Epidemiology, short and mid-term consequences on human health of the mpox virus infection in the Central Africa

Mpox is a zoonotic disease whose endemicity is primarily concentrated in West and Central Africa. Since the detection of the first human cases in the Democratic Republic of the Congo (DRC) in 1970, this disease has caused sporadic outbreaks, with a notable intensification in 2022 followed by a global epidemic, and then more dramatically in Central Africa in 2024, leading the World Health Organization (WHO) to declare a Public Health Emergency of International Concern in 2022 and again in 2024. In 2024, the DRC remains the most affected country, with alarming spread across multiple provinces. Despite the disease's existence for several decades, knowledge regarding mpox transmission, virulence, and clinical impacts remains limited. The current outbreak is characterized by a continuous increase in suspected and confirmed cases, associated with particularly high fatality rates among children and vulnerable populations. Initially driven by zoonotic transmissions, the outbreak has evolved with a high rate of human-to-human transmission affecting high-density areas, along with viral adaptation marked by the emergence of Clade Ib, characterized by a significant increase in APOBEC3 mutations, raising questions about potential differences in virulence. The mechanisms of transmission, such as sexual transmission, as well as specific risk factors, remain poorly understood, as do the medium- and long-term health consequences for infected individuals. This study aims to generate epidemiological, clinical, and virological data to better understand the dynamics of the mpox epidemic in Central Africa, particularly in the DRC, the Central African Republic (CAR), and the Republic of the Congo, and to assess the short- and medium-term health consequences of mpox infection while considering different clades and modes of transmission. The study's specific objectives are divided into three main areas: Clinical and epidemiological component: Analysis of clinical manifestations, complications and hospitalization outcomes, transmission modes, and risk factors for mpox across different outbreak sites in the DRC. Serological and virological component: Assessment of genetic diversity, analysis of APOBEC3 mutations and the presence of the virus in various tissues and bodily fluids, as well as the humoral immune response. Socio-anthropological component: Exploration of community and healthcare professionals' perceptions of mpox infection, social discourses associated with the disease, home and healthcare center management of cases, the impact of public health response measures, and practices linked to potential zoonotic transmissions. The adopted methodology is that of a multicenter observational cohort study, including 500 individuals with PCR-confirmed mpox. The study will span 30 months, including a six-month preparatory phase, a six-month enrollment phase, a 12-month follow-up period for confirmed cases (index cases), and a six-month analysis and site closure phase. The study will be conducted in four provinces of the DRC, covering historically endemic rural areas (Équateur province) and recent urban outbreak sites (South Kivu and Kinshasa provinces). In CAR, the study will take place in three endemic health regions in the south of the country: RS1 (Mbaïki district, southwest), RS5 (Mbomou district, southeast), and RS7 (Bangui, a recent urban outbreak site). An exploratory study will also be initiated in neighboring countries, such as the Republic of the Congo (Brazzaville). These different outbreak sites will allow for analysis of the infection based on various modes of transmission (zoonotic or human-to-human) and different mpox viral subclades and variants. For the socio-anthropological component, a mixed-methods approach will be used, including ethnographic surveys in healthcare centers (hospital settings) to better understand care organization and response impact, and knowledge, attitudes, and practices (KAP) surveys on perceptions and narratives surrounding the disease. Contacts established with participants and key individuals through ethnographic studies and surveys will serve as a starting point for in-depth exploration of practices linked to potential zoonotic transmissions. The results of this study will provide crucial insights into the dynamics and evolution of the epidemic, its characteristics, and particularly the consequences of the emergence of the mpox Clade Ib. The severity factors of the disease will help guide policymakers in developing appropriate public health policies and contribute to improving prevention strategies against mpox virus disease.