Feature Article UNMET HEALTH NEEDS Painful Our fight against polio—a vaccine- preventable infectious disease—is at its peak. Ensuring complete immunization of every child is the key to oust the deadly polio virus from our planet.. P. CHEENA CHAWLA

HILDREN are beautiful gifts of Nature. Sheer neglect of hygiene in the early days of life can play havoc in the Cinfant body, letting germs of a wide Although polio was well the capsid. Besides protecting the variety make home in the tiny organs recognized as a human affliction for genetic material of poliovirus, the playing a dangerous game of life and long, it was only in 1908 that the culprit capsid proteins enable this virus to death. The aftermath of an infectious bug for this disease, the polio virus, infect certain types of cells. childhood illness is most appalling if was identified by Karl Landsteiner. Three different serotypes of polio survival is at the cost of living with a Polio spread widely in Europe and the virus are known to cause the disease — crippled body for whole life. This United States in late 1880s and as the poliovirus type 1 (PV1), type 2 (PV2), exactly happens when the deadly virus, virus circulated rampantly around the and type 3 (PV3) — each having a known to cause polio, strikes! globe, polio cases dramatically slightly different capsid protein. One of the most dreaded childhood increased. It was in the face of such Although all these viral serotypes are diseases, polio mostly strikes children epidemics in early 1900s, paralyzing extremely dangerous and result in the under five years of age. What saddens primarily the young, that serious work same disease symptoms, PV1 is most most is that despite the availability of on developing a potent polio vaccine closely associated with paralysis. time-tested vaccines and global efforts began. Jonas Salk first developed a in full swing to eradicate this disease, polio vaccine in 1952, and a decade From Infection to Paralysis polio still incapacitates innocent, young later, Albert Sabin designed yet Polio is an acute viral disease. The lives in a few parts of the world that another vaccine to combat polio. No word ‘poliomyelitis’ is derived from includes India. doubt, these potent protective tools the Greek poliós that means ‘grey’ and have helped in reducing the global myelós referring to the ‘’, Dreadful Past burden of polio as the number of polio while the suffix -itis, denotes The crippling effects of polio have been cases, per year, have significantly inflammation. This disease is highly known since ancient times. Egyptian lessened over the years. infectious as it spreads through the paintings and carvings clearly depict fecal-oral route, and thus, gets people with droopy limbs and children The Polio Virus transmitted through contaminated walking with canes. An English The polio virus belongs to the genus food and water in mainly places with physician, Michael Underwood in 1789 enterovirus, which is a group of RNA poor sanitation facilities. The virus gave the first clinical description on viruses that make home in the human particles start getting excreted in the polio as ‘a debility of the lower gastrointestinal feces for several weeks following extremities’. Due to the work of tract. The basic initial infection, which is the most physicians, Jakob Heine in 1840 and structure of this infective stage as the virus quickly Karl Oskar Medin in 1890, polio was virus is very simple spreads from one to more hosts, also known as Heine-Medin disease. as it comprises a especially in areas endemic to the ‘Infantile paralysis’ is yet another single strand of virus. Sometimes, the virus also gets name for polio as it primarily affects RNA enclosed in a transmitted via the oral-oral route. children. Polio Virus protein shell called Thus, transmission of polio virus SCIENCE REPORTER, January 2010 19

C M C M C M Feature Article Scoliotic Spine Normal Spine

Polio affected children (left); Equinous foot ( bottom left) and polio-affected spine (above)

initial symptoms of polio infection development of minor influenza-like include sore throat, fever, fatigue, symptoms. Patients with abortive polio , vomiting, stiffness in the infection recover completely. , abdominal pain and pain in the In rare cases though, about 3% of limbs. In about 90% of cases, however, infections, the virus chooses to invade there are no perceptible symptoms, but the (CNS). Why the polio virus is excreted in the faeces, the polio virus diverts its attention from which is why the spread of infection by gastrointestinal tract to causing such cases is very high. infection in the parts of CNS is, After dividing within however, not fully understood, though occurs if the virus is present in the saliva gastrointestinal cells for about a week, it appears to be only a chance event. or feces. The incubation period, which the polio virus spreads to the tonsils Most patients with CNS involvement is the time between the first exposure (specifically the follicular dendritic develop non-paralytic aseptic and appearance of first symptoms, is cells), the intestinal lymphoid tissue (M meningitis, which is the inflammation normally 6 to 20 days. cells of Peyer’s patches), and other of meninges—the layers of tissue As the polio virus enters the body lymph nodes. Soon the virus gets surrounding the brain. The symptoms through the mouth, it infects the cells absorbed into the bloodstream. This last for 2 to 10 days, followed by lining the throat and intestine. stage when the polio virus appears in complete recovery. On an average, 1 in Interestingly, the polio virus gains the bloodstream and starts its journey 200 of such cases progress to paralytic cellular entry by binding to special of spreading across the whole body is disease, as the virus attacks the receptors, which are proteins sitting on called viremia. The polio virus is able cells that control muscle movement, due the surface of host cells. The virus then to survive and multiply within blood to which the muscles become weak, hijacks the machinery of the host cell and lymphatics for periods as long as floppy and poorly controlled, and and begins to replicate furiously. The 17 weeks, which leads to the finally completely paralyzed—a

