Browsing by Author "Kizito, Dennison"
Now showing 1 - 12 of 12
Results Per Page
Sort Options
Item Associations between mild-to-moderate anaemia in pregnancy and helminth, malaria and HIV infection in Entebbe, Uganda(Transactions of the Royal Society of Tropical Medicine and Hygiene, 2017) Muhangi, Lawrence; Woodburna, Patrick; Omara, Mildred; Omoding, Nicholas; Kizito, Dennison; Mpairwe, Harriet; Nabulime, Juliet; Ameke, Christine; Morison, Linda A.; Elliott, Alison M.It is suggested that helminths, particularly hookworm and schistosomiasis, may be important causes of anaemia in pregnancy. We assessed the associations between mildto-moderate anaemia (haemoglobin >8.0 g/dl and HIV among 2507 otherwise healthy pregnant women at enrolment to a trial of deworming in pregnancy in Entebbe, Uganda. The prevalence of anaemia was 39.7%. The prevalence of hookworm was 44.5%, Mansonella perstans 21.3%, Schistosoma mansoni 18.3%, Strongyloides 12.3%, Trichuris 9.1%, Ascaris 2.3%, asymptomatic Plasmodium falciparum parasitaemia 10.9% and HIV 11.9%. Anaemia showed little association with the presence of any helminth, but showed a strong association with malaria (adjusted odds ratio (AOR) 3.22, 95% CI 2.43—4.26) and HIV (AOR 2.46, 95% CI 1.90—3.19). There was a weak association between anaemia and increasing hookworm infection intensity. Thus, although highly prevalent, helminths showed little association with mild-to-moderate anaemia in this population, but HIV and malaria both showed a strong association. This result may relate to relatively good nutrition and low helminth infection intensity. These findings are pertinent to estimating the disease burden of helminths and other infections in pregnancy. [Clinical Trial No. ISRCTN32849447]Item The Effect of Current Schistosoma Mansoni Infection on the Immunogenicity of A Candidate TB vaccine, MVA85A, in BCG Vaccinated Adolescents: An open-label trial(PLoS neglected tropical diseases, 2017) Wajja, Anne; Kizito, Dennison; Nassanga, Beatrice; Nalwoga, Angela; Kabagenyi, Joyce; Kimuda, Simon; Galiwango, Ronald; Mutonyi, Gertrude; Vermaak, Samantha; Tukahebwa, Edridah; McShane, HelenHelminth infection may affect vaccine immunogenicity and efficacy. Adolescents, a target population for tuberculosis booster vaccines, often have a high helminth burden. We investigated effects of Schistosoma mansoni (Sm) on the immunogenicity and safety of MVA85A, a model candidate tuberculosis vaccine, in BCG-vaccinated Ugandan adolescents.In this phase II open label trial we enrolled 36 healthy, previously BCG-vaccinated adolescents, 18 with no helminth infection detected, 18 with Sm only. The primary outcome was immunogenicity measured by Ag85A-specific interferon gamma ELISpot assay. Tuberculosis and schistosome-specific responses were also assessed by whole-blood stimulation and multiplex cytokine assay, and by antibody ELISAs.Ag85A-specific cellular responses increased significantly following immunisation but with no differences between the two groups. Sm infection was associated with higher pre-immunisation Ag85A-specific IgG4 but with no change in antibody levels following immunisation. There were no serious adverse events. Most reactogenicity events were of mild or moderate severity and resolved quickly.The significant Ag85A-specific T cell responses and lack of difference between Sm-infected and uninfected participants is encouraging for tuberculosis vaccine development. The implications of pre-existing Ag85A-specific IgG4 antibodies for protective immunity against tuberculosis among those infected with Sm are not known. MVA85A was safe in this population.Item Effect of single-dose anthelmintic treatment during pregnancy on an infant’s response to immunisation and on susceptibility to infectious diseases in infancy: a randomised, double-blind, placebo-controlled tria(The Lancet, 2011) Webb, Emily L.; Mawa, Patrice A; Ndibazza, Juliet; Kizito, Dennison; Nanteza, Bridget; Nampijja, Margaret; Muhangi, LawrenceHelminth infections affect the human immune response. We investigated whether prenatal exposure to and treatment of maternal helminth infections affects development of an infant's immune response to immunisations and unrelated infections. In this randomised, double-blind, placebo-controlled trial, we enrolled 2507 women in the second or third trimester of pregnancy who were planning to deliver in Entebbe General Hospital, Entebbe, Uganda. With a computer-generated random number sequence in blocks of 100, we