Biology subjects

Tweyongyere, R.

Publications and source records attributed to Tweyongyere, R..

4 recordsLinked to original sources

bioRxiv2023

Transcriptome analysis of peripheral blood of Schistosoma mansoni infected children from the Albert Nile region in Uganda reveals genes implicated in fibrosis pathology.

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 all Schistosoma species. 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 of Schistosoma mansoni infection living along the Albert Nile in Uganda. RNA extracted from peripheral blood collected from 44 S. mansoni infected (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. Principal component analysis revealed clustering of gene expression by gender when S. mansoni infected children were compared with uninfected children. In addition, we identified 14 DEGs between S. mansoni infected and uninfected individuals, 56 DEGs between children with high infection intensity and uninfected individuals, 33 DEGs between those with high infection intensity and low infection intensity and no DEGs between those with low infection and uninfected individuals. We also observed upregulation and downregulation of some DEGs that are associated with fibrosis and its regulation. These data suggest expression of fibrosis associated genes as well as genes that regulate fibrosis in S. mansoni infection. The relatively few significant DEGS observed in children with schistosomiasis suggests that chronic S. mansoni infection is a stealth infection that does not stimulate a strong immune response. Author SummarySchistosomiasis is a neglected tropical disease transmitted via an intermediate snail host through contact with contaminated fresh water. Even with routine Mass Drug Administration for treatment of the infection, re-infections are still common and variations in infection intensity and pathology are still observed in individuals in the same location. These may be due to differences in individuals response to S. mansoni infection. In this study, we used RNAseq to identify differentially expressed genes associated with S. mansoni infection in children between 10-15 years. We conducted comparisons between phenotypes including infection intensities measured by circulating anodic antigen, wasting by body mass index and stunting by height-for-age z score. Our data showed very low numbers of significant differentially expressed genes in all comparisons. Some of the few differentially expressed genes that were observed were associated with fibrosis which is the cause of pathology in humans and has been observed in late stages of S. mansoni infection in murine studies.

genomics↗

bioRxiv2023

Wide distribution of Mediterranean and African Spotted fever agents and the first identification of Israeli Spotted Fever agent in ticks in Uganda

Rickettsia microorganisms are causative agents of several neglected emerging infectious diseases transmitted to humans by ticks among other arthropod vectors. In this study, ticks were collected from four geographical regions of Uganda, pooled in sizes of 1-179 ticks based on location, tick species, life stage, host, and time of collection, and were tested by real time PCR for Rickettsia species harboured. The tick pools were tested with primers targeting gltA, 17kDa and ompA genes, followed by Sanger sequencing of 17kDa and ompA genes. Of the 471 tick pools tested, 116 (24.6%) were positive for Rickettsia spp. by the gltA primers. The prevalence of Rickettsia varied by district with Gulu recording the highest (30.1%) followed by Luwero (28.1%) and Kasese had the lowest (14%). Tick pools with highest positivity rates were from livestock (cattle, goats, sheep, and pigs), 26.9%, followed by vegetation 23.1% and pets (dogs and cats) 19.7%. Of 116 gltA-positive tick pools, 86 pools were positive using 17kDa primers of which 48 purified PCR products were successfully sequenced. The predominant Rickettsia spp. identified was R. africae (n=15) in four tick species, followed by R. conorii (n=5) in three tick species (Haemaphysalis elliptica, Rhipicephalus appendiculatus, and Rh. decoloratus). Rickettsia conorii subsp. israelensis was detected in one tick pool. These findings indicate that multiple Rickettsia spp. capable of causing human illness are circulating in the four diverse geographical regions of Uganda including new strains previously known to occur in the Mediterranean region. Physicians should be informed about Rickettsia spp. infections as potential causes for acute febrile illnesses in these regions. Continued and expanded surveillance is essential to further identify and locate potential hotspots with Rickettsia spp. of concern. Author SummaryTick-borne rickettsioses are emerging infectious diseases of public health importance worldwide. Spotted fever rickettsioses transmitted by ticks can cause mild to severe human illness depending on the Rickettsia spp. and co-morbidities. Their diagnosis is challenging due to non-specific symptoms particularly in limited resource settings. Little is known about their prevalence in Uganda. Using entomological and molecular tools, we surveyed and studied tick-borne spotted fever rickettsioses in five districts from four diverse eco-regions of Uganda. Overall, 24.6% (116/471) tick pools were positive for Rickettsia species. By sequencing the 17kDa and ompA genes of Rickettsia, we identified R. africae as the most common agent, followed by R. conorii and R. conorii subsp. israelensis. The findings indicate multiple Rickettsia spp. that can cause febrile illness in humans are circulating in the four geographically diverse regions of Uganda. Physicians should be aware these agents are potential causes of febrile illness in these areas, particularly in individuals who encounter livestock or their grazing areas.

