Monkeypox

See Also

Epidemiology

As of July 2023
1. Worldwide: 88,000 cases (146 deaths) in 75 countries
2. United States: >33,000 cases
3. CDC MPox Data
  1. https://www.cdc.gov/poxvirus/mpox/response/2022/index.html
Outbreak 2022 globally (including U.S.) infected >16,000 in 75 countries
1. Of 528 cases studied, 98% were in Men who have Sex with Men
2. Of these cases, 95% of transmission occurred during sex
3. Coinfection with HIV in 41% of patients (other STI in 29%)
4. Thornhill (2022) N Engl J Med 387(8): 679-91 [PubMed]
Outbreaks
1. FIrst known human outbreak in Congo 1970
2. Originally limited to Democratic Republic of Congo (and Refugees and Immigrants from that region)
3. Cases seen primarily in Africa (e.g. Cameroon, Liberia, Nigeria, Sierra Leone) with rare reported cases in Europe
4. Isolated outbreak occurred in midwest U.S. in 2003, related to rodents imported from Ghana in West Africa
Strains
1. MPox Clade II
  1. Outbreak in 2022, and markedly reduced infected by fall 2024
2. MPox Clade I
  1. More severe outbreak in 2024, isolated to Democratic Republic of Congo (DRC) as of fall 2024

Pathophysiology

Virus in the Orthopoxvirus genus (same genus as Smallpox/Variola, and Cowpox/Vaccinia)
1. Large enveloped virus
2. Linear double stranded DNA Poxvirus
Viral Infection whose natural hosts are primates and rodents
1. First described in 1958, during an infectious outbreak in a research monkey colony
2. Endemic primarily in the tropical forests of West and Central Africa (esp. Congo Basin)
3. Animal reservoirs are mostly small rodents (tree squirrels, Gambian rats, prairie dogs)
Zoonotic transmission to humans from animals is typically via bites or contact with the animal's blood
Human to human transmission (much less common than with Smallpox)
1. Respiratory transmission with prolonged, close face-to-face contact (primary route)
2. Mucous membrane or body fluid contact with broken skin
  1. Sexually Transmitted Infection especially among Men who have Sex with Men
  2. Receptive anal intercourse appears to be a common mode of transmission
3. Contact with infectious skin lesions (or contaminated clothing or bedding)
  1. Unlikely with brief contact (e.g. touching a doorknob or sitting on a toilet seat)
  2. Lesions are infectious until they re-epithelialize
Course
1. Incubation Period: 7 to 10 days (range 5 to 21 days)
2. Duration: 2 to 4 weeks

Types
Strains

West African Monkeypox
1. Milder illness with fewer deaths than with Central African Monkeypox
2. Limited human-to-human transmission
Central African Monkeypox Virus
1. More severe cases with higher mortality
2. Higher risk of person-to-person spread

Risk Factors

Recent travel to endemic regions (esp. central and west african countries)
Men who have Sex with Men (esp. multiple partners)
HIV Infection
Commercial sex workers
Patients taking HIV PrEP

Findings
Classic Prodrome

General
1. Classic MPox presentation is more common in children and young adults
2. Classic prodrome may be absent in epidemic cases
Onset 5 to 21 days after exposure
Febrile Prodrome (duration 1 to 4 days)
1. Fever (65%)
2. Chills
3. Malaise or Fatigue (41%)
4. Headache (27%)
5. Myalgias (31%)
6. Pharyngitis
Marked Lymphadenopathy (generalized or localized, 56%)
1. Less prominent in epidemic cases

