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- ItemRestrictedA pharmacokinetic randomised interventional study to optimise dihydroartemisinin-piperaquine dosing for malaria preventive treatment in Malawian infants (OPTIMAL Study) version 1.0(Kamuzu University of Health Sciences, 2022-09-08) Banda, Clifford George Dr.Type of study This is an open-label randomised interventional study (with 1:1 allocation into intervention and control groups) to optimise the dosing of an antimalarial drug, dihydroartemisininpiperaquine (DP), administered with routine vaccinations, for malaria preventive treatment in infants. Problem to be studied The World Health Organisation (WHO) recommends the use of sulphadoxine-pyrimethamine (SP), administered with routine immunisation, for intermittent preventive treatment of malaria in infancy (IPTi) in areas of moderate to high transmission in sub-Saharan Africa. However, there is limited uptake of this recommendation and increasing resistance of malaria parasites to SP. Fortunately, another antimalarial drug, DP, has shown higher protective efficacy than SP. Nevertheless, there is a paucity of evidence to guide its optimal dosing when administered together with routine vaccinations in infancy. The present study seeks to define the optimal dose of DP for IPTi when administered with routine vaccinations. Overall objective The overall objective of this study is to define the optimal dose of DP for IPTi when administered with routine vaccinations Specific objectives 1. To describe age-related changes in population pharmacokinetic properties of piperaquine following partially supervised administration of IPTi-DP at four different routine immunization time points in infancy (i.e., at 10-, 14 weeks, 6 months, and 9 months of age). 2. To evaluate the association between piperaquine exposure and incidence of symptomatic and asymptomatic malaria during IPTi-DP. 3. To compare the safety and tolerability of DP following supervised administration of IPTi-DP at routine immunizations with routine immunizations alone. 4. To apply population pharmacokinetic modelling and simulation techniques to optimise the dose of piperaquine when administered as IPTi-DP Methodology 220 infants will be randomised, from 10 weeks of age, to receive DP with routine vaccines (intervention group, n=110) or standard of care; routine vaccines only (control group, n=110). They will be followed up until 12 months of age. In the intervention group, infants will contribute capillary samples for piperaquine concentrations, at different time points after administration of DP, and capillary samples to quantify malaria parasitaemia using microscopy and quantitative PCR. In the control group, infants will contribute capillary blood samples at the same time points as those in the intervention group for malaria parasitaemia over the first year of life. Additionally, the safety and tolerability of DP for IPTi with routine vaccinations will be monitored by comparing adverse events in the intervention and control groups Expected findings and their dissemination Optimised dosing regimens of DP for IPTi will be developed by applying population pharmacokinetic-pharmacodynamic modelling techniques on data obtained from: 1. Understanding age-related changes in piperaquine pharmacokinetics from infants in the intervention group. 2. Evaluating the pharmacokinetics, efficacy and safety of DP for IPTi in infants in the intervention group compared with malaria incidence and adverse events in the control group. This work will provide the much-needed evidence to inform DP dosing for IPTi when administered with routine immunisation. Additionally, it will inform future work on optimal DP dosing for malaria treatment in infants. The findings will be disseminated to study participants, in peer-reviewed scientific journals, WHO, national malaria control programs in malaria-endemic settings and ethics committees that will review and approve the study (COMREC, LSTM REC and UCT HREC).
- ItemRestrictedIdentifying functional antibody responses that protect against malaria in children, version 1.0(Kamuzu University of Health Sciences, 2022-08-03) Rogerson, Stephen; Seydel, KarlType of study: Observational cohort study The Problem: Although antibodies have been shown to be important for the protection against malarial disease, the specific characteristics of these protective antibodies have not been well delineated. Methodology: The study population of interest will be children aged 1-8 years of age drawn from three ongoing COMREC-approved studies. This is a secondary analysis of samples already being collected from three ongoing COMREC-approved studies. Children in the ongoing “Treatment of brain swelling in pediatric cerebral malaria” study (P. 09/16/2024, PI: Taylor) with cerebral malaria will be matched with children with uncomplicated malaria from the study “Characterization of Plasmodium falciparum var/PfEMP1 type and immune response to PfEMP1 in severe and uncomplicated clinical malaria” (P.01/15/1668, PI:Kim) and children with asymptomatic parasitemia from the “Malaria pathogenesis: Progression cohort and extremes, case control study” (P.11/18/2530, PI: Seydel). Children with no evidence of malaria infection in the “Malaria pathogenesis” study will be used as uninfected controls. After obtaining informed consent from their primary caretaker, a brief medical history and demographic information will be collected from all participants. Children with cerebral malaria are having a 10ml blood sample collected. Children in the uncomplicated and asymptomatic cohorts are having 4mls of blood collected. Plasma from this sample, as well as peripheral blood mononuclear cells from these samples will be purposed for this proposed study. No additional blood will be drawn