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Polioviruses are the cause of poliomyelitis, a systemic viral infection that predominantly affects the central nervous system (CNS), causing paralysis. The name of the disease ( polios, “gray”; myelos, “marrow” or “spinal cord”), now commonly shortened to polio, is descriptive of the pathologic lesions that involve neurons in the gray matter, especially in the anterior horns of the spinal cord. Paralytic poliomyelitis has been completely controlled in the United States and other developed countries through routine childhood immunization with either inactivated poliovirus vaccine (IPV), live-attenuated oral poliovirus vaccine (OPV), or both. However, as of 2017, the goal of worldwide poliomyelitis eradication has not yet been achieved, having been hampered by unforeseen scientific challenges, geopolitical unrest, and social disruption, among other factors.
History
Perhaps the earliest representation of poliomyelitis is found in a funerary stele from the Ramesside period (1300 bc ) of Ancient Egypt, housed in the Carlsberg Museum, Copenhagen. It depicts the priest Rom with an atrophic lower extremity and foot held in a talipes equinus position. Sporadic poliomyelitis cases were published as early as 1840, and the first descriptions of the natural history and neurologic complications of poliomyelitis were recorded in Sweden by Karl Oskar Medin in 1890. There is little record of epidemic poliomyelitis until the late 19th century, when outbreaks were first recorded in Scandinavia, Western Europe, and the United States. Charles Caverly wrote the first description of epidemic poliomyelitis in the United States, an outbreak of 132 cases near Rutland, Vermont, in 1894. Thereafter, sporadic epidemic disease occurred during the first half of the 20th century, and by the 1950s, epidemic polio occurred regularly, with approximately 25 cases per 100,000 population reported annually in the United States. Accompanying the increased incidence was a shift in the peak-affected age group from infants to school-aged children and young adults. Both the appearance of epidemic disease and the rising age incidence have been attributed to rising standards of hygiene, which delayed the age of infection beyond infancy and loss of maternal antibody, thus creating a pool of susceptible people large enough to permit the spread of epidemic disease.
In 1908, Landsteiner and Popper demonstrated that polio was caused by a “filterable virus” when they transmitted disease to monkeys from human spinal cord homogenates. Scientific progress remained somewhat limited until the landmark discovery in 1949 by Enders, Weller, and Robbins that poliovirus could be propagated in vitro in cultures of human embryonic cells of nonneural origin. This discovery facilitated experimental investigation of the pathogenesis of the disease in primates and the development of vaccines. Bodian and associates first recognized the three distinct serotypes of poliovirus. By 1952, Bodian and Horstmann had independently discovered that viremia occurred early in infection, which explained the systemic phase of the illness.
Salk reported in 1953 that human subjects could be successfully immunized with formalin-inactivated poliovirus, a discovery that rapidly led to an extensive field trial and licensure of IPV in 1955. The introduction of IPV led to a sudden dramatic reduction in the incidence of paralytic poliomyelitis in the United States to 0.4 cases per 100,000 population in 1962, when OPV replaced IPV for routine use. The last case of endemic wild-type poliomyelitis occurred in 1979, indicating complete cessation of transmission of naturally occurring polioviruses. However, in addition to rare cases of wild-type disease imported from other countries, the United States continued to experience 6 to 10 cases of OPV vaccine-associated paralytic poliomyelitis (VAPP) each year until 1997, when IPV was reintroduced into the routine childhood immunization schedule in combination with OPV. Since 2000, only IPV has been used.
Under the leadership of the Pan American Health Organization, the entire Western Hemisphere became free of paralytic polio by 1991. Poliovirus type 2 was certified as globally eradicated in 2015. As of the end of 2017, worldwide, endemic circulation of polioviruses had been controlled by all countries with the exception of Pakistan, Afghanistan, and Nigeria. No naturally occurring polioviruses have been identified from any other country since 2014. Virulent polioviruses derived from OPV strains (circulating vaccine-derived polioviruses [cVDPVs]) also cause periodic outbreaks of paralytic polio in some regions with low population immunity.
