Browsing by Author "Swarthout, Todd"

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    Impact of pneumococcal and malaria vaccines for children on antimicrobial resistance in Malawi
    (Kamuzu University of Health Sciences, 2021-03-15) Swarthout, Todd
    Type of research study: A series of community and health centre based cross-sectional surveys Problem: Pneumonia is a leading cause of child mortality globally and Streptococcus pneumoniae a leading cause of lower respiratory tract infections (LRTI) in under-fives. Malaria remains endemic in much of sub- Saharan Africa, commonly causing febrile illness in children and despite substantial progress with control programmes, Malaria continues to be a leading cause of child mortality. Vaccination is therefore an attractive solution. Vaccines are thought to be crucial to Anti-Microbial Resistance (AMR) control but their impact on AMR may be more complex than originally thought. Both the direct and indirect impacts of vaccine on AMR require a systematic evaluation. In collaboration with the Malawi Ministry of Health, we are commencing two funded, regulatory approved, cluster-randomised evaluations of vaccines that target two of the commonest causes of febrile illness and life-threatening disease in children under 5 years in Africa: pneumococcal invasive infection, and malaria. This study will leverage two large funded cluster randomised vaccine evaluations (13-valent Pneumococcal Conjugate Vaccine (PCV13) schedule change of 3+0 to 2+1 and RTS,S/AS01 (trade name Mosquirix) malaria vaccine introduction). We will assess the selective effects of pneumococcal and malaria vaccines on antibiotic resistance, febrile illness and antibiotic usage in children <3 years. Hypothesis: Extending vaccine-mediated protection against Streptococcus pneumoniae through a 3+0 to 2+1 schedule change will be associated with a reduction in the prevalence of S. pneumoniae carriage isolates with increased AMR in children <3 years. The introduction of the malaria vaccine will reduce the frequency of healthcare attendances resulting in antibiotic prescription, reduce the prevalence of Extended spectrum beta-lactamases (ESBL) Escheriquia coli or Klebsiellae in the stool of children <3 years, and change the upper respiratory tract resistome profile in children <3years. Aim: To establish the direct and indirect selective effects of pneumococcal and malaria vaccines on antibiotic resistance, febrile illness, and antibiotic usage in young children in Malawi. Objectives: 1. To establish the antibiotic resistance profile of S. pneumoniae carriage isolates from children <3 years following a PCV13 schedule change that extends protection (2+1 vs. 3+0), or the introduction of malaria vaccine (RTS,S/AS01) 2. To assess the frequency of febrile illness and antibiotic use in children <3 years after PCV13 schedule change or malaria vaccine introduction 3. To investigate change in the upper respiratory tract resistome in children <3 years after PCV13 schedule change or malaria vaccine introduction. Methodology: Cross sectional surveys shall be conducted at baseline of PCV13 2+1 and RTS,S/AS01 introduction, 18 months after introduction, and 33 months after introduction in clusters defined through two large cluster-randomised vaccine evaluation studies. These will include the collection of nasopharyngeal and rectal swabs, and the completion of an Individual questionnaire on febrile illness episodes and antibiotic usage. Data on Febrile illness episodes (malaria Rapid Diagnostic Test (RDT) use) and antibiotic usage will be obtained from Health Centre (HC) records. Expected Results Nasopharyngeal and rectal swabs obtained from participants will be tested for the presence of S. pneumoniae, and E. coli and Klebsiella isolates respectively. Bacterial isolates will be tested for the presence of AMR genes, and resistance profiles will be analysed in relation to their association to either the introduction of the RTS,S/AS01 vaccine or the PCV13 schedule change, and in the context of antibiotic prescription and usage for febrile illness episodes. Outcome Measures: Primary: The antibiotic resistance profile of S. pneumoniae carriage isolates from children <3 years following a PCV13 schedule that extends protection (2+1 vs. 3+0) or the introduction of malaria vaccine (RTS,S/AS01) Secondary:  The frequency of febrile illness and antibiotic use in children <3 years after PCV13 schedule change or malaria vaccine introduction.  The stool carriage of ESBL E. coli or Klebsiella in children <3 years after PCV13 schedule change or malaria vaccine introduction.  The change in the upper respiratory tract resistome in children <3 years after PCV13 schedule change or malaria vaccine introduction. Population Eligibility: Each cross-sectional survey shall recruit children between the ages of 15 and 24 months old, resident in Blantyre or Mangochi district, recruited from the community and health centres (PCV13), and community-based visits (RTS,S/AS01). Findings dissemination: Investigators will seek timely publication in peer-reviewed journals. Partial results and interim analyses will be shared with the Malawi Ministry of Health (MoH), and other relevant policymakers and decision-making stakeholders. Partial and final findings will be presented at the College of Medicine (COM Research Dissemination Day, Malawi-Liverpool Wellcome Trust (MWL) research in progress meetings and international scientific conferences. A copy of all published materials and reports will be shared with College of Medicine Research Ethics Committee (COMREC), and the Malawi College of Medicine Library.