In addition to routine immunization, the Pulse Polio Immunization Programme was launched in 1995-96.

SCIENCE REPORTER, January 2010 C M 20 Y K 21 Feature Article In India, vaccination against polio was initiated in 1978 under Muscles commonly weakened by polio the Expanded Programme on Immunization (EPI) and the coverage achieved by 1984 was around 40% of all infants with three doses of OPV Shoulder Muscles condition known as acute flaccid Wiping out an Muscles that Muscles behind paralysis. This is the most horrific form straighten or arm of polio as the patient is reduced to a age-old disease bend hip, or that (weakness pathetic figure of constant suffering. spread or close straightening arm) from the face of legs Back Muscles Paralytic Polio the Earth that (either side of A hapless 1% of polio cases are those houses more backbone) where the virus spreads along certain Muscles that Thumb Muscle nerve fiber pathways, mainly than 6.5 billion straighten destroying the motor within people is not knee the spinal cord, brain stem, or motor cortex, which leads to the development easy. Although it Contractures of paralytic poliomyelitis. Different poses a difficult causing tight types of paralysis may occur, Muscles that cords depending on the involved. challenge but lift foot Although the molecular mechanisms of paralytic polio needs to certainly, it is not be understood more clearly, there insurmountable. visibly occur various lesions/cellular abnormalities within the spinal ganglia are highest while the rate of paralysis is permanent, while cells that as these nerve cells get destroyed by the occurrence of paralysis is lowest with simply lose function temporarily invasion of polio virus. The type 2 polio virus. recover within four to six weeks. Half inflammation associated with nerve cell the patients with spinal polio recover destruction often alters the colour and Spinal Polio fully, one quarter recover with mild appearance of the gray matter in the Spinal polio is the most common form disability and the remaining quarter are spinal region, causing it to appear of paralytic polio. It occurs when the left with severe disability reddish and swollen. Other destructive polio virus invades the motor neurons changes associated with paralytic polio of the anterior horn cells, or the front Bulbar Polio occur in the hypothalamus and gray matter in the spinal column, which About 2% of cases of paralytic polio are thalamus regions of the brain. are responsible for movement of the bulbar polio, where the polio virus Early symptoms of paralytic polio muscles located in the trunk, limbs and invades and destroys nerves within the include high fever, headache, the intercostal muscles. Basically, there bulbar region of the brain stem, which difficulty in , stiffness in occurs inflammation of the nerve cells, is the region of white matter that the back and neck, asymmetrical leading to damage of motor connects the cerebral cortex to the brain weakness of various muscles, loss of ganglia. Innervated by the dead stem. The destruction of nerves in this reflexes and sensitivity to touch. neurons, the muscle tissue now no region weakens the muscles, which are Paralysis generally develops between longer receives signals from the brain stimulated by , thus 1 to 10 days after early symptoms or spinal cord, which is why the affected resulting in symptoms of encephalitis, begin, which progresses for two to muscles become weak. A continuous besides causing difficulty in breathing, three days, and is complete thereafter. lack of nerve stimulation, slowly leads speaking and swallowing. The set of The chances of developing paralytic to muscle atrophy that is manifested as nerves that are affected in bulbar polio polio increase with age. In children poorly controlled, floppy muscles and comprise the ‘glossopharyngeal’ nerve, non-paralytic meningitis occurs ultimately, complete paralysis. which partially controls swallowing commonly if the polio virus infects the Progression to paralysis is rapid as it and functions in the throat, tongue central nervous system, and paralysis occurs within two to four days, and is movement and taste; the ‘vagus’ nerve, occurs in only 1 in 1000 cases, while usually associated with fever and which sends signals to the heart, In adults, paralysis occurs in 1 in 75 muscle pain.] intestines, and lungs; and the cases. In children under five years of The extent of spinal paralysis, ‘accessory’ nerve, which controls upper age, paralysis of one leg is most however, depends on the region of the neck movement. Besides, there occurs common; whereas in adults, extensive cord affected. Although any limb or facial weakness caused by the paralysis of the chest and combination of limbs may be affected, destruction of ‘trigeminal’ nerve and also affecting all four limbs— paralysis is mostly asymmetrical as the ‘facial’ nerve, which innervate the quadriplegia— commonly occurs. virus normally affects muscles on one cheeks, tear ducts, gums, and muscles Moreover, if infection is with side of the body. If the affected nerve of the face. Respiratory difficulties also poliovirus type 1, then paralysis rates cells are completely destroyed, arise, which may be fatal. SCIENCE REPORTER, January 2010 21

