3/01/2010

Salk vaccine fiftieth anniversary Dr. Jesús Kumate

 

Boletín médico del Hospital Infantil de México
Print version ISSN 1665-1146
Bol. Med. Hosp. Infant. Mex. vol.62 no.4 México Jul./Aug. 2005

Editorial
Cincuentenario de la vacuna Salk
de la vacuna Salk
Salk vaccine fiftieth anniversary
Dr. Jesús Kumate
                            http://amcath.ccadet.unam.mx/archivos/kumate.pdf
El terror estacional de los padres y niños en el mundo industrializado terminó el 12 de abril de 1955, cuando el profesor Thomas Francis, del Departamento de Epidemiología de la Escuela de Salud Pública, Universidad de Michigan en Ann Arbor, anunció que la vacuna anti poliomielitis con virus inactivados era: efectiva, inocua e inmunogénica.
Desde el 11 de abril de 1954 a marzo de 1955 se había realizado un ensayo clínico de la vacuna trivalente en niños escolares del primero al tercer grado de escuelas públicas de Estados Unidos y ensayos simultáneos en Canadá y Finlandia.
Un ensayo fue doble ciego, aleatorio en 221 998 alumnos de segundo año, que recibieron tres dosis de vacuna en los tiempos cero, primera y quinta semanas del inicio y 321 315 niños de primero y tercer año, a los que se administró un placebo en los mismos tiempos que los vacunados.
Un grupo de 749 326 alumnos de primero, segundo y tercer año recibieron alternativamente vacuna o placebo:
Durante el estudio se cultivaron 426 cepas de poliovirus: 238 (55.9%) serotipo 1,53 (12%) serotipo 2 y 135 (31.7%) serotipo 3. La protección vacunal según el serotipo fue:
68% para el poliovirus 1
100% frente al poliovirus 2
92% versus el poliovirus 3
94% ante las formas bulboespinales
80% global versus los tres serotipos.
El número de casos registrados en 1954 fue similar a los informados en el lapso 1949– 1953.
El desarrollo de la vacuna Salk fue la culminación de una historia de observaciones clínicas, epidemiológicas, biomédicas y tecnológicas a lo largo de 33 siglos.
• Una estela egipcia de la XVIII dinastía muestra a Roma, sacerdote de la diosa Astarté, con secuelas de polio;
• Galeno en el siglo II d.C. distinguía entre pie equino congénito y el adquirido;
• Monteggia en 1813 describió debilidad de los miembros inferiores desde la fase aguda hasta la discapacidad crónica;
• Jacob von Heine en Prusia, 1840, describió un cuadro clínico de parálisis arrefléctica en miembros inferiores, asimétrica sin trastornos sensoriales;
• Charcot y Joffroy en 1855 confirman atrofia de las astas anteriores de la médula señalada anteriormente por Camil;
• Vulpian en Francia, 1870, describió el cuadro clínico tal como se conoce actualmente; infería que la enfermedad era infecciosa localizada a un segmento limitado de la médula espinal;
• Oskar Medin en Estocolmo, 1887, informa de 44 niños con un cuadro de diarrea, fiebre y malestar general que evolucionó a parálisis de los miembros inferiores. Un cuadro semejante en 20 niños observados siete años antes en un poblado del norte de Suecia le hizo proponer la etiología infecciosa del brote epidémico;
• Kart Landsteiner, Erwin Popper y Constantin Levaditi inocularon i.p. a un babuino y a un mono rhesus con el extracto filtrado de la médula espinal de un niño fallecido por poliomielitis; al cuarto día postinoculación el babuino murió y el mono rhesus presentó parálisis del tren posterior La inoculación posterior del rhesus resultó inocua;
• Frank M. Burnet y Jean Mac Namara encuentran dos serotipos de polivirus en 1931;
• Maurice Brodie y William Park usan preparaciones tisulares infectadas "inactivadas" con ricinoleato o formol y las aplican a mas de 3 000 niños con resultados catastróficos: parálisis y fallecimientos en varios casos;
• Hasta 1949 la investigación de poliomielitis requería monos rhesus para probar la neurovirulencia de cada cepa del serotipo en estudio; impráctico, costoso y difícil por el manejo de los monos. Como fuente de virus para vacuna imposible, dado el escaso rendimiento de las médulas infectadas;
• John Enders,Thomas Weller y Frederick Robbins en 1949 publicaron en Science 109:85– 7, "Cultivation of the Lansing strain of poliomyelitis virus in cultures of various human embryonic tissues". Por primera vez se cultivaba un poliovirus en tejidos no– neurales,con rendimientos casi astronómicos: 1015, posteriormente simplificaron el medio de cultivo, descubrieron el efecto citopatogénico y encontraron, como lo había señalado Theiler en 1937 con el virus de la fiebre amarilla, los "pases" subsecuentes, atenuaban la neurovirulencia en monos rhesus.
El cultivo en tubos de ensayo y la titulación en placas eran la sustitución de cientos de monos y la dilución de los sueros en estudio sustituyó a los monos. Estaban dadas todas las condiciones para producir una vacuna efectiva, el resto sería una tarea tecnológica. Con toda justicia se les adjudicó el Premio Nobel de Medicina y Fisiología de 1954

