Poliomyelitis

Etiology

Poliovirus, enterovirus subtype C, is a small, single positive-stranded ribonucleic acid virus that is acid-resistant, non-enveloped, and encapsulated. This causative agent of acute polio and postpolio syndrome belongs to the family Picornaviridae and reproduces only in humans and some great apes. Poliovirus is extremely contagious, with seroconversion occurring in more than 90% of household contacts.[8] Wild poliovirus (WPV) has 3 distinct serotypes (1, 2, and 3), each with a slightly different capsid protein (WPV1, WPV2, and WPV3). Surviving an infection confers complete and lifelong immunity, but only to the specific infecting serotype.[GPEI. Polio Eradication]

Vaccine-associated paralytic polio (VAPP) and circulating vaccine-derived polioviruses (cVDPVs) cause illness that is clinically indistinguishable from poliomyelitis caused by WPV.[WHO. Vaccine Position] VAPP results from the proliferation and mutation of polioviruses in OPV recipients or their contacts. Replicating viruses in the intestine revert to neurovirulent variants demonstrating close genetic similarity to the vaccine strain. VAPP is an adverse event triggered by immunization and is reportable under the Vaccine Adverse Event Reporting System.

VDPVs result from the naturally selective proliferation of OPV viruses in populations with low herd immunity (cVDPVs) or prolonged carriage in immunocompromised individuals (iVDVPs). Recombination with other enteroviruses or reversion of OPV strains allows the resulting cVDPVs to regain the neurovirulence and transmissibility of WPV.[9][WHO. Vaccine Position] Genetic divergence of cVDPVs from the attenuated OPV virus indicates prolonged replication and circulation. cVDPVs derived from OPV type 2 (cVDPV2) are the most common, although cVDVP types 1 and 3 also occur.

Epidemiology

Poliovirus primarily spreads via the fecal-oral route and less commonly via respiratory droplets or oral-oral contact with nasopharyngeal secretions.[CDC. Polio_HCP][9] In temperate climates, infections occur more commonly during the late summer and fall. Children younger than 5 face the highest infection risk, although unvaccinated individuals of any age can become infected.[8] The infection is asymptomatic in 75% to 90% of patients.[WHO. About_Polio][CDC. About Polio] Central nervous system invasion resulting in paralytic disease occurs in up to 1 in every 200 patients with a poliovirus infection. The mortality rate of paralytic polio can be as high as 20%, although most references cite a rate closer to 10%.[CDC. Polio_HCP] The risk and severity of paralysis increase with patient age and immune status.[WHO. Vaccine Position] The incubation period is usually 7 to 10 days but may range from 4 to 35 days.[WHO. About_Polio]

Polio has afflicted humans since ancient times, first exposing infants at an early age when maternal antibodies are present and then repeatedly over the lifetime, resulting in persistently high antibody levels. As such, paralytic polio was likely uncommon.[10][11] With the advent of modern sanitation, medical anthropologists believe early exposure to poliovirus became less common, and maternal antibody levels decreased, leading to massive outbreaks with high rates of paralysis in the early 20th century.[11][GPEI. Polio History] By the mid-20th century, the virus killed or paralyzed about 500,000 people worldwide yearly. A United States (US) outbreak in 1916 killed more than 8000 people; another in 1952 killed 3000 and resulted in 20,000 cases of paralysis.[9] Case rates in the US dropped by 99% only 6 years after the first poliovirus vaccine became available.[9] The most recent case of WPV acquired in the US was in 1979. The most recent case in all of the Americas occurred in 1991.[CDC. Yellow_Book] WPV1 has been the primary cause of most of the world's paralytic polio cases throughout history and is the only circulating subtype; WPV1 remains endemic in Pakistan and Afghanistan.

