Acute poliomyelitis

Acute poliomyelitis

Definition:

Acute poliomyelitis is a disease of the anterior horn motor neurons of the spinal cord and brainstem caused by poliovirus. Flaccid asymmetric weakness and muscle atrophy are the hallmarks of its clinical manifestations, due to loss of motor neurons and denervation of their associated skeletal muscles.

Poliomyelitis, often called polio or infantile paralysis, is an infectious disease caused by the poliovirus. Poliovirus is usually spread from person to person through infected fecal matter entering the mouth. Once infected there is no specific treatment. In 2014 the disease was only spreading between people in Afghanistan, Nigeria, and Pakistan. Poliomyelitis has existed for thousands of years, with depictions of the disease in ancient art. Signs and symptoms The term "poliomyelitis" is used to identify the disease caused by any of the three serotypes of poliovirus. Two basic patterns of polio infection are described: a minor illness which does not involve the central nervous system, sometimes called abortive poliomyelitis, and a major illness involving the CNS, which may be paralytic or nonparalytic. In most people with a normal immune system, a poliovirus infection is asymptomatic. Rarely, the infection produces minor symptoms; these may include upper respiratory tract infection, gastrointestinal disturbances, and influenza­like illness. About one to five in 1000 cases progress to paralytic disease, in which the muscles become weak, floppy and poorly controlled, and, finally, completely paralyzed; this condition is known as acute flaccid paralysis. Cause Poliomyelitis is caused by infection with a member of the genus Enterovirus known as poliovirus . This group of RNA viruses colonize the gastrointestinal tract — specifically the oropharynx and the intestine. The incubation time ranges from three to 35 days, with a more common span of six to 20 days. Its structure is very simple, composed of a single sense RNA genome enclosed in a protein shell called a capsid. All three are extremely virulent and produce the same disease symptoms. Transmission Poliomyelitis is highly contagious via the fecal­oral and the oral­oral routes. In endemic areas, wild polioviruses can infect virtually the entire human population. It is seasonal in temperate climates, with peak transmission occurring in summer and autumn. Virus particles are excreted in the feces for several weeks following initial infection. a mode especially visible in areas with good sanitation and hygiene. malnutrition, physical activity immediately following the onset of paralysis, skeletal muscle injury due to injection of vaccines or therapeutic agents, and pregnancy. Although the virus can cross the maternal­fetal barrier during pregnancy, the fetus does not appear to be affected by either maternal infection or polio vaccination. Maternal antibodies also cross the placenta, providing passive immunity that protects the infant from polio infection during the first few months of life. As a precaution against infection, public swimming pools were often closed in affected areas during poliomyelitis epidemics. Pathophysiology Poliovirus enters the body through the mouth, infecting the first cells with which it comes in contact — the pharynx and intestinal mucosa. It gains entry by binding to an immunoglobulin­like receptor, known as the poliovirus receptor or CD155, on the cell membrane. The virus then hijacks the host cell's own machinery, and begins to replicate. Poliovirus divides within gastrointestinal cells for about a week, from where it spreads to the tonsils, the intestinal lymphoid tissue including the M cells of Peyer's patches, and the deep cervical and mesenteric lymph nodes, where it multiplies abundantly. The virus is subsequently absorbed into the bloodstream. Known as viremia, the presence of a virus in the bloodstream enables it to be widely distributed throughout the body. Poliovirus can survive and multiply within the blood and lymphatics for long periods of time, sometimes as long as 17 weeks. In a small percentage of cases, it can spread and replicate in other sites, such as brown fat, the reticuloendothelial tissues, and muscle. This sustained replication causes a major viremia, and leads to the development of minor influenza­like symptoms. Rarely, this may progress and the virus may invade the central nervous system, provoking a local inflammatory response. In most cases, this causes a self­limiting inflammation of the meninges, the layers of tissue surrounding the brain, which is known as nonparalytic aseptic meningitis. The mechanisms by which poliovirus spreads to the CNS are poorly understood, but it appears to be primarily a chance event—largely independent of the age, gender, or socioeconomic position of the individual. The likelihood of developing paralytic polio increases with age, as does the extent of paralysis. In children, nonparalytic meningitis is the most likely consequence of CNS involvement, and paralysis occurs in