Polio vaccine

Polio; A major breakthrough

1. POLIO VACCINE

2. INTRODUCTION Poliovirus, the causative agent of poliomyelitis (commonly known as polio), is a human enterovirus and member of the family of Picornaviridae. Poliovirus was first isolated in 1909 by Karl Landsteiner and Erwin Popper . Poliovirus is one of the most well-characterized viruses, and has become a useful model system for understanding the biology of RNA viruses.

3. STRUCTURE Poliovirus is composed of an RNA genome and a protein capsid. The genome is a single-stranded positive-sense RNA genome that is about 7500 nucleotides long. The viral particle is about 30 nm in diameter Icosahedral symmetry Non enveloped

4. TYPES OF POLIO VIRUS The three serotypes of poliovirus, PV1, PV2, and PV3, each have a slightly different capsid protein. Capsid proteins define cellular receptor specificity and virus antigenicity. Type 1 (also known as Brunhilde), As of November 2014, wild PV1 is highly localized to regions in Pakistan and Afghanistan . It is the type most often isolated from paralytic cases, most often the cause of epidemics Type 2(Lansing ), Wild PV2 was declared eradicated in September 2014 after last being detected in October 1999 in  Uttar Pradesh, India. Type 3 (Leon ), As of November 2014, wild PV3 has not been seen since its 2012 detection in parts of Nigeria and Pakistan. They got their names from the cases in which they were first isolated.

5. TRANSMISSION The virus usually enters the environment in the feces of someone who is infected. In areas with poor sanitation, the virus easily spreads from feces into the water supply, or, by touch, into food. Individuals who carry the poliovirus can spread it via their feces for weeks, even if they have shown no symptoms themselves. The time between infection and onset of paralysis (incubation period) is 10–21 days 

6. PATHOGENESIS

7. There are 3 possible outcomes

8. DIAGRAMATIC REPRESENTATION OF VIRUS ATTACHMENT TO NERVE CELL

9. SPINAL POLIO BULBAR POLIO BULBOSPINAL POLIO % OF CASES 79 % 2% 19% CAUSE Viral invasion of in motor neurons of anterior horn , gray matter of spinal cord. Viral invasion In bulbar region of brain stem. Virus affects the upper part of cervical spinal cord. PART OF THE NERVES AFFECTED Destruction of motor neuron ganglia resulting in maximum paralysis in 2-4 days. Glossopharyngeal and trigeminal nerves are mainly affected. Phrenic nerves are mainly involved. OUTCOME Muscles become floppy, poorly controlled . Paralysis is often asymmetric. Facial weakness , double vision, difficulty in chewing. Paralysis of diaphragm , difficulty in breathing , swallowing and may impair heart function .

10. WHY THERE IS A NEED OF VACCINE ? Polio (poliomyelitis) mainly affects children under 5 years of age. 1 in 200 infections leads to irreversible paralysis. Among those paralyzed, 5% to 10% die when their breathing muscles become immobilized. Polio cases have decreased by over 99% since 1988, from an estimated 350 000 cases then, to 74 reported cases in 2015. The reduction is the result of the global effort to eradicate the disease. As long as a single child remains infected, children in all countries are at risk of contracting polio. Failure to eradicate polio from these last remaining strongholds could result in as many as 200 000 new cases every year, within 10 years, all over the world. In most countries, the global effort has expanded capacities to tackle other infectious diseases by building effective surveillance and immunization systems.

