The Current State

Abstract

Acute polio, once epidemic and a significant source of paralysis and disability, has been dramatically reduced through global vaccination programs. Although vaccination efforts have experienced a setback because of COVID-19, resulting in increased number of vaccine-associated and wild virus infections, polio eradication is still a realistic goal that will result in significant cost savings. The secondary health issues related to aging with the residual effects of polio, including postpolio syndrome, will persist for many years posteradication. Continued education of medical professionals is essential to ensure provision of the necessary care to this population.

Key points

• •Acute polio infections have been dramatically reduced through global vaccination programs.
• •The World Health Organization has designated five of the six world regions as polio-free, reporting no recent cases of wild polio virus infection.
• •Vaccination efforts have experienced a setback because of COVID-19, resulting in increased number of reported infections caused by wild virus in Afghanistan and Pakistan, the only countries with continued endemic polio virus, in 2020.
• •Postpolio syndrome will continue for many years after eradication of polio has been achieved as survivors of acute polio age with residual weakness.

Acute poliomyelitis

Polio Virus

Polio, or poliomyelitis, is the clinical presentation of infection with the poliovirus. The poliovirus is a member of the Enterovirus genus, Picornaviridae family. In the wild there are three serotypes: poliovirus 1, 2, and 3.¹ The virus is transmitted via excretion in feces and pharyngeal secretions with spread occurring in either oral-fecal or oral-oral manner. It then replicates in the gastrointestinal tract and can cause viremia and cross the blood-brain barrier.² Maximum virus excretion begins a few days before clinical symptoms and continues through the first week. The virus has a predilection for the anterior horn cells thus destroying motor neurons resulting in flaccid paralysis. It can also affect posterior horn cells, motor neurons of the thalamus, and hypothalamus.³ Although paralysis is the most widely thought of presentation of disease, most cases are subclinical resulting in mild flulike illness. It is estimated that 1% to 5% of cases cause “nonparalytic aseptic meningitis” and less than 1% result in permanent paralysis.^{4 , 5} Of the three serotypes, type 1 is most likely to cause paralysis, accounting for about 80% of cases.⁶

Acute Polio Infection

Clinically, patients present with a viral prodrome that may include any of the following: fever, headaches, neck stiffness, myalgias, fatigue, nausea, pharyngitis. The mild form of the disease usually subsides within a week. If the virus invades the central nervous system, severe muscle spasms and myalgias occur, which may be followed by asymmetrical flaccid paralysis, with sensory sparing. Muscle weakness is most profound during the acute stage of illness.

In the recovery stage, the paralysis may improve. Initial recovery is primarily through motor units recovering function. Secondary improvement occurs via axonal collateral sprouting, as residual motor units reinnervate adjacent denervated muscle fibers, resulting in enlarged or giant motor units. The recovery stage can last up to 2 years.⁷

Management of Acute Polio

Treatment during the acute and recovery stages is primarily supportive given that there are no antiviral medications approved for polio. Initially, management may include treatment of fever, prevention of respiratory infections and skin breakdown, and ventilatory support if respiratory muscles are affected. The paralyzed limbs are often splinted. Sister Elizabeth Kenny, an Australian nurse, introduced the notion of using hot packs to relieve muscle spasms. She also discouraged prolonged immobilization of the affected limbs.³ Contracture prevention is an important part of management. During recovery, more intensive therapy is introduced with the tenets of nonfatiguing exercise and gradual progression of mobility and activities of daily living training. Orthotics and assistive devices are commonly used to support and protect weak muscles and joints. Surgical intervention may be used to reduce limb length discrepancy, restore useful function through tendon and muscle transfers, or prevention of deformity through tendon lengthening or joint fusion. More severely involved survivors may be wheelchair dependent or require ongoing ventilator assistance. A significant number of polio survivors have lived their entire lives dependent on the iron lung.

Differential Diagnosis

Other enteroviruses (enterovirus E71/D68, coxsackievirus A), West Nile virus, herpes zoster virus, Japanese encephalitis, and rabies can all cause similar presentations to acute poliomyelitis with flaccid paralysis.^{8 , 9} Other potential causes of acute paralysis must also be considered including: acute inflammatory demyelinating polyradiculopathy, spinal cord infarction, myasthenia gravis, or rhabdomyolysis. Diagnostic tests used include: blood work, cerebrospinal fluid (CSF) analysis, stool tests, evaluation of respiratory function, electrodiagnostic studies, and central neuraxis MRI.

