Peer reviewer: A/Prof Mike Cadogan

  • Monkeypox is a zoonotic infection characterized by a flu-like prodrome followed by a rash resembling chickenpox
  • The 2022 Monkeypox outbreak is the first significant outbreak resulting from human-to-human transmission outside of Africa
  • The CDC has developed case definitions for the 2022 Monkeypox outbreak
  • Monkeypox is a misnomer and will likely be renamed by the WHO

Monkeypox virus (MPV) (Alakunle et al, 2020)

  • belongs to the Orthopoxvirus genus (also includes cowpox and smallpox)
  • contains linear double-stranded DNA within lipoprotein envelope
  • ovoid or brick-shaped and 200-250 nm in length
  • Two clades (strains) are endemic to the Congo/ Central Africa (more virulent) and West Africa (less virulent), causing sporadic outbreaks averaging a few thousand cases per year in these regions

Transmission (Beer and Rao, 2019; Alakunle et al, 2020)

  • contact with fomites through broken skin, mucous membranes, or the respiratory tract
    • Direct, e.g. skin-to-skin, including during sexual activity
    • Indirect, e.g. contact with linen and bedding
  • Respiratory droplets (airborne transmission)
  • Maternal-fetal transmission during pregnancy
  • Potential sexual transmission as virus isolated from seminal fluid, however transmission during sexual activity probably mostly results from direct contact
  • In endemic areas most transmission is animal-to-human from contact with infected animal carcasses, meat, and blood

Animal reservoir (Parker and Buller, 2013; Alakunle et al, 2020)

  • Rodents such as Gambian giant pouched rats, rope squirrels, and dormice
  • Pet prairie dogs were important intermediate hosts in the 2003 outbreak in the USA (47 human cases)

Incubation period (Alakunle et al, 2020)

  • 4-21 days

Complications (Beer and Rao, 2019; McCollum and Damon, 2014)

  • Dehydration (vomiting and diarrhea)
  • Pneumonitis
  • Keratitis (potentially sight-threatening)
  • Sepsis and disseminated rash are more common in immunocompromised
  • Deep abscesses (including retropharyngeal abscess)
  • Reactive depression and psychosocial distress is common (e.g. stigma, pain, and disfiguring lesions)
  • Encephalitis is rare
  • Scarring
  • Miscarriage if pregnant

(McCollum and Damon, 2014; Girometti et al, 2022; Adler et al, 2022; Tarín-Vicente et al, 2022; Thornhill et al, 2022)


  • “Flu-like” prodrome for the first 5 days, including:
    • Fever and chills
    • Headache
    • Malaise
    • Myalgia
    • Respiratory symptoms (e.g. sore throat, nasal congestion, or cough)
    • Lymphadenopathy (>50%)
      • key feature, as not typically seen in influenza or chickenpox
      • may develop before or during the rash
      • Typically maxillary, cervical, or inguinal (1-4 cm)
  • Rash
    • may develop without “flu-like” prodrome
    • lasts an average of 10 days
    • 2-5mm diameter pleomorphic lesions that synchronously progress through 4 stages before scabbing over and desquamation:
      • Macular (1-2 days),
      • Papular (1-2 days),
      • Vesicular (1-2 days),
      • Pustular (5-7 days) (filled with opaque fluid; initially firm then become umbilicated), to
      • Scabs (7-14 days)
    • Lesions have a centrifugal distribution
      • typically predominate on the face (including the eyes and oropharynx) but may develop on the hands and feet (both dorsal and ventral surfaces; subungual lesions may occur)
      • the torso is relatively spared but can be affected
      • Initial lesions may occur in the mouth, including on the tongue, and may not be visible on the skin or may only be present in the perineal/genital area
      • Number of lesions may range from 1 to >1000; many patients have <10 at presentation
    • Genital and peri-genital lesions are common features of the 2022 outbreak, including proctitis (e.g. purulent or bloody stools, rectal pain, or rectal bleeding)
    • Lesions are usually painful and pruritic (itchy)
  • Exposure history
    • Men who have sex with men (MSM)
    • oral or anal receptive sex (risk factors for tonsilitis and proctitis respectively)
    • Travel history – Travel to an endemic area (Congo/ Central Africa and West Africa)
    • Animal contact – rodents
    • Age <50 years (born since discontinuation of routine smallpox vaccination)

