Browsing by Author "Tumusiime, Josephine"

Now showing 1 - 5 of 5
  • Thumbnail Image
    Item
    Contrasting Impact of Rural, Versus Urban, Living on Glucose Metabolism and Blood Pressure in Uganda
    (Wellcome open research, 2020) Sanya, Richard E.; Biraro, Irene Andia; Nampijja, Margaret; Zziwa, Christopher; Nanyunja, Carol; Nsubuga, Denis; Kiwanuka, Samuel; Tumusiime, Josephine; Walusimbi, Bridgious; Cose, Stephen; Ocama, Ponsiano; Grencis, Richard K.; Elliott, Alison M.; Webb, Emily L.
    The burden of cardiometabolic diseases, including cardiovascular diseases and diabetes, is increasing in sub-Saharan Africa and this has been linked to urbanisation. Helminths, through their immunomodulatory properties, may protect against these disorders. We hypothesised that the rural environment protects against cardiometabolic diseases and that helminths may influence rural-urban disparity of cardiometabolic disease risk.We compared metabolic parameters of individuals aged ≥10 years living in rural, high-helminth-transmission and urban, lower-helminth-transmission settings in Uganda. Cross-sectional surveys were conducted in rural Lake Victoria island fishing communities and in urban sub-wards in Entebbe municipality. Helminth infection and outcomes, including insulin resistance (computed using the homeostatic model assessment of insulin resistance [HOMA-IR]), fasting blood glucose, fasting blood lipids, blood pressure, body mass index (BMI), waist and hip circumference, were assessed.We analysed 1,898 rural and 930 urban participants. Adjusting for BMI, exercise, smoking, alcohol intake, age and sex, urban residents had lower mean fasting glucose (adjusted mean difference [95%CI] 0.18 [-0.32, -0.05] p=0.01) and HOMA-IR (-0.26 [-0.40, -0.11] p=0.001) but higher blood pressure (systolic, 5.45 [3.75, 7.15] p<0.001; diastolic, 1.93 [0.57, 3.29] p=0.006). Current helminth infection did not explain the observed differences.In the Ugandan context, living in rural fishing communities may protect against hypertension but worsen glucose metabolism.
  • Thumbnail Image
    Item
    The Effect of Helminth Infections and Their Treatment on Metabolic Outcomes: Results of a Cluster-Randomized Trial
    (Clinical infectious diseases, 2020) Sanya, Richard E.; Webb, Emily L.; Zziwa, Christopher; Kizindo, Robert; Sewankambo, Moses; Tumusiime, Josephine; Nakazibwe, Esther; Oduru, Gloria; Niwagaba, Emmanuel; Nakawungu, Prossy Kabuubi; Kabagenyi, Joyce; Nassuuna, Jacent; Walusimbi, Bridgious; Andia-Biraro, Irene; Elliot, Alison M.
    Helminths may protect against cardiometabolic risk through effects on inflammation and metabolism; their treatment may be detrimental to metabolic outcomes. In a cluster-randomized trial in 26 Ugandan fishing communities we investigated effects of community-wide intensive (quarterly single-dose praziquantel, triple-dose albendazole) vs standard (annual single-dose praziquantel, biannual single-dose albendazole) anthelminthic treatment on metabolic outcomes, and observational associations between helminths and metabolic outcomes. The primary outcome, homeostatic model assessment of insulin resistance (HOMA-IR), and secondary outcomes (including blood pressure, fasting blood glucose, lipids) were assessed after 4 years' intervention among individuals aged ≥10 years. We analyzed 1898 participants. Intensive treatment had no effect on HOMA-IR (adjusted geometric mean ratio, 0.96 [95% confidence interval {CI}, .86–1.07]; P = .42) but resulted in higher mean low-density lipoprotein cholesterol (LDL-c) (2.86 vs 2.60 mmol/L; adjusted mean difference, 0.26 [95% CI, −.03 to .56]; P = .08). Lower LDL-c levels were associated with Schistosoma mansoni (2.37 vs 2.80 mmol/L; −0.25 [95% CI, −.49 to −.02]; P = .04) or Strongyloides (2.34 vs 2.69 mmol/L; −0.32 [95% CI, −.53 to −.12]; P = .003) infection. Schistosoma mansoni was associated with lower total cholesterol (4.24 vs 4.64 mmol/L; −0.25 [95% CI, −.44 to −.07]; P = .01) and moderate to heavy S. mansoni infection with lower triglycerides, LDL-c, and diastolic blood pressure. Helminth infections improve lipid profiles and may lower blood pressure. Studies to confirm causality and investigate mechanisms may contribute to understanding the epidemiological transition and suggest new approaches to prevent cardiometabolic disease.
