Browsing by Author "Biryomumaisho, Savino"
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Item Diatomaceous Earth Usage in The Agriculture Sector in Uganda And Its Characterization: Current Status and Anticipated Developments(Journal of Agricultural Science and Food Technology, 2019) Isabirye, Robert Alex; Waiswa, Charles; Kabi, Fred; Nanyeenya, William N.; Biryomumaisho, Savino; Acai-Okwee, James; Okello, Samuel; Omonuk Akello, Beatrice; Mwesigwa, Moses; Lumu, Richard; Nasinyama, George WilliamThe study was conducted in the districts of Nebbi, Wakiso and Gomba in Uganda to characterize Diatomaceous Earth (DE) from the 3 major deposits in Uganda; explore status of exploitation and usage in agriculture, and anticipate associated effects. DE aka diatomite originated from fossilized remains of diatom shells. In agriculture, it’s used in controlling livestock internal and external parasites; post-harvest crop insect pests; and aflatoxins in stored feeds. DE has silica, Ca, Na, Mg, Fe, and other trace minerals making it valuable. Unlike synthetic drugs, DE is safer to consumers. Data collection employed both qualitative and quantitative approaches. Most respondents (94.6%) didn’t know of any agricultural DE usage, and the remaining (5.4%) knew it as a remedy against post-harvest weevils in stored grains. Residents in the mining area used DE in painting houses; craved by pregnant women; and relieving diarrhea in humans. Characterization revealed that Ugandan DE deposits were premium for various purposes. No commercial DE exploitation had started however when it’s due, the government would guide regulatory framework. Additionally, the socio-economic transformation was anticipated through employment creation; and foreign exchange. Since DE’s availability in Uganda is confirmed, more research and programs to promote its exploitation are needed.Item Efficacy of Diatomaceous Earth on Ascaridia galli, Blood Parameters: And on Ectoparasites In Chicken(Journal of Agricultural Science and Food Technology, 2019) Isabirye, Robert Alex; Waiswa, Charles; Kabi, Fred; Nanyeenya, William N.; Biryomumaisho, Savino; Acai-Okwee, James; Okello, Samuel; Omonuk Akello, Beatrice; Mwesigwa, Moses; Lumu, Richard; Nasinyama, George WilliamThe efficacy of diatomaceous earth (DE) in the treatment of chicken against Ascaridia galli and ectoparasites; and its effect on blood parameters in chicken was investigated. Four hundred hens were divided into 5 treatment groups, A, B, C, D and E (n = 80 per group). Groups C, D and E were orally infected with 250 embryonated A. galli eggs while groups A and B were not. Meanwhile, groups A and C fed diets with 2% DE and group D was fed with piperazine; and groups B and E was neither fed with DE nor piperazine. Fecal samples and blood samples were analyzed at week 16 to 22 and; 16 and 36, respectively for fecal egg counts (FEC) and blood parameters (erythrocyte count, hemoglobin content and hematocrit value), respectively. In another experiment, to assess efficacy of DE in treating poultry ectoparasites (fleas, mites and lice) DE was topically applied. Results from biweekly fecal analyses showed significant differences in FEC (P<0.05); and treatment by group (P<0.05) implying that DE had a significant effect in treating A. galli. No significant effects on hematological values were noted (P>0.05). Findings from ectoparasite trials indicated that at certain time points DE eliminated all targeted parasites (efficacy =100%). This study concludes that DE has the potential to control A. galli; and ectoparasites in chicken. Further studies should target effect of DE on internal parasite dynamics for longer periods in chicken. Additionally, to quicken the action of DE against ectoparasites, organic approaches should be studied.Item Emerging Anthelmintic Resistance in Poultry: Can Ethnopharmacological Approaches Offer a Solution?