Prognosis

The extent and severity of paralytic polio symptoms is highly variable. Clinically, cases were identified as encephalitic, bulbar, spinal, or bulbospinal. In the early epidemics and in areas of the world with limited medical care, encephalitic and bulbar cases have a high mortality rate. The invention of the iron lung in 1928 with subsequent mass distribution at low cost significantly reduced the mortality rate.^{5 , 10} Resultant paralysis varies from apparent full recovery (with reduced number of motor units in functional muscles) to localized single limb weakness, patchy weakness, or complete tetraplegia. Bulbar involvement often results in cranial nerve deficits, dysphagia, and respiratory problems.

Epidemiology

Polio did not start as an epidemic disease. One of the first known historical references goes back to a stone plaque, the Stele of Ruma, from ancient Egypt that dates back to the thirteenth century bc on which a priest with an atrophied limb and crutch is depicted. There were sporadic descriptions of acute febrile illness with paralysis, but few cases reported in the medical literature.¹¹

In the late nineteenth century, reports of more widespread outbreaks in the United States and European countries started to appear.¹² By 1913, polio had been reported in every state with the first major US epidemic occurring in New York City in 1916.¹³ Epidemics occurred regularly throughout the 1920s to 1950s, but were limited to Europe, United States, and Canada. The most prominent theory as to why the epidemics were localized to the western world is that with the development of improved sanitation, transmission of enteric infections was delayed until infants were older than 12 months, when the number of passive infant antibodies were reduced. Before the epidemic times, polio is thought to have been so common in the environment that infants were infected early in life when they had antibodies from their mothers, likely enough to prevent viremia and invasion of the central nervous system with subsequent paralysis.¹¹

From the early 1900s through 1955 when the vaccine was introduced, the age distribution of those affected gradually increased, with the prevailing theory being because of reduction in circulation of the virus resulting in fewer early infections.¹⁴ Longitudinal data from Sweden demonstrated that the rate of paralytic cases to number of infections does not increase with age, but the severity of the paralysis and fatality increases in the older population.¹⁵ As public health improved in less developed countries, outbreaks of polio increased in those countries.¹³

Vaccine

The history of the development of the National Foundation for Infantile Paralysis, later to become the March of Dimes, which provided the funding and incentive that led to the race to develop a vaccine for polio, is a fascinating story.¹⁶

Albert Sabin and Jonas Salk were the primary scientists involved in vaccine development. The Salk vaccine, an inactivated polio vaccine (IPV) that is injected intramuscularly, was announced on April 12, 1955. The Sabin vaccine, the oral polio vaccine (OPV) that uses attenuated virus, became available in 1961. After release of the Sabin vaccine, the benefits of increased immunogenicity in the community through spread of the weakened live virus from those immunized (children) to others (adults and unvaccinated children) and easier administration led to predominate use of the OPV.

There is risk of vaccine-related polio infection caused by the OPV. The vaccine-induced polio (VAPP) occurs in an estimated 1 to 2 cases per million primary immunizations among vaccines and their close contacts. When entire families are vaccinated, almost all cases occur in vaccines; when immunization was only given to children, cases occurred in about equal numbers among close contacts. About 20% of vaccine-associated infection was reported in children with immunodeficiency. The risk of VAPP varies by serotype with normal vaccines at highest risk from type 3 virus, immunodeficient recipients, and contacts at highest risk from type 2. As of 1997, the US immunization recommendation was changed to one dose of IPV before OPV. In 2000 the recommendation was to use IPV exclusively, eliminating cases of VAPP in the United States.¹⁷

Polio Eradication

As the vaccines were disseminated through the United States, the incidence of polio fell dramatically. The last cases caused by indigenous wild poliovirus occurred in 1972. Subsequent cases in the United States were either vaccine-associated or imported.¹⁸ In 1979 the United States was declared polio-free, although vaccine associated cases continued into the 1990s.

