Smallpox and Monkeypox (Mpox) Lecture Notes

Smallpox Overview

  • Severe human disease known for at least 2000 years.

Poxvirus Characteristics

  • Complex, ovoid or brick-shaped virion (300 x 250 x 150 nm).

  • Largest known animal virus.

  • Genome: Linear double-stranded DNA encoding 150-250 virus proteins.

Forms of Smallpox

  • Variola Major: 10-30% mortality rate.

  • Variola Minor: ~1% mortality rate.

Transmission

  • Humans are the only natural host.

  • Routes: Aerosols, direct contact with vesicles, fomites (bedding and clothing).

Pathogenesis

  • Infection starts in oropharynx; spreads to lymph nodes.

  • Asymptomatic viremia occurs 3-4 days post-infection.

  • Secondary viremia from day 8-12, with clinical signs appearing around day 14.

Clinical Disease Phases

  • Incubation: 12-14 days, initial symptoms (fever, headache, malaise).

  • Rash Development: Starts with red spots in mouth, then spreads to entire body in 24 hours.

  • Vesicle to Pustule Transition: Vesicles form by day 4 of rash, pustules reach maximum size by days 7-10.

  • Crusting and Healing: Scabs form by day 14; scarring after lesions heal.

Mortality

  • Death between days 10-16 can be due to organ failure, overwhelming viremia, or secondary infections.

Vaccination History

  • Variolation: Middle Eastern practice of injecting smallpox scabs.

  • Smallpox Vaccine: Derived from Vaccinia, a hybrid of cowpox and variola.

  • High rates of adverse reactions; smallpox eradicated in 1977 by WHO.

Laboratory Concerns

  • Virus escapes resulted in fatalities; debate on virus destruction to prevent bioterrorism vs. the need for research.

Mpox Overview

  • Zoonotic virus with symptoms similar to smallpox but less severe.

  • Enveloped double-stranded DNA, classified as Orthopoxvirus.

  • Two genetic clades: Clade I (Central Africa), Clade II (West Africa).

U.S. Outbreaks

  • Ongoing Clade II mpox circulation since 2022; major outbreak from 2022-2023 (32,063 cases).

Transmission

  • Animal-to-human (direct contact), and human-to-human (respiratory droplets, lesions).

Clinical Disease

  • Incubation: 6-13 days; initial fever and headaches, lymphadenopathy distinctive.

  • Skin eruptions concentrated on face and extremities.

Vaccination for Mpox

  • Smallpox vaccination ~85% effective against mpox.

  • New vaccines (JYNNEOS and ACAM2000) approved in 2019, with JYNNEOS as primary.

Treatment

  • Tecovirimat (Tpoxx): FDA-approved antiviral for orthopoxviruses; inhibits VP37 protein.

  • Stockpiled for potential orthopoxvirus bioterror attacks; recent trial showed limited effectiveness against Clade I mpox.