Poliomyelitis is an acute infectious disease that in its serious form affects the central nervous system (CNS). The destruction of motor neurons in the spinal cord results in flaccid paralysis. However, most poliovirus infections are subclinical.
Poliovirus has served as a model enterovirus in many laboratory studies of the molecular biology of picornavirus replication.
Properties of the Virus
A. General Properties
Poliovirus particles are typical enteroviruses (see earlier). They are inactivated when heated at 55°C for 30 minutes, but Mg2+, 1 mol/L, prevents this inactivation. Whereas purified poliovirus is inactivated by a chlorine concentration of 0.1 ppm, much higher concentrations of chlorine are required to disinfect sewage containing virus in fecal suspensions and in the presence of other organic matter. Polioviruses are not affected by ether or sodium deoxycholate.
B. Animal Susceptibility and Growth of Virus
Polioviruses have a very restricted host range. Most strains will infect monkeys when inoculated directly into the brain or spinal cord. Chimpanzees and cynomolgus monkeys can also be infected by the oral route; in chimpanzees, the infection is usually asymptomatic and the animals become intestinal carriers of the virus.
Most strains can be grown in primary or continuous cell line cultures derived from a variety of human tissues or from monkey kidney, testis, or muscle but not from tissues of lower animals.
Poliovirus requires a primate-specific membrane receptor for infection, and the absence of this receptor on the surface of nonprimate cells makes them virus resistant. This restriction can be overcome by transfection of infectious poliovirus RNA into resistant cells. Introduction of the viral receptor gene converts resistant cells to susceptible cells. Transgenic mice harboring the primate receptor gene have been developed; they are susceptible to human polioviruses.
C. Antigenic Properties
There are three antigenic types of polioviruses based on epitopes found in the VP1, VP2, and VP3 proteins.
Pathogenesis and Pathology
The mouth is the portal of entry of the virus, and primary multiplication takes place in the oropharynx or intestine. The virus is regularly present in the throat and in the stools before the onset of illness. One week after infection, there is little virus in the throat, but virus continues to be excreted in the stools for several weeks even though high antibody levels are present in the blood.
The virus may be found in the blood of patients with nonparalytic poliomyelitis. Antibodies to the virus appear early in the disease, usually before paralysis occurs.
It is believed that the virus first multiplies in the tonsils, the lymph nodes of the neck, Peyer’s patches, and the small intestine. The CNS may then be invaded by way of the circulating blood.
Poliovirus can spread along axons of peripheral nerves to the CNS, where it continues to progress along the fibers of the lower motor neurons to increasingly involve the spinal cord or the brain. Poliovirus invades certain types of nerve cells, and in the process of its intracellular multiplication, it may damage or completely destroy these cells.
Poliovirus does not multiply in muscle in vivo. The changes that occur in peripheral nerves and voluntary muscles are secondary to the destruction of nerve cells. Some cells that lose their function may recover completely. Inflammation occurs secondary to the attack on the nerve cells.
In addition to pathologic changes in the nervous system, there may be myocarditis, lymphatic hyperplasia, and ulceration of Peyer’s patches.
Clinical Findings
When an individual susceptible to infection is exposed to the virus, the response ranges from inapparent infection without symptoms to a mild febrile illness to severe and permanent paralysis. Most infections are subclinical; only about 1% of infections result in clinical illness.
The incubation period is usually 7–14 days, but it may range from 3 to 35 days.
A. Mild Disease
This is the most common form of disease. The patient has only a minor illness, characterized by fever, malaise, drowsiness, headache, nausea, vomiting, constipation, and sore throat in various combinations. Recovery occurs in a few days.
B. Nonparalytic Poliomyelitis (Aseptic Meningitis)
In addition to the symptoms and signs listed in the preceding paragraph, the patient with the nonparalytic form has stiffness and pain in the back and neck. The disease lasts 2–10 days, and recovery is rapid and complete. Poliovirus is only one of many viruses that produce aseptic meningitis. In a small per centage of cases, the disease advances to paralysis.