(Frontiers in pharmacology, 2021) Zirintunda, Gerald; Biryomumaisho, Savino; Kasozi, Keneth Iceland; Kateregga, John; Vudriko, Patrick; Nalule, Sarah; Olila, Deogracious; Kajoba, Mariam; Matama, Kevin; Kwizera, Mercy Rukundo; Abdelgawad, Mohamed A.; Acai-Okwee, JamesLimited pharmacological studies have been conducted on plant species used against poultry helminths. The objective of this study was to provide a basis for plant based anthelmintics as possible alternatives against poultry anthelmintic resistance. The study justified the need for alternative anthelmintics. The study places emphasis on the increasing anthelmintic resistance, mechanism of resistance, and preparational protocols for plant anthelmintics and their associated mechanism of action. Pharmaceutical studies on plants as alternative therapies for the control of helminth parasites have not been fully explored especially in several developing countries. Plants from a broad range of species produce a wide variety of compounds that are potential anthelmintics candidates. Important phenolic acids have been found in Brassica rapa L. and Terminalia avicenniodes Guill. and Perri that affect the cell signaling pathways and gene expression. Benzo (c) phenanthridine and isoquinoline alkaloids are neurotoxic to helminths. Steroidal saponins (polyphyllin D and dioscin) interact with helminthic mitochondrial activity, alter cell membrane permeability, vacuolation and membrane damage. Benzyl isothiocyanate glucosinolates interfere with DNA replication and protein expression, while isoflavones from Acacia oxyphylla cause helminth flaccid paralysis, inhibit energy generation, and affect calcium utilization. Condensed tannins have been shown to cause the death of nematodes and paralysis leading to expulsion from the gastro-intestinal tract. Flavonoids from Chenopodium album L and Mangifera indica L act through the action of phosphodiesterase and Ca2+-ATPase, and flavonoids and tannins have been shown to act synergistically and are complementary to praziquantel. Artemisinins from Artemisia cina O. Berg are known to disrupt mitochondrial ATP production. Terpenoids from Cucurbita moschata L disrupt neurotransmission leading to paralysis as well as disruption of egg hatching. Yeast particle encapsulated terpenes are effective for the control of albendazole-resistant helminths.Item Livestock Trypanosomosis In Uganda: Parasite Heterogeneity And Anaemia Status Of Naturally Infected Cattle, Goats And Pigs(Parasitology research, 2013) Biryomumaisho, Savino; Rwakishaya, Eli-Katunguka; Melville, Sara Elizabeth; Cailleau, Aurélie; Lubega, George WilliamThe prevalence and pathogenic effects of trypanosomosis were determined in cattle, goats and pigs reared in Kasese, Jinja and Rakai districts, Uganda; presence of trypanosomes was detected by buffy coat technique (BCT). The overall prevalence of trypanosomosis in cattle was 7.6 % (144/1,891), 0.7 % in goats (4/573) and 2.3 % in pigs (9/386). Internal transcribed spacer 1 (ITS1) of ribosomal DNA polymerase chain reaction was utilised to identify trypanosomes to species level and revealed infections in 108 of the 144 trypanosome-positive cattle while all infected goats and pigs gave amplicons. Trypanosoma vivax was the most prevalent trypanosome species in cattle in single and mixed infections compared to infections involving Trypanosoma congolense and Trypanosoma brucei; in pigs, eight were mixed infections with one single T. vivax infection. No predominant trypanosome species was detected in goats. Anaemia, the main trypanosomosis pathological feature, was investigated by determining packed cell volume (PCV). Mean PCV values by t test in infected individuals were significantly lower than non-infected individuals (P < 0.05) for all animal species. However, the proportion of anaemic animals was not significantly different in infected and non-infected individuals. In addition, the percent of infected animals by Fisher’s exact test depended on district of origin and species but not sex. These findings show that trypanosomosis is a major cause of anaemia in livestock in endemic areas. Cattle were the major animal species affected by trypanosomosis; similar genotypes of trypanosomes were detected in the three animal