MICROBIOLOGY

  • DNA virus and member of the orthopoxvirus genus of the Poxviridae family, monkeypox is similar to smallpox (variola virus), smallpox vaccine (vaccinia virus), and cowpox virus.
    • Two clades are described:
      • West African clade, causes a mild illness with limited human-to-human transmission and low mortality (~1%).
      • Central African/Congo Basin clade, higher reported human-to-human transmission and mortality (up to 10%).
  • Although named monkeypox, the animal reservoir is believed to be African rodents but has not been fully defined.

CLINICAL

  • Rare zoonotic disease spreads between infected animals, humans, and contaminated materials.
    • First isolated in 1958, with the first human case in 1970; most human cases are seen in Central and West Africa.
      • Cases in the U.S. are predominantly imported or due to contact with animals.
    • Resembles smallpox, but milder and less transmissible.
    • A large number of cases (> 450) since 2017 in Nigeria.
  • Outbreaks in the U.S.
    • 2003: 71 confirmed or suspected cases.
      • The first U.S. outbreak was traced to the importation of Gambian giant rats, squirrels, and dormice that spread to prairie dogs sold as pets.[7]
        • 18 hospitalized, no deaths.
    • Current (as of June 20, 2022): >2100 cases worldwide,
      • 42 countries reporting infections to date including many European countries, Argentina, and Australia.
      • In the U.S., California, Colorado, Florida, Massachusetts, Maryland, New York, Utah, Virginia, and Washington have confirmed monkeypox virus-infected patients.
      • Spread within sexual networks implicated, reported in men who have sex with men (MSM).[9]
      • No deaths reported as of this writing; it appears milder than disease acquired in Africa.
  • Transmission
    • The virus may be acquired through contact including intact skin and mucous membranes. Most human infections are believed to be respiratory droplet-acquired.
      • Animal-to-human transmission is seen following an infected animal bite or scratch, butchering bush meat, direct contact with body fluids or lesions, or contaminated materials.
      • Acquisition by human-to-human is believed to be predominantly large respiratory droplets, although may also be sexually transmitted through social networks.
        • As a large pox virus, not believed to be aerosolizable.
        • Virus enters the body via broken skin, respiratory tract or mucous membranes
        • Household and nosocomial transmission described
        • Fomite transmission occurs via contaminated clothing or bedsheets
      • From acquisition to first symptoms may range 5-21 days but average 1-2 weeks.
  • Symptoms: note that some get rash first then symptoms; others experience only a rash.
    • Initial viral prodrome
      • Fever, chills, headache, myalgia, back pain, fatigue
        • Occasionally sore throat with lesions on the tongue and oral mucosa
    • Rash phase, typically 1 to 3 days after symptom onset.
      • Viral exanthem, flat/red that then becomes nodular, umbilicated, and pox-like with fluid/pus before crusting.
        • Lesions, described as painful, appear in the same stage of development on a single site of the body.
        • Lymphadenopathy often accompanies this phase.
      • Examples from Africa, the rash often begins on the face [Fig 1], then spreads [FIg 2] including the palms [Fig 3].
        • Skin lesions do not develop in all infected people.
      • 2022 outbreak: nodular, pustular, pox-like and may have eschar, [Fig 4] and [Fig 5]
        • Consider genital lesions as potentially due to monkeypox.
    • Illness resolves within four weeks.
    • Mortality ranges from 1 to 10% in reported series from Africa.
      • Most deaths occur in children or people with HIV.
      • Risk factors for severe illness appear to be fever ≥ 38.3ºC and > 100 skin lesions.
  • Differential diagnosis: varicella zoster (primary infection, aka chickenpox), other pox infections (cowpox, orf), smallpox.
    • Consider herpes zoster (shingles), measles, and STIs, i.e., syphilis, HSV, and chancroid.
  • Diagnosis:
    • Clinical suspicion necessary, contact local/state health department for assistance in diagnosis.
    • Real-time PCR of skin lesion material
    • Serology is perhaps helpful if specimens are not present.
      • CDC specimen and handling directions link.
    • CDC 2022 Case Definition
      • Suspect, probable and confirmed
      • Confirmed requires demonstration of viral DNA by PCR or NGS of a clinical specimen or isolation of the virus in culture.

SITES OF INFECTION

Oral: oral ulceration or pharyngitis is described in some West African series.

Ocular: may threaten vision

Cutaneous: macular or papular lesions evolve into nodules and then vesicles or pustules (pox lesions) before crusting. Lesions often start on the face or genitals but spread over the body including palms and soles.

