The editors and current author would like to thank and acknowledge the significant contribution of the previous author of this chapter from the 2004 first edition, Dr. Rodney K. Yamaki. This current third edition chapter is a revision and update of the original author’s work.
This case takes place in 1997. A 4.5 month old female presents to the Emergency Room with weakness in her right leg. She is afebrile and does not appear to have any difficulty breathing. Her right leg appears flaccid with no deep tendon reflexes or Babinski that can be elicited. Sensation is intact. Her muscle tone, movement, sensation, and reflexes of her other limbs are normal. Her cardiovascular, respiratory and abdominal examination are normal. Upon further investigation, her father reports that she had a cough and fever of 38.3 degrees that resolved one week prior to presentation. Her father also notes both a normal birth history and appropriate well baby checkups. Her immunization records are up to date and at her 4 month visit (2 weeks prior to presentation), she received her 2nd doses of HiB, DTaP, and OPV.
A complete blood cell count (CBC) is normal and the cerebrospinal fluid demonstrates elevated white blood cells, elevated protein, and normal glucose. Radiographs of her spine and right lower extremity are normal. Electrophysiological studies (electromyography and nerve conduction studies) show absent motor responses to stimulation of her right tibial nerve. Fecal sample culture shows poliovirus type 3. The isolate is then sent to the Centers for Disease Control and Prevention (CDC) where the poliovirus is identified as a vaccine strain of poliovirus (not the wild-type strain). Serum immunoglobulins (IgG/IgA/IgM) are tested and found to be normal.
She is admitted to the hospital for treatment and monitoring. Her immunocompromised grandfather who changes diapers occasionally is informed about her spinal polio and is encouraged to seek medical attention. During her inpatient care, mechanical ventilation is not required and she does not experience any urinary or fecal difficulties. One week after admission, she is discharged with mild residual weakness of her right leg.
Poliomyelitis (or polio) is a disabling and potentially life threatening infectious neurological disease in which poliovirus, a neurotropic enterovirus, infects the motor neurons of the spinal cord and brainstem. Although wild polio had been previously eradicated in the U.S and most of the world, there are still areas of ongoing disease. Since wild polio has been eradicated from the western hemisphere, the more recent cases of poliomyelitis in the U.S. have been caused by the oral polio vaccine virus; a phenomenon known as vaccine associated paralytic poliomyelitis (VAPP) which is what the above case described. Also of concern in the U.S., is a late sequela of patients with previous poliomyelitis, called post-polio syndrome, which is a neurological disorder characterized by a new onset of muscle weakness occurring decades after the initial poliomyelitis infection (1).
Polio can be traced throughout recorded history. Egyptian murals depict a man (likely a priest) with an atrophied, shortened leg, characteristic of the late complications of polio (1). The first clinical description of polio was registered in 1789 when Michael Underwood linked this condition to the disease that affected the lower extremities of children (2). Since then, polio epidemics have plagued the world over the next centuries. The 1952 epidemic is widely known for infecting more than 50,000 Americans with a mortality rate of about 12%. The incidence of polio declined following vaccine developments by Jonas Salk in the 1950s and Albert Sabin in the 1960s.
Polioviruses belong to the Picornaviridae family (pico=small, RNAviridae=RNA virus), within the human enterovirus C species. As the family name suggests, the polioviruses are relatively small; its non-enveloped protein capsid of icosahedral symmetry measures less than 30 nm in diameter and contains single, positive-stranded RNA. Polio is caused by 3 different serotypes of the poliovirus: Poliovirus 1 (cause of the majority of cases), 2, and 3 (3).