species. BCT was more effective than ITS1 rDNA detecting trypanosomes in naturally infected cattle.Item Molecular detection and characterization of emerging pathogens of Rickettsia- felis and felis-like organisms from peri-domestic eas in Uganda(Research Article, 2023) Eneku, Wilfred; Erima, Bernard; Maranda Byaruhanga, Anatoli; Nora, G. Cleary; Atim, Gladys; Tugume, Titus; Ukuli, Qouilazoni A.; Kibuuka, Hannah; Mworozi, Edison; Christina Douglas; Jeffrey W. Koehler; Michael E. Fricken; Biryomumaisho, Savino; Matovu, Enock; Tweyongyere, Robert; Wabwire-Mangen, Fred; Byarugaba, Denis K.Background: Flea-borne spotted fever is an emerging zoonosis caused by Rikecttsia felis, a Gram-negative obligate intracellular bacterium. The agent is believed to be cosmopolitan, following the distribution pattern of its host and reservoir, Ctenocephalides felis. However, the epidemiology and public health risk it poses remains poorly understood in sub-Saharan Africa, including Uganda. Yersinia pestis, is primarily transmitted by rodent fleas, Xenopsylla cheopis, but other fleas, particularly C. felis, have vectoral capacity. They are neglected in Ugandan entomological surveillance and public health practices, particularly outside endemic foci of bubonic plague. Methods: We collected 14,641 fleas from domestic animals, rodents and homestead environment; compared their diversity and abundance. Pooled into 714 flea pools by species, collection time, host, and host species, 172 pools were selected based on seasons and analyzed for Yersinia pestis Pla genes, while 62 pools were tested for Rickettsia species gltA, ompA, and 17kDA genes by qPCR and Sanger sequencing. Results: Five flea species were identified from the collections: Ctenocephalides canis, C. felis, Echidnophaga gallinacea, Pulex irritans, and Xenopsylla cheopis. Ctenocephalides was the predominant genus, accounting for 84.8% of fleas collected, mostly found on dogs and goats. Except for P. irritans (which was found in Gulu district) the other four flea species were found across all districts, year-round, with higher numbers collected in dry seasons compared to rainy seasons (c2=47.64, df=20, p<0.001). Rattus rattus constituted 74% of rodents captured from human dwellings and was the only rodent species with fleas, where X. cheopis was the predominant species and E. gallinacea found on only three rodents. All 172 pools of fleas tested negative for Yersinia pestis. Of the 62 pools tested for Rickettsia spp., 29 (46.8%) were positive. Twenty-five PCR amplicons were successfully sequenced for 17kDa and two for ompA genes. Based on 17kDa, two were identified as R. felis from C. canis and 23 were R. asembonensis from multiple flea species, including C. canis collected goats and C. felis from cats. Conclusion: Our survey identified a high pooled detection rate (~50%) of Rickettsia spp. in fleas tested, suggesting a potential risk of human exposure and infection. Rickettsia felis and R. asembonensis were the predominant flea-borne Rickettsia spp. identified, with this study also representing the first report of Rickettsia spp. in E. gallinacea in Uganda.Item Schistosoma mansoni coinfection is associated with high Plasmodium falciparum infection intensity among 10 -15 year old children living along the Albert Nile in Uganda(Research Sqaure, 2024) Namulondo, Joyce; Nyangiri, Oscar Asanya; Kimuda, Magambo Phillip; Nambala, Peter; Nassuuna, Jacent; Kabagenyi, Joyce; Egesa, Moses; Nerima, Barbara; Biryomumaisho, Savino; Mugasa, Claire Mack; Alison, Elliott; Harry, Noyes; Tweyongyere, Robert; Matovu, Enock; Mulindwa, JuliusBackground: Malaria and schistosomiasis are important parasitic diseases. Coinfections of these have been reported in areas endemic to both parasites. The aim of this study was to determine the association between Schistosoma mansoni (S. mansoni) and Plasmodium falciparum (P. falciparum) infection intensities among school age children living along the Albert Nile. Methods: A cross sectional study of 210 children aged 10–15 years, was conducted in selected sites along the