Poliovirus

Epidemiology and Risk Factors. Poliomyelitis was the most frightening infectious disease during the first half of the twentieth century. Large epidemics led to extensive research in the epidemiology and pathogenesis of the disease. The poliovirus was first isolated in 1908 by inoculation of monkeys with a cell-free extract made from the spinal cord of a patient with fatal poliomyelitis. y , y It was not, however, until 1937 that the virus was isolated from intestinal washings, and by 1941 it was clear that the gastrointestinal tract played a major role in the pathogenesis of this infection. '23' Shortly thereafter it was recognized that the majority of poliovirus infections are a form of acute gastroenteritis. Paralysis develops in less than 1 in 100 individuals infected with the poliovirus. '24] In 1949 Enders, Weller, and Robbins made the major discovery that the poliovirus could be grown in tissue cultures of human embryonic skin, muscle cells, and intestinal tissue. Prior to that the only source of the poliovirus was nervous tissue from infected monkeys, an unacceptable inoculum in humans. y The work of Enders and his colleagues, combined with the efforts of the National Foundation for Infantile Paralysis, led to the recognition that there were only three serotypes of poliovirus and laid the groundwork for the development of the killed virus vaccine by Jonas Salk in 1955, and the oral live attenuated virus vaccine by Albert Sabin in 1961. y , y Poliomyelitis has been nearly eradicated from North America and Europe, but outbreaks of the disease continue to occur in Asia and Africa, where an estimated 250,000 cases and 25,000 deaths currently occur annually.y

Pathogenesis and Pathophysiology. Poliovirus is a member of the Picornaviridae. There are three immunologically defined serotypes of poliovirus, all of which are capable of causing paralytic disease. The poliovirus is a single-stranded RNA enterovirus. y Natural polio infection occurs through ingestion of the virus, which initially multiplies in the oropharyngeal and intestinal mucosa. Poliovirus either enters the CNS via the bloodstream or, alternatively, may be transmitted to the CNS through vagal autonomic nerve fibers in the intestinal lumen. y A temporal association corresponding to the incubation period of the disease was observed between tonsillectomy and the development of bulbar poliomyelitis, suggesting that the exposure of nerve endings via tonsillectomy could transmit poliovirus to the CNS. '27' A third hypothesis is that ingested poliovirus initially replicates in the gastrointestinal tract; then a viremia ensues, and disseminated virus replicates at an extraneural site (i.e., skeletal muscle cells). Virus is then transported from the muscle cells via the peripheral nerves to the CNS. The hypothesis that poliovirus replicates in muscle cells and then enters the CNS through the peripheral nerves has been supported by the clinical observations that vigorous exertion or injury of a limb was temporally associated with limb paralysis. '22' In the Cutter incident, children inoculated intramuscularly with incompletely inactivated polio vaccine developed focal limb paralysis.y , y Poliovirus replicates in the muscles of monkeys after intramuscular injection and causes limb paralysis of the injected limb. y The poliovirus receptor (PVR), a member of the immunoglobulin superfamily of proteins, is present at the motor endplate. During acute infection, the poliovirus may bind to the PVR-expressing motor endplate and travel by way of endocytosis and retrograde transport to the anterior horn cells in the spinal cord and brain stem. y Acute paralytic poliomyelitis is then characterized pathologically by severe anterior horn inflammation with loss of spinal and bulbar motor neurons. y

In his classic work on acute polio infection, Bodian noted evidence of a marked scarcity of normal-appearing neurons, even in cases of very mild paralysis, suggesting that acute paralytic polio was a generalized neuronal disease. The earliest cellular change in the motor neurons was dissolution of the cytoplasmic Nissl substance (chromatolysis). Infected neurons that exhibited only a mild degree of diffuse chromatolysis survived and continued to support motor units; in contrast, neurons that had severe chromatolysis followed by nuclear invagination and perinuclear chromatin aggregation could not support motor units, and subsequently permanent loss of function occurred in these muscle groups.y , y

Postpolio syndrome, defined as "the development of new muscle weakness and fatigue in skeletal or bulbar muscles, unrelated to any known cause, that begins 25 to 30 years after an acute attack of paralytic poliomyelitis," is most likely explained by the status of the motor neurons that survived the initial infection. The surviving motor neurons, in an attempt to reinnervate the muscle fibers orphaned by the death of their parent motor neurons, adopt in their motor unit territory additional muscle fibers, so that the number of muscle fibers innervated by a single motor neuron may be four to five times the normal number. This puts metabolic stress on the neuronal cell bodies that, after a number of years, leads to a slow deterioration of nerve terminals. As each terminal dies, muscle fibers drop out, and weakness slowly progresses.y

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