11. TO KILL POLIOVIRUS

12. DEVELOPMENT OF POLIOVIRUS VACCINES In 1935 , Brodie tried an inactivated vaccine with 10% formalin suspension of PV taken from infected monkey spinal cord; he tried it first on 20 monkeys, then on 3000 Californian children. The results were poor. In the same year , Kollmer tried a live attenuated virus consisting of a 4% suspension of PV from infected monkey spinal cord, treated with sodium ricinoleate. He used it on monkeys and then on 10,000 children . The acute paralysis occurred, several died, and many were paralyzed or suffered allergic reactions shortly after . A breakthrough came in 1948 when the virus was successfully cultivated in human tissue in the laboratory by John Enders. Also reduction of the virulence of the PV strains was recorded by Theiler , who passaged the Lansing strain in rats and mice more than 50 times and by Enders, Weller and Robins, who passaged the same strain in non neuronal cell culture. The discovery that the various antigenic strains of PVs could be grouped into three distinct viral types and the propagation of the PV in vitro led to the development of the vaccines against poliomyelitis: the formalin-inactivated vaccine (IPV) by Jonas Salk (1953) and the live-attenuated vaccines (OPV) by Albert Sabin (1956) .

13. In 1954 , the inactivated vaccine was tested in a placebo-controlled trial, which enrolled 1.6 million children in Canada, Finland and the United States. In April 1955 , Salk’s vaccine was adopted throughout the United States. The incidence of paralytic poliomyelitis in the United States decreased from 13.9 cases per 100 000 in 1954 to 0.8 cases per 100 000 in 1961. In 1960 , Sabin described, in an article published in  JAMA ,  Live ,  orally given poliovirus vaccine , the results obtained with his newly developed trivalent oral vaccine to 26 033 children from a city of 100 000 people in South America. Because the strains developed by Sabin provided good antibody levels and were less neurotropic for monkeys, they were selected and licensed between 1961 and 1963 in the United States for widespread application. 

14. POLIO VIRUS VACCINE ︎ ORAL POLIO VACCINE(OPV) Uses attenuated poliovirus INACTIVATED POLIO VACCINE (IPV) Uses inactivated poliovirus

15. OPV IPV NATURE OF VACCINE Attenuated vaccine , also called SABIN VACCINE . Killed vaccine, also called the SALK VACCINE . VACCINE DEVELOPMENT OPV was developed in 1960 by Dr. Albert Sabin. It consists of live polioviruses attenuated by extensive passage of the original wild-type strains of poliovirus in cell cultures or in monkey brain in vivo. This results in mutation of the virus, which weakens its potential to cause paralysis, while maintaining the antigenicity by inducing the production of antibodies by the immune systems of the human body. IPV was developed in 1955 by Dr. Jonas Salk . It consists of killed viruses, which are cultivated in monkey kidney cells and inactivated by incubation of the viruses in 1:1000 formalin for 12-14 days at 37 ° C. IMMUNE RESPONSE GENERATED serum immunity which protects the individual against polio paralysis by preventing the spread of poliovirus to the nervous system. Intestinal immunity(local immunity) which limits the multiplication of wild virus inside the gut and thus reduces fecal excretion (hence possible transmission) of the wild virus. IPV only induces serum immunity, not intestinal immunity . As a result, when a person immunized with IPV is infected with wild poliovirus, the virus can still multiply inside the intestines and be shed in the faeces, risking continued circulation.

16. TYPES Monovalent oral poliovirus vaccine (mOPV) Bivalent oral poliovirus vaccine (bOPV) Trivalent oral poliovirus vaccine (tOPV) No distinct types . STRAINS USED The virulent strains P1/Mahoney/41, P2/P712/56 and P3/Leon/37 served as a source for the attenuated Sabin strains: P1/Lsc,2ab, P2/P712,Ch,2ab and P3/Leon,12a1b. The strains of virus used in the vaccine were Mahoney (type l), MEF-I (type 2) and Saukett (type 3). TCID / ANTIGEN UNITS By using a balanced formulation of trivalent OPV which contained 10 6 , 10 5 and 10 5.5 TCID50 (50% tissue culture infective dose) of Sabin types 1, 2 and 3, the neutralizing antibodies against all three PV types were detected in almost all persons. Increasing the amount of type 3 virus in the trivalent vaccine improved the immunogenicity so the Expanded Program on Immunization Global Advisory Group recommended a formulation of trivalent OPV which contained 10 6 , 10 5 , 10 5.8 TCID50 of Sabin types 1, 2 and 3 per dose. Original IPV contained 20, 2 and 4 D antigen units of PV types 1, 2 and 3. Van Wezel introduced a technology to produce enhanced potency IPV. He decided to concentrate and purify the virus before treatment with formalin. A more potent IPV containing 40, 8 and 32 D antigen units of types 1, 2 and 3 was produced .

