Clinical manifestations

Presentation and course

More than 90% of poliovirus infections are asymptomatic. Approximately 4% to 8% of infected patients develop symptoms of acute poliomyelitis, which can be separated into 2 distinct clinical phases: the “minor illness,” with an incubation period of 3 to 7 days, and the “major illness,” with onset of symptoms generally 9 to 12 days after exposure (51). During the minor illness, patients present with constitutional symptoms (eg, fever, headache, nausea and vomiting, coryza, and sore throat), which are typically self-limiting, lasting 1 to 2 days. Major illness is associated with CNS infection, which has been estimated to occur in 0.1% to 1.0% of all poliovirus infections (Melnick and Ledinko 1951; 92).

During the major illness, patients may demonstrate signs of meningeal irritation, asymmetric flaccid weakness, muscle spasms, normal or accentuated muscle stretch reflexes, and hyperesthesias with preserved somatosensation. The major illness includes all forms of CNS disease caused by poliovirus, including aseptic meningitis, polioencephalitis, bulbar polio, and paralytic poliomyelitis. These manifestations may occur alone or in combination. About one third of young children who develop the major illness experience a biphasic illness with symptoms of the minor illness preceding onset of CNS disease (49; 115). The major illness often begins with an aseptic meningitis. One third of cases are limited to meningitis without detectable motor neuron impairment, which resolves within 5 to 10 days. Polioencephalitis can occur as well, manifesting as obtundation or agitation, autonomic dysfunction and upper motor neuron signs of spasticity, increased deep tendon reflexes, and Babinski signs. Muscle pains, muscle cramps, fasciculations, and radicular pain rarely occur without paralysis, which they precede by 24 to 48 hours.

Paralytic poliomyelitis accounts for only 0.1% to 2.0% of all poliovirus infections and can be divided into 3 types: spinal, bulbar, and bulbospinal (84; 50; 86). Muscle weakness is preceded by intense myalgias of the involved limbs and the axial skeleton, and it may be relieved by exercise. The hallmark of paralytic poliomyelitis is asymmetric motor paresis, which ranges from mild weakness of a single extremity to complete quadriplegia. Proximal limb muscles are more involved than distal, and legs are more commonly involved than arms. The reflexes are initially brisk and then become absent over time. The pace of development of the paresis ranges from several hours to several days. Rarely, a transverse myelitis with paraparesis, urinary retention, sensory complaints and signs, and autonomic dysfunction may be seen (99; 35). Bulbar poliomyelitis occurs in 5% to 35% of paralytic cases and most commonly affects the ninth and tenth cranial nerves.

Chronic poliomyelitis infections have occurred infrequently in children with immunodeficiencies who have received the live oral vaccine (103; 120; 118). Onset usually occurs several months after vaccination, and patients may present with a lower motor neuron paralysis or progressive cerebral dysfunction. As many as 20% to 30% of patients who recover from paralytic poliomyelitis experience new onset of slowly progressive muscle weakness, pain, atrophy, and fatigue many years after the acute illness, most commonly 3 to 4 decades after acute illness (61; 73; 74; 24). This is known as post-polio syndrome. Both muscle and joint pain are frequent. Patients with a history of bulbar poliomyelitis are particularly at risk of developing dysphagia as well as sleep-disordered breathing abnormalities.

Prognosis and complications

Morbidity and mortality in poliomyelitis vary depending on the severity of illness. Although a minor illness typically causes little or no sequelae, major illness can lead to muscle paralysis, respiratory arrest, and death. Case fatality is1.5% to 6.7%, assuming availability of optimal care (29). A study on a particularly virulent outbreak of wild poliovirus in the Republic of Congo found up to 92% of cases had residual paralysis 60 days after disease onset (96). Efficient surveillance and proactive case management may improve morbidity and mortality. Complications of poliomyelitis include respiratory distress often necessitating mechanical ventilation, dysphagia, and pneumonia (Kaplan 1951; 34; 37). Prolonged immobility may lead to decubitus ulcers and limb contractures (37). Provocative paralysis (which can occur following intramuscular injection) should also be anticipated when managing poliomyelitis.