Polioviruses:
To view a high resolution computer-generated image reconstruction of a poliovirus particle, click here. Note the icosahedral symmetry which is clearly visible in this image. These are the prototypic Picornaviruses; there are 3 distinct serotypes. They cause poliomyelitis (flaccid muscular paralysis).
As with all the Enteroviruses, they are transmitted by the faecal-oral route.

 Primary site of infection is lymphoid tissue associated with the oropharynx and gut
(GALT).
Virus production at this site leads to a transient viraemia, following which the virus
may infect the CNS. This is of interest because of this apparent 'dual tropism' of the
virus for two distinct cell types - reflects the distribution of the poliovirus receptor
CD155 on cells lymphoid/ epithelial cells in the gut and on neurons in the CNS.
Replication of the virus in the CNS occurs in the 'grey matter', particularly motor
neurones in the anterior horns of the spinal cord and brain stem. Distinctive 'plaques'
produced in the grey matter are due to lytic replication of the virus & probably
 inflammation caused by an over-enthusiastic immune response.

Pri
~1% of people infected with the most virulent strains experience paralysis (99% asymptomatic infections). Death is usually due to respiratory failure by paralysis of the intercostal muscles and diaphragm.
Effective polyvalent vaccines are available against polioviruses - OPV/IPV . In 1988, the World Health Assembly established the year 2000 for achieving global poliomyelitis eradication. By 1994, the Americas were certified as polio-free. All other regions are making steady progress towards this goal
David Bodian en 1949 descubrió el tercer serotipo de poliovirus;
• W M. Harmmon y col., en 1953 demostraron la efectividad profiláctica de la globulina gamma; sin posibilidad práctica para su aplicación universal, pero probaron que la efectividad protectora era función de la presencia de anticuerpos específicos versus los poliovirus;

“Breaking the back of polio”

In the 1940s, Yale’s Dorothy Horstmann solved a puzzle that would lead to the first polio vaccines 50 years ago this year.

by David M. Oshinsky, Ph.D.

Fifty years ago this year, following the largest public health trial in American history, a killed-virus polio vaccine developed by Jonas Salk, M.D., was found to be safe, potent and effective. The news set off a national celebration. Salk became an instant hero, the country’s first celebrity-scientist, a miracle worker in a starched white lab coat. But as the years passed, the essential contributions of other researchers to this lifesaving vaccine were lost to history. Dozens of men and women had been involved—at Harvard and Yale, at Johns Hopkins and the Rockefeller Institute for Medical Research, at the University of Michigan, the University of Pittsburgh and the University of Cincinnati. What follows is the story of Dorothy Millicent Horstmann, M.D., FW ’43, whose patience and intuition produced a stunning breakthrough that made polio vaccines possible.

