of the nerve cells, leading to damage or destruction of motor neuron ganglia. when spinal neurons die, wallerian degeneration takes place, leading to weakness of those muscles formerly innervated by the now-dead neurons. with the destruction of nerve cells, the muscles no longer receive signals from the brain or spinal cord; without nerve stimulation, the muscles atrophy, becoming weak, floppy and poorly controlled, and finally completely paralyzed. maximum paralysis progresses rapidly (two to four days), and usually involves fever and muscle pain. deep tendon reflexes are also affected, and are typically absent or diminished; sensation (the ability to feel) in the paralyzed limbs, however, is not affected. the extent of spinal paralysis depends on the region of the cord affected, which may be cervical, thoracic, or lumbar. the virus may affect muscles on both sides of the body, but more often the paralysis is asymmetrical. any limb or combination of limbs may be affected – one leg, one arm, or both legs and both arms. paralysis is often more severe proximally (where the limb joins the body) than distally (the fingertips and toes). bulbar polio the location and anatomy of the bulbar region (in orange) making up about two percent of cases of paralytic polio, bulbar polio occurs when poliovirus invades and destroys nerves within the bulbar region of the brain stem. the bulbar region is a white matter pathway that connects the cerebral cortex to the brain stem. the destruction of these nerves weakens the muscles supplied by the cranial nerves, producing symptoms of encephalitis, and causes difficulty breathing, speaking and swallowing. critical nerves affected are the glossopharyngeal nerve (which partially controls swallowing and functions in the throat, tongue movement, and taste), the vagus nerve (which sends signals to the heart, intestines, and lungs), and the accessory nerve (which controls upper neck movement). due to the effect on swallowing, secretions of mucus may build up in the airway, causing suffocation. other signs and symptoms include facial weakness (caused by destruction of the trigeminal nerve and facial nerve, which innervate the cheeks, tear ducts, gums, and muscles of the face, among other structures), double vision, difficulty in chewing, and abnormal respiratory rate, depth, and rhythm (which may lead to respiratory arrest). pulmonary edema and shock are also possible and may be fatal. bulbospinal polio approximately 19 percent of all paralytic polio cases have both bulbar and spinal symptoms; this subtype is called respiratory or bulbospinal polio. here, the virus affects the upper part of the cervical spinal cord (cervical vertebrae c3 through c5), and paralysis of the diaphragm occurs. the critical nerves affected are the phrenic nerve (which drives the diaphragm to inflate the lungs) and those that drive the muscles needed for swallowing. by destroying these nerves, this form of polio affects breathing, making it difficult or impossible for the patient to breathe without the support of a ventilator. it can lead to paralysis of the arms and legs and may also affect swallowing and heart functions. diagnosis paralytic poliomyelitis may be clinically suspected in individuals experiencing acute onset of flaccid paralysis in one or more limbs with decreased or absent tendon reflexes in the affected limbs that cannot be attributed to another apparent cause, and without sensory or cognitive loss. a laboratory diagnosis is usually made based on the recovery of poliovirus from a stool sample or a swab of the pharynx. rarely, it may be possible to identify poliovirus in the blood or in the cerebrospinal fluid. poliovirus samples are further analysed using reverse transcription polymerase chain reaction (rt-pcr) or genomic sequencing to determine the serotype (i.e., 1, 2, or 3), and whether the virus is a wild or vaccine-derived strain. prevention passive immunization in 1950, william hammon at the university of pittsburgh purified the gamma globulin component of the blood plasma of polio survivors. hammon proposed the gamma globulin, which contained antibodies to poliovirus, could be used to halt poliovirus infection, prevent disease, and reduce the severity of disease in other patients who had contracted polio. the results of a large clinical trial were promising; the gamma globulin was shown to be about 80 percent effective in preventing the development of paralytic poliomyelitis. it was also shown to reduce the severity of the disease in patients who developed polio. due to the limited supply of blood plasma gamma globulin was later deemed impractical for widespread use and the medical community focused on the development of a polio vaccine. vaccine main article: polio vaccine a child receiving an oral polio vaccine two types of vaccine are used throughout the world to combat polio. both types induce immunity to polio and are effective in protecting individuals from disease. the first candidate polio vaccine, based on one serotype of a live but attenuated (weakened) virus, was developed by the virologist hilary koprowski. koprowski's prototype vaccine was given to an eight-year-old boy on 27 february 1950. koprowski continued to work on the vaccine throughout the 1950s, leading to large-scale trials in the then belgian congo and the vaccination of seven million children in poland against serotypes pv1 and pv3 between 1958 and 1960. the second polio virus vaccine was developed in 1952 by jonas salk at the university of pittsburgh, and announced to the world on 12 april 1955. the salk vaccine, or inactivated poliovirus vaccine (ipv), is based on poliovirus grown in a type of monkey kidney tissue culture (vero cell line), which is chemically inactivated with formalin. after two doses of inactivated poliovirus vaccine (given by injection), 90 percent or more of individuals develop protective antibody to all three serotypes of poliovirus, and at least 99 percent are immune to poliovirus following three doses. subsequently, albert sabin developed another live, oral polio vaccine (opv). it was produced by the repeated passage of the virus through nonhuman cells at subphysiological temperatures. the attenuated poliovirus in the sabin vaccine replicates very efficiently in the gut, the primary site of wild poliovirus infection and replication, but the vaccine strain is unable to replicate efficiently within nervous system tissue. a single dose of sabin's oral polio vaccine produces immunity to all three poliovirus serotypes in about 50 percent of recipients. three doses of live-attenuated oral vaccine produce protective antibody to all three poliovirus