In 1988, 350,000 cases of endemic poliomyelitis occurred across 125 countries. Based on success in the Americas, the World Health Assembly adopted a resolution to eradicate WPV worldwide by 2000 under the Global Polio Eradication Initiative.[12][GPEI. Polio Eradication][CDC. VPD Manual_Polio] While eradication remains elusive, establishing the polio vaccine in routine childhood immunization schedules has led to a greater than 99.9% worldwide reduction in WPV cases since 1988.[GPEI. Polio Eradication] The declaration of WPV2 eradication occurred in 2015, 6 years after the last case was reported in India. The WHO declared the eradication of WPV3 in October 2019, 7 years after the last reported case. The WHO declared Africa polio-free in 2020. A worldwide low of 6 cases of WPV1 was reported for 2021.

Sporadic outbreaks continue to occur, including in countries previously declared polio-free. From late 2021 to early 2022, WPV1 caused paralytic polio in 9 patients in Malawi and Mozambique; this outbreak was traced to a transmission in Pakistan.[13] The total number of reported WPV1 cases was 22 in 2022 and 12 in 2023. The WHO reported 23 cases between 2023 and 2024, for which recent statistics are available.[GPEI. Polio Eradication] When polio is reintroduced into a country, transmission must be traced and halted within 12 months for that country to maintain polio-free status.[13]

VAPP is extremely rare, occurring an estimated 0.42 times per million doses of OPV [9][14][CDC. VPD Manual_Polio] or 3.8 times (range 2.9 to 4.7) per million births in countries that use trivalent OPV.[6][14][WHO. Vaccine Position] In high-resource countries, VAPP occurs most commonly after the first dose of OPV. In immunocompromised individuals, the risk of VAPP is approximately 3000 times higher than in healthy patients.[9] In low-resource countries, VAPP primarily affects children aged 1 to 4 receiving second or subsequent doses.[14][WHO. Vaccine Position] Providing IPV before OPV reduces or eliminates VAPP risk.[WHO. Vaccine Position]

First detected in an outbreak on the island of Hispaniola in 2001, cVDPVs are responsible for most cases of poliomyelitis today. cVDPV-associated paralysis occurs primarily in sub-Saharan Africa and Asia. A total of 345 people reported an onset of paralysis in the 12 months leading up to July 2024. Forty-nine cases of cVDPV type 1 were reported in Mozambique, DR Congo, and Madagascar, and 296 cases of cVDPV type 2 were reported in 20 other countries.[GPEI. Polio Eradication] This is a reduction from 881 total cases in 2022 and 524 in 2023. While the number of cases in 2023 was reduced compared to 2022, cVDPV cases were more widespread geographically in 2023.[3]

In 2022, an unvaccinated young adult from New York presented with acute flaccid paralysis; stool testing revealed VDPV2. Environmental testing of samples taken before and after the patient's illness onset subsequently found VDPV2 in wastewater in surrounding counties. The virus was likely imported from a country that administers OPV but where the population remains under-vaccinated. In addition to this case, a case of polio in a young boy in Gaza, sporadic cases of WPV polio in Africa, and the discovery of cVDPV in wastewater across multiple countries, including the United Kingdom and Israel, emphasize the importance of maintaining high vaccination rates across all populations until polio is eradicated globally. For further information on vaccination rates in the United States and globally, see StatPearls' companion article, "Polio Vaccine."

Pathophysiology

Following exposure, poliovirus replicates in oropharynx and gastrointestinal tract tissues. Maternal antibodies or those acquired during a previous infection or oral vaccination often confine the virus to these tissues.[9] In the absence of antibodies, a typically transient and asymptomatic viremia occurs.[9] However, in a small minority of viremic cases, the virus enters the central nervous system (CNS) by crossing the blood-brain barrier or via peripheral nerve retrograde axonal transport.[9] Depending on the virus type and location of invasion, CNS invasion causes non-paralytic aseptic meningitis in up to 5% of symptomatic infections.[CDC. Polio_HCP] CNS invasion can also result in infection and destruction of alpha motor neurons in the anterior horns of the spinal cord, the cranial nerve nuclei of the medulla oblongata, and the pons and midbrain. Inflammatory infiltration of these motor neurons causes cell destruction and eventual glial cell scarring.

