Poliomyelitis

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101 reported cases in 2015 worldwide

In the pre-vaccine era, poliomyelitis affected over 600,000 children a year throughout the world

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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 around one infected person out of 200. Without palliative measures, between 5 and 10% of paralyzed patients die by asphyxia because of the paralysis of the muscles in charge of ventilation. In the surviving patients, Residual paralysis can be observed causing varying degrees of disability. This can range from minor paralysis with complete independence to extremely debilitating paralysis requiring lifelong 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.

Cause

The poliomyelitis virus is part of the Picornaviridae family which belongs to the Enterovirus genre. There are three poliovirus serotypes (1, 2 and 3), each being capable of inducing the disease.

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.

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, 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. In the 1980s, poliomyelitis still affected several hundred thousand of children every year. To fight the disease, the WHO launched the Global Polio Eradication Initiative in 1988. It is based on two main actions: surveillance, aiming to detect as early as possible the circulation of the virus, and the vaccination of all children in the world.

The two types of vaccine

The Injectable 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 its cost of production and the logistics associated with its use have long limited the distribution to some developed countries, like France. Its use is however in constant increase.

An Oral Polio Vaccine (OPV) was developed by Albert Sabin, also in the 1950s. The OPV contains live viruses but attenuated by mutations: the strains contained in the vaccine (one of each of the three serotype) infect vaccinated persons but are way less susceptible of infecting the central nervous system than non-attenuated strains. This vaccine has many advantages, which explains why, until now, it has been the key tool in the eradication program: it is easy to administer 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 those of live attenuated vaccines in general : the possibility of inducing the disease among some vaccinated people and the introduction in the environment of strains of live poliovirus, attenuated but which can establish transmission chains when vaccination is low, after their excretion by vaccinated people.

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. In addition, in countries where there is a greater risk of the disease, additional doses of the OPV are administered to all children under 5 during National Immunization Days.

Poliomyelitis monitoring is carried out thanks to the world network of polio laboratories, a network coordinated by the WHO which includes around 150 laboratories that test for polioviruses in all children under 15 with acute flaccid paralysis (AFP), the symptom that characterizes the disease. This network is also in charge of detecting the presence of poliovirus in used water which is a sign of an active circulation of the virus.

In 1988, the estimated world incidence rate of poliomyelitis was over 350,000 cases a year. Thanks to vaccination, the Americas (36 countries) were certified free of wild poliovirus (which is to say natural strain as opposed to attenuated strains of VPO) in 1994, followed by the Western Pacific Region (37 countries and territories, including China) in 2000, by Europe (51 countries) in June 2002, by the South-East of Asia in 2014 (11 countries including India) and in 2020 by Africa (47 countries). The wild serotype 2 strains have not circulated since 1999 and no cases associated with type 3 strains have been reported since November 2012: these two serotypes have therefore already been declared eradicated. So only wild type 1 strains are still circulating today.

The WHO initiative has therefore reduced the incidence rate of poliomyelitis by more than 99% (today it stands at a few hundred cases per year), eradicated two of the three serotypes and to lessen the circulation of the last serotype in two countries, Afghanistan and Pakistan.

A disease that is still present

Unprecedented vaccination campaigns have been organized in recent years to stop the virus from circulating. However, following the disappearance of the disease, some countries are failing to maintain sufficient vaccination coverage. Poliomyelitis therefore sometimes returns due to wild viruses, imported from the two countries where the disease remains endemic. In addition, the political instability of certain regions, conflicts, population displacements and the deficiencies of certain states complicate the implementation of systematic vaccination campaigns and an efficient surveillance system. Finally, the rejection of vaccination on religious grounds or based on unfounded rumours leads to extremely low vaccination rates in some parts of the world.

Not only does low vaccination coverage allow the circulation of wild poliovirus, it is sometimes also responsible for outbreaks of a new type of poliomyelitis, which has been reported in some countries since 2000. Natural transmission of the virus strains contained in the OPV in non-vaccinated children can contribute to the genetic drift of vaccine strains, which thereby regain a pathogenic nature. The vaccine strains that become pathogenic again are then responsible for paralysis identical to that induced by wild strains. The forthcoming use of a new OPV with the same advantages as the original OPV but containing attenuated strains that are much more genetically stable should limit the risk of reversion of vaccine strains.

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 (unlike cases of smallpox where all infections produced visible symptoms); it is therefore possible for poliovirus to circulate unnoticed which delays the implementation of countermeasures to contain them. The effectiveness of the surveillance system therefore needs to increase while the number of polio cases is declining..

At the Institut Pasteur

The Institut is involved in the study of poliovirus circulation and the emergence of pathogenic strains from poliovirus vaccine strains thanks to the WHO collaborating centre dedicated to research on the epidemiology and macroevolution of polio and non-polio enteroviruses which it hosts. This laboratory is one of the six reference laboratories of the WHO Global Polio Laboratory Network. It works in close collaboration with polio laboratories in several Institut Pasteur International Network institutes. Institutes in Madagascar, Central African Republic, Cameroon, Côte d'Ivoire, Senegal, Morocco, Algeria, Tunisia and Russia (St Petersburg) are responsible for poliovirus surveillance in their respective countries and in some neighbouring countries, and at the same time help identify other circulating enteroviruses.

Together, researchers in these different laboratories are working to improve surveillance for vaccine-derived poliovirus pathogens and to identify the viral and environmental factors that promote the emergence of these strains. Thus, the Institut Pasteur team in Paris and the International Network of Pasteur Institutes are fighting poliomyelitis on two fronts :

  • Monitoring the viruses circulating in healthy or paralysed children makes it possible, if pathogenic strains are detected, to alert the public health authorities, who then step up vaccination campaigns to stop and prevent epidemics.
  • The study of the epidemiological context and the viral and cellular factors that promote the emergence and pathogenicity of polioviruses from vaccine strains, as understanding these mechanisms can improve the prevention of epidemics. All this research also provides a model for understanding the emergence of new lineages of viruses with increased pathogenicity.

January 2021



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