Impact of Vaccines on Antimicrobial Microbial Resistance

NCT06450379 | Completed DMC

• 1 other identifier: P.01/21/3249
• Study Type: observational
• Target: 13,200
• Locations: 1 country
• Sites: 1

Brief Summary

Vaccination is a potentially critical component of efforts to arrest development and dissemination of antimicrobial resistance (AMR), though little is known about vaccination impact within low-income and middle-income countries. This study will evaluate the impact of vaccination on reducing carriage prevalence of resistant Streptococcus pneumoniae and extended spectrum beta-lactamase-producing Escherichia coli and Klebsiella species. We will leverage two large ongoing cluster-randomised vaccine evaluations in Malawi assessing; first, adding a booster dose to the 13-valent pneumococcal conjugate vaccine (PCV13) schedule, and second, introduction of the RTS,S/AS01 malaria vaccine. Six cross-sectional surveys will be implemented within primary healthcare centres (n=3000 users of outpatient facilities per survey) and their local communities (n=700 healthy children per survey): three surveys in Blantyre district (PCV13 component) and three surveys in Mangochi district (RTS,S/AS01 component). We will evaluate antibiotic prescription practices and AMR carriage in children ≤3 years. For the PCV13 component, surveys will be conducted 9, 18 and 33 months following a 3+0 to 2+1 schedule change. For the RTS,S/AS01 component, surveys will be conducted 32, 44 and 56 months post-RTS,S/AS01 introduction. Six health centres in each study component will be randomly selected for study inclusion. Between intervention arms, the primary outcome will be the difference in penicillin non-susceptibility prevalence among S. pneumoniae nasopharyngeal carriage isolates in healthy children. The study is powered to detect an absolute change of 13 percentage points (ie, 35% vs 22% penicillin non-susceptibility). This study has been approved by the Kamuzu University of Health Sciences (Ref: P01-21-3249), University College London (Ref: 18331/002) and University of Liverpool (Ref: 9908) Research Ethics Committees. Parental/caregiver verbal or written informed consent will be obtained prior to inclusion or recruitment in the health centre-based and community-based activities, respectively. Results will be disseminated via the Malawi Ministry of Health, WHO, peer-reviewed publications and conference presentations.

Conditions

Vaccine

Outcome Measures

Primary Outcomes (1)

• 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)

  This outcome measure focused on assessing the antibiotic resistance profile of Streptococcus pneumoniae isolates obtained from nasal or throat swabs of children under the age of 3. We compared two different vaccination schedules for the pneumococcal conjugate vaccine (PCV13) through a 3+0 dosing schedule and through a 2+1 dosing schedule (two primary doses followed by a booster). Additionally, the impact of the introduction of the malaria vaccine (RTS,S/AS01) on the antibiotic resistance profile of S. pneumoniae isolates was evaluated. This outcome measure aimed to determine whether different vaccination schedules or the introduction of the malaria vaccine influenced the prevalence or patterns of antibiotic resistance in S. pneumoniae, a common bacterial pathogen associated with respiratory infections in young children.

  less than 3 years

Secondary Outcomes (3)

• The frequency of febrile illness and antibiotic use in children <3 years after PCV13 schedule change or malaria vaccine introduction.

  less than 3 years

• The stool carriage of ESBL E. coli or Klebsiella in children <3 years after PCV13 schedule change or malaria vaccine introduction.

  less than 3 years

• The change in the upper respiratory tract resistome in children <3 years after PCV13 schedule change or malaria vaccine introduction.

  less than 3 years

Study Arms (4)

13-valent pneumococcal conjugate vaccine (PCV13): 3+0 group

Children less than 3 years having received 1 dose of (PCV13) at 6, 10 and 14 weeks of age

13-valent pneumococcal conjugate vaccine (PCV13): 2+1 booster group

Children less than 3 years having received 1 dose of (PCV13) at 6 and 14 weeks of age and a booster at 9 months of age

RTS,S/AS01 Vaccine-exposed

Children less than 3 years having received RTS,S/AS01 vaccine

RTS,S/AS01 Vaccine-non exposed

Children less than 3 years having not received RTS,S/AS01 vaccine

Eligibility Criteria

• Age: 5 Months - 3 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17)
• Sampling Method: Non-Probability Sample

Study Population

Children under the age of 3 years.

You may qualify if:

• Permanent residence in Blantyre (PCV cohort) or Mangochi (RTS,S/AS01 cohort)
• Parent/legal guardian consent
• Evidence of having received an initial 2 or 3 doses of the PCV13 vaccine (survey 1) or the full PCV13 schedule (surveys 2 and 3: Either 2+1 or 3+0 depending on cluster) or full initial (+/- booster) course of the RTS,S/SA01 vaccine (in Mangochi intervention cluster).

You may not qualify if:

• Current tuberculosis (TB) treatment
• Terminal illness (Defined as a condition that cannot be cured and it is likely to lead to the individual's death)
• Having received antibiotic treatment \<14 days before study enrolment
• Hospitalisation for pneumonia \<14 days before study enrolment
• Presence of gross respiratory tract pathology
• For the HC audits, we will request to review the health information from attendees that comply with the following characteristics:
• \<3 years of age
• HC attendance for investigation and/or treatment of ill health

Sponsors & Collaborators

• Malawi Liverpool Wellcome Programme: lead
• Wellcome Trust: collaborator
• University of Liverpool: collaborator
• Kamuzu University of Health Sciences: collaborator
• Liverpool School of Tropical Medicine: collaborator
• University of Oxford: collaborator
• Wellcome Sanger Institute: collaborator

Study Sites (1)

Malawi Liverpool Wellcome Programme

Blantyre, Malawi

Location

Study Officials

• Robert Heyderman, Professor

  University College, London

  STUDY CHAIR

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: CROSS SECTIONAL
• Target Duration: 9 Months
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Local Principal Investigator

Study Record Dates

• First Submitted: June 4, 2024
• First Posted: June 10, 2024
• Study Start: March 15, 2021
• Primary Completion: April 26, 2024
• Study Completion: April 30, 2024
• Last Updated: June 10, 2024

Record last verified: 2024-06

Locations

MA (1)