Case Series Paints Picture of Monkeypox Clinical Management

Seven patients with monkeypox infection had prolonged illness, and only one antiviral appeared to be effective, a retrospective U.K. series from 2018 to 2021 found.

Three patients treated with brincidofovir (Tembexa) once a week developed elevated liver enzymes and were forced to stop the drug, while one patient treated with tecovirimat (Tpoxx) had no adverse events, a shorter hospital stay, and fewer days of viral shedding, reported Nicholas Price, PhD, of NHS Foundation Trust in London, and colleagues.

Both antivirals are approved in the U.S. for smallpox, while tecovirimat also carries an indication in the EU for monkeypox.

Notable clinical features of the illness included prolonged viral DNA detection in patients’ upper respiratory tract, even after skin lesions had resolved, the authors wrote in Lancet Infectious Diseases.

“During previous outbreaks of monkeypox, patients were considered infectious until all lesions crusted over. In these seven … cases, viral shedding was observed for at least three weeks following infection. However, data on infectivity remains limited, and is an important area for future study,” co-author Catherine Houlihan, PhD, of University College London, said in a statement.

“Our study offers some of the first insights into the use of antivirals for the treatment of monkeypox in humans,” added co-author Hugh Adler, PhD, of Liverpool University Hospitals NHS Foundation Trust.

Price’s group also noted that their data includes three cases of local transmission in the U.K., including the first reported case of nosocomial transmission of monkeypox (in a healthcare worker), as well as the first case of household transmission of monkeypox outside of Africa: an adult and child in the household of a travel-associated case contracted the virus.

Data were examined from Aug. 15, 2018 to Sept. 10, 2021, with cases defined via a positive PCR test for monkeypox and “compatible clinical illness.”

Of the seven patients, four were female — including a girl younger than 2. Four patients were in the 30-40 age range, and only one had post-exposure prophylaxis.

Interestingly, the four cases in 2018-2019 had fever or a preceding illness, while the three in 2021 had no prior symptoms to the appearance of lesions. All patients had “pleiomorphic skin lesions,” such as papules, vesicles, and pustules, and all had detectable virus in upper respiratory tract swabs. Six patients had detectable virus in blood and four in urine.

Duration of hospital stay ranged from 10 to 39 days, and all patients made a full recovery.

The earliest three patients were treated with brincidofovir about a week after the rash onset, but all three developed elevated alanine transaminase levels and treatment was discontinued. The authors noted two of three patients experienced “transient” reduction in viral load following their second doses, and other adverse events included possible “mood disturbance.”

In 2021, a patient was treated with 2 weeks of antiviral tecovirimat, which produced a different result. Within 48 hours, the patient tested negative for monkeypox via PCR in blood and upper respiratory samples after 48 hours of treatment, and no new lesions developed after 24 hours. After a week of treatment, the patient was discharged and completed her second week of treatment at home. Three patients in the series received no antiviral treatment.

Limitations to the data include its small sample size and observational nature. The authors added they were unable to confirm positive PCR results with “viral culture assays to demonstrate ongoing shedding of viable virus.”

“The cases we observed were challenging and resource-intensive to manage,” said Price in a statement, adding that the cases “in addition to the recent outbreaks, highlight the importance of maintaining a collaborative network of centers on standby to manage sporadic, outbreaks of high consequence pathogens.”