for the purpose of this study. The serum from these studies will first be used in a Luminex assay to determine the strongest candidates that might be leading to protective immunity. Antibody and PBMC responses to these antigens will then be prioritized in the subsequent assays. These assays will involve the functional and biochemical characterization of antibodies in ~50 ways (see Research Strategy below). Comparison groups will be among the three disease severity types as well as between acute and convalescent sera. Data from these assays will be analyzed using elastic net regularized logistic regression and partial least squares discriminant analysis to identify the antibody characteristics associated with disease severity. Broad Objective: To identify the biophysical and functional characteristics of antibodies that protect against clinical malaria in children. Specific Objectives: 1) To use the Luminex bead approach to identify a subset of five P. falciparum expressed proteins that serve as targets of protection against cerebral malaria. To use the Systems Serology approach to identify biophysical and functional characteristics of antibodies against the targets identified in Aim 1, that either protect from cerebral malaria or develop during convalescence from cerebral malaria. 3) To use the Systems Serology approach to identify the biophysical and functional characteristics of antibodies that are present in children with asymptomatic P. falciparum infection and not in children with clinical disease. Expected Findings: We expect to find a subset of PfEMP1 domains, as well as a subset of proteins expressed on the merozoite stage of the parasite, that are most important in the protection of children from severe malaria. We also expect to find a distinct antibody profile that is most effective at controlling the P. falciparum infection. This will be accomplished by comparing the antibody characteristics seen in children with severe disease to those seen in children with milder infection, and (for the second question) comparing antibody responses in children with asymptomatic parasite infection to children with symptomatic malaria. Dissemination: Results will be disseminated to the medical community through peerreviewed publications and presentations at relevant scientific conferences. Results will also be shared with KUHeS at the annual Research Dissemination Conference. Annually, we will also be providing COMREC updates as required in the annual report.
- ItemRestrictedThe effect of repeated washing of the royal guard, Interceptor G1 and G2 nets on behaviour (Host seeking and blood feeding) and survival of anopheles mosquitoes(Kamuzu University of Health Sciences, 2022-08-17) Banda, Judith SinkanakoInsecticide treated mosquito nets on behaviour and survival of Anopheles mosquitoes the effect of repeated washing of the royal guard and interceptor G2 nets on behaviour (host seeking and blood feeding) and mortality on Anopheles mosquitoes. This is a sub study which will be conducted under ESSENTIALS project IRB number P.10/20/3155 being hosted by the Malaria Alert Centre in Blantyre. Problem statement Insecticide-treated nets remain important in preventing transmissions of mosquito borne pathogens. Long-lasting insecticide-treated nets (LLINs) offer longer time protection against such bites because they are more wash resistant, and are preferred to conventionally treated nets. Whether the new LLINs (IG2 and RG) are wash resistant compared to the conventional nets is unknown. Moreover, how the repeated washing affects host seeking and feeding behaviour and survivor of Anophelines success remains elusive. Therefore, this study will assess the effect of Royal guard, Interceptor G1 and G2 on blood feeding, host seeking behaviours and survival of the effect of repeated washing of insecticide treated mosquito nets on behaviour and survival of Anopheles mosquitoes after repeated washing under laboratory conditions Main objective To assess the effect of repeated washing of insecticide treated mosquito nets on behaviour and survival of Anopheles mosquitoes To assess the effect of repeated washing of the royal guard, interceptor g1 and g2 nets on host seeking and blood feeding behaviour and survival of Anopheles mosquitoes Specific objectives 1. To determine the number of knocked down and dead mosquitoes post exposure to both washed and unwashed nets 2. To determine the number of blood fed mosquitoes post exposure to washed and un washed nets. 3. To evaluate the host seeking behavior of mosquitoes post exposure to washed and un washed net. 1. To assess the knockdowns and survival of mosquitoes when exposed to unwashed nets and washed nets. 2. To determine the number of blood fed mosquitoes post exposure to washed and un washed nets. 3. To evaluate the host seeking behaviour of mosquitoes post exposure to washed and un washed net. Methodology The researcher will conduct a cross-section study and will perform host seeking and WHO Cone bioassays on Kisumu, Anopheles funestus and Anopheles gambiae. Data will be collected and recorded in a laboratory note book. Collected data will be manually entered into Microsoft excel and analyzed using R software version 20. Expected Findings and Dissemination The researcher hypothesizes that blood fed mosquitoes and host seeking behaviour will increase with increase in number of net washes while mortality of mosquitoes will decrease with increase in the number of net washes. Findings from this study will be disseminated through peer-reviewed publications, presentations at scientific conferences including the KUHeS annual dissemination conference. A researcher will submit a project completion report to the College of Medicine Research and Ethics Committee and Liverpool school of tropical medicine.