assigned patients to 440 mg albendazole and 40 mg/kg praziquantel (n=628), 440 mg albendazole and a praziquantel-matching placebo (n=625), 40 mg/kg praziquantel and an albendazole-matching placebo (n=626), or an albendazole-matching placebo and praziquantel-matching placebo (n=628). All participants and hospital staff were masked to allocation. Primary outcomes were immune response at age 1 year to BCG, tetanus, and measles immunisation; incidence of infectious diseases during infancy; and vertical HIV transmission. Analysis was by intention-to-treat. This trial is registered, number ISRCTN32849447.Item Effect of single-dose anthelmintic treatment during pregnancy on an infant’s response to immunisation and on susceptibility to infectious diseases in infancy: a randomised, double-blind, placebo-controlled trial(The Lancet,, 2011) Webb, Emily L.; Mawa, Patrice A.; Ndibazza, Juliet; Kizito, Dennison; Namatovu, Alice; Kyosiimire-Lugemwa, Jacqueline; Nanteza, Bridget; Nampijja, Margaret; Muhangi, Lawrence; Woodburn, Patrick W; Akurut, Hellen; Mpairwe, Harriet; Akello, Miriam; Lyadda, Nancy; Bukusuba, Joseph; Kihembo, Macklyn; Kizza, Moses; Kizindo, Robert; Nabulime, Juliet; Ameke, Christine; Namujju, Proscovia B.; Tweyongyere, Robert; Muwanga, Moses; Whitworth, James A. G.; Elliott, Alison M.Helminth infections affect the human immune response. We investigated whether prenatal exposure to and treatment of maternal helminth infections affects development of an infant's immune response to immunisations and unrelated infections.In this randomised, double-blind, placebo-controlled trial, we enrolled 2507 women in the second or third trimester of pregnancy who were planning to deliver in Entebbe General Hospital, Entebbe, Uganda. With a computer-generated random number sequence in blocks of 100, we assigned patients to 440 mg albendazole and 40 mg/kg praziquantel (n=628), 440 mg albendazole and a praziquantel-matching placebo (n=625), 40 mg/kg praziquantel and an albendazole-matching placebo (n=626), or an albendazole-matching placebo and praziquantel-matching placebo (n=628). All participants and hospital staff were masked to allocation. Primary outcomes were immune response at age 1 year to BCG, tetanus, and measles immunisation; incidence of infectious diseases during infancy; and vertical HIV transmission. Analysis was by intention-to-treat. This trial is registered, number ISRCTN32849447.Data were available at delivery for 2356 women, with 2345 livebirths; 2115 (90%) of liveborn infants remained in follow-up at 1 year of age. Neither albendazole nor praziquantel treatments affected infant response to BCG, tetanus, or measles immunisation. However, in infants of mothers with hookworm infection, albendazole treatment reduced interleukin-5 (geometric mean ratio 0·50, 95% CI 0·30–0·81, interaction p=0·02) and interleukin-13 (0·52, 0·34–0·82, 0·0005) response to tetanus toxoid. The rate per 100 person-years of malaria was 40·9 (95% CI 38·3–43·7), of diarrhoea was 134·1 (129·2–139·2), and of pneumonia was 22·3 (20·4–24·4). We noted no effect on infectious disease incidence for albendazole treatment (malaria [hazard ratio 0·95, 95% CI 0·79–1.14], diarrhoea [1·06, 0·96–1·16], pneumonia [1·11, 0·90–1·38]) or praziquantel treatment (malaria [1·00, 0·84–1·20], diarrhoea [1·07, 0·98–1·18], pneumonia [1·00, 0·80–1·24]). In HIV-exposed infants, 39 (18%) were infected at 6 weeks; vertical transmission was not associated with albendazole (odds ratio 0·70, 95% CI 0·35–1·42) or praziquantel (0·60, 0·29–1·23) treatment.These results do not accord with the recently advocated policy of routine antenatal anthelmintic treatment, and the value of such a policy may need to be reviewed.Item Effect of single-dose anthelmintic treatment during pregnancy on an infant’s response to immunization and on susceptibility to infectious diseases in infancy: a randomized, double-blind, placebo-controlled trial(The Lancet, 2011) Webb, Emily L; Mawa, Patrice A; Ndibazza, Juliet; Kizito, Dennison; Namatovu, Alice; Kyosiimire-Lugemwa, Jacqueline; Nanteza, Bridget; Nampijja, Margaret; Muhangi, Lawrence; Woodburn, Patrick W; Akurut, Hellen; Mpairwe, Harriet; Akello, Miriam; Lyadda, Nancy; Bukusuba, Joseph; Kihembo, Macklyn; Kizza, Moses; Kizindo, Robert; Nabulime, Juliet; Ameke, Christine; Namujju, Proscovia B; Tweyongyere, Robert; Muwanga, Moses; Whitworth, James A G; Elliott, Alison MHelminth infections aff ect the human immune response. We investigated whether prenatal