Albert Nile in Pakwach District in northwest Uganda. The Circulating Anodic Antigen (CAA) test and quantitative PCR (qPCR) were used to test for S. mansoni infection intensity and quantitative PCR used to test for P. falciparum infection intensity. Results: Of the 210 study particpants, 76.2% (160/210) were malaria positive whereas 91% (191/210) were S. mansoni positive. There were only 1% (3/210) infections of each of Necator americanus and Strongyloides stercolaris. Of the P. falciparum positive children 57.5% (92/160) were male; on the other hand 53.4% (102/191) of the S. mansoni positive children were male. Overall, 150 of the 210 children tested (71%) had co-infection with both P. falciparum and S. mansoni. There was a significant association (p-value = 7.306e-10, r2 = 0.17) between P. falciparum qPCR Ct-value and S. mansoni qPCR Ct-value. There was a significant association (p-value = 7.306e-10, r2 = 0.17) between P. falciparum intensity (qPCR Ct-value) and S. mansoni intensity (qPCR Ct-value) among the children test. Conclusions: By molecular detection, this study observed a high prevalence of P. falciparum among the school age children (10–15 years) living in the S. mansoni endemic hotspots along the Albert-Nile region of Pakwach district, northwestern Uganda.Item Seroprevalence of Q-fever, spotted fever, typhus group Rickettsia and Orientia among febrile patients visiting hospital-based sentinel sites in Uganda(PAMJ - One Health, 2023) Eneku, Wilfred; Erima, Bernard; Byaruhanga, Anatoli Maranda; Nora, Gillian Cleary; Atim, Gladys; Tugume, Titus; Ukuli, Qouilazoni Aquino; Kibuuka, Hannah; Mworozi, Edison; Christina, Douglas; Jeffrey, William Koehler; Michael, Emery von Fricken; Biryomumaisho, Savino; Tweyongyere, Robert; Wabwire-Mangen, Fred; Byarugaba, Denis KaruhizeIntroduction: rickettsioses are emerging zoonotic febrile illnesses transmitted to humans by ticks, fleas, lice, and mites. Q-fever, Spotted fever group (SFG), Typhus group (TG) rickettsia and Scrub typhus (STG) have been reported with varying prevalence across East Africa. However, little is known about the burden of exposure in Uganda. The aim of this study was to determine the seroprevalence and associated risk factors of rickettsial diseases in Uganda. Methods: a total of 460 archived serum samples collected from patients with fever of unknown origin after screening across five hospital-based sentinel sites were analysed. The samples were collected during 18-month period of active surveillance for acute febrile illnesses, from January 2018 through June 2019. We performed IgM ELISA tests on the 460 sera for SFG and TG rickettsia, IgM IFA for STG and Phase 2 IgG ELISA for Q-fever. We also assessed risk factors associated with the serostatus. Results: the population comprised predominantly children, had balanced gender proportions, with 66% coming from rural areas. The overall seroprevalence of SFG rickettsiosis was 6.3%; however, 11.5% and 10.8% prevalence rates were observed in Gulu and Bwera hospitals respectively. This was higher than the 3.7% observed in the capital city Kampala, although the differences were not statistically significant (Fisher's exact = 0.489). Overall seropositivity of Q-fever was 7.6%, although Bwera Hospital had the highest rate (12.5%) and Mulago had the lowest rate (2%). The differences were not considered statistically significant (Fishers exact= 0.075). Increasing age (OR-adjusted=1.4, 95%CI=1.0-1.9, p=0.026) and rural background (OR-adjusted=2.6, 95%CI=1.6- 6.4, p=0.037) were both significantly associated with seropositivity for Q-fever, while only increasing age had higher odds for seropositivity for SFG rickettsia (OR-adjusted= 1.9, 95% CI= 1.4- 2.6, p<0.001). One serum sample of a 10-monthold male from Bwera hospital was reactive to both SFG and Q-fever antibodies. We found four sera reactive cases to typhus group IgM and another four reactive to Orientia spp. IgM. However, we were not able to determine associating factors due to low seropositivity rates. Conclusion: here, we report for the first time the