The story begins in June 1916, with a health crisis in Pigtown, a densely populated immigrant neighborhood of Brooklyn, N.Y. Frightened Italian parents had approached local doctors and priests, according to news accounts, “complaining that their child could not hold a bottle or that the leg seemed limp.” When the first deaths followed a few days later, health department investigators rushed to Pigtown for a house-to-house inspection. All signs pointed to a disease known as infantile paralysis, or poliomyelitis (soon shortened to “polio” by the newspapers to save headline space). As it spread from Brooklyn, communities across the Northeast closed their doors to outsiders, using heavily armed policemen to patrol the train stations and the roads. The epidemic, which lasted through October 1916, claimed 6,000 lives and left 27,000 people paralyzed. New York City alone reported 8,900 cases and 2,400 deaths, 80 percent of the fatalities being children under 5. There had been minor polio outbreaks in previous years, but nothing like this.

“The menace for the future,” warned a federal health official, “is very real.”

Polio is an intestinal infection spread by contact with fecal waste. The virus enters the body through the mouth, travels down the digestive tract and is excreted in the stool. Usually the infection is slight, with minor symptoms. In a small number of cases—about one in 100—the virus invades the central nervous system, destroying the motor neurons that stimulate the muscle fibers to contract. At its worst, polio causes irreversible paralysis, most often in the legs. Most deaths occur when the breathing muscles are immobilized, a condition known as bulbar polio, in which the brain stem is badly damaged.

Though poliovirus has long been present in the environment, the disease, unlike smallpox or influenza, had triggered no major outbreaks around the world. Why it took root in Western nations, especially the United States, during the 20th century is still a matter of debate. Some researchers pointed to more careful reporting and better diagnostic techniques. Others noted the circulation of more virulent strains of poliovirus, capable of multiplying at a ferocious rate. Still others saw a correlation between the spread of polio and the ever-increasing standards of personal hygiene in the United States—people were less likely to come into contact with poliovirus early in life when the infection is milder and maternal antibodies offer temporary protection. Put simply, America’s antiseptic revolution brought risks as well as rewards.

A dread disease strikes at random
By mid-century, polio had become the nation’s most feared disease. And with good reason. It hit without warning. It killed some victims and marked others for life, leaving behind vivid reminders for all to see: wheelchairs, crutches, leg braces and deformed limbs. In 1921, it paralyzed 39-year-old Franklin Delano Roosevelt, robust and athletic, with a long pedigree and a cherished family name. If a man like Roosevelt could be stricken, then no one was immune.

Each June in America, like clockwork, came newspaper photos of jam-packed polio wards and eerily deserted beaches. Newspapers ran tallies of the victims—age, sex, type of paralysis—akin to baseball box scores. Children were warned not to jump into puddles or share a friend’s ice cream cone. Parents checked for every known symptom: a sore throat, a fever, the chills, nausea, an aching limb. Some gave their children a daily “polio test.” Did the neck swivel? Did the toes wiggle? Could the chin reach the chest?

In truth, polio was never the raging epidemic portrayed by the media, not even at its height in the late 1940s and early 1950s. Ten times as many children would be killed in accidents in these years, and three times as many would die of cancer. What had changed following World War II was the incidence of polio in the United States as well as the rising age of the victims, a quarter of whom were now older than 10. From 1940 to 1944, reported polio cases doubled to eight per 100,000, doubled again to 16 per 100,000 between 1945 and 1949, and climbed to 25 per 100,000 from 1950 to 1954, before peaking at 37 per 100,000 in 1952. “The United States had never experienced a higher crest of the epidemiological wave,” a journalist noted of the 57,000 reported cases that year, “and never would again.”

The drive to combat polio was led by the National Foundation for Infantile Paralysis, now known as the March of Dimes. The genius of this foundation lay in its ability to single out polio for special attention, making it seem more ominous, and curable, than other diseases. Its strategy would revolutionize the way charities raised money and penetrated the world of medical research. Millions of foundation dollars would be spent to set up virology programs and polio units across the country, with the first grant going to the Yale School of Medicine in 1936. Although research funding went in many directions, one point became increasingly clear: the best way to prevent polio would come through a vaccine.

This was hardly a revelation. Vaccines already had proved successful against other viruses—smallpox and rabies being notable examples. But producing a safe and effective one against polio would not be easy. Three major problems had to be solved. First, researchers would have to determine how many different types of poliovirus there were. Second, they would have to develop a safe and steady supply of each virus type for use in a vaccine. Third, they would have to discover the true pathogenesis of polio—its route to the central nervous system—in order to fix the exact time and place for the vaccine to do its work.

