Poliomyelitis

Poliomyelitis is a highly contagious disease caused by a virus (the poliovirus), which invades the nervous system and can lead to irreversible paralysis in just a few hours. This disease has been preventable since the 1960s thanks to effective vaccines. A global program, aiming to eradicate the disease through vaccination, was launched under the supervision of the WHO.

 

 

 

 

> Cause
> Epidemiology and prevention
> Symptoms
Transmission
> At the Institut Pasteur
> The INstitut Pasteur teams

 

Cause

The poliomyelitis virus is part of the Picornaviridae family, along with rhinoviruses (common cold agents), and belongs to the enterovirus genus. There are three poliovirus serotypes (1, 2 and 3).

 

Epidemiology and prevention

As the disease is mainly spread by the fecal-oral route, key preventive measures focus on improved hygiene. There is no treatment for the disease (only resulting disabilities are managed with physical therapy), and the only preventive medical defense is vaccination which, when repeated several times, protects the child.

In the pre-vaccine era, poliomyelitis was one of the worst childhood diseases. It affected over 600,000 children a year throughout the world. To fight the disease, the WHO launched the Global Polio Eradication Initiative in 1988. It focuses on the vaccination of all children in the world.

 

 

The 2 types of vaccine

  • An Inactivated Polio Vaccine (IPV), developed by Jonas Salk in the 1950s, contains the three serotypes of inactivated viruses and provides protection thanks to good overall immunity. As this vaccine requires several injections and regular boosters, it must be used in controlled sterile conditions. It is completely safe but, for a long time, its cost limited its distribution to some developed countries, like France. It has been used in many other countries for several years.

 

  • An Oral Polio Vaccine (OPV) was developed by Albert Sabin, also in the 1950s. The OPV contains the three serotypes of live viruses, attenuated by mutations. This vaccine has many advantages, which explains why, until now, it has been the key tool in the eradication program — it is easy to use as it does not require injection and it quickly confers good overall immunity and local immune response in the intestine, thus reducing the spread of the wild poliovirus (much more effectively that the IPV). Furthermore, the OPV is inexpensive. Its main disadvantages are its short shelf life at ambient temperatures and its genetic instability — a possible cause of the extremely rare cases of “vaccine-associated paralytic polio”, which develop several days after vaccination in vaccinated individuals or their non-vaccinated relatives and contacts.

 

 

A control strategy that has paid off

The strategy for stopping the spread of the wild poliovirus is based, firstly, on the introduction of routine vaccination coverage for all infants (administration of four doses of the oral polio vaccine in the first year). In addition, in countries where there is a greater risk of the disease, additional doses of the oral polio vaccine are administered to all children under 5 during National Immunization Days (NIDs). As regards poliomyelitis monitoring, it is carried out thanks to a network of laboratories that test for polioviruses in all children under 15 with acute flaccid paralysis (AFP), the symptom that characterizes the disease.

In 1988, the incidence rate of poliomyelitis was over 350,000 estimated cases a year. Thanks to vaccination, the Americas (36 countries) were certified polio-free in 1994, followed by the Western Pacific Region (37 countries and territories, including China) in 2000, and by Europe (51 countries) in June 2002. The wild serotype 2 strains have not circulated since 1999 and no cases associated with type 3 strains have been reported since November 2012. So only wild type 1 strains are still circulating today. The WHO South-East Asia Region was certified polio-free in March 2014 (11 countries, including Indonesia and India). The WHO initiative has therefore reduced the incidence rate of poliomyelitis by more than 99% and today it stands at around one hundred cases per year (101 reported cases in 2015). The disease is now only considered endemic in two countries — Afghanistan and Pakistan.

 

A disease that is still present

Unprecedented vaccination campaigns have been organized in recent years to prevent outbreaks and stop the virus from circulating. However, following the disappearance of the disease, some developing countries are failing to maintain sufficient vaccination coverage. Poliomyelitis therefore sometimes returns due to wild viruses, imported from countries where the disease remains endemic.

 

In addition, low vaccination coverage is also responsible for outbreaks of a new type of poliomyelitis, which has been reported in around twenty countries since 2000. Natural transmission of the vaccine virus in non-vaccinated children can contribute to the genetic drift of vaccine strains, which thereby acquire a pathogenic nature. These outbreaks are very often caused by recombinant viruses between mutated poliovirus strains, derived from OPV, and other enteroviruses, most likely coxsackieviruses.

Issues related to insufficient vaccination coverage tend to considerably delay the final eradication program deadlines. Another challenge to the program is that the great majority of poliovirus infections are asymptomatic, making it easier for the virus to circulate (unlike cases of smallpox where all infections produced visible symptoms).

 

Symptoms

The disease begins with flu-like symptoms, fever, tiredness, headaches and sometimes vomiting, neck stiffness and pain in the limbs. Irreversible paralysis (of the legs in general) occurs in one in 200 cases. Between 5 and 10% of paralyzed patients die when their respiratory muscles become paralyzed. Residual paralysis can be observed in patients who survive and it causes varying degrees of disability. This can range from minor paralysis with complete independence to extremely debilitating paralysis requiring respiratory support.

 

Several decades after acute poliomyelitis, some former patients develop “post-polio” syndrome, which is characterized by new, slowly progressive muscle weakness. The exact causes of the development of this syndrome have not yet been clearly identified. It may be due to the persistence of the virus in some patients.

 

Transmission

The poliomyelitis virus multiplies in the pharyngeal mucosa and small intestine and can be found in the throat and stools. It is spread exclusively through person-to-person contact, mainly by the fecal-oral route and particularly through contaminated water, aerosols or food contaminated by feces. Infected individuals can spread the infection as long as the virus remains in their throats (a week) and feces (3 to 6 weeks or more).

 

The virus enters the body through the mouth and travels through the mucous membrane of the throat or intestine to multiply in the cervical and mesenteric (small intestine) lymph nodes. In about 1% of infected individuals, the virus reaches the motor neurons in the anterior horn of the spinal cord or other motor areas of the central nervous system (most likely through the blood) and the destruction of these nerve cells is responsible for the forms of flaccid paralysis. It is generally accepted that motor neuron cell death is a direct consequence of viral replication.

 

 

At the Institut Pasteur

The Institut Pasteur is involved in poliovirus monitoring through the Enterovirus Monitoring and Research Network, which brings together laboratories from 12 Institut Pasteur International Network institutes. Most of these laboratories are part of the WHO Global Polio Laboratory Network, a network of over 150 laboratories designed and structured to detect the latest cases of the disease.

 

The emergence of new recombinant poliovirus strains is being studied at the Institut Pasteur in Paris, in collaboration with many Institut Pasteur International Network institutes. Institutes in Madagascar, Central African Republic, Cameroon, Côte d’Ivoire, Senegal, Morocco, Algeria, Tunisia, Romania and Russia (Saint Petersburg) are taking part in this research. The work is being coordinated by Francis Delpeyroux, Head of the Biology of Enteric Viruses Unit. The institutes are now aiming to identify the enteroviruses circulating in their respective countries, and in particular those likely to recombine with the poliovirus. Researchers are trying to improve the monitoring of pathogenic vaccine-derived polioviruses, and understand which viral and environmental factors could contribute to the emergence of these pathogenic recombinant strains.

 

More specifically, Francis Delpeyroux’s team is studying the mechanisms involved in the recombination between different enterovirus strain types, the characteristics of unknown viral sequences found in recombinant poliovirus strains, and their role in the pathogenicity of these viruses. With the same aim, cellular level research is being conducted in the Unit under Bruno Blondel.

The team at the Institut Pasteur in Paris and the Institut Pasteur International Network are therefore fighting poliomyelitis on two fronts:

- monitoring pathogenic viruses circulating in healthy children or those suffering from paralysis means that the public health authorities can be informed and can, in turn, step up the vaccination campaigns to stop and prevent outbreaks.

- the teams are conducting research on viral and cellular factors that contribute to the emergence and pathogenicity of recombinant polioviruses, as an understanding of these mechanisms can help to prevent outbreaks. All this research also constitutes a model for understanding the emergence of new viruses.

 

 

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Illustration - Copyright Institut Pasteur

Caption - Poliovirus, the agent of poliomyelitis, of which humans are the only natural host.

 

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April 2016

 

 

The Institut Pasteur teams

 

Research units

 

Biology of Enteric Viruses Unit

led by Francis Delpeyroux