The goal of this observational study is to characterize the clinical features of the 2024 mpox outbreak in Equateur Province of DRC and to identify associated risk factors. The main question it aims to answer is:

• What are the clinical features of the 2024 mpox outbreak in Equateur Province of DRC?
• What are the associated risk factors of the 2024 mpox outbreak? Participants which has mpox like symptoms will answer mpox investigations related questions and be collected skin lesions and whole blood samples.

Mpox is caused by the monkeypox virus (MPXV), a member of the genus Orthopoxvirus (family Poxviridae). This virus is closely related to the variola virus, which causes smallpox. MPXV was first identified in 1958, and the first human case was reported in the Democratic Republic of the Congo (DRC) in 1970. It was presumed that the smallpox (vaccinia) vaccine would confer cross-protection against mpox. Following the global eradication of smallpox in 1980, mpox remained largely confined to limited regions in Central Africa-where zoonotic spillover from wild animal reservoirs constituted the primary route of transmission. Equateur Province is among the areas in the DRC with a notably high burden of reported mpox cases.

Over the past five decades, routine smallpox vaccination ceased worldwide, resulting in waning herd immunity against orthopoxviruses. During this period, mpox incidence rose markedly, with an estimated tenfold increase in global cases. Two principal genetic clades of MPXV have been identified: clade I (historically referred to as the Congo Basin clade) and clade II (the West African clade). In 2018, Nigeria experienced a resurgence of mpox, highlighting the virus's potential to emerge in previously controlled areas. Starting in 2022, clade II mpox circulated globally, especially among men who have sex with men (MSM), peaking in mid-2022 before declining to persistently lower levels by early 2023. Although clade II mpox typically exhibits a low case-fatality ratio (<1%), clade I has historically been associated with more severe disease and higher mortality. In 2023, the number of reported mpox cases continued to climb in the DRC, prompting the World Health Organization (WHO) to declare a Public Health Emergency of International Concern (PHEIC) in August 2024.

Recent surveillance indicates that sub-clade Ia MPXV is spreading in western DRC through multiple transmission modes, including contact with infected wild animals, household exposure, or sexual contact. By contrast, sub-clade Ib mpox in the eastern part of the country appears initially to spread via intimate or sexual contact between adults, followed by household transmission. Numerous environmental and social risk factors-including the consumption of rodent species, deforestation, climate change, civil unrest, population displacement, emerging MPXV variants, and weakened immunity-may be driving mpox incidence. Clade Ia mpox is currently affecting western parts of the DRC, yet the epidemiology remains poorly understood due to the limited number of laboratory-confirmed cases.

This study aims to characterize the clinical features of the 2024 mpox outbreak in Equateur Province of DRC and to identify associated risk factors. The findings will advance understanding of mpox transmission dynamics and disease severity, ultimately informing more effective prevention and control strategies in endemic settings.

Inclusion Criteria:

• Provision of informed consent: Proxy-assisted informed consent is allowed under safety considerations. Following oral consent, the investigator will document this on the informed consent form as a witness.

• Fulfillment of the current mpox clinical case definition in the DRC, which includes: Presence of a vesicular or pustular eruption with deep-seated, firm pustules.

At least one of the following symptoms:

Fever preceding the eruption. Lymphadenopathy (inguinal, axillary, or cervical). Presence of pustules or crusts on the palms of the hands or soles of the feet. • Laboratory confirmation: At least one molecular-based mpox diagnostic test confirming the diagnosis.

Exclusion Criteria:

Participants will be excluded from the study under the following conditions:

• Refusal to participate in the study: Individuals who decline to provide consent for study participation will be excluded.

This study targets patients reported as suspected mpox cases (all ages, both sexes) to the Health District Central Office in the selected sites. For participants aged under 15 years or those with impaired communication abilities (e.g., due to altered consciousness or severe medical conditions), consent must be obtained from a parent, legal guardian, or responsible caregiver. The study population is designed to minimize selection bias related to health-seeking behavior.

All patients suspected of having mpox and who provide proxy-assisted written informed consent to participate in the study are eligible for inclusion due to reduction of the risk of contact transmission with verbal agreement documented and confirmed by a witness. This approach prioritizes participant and staff safety while adhering to ethical standards.