Findings
Mucocutaneous Lesions

General
1. Classic case lesions are in a similar state of progression
2. Epidemic cases, in contrast, gradually develop lesions that lead to varying lesion age apperance
  1. Lesions may erupt in fulminant, widespread form
  2. Lesions may be pruritic or painful
Common focal lesions in epidemic form are often sexually transmitted (oral sex, receptive anal sex)
1. Tonsillitis
2. Anogenital lesions (73% of cases)
  1. Vessicle, Pustules, or firm well circumscribed ulcers
3. Proctitis (Rectal Pain)
  1. May present with Rectal Pain, tenesmus and non-bloody Diarrhea
Rash
1. Characteristics
  1. Vesiculopustular rash (Blisters, Pustules)
  2. Deep seated, firm, well-circumscribed lesions that may be centrally umbilicated
  3. Lesion are larger than Shingles or HSV lesions
  4. Lesions are of similar size to one another and are typically in same stage in a particular body region
  5. Lesions are painful until they crust or scab and begin to heal, at which time they are pruritic
2. Distribution: Generalizes over first 24 hours as Centrifugal Rash (trunk is more spared)
  1. Initial Lesions on Mucous membranes
    1. Tongue or mouth lesions or Tonsillitis (often related to oral sex)
    2. Perianal and genital regions (sexually transmitted, often related to receptive anal intercourse)
  2. Next: Face is often involved
  3. Next: Extremities (esp. Palms and soles)
    1. Less commonly involved in the epidemic form
3. Lesions progress over a 2 to 4 week period
  1. Macule (1 to 2 days)
  2. Papule (1 to 2 days)
  3. Vesicles with clear fluid (1 to 2 days)
  4. Pustule with opaque fluid and Central DImple or umbilication (5 to 7 days)
  5. Crust or scab (7 to 14 days)
  6. Desquamation (lesions no longer contagious)
  7. Hypopigmentation, then Hyperpigmentation
  8. Resolve (2 to 3 weeks)
4. Variations
  1. Lesion may coalesce into larger scabs
Associated Symptoms
1. Pruritus
2. Myalgias

Labs

Consider other STI testing (e.g. HIV, Syphillis, Gonorrhea, Chlamydia)
General
1. Obtain swabs of at least 2-3 lesions and exudate
2. Lesion skin biopsy may also be used
Orthopoxvirus DNA PCR
1. Preferred primary test in U.S.
2. Use nylon, polyester or Dacron swabs
3. Store specimens in dry, sterile containers with tight fitting lids in refrigerator or freezer until testing
Orthopoxvirus Immunochemical stain
Anti-Orthopoxvirus IgM
1. Positive from day 5 to day 56 after rash onset

Differential Diagnosis

Varicella Zoster Virus (Chicken Pox, Shingles)
1. Chicken Pox lesions are soft, fragile, thin-walled, clear-fluid filled (rarely on palms and soles), and heal within 14 days
2. Mpox lesions are larger, deeper as well as more firm and Rubbery and heal within 28 days
3. Mpox lesions more commonly affect the palms and soles
Sexually Transmitted Infection
Scabies
Other Pox Viruses
1. Cowpox
2. Molluscum Contagiousum
3. Smallpox
  1. No natural outbreaks have occurred after 1978
  2. Associated with Influenza-like and gastrointestinal prodrome
  3. Lesions are widespread, and rapid onset within 36 hours
Non-infectious lesions
1. Behcet Syndrome
2. Aphthous Stomatitis

Complications

Superimposed Cellulitis or other Bacterial Skin Infection (most common)
Pneumonitis and respiratory distress
Keratitis
Neuralgia
Encephalitis or Seizures (rare)

Management
General

Most Mpox cases are mild and self-limited
Supportive Care
1. Analgesics (Ibuprofen, Acetaminophen)
2. Maintain hydration (esp. Tonsillitis related Dysphagia)
3. Antiemetics (e.g. Ondansetron) as needed
4. Proctitis symptom relief (e.g. sitz baths, Stool Softeners)
Consult with local public health regarding testing and treatment
1. Rapid diagnosis and quarantine is critical to outbreak containment
Isolation for 2 to 4 weeks until rash fully heals (lesions desquamate)
1. When around others, mask and cover wound with dressing
2. Avoid public transportation and other crowded palces
3. Strict hygiene