Similar to other enteroviruses, poliovirus transiently inhabits the gastrointestinal (GI) tract, migrating then to the lymphatic tissues of the GI system and, less frequently, to the oropharynx. After attachment to specific human cell receptors, the single, positive-stranded RNA is uncoated in the cytoplasm where it translates into progeny protein capsids and replication enzymes. Replication of the genome is accomplished through a complementary negative strand, with the genome then assembled inside the protein capsids and released upon death of the host cell as new virions. Viremia follows resulting in systemic dissemination, eventually reaching the central nervous system (CNS). Virions are secreted into saliva and swallowed, allowing spread throughout the GI system. Viruses can be found, and shed from, the throat for 1 to 2 weeks and from feces for 3 to 6 weeks. In a minority of patients, the virus will spread to the nervous system either through viremia or via retrograde axonal transport from muscle to spinal cord and brain. Viral replication in spinal motor neurons of the anterior horn and the brain stem result in cell death and consequently acute flaccid paralysis and weakness of affected muscle fibers. Proximal muscles are affected more frequently than distal muscles with lower extremities affected more commonly than upper extremities (1). Weakness worsens over 2 to 3 days. Concurrent symptoms can include meningismus (nuchal rigidity, fever, vomiting, headache) and muscle pain. Nerve conduction studies and electromyography of patients with polio demonstrate selective injury to motor neurons.
Polio is a highly contagious disease. It spreads from person to person, via fecal-oral or respiratory routes. An infected person is most contagious from the moment immediately before the appearance of symptoms and for the following 2 weeks on average, when the virus is present in the throat and feces at high concentrations. Even people who don’t have symptoms transmit polio efficiently and inadvertently. Infants and young children hospitalized with polio should be under contact precautions for the duration of their hospitalization (3). Polio is a nationally reportable disease. Any case should be reported to the local Health Department and to CDC. The viral isolate should be referred for proper typing (wild-type vs. vaccine-type isolate).
There are various clinical presentations of polio infections (3) that can be grouped roughly into four presentations: 1) asymptomatic, 2) abortive, 3) nonparalytic aseptic meningitis, and 4) paralytic poliomyelitis. Asymptomatic poliomyelitis occurs in the majority (about 70%) of affected individuals. While these patients have no symptoms, they are infectious and shed the virus in their stool, potentially infecting their contacts. The second form is abortive poliomyelitis which occurs in about 25% of cases. These individuals undergo an incubation period of 9 to 12 days followed by 2 to 3 days of fever and nonspecific viral like symptoms: malaise, anorexia, nausea, vomiting, headache, sore throat, constipation, and diffuse abdominal pain. This subset does not present CNS complications, and patients usually undergo a complete recovery in less than a week.
The third form is the nonparalytic aseptic meningitis form of polio which occurs in 1% to 5% of all cases and involves meningeal irritation (5). This group exhibits prodromal symptoms that are similar to those listed in abortive poliomyelitis but is further complicated by posterior muscle stiffness of the neck, back, and limbs which can be accompanied by paresthesia. Meningeal irritation and muscle spasm will typically resolve after 2 to 10 days.
Paralytic poliomyelitis represents images of the typical polio patient, even though it occurs in less than 2% of cases. Paralytic symptoms can present 11 to 17 days after initial prodromal symptoms. Paralytic poliomyelitis can be classified into three types: spinal polio, bulbar polio, and bulbospinal polio. Spinal polio is the most common form and usually involves an asymmetric involvement of the legs and decreased deep tendon reflexes with no changes in cognition or sensation. Long-term, they typically suffer from musculoskeletal deformities such as leg-length discrepancies, joint malalignments, spinal deformities/scoliosis, and contractures. Bulbar paralytic poliomyelitis can present with dysphagia, nasal speech, and dyspnea due to paralysis of muscle groups innervated by the cranial nerves. Progression of the disease can result in respiratory insufficiency secondary to involvement of the thoracic muscles. Of historical interest, the iron lung was a negative pressure ventilator fitted outside the patient's body to chronically ventilate patients with respiratory paralysis.
