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 Ångström 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 90%

Weakest, only 1% causes neuroparalysis

• Type 2 polio 9% (Eliminated)

• Type 3 polio 1%

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

1700’s with the first

epidemic in the late

1800’s.

• 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 with—the 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.

0 20 40 60 80 100

Percent

Asymptomatic Minor non-CNS illness

Aseptic menigitis Paralytic

Outcomes of Poliovirus Infection

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)

• Sabin’s 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

•Sabin’s 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 International’s

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 polio-

endemic, 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

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•Email

•doctortvrao@gmail.com

Dr.T.V.Rao MD 65