seroprevalence of Qfever, SFG and STG in febrile patients in Uganda. This report also provides the second study in over five decades since the earliest report of TG rickettsia. Testing for these pathogens in patients with acute febrile illness with unknown etiology may hold value, however more studies are required to provide information on disease ecology, risk factors, and transmission dynamics of these pathogens in Uganda.Item Spatio-temporal analysis of sheep and goat pox outbreaks in Uganda during 2011–2022(BMC Veterinary Research, 2023) Nizeyimana, Gerald; Vudriko, Patrick; Erume, Joseph; Mubiru, Frank; Eneku, Wilfred; Biryomumaisho, Savino; Mwebe, Robert; Arinaitwe, Eugene; Rose, Ademun; Atim, Stella; Ayebazibwe, Chrisostom; Muhanguzi, Dennis; Tweyongyere, RobertBackground Sheep and goat pox (SGP) caused by sheep poxvirus (SPV) and goat poxvirus (GPV) respectively; are transboundary and World Organisation for Animal Health (WOAH)-notifiable viral diseases. There is barely any coherent information about the distribution and prevalence of SGP for Uganda. We therefore conducted this study to describe the temporal and spatial distribution of SGP suspected outbreaks in Uganda for the period 2011–2020 as well as serologically confirm presence of SGP antibodies in suspected SGP outbreaks reported in 2021–2022. Results Thirty-seven [37] SGP outbreaks were reported across the country during the study period. North-eastern region [that comprises of Karamoja region] had the highest number of outbreaks [n = 17, 45%]; followed by Central [n = 9, 2.4%], Northern [n = 8, 2.2%] and Western region [n = 3, 0.08%]. Reports from district veterinary personnel indicate that the prevalence of; and mortality rate and case fatality rate associated with SGP were 0.06%, 0.02% and 32% respectively. There was a steady increase in the number of reported SGP outbreaks [x̄ = 4] over the study period. Seropositivity of SGPV antibodies in outbreak sheep and goats that were investigated during the study period [2021–2022] was [n = 41, 27%, 95 CI;] Conclusion Our analyses of SGPV passive and active reports indicate that SGP is present in Uganda with a decade long average of four outbreaks per annum. During this period, about a third of all SGPV-clinically infected animals died. SPG is therefore a major constraint to small ruminant health and productivity in Uganda. Introduction of animals from infected herds and breach in farm biosecurity were the most important predictors of SGP outbreaks. In addition to the already existing SGP commercial vaccines, small ruminant screening for SGPV before introducing them to naïve herds and ensuring on farm biosecurity should be part of the SGP control tool pack for Ugandan small ruminant farmers.Item The danger of free roaming dogs in urban settings: A report of two suspected rabid dogs on rampage that inicted 47 bites to people and domestic animals in peri-urban Uganda(Reseaech Sqaure, 2023) Tayebwa, Dickson; Njalira, Kassim Rashid; Eneku, Wilfred; Ssekandi, Colin; Kyabarongo, Alex; Mutesasira, Jesse; Komugisha, Mariam; Atim, Stella Acaye; Kateregga, John; Muhangi, Denis; Tweyongyere, Robert; Tony, Lawrence Goldberg; Biryomumaisho, Savino; Okwee Acai, JamesBackground Human rabies cases associated with bites from rabid roaming dogs are prevalent in Uganda. Unfortunately, there is limited documentation of the circumstances surrounding those bites. Here, we documented dog attacks to humans and animals in two peri-urban areas in Central Uganda. Methods We responded to alerts of two suspected rabid dogs on rampage. We traced the dogs responsible for the attacks to diagnose the cause of the aggression and we interviewed the victims and community members to determine the circumstances of the bites and health care sought by the victims. We scheduled follow-up visits after 40 days, to assess compliance of the victims to rabies postexposure prophylaxis (PEP) and to document any challenges encountered in the process. Results The two rabid dogs inflicted 47 recorded attacks to 29 humans, mostly children (75.8%) and 18 domestic