only one in 1000 cases. In adults, paralysis occurs in one in 75 cases. In children under five years of age, paralysis of one leg is most common; in adults, extensive paralysis of the chest and abdomen also affecting all four limbs—quadriplegia—is more likely. Paralysis rates also vary depending on the serotype of the infecting poliovirus; the highest rates of paralysis are associated with poliovirus type 1, the lowest rates are associated with type 2. Spinal polio Spinal polio, the most common form of paralytic poliomyelitis, results from viral invasion of the motor neurons of the anterior horn cells, or the ventral grey matter section in the spinal column, which are responsible for movement of the muscles, including those of the trunk, limbs, and the intercostal muscles. Virus invasion causes inflammation 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 now­dead 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. 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. A laboratory diagnosis is usually made based on recovery of poliovirus from a stool sample or a swab of the pharynx. Antibodies to poliovirus can be diagnostic, and are generally detected in the blood of infected patients early in the course of infection. It is important to determine the source of the virus because for each reported case of paralytic polio caused by wild poliovirus, an estimated 200 to 3,000 other contagious asymptomatic carriers exist. Prevention Passive immunization In 1950, William Hammon at the University of Pittsburgh purified the gamma globulin component of the blood plasma of polio  2/4 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% effective in preventing the development of paralytic poliomyelitis. It was also shown to reduce the severity of the disease in patients who developed polio. Vaccine Two types of vaccine are used throughout the world to combat polio. Both types induce immunity to polio, efficiently blocking person­to­person transmission of wild poliovirus, thereby protecting both individual vaccine recipients and the wider community . The first candidate polio vaccine, based on one serotype of a live but attenuated virus, was developed by the virologist Hilary Koprowski. Koprowski's prototype vaccine was given to an eight­year­old boy on 27 February 1950. Koprowski continued to work on the vaccine throughout the 1950s, leading to large­scale 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 inactivated 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, is based on poliovirus grown in a type of monkey kidney tissue culture, which is chemically inactivated with formalin. 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% of recipients. Three doses of live­attenuated OPV produce protective antibody to all three poliovirus types in more than 95% of recipients. and in 1958 it was selected, in competition with the live vaccines of Koprowski and other researchers, by the US National Institutes of Health. On very rare occasions, the attenuated virus in OPV reverts into a form that can paralyze. Treatment There is no cure for polio. 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 long­term rehabilitation, including occupational therapy, physical therapy, braces, corrective shoes and, in some cases, orthopedic surgery. Half the patients with spinal polio recover fully; onequarter 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. Overall, 5–10% of patients with paralytic polio die due to the paralysis of muscles used for breathing. The case fatality rate varies by age: 2– 5% of children and up to 15–30% of adults die. When intermittent positive pressure ventilation is available, the fatalities can be reduced to 15%. Recovery Many cases of poliomyelitis result in only temporary paralysis. Paralysis remaining after one year is likely to be permanent, although modest recoveries of muscle strength are possible 12 to 18 months after infection. 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: In addition to these physiological processes, the body possesses a number of compensatory mechanisms to maintain function in the presence of residual paralysis. These include the use of weaker muscles at a higher than usual intensity relative to the muscle's maximal capacity, enhancing athletic development of previously little­used muscles, and using ligaments for stability, which enables greater mobility. In some cases the growth of an affected leg is slowed by polio, while the other leg continues to grow normally. The result is that one leg is shorter than the other and the person limps and leans to one side, in turn leading to deformities of the spine . Complications from prolonged immobility involving the lungs, kidneys and heart include pulmonary edema, aspiration pneumonia, urinary tract infections, kidney stones, paralytic ileus, myocarditis and cor pulmonale. notably new muscle weakness and extreme fatigue. This condition is known as post­polio syndrome or post­polio sequelae. The symptoms of PPS are thought to involve a failure of the