Poxviruses Dr Ömer Küçükbasmacı

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.

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.

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.

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

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

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.

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.

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).

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.

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

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.

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.

Smallpox

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.

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.

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.

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.

Orf

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).

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.

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.

Diagnosis Epidermis is filled with molluscum bodies

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.