Poliovirus Case File

Poliovirus Case File

Eugene C.Toy, MD, Cynthia Debord, PHD, Audrey Wanger, PHD, Gilbert Castro, PHD, James D. Kettering, PHD, Donald Briscoe, MD

CASE 34

A 62-year-old man presents to the emergency room after suddenly losing the use of his right leg. He reports that he had a few days of headache, fever, and sore throat, which was treated with oral antibiotics and resolved approximately 4 days ago. He was feeling fine until this morning, when he could not lift his right leg to get out of bed. All of his other limbs are functioning normally, and he has normal sensation in them. He has a medical history significant for lung cancer for which he is receiving chemotherapy, with his most recent cycle having been completed a few days prior to the onset of his febrile illness. He denies having any recent falls, injuries, current headache, or neurologic symptoms other than in the right leg. He has not traveled outside of the United States. His only current medication is amoxicillin/clavulanic acid, which was prescribed for his recent febrile illness. He lives with his son, daughter-in-law, and two young grandchildren. The children are healthy, and each had their routine well-child checkups and vaccinations about a month ago, including an oral vaccine. On examination, he is anxious appearing but has normal vital signs and has unremarkable head and neck, cardiovascular, pulmonary, and abdominal examinations. He has flaccid paralysis with normal sensation of the right leg, with normal movement and strength in all other extremities and a normal cranial nerve examination. A head CT scan and lumbar magnetic resonance imaging (MRI) are also normal.

◆ What is the most likely infectious cause of this man’s flaccid paralysis?

◆ Assuming that he was infected at home, what is the most likely source of his infection?

ANSWERS TO CASE 34: POLIOVIRUS

Summary: A 62-year-old man with flaccid paralysis of the right leg. He lives with his grandchildren, who were recently given an oral vaccine.

◆ Most likely infectious cause of this man’s flaccid paralysis: Poliomyelitis, caused by poliovirus.

◆ Most likely source of his infection: Fecal-oral transmission of viral particles shed from one of his grandchildren recently vaccinated with live attenuated poliovirus vaccine.

CLINICAL CORRELATION

Poliovirus is an exclusive human pathogen, which causes an acute infectious disease that can result in flaccid paralysis from the destruction of motor neurons in the spinal cord. Although most childhood infections tend to be subclinical, the risk of more serious paralytic disease increases with age. Infections are spread through fecal-oral transfer and poor sanitation and crowded conditions help to promote viral spread. Both attenuated live (orally administered) and inactivated poliomyelitis (injected) viral vaccines have been available for over 40 years, and most industrialized countries have been free from wild poliovirus infections since the late 1990s or early 2000s. Use of the killed-virus vaccine for childhood immunizations is currently recommended in the United States because of safety issues with the live-attenuated vaccine, including possible transfer of live virus to close contacts. Efforts are being continued to globally eradicate poliovirus from residual areas such as Africa and India.

APPROACH TO SUSPECTED POLIOVIRUS INFECTION

Objectives

1. Be able to describe the characteristics of the virus.
2. Be able to describe the strategies for prevention and treatment of the infection.

Definitions

Poliomyelitis: Inflammation and destruction of the gray matter of the spinal cord, which can result in paralysis.

Attenuated live poliovirus vaccine or oral polio vaccine (OPV): A viral vaccine consisting of a less virulent form of poliovirus, obtained through multiple passages of three types of poliovirus through tissue culture cells.

Inactivated poliomyelitis vaccine (IPV): A viral vaccine consisting of a large dose of viral antigen that will elicit a protective antibody response without risk of spreading the infection.

DISCUSSION

Characteristics of Poliovirus That Impact Transmission

Poliovirus is a member of the enterovirus genus of the Picornaviridae family. It is a small, nonenveloped virus with a single-stranded, positive-sense RNA genome that resembles cellular mRNA. It is contained within an icosahedral capsid composed of four polypeptides (VP1-VP4) that are necessary for maintaining virion structure, attachment to specific host cell receptors, and entry into cells. The viral genome contains a small protein at the 5′ end, termed VPg, and is polyadenylated at the 3′ end. The genome is transcribed into a single polyprotein that is proteolytically cleaved to produce all of the virally encoded proteins. One of these proteins is a viral protease, which specifically degrades the 5′ cap proteins from cellular mRNAs and thus preferentially inhibits translation of host mRNA. The 5′ viral VPg protein promotes cap-independent association of the poliovirus genome with host cell ribosomes and allows translation of viral proteins to occur. Polioviruses are cytolytic and cause direct damage to infected cells.

