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- ItemRestrictedPhylodynamic analysis of re-emergent G3 rotavirus strains in Blantyre, Malawi(Kamuzu University of Health Sciences, 2022-08-17) Mhango, ChimwemweStudy type: Retrospective study Problem: Malawi has experienced the re-emergence of genotype G3 rotavirus strains 6 years after the introduction of Rotarix rotavirus vaccine into the national immunization program in October 2012. Genotype G3 strains were previously detected in 1999, approximately 17 years before the current re-emergence in November 2017. By 2019, genotype G3 had become the predominant genotype causing acute gastroenteritis among under five children in Blantyre, Malawi. It is however, not known how these genotype G3 strains re-emerged in Malawi as wel as how effective the currently used vaccine would be against the genotype G3 strains. Main objective: To investigate the phylodynamic of re-emerging “G3” rotavirus strains in Malawi through whole genome analysis. Specific objectives 1 To describe the complete genotype constellations of G3 rotavirus strains circulating in Malawi. 2 To identify lineages among G3 rotavirus strains circulating in Malawi. 3 To determine the relationship between global and Malawian G3 rotaviruses. 4 To estimate time to most recent common ancestor for G3 rotaviruses in Malawi. 5 To compare the structural conformation of neutralizing epitopes of G3 rotaviruses to RV1’s G1P[8] strain. Methodology The study will utilise already generated sequences of genotype G3 positive rotavirus specimens that were isolated from under-five children recruited for the diarrhea surveillance project. Convenient sampling was used to sample at least one representative genotype G3 strain per calendar month from November 2017 to August 2019 for whole genome sequencing. 27 representative whole genomes of genotype G3 strains passed the final quality control after the whole genome sequencing and will be utilized in this study. In addition, whole genomes of 3 representative genotype G3 strains that circulated from 1997 to 1999 will also be included in the analysis. To understand how these strains emerged, maximum likelihood analysis will be used to generate phylogenetic trees with globally circulating G3 strains to determine the origins. In addition to that, protein modelling will be used to assess vaccine effectiveness against the emerging January G3 strains. Expected Findings and Dissemination of Results The study will uncover the precise origins of the G3 rotavirus strains as well as assess predict whether the current vaccine will be effective against the emerging strains. The findings of this study will be disseminated through national and international conferences as well as peer reviewed journals. A detailed report of the project will be submitted to COMREC while a detailed thesis compiling everything that will be done as well as the results and implication of this work will be submitted to the College of Medicine library for future references.
- ItemRestrictedAclinicaly oriented Microbial resistance surveillance network(2022-06-22) Lissauer, SamathaEXECUTIVE SUMMARY Type of study: Descriptive prospective surveillance Problem to be studied: Antimicrobial resistance (AMR) is a major threat to human health with estimates of 10 million AMR deaths per year by 2050. However, these estimates are based on limited data, largely from high-income settings. There is an urgent need to generate better data on the clinical impact on AMR, especially from resource-limited settings. Currently many AMS surveillance systems are passive, pathogen focused, using information from medical laboratories only. As such, we are missing critical information such as impact and cost of drug resistant infection (DRI) at the patient level and patient-level risk factors. This information is crucial in making local and global decisions about treatment and policies. The ACORN2 project is implementation of a clinically orientated antimicrobial resistance surveillance programme of hospitalized patients with suspected acute bacterial infections across 15 sites in 9 countries, of which QECH will be the only site in Malawi. Objectives Primary objective: Implement clinical antimicrobial resistance (AMR) surveillance of hospitalised patients between 0 to 17 years with suspected acute bacterial infections Secondary Objectives To characterise drug-resistant infections (DRI) by clinical syndrome, place of acquisition (CAI, HAI, HCAI), patient group (adult, paediatric, and neonatal), and location (site, country, region) To determine the attributable mortality for extended spectrum beta-lactamase producing