17. COMPOSITION Particulars Quantity Attenuated Sabin strain - 10 6 CCID 50 viruses Type 1 Attenuated Sabin strain viruses Type 3 - 10 5.8 CCID 50 MgCl 2 (Stabilizer) - 1M Kanamycin Sulphate - 20mcg per dose Pertaining to the b(OPV) which is being used at present . One dose of 0.5 ml poliomyelitis vaccine contains the following active components Inactivated poliomyelitis virus type 1 (Mahoney) - 40 D Antigen units Inactivated poliomyelitis virus type 2 (MEF 1) - 8 D Antigen units Inactivated poliomyelitis virus type 3 (Saukett) - 32 D Antigen units EXCIPIENTS-Formaldehyde (12.5ug), 2-phenoxyethanol (2.5mg), Medium 199 (0.1ml) and diluent solution & phosphate buffer (together 0.08ml) with the following composition; sodium phosphate, sodium chloride, potassium chloride, magnesium sulphate , phenol red and calcium chloride. COST costs about Rs727 for 10 doses so Rs72 per dose approx. It costs about Rs450 per dose. ROUTE Orally IPV is given by intramuscular or intradermal injection and needs to be administered by a trained health worker.

18. SAFETY Though it is safe but not 100% safe as there is a chance of reversion and may cause VAPP. IPV is one of the safest vaccines in use. No serious systemic adverse reactions have been shown to follow vaccination. EFFICACY Vaccine  efficacy  was estimated at 82% after one dose, 96% after two doses and 98% after three or more doses Trials with this enhanced IPV (eIPV) showed greater than 90% seropositivity against all 3 PV types after one dose and 100% seropositivity after two doses. DOSAGE WHO also recommends an OPV dose at birth (also called 'zero dose'), followed by the primary series of 3 OPV doses at 6, 10 , 14 weeks. 4 doses administered at ages 2 months, 4 months, 6--18 months, and 4--6 years with the minimum interval between all IPV doses as 4 weeks. STORAGE The vaccine must be stored at -20 C or below under frozen state for long term storage up to 2 years. When the vaccine is thawed ( liquid form), it must be kept in refrigerator at 2 C to 8 C. Vaccine if stored at 2 C to 8 C shall remain good for only 4-6 months. The vaccine requires a storage temperature between 2 and 8°C. Do not freeze.

19. ADVANTAGES Induces both types of immunities. immunization with OPV can result in ‘ passive’ immunization of people who have not been vaccinated. OPV is of low cost than that of IPV because OPV is administered orally, so does not need professionally trained health workers and injection-related supplies (e.g., syringes). Also unsafe injection is not an issue It can effectively protect individual children against paralysis after four doses with a protection rate of nearly 100 percent. It does not cause VAPP because the vaccine consists of killed poliovirus. DISADVANTAGES It can cause vaccine-associated paralytic poliomyelitis (VAPP), although the probability is very low (1 case per 2.5 million doses), because some people are sensitive to vaccine virus, especially those who are immunodeficient. OPV may be less potent than IPV in inducing serum immunity .Thus it often needs repeated vaccination of up to five to 10 doses to protect all children .  IPV only induces serum immunity, not intestinal immunity. There is not a secondary or passive immunization effect. The cost of IPV vaccination is higher than OPV because its price is higher and it require injections by trained health workers. Wild poliovirus could escape from the production process. There is a risk of unsafe injections, which can lead to transmission of blood-borne diseases.