The possibility of poliomyelitis should be investigated in all patients presenting with acute flaccid paralysis (with no obvious cause). Workup should include blood, cerebrospinal fluid (CSF), stool, and respiratory specimens (1). CSF typically shows a viral (aseptic) meningitis profile with moderate pleocytosis (10 to 200 cells/microliter, mainly lymphocytes), elevated protein (40 to 50 mg/dL) and normal glucose level (4). Viral culture is the most sensitive method, especially from fecal specimens (if possible, more than 1 specimen should be obtained, 24 hours apart, and early in the disease, e.g., in the first 14 days of illness). CSF culture is less sensitive. Polymerase chain reaction (PCR) testing is also helpful, especially for throat and CSF specimens. Serology is of limited value since most of the population has received polio vaccine (2).
Treatment of polio relies on supportive care, symptomatic pain relief (hot moist pack applied to muscles) and rehabilitation of affected muscles once paralysis progression has stopped. Hospitalization and bed rest are indicated in the acute phase of paralytic poliomyelitis to prevent worsening of the paralysis. Respiratory support (i.e., mechanical ventilation) is provided as needed if respiratory failure occurs. Patients with bulbar involvement would also require close monitoring of cardiovascular status due to blood pressure fluctuations, circulatory collapse, and autonomic dysfunction, sometimes requiring intubation to protect their airways (1,3).
The dramatic decrease in the incidence of polio worldwide is attributed to the use of two types of vaccines. Inactivated poliovirus vaccine (IPV) administered parenterally was developed in the 1950s and the oral poliovirus vaccine (OPV) was utilized in the 1960s. OPV induced GI immunity and it did not require an injection (5).
In the U.S, more than 35,000 cases of paralytic polio were reported in the 1940s (which represent only 1% of total world cases), decreasing to 10 cases in the 1970s. The U.S. started its polio vaccination campaign in 1955 with IPV, switched to OPV in 1963 and back to IPV in 1999. As a result, the last case of endemic polio in the U.S. occurred in 1979, and the last imported case in 1993 (1). In 1988 the World Health Assembly resolved to eliminate polio worldwide, and massive vaccination campaigns were started worldwide. The result has been a 99.9% decrease in polio cases from an estimated millions of cases in the 1980s to only single- or double-digit cases in the 2000s (7). Two of the 3 wild polio viruses are considered eradicated: poliovirus 2 in 2015 (last case seen in 1999) and poliovirus 3 in 2019 (last case seen in 2012). Only wild poliovirus 1 remains. In 2022, only 2 countries in the world continue to have wild polio circulation (9). In 2016, the world switched from trivalent OPV (tOPV) (serotypes 1, 2, and 3) to bivalent OPV (bOPV) (serotypes 1 and 3). Since bOPV does not protect against wild poliovirus 2, they have added a single dose of trivalent IPV to their regimen (7). More cases of polio are now caused by VAPP and circulation of vaccine-derived poliovirus (cVDPV) than by wild-type polioviruses. In 2019, there were only 29 cases of wild polio in 2 countries but 400 cVDPV cases in 22 countries (10). The ultimate end goal is to switch to IPV (always trivalent) as the only vaccine worldwide to avoid cVDPV and VAPP.
IPV (Salk vaccine), is now given for routine infant and childhood immunizations in the U.S. The American Academy of Pediatrics (AAP), American Academy of Family Physicians (AAFP), and the Advisory Committee on Immunization Practices (ACIP) recommend that all children receive four total doses of IPV with single doses at ages: 2 months, 4 months, between 6 to18 months, and between 4 to 6 years (1,3). Three doses are expected to induce seroconversion in >95% of infants (3,6). Advantages of IPV include excellent immunity, long-term duration of immunity, and it can be combined with other vaccines administered intramuscularly (e.g. diphtheria tetanus acellular pertussis, hepatitis B vaccine). It is safe for use in immunocompromised patients and their contacts. The disadvantages of IPV are its exclusive administration by injection, and its poor GI immunity. Decreased GI immunity can be a problem since it creates a situation whereby a vaccinated person will be protected against poliomyelitis, yet can still replicate wild-type polio virus in the GI tract, shed to the environment, and transmit to an unvaccinated, unprotected person.