The first problem took the longest to solve. Dozens of strains were examined, using the stools, throat cultures and, in fatal cases, nerve tissue of polio victims. Most of this work was done by ambitious young researchers hoping to attract March of Dimes grant money. (The list included Salk at the University of Pittsburgh.) As it turned out, all of the 196 tested strains of poliovirus fit neatly into three distinct types. The poliovirus family proved remarkably, conveniently, small.

A polio vaccine, then, would have to protect against all three virus types to be successful. The next step involved the harvesting of poliovirus that was safe enough, and plentiful enough, for use in that vaccine. At Harvard, John F. Enders, Ph.D., a Yale College graduate, Frederick C. Robbins, M.D., and Thomas H. Weller, M.D., using in vitro cultivation, grew poliovirus in non-nerve tissue—a breakthrough that would win them the Nobel Prize in physiology or medicine. By cultivating these viruses in a test tube, rather than in the brain or spinal column of a monkey, researchers could get a better look at the changes occurring in polio-infected cells. Far more important, a safe reservoir of poliovirus had now been created, free from the contaminating effects of animal nerve tissue. And that, in turn, made possible the mass production of a vaccine.

But a major problem remained to be solved. Though Albert B. Sabin, M.D., and others had speculated that poliovirus entered the body through the mouth and worked its way down the digestive tract, no one had yet discovered traces of the virus in the victim’s bloodstream. How, then, did it wind up in the central nervous system? The answer would come from a research laboratory at Yale.

A girl’s impossible dream in a world of men
Horstmann had a powerful fantasy as a child: she imagined herself as a doctor. Born in Spokane, Wash., in 1911, she grew up in San Francisco, where as a teenager she accompanied a physician friend of the family as he made his rounds through the local hospital. Earning her undergraduate (1936) and medical (1940) degrees from the University of California, San Francisco, Horstmann recalled that it had “never crossed my mind that [this] was in any way unusual for a woman. … It was quite natural.”

In 1941, Horstmann applied for a residency at Vanderbilt University Hospital in Nashville, where the chief of medicine, Hugh Morgan, M.D., had a strict policy of choosing only men. “I got back a polite letter, saying no,” she recalled in an unpublished interview with historian Daniel J. Wilson, Ph.D., of Muhlenberg College in Pennsylvania. “I wasn’t exactly crushed, but I was disappointed.” Six months later, while considering an offer to enter private practice in San Francisco, she received a note from Morgan asking if “Dr. Horstmann” was still interested. She was, indeed. Somehow, Morgan had forgotten that Dr. Horstmann was a woman. Horstmann later learned from his secretary that when Morgan discovered his error, he “all but went into shock. … But we became friends, and I had a very good year there.”

When Horstmann subsequently applied for a postdoctoral fellowship at Yale, her first visit to New Haven did not go well. She had hoped to study with John R. Paul, M.D., a young pathologist who had co-founded the Yale Poliomyelitis Study Unit in 1931 with James D. Trask, M.D. As luck would have it, Paul had been called away to study a polio epidemic, leaving Horstmann to meet with Francis G. Blake, M.D., the acting dean. A giant in the field of infectious disease who was known to generations of medical students as “stuffy and remote,” Blake couldn’t quite picture Horstmann at Yale. Indeed, she recalled, he “went on to tell me how the last woman he had on the house staff did something awful.” Offended, and blissfully ignorant of the dean’s imposing reputation, she replied that “if a woman on the house staff did not live up to expectations it was remembered for the next 50 years, but if the person was a man, it was forgotten by the next year.” Horstmann was told the decision would be up to Paul. “He accepted me,” she said, “and that is how it all began.”

In 1942, with World War II under way, she arrived at Yale. As head of the Commission on Neurotropic Virus Diseases of the Army Epidemiological Board, Paul was constantly traveling to remote parts of the world. Concentrating on the spread of polio among Allied troops in North Africa, Paul confirmed the theory that adults from areas with high sanitary standards, such as Western Europe and the United States, were far more susceptible to the disease than the local population, which had built up immunity following generations of exposure.