molecular biology↗

bioRxiv2023

Ticks; a reservoir for virus emergence at the human-livestock interface in Uganda

BackgroundUganda is one of the most biodiverse regions on the planet and a hotspot for virus emergence. In particular, the warm-humid lowlands favour tick population growth with the associated risk of tick-borne disease. The prevalent tick species Rhipicephalus appendiculatus, R. evertsi evertsi and Amblyomma variegatum harbour a diverse range of viruses, from harmless to highly pathogenic. Notably, the orthonairoviruses cause human outbreaks of Crimean-Congo haemorrhagic fever (CCHF) regularly within the cattle corridor of Uganda, a region spanning from the south-west to the north-east of the country. MethodsIn the ArboViral Infection (AVI) study, the first to explore the virome of ticks in Uganda using next generation sequencing (NGS), we collected ticks from three geographically diverse areas and subjected these to target-enrichment (TE) NGS. Viral genomes were detected by de novo assembly, mapping and BLASTn. ResultsWe analyzed a total of 2,754 ticks collected from 31 livestock farms in the districts of Arua, Nakaseke and Lyantonde. These were combined into 219 pools by site of collection and tick species, including R. appendiculatus, R. evertsi evertsi, A. variegatum and Hyalomma rufipes. We detected partial or near-complete viral genomes in 163 tick pools; 110 (67%) of which were from Arua, 39 (24%) from Nakaseke and 12 (7%) from Lyantonde districts. 2 pools (2%) were from Arua/Lyantonde. These included 22 species of virus, representing 15 genera and 9 families, including the Nairoviridae, Retroviridae, Orthomyxoviridae, Chuviridae, Rhabdoviridae, Phenuiviridae, Parvoviridae, Poxviridae and Flaviviridae. There were 8 viral species known to be pathogens of humans or animals and 5 highly divergent genomes detected, representing novel virus species. A high abundance of orthonairoviruses was notable, including CCHFV, Dugbe virus and a novel Orthonairovirus species that we have named Macira virus. InterpretationTicks in Uganda are an important reservoir of diverse virus species, many of which remain uncharacterised and of unknown pathogenic potential. Author SummaryTicks are parasitic arachnids that may transmit a spectrum of viral diseases to humans and animals. Uganda is a hotspot for such tick-borne diseases. In this study, we sequenced ticks collected from three geographically diverse regions of Uganda using a semi-agnostic next- generation sequencing method in order to detect viruses from all known virus families. We collected and analyzed 2,754 ticks from 31 farms across the country. Within these ticks, we detected 22 species of virus from 15 genera and 9 viral families, including 8 animal or human pathogens and 5 new novel virus species. Notably, orthonairoviruses, including the highly pathogenic Crimean-Congo haemorrhagic fever virus, were highly prevalent in the ticks. The researchers suggest that ticks in Uganda serve as an important reservoir for diverse viruses, many of which have significant pathogenic potential. This information will inform public health efforts to prevent and control tick-borne diseases in Uganda and other similar regions.

microbiology↗

bioRxiv2019

In Silico Analysis of Ixodid Tick Aqauporin-1 Protein as a Candidate Anti-Tick Vaccine Antigen

Ticks are arthropod vectors of pathogens of both Veterinary and Public health importance. Ticks are largely controlled by acaricide application. However, acaricide efficacy is hampered by high cost, the need for regular application and selection of multi-acaricide resistant tick populations. In light of this, future tick control approaches are poised to rely on integration of rational acaricide application and other methods such as vaccination. To contribute to systematic research-guided efforts to produce anti-tick vaccines, we carried out an in silico tick Aquaporin-1 protein (AQP1) analysis to identify unique tick AQP1 peptide motifs that can be used in future peptide anti-tick vaccine development. We used multiple sequence alignment (MSA), motif analysis, homology modeling, and structural analysis to identify unique tick AQP1 peptide motifs. BepiPred, Chou & Fasman-Turn, Karplus & Schulz Flexibility and Parker-Hydrophilicity prediction models were used to asses these motifs abilities to induce antibody mediated immune responses. Tick AQP1 (MK334178) protein homology was largely similar to the bovine AQP1 (PDB:1J4N) (23% sequence similarity; Structural superimposition RMS=1.475). The highest similarities were observed in the transmembrane domains while differences were observed in the extra and intra cellular protein loops. Two unique tick AQP1 (MK334178) motifs, M7 (residues 106-125, p=5.4e-25) and M8 (residues 85-104, p=3.3e-24) were identified. These two motifs are located on the extra-cellular AQP1 domain and showed the highest Parker-Hydrophilicity prediction immunogenic scores of 1.153 and 2.612 respectively. The M7 and M8 motifs are a good starting point for the development of potential peptide-based anti-tick vaccine. Further analyses such as in vivo immunization assays are required to validate these findings.

bioinformatics↗