An Evaluation of PCV13 Vaccine Schedules, Comparing Impact of 2+1 vs 3+0 on Pneumococcal Carriage in Blantyre, Malawi

NCT04078997 | Completed

• 2 other identifiers: 5270OPP1208803
• Study Type: observational
• Target: 3,507
• Locations: 1 country
• Sites: 1

Brief Summary

Pneumococcal conjugate vaccines (PCV) have been shown to be effective against invasive pneumococcal disease (IPD; including pneumococcal meningitis and sepsis) and all-cause mortality among young children when introduced into infant expanded programs on immunization (EPI). Colonization of the nasopharynx by Streptococcus pneumoniae is a necessary prerequisite to pneumococcal disease. Critically important to the population impact of PCV is therefore reducing vaccine serotype (VT) carriage prevalence, and therefore reducing both disease and onward transmission to vulnerable individuals. Thus, as well as protecting the vaccinated individual (direct protection), PCV confers indirect protection (herd immunity) to unvaccinated populations and to vaccinated individuals who have insufficient protective immunity. While the ability of PCVs to induce herd immunity has been strong enough to control pneumococcal carriage in industrialized countries, such benefits have not been as marked in low-income countries. Carriage surveillance in Blantyre, Malawi from 4 to 7 years post-vaccine implementation shows persistent VT carriage. With the exception of South Africa, most sub-Saharan African countries, including Malawi, have introduced PCV using a 3+0 schedule. Whether the WHO-approved 2+1 schedule will maximize vaccine-induced protection has been identified as a research gap by the WHO. In this context, the Malawian Ministry of Health (MoH) and the National Immunizations Technical Advisory Committee (NITAG) are seeking evidence of adequate superiority of a 2+1 schedule to inform a change to the current Malawi EPI schedule. HYPOTHESIS: Prolonging the period of vaccine-induced protection with a booster vaccine dose at 9 months will extend the period of low VT carriage, hence providing longer direct vaccine-induced protection as well as boosting the indirect herd immunity effect. METHOD: The MoH will implement an evaluation, comparing a 2+1 to the current 3+0 PCV13 vaccine schedule in Blantyre District. This will use a pragmatic health centre-based randomization protocol, implemented within the scope of the EPI programme. This MoH-led change will be evaluated in partnership with the Malawi Liverpool Wellcome Trust Clinical Research Programme. Community carriage surveillance will be undertaken at 15 and 33 months after the introduction of the 2+1 schedule. The primary endpoint will be VT carriage prevalence among children 15-24 months of age 36 months after schedule change. Other targeted study groups will include children aged 5-10 years who have received PCV13 on a 3+0 schedule, children aged 9 months who have received PCV13 in either a 3+0 or a 2+0 schedule, and HIV-infected adults aged 18-40 years receiving ART and PCV13-unvaccinated. EXPECTED FINDINGS: Data will inform NITAG decisions on national vaccine policy, with implications at a national, regional and global level.

Conditions

13-valent Pneumococcal Vaccine; Streptococcus Pneumoniae

Keywords

Pneumococcal carriage; Pneumococcal conjugate vaccine; Vaccine schedule; Evaluation; Children; Herd immunity; Malawi

Outcome Measures

Primary Outcomes (1)

• Vaccine-type pneumococcal carriage prevalence among children 15-24 months old

  36 months after 2+1 vaccine schedule implementation

Secondary Outcomes (5)

• Vaccine-type pneumococcal carriage prevalence among children 5-10 years old

  36 months after 2+1 vaccine schedule implementation

• Vaccine-type pneumococcal carriage prevalence among HIV infected adults 18-40 years old

  36 months after 2+1 vaccine schedule implementation

• Vaccine-type pneumococcal carriage prevalence among children 9 months old

  9 months after 2+1 vaccine schedule implementation

• Prevalence of multiple pneumococcal serotype carriage

  36 months after 2+1 vaccine schedule implementation

• Proportion of children receiving a full 3-dose PCV13 vaccination schedule

  36 months after 2+1 vaccine schedule implementation

Study Arms (4)

PCV13-vaccinated,15-24 months of age

Recruitment for carriage surveillance (primary endpoint) will take place at randomly selected households within each of the catchment areas (zones) of the 20 selected health centers. Sampling: Random sampling from populations will occur preferentially around the health centers and not from the population on the zonal interfaces. Researchers will designate two geographic sampling areas within each zone around each health center that allows a buffer against zonal borders. If the recruitment target within first sampling area is not met, sampling will move into the second area.

Other: nasopharyngeal swab

PCV13-vaccinated, 5-10 years of age

Six schools will be selected: three located centrally in each of the 3+0 zones, and three in the 2+1 zones. Sampling: Children will be randomly chosen and recruited from each school. NP swab collection will occur during two surveys, starting 21 and 34 months after the switch to 2+11. Mapping analysis from our current surveillance activities shows good clustering of recruited children living around the school, suggesting limited movement and thus low risk of contamination between zones with different vaccination schedules.

Other: nasopharyngeal swab

PCV13-unvaccinated HIV-infected adults on ART 18 - 40 years of

Adults will be recruited from the Queen Elizabeth Central Hospital (QECH), Lighthouse ART clinic in Blantyre. Sampling: Mapping analysis from current surveillance activities shows good distribution throughout the Blantyre area, suggesting it is possible to achieve balance between those adults residing in 2+1 vs 3+0 areas. Sample collection will be on a rolling basis throughout the study period, starting 18 months after switch to 2+1.

