Context

On 09 December 2021, one of the largest mpox epidemics ever recorded in the DRC was declared in Maniema province. The epidemic began in the Tunda area of Kimbombo territory in southern Maniema, with the first suspected cases reported in September 2021. From October 2021 to May 2022, a total of 513 suspected mpox cases and 50 deaths were reported, representing an overall unusual case-fatality rate of ~9.7%.

Since then, the Tunda Health Zone has continued to report new suspected cases and a few deaths due to mpox. Given the scale of the epidemic and the continuing atypically high mortality, there was an urgent need for research into the scope and drivers of the epidemic. In May 2022, the Institut National de Recherche Biomédicale (INRB) in Kinshasa, the Antwerp Institute of Tropical Medicine (ITM), the Programme National de Lutte contre le MPX et la Fièvre Hémorragique Virale en RDC and the Alliance for International Medical Action (ALIMA), launched an interdisciplinary investigation mission in the Tunda Health Zone, the epicentre of the epidemic .

During this investigation, circumstantial evidence highlighted two potential events: the human behaviour that led to the animal-human contact that was likely to have triggered the epidemic, and its intensive human-to-human spread. However, there were no reliable data to support these conclusions, as the Tunda Health Zone is a remote area with insufficient resources and significant logistical challenges, making decent surveillance difficult. In addition, the Tunda Health Zone faced a number of difficulties, particularly technical and financial. The lack of partners, support for free care and supplies of drugs and equipment made it very difficult to treat Mpox patients. The Health Zone did not have the appropriate infrastructure or qualified human resources to provide care, and there was no circuit for isolating patients.

Apart from these aspects of response and management, there was still no operational research in Maniema province in general and in the Tunda Health Zone to understand the epidemic in terms of who, where and when, the clinical presentation of the disease (case definition), the mode of transmission, exposure and risk factors, the secondary attack rate and the seroconversion time after exposure.

In response to these needs, ALIMA, in partnership with the ITM and the INRB for the research component, made a plea for urgent funding from ECHO to support the response and operational research into the epidemic. This funding, shared between the partners, was intended to improve the management of patients suffering from MPX, to strengthen surveillance and active case-finding, and to carry out additional operational and clinical research in order to better understand the determinants of the current epidemic.

ALIMA's operational strategy was based on 6 priorities:

- Improving access to free, high-quality healthcare for children under 5 in the health centres supported   

• Providing medical care for cases of Mpox
• Strengthening infection prevention and control and waste management
• Strengthen epidemiological surveillance in the Tunda health zone
• Strengthen diagnosis and research into Mpox disease in the Tunda health zone: characterisation of the disease and its clinical, biological and biochemical profile, in collaboration with its research partners (national and international).
• Raising community awareness

The Mpox, Biology, Outcome, Transmission and Epidemiology (Mbote) study aims to understand better the clinical presentation, risk factors, transmission patterns and epidemic potential of mpox. The research projected is nested on the humanitarian response and feeds into it.

The overall objectives are:

• To provide an epidemiological description of the mpox epidemic in Maniema and find indications for the cause of the epidemic
• Collect samples to confirm the diagnosis of mpox in suspected cases.
• Carry out a clinical description of patients with mpox
• Estimate the contribution of human-to-human transmission to the current epidemic and estimate the secondary attack rate.
• To estimate the scale of the epidemic by means of a seroprevalence study.
• To estimate the rate of asymptomatic or pauci-symptomatic carriage, by sampling high-risk family contacts in the vicinity of confirmed cases.
• To describe the phylogeny of isolated MPXV using whole genome sequencing

Overall Approach

To comprehensively study the outbreak in Maniema, the Mbote study was designed as a modular protocol, with each module targeting distinct aspects of the outbreak. The project consisted of the following modules:

• Module A: studying existing epidemiological data. Module A consisted of studying routine surveillance data to reconstruct the outbreak and figure out what is happening with mpox both on the country level as well as in Maniema. This will be triangulated with genomic data.
• Module B in-depth investigation into mpox suspect cases: in this module, we supported active case finding within the health zone. Each suspect case was investigated in detail, to assess the clinical description, case definition and risk factors. Data on presenting signs, symptoms, exposure and risk factors were collected, as well as bioligical samples for confirmatory diagnosis.
• Module C transmission studies in the community: consist of a unique longitidunal follow-up of  high-risk contacts in the community in order to assess the secondary transmission rate of the disease, as well as describe the early stage of monkeypoxvirus infection and investigate wether assymptomatic or presymptomatic occurs
• Module D a seroprevalence study. This module tries to estimate the burden of the disease in the community and the seroconversion rate by comparing affected villages with non-affected villages.
• (Module E animal reservoir studies: in this module animal specimens were extensively investigated as part of attempts to find the animal reservoir. This module, however, was outside of the scope of ECHO funding)