- ItemRestrictedIdentifying Determinants of Submicroscopic Malaria in Malawi, version 1.0(Kamuzu University of Health Sciences, 2022-07-12) Msowoya, GiftType of Study This is a cross sectional study that aims at identifying factors associated with submicroscopic malaria infection in three districts in Malawi; Blantyre, Chikwawa and Thyolo districts. Malaria continues to be a burden to the health of people globally with about 229 million cases with a reported 409 000 deaths in 2019 alone. In Africa specifically sub-Saharan Africa malaria also continues to be a big burden with 95 percent of all malaria cases in the world occurring in this region of which resulted into 12 percent increase in deaths in 2020 as compare to 2019. In Malawi malaria is big burden contributing to about 23 percent of all outpatient visits and 5.2 million cases in 2019 alone. Submicroscopic malaria which is malaria infection that is negative on microscopy testing and positive on polymerase chain reaction (PCR) test contributes to the human reservoir for the plasmodium parasites that ensures continuous presence of the parasites in the population hence favoring onwards transmission. The human reservoirs are people who are infected but are not sick harboring either microscopic or submicroscopic infection. Because they are not sick these are the populations which are not treated hence making malaria control and elimination difficult. Problem; In Malawi there is paucity of data on determinants of submicroscopic malaria which would help with mass drug administration as a strategy in targeting those human reservoirs of plasmodium. If factors associated with submicroscopic malaria could be studied it would help in targeting the screening and treatment plus in targeting the right group for mass drug administration (MDA) to deal with these cases of these submicroscopic cases in order to reduce the human reservoirs of plasmodium. This study therefore seeks to identify factors associated with submicroscopic infection in different transmission settings in Malawi. If we can identify those at risk of submicroscopic malaria infection, we can then better tailor interventions to target them hence reducing the prevalence and helping with malaria control while contributing to malaria elimination in the long run. Broad objective: To establish the determinants of submicroscopic malaria across different transmission settings in Malawi. Specific objectives: 1. To determine prevalence of malaria cases among population from Blantyre city, Chikwawa and Thyolo districts 2. To estimate the proportion of submicroscopic malaria infections among population from Blantyre city, Chikwawa and Thyolo districts. 3. To analyze determinants of submicroscopic malaria infection in the population from among populations from Blantyre city, Chikwawa and Thyolo districts Methodology Type of study: This is a cross sectional study design which will utilize secondary data that was collected for cross sectional survey conducted by malaria alert center in three districts names; Blantyre city, Thyolo and Chikwawa between 2012 and 2016. In the surveys, houses were sampled from sampled areas withing these districts and all people belonging to selected household were interviewed, their blood samples collected, the area around the house inspected and mosquitoes collected from the houses for analysis. Microscopy was done to test for malaria parasites and those that tested negative were tested using PCR to determine those with submicroscopic infections. We will look at those with submicroscopic infection to look for determinants of this infection. Expected findings and Their dissemination The project is expected to produce results on determinants of submicroscopic malaria infection which will be added knowledge to the already known prevalence of submicroscopic malaria in these districts which could help drive policy as well as strategies to help with control and elimination of malaria in Malawi. Results will be disseminated locally at the Malaria alert center, college of medicine, Kamuzu college of health sciences, college of medicine research ethics committee, and shared with the district health officers and other partners in malaria control and management working in these districts as well as published in medical journals.
- ItemRestrictedDeveloping a digital platform for sub-district level malaria burden stratification mapping using routine health facility case data – guiding the national transition to targeted malaria control, version 1.0(Kamuzu University of Health Sciences, 2022-07-26) Stanton, Michelle; Chirombo, JamesStudy type: Secondary data analysis Research problem: With the continued reduction of malaria prevalence at the national level after many years of intensive malaria interventions, community-level transmission becomes more important. Focusing on the trends in malaria transmission at the national level may mask the heterogeneities that exist at the sub-district level. Therefore, it is important to understand the disease dynamics at the community level to inform strategies that can eventually lead to the elimination of the disease. Main objective: The main objective is to use routinely reported health facility-level malaria case data to produce sub-district level estimates of clinical malaria incidence in Malawi and stratify the country by different levels of incidence for more targeted malaria intervention. Specific objectives: • Develop standardised procedures for data collation and data management of routinely reported data • Undertake a spatial analysis to stratify the country into the predefined risk categories at regular intervals, using available data on current intervention coverage, climate/environment, and evidence of insecticide resistance. • Develop a digital dashboard which can be accessed by the National Malaria Control Programme (NMCP) and district programme coordinators to display interactive maps, summaries of the resulting analysis and generate automated reports • Train staff at the NMCP and the Central Monitoring and Evaluation Division (CMED) to update the data and maintenance analyses on a regular basis with the support of the Ministry of Health’s Digital Heath Division (DHD). • Support relevant technical working groups (TWGs) to use the maps when planning upcoming interventions. Methodology: We will obtain monthly aggregated malaria case data from the Health Management Information System (HMIS) known as DHIS21 at the health facility level. After data processing, we will apply geospatial statistical methods to estimate malaria incidence over time, incorporating the effects of climate, environment, and malaria intervention activities. Our results will then be visualised within a digital dashboard which will be integrated within NMCP surveillance systems at the national and district levels. Expected results and their dissemination We anticipate that our analysis will reveal the spatial and temporal heterogeneities in malaria transmission across the country. Results will be shared with COMREC and the Ministry of Health at relevant technical working group meetings and the joint KUHeS and MLW research dissemination conference. We will also publish the results in peer-reviewed journals.