Journal name: The Lancet Infectious Diseases

Publishing date: May 24, 2022

Author: Hugh Adler, PhD et.al

A retrospective observational study on the clinical features and management of monkeypox in the UK among 7 diagnosed cases showed prolonged respiratory viral shedding after resolution of skin lesions and the urgent need for research on antivirals for monkeypox and similar tropical diseases.

Why does this study matter?

Monkeypox is rarely exported from the African continent. In 2003, there was a zoonotic outbreak in the USA causing 47 confirmed or suspected cases. This outbreak was linked to the importation of Gambian giant rats, squirrels, and dormice, which had transmitted the virus to prairie dogs that were then sold as pets. Only 14 patients were hospitalised and there were no confirmed cases of person-to-person transmission. Imported monkeypox infections in humans following travel have been reported before in other countries.

Currently, there are no licensed treatments for human monkeypox; two orally bioavailable drugs, brincidofovir and tecovirimat, have been approved in the USA for the treatment of smallpox in preparation for a potential bioterrorism event. Neither drug has been studied in human efficacy trials; however, both drugs demonstrated efficacy against other orthopoxviruses (including monkeypox) in experimental models.

There are reports of compassionate use of tecovirimat for complicated vaccinia and cowpox, with no concerning safety signals identified. An expanded access programme for tecovirimat is in preparation in the central African republic, where monkeypox outbreaks are common.

Study Design

Cases of human monkeypox are rarely seen outside of west and central Africa. There are few data regarding viral kinetics or the duration of viral shedding and no licensed treatments. Two oral drugs, brincidofovir and tecovirimat, have been approved for the treatment of smallpox and have demonstrated efficacy against monkeypox in animals. This study aimed to describe the longitudinal clinical course of monkeypox in a high-income setting, coupled with viral dynamics, and any adverse events related to novel antiviral therapies.

In this retrospective observational study, they reported the clinical features, longitudinal virological findings, and response to off-label antivirals in seven patients with monkeypox who were diagnosed in the UK between 2018 and 2021, identified through a retrospective case-note review. This study included all patients who were managed in dedicated HCID centres in Liverpool, London, and Newcastle, coordinated via a national HCID network.

Of the seven patients, four were men and three were women. Three acquired monkeypox in the UK: one patient was a health-care worker who acquired the virus nosocomially, and one patient who acquired the virus abroad transmitted it to an adult and child within their household cluster. Notable disease features included viraemia, prolonged monkeypox virus DNA detection in upper respiratory tract swabs, reactive low mood, and one patient had a monkeypox virus PCR-positive deep tissue abscess. Five patients spent more than 3 weeks (range 22–39 days) in isolation due to prolonged PCR positivity.

Three patients were treated with brincidofovir (200 mg once a week orally), all of whom developed elevated liver enzymes resulting in cessation of therapy. One patient was treated with tecovirimat (600 mg twice daily for 2 weeks orally), experienced no adverse effects, and had a shorter duration of viral shedding and illness (10 days hospitalisation) compared with the other six patients. One patient experienced a mild relapse 6 weeks after hospital discharge.

Results and Conclusion

Human monkeypox poses unique challenges, even to well-resourced healthcare systems with HCID networks. Prolonged upper respiratory tract viral DNA shedding after skin lesion resolution challenged current infection prevention and control guidance. There is an urgent need for prospective studies of antivirals for this disease.

This case series highlights the value of maintaining a collaborative network of centres on standby to manage sporadic, small numbers of patients with high consequence pathogens such as the monkeypox virus. The disease course of the patients they reported was challenging and resource-intensive to manage, even in the high-income setting of the UK.

Monkeypox outbreaks will continue to occur in west and central Africa, and healthcare workers around the world must remain vigilant to the possibility of monkeypox in travellers presenting with fever and rash. This study also supports further research into antivirals to treat this neglected tropical disease.

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