For patients who recover from acute polio, regeneration of reversibly damaged neurons, collateral axonal sprouting, and the development of other reparative and compensatory processes can result in the slow improvement of paralysis.[15] Human axons may be able to reinnervate as much as 5 times their original muscle fiber territory. In chronic cases, de-innervated muscles atrophy and cause functional disorders of the limbs, trunk, and respiratory muscles, including the diaphragm. In children, deformities progressively develop due to the influence of muscular imbalances or dysfunction on the growing skeleton. This can result in joint contractures, kyphosis, scoliosis, foot deformities, or leg-length discrepancies. Chronic overloading results in joint instabilities, degenerative changes, and pain.[15] Following infection, immunocompetent individuals develop complete immunity to poliovirus, which involves various mucosal and humoral immune responses. Mucosal immunity reduces viral replication and excretion, thereby reducing transmission risk.[WHO. Vaccine Position] Therefore, patients with B-cell immunodeficiency are at an increased risk of paralytic disease and prolonged shedding.

Histopathology

Enlarged motor neurons are characteristic but not pathognomonic of infection with poliovirus. In acute poliomyelitis, poliovirus destroys the original innervating neurons in the muscle fibers. Neighboring neurons attempt to reinnervate the denervated tissue; this leaves the surrounding motor units innervating more muscle fibers than before. This extra workload enlarges the affected neuron and is suspected to be part of the fatigue associated with post-polio syndrome later in life.[16]

History and Physical

Until it is eradicated globally, clinicians must consider polio in the differential diagnosis of patients presenting with acute flaccid paralysis. The rapid onset of pure motor deficits without sensory or cognitive involvement following a flu-like prodrome is suggestive of paralytic polio. However, not all patients with acute polio report a prodrome. Various conditions can cause acute onset flaccid paralysis, and the clinician must differentiate between poliovirus infection, other viral infections, and noninfectious causes. Disease caused by cVDPVs is clinically indistinguishable from that caused by WPVs. More information can be found in the Differential Diagnosis section.

Obtaining a thorough medical history and performing a comprehensive neurological exam are crucial. In addition to a complete review of systems, the history must include the patient's vaccination status, recent travel, ill contacts, recent attendance at large gatherings, socioeconomic status, and living situation. Clinicians should consider polio in patients with sudden-onset limb weakness and a history of fever or gastrointestinal symptoms. This suspicion should be heightened further for patients who are also incompletely vaccinated or unvaccinated and residing in or have recently traveled to regions with known polio transmission or in contact with someone who has traveled to such an area. The cranial nerves should be examined, and reflexes, tone, and strength in all limbs should be documented. Adequate hand hygiene and contact precautions must be observed during the physical examination of any patient with suspected polio.

The acute, prodromal, or pre-paralytic stage of poliovirus infection is similar to many other viral illnesses; fever, malaise, headache, myalgia, fatigue, nausea, vomiting, abdominal pain, and sore throat are commonly observed.[WHO. About_Polio] In almost all cases, the infection resolves in 2 to 10 days without further sequelae.[WHO. About_Polio]  Meningitis develops within a few days after the prodrome resolves. While usually asymptomatic, recurrent fever, neck stiffness, back pain, and muscle spasms may be observed. These symptoms resolve within 2 to 10 days, typically resulting in a rapid and complete recovery.[WHO. Vaccine Position] The return of the fever with severe muscle pain, fasciculations, spasms, and hyperreflexia occurring 1 to 3 days after apparent recovery heralds paralytic polio.[WHO. Vaccine Position] Weakness or flaccid paralysis ensues in an asymmetric distribution, with proximal to distal progression. Maximum paralysis is reached within 2 to 4 days, rarely progressing further after fever resolution.[CDC. Polio_HCP][CDC. Polio_HCP]

The clinical manifestations depend on the site of viral invasion and the extent of viral replication, resulting in paralysis with a variable distribution and severity, affecting whole or parts of muscles or entire muscle groups. In most cases, spinal paralysis results in paralysis of the muscles of the lower limbs and, less commonly, of the arms, trunk, or diaphragm.[WHO. About_Polio][8] Autonomic dysfunction occurs infrequently, resulting in bladder emptying problems, constipation, or sweat secretion abnormalities. Poliovirus can invade the bulbar aspect of the brain, affecting the control of breathing and other vital functions, as well as the muscles for facial and eye movements and swallowing. Bulbar invasion can lead to respiratory insufficiency, vegetative crises, tachycardia, hypertension, and collapse. Fortunately, invasion of this severity rarely occurs.

