Browsing by Author "Gordon, Melita"

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    Optivants – Optimising vaccination for iNTS disease in Africa
    (Kamuzu University of Health Sciences, 2021-07-26) Gordon, Melita
    Study design: Prospective systems serology analysis of serological samples collected in several studies of children 0-5 years across sub-Saharan Africa: 1. STRATAA – 500-1000 paired samples available collected between 2015-2018 in peri-Urban Malawi, 2. SAiNTS 2000 paired samples due to be collected 2021-2022, 3. 1000 single samples VacciNTS sites in Kenya, Burkina Faso, Ghana 2021-2022. Problem statement: Invasive non-Typhoid salmonella (iNTS) is responsible for >500,000 illnesses, 77,500 deaths, and the loss of 4,263,500 DALYs every year. Despite its high burden, iNTS remains a Neglected Infectious Disease. It is pre-dominantly a disease of infants in sub-Saharan Africa (sSA). Although risk is amplified by HIV co-infection, this is a factor in only a minority of paediatric cases. The key feature of severe infection is systemic spread from the gut to systemic sites. The two major strategies to control these invasive infections are antimicrobial treatment and vaccination. However, emerging anti-microbial resistance limits benefit and there is no licensed vaccine currently available against iNTS. Broad Objective: To comprehensively elucidate the effector functional humoral profiles and antigenspecificities of protective antibody against iNTS to define a correlate of humoral protection that can be applied to vaccine design and evaluation. Specific Objectives: 1. Identify key novel antigens (Ags), in addition to those already known, that induce protective antibodies (Abs). 2. Describe the mechanisms of action by which different subclasses of antibodies control NTS. 3. To contextualize the value of single-antigens vs multi-component vaccines against iNTS 4. Understand how different co-morbidities (malaria, malnutrition, and anaemia) modulate these functional immune responses and specific protective functions. 5. Provide robust Correlates of Protection (CoP) to accelerate licensure of both current and new vaccines. Methodology: This will be a lab based cross-sectional study conducting systems serology analysis utilising pre-existing serological samples from approved studies in Malawi and across sub-Saharan Africa. STRATAA samples will be utilized for the antigen discovery phase, SAiNTS samples are set for evaluating the range of antigenic exposure to different NTS strains right across the continent, and detailed characterisation of susceptibilities, allowing further dissection and validation of the systems serology signature, to be layered onto the findings from the initial STRATAA discovery cohort. Expected findings and their dissemination: Firstly, Identification of functional-correlates of protection which may provide critical insights for the selection of promising adjuvants that may directly influence the functional (isotype, subclass, and Fc-glycosylation) quality of the humoral immune response. Secondly, data generated under this consortium is likely to provide key insights into the specific assays that interrogate and capture readouts of protective immunity. Linked to Ag discovery, qualified, and validated assays may be rapidly developed and deployed to support the evaluation of current and future vaccines. Finally, these data may provide critical clues for the generation of functionally optimized monoclonal therapeutics that can act to complement or replace current antibiotic strategies, considering the emergence of multi-drug resistance. The results will be presented locally (MLW, COMREC and Joint COM/MLW Research Dissemination conference), nationally, and internationally including other partner sites in the sero-epidemiology work package of the VacciNTS consortium contributing to key knowledge for vaccine development and deployment. This will have relevance for policy decision regarding iNTS control in Malawi and other sub-Saharan African countries. Results will be submitted for publication in a peer reviewed academic journal.
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    Understanding the epidemiology of iNTS disease in Africa in preparation for future iNTS
    (Kamuzu University of Health Sciences, 2020-10-08) Gordon, Melita
    Type of study Clinical research study involving collecting samples from human participants. Prospective serological studies will be carried out across 4 sub-Saharan African sites (Malawi, Kenya, Burkina Faso, Ghana), for which Malawi will be the leading site. A core protocol has been written for all 4 sites in a separate document. This protocol focuses on the Malawi site. Methods to measure age-stratified acquisition of antibody and bactericidal activity to NTS. Data will be collected on the key risk factors for invasive disease: malaria, anaemia and malnutrition and stool samples to measure enteric NTS exposure. Children 0 to 5 years selected from mapped and censused randomly selected households Chikwawa, Malawi; an area with substantial malaria burden - a key risk factor for iNTS. Paired immunology and stool samples for NTS taken 3 months apart for 2000 children; distributed over each age stratum of 1 year, from the age of 0 to 5 years (4000 samples in total). A small number of confirmed invasive NTS cases identified at Queen Elizabeth Hospital (QECH), Blantyre, Malawi, will also have samples for investigated for antibody and bactericidal activity at presentation and 1 month follow-up. Other sites (Kenya, Burkina Faso, Ghana): Prospective serological community study with unpaired/ single samples taken from children aged 0-5 years. No data collected on risk factors. Expected findings and dissemination We will describe the pattern of immunological susceptibility to NTS and enteric exposure in relation to risk factors and geographical settings to facilitate early iNTS vaccine licensure. The final study report will be submitted to the College of Medicine Research Ethics Committee (COMREC) University of Malawi, University of Liverpool IRB and the funders (Wellcome Trust and VacciNTS project). The results will be presented locally, nationally and internationally including other partner sites in the seroepidemiology work package of the VacciNTS consortium contributing to key knowledge for vaccine development and deployment. This will have relevance for policy decisions regarding iNTS control in Malawi and other sub-Saharan African countries. Results will be submitted for publication in a peer reviewed academic journal.
