Browsing by Author "Mathanga, Don"

Now showing 1 - 3 of 3
  • Thumbnail Image
    Item
    Restricted
    Covid 19 transmission and morbidity in Malawi
    (2022-06-15) Mathanga, Don
    COVID Transmission and Morbidity in Malawi (COVID-TMM) Type of research study: Prospective cohort study The problem to be studied: To assess whether infection rates and morbidity of SARS CoV-2, as well as acquisition and duration of antibody-induced immunity in Malawi may be impacted by a trained and/or tolerant innate immunity, resulting in particular from malaria, helminth infections, anemia and nutrient deficiency Population: A total of 1,200 participants will be recruited in Malawi (300 in the vaccine cohort and 900 in the natural infection cohort). Participants will have 5 to 75 years of age and any sex. Objectives: 1. To determine the risk and predictors of infection and disease among contacts of SARS-CoV-2 infected subjects in Malawi. 2. To determine whether innate immune responses lower the risk of SARS-CoV-2 infection and disease, and acquisition and duration of vaccine responses. 3. To assess whether alterations in innate immune responses relevant to SARS-CoV-2 are associated with malaria or intestinal parasite infections. 4. To assess the acquisition and longevity of Abs and cellular adaptive responses elicited by SARS-CoV-2 infection and vaccination. 5. To assess whether malaria and intestinal parasite infections, chronic/mild undernutrition, and anemia mediate alterations in Ab and other adaptive cellular responses to SARS-CoV-2 through innate immune responses or a different unknown mechanism. Methodology: We will enroll up to 1,200 participants aged 5 to 75 years from four peri-urban health centres in Blantyre district Malawi. SARS-CoV-2 symptomatic individuals (index cases) and their household contacts and recently vaccinated individuals will be selected and screened for eligibility. Specifically, two cohorts will be enrolled: a) Natural infection cohort– 200 symptomatic subjects (index cases) will be enrolled when they seek diagnosis for their symptoms of COVID-19 and have their SARS-CoV-2 infection confirmed. All their household contacts (anticipated 700) aged 5 years or older will be examined for infection. Blood will be drawn from all eligible subjects who provide consent. One week later, SARS-CoV-2 testing will be repeated in household contacts who tested negative in the first visit. Individuals who test negative after this second test will be excluded from visits that take place more 15-Jun-2022 COVID TMM Version 1.1; June 2, 2022 2 than 2 weeks after enrollment. Participants will be followed up for 18 months after enrollment. b) Vaccine cohort – 300 subjects aged 15-75 years will be recruited when they attend a vaccination clinic at any of the study sites for their first dose of the AstraZeneca or the Johnson and Johnson vaccines. Venous blood will be collected at that time. For AstraZeneca vaccinees, when they come for their 2nd vaccine dose, approximately 90 days after the 1st vaccine dose, they will receive material for collection of a stool sample. Johnson and Johnson vaccinees will receive the container for collection of the stool sample when they receive the first vaccine dose. Two weeks after completion of the primary regimen (2 nd dose of the AstraZeneca and 1st dose of the Johnson and Johnson vaccines), a venous blood draw will be repeated. Subsequent visits and procedures will happen at the same schedule of the “Natural Infection” cohort. Venous blood samples from participants in both the natural infection and vaccine cohort will be used to quantify innate immune phenotypes and stimulation, quantification of micronutrients, quantification of antibody magnitude and function, quantification of T cell phenotypes and stimulation, and detection of malaria infection. Total Study Duration: 5 years Subject Participation Duration: 18 months after the first visit. Expected findings and dissemination Our findings will help understand the lower morbidity of SARS CoV-2 that has been registered in Malawi and other sub Saharan African countries and the effect that malaria, helminth infection, anemia, and nutrient deficiency may have on SARS CoV-2 in Malawi. Furthermore, we will assess acquisition and duration of responses to infection and immunity in Malawi. Our study may inform vaccination policy in Malawi by identifying high risk groups, optimal target coverage, and determining intervals at which booster doses should be provided. The results will be distributed and discussed with the local community, Ministry of Health, Kamuzu University of Health Sciences, and the College of Medicine Research Ethics Committee (COMREC). Main findings will be presented in international conferences, College of Medicine Research Dissemination Conference, and published in international peer reviewed journals. 15-Jun-2022 COVID TMM Version 1.1; June
  • Thumbnail Image
    Item
    Restricted
    Strengthening the evidence on the RTS,S/AS01 malaria vaccine: assessment of safety and effectiveness using case-control studies
    (Kamuzu University of Health Sciences, 2021-05-26) Mathanga, Don
    Problem statement: Malaria remains a major cause of childhood morbidity and mortality, particularly in sub-Saharan Africa, where over 90% of all cases occur. In 2018, 228 million malaria cases and 405 000 deaths were estimated worldwide, with the majority of deaths in African children. New tools are urgently needed to change the trajectory of malaria morbidity and mortality and the RTS,S/AS01 (RTS,S) malaria vaccine currently being piloted in 3 countries including Malawi is the first and only vaccine that has been shown to provide protection against malaria. Recent review of data on the RTS,S vaccine, including long term follow-up, brought into question the necessity of the 4th dose. Additionally, data generated from the MVPE show lower than expected event rates for the safety outcomes of interest such as cerebral malaria and meningitis. The Malaria Vaccine Implementation Programme Advisory group therefore recommened that a case-control study should complement data being collected through