Monkeypox

Monkeypox virus is an Orthopoxvirus, a genus that includes camelpox, cowpox, vaccinia, and variola viruses. The virus is the foremost Orthopoxvirus affecting human populations since smallpox eradication, confirmed by the World Health Organization in 1980.

• was not recognized as a distinct infection in humans until 1970 during efforts to eradicate smallpox, when the virus was isolated from a patient with suspected smallpox infection in The Democratic Republic of the Congo (DRC) (1,2)
  • was first isolated in late 1958 in Copenhagen during two outbreaks of a smallpox-like disease in a colony of cynomolgus monkeys (5)
    • no clinical signs were noted before the eruptive phase of the disease, which was characterized by a maculopapular rash
    • virus was named monkeypox virus because of its close similarity to other known poxviruses
    • monkeypox is a zoonotic disease, but its animal reservoir remains unknown (5)
      • various rodent species from Central and West African tropical rainforests, including tree squirrels and Gambian pouched rats, are currently considered to be strong candidates
• typically, up to a tenth of persons ill with monkeypox may die, with most deaths occurring in younger age groups (3)
  • case fatality ratio of monkeypox has varied between 0 and 11 % in the general population, and has been higher among young children
    • in persons younger than 40 or 50 years of age (depending on the country) then they may be more susceptible to monkeypox as a result of the termination of routine smallpox vaccination worldwide after the eradication of smallpox
• analysis (226 cases; 211 male) found the majority (99%) were gay, bisexual or men who have sex with men; 44% had HIV infection (4)
  • clinical manifestations differed by HIV status; those with HIV were more likely to have diarrhoea, perianal rash or lesions and a higher rash burden

Monkeypox virus

• belongs to the family Poxviridae, subfamily Chordopoxvirinae, and genus orthopoxvirus
  • genus encompasses many other poxviruses, including the smallpox, vaccinia, cowpox, and camelpox viruses, as well as more recently isolated poxviruses
    • cross-immunity among viruses in this genus occurs because these double-stranded DNA viruses are very similar genetically and antigenically
    • smallpox vaccination generally provides some protection against monkeypox

Spread of monkeypox

• spread through animal-to-human transmission,
  • therefore only occurs in people who have been in contact with an animal carrying the disease
  • monkeypox is a zoonotic disease, but its animal reservoir remains unknown (5)
    • various rodent species from Central and West African tropical rainforests, including tree squirrels and Gambian pouched rats, are currently considered to be strong candidates
  • monkeypox virus is transmitted from one person to another by contact with lesions, body fluids, respiratory droplets and contaminated materials such as bedding (3)
    • typically occurs through skin-to-skin contact with a person who has monkeypox rash, sores, or scabs (10)
      • can also be spread through intimate sexual contact (kissing; oral, anal, or vaginal sex) or through respiratory droplets
      • contact with infected urine or faeces or objects contaminated with the monkeypox virus (such as towels or sex toys) may also be a potential source of infection
  • outbreaks of monkeypox have been confined to the tropical rainforests of central and western Africa, particularly in the Democratic Republic of Congo
    • more recently there have been outbreaks of the disease in the USA and Sudan
  • risk of human-to-human transmission of the virus is low, but has been documented in people who have had very close contact with an infected individual
  • eating inadequately cooked meat and other animal products of infected animals is a possible risk factor (3)

Clinical features:

• majority of the clinical characteristics of human monkeypox infection mirror those of smallpox (discrete ordinary type or modified type)
  • initial febrile prodrome is accompanied by generalized headache and fatigue
    • can take up to 12 days for these 'flu-like symptoms of monkeypox to develop from the initial exposure to the virus (2)
      • these symptoms usually last 14 to 21 days
    • prior to, and concomitant with, rash development is the presence of maxillary, cervical, or inguinal lymphadenopathy (1-4 cm in diameter) in many patients
      • enlarged lymph nodes are firm, tender, and sometimes painful
      • lymphadenopathy was not characteristic of smallpox
      • presence of lymphadenopathy is the key symptom which differentiates monkeypox from chickenpox
        • lymphadenopathy distinguishes monkeypox from chickenpox
        • during the eruptive phase, which lasts for 14 to 28 days, skin lesions appear in a centrifugal distribution and progress through several stages: macules, papules, vesicles, and finally, pustules (5)
          • lesions are firm and well delimited and display umbilication (5)
            
            
  • images of possible monkeypox rash - click here
    
    
  • fever often declines on the day of or up to 3 days after rash onset
    • often, the rash first appears on the face and quickly appears in a centrifugal distribution on the body
      • the distinctive lesions often present as first macular, then papular, then vesicular and pustular
      • number of lesions on a given patient may range from a few to thousands
      • lesions are often noted in the oral cavity and can cause difficulties with drinking and eating
      • rash usually lasts approximately 10 days or more (2)
      • vesiculopustular rash illnesses included on the differential are other herpetic infections, drug-associated eruptions, syphilis, yaws, scabies, and, more rarely, rickettsialpox (1)

Monkeypox is usually a self-limited disease with the symptoms lasting from 2 to 4 weeks

• most patients have a self-limited illness; between 1% and 13% require hospital admission (for treatment or isolation), and the case-fatality rate is less than 0·1% (7)

Severe cases occur more commonly among children and are related to the extent of virus exposure, patient health status and nature of complications (3)

• complications of monkeypox can include secondary infections, bronchopneumonia, sepsis, encephalitis, and infection of the cornea with ensuing loss of vision