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    Vacc-iNTS Invasive Non-Typhoidal salmonellosis cost of illness study and cost effectiveness
    (Kamuzu University of Health Sciences, 2021-03-15) Gordon, Melita
    Type of research: This is a cost of illness and cost of effective analysis study. It is a prospective facility-based cohort study to determine the individual, healthcare provider, and societal economic burden of non-invasive typhoidal Salmonella (iNTS). This is a multisite study in Sub-Saharan Africa that includes Malawi, Burkina Faso Ghana. Problem : iNTS disease poses a substantial economic burden on poor families as well as depletes already limited health care resources. Economic burden of iNTS disease can be better understood by cost of illness (COI) studies and the lack of iNTs Typhoid Fever (TF) COI data is considered a major knowledge gap. As such, data from this study is essential for measuring the cost-effectiveness of vaccination or other disease preventative interventions which will help set priorities, guide policies, and allocate resources accordingly. Objectives: The primary objectives of this study is are to estimate the cost of illness of laboratory confirmed iNTS disease. and to estimate the cost effectiveness of GMMA-based iNTS vaccine introduction in Ghana, Burkina Faso and Malawi. Secondary objectives will estimate the excess costs of drug resistant iNTS disease in comparison with drug susceptible iNTS . and to estimate the cost effectiveness of GMMA-based iNTS vaccine introduction in Ghana, Burkina Faso and Malawi. Methodology There are two health economic components under proposed COI study, health facility costing and patient out of pocket costing (Figure 1). The health facility costing will be a one-time activity, whereas patient out of pocket costing will involve prospective follow-up with a serial cross-sectional survey of incident cases. These health economic studies are embedded into existing iNTS case surveillance and will use the same platform set-up for surveillance. The COI study will involve recruitment of blood culture confirmed iNTS cases. Consented laboratory confirmed blood culture positive cases will be enrolled soon after their blood culture results are available. At the time of first COI survey contact, cases will be interviewed after providing written informed consent to collect their expenditures and loss of income until the previous day. A second interview will be conducted between 10-20 days from the blood sample collection day to collect subsequent costs and loss of income. If the subject continues to feel sick, a third interview will be conducted 4 weeks from the blood sample collection day (day 28-30). We expect that most subjects will have 2 to 3 interviews, however if subjects continue to be sick, the last interview will be collected on 90th day. Expected findings and dissemination The International Vaccine Institute(IVI) will prepare one or more summary manuscripts reporting cost of illness of laboratory confirmed cases (iNTS) along with country investigators. Authorships and their order will be determined based on individual contributions to the study. Site investigators will be included as co-authors in order decided by their contributions. Following the publication of an initial article the project’s principal investigator and project coordinator will discuss publication scenarios with site representatives, help identify the lead scientists who will be responsible for drafting of the manuscript and provide scientific oversight for each possible publication. Authorships and their order will be determined based on individual contributions to the studies. Research findings will be disseminated locally through scientific group meetings, research and group meetings, research and progress meetings at the College Of medicine and MLW and nationally through the annual College of Medicine research dissemination conference. Results will also be reported to College of Medicine Research Ethics Committee (COMREC). Peer reviewed publication of findings is anticipated. We anticipate the following constraints in the study: Delay in completing the planned activities on time due to travel restriction or general hindrance caused by the COVID-19 situation, slow enrolment due to insufficient number of iNTS disease cases or in general we may have too few cases and if COVID-19 continues into 2021 study staff visiting and interviewing patients may be at risk.