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- ItemRestrictedTrypanosomiasis cases cluster analysis for localization of interventions in endemic Malawi sites(Kamuzu University of Health Sciences, 2021-12-16) Musaya, JanelisaStudy type We are proposing to conduct the following study types Desk analysis of patient archived samples leading to geospatial maps Cross-sectional surveys of tsetse densities and HAT in mapped cluster sites Problem In Malawi, trypanosomiasis is a latent threat due to interaction between humans and wild animals. Human cases usually occur as a result of tsetse fly bites in animal reserves where the vectors are found. For the past five years, Rumphi and Nkhotakota districts have experiencing outbreaks which demonstrates that the risk in this environment is growing. It was noted however in our recent work in these districts that the infected individuals present very late at the hospitals. Late presentation means case management with very toxic drugs, and which also requires hospitalization. It is not yet understood why a lot of people prefer to report late at the hospital. But of most importance is to influence people to recognize signs and symptoms early enough for them to seek medical care. We propose to use the already existing medical records of the trypanosomiasis cases admitted at the district hospitals to trace where they came from in order for us to understand factors that are affecting transmission in those areas. Once the areas are identified we would want to engage with the people in those area and train them on how to use Targets (tsetse control measure) to reduce the area density of tsetse flies. Tsetse flies are vectors of transmission for trypanosomiasis. Our major hypothesize therefore is that mapping human cases will show area clusters of infections which can be easily targeted for interventions. Objectives The main aim is to trace geospatially where trypanosomiasis cases are coming from in order to find ways of introducing area specific control interventions in Rumphi and Nkhotakota districts Methodology The study is divided into two interacting work packages: Work package one (WP1) is to use case report forms from the hospital archives, to identify villages where trypanosomiasisi casescome from in order to understand factors influencing transmission. Work package two (WP2) is to train communities in WP1 above on how to identify Tsetse high density areas and how they can control transmission by using tsetse targets (insecticide treated cloths). Expected Findings and Dissemination We hope to pinpoint exactly where the interventions should be targeted and inform them what interventions will work in those areas. With current Centre for Disease Control efforts of using Tsetse targets to reduce transmission we want to empower communities to be able to make and deploy targets on their own as a control strategy. The results will be shared with the local communities, the district executive committee and the ministry of health for policy decision making.
- ItemRestrictedThe role of Schistosoma mansoni infection in chronic non– communicable disease burden among adults in Mangochi district(Kamuzu University of Health Sciences, 2020-11-11) Nyangulu, WonganiType of study: Cross sectional study. Problem to be studied: Schistosomiasis is a Neglected Tropical Disease (NTD) caused by infection with parasitic flatworms of the Schistosoma genus. The two species prevalent in Malawi are Schistosoma haematobium and Schistosoma mansoni which cause genitourinary and intestinal disease respectively. S. haematobium is recognized as an etiological agent in the causal pathway for cervical and bladder cancer. However, the contribution of S. mansoni infection to the chronic non – communicable disease burden in Malawi is not known. Objectives: The objectives of the study are: i. To estimate prevalence of urinary and intestinal schistosomiasis among adult patients aged 18 years and above with newly diagnosed or existing NCD at Mangochi District Hospital. ii. To evaluate risk factors for urinary and intestinal schistosomiasis infection in in- and outpatient adults aged 18 years and above presenting with newly diagnosed or existing NCDs at mangochi district hospital. iii. To evaluate the association between schistosomiasis infection and NCDs in in- and outpatients presenting with existing or newly diagnosed NCDs at Mangochi District Hospital. Methodology: This is a cross sectional study. The study population are adults over 18 years old who have existing or newly diagnosed NCD. They will be identified in OPD clinics, NCD clinics and among in – patients admitted at Mangochi Hospital. Data will be obtained from a questionnaire and abstracted from in – and outpatient notes using a form on ODK. Patients will also provide urine and stool samples on the same day which will be tested for S. mansoni. Point of care (POC) Circulating Cathodic Antigen (CCA) tests will be used to detect S. mansoni in urine. Microscopy using Kato – Katz method will detect S. mansoni eggs in stool. Expected findings and dissemination: We will describe the prevalence of S. mansoni infection among patients with non – communicable diseases, its risk factors in this population and association of schistosomiasis with NCDs. We will therefore share our findings with the University of Malawi College of Medicine, COMREC, Mangochi District Health Office, District Health Management Team, Communities in Mangochi, the District Commissioner and District Executive Committee. We will also present findings at local and international conferences and in peer reviewed publications.