20. TYPES OF OPV

21. MONOVALENT OPV TRIVALENT OPV BIVALENT OPV monovalent OPVs (mOPVs) were developed in the early 1950s, but largely dropped out of use upon the adoption of tOPV. Monovalent oral polio vaccines confer immunity to just one of the three serotypes of OPV. They are more successful in conferring immunity to the serotype targeted than tOPV, but do not provide protection to the other two types. Monovalent OPVs for type 1 (mOPV1) and type 3 (mOPV3) poliovirus were licensed but Monovalent OPV type 2 (mOPV2) has been stockpiled in the event of a cVDPV2 outbreak. Prior to April 2016, the trivalent oral poliovirus vaccine (tOPV) was the predominant vaccine used for routine immunization against poliovirus. Developed in the 1950s by Albert Sabin, tOPV consists of a mixture of live, attenuated polioviruses of all three serotypes. The trivalent vaccine was withdrawn in April 2016 and replaced with the bivalent oral poliovirus vaccine (bOPV), which contains only attenuated virus of types 1 and 3. This is because continued use of tOPV threatened to continue seeding new type 2 circulating vaccine-derived polioviruses (cVDPV2) , despite the wild type 2 virus being eradicated in 1999. Also because in Indi , the type 2 is less prevalent and unnecessary administration would result in reduced immunogenicity. Following April 2016, the trivalent oral poliovirus vaccine was replaced with the bivalent oral poliovirus vaccine (bOPV) in routine immunization around the world. Bivalent OPV contains only attenuated virus of serotypes 1 and 3, in the same number as in the trivalent vaccine. Bivalent OPV elicits a better immune response against poliovirus types 1 and 3 than trivalent OPV, but does not give immunity against serotype 2.

22. VAPP The major risks of OPV vaccination are the appearance of Vaccine-Associated Paralytic Poliomyelitis cases (VAPP) and the emergence of Vaccine Derived Polioviruses strains (VDPV). The VDPV strains could be circulant (cVDPV, which can spread in populations with low level of vaccine coverage), could emerge after replication in immunodeficient persons exposed to OPV (iVDPV), or could be ambiguous VDPV (aVDPV, when they are isolated from immunocompetent persons or the environmental source has not been identified). These are the OPV strains having more than 1% nucleotide divergence from the original vaccine strains in the VP1 coding region of the genome. During replication in intestine, the OPV strains can undergo genetic variation by point mutations due to RNA polymerase or through natural recombination. The incidence of VAPP for immunocompetent children receiving their first dose of OPV was estimated at one case per 750 000 doses and one case per 6.9 million subsequent doses

23. LATEST RECOMMENDED USE An increasing number of industrialized, polio-free countries are using IPV as the vaccine of choice. This is because the risk of paralytic polio associated with continued routine use of OPV is deemed greater than the risk of imported wild virus. However, as IPV does not stop transmission of the virus, OPV is used wherever a polio outbreak needs to be contained, even in countries which rely exclusively on IPV for their routine immunization programme . WHO also recommends that all countries currently using only OPV add at least 1 dose of IPV to the schedule. Once polio has been eradicated, use of all OPV will need to be stopped to prevent re-establishment of transmission due to VDPVs.

24. MASS IMMUNIZATION PROGRAMMES AGAIST POLIO

25. PULSE POLIO PROGRAMME History In India, vaccination against polio started in 1978 with Expanded Program on Immunization (EPI). By 1984, it covered around 40% of infants, giving three doses of OPV to each. In 1985, the Universal Immunization Program (UIP) was launched to cover all the districts of the country. UIP became a part of child survival and safe motherhood program (CSSM) in 1992 and Reproductive and Child Health Program (RCH) in 1997. This program led to a significant increase in coverage, up to 95%. The number of reported cases of polio also declined from 28,757 during 1987 to 3,265 in 1995. In 1995, following the Global Polio Eradication Initiative of the World Health Organization (1988), India launched Pulse Polio immunization program with Universal Immunization Program which aimed at 100% coverage .

26. KEY OBJECTIVES The Pulse Polio Initiative (PPI) aims at covering every individual in the country. It aspires to reach even children in remote communities through an improved social mobilization plan . Not a single child should miss the immunization, leaving no chance of polio occurrence. Cases of acute flaccid paralysis (AFP) to be reported in time and stool specimens of them to be collected within 14 days. Outbreak response immunization (ORI) to be conducted as early as possible. Maintaining a high level of surveillance. Performance of good mop-up operations where polio has disappeared.

