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

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

Interventions

OTHER

nasopharyngeal swab

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

Sponsors & Collaborators

• Malawi-Liverpool-Wellcome Trust Clinical Research Programme

  collaborator OTHER

• Ministry of Health, Malawi

  collaborator OTHER_GOV

• Blantyre District Health Office

  collaborator UNKNOWN

• UNICEF

  collaborator OTHER

• World Health Organization

  collaborator OTHER

• University College, London

  collaborator OTHER

• Liverpool School of Tropical Medicine

  collaborator OTHER

• University of Liverpool

  lead OTHER

Principal Investigators

• Robert Heyderman, PhD · University College, London

• Stephen Gordon, PhD · Malawi-Liverpool-Wellcome Trust Clinical Research Programme

Eligibility

Min Age

15 Months

Max Age

40 Years

Sex

ALL

Healthy Volunteers

Yes

Timeline & Regulatory

Start

2019-07-21

Primary Completion

2024-02-16

Completion

2024-02-16

Countries

• Malawi

Study Locations