Diseases

Poliomyelitis

Poliomyelitis is a viral disease mostly affecting children that can paralyse them. The pharmaceutical industry has developed highly successful vaccines and is working to eradicate the disease from the world completely.

What is poliomyelitis? Top

Poliomyelitis is a highly infectious disease caused by a small RNA-virus. The word for the disease derives from the Greek words “polio“ (grey) and “myelon“ (marrow), and points to the inflammatory process of the grey substance of the spinal cord. Poliovirus is mainly passed through person-to-person contact. The virus is taken up through smear infection, enters the mouth and multiplies in the intestine. First symptoms after an incubation period of 3-30 days are fever, fatigue, headache, vomiting, and pain in the limbs. After initial infection, poliovirus is shed intermittently in the stool for several weeks. During that time, the infection can spread rapidly through the community, before cases of paralysis are seen. As most people infected with poliovirus have no signs of illness, they are not aware they have acquired the disease.

Once established in the intestines, poliovirus may enter the blood stream and invade the central nervous system. As it multiplies, the virus destroys the nerve cells known as motor neurons which activate muscles. As these nerve cells cannot be regenerated, the affected muscles no longer function. About one in 200 infections leads to irreversible paralysis. Sometimes, poliomyelitis causes total paralysis in a matter of hours. Extensive paralysis, involving the trunk and muscles of the chest and abdomen, results in quadriplegia. In the most severe cases, poliovirus attacks the motor neurons of the brain stem, thus reducing breathing capacity and causing difficulty in swallowing and speaking. Without respiratory support, death results.

Large epidemics caused panic every summer during the 1940s and 50s in Europe and the USA, because the disease crippled thousands of children every year. At that time, patients with poliomyelitis affecting the respiratory muscles were immobilised inside “iron lungs“ - huge metal cylinders to regulate the breathing and keep the patients alive. Today, treatment with the iron lung has been replaced by positive pressure ventilation.

Iron lung.
© Centers for Disease Control, USA, 2004.

Who does poliomyelitis affect? Top

Poliomyelitis can affect people at any age, but 50 per cent of all cases occur in children under three years of age. Girls and boys are affected with equal frequency. Partially immune adults and children can still be carriers of the virus and take the agent from one place to another, infecting close contacts and contaminating sanitation systems, especially in countries where sanitary standards are poor. Poliomyelitis may affect thousands of people before the first case of polio paralysis emerges. For this reason, the WHO considers a single confirmed case of polio paralysis to be evidence of an epidemic.

According to the objective of the “Global Eradication Initiative“ (GEI), commonly supported by the WHO and the United Nations Children Fund (UNICEF), it had been planned to wipe out the disease by 2005. Apparently, this ambitious target has been missed. In 2005, some 1,600 cases of poliomyelitis were reported from several regions. The countries with the highest disease burden were Yemen and Nigeria, with 500 and 600 cases respectively. After ten years of absence of the infection, Indonesia reported some 270 cases. For the first time after 26 years, a small outbreak of poliomyelitis took place in the USA. Four children with the disease were detected in a small community in Minnesota. The recurrence of poliomyelitis in many parts of the world highlights the need for continuing vigilance and for rigorous vaccination programmes.

Electron-microscopic picture of poliovirus 

Present treatments Top

Because no medicine developed so far has proven effective, treatment is entirely symptomatic. Application of moist heat is coupled with physical therapy to stimulate the muscles and antispasmodic medication is given to produce muscular relaxation. While this can improve mobility, it cannot reverse permanent paralysis. Children whose legs are paralysed often require crutches, special braces or wheelchairs in order to move around.

Poliomyelitis can be prevented through immunisation. Polio vaccine, given several times, almost always protects for life. Full immunisation will protect nearly all people. However, under certain circumstances, a few individuals can still contract the disease due to their failure to respond to the vaccine. The vaccine must contain all three types (1, 2 and 3) of the virus as the single types do not confer cross-protection. The two types of vaccines used in the prevention of poliomyelitis are inactivated poliovirus vaccine (IPV) administered by injection and oral attenuated poliovirus vaccine (OPV).

IPV was the first available vaccine, and its widespread administration began in the 1950s. Early formulations had the disadvantage of being less immunogenic than OPV, not being able to induce mucosal immunity, and having to be administered by injection. IPV contains an inactivated virus; for that reason, the vaccine cannot cause vaccine-associated poliomyelitis (VAP). Although they do not induce mucosal immunity, new formulations have been proven to be as immunogenic as OPV. Many countries have now adopted IPV immunization schedules. The vaccine is administered when individuals are aged two months, four months, and 6-12 months and before starting school.

OPV has been in use since the early 1960s. This formulation was responsible for the significant decrease in the prevalence of poliomyelitis throughout the world. The vaccine has the advantages of inducing mucosal immunity, providing appropriate herd immunity, and of good compliance because of its oral administration. The major disadvantage is its association with VAP. Although the virus is attenuated, it may occasionally become neurotropic and produce disease similar to wild type virus. OPV is administered when children are aged two months, four months and six months, with a booster at the age of four years.

What’s in the development pipeline? Top

It is increasingly recognised that people who suffered polio as a child risk “post-polio syndrome“, usually 15 to 40 years after the original illness. The main symptoms are new progressive muscle weakness, fatigue and pain in muscles and joints. The exact mechanism of the disorder is thought to be related to the gradual loss of individual nerve cells.

During the acute phase of the infection, the poliovirus destroys motor neurons. To compensate for this loss, surviving nerve cells sprout extra branches, or axonal sprouts that are able to attach to muscle fibres that have lost their original nerve supply. After this reattachment, the muscle fibres are able to work again, but these extra axonal sprouts probably cannot sustain forever. Eventually, the sprouts degenerate, and the fibres lose their ability to contract. Research into the causes of post-polio syndrome is ongoing, as is the development of guidelines on how best to diagnose, treat and rehabilitate people with it.

Today, there is still no polio antiviral medicine which would constitute an important element of the GEI. Ground research is still investigating possible targets which could serve as first hints for the development of a polio antiviral compound in the post-eradication area. Potential approaches could include capsid-binding compounds, protease inhibitors and blockers of virus attachment.

 

Polio patient

The longer-term future Top

In 1988, when the world-wide programme to eradicate poliomyelitis was set up, it was estimated that the number of cases was higher than 300,000. Following intensive immunisation campaigns and the development of a surveillance network, 6,179 cases were counted in 1995 and 2,971 cases in 2000; figures that illustrate the effectiveness of the WHO’s Expanded Programme of Immunisation (EPI) and the usefulness of surveillance. However, pockets of poliomyelitis still persist throughout the world.

The eradication of wild poliovirus, a long-sought public health goal is possible and close. The “endgame“ in eradication poses a new challenge. Once complete eradication of wild poliovirus has been achieved, there are several options including discontinuation of OPV and replacement by IPV that may also be discontinued provided the assurance that OPV and VAP have disappeared from the world. Actually, the ultimate goal of the eradication programme is the discontinuation of all polio immunisation. Inevitably, an increasing number of people would become susceptible to these viruses. However, the destruction of virus stocks and the possible threat of biological terrorism would be new challenges to face.