In New Haven, Horstmann joined the Yale polio unit. Missing its two founders—Trask died of a bacterial infection in 1942 while working at an Army camp—the ranks included a handful of superb researchers, such as Joseph L. Melnick, M.D., and Robert Ward, M.D. Using an approach pioneered by Paul and known as “clinical epidemiology,” the polio unit, including Horstmann, tracked polio epidemics in Connecticut, Illinois, New Jersey, western New York state and Hickory, N.C., site of one of the worst outbreaks of the 20th century. The unit tested water and sewage, trapped flies and other insects and took blood samples from those who had the disease and those without symptoms, hoping to discover both the route of poliovirus through the body and the manner of transmission from one person to another. For Horstmann, who had come to Yale to study Streptococci, the switch to polio was inspiring. “It had a dramatic immediacy,” she said. “When you deal with an epidemic you realize it’s an urgent thing. There was so much to be learned.”

Tracking polio’s pathogenesis
Like others in the polio group, Horstmann combined her clinical studies with laboratory research. During a polio epidemic in New Haven in 1943, she collected blood specimens from every patient admitted to the hospital with symptoms of the disease—111 in all. Only one tested positive for poliovirus, a little girl with minor neck pain. Was it possible, Horstmann wondered, that poliovirus was only present in the bloodstream during the brief period before a victim took sick and the physical symptoms became apparent?

To test this theory, she began a series of experiments on monkeys, feeding them poliovirus by mouth to determine if, and when, it turned up in their blood. The results were dramatic. Poliovirus was detected within days of the feedings. Why had so many others failed to discover this? The answer was deceptively simple: they had waited too long before looking. Horstmann’s discovery, published in 1952, would pave the way for both the Salk killed-virus polio vaccine and the Sabin live-virus polio vaccine.

Working independently at Johns Hopkins, researcher David Bodian, Ph.D., M.D., later reported almost identical results. When poliovirus enters the blood, it creates the very antibodies that will soon destroy it, wiping away the signs of its existence. Horstmann had determined the time (early in the infection) and the place (the bloodstream) for the battle against polio to be waged. Her findings meant that an immunizing vaccine, packing low levels of antibody, could destroy the virus before it entered the central nervous system. In a personal letter to Horstmann in 1953, John F. Fulton, M.D., D.Phil., Yale’s distinguished historian of medicine, proclaimed: “This disclosure is as exciting as anything that has happened in the Yale Medical School since I first came here in 1930 and is a tremendous credit to your industry and scientific imagination. … It is also medical history.”

That history would continue. In 1959, the World Health Organization sent Horstmann to the Soviet Union, Czechoslovakia and Poland to evaluate the massive public health trial involving Sabin’s oral polio vaccine. Her favorable report led the way to its licensing, and widespread acceptance, in the United States and beyond. Worldwide the incidence of polio fell to 1,919 cases in 2002, a decline of 99 percent since 1988, when 350,000 cases were reported. The United States has not seen a case of wild polio since 1979.

In later years, Horstmann became the first female professor of medicine at Yale (1961), the first woman in the university to hold an endowed chair (1969) and an elected member of the National Academy of Sciences (1975).

Horstmann died in 2001. Today her portrait hangs at the School of Medicine in a gallery of luminaries from the 19th and early 20th centuries. She is the only woman honored on these walls.YM

David M. Oshinsky, Ph.D., the George Littlefield Professor of American History, University of Texas at Austin, is the author ofPolio, An American Story: The Crusade That Mobilized the Nation Against the 20th Century’s Most Feared Disease, published this year by Oxford University Press.

