This is a 4-1/2 month old female who presents to the ER with weakness in her right leg. She is afebrile and does not appear to have any difficulty breathing. Her right leg appears flaccid and no DTR or Babinski can be elicited although sensation is intact. The 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 C that resolved one week prior to presentation. Her father also notes both a normal birth history and appropriate well baby check ups. 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, OPV and pneumococcal vaccine.
CBC and Serum IgG/IgA/IgM are normal and CSF demonstrates elevated protein with normal glucose. Radiographs of her spine and right lower extremity are unremarkable. Electrophysiological studies (electromyography and nerve conduction studies) show absent motor responses to stimulation of her right tibial nerve. Fecal samples culture the Poliovirus type 3. It is then sent to the CDC where the poliovirus is identified as a vaccine strain of poliovirus (not the "wild-type" strain).
She is admitted to the hospital for monitoring. Her immunocompromised grandfather who changes diapers occasionally is informed about her spinal polio and 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 is a disease that can be traced throughout recorded history. Egyptian murals note a man with an atrophied, shortened leg that appear to describe the late effects of polio. However, its first clinical description occurred in 1789 when Michael Underwood ascribed this condition to the disease that affected the lower extremities of children. Polio epidemics plagued the world over the next centuries. It is difficult for those of us living in the post-vaccine era to imagine the extent of these outbreaks, but an example is the 1952 epidemic that infected more than 50,000 Americans with a mortality rate of about 12% (1). Fortunately, the incidence of polio finally peaked in the 1950s and 1960s with the vaccine discoveries of Jonas Salk and Albert Sabin. The widespread use of these vaccines has dramatically decreased its incidence and has allowed us to target polio for global eradication.
Poliomyelitis is a highly contagious and infectious illness that exclusively affects humans. It is caused by 3 different serotypes of the poliovirus: P1 (majority of cases), P2, and P3. All of the poliovirus subtypes are included in the Picornaviridae family (pico=small, RNAviridae=RNA virus). Similar to other enteroviruses, the poliovirus is a transient inhabitant of the gastrointestinal system and is able to tolerate low pH settings. As the family name suggests, the poliovirus is relatively small. It is non-enveloped and its protein capsid of icosahedral symmetry measures less than 30 nm in diameter. Furthermore, its family name describes its genome as being RNA; specifically, it is single and positively stranded.
After the poliovirus attaches to specific human cell receptors, this single, positive stranded RNA is uncoated in the cytoplasm where it can be directly translated into products such as progeny protein capsids and replication enzymes. The replication of the genome itself is through a complementary negative strand. Once the genome is replicated, it is assembled into the protein capsids where the virions accumulate until they are released upon the death of the host cell.
The communicability of the poliovirus is mainly through the fecal-oral route, but oral-to-oral transmission is possible. Following exposure, the poliovirus infects the tissues of the oropharynx. It is then secreted into saliva and swallowed, allowing the virus to spread to the gastrointestinal system. There, the virus replicates and can subsequently invade the local lymphoid tissue, the bloodstream, and the CNS. The response to the infection is variable as seen in the range of clinical presentations. In a minority of patients, the virus can spread to the nervous system possibly through viremia or through retrograde transport along motor axons. Poliomyelitis has a selectivity toward the motor neurons of the anterior horn and the brain stem. It is the cell destruction at these sites that cause the paralysis that is associated with polio.
There are various responses to polio infections. The first subgroup encompasses the vast majority of polio cases. Up to 95% of polio patients have inapparent or asymptomatic infections (2). While these patients have no symptoms, they are infectious and briefly shed the virus in their stool to their contacts. The second subgroup is the abortive poliomyelitis which occurs in 4-8% of the cases (2). This subset is also spared CNS complications but can present with symptoms of malaise, anorexia, nausea, vomiting, headache, sore throat, constipation, and diffuse abdominal pain. These patients usually undergo a complete recovery in less than a week. The third subgroup is the nonparalytic aseptic meningitis form of poliomyelitis which includes 1-2% of all cases (2). This group exhibits prodromal symptoms that are similar to those in abortive poliomyelitis but is complicated by posterior muscle stiffness of the neck, back, and limbs which can be accompanied by paresthesias. These signs of meningeal irritation and muscle spasm will typically resolve after 2-10 days. The final subgroup conjures up images of what most people think as the typical polio patient. Less than 2% constitute this form of poliomyelitis (2). Paralytic symptoms can present 1-10 days after initial prodromal symptoms. These paralytic symptoms are usually asymmetrical and include decreased deep tendon reflexes with no changes in cognition or sensation. Paralytic polio can be further separated 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. Cranial nerves can also be involved along with the muscles of respiration. Of historical interest, the "iron lung" was a negative pressure ventilator fitted outside the patient's body to chronically ventilate patients with respiratory paralysis. Of contemporary concern is that patients who contracted paralytic polio as children can develop a post-polio syndrome decades later.