Being a live, replicating viral vaccine, a unique set of problems for OPV is the occurrence of paralytic polio or polio outbreaks due to vaccine associated paralytic poliomyelitis (VAPP) or the circulation of vaccine-derived poliovirus (cVDPV). VAPP is a rare complication occurring in OPV vaccinated individuals, in which the vaccine strain reverts to its virulent form and causes paralytic polio. It is an unfortunate outcome, with an estimated frequency of 1 case per 2.4 million doses of OPV administered (3); more common among first dose recipients (1 case per 750,000 doses) and among persons with B-cell immune deficiencies and prolonged viral replication (3,4). Polio 3 strains were the main cause of VAPP in the US when OPV was used for routine immunization. VAPP caused the U.S. to switch from OPV to IPV (which does not cause VAPP). The other problem, cVDPV, occurs in regions with low immunization rates, where OPV is introduced, allowed to replicate in the community and eventually to acquire virulence that can cause outbreaks of its own, sometimes even leading to paralytic poliomyelitis (7). Since cVDPV is caused mainly by polio 2 strains and the last case of polio 2 in the world was detected in 1999, the WHO switched from trivalent OPV (tOPV) containing Polio 1, 2 and 3, to bivalent OPV (bOPV) formulations, containing Polio 1 and 3 only (8). Of course, that leaves the population unprotected against polio 2 and in the unlikely event of its reemergence (as in cVDPV-2), reimmunization campaigns can be conducted with either monovalent OPV2 (mOPV2), trivalent OPV (tOPV), or IPV (which always has been and remains trivalent). This attests to the difficulties of eradicating polio worldwide.
OPV (Sabin vaccine) is still used to control the transmission of poliovirus in developing countries. According to the World Health Organization (WHO), bOPV is routinely used for infant immunization worldwide at birth and at 6, 10, and 14 weeks of age plus an IPV dose with the 14 week bOPV (7). The advantages of OPV are its low cost, easier administration, superior GI immunity, and excellent immunity against the serotypes contained in the vaccine. For those reasons, in the unlikely event of wild-type poliovirus outbreak anywhere in the world, OPV is preferred for rapid and efficient control (7). The main disadvantage of OPV is that, being a live vaccine, it is contraindicated in severely immunocompromised individuals, such as those with primary immunodeficiencies, thymic disorders, symptomatic HIV with low CD4 T-cell counts, malignant neoplasm treated with chemotherapy, or recent stem cell transplantation. Similarly, OPV is contraindicated for patients who are taking medications that cause immunosuppression such as high dose systemic corticosteroids and/or monoclonal antibodies that target immune cells. In all of these cases, patients can safely receive IPV (3). There is no evidence that OPV negatively affects pregnant women or their fetuses, however the CDC recommends that pregnant women who are at increased risk should receive IPV instead. Both vaccines (IPV or OPV) can be given to breastfeeding persons, or during bouts of mild diarrhea, or minor upper respiratory illnesses (3).
While much has been accomplished to eradicate polio, the world must still deal with the sequelae of the disease. In 2016, there were approximately 15 to 20 million polio survivors worldwide with 573,000 of them living in the United States (1). Of those initially affected by acute paralytic poliomyelitis, 25% to 40% can subsequently develop the so called Post-Polio syndrome (PPS), a neurological disorder characterized by new onset, exacerbation of muscle weakness and/or muscle fatigability occurring approximately 15 to 40 years after the initial diagnosis of poliomyelitis (3,4). The pathogenesis of PPS is not fully understood but is thought to be related to distal degeneration of the enlarged motor units that form following an initial poliomyelitis infection. An inflammatory process may also be involved as evidenced by the presence of perivascular and intraparenchymal inflammation seen in autopsy specimens of spinal cord of post-polio patients (11). The widespread use of the OPV and IPV vaccines has dramatically decreased the incidence of poliomyelitis and has allowed us to target polio for global eradication. The last case of wild-type poliomyelitis in the United States occurred in 1979. While American physicians may not get to see acute poliomyelitis, post-polio syndrome is still a reality.