Escherichia coli, methicillin resistant Staphylococcus aureus bloodstream infection and Enterococci. To determine the major indications for prescribing parenteral antibiotics by patient group (adult, paediatric, neonatal), timing of prescription (day of admission versus >2 days after admission), and location (site, country, region) To determine the major empiric antibiotics used by clinical syndrome, place of acquisition (CAI, HAI, HCAI), patient group (adult, paediatric, and neonatal), and location (site, country, region) To explore clinician knowledge, attitudes, and practice towards AMR surveillance Methodology Setting: Queen Elizabeth Central Hospital Population to be studied: Hospitalised patients aged 0t0 to 17 years at QECH, Blantyre with suspected or confirmed bacterial infection with a focus on paediatric in-patients. 06-Jun-2022 8 ACORN2,Version 12.0, 9 November 20215th May 2022 Number of Participants: 2500 patients for the surveillance data and 30 clinicians for KAP survey. Duration: 24 months of recruitment with follow up at 28 days post enrollment. There will be 6 month follow up for a subgroup of patients with gram positive invasive infection (Staphylococcus Aureus, Escherichia coli and Enterococci)). Expected Findings and Dissemination As forin ACORN1, 88% and 75% of enrolled patients had a blood culture taken for Cambodia and Laos respectively. Of those, approximately 5% of blood cultures will yieldyielded a target organism (pilot: 4.9% for Cambodia and 7.4% for Laos), therefore it is expected that the surveillance across all ACORN 2 sites will yield 37,500 patient episodes, 30,000 blood culture results, and 1,500 target pathogen blood culture isolates with AST data (1). The In Malawi, the study findings will be shared weekly with the paediatric department as part of an existing dashboard, and with the Antimicrobial Resistance Committee at Queen Elizabeth Central Hospital to which the chairperson for the committee has agreed. A final report including any published papers will be submitted to the 7CollegeCollege of Medicine Research Ethics CommitteeSecretariat ,Committee Secretariat, the Kamuzu University of Health Sciences Library and other international conferences.
- ItemRestrictedSynthesis and characterisation of betulinic acid derivatives(Kamuzu University of Health Sciences, 2022-05-09) Kumpalume, PeterType and Place of Study: This is an experimental laboratory study that will be conducted at the department of Pharmacy, Kamuzu University of Health Sciences (KUHeS). Problem: Antimicrobial resistance, particularly MDR-TB, remains a major public health threat worldwide. The current MDR-TB medications have been associated with adverse effects and thus, research in new drugs with proven therapeutic effect and safety, is critically important for providing potential solutions for MDR TB. Therefore, we propose to create a new drug entity with increased potency and improved pharmacokinetics properties which will contribute to the fight against antimicrobial resistance. Objectives: The main objective is to investigate the potency of synthesized betulinic acid derivatives against MDR-TB. The specific objectives are four-fold: i) to synthesize new analogues of betulinic acid, ii) to evaluate potency of the derivatives against MDR-TB, iii) to evaluate the stability and solubility of the selected derivatives, and iv) to establish the toxicity profiles of the drug candidate. Methodology: In order to address the objectives, chemical modifications of the identified betulinic acid variant to create new chemical entities will be undertaken. We will explore chemical transformations that involve alkylation, hydroxylation, palladium-catalysed cross coupling and aldol condensation reactions. The synthesized derivatives will be subjected to in vitro anti-TB activity assay using the modified Microplate Alamar Blue Assay (MABA) method. Expected Findings: In this study, we hypothesise that derivatives of betulinic acid will have potency against MDR-TB. It is, therefore, expected that Infrared spectroscopy, Mass spectrometry and NMR spectra of the synthesized chemical entities products will be generated to elucidate their structures. Additionally, in vitro anti-TB activity, pharmacokinetic and cytotoxicity profiles of the products will be determined. Dissemination: The results from this research will be shared with the College of Medicine Research and Ethics Committee (COMREC) and presented at seminars and dissemination workshops at the Kamuzu University of Health Sciences (KUHeS), Ministry of Health and The World Academy of Sciences (TWAS). The results will also be published in peer-reviewed journals.