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Dorothy Hortsmann en 1951 encuentra que la viremia de poliovirus precede al desarrollo de las parálisis;
• Se define que la vacuna antipolio debe inducir anticuerpos neutralizantes del efecto citopatogénico de los tres serotipos de poliovirus y que debe desarrollar memoria inmunológica.
Se trabajó en las dos posibilidades:
1. Vacuna trivalente de virus inactivos y
2. Vacunas monovalentes o trivalentes de virus atenuados para evitar la interferencia de los serotipos vivos atenuados;
• Jonas Salk había colaborado con Thomas Francis en el desarrollo de la vacuna de la influenza mediante la inactivación de virus cosechados de embrión de pollo con formol. Se aplica desde 1944 hasta la fecha;
• El desarrollo de la vacuna requirió la producción de grandes cantidades de los virus en los Laboratorios Connaught en Toronto, Canadá, y los ensayos necesarios para garantizar la inactivación viral y la preservación de la inmunogenicidad;
• Los ensayos en seres humanos (la actual Fase I) se realizaron primero en la Escuela Estatal Polk para niños y adultos con retardo mental y en el Hospital Watson para niños discapacitados en Pittsburg. Las pruebas serológicas revelaron que los títulos de anticuerpos post vacunales eran mayores que los desarrollados al padecer la enfermedad natural.
• Salk vacunó a sus tres hijos y varios empleados de su laboratorio. En 1953 había vacunado a 700 personas sin efectos adversos y con respuestas de anticuerpos a títulos elevados. En el momento actual los requerimientos para realizar un ensayo semejante serían mucho más difíciles de aprobar y llevarían mucho tiempo. Sólo quedaba por probar el ensayo de protección en 1954;
• El mismo día del anuncio de Francis sobre la vacuna, 12 de abril de 1955, la Agencia Federal de Drogas (FDA) autorizó la licencia sanitaria para producir la vacuna a los laboratorios Eli íi% Parke Davis, Wyeth, Pittman Moore y Cutter;
• El 26 de abril se recibieron reportes de California sobre niños vacunados con parálisis en los brazos, en donde había sido aplicada la vacuna; el número de casos aumentó. Los casos ocurrieron en vacunados con lotes del laboratorio Cutter De inmediato se suspendió la vacuna de ese origen y el 7 de junio se detuvo el programa de vacunación hasta nueva orientación;
• De los 380 000 niños que recibieron la vacuna de Cutter, 120 000 fueron inmunizados con lotes contaminados. Ocurrieron 50 casos en vacunados, 101 en contactos familiares no– vacunados y en 32 casos de contactos comunitarios;
• La causa: inactivación incompleta en 2/8 lotes con predominio del serotipo 1. Hubo 60 demandas judiciales que en 54 casos se arreglaron con indemnizaciones por más de tres millones de dólares;
• El accidente Cutter obligó a reforzar las medidas de inactivación con la consiguiente reducción en la inmunogenicidad. Posteriormente la potencia inmunogénica se recuperó, y aún incrementó, por Anton von Wezel en Bilthoven, Holanda, 1967, mediante el cultivo en microesferas y su concentración ulterior Bernard Montagnon en Lyon, 1988, consiguió cosechar los virus en células Vero transformadoras para cultivo continuo;
• El cambio progresivo de vacuna Salk por la vacuna Sabin obedeció a la facilidad de administración, la inducción de inmunidad local amén de la generalizada y de la rapidez en la aparición de anticuerpos protectores y de su costo más reducido;
• El cambio de Sabin a Salk obedece a no aceptar los casos de parálisis asociada a la vacuna Sabin. En el futuro, a mediano plazo, se impondrá la vacuna Salk por su inocuidad, inmunogenicidad y facilidad de combinarla con tres o cuatro inmunógenos vacunales v.gr. toxoides diftérico y tetánico, antígenos purificados de Bortedella pertussis y antígeno de superficie de la HVB
Referencias
1. Brodie M, Park WH. Active immunization against poliomyelitis. Am J Pub Health. 1936; 26: 119– 25.
2. Enders J, Weller T, Robbins F. Cultivation of the Lansing strain of poliomyelitis virus in cultures of various human embryonic tissues. Science. 1949; 109:85– 7.
3. Francis T, Korns R, Voight R, et. al. An evaluation of the 1954 poliomyelitis vaccine trials. Ann Arbor: University of Michigan; 1955.
4. Wilson G. The Cutter incident. En:"The hazards of immunization". London:The Athlone Press; 1967. p. 44– 8.
5. Katz SL. From culture to vaccine – Salk and Sabin. N Engl J Med. 2004; 315: 1485– 7.
6. Kolmer JA.Vaccination against acute anterior poliomyelitis. Am J Pub Health. 1936; 26: 126– 35.
7. Lepow ML. Advances in virology – Weller and Robbins. N Engl J Med. 2004; 315: 1485– 7.
8. Markel H. April 12, 1955 – Tommy Francis and the Salk vaccine. N Engl J Med. 2005; 352: 1408– 10.
9. Offit PA. The Cutter incident, 50 years later. N Engl J Med. 2005; 352: 1411– 2.
10. Paul JE. Indications for vaccination against poliomyelitis. JAMA. 1956; 162: 1585– 96.
11. Paul JR. Endemic and epidemic trends of poliomyelitis in Central and South America. Bull World Health Organ 1958; 19: 747– 58.
12. Paul JR, Riordan JT, Melnick JL. Antibodies to three different antigenic types of poliomyelitis in sera from north alaskan eskimos.Am J Hyg. 1951; 54: 275– 85.
13. Plotkin SA, Vidas E. Poliovirus vaccine inactivated. En: "Vaccines". 4th. ed. Philadelphia: Plotkin & Orenstein, Saunders; 2004. p. 625– 49.
14. Robbins FC. The history of polio vaccine development En:"Vaccines". 4th. ed. Philadelphia: Plotkin & Orenstein, Saunders; 2004. p. 17– 30.
15. Rosen FS. Isolation of poliovirus – John Enders and the Nobel Prize. N Engl J Med. 2004; 351: 1481 – 3
16. Setre B, Shaffer M. A world without polio. St.André lesverges. Aventis Pasteur. 2003.

