Lecture 16-2 Monkeypox

Monkeypox

viral zoonosis w/ symptoms similar to smallpox, but less severe

•Enveloped double-stranded DNA virus

•Classified as an Orthopoxvirus in the Poxviridae family

•Two distinct genetic clades recognized
>Clade I - Central Africa Clade (Congo Basin)
>Clade II - West Africa Clade 

US Outbreaks

•Ongoing Clade II mpox circulation that has persisted since 2022

•Handful of Clade I mpox cases travel-associated

•First human mpox case in the U.S. was in 2003 → over 70 cases
>Linked to infected pet prairie dogs that had been housed with infected Gambian rats

•A major mpox outbreak occurred in 2022–2023, spread to all 50 states + Washington, D.C. and Puerto Rico

•U.S. risk assessment level is low

Animals susceptible to Mpox

squirrels, rats, primates, humans

reservoir unknown

Transmission

•Animal→ human (zoonotic) transmission
direct contact with blood, bodily fluids, or cutaneous/mucosal lesions of an infected animal

•Human→ human transmission
respiratory droplets, skin lesions, or fomites

•Transmission via sexual routes has been documented but unclear if mpox is a STI

•Longest documented chain of community transmission is up to 9 successive person-to-person infections that may reflect declining immunity in all communities to ending smallpox vaccination

Clinical disease

Incubation average 6-13 days, range 5-21 days

•Initial symptoms: fever, intense headache, back pain, myalgia, and significant lack of energy that last up to 5 days after infection

•Lymphadenopathy is a distinctive feature of mpox when compared with smallpox, chickenpox, and measles

•Skin eruptions usually begin 1-3 days after appearance of fever, more concentrated on face and extremities rather than trunk

•Skin eruptions are found on face (95%), palms of hands / soles of feet (75%), oral mucous membranes (70%), genitalia (30%), and conjunctiva (20%)

•Mpox is usually a self-limited disease with symptoms lasting from 2 to 4 weeks

•Persons younger than 40-50 years may be more susceptible to mpox due to ending smallpox vaccination globally after eradication of the disease

•Complications of mpox: secondary bacterial infections, sepsis, encephalitis, + infection of cornea with vision loss

•Mortality historically has ranged from 0.1 to 10% in the general population and higher among young children

Vaccination

•Vaccination against smallpox has been demonstrated to be ~85% effective against preventing mpox

•Two new two-dose vaccines (JYNNEOS and ACAM2000) based on a modified attenuated vaccinia virus (Ankara strain) was approved for prevention of mpox in 2019

•The JYNNEOS vaccine is the primary vaccine used in the U.S.

•The ACAM2000 vaccine has been shown to have more frequent side effects and not recommended for persons with a weakened immune system

Tecovirimat

•Tecovirimat (Tpoxx) is an FDA-approved antiviral with activity against orthopoxviruses [smallpox and mpox]

•Inhibits the function of a major envelope protein (VP37) required for the production of extracellular infectious virus [Mechanism of Action]

•First used for treatment of laboratory-acquired vaccinia virus infection in 2018

•Generally well tolerated with no serious adverse reactions

•2 mil doses are stockpiled in case of orthopoxvirus-based bioterror attack

•Recent clinical trial did not show effectiveness against Clade I mpox in the Democratic Republic of the Congo