Since the beginning of the SARS-CoV-2 pandemic in 2020, there has been a disruption in routine vaccination schedules for infants and children resulting in a dip in the number of vaccines being administered and dwindling coverage against vaccine preventable diseases. The WHO Region of the Americas declared themselves as polio-free in 1979 after the last case of wild poliovirus occurring in the U.S. during that year (12). However, in 2022 the CDC Morbidity and Mortality Weekly Report (MMWR) reported a case of paralytic poliomyelitis due to vaccine-derived poliovirus acquired through community spread (not vaccination). This unvaccinated immunocompetent young adult from Rockland County, New York presented on July 18, 2022 with a 5 day history of fever, neck stiffness, back and abdominal pain, and constipation and a 2 day history of bilateral lower extremity weakness. He did not travel internationally prior to symptom onset. He was subsequently admitted for suspected acute flaccid myelitis. Diagnostic workup was significant for vaccine-derived poliovirus type 2 in the patient's stool specimens on day 11 and day 12 after symptom onset. Sabin-like type 2 polioviruses were also detected in sewage water in the patient's county of residence and the adjacent Orange County up to 25 days before and 41 days after the patient's symptom onset indicating community spread of the vaccine-derived poliovirus (12). The genetic sequences of these samples have also been linked to wastewater samples in Jerusalem, Israel, London, and the United Kingdom suggesting community transmission (13). This information was submitted by the CDC to the WHO for inclusion of the U.S. on the list of countries with cVDPV. As of December 2022, no additional cases, thus far, have been reported in the U.S.
The probable source of infection may be from someone who received the OPV internationally leading to community transmission in the US. OPV is safe and effective, containing 1 to 3 strains of live weakened poliovirus and works to stop the spread of the virus by inducing gut immunity. However, OPV can be less effective in areas where vaccine coverage is low. The weakened strain from OPV can spread among underimmunized populations giving the virus an opportunity to replicate and mutate and therefore regain its ability to infect the CNS and cause paralysis (14). Since 2000, IPV is the only polio vaccine used in the US. IPV is >99% effective in preventing polio-induced paralysis, but it does not prevent intestinal infection and poliovirus transmission. Therefore, vaccination plays a critical role in protecting individuals from paralysis if they are exposed to poliovirus.
Questions
1. To which family of viruses do the 3 serotypes of the poliovirus belong?
a. Rhabdoviridae
b. Picornaviridae
c. Adenoviridae
d. Coronaviridae
2. Of the 4 acute clinical presentations, which is the most common?
a. Asymptomatic
b. Abortive
c. Nonparalytic aseptic meningitis
d. Flaccid paralysis poliomyelitis
3. What are the AAFP, AAP, ACIP childhood immunization schedule recommendations for polio vaccination?
a. Exclusive OPV
b. Exclusive IPV
c. Mixed IPV/OPV (first two doses being with IPV)
d. Four doses of the Sabin vaccine
4. Which vaccination (OPV or IPV) should be used for the following clinical situations?
a. Vaccination of children in an endemic country
b. Third dose for an infant living with a Grandpa with agammaglobulinemia
c. Third dose for a child whose parents refuse any more injections
d. 2-month old's first polio immunization
e. Outbreak of wild type polio in the United States
5. Describe the proposed pathophysiology of post-polio syndrome
a. Autoimmune
b. Persistent polio infection
c. Neuronal toxicity by cross-reacting polio antigens
d. Distal degeneration of the enlarged motor units that form following an initial poliomyelitis infection
References
1. Centers for Disease Control and Prevention. Global Health Polio (March 7, 2022). Available at: https://www.cdc.gov/polio/index Accessed 04/20/2022.
