Diseases and conditions
Poliomyelitis | Poliovirus and vaccine

Poliomyelitis | Poliovirus and vaccine

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Poliomyelitis is an acute viral infection which ranges in severity from a nonspecific illness to paralysis with permanent disability. The words polio (grey) and myelon (marrow, indicating the spinal cord) are derived from the Greek. It is the effect of poliomyelitis virus on the spinal cord that leads to the classic manifestation of paralysis.

Poliomyelitis and vaccine


Records from antiquity mention crippling diseases compatible with poliomyelitis. Michael Underwood first described a debility of the lower extremities in children that was recognizable as poliomyelitis in England in 1789. The first outbreaks in Europe were reported in the early 19th century, and outbreaks were first reported in the United States in 1843. For the next hundred years, epidemics of polio were reported from developed countries in the Northern Hemisphere each summer and fall. 


These epidemics became increasingly severe, and the average age of persons affected rose. The increasingly older age of persons with primary infection increased both the disease severity and number of deaths from polio. Polio reached a peak in the United States in 1952, with more than 21,000 paralytic cases. However, following introduction of effective vaccines, polio incidence declined rapidly. The last case of wild-virus polio acquired in the United States was in 1979, and global polio eradication may be achieved within this decade. 

The virus


Polioviruses are classified into three distinct serotypes (type 1, type 2, and type 3) based on their reaction with reference panels of neutralizing antisera (Bodian et al. 1949). They belong to the genus enterovirus in the family picornaviridae. 


Polioviruses are stable at acid pH and can survive for weeks at room temperature and for many months at 0°C to 8°C. As with other enteroviruses, polioviruses are resistant to ether, 70% alcohol and other laboratory disinfectants. Treatment with 0.3% formaldehyde, 0.1 N HCl, or free residual chlorine at a level of 0.3 to 0.45 parts per million rapidly inactivates polioviruses, as does exposure to a temperature of 50°C or higher or to ultraviolet light (Minor and Bell 1990).
 

Pathogenesis


The mouth is the portal of entry of the virus and primary multiplication of the virus occurs at the site of implantation in the pharynx and gastrointestinal tract.  The virus is usually present in the throat and in the stools before the onset of illness.  One week after onset there is little virus in the throat, but virus continues to be excreted in the stools for several weeks.  The virus invades local lymphoid tissue, enters the blood stream, and then may infect cells of the central nervous system.  Replication of poliovirus in motor neurons of the anterior horn and brain stem results in cell destruction and causes the typical manifestations of poliomyelitis.

 Risk factors 


A number of factors may affect the potential for infection with poliovirus or the severity of clinical poliomyelitis.


Immune deficiency 


Infection with poliovirus poses an increased risk for persons with primary B cell immunodeficienties. In these persons, infection with wild virus or vaccine strains may develop in an atypical manner, with an incubation period longer than 28 days, a high mortality rate after a long chronic illness, and unusual lesions in the central nervous system (Davis et al. 1977, Wyatt 1973). Among vaccine- associated cases in immunologically abnormal persons in the United States types 2 and 1 were the polioviruses most commonly isolated from stool specimens (Strebel et al. 1992). 


HIV-infected persons could potentially be at risk of wild or vaccine-associated poliomyelitis when B cell function decreases late in the clinical course of the disease. However, based on global data reported to WHO as of October 1992, only four cases of paralytic poliomyelitis have been reported in HIV-infected persons. A case-control study conducted in 1988-1989 in Zaire did not find an elevated risk of paralytic poliomyelitis among HIV-infected children (Vernon et al. 1990). Prospective and retrospective studies in both developing and industrialized countries report no serious adverse events in over 400 HIV-infected children who received live attenuated oral polio vaccine (OPV) (Onorato and Markowitz 1992).


Malnutrition 


Data on the risk of infection with wild poliovirus in malnourished children are not available. Following a dose of OPV, serum neutralizing antibody titers were similar in malnourished and well-nourished children; however, in malnourished children, secretory IgA antibody has been detected significantly less often, at lower levels, and with a delayed appearance (Chandra 1975, 1981).


