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Observational Study
. 2022 Aug;22(8):1153-1162.
doi: 10.1016/S1473-3099(22)00228-6. Epub 2022 May 24.

Clinical features and management of human monkeypox: a retrospective observational study in the UK

Hugh Adler  1 , Susan Gould  1 , Paul Hine  1 , Luke B Snell  2 , Waison Wong  3 , Catherine F Houlihan  4 , Jane C Osborne  5 , Tommy Rampling  4 , Mike Bj Beadsworth  1 , Christopher Ja Duncan  6 , Jake Dunning  7 , Tom E Fletcher  1 , Ewan R Hunter  8 , Michael Jacobs  9 , Saye H Khoo  10 , William Newsholme  2 , David Porter  3 , Robert J Porter  11 , Libuše Ratcliffe  12 , Matthias L Schmid  8 , Malcolm G Semple  13 , Anne J Tunbridge  14 , Tom Wingfield  15 , Nicholas M Price  16 ; NHS England High Consequence Infectious Diseases (Airborne) Network
Collaborators, Affiliations
Observational Study

Clinical features and management of human monkeypox: a retrospective observational study in the UK

Hugh Adler et al. Lancet Infect Dis. 2022 Aug.

Erratum in

Abstract

Background: 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 treatment of smallpox and have demonstrated efficacy against monkeypox in animals. Our aim was 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.

Methods: In this retrospective observational study, we report 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 retrospective case-note review. This study included all patients who were managed in dedicated high consequence infectious diseases (HCID) centres in Liverpool, London, and Newcastle, coordinated via a national HCID network.

Findings: We reviewed all cases since the inception of the HCID (airborne) network between Aug 15, 2018, and Sept 10, 2021, identifying seven patients. 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.

Interpretation: Human monkeypox poses unique challenges, even to well resourced health-care 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.

Funding: None.

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Conflict of interest statement

Declaration of interests JD reports an unremunerated role on a Data Safety and Monitoring Board (DSMB) for an extended access programme for tecovirimat. MGS reports non-remunerated roles in a DSMB for Pfizer's mRNA vaccine programme, the UK Scientific Advisory Group for Emergencies, and New Emerging Respiratory Virus Threats Advisory Group; and reports chairing a Scientific Advisory Board and holding stock or stock options in Integrum Scientific LLC, Greensboro, NC, USA. SHK reports grants (unrelated to the current work) from ViiV, Merck, and Gilead Sciences; advisory board membership for ViiV and Merck; honoraria from ViiV; and being an unremunerated chair of a DSMB for a Gates Foundation-funded trial.

Figures

Figure 1
Figure 1
Clinical and virological timelines of seven cases of human monkeypox Each patient's self-reported identification of a rash is taken as the first date of illness (patient 2's (2021) rash was detected by her mother). Cycle threshold denotes the number of PCR cycles required to detect monkeypox virus, with higher cycle thresholds indicating lower levels of viral DNA and a cut-off of 40 cycles indicating undetectable DNA. In most cases, the rash crusted and desquamated early in the course of illness and the duration of rash is denoted by the dashed line (ongoing rash). Two patients (patient 1 (2018) and patient 4 (2019)) had their admissions prolonged due to isolated ulcerated lesions that remained persistently positive for monkeypox virus DNA, as indicated on their respective graphs. Black arrows indicate doses of brincidofovir, whereas the blue crosses indicate doses of tecovirimat. The grey background indicates time spent admitted in a High Consequence Infectious Diseases unit: patient 7 (2021) was already in hospital caring for patient 6 (2021; her daughter) when she developed symptoms. *marks the date of drainage of a large intramuscular abscess in patient 2 (2018).
Figure 1
Figure 1
Clinical and virological timelines of seven cases of human monkeypox Each patient's self-reported identification of a rash is taken as the first date of illness (patient 2's (2021) rash was detected by her mother). Cycle threshold denotes the number of PCR cycles required to detect monkeypox virus, with higher cycle thresholds indicating lower levels of viral DNA and a cut-off of 40 cycles indicating undetectable DNA. In most cases, the rash crusted and desquamated early in the course of illness and the duration of rash is denoted by the dashed line (ongoing rash). Two patients (patient 1 (2018) and patient 4 (2019)) had their admissions prolonged due to isolated ulcerated lesions that remained persistently positive for monkeypox virus DNA, as indicated on their respective graphs. Black arrows indicate doses of brincidofovir, whereas the blue crosses indicate doses of tecovirimat. The grey background indicates time spent admitted in a High Consequence Infectious Diseases unit: patient 7 (2021) was already in hospital caring for patient 6 (2021; her daughter) when she developed symptoms. *marks the date of drainage of a large intramuscular abscess in patient 2 (2018).
Figure 2
Figure 2
Skin and soft tissue manifestations of monkeypox Skin and soft tissue features included: (A and D) vesicular or pustular lesions; (B and C) macular lesions involving the palms and soles; (D and E) a sub-ungual lesion; (F and G) more subtle papules and smaller vesicles; (H) and a deep abscess (arrow, image obtained during ultrasound-guided drainage).
Figure 3
Figure 3
Alanine transaminase values of the three patients who received therapy with brincidofovir Doses of brincidofovir are denoted by arrows, with the colour of the arrow corresponding with the colour of the relevant patient's alanine transaminase graph. Normal range of alanine transaminase is less than 30 U/L.
Figure 4
Figure 4
Timeline of the 2021 monkeypox household cluster The duration of monkeypox infection is represented by active (uncrusted) skin lesions and positive PCR results from blood or upper respiratory tract swabs (skin lesions were typically PCR positive until crusted over). Black arrows denote hospital admission.
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