As with other enteroviruses, poliovirus is transmitted primarily by the fecal-oral route. Viral particles enter through the mouth and primary replication is thought to occur in the oropharynx, tonsils, and lymph nodes or in the intestinal epithelium and adjacent lymphoid tissue. The virus is resistant to a wide range of pH levels, allowing it to survive the acidity of the stomach. Depending on the host immune response and the ability of the virus to spread, infection with poliovirus can result in one of four different types of infection: asymptomatic illness, abortive poliomyelitis, nonparalytic poliomyelitis, or paralytic poliomyelitis. After initial viral replication, an immune competent host will make specific antibodies to the virus, and if the infection is limited to this stage the infection remains asymptomatic. Host antibodies provide the major immune response to poliovirus infections. However, if infection is not contained by the host antibody response, there may be a “minor” viremic spread to cells containing a specific receptor recognized by the capsid VP proteins. The specificity of poliovirus infection via these receptors restricts the tropism for poliovirus to cells such as the anterior horn cells of the spinal cord, dorsal root ganglia, motor neurons, skeletal muscle cells, and lymphoid cells.

After binding to the receptor, the RNA genome is inserted into the host cytoplasm through a channel created in the cell membrane. Viral transcription and replication occur in the cytoplasm, and new virions are released by cell lysis. Replication in these cells can then lead to a “major” viremia that, when controlled by host antibody response, produces the “minor” illness of abortive poliomyelitis. Abortive poliomyelitis causes nonspecific symptoms that include fever, sore throat, and headache. In a small percentage of infected people, the virus may continue to spread to involve the central nervous system (CNS) or the meninges. This can occur either as a result of viremic dissemination or ascending infection through peripheral nerves into the CNS. This can then result in nonparalytic poliomyelitis, aseptic meningitis, or, when anterior horn cells of the spinal cord or motor cortex are involved, paralytic poliomyelitis. Paralytic poliomyelitis is the least common complication of poliovirus infection and appears less than a week following initial symptoms of abortive poliomyelitis. Paralytic disease is caused by cytolytic damage caused by the virus, not by the immune response.

Diagnosis

In addition to the presentation of the above clinical findings, a suspected poliovirus infection can be diagnosed by the recovery and culture of the virus from clinical samples. The best clinical specimens include throat swabs if collected shortly after the onset of infection or rectal swabs and stool specimens collected up to 30 days post onset. Cells inoculated with poliovirus will show cytopathic effects of viral infection in less than a week of culture. Even when there is CNS and meningeal involvement, poliovirus is rarely recovered from CNS fluid. RT-PCR can also be used to detect RNA sequences in tissues and body fluids, increasing the sensitivity and speed of diagnosis.

Treatment and Prevention

Universal vaccination has eliminated wild-type polio from the western hemisphere and has greatly reduced the incidence of the disease worldwide. Two vaccine types exist—a live, attenuated virus vaccine given orally and an inactivated vaccine given by injection. The live, attenuated virus vaccine has the advantages of creating a secretory antibody in the gastrointestinal (GI) tract and is easily administered. However, viral shedding in the stool of the vaccinated person does occur and has been a source of polio infections during the era of widespread vaccination. In very rare cases, the polio vaccine caused disease either in the vaccinated individual or a close, usually immunocompromised, contact. Because of this, the current recommendation in the United States is to give only the inactivated vaccine, which induces humoral antibodies, but does not carry the risk of vaccine-induced disease. A primary series of four inoculations is recommended within a 1–2 year period, with periodic boosters administered as necessary later in life. However, the inactivated vaccine does not induce local intestinal immunity, allowing poliovirus to still replicate in the GI tract.

