High residual prevalence of vaccine-serotype Streptococcus pneumoniae carriage after introduction of a pneumococcal conjugate vaccine in Malawi: a prospective serial cross-sectional study

• Published in: bioRxiv
• Main Authors: Swarthout, Todd D, Fronterre, Claudio, Lourenço, José, Obolski, Uri, Gori, Andrea, Bar-Zeev, Naor, Everett, Dean, Kamng'ona, Arox W, Mwalukomo, Thandie S, Mataya, Andrew A, Mwansambo, Charles, Banda, Marjory, Gupta, Sunetra, Diggle, Peter, French, Neil, Heyderman, Robert S
• Format: Paper
• Language: English
• Published: Cold Spring Harbor Cold Spring Harbor Laboratory Press 19.06.2019; Cold Spring Harbor Laboratory
• Edition: 1.2
• Subjects: Age; Antiretroviral therapy; Children; Epidemiology; HIV; Human immunodeficiency virus; Streptococcus infections; Streptococcus pneumoniae; Vaccines; Malawi; Pneumococcal conjugate vaccine; HIV; Indirect protection; Africa; Adults; Children; Pneumococcal carriage
• ISSN: 2692-8205; 2692-8205
• DOI: 10.1101/445999

Background: There are concerns that pneumococcal conjugate vaccines (PCV) in sub-Saharan Africa sub-optimally interrupt vaccine-serotype (VT) carriage and transmission, thus limiting vaccine-induced direct and indirect protection. We assessed carriage in vaccinated children and unvaccinated populations targeted for indirect protection, between 4 and 7 years after Malawi's November 2011 introduction of PCV13 using a 3+0 schedule. Methods: We conducted sequential prospective nasopharyngeal carriage surveys between 2015 and 2018 among healthy PCV-vaccinated and PCV-unvaccinated children, and HIV-infected adults. VT and NVT carriage risk by age was analysed by non-linear regression. Results: Among PCV-vaccinated children, there was a 24% relative reduction in carriage, from a mean 21.1% to 16.1%; 45% reduction among older PCV-unvaccinated children, from 27.5% to 15.2%; 41.4% reduction among adults, from 15.2% to 8.9%. Using carriage data from children 3.6 to 10 years of age, VT carriage probability declined with age, with a similar prevalence half-life among PCV-vaccinated (3.34 years) and PCV-unvaccinated (3.26 years) children. Conclusion: Compared to high-income settings, the 3+0 schedule in Malawi has led to a sub-optimal reduction in pneumococcal carriage prevalence. This is likely due to recolonisation of vaccinated children with waning vaccine-induced immunity, resulting in insufficient indirect protection of unvaccinated populations. Rigorous evaluation of strategies to augment vaccine-induced control of carriage, including alternative schedules and catch-up campaigns is required. Keywords: Streptococcus pneumoniae; Pneumococcal carriage; Pneumococcal conjugate vaccine; Children; Adults; HIV; Africa; Indirect protection Footnotes * The previous version included analysis from approximately 2 years of pneumococcal carriage surveillance from children 3-10 years of age and HIV-infected adults on ART. This revised version has an expanded analysis that includes data from a total of approximately 3.5 years of pneumococcal carriage surveillance. This includes pneumococcal carriage data from data included in our first version, as well as children 4-8 weeks of age (prior to first dose PCV) add PCV-vaccinated children 18 weeks to 2 years of age. These younger age groups were recruited starting approximately 1.5 years after study start. The non-linear model analysis, used to assess risk of VT carriage by age, was expanded to included risk of NVT carriage by age.