Management
Antivirals

Background
1. These agents were primarily developed for use in Smallpox, and efficacy in Monkeypox is unclear
2. Antivirals may reduce disease severity, pain and swelling, abscess formation and scarring
Indications
1. Severe Disease
  1. Encephalitis
  2. Myocarditis
  3. Sepsis
  4. Hemorrhagic Disease
  5. Hospitalized patients
  6. Large number of confluent lesions
2. Anogenital lesions or other sensitive sites (e.g. Tonsillitis)
3. CNS or Eye lesions
4. High risk of severe disease (see prognosis below)
  1. Immunocompromised
  2. Age <8 years
  3. Pregnancy
  4. Atopic Dermatitis
Agents
1. Tecovirimat (TPOXX, ST-246) - preferred in 2022 U.S.
  1. Blocks Orthopoxvirus envelope Protein vp37 (decreases cell to cell transmission)
  2. Decreases pain and prevents severe disease
  3. Dosing
    1. Oral: 600 mg orally every 12 hours for weight > 40 kg (every 8 hours for weight >120 kg)
    2. IV: 200 mg IV every 12 hours for weight >40 kg (300 mg IV if weight >120 kg)
      1. IV formulation is contraindicated in Creatinine Clearance <30 ml/min
  4. Adverse effects include Headaches, Nausea, Vomiting and Abdominal Pain (and uncommon Allergic Reactions)
  5. Unknown safety in pregnancy, but limited systemic absorption
  6. As of 2024, available via NIH STOMP trial
  7. LoVecchio (2022) Crit Dec Emerg Med 36(10): 32
2. Brincidofovir (CMX001, Tembexa)
  1. Consider as second-line adjunct to Tecovirimat for refractory cases
  2. Inhibits Orthopoxvirus DNA Polymerase (as with Cidofovir)
  3. Oral dosing only
  4. Adverse effects
    1. Increased liver transaminases and Bilirubin (obtain baseline hepatic panel before starting)
    2. Nausea and Vomiting
    3. Diarrhea
    4. Abdominal Pain
3. Cidofovir (Vistide, primary indication is for CMV Retinitis)
  1. Consider as second-line adjunct to Tecovirimat for refractory cases
  2. Inhibits Orthopoxvirus DNA Polymerase (as with Brincidofovir)
  3. IV dosing
  4. Adverse effects
    1. Drug-induced Nephrotoxicity and Proteinuria
    2. Fever
    3. Decreased serum bicarbonate
    4. Neutropenia
    5. Iritis and Uveitis
4. Vaccinia Immune Globulin Intravenous (VIGIV, CNJ-016)
  1. FDA approved for Smallpox Vaccine complications
  2. Offers Mpox passive Immunity (from pooled samples of Smallpox immunized patients)
  3. Indications in Mpox
    1. Impaired Antibody response AND Mpox refractory to other treatments
  4. Adverse Effects
    1. Headache
    2. Nausea
    3. Rigors
    4. Dizziness

Prognosis
High Risk Patients for Severe Disease

Immunocompromised State
1. Human Immunodeficiency Virus Infection (HIV or AIDS)
2. Generalized Malignancy
3. Leukemia
4. Lymphoma
5. Solid Organ Transplantation
6. Immunosuppressants (e.g. Alkylating Agents, antimetabolites, Tumor Necrosis Factor Inhibitors, high-dose Corticosteroids)
7. Status Hematopoietic Stem Cell Transplant (<24 months post-transplant or =24 months with graft-versus-host disease)
8. Other Immunodeficiency (e.g. Autoimmune Condition)
Other factors
1. Age <8 years old
2. Atopic Dermatitis
3. Active exfoliative skin conditions (e.g. Eczema, burns, Impetigo, VZV, HSV, severe acne, severe Diaper Dermatitis, Psoriasis)
4. Women in pregnancy or Lactation
5. Travel to regions affected by Clade I strains (Democratic Republic of Congo in fall 2024)
Disease complications
1. Secondary Bacterial Skin Infection
2. Gastroenteritis with severe Nausea, Vomiting, Diarrhea or Dehydration
3. Bronchopneumonia

