasis as shown in gene expression studies. These studies highlight gene profiles expressed at different time points of infection using model animals. Immune function related genes; cytokines (Th1 and Th17) are upregulated earlier in infection and Th2 upregulated later indicating a mixed Th1/Th2 response. However, Th1 response has been shown to be ...
Additional file 9: Table S8. Counts of CNVR and SNP with tagged SNP and SNP with Signatures of Se... more Additional file 9: Table S8. Counts of CNVR and SNP with tagged SNP and SNP with Signatures of Selection (iHS > 3).
Over 290 million people are infected by schistosomes worldwide. Schistosomiasis control efforts f... more Over 290 million people are infected by schistosomes worldwide. Schistosomiasis control efforts focus on mass drug treatment with praziquantel (PZQ), a drug that kills the adult worm of allSchistosomaspecies. Nonetheless, re-infections have continued to be detected in endemic areas with individuals living in the same area presenting with varying infection intensities. Our objective was to characterize the transcriptome profiles in peripheral blood of children between 10 - 15 years with varying intensities ofSchistosoma mansoniinfection living along the Albert Nile in Uganda. RNA extracted from peripheral blood collected from 44S. mansoniinfected (34 high and 10 low by circulating anodic antigen [CAA] level) and 20 uninfected children was sequenced using Illumina NovaSeq S4 and the reads aligned to the GRCh38 human genome. Differential gene expression analysis was done using DESeq2 and enriched pathways in differentially expressed genes (DEGs) were identified using REACTOME. Principa...
Human genetic factors confer protection or susceptibility to malaria. Classical examples include ... more Human genetic factors confer protection or susceptibility to malaria. Classical examples include sickle cell trait, which confers up to 90% protection from severe <i>Plasmodium falciparum</i> malaria and Duffy antigen negativity, which offers almost complete resistance to <i>Plasmodium vivax</i> infection. Unfortunately, such genetic factors are insufficiently understood to design interventions. I conducted the current study in Asembo, western Kenya by recruiting a paediatric cohort, characterizing malaria epidemiology, genotyping for single nucleotide polymorphisms (SNPs) to identify genetic factors affecting malaria incidence and investigating their possible relationships with naturally acquired immunity. In addition, I investigated the effect of co-inheritance of genetic factors on malaria incidence. Children under 12 years were followed up over a 6 year period (2008-2013) to calculate malaria incidence. Odds ratios for malaria were also calculated for cat...
Warnings about the expected increase of the global public health burden of malaria-related red ce... more Warnings about the expected increase of the global public health burden of malaria-related red cell disorders are accruing. Past and present epidemiological data are necessary to track spatial and temporal changes in the frequencies of these genetic disorders. A number of open access biomedical databases including data on malaria-related red cell disorders have been launched over the last two decades. Here, we review the content of these databases, most of which focus on genetic diversity, and we describe a new epidemiological resource developed by the Malaria Atlas Project. To tackle upcoming public health challenges, the integration of epidemiological and genetic data is important. As many countries are considering implementing national screening programs, strategies to make such data more accessible are also needed.
geographic patterns. Interest in the global prevalence of the Duffy blood group variants is multi... more geographic patterns. Interest in the global prevalence of the Duffy blood group variants is multidisciplinary, but of particular importance to malariologists due to the resistance generally conferred by the Duffy-negative phenotype against Plasmodium vivax infection. Here we collate an extensive geo-database of surveys, forming the evidence-base for a multi-locus Bayesian geostatistical model to generate global frequency maps of the common Duffy alleles to refine the global cartography of the common Duffy variants. We show that the most prevalent allele globally was FY*A, while across sub-Saharan Africa the predominant allele was the silent FY*BES variant, commonly reaching fixation across stretches of the continent. The maps presented not only represent the first spatially and genetically comprehensive description of variation at this locus, but also constitute an advance towards understanding the transmission patterns of the neglected P. vivax malaria parasite.