oversized motor units created during the recovery phase of the paralytic disease. Contributing factors that increase the risk of PPS include aging with loss of neuron units, the presence of a permanent residual impairment after recovery from the acute illness, and both overuse and disuse of neurons. PPS is a slow, progressive disease, and there is no specific treatment for it. These efforts have reduced the number of annual diagnosed cases by 99.9%; from an estimated 350,000 cases in 1988 to a low of 483 cases in 2001, after which it remained at a level of about 1,000 ­ 2000 cases per year for a number of years. In 2015, cases decreased to 98 and further decreased in 2016 to 37 wild cases and 5 circulating vaccine­derived cases. Polio is one of only two diseases currently the subject of a global eradication program, the other being Guinea worm disease. So far, the only diseases completely eradicated by humankind are smallpox, declared so, in 1980, and rinderpest, likewise, in 2011. A number of eradication milestones have already been reached, and several regions of the world have been certified polio­free. A concern is the presence of circulating vaccine­derived polioviruses . The OPV is not perfect: while the genetic characteristics are carefully balanced to maximize efficacy and minimize virulence, it is possible for the OPV to mutate. As a result, persons given the OPV can acquire acute or chronic infections; or can transmit mutated OPV to other people. It is likely that cVDPV cases will exceed wild cases in the near future, making it desirable to discontinue use of the OPV as soon as safely possible. Emergency declaration In April 2012, the World Health Assembly declared the completion of polio eradication a programmatic emergency for global public health. Americas The Americas were declared polio­free in 1994. Western Pacific In 2000 polio was declared to have been officially eliminated in 37 Western Pacific countries, including China and Australia. Despite eradication ten years prior, an outbreak was confirmed in China in September 2011 involving a strain prevalent in neighboring Pakistan. Europe Europe was declared polio­free in 2002. On 1 September 2015, WHO confirmed 2 cases of circulating vaccine­derived poliovirus type 1 in Ukraine. South­East Asia The last case of polio in the region was in India in January 2011. Since January 2011, there have been no reported cases of the wild polio infections in India, and in February 2012 the country was taken off the WHO list of polio endemic countries. It was reported that if there are no cases of wild polio in the country for two more years, it would be declared as a polio­free country. On 27 March 2014 the WHO announced the eradication of poliomyelitis in the South­East Asia Region, which includes eleven countries: Bangladesh, Bhutan, North Korea, India, Indonesia, Maldives, Myanmar, Nepal, Sri Lanka, Thailand and Timor­Leste. With the addition of this region, 80 per cent of the world population lives in polio­free regions. although it continued to cause epidemics in other nearby countries due to hidden or reestablished transmission. In Syria difficulties in executing immunization programs in the ongoing civil war led to a return of polio, probably in 2012, acknowledged by the WHO in 2013. 15 cases were confirmed among children in Syria between October and November 2013 in Deir Ezzor. Later, two more cases, each one in rural Damascus and Aleppo, were identified. It was the first outbreak in Syria since 1999. Doctors and international public health agencies report more than 90 cases of polio in Syria, with fears of contagion in rebel areas from lack of sanitation and safe­water services. In May 2014, the World Health Organization declared polio's renewed spread a world health emergency. A vaccination campaign in Syria operated literally under fire and led to the deaths of several vaccinators, but returned vaccination coverage to pre­war levels. No new cases have been reported since January 2014; vaccination continues, and Iraq is also being closely monitored. Africa In 2003 in northern Nigeria—a country which at that time was considered provisionally polio free—a fatwa was issued declaring that the polio vaccine was designed to render children sterile. Subsequently, polio reappeared in Nigeria and spread from there to several other countries. In 2013, nine health workers administering polio vaccine were targeted and killed by gunmen on motorcycles in Kano, but this was the first and last attack. Local traditional and religious leaders and polio survivors worked to revive the campaign, and Nigeria has not had a polio case since July 24, 2014. In September 2015, Nigeria was removed from the polio­endemic list. In 2016 two cases recurred. but Africa had no confirmed cases of wild poliovirus in 2015. In September 2015, a case of cVDPV in Mali was confirmed by the WHO. and polio rates are declining rapidly in Afghanistan, with 19 cases in 2015 In Pakistan there were 53 cases in 2015, the highest number for any