2. Maloney WJ. Michael Underwood: a surgeon practising midwifery from 1764 to 1784. Journal of the History of Medicine and Allied Sciences. 1950;5:289-314.
3. American Academy of Pediatrics. Poliovirus Infections. In: Kimberlin DW, Barnett ED, Lynfield R, Sawyer MH (eds). Red Book: 2021 Report of the Committee on Infectious Diseases. 2021. American Academy of Pediatrics, Itasca, IL. pp 601-607.
4. Romero JR. Poliovirus. In: Mandell GL, Bennett JE, Dolin R (eds). Principles and Practice of Infectious Diseases. 2020. 9th Edition. Elsevier, Philadelphia, PA. pp 2220-2226.e2. doi:10.1016/B978-0-323-48255-4.00171-5.
5. Centers for Disease Control and Prevention. Child and Adolescent Immunization Schedule: Recommendations for Ages 18 Years or Younger, United States, 2022 (February 17, 2022). Available at: https://www.cdc.gov/vaccines/schedules/hcp/imz/child-adolescent.html Accessed 04/20/2022.
6. Centers for Disease Control and Prevention: Polio vaccination: Information for healthcare professionals. www.cdc.gov/vaccines/vpd/polio/hcp/index.html Accessed 04/20/2022.
7. World Health Organization. Polio vaccines: WHO position paper, March 2016–recommendations. Vaccine. 2017;35(9):1197-1199. doi:10.1016/j.vaccine.2016.11.017.
8. O’Connor P, Huseynov S, Nielsen CF, et al. Readiness for Use of Type 2 Novel Oral Poliovirus Vaccine in Response to a Type 2 Circulating Vaccine-Derived Poliovirus Outbreak – Tajikistan, 2020-2021. MMWR Morb Mortal Wkly Rep 2022;71(9):361-362.
9. Rachlin A, Patel JC, Burns CC, et al. Progress Toward Polio Eradication – Worldwide, January 2020-April 2022. MMWR Morb Mortal Wkly Rep 2022;71(19):650-655.
10. Sadigh KS, Akbar IE, Wadood MZ, et al. Progress Toward Poliomyelitis Eradication – Afghanistan, January 2020-November 2021. MMWR Morb Moratl Wkly Rep 2022;71(3):85-89.
11. Lo JK, Robinson LR. Postpolio syndrome and the late effects of poliomyelitis. Part 1. pathogenesis, biomechanical considerations, diagnosis, and investigations. Muscle Nerve. 2018;58(6):751-759. doi:10.1002/mus.26168.
12. Link-Gelles R, Lutterloh E, Schnabel Ruppert P, et al. Public Health Response to a Case of Paralytic Poliomyelitis in an Unvaccinated Person and Detection of Poliovirus in Wastewater — New York, June–August 2022. MMWR Morb Mortal Wkly Rep 2022;71:1065-1068. DOI: http://dx.doi.org/10.15585/mmwr.mm7133e2
13. Centers For Disease Control and Prevention. United States Confirmed as Country with Circulating Vaccine-Derived Poliovirus. September 2022. https://www.cdc.gov/media/releases/2022/s0913-polio.html. Accessed December 2022.
14. Centers For Disease Control and Prevention. Polio Vaccine: Vaccine-Derived Poliovirus. September 2022. https://www.cdc.gov/vaccines/vpd/polio/hcp/vaccine-derived-poliovirus-faq.html. Accessed December 2022.
Answers to questions
1. b. Picornaviridae family (Pico=small, RNAviridae=RNA virus)
2. a. Asymptomatic presentation is up to 95% of the cases
3. b. Exclusive IPV immunization
4a. OPV (for endemic countries)
4b. IPV (living with an immunodeficient household contact)
4c. OPV (may receive as 3rd and/or 4th oral doses)
4d. IPV (immunization through an all IPV schedule)
4e. OPV (mass vaccination campaign to control outbreaks)
5. d. Distal degeneration of the enlarged motor units that form following an initial poliomyelitis infection