POLIOMYELITIS

AN UPDATE
Dr.T.V.Rao MD

Polio An Enterovirus
Poliovirus, the causative agent of

poliomyelitis, is a human enterovirus and member of the family of Picornaviridae.Poliovirus is composed of a RNA genome and a protein capsid. The genome is single-stranded positive-sense RNA genome that is about 7500 nucleotides long. The viral particle is about 300 ngstrm in diameter with icosahedral symmetry.

Prehistory of Polio disease

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.

Wild Poliovirus 2006

Properties of Polio virus,

Size is 27 nm

Contains 4 viral protein

VP1 to VP 4 VP1 Carries the major antigenic site, and combines with type specific neutralizing antibodies

Properties of Polio virus.

Typical Entero virus.

Inactivated at 550 c for 30 mt.

Chlorine at 0.1 ppm Ether is not effective. Animal susceptibility.

Monkey brain Requires Primate specific membranes. Contains 3 Antigenic types 1,2,3 Can be differentiated by ELISA and CF methods.

Structure

Poliovirus Genome
Single RNA molecule ~7500 nucleotides 3 sub-regions with 10 protein products IRES important for virulence

Serotypes
Specificity to receptor restricts mutation rate; slow genetic

drift Occur because of immunological reasons, vary at sequence canyon Three serotypes with no cross immunity
Type 1 polio Type 2 polio Type 3 polio

90% 9% (Eliminated) 1%

Weakest, only 1% causes neuroparalysis

Greater temperature stability

Requires trivalent polio vaccine Polioviruses can also vary in phenotype of virulence, host

cell lysis, and ability to raise host defense triggers

Polio Infection.
Incubation 3 21 days On average 14 days Predisposing factors.

Severe muscular acitivity can lead to paralysis, as it increases the blood flow May produce paralysis in the limb or bulbar region Injecting vaccines with adjuvant can predispose to paralysis Patients who underwent tonsillectomy have higher incidence as Ig G secretion is reduced Rarely oral Polio vaccine produces poliomyelitis.

What is Poliomyelitis?
polio= gray matter

Myelitis= inflammation of the spinal cord

This disease result in the destruction of

motor neurons caused by the poliovirus. Polio is causes by a virus that attacks the nerve cells of the brain & spinal cord although not all infections result in sever injuries and paralysis.

When was it reported?

Poliomyelitis was

recorded in the late 1700s with the first epidemic in the late 1800s. The cases that were reported in 1979 where mild and self-limited and do not result in paralysis.

Documented History of Polio

Poliomyelitis was first recognized as a distinct condition

by Jakob Heine in 1840. Its causative agent, poliovirus, was identified in 1908 by Karl Landsteiner.[Although major polio epidemics were unknown before the late 19th century, polio was one of the most dreaded childhood diseases of the 20th century. Polio epidemics have crippled thousands of people, mostly young children; the disease has caused paralysis and death for much of human history. Polio had existed for thousands of years quietly as an endemic pathogen until the 1880s, when major epidemics began to occur in Europe; soon after, widespread epidemics appeared in the United States.

What is Poliomyelitis
Poliomyelitis (polio) is

a highly infectious viral disease, which mainly affects young children. The virus is transmitted through contaminated food and water, and multiplies in the intestine, from where it can invade the nervous system.

Can it cause paralyzes?

Paralytic disease occurs 0.1% to 1% of those

who become infected with the polio virus. Paralysis of the respiratory muscles or from cardiac arrest if the neurons in the medulla oblongata are destroyed. Patients have some or full recovery from paralysis usually apparent with proximally 6 months Physical therapy is recommended for full recovery.

How is polio transmitted?

Poliovirus is transmitted

through both oral and fecal routes with implantation and replication occurring in either the orapgaryngeal and or in the intestine of mucosa. Polio cases are most infected for 7-10 days before and after clinical symptoms begin.

Pathophysiology
Poliovirus enters the body through the mouth, infecting

the first cells it comes in contact withthe pharynx (throat) and intestinal mucosa. It gains entry by binding to an immunoglobulin-like 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 (specifically the follicular dendritic cells residing within the tonsilar germinal centers), 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.

Pathogenesis and pathology.

Enter through Mouth,

Multiplies in Oropharynx tonsils and

Intestines, Excreted in Stool. Enters the CNS from Blood. Spread along the Axons of peripheral nerves to CNS. Progress along the fibers of the lower motor neurons spinal cord or brain.

Cell Binding and Entry

Pathology and Pathogenesis.

