Ignite Creation Date:
2024-06-16 @ 11:52 AM
Last Modification Date:
2024-10-26 @ 3:31 PM
Study NCT ID:
NCT06450379
Status:
COMPLETED
Last Update Posted:
2024-06-10
First Post:
2024-06-04
Brief Title:
Impact of Vaccines on Antimicrobial Microbial Resistance
Sponsor:
Malawi Liverpool Wellcome Programme
Organization:
Malawi Liverpool Wellcome Programme
Study Overview
Official Title:
The Impact of Pneumococcal and Malaria Vaccines on Bacterial Resistance Febrile Illness and Antibiotic Usage in Young Children in Malawi
Status:
COMPLETED
Status Verified Date:
2024-06
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
IVAR
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 RTSSAS01 malaria vaccine
Six cross-sectional surveys will be implemented within primary healthcare centres n3000 users of outpatient facilities per survey and their local communities n700 healthy children per survey three surveys in Blantyre district PCV13 component and three surveys in Mangochi district RTSSAS01 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 30 to 21 schedule change For the RTSSAS01 component surveys will be conducted 32 44 and 56 months post-RTSSAS01 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 18331002 and University of Liverpool Ref 9908 Research Ethics Committees Parentalcaregiver 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
Six cross-sectional surveys will be implemented within primary healthcare centres n3000 users of outpatient facilities per survey and their local communities n700 healthy children per survey three surveys in Blantyre district PCV13 component and three surveys in Mangochi district RTSSAS01 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 30 to 21 schedule change For the RTSSAS01 component surveys will be conducted 32 44 and 56 months post-RTSSAS01 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 18331002 and University of Liverpool Ref 9908 Research Ethics Committees Parentalcaregiver 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
Detailed Description:
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 30 to 21 and RTSSAS01 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 30 to 21 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 21 vs 30 or the introduction of malaria vaccine RTSSAS01
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 Three cross sectional sampling surveys shall be conducted 1 shortly following introduction of PCV13 21 followed by surveys 18 and 33 months after introduction and 2 for RTSSAS01 25 years 3 years and 35 years 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 malaria Rapid Diagnostic Test RDT use and medicine usage with a focus on antibiotics Additionally we will monitor antimicrobial prescription and febrile illness at health centre level within the communities where the study will take place by conducting Health Centre HC Audits These will consist of very brief anonymized exit interviews to randomly selected Outer-Patient Department OPD users in which we will record information on the relevant vaccine either RTSSAS01 or PCV13 malaria RDT as a proxy for febrile illness and medicine prescription
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 RTSSAS01 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 21 vs 30 or the introduction of malaria vaccine RTSSAS01
Secondary
1 The frequency of febrile illness and antibiotic use in children 3 years after PCV13 schedule changeor malaria vaccine introduction
2 The stool carriage of ESBL E coli or Klebsiella in children 3 years after PCV13 schedule change or malaria vaccine introduction
3 The change in the upper respiratory tract resistome in children 3 years after PCV13 schedule change or malaria vaccine introduction
Population Eligibility For the PCV13 schedule change each cross-sectional survey shall recruit children between the ages of 4-9 months for the baseline survey and 15 and 24 months old for the subsequent surveys resident in Blantyre district recruited from the community For RTSSAS01 each cross-sectional survey shall recruit children between the ages of 18 and 36 months resident in Mangochi recruited from the community Anonymous audits of RDT and medicine use in children 3 years attending a subset of HCs for investigation of ill health will also be conducted
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
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 30 to 21 and RTSSAS01 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 30 to 21 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 21 vs 30 or the introduction of malaria vaccine RTSSAS01
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 Three cross sectional sampling surveys shall be conducted 1 shortly following introduction of PCV13 21 followed by surveys 18 and 33 months after introduction and 2 for RTSSAS01 25 years 3 years and 35 years 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 malaria Rapid Diagnostic Test RDT use and medicine usage with a focus on antibiotics Additionally we will monitor antimicrobial prescription and febrile illness at health centre level within the communities where the study will take place by conducting Health Centre HC Audits These will consist of very brief anonymized exit interviews to randomly selected Outer-Patient Department OPD users in which we will record information on the relevant vaccine either RTSSAS01 or PCV13 malaria RDT as a proxy for febrile illness and medicine prescription
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 RTSSAS01 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 21 vs 30 or the introduction of malaria vaccine RTSSAS01
Secondary
1 The frequency of febrile illness and antibiotic use in children 3 years after PCV13 schedule changeor malaria vaccine introduction
2 The stool carriage of ESBL E coli or Klebsiella in children 3 years after PCV13 schedule change or malaria vaccine introduction
3 The change in the upper respiratory tract resistome in children 3 years after PCV13 schedule change or malaria vaccine introduction
Population Eligibility For the PCV13 schedule change each cross-sectional survey shall recruit children between the ages of 4-9 months for the baseline survey and 15 and 24 months old for the subsequent surveys resident in Blantyre district recruited from the community For RTSSAS01 each cross-sectional survey shall recruit children between the ages of 18 and 36 months resident in Mangochi recruited from the community Anonymous audits of RDT and medicine use in children 3 years attending a subset of HCs for investigation of ill health will also be conducted
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
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None