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.

Seroprevalence of anti-SARS-CoV-2 antibodies before and after implementation of anti-COVID-19 vaccination among hospital staff in Bangui, Central African Republic.

Healthcare workers (HCWs) are at high to very high risk for SARS-CoV-2 infection. The persistence of this pandemic worldwide has instigated the need for an investigation of the level of prevention through immunization and vaccination against SARS-CoV-2 among HCWs. The objective of our study was to evaluate any changes in anti-COVID-19 serological status before and after the vaccination campaign of health personnel in the Central African Republic. We carried out a repeated cross-sectional serological study on HCWs at the university hospital centers of Bangui. Blood samples were collected and tested for anti-SARS-CoV-2 IgM and IgG using the ELISA technique on blood samples. A total of 179 and 141 HCWs were included in the first and second surveys, respectively. Of these staff, 31.8% of HCWs were positive for anti-SARS-CoV-2 IgG in the first survey, whereas 95.7% were positive for anti-SARS-CoV-2 IgG in the second survey. However, the proportion of HCWs positive for SARS-CoV-2 IgM antibodies was low (9.7% in the first survey and 3.6% in the second survey). These findings showed a sharp increase in seroprevalence over a one-year period. This increase is primarily due to the synergistic effect of the infection and the implementation of vaccines against COVID-19. Further studies to assess the persistence of anti-SARS-CoV-2 antibodies are needed.

Sero-prevalence of anti-SARS-CoV-2 antibodies among communities between July and August 2022 in Bangui, Central African Republic.

Background: Large-scale population-based seroprevalence studies of SARS-CoV-2 are essential to characterize the cumulative incidence of SARS-CoV-2 infection and to extrapolate the prevalence of presumptive immunity at the population level. Objective. The objective of our survey was to estimate the cumulative population immunity for COVID-19 and to identify individual characteristics associated with positive serostatus. Materials and Methods: This was a clustered cross-sectional study conducted from July 12 to August 20, 2021, in households in the city of Bangui, the capital of the Central African Republic. Information regarding demographic characteristics (age, gender, and place of residence), and comorbidities (chronic diseases) was collected. A venous blood sample was obtained from each participant to determine the level of total anti-SARS-CoV-2 antibodies using a WANTAI SARS-CoV-2 Ab ELISA kit. Results: All up, 799 participants were surveyed. The average age was 27 years, and 45.8% of the respondents were male (sex ratio: 0.8). The overall proportion of respondents with positive serostatus was 74.1%. Participants over 20 years of age were twice as likely to have positive serostatus, with an OR of 2.2 [95% CI: (1.6, 3.1)]. Conclusions: The results of this survey revealed a high cumulative level of immunity in Bangui, thus indicating a significant degree of spread of SARS-CoV-2 in the population. The public health implications of this immunity to SARS-CoV-2 such as the post-vaccination total antibody kinetics remain to be determined.

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.