animals in Matugga and Mawale parishes in Wakiso and Luweero districts, respectively. Two individuals washed the wound with water and 7 individuals reported to the health facility for treatment in accordance with the WHO-guidelines for preclinical management of bites from suspected rabies cases. By contrast, 17 individuals sought treatment from a traditional healer while 5 individuals self-medicated with herbs at home. We advised those individuals to visit health facilities for proper medical care. All the victims started rabies PEP treatment; however, 2 individuals did not complete their prescription. Although rabies PEP at public health facilities was free, regularly the victims paid 3–5 USD to the clinician as an incentive while the cost at private health facilities was 13–15 USD for a single dose. Due to the unprovoked attacks, the victims and local leaders advocated for elimination of roaming dogs, but the roaming dog owners objected. Conclusions Overall, our results demonstrate the outsized impact that a single-rabid dog can have on a community. They also reveal how poverty, knowledge gaps, community trust in traditional healers, and barriers to healthcare access negatively affect medical care given to dog bite victims in this setting. Educational campaigns and control of roaming dogs should help improve the situation in Central Uganda, as well as in other socioeconomically similar settings.Item The danger of free-roaming dogs in peri urban settings: Two rabid dogs on rampage that bit 29 humans and 18 domestic animals in Wakiso and Luweero districts, Central Uganda(Research Square, 2024) Tayebwa, Dickson Stuart; Njalira, Kassim Rashid; Eneku, Wilfred; Ssekandi, Colin; Kyabarongo, Alex; Mutesasira, Jesse; Komugisha, Mariam; Atim, Stella Acaye; Kateregga, John; Muhangi, Denis; Tweyongyere, Robert; Biryomumaisho, Savino; Okwee Acai, JamesBackground Uganda averages 14,000 dog bites annually, with 86% caused by free-roaming dogs. Unfortunately, there is limited documentation to inform interventions. Here, we documented circumstances of attacks from free-roaming dogs on rampage in Central Uganda to identify critical gaps in the detection, preparedness, and response of the community. Methods We conducted an exploratory case study to actively survey attacks from rampaging dogs in Kampala Metropolitan Area, Central Uganda between November 2022 - November 2023. We traced the dogs responsible to immobilise and rule out rabies. We interviewed the victims and community to determine the circumstances of the bites, the healthcare sought and sentiments towards free-roaming dogs. We followed-up after 40 days, to assess adherence to rabies post exposure prophylaxis and to document any challenges encountered. Results Of the 8 cases reported, only two cases that occurred in Matugga and Mawale parishes fulfilled our criteria for rampage while the rest were predation, an incidental bite and straying into someone’s residence. The two rampaging dogs’ bit 29 humans, mostly children (75.8%) and 18 domestic animals. Immobilisation in Matugga failed while the dog in Mawale was killed by the community in a mob. Due to limited knowledge, 93.1% of the victims did not wash the wound and go the medical facility as recommended by WHO. Instead, they sought healthcare from the traditional healer (58.6%), stayed home or applied herbs (20.7%). Parallel with our advice, those victims sought medical care however they encountered challenges not limited to lack of funds and poor services at public health facilities. After inflicting bites, the dogs responsible and other free-roaming dogs were killed by hitting them with sticks in a mob. Conclusions Overall, our findings demonstrate the impact that a lone free-roaming dog with rabies can have on a community. They also reveal how poverty, limited awareness, reliance on traditional healers, and barriers to medical care access impede health care received by dog bite victims in this setting. Implementing educational campaigns and responsible ownership of free-roaming dogs should help reduce dog bites