In a recent publication Open Forum Infectious Diseases, a team of US-based scientists has described the therapeutic efficacy of a pan-Orthopoxvirus inhibitor, tecovirimat, in patients with monkeypox infection. This drug is currently available under an expanded access investigational new drug protocol for monkeypox.
Study: Tecovirimat for the treatment of human monkeypox: an initial series from Massachusetts, United States. Image Credit: Berkay Ataseven/Shutterstock
Background
Monkeypox virus is a zoonotic virus belonging to the Orthopoxvirus family. The virus was endemic to Central and West Africa for many decades, and its transmission to non-African countries was initially limited. However, because of the global reduction in herd immunity against related smallpox viruses, many countries outside of Africa are currently experiencing monkeypox outbreaks.
Large outbreaks of West African monkeypox strain (clade 3) have been detected in multiple non-endemic countries in May 2022, including the USA and UK. The human-to-human transmission, a rare event initially, has also increased considerably in recent years.
Although the Central African strain of monkeypox is more pathogenic than the West African strain, the latter has been found to cause serious complications in children, pregnant women, and immunocompromised patients. This highlights the need for developing effective therapeutic as well as preventive interventions against monkeypox infection.
In the current article, scientists have presented three case reports of monkeypox infection treated with tecovirimat in Massachusetts hospitals. Tecovirimat is a small molecule inhibitor that has been approved by the US Food and Drug Administration (FDA) for the treatment of smallpox infection.
First case report
The first case report was about a 20-year-old man with a history of gonococcal urethritis. During an international trip to a non-endemic country with the current outbreak of monkeypox, he developed a subjective fever. He had unprotected sex with multiple men during his trip.
After one week, he developed subjective chills, malaise, and a mildly painful, shallow ulcer on the foreskin of the penis and presented to outpatient care in the USA. He tested negative for syphilis, gonorrhea, and chlamydia, which are sexually transmitted diseases. Afterward, he developed painful lesions on the face, oropharynx, hands, and feet and was admitted to the hospital.
The biological specimens collected from the patient were analyzed by polymerase chain reaction (PCR), which confirmed monkeypox infection. Based on the diagnosis, he was treated orally with 600 mg of tecovirimat twice daily for 14 days.
At day 4, the treatment caused a reduction in pain and skin itchiness, cessation of new lesion formation, and size reduction or resolution of pre-existing lesions. A mild induction in alanine aminotransferase level was observed on day 6 of the treatment, which gradually normalized by day 8.
The majority of lesions were resolved by the end of the treatment (day 14). The only one adverse side-effect reported by the patient was mild headache, which was associated with the first medicine dose.
Second case report
The second case report was about a 20-year-old man with human immunodeficiency virus (HIV) infection who was under antiretroviral treatment. Seven days after having anal receptive intercourse, he visited the outpatient care and received one dose of a replication-deficient modified vaccinia Ankara vaccine, which is used as a post-exposure prophylaxis against monkeypox infection.
The next day, he developed subjective fevers, chills, myalgias, and painful swallowing. After two days, he presented to the hospital immediately after developing scattered skin eruptions on the forearms and hands.
The diagnosis made in the hospital confirmed monkeypox infection. His neck CT scan findings showed abnormal enlargement of lymph nodes and a prominent left palatine tonsil without edema. Because of the fever and painful swallowing, he was treated with 600 mg of tecovirimat twice daily for 14 days.
After 5 days of treatment, the swallowing problem was resolved, and he was discharged from the hospital. A considerable improvement in skin lesions occurred on day 9 post-treatment. The only treatment-related adversity reported by the patient was loose bowel movements.
Third case report
The third case report was about a 40-year-old man on pre-exposure prophylaxis against HIV infection. He presented to outpatient care because of fever, malaise, rashes, noticeable vesicles on the penis foreskin, and lesions on the right lower eyelid.
About 8 – 10 days before the development of these symptoms, he had unprotected sex with multiple men during an international trip to an endemic country with the current monkeypox outbreak.
He was admitted to the hospital because of cellulitis and eye problem evaluation. The PCR testing of biological specimens confirmed monkeypox infection. After an unsuccessful initial antibiotic treatment, he was administered 600 mg of tecovirimat twice daily for 14 days.
After two days of the treatment, rashes and lesions started resolving, and he was discharged from the hospital on day 4. He reported almost complete resolution of rashes and significant improvement in eyelid lesions on day 7 of the treatment. Moreover, he did not report any treatment-related adversities.
Significance
The overall findings of three case reports indicate that tecovirimat might be used clinically to improve symptoms and prevent the progression of monkeypox infection. The scientists mention that further large-scale studies are needed to determine the therapeutic efficacy of tecovirimat more conclusively.
Case study: Monkeypox breakthrough infection in fully vaccinated individual