Evaluation

Rapid investigation of acute flaccid paralysis is critical to identifying a possible polio infection and implementing control measures. Poliovirus infection is assessed through viral cultures or detection of viral ribonucleic acid in stool or throat irrigation or swabs.[CDC. Polio_HCP] The CDC recommends 2 specimens taken at least 24 hours apart during the first 14 days after the onset of paralysis. Specimens must be maintained at -20 ºC and shipped frozen.[CDC. Polio_HCP]

Clinical confirmation of polio requires 1 of the following:

• Poliovirus detected by sequencing of the capsid region of the genome by the CDC Poliovirus Laboratory
• Poliovirus identified in an appropriate clinical specimen (eg, stool [preferred], cerebrospinal fluid, oropharyngeal secretions) using a validated assay, AND specimen is unavailable for sequencing by the CDC Poliovirus Laboratory.[CDC. Polio_HCP]

Confirmed cases of nonparalytic poliovirus infections are those that meet laboratory but not clinical criteria. Maximum viral excretion in the stool and nasopharyngeal fluids begins 2 to 3 days before (and lasts for a week after) symptom onset.[17] However, the virus may be present in the nasopharyngeal secretions for up to 2 weeks and 3 to 6 weeks in the stool, even in asymptomatic individuals.[CDC. Polio][CDC. Yellow_Book] Finding poliovirus in cerebral spinal fluid is uncommon. A cerebral spinal fluid test result negative for poliovirus does not exclude polio.

Polioviruses undergo reverse transcriptase polymerase chain reaction testing following culture to differentiate between WPV and VDPVs. Serology is not helpful due to the high seroprevalence of anti-polio antibodies due to vaccination or previous asymptomatic infection. Researchers continue to seek direct molecular methods to diagnose polio, replacing culture-dependent methods.[WHO. Vaccine Position] Magnetic resonance imaging of the brain and spinal cord may identify typical patterns of poliomyelitis and rule out other pathologies, such as spinal cord infarction. Characteristic electromyographic findings develop later in the course of illness.

Treatment / Management

Supportive care is the mainstay of treatment for acute poliomyelitis, as no effective antiviral therapy exists. Therapy may include providing medication for fever and irritation, preventing respiratory tract infections, and managing respiratory paralysis via mechanical ventilation if required. Physiotherapists use splints to relieve pain and spasms; splints also play an imperative role in preventing the development of deformities. Following the acute stage, rehabilitation, exercise, counseling, and education help patients achieve their best functional status. Orthopedic surgery may be warranted to help patients walk and correct factors potentially leading to deformity as the patient grows and ages. Surgery may include joint contracture release, correction of muscle imbalances around the joint to prevent deformities, or correction of deformities.[18] Following phase 1 trials, the capsid inhibitor pocapavir is available for compassionate use in patients who cannot clear the virus due to primary immunodeficiency disorder.[WHO. Vaccine Position](B3)

Differential Diagnosis

Globally, acute flaccid paralysis occurs at a rate of about 1 of every 100,000 children younger than 15 per year. These are due to a wide variety of infectious and noninfectious causes. Other enteroviruses cause acute flaccid paralysis with greater frequency than poliovirus, including enteroviruses A71 and D68, coxsackievirus A, and rarely enteroviruses such as C105 and C109.[4] Like polio, enterovirus infections are frequently asymptomatic or present with a mild viral prodrome.[8] While paralytic polio predominantly affects the lower limbs, most other enterovirus-related acute flaccid paralysis have an upper extremity predilection.[19]

