Polioviruses

Etiology

The polioviruses are nonenveloped, positive-stranded RNA viruses belonging to the Picornaviridae family, in the genus Enterovirus, species Enterovirus C and consist of 3 antigenically distinct serotypes (types 1, 2, and 3). Polioviruses spread from the intestinal tract to the central nervous system (CNS), where they cause aseptic meningitis and poliomyelitis, or polio. The polioviruses are extremely hardy and can retain infectivity for several days at room temperature.

Epidemiology

The most devastating result of poliovirus infection is paralysis, although 90–95% of infections are inapparent. Despite the absence of symptoms, clinically inapparent infections induce protective immunity. Clinically apparent but nonparalytic illness occurs in approximately 5% of all infections, with paralytic polio occurring in approximately 1 in 1,000 infections among infants to approximately 1 in 100 infections among adolescents. In industrialized countries prior to universal vaccination, epidemics of paralytic poliomyelitis occurred primarily in adolescents. Conversely, in developing countries with poor sanitation, infection early in life results in infantile paralysis. Improved sanitation explains the virtual eradication of polio from the United States in the early 1960s, when only approximately 65% of the population was immunized with the Salk vaccine, which contributed to the disappearance of circulating wild-type poliovirus in the United States and Europe.

Transmission

Humans are the only known reservoir for the polioviruses, which are spread by the fecal-oral route. Poliovirus has been isolated from feces for longer than 2 wk before paralysis to several wk after the onset of symptoms.

Pathogenesis

Polioviruses infect cells by adsorbing to the genetically determined poliovirus receptor (CD155). The virus penetrates the cell, is uncoated, and releases viral RNA. The RNA is translated to produce proteins responsible for replication of the RNA, shutoff of host cell protein synthesis, and synthesis of structural elements that compose the capsid. Mature virus particles are produced in 6-8 hr and are released into the environment by disruption of the cell.

In the contact host, wild-type and vaccine strains of polioviruses gain host entry via the gastrointestinal tract. Recent studies in nonhuman primates demonstrate that the primary sites of replication are in the CD155 ⁺ epithelial cells lining the mucosa of the tonsil follicle and small intestine, as well as see the macrophages/dendritic cells in the tonsil follicle and Peyer patches. Regional lymph nodes are infected, and primary viremia occurs after 2-3 days. The virus seeds multiple sites, including the reticuloendothelial system, brown fat deposits, and skeletal muscle. Wild-type poliovirus probably accesses the CNS along peripheral nerves. Vaccine strains of polioviruses do not replicate in the CNS, a feature that accounts for the safety of the live-attenuated vaccine. Occasional revertants (by nucleotide substitution) of these vaccine strains develop a neurovirulent phenotype and cause vaccine-associated paralytic poliomyelitis (VAPP). Reversion occurs in the small intestine and probably accesses the CNS via the peripheral nerves. Poliovirus has almost never been cultured from the cerebrospinal fluid (CSF) of patients with paralytic disease, and patients with aseptic meningitis caused by poliovirus never have paralytic disease. With the 1st appearance of non-CNS symptoms, a secondary viremia probably occurs as a result of enormous viral replication in the reticuloendothelial system.

The exact mechanism of entry into the CNS is not known. However, once entry is gained, the virus may traverse neural pathways and multiple sites within the CNS are often affected. The effect on motor and vegetative neurons is most striking and correlates with the clinical manifestations. Perineuronal inflammation, a mixed inflammatory reaction with both polymorphonuclear leukocytes and lymphocytes, is associated with extensive neuronal destruction. Petechial hemorrhages and considerable inflammatory edema also occur in areas of poliovirus infection. The poliovirus primarily infects motor neuron cells in the spinal cord ( the anterior horn cells ) and the medulla oblongata (the cranial nerve nuclei). Because of the overlap in muscle innervation by 2-3 adjacent segments of the spinal cord, clinical signs of weakness in the limbs develop when more than 50% of motor neurons are destroyed. In the medulla, less-extensive lesions cause paralysis, and involvement of the reticular formation that contains the vital centers controlling respiration and circulation may have a catastrophic outcome. Involvement of the intermediate and dorsal areas of the horn and the dorsal root ganglia in the spinal cord results in hyperesthesia and myalgias that are typical of acute poliomyelitis. Other neurons affected are the nuclei in the roof and vermis of the cerebellum, the substantia nigra, and, occasionally, the red nucleus in the pons; there may be variable involvement of thalamic, hypothalamic, and pallidal nuclei and the motor cortex.

Apart from the histopathology of the CNS, inflammatory changes occur generally in the reticuloendothelial system. Inflammatory edema and sparse lymphocytic infiltration are prominently associated with hyperplastic lymphocytic follicles.

Infants acquire immunity transplacentally from their mothers. Transplacental immunity disappears at a variable rate during the 1st 4-6 mo of life. Active immunity after natural infection is probably lifelong but protects against the infecting serotype only; infections with other serotypes are possible. Poliovirus-neutralizing antibodies develop within several days after exposure as a result of replication of the virus in the tonsils and in the intestinal tract and deep lymphatic tissues. This early production of circulating immunoglobulin (Ig) G antibodies protects against CNS invasion. Local (mucosal) immunity, conferred mainly by secretory IgA, is an important defense against subsequent reinfection of the gastrointestinal tract.

Clinical Manifestations

The incubation period of poliovirus from contact to initial clinical symptoms is usually considered to be 8-12 days, with a range of 5-35 days. Poliovirus infections with wild-type virus may follow 1 of several courses: inapparent infection, which occurs in 90–95% of cases and causes no disease and no sequelae; abortive poliomyelitis; nonparalytic poliomyelitis; or paralytic poliomyelitis. Paralysis, if it occurs, appears 3-8 days after the initial symptoms. The clinical manifestations of paralytic polio caused by wild or vaccine strains are comparable, although the incidence of abortive and nonparalytic paralysis with vaccine-associated poliomyelitis is unknown.