Considerations in planning a controlled human infection model in at-risk groups in sub-Saharan Africa: the case for pneumococcal challenge in people living with HIV in Malawi and a report of stakeholder consultation

Controlled human infection models offer a unique opportunity to understand infectious disease pathogenesis and have accelerated vaccine development and evaluations in malaria and typhoid. One major limitation of most CHIMs is that they are typically conducted in healthy young adults who are generally the population least affected by infectious disease, and who exhibit distinct disease profiles to more at-risk populations such as people living with HIV, young children, and older adults. However, the added value of studying these populations with high relevance is only desirable if it can be done safely, robustly and acceptably. We present a framework to guide the conduct of a controlled human infection model in people living with HIV using a case-example of an experimental human pneumococcal carriage model in a setting of high disease-burden and transmission.