exposure to and treatment of maternal helminth infections aff ects development of an infant’s immune response to immunisations and unrelated infections. Methods In this randomised, double-blind, placebo-controlled trial, we enrolled 2507 women in the second or third trimester of pregnancy who were planning to deliver in Entebbe General Hospital, Entebbe, Uganda. With a computergenerated random number sequence in blocks of 100, we assigned patients to 440 mg albendazole and 40 mg/kg praziquantel (n=628), 440 mg albendazole and a praziquantel-matching placebo (n=625), 40 mg/kg praziquantel and an albendazole-matching placebo (n=626), or an albendazole-matching placebo and praziquantel-matching placebo (n=628). All participants and hospital staff were masked to allocation. Primary outcomes were immune response at age 1 year to BCG, tetanus, and measles immunisation; incidence of infectious diseases during infancy; and vertical HIV transmission. Analysis was by intention-to-treat. This trial is registered, number ISRCTN32849447. Findings Data were available at delivery for 2356 women, with 2345 livebirths; 2115 (90%) of liveborn infants remained in follow-up at 1 year of age. Neither albendazole nor praziquantel treatments aff ected infant response to BCG, tetanus, or measles immunisation. However, in infants of mothers with hookworm infection, albendazole treatment reduced interleukin-5 (geometric mean ratio 0·50, 95% CI 0·30–0·81, interaction p=0·02) and interleukin-13 (0·52, 0·34–0·82, 0·0005) response to tetanus toxoid. The rate per 100 person-years of malaria was 40·9 (95% CI 38·3–43·7), of diarrhoea was 134·1 (129·2–139·2), and of pneumonia was 22·3 (20·4–24·4). We noted no eff ect on infectious disease incidence for albendazole treatment (malaria [hazard ratio 0·95, 95% CI 0·79–1.14], diarrhoea [1·06, 0·96–1·16], pneumonia [1·11, 0·90–1·38]) or praziquantel treatment (malaria [1·00, 0·84–1·20], diarrhoea [1·07, 0·98–1·18], pneumonia [1·00, 0·80–1·24]). In HIV-exposed infants, 39 (18%) were infected at 6 weeks; vertical transmission was not associated with albendazole (odds ratio 0·70, 95% CI 0·35–1·42) or praziquantel (0·60, 0·29–1·23) treatment.Item Factors affecting the infant antibody response to measles immunisation in Entebbe-Uganda(BMC public health,, 2013) Kizito, Dennison; Tweyongyere, Robert; Namatovu, Alice; Webb, Emily L.; Muhangi, Lawrence; Lule, Swaib A.; Bukenya, Henry; Cose, Stephen; Elliott, Alison M.Background: Vaccine failure is an important concern in the tropics with many contributing elements. Among them, it has been suggested that exposure to natural infections might contribute to vaccine failure and recurrent disease outbreaks. We tested this hypothesis by examining the influence of co-infections on maternal and infant measles-specific IgG levels. Methods: We conducted an observational analysis using samples and data that had been collected during a larger randomised controlled trial, the Entebbe Mother and Baby Study (ISRCTN32849447). For the present study, 711 pregnant women and their offspring were considered. Helminth infections including hookworm, Schistosoma mansoni and Mansonella perstans, along with HIV, malaria, and other potential confounding factors were determined in mothers during pregnancy and in their infants at age one year. Infants received their measles immunisation at age nine months. Levels of total IgG against measles were measured in mothers during pregnancy and at delivery, as well as in cord blood and from infants at age one year. Results: Among the 711 pregnant women studied, 66% had at least one helminth infection at enrolment, 41% had hookworm, 20% M. perstans and 19% S. mansoni. Asymptomatic malaria and HIV prevalence was 8% and 10% respectively. At enrolment, 96% of the women had measles-specific IgG levels considered protective (median 4274 mIU/ml (IQR 1784, 7767)). IgG levels in cord blood were positively correlated to maternal measles-specific IgG levels at delivery (r = 0.81, p < 0.0001). Among the infants at one year of age, median measles-specific IgG levels were markedly lower than in maternal and cord blood (median 370 mIU/ml (IQR 198, 656) p < 0.0001). In addition, only 75% of the infants had measles-specific IgG levels considered to be protective. In a multivariate regression analysis, factors associated with reduced measles-specific antibody levels in infancy were maternal malaria infection, infant malaria parasitaemia, infant HIV and infant wasting. There was no association with maternal helminth infection. Conclusion: Malaria and HIV infection in mothers during pregnancy, and in their infants, along with infant malnutrition, may result in reduction of the antibody response to measles immunisation in infancy. This re-emphasises the importance of malaria and HIV control, and support for infant nutrition, as these interventions may have benefits for vaccine efficacy in tropical settings.Item Impact of Anthelminthic Treatment in Pregnancy and Childhood on Immunisations, Infections and Eczema in Childhood: A Randomised Controlled Trial(PloS one, 2012) Ndibazza, Juliet; Mpairwe, Harriet; Webb, Emily L.; Mawa, Patrice A.; Nampijja, Margaret; Muhangi, Lawrence; Kihembo, Macklyn; Lule, Swaib A.; Rutebarika, Diana; Apule, Barbara; Akello, Florence; Akurut, Hellen; Oduru, Gloria; Naniima, Peter; Kizito, Dennison; Kizza, Moses; Kizindo, Robert; Tweyongere, Robert; Alcock, Katherine J.; Muwanga, Moses; Alison M., ElliottHelminth infections may modulate immune responses to unrelated pathogens and allergens; these effects may commence prenatally. We addressed the hypothesis that anthelminthic treatment in pregnancy and early childhood would improve responses to immunisation and modulate disease incidence in early childhood with both beneficial and detrimental effects. A randomised, double-blind, placebo-controlled trial was conducted in Entebbe, Uganda [ISRCTN32849447]. In three independent randomisations, 2507 pregnant women were allocated to receive single-dose albendazole or placebo, and praziquantel or placebo; 2016 of their offspring were randomised to receive quarterly singledose albendazole or placebo from age 15 months to 5 years. Primary outcomes were post-immunisation recall responses to BCG and tetanus antigens, and incidence of malaria, diarrhoea, and pneumonia; incidence of eczema was an important secondary outcome. Analysis was by intention-to-treat. Of 2345 live births, 1622 (69%) children remained in follow-up at age 5 years. 68% of mothers at enrolment, and 11% of five-year-olds, had helminth infections. Maternal hookworm and Schistosoma mansoni were effectively treated by albendazole and praziquantel, respectively; and childhood hookworm and Ascaris by quarterly albendazole. Incidence rates of malaria, diarrhoea, pneumonia, and eczema were 34, 65, 10 and 5 per 100 py, respectively. Albendazole during pregnancy caused an increased rate of eczema in the children (HR 1.58 (95% CI 1.15–2.17), p = 0.005). Quarterly albendazole during childhood was associated with reduced incidence of clinical malaria (HR 0.85 (95% CI 0.73–0.98), p = 0.03). There were no consistent effects of the interventions on any other outcome. Routine use of albendazole in pregnancy may not always be beneficial, even in tropical developing countries. By contrast, regular albendazole treatment in preschool children may have an additional benefit for malaria control where helminths and malaria are co-endemic. Given the low helminth prevalence in our children, the effect of albendazole on malaria is likely to be direct.Item The Lake Victoria Island Intervention Study on Worms and Allergy-related diseases (LaVIISWA): Study Protocol for a Randomised Controlled Trial(Trials, 2015) Nampijja, Margaret; Webb, Emily L.; Kaweesa, James; Kizindo, Robert; Namutebi, Milly; Nakazibwe, Esther; Oduru, Gloria; Kabuubi, Prossy; Kabagenyi, Joyce; Kizito, Dennison; Muhangi, Lawrence; Akello, Mirriam; Verweij, Jaco J.; Nerima, Barbara; Tukahebwa, Edridah; Elliott, Alison M.The Hygiene Hypothesis proposes that infection exposure protects against inflammatory conditions. Helminths possess allergen-like molecules and may specifically modulate allergy-related immunological pathways to inhibit responses which protect against them. Mass drug administration is recommended for helminth-endemic communities to control helminth-induced pathology, but may also result in increased rates of inflammation-mediated diseases in resource-poor settings. Immunological studies integrated with implementation of helminth control measures may elucidate how helminth elimination contributes to ongoing epidemics of inflammatory diseases. We present the design of the Lake Victoria Island Intervention Study on Worms and Allergy-related diseases (LaVIISWA), a cluster-randomised trial evaluating the risks and benefits of intensive versus standard anthelminthic treatment for allergy-related diseases and other health outcomes.Item Maternal hookworm modifies risk