Other: nasopharyngeal swab

PCV13-vaccinated, 9 months of age

Recruitment will take place at vaccination centers. Sampling: A convenience sample of NP swabs will be collected at the 9-month (measles-1) visit. Sample collection will occur 9 months after the switch to 2+1 schedule.

Other: nasopharyngeal swab

Interventions

nasopharyngeal swab OTHER

A nasopharyngeal swab will be collected from consenting individuals by inserting a commercially-available dacron swab to the nasopharynx, gently rotating before removing.

PCV13-unvaccinated HIV-infected adults on ART 18 - 40 years of; PCV13-vaccinated, 5-10 years of age; PCV13-vaccinated, 9 months of age; PCV13-vaccinated,15-24 months of age

Eligibility Criteria

• Age: 15 Months - 40 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64)
• Sampling Method: Probability Sample

Study Population

PCV13-vaccinated,15-24 months of age: Recruitment at randomly selected households within each of the catchment areas (zones) of the 20 selected health centers. PCV13-vaccinated, 9 months of age: Recruitment will take place at MoH EPI vaccination centers. PCV13-vaccinated, 5-10 years of age: Recruitment from six selected six schools: three located centrally in each of the 3+0 zones, and three in the 2+1 zones. PCV13-unvaccinated HIV-infected adults on ART 18 - 40 years old: Recruitment from the Queen Elizabeth Central Hospital (QECH), Lighthouse ART clinic in Blantyre.

You may qualify if:

• PCV13-vaccinated children, 15-24 months of age (schedule 2+1 or 3+1):
• Aged between 15-24 month
• Permanent resident in Blantyre District
• Parent/legal guardian consent for the child to have a NP swab taken
• Evidence of having received a full schedule of PCV13 vaccination recorded in the health passport and which schedule given
• PCV13-vaccinated children, 9 months of age (schedule 2+0 or 3+0):
• Aged 9 months
• Permanent resident in Blantyre District
• Parent/legal guardian consent for the child to have a NP swab taken
• Evidence of having received either a full 3+0 schedule or both primary doses (at approximately 6 and 14 weeks of age) of the 2+1 schedule of PCV13 vaccination recorded in the health passport
• PCV13-vaccinated children, 5-10 years of age (schedule 3+0):
• Aged between 5-10 years
• Parent/legal guardian consent for the child to have a NP swab taken
• If the child is ≥8 years old, child assent to have a NP swab taken
• Either verbal or documented evidence of having received primary immunization with PCV

You may not qualify if:

• For all participants:
• Current TB treatment
• Pneumonia hospitalization \<14 days before study enrolment
• Terminal illness
• For Children:
• No parental/legal guardian consent
• No child assent (children aged \>8 years old)
• Having received antibiotic treatment \<14 days before study enrolment
• For Adults:
• Unable or unwilling to provide consent
• Prior vaccination with pneumococcal vaccine

Sponsors & Collaborators

• University of Liverpool: lead
• Malawi-Liverpool-Wellcome Trust Clinical Research Programme: collaborator
• Ministry of Health, Malawi: collaborator
• Blantyre District Health Office: collaborator
• UNICEF: collaborator
• World Health Organization: collaborator
• University College, London: collaborator
• Liverpool School of Tropical Medicine: collaborator

Study Sites (1)

Malawi-Liverpool-Wellcome Research Programme

Blantyre, Chichiri, P.O. Box 30096, Malawi

Location

Related Publications (2)

• Roessler W, Steinbach P, Nicolai H, Hofstaedter F, Wieland WF. Effects of high-energy shock waves on the viable human kidney. Urol Res. 1993;21(4):273-7. doi: 10.1007/BF00307710.

  PMID: 8212416 BACKGROUND

• Swarthout TD, Ibarz-Pavon A, Kawalazira G, Sinjani G, Chirombo J, Gori A, Chalusa P, Bonomali F, Nyirenda R, Bulla E, Brown C, Msefula J, Banda M, Kachala J, Mwansambo C, Henrion MY, Gordon SB, French N, Heyderman RS. A pragmatic health centre-based evaluation comparing the effectiveness of a PCV13 schedule change from 3+0 to 2+1 in a high pneumococcal carriage and disease burden setting in Malawi: a study protocol. BMJ Open. 2021 Jun 17;11(6):e050312. doi: 10.1136/bmjopen-2021-050312.

  PMID: 34140345 DERIVED

Biospecimen

Retention: SAMPLES WITH DNA

Frozen samples with isolated DNA will be retained, confirming to requirements of the local research ethics committee.

Study Officials

• Robert Heyderman, PhD

  University College, London

  PRINCIPAL INVESTIGATOR

• Stephen Gordon, PhD

  Malawi-Liverpool-Wellcome Trust Clinical Research Programme

  STUDY CHAIR

Study Design

• Study Type: observational
• Observational Model: ECOLOGIC OR COMMUNITY
• Time Perspective: CROSS SECTIONAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 28, 2019
• First Posted: September 6, 2019
• Study Start: July 21, 2019
• Primary Completion: February 16, 2024
• Study Completion: February 16, 2024
• Last Updated: September 4, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will not share

Locations

MA (1)