Examination (McCollum and Damon, 2014)

  • Fever
  • Lymphadenopathy
  • Rash on skin – see Dermnet for Monkeypox images – and/or mucous membranes (early oropharyngeal lesions may resemble pharyngitis; anoscopy may be required)
  • Chickenpox (similar rash but does not usually occur on feet and lacks lymphadenopathy)
  • Smallpox
  • Cowpox
  • Impetigo
  • Infected scabies
  • Syphilis (lesions on hands and feet)
  • Herpes simplex virus
  • Hand-foot-mouth disease (children)
  • Gonococcal infection (e.g. pharyngitis, proctitis; may also have rash) and other STIs with symptoms of proctitis and skin lesions (e.g. chancroid, lymphogranuloma venereum, granuloma inguinale)
  • Influenza and other flu-like illness (prior to development of rash)

Laboratory (McCollum and Damon, 2014)

  • Viral swab PCR
    • Deroofed skin lesions
    • Respiratory swabs
    • Blood (may be negative as virus may only transiently be in blood)
    • Urine
    • Rectal
  • Serology
    • orthopoxvirus IgG (prior exposure) and IgM (recent exposure) immunofluorescence assay
    • Antibodies usually detectable once rash appears
    • Less sensitive than PCR
  • Other diagnostic tests may be considered in specific settings:
    • Viral culture
    • Electron microscopy
    • Immunohistochemistry
    • Rapid antigen tests
  • Consider baseline bloods (e.g. if risk of severe disease) and repeat if clinical deterioration
  • STI screen if appropriate based on risk factors (STIs may coexist with Monkeypox)


  • CT – lymphadenopathy, secondary infection (e.g. pneumonia)
  • MRI brain – if encephalitis suspected

Address life/limb/sight threats:

  • pharyngeal/ tracheal lesions causing airway compromise are rare 
  • Secondary sepsis, requiring resuscitation, may occur in immunocompromised patients
  • Keratitis may be sight-threatening

Specific management

  • Antivirals
    • Consider for severe cases or cases at risk of severe disease such as:
      • Immunocompromised
      • Children <8yo
      • history or presence of atopic dermatitis, persons with other active exfoliative skin conditions
      • Pregnancy or breastfeeding
      • Complications (e.g. secondary infection, dehydration)
      • Complicated locations (e.g. eyes, mouth, airway, anus, genitals)
    • studies of clinical effectiveness in humans are currently lacking
    • Options include (Adler et al, 2022):
      • Tecovirimat 600mg bd po for 14d (Tpoxx)
        • An antiviral agent that acts inhibitor of the orthopoxvirus VP37 envelope wrapping protein
      • Brincidofovir 200mg po on days 1, 8, and 15 (3 doses) (Tembexa)
        • Prodrug of cidofovir, with activity against dsDNA viruses

Seek and treat complications

  • Secondary infections (e.g. pneumonia)
  • Corneal lesions
  • Disseminated rash
  • Severe pain (may be neuropathic)

Supportive care and monitoring

  • Multimodal analgesia (pain may be severe especially if perineal/rectal lesions)
    • Pracetamol, NSAIDs
    • Opioids and additional measures (e.g. ketamine; lignocaine gel) may be required for severe or refractory cases
  • Psychosocial support


  • May require hospital admission if:
    • Severe pain
    • Secondary complications
    • Significant comorbidities
    • Social reasons
  • Referrals:
    • ICU if risk of critical illness
    • Anaesthesia/ENT if risk of airway compromise
    • Neurology if suspected encephalitis
    • Ophthalmology if keratitis
  • 1-10% mortality in endemic regions (Beer and Rao, 2019)
    • 3% in Nigeria (West Africa clade)
    • Up to 10% in Congo (Central Africa clade)
    • Primarily infants and immunocompromised (HIV/AIDS)
  • <10% of patients in the UK 2022 outbreak require hospital admission (Girometti et al, 2022)
  • Patients with well controlled HIV receiving antiretroviral therapy do not appear to have more severe disease when infected with monkeypox
  • Duration of illness is usually 2-4 weeks

