Browsing by Author "Nkurunungi, Gyaviira"

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    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.
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    The impact of maternal infection with Mycobacterium tuberculosis on the infant response to bacille Calmette–Gue´rin immunization
    (Philosophical Transactions of the Royal Society B: Biological Sciences, 2015) Mawa, Patrice A.; Nkurunungi, Gyaviira; Egesa, Moses; Webb, Emily L.; Smith, Steven G.; Kizindo, Robert; Akello, Mirriam; Lule, Swaib A.; Muwanga, Moses; Dockrell, Hazel M.; Cose, Stephen; Elliott, Alison M.
    Bacille Calmette–Gue´rin (BCG) immunization provides variable protection against tuberculosis. Prenatal antigen exposure may have lifelong effects on responses to related antigens and pathogens. We therefore hypothesized that maternal latent Mycobacterium tuberculosis infection (LTBI) influences infant responses to BCG immunization at birth. We measured antibody (n ¼ 53) and cellular (n ¼ 31) responses to M. tuberculosis purified protein derivative (PPD) in infants of mothers with and without LTBI, in cord blood and at one and six weeks after BCG. The concentrations of PPD-specific antibodies declined between birth (median [interquartile range (IQR)]) 5600 ng ml21 [3300–11 050] in cord blood) and sixweeks (0.00 ng ml21 [0–288]). Frequencies of PPD-specific IFN-g-expressing CD4þT cells increased at one week and declined between one and six weeks ( p ¼ 0.031). Frequencies of IL-2- and TNF-a-expressing PPD-specific CD4þT cells increased between one and six weeks ( p ¼ 0.019, p ¼ 0.009, respectively). At one week, the frequency of PPD-specific CD4þT cells expressing any of the three cytokines, combined, was lower among infants of mothers with LTBI, in crude analyses ( p ¼ 0.002) and after adjusting for confounders (mean difference, 95% CI 20.041% (20.082, 20.001)). In conclusion, maternal LTBI was associated with lower infant anti-mycobacterial T-cell responses immediately following BCGimmunization. These findings are being explored further in a larger study.
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    Risk Assessment for the Implementation of Controlled Human Schistosoma Mansoni Infection Trials in Uganda
    (AAS open research, 2019) Koopman, Jan Pieter; Egesa, Moses; Wajja, Anne; Adriko, Moses; Nassuuna, Jacent; Nkurunungi, Gyaviira; Driciru, Emmanuella; Cose, Stephen; Kaleebu, Pontiano; Kabatereine, Narcis; Tukahebwa, Edridah; Elliott, Alison M.
    Schistosomiasis is a parasitic infection highly prevalent in sub-Saharan Africa, and a significant cause of morbidity; it is a priority for vaccine development. A controlled human infection model for Schistosoma mansoni (CHI-S) with potential to accelerate vaccine development has been developed among naïve volunteers in the Netherlands. Because responses both to infections and candidate vaccines are likely to differ between endemic and non-endemic settings, we propose to establish a CHI-S in Uganda where Schistosoma mansoni is endemic. As part of a “road-map” to this goal, we have undertaken a risk assessment. We identified risks related to importing of laboratory vector snails and schistosome strains from the Netherlands to Uganda; exposure to natural infection in endemic settings concurrently with CHI-S studies, and unfamiliarity of the community with the nature, risks and rationale for CHI. Mitigating strategies are proposed. With careful implementation of the latter, we believe that CHI-S can be implemented safely in Uganda. Our reflections are presented here to promote feedback and discussion.
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    Risk factors for asthma among schoolchildren who participated in a casecontrol study in urban Uganda
    (Elife, 8,, 2019) Mpairwe, Harriet; Namutebi, Milly; Nkurunungi, Gyaviira; Tumwesige, Pius; Nambuya, Irene; Mukasa, Mike; Onen, Caroline; Nnaluwooza, Marble; Apule, Barbara; Katongole, Tonny; Oduru, Gloria; Kahwa, Joseph; Webb, Emily L; Lubyayi, Lawrence; Pearce, Neil; Elliott, Alison M
    Data on asthma aetiology in Africa are scarce. We investigated the risk factors for asthma among schoolchildren (5–17 years) in urban Uganda. We conducted a case-control study, among 555 cases and 1115 controls. Asthma was diagnosed by study clinicians. The main risk factors for asthma were tertiary education for fathers (adjusted OR (95% CI); 2.32 (1.71–3.16)) and mothers (1.85 (1.38–2.48)); area of residence at birth, with children born in a small town or in the city having an increased asthma risk compared to schoolchildren born in rural areas (2.16 (1.60–2.92)) and (2.79 (1.79–4.35)), respectively; father’s and mother’s history of asthma; children’s own allergic conditions; atopy; and cooking on gas/electricity. In conclusion, asthma was associated with a strong rural-town-city risk gradient, higher parental socio-economic status and urbanicity. This work provides the basis for future studies to identify specific environmental/lifestyle factors responsible for increasing asthma risk among children in urban areas in LMICs.
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    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.
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    Uganda Schistosomiasis Symposium 2023: understanding morbidity drivers and developing controlled human infection models for vaccine research
    (Trends in Parasitology, 2023) Egesa, Moses; Kiberu, Davis; Sanya, Richard E.; Alabi, Ayodele; Baluku, Joseph Baruch; Oguttu, David W.; Driciru, Emmanuella; Odongo, Matthew; Elliott, Alison M.; Walusimbi, Bridgious; Nkurunungi, Gyaviira
    Schistosomiasis impacts African populations most strongly. Despite Uganda’s leading role in the Schistosomiasis Control Initiative for mass drug administration (MDA), about half the population remains at risk and a quarter infected. Prevalence and intensity remain high, and morbidity severe, in northwest Uganda around Lake Albert and the Albert Nile. An effective vaccine could combat repeated infection following MDA, and controlled human infection (CHI) studies could enable such vaccine development. Therefore, the Uganda Schistosomiasis Multidisciplinary Research Center and CHI-in-Africa Network hosted a symposium in Uganda bringing together local and international partners to discuss research on the drivers of schistosomal morbidity and the development of CHI studies for helminth vaccine development in Africa. In this TrendsTalk, we invited 10 early- to mid-career researchers to summarise the symposium proceedings.