C M C M Y K Y K Feature Article Common deformity arises when the neurons of the CNS. However, an Sabin Vaccine growth of an affected leg is slowed by exposure to one serotype of polio virus Albert Sabin developed an oral polio does not provide immunity against the polio. vaccine (OPV) using live but weakened other serotypes, which means that to (attenuated) polio virus, that was Bulbospinal Polio acquire immunity against all the produced by the repeated passage of About 19% of all paralytic polio cases serotypes exposure to each serotype is this virus through non-human cells have both bulbar and spinal symptoms, required. grown at specific temperatures. Sabin where the polio virus affects the upper vaccine was ready for human trials in part of the spinal cord, as well as the Passive immunization 1957 and was finally licensed in 1962. diaphragm. The nerves affected are the The idea for this approach, to prevent This weakened form of polio virus ‘phrenic’ nerve, which controls the polio, was put forth by William replicates very efficiently in the gut, movement of diaphragm during the Hammon of the University of which is the primary site of wild polio process of breathing, as well as nerves Pittsburgh in 1950, who purified virus infection. A single dose of OPV that drive the muscles needed for antibodies to poliovirus from the blood produces immunity to all three polio swallowing. Destruction of these plasma of polio survivors. In a clinical virus serotypes in about 50% of nerves affects breathing, making it trial, the use of protective antibodies recipients, while three doses of this live- difficult for the patient to breathe was shown to be about 80% effective attenuated vaccine produce protective without the support of a ventilator. It in preventing the development of antibody to all three poliovirus types in also leads to paralysis of the arms and paralytic poliomyelitis, while reducing more than 95% of recipients. Besides, legs and may even affect heart the severity of polio in those infected OPV is inexpensive, easy to administer, functions. Overall, 5–10% of patients by the virus. This approach, however, and produces good gut immunity with paralytic polio die due to the had its limitation of large-scale which is why this has been the vaccine paralysis of muscles used for breathing. production, which thus paved the way of choice for controlling polio in many for designing polio vaccines. countries. Unfortunately, however, in Polio Diagnosis about 1 case per 750,000 vaccine Cases showing acute onset of flaccid Salk Vaccine recipients, the attenuated virus in OPV paralysis, with decreased or absent There are basically two vaccines, used reverts into a virulent form that can tendon reflexes in one or more limbs, throughout the world, for combating cause paralysis. Therefore, many are suspected to progress to complete polio. Both vaccines induce active countries have switched to IPV, where paralytic poliomyelitis. A laboratory immunity to polio, and blocks person- the virus is killed and cannot revert, diagnosis is usually made by the to-person transmission of the wild either as the sole vaccine against polio detection of polio virus from the stool polio virus. The first polio vaccine was or in combination with OPV. sample or a throat swab sample. developed in 1952 by Jonas Salk, Analysis of the patient’s cerebrospinal which comprised the killed or Polio Treatment fluid (CSF), collected by lumbar inactivated polio virus (IPV). Many cases of poliomyelitis result in puncture, also reveals an increased Popularly called the Salk vaccine, it only temporary paralysis. Nerve number of lymphocytes (white blood is based on growing the polio virus, impulses resume normal function cells). Detection of virus in the CSF is of all three serotypes, in a type of within a month with complete diagnostic of paralytic polio. Once the monkey kidney tissue culture (Vero recovery in six to eight months. polio virus is detected in the patient, the cell line), which is chemically However, body parts that remain DNA-based PCR (Polymerase Chain inactivated using formalin. Two doses paralyzed for more than a year do not Reaction) test could be employed to of IPV (given by injection), helps to mostly recover their muscle strength. confirm the type of the infecting polio develop protective antibodies to all Therefore, once the virus has virus. If the source of a reported case of the three serotypes of polio virus in completely damaged the specific motor paralytic polio is some wild strain of the about 90% of vaccinated individuals nerves, there is no going back and the virus, then it is estimated that about 200 while three doses of this vaccine victim has to live with paralyzed body to 3,000 infectious asymptomatic provide protective immunity to 99% parts. In other words, there is no cure carriers may be present in that of the recipients. for polio. population.