Pathophysiology
Virology
Polioviruses are prototypic members of the genus Enterovirus (see Chapter 171). Three poliovirus serotypes exist, and infection with each confers serotype-specific, lifelong immunity to disease but little or no immunity to infection or disease caused by heterologous serotypes. Before the introduction of poliovirus vaccines, most paralytic disease was caused by type 1. Polioviruses are categorized into three groups: wild-type (naturally occurring) polioviruses (WPVs), vaccine-related poliovirus (VRPV) strains (live-attenuated OPV viruses), and vaccine-derived polioviruses (VDPVs) arising from OPV strains. The VDPVs are further classified as cVDPV when evidence of person-to-person transmission exists; immunodeficiency-associated VDPV (iVDPV) when isolated from persons with primary immunodeficiencies; and ambiguous VDPV (aVDPV) when isolated from individuals without immunodeficiency and evidence of transmission, or in the case of sewage isolates unrelated to other known VDPVs and whose source is unknown. WPV, VPDV and VDPD may be encountered in different populations, depending on whether endemic transmission of WPV has been eliminated, on whether OPV is used, and on the vaccine-induced immunity rates in the population.
Humans are the only natural host and reservoir of polioviruses. Experimental infections and paralysis can be produced in other primates, polioviruses can be adapted to replicate in subprimate mammals, and transgenic (tg) mice expressing the poliovirus receptor (PVR) can be paralyzed by injection into the CNS or peripheral muscle but not by the oral route. Recently, tg mice expressing PVR under the control of the murine promotor Tage4 have been demonstrated to be moderately susceptible to oral infection by poliovirus. Naturally occurring strains vary over a 10 7 -fold range in neurovirulence. Polioviruses are more infectious for the human gut than for the gut of lower primates.
Attenuated OPV strains are occasionally able to paralyze rhesus and cynomolgus monkeys but only when injected in high doses directly into the CNS. In addition to low neurovirulence, vaccine strains can often be distinguished from WPV strains by their temperature sensitivity and by subtle antigenic differences. The RNA sequences of the vaccine strains differ from the sequences of their naturally occurring parents by less than 0.2% across the full genome, with the smallest difference occurring between the type 2 vaccine and parent strains. For all three serotypes, analogous nucleotide substitutions in the 5′-noncoding region are associated with reduced neurovirulence. Attenuating mutations also map to capsid proteins for individual serotypes.
In contrast, cVDPVs have been permitted to circulate because of low population immunity for long periods of time and, by continuous mutation, acquire biologic properties indistinguishable from those of WPVs. The cVDPVs isolated have RNA sequences that vary by more than 0.6% to 1.0% from the corresponding OPV parent strain within the region encoded for the VP1 capsid protein, have undergone genomic recombination with other C species enteroviruses, and have acquired virulence markers characteristic of WPV strains.
Pathogenesis
The early events in the pathogenesis of poliomyelitis are similar to those in other enterovirus infections described in Chapter 171. After implantation at a mucosal site and replication in the gut, or less frequently the throat and adjacent lymphoid tissues, polioviruses disseminate to susceptible reticuloendothelial tissues via a minor viremia. In asymptomatic infections, the virus is contained at this point and elicits the formation of type-specific antibodies. In a few infected persons, replication in the reticuloendothelial system gives rise to a major viremia, which corresponds temporally with the minor illness and causes the symptoms associated with abortive poliomyelitis. At this point, the course of poliomyelitis deviates from that of other enteroviral diseases in the ability of polioviruses to infect neurons in the gray matter of the brain and spinal cord. Although the preponderance of evidence indicates that viremia precedes paralysis in both experimental primates and humans, the exact routes whereby the CNS becomes infected remain uncertain. Studies in the PVR tg mouse suggest that polioviruses may enter the CNS via the bloodstream or by retrograde axonal transport in peripheral nerve fibers. Neuropathologic studies and animal experiments have indicated that spread is neural once the virus reaches the CNS.
Poliovirus principally affects motor and autonomic neurons. Neuronal destruction is accompanied by inflammatory lesions consisting of polymorphonuclear leukocytes, lymphocytes, and macrophages that are distributed throughout the gray matter of the anterior horns of the spinal cord and the motor nuclei of the pons and medulla. The mesencephalon, cerebellar roof nuclei, and precentral gyrus of the cerebral cortex are less severely involved. Clinical symptoms depend on the severity of lesions rather than on their distribution, which is similar in essentially all cases; almost all fatal cases have involvement of both the spinal cord and cranial nerve nuclei and brainstem, even in the absence of bulbar signs. The dorsal root ganglia are commonly involved pathologically, but this does not result in sensory deficits. Polioviruses can be isolated from the spinal cord for only the first few days after the onset of paralysis, but the inflammatory lesions may persist for months.