Orthopedic issues include hip, back, and extremity pain; muscle strain; ligament sprain; spondylosis; kyphoscoliosis; exaggerated lumbar lordosis; genu recurvatum; and other deformities (25; 37).

In the past, poliomyelitis was probably the most common cause of an acquired quadrupedal human gait (as opposed to normal developmental or volitional quadrupedal gaits) (69; 70; 71).

Indeed, in a large series of patients hospitalized with poliomyelitis, 3 of 98 patients (3%) with disturbances of locomotion were noted to be “hand walkers” (among a total of 108 for whom function was recorded) (Hatt and Hough 1930). Note that the term “hand walkers” generally denoted those that walked with a quadrupedal gait but very rarely referred to individuals who learned to walk exclusively on their hands.

Sleep disturbances also occur more frequently and are most commonly associated with the bulbar variant of poliomyelitis (25; 33; 06).

Physical disabilities experienced often lead to emotional symptoms (37). Psychotherapy, group rehabilitation, regular follow-ups, and patient education methods can be used to improve mental status and overall well-being (33).

Patients with post-polio syndrome develop generalized fatigue, muscle weakness, atrophy, pain, fasciculations, cramps, and cold intolerance occurring several years (usually more than 15 years) after the acute episode (44; 25; 61; 73; 74; 24).

Clinical vignette

A 10-year-old boy living in Nigeria was brought to the pediatric emergency department for evaluation of a 2-day history of malaise and diarrhea, with both an increased frequency of stooling and the passage of watery, non-bloody stools. On examination, he was febrile with a temperature of 38.5 degrees Celsius. His abdomen was non-tender, and he had no palpable organomegaly. On neurologic examination, he was conscious and fully oriented but lethargic with mild neck stiffness. He had no cranial nerve palsy. Muscle tone was mildly reduced in the right leg compared to the left. Power was grade 4/5 on the Medical Research Council scale in the right ankle and 5/5 in all other muscle groups. Deep tendon reflexes were grade 1 at the right ankle and grade 2 at the other sites. Plantar response was flexor bilaterally. Sensory examination was unremarkable. Complete blood count, erythrocyte sedimentation rate, electrolytes, and stool (for microscopy, culture, and sensitivity) were ordered.

The following day, his motor strength was reduced to 3/5 in the right leg, and within 48 hours, it was 1/5 and 4/5 on the right and left legs, respectively. Blood count was unremarkable. CSF analysis revealed a mild increase in leukocytes (18 cells/µl) and protein (45 mg/dl). CSF glucose was normal (70 mg/dl). Stool was negative for pathogenic bacteria or blood. Stool samples were positive for wild-type poliovirus 1. He was maintained on bed rest, and specific instruction was given to be vigilant for respiratory distress and to avoid intramuscular injections.

Further interview with the mother revealed that the boy did not complete his polio immunizations as he had only the oral polio vaccine 1 at 6 weeks after birth but did not receive the second and third oral polio vaccine doses in the subsequent months. She could not remember if he had any booster doses at 18 months or later. Three weeks later, power was 2/5 on the right and 4/5 on the left legs.

Biological basis

Etiology and pathogenesis

Poliomyelitis is an infection caused by the polioviruses, which are human enteroviruses.

Three poliovirus serotypes are distinguished from one another by type-specific antisera (04). Before the introduction of poliovirus vaccines, naturally occurring polioviruses circulated in temperate climates with a marked seasonal variation resulting in peak activity between July and October and low levels between December and May. Poliovirus type 1 was responsible for 80% to 90% of all epidemics of paralytic poliomyelitis in the United States (09; 92).