Polio Prevention Jonas Salk Albert Sabin On exposure to the polio virus, either by natural infection or by vaccination, the immune system gets into gear resulting in the production of antibodies, namely immunoglobulins A (IgA) against the virus that blocks viral replication. Subsequently, other special immunoglobulins are produced (IgG and IgM) that prevent the spread of the polio virus to motor 22 SCIENCE REPORTER, January 2010

C M C M Y K Y K Feature Article Routine Polio Immunization Age of the Child OPV (Two Drops)

At Birth 1st dose 6 weeks 2nd dose 10 weeks 3rd dose

14 weeks 4th dose 6-9 months 5th dose

15-18 months 1st booster dose 5 years 2nd booster dose

The focus of modern treatment is proper exercises. Besides, the body after recovering from the acute basically on providing relief of naturally begins to use weaker muscles infection. Called ‘post-polio symptoms. While antibiotics come to at a higher than normal capacity of that syndrome’, it occurs due to both the rescue to prevent infections in the muscle. overuse and disuse of existing motor weakened muscles, analgesics help to Despite the body’s inherent neurons. relieve pain, and long-term processes working in full swing to rehabilitation involves the use of braces, bring back strength to damaged Global Polio Eradication corrective shoes and also orthopedic muscles post polio infection, several In 1988, the World Health Assembly, surgery in some cases. Besides, movement disabilities may take root in comprising delegates from 166 moderate exercise and a nutritious diet the body due to skeletal deformities Member States, adopted a resolution play a key role in providing victims the and tightening of the joints. For for the worldwide eradication of polio. strength to carry on with the daily example, ‘equinus foot’ is a deformity It marked the launch of the ‘Global chores of life. that develops when the muscles that Polio Eradication Initiative’, Some victims, with permanent pull the toes downward are working, spearheaded by the World Health respiratory paralysis, require but those that pull it upward are not, Organization (WHO), Rotary ventilators to support breathing. and the foot naturally tends to drop International, the US Centers for Modern portable ventilators help such towards the ground. If left untreated, Disease Control and Prevention (CDC) victims to survive. Some age-old the Achilles tendons at the back of the and UNICEF. It is the largest public treatments for improving the life of foot retract and the foot cannot take on health project in the world, which is paralytic polio cases include water a normal position. Polio victims that tirelessly working to ensure that no , electrotherapy, and develop this condition cannot walk child ever comes under the crippling even surgical treatments like tendon properly because they cannot put their effects of polio. It is heartening that this lengthening and nerve grafting. heel on the ground. Project has resulted in reducing the Another common deformity arises globally estimated 3.5 lakh cases in Road to Recovery when the growth of an affected leg is 1988 to 1310 cases in 2007. Once polio infection has been checked, slowed by polio, while the other leg Improvements in community the body’s inherent recovery processes continues to grow normally. This sanitation like better sewage disposal take over and facilitate the restoration makes one leg shorter than the other, and supply of clean drinking water of muscle functioning of the affected due to which the person limps and have reduced childhood exposure to parts. One such process is nerve leans to one side that in turn leading to polio virus in many regions of the terminal sprouting, by which the deformities of the spine. Other world. Thanks to the widespread use normal motor neurons of the disturbing complications include of polio vaccine since the mid-1950s, the and spinal cord develop new branches osteoporosis that increases the chance incidence of this disease has or sprouts that reinnervate those of bone fractures, extended use of dramatically declined in the developed muscle fibers whose motor neurons braces or wheelchairs resulting in loss world and many countries have been were damaged by acute polio infection, of proper function of the veins in lower even certified polio-free. For example, thus improving the strength of such limbs, besides scores of medical the US was declared polio-free in 1994, fibres. Through terminal sprouting, a problems involving the lungs, kidneys while in 2000 polio was officially single that earlier and heart that arise due to extended eradicated in 36 Western Pacific controlled 200 muscle cells might immobility of body parts. Several polio countries, including China and control 800 to 1000 cells. Muscle victims who have survived an attack of Australia. Europe was declared polio- strength restoration also occurs by paralytic polio in childhood develop free in 2002. However, between 2003 myofiber hypertrophy, which is the additional symptoms, like muscle and 2005, 25 previously polio-free enlargement of muscle fibers through weakness and extreme fatigue, decades countries were re-infected due to SCIENCE REPORTER, January 2010 23