surveys and cohort studies to comperehesively address questions on vaccine safety. Objectives: The overall objectives of the case-control study is to determine the association of the RTS,S vaccine with the safety signals identified in the Phase 3 trial of RTS,S. The specific objectives include:: To determine if children who receive RTS,S vaccination (at least one dose) are at increased risk of meningitis compared to unvaccinated children. To determine if children who receive RTS,S vaccine (at least one dose), or children who receive 3 doses, are at increased risk of cerebral malaria compared to unvaccinated children. To estimate the incidence of severe malaria in children who received 3 doses, but failed to receive a 4th dose, compared to children who did not receive the vaccine (the rebound effect). To determine the effectiveness of RTS,S (following 3 doses and following the 4th dose) in preventing severe malaria. To assess if RTS,S vaccine increase mortality in girls, or is less effective in preventing deaths in girls than in boys. Type of research study: Case control Study. Methods: The sites of the study are Balaka and Machinga, Ntchisi and Mchinji districts. Cases will be children with either confirmed meningitis, or severe malaria or who die. For each case, four control children born within one month of the date of birth of the case will be recruited from the neighbourhood of the case’s home, after moving a distance of at least 100m from the home of the case. The case will be visited at home, to confirm details recorded in hospital and to collect further information about the case and their household. Then the same field team will recruit controls from the same neighbourhood. Controls for deaths will be recruited following completion of the verbal autopsy (VA), the VA team will then recruit controls from the same neighbourhood where the case child was living. Expected findings and their dissemination: Findings will provide important evidence to inform policy guidelines and clinical practice at the global level. A finding that a 3-dose regimen is sufficiently effective (and the 4th dose provided at 2 years of age unnecessary) would result in improved cost effectiveness and improved adherence. The results will be shared with stakeholders including the Ministry of Health, the World Health Organization and the global community through reports, local and international meetings and through peer reviewed publicactions.
  • Thumbnail Image
    Item
    Restricted
    Strengthening the evidence on the RTS,S/AS01 malaria vaccine: assessment of safety and effectiveness using case-control studies
    (Kamuzu University of Health Sciences, 2021-05-26) Mathanga, Don
    Problem statement: Malaria remains a major cause of childhood morbidity and mortality, particularly in sub-Saharan Africa, where over 90% of all cases occur. In 2018, 228 million malaria cases and 405 000 deaths were estimated worldwide, with the majority of deaths in African children. New tools are urgently needed to change the trajectory of malaria morbidity and mortality and the RTS,S/AS01 (RTS,S) malaria vaccine currently being piloted in 3 countries including Malawi is the first and only vaccine that has been shown to provide protection against malaria. Recent review of data on the RTS,S vaccine, including long term follow-up, brought into question the necessity of the 4th dose. Additionally, data generated from the MVPE show lower than expected event rates for the safety outcomes of interest such as cerebral malaria and meningitis. The Malaria Vaccine Implementation Programme Advisory group therefore recommened that a case-control study should complement data being collected through surveys and cohort studies to comperehesively address questions on vaccine safety. Objectives: The overall objectives of the case-control study is to determine the association of the RTS,S vaccine with the safety signals identified in the Phase 3 trial of RTS,S. The specific objectives include:  To determine if children who receive RTS,S vaccination (at least one dose) are at increased risk of meningitis compared to unvaccinated children.  To determine if children who receive RTS,S vaccine (at least one dose), or children who receive 3 doses, are at increased risk of cerebral malaria compared to unvaccinated children.  To estimate the incidence of severe malaria in children who received 3 doses, but failed to receive a 4th dose, compared to children who did not receive the vaccine (the rebound effect).  To determine the effectiveness of RTS,S (following 3 doses and following the 4th dose) in preventing severe malaria.  To assess if RTS,S vaccine increase mortality in girls, or is less effective in preventing deaths in girls than in boys. Type of research study: Case control Study. Methods: The sites of the study are Balaka and Machinga, Ntchisi and Mchinji districts. Cases will be children with either confirmed meningitis, or severe malaria or who die. For each case, four control children born within one month of the date of birth of the case will be recruited from the neighbourhood of the case’s home, after moving a distance of at least 100m from the home of the case. The case will be visited at home, to confirm details recorded in hospital and to collect further information about the case and their household. Then the same field team will recruit controls from the same neighbourhood. Controls for deaths will be recruited following completion of the verbal autopsy (VA), the VA team will then recruit controls from the same neighbourhood where the case child was living.Expected findings and their dissemination: Findings will provide important evidence to inform policy guidelines and clinical practice at the global level. A finding that a 3-dose regimen is sufficiently effective (and the 4th dose provided at 2 years of age unnecessary) would result in improved cost effectiveness and improved adherence. The results will be shared with stakeholders including the Ministry of Health, the World Health Organization and the global community through reports, local and international meetings and through peer reviewed publications.