Physical activity 


Early studies showed that for persons who developed paralytic poliomyelitis, the intensity of physical activity in the first 48 hours after the onset of paralysis correlated with the severity of paralysis (Horstmann 1950). In contrast, physical activity prior to the onset of paralysis did not relate to subsequent paralysis.


Pregnancy 


Outbreaks in industrialized countries in the period when large numbers of cases occurred in adults allowed assessment of pregnancy as a risk factor for paralytic poliomyelitis. Among adults aged 15 to 44 years, pregnant contacts of a polio case had an increased risk of paralysis compared with other female or male contacts (Paffenbarger and Wilson 1955). 


Poliovirus can cross the placenta; however, there is no evidence that the fetus is affected either by maternal infection with wild poliovirus or by maternal immunization with live attenuated vaccine. A pro-spective study conducted in New York City from 1949 to 1953 found no evidence of an increase in congenital defects among 87 infants born to mothers infected with poliovirus during their pregnancies (Siegel and Greenberg 1956).
 

Tonsillectomy 


Aycock reported in 1942 that tonsillectomy in a person incubating poliovirus was likely to lead to bulbar poliomyelitis; later studies indicated that previous tonsillectomy at any time increased the risk of bulbar poliomyelitis (Bodian and Horstmann 1965). Studies based on the immune response to OPV provided further clarification. Among children 3 to 11 years old previously immunized with OPV, IgA was present in the nasopharynx pre-tonsillectomy. After tonsillectomy, mean IgA titers declined abruptly and remained low for several months; serum antibody levels remained unchanged. Compared with children who had intact tonsils, seronegative children who had had their tonsils removed had a lower level of secretory antibody response in the pharynx when immunized with OPV (Ogra and Karzon 1971).


Clinical Features


The incubation period for poliomyelitis is commonly 6 to 20 days with a range from 3 to 35 days. The response to poliovirus infection is highly variable and has been categorized based on the severity of clinical presentation.


Inapparent infection without symptoms


Up to 95% of all polio infections are inapparent or subclinical.  Estimates of the ratio of inapparent to paralytic illness vary from 50:1 to 1,000:1 (usually 200:1).  Infected persons without symptoms shed virus in the stool, and are able to transmit the virus to others.


Minor illness (abortive poliomyelitis)


Approximately 5% (4%-8%) of polio infections consist of a nonspecific illness without clinical or laboratory evidence of central nervous system invasion and are characterized by complete recovery in less than a week.  Three syndromes observed with this form of poliovirus infection are upper respiratory tract infection (sore throat and fever), gastrointestinal disturbances (nausea, vomiting, abdominal pain, constipation or, rarely, diarrhea), and influenza-like illness.  These syndromes are indistinguishable from other viral illnesses.
 

Nonparalytic poliomyelitis


Nonparalytic aseptic meningitis (symptoms of stiffness of the neck, back, and/or legs) usually following several days after a prodrome similar to that of minor illness occur in 1%-2% of polio infections. Increased or abnormal sensations can also occur.  Typically these symptoms will last from 2 to 10 days followed by complete recovery.

Paralytic poliomyelitis


Less than 2% of all polio infections result in a flaccid paralysis (usually less than 1%).  Paralytic symptoms generally begin 1 to 10 days after prodromal symptoms and progress for 2 to 3 days.  Generally, no further paralysis occurs after the temperature returns to normal.  The prodrome may be biphasic, especially in children, with initial minor symptoms separated by a 1- to 7-day period from more major symptoms. 

Additional prodromal signs and symptoms can include a loss of superficial reflexes, initially increased deep tendon reflexes and severe muscle aches and spasms in the limbs or back.  The illness progresses to flaccid paralysis with diminished deep tendon reflexes which reaches a plateau without change for days to weeks and is usually asymmetrical. Strength then begins to return.  Patients do not experience sensory losses or changes in cognition.


Many persons with paralytic poliomyelitis recover completely and, in most, muscle function returns to some degree.  Patients with weakness or paralysis 12 months after onset will usually be left with permanent residua.


