KC Jambo, Malawi College of Medicine - Defining changes in nasal immunity that favour propensity for pneumococcal colonisation in HIV-infected adults

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The bacterium, Streptococcus pneumoniae (pneumococcus), is the major cause of pneumonia-related deaths worldwide. The pneumococcus resides in the nose and at the back of the throat, where it does not normally cause disease, but when conditions change it causes life-threatening illness, such as pneumonia. The pneumococcus is transmitted from person to person via the respiratory route. In Europe and North America, immunisation of children with the pneumococcal conjugate vaccine (PCV13) has greatly reduced the burden of pneumococcal disease and prevalence of the pneumococcus in the community because children no longer infect adults. Similar impact has not been observed in low income countries, such as Malawi, because children continue to carry pneumococci even after vaccination. Instead, the prevalence of the pneumococcus among HIV-infected adults on antiretroviral therapy (ART) has remained high despite the introduction of PCV13 as routine childhood vaccine in Malawi in 2011. Persistence of pneumococcus among HIV-infected adults on ART threatens to reverse the potential public health benefits of PCV13 that have been reported from high income countries. HIV-infected adults on ART serve as a haven for pneumococcus and may promote transmission of the bacterium in the community. However, the factors that promote persistence of pneumococcus among HIV-infected adults on ART are still unknown. I propose to recruit 100 Malawian adults, of which half will be HIV-uninfected and the other half will be ART-naïve HIV-infected. I will collect samples from the nose from all study participants and follow them up for 12months. I will quantify the number of times an individual is found with the pneumococcus in their nose, and compare this between the study groups. I will also investigate differences in immune parameters in the nose between the study groups. This comparison will also focus on relating the changes in the immune parameters in the nose with the number of times an individual is found with the pneumococcus in their nose. This will generate information on some of the factors that make HIV-infected infected adults on ART more susceptible to the pneumococcus. Furthermore, I will grow cells obtained from the nose of HIV-infected and uninfected adults in laboratory to generate a deeper understanding of how they interact with pneumococcus. I anticipate that this research study will will improve current understanding of why the pneumococcus is persistently found among HIV-infected adults on ART. This work will allow choices in optimal therapy against HIV and optimal vaccination strategies against pneumococcus, that could significantly impact pneumococcal transmission and disease in high transmission settings.