The eradication of wild poliovirus in the United States was not initially expected, but with the success of the vaccination programs in the developed countries, eradication of wild polio in other regions became plausible. Success in Cuba and Brazil led the Pan American Health Organization to start an aggressive campaign to eradicate the virus in the Americas. The program included routine pediatric immunizations supplemented by mass immunization days and mop-up in outbreak areas, providing at least three doses of the OPV to about 80% of children by the age of 1 year.¹⁹

With the success of the eradication campaign in the Americas, in 1988 the World Health Assembly established the Global Polio Eradication Initiative (GPEI) with a goal for global eradication of the wild polio virus.²⁰ The GPEI is a public-private partnership, which includes the World Health Organization (WHO), the United Nations Children’s Fund, the US Centers for Disease Control and Prevention, the Bill and Melinda Gates Foundation, and Rotary International.²¹ The initiative has been successful, but an early goal of global eradication by the year 2000 was not achieved. Worldwide cases were reduced from approximately 50,000 in 1980 to less than 1000 in 2001. By 2001, the number of countries with endemic wild polio had been reduced from more than 100 to less than 10. The original goal of eradication by the year 2000 has been delayed because of several factors.

Factors leading to delay in polio eradication:

• •Interruption of transmission of the virus is more difficult in tropical climates that lack seasonal variation in case numbers.²²
• •Administration of OPV to children concurrently infected with other enteroviruses is less effective.
• •Conversion rates with use of trivalent OPV (protective against serotypes 1, 2, and 3) is lower than with monovalent.
• •Emergence of vaccine-derived polio virus (cVDPV), which occurs when the attenuated virus in the oral vaccine regains virulence circulating in an underimmunized population,²³ identified in 2000.
• •cVDPV outbreaks occur when less than 50% of children receive the recommended three doses of OPV during immunization programs.

The WHO certifies individual countries and world regions (Africa, Americas, Eastern Mediterranean, Europe, South-East Asia, and Western Pacific) as polio-free. To be certified, a region needs to: record no wild polio case for at least 3 years, have a reliable surveillance system, and prove its capacity to detect and respond to imported cases of polio.²¹

With the decline in incidences of poliomyelitis caused by the wild virus, the cases of paralysis from vaccine-associated paralytic polio and vaccine-derived polio virus became more frequent than those related to wild virus. More than 90% of the vaccine-derived cases were caused by type 2, the wild type of which had been certified as globally eradicated in 2015. In 2016, the GPEI and the WHO switched from the trivalent OPV to a bivalent OPV protective against serotypes 1 and 3. The GPEI also recommended that at least one dose of IPV precede routine immunization with OPV. In October 2019, eradication of WPV type 3, last detected in 2012, was certified.²³

In 2017, the virus was endemic in three countries: Nigeria, Afghanistan, and Pakistan. Nigeria has had no evidence of wild polio virus since September of 2016, and on August 25, 2020, Africa was officially certified as free of the wild polio virus.¹⁸

The most recent vaccination data from 2018 estimate global coverage of recommended routine immunization with three doses of poliovirus vaccine among infants younger than age 1 as 89%. Those receiving the recommended one full or two fractional doses of IPV is 72%.²⁴

Current Status

At this time, two of the three wild polio serotypes (type 2 and 3) have been eradicated. Wild polio virus serotype 1 remains persistent only in Afghanistan and Pakistan.

In 2019, Afghanistan and Pakistan reported a significant increase in the number of endemic polio infections, 176 cases.²¹ Between January 1, 2020, and August 12, 2020, 85 WPV1 cases were reported, compared with 64 year to date in 2019. Both countries continue to face problems with mobile populations, vaccine refusal, and polio campaign fatigue.²⁵ Continued political unrest in Afghanistan has led to temporary restrictions and banning of the vaccination effort.

In addition, since the change to bivalent OPV in 2016, type 2 cVDPV outbreaks have increased in number and countries reporting. To date in 2020, 210 cVDPV cases have been reported compared with 69 in 2019. Since 2018, cVDPV outbreaks have affected four of the six WHO world regions (Africa, Eastern Mediterranean, South-East Asia, and Western Pacific). Outbreaks are treated with monovalent OPV2 vaccines. A new genetically stabilized novel OPV2 (nOPV2) with lower risk of conversion to virulent form has been developed for distribution later this year.²⁶

Impact of COVID-19

In March 2020, GPEI committed its laboratory and surveillance network and workers to support preparedness and response to the COVID-19 pandemic. This included postponing outbreak response mass immunization campaigns until June and preventive mass immunization campaigns until the second half of 2020. Surveillance continued, although with disruptions. In July 2020 outbreak responses resumed but preventative campaigns are still on hold.²⁷

Pakistan and Afghanistan are fighting increased numbers of wild virus cases and outbreaks of vaccine-related polio virus infections. It is essential that community engagement and trust be re-established and the management and provision of health services improved to reach the chronically missed children.²³

Endgame

It is estimated that since it was started, the GPEI has prevented 18 million cases of paralysis and 1.5 million childhood deaths. Eradication of polio will translate into significant economic savings, estimated at $40 to $50 billion US dollars (in vaccination costs and in relation to impact of the disease). More importantly, it will mean elimination of lifelong paralysis caused by the polio virus, postpolio syndrome, and its subsequent impact on health and society.

Postpolio syndrome

History

The diagnosis of postpolio syndrome gained recognition in the 1970s and 1980s when several acute polio survivors started to present with new symptoms of increased weakness and fatigue.²⁸ Although the sequelae of the polio epidemics was not felt until this time period, the first reported cases of postpolio syndrome can be traced back to 1875, when French neurologist Jean Martin-Charcot described three young men, who all had polio as infants, and who developed new-onset weakness and atrophy during their adult years.²⁹ Early reports in the medical literature used several different terms to describe the symptoms that polio survivors were experiencing, including “postpolio muscular atrophy,” “the late effects of polio,” “postpolio sequelae,” and “postpolio syndrome.”

In 1984, a scientific conference for clinicians and researchers was held at the Roosevelt Warm Springs Institute for Rehabilitation to define postpolio syndrome. The conference attracted the attention of the news media, many of whom attended the final day. Reports sparked fear of polio virus reactivation and another polio epidemic. The interest generated by this false narrative led to increased research and the establishment of multiple support groups and 96 specialty clinics in response to deal with what had yet to be recognized as postpolio syndrome. A subsequent conference at Warm Springs Institute in 1986 helped to further legitimize postpolio syndrome as a greater number of researchers from seven countries presented evidence that postpolio syndrome was a distinct clinical entity.²⁸

Despite the increasing number of cases of polio survivors presenting with new weakness and expanding medical literature on the subject, postpolio syndrome was not fully legitimized as a diagnosis until 1994. A conference hosted by the National Institutes of Health and the New York Academy of Sciences brought together prominent polio researchers from across the globe²⁹ to present and discuss current understanding. Today, postpolio syndrome is a well-recognized entity; however, much remains unknown about pathophysiology and the true prevalence.

Current Prevalence

The true prevalence of postpolio syndrome remains unclear. Because no national database of polio survivors exists, it is difficult to ascertain accurate disease statistics. In 2010, the March of Dimes estimated that there were between 10 and 20 million polio survivors globally. More recently in 2016, Groce and colleagues³⁰ narrowed that estimate to 15 to 20 million with an estimated 573,000 survivors in the United States. Because of the nature of the disease, many cases of mild polio may be missed in the estimates. Given that the estimate of polio survivors is fundamentally inaccurate, it follows that the number of survivors who develop postpolio syndrome shares the same inaccuracies.

Prevalence ranges for postpolio syndrome are generally broad and highly variable. One 1994 to 1995 survey estimated that the prevalence of postpolio syndrome ranged from 11% to 25%,²⁸ but Ramlow and colleagues³¹ estimated that the prevalence of postpolio syndrome may be up to 78%. In 2005, Ragonese and colleagues³² published an estimate of 20% to 100%. The reasons that the estimates vary so greatly include variation in populations studied, differing diagnostic criteria used for assessment, and variable study duration.

Pathogenesis

Although postpolio syndrome is now a well-recognized entity, pathophysiology is not completely understood. The most widely accepted theory was proposed by Weichers and Hubbell³³ in 1981. They hypothesized that the symptoms of new muscle weakness and fatigability are caused by distal degeneration of axon sprouts supplied by enlarged motor units that developed during the recovery of acute polio resulting in denervation of muscle fibers.³³ This theory has been supported by histologic studies that found isolated, angular, atrophic fibers on muscle biopsy of postpolio patients. This implies local denervation as opposed to entire muscle group atrophy indicative of the loss of entire motor units, such as in amyotrophic lateral sclerosis.³⁴ Although this hypothesis provides a general framework for the pathophysiology of postpolio muscle weakness it does not delineate factors that may contribute to the distal axonal sprout degeneration.