Prevention
General

Limit sexual partners
1. Avoid sex clubs and sex parties
2. Avoid sex or intimate contact with MPox patients
3. Recovering MPox patients should use barrier protection (e.g. Condoms) for at least 12 weeks after symptom resolution
Avoid skin to skin contact with lesions
1. Cover lesions with clothing or bandages
2. Lesions are often outside of Condom protection
Avoid exposure to body fluids (throat, blood, urine, semen, stool)
1. Use gloves when handling a patient's laundry
Personal Protection Equipment (healthcare workers)
1. Gown and gloves
2. N95 Mask (respiratory transmission may occur)
3. Patients in the hospital should have their own bathroom
4. Negative airflow is NOT needed

Prevention
Vaccination

Indications
1. Pre-exposure prophylaxis
  1. Occupational exposure (e.g. lab workers)
  2. High risk patients in regions of Monkey Pox outbreaks
    1. Men who have Sex with Men
    2. Multiple sexual partners
    3. Sex workers
    4. HIV Infection (esp. those on HIV PrEP)
2. Post-exposure Prophylaxis (sexual or other close contact)
  1. Ideal if within 4 days of exposure
  2. May be given up to 14 days after exposure
  3. Prior infection with MPox (confirmed cases) do not require Vaccination
    1. Immunity after infection is strong and reinfection is rare
Preparations
1. JYNNEOS Small Pox and Monkey Pox Vaccine
  1. Preferred (approved for Monkeypox)
  2. Consider safe in Immunocompromised patients
  3. Third-Generation, Replication deficient Live Vaccinia Virus Vaccine
  4. Two dose Vaccine (28 days apart) with Immunity developed by 2 weeks after second dose
    1. Each dose 0.1 ml intradermal in adults (0.5 ml SQ for age <18 years old)
    2. Booster dose every 4 years as needed
  5. Adverse Effects
    1. Injection site reactions are common (redness, swelling, pain)
    2. Minor cardiac effects in 1.3% (transient Troponin Increase, EKG abnormalities, Palpitations)
2. ACAM2000 (Smallpox Vaccine, live Vaccinia virus)
  1. See Smallpox Vaccine
  2. Second Generation Smallpox, Live attenuated Vaccinia virus Vaccine
  3. Rare adverse effects include Myocarditis, Guillain-Barre Syndrome, Stevens-Johnson Syndrome
  4. Not recommended for Immunocompromised, HIV/AIDS, pregnant or lactating patients, heart disease, Eczema
  5. One dose Vaccination by scarification (multiple skin punctures)
    1. Successful Vaccination is followed by open lesion formation at Immunization site within 28 days
    2. Booster dose every 3 years as needed
    3. Avoid transmission to others (see Smallpox Vaccine)

Resources

McCollum (2020) Smallpox and Other Orthopoxvirus-Associated Infections, Yellow Book, Accessed 6/27/2022
1. https://wwwnc.cdc.gov/travel/yellowbook/2020/travel-related-infectious-diseases/smallpox-and-other-orthopoxvirus-associated-infections
Monkeypox Response (CDC), Accessed 6/27/2022
1. https://www.cdc.gov/poxvirus/monkeypox/response/2022/hcp/index.html
Monkeypox Clinical Recognition (CDC), Accessed 6/27/2022
1. https://www.cdc.gov/poxvirus/monkeypox/clinicians/clinical-recognition.html
Monkeypox Treatment (CDC), Accessed 6/27/2022
1. https://www.cdc.gov/poxvirus/monkeypox/clinicians/treatment.html

References

(2024) Presc Lett 31(10): 59
(2022) Presc Lett 29(9): 49-50
Gianuzzi (2023) Crit Dec Emerg Med 37(2): 4-10
Marx (2022) Crit Dec Emerg Med 36(11): 12-3
Saguil (2023) Am Fam Physician 108(1): 78-83 [PubMed]