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    Seroprevalence of SARS-CoV-2 antibodies in Malawi blood donors
    (Kamuzu University of Health Sciences & Malawi-Liverpool-Wellcome Trust, 2020-09-07) Jambo, Kondwani; Swarthout, Todd; M'baya, Bridon; Heyderman, Robert; Jere, Khuzwayo; French, Neil; Gordon, Stephen; Muula, Adamson; Chibwana, Marah; Kalata, Newton; Hosseinipour, Mina
    Type of study: Cross-sectional observation study. Problem: In low-income countries, such as Malawi, important public health measures including universal face mask use, social distancing or a lockdown, have been challenging to implement owing to socioeconomic constraints, leading to predictions that the COVID-19 pandemic would progress rapidly. However, due to limited capacity to test for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, there are no reliable estimates of the true burden of infection and death. SARS-CoV-2 serosurveys of blood donor samples in blood banks are supported by WHO as a potential useful tool for tracking the emergence and progression of the COVID-19 pandemic. Broad and Specific Objectives: Broad objective: to identify for SARS-CoV-2 antibodies in blood donors in Malawi, as a marker of past infection and an estimate of population exposure. Specific objectives: Primary objective: to estimate the seroprevalence of SARS CoV-2-specific antibodies in blood donor sera of different age-strata across the entire country. Secondary objectives a) to establish when COVID-19 started circulating in Malawi, and b) to determine the COVID-19 epidemic trajectory over time in Malawi Methodology: Repeated cross-sectional investigation of blood donors from across the country. Using the MBTS sample archive database, we will identify sera collected from multiple age groups, including 15-19, 20-29, 30-39, 40-49, 50-59 and 60+. We will conduct two serosurveys using sera collected between December 2019 to May 2020 (Serosurvey 1), and also those to be collected between June 2020 to December 2020 (Serosurvey 2). SARSCoV-2 antibodies will be measured from the sera using ELISA and Luminex-based IgG/IgM multiplex assay targeting Spike (S) and Nucleoprotein (N). We will also measure neutralisation potency of the detected SARS-CoV-2 antibodies. Study setting and period: The laboratory experiments will be conducted at the MLW laboratories. The study will be conducted between October 2020 to July 2021. Ethical considerations: At time of donation, blood donors provide consent to participate in studies of public health importance or those aimed at improving availability of supplies of safe blood. COVID-19 research qualifies for an activity of emergency Public Health importance. We will generate unique sample identifiers and will not have access to the donor details with identifiable names. Data Management and analysis: All data will be stored in secure password protected computers at the MLW. Only study investigators will have access to the data, unless prior collaborative agreements are in place or data has been released as part of open access. We will calculate population and age-specific seroprevalence of SARS CoV-2. These will be reported as proportions of SARS CoV-2 antibody positive individual in the total population or per age strata. We will also estimate the potential period of SARS-CoV-2 entry into Malawi, by using the latest known validated SARS-CoV-2 antibody positive sample. Expected findings: a) Prevalence of SARS CoV-2 exposure amongst blood donors, as a surrogate of population exposure, b) An estimate of potential time of SARS CoV-2 entry into Malawi. Dissemination: The results will be disseminated at local and international conference and manuscripts will be published in an international peer-reviewed journal, and policy-related findings will be shared via the MLW Policy unit. The results will also be shared with COMREC.