Unraveling the Drivers of Persistent Malaria Transmission in Cameroon: A Systems Approach (REDIAL) - PROGRAM SUMMARY Despite concerted efforts, the global incidence of malaria has been on the rise since 2015, with a 7.4% increase reported in 2021. This increase is largely driven by a subset of high-burden countries, primarily located in sub- Saharan Africa, where approximately 95% of cases and deaths occur. To reverse this trend, it is imperative to gain insights into the underlying mechanisms responsible for the persistent transmission of malaria in spite of the deployment of proven control interventions. Our International Center of Excellence for Malaria Research program called “REDIAL” will be based in Cameroon, a Central African country that epitomizes the malaria challenge faced by high-burden countries. Cameroon, one of the top 11 malaria high-burden countries, has experienced a malaria resurgence, with the disease incidence increased by 24% since 2012. The reasons for this rising malaria trend are unknown but indicate that the current control measures do not adequately target the critical transmission reservoirs to disrupt malaria transmission. Cameroon, renowned as Africa in miniature due to its diverse ecology, exhibits highly heterogeneous malaria transmission patterns across its five distinct eco- climatic zones, where various vectors play remarkably different roles in transmitting the disease. The routine malaria surveillance systems in Cameroon are inadequate and do not offer the spatial granularity and longitudinal views that are needed to assess the malaria trend and monitor the impact of control interventions. In addition, the malaria situation is compounded by the emergence and spread of insecticide-resistant vectors and multidrug- resistant malaria parasites, further aggravating the problem. Therefore, the central goal of this program is to improve our understanding of how the evolving parasite and vector populations evade contemporary malaria control measures to sustain high-level malaria transmission in divergent ecological zones in Cameroon so that innovative integrated strategies can be developed to control and ultimately eliminate malaria. To achieve this overarching objective, we have selected study sites in Cameroon with drastically different malaria epidemiology to conduct comprehensive research on humans, vectors, and parasites in two interrelated projects. Project 1 will conduct longitudinal cohort studies and mosquito-feeding experiments to elucidate the critical transmission reservoirs and determine how the malaria control interventions affect the reservoirs, vectorial capacity, and evolution of parasite populations. Project 2 will comprehensively investigate the evolution of insecticide resistance in major vector species and antimalarial drug resistance in malaria parasites in response to control interventions and how these affect the effectiveness of current interventions. By dissecting the complex interactions between the human host, diverse mosquito vectors, and drug-resistant parasites, this study will unravel the mechanisms underlying the high-level malaria transmission and provide the critical evidence needed by the national malaria control program to optimize strategies to effectively control malaria in Cameroon.