C. Paralytic Poliomyelitis
The predominating complaint is flaccid paralysis resulting from lower motor neuron damage. However, incoordination secondary to brain stem invasion and painful spasms of nonparalyzed muscles may also occur. The amount of dam age varies greatly. Maximal recovery usually occurs within 6 months, with residual paralysis lasting much longer.
D. Progressive Postpoliomyelitis Muscle Atrophy
A recrudescence of paralysis and muscle wasting has been observed in individuals decades after their experience with paralytic poliomyelitis. Although progressive postpoliomyeli tis muscle atrophy is rare, it is a specific syndrome. It does not appear to be a consequence of persistent infection but rather a result of physiologic and aging changes in paralytic patients already burdened by loss of neuromuscular functions.
Laboratory Diagnosis
The virus may be recovered from throat swabs taken soon after onset of illness and from rectal swabs or stool samples collected over long periods. No permanent carriers have been identified among immunocompetent individuals, but long-term excretion of poliovirus has been observed in some immunodeficient persons. Poliovirus is uncommonly recovered from the cerebrospinal fluid—unlike some coxsackievi ruses and echoviruses.
Specimens should be submitted immediately to the laboratory, and frozen if testing is delayed. Cultures of human or monkey cells are inoculated, incubated, and observed. Cytopathogenic effects appear in 3–6 days. An isolated virus is identified and typed by neutralization with specific antiserum. Virus can also be identified more rapidly by polymerase chain reaction (PCR) assays.
Paired serum specimens are required to show a rise in antibody titer during the course of the disease. Only first infection with poliovirus produces strictly type-specific responses. Subsequent infections with heterotypic polioviruses induce antibodies against a group antigen shared by all three types.
Immunity
Immunity is permanent to the virus type causing the infection and is predominantly antibody mediated. There may be a low degree of heterotypic resistance induced by infection, especially between type 1 and type 2 polioviruses.
Passive immunity is transferred from mother to off spring. The maternal antibodies gradually disappear during the first 6 months of life. Passively administered antibody lasts only 3–5 weeks.
Virus-neutralizing antibody forms soon after exposure to the virus, often before the onset of illness, and apparently persists for life. Its formation early in the disease reflects the fact that viral multiplication occurs in the body before the invasion of the nervous system. Because the virus in the brain and spinal cord is not influenced by high titers of antibodies in the blood, immunization is of value only if it precedes the onset of symptoms referable to the nervous system.
The VP1 surface protein of poliovirus contains several virus-neutralizing epitopes, each of which may contain fewer than 10 amino acids. Each epitope is capable of inducing virus-neutralizing antibodies.
Global Eradication
A major campaign was launched by the World Health Organization in 1988 to eradicate poliovirus from the world as was done for smallpox virus. There were an estimated 350,000 cases of polio worldwide in 1988. The Americas were certified as free from wild poliovirus in 1994, the Western Pacific Region in 2000, and Europe in 2002. Progress is being made globally; fewer than 2000 cases of polio still occur each year, principally in Africa and the Indian subcontinent. No cases of wild poliovirus type 2 have been seen since 1999.
In 2016, only three countries—Afghanistan, Nigeria, and Pakistan—remained polio endemic. India was certified as polio-free in March 2014. However, outbreaks of wild poliovirus sometimes occur in previously polio-free countries because of importation of the virus by travel and migration. Surveillance of cases of acute flaccid paralysis, testing of sewage for polioviruses, and vaccination coverage of infants with oral polio vaccine is the strategy followed to identify and interrupt poliovirus transmission.
Epidemiology
Poliomyelitis has had three epidemiologic phases: endemic, epidemic, and the vaccine era. The first two reflect prevaccine patterns. The generally accepted explanation is that improved systems of hygiene and sanitation in cooler climates promoted the transition from endemic to epidemic paralytic disease in those societies.
Before global eradication efforts began, poliomyelitis occurred worldwide—year-round in the tropics and during summer and fall in the temperate zones. Winter outbreaks were rare.
The disease occurs in all age groups, but children are usually more susceptible than adults because of the acquired immunity of the adult population. In developing areas, where living conditions favor the wide dissemination of virus, poliomyelitis is a disease of infancy and early child hood (“infantile paralysis”). In developed countries, before the advent of vaccination, the age distribution shifted so that most patients were older than age 5 years, and 25% were older than age 15 years. The case fatality rate is variable. It is highest in the oldest patients and may reach from 5% to 10%.