LN: lymphadenopathy

Pulmonary: pneumonitis, particularly in severe cases

Proctitis: localized lesions may present on the genital or perianal area

TREATMENT

General

  • There are no approved treatments for monkeypox.
  • CDC recommends approaching it as similar to smallpox, as a consideration for those with severe disease (CNS, hemorrhagic, requiring hospitalization) or those at high-risk (immunocompromised, children < 8 yrs, pregnant/breastfeeding women, or experiencing complications).
    • State and territorial health authorities can direct their requests for medical countermeasures for the treatment of monkeypox to the CDC Emergency Operations Center (770-488-7100).
    • Antivirals (see smallpox module for details)
      • Tecovirimat (TPOXX): oral or IV drug, FDA-approved for smallpox treatment in adults and children ≥ 13 kg.
        • CDC has Expanded Access Investigational New Drug (EA-IND) protocol.
      • Brincidofovir: oral drug, FDA-approved on June 4, 2021, for smallpox in all ages, including neonates. CDC developing EA-IND.
        • CDC developing EA-IND to facilitate use for monkeypox.
      • Cidofovir: injectable, has in vitro activity but no human data regarding smallpox.
    • Vaccinia immune globulin (VIVIG)
      • Potentially has cross-reactivity, unknown if effective for monkeypox.
      • Licensed for treatment of complications or aberrant infections due to vaccinia vaccination
      • CDC holds EA-IND allows the use of VIG in an orthopoxvirus outbreak, which would include monkeypox.

Prevention

  • General measures if suspected or confirmed monkeypox:
    • Isolate infected patients from others.
    • Hand hygiene after contact with infected animals or humans.
      • Use soap and water or an alcohol-based sanitizer.
    • Avoid contact with animals that could harbor the virus (including animals that are sick or that have been found dead in areas where monkeypox occurs).
    • Avoid direct contact with any potentially contaminated materials.
      • CDC notes that the monkeypox virus can be killed with a standard washing machine with warm water and detergent.
    • Use appropriate personal protective equipment (PPE) for patient care (gown, gloves, respirator, and eye protection).
    • CDC Infection Prevention and Control of Monkeypox for healthcare settings; for those sent home, CDC isolation recommendations vary depending on the home situation and if people at high-risk present (young children, immunocompromised).
  • Vaccines: smallpox vaccines have been given to some monkeypox patients or their contacts.[7]
    • FDA has approved JYNNEOSTM (MVA-BN in 2019, also known as Imvamune or Imvanex in the UK, an attenuated live virus vaccine for the prevention of monkeypox).
    • Smallpox vaccine
      • A far larger supply in the U.S. stockpile but aging status may mean lower potency.

Selected Drug Comments

Drug

Recommendation

Brincidofovir

FDA-approved oral drug available in tablets or suspension for smallpox in ages neonates and above. Three patients received the drug for monkeypox in a UK case series, though uncertain if it helped in their good outcome[1]. In this series, none of the 3 completed the course due to rising LFTs.

Cidofovir

The US maintains a Strategic National Stockpile for use in the case of smallpox. The drug has in vitro activity; however, there is no human data for monkeypox.

Tecovirimat

FDA-approved for smallpox. Case report of use in monkeypox (1 patient[1]), cowpox, and complicated vaccinia infections.

VIVIG

Vaccinia immune globulin (IV) is controlled by the CDC, primarily for the use of complications of vaccinia vaccination including EZ, progressive vaccinia, and generalized vaccinia. Unknown how effective its use would be in monkeypox.

FOLLOW UP

  • Patients are thought to be non-infectious upon crusting of lesions; however, viral kinetics in monkeypox is not fully described.
  • Sterile abscesses, bacterial superinfection, and bacteremia are seen.

OTHER INFORMATION

  • An increase in the number of monkeypox cases has been ascribed to the successful eradication of smallpox and the cessation of vaccinia immunization programs.
  • There are insufficient data to make particular recommendations for the treatment of monkeypox.
  • UK offering vaccine to some gay, bisexual men (June 2022).

Basis for recommendation

  1. Adler H, Gould S, Hine P, Snell LB, Wong W, Houlihan CF, et al.Clinical features and management of human monkeypox: a retrospective observational study in the UK, Lancet Infectious Diseases, May 24, 2022, DOI: https://doi.org/10.1016/S1473-3099(22)00228-6

    Comment:
    The current state of the art review and clinical experience regarding management. Oral antivirals were used (brincidofovir and tecovirimat) but had an uncertain effect in this small patient series. Patients had a surprisingly long period of PCR detection of viral DNA.


References

  1. Russo AT, Grosenbach DW, Chinsangaram J, et al. An overview of tecovirimat for smallpox treatment and expanded anti-orthopoxvirus applications. Expert Rev Anti Infect Ther. 2021;19(3):331-344.  [PMID:32882158]

    Comment: This oral drug has broad activity against many known orthopox viruses.