Poliovirus, as with other enteroviruses, is most commonly spread by fecal-hand-oral transmission. After ingestion, the poliovirus implants in the oropharynx and small bowel and penetrates the mucosa via specialized microfold cells and other epithelial cells overlying submucosal lymphoid tissues (50; 93). After replication in the submucosal lymphatic tissue, the virus spreads to the lymph nodes, and then to the bloodstream (11). In a minority of infections, further replication of virus in reticuloendothelial tissues leads to a major viremia. CNS invasion is much more likely to occur during secondary viremia, but can infrequently occur during primary viremia. As demonstrated in experimental studies in primates, tonsils, mesentery lymph nodes, and intestinal mucosa are major target sites of viral replication (107). Early in the infectious process, poliovirus replication occurs in both epithelial cells (which accounts for virus shedding in the gastrointestinal tract) and lymphoid/monocytic cells in tonsils and Peyer patches (which accounts for viremia) (107). Genetic variants in innate immune defenses and cell death pathways may contribute to the clinical presentation of poliovirus infection (05).

The exact route through which poliovirus enters the CNS is unclear (89; 90; 91). There is some suggestion based on animal models that viral replication in skeletal muscles precedes transport of poliovirus to the spinal cord via the peripheral nerve (15). The anterior horn cells and other motor neurons are selectively vulnerable to poliovirus infection (12; 60; 45; 27). Mitochondria are important in poliovirus-induced apoptosis and mitochondrial dysfunction results from an imbalance between pro- and anti-apoptotic pathways (10). Pathologic changes occur within 1 to 2 days after poliovirus infects the neuron, and an inflammatory response ensues with meningeal, perivascular, and parenchymal infiltrates (14; 13; 58; 117). Nevertheless, individuals who have had polio experience denervation with subsequent reinnervation for many years.

Although the precise cause of post-polio syndrome is unknown, the cause is probably related to overstress or exhaustion of the residual surviving motor units following acute poliovirus infection. Terminal elements of surviving alpha motor neurons that sprout to reinnervate adjacent myofibrils following initial infection are believed to become overstressed (42; 03; 94; 106). Muscle fatigue in post-polio syndrome may be due to impaired activation beyond the muscle membrane at the level of excitation-contraction coupling or may have a central origin. Other possible mechanisms have been considered, including immunologic events and other virus-host interactions (28).

Epidemiology

Accurate prevalence figures estimating the number of survivors of poliomyelitis are not available (57).

Polio cases have decreased by over 99% since 1988, from an estimated 350,000 cases in more than 125 endemic countries to 42 reported cases in 2016 (37 wild-type and 5 vaccine-derived) (32; 38; 82; 83; 88; 40; 53). Due to the World Health Organization's polio eradication campaign, poliomyelitis due to wild-type virus has now been eliminated from the Americas, Europe, and Western Pacific, whereas cases in Africa and Asia have markedly decreased (21; 22). In 1994, the WHO Region of the Americas was certified polio-free, followed by the WHO Western Pacific Region in 2000 and the WHO European Region in June 2002. In 2014, the WHO Southeast Asia Region was certified polio-free, meaning that transmission of wild poliovirus has been interrupted in 11 countries stretching from Indonesia to India.

There are now 3 countries with endemic poliomyelitis—Afghanistan, Pakistan, and Papau New Guinea—and there are major threats to increasing polio outbreaks due to lack of accessibility to polio vaccines in these regions and neighboring areas (31; 79; 80; 77; 17; 54; 43). Afghanistan and Pakistan are the only countries that continue to have ongoing wild poliovirus type 1 transmission (52). The number of cases in Pakistan has increased markedly from 2018 to 2019 (from 8 to 80 cases as of November 7 of each year, respectively) due to a breakdown of vaccinations resulting from vaccine refusals, chronically missed children, community campaign fatigue, and poor vaccination management and implementation (52). The number of cases in Afghanistan has increased since 2017 (80; 77). Insurgent groups banned house-to-house vaccination in effect from May to December 2018 in most southern and southeastern provinces, leaving approximately 1 million children inaccessible to oral poliovirus vaccine administration (80). From January to April 2019 vaccination was allowed at designated community sites, but since April 2019 vaccination campaigns were banned nationally in Afghanistan (80). During March through June 2020, all campaigns were paused because of the coronavirus disease 2019 (COVID-19) pandemic (77). Since June 2018 it was confirmed that poliovirus is again circulating in Papua New Guinea after that country was polio-free for 18 years (43); the current outbreak is caused by vaccine-derived poliovirus, an indicator of low polio vaccine coverage in the country.