Paralytic polio is classified into three types, depending on the level of involvement. Spinal polio is most common, and accounted for 79% of paralytic cases from 1969-1979. It is characterized by asymmetric paralysis that most often involves the legs. Bulbar polio accounts for 2% of cases and leads to weakness of muscles innervated by cranial nerves. Bulbospinal polio accounts for 19% of cases and is a combination of bulbar and spinal paralysis.
 

Oral Poliovirus vaccine


Candidate strains of attenuated poliovirus suitable for immunizing humans were developed independently by scientists at three different institutions in the United States: the Children’s Hospital Research Foundation, Cincinnati (A.B. Sabin), Lederle Laboratories (H.R. Cox), and the Wistar Institute, Philadelphia (H. Koprowski). Because they provided good antibody levels and were less neurotropic for monkeys, the strains developed by Sabin were selected for widespread application. 

OPV began to be used in several countries during the spring of 1960. Initially, each serotype was given separately as a monovalent vaccine, with sequential administration of types 1,3, and 2. Trivalent vaccine came into use a few years later, although a few countries have continued to usemonovalent OPV up to the present. 


Since 1973 WHO has been directly responsible for the custody and distribution of the Sabin strains of OPV and has exercised strict supervision over production laboratories in cooperation with national control authorities (Cockburn 1988). Sufficient quantities of the master seed have been prepared to supply the global requirements for the next 200 years. 


Inactivated poliovirus vaccine (IPV)


Inactivated polio vaccine (IPV) In 1949 Enders, Weller and Robbins described the successful. cultivation of the Lansing strain of poliovirus in cultures of non-nervous human tissues (Enders et al. 1949). This was the breakthrough that allowed development of polio vaccines. The first inactivated polio vaccine (IPV) was produced by Salk using virus grown on monkey kidney cells and inactivated with: formalin. 

After extensive field testing, IPV was licensed in the United States in 1955. The strains of virus used in the vaccine were Mahoney (type l), MEF-I (type 2) and Saukett (type 3). The same strains: are used by all manufacturers of IPV today, except in Sweden where the Brunenders strain is used for type 1 (Salk and Drucker 1988). 


Shortly after IPV became widely available in the United States; cases of paralytic disease were reportedin recipients. Epidemiological and laboratory investigation revealed that active virus was present in several lots of vaccine from one manufacturer, Cutter. As a result, new filtration steps were introduced in the production process to remove aggregated, possibly poorly inactivated virus particles and safety tests were improved.


IPV is standardized in D antigen units. The D antigen content of IPV is measured in vitro by ELISA or by a double immunodiffusion assay. These tests need to be correlated with an in vivo system, usually in rats or chickens (Minor 1990). The original IPV contained 20, 2, and 4 D antigen units of poliovirus types 1, 2, and 3, respectively, although the potency varied considerably. 

In 1978 the Rijks Instituut in Holland introduced a new culture technique using cells on microcarriers to produce a more potent IPV containing 40, 8, and 32 D antigen units of types 1, 2, and 3, respectively (van Wezel et al. 1984). Vaccine of this potency is known as enhanced potency IPV, or eIPV. DPT vaccine has been combined with eIPV with good serological response to both vaccines and the convenience of a single injection.


Vaccine-Associated Paralytic Poliomyelitis (VAPP)


Vaccine-associated paralytic polio (VAPP) is a rare adverse event following live oral poliovirus vaccine.  Inactivated poliovirus vaccine does not contain live virus, so it cannot cause VAPP.
The mechanism of VAPP is believed to be a mutation, or reversion, of the vaccine virus to a more neurotropic form. These mutated viruses are called revertants.  Reversion is believed to occur in almost all vaccine recipients, but it only rarely results in paralytic disease.  The paralysis that results is identical to that caused by wild virus, and may be permanent.


It is likely that the longer the vaccine virus replicates in the intestine, the more reversion occurs. The longer that revertants are present, the more likely it is that one will make its way into the central nervous system and cause damage

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