Other hypotheses have expanded on the explanation proposed by Weichers and Hubbell. The normal process of aging has been postulated to have a significant effect on the development of postpolio syndrome. The neuromuscular sequelae of normal aging include: a reduction in the total number of muscle fibers and motor units, sarcopenia, lean tissues loss, and decreased strength because of deconditioning. When these consequences are superimposed on the already limited number of motor neurons caused by polio infection it may contribute to progressive loss of strength and lead to development of symptoms consistent with postpolio syndrome.^{34 , 35} Aging has also been shown to decrease levels of circulating growth hormone and insulin-like growth factor-1. These hormones have been linked with the development of axonal sprouting and muscle fiber hypertrophy; therefore, their absence may contribute to the degeneration of distal axonal sprouts. Although there seems to be significant rationale for the contribution of aging to the development of postpolio syndrome, studies have been conflicting in confirmation of aging as a risk factor.³⁶

Overuse myopathy has also been theorized as a mechanism contributing to the development of postpolio syndrome. Some studies have described the finding of elevated creatine kinase in symptomatic patients directly correlated significantly with distance of ambulation, the implication being that increased activity contributes to the development of postpolio syndrome.³⁷ Peach³⁸ reported a case where clinical intervention of reduced activity resulted in symptom resolution and decline in serum creatine kinase.

Theories of poliovirus reactivation or persistence have been controversial. Studies have described the presence of poliovirus RNA in the CSF of patients with postpolio syndrome but additional studies did not confirm either viral fragments or poliovirus-specific immunoglobulin antibodies.³⁹ An immune or inflammatory response to these viral fragments has been postulated based on increased levels of proinflammatory cytokines in the CSF of postpolio patients leading to clinical trials of intravenous immunoglobulin treatment of postpolio syndrome.⁴⁰ Not all patients respond to treatment and further evaluation of responders and nonresponders has led to a hypothesis that the pathogenesis may vary.⁴¹

In summary, there is no consensus for the exact pathophysiology of postpolio syndrome. Wiechers and Hubbell proposed the most widely accepted hypothesis that seems to explain the development of the new muscle weakness reported in postpolio syndrome. Other explanations, such as factors associated with aging, overuse myopathy, and immunologic response, may contribute to pathophysiology. It is likely that not all patients have the same pathogenesis but rather a combination of etiologies that contribute to the symptoms of postpolio syndrome.

Diagnosis

A specific diagnostic test for postpolio syndrome does not exist; however, diagnostic criteria have been developed by a consensus of experts. These criteria have changed over the years. The guidelines that are the most widely accepted currently were published in 2000 by the March of Dimes (Box 1 ).⁴² The most common complaint exhibited by patients is either fatigue or weakness. With an aging patient population these symptoms are experienced in a wide range of diagnoses spanning multiple organ systems.³⁶ For this reason, many tests may be necessary to arrive at the diagnosis of postpolio syndrome given it is a diagnosis of exclusion. MRI of the lumbar spine and electrodiagnostic studies can assess for spinal or peripheral nerve or muscle pathology. Laboratory work, such as complete blood count, complete metabolic panel, and thyroid studies, can assess contributing factors of anemia, electrolyte imbalance, and hypothyroidism. Pulmonary function testing and sleep studies may identify sleep apnea or hypoventilation with hypercarbia. These tests serve to exclude diagnoses other than postpolio syndrome as explanatory etiologies for presenting symptoms; they do not provide findings that are sensitive or specific to postpolio syndrome. Although identification of concurrent problems does not confirm diagnosis, medical management of identified contributing conditions can reduce the symptoms of postpolio syndrome.

Box 1. March of Dimes criteria for postpoliomyelitis syndrome.

• Prior paralytic poliomyelitis with evidence of motor neuron loss, as confirmed by history of the acute paralytic illness, signs of residual weakness and atrophy of muscles on neurologic examination, and signs of denervation on electromyography.

• A period of partial or complete functional recovery after acute paralytic poliomyelitis, followed by an interval (usually 15 years or more) of stable neurologic function.

• Gradual or sudden onset of progressive and persistent new muscle weakness or abnormal muscle fatigability (decreased endurance), with or without generalized fatigue, muscle atrophy, or muscle and joint pain. Sudden onset may follow a period of inactivity, or trauma or surgery. Less commonly, symptoms attributed to postpolio syndrome include new problems with breathing or swallowing.

• Symptoms persist for at least 1 year.

• Exclusion of other neurologic, medical, and orthopedic problems as causes of symptoms.

Summary

Eradication of acute poliovirus is still an achievable goal that despite recent setbacks because of Covid-19 should be attainable in the next decade. Despite decreasing numbers of acute polio infections, postpolio syndrome will remain a clinical problem for many survivors of paralytic polio as they age for years to come. Clinicians need to be educated and aware of the conditions associated with sequelae of polio to provide the needed medical care and rehabilitation interventions that this population requires.