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Kampala, Uganda

Olobo-Okao J.,Makerere University | Olobo-Okao J.,Med Biotech Laboratories | Sagaki P.,Amudat Hospital
Pan African Medical Journal | Year: 2014

Visceral leishmaniasis (VL) or kala azar is a fatal and neglected disease caused by protozoan parasites. It occurs worldwide including north-eastern Uganda. This review gives a historical account of and reviews available literature on VL in Uganda to raise more awareness about the disease. Information was collected from: MEDLINE searches; records of Ministry of Health (Uganda), Amudat hospital records; records of NGOs and multilateral institutions; dissertations and personal communication. Results show that VL in Uganda was first reported in the 1950's, followed by almost four decades of neglect. Earlier records from the ministry of health and Amudat hospital on VL are also incomplete. From early 2000, reports mainly on the disease management and risk factors, started to appear in the literature. Management of VL has mainly been by NGOs and multilateral institutions including MSF Swiss. Currently DNDi is funding its management and clinical trials in Amudat hospital through LEAP. New cases of VL were reported recently from Moroto and Kotido districts and more patients continue to be received from these areas. In conclusion, management of VL is well established in Amudat hospital. However its sustainability and wider coverage remains a challenge. First-line drugs have now been registered in the country. Visceral leishmaniasis is apparently more widespread in north-eastern Uganda than originally thought. Research and surveillance on leishmaniasis is still weak. Strengthening the capacity of local institutions to; conduct surveillance and research, combined with effective management should mitigate VL in Uganda. © Joseph Olobo-Okao et al. Source


Yagi M.,Osaka University | Bang G.,Institute Pasteur Paris | Tougan T.,Osaka University | Palacpac N.M.Q.,Osaka University | And 9 more authors.
PLoS ONE | Year: 2014

The malaria vaccine candidate antigen, SE36, is based on the N-terminal 47 kDa domain of Plasmodium falciparum serine repeat antigen 5 (SERA5). In epidemiological studies, we have previously shown the inhibitory effects of SE36 specific antibodies on in vitro parasite growth and the negative correlation between antibody level and malaria symptoms. A phase 1 b trial of the BK-SE36 vaccine in Uganda elicited 72% protective efficacy against symptomatic malaria in children aged 6- 20 years during the follow-up period 130-365 days post-second vaccination. Here, we performed epitope mapping with synthetic peptides covering the whole sequence of SE36 to identify and map dominant epitopes in Ugandan adult serum presumed to have clinical immunity to P. falciparum malaria. High titer sera from the Ugandan adults predominantly reacted with peptides corresponding to two successive N-terminal regions of SERA5 containing octamer repeats and serine rich sequences, regions of SERA5 that were previously reported to have limited polymorphism. Affinity purified antibodies specifically recognizing the octamer repeats and serine rich sequences exhibited a high antibody-dependent cellular inhibition (ADCI) activity that inhibited parasite growth. Furthermore, protein structure predictions and structural analysis of SE36 using spectroscopic methods indicated that N-terminal regions possessing inhibitory epitopes are intrinsically unstructured. Collectively, these results suggest that strict tertiary structure of SE36 epitopes is not required to elicit protective antibodies in naturally immune Ugandan adults. © 2014 Yagi et al. Source


Palacpac N.M.Q.,Osaka University | Ntege E.,Med Biotech Laboratories | Yeka A.,Med Biotech Laboratories | Yeka A.,Makerere University | And 21 more authors.
PLoS ONE | Year: 2013

Background:Up to now a malaria vaccine remains elusive. The Plasmodium falciparum serine repeat antigen-5 formulated with aluminum hydroxyl gel (BK-SE36) is a blood-stage malaria vaccine candidate that has undergone phase 1a trial in malaria-naive Japanese adults. We have now assessed the safety and immunogenicity of BK-SE36 in a malaria endemic area in Northern Uganda.Methods:We performed a two-stage, randomized, single-blinded, placebo-controlled phase 1b trial (Current Controlled trials ISRCTN71619711). A computer-generated sequence randomized healthy subjects for 2 subcutaneous injections at 21-day intervals in Stage1 (21-40 year-olds) to 1-mL BK-SE36 (BKSE1.0) (n = 36) or saline (n = 20) and in Stage2 (6-20 year-olds) to BKSE1.0 (n = 33), 0.5-mL BK-SE36 (BKSE0.5) (n = 33), or saline (n = 18). Subjects and laboratory personnel were blinded. Safety and antibody responses 21-days post-second vaccination (Day42) were assessed. Post-trial, to compare the risk of malaria episodes 130-365 days post-second vaccination, Stage2 subjects were age-matched to 50 control individuals.Results:Nearly all subjects who received BK-SE36 had induration (Stage1, n = 33, 92%; Stage2, n = 63, 96%) as a local adverse event. No serious adverse event related to BK-SE36 was reported. Pre-existing anti-SE36 antibody titers negatively correlated with vaccination-induced antibody response. At Day42, change in antibody titers was significant for seronegative adults (1.95-fold higher than baseline [95% CI, 1.56-2.43], p = 0.004) and 6-10 year-olds (5.71-fold [95% CI, 2.38-13.72], p = 0.002) vaccinated with BKSE1.0. Immunogenicity response to BKSE0.5 was low and not significant (1.55-fold [95% CI, 1.24-1.94], p = 0.75). In the ancillary analysis, cumulative incidence of first malaria episodes with ≥5000 parasites/μL was 7 cases/33 subjects in BKSE1.0 and 10 cases/33 subjects in BKSE0.5 vs. 29 cases/66 subjects in the control group. Risk ratio for BKSE1.0 was 0.48 (95% CI, 0.24-0.98; p = 0.04).Conclusion:BK-SE36 is safe and immunogenic. The promising potential of BK-SE36, observed in the follow-up study, warrants a double-blind phase 1/2b trial in children under 5 years.Trial Registration:Controlled-Trials.com ISRCTN71619711. © 2013 Palacpac et al. Source


Grant
Agency: Cordis | Branch: FP7 | Program: MC-IAPP | Phase: PEOPLE-2007-3-1-IAPP | Award Amount: 1.87M | Year: 2008

People living in malaria endemic areas develop, with time, a form of immunity to infection and clinical disease mediated by antibodies directed against P. falciparum antigens. Currently there are no assays or clinical parameters that predict whether an exposed person is protected against malaria. This represents a major obstacle for vaccine development. Here research institutions and industrial partners, combining cutting edge expertise in protein microarrays, immunoassay development, immunology, protein expression and epidemiology join their efforts with the objective of translating the genome sequence information of Plasmodium falciparum into a tool to unravel correlates of protection against human malaria. Recombinant P. falciparum proteins, encompassing the repertoire of secreted and surface antigens, will be printed onto microarrays to develop an immunoassay capable of unraveling antibodies directed against a vast number of parasite molecules. This assay will be utilized to compare the antigen-antibody recognition profiles of protected and non-protected persons in malaria-exposed communities, thus facilitating the identification of the antigens that either alone or in combination function as targets of protective immunity. The underlying project structure in terms of research activities, task distribution and management has been planned with the priority of facilitating the interactions of human resources, between academic institutions and industry. Exchange of staff and networking activities will bridge the scientific and cultural differences existing between the academic and industrial partners. Exchange of scientific knowledge and technical skill will unleash the full potential of the collective expertise of the participating laboratories towards the objectives of the proposal and will be instrumental in building collaborative links that will extend beyond the duration of the project.


Palacpac N.M.Q.,Osaka University | Ntege E.,Med Biotech Laboratories | Ntege E.,Ehime University | Balikagala B.,Med Biotech Laboratories | And 13 more authors.
International Journal of Environmental Research and Public Health | Year: 2014

Reference intervals for common hematological and clinical chemistry parameters constitute an important basis for health care. Moreover, with increasing priority in drug and vaccine development for infectious diseases in Africa, the first priority is the safety evaluation and tolerability of the candidate interventions in healthy populations. To accurately assess health status and address adverse events, clinical reference intervals in the target population are necessary. We report on hematological and biochemical indices from healthy volunteers who participated in a clinical trial in Lira, northern Uganda. Median and nonparametric 95% percentiles on five hematology and 15 biochemistry analytes are shown. Although most hematological analytes conformed to reported reference intervals and trends in Africa, literature review from different African countries highlight the need for a region-specific children reference interval that can be appropriate for the population. Source

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