Impact of pneumococcal and malaria vaccines for children on antimicrobial resistance in Malawi
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Date
2021-03-15
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Kamuzu University of Health Sciences
Abstract
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.