Monkeypox is a notifiable disease in many jurisdictions


  • CDC infection control recommendations:
    • isolation precautions for monkeypox maintained until all lesions have crusted, those crusts have separated, and a fresh layer of healthy skin has formed underneath
    • patients should be in a single isolated room (no special air handling required)
    • 21 days for close contacts

Personal protective equipment (CDC infection control)

  • Contact and airborne precautions required
  • PPE: gown, gloves, googles, N95 mask

Other measures

  • Education of the public
  • Case contact tracing

Vaccination (McCollum and Damon, 2014)

  • Cross-protection from the smallpox vaccine (85% effective against MPV), which was discontinued in the 1970s after the eradication of smallpox
  • Revaccination after 3 years is recommended
  • Different smallpox/ monkeypox vaccines (CDC recommendations) include:
    • JYNNEOS is a two-dose live virus vaccine that uses non-replicating modified vaccinia Ankara (MVA); which does not produce skin lesions
    • ACAM2000 is a live Vaccinia virus preparation that is inoculated into the skin; produces skin lesions and may be transmissible to others

Pre-exposure prophylaxis (PrEP) (CDC infection control)

  • Vaccination considered for certain clinical and laboratory staff at high risk of exposure

Post-exposure prophylaxis (PEP) (CDC infection control)

  • Modified vaccinia Ankara vaccination is indicated within 4 days of exposure, although it can be considered up to a maximum of 14 days
  • Potential role for antivirals (application in progress for Tecovirimat)
  • Vaccinia Immune Globulin Intravenous (VIGIV) can be considered for exposed patients with T cell dysfunction who have a contraindication to smallpox vaccination

Discovery (Parker and Buller, 2013)

  • First identified in monkeys in a Danish laboratory in 1958
  • First identified in humans in the Congo in 1970
  • First identified in the USA in 2002

Potential reasons for the emergency of Monkeypox in 2022 include:

  • Declining Smallpox immunity
  • Environmental degradation and closer contact with reservoir animal species
  • Return of global travel following the coronavirus pandemic
  • Outbreak may have arisen from crowded public events in Spain and Belgium

Pearls and pitfalls

  • May coexist with HIV, syphilis, HSV, or other STIs – so test any suspected lesions
  • Disease is not restricted to patients with a history of MSM
  • Take a detailed sexual history (including oral and.or anal receptive sex) and travel history
  • Consider assessing HIV status and for presence of STIs
  • Patients may present with 1 single skin lesion or with no rash but a flu-like illness