Clinical Manifestations
Incubation Period
Best estimates of the incubation period of poliomyelitis are 9 to 12 days (range, 5–35 days), measured from presumed contact until the onset of the prodromal symptoms, and 11 to 17 days (range, 8–36 days) until the onset of paralysis.
Clinical Manifestations of Infection
The manifestations of infection by polioviruses range from unapparent illness to severe paralysis and death. Usual estimates of the ratio of unapparent to clinically recognized polio infection, which vary by serotype, range from 60 : 1 to 1000 : 1. Fig. 171.1 depicts the time course for the clinical manifestations of poliovirus infection. At least 95% of infections are asymptomatic or unapparent and can be recognized only by the isolation of poliovirus from feces or oropharynx or by a rise in antibody titer. Abortive poliomyelitis, which occurs in 4% to 8% of infections, is characterized by a 2- to 3-day period of fever, which may be accompanied by headache, sore throat, listlessness, anorexia, vomiting, or abdominal pain. Because the neurologic examination findings are normal, abortive poliomyelitis cannot be distinguished from other viral infections and can be clinically suspected only during an epidemic. Nonparalytic poliomyelitis differs from abortive poliomyelitis by the presence of signs of meningeal irritation. The disease is identical to meningitis caused by other enteroviruses. The systemic manifestations of nonparalytic poliomyelitis are generally more severe than in abortive poliomyelitis.
Spinal Paralytic Poliomyelitis
Frank paralysis occurs in roughly 0.1% of all poliovirus infections. A biphasic course with minor and major illnesses is observed in approximately one-third of children with paralytic poliomyelitis. The minor illness, coinciding with viremia, corresponds to the symptoms of abortive poliomyelitis and lasts 1 to 3 days. The patient appears to be recovering and remains symptom free for 2 to 5 days before the abrupt onset of the major illness, which is heralded by symptoms and signs of meningitis, including fever, chills, headache, fever, malaise, vomiting, neck stiffness, and cerebrospinal fluid (CSF) pleocytosis. Adults usually experience a single phase of illness, with a prolonged prodrome of symptoms preceding the gradual onset of paralysis. The major illness begins with severe myalgias and occasionally localized cutaneous hyperesthesia, paresthesias, involuntary muscle spasm, or muscular fasciculations. The meningismus and muscle pain are present for 1 to 2 days before frank weakness and paralysis ensue. The severity of the disease varies from weakness of a single portion of one muscle to complete quadriplegia. The paralysis is flaccid; deep tendon reflexes are initially hyperactive and then become absent. The most characteristic feature of the paralysis is its asymmetrical distribution, which affects some muscle groups while sparing others. Proximal muscles of the extremities tend to be more involved than distal muscles, the legs are more commonly involved than the arms, and the large muscle groups of the hand are at greater risk than the small ones. Any combination of limbs may be paralyzed, but the most common pattern is involvement of one leg, followed by one arm, or both legs and both arms. Quadriplegia is almost never observed in infants. Although occasional cases progress from the onset of weakness to complete quadriplegia and bulbar involvement in a few hours, more commonly the paralysis extends over 2 to 3 days. Progression of paralysis stops when the patient becomes afebrile. Paralysis of the bladder is usually associated with paralysis of the legs. It occurs in about 25% of adults but is uncommon in children. Sensory loss in poliomyelitis is very rare, and its occurrence should strongly suggest some other diagnosis (e.g., Guillain-Barré syndrome).
Bulbar Paralytic Poliomyelitis
Bulbar poliomyelitis results from paralysis of muscle groups innervated by the cranial nerves, especially those of the soft palate and pharynx, which may manifest as dysphagia, nasal speech, and sometimes dyspnea. The frequency of the bulbar form of the disease has varied in different epidemics from 5% to 35% of paralytic cases. The ninth and tenth cranial nerves are most commonly involved, and pharyngeal paralysis with pooling of secretions often is the only obvious sign. Patients usually are extremely anxious and agitated about their inability to swallow and breathe. Involvement of the circulatory and respiratory centers of the medulla represents the most serious form of bulbar poliomyelitis.
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