Destroy the Anterior horn cells of the

Spinal Cord Do not Multiply in Muscles only muscles manifest with weakness and flaccid paralysis result is secondary. Occasionally produce Myocarditis, Lymphatic hyperplasia.

Spinal polio
Spinal polio is the most

common form of paralytic poliomyelitis; it results from viral invasion of the motor neurons of the anterior horn cells, or the ventral (front) gray 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.

Bulbar polio
Making up about 2% 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,

What are the symptoms?

Many include fever, pharyngitis,

headache, anorexia, nausea, and vomiting. Illness may progress to aseptic meningitis and menigoencephalitis in 1% to 4% of patients. These patients develop a higher fever, myalgia and sever headache with stiffness of the neck and back.

How Polio presents

Initial symptoms of

polio include fever, fatigue, headache, vomiting, stiffness in the neck, and pain in the limbs. In a small proportion of cases, the disease causes paralysis, which is often permanent. Polio can only be prevented by immunization.

Outcomes of Poliovirus Infection

Asymptomatic Aseptic menigitis Minor non-CNS illness Paralytic

20

40

60

80

100

Percent

Paralytic Poliomyelitis.
Manifest as Flaccid Paralysis.( Caused due to

damage to Lower Motor Neurons.) Partial recovery within 6 months. Patient may continue with life time disability Can involve Spinal cord, and Bulbo spinal region Bulb spinal involvement can paralyze respiratory muscle and lead to Respiratory failure .

Clinical Manifestations.
In apparent, Only 1% manifest with clinical

features. Can lead to permanent paralysis. Incubation 7-14 days, ( 3-35 ) May be abortive Poliomyelitis, Only Fever, Malaise, Drowsiness, Non paralytic Poliomyelitis, Aseptic Meningitis.

Cripples a Growing Child

Clinical presentation of typical Polio

Aseptic Meningitis
Present with Non

paralytic form with stiffness and pain in the back and neck region Lasts for 2 -10 days Recovery rapid and complete On rare occasions advance to paralysis

Immunity.
Permanent type

specific. 1 and 2 types have Heterotypic resistance. Mother to Off spring immunity lasts for less than 6 months.

Laboratory Diagnosis.
Viral isolation from

Throat swabs, Rectal swabs. Stool specimens, Transported in frozen containers. Produce cytopathic effect on Human and Monkey cells Produce cytopathic effects.

Viral Isolation
From feces - present in 80% of cases in 1st

week In 50 % till 3rd week In 25 % till several weeks Collect the fecal sample at the earliest. Primary monkey kidney is the ideal cell line for isolation of virus Viral isolation must be interpreted with caution and clinical presentation

Laboratory Diagnosis (Serology )

Estimation of

Antibodies Ig M A paired sample is

essential.

Treating Polio cases

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 long-term rehabilitation, including physical therapy, braces, corrective shoes and, in some cases, orthopedic surgery

Epidemiology
Endemic Epidemic Hygiene plays in

spread of diseases. Children < 5 in Developing countries.

Pioneers who Discovered Vaccine

Types of Vaccinations in Use

Two types of vaccine are

used throughout the world to combat polio. Both types induce immunity to polio, efficiently blocking person-to-person transmission of wild poliovirus, thereby protecting both individual vaccine recipients and the wider community (so-called herd immunity)

Polio fact A dime makes the Difference

The march of dimes began in 1938 a fund-raising campaign for polio. People were asked to send one dime directly to the White House to help fight the disease. In the first 3 days the White House received 230,000 dimes. President Franklin D. Roosevelt, whose profile is now on the dimes was himself paralyzed by polio.

Vaccine
Polio vaccine first appeared to be licensed in the

United States in 1955. Advantages: Ease to administration Good local mucosal immunity Disadvantage: Strict cold shipping & storage requirements Multiple doses required to achieve high humeral conservation rates against all virus types

Prevention and Control. (Vaccines)

Sabins Live attenuated vaccine Grown in Monkey kidney cells, Human

Diploid cells. Preserved at 4 c Multiple doses are given Given as oral Drops At present only vaccine given in our National Programme of Immunization Boosts Immunity with Production Ig G ,Ig M And also Ig A Participate as participant in Prevention.

Vaccination Sabin's- Oral Administration Sabins vaccine is administered orally. Contains Type 1 10 lakhs, Type 2- 2 lakhs Type 3- 3 Lakhs. The virus are stable with Mg cl.