types in more than 95 percent of recipients. human trials of sabin's vaccine began in 1957, and in 1958 it was selected, in competition with the live vaccines of koprowski and other researchers, by the us national institutes of health. licensed in 1962, it rapidly became the only polio vaccine used worldwide. opv efficiently blocks person-to-person transmission of wild poliovirus by oral-oral and fecal-oral routes, thereby protecting both individual vaccine recipients and the wider community (herd immunity). ipv confers good immunity but is less effective at preventing spread of wild poliovirus by the fecal-oral route. wild polio vs cvdvp cases (2000–2019) because the oral polio vaccine is inexpensive, easy to administer, and produces excellent immunity in the intestine (which helps prevent infection with wild virus in areas where it is endemic), it has been the vaccine of choice for controlling poliomyelitis in many countries. on very rare occasions (about one case per 750,000 vaccine recipients), the attenuated virus in the oral polio vaccine reverts into a form that can paralyze. in 2017, cases caused by vaccine-derived poliovirus (cvdpv) outnumbered wild poliovirus cases for the first time, due to wild polio cases hitting record lows. most industrialized countries have switched to inactivated polio vaccine, which cannot revert, either as the sole vaccine against poliomyelitis or in combination with oral polio vaccine. treatment there is no cure for polio, but there are treatments. the focus of modern treatment has been on providing relief of symptoms, speeding recovery and preventing complications. supportive measures include antibiotics to prevent infections in weakened muscles, analgesics for pain, moderate exercise and a nutritious diet. treatment of polio often requires long-term rehabilitation, including occupational therapy, physical therapy, braces, corrective shoes and, in some cases, orthopedic surgery. portable ventilators may be required to support breathing. historically, a noninvasive, negative-pressure ventilator, more commonly called an iron lung, was used to artificially maintain respiration during an acute polio infection until a person could breathe independently (generally about one to two weeks). today, many polio survivors with permanent respiratory paralysis use modern jacket-type negative-pressure ventilators worn over the chest and abdomen. other historical treatments for polio include hydrotherapy, electrotherapy, massage and passive motion exercises, and surgical treatments, such as tendon lengthening and nerve grafting. sister elizabeth kenny's kenny regimen is now the hallmark for the treatment of paralytic polio. prognosis a girl with genu recurvatum of her right leg due to polio patients with abortive polio infections recover completely. in those who develop only aseptic meningitis, the symptoms can be expected to persist for two to ten days, followed by complete recovery. in cases of spinal polio, if the affected nerve cells are completely destroyed, paralysis will be permanent; cells that are not destroyed, but lose function temporarily, may recover within four to six weeks after onset. half the patients with spinal polio recover fully; one-quarter recover with mild disability, and the remaining quarter are left with severe disability. the degree of both acute paralysis and residual paralysis is likely to be proportional to the degree of viremia, and inversely proportional to the degree of immunity. spinal polio is rarely fatal. without respiratory support, consequences of poliomyelitis with respiratory involvement include suffocation or pneumonia from aspiration of secretions. overall, 5 to 10 percent of patients with paralytic polio die due to the paralysis of muscles used for breathing. the case fatality rate (cfr) varies by age: 2 to 5 percent of children and up to 15 to 30 percent of adults die. bulbar polio often causes death if respiratory support is not provided; with support, its cfr ranges from 25 to 75 percent, depending on the age of the patient. when intermittent positive pressure ventilation is available, the fatalities can be reduced to 15 percent. recovery many cases of poliomyelitis result in only temporary paralysis. generally in these cases, nerve impulses return to the paralyzed muscle within a month, and recovery is complete in six to eight months. the neurophysiological processes involved in recovery following acute paralytic poliomyelitis are quite effective; muscles are able to retain normal strength even if half the original motor neurons have been lost. paralysis remaining after one year is likely to be permanent, although some recovery of muscle strength is possible up to 18 months after infection. one mechanism involved in recovery is nerve terminal sprouting, in which remaining brainstem and spinal cord motor neurons develop new branches, or axonal sprouts. these sprouts can reinnervate orphaned muscle fibers that have been denervated by acute polio infection, restoring the fibers' capacity to contract and improving strength. terminal sprouting may generate a few significantly enlarged motor neurons doing work previously performed by as many as four or five units: a single motor neuron that once controlled 200 muscle cells might control 800 to 1000 cells. other mechanisms that occur during the rehabilitation phase, and contribute to muscle strength restoration, include myofiber hypertrophy – enlargement of muscle fibers through exercise and activity – and transformation of type ii muscle fibers to type i muscle fibers. in addition to these physiological processes, the body can compensate for residual paralysis in other ways. weaker muscles can be used at a higher than usual intensity relative to the muscle's maximal capacity, little-used muscles can be developed, and ligaments can enable stability and mobility. complications residual complications of paralytic polio often occur following the initial recovery process. muscle paresis and paralysis can sometimes result in skeletal deformities, tightening of the joints, and movement disability. once the muscles in the limb become flaccid, they may interfere with the function of other muscles. a typical manifestation of this problem is equinus foot (similar to club foot). this deformity develops when the muscles that pull the toes downward are working, but those that pull it upward are not, and the foot naturally tends to drop toward the ground. if the problem is left untreated, the achilles tendons at the back of the foot retract and the foot cannot take on a normal position. people with polio that develop equinus foot cannot walk properly because