Nigeria was also recently among the countries with endemic poliomyelitis. However, the last confirmed case due to wild poliovirus type 1 in Nigeria was in August 2016 (17; 02). However, since 2018 circulating vaccine-derived poliovirus type 2 has emerged and spread from Nigeria to Niger and Cameroon; outbreak responses so far have not interrupted transmission (02).

Among the 3 wild poliovirus serotypes, only type 1 has been reported in polio cases or detected from environmental surveillance globally since 2012 (54; 52; 78; 80). Type 1 continues to be isolated regularly from environmental surveillance sites in Pakistan and Afghanistan, signifying persistent transmission (54; 52; 78; 80).

On September 20, 2015, the Global Commission for the Certification of Eradication declared that poliovirus type 2 has been eradicated worldwide. With that declaration, it was necessary to develop a new immunization regimen that addresses solely serotypes 1 and 3 using oral polio vaccine (to minimize the risk of vaccine-derived cases of type 2) (88; 111).

Vaccine-derived polioviruses (VDPVs) are rare strains of poliovirus that have genetically mutated from the attenuated strains contained in the oral polio vaccine. Normally, when a child is vaccinated, the weakened vaccine strains replicate in the intestine and enter the bloodstream, triggering a protective immune response. Like infections with wild polioviruses, vaccinated children typically excrete the vaccine strains of poliovirus for 6 to 8 weeks. Some of the excreted vaccine strains of poliovirus may mutate during replication, forming vaccine-derived polioviruses. If a population is under-immunized, there may be sufficient susceptible children for the excreted VDPVs to begin circulating in the community; and, with sufficient time of uninterrupted recirculation, vaccine-derived poliovirus may reacquire neurovirulence and are then called circulating vaccine-derived polioviruses (cVDPV). Prolonged replication of vaccine-derived polioviruses has also been observed in people with immune deficiency disorders; in the absence of an adequate immune response, such individuals may excrete immunodeficiency-related vaccine-derived polioviruses (or iVDPVs) for prolonged periods. Most of patients with iVDPVs stop excretion within 6 months and/or die. Finally, ambiguous vaccine-derived poliovirus (aVDPV) are vaccine-derived polioviruses that are either isolated from people with no known immunodeficiency or isolated from sewage whose ultimate source is unknown. As poliovirus serotypes are eliminated, it is necessary to continue to shift away from use of live attenuated vaccines to minimize the risk of vaccine-derived poliovirus cases.

Prevention

Vaccination has been essential in the fight to eradicate polio because the virus can only be transmitted from person to person, and vaccination breaks this cycle of infection. Both the inactivated poliomyelitis vaccine (the Salk vaccine) and the live, attenuated oral poliovirus vaccine (the Sabin vaccine) have been effective in decreasing the incidence of poliomyelitis (97; 19). Today, a person is considered fully immunized if he or she has received a primary series of at least 3 doses of inactivated poliovirus vaccine, live oral poliovirus vaccine, or 4 doses of any combination of inactivated poliovirus vaccine and oral poliovirus vaccine.

Previously, the benefits of oral poliovirus vaccine use (ie, intestinal immunity, secondary spread) outweighed the risk for vaccine-associated paralytic poliomyelitis, which occurred in 1 child out of every 2.4 to 2.5 million oral poliovirus vaccine doses distributed (119).

To eliminate the risk of vaccine-associated paralytic poliomyelitis, as of 2000, oral poliovirus vaccine was no longer recommended for routine immunization in the United States. Russia used oral polio vaccine from 1998 to 2007 and inactivated polio vaccine followed by oral polio vaccine from 2008 to 2014 (55). China began introducing inactivated polio vaccine at the end of 2014, and so far, it has been successful (121). However, oral poliovirus vaccine continues to be used in the countries where polio is endemic or the risk of importation and transmission is high. Prevention can also occur by stopping the spread of infection using good personal, family, and public hygiene.