- ItemRestrictedQuality assessment of alcohol based hand sanitizers available on market in Blantyre during the Covid-19 pandemic(2022-03-08) Gwedeza, Patrick; Luntha, RhodaSanitizers have been used for a long period of time as disinfectants in different public settings, especially in hospitals. However of the late, there has been an increase in the use of alcoholbased hand sanitizers due to the COVID-19 pandemic. COVID-19 pandemic has also caused an upsurge in the production and importation of alcohol-based hand sanitizers in order to meet the demand whilst raising the likelihood of an influx of substandard products flooding the market. Due to this increase, the risk which can come with these products has also escalated since most of them are under-regulated to check if they are meeting the stipulated regulatory requirements. Therefore, this research project will dwell much on assessing the quality of alcohol based hand sanitizers available on market in Blantyre during the COVID-19 pandemic. This research study is an experimental design involving both qualitative and quantitative analysis because some of the parameters will involve assessing the presence of methanol and determination of other ingredients of hand sanitizers which is qualitative while others will involve assessing the concentration of ethanol which is quantitative in nature. The main objective of this study is to assess the quality of ABHS alcohol-based hand sanitizers commercially available on the market in Blantyre and to be specific the study will assess the concentration of ethanol, the presence of methanol and it will also examine and or determineine other ingredients used by manufacturers during the production of alcohol-based hand sanitizers. The concentration of ethanol and presence of methanol will be assessed by using a gas chromatography machine equipped with flame ionization detector (FID) while the other ingredients present in all the hand sanitizers will be examined physically by looking at the labels of the manufacturer against the ingredients recommended by World Health Organization (WHO) and local regulators especially Pharmacy Medicine Regulatory Authority (PMRA). This study will be carried out using procedures as stipulated in the US Pharmacopeia for quality control method for alcohol determination as well as methods adoapted from other similar and relevant studies. The study will be conducted within a period of four weeks as directed by the pharmacy department. A random sampling technique will be used in selecting the samples and a sample size of 7 hand sanitizers from different manufactures which will be collected in triplicates per manufacturer will be used in this study. 08
- ItemRestrictedDrivers of health systems corruption in the area of laboratory services(Kamuzu University of Health Sciences, 2022-03-10) Mkwezalamba, ElitaTYPE OF STUDY: This is a qualitative study design that will utilize phenomenological study design. BACKGROUND: Corruption is a substantial cost-related driver that affects a program's sustainability and effectiveness as well as the possibility of a country's graduation from aid or support. Corruption is spread all over the world. It still remains a challenge in both developed and developing countries. Corruption is more embedded in the health system, which makes it hard to achieve the sustainable development goals and ensure healthy lives for everyone. This is why we must think of corruption as an important area of study in the same way we think about diseases. There are no known studies that have looked at corruption in the laboratory. This study seeks to look for the drivers of corruption, particularly in the laboratory services within the health systems of Malawi. This will help in designing viable interventions for dealing with corruption in the laboratory. MAIN OBJECTIVE: The main objective of this study is to identify potential drivers for corruption in the health facility laboratory services. SPECIFIC OBJECTIVES To identify potential causes of corruption in laboratory services, To explore the existence of accountability mechanisms in the health system, to establish the conditions that incentivize corruption among laboratory workers. METHODS: The study will be conducted at Queen Elizabeth Central Hospital and Ndirande Health Centre. A question guide containing relevant questions to answer the study objectives will be used to conduct interviews among laboratory staff and clients that will have access to laboratory services. As this is a qualitative study whose sample size is determined throughsaturation, a sample size of 20 participants will be purposively sampled. An audio recording device will be used during the interviews. Data will be transcribed and managed using a qualitative package called NVivo. Thematic content analysis will be conducted, aided by NVivo. EXPECTED FINDINGS: Based on literature, the following are expected to be some of the drivers of health system corruption: large amounts of resources, information asymmetry, large numbers of actors, system complexity and fragmentation, the globalized nature of the supply chain for drugs and medical devices, inadequate salaries for health workers, poor working conditions, among others. DISSEMINATION OF RESULTS: The results will be presented to the college faculty. A copy of the results will be submitted to COMREC and will also be peer reviewed