  2. Hutson CL, Kondas AV, Mauldin MR, et al. Pharmacokinetics and Efficacy of a Potential Smallpox Therapeutic, Brincidofovir, in a Lethal Monkeypox Virus Animal Model. mSphere. 2021;6(1).  [PMID:33536322]

    Comment: Animal model of monkeypox, however, authors state that dosing selection may have impacted results.

  3. Petersen E, Kantele A, Koopmans M, et al. Human Monkeypox: Epidemiologic and Clinical Characteristics, Diagnosis, and Prevention. Infect Dis Clin North Am. 2019;33(4):1027-1043.  [PMID:30981594]

    Comment: Authors have organized clinical data and impressions from outbreaks of monkeypox in Africa and the UK. Increase in monkeypox cases has been ascribed to the successful eradication of smallpox and the cessation of vaccinia immunization programs.

  4. Huhn GD, Bauer AM, Yorita K, et al. Clinical characteristics of human monkeypox, and risk factors for severe disease. Clin Infect Dis. 2005;41(12):1742-51.  [PMID:16288398]

    Comment: Risk factors for severe disease appeared to be two: fever ≥ 38.3°C and > 100 lesions.

  5. Learned LA, Reynolds MG, Wassa DW, et al. Extended interhuman transmission of monkeypox in a hospital community in the Republic of the Congo, 2003. Am J Trop Med Hyg. 2005;73(2):428-34.  [PMID:16103616]

    Comment: Six cases among those in this pediatric outbreak had an extended chain of transmission among humans. Authors aptly noted the potential for more concerning and widespread transmission among humans in future if cases are not contained early in an outbreak.

  6. Centers for Disease Control and Prevention (CDC). Update: multistate outbreak of monkeypox--Illinois, Indiana, Kansas, Missouri, Ohio, and Wisconsin, 2003. MMWR Morb Mortal Wkly Rep. 2003;52(27):642-6.  [PMID:12855947]

    Comment: Report describes 71 cases, 35 lab-confirmed and 36 suspected cases, with majority exposed to prairie dogs. Use of smallpox vaccine included pre-exposure administration to 3 veterinarians, 2 lab workers, and 2 healthcare workers and post-exposure to 23 individuals. All 35 confirmed cases traced back to prairie dogs housed, at an Illinois animal distributor, with Gambian giant rats and dormice that originated from Ghana.
    Rating: Important

  7. CDC; Rao AK, Petersen BW, Whitehill F, et al. Use of JYNNEOS (Smallpox and Monkeypox Vaccine, Live, Nonreplicating) for Preexposure Vaccination of Persons at Risk for Occupational Exposure to Orthopoxviruses: Recommendations of the Advisory Committee on Immunization Practices — the United States, 2022. MMWR Morb Mortal Wkly Rep. ePub: 27 May 2022. DOI: http://dx.doi.org/10.15585/mmwr.mm7122e1

    Comment:
    The ACIP recommended use of this replication-deficient live Vaccinia virus vaccine for people at risk of orthopox infection from potential occupational exposures. On November 3, 2021, ACIP voted to recommend JYNNEOS preexposure prophylaxis as an alternative to ACAM2000 for certain persons at risk for exposure to orthopoxviruses.


  8. WHO Emergency Seasonal Updates. Monkeypox: public health advice for gay, bisexual and other men who have sex with men. 22 May 2022. Accessed 5/31/22 at: https://www.who.int/publications/m/item/monkeypox-public-health-advice-for...

    Comment: Public health advisory reports association of monkeypox outbreak and transmission among communities of gay, bisexual, and men who have sex with men. Sexual health providers and primary care providers of MSM may recognize cases early and reduce risk of outbreak by isolating and testing indivuduals for monkeypox virus.
    Rating: Important

Media

Monkeypox

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Pox lesions on a child from a 1997 outbreak in the DRC.

Source:

CDC/ Brian W.J. Mahy, BSc, MA, PhD, ScD, DSc

Monkeypox

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A child with numerous lesions on the face, from a 1997 outbreak in DRC.

Source: World Health Organization (WHO)/ Brian W.J. Mahy, BSc, MA, PhD, ScD, DSc

Monkeypox palms

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Palms with maculopapular skin lesions appearing similar to smallpox but due to monkeypox (from 1997 DRC outbreak).

Source: CDC/ Brian W.J. Mahy, BSc, MA, PhD, ScD, DSc

Monkeypox lesions 2022

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UK Health Security Agency

Monkeypox lesions

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Source: NHS England High Consequence Infectious Diseases Network

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Last updated: June 24, 2022