factors for childhood eczema: results from a birth cohort in Uganda(Pediatric Allergy and Immunology, 2014) Mpairwe, Harriet; Ndibazza, Juliet; Webb, Emily L.; Nampijja, Margaret; Muhangi, Lawrence; Apule, Barbara; Akurut, Hellen; Kizito, Dennison; Kakande, Mohammed; Jones, Frances M.; Fitzsimmons, Colin M.; Muwanga, Moses; Rodrigues, Laura C.; Dunne, David W.; Elliott, Alison M.Worms may protect against allergy. Early-life worm exposure may be critical, but this has not been fully investigated. Objectives: To investigate whether worms in pregnancy and in early childhood are associated with childhood eczema incidence. The Entebbe Mother and Baby Study, an anthelminthic treatment trial, enrolled pregnant women between 2003 and 2005 in Uganda. Mothers were investigated for worms during pregnancy and children annually. Eczema was doctor-diagnosed from birth to age five years. A planned observational analysis was conducted within the trial cohort to investigate associations between worms and eczema. Data for 2345 live-born children were analysed. Hookworm was the most prevalent maternal worm (45%). Childhood worms were less prevalent. Eczema incidence was 4.68/100 person-years. Maternal hookworm was associated with reduced eczema incidence [adjusted hazard ratio (95% confidence interval), p-value: 0.71(0.51–0.99), 0.04] and modified effects of known risk factors for eczema: Dermatophagoides-specific IgE in children was positively associated with eczema incidence if the mother had no hookworm [2.72(1.11–6.63), 0.03], but not if the mother had hookworm [0.41(0.10–1.69), 0.22], interaction p-value = 0.03. Similar interactions were seen for maternal history of eczema {[2.87(1.31–6.27, 0.008) vs. [0.73(0.23–2.30), 0.60], interaction p-value = 0.05}, female gender {[1.82(1.22–2.73), 0.004 vs. [0.96 (0.60–1.53), 0.87], interaction p-value = 0.04} and allergen-specific IgE. Childhood Trichuris trichiura and hookworm were inversely associated with eczema. Maternal hookworm modifies effects of known risk factors for eczema. Mechanisms by which early-life worm exposures influence allergy need investigation. Worms or worm products, and intervention during pregnancy have potential for primary prevention of allergy.Item Retrospective in silico mutation profiling of SARS-CoV-2 structural proteins circulating in Uganda by July 2021: Towards refinement of COVID-19 disease vaccines, diagnostics, and therapeutics(Plos one, 2022) Odongo, Steven; Okella, Hedmon; Ndekezi, Christian; Okee, Moses; Namayanja, Monica; Mujuni, Brian; Sterckx, Yann G. J.; Kizito, Dennison; Mwiine, Frank Nobert; Lutwama, Julius Julian; Ibingira, CharlesThe SARS-CoV-2 virus, the agent of COVID-19, caused unprecedented loss of lives and economic decline worldwide. Although the introduction of public health measures, vaccines, diagnostics, and therapeutics disrupted the spread of the SARS-CoV-2, the emergence of variants poses substantial threat. This study traced SARS-CoV-2 variants circulating in Uganda by July 2021 to inform the necessity for refinement of the intervention medical products. A comprehensive in silico analysis of the SARS-CoV-2 genomes detected in clinical samples collected from COVID-19 patients in Uganda revealed occurrence of structural protein variants with potential of escaping detection, resisting antibody therapy, or increased infectivity. The genome sequence dataset was retrieved from the GISAID database and the open reading frame encoding the spike, envelope, membrane, or nucleocapsid proteins was translated. The obtained protein sequences were aligned and inspected for existence of variants. The variant positions on each of the four alignment sets were mapped on predicted epitopes as well as the 3D structures. Additionally, sequences within each of the sets were clustered by family. A phylogenetic tree was constructed to assess relationship between the encountered spike protein sequences and Wuhan-Hu-1 wild-type, or the Alpha, Beta, Delta and Gamma variants of concern. Strikingly, the frequency of each of the spike protein point mutations F157L/Del, D614G and P681H/R was over 50%. The furin and the transmembrane serine protease 2 cleavage sites were unaffected by mutation. Whereas the Delta dominated the spike sequences (16.5%, 91/550), Gamma was not detected. The envelope protein was the most conserved with 96.3% (525/545) sequences being wild-type followed by membrane at 68.4% (397/580). Although the nucleocapsid protein sequences varied, the variant residue positions were less concentrated at the RNA binding domains. The dominant nucleocapsid sequence variant was S202N (34.5%, 205/595). These findings offer baseline information required for refining the existing COVID-19 vaccines, diagnostics, and therapeutics.Item Treatment with anthelminthics during pregnancy: what gains and what risks for the mother and child?