Tecovirimat for Monkeypox in Central African Republic under Expanded Access

To the Editor:

We report on the protocolized use of tecovirimat (SIGA Technologies), an antiviral drug with activity against orthopoxviruses (including monkeypox and smallpox),¹ under an expanded access program for all patients with monkeypox virus (MPXV) disease in Mbaïki, Central African Republic, between December 2021 and February 2022.² Included in the study were 14 patients in whom MPXV infection had been diagnosed. All 14 patients tested positive for MPXV on at least one admission sample; of these patients, 12 had positive results on a real-time polymerase-chain-reaction (PCR) assay with a mean cycle threshold of 32 (range, 21 to 42); 12 were also positive on an MPXV CL3 assay that was specific for clade I (see the Methods section in the Supplementary Appendix, available with the full text of this letter at NEJM.org).

Data regarding the patients’ clinical signs and symptoms were recorded daily throughout treatment and at follow-up visits (Table S2 in the Supplementary Appendix). Blood or lesion samples were obtained on admission, throughout treatment, and on day 28 to assess MPXV status. Ethics-committee approval was obtained from the University of Oxford and the University of Bangui before enrollment began. All the patients provided written informed consent to participate in the study.

Table 1. Table 1. Characteristics of the 14 Patients at Baseline and Outcomes.

The median age of the patients was 23 years (range, 4 to 38), 71% were female, and the median time from symptom onset to the initiation of treatment was 21 days (range, 5 to 45) (Table 1 and Table S3). At the time of admission, all 14 patients presented with muscle pain, headache, lymphadenopathy, and lesions that are characteristic of MPXV infection; of these patients, 11 had more than 100 lesions. Active lesions were reported in 10 patients.

All the patients received a 14-day course of oral tecovirimat (600 mg twice daily in adults; doses for children according to weight category are detailed in the Supplementary Appendix). A total of 13 patients completed the 28-day follow-up.

MPXV was detected in at least one sample in 7 of 14 patients by day 4, in 1 of 10 patients by day 8, in 1 of 8 patients by day 14, in 1 of 2 patients by day 21, and in 1 patient by day 28. By day 14, a total of 12 of 14 patients had been discharged with no active lesions; of the remaining 2 patients, 1 was discharged on day 21 with negative results on a PCR assay, and 1 remained positive on day 28. By the final study visit, 12 of 13 patients were PCR-negative and had recovered; scarring was visible in 9 patients. The median time from the initiation of treatment until the absence of active lesions was 5 days (Fig. S4). Two serious adverse events were reported: life-threatening anemia during treatment in an HIV-positive patient and an unexplained death after discharge; neither event was considered to be related to the study treatment.

Data collected through this study have increased our knowledge of the use of tecovirimat in a country in which clade I MPXV is endemic and 106 confirmed cases were recorded between 2010 and September 2022, with 11 deaths (10.4%) (Table S5). This program has also piloted a community outreach program and sustainable community-based surveillance system and increased clinical research capacity in the Central African Republic.

Festus Mbrenga, M.D.
Emmanuel Nakouné, Ph.D.
Christian Malaka, Ph.D.
Institut Pasteur de Bangui, Bangui, Central African Republic

Josephine Bourner, M.Sc.
Jake Dunning, M.D., Ph.D.
University of Oxford, Oxford, United Kingdom

Guy Vernet, Ph.D.
Institut Pasteur de Bangui, Bangui, Central African Republic

Peter Horby, M.D., Ph.D.
Piero Olliaro, M.D., Ph.D.
University of Oxford, Oxford, United Kingdom
[email protected]

This letter was published on November 30, 2022, at NEJM.org.