monkeypox (mpox)

Introduction

• World Health Organization (WHO) announced Nov 28, 2022 it will start using the term mpox in reference to monkeypox
  • WHO will use both monkeypox & mpox through 2023
  • WHO is responsible under the International Classification of Diseases for assigning names to new diseases & infrequently existing diseases
  • WHO can not rename the monkeypox virus
  • that is the jusidication of the International Committee on the Taxonomy of Viruses
  • WHO will adopt the term mpox in its communications

• U.S, Health and Human Services Secretary Xavier Becerra declared monkeypox a public health emergency on August 4, 2022.

Etiology

• orthopox virus, indistinguishable from vaccinia or variola viruses by electron microscopy*
• risk factors
  • travel history to a country with confirmed cases
  • men engaging in casual sex

* electron microscopic image of monkeypox virions, obtained from a skin specimen associated with the 2003 prairie dog outbreak is shown

• a high-resolution (5.2 MB) is also available on the page

Epidemiology

• first isolated in 1958 from monkeys at the Statens Serum Institut in Copenhagen, Denmark (thus the name monkeypox)
• zoonotic infection with most cases from consumption or contact with small mammals, particularly rodents (rope squirrels, tree squirrels, Gambian pouched rats, & dormice)
• associated with exposure to small forest animals (blood contact, bite)
• first known human case of monkeypox in 1970 in the Democratic Republic of the Congo
• 59 cases reported between 1970 and 1980 in rain forests of western & central Africa
• 404 cases between 1981 and 1986 (WHO sponsered active surveillance program)
• ~800 cases Africa 1996-1998
• 53 cases (as of 6/03/22) in United States associated with prairie dogs acquired as pets, which were presumed to have acquired the virus from Gambian giant rats housed with them
• cases reported in Europe & Canada 2022
  • several confirmed cases in 2022 outbreak in men who have sex with men
  • one time encounters in men who have sex with men account for 50% of momkeypox cases
• Spain, Brazil, & India reported the first monkeypox-related deaths outside of Africa since the start of the 2022 international outbreak
• 6 people who have tested positive for monkeypox in th U.S. have died as of October 23, 2022
• > 80% of hospitalized patients with monkeypox have HIV1 co-infection
• deadly type of MPOX spreading in the Democratic Republic of the Congo in Fall of 2023

transmission

• low person to person transmission
• monkeypox is not spread by casual contact
• average incubation period for symptom onset is 5-13 days
• considerable pre-symptomatic transmission
  • in cases of documented pre-symptomatic transmission, 4 days max between transmission & symptoms manifested
• transmitted through contact with bodily fluids & sores, or via large respiratory droplets with prolonged face-to-face contact
• unknown if monkeypox can be transmitted by persons without skin lesions
• transmission through fomites (bedding or clothes contaminated with material from monkeypox lesions) & from animals to humans have been reported
• transmission may occur across the placenta to the fetus
• patient is no longer contagious when lesions crust over to scabs
  • crusts have separated & fresh skin forms underneath
• household surfaces of symptomatic patients may be contaminated with PCR-detected virus, but no samples have been culturable implying lack of risk for transmission (single home tested)
• second home tested found viable virus cultured from 60% of porous surfaces (bedding, clothing) after 15 days at low titers indicative of limited potential for indirect transmission
• potential risk of transmission of monkeypox virus through fecal microbiota for transplantation
• a Florida nurse developed monkeypox infection after an accidental needlestick

Pathology

• intracytoplasmic eosinophilic inclusions in epithelial cells
• other changes in the epidermis
  • ballooning degeneration
  • keratinocyte necrosis
  • hyperplasia
• in the dermis
  • lymphocytic inflammation
  • with ulceration, infiltration by neutrophils, eosinophils, & multinucleated giant cells
  • vasculitis

Genetics

• dsDNA virus
• monkeypox of 2022 outbreak belongs to clade 3, most likely of a single origin.
• 2022 outbreak lineage B.1 clusters with 2018-2019 cases linked to an endemic country, but segregates in a divergent phylogenetic branch, a result of continuous accelerated evolution

