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Title: Pneumococcal carriage and transmission in Karonga district, Malawi, before and after introduction of 13-valent pneumococcal conjugate vaccination
Author: Heinsbroek, E.
ISNI:       0000 0004 6059 5894
Awarding Body: University of Liverpool
Current Institution: University of Liverpool
Date of Award: 2016
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Streptococcus pneumoniae (pneumococcus) is a leading cause of childhood morbidity and mortality worldwide. Thirteen-valent pneumococcal conjugate vaccine (PCV-13) was introduced in the Malawian infant immunisation programme in November 2011. PCV-13 is currently given at a “3+0” schedule: doses are given at 6, 10 and 14 weeks and no booster dose is currently implemented. The aim of this thesis was to study pneumococcal carriage and transmission in Karonga District, Malawi, before and after introduction of PCV-13, in order to review the effect of the current pneumococcal vaccination programme on carriage, and to give recommendations on the implementation of different vaccination strategies in Malawi. Pneumococcal carriage studies were conducted in Karonga between 2008 and 2014, with a focus on infants born to an HIV-positive mother, and HIV-positive adults, both of whom are at high risk of invasive pneumococcal disease. We found no difference in pneumococcal acquisition in infants by maternal HIV-status. A greater proportion of infant pneumococcal acquisition was attributable to carriage in other children < 5 years in the household than to maternal carriage. Pneumococcal carriage in HIV-positive adults in Malawi remained high despite up to two years of antiretroviral treatment, indicating a failure of reconstitution of respiratory mucosal immune response. An analysis on the uptake and timeliness of PCV-13 vaccination showed that despite high vaccination coverage in this setting, delays in vaccination were common. Infants born to lower educated or farming mothers and those living more remotely were at greater risk of being not fully vaccinated and being vaccinated late. Carriage studies conducted in 2014, two years post PCV-13 introduction, showed that carriage of vaccine type (VT) pneumococci had decreased in vaccinated children and unvaccinated older age groups, but that a reservoir of VT carriage was still present. VT carriage had not decreased in unvaccinated children < 5 years. Carriage of non-vaccine type pneumococci (NVT) had increased in vaccinated children. Our results suggest that a herd immunity effect is taking place albeit slowly in comparison to other countries. Waning immunity seemed to occur in vaccinated children 1-4 years. Our mathematical modelling studies provided further evidence for waning immunity. An immunity half-life between 6 months and 1 year was found to fit best with the observed post-vaccination carriage prevalence. If the immunity half-life were to be increased to 2 years, this would have a large impact on VT carriage decline in vaccinated and unvaccinated age groups. In the stochastic individual-based transmission models, which included explicit household transmission, an indirect vaccine effect was observed immediately after introduction of PCV-13. Adding a booster dose to the current three-dose schedule (3+1 schedule) would be beneficial for vaccinated and unvaccinated groups. Replacing the current 3+0 schedule with a 2+1 schedule (booster dose at 9 months) initially resulted in slower VT decline, but seemed to be associated with a longer-term gain in lower VT carriage in 1-4 year olds. Maternal vaccination did not result in additional VT carriage reduction in the infant. Ongoing surveillance is required to assess VT carriage in this population and monitor waning immunity and serotype replacement in vaccination individuals. A review of the vaccination schedule may be required to optimise total population impact in this high carriage setting. There is need for cheaper, more effective, serotype-independent pneumococcal vaccines. Potentially cheaper PCVs produced in India are in the pipeline, as well as a couple of new generation vaccines that are currently in phase 2 clinical trials. The next decade is promising to be an exciting time for pneumococcal researchers and policy makers worldwide, as new vaccines will pose interesting possibilities to further decrease pneumococcal carriage and disease worldwide.
Supervisor: French, N. ; Read, J. M. Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral