Human vaccinations ppt by dr. hussein abass

Human
Vaccinations
By
Dr. Hussein Abass
Consultant of Pediatrics
22/10/2018

•Egypt annually spends 600 million pounds on
immunization program, where the child is given 10
compulsory vaccinations and the number of births
annually in Egypt 2596000 children according to figures
of the Central Agency for Mobilization and Statistics for
the year 2016. Egypt is free from poliomyelitis, the last
confirmed case of polio recorded in Egypt In 2004,
•Egypt declared polio-free in 2006 by the World Health
Organization.

• History of Vaccination
• 1- 1796 -Jenner – cowpox
• 2- 1885 - Pasteur – cholera, diphtheria, chickenpox, rabies
• 3- 1911 - first typhoid vaccine
• 4- 1927 - first tetanus vaccine
• 5- 1931 - Calmette & Guerin – first crude BCG
• 6- 1936 - influenza
• Modern era of vaccination
• 7- 1940 - diphtheria national programme in UK
• 8- 1950’s - polio, pertussis, modern BCG
• 9- 1960’s - measles, mumps & rubella, modern tetanus
• 10- 1980’s - H. Influenzae B (Hib)
• 11- 2000’s - Meningitis C, Human papilloma virus (HPV)

Smallpox caused more deaths than all the wars in history ,
300 Million people are died .
The world's first immunization campaign: the Spanish Smallpox
Vaccine Expedition, 1803-1813.
1- The first vaccine-preventable disease targeted for eradication
was smallpox
2- The last naturally occurring case of smallpox occurred in
Somalia in 1977.

According to (UNICEF)
vaccine preventable diseases (VPDs) cause an estimated 2
million deaths or more every year, of which approximately
1.5 million deaths occur among children below five year
age.
74 Vaccines present now day in 2018

The Cold Chain
1- The "cold chain" is a system of storage and transport of
vaccines at low temperature from the manufacturer to the
actual vaccination site.
2- The cold chain system is necessary because vaccine failure
may occur due to failure to store and transport under strict
temperature controls.
3- System of transporting and storing vaccines within the recommended
temperature range of 2 – 8‫ﹾ‬ C

Vaccination Coverage
1- Vaccination coverage is the percent of at risk or susceptible
individuals, or population who have been fully immunized
against particular diseases by vaccines or toxoids.
2- To be significantly effective in prevention of disease on mass
or community level at least a satisfactory proportion (75% or
more) of the at risk population must be immunized.

Vaccination for special occupations
1- Health care workers: hepatitis B, influenza, MMR, polio
2- Public safety personnel (police, fire fighters) and staff of institutions
for the developmentally disabled: hepatitis B, influenza
3- Vets and animal handlers: rabies, plague and anthrax
4-Sewage workers: DT, hepatitis A, polio, TAB
5- Food handlers: TAB
6- Military troops and camp dwellers: pneumococcal, meningococcal,
influenza, BCG (for non reactors), tetanus.

• Vaccination for Preterm babies
• All vaccine to be given as per Chronological age
• unless birth weight is less than 2 kgs.
• Recent data confirm that preterm infants should be vaccinated using the same schedule as
term infants, with the exception of the HBV vaccine, where the full schedule needs to be
repeated in infants who received their first dose when they weighed less than 2000 g.
However, despite this recommendation, routine immunization of preterm infants is often
delayed. The most important factor explaining the delay in administering routine vaccines is
likely the lack of knowledge regarding the safety and effectiveness of vaccines in preterm
infants among healthcare workers and parents. Every effort should be made to elaborate
universal guidelines defining modalities and duration of monitoring following preterm infant
immunization, but also to convince pediatricians and parents that vaccines are immunogenic,
safe and well tolerated in preterm infants. A cocooning strategy for pertussis and influenza
should also be proposed to parents. Early active immunity is particularly important in preterm
infants because they are among the most vulnerable populations to pediatric infectious
diseases.

Hepatitis B Vaccine in Preterm Babies :
1-Babies weighing > 2 kg: The birth dose of hepatitis B vaccine
can be administered at any time after birth.
2-Babies weighing < 2 kg: The immunogenicity of the birth
dose of the vaccine has been shown to be suboptimal in some
studies. Hence the birth dose of hepatitis B vaccine in these
babies should be delayed till the age of 1 month.
Alternatively, these babies may also be given the first dose of
the vaccine at the time of discharge if consistent weight gain
is achieved.
3- In babies less < 2 kg born to a hepatitis B positive mother:
Hepatitis B vaccine should be given along with HBIG within
12 hours of birth and 3 more doses at 1, 2 and 6 months are
recommended

All other Vaccines in Preterms :
1- Can be given as per chronologic age and have acceptable safety,
immunogenicity and efficacy. Full dose of the vaccines should be
used.
2- Since preterm and LBW babies may have low muscle mass, the use
of needles with lengths of 5/8 inch or less is appropriate to ensure
effective, safe, and deep anterolateral thigh intramuscular
administration.
3- As preterm, low birth weight babies have increased susceptibility to
infections, vaccines such as pneumococcal conjugate vaccines,
rotavirus and influenza should be offered if resources permit.

Vaccination in specific infections
1- HIV
live vaccines to be avoided and killed vaccines in double strength doses
2- Diseases with no or poor spleen
Pnemococcal, Meningiococcal & Influenza vaccines (capsulated
organisms)
3- Progressive Neurological disorder : DPT should not be given

Vaccinations for special health status persons
1- Immuno-compromised persons ( Leukemia, lymphoma, HIV,
malignancy)
2- Hemodialysis and transplantation Should receive the
following vaccines according to their situation:
HBV, Influenza, Pneuomococcal vaccines

Corticosteroids & Other Immunosuppressive Therapy
1-Killed vaccines: They are safe but may be less efficacious.
2- Live vaccines:
-Children receiving oral corticosteroids in high doses: (prednisolone
> 2 mg/kg/day or for those weighing more than 10 kg, 20 mg/day or
its equivalent) for > 2 weeks should not receive live virus vaccines
until the steroids have been discontinued for at least one month.
-Children on lesser dose of steroids or those on inhaled or topical
therapy: may be safely and effectively given their age appropriate vaccines.
3-Children on immunosuppressive therapy other than corticosteroids: should avoid
live vaccines during therapy unless benefits outweigh risks.

Malignancies on Chemotherapy or Radiotherapy :
1-Influence of cancer per se on immune function is minimal and
does not contribute to a major extent in inducing immunocompromised state.
2-Total immunoglobulin concentrations, specific antibody
concentrations to already given vaccines are normal at the time of diagnosis
indicating that the effect of the cancer on the adaptive immune system is likely to
be small.
3-However, chemotherapy for cancer causes major secondary immunodeficiency.
4- The effects of radiotherapy on immune function are likely to
be small in comparison to chemotherapy.

1-Patients aged ≥6 months with hematological malignancies or
solid tumor malignancies except those receiving anti-B-cell
antibodies or intensive chemotherapy, such as for induction or
consolidation chemotherapy for acute leukemia should receive
inactive influenza vaccine (IIV) annually.
2- Pneumococcal conjugated vaccine (PCV) should be administered
to newly diagnosed children with hematological or solid
malignancies. PPSV23 should be administered to children aged ≥
2 years at least 8 weeks after PCV.
3- Inactivated vaccines (other than IIV) recommended for
immunocompetent children can be considered for children who
are receiving maintenance chemotherapy.

4-However, vaccines administered during cancer chemotherapy
should not be considered valid doses unless there is
documentation of a protective antibody level.
5- Live viral vaccines should not be administered during chemotherapy.
6-Three months after cancer chemotherapy, patients should be
vaccinated with inactivated vaccines and the live vaccines
for varicella, MMR as per schedule that is routinely
indicated for immunocompetent persons.
7- In regimens that included anti-B-cell antibodies, vaccinations
should be delayed at least 6 months.

Asplenia Or Hyposplenia
1- Asplenia or hyposplenia may result from sickle cell disease or
radiation therapy involving spleen. Children with asplenia
/hyposplenia are at high risk of serious infections with
encapsulated organisms.
2-Vaccination with pneumococcal (both conjugate and
polysaccharide),Hib, meningococcal and typhoid vaccines is
indicated in addition to all routine vaccines.
3- Planned splenectomy: vaccination should be initiated at least
2 weeks prior to splenectomy for achieving a superior
immunologic response.
4-Emergency splenectomy: vaccination given 2 weeks after
splenectomy is associated with a superior functional antibody
response as compared to vaccination immediately following
surgery.
5-All live vaccines may be safely given.

Congenital Immunodeficiency :
1-Severe B cell immunodeficiency: (X linked agammaglobulinemia)
Live vaccines including OPV, BCG, oral typhoid, and live attenuated
influenza are contraindicated.
Measles and varicella vaccines may be given but are ineffective due to
concomitant immunoglobulin therapy.
Inactivated vaccines may be given but are ineffective.
2-Less severe B cell deficiencies: (IgA and IgG subclass deficiency)
Only OPV is contraindicated.
3-Severe T cell immunodeficiencies: (SCID)
All live vaccines are contraindicated and all vaccines are ineffective.
Patients who have received live vaccines especially BCG prior to
diagnosis face an increased risk of complications including disseminated
BCG disease.

1-Combined immunodeficiencies: (Di George syndrome, Wiskott
Aldrich and Ataxia telangiectasia)
- Inactivated vaccines may be given.
-Live vaccines are contraindicated.
2-Complement deficiencies:
-All vaccines may be safely given.
-pneumococcal, Hib and meningococcal vaccines are
particularly indicated.
3-Phagocyte defects: Chronic granulomatous disease
-Only live bacterial vaccines are contraindicated, other
vaccines may be safely and effectively given.

Vaccination with Chronic Diseases :
Children with chronic neurologic, endocrinologic (diabetes), liver, renal,
hematologic, cardiac, pulmonary and gastrointestinal disease are at increased
risk of infections.
- Live vaccines may be given safely in these children.
- These children should be offered pneumococcal, hepatitis A, varicella,
influenza and rotavirus vaccines.
- The immunogenicity, efficacy and duration of protection of vaccines are
lower than healthy children and hence if indicated higher antigen content/
more doses (hepatitis B), assessment for antibody response and frequent
boosters (hepatitis A and B) are recommended.
- It is important to stress the role of hepatitis A vaccine in patients with liver
disease, pertussis booster in those with stable neurologic disease.
- Children with severe cardiac and pulmonary diseases should receive
pneumococcal and annual influenza vaccines.

Children with History of Allergy :
- First time immunization with any vaccine is contraindicated
in children with history of serious hypersensitivity/
anaphylaxis to any of vaccine components.
- The package label should always be checked for vaccine
constituents which in addition to antigen include stabilizers/
buffers, preservatives, antibiotics and residue from the
manufacturing process.
- Children with history of serious egg allergy should not
receive influenza and yellow fever vaccines but can safely
receive other vaccines including measles and MMR vaccines.

-Children with history of any hypersensitivity are at increased
risk for allergic reactions , Japanese Encephalitis vaccines and thus should be
monitored carefully.
- Children who have had a serious hypersensitivity
reaction/anaphylaxis to a particular vaccine must never
receive it again. A mild reaction is not a contraindication to
vaccination.
- In any case all children should be watched for at least 15
minutes after vaccination for allergy and resuscitation
equipment should be kept standby.

Children with Bleeding Disorders or Those Receiving Anticoagulants :
- These children are at increased risk for bleeding after intramuscular injection.
-When vaccines recommended to be given only by the IM route are
to be given, vaccination can be scheduled shortly after administration
of clotting factor replacement. A 23 gauge or smaller needle should
be used for the vaccination and firm pressure without rubbing should
be applied to the site for at least 5–10 minutes.
- Alternately, vaccines recommended for intramuscular injection could
be administered subcutaneously to persons with a bleeding disorder
if the immune response and clinical reaction to these vaccines are
expected to be comparable by either route of injection, such as Hib
conjugate vaccine, IPV, pneumococcal polysaccharide vaccine, etc.

Immunization During Acute illness :
Moderate or severe acute illness:
-Immunization during acute illness may lead to lower
immunogenicity or vaccine failure. Hence, vaccination
should be postponed and parents instructed to return for
vaccination when the illness resolves.
-Vaccination is also postponed to avoid superimposing
vaccine reaction on the underlying illness and to
mistakenly attribute a manifestation of underlying illness to
vaccination.
Minor illness:
-However, vaccination opportunity should not be missed
during like upper respiratory tract infections, mild diarrhea
and otitis media.

Immunization in Pregnancy :
Live vaccines:
-Generally contraindicated in pregnant women.
- The yellow fever vaccine should be avoided in pregnant
women as far as possible. However, if travel is unavoidable,
the vaccine should be given as the risks of infection outweigh
the risks of vaccination (preferably in the 1st trimester).
-Measles, MMR and varicella vaccines are contraindicated
in pregnancy and pregnancy should be avoided for 4 weeks
after vaccination.

-If the vaccine is inadvertently given during pregnancy or
pregnancy occurs within 4 weeks of vaccination,
termination of pregnancy is not warranted.
-Small cohort studies show no increased rates of congenital
abnormalities in infants born to mothers inadvertently
vaccinated in pregnancy.
-Measles, MMR and varicella vaccines can be safely given to
contacts of pregnant women as these vaccines do not spread
from vaccine to contacts.
-Smallpox vaccine is the only vaccine known to be harmful
to the fetus.

Inactivated vaccines:
- All inactivated vaccines may be safely given during pregnancy
- Influenza and hepatitis B are other vaccines of importance
in pregnant women can be given.
-Rabies vaccine should be administered to pregnant women
if indicated and is safe.

Tetanus Toxoid in Pregnancy :
1. Unimmunized:
- 2 doses of TT at least one month apart should be given during
pregnancy so that protective antibodies in adequate titers are
transferred to the newborn for prevention of neonatal tetanus.
- The first dose should be administered at the time of first contact/ as
early as possible and the second dose of TT should be administered
1 month later and at least 2 weeks before delivery.
- A single dose of TT would suffice for subsequent pregnancies that
occur in the next 5 years; thereafter, 2 doses of TT would again be
necessary.

• 2. Fully immunized: Five childhood doses (3 primary doses plus two
• boosters) and one adolescent booster Tdap: No further doses are
• necessary in pregnancy.
• 3. Partially immunized:
• - Three primary doses: 2 doses during the 1st pregnancy are
• indicated. The 2nd pregnancy requires 1 more dose and gives
• lasting protection for the reproductive years.
• -Three primary and one childhood booster: 1 dose each in the first
• and second pregnancy provide lasting protection.
• - Three primary and two childhood boosters: Only 1 dose in the first
• pregnancy provides lasting protection.

• Tdap during pregnancy: DPT
• -A single dose of Tdap during the third trimester (preferred
• during 27 through 36 weeks gestation) regardless of number of
• years from prior Td or Tdap vaccination.
• -Tdap has to be repeated in every pregnancy irrespective of the
• status of previous immunization (with Tdap).
• -Even if an adolescent girl who had received Tdap one year
• prior to becoming pregnant will have to take it since there is
• rapid waning of immunity following pertussis immunization.

Passive immunization During Pregnancy:
- Passive immunization with immunoglobulin containing
preparations is safe in pregnancy.
- All pregnant women should be evaluated for immunity to
rubella, varicella and hepatitis B and those found susceptible
should be vaccinated immediately after delivery.
- All pregnant women should be tested for HbsAg and if found
HBsAg-positive should be followed carefully to ensure that the
infant receives HBIG and begins the hepatitis B vaccine
series no later than 12 hours after birth and completes the
recommended hepatitis B vaccine series on schedule.

• Immunization during Lactation :
• Inactivated vaccines:
• - All inactivated vaccines whether conjugated, toxoid, or subunit vaccines are
• safe in breast feeding women and pose no harm to the babies.
• Live vaccines:
• - Although live vaccines multiply in the body of the mother, most pose no
• harm to the babies as they are generally not excreted in breast milk.
• - Rubella vaccine may be excreted in milk but does not infect the baby or if it
• all causes mild asymptomatic infection.
• - The only exception to live vaccine use is yellow fever vaccine.
• Transmission of the yellow fever vaccine virus through breast milk and
• resulting in infantile meningoencephalitis has been described.
• - Hence, yellow fever vaccine should be avoided in breast feeding mothers. If
• mandatory, then breast feeding should be interrupted for the 10 day postvaccination
• viremic period.

• Lapsed immunization/Prepond immunization/Unkown immunization Status :
• - There is no need to restart a vaccine series regardless of the
• time that has elapsed between individual doses due to immune
• memory.
• -Immunizations should be given at the next visit as if the usual
• interval had elapsed and the immunization scheduled should
• be completed at the next available opportunity.
• - Doses should not be given 4 or less days from the minimum
• interval. If inadvertently given 5 or more days before the
• minimum interval, the dose should not be counted.

- In case of unknown immunization status, the child should be
considered unimmunized and vaccinated accordingly.
- Self-reported doses should not be accepted in the absence of
documentation with the exception of influenza and PPSV
vaccines.
-Serologic testing is also an option in patients with uncertain
status but is usually not cost effective, may reduce compliance
and may result in missed opportunities for vaccination.

• Catch-Up Immunization :
• - Vaccination catch up regimens should preferably be individualized.
• - Any number of vaccines live/ inactivated may be given on the same
• day either singly or as combination vaccines maintaining a gap of 5 cm
• between different vaccines.
• - Inactivated vaccines can be given at any time in relation to any other
• live/ inactivated vaccines.
• - If not given on the same day, a gap of 4 weeks should be maintained
• between two live injectable vaccines, especially MMR and varicella
• and also yellow fever and live attenuated influenza vaccines.
• - However OPV, rotavirus and oral typhoid vaccines may be given at
• any time in relation to any live/ inactivated vaccine.
• - For catch-up immunization, doses should preferably be given at the
• minimum possible interval to entail early protection.

In Relation To Antibody Containing Products :
• Live vaccines:
• - Blood (e.g., whole blood, packed red blood cells, and plasma) and other
• antibody-containing blood products (e.g., immune globulin, hyperimmune
• globulin, and IGIV) can inhibit the immune response to live vaccines
• such as, measles and rubella vaccines for ≥3 months.
• - The effect of blood and immune globulin preparations on the response to
• mumps and varicella vaccines is unknown; however, commercial
• immune globulin preparations contain antibodies to these viruses.
• - Other live vaccines like Ty21a typhoid, rotavirus, yellow fever, LAIV,
• and zoster vaccines may be administered at any time before, concurrent
• with, or after administration of any immune globulin, hyperimmune
• globulin, or intravenous immune globulin (IGIV).

-The length of time that interference with injectable live-virus
vaccine can persist after the antibody-containing product depends
upon the amount of antigen-specific antibody contained in the
product.
-Therefore, after an antibody-containing product is received, live
vaccines (other than oral Ty21a typhoid, LAIV, rotavirus zoster,
and yellow fever) should be delayed until the passive antibody has
degraded.
-If a dose of injectable live-virus vaccine (other than yellow fever
and zoster) is administered after an antibody-containing product
but at an interval shorter than recommended, the vaccine dose
should be repeated unless serologic testing is feasible and
indicates a response to the vaccine.

• Vaccination
• Vaccination is a method of giving antigen to stimulate the immune response
through active immunization.
• A vaccine is an immuno-biological substance designed to produce specific
protection against a given disease.
• 1800, used by British physician Edward Jenner (1749-1823) for the technique he
devised of preventing smallpox by injecting people with the cowpox virus
(variolae vaccinae), from vaccine (adj.) "pertaining to cows, from cows" (1798),
from Latin vaccinus "from cows," from vacca "cow," a word of uncertain origin.
"The use of the term for diseases other than smallpox is due to Pasteur"

• it is not possible to eradicate all vaccine
preventable diseases:
•1-Asymptomatic carriage
•2-Mutating organisms e.g. influenza
•3-Animal reservoirs e.g. SARS, avian influenza
•4-Environmental reservoirs e.g. tetanus
•5-Global travel/mass immigration

•In 1960, the Expanded Programme on
Immunization started in Egypt targeting 6 diseases
for eradication: diphtheria, whooping cough,
tetanus, measles, poliomyelitis and tuberculosis. 4
additional vaccines have been added to the routine
infant immunization schedule in 2016 ; including
hepatitis B, German measles, mumps and
Haemophilus influenza type b (Hib) i.e. 10 Vaccines.

Vaccine Preventable Diseases :
1- Bacterial
- Diptheria
- Haemophilus influenzae B (Hib)
- Meningococcal (meningitis)
- Pneumococcal disease
- Tetanus
- Tuberculosis
- Whooping cough (pertussis)
2- Viral
- Chicken pox
- Flu
- Measles
- Mumps
- Polio
- Rubella
- HPV

•Types of vaccines
•1- Live vaccines
•2- Attenuated live vaccines
•3- Inactivated (killed vaccines)
•4- Toxoids
•5- Polysaccharide and polypeptide (cellular fraction) vaccines
•6- Surface antigen (recombinant) vaccines.

1- Live vaccines
- Live vaccines are made from live infectious agents without any alteration .
- The only live vaccine is “Variola” small pox vaccine, made of
live vaccine cow-pox virus which is not pathogenic, giving
cross immunity for variola.

2- Live attenuated (avirulent) vaccines
- Virulent pathogenic organisms are treated to become attenuated
and avirulent. They have lost their capacity to induce full-blown
disease but retain their immunogenicity.
- Live attenuated vaccines should not be administered to persons
with suppressed immune response due to:
-Leukemia and lymphoma
-Other malignancies
-Receiving corticosteroids and anti-metabolic agents
-Radiation
-pregnancