Expanded Access Programme for the use of tecovirimat for the treatment of monkeypox infection: A study protocol for an Expanded Access Programme.

BACKGROUND: Monkeypox is a viral zoonotic disease commonly reported in humans in parts of Central and West Africa. This protocol is for an Expanded Access Programme (EAP) to be implemented in the Central African Republic, where Clade I monkeypox virus diseases is primarily responsible for most monkeypox infections. The objective of the programme is to provide patients with confirmed monkeypox with access to tecovirimat, a novel antiviral targeting orthopoxviruses, and collect data on clinical and virological outcomes of patients to inform future research. METHODS: The study will be conducted at participating hospitals in the Central African Republic. All patients who provide informed consent to enrol in the programme will receive tecovirimat. Patients will remain in hospital for the duration of treatment. Data on clinical signs and symptoms will be collected every day while the patient is hospitalised. Blood, throat and lesion samples will be collected at baseline and then on days 4, 8, 14 and 28. Patient outcomes will be assessed on Day 14 -end of treatment-and at Day 28. Adverse event and serious adverse event data will be collected from the point of consent until Day 28. DISCUSSION: This EAP is the first protocolised treatment programme in Clade I MPXV. The data generated under this protocol aims to describe the use of tecovirimat for Clade I disease in a monkeypox endemic region of Central Africa. It is hoped that this data can inform the definition of outcome measures used in future research and contribute to the academic literature around the use of tecovirimat for the treatment of monkeypox. The EAP also aims to bolster research capacity in the region in order for robust randomised controlled trials to take place for monkeypox and other diseases. TRIAL REGISTRATION: {2a & 2b}: ISRCTN43307947.

Seasonal Patterns of Mpox Index Cases, Africa, 1970-2021.

Across 133 confirmed mpox zoonotic index cases reported during 1970-2021 in Africa, cases occurred year-round near the equator, where climate is consistent. However, in tropical regions of the northern hemisphere under a dry/wet season cycle, cases occurred seasonally. Our findings further support the seasonality of mpox zoonotic transmission risk.

A time of decline: An eco-anthropological and ethnohistorical investigation of mpox in the Central African Republic.

The Central African Republic (CAR) has experienced repeated mpox outbreaks since 2001. Although several mpox epidemiological risk factors for zoonotic and interhuman transmission have been documented, the reasons for more frequent epidemic outbreaks are less well understood, relying on vague explanatory categories, including deforestation, hunting, and civil unrest. To gain insight into increasingly frequent outbreaks, we undertook an ethnohistorical, eco-anthropological analysis in two CAR regions: the Lobaye prefecture, experiencing one or more annual outbreaks in the past decade, and the Sangha-Mbaere prefecture, with a longer history of mpox but less frequent outbreaks. We comparatively examined changing political economies, forest use practices, and understandings of mpox. In 2022, we conducted 40 qualitative ethnohistorical, anthropological interviews and participant-observation of forest activities in two languages (Sango and French). We compared contemporary practices with hunting, trapping, and meet consumption practices, documented through quantitative and qualitative observation in one research site, over 6 months in 1993. We find increased rodent capture and consumption in both sites in the past 30 years and expanded practices of other potentially risky activities. Simultaneously, we also identify important differences in risky practices between our Lobaye and Sangha-Mbaere participants. In addition, Lobaye and Sangha participants underscored historical processes of decline producing mpox among other emergences, but they framed these declension processes diversely as economic, political, nutritional, and moral. Our findings are important because they mobilize new types of evidence to shed light on the processual dynamics of mpox outbreaks in the CAR. This study also reveals variability across two sites within the same country, highlighting the importance of comparative, fine-grained anthropological and historical research to identify underlying dynamics of mpox outbreaks. Finally, our study points to the need for mpox interventions and risk communication accounting for these regional differences, even within a single country.

Laboratory Diagnosis of Mpox, Central African Republic, 2016-2022.

During 2016-2022, PCR testing confirmed 100 mpox cases among 302 suspected cases in the Central African Republic. The highest detection rates were from active lesions (40%) and scabs (36%); cycle thresholds were lower (≈18) than those for blood samples (≈33). Results were consistent for generic primer- and clade I primer-specific PCR tests.

National Monkeypox Surveillance, Central African Republic, 2001-2021.

We analyzed monkeypox disease surveillance in Central African Republic (CAR) during 2001-2021. Surveillance data show 95 suspected outbreaks, 40 of which were confirmed as monkeypox, comprising 99 confirmed and 61 suspected monkeypox cases. After 2018, CAR's annual rate of confirmed outbreaks increased, and 65% of outbreaks occurred in 2 forested regions bordering the Democratic Republic of the Congo. The median patient age for confirmed cases was 15.5 years. The overall case-fatality ratio was 7.5% (12/160) for confirmed and suspected cases, 9.6% (8/83) for children <16 years of age. Decreasing cross-protective immunity from smallpox vaccination and recent ecologic alterations likely contribute to increased monkeypox outbreaks in Central Africa. High fatality rates associated with monkeypox virus clade I also are a local and international concern. Ongoing investigations of zoonotic sources and environmental changes that increase human exposure could inform practices to prevent monkeypox expansion into local communities and beyond endemic areas.