(Parasitology, 2011) Elliott, Alison M.; Ndibazza, Juliet; Mpairwe, Harriet; Muhangi, Lawrence; Webb, Emily L.; Kizito, Dennison; Mawa, Patrice; Tweyongyere, Robert; Muwanga, MosesIn 1994 and 2002, respectively, the World Health Organization proposed that treatment for hookworm and schistosomiasis could be provided during pregnancy. It was hoped that this might have benefits for maternal anaemia, fetal growth and perinatal mortality; a beneficial effect on the infant response to immunization was also hypothesised. Three trials have now been conducted. Two have examined the effects of benzimidazoles; one (the Entebbe Mother and Baby Study) the effects of albendazole and praziquantel. All three were conducted in settings of high prevalence but low intensity helminth infection. Results suggest that, in such settings and given adequate provision of haematinics, the benefit of routine anthelminthics during pregnancy for maternal anaemia may be small; none of the other expected benefits has yet been demonstrated. The Entebbe Mother and Baby Study found a significant adverse effect of albendazole on the incidence of infantile eczema in the whole study population, and of praziquantel on the incidence of eczema among infants of mothers with Schistosoma mansoni. Further studies are required in settings that differ in helminth species and infection intensities. Further research is required to determine whether increased rates of infantile eczema translate to long-term susceptibility to allergy, and to explore the underlying mechanisms of these effects. The risks and benefits of routine anthelminthic treatment in antenatal clinics may need to be reconsidered.Item Widespread exposure to Crimean-Congo haemorrhagic fever in Uganda might be driven by transmission from Rhipicephalus ticks: Evidence from cross-sectional and modelling studies(Journal of Infection, 2022-12-13) Lule, Swaib A.; Kizito, Dennison; Nakanjako, Gladys; Balinandi, Stephen; Lutwama, Julius J.; Field, NigelCrimean-Congo haemorrhagic fever (CCHF) is a widespread tick-borne viral infection, present across Africa and Eurasia, which might pose a cryptic public health problem in Uganda. We aimed to understand the magnitude and distribution of CCHF risk in humans, livestock and ticks across Uganda by synthesising epidemiological (cross-sectional) and ecological (modelling) studies. We conducted a cross-sectional study at three urban abattoirs receiving cattle from across Uganda. We sampled humans (n = 478), livestock (n = 419) and ticks (n = 1065) and used commercially-available kits to detect human and livestock CCHF virus (CCHFV) antibodies and antigen in tick pools. We developed boosted regression tree models to evaluate the correlates and geographical distribution of expected tick and wildlife hosts, and of human CCHF exposures, drawing on continent-wide data. The cross-sectional study found CCHFV IgG/IgM seroprevalence in humans of 10·3% (7·8–13·3), with antibody detection positively associated with reported history of tick bite (age-adjusted odds ratio = 2·09 (1·09–3·98)). Cattle had a seroprevalence of 69·7% (65·1–73·4). Only one Hyalomma tick (CCHFV-negative) was found. However, CCHFV antigen was detected in Rhipicephalus (5·9% of 304 pools) and Amblyomma (2·9% of 34 pools) species. Modelling predicted high human CCHF risk across much of Uganda, low environmental suitability for Hyalomma, and high suitability for Rhipicephalus and Amblyomma. Our epidemiological and ecological studies provide complementary evidence that CCHF exposure risk is widespread across Uganda. We challenge the idea that Hyalomma ticks are consistently the principal reservoir and vector for CCHFV, and postulate that Rhipicephalus might be important for CCHFV transmission in Uganda, due to high frequency of infected ticks and predicted environmental suitability. UCL Global Challenges Research Fund (GCRF) and Pan-African Network on Emerging and Re-Emerging Infections (PANDORA-ID-NET) funded by the European and Developing Countries Clinical Trials Partnership (EDCTP) under the EU Horizon 2020 Framework Programme for Research and Innovation.