and rabies in Central Uganda, as well as in other socioeconomically similar settings.Item Transcriptome analysis of peripheral blood of Schistosoma mansoni infected children from the Albert Nile region in Uganda reveals genes implicated in fibrosis pathology(PLOS NEGLECTED TROPICAL DISEASES, 2023) Namulondo, Joyce; Nyangiri, Oscar Asanya; Kimuda, Magambo Phillip; Nambala, Peter; Nassuuna, Jacent; Egesa, Moses; Nerima, Barbara; Biryomumaisho, Savino; Mugasa, Claire Mack; Nabukenya, Immaculate; Kato, Drago; Alison, Elliott; Harry, Noye; Tweyongyere, Robert; Matovu, Enock; Mulindwa, JuliusOver 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. 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.Item Transcriptome analysis of peripheral blood of Schistosoma Mansoni Infected Children from the Albert Nile Region in Uganda Reveals Genes Implicated in Fibrosis Pathology.(bioRxiv, 2023) Namulondo, Joyce; Nyangiri, Oscar Asanya; Kimuda, Magambo Phillip; Nambala, Peter; Nassuuna, Jacent; Egesa, Moses; Nerima, Barbara; Biryomumaisho, Savino; Nabukenya, Immaculate; Drago, Kato; Tweyongyere, Robert; Matovu, Enock; Mulindwa, Julius; Mugasa, Claire MackOver 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.Item Transcriptome profiling reveals genes associated with inflammation and fibrosis among 10 - 15-yearold children with Schistosoma mansoni and Plasmodium falciparum coinfection along the Albert Nile in Uganda(Research Square, 2024) Namulondo, Joyce; Nyangiri Oscar Asanya; Nyangiri, Magambo Phillip Kimuda; Nambala, Peter; Nassuuna, Jacent; Kabagenyi, Joyce; Egesa, Moses; Nerima, Barbara; Biryomumaisho, Savino; Mugasa, Claire Mack; Harry, Noyes; Tweyongyere, Robert; Matovu, Enock; Mulindwa, JuliusBackground: Malaria and schistosomiasis are significant parasitic diseases in Uganda and coinfections with the two are not uncommon in areas endemic to both parasites. The aim of this study was to determine the effect of P. falciparum and S. mansoni coinfection on the gene expression in peripheral blood of school age children aged between 10–15 years. Methods: A cross sectional study of children aged 10–15 years, was conducted in selected sites along the Albert Nile in Pakwach District in northwest Uganda. Quantitative PCR (qPCR) was used to test for S. mansoni and P. falciparum infection. Furthermore samples that were sequenced using Illumina NovaSeq S4 and the reads aligned to the GRCh38 human genome were matched with those with S. mansoni and P. falciparum qPCR results. Differential gene expression analysis was done using DESeq2. Results: Of the 210 study particpants, 76.2% (160/210) were P. falciparum positive, 91% (191/210) were S. mansoni positive and 150 (71%) had coinfection with both P. falciparum and S. mansoni, which was slightly fewer coinfections than expected by chance (Fisher exact test p-value of 0.02). RNAseq data was obtained for 33 participants of which 17 had P. falciparum and S. mansoni coinfection, 4 S. mansoni infection only, 1 had P. falciparum infection only while 11 were uninfected. Principal component analysis revealed clustering of gene expression by gender and infection status when S. mansoni and P. falciparum coinfected children were compared with uninfected children. We observed 15 DEGs of which 2 (CEPT1 and RETREG1) were downregulated and 13 (GAS6, DEXI, PALMD, SAMD15 AC138028.4, GFOD1-AS1, AC034102.6, AC005153.1, AC020914.1, AC017028.2, AC244502.3, AC013486.1, AC106760.1) upregulated when S. mansoni and P. falciparum coinfected children were compared with uninfected children. The differentially expressed genes are associated with inflammation and fibrosis and also included regulatory long noncoding RNA. Conclusions: By molecular detection, this study observed a high prevalence of P. falciparum among the school age children (10–15 years) living in the S. mansoni endemic hotspots along the Albert-Nile region of Pakwach district, northwestern Uganda. The study shows differential expression of genes associated with inflammation and fibrosis among coinfected when compared to the uninfected children.