country, Cases have dropped by 70% in 2015; reasons include Dh440 million support from the United Arab Emirates to vaccinate more than ten million children, changes in the military situation, and arrests of some of those who attacked polio workers. History The effects of polio have been known since prehistory; Egyptian paintings and carvings depict otherwise healthy people with withered limbs, and children walking with canes at a young age. The first clinical description was provided by the English physician Michael Underwood in 1789, where he refers to polio as "a debility of the lower extremities". The work of physicians Jakob Heine in 1840 and Karl Oskar Medin in 1890 led to it being known as Heine–Medin disease. The disease was later called infantile paralysis, based on its propensity to affect children. Before the 20th century, polio infections were rarely seen in infants before six months of age, most cases occurring in children six months to four years of age. Poorer sanitation of the time resulted in a constant exposure to the virus, which enhanced a natural immunity within the population. In developed countries during the late 19th and early 20th centuries, improvements were made in community sanitation, including better sewage disposal and clean water supplies. These changes drastically increased the proportion of children and adults at risk of paralytic polio infection, by reducing childhood exposure and immunity to the disease. Small localized paralytic polio epidemics began to appear in Europe and the United States around 1900. Outbreaks reached pandemic proportions in Europe, North America, Australia, and New Zealand during the first half of the 20th century. By 1950 the peak age incidence of paralytic poliomyelitis in the United States had shifted from infants to children aged five to nine years, when the risk of paralysis is greater; about one­third of the cases were reported in persons over 15 years of age. Accordingly, the rate of paralysis and death due to polio infection also increased during this time. Intensive care medicine has its origin in the fight against polio. Most hospitals in the 1950s had limited access to iron lungs for patients unable to breathe without mechanical assistance. Respiratory centers designed to assist the most severe polio patients, first established in 1952 at the Blegdam Hospital of Copenhagen by Danish anesthesiologist Bjørn Ibsen, were the harbingers of subsequent intensive care units . The polio epidemics not only altered the lives of those who survived them, but also brought profound cultural changes, spurring grassroots fund­raising campaigns that would revolutionize medical philanthropy, and giving rise to the modern field of rehabilitation therapy. As one of the largest disabled groups in the world, polio survivors also helped to advance the modern disability rights movement through campaigns for the social and civil rights of the disabled. The World Health Organization estimates that there are 10 to 20 million polio survivors worldwide. In 1977 there were 254,000 persons living in the United States who had been paralyzed by polio. According to doctors and local polio support groups, some 40,000 polio survivors with varying degrees of paralysis live in Germany, 30,000 in Japan, 24,000 in France, 16,000 in Australia, 12,000 in Canada and 12,000 in the United Kingdom. The disease was very well publicized during the polio epidemics of the 1950s, with extensive media coverage of any scientific advancements that might lead to a cure. Thus, the scientists working on polio became some of the most famous of the century. Fifteen scientists and two laymen who made important contributions to the knowledge and treatment of poliomyelitis are honored by the Polio Hall of Fame, which was dedicated in 1957 at the Roosevelt Warm Springs Institute for Rehabilitation in Warm Springs, Georgia, US. In 2008 four organizations were added to the Hall of Fame. World Polio Day was established by Rotary International to commemorate the birth of Jonas Salk, who led the first team to develop a vaccine against poliomyelitis. Use of this inactivated poliovirus vaccine and subsequent widespread use of the oral poliovirus vaccine developed by Albert Sabin led to establishment of the Global Polio Eradication Initiative in 1988. Since then, GPEI has reduced polio worldwide by 99%. Etymology The term derives from the Ancient Greek, meaning "grey",, referring to the grey matter of the spinal cord, and the suffix ­itis, which denotes inflammation., i.e., inflammation of the spinal cord’s grey matter, although a severe infection can extend into the brainstem and even higher structures, resulting in polioencephalitis, producing a lack of ability to breathe that requires mechanical assistance such as an iron lung. Research The Poliovirus Antivirals Initiative was launched in 2007 with the aim of developing antiviral medications for polio, but while several promising candidates were identified, none have progressed beyond Phase II clinical trials.