C M C M Y K Y K Feature Article One of the most dreaded childhood diseases, polio mostly strikes children under five years of age.

polio doses need to be administered in the first year of life, under the routine polio immunization. The number of reported cases of polio declined from 28757 during 1987 to 3265 in 1995. Besides a number of initiatives have been implemented in India to intensify efforts to stop the transmission of wild poliovirus. These transport of the virus. This only proves that are more effective in detecting and include widespread advocacy efforts, the point that even if a single child stopping polio transmission. introduction of monovalent oral polio remains infected, children in all A country is certified polio-free if vaccine (mOPV1) in high-risk areas and countries are at risk of contracting it satisfies three conditions: First, there expanding the reach of immunization polio. are no polio cases due to wild polio campaigns. Today polio mainly afflicts people virus since at least three years; Second, In addition to routine in Asia and Northern Africa. As of 2006, disease surveillance efforts of the immunization, the Pulse Polio polio remains endemic in parts of only region meet international standards; Immunization Programme was four countries: Nigeria, India (mainly and third, the country illustrates the launched in 1995-96 that consisted of Uttar Pradesh and Bihar), Pakistan, and capacity to detect, report and respond administering OPV to children, under Afghanistan. The thrust of current to ‘imported’ polio cases. Finally, for three years of age, at fixed booths on efforts to eradicate polio is on the world to be certified polio-free, it select National Immunization Days. In strengthening the routine is pertinent that laboratory stocks are order to reach the global goal of being immunization systems and surveillance contained and safe management of the polio free, the pulse polio drive was for communicable diseases in polio- wild virus in polio vaccine later intensified with multiple affected nations. manufacturing sites is assured. nationwide rounds of polio The four core strategies to stop immunization and sub-national transmission of the wild polio virus in Polio in India rounds in Assam, Bihar, Gujarat, such areas include high infant It is unfortunate that in 2009 India has Madhya Pradesh, Orissa, Rajasthan, immunization coverage with four doses earned the dubious distinction of Uttar Pradesh and West Bengal in of OPV in the first year of life; reporting the highest number of polio addition to routine immunization, supplementary doses of OPV to all cases in the world. According to data covering all children under the age of children under five years of age; from the Global Polio Eradication 5 years. In addition to booth surveillance for wild polio virus Initiative, India reported 624 polio immunization, a house-to-house through reporting and laboratory cases in 2009 compared to 559 polio search of missed children and testing of all acute flaccid paralysis cases reported from the country in vaccinating them on the next 2-3 days (AFP) cases among children under 15 2008. Another high burden country, following the pulse polio day was also years of age; and targeted ‘mop-up’ Nigeria, reported 383 polio cases in campaigns once wild polio virus 2009 and 798 cases in 2008. started to further increase the transmission has been limited to a In India, vaccination against polio immunization coverage. specific area. was initiated in 1978 under the Wiping out an age-old disease from Needless to say, the key to Expanded Programme on the face of the Earth that houses more stopping wild polio virus transmission Immunization (EPI) and the coverage than 6.5 billion people is not easy. in endemic countries is the presence of achieved by 1984 was around 40% of Although it poses a difficult challenge, a high level of political commitment at all infants with three doses of OPV. In it is not insurmountable. The current, National, State and District levels. In 1985 the Universal Immunization concerted global efforts to combat polio 2007 an intensified effort to eradicate Programme (UIP) was launched that are indeed praiseworthy. It surely seems polio was initiated in all these four covered all districts in the country by that the day, when human populations countries, with focus on new 1989-90. According to the Indian will awake to a polio free world, would monovalent vaccines and diagnostics Academy of Pediatrics, a total of five dawn sooner than later. 24 SCIENCE REPORTER, January 2010