Other infections that may present similarly include adeno-associated virus, West Nile virus, varicella-zoster virus, Japanese encephalitis virus, rabies virus, and Clostridium botulinum.[20][21] A careful history and physical exam usually differentiate these infections from polio.[8] Noninfectious considerations include spinal cord infarctions, transverse myelitis, acquired axonal neuropathies, myasthenia gravis, and Lambert-Eaton myasthenic syndrome. Guillain-Barré syndrome is a common cause of acute flaccid paralysis, clinically differentiated from polio by ascending, symmetrical onset, sensory defects, and the absence of preceding meningeal symptoms.[8] See StatPearls' companion article "Acute Flaccid Myelitis" for more information on acute flaccid paralysis associated with other viruses.

Prognosis

Most poliovirus infections are asymptomatic or self-limiting. For those with poliomyelitis (ie, symptomatic poliovirus infection), 10% to 15% will die due to bulbar involvement, with respiratory and cardiovascular collapse. For those who survive, recovery and residual paralysis stages follow. Convalescence or recovery begins when the acute, flu-like illness resolves and no further paralysis occurs. Neighboring nerves or axonal regeneration reinnervates paralyzed muscles. Recovery can last up to 2 years, with maximal improvement occurring in the first 6 months. Approximately 60% of polio survivors have permanent deficits. The more severe the acute phase of the disease, the greater the likelihood of residual deficits and the development of postpolio syndrome in the future.[22]

Complications

Morbidity following paralytic polio commonly results from biomechanical alterations due to muscle weakness, imbalances of muscle power, deformities, and complications of polio-related surgeries.[15] Pain, easy fatiguability, limited function, and reduced quality of life are common. Osteoporosis develops due to lack of function and other factors, with frequent fractures.[15] Approximately 25% to 40% of patients with previous paralytic polio also develop PPS over their lifetime.[CDC. Polio_HCP] The diagnosis of post-polio syndrome (PPS) requires at least 1 year of new and progressive muscle weakness or fatiguability following decades of stable paralysis after the acute infection. Other symptoms include generalized fatigue, muscle or joint pain, worsening respiratory function, and dysphagia.[23] The true prevalence of PPS is not known, partly due to a lack of established biomarkers to diagnose postpolio syndrome.[24] While the prevalence of PPS is decreasing in industrialized nations due to the elimination of the virus, it remains highly prevalent in developing nations.

The pathogenic mechanisms resulting in PPS are incompletely understood. The most common theory involves degeneration of the enlarged motor units formed following the initial infection. Longitudinal research results demonstrate a parallel between a decreasing size and number of active motor units and a gradual strength decline in PPS.[15] The precise etiology of this decline is unclear; it likely results from the overuse of remaining motor units, stress-induced aging of motor units, deteriorating neuromuscular junctions, weight gain, deconditioning, and other factors.[18][25] Although some authors suggest subgroups of patients may have a predominantly neuroinflammatory pathogenesis of their PPS, recent evidence does not support the role of humoral or cellular pro-inflammatory processes.[6][25] Normal age-related sarcopenia contributes significantly and independently to decreasing muscle mass and strength; however, PPS may accelerate the decline in some patients, with an annual loss of up to 8% of muscle strength.[6]

PPS is a clinical diagnosis using Halstead, March of Dimes, or other criteria. Neither electromyography nor muscle biopsy reliably differentiates patients with or without PPS.[15] Clinicians must carefully exclude other treatable medical and orthopedic conditions that may cause or contribute to the condition.[15][24][25] Depending on the presenting symptomatology, the differential includes a wide variety of disorders, including the following:

• Metabolic: Iron deficiency, hypothyroidism, type 2 diabetes
• Sleep: Apnea, restless leg syndrome
• Inflammatory: Rheumatoid arthritis, polymyalgia rheumatica
• Chronic pain: Fibromyalgia

The severity and speed of progression are variable and are influenced by factors such as the severity of acute paralysis, age of onset, and socioeconomic status.[15][22][26] Complications include respiratory failure, fractures, decreased function, and worsening quality of life. Tailored muscle strengthening, aquatic conditioning, and pain control are the mainstays of treatment.[6]