On August 14, 2024, the World Health Organization declared mpox a Public Health Emergency of International Concern due to rising cases in Africa, the emergence of the sexually transmissible Clade Ib, and increased morbidity and mortality, especially among children. By September 2024, 14 African countries were facing mpox outbreaks involving both Clade I and II strains. However, critical gaps remain in understanding the epidemiology, transmission dynamics, genomic diversity, and natural history of mpox, particularly regarding the impact of different viral clades. Our study aims to investigate factors influencing MPXV transmission and outcomes in the Democratic Republic of the Congo (DRC), Cameroon, and Nigeria to inform mpox control efforts. The specific aims are: 1)To estimate mpox incidence through community-based case- finding using rapid molecular diagnostics. 2)To characterize clinical features, outcomes, and severity by socio-demographics, transmission route, and viral clade in MPXV-PCR+ patients. 3) To conduct genomic sequencing to track viral evolution and clade-specific transmission dynamics. 4) To raise awareness and disseminate information to understand factors associated with MPXV infection. These outcomes will help address key knowledge gaps and guide strategies for ongoing mpox prevention and control in Africa. "