FOAM and web resources

Journal articles

  • Adler H, Gould S, Hine P, et al. Clinical features and management of human monkeypox: a retrospective observational study in the UK [published correction appears in Lancet Infect Dis. 2022 Jul;22(7):e177]. Lancet Infect Dis. 2022;22(8):1153-1162. doi:10.1016/S1473-3099(22)00228-6 [article]
  • Alakunle E, Moens U, Nchinda G, Okeke MI. Monkeypox Virus in Nigeria: Infection Biology, Epidemiology, and Evolution. Viruses. 2020;12(11):1257. Published 2020 Nov 5. doi:10.3390/v12111257 [article]
  • Basgoz N, Brown CM, Smole SC, et al. Case 24-2022: A 31-Year-Old Man with Perianal and Penile Ulcers, Rectal Pain, and Rash. N Engl J Med. 2022;387(6):547-556. doi:10.1056/NEJMcpc2201244 [article]
  • Beer EM, Rao VB. A systematic review of the epidemiology of human monkeypox outbreaks and implications for outbreak strategy. PLoS Negl Trop Dis. 2019;13(10):e0007791. Published 2019 Oct 16. doi:10.1371/journal.pntd.0007791 [article]
  • Cohen J. Global outbreak puts spotlight on neglected virus. Science. 2022;376(6597):1032-1033. doi:10.1126/science.add2701 [article]
  • Girometti N, Byrne R, Bracchi M, et al. Demographic and clinical characteristics of confirmed human monkeypox virus cases in individuals attending a sexual health centre in London, UK: an observational analysis [published online ahead of print, 2022 Jul 1]. Lancet Infect Dis. 2022;S1473-3099(22)00411-X. doi:10.1016/S1473-3099(22)00411-X [article]
  • McCollum AM, Damon IK. Human monkeypox [published correction appears in Clin Infect Dis. 2014 Jun;58(12):1792]. Clin Infect Dis. 2014;58(2):260-267. doi:10.1093/cid/cit703 [article]
  • Parker S, Buller RM. A review of experimental and natural infections of animals with monkeypox virus between 1958 and 2012. Future Virol. 2013 Feb 1;8(2):129-157. doi: 10.2217/fvl.12.130. PMID: 23626656; PMCID: PMC3635111. [article]
  • Patrocinio-Jesus R, Peruzzu F. Monkeypox Genital Lesions. N Engl J Med. 2022;387(1):66. doi:10.1056/NEJMicm2206893 [article]
  • Sherwat A, Brooks JT, Birnkrant D, Kim P. Tecovirimat and the Treatment of Monkeypox – Past, Present, and Future Considerations [published online ahead of print, 2022 Aug 3]. N Engl J Med. 2022;10.1056/NEJMp2210125. doi:10.1056/NEJMp2210125 [article]
  • Tarín-Vicente EJ, Alemany A, Agud-Dios M, et al. Clinical presentation and virological assessment of confirmed human monkeypox virus cases in Spain: a prospective observational cohort study [published online ahead of print, 2022 Aug 8]. Lancet. 2022;S0140-6736(22)01436-2. doi:10.1016/S0140-6736(22)01436-2 [article]
  • Thornhill JP, Barkati S, Walmsley S, et al. Monkeypox Virus Infection in Humans across 16 Countries – April-June 2022 [published online ahead of print, 2022 Jul 21]. N Engl J Med. 2022;10.1056/NEJMoa2207323. doi:10.1056/NEJMoa2207323 [article]
  • The Lancet Infectious Diseases. Monkeypox: a neglected old foe. Lancet Infect Dis. 2022;22(7):913. doi:10.1016/S1473-3099(22)00377-2 [article]

CCC 700 6

Critical Care


Chris is an Intensivist and ECMO specialist at the Alfred ICU in Melbourne. He is also a Clinical Adjunct Associate Professor at Monash University. He is a co-founder of the Australia and New Zealand Clinician Educator Network (ANZCEN) and is the Lead for the ANZCEN Clinician Educator Incubator programme. He is on the Board of Directors for the Intensive Care Foundation and is a First Part Examiner for the College of Intensive Care Medicine. He is an internationally recognised Clinician Educator with a passion for helping clinicians learn and for improving the clinical performance of individuals and collectives.

After finishing his medical degree at the University of Auckland, he continued post-graduate training in New Zealand as well as Australia’s Northern Territory, Perth and Melbourne. He has completed fellowship training in both intensive care medicine and emergency medicine, as well as post-graduate training in biochemistry, clinical toxicology, clinical epidemiology, and health professional education.

He is actively involved in in using translational simulation to improve patient care and the design of processes and systems at Alfred Health. He coordinates the Alfred ICU’s education and simulation programmes and runs the unit’s education website, INTENSIVE.  He created the ‘Critically Ill Airway’ course and teaches on numerous courses around the world. He is one of the founders of the FOAM movement (Free Open-Access Medical education) and is co-creator of litfl.com, the RAGE podcast, the Resuscitology course, and the SMACC conference.

His one great achievement is being the father of three amazing children.

On Twitter, he is @precordialthump.

| INTENSIVE | RAGE | Resuscitology | SMACC

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