Oral Polio Vaccine

Highly effective in

producing immunity to poliovirus 50% immune after 1 dose >95% immune after 3 doses Immunity probably lifelong

Live Polio vaccines Protects Society too

The Live Polio vaccine infects

multiples in the Intestines and thus Immunizes the Individual Vaccines not only produces IgM and IgG in the blood but also IgA antibodies in the Intestines. Which help the gut immunity

Salk Vaccines
Salk Vaccine - A Killed

Vaccine. Four Injections are administered in a period of two years, Administration of periodic booster recommended. Most of the Western Nations do use it.

Salk Vaccine ( Killed-Inject able)

Vaccination in Immunodeficient
Only Killed viral vaccines used in
Immunodeficient persons

( SALK )

Polio Vaccination of Unvaccinated Adults

IPV Use standard IPV

schedule if possible (0, 1-2 months, 6-12 months) May separate doses by 4 weeks if accelerated schedule needed

Vaccine-Associated Paralytic Polio

Increased risk in persons >18 years
Increased risk in persons with

immunodeficiency No procedure available for identifying persons at risk of paralytic disease 5-10 cases per year with exclusive use of OPV Most cases in healthy children and their household contacts

Pediarix A new approved Vaccine

Contains IPV, DTaP,

and hepatitis B vaccines Minimum age 6 weeks, maximum age 6 years Approved by FDA for first 3 doses of the IPV and DTaP series Not approved for booster doses

Present prevalence of Polio attacks

Global Eradication
WHO target

date - year 2000 Yet in 2008 we have Polio cases

The Global Polio Eradication Initiative Launch

In 1988, the forty-first World Health Assembly, consisting

then of delegates from 166 Member States, adopted a resolution for the worldwide eradication of polio. It marked the launch of the Global Polio Eradication Initiative, spearheaded by the World Health Organization (WHO), Rotary International, the US Centers for Disease Control and Prevention (CDC) and UNICEF. This followed the certification of the eradication of smallpox in 1980, progress during the 1980s towards elimination of the poliovirus in the Americas, and Rotary Internationals commitment to raise funds to protect all children from the disease.

Pulse Polio Immunization

 One of the major steps in achieving the goal for zero Polio

children in any state or region is the introduction of Pulse Polio immunization program. This Pulse Polio immunization programme is one of the most sophisticated plans which also got a huge success in our country regarding the targets. These introduced Pulse Polio immunization programme are also proving the best methods to eradicate this disease from its origin too. Moreover according to the scales of years, in 2000 it was measured by the general surveys as the largest effort recorded with these camps and spreading awareness through this Pulse Polio immunization program.

Global Eradication.
The Indian Programme of PULSE

POLIO Immunization is a part of it to eradicate Polio Recent resurgence in UP and Bihar is a threat to the desired Goal. In spite of best efforts thousands occur globally in Africa and Indian subcontinent.

Live Vaccine Associated Polio

On few occasions

type 2 and type 3 virus may mutate in the course of multiplication May lead to Vaccine associated Polio But very negligible

Role Of Immunoglobulin's in Prevention

Immunoglobulin's can

provide protection for a few weeks against the paralytic polio But does not prevent subclinical infection Effective if given shortly before infection No value once the clinical symptoms develop

Update on India August 2011*

India has not reported a single case in more than six months.

The most recent case had onset of paralysis on 13 January in West Bengal (WPV1).
SNIDs took place beginning 26 June in Uttar Pradesh, Bihar,

Delhi and parts of West Bengal and other high-risk areas. The next SIAs will be SNIDs using bivalent oral polio vaccine (bOPV) in August.
India has also gone eight months without detecting any wild

poliovirus from environmental sampling. The last positive environmental sample was taken from Mumbai in November, 2010.
*Global polio eradication Initiative

Polio eradication helps in Progress of the World

Once polio is eradicated,

the world can celebrate the delivery of a major global public good something that will equally benefit all people, no matter where they live. Economic modeling has established that significant financial benefits will also accrue from eradication.

Where is Polio present TODAY

In 2008, only four

countries in the world remain with polioendemic, down from more than 125 in 1988. The remaining countries are Afghanistan, India, Nigeria and Pakistan.

Bivalent Oral Polio

India launched

Bivalent Oral Polio Vaccine in January 2010 in place of a monovalent one which protects against a single strain. A recent scientific analysis of the BOPV found that it induced a significantly higher immune response 30% more than other trivalent or monovalent vaccines.

Dr.T.V.Rao MD

64

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Dr.T.V.Rao MD for Medical and Health care Workers in the Developing World Email doctortvrao@gmail.com