The World Health Organization plans to withdraw all oral polio vaccines and switch to the sole use of inactivated poliovirus vaccine (98). However, this will only occur after global eradication of wild poliovirus has been certified, which will be at least 3 years after the last case of wild poliovirus infection (98). Given the most recent cases of polio, which occurred in February 2018 in Afghanistan, oral polio vaccine will not be withdrawn until at least 2022 (98).

Because poliovirus type 2 has been eradicated worldwide, the type 2 component of the oral poliovirus vaccine is targeted for global withdrawal through a switch from the trivalent oral poliovirus vaccine to a bivalent oral poliovirus vaccine (101). This change is intended to prevent paralytic polio caused by circulating vaccine-derived poliovirus type 2.

Differential diagnosis

A clinical diagnosis of paralytic poliomyelitis is usually straightforward in countries where polio has not been eradicated. A physician should have a high index of suspicion of polio in any patient presenting with acute-onset fever, nuchal rigidity, and asymmetrical flaccid muscle paresis with hyperesthesia and relative preservation of somatosensation. Absent or poor immunization history against poliomyelitis will also strengthen the clinical suspicion. Identification of poliovirus in stool or CSF confirms the diagnosis.

Other causes of acute flaccid paralysis include Guillain-Barre syndrome and acute transverse myelitis. Although polio is not as common as Guillain-Barre syndrome or acute transverse myelitis, the importance of correct diagnosis cannot be overemphasized due to its high risk of transmission (36).

Guillain-Barre syndrome is a leading cause of acute flaccid paralysis and presents as a rapidly progressive, symmetric flaccid paralysis; there may also be a distal paresthesia with CSF cytoalbuminologic dissociation early in the disease. Although myalgias and fever at onset of paralysis are prominent features in paralytic polio, they are not as common during Guillain-Barre syndrome (36).

Flaccid paralysis may also occur in the early phase of acute transverse myelitis; however, accompanying sensory symptoms (eg, anesthesia, paresthesia with a sensory level) and neurogenic bowel and bladder dysfunction differentiates it from polio (36).

In recent years, West Nile virus has increased in geographical spread. Although the neurologic manifestations of West Nile virus typically include meningitis and encephalitis, an acute flaccid paralysis may also occur, ranging from monoparesis to quadriparesis, with or without bulbar symptoms. Acute flaccid paralysis due to West Nile virus can be clinically difficult to differentiate from poliomyelitis. A history of mosquito bites, a “summer flu,” and acute flaccid paralysis may suggest West Nile virus in endemic areas.

Diphtheric polyneuropathy is a vaccine-preventable bacterial infection that can also produce fever and acute flaccid paralysis (commonly symmetric) and should be considered in the differential diagnosis of patients presenting with acute flaccid paralysis in countries where poliomyelitis and diphtheria have not been eradicated (81).

Other viral respiratory or gastrointestinal illnesses can present with features similar to the minor nonparalytic poliomyelitis (36). In addition, other non-polio enteroviruses (NPEV) have been found to be associated with acute flaccid paralysis (48). An acute flaccid paralysis surveillance report in India found Coxsackie and Echovirus the most common NPEV isolates implicated (72). In 2014, the United States experienced a nationwide outbreak of enterovirus D68 (EV-D68) in which a total of 1152 people, particularly children, in 49 states and the District of Columbia, were confirmed with respiratory illness.

During the outbreak, the Centers for Disease Control and Prevention was notified by the Colorado Department of Public Health and Environment of a cluster of 9 children evaluated at Children's Hospital Colorado with acute neurologic illness characterized by extremity weakness, cranial nerve dysfunction (eg, diplopia, facial droop, dysphagia, or dysarthria), or both (95). Enterovirus D68 has since been recognized as a cause of polio-like illness (07; 20; 65; Schuffenecker et al 2014; 76; 85; Williams et al 2015; 26). Isolated cases of poliomyelitis-like illness have been reported elsewhere since the 2014 United States outbreak (110).

The paralytic presentation of rabies virus infection (so-called “dumb” rabies) may also be confused with poliomyelitis. A history of an animal bite should warrant consideration of rabies (41). Outbreaks of dumb rabies have occurred in humans as a result of bites from vampire bats (66; 67).