COMPREHENSION QUESTIONS

[34.1] Which of the following statements best describes an advantage of the oral polio vaccine when compared to the inactivated poliomyelitis vaccine?

A. It can be administered to immunocompromised patients.

B. It is not associated with vaccine-related cases of poliomyelitis.

C. It induces local intestinal immunity.

D. It is easily administered as a series of multiple injections.

E. It can be given to young children with other scheduled immunizations.

[34.2] The primary pathologic effect of polioviral infection is a result of which of the following?

A. Destruction of infected cells

B. Paralysis of muscle cells

C. Immune complex formation

D. Aseptic meningitis

E. Persistent viremia

[34.3] The majority of nonimmunized patients infected with poliovirus would be expected to experience which of the following symptoms?

A. Flu-like illness

B. Aseptic meningitis

C. Muscle spasms and pain

D. Flaccid paralysis of one or more extremities

E. Asymptomatic infection

Answers

[34.1] C. The oral polio vaccine or “live” vaccine produces not only IgM and IgG antibodies in the blood but also secretory IgA antibodies in the intestine, resulting in intestinal immunity; the inactivated poliomyelitis vaccine produces humoral immunity, but not localized intestinal immunity. Answers A, B, D, and E are incorrect: (A) only the inactivated poliomyelitis vaccine is administered to immunocompromised patients; (B) the oral polio vaccine has been associated with transfer of live poliovirus to close contacts of immunized patients, and therefore, use of the inactivated poliomyelitis vaccine is currently recommended in the United States for childhood immunizations; (D) it is easily administered in multiple oral doses, not injections; (E) both the oral polio vaccine and the inactivated poliomyelitis vaccine can be given to young children with other scheduled immunizations.

[34.2] A. Polioviruses are cytolytic and cause direct damage to infected cells; answers B, C, D, and E are incorrect: (B) paralysis results in less than 2 percent of patients infected with poliovirus and is a direct result of the destruction of infected neurons in the spinal cord and brain; (C) paralytic disease is caused by cytolytic damage because of the virus, not by the immune response; (D) aseptic meningitis is a result of poliovirus infection which occurs in less than 1–2 percent of patients infected, and is a result of the destruction of infected cells; (E) if not contained by the host antibody response, polioviral infection may result in “minor” and “major” viremic spread within the patient, however, the primary pathologic effect of poliovirus is still the cell lysis of infected cells.

[34.3] E. Greater than 90 percent of infections with poliovirus result in asymptomatic infections; answers A, B, C, and D are incorrect; all are potential outcomes of polioviral infections that remain uncontrolled by a host immune response, but are much less common outcomes of poliovirus infection.

MICROBIOLOGY PEARLS ❖ Poliovirus is a small, nonenveloped virus with a single-stranded, positive-sense RNA genome. ❖ More than 90 percent of poliovirus infections are asymptomatic. ❖ Clinical manifestations: “minor” illness of abortive poliomyelitis includes fever, sore throat, and headache; “major” illness of nonparalytic poliomyelitis or paralytic poliomyelitis also includes back pain, muscle spasm, aseptic meningitis, and spinal paralysis of one or more limbs. ❖ Vaccines available: attenuated live poliovirus vaccine or oral polio vaccine (OPV) and inactivated poliomyelitis vaccine (IPV).

REFERENCES

Brooks GF, Butel JS, Morse SA. Jawetz, Melnick, & Adelberg’s Medical Microbiology, 23rd ed. New York: McGraw-Hill, 2004:491–2. 

Ryan JR, Ray CG. Sherris Medical Microbiology, 4th ed. New York: McGraw-Hill, 2004:532–7. 

Plotkin SA, Vidor E. Poliovirus vaccine–Inactive. In Plotkin SA, Orenstein WA. Vaccines, 4th ed. Philadelphia, PA: WB Saunders, 2004. 

Sutter RW, et al. Poliovirus–Live. In Plotkin SA, Orenstein WA. Vaccines, 4th ed. Philadelphia, PA:WB Saunders, 2004.

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