Polio has been eradicated from North America so it is unlikely that we will ever see a case. In regions where polio still exists, poliomyelitis should be considered in an unimmunized or partially immunized patient with the clinical symptoms listed in the prior section. The choice of diagnostic tests include stool and throat cultures with greater success in isolating the virus from the stool. If the paralytic form of the polio is suspected, two or more samples are collected at least 24 hours apart and should be obtained within the first 14 days of symptoms. If the poliovirus is identified through the cultures, the isolate should then be sent to the Centers for Disease Control and Prevention to differentiate the naturally occurring "wild type" from the oral attenuated vaccine strain (which can cause poliomyelitis, rarely). In the absence of an isolate, poliomyelitis can be diagnosed with paired measurements of acute and convalescent sera. It is possible to witness a four fold or more increase in antibody titers. However, these results do not differentiate the "wild type" from the vaccine strain and can at times be equivocal. If CSF is obtained in the workup, it rarely isolates the poliovirus, but it can demonstrate pleocytosis with mildly elevated protein.
Treatment involves isolation of the hospitalized patient, strict bed rest, symptomatic pain relief, respiratory support as needed, and subsequent rehabilitation of affected muscles.
The last case of "wild type" poliomyelitis in the United States occurred in 1979. Through the efforts of the Global Polio Eradication Program, the number of endemic countries has decreased from 125 in 1988 to 10 as of 2001. In addition, the number of reported polio cases has substantially decreased over the same period (3). These efforts now focus on eliminating the virus from the Indian subcontinent and Africa through the use of the polio vaccine.
The dramatic decreases in the incidence of polio are attributed to the two types of vaccines that are currently available in the United States: the inactivated poliovirus vaccine (IPV) and the oral poliovirus vaccine (OPV).
IPV is also known as the Salk vaccine. Because it contains the inactivated forms of all three serotypes, it confers effective immunity to the polioviruses. Furthermore, since it does not contain the live virus, it is safe for use in immunocompromised patients and their contacts. It also does not cause the vaccine associated paralytic poliomyelitis (VAPP) seen with the oral vaccine. The disadvantages of the IPV are the exclusive administration through injection, less gastrointestinal immunity, and an unknown duration of immunity (4). Decreased gastrointestinal immunity could allow possible infection of the "wild type" strain through the GI tract. While the immunized person would be protected from the paralytic form of poliomyelitis, the patient would shed the poliovirus to other contacts. This lack of gastrointestinal immunity is part of the reason that the OPV is used by the World Health Organization for its global eradication efforts.
OPV is also referred to as the Sabin vaccine. OPV also provides effective immunity against all three serotypes of the poliovirus. The advantages of the oral vaccine include easier administration, probable lifelong protection, and better gastrointestinal immunity (4). The main disadvantage of the OPV is the risk of VAPP. Vaccine Associated Paralytic Poliomyelitis occurs when the live oral virus reverts to a virulent form. The risk of this occurrence is estimated to be 1 per 2.4 million doses distributed (125 cases for 303 million doses distributed) with most cases usually occurring after the administration of the first dose (4). This translates to five cases of VAPP reported in 1997 and two cases in 1998 (5). VAPP is also associated with patients who are immunocompromised. Because of this risk, the Advisory Committee on Immunization Practices (ACIP), the American Academy of Pediatrics (AAP), and the American Academy of Family Physicians (AAFP), now recommend an all-IPV schedule for routine childhood polio vaccination in the United States. All children should receive four total doses of IPV with single doses at ages: 2 months, 4 months, between 6-18 months, and between 4-6 years.
There are special circumstances that allow the use of the oral vaccine. These include: 1) Mass vaccination campaigns to control paralytic poliomyelitis outbreaks; 2) Unvaccinated children traveling to endemic or epidemic areas without enough time to administer 2 doses of the IPV; 3) Children whose parents do not accept the immunization schedule can receive the OPV for the third and/or fourth doses only; 4) Depletion of remaining supplies of OPV to children for their third and/or fourth doses although it is preferred that the OPV reserves be used preferentially on 4-6 year old for their fourth dose (6).
There are certain precautions and contraindications to childhood polio immunization. Immunocompromised patients should only receive IPV. Similarly, household contacts (immunocompromised patient in the household) should not receive the OPV because of the risk of excreting live polio vaccine virus and exposing household contacts. If these people happen to be vaccinated with the OPV, they should have minimal close contact with the immunocompromised person for between 4-6 weeks after immunization. Immunization should also be avoided during pregnancy because of the possible adverse effects of the vaccine on the fetus. If vaccination is required during pregnancy, IPV is recommended. Finally, since IPV contains trace amounts of streptomycin, polymyxin B, and neomycin, IPV is contraindicated for those with reactions to these antibiotics or those who have had prior reactions to previous doses. Both vaccinations can be used with breastfeeding and during bouts of mild diarrhea (7).
