Poxviruses

1. Poxviruses Dr Ömer Küçükbasmacı

2. Poxviruses • Include the human viruses variola (smallpox) and molluscum contagiosum • Some viruses naturally infect animals and can cause incidental infection in humans (zoonosis). • Many of these viruses share antigenic determinants with smallpox, allowing the use of an animal poxvirus for a human vaccine.

3. Poxviruses • In eighteenth-century England, smallpox accounted the deaths of one third of children. • The development of the first live vaccine in 1796 and the later worldwide distribution of this vaccine led to the eradication of smallpox by 1980. • Reference stocks of smallpox virus in two World Health Organization (WHO) laboratories were destroyed in 1996.

4. Poxviruses • Unfortunately stocks of the virus still exist in the United States and in Russia. • Smallpox is considered a category A agent by the Centers for Disease Control and Prevention (CDC), with anthrax, plague, botulism, tularemia because of their great potential as bioterrorism-biowarfare agents.

5. The largest viruses, almost visible on light microscopy (300 nm) and are ovoid to brick shaped with a complex morphology.

6. The viral genome consists of a large double-stranded, linear DNA

7. Structure and Replication • The replication of poxviruses is unique among the DNA-containing viruses, in that the entire multiplication cycle takes place within the host cell cytoplasm. • Viral DNA then replicates in electron-dense cytoplasmic inclusions (Guarnieri's inclusion bodies), referred to as factories.

9. Pathogenesis and Immunity • After being inhaled, smallpox virus replicates in the upper respiratory tract. • Dissemination occurs via lymphatic and cell-associated viremic spread. • Internal and dermal tissues are inoculated after a second viremia, causing the simultaneous eruption of the characteristic "pocks.“ • Molluscum contagiosum and the other poxviruses, however, are acquired through direct contact with lesions.

11. Epidemiology • Smallpox and molluscum contagiousum are strictly human viruses. • In contrast, the natural hosts for the other poxviruses important to humans are vertebrates other than humans (e.g., cow, sheep, goats). • The viruses infect humans only through accidental or occupational exposure (zoonosis).

12. Epidemiology • Smallpox (variola) was very contagious and was spread primarily by the respiratory route. It was also spread less efficiently through close contact with dried virus on clothes or other materials. • Despite the severity of the disease and its tendency to spread, several factors contributed to its elimination.

13. Properties of Natural Smallpox That Led to Its Eradication • Viral Characteristics • Exclusive human host range (no animal reservoirs or vectors) • Single serotype (immunization protected against all infections) • Disease Characteristics • Consistent disease presentation with visible pustules (identification of sources of contagion allowed quarantine and vaccination of contacts) • Vaccine • Immunization with animal poxviruses protects against smallpox • Stable, inexpensive, and easy-to-administer vaccine • Presence of scar indicating successful vaccination • Public Health Service • Successful worldwide WHO program combining vaccination and quarantine

14. Clinical Syndromes • SMALLPOX • The two variants of smallpox were variola major, which was associated with a mortality of 15% to 40%, and variola minor, which was associated with a mortality of 1%. • Smallpox was usually initiated by infection of the respiratory tract with subsequent involvement of local lymph glands, which in turn led to viremia.

15. Smallpox • After a 5- to 17-day incubation period, the infected person experienced high fever, fatigue, severe headache, and malaise, followed by the vesicular rash in the mouth and on the body. • Vomiting, diarrhea, and excessive bleeding • The simultaneous outbreak of the vesicular rash distinguishes smallpox from the vesicles of varicella-zoster, which erupt in successive crops.

16. Smallpox

17. Smallpox • Was the first disease to be controlled by immunization, and its eradication is one of the greatest triumphs of medical epidemiology. • Eradication resulted from a massive WHO campaign to vaccinate all susceptible people, • The campaign began in 1967 and succeeded. • The last case of naturally acquired infection was reported in 1977, and eradication of the disease was acknowledged in 1980.

18. Variolation • An early approach to immunization, involved the inoculation of susceptible people with the virulent smallpox pus. It was first performed in the Far East and later in England. • Variolation was associated with a fatality rate of approximately 1%, a better risk than that associated with smallpox itself. • In 1796, Jenner developed and then popularized a vaccine using the less virulent cowpox virus, which shares antigenic determinants with smallpox.

19. VACCINIA • Vaccinia, a form of cowpox, was used for the smallpox vaccine. • The vaccination procedure consisted of scratching live virus into the patient's skin and then observing for the development of vesicles and pustules. • Encephalitis and progressive infection (vaccinia necrosum), the latter occurring occasionally in immunocompromised patients.

20. ORF, COWPOX, AND MONKEYPOX • Human infection with the orf (poxvirus of sheep and goat) or cowpox (vaccinia) virus is usually an occupational hazard resulting from direct contact with the lesions on the animal. • A single nodular lesion usually forms on the point of contact, such as the fingers, hand and is hemorrhagic or granulomatous. • Then regress in 25 to 35 days, generally without scar formation. The lesions may be mistaken for anthrax. • Monkeypox causes a milder version of smallpox disease.

21. Orf

22. MOLLUSCUM CONTAGIOSUM • The lesions differ significantly from pox lesions in being nodular to wartlike. • Begin as papules and then become pearl-like, umbilicated nodules that have a central caseous plug. • The incubation period for molluscum contagiosum is 2 to 8 weeks, and the disease is spread by direct contact (e.g., sexual contact, wrestling) or fomites (e.g., towels).

23. MOLLUSCUM CONTAGIOSUM • They are most common on the trunk, genitalia, and proximal extremities and usually occur in a cluster of five to 20 nodules. • The disease is more common in children than adults, but its incidence is increasing in sexually active individuals.

24. Diagnosis • Confirmed histologically by the finding of characteristic large, eosinophilic cytoplasmic inclusions (molluscum bodies) in epithelial cells. • These bodies can be seen in biopsy specimens.

25. Diagnosis • Epidermis is filled with molluscum bodies

26. Lesions of molluscum contagiosum disappear in 2 to 12 months, presumably as a result of immune responses. • The nodules can be removed by curettage (scraping) or the application of liquid nitrogen or iodine solutions.