- ItemRestrictedHybridization in urogenital schistosomiasis (HUGS)(Kamuzu University of Health Sciences, 2021-10-18) Musaya, JanelisaType of study: Cohort study, with cross-sectional snail surveys Problem to be studied: Schistosomiasis is a Neglected Tropical Disease (NTD) caused by infection with parasitic flatworms of the Schistosoma genus. With our discovery of novel Schistosoma haematobium hybrids commonly co-infecting Malawian school children, critical knowledge gaps in the biology and control of schistosomiasis in Central Africa have emerged. These amplify formal concerns of the WHO’s preventive chemotherapy (PC) strategy and underpinning targets within their 2021-2030 Roadmap. Our HUGS (hybridisation in urogenital schistosomiasis) investigation aims to address these critical knowledge gaps in the transmission biology, applied epidemiology and clinical importance of S. haematobium hybrids. Objectives: The objectives of the study are: i. To test if the proportion of hybrid coinfection is uniform across two representative communities in Mangochi and Nsanje districts where S. haematobium-mattheei or S. haematobiumbovis occur, inclusive of household GPS mapping and identification of associated risk factors by questionnaire. ii. To verifyassess any changes in the proportions and spatial patterns of hybrid coinfection with annual praziquantel treatment, in a 2-year longitudinal population follow-up studystudy, if the above proportions and spatial patterns of hybrid coinfection hold, or alter, with annual praziquantel treatment. iii. To ascertain if there is any altered host morbidity (e.g. urogenital inflammation) in hybrid coinfection(s) as measured by portable ultrasonography and point-of-contact assays. iv. To reveal describe the hybrid environmental transmission dynamics of the hybrid coinfection(s) upon malacological, livestock tracking and abattoir surveys, dissecting schistosome material by advanced genetic profiling. Methodology: This multi-study will comprise of environmental snail surveys, animal-abattoir surveys and human cohort studies. Twelve quarterly spaced environmental snail surveys will commence before, during and complete after, examinations for hybrids in livestock and people to give best chance of revealing environmental transmission. Three inspections of slaughtered livestock at abattoir, each precede human sampling to better alert novel hybrids/animal schistosomes before three annual examinations of the human cohort, baseline and two follow-up surveys. Data will be obtained from a questionnaire and participants will also provide urine and stool samples on the same day which will be tested for Schistosoma-hybrids. Expected findings and dissemination: We will describe the prevalence of Schistosomahybrids. We will therefore share our findings with the Kamuzu University of Health Sciences, (COMREC), Mangochi District Health Office,District Health Management Team, Communities in Mangochi, the District Commissioner and District Executive Committee. We will also present findings at local and international conferences and in peer reviewed publications.
- ItemRestrictedInvestigating effects of topoisomerase mutations on topoisomeraseciprofloxacin interaction in Salmonella typhi isolated in Blantyre(Kamuzu Universiyt of Health Sciences, 2021-10-06) Matambo, ErnestIntroduction Typhoid fever accounts for about 135, 000 deaths in adults and children in south Asia, central and southern Africa. The recommended antibiotic treatment of typhoid fever in Malawi is the fluoroquinolone ciprofloxacin, however, Salmonella enterica subspecies enterica serovar Typhi (S. Typhi) decreased susceptibility to ciprofloxacin has been detected in Blantyre, Malawi. S. Typhi can become resistant to fluoroquinolones by two mechanisms; either due to the acquisition of plasmid mediated resistance genes or mutations in gyrA, gyrB, parC and parE genes in topoisomerase II and IV. This study will use in silico methods to identify mutations in gyrA, gyrB, parC and parE genes in S. Typhi from Blantyre and to investigate the effects of topoisomerase II and IV mutations on topoisomerase-ciprofloxacin interaction. Main objective To investigate the effect of gyrA, gyrB, parC and parE mutations on ciprofloxacintopoisomerase interaction in S. Typhi isolated in Blantyre. Specific objectives To identify mutations in Quinolone Resistance Determining Region of S. Typhi with decreased ciprofloxacin susceptibility isolated in Blantyre. To describe effects of mutations in gyrA, gyrB, parC and parE genes on their protein structure in S. Typhi with decreased ciprofloxacin susceptibility isolated in Blantyre. To compare folding energy of topoisomerase protein structure of S. Typhi with decreased ciprofloxacin susceptibility to topoisomerase protein structure of ciprofloxacin-sensitive S. Typhi. To compare ciprofloxacin-topoisomerase interaction in topoisomerase of S. Typhi with decreased ciprofloxacin susceptibility to ciprofloxacin-sensitive S. Typhi Methodology This will be a retrospective study. Reads of S. Typhi with reduced susceptibility to ciprofloxacin (n=14) and of ciprofloxacin sensitive S. Typhi (n=14) will be assembled using de novo assembly. Topoisomerase II and IV genes will then be extracted from the assembled genomes. Topoisomerase II and IV gene mutations will be identified in the genomes of S. Typhi with decreased susceptibility to ciprofloxacin by comparing the 06-Oct-2021 Ver1.1 September 2021 gene sequences to the CT18 reference genome. The topoisomerase II and IV gene sequences will be translated into protein sequences and then their protein structures predicted. The protein structures will be analysed for structural differences in the S. Typhi with decreased ciprofloxacin susceptibility and ciprofloxacin-sensitive S. Typhi. Folding energy between S. Typhi with decreased ciprofloxacin susceptibility and ciprofloxacin-sensitive S. Typhi protein structures will be compared. Bonding energy with ciprofloxacin between the two groups of protein structures will also be compared. Expected findings and their dissemination Expected findings are that there will be mutations in topoisomerase II and IV gene sequences and that the mutations will be in the ciprofloxacin binding pockets of the predicted protein structures in the S. Typhi with decreased ciprofloxacin susceptibility. Folding energy is expected to be low in protein structures without mutations as compared to protein structures with mutations. Protein structures with mutations will have high binding energy as compared to those without mutations. The study findings and write up will be submitted to COMREC, Kamuzu University of Health Sciences Library and to a peer-reviewed journal for publication. 06