27. STEPS Setting up of booths in all parts of the country . Initializing walk-in cold rooms, freezer rooms, deep freezers, ice-lined refrigerators and cold boxes for a steady supply of vaccine to booths. Arranging employees, volunteers, and vaccines. Ensuring vaccine vial monitor on each vial . Immunizing children with OPV on national immunization days. Identifying missing children from immunization process. Surveillance of efficacy. Publicity was extensive and included replacing the national telecoms' authority ringtone with a vaccination day awareness message, posters, TV and cinema spots, parades, rallies, and one-to-one communication from volunteers . Two million healthcare workers and US$2.3 billion in government funding went into the campaign .

28. DIFFICULTIES Testing showed that three doses of vaccine was enough to protect children in developed countries, but it became obvious that this was not enough in some areas of India. The Ministry of Health and Family Welfare recommended eight to ten doses for each child. Children in some areas of India are weaker and often had diarrhoea, which reduced the efficiency of the vaccine. Open defecation, monsoon flooding, and a lack of water treatment made it easier for a child to swallow more polio virus. As a result, children with too few doses of vaccine were not fully protected and sometimes got polio . The eradication program therefore gave drops over and over again, to boost children's immunity higher and as a precaution against missed children .

29. ELIMINATION OF POLIO IN INDIA The last reported cases of wild polio in India were in West Bengal and Gujarat on 13 January 2011. On 27 March 2014, the World Health Organization (WHO) declared India a polio free country, since no cases of wild polio had been reported in for three years . As of mid-2016, only Afghanistan, Nigeria and Pakistan have wild polio cases

30. INDRADHANUSH PROGRAMME LAUNCH DATE Mission Indradhanush is a health mission of the government of India. It was launched by Union Health Minister J. P. Nadda on  25 December 2014 . Objective Aims to cover all those children by 2020 who are either unvaccinated, or are partially vaccinated against 7 vaccine preventable diseases The diseases are –  diphtheria, whooping cough, tetanus, polio, tuberculosis, measles and hepatitis B

31. How is the government going about the implementation ? Implementation will be done in phases in a “catch up” mode – the aim is to cover all the children who have been left out or missed out for immunization Technically supported by WHO, UNICEF, rotary international and other donor partners Phase 1 targets 201 districts phase 2 targets 352 districts The first round of the first phase started from 7 April 2015-world health day What’s interesting about the phase 1 districts? These 201 high focus districts in the country have nearly 50% of all unvaccinated or partially vaccinated children! Out of the 201 districts, 82 districts are in just four states of up, Bihar, M adhya P radesh and Rajasthan.

32. What are the 4 pillars of strategy for Mission Indradhanush? #1. Meticulous planning of campaigns/sessions at all levels Within the districts, the mission will focus on the 400,000 high risk settlements identified by the polio eradication #2. Effective communication and social mobilization efforts Generate awareness and demand for immunization services through need-based communication strategies and social mobilization activities on programme #3. Intensive training of the health officials and frontline workers #4. Establish accountability framework through task forces Strengthening the district task forces for immunization in all districts Ensuring the use of concurrent session monitoring data to plug the gaps in implementation on a real time basis Collaboration with other ministries, ongoing programmes and international partners to promote a coordinated and synergistic approach

33. RECENT ADVANCES New Delhi : The government's ambitious ‘Mission Indradhanush’ programme, which provides immunization against seven life threatening diseases, is all set to be re-christened as four new vaccines have been added into it. F our new vaccinations - rotavirus, measles rubella, inactivated polio vaccine bivalent and Japanese Encephalitis are to be added for adults. In that, very important is rotavirus. 10 lakh children get hospitalized every year suffering from diarrhoea and 80,000 lose their lives every year..

34. REFERENCES www.cdc.gov www.nhp.gov.in www.wikipedia.org www.ncbi.nih.com www.healthline.com www.medicalnewstoday.com