31 research outputs found

    The PROCESS study: a protocol to evaluate the implementation, mechanisms of effect and context of an intervention to enhance public health centres in Tororo, Uganda.

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    BACKGROUND: Despite significant investments into health improvement programmes in Uganda, health indicators and access to healthcare remain poor across the country. The PRIME trial aims to evaluate the impact of a complex intervention delivered in public health centres on health outcomes of children and management of malaria in rural Uganda. The intervention consists of four components: Health Centre Management; Fever Case Management; Patient- Centered Services; and support for supplies of malaria diagnostics and antimalarial drugs. METHODS: The PROCESS study will use mixed methods to evaluate the processes, mechanisms of change, and context of the PRIME intervention by addressing five objectives. First, to develop a comprehensive logic model of the intervention, articulating the project's hypothesised pathways to trial outcomes. Second, to evaluate the implementation of the intervention, including health worker training, health centre management tools, and the supply of artemether-lumefantrine (AL) and rapid diagnostic tests (RDTs) for malaria. Third, to understand mechanisms of change of the intervention components, including testing hypotheses and interpreting realities of the intervention, including resistance, in context. Fourth, to develop a contextual record over time of factors that may have affected implementation of the intervention, mechanisms of change, and trial outcomes, including factors at population, health centre and district levels. Fifth, to capture broader expected and unexpected impacts of the intervention and trial activities among community members, health centre workers, and private providers. Methods will include intervention logic mapping, questionnaires, recorded consultations, in-depth interviews, focus group discussions, and contextual data documentation. DISCUSSION: The findings of this PROCESS study will be interpreted alongside the PRIME trial results. This will enable a greater ability to generalise the findings of the main trial. The investigators will attempt to assess which methods are most informative in such evaluations of complex interventions in low-resource settings. TRIAL REGISTRATION: Clinicaltrials.gov, NCT01024426

    High-resolution African HLA resource uncovers HLA-DRB1 expression effects underlying vaccine response

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    How human genetic variation contributes to vaccine effectiveness in infants is unclear, and data are limited on these relationships in populations with African ancestries. We undertook genetic analyses of vaccine antibody responses in infants from Uganda (n = 1391), Burkina Faso (n = 353) and South Africa (n = 755), identifying associations between human leukocyte antigen (HLA) and antibody response for five of eight tested antigens spanning pertussis, diphtheria and hepatitis B vaccines. In addition, through HLA typing 1,702 individuals from 11 populations of African ancestry derived predominantly from the 1000 Genomes Project, we constructed an imputation resource, fine-mapping class II HLA-DR and DQ associations explaining up to 10% of antibody response variance in our infant cohorts. We observed differences in the genetic architecture of pertussis antibody response between the cohorts with African ancestries and an independent cohort with European ancestry, but found no in silico evidence of differences in HLA peptide binding affinity or breadth. Using immune cell expression quantitative trait loci datasets derived from African-ancestry samples from the 1000 Genomes Project, we found evidence of differential HLA-DRB1 expression correlating with inferred protection from pertussis following vaccination. This work suggests that HLA-DRB1 expression may play a role in vaccine response and should be considered alongside peptide selection to improve vaccine design

    Trends and spatial distribution of Human African Trypanosomiasis (HAT), Uganda, 2005 – 2015: A descriptive analysis of surveillance data

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    Background: Human African Trypanosomiasis (HAT), commonly referred to as sleeping sickness, is a neglected tropical disease endemic in Sub-Saharan Africa. It is caused by Trypanosoma brucei (T.b.) sub-species: rhodesiense (Rhodesian HAT) and gambiense (Gambian HAT) parasites. The World Health Organization (WHO) targeted HAT for elimination as a public health problem by 2020 (annual incidence ≤1/10,000, and early diagnosis for all cases). We evaluated progress towards HAT elimination in Uganda and described its epidemiological characteristics. Methods: We analysed data reported from sleeping sickness treatment centres (SSTCs) to the Uganda National Sleeping Sickness Control Program during 2005–2015. A HAT case was defined as identification of T.b. rhodesiense or T.b. gambiense parasites in the blood (early-stage) or cerebrospinal fluid (late-stage) of patients at a SSTC. We analysed the cases’ distribution by person, time, and place. We used projected population data from 2002 and 2014 censuses, and linear regression to evaluate temporal trends. Results: During 2005–2015, SSTCs reported 2,032 HAT cases, (55% Rhodesian and 45% Gambian). The number of districts reporting AT reduced from 18 in 2005 to three districts in 2015. The average annual incidence rate (/10,000) during 2005–2015 was similar between males (Gambian=0.1, Rhodesian=0.76) and females (Gambian=0.09, Rhodesian=0.74). Gambian AT incidence declined annually by 24% (IRR=0.76; CI: 0.74-0.78) while Rhodesian AT declined annually by 13% (IRR=0.87; CI: 0.85-0.89). However, for both diseases more than 50% of cases were diagnosed in the late stage. Conclusion: Uganda has achieved the WHO 2020 elimination target for AT incidence. However, many cases are still diagnosed late. We recommend sustaining efforts to achieve eradication, emphasizing early case detection and diagnosis and follow up of all AT cases to ensure good treatment success
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