©  2010  Instituto Nacional de Salud, Hospital Infantil de México Federico Gómez

Departamento de Ediciones Médicas,
Dr. Márquez núm.162,
Col. Doctores,
Delegación Cuauhtémoc,
México, D.F., México

                                                           bolmedhim@prodigy.net.mx





Poliovirus
 
El Objetivo del laboratorio es llevar acabo la vigilancia epidemiológica de poliovirus mediante técnicas de vanguardia para el diagnóstico en casos de parálisis flácida aguda así como el apoyo en brotes y casos esporádicos de meningitis y encefalitis asociados a enterovirus no polio.


 

viñeta Técnicas para el diagnóstico de poliovirus
viñeta RT-PCR PARA EL GÉNERO DE EV

Este gel de poliacrilamida muestra la identificación RT-PCR del género enterovirus con la amplificación de un fragmento de 114 pb de la región NTR´5.
El carril 13 tiene un marcador de peso molecular V, con fragmentos de DNA cuyo tamaño debe corresponder con el que se ha amplificado.
(pb=pares de bases, PV=poliovirus, CVB1= Cosxackievirus B1).

RT-PCR PARA IDENTIFICAR EL GÉNERO ENTEROVIRUS

el de Poliacrilamida G
 al 10%. Filas del 1) al 7) muestras de virales aisladas, 8)Control positivo CVB1, 9)Control  positivo E30, 10)Control  positivo PV1, 11) Control positivo PV2, 12) Control positivo PV3, 13)Marcador V, 14) Control celular, 15) Control Negativo.




 RT-PCR  PARA POLIOVIRUS VACUNAL
El gel de poliacrilamida muestra la identificación por RT-PCR múltiple para la diferenciación intratípica de los 3 serotipos vacunales de poliovirus:PV1=97pb, PV2=72pb y PV3=53pb.
Los carriles 1 y 13 tiene un marcador de peso molecular V, con fragmentos de DNA cuyo tamaño debe corresponder con los que se han amplificado.
  (pb=pares de bases, PV=poliovirus, S=Sabin).
RT-PCR para identificar los 3 serotipos de PV vacunal S1, S2 Y S3
 
RT-PCR PARA IDENTIFICAR LOS 3 SEROTIPOS DE PV VACUNAL S1, S2 Y S3
Gel de Poliacrilamida al 10%. 1) Marcador V, del 2) al 6) Cepas virales aisladas, 7) Control Positivo  PV3 , 8)  Control Positivo  PV2, 9) Control Positivo  PV1, 10) y 11) cepas virales en 
estudio, 12) Control celular, 13) Marcador V.



 Imágenes  Originales Que Conmueven El Alma.















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