Complications that require medical treatment (eg, antiviral therapy, antibacterials, and pain control) occur in up to 40% of patients and include rectal pain, odynophagia, penile oedema, and skin and anorectal abscesses (7)

Diagnosis:

• lymphadenopathy during the prodromal stage of illness can be a clinical feature to distinguish monkeypox from chickenpox or smallpox
• confirmation of monkeypox depends on the type and quality of the specimen and the type of laboratory test
  • Polymerase chain reaction (PCR) is the preferred laboratory test given its accuracy and sensitivity
  • as orthopoxviruses are serologically cross-reactive, antigen and antibody detection methods do not provide monkeypox-specific confirmation
    • serology and antigen detection methods are therefore not recommended for diagnosis or case investigation where resources are limited
      • also, recent or remote vaccination with vaccinia vaccine (e.g. anyone vaccinated before smallpox eradication, or more recently vaccinated due to higher risk such as orthopoxvirus laboratory personnel) might lead to false positive results

Management:

• are no specific treatments or vaccinations currently available for monkeypox
  • patients with severe manifestations and people at risk of severe disease (eg, immunosuppressed people) could benefit from antiviral treatment (eg, tecovirimat) (7)
• Vaccinia vaccine used during the smallpox eradication programme was also protective against monkeypox (3)
  • a new third generation vaccinia vaccine has now been approved for prevention of smallpox and monkeypox
  • in the UK, the smallpox vaccine (Imvanex) is the recommended vaccine for post-exposure prophylaxis against monkeypox - the vaccine is most effective if given within four days of exposure but it can be given up to 14 days post-exposure if required

Case definitions (4):

• Confirmed case
  • a person with a laboratory-confirmed monkeypox infection (monkeypox PCR positive) since 15th March 2022
• Probable case
  • a person with an unexplained rash on any part of their body plus one or more classical symptom(s) of monkeypox infection** since 15th March 2022 and either:
    • Has an epidemiological link to a confirmed or probable case of monkeypox in the 21 days before symptom onset OR
    • Reported a travel history to West or Central Africa in the 21 days before symptom onset OR
    • Is a gay, bisexual or other man who has sex with men (GBMSM)
  • ** Acute illness with fever (>38.5 degrees C), intense headaches, myalgia, arthralgia, back pain, lymphadenopathy
  • Such cases should be discussed with local infection consultant (microbiology, virology or infectious diseases). The relevant local infection prevention and control team should be informed of any suspect cases admitted. Where there is no local infection consultant available, the UKHSA Imported Fever Service may be contacted directly - enquiries process and contact information is available via https://www.gov.uk/guidance/imported-fever-service-ifs.
• Resources on monkeypox are available at Monkeypox - GOV.UK (www.gov.uk), including epidemiology, clinical features, diagnostic testing and infection prevention and control

Summary advice (8):

• a clinician should consider coinfections with monkeypox and other sexually transmitted infections among patients presenting with an acute rash or skin lesions and systemic symptoms
• while it is safe to manage monkeypox patients via a virtual consultation, patients may need advice to maintain infection control measures and interventions to manage complications
• if high risk patientsnt then management should be via a specialist infectious disease unit with access to novel antivirals such as tecovirimat and cidofovir
• consider the psychosocial context when managing patients with monkeypox
  • healthcare workers should be aware of the stigma surrounding monkeypox, which may result in reduced health-seeking behaviours;
  • healthcare staff should screen patients sensitively, using inclusive language to avoid alienating patients

Notes:

• HIV and monkeypox
  • study findings support the consideration of a severe, disseminated, and necrotising form of monkeypox as an AIDS-defining condition in CDC and WHO HIV disease classifications (9,10)
    • finding is based on the observation of protracted illness with fulminant disseminated necrotising cutaneous lesions, systemic complications, and mortality in those with CD4 cell counts of less than 200 cells per mm3

Reference:

1. Macneil A, Reynolds MG, Braden Z, et al. Transmission of atypical varicella-zoster virus infections involving palm and sole manifestations in an area with monkeypox endemicity. Clin Infect Dis. 2009;48(1):e6-e8. doi:10.1086/595552
2. Dermnet - monkeypox (Accessed 29/10/2022)
3. World Health Organization. Monkeypox. WHO Monkeypox fact sheet. Dec 2019. - WHO
4. UK Health Security Agency (May 2022). CEM/CMO/2022/008 - Immediate Actions in Response to Cases of Monkeypox Virus in UK with no known travel history
5. Angelo KM et al. Epidemiological and clinical characteristics of patients with monkeypox in the GeoSentinel Network: a cross-sectional study. Lancet - Infectious Diseases https://doi.org/10.1016/S1473-3099(22)00651-X
6. Gessain A et al. Monkeypox. NEJM October 26th 2022. https://www.nejm.org/doi/full/10.1056/NEJMra2208860
7. Mitja O et al. Monkeypox. Lancet November 17th 2022. https://doi.org/10.1016/S0140-6736(22)02075-X
8. Mansour R et al. Human monkeypox: diagnosis and management BMJ 2023; 380 :e073352 doi:10.1136/bmj-2022-073352
9. Mitja O et al. Mpox in people with advanced HIV infection: a global case series. Lancet February 21st 2023.
10. Walter K, Malani PN. Update on Mpox. JAMA. Published online May 22, 2023. doi:10.1001/jama.2023.9142