Prevention of infectious diseases Vaccination and chemoprophylaxis strategies and the occurrence of breakthrough infections

This thesis provides insights into optimising infectious diseases preventive strategies for travellers and at-risk populations. We demonstrated that yellow fever and hepatitis A vaccines provide long-lasting protection in immunocompetent adults, while pneumococcal vaccination (PCV13/PPSV23) has poor long-term immunogenicity. In people living with HIV (PLWH) and patients on immunosuppressive therapy, long-term protection may be impaired for yellow fever, hepatitis A and pneumococcal vaccination, particularly for those on immunosuppressive combination therapy. However, PLWH and those on immunosuppressive monotherapy may maintain long-term hepatitis A protection through immunological memory. Vaccination before starting immunosuppressive therapy, as demonstrated for rabies vaccination, enhances immunogenicity. Tailoring vaccination guidelines to the needs of immunocompromised populations is essential to optimise long-term protection. Additionally, we showed substantial non-adherence to atovaquone-proguanil (AP) malaria chemoprophylaxis among travellers, especially post-travel, and propose a controlled human malaria infection (CHMI) model to study abbreviated AP regimens. Furthermore, we showed that malaria recrudescence after artemether-lumefantrine (AL) is rare in travellers but can be effectively retreated with AL, and we propose hair analysis as a future and novel tool to retrospectively assess drug exposure in malaria recrudescence. Future research should refine vaccination strategies, develop more appealing and cost-effective AP regimens, and further investigate the role of drug exposure in recrudescence.