Poliomyelitis

Paul R. EarlFacultad de Ciencias Biológicas

Universidad Autónoma de Nuevo León

San Nicolás, NL, Mexico 66451

pearl@dsi.uanl.mx

Poliomyelitis is an acute infectious disease of humans, particularly children, caused by any of three serotypes of human enteric poliovirus. Usually the infection is limited to the gastrointestinal tract and nasopharynx and is often asymptomatic. The central nervous system (CNS), primarily the spinal cord, may be affected, leading to rapidly progressive paralysis, coarse fasciculation and hyporeflexia. Motor neurons are primarily affected. Encephalitis may also occur. The virus multiplies in the nervous system and may cause significant neuronal loss, most notably in the spinal cord. Acute flaccid paralysis of the legs is common.

The reality of infantile paralysis in the days before persistent

vaccination solved this tragedy.

The wartime President and Eleanor

History. Michael Underwood described poliomyelitis as a debility of the lower extremities in the second edition of his book Treatise on the Diseases of Children, 1789. In 1840, Jacob von Heine described anterior acute poliomyelitis and the differences with other types of paralysis. Lesions in the spinal medula were demonstrated in 1870 by Jean-Martin Charcot & Alex Joffroy. The Bavarian neurologist Wilhelm Heinrich Erb coined the term “anterior acuta poliomielitis” for clinical adult cases. In Greek, polios means grey and myelos medula. Of course, the ending –itis means inflammation of.

Karl Landsteiner (1868-1943)

(1906-1993)

In 1953-55, Jonas Salk at the University of Pittsburgh, Pittsburgh, Pennsylvania, using primary monkey kidney cells, produced a successful formalin-killed trivalent (all 3 serotypes) vaccine that had production and field trials at the Connaught Laboratories then affiliated to the University of Toronto now Aventis Pasteur. Salk’s inactive vaccine was also tested in the US.

Look at the term PRIMARY. That cell line originated from some animal or human, and in this case rhesus monkeys that are very expensive and sometimes protected by religions in Asia. As the primary line will become senescent and die out, the practical polio vaccine problem is paying for enough monkeys. Only sex and cancer cells are immortal. Secondary lines like HeLa cells (Helen Lane, donor, cancer of uterus) cannot be used for vaccine production. Human diploid cells can be used as they have fairly normal chromosome behavior (2n = 46).

Oral vaccines.

Except for oral live vaccines by 1955, the stage was set for polio eradication, although it was never considered at that time. Generally, live vaccines leave a higher neutralizing antibody titer than formalinized or otherwise killed vaccines.

Three teams engaged in the vaccine race: a) Lederle’s, b) Wistar and c) Cincinnati.More fully, these were Lederle Laboratories, Pearl River, NY under Herald Cox, Wistar Institue of the University of Pennsylvania, Philadelphia, PA under Hilary Kaproski, and Microbiology of the University of Cincinnati, Cincinnati, OH under Albert Sabin. The Lederle’s attenuated strains has been under development since 1946 by Cox & Kaprowski.

In a half century, 2 emminently successful vaccines, oral (OPV) vs inactivated (IPV) have driven wild serotypes to virtual extinction. In 1952, 58,000 cases of polio were registered in the US. In 1960 with vaccinations started in 1957, cases dropped to 3,000 which is amazing. Persistant high-coverage vaccines have driven some of the formerly vicious infections out of business. In 2001, in the world 537 cases of polio were recognized in 10 countries: Angola, Nigeria, Niger, Ethiopía, Afganistán, Pakistán, Egypt, Sudan, Somalia and

India. Eradication is on the horizon.

Vaccine recommendations. 1/ IPV is routinely recommended for all children at 2-4 months of age for the first 2 doses of the poliovirus vaccine schedule. Immunization with OPV is acceptable when parents refuse either IPV or the number of injections needed

to administer the other recommended vaccines for infants. 2/ With either the sequential or IPV-only regimen, OPV or IPV should be given at 6-18 months and 4-6 years of age for a total of 4 doses of polio vaccine administered before school entry. Note that a child can have an underlying,

unrecognized immunodeficiency.

Vaccine recommendations. (cont) 3/ Only IPV is recommended for the following: a) immunocompromised persons and their household contacts because OPV is contraindicated in these individuals; and b) infants and children in households with persons older than 17 years who are known to be inadequately vaccinated against polio, because of the increased risk of VAPP in susceptible adults. 4/ For infants and children in whom the routine immunization schedule is not initiated until after 6 months of age and in whom an accelerated schedule is necessary to fulfill immunization recommendations, an OPV-only regimen is acceptable to minimize the number of injections at each visit.

5/ For children who may be traveling to areas where wild-type polioviruses like Mahoney are still endemic, selection of IPV or OPV depends on the interval until departure and the number of doses of polio vaccine previously received. For children who already have received 2 doses of IPV, administration of 2 doses of OPV at an interval of 1 month will provide optimal intestinal immunity. 6/ If an outbreak of wild-type poliovirus infection occurs in the United States, OPV is the vaccine of choice to control most effectively the spread of infection. 7/ As with administration of all vaccines, parents and child care people should be informed of the benefits and risks of the different poliovirus vaccines and regimens, including the risk of VAPP from OPV. But all polio vaccines are on the way out.

The Global Polio Eradication Initiative.

In 1988, the 41st World Health Assembly of the delegates from 166 Member States, launched a global initiative to eradicate polio by the end of the year 2000. This followed the certification of the eradication of smallpox in 1980, progress during the 1980s towards elimination of the poliovirus in the Americas, and Rotary International’s commitment to raise funds to protect all children from the disease.

In 1994, the World Health Organization (WHO) Region of the Americas (36 countries) was certified polio-free, followed by the WHO Western Pacific Region (37 countries and areas including China) in 2000 and the WHO European Region (51 countries) in June 2002. Widely endemic on five continents in 1988, polio is now found only in parts of Africa and south Asia.

Before a WHO region can be certified polio-free, three conditions must be satisfied: a) at least three years of zero polio cases due to wild poliovirus; b) excellent certification standard surveillance; c) each country must illustrate the capacity to detect, report and respond to “imported” polio cases. Laboratory stocks must be contained and safe management of the wild virus in Inactivated Polio Vaccine (IPV) manufacturing sites must be assured before the world can be certified polio-free.

The Global Polio Eradication Technical Consultative Group (TCG) is overseeing a program of research and consensus-building which will lead to the development of posteradication polio immunization policy options. WHO, Rotary International, the US Centers for Disease Control and Prevention (CDC) and the United Nations Children’s Fund (UNICEF) form a coalition financing world eradication as shown in the pie chart.

The polio eradication coalition includes: the governments of affected countries, private foundations like the United Nations Foundation and Bill & Melinda Gates Foundation, development banks, donor governments as Australia, Austria, Belgium, Canada, Denmark, Finland, Germany, Ireland, Italy, Japan, Luxembourg, Netherlands, Norway, United Kingdom and US, the European Commission, humanitarian and non-governmental organizations like the International Red Cross and Red Crescent societies, and corporate partners of Aventis Pasteur, De Beers

and Wyeth.