Clinical manifestations

• wide incubation period ranging from 5 days to 3 weeks
• prodrome of fever, respiratory symptoms, lymphadenopathy, pharyngitis, headache, myalgias, nausea, vomiting, chills
  • prodrome may not occur prior to appearance of anogenital lesions in men who have sex with men
• skin lesions evolve from macules & papules to vesicles & pustules that ulcerate & crust
  • pustular rash affects head, trunk & extremities
    • pustular rash may begin in genital & perianal region
  • after crusting, healing over several weeks
• in a U.K. sexual health clinic in London May 2022
  • fevers 57%
  • anogenital lesions 94%
  • lymphadenopathy (largely inguinal) 56%
  • concurrent sexually transmitted infection 25%
    • HIV1 infection 24%, all receiving ART with normal CD4 counts
  • skin lesions at >3 sites in 22% without HIV1 & 54% with HIV1 infection
  • no deaths
• majority of infections are asymptomatic
• generally, monkeypox is self-limited, lasting 2-4 weeks

* images

Laboratory

• samples for diagnosis of monkeypox should be collected using a nylon, polyester, or Dacron swab preferably from an open skin lesion place swabbed specimen in a dry, sterile container & keep refrigerated or frozen until testing
  • no date to support use of other sample types (blood, saliva ...)
• CDC's nonvariola orthopoxvirus polymerase chain reactio n test (FDA-approved)
  • testing has expanded to 5 commercial laboratories
  • details can be obtained from the CDC
• HIV1 serology if HIV1 status unknown

Complications

• most common in children < 8, pregnant women, immunocompromised
  • pneumonia, encephalitis, eye infections
• two cases of encephalomyelitis in men with monkeypox infection
• case of anterior scleritis/keratitis/uveitis

Differential diagnosis

• chickenpox
• other poxviruses & herpes viruses
• sexually-transmitted infections

Management

• For most patients, management is symptomatic, including pain management
  • post-exposure prophylaxis via smallpox vaccine (85% cross-protection)
    • Jynneos is preferred vaccine
      • live attenuated vaccinia virus vaccine administered as a 2 dose series
    • ACAM2000 is a 2nd vaccine approved only for smallpox but granted an expanded access Investigational New Drug (IND) protocol allowing use against monkeypox
      • live vaccinia virus vaccine administered as a single dose but requires multiple skin punctures
      • associated with high rate of myocarditis & pericarditis
    • U.S. is expanding its monkeypox vaccination strategy to include those with a presumed exposure to monkeypox, not just a confirmed exposure
    • FDA cites evidence that a reduced dose, 1/5 of full dose, works as well as full dose & that intradermal administration may be more effective than subcutaneous injection
    • both Jynneos & ACAM2000 thought to be ~85% effective
  • full protection with either vaccine when administered within 4 days of exposure
    • vaccination up to 2 weeks after exposure can reduce symptom severity
  • intravenous vaccinia immune globulin may be considered for patients with T-cell immunodeficiency, for whom Jynneos or smallpox vaccination is contraindicated
• smallpox treatment may be of benefit*
  • currently 2 antiviral drugs may be used for monkeypox infections:
    • tecovirimat approved for treatment of smallpox is available via an expanded access Investigational New Drug (IND) protocol
    • tecovirimat 600 mg PO BID may be of benefit for anterior scleritis/ keratitis/uveitis
    • brincidofovir
• contact tracing for persons with contact with symptomatic patient
  • monitor contacts for 21 days
• prevention:
  • avoid direct contact with skin lesions, clothing, bedding, or towels that may have come in contact with skin lesions
  • personal protective equipment including gown, gloves, eye protection, & a fitted N95 mask recommended for clinicians caring for patients with skin lesions
  • patients should be isolated, masked & lesions covered
  • if hospitalized, a negative-pressure room if available
  • standard cleaning & disinfection procedures are sufficient for environmental infection control
  • soiled laundry should be handled with gloves to avoid contact with lesion material
  • isolation period of 16-23 days required to detect 95% of people with a potential infection

* both monkeypox & smallpox are orthopoxviruses

More general terms

• viral infection
• orthopoxvirus

Patient information

monkeypox (Mpox) patient information