Before the beginning of vaccination campaigns in the United States, there were about 21,000 cases of paralytic poliomyelitis per year.
Humans are the only known reservoir of infection. Under crowded conditions of poor hygiene and sanitation in warm areas, where almost all children become immune early in life, polioviruses maintain themselves by continuously infecting a small part of the population. In temperate zones with high levels of hygiene, epidemics have been followed by periods of little spread of virus until sufficient numbers of susceptible children have grown up to provide a pool for transmission in the area. Virus can be recovered from pharynx and intestine of patients and healthy carriers. The prevalence of infection is highest among household contacts.
In temperate climates, infection with enteroviruses, including poliovirus, occurs mainly during the summer. Virus is present in sewage during periods of high prevalence and can serve as a source of contamination of water used for drinking, bathing, or irrigation. There is a direct correlation between poor hygiene, sanitation, and crowding and the acquisition of infection and antibodies at an early age.
Prevention and Control
Both live-virus and killed-virus vaccines are available. Formalin-inactivated vaccine (Salk) is prepared from virus grown in monkey kidney cultures. Killed-virus vaccine induces humoral antibodies but does not induce local intestinal immunity so that virus is still able to multiply in the gut. Live attenuated vaccine (Sabin) is grown in primary monkey or human diploid cell cultures and delivered orally. The vac cine can be stabilized by magnesium chloride so that it can be kept without losing potency for a year at 4°C and for weeks at moderate room temperature (∼25°C). Nonstabilized vaccine must be kept frozen until used.
The live polio vaccine infects, multiplies, and immunizes the host against virulent strains. In the process, infectious progeny of the vaccine virus are disseminated in the community. The vaccine produces not only immunoglobulin M (IgM) and IgG antibodies in the blood but also secretory IgA antibodies in the intestine, enabling mucosal immunity.
Both killed-virus and live-virus vaccines induce anti bodies and protect the CNS from subsequent invasion by wild virus. However, the gut develops a far greater degree of resistance after administration of live-virus vaccine.
A potential limiting factor for oral vaccine is interference. If the alimentary tract of a child is infected with another enterovirus at the time the vaccine is given, the establishment of polio infection and immunity may be blocked. This may be an important problem in areas—particularly in tropical regions—where enterovirus infections are common.
The vaccine viruses—particularly types 2 and 3—may mutate in the course of their multiplication in vaccinated children to a more virulent form. However, only extremely rare cases of paralytic poliomyelitis have occurred in recipients of oral polio vaccine or their close contacts (no more than one vaccine-associated case for every 2 million persons vaccinated).
Trivalent oral polio vaccine was generally used in the United States. However, in 2000, the Advisory Committee on Immunization Practices recommended a switch to the use of only inactivated polio vaccine (four doses) for children in the United States. The change was made because of the reduced risk for wild virus-associated disease resulting from continuing progress in global eradication of poliovirus. This schedule will reduce the incidence of vaccine-associated dis ease while maintaining individual and population immunity against polioviruses.
The oral polio vaccine is being used in the global eradication program. After global eradication is achieved, the use of oral polio vaccine will cease. Continuation of its use could lead to the reemergence of polio caused by mutation and increased transmissibility and neurovirulence of vaccine virus.
Pregnancy is neither an indication for nor a contraindication to required immunization. Live-virus vaccine should not be administered to immunodeficient or immunosuppressed individuals or their household contacts. Only killed virus vaccine is to be used in those cases.
There are no antiviral drugs for treatment of poliovirus infection, and treatment is symptomatic. Immune globulin can provide protection for a few weeks against the paralytic disease but does not prevent subclinical infection. Immune globulin is effective only if given shortly before infection; it is of no value after clinical symptoms develop. The primary public health response to interrupt transmission of reimported cases is large-scale vaccination.
الاكثر قراءة في الفايروسات
اخر الاخبار
اخبار العتبة العباسية المقدسة