T. b. rhodesienseis the causative agent of rhodesian Human African trypanosomiasis (r-HAT) in Mal... more T. b. rhodesienseis the causative agent of rhodesian Human African trypanosomiasis (r-HAT) in Malawi. Clinical presentation of r-HAT in Malawi varies between the different foci and differs from East African HAT clinical phenotypes. The purpose of this study was to gain more insights into the transcriptomic profiles of patients with early stage 1 and late stage 2 HAT disease in Malawi. Whole blood from individuals infected withT. b. rhodesiensewas used for RNA-Seq. Control samples were from healthy trypanosome negative individuals matched on sex, age range, and disease focus. Illumina sequence FASTQ reads were aligned to the GRCh38 release 84 human genome sequence using HiSat2 and differential analysis was done in R using the DESeq2 package. XGR, ExpressAnalyst and InnateDB algorithms were used for functional annotation and gene enrichment analysis of significant differentially expressed genes. RNA-seq was done on 25 healthy controls and 23 r-HAT case samples of which 3 case samples ...
BackgroundSleeping sickness caused byT.b. rhodesienseis a fatal disease and endemic in Southern a... more BackgroundSleeping sickness caused byT.b. rhodesienseis a fatal disease and endemic in Southern and Eastern Africa. There is an urgent need to develop novel diagnostic and control tools in order to achieve elimination of rhodesiense sleeping sickness which might be achieved through a better understanding of trypanosome gene expression and genetics using endemic isolates. Here, we describe transcriptome profiles and population structure of endemicT. b. rhodesienseisolates in human blood in Malawi.MethodologyBlood samples of r-HAT cases from Nkhotakota and Rumphi foci were collected in PaxGene tubes for RNA extraction before initiation of r-HAT treatment. 100 million reads were obtained per sample, reads were initially mapped to the human genome reference GRCh38 using HiSat2 and then the unmapped reads were mapped againstTrypanosoma bruceireference transcriptome (TriTrypDB54_TbruceiTREU927) using HiSat2. Differential gene expression analysis was done using the DeSeq2 package in R. SNP...
Background Knowing the prevalence of schistosomiasis is key to informing programmes to control an... more Background Knowing the prevalence of schistosomiasis is key to informing programmes to control and eliminate the disease as a public health problem. It is also important to understand the impact of infection on child growth and development in order to allocate appropriate resources and effort to the control of the disease. Methods We conducted a survey to estimate the prevalence of schistosomiasis among school aged children in villages along the Albert-Nile shore line in the district of Pakwach, North Western Uganda. A total of 914 children aged between 10–15 years were screened for Schistosoma mansoni using the POC-CCA and Kato Katz (KK) techniques. The infection intensities were assessed by POC-CCA and KK as well as CAA tests. The KK intensities were also correlated with POC-CCA and with CAA intensity. Anthropometric measurements were also taken and multivariate analysis was carried out to investigate their association with infection status. Results The prevalence of schistosomias...
Schistosomiasis affects over 250 million people worldwide with an estimated mortality of more tha... more Schistosomiasis affects over 250 million people worldwide with an estimated mortality of more than 200,000 deaths per year in sub-Saharan Africa. Efforts to control schistosomiasis in the affected areas have mainly relied on mass administration of praziquantel, which kills adult but not immature worms of all Schistosoma species. Mammalian hosts respond differently to Schistosoma infection with some being more susceptible than others, which is associated with risk factors such as sociodemographic, epidemiological, immunological and/or genetic. Host genetic factors play a major role in influencing molecular processes in response to schistosomiasis as shown in gene expression studies. These studies highlight gene profiles expressed at different time points of infection using model animals. Immune function related genes; cytokines (Th1 and Th17) are upregulated earlier in infection and Th2 upregulated later indicating a mixed Th1/Th2 response. However, Th1 response has been shown to be ...
Additional file 9: Table S8. Counts of CNVR and SNP with tagged SNP and SNP with Signatures of Se... more Additional file 9: Table S8. Counts of CNVR and SNP with tagged SNP and SNP with Signatures of Selection (iHS > 3).
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Papers by Oscar Nyangiri