Those affected with acute paralytic poliomyelitis can experience Post-Polio syndrome (PPS) an average of 35 years after an infection. It was first described in the French medical literature in 1875. In a commentary on one of these cases, neuropathologist Jean Martin Charcot astutely hypothesized that one spinal disorder laid a patient more susceptible to a subsequent spinal disorder due to the overuse of the involved limbs. For reasons unknown, the late sequelae of paralytic poliomyelitis were not investigated further and prior to 1980, there was not even a name associated with this condition. In 1987, the National Health Interview Survey estimated more than 640,000 survivors of paralytic polio in the United States with more than half of these survivors demonstrating new late manifestations of post-polio syndrome (8). It is unclear how many of these polio survivors are still alive today, nor is it clear the added contribution of immigrants, refugees, and illegal aliens moving to the United States who are also survivors of paralytic polio.
Risk factors for PPS include: the severity of the acute poliomyelitis paralysis, age at onset of the acute poliomyelitis (higher risk with adolescent and adult onset), the amount of recovery, and greater physical activity during the intervening years (8). In a summary of four major studies, the frequency of symptoms were consolidated into the following data: fatigue 62-89%; weakness in previously affected muscles 54-87%; weakness in previously unaffected muscles 33-77%; muscle pain 39-86%; joint pain 51-79%; cold intolerance 29-56%; muscle atrophy 28-39%; new difficulties with walking 52-85%; new problems with climbing stairs 54-83%; new difficulties with dressing 16-62% (9).
Although there is no definitive origin of PPS, one leading hypothesis suggests that once the motor neurons are reinnervated, the excessive metabolic stress over the years eventually leads to the eventual dropout of the motor neurons. Many of us associate The March of Dimes with preventing birth defects and infant mortality. However, The March of Dimes was originally created to combat the polio epidemics. The March of Dimes continues its polio efforts as evidenced by its involvement in the 2000 International Conference on Post Polio Syndrome which developed the following diagnostic criteria (10).
1. 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 EMG.
2. 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.
3. Gradual or sudden onset of progressive and persistent new muscle weakness or abdominal muscle fatigability (decreased endurance), with or without generalized fatigue, muscle atrophy, or muscle and joint pain.
4. Symptoms persist for at least a year.
5. Exclusion of other neurologic, medical and orthopedic problems as causes of symptoms.
It is very unlikely that we will witness patients with acute poliomyelitis. The wild-type poliovirus has nearly been eradicated from the globe, and due to current vaccination recommendations, VAPP can be avoided by using IPV. Although this discussion of Post-Polio Syndrome is beyond the scope of a pediatrics textbook, modern experiences with poliomyelitis will more likely to be with adults with post-polio syndrome.
1. The 3 serotypes of the poliovirus belong to which family of viruses?
2. Of the 4 acute clinical presentations (asymptomatic, abortive, nonparalytic aseptic meningitis, or flaccid paralysis poliomyelitis) which is the most common?
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. Doctor has remaining OPV supplies. Third does for an infant living with an agammaglobulinemic Grandpa.
. . . . . c. Doctor has remaining OPV supplies. Third dose for a child whose parents refuse any more injections.
. . . . . d. Doctor has remaining OPV supplies. 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.
6. True/False: The March of Dimes is named after the campaign where Americans mailed in their dimes to fight polio.
1. Halstead L. Post-Polio Syndrome. Scientific American 1998;278(4):42-47.
2. Chapter 7- Poliomyelitis www.cdc.gov/nip/publications/pink/polio.pdf:85-100.
3. Morbidity and Mortality Weekly Report 2002;51(12):253-256.
4. Zimmerman R. Poliovirus Vaccine Options. Am Fam Phys 1999;59(1):113-118.
5. Morey S. Practice Guidelines ACIP Issues Updated Recommendations for Polio Vaccine. Am Fam Phys 2001;63(2):376-377.
6. AAP Committee on Infectious Diseases. Prevention of Poliomyelitis: Recommendations for Use of Only Inactivated Poliovirus Vaccine for Routine Immunization (RE9949). Pediatrics 1999;104(6):1404-1406.
7. American Academy of Pediatrics. AAP 2000 Red Book: Report of the Committee on Infectious Diseases, 25th ed. Elk Grove Village: American Academy of Pediatrics, pp. 467-470.
8. Jubelt B, Agre J. Characteristics of Postpolio Syndrome. JAMA 2000;284(4):412-414.
9. Thorsteinsson G. Management of Postpolio Syndrome. Mayo Clinic Proceedings 1997;72(7):627-638.
10. March of Dimes International Conference on Identifying Best Practices in Diagnosis & Care. Report from May 2000 international conference on post-polio syndrome.
Answers to questions
1. Picornaviridae family (Pico=small, RNAviridae=RNA virus).
2. Asymptomatic presentation is up to 95% of the cases.
3. The correct answer is b, exclusive IPV immunization.
4a. OPV (for endemic countries).
4b. IPV (Household contact, especially since Grandpa might be changing the diapers).
4c. OPV (May receive 3rd and/or 4th oral doses).
4d. IPV (Immunization through all IPV schedule).
4e. OPV (Mass vaccination campaign to control outbreaks).
5. The proposed mechanism includes the dropout of neurons that were reinnervated after the initial paralytic poliomyelitis infection due to increased metabolic stresses.
6. True. The March of Dimes was originally named the National Foundation for Infantile Paralysis.