Other conditions that may give a polio-like picture include spinal cord compression; tick, snake, or spider bite; botulism; and toxic substances such as arsenic (39; 07).

Diagnostic workup

Following a clinical suspicion of polio, it is imperative to confirm the diagnosis and report the case to the local and national public health department. Early detection will allow timely measures, such as successful vaccination, to limit the spread and promote eradication of poliomyelitis. Viral isolation, serology, and polymerase chain reaction assays can be used to confirm the laboratory diagnosis of poliomyelitis.

A laboratory diagnosis of poliomyelitis is made by isolation of the virus from stool or pharynx. Virus isolation is highest in stool, lower in the pharynx, and lowest in blood and CSF. CSF viral isolation, though rare, is diagnostic (114). It is recommended that at least 2 stool specimens and 2 throat swabs be obtained 24 hours apart from suspected poliomyelitis patients as early as possible (114). The frequency of obtaining samples increases the likelihood of viral isolation as there is intermittent shedding of the virus from the mucous membranes. Although poliovirus has been the most common enterovirus isolated in the stool in cases of acute flaccid paralysis, a small proportion of non-poliovirus infections can also be isolated (01).

The use of serological tests in the diagnosis of polio depends on the rise in antibody titer between the acute and convalescent phases; a serum specimen should be obtained as early as possible during the acute phase as well as 4 weeks later (convalescent phase). A 4-fold rise in titer between the acute and convalescent phase specimens suggests infection (114). False negatives can occur in the immunocompromised. Serology cannot differentiate wild virus from antibodies generated from vaccination. Serology is used to detect the degree of protection conferred by polio vaccination (109). Polymerase chain reaction can be used to differentiate between wild and vaccine types of poliovirus as well as the various strains of poliovirus (01).

CSF abnormalities are present in up to 90% of poliomyelitis cases. Typically, the CSF white blood cell count ranges from 10 to 200 cells/µl. A polymorphonuclear leukocytosis is followed by a mononuclear response. CSF protein is typically normal or mildly elevated (36).

Post-polio syndrome is a diagnosis of exclusion that is made based on evidence of new muscle weakness and/or muscle fatigability that is persistent for at least 1 year (73). Electromyographic and muscle biopsy findings, including evidence of ongoing denervation, cannot reliably distinguish between patients with or without post-polio syndrome (73).

Management

Initial treatment of paralytic poliomyelitis relies on supportive care, followed by passive, and then active, physical therapy and orthopedic measures. During the preparalytic stage, which would only be suspected during epidemics, bed rest is recommended because physical exercise can increase the severity of paralysis (59). In addition, sore muscles can be treated with hot packs, fever with acetaminophen, and anxiety with anxiolytics. Paralytic disease in the acute stage should be treated in a similar fashion as the pre-paralytic stage with the following additions: (1) hospitalization is required; (2) respiratory support on a ventilator may be required; and (3) appropriate positioning such as splints to prevent contractures, foot boards to prevent foot-drop, and frequent turning to prevent decubiti should be provided (100). Patients with bulbar involvement may require fluid and electrolyte support and additional support if cardiovascular, respiratory, or autonomic dysfunction occurs (113). Physical therapy is deferred until the convalescent stage, except for gentle passive range of motion to prevent contractures. During the convalescent period, active physical therapy with non-fatiguing muscle-strengthening exercises and hydrotherapy can be instituted. Patients with late and new effects of polio may need individualized multidisciplinary intervention and physiotherapy (08; 73; 74). Interventions may include adaptive equipment, orthotic equipment, gait/mobility aids, and a variety of therapeutic exercises (74).

Orthopedic surgical intervention (eg, arthrodesis, tendon transfers, leg-shortening measures) should be deferred for 1.5 to 2 years, after maximum recovery has been obtained (102; 56). For patients with residual effects of poliomyelitis, surgeons should optimize the position, choice, approach, and soft tissue tensioning because stability of prosthesis may be difficult to ensure and maintain (63).

Special considerations

Pregnancy

Pregnancy increases the incidence of paralytic disease by about 3-fold (104). It is unclear if this increased risk is related to hormonal changes or a greater exposure to small children (108).