  • Thumbnail Image
    Item
    The Impact of Intensive Versus Standard Anthelminthic Treatment on Allergy-related Outcomes, Helminth Infection Intensity, and Helminth-related Morbidity in Lake Victoria Fishing Communities, Uganda: Results From the LaVIISWA Cluster-randomized Trial
    (Clinical infectious diseases, 2019) Sanya, Richard E.; Nkurunungi, Gyaviira; Hoek Spaans, Remy; Nampijja, Margaret; O’Hara, Geraldine; Kizindo, Robert; Oduru, Gloria; Kabuubi Nakawungu, Prossy; Niwagaba, Emmanuel; Abayo, Elson; Kabagenyi, Joyce; Zziwa, Christopher; Tumusiime, Josephine; Nakazibwe, Esther; Kaweesa, James; Muwonge Kakooza, Fred; Akello, Mirriam; Lubyayi, Lawrence; Verweij, Jaco; Nash, Stephen; Ree, Ronald van; Mpairwe, Harriet; Tukahebwa, Edridah; Webb, Emily L.; Elliott, Alison M.
    The prevalence of allergy-related diseases is increasing in low-income countries. Parasitic helminths, common in these settings, may be protective. We hypothesized that intensive, community-wide, anthelminthic mass drug administration (MDA) would increase allergy-related diseases, while reducing helminth-related morbidity. Methods. In an open, cluster-randomized trial (ISRCTN47196031), we randomized 26 high-schistosomiasis-transmission fishing villages in Lake Victoria, Uganda, in a 1:1 ratio to receive community-wide intensive (quarterly single-dose praziquantel plus albendazole daily for 3 days) or standard (annual praziquantel plus 6 monthly single-dose albendazole) MDA. Primary outcomes were recent wheezing, skin prick test positivity (SPT), and allergen-specific immunoglobulin E (asIgE) after 3 years of intervention. Secondary outcomes included helminths, haemoglobin, and hepatosplenomegaly. Results. The outcome survey comprised 3350 individuals. Intensive MDA had no effect on wheezing (risk ratio [RR] 1.11, 95% confidence interval [CI] 0.64–1.93), SPT (RR 1.10, 95% CI 0.85–1.42), or asIgE (RR 0.96, 95% CI 0.82–1.12). Intensive MDA reduced Schistosoma mansoni infection intensity: the prevalence from Kato Katz examinations of single stool samples from each patient was 23% versus 39% (RR 0.70, 95% CI 0.55–0.88), but the urine circulating cathodic antigen test remained positive in 85% participants in both trial arms. Hookworm prevalence was 8% versus 11% (RR 0.55, 95% CI 0.31–1.00). There were no differences in anemia or hepatospenomegaly between trial arms. Conclusions. Despite reductions in S. mansoni intensity and hookworm prevalence, intensive MDA had no effect on atopy, allergy- related diseases, or helminth-related pathology. This could be due to sustained low-intensity infections; thus, a causal link between helminths and allergy outcomes cannot be discounted. Intensive community-based MDA has a limited impact in high-schistosomiasis- transmission fishing communities, in the absence of other interventions.
  • Thumbnail Image
    Item
    Safety and immunogenicity of ChAdOx1 85A prime followed by MVA85A boost compared with BCG revaccination among Ugandan adolescents who received BCG at birth: a randomised, open-label trial
    (Elsevier Ltd, 2024-03) Wajja, Anne; Nassanga, Beatrice; Natukunda, Agnes; Serubanja, Joel; Tumusiime, Josephine; Akurut, Helen; Oduru, Gloria; Nassuuna, Jacent; Kabagenyi, Joyce; Morrison, Hazel; Scott, Hannah; Doherty, Rebecca Powell; Marshall, Julia L; Puig, Ingrid Cabrera; Cose, Stephen; Kaleebu, Pontiano; Webb, Emily L; Satti, Iman; McShane, Helen; Elliott, Alison M; Namutebi, Milly; Nakazibwe, Esther; Onen, Caroline; Apuule, Barbara; Akello, Florence; Mukasa, Mike; Nnaluwooza, Marble; Sewankambo, Moses; Kiwanuka, Sam; Kiwudhu, Fred; Imede, Esther; Nkurunungi, Gyaviira; Nakawungu, Prossy Kabuubi; Kabami, Grace; Nuwagaba, Emmanuel; Akello, Mirriam
    Abstract BACKGROUNDBCG confers reduced, variable protection against pulmonary tuberculosis. A more effective vaccine is needed. We evaluated the safety and immunogenicity of candidate regimen ChAdOx1 85A-MVA85A compared with BCG revaccination among Ugandan adolescents.METHODSAfter ChAdOx1 85A dose escalation and age de-escalation, we did a randomised open-label phase 2a trial among healthy adolescents aged 12-17 years, who were BCG vaccinated at birth, without evident tuberculosis exposure, in Entebbe, Uganda. Participants were randomly assigned (1:1) using a block size of 6, to ChAdOx1 85A followed by MVA85A (on day 56) or BCG (Moscow strain). Laboratory staff were masked to group assignment. Primary outcomes were solicited and unsolicited adverse events (AEs) up to day 28 and serious adverse events (SAEs) throughout the trial; and IFN-γ ELISpot response to antigen 85A (day 63 [geometric mean] and days 0-224 [area under the curve; AUC).FINDINGSSix adults (group 1, n=3; group 2, n=3) and six adolescents (group 3, n=3; group 4, n=3) were enrolled in the ChAdOx1 85A-only dose-escalation and age de-escalation studies (July to August, 2019). In the phase 2a trial, 60 adolescents were randomly assigned to ChAdOx1 85A-MVA85A (group 5, n=30) or BCG (group 6, n=30; December, 2019, to October, 2020). All 60 participants from groups 5 and 6 were included in the safety analysis, with 28 of 30 from group 5 (ChAdOx1 85A-MVA85A) and 29 of 30 from group 6 (BCG revaccination) analysed for immunogenicity outcomes. In the randomised trial, 60 AEs were reported among 23 (77%) of 30 participants following ChAdOx1 85A-MVA85A, 31 were systemic, with one severe event that occurred after the MVA85A boost that was rapidly self-limiting. All 30 participants in the BCG revaccination group reported at least one mild to moderate solicited AE; most were local reactions. There were no SAEs in either group. Ag85A-specific IFN-γ ELISpot responses peaked on day 63 in the ChAdOx1 85A-MVA85A group and were higher in the ChAdOx1 85A-MVA85A group compared with the BCG revaccination group (geometric mean ratio 30·59 [95% CI 17·46-53·59], p<0·0001, day 63; AUC mean difference 57 091 [95% CI 40 524-73 658], p<0·0001, days 0-224).INTERPRETATIONThe ChAdOx1 85A-MVA85A regimen was safe and induced stronger Ag85A-specific responses than BCG revaccination. Our findings support further development of booster tuberculosis vaccines.FUNDINGUK Research and Innovations and Medical Research Council.TRANSLATIONSFor the Swahili and Luganda translations of the abstract see Supplementary Materials section.
  • Thumbnail Image
    Item
    Skin prick test reactivity to common allergens among women in Entebbe, Uganda
    (Royal Society of Tropical Medicine and Hygiene, 2008) Mpairwe, Harriet; Muhangi, Lawrence; Ndibazza, Juliet; Tumusiime, Josephine; Muwanga, Moses; Rodrigues, Laura C.; Elliott, Alison M.
    The objectives of this study were to estimate the prevalence of atopic sensitization, and to identify common aeroallergens associated with atopic sensitization among women in Entebbe, Uganda, and to determine risk factors for atopic sensitization among those with and without a history of asthma or eczema. A case—control study was conducted within a trial of deworming in pregnancy, approximately 2 years after the intervention. Skin prick test reactivity was assessed among 20 women with a history of asthma, 25 with history of eczema and 95 controls. Overall prevalence of reactivity was estimated by adjusting for the prevalence of asthma in the whole cohort. Overall skin prick test prevalence was: any allergen 30.7%, Blomia tropicalis 10.9%, Dermatophagoides mix 16.8%, cockroach 15.8%. The prevalence of a positive skin prick test was significantly associated with a history of asthma (70% to any allergen vs. 32%, P = 0.002) but not with a history of eczema (44% vs. 36%, P = 0.49). Women with Mansonella perstans had significantly reduced odds for atopic sensitization (adjusted odds ratio 0.14, 95% CI 0.03—0.69); women with a history of asthma were less likely to have hookworm (adjusted odds ratio 0.24, 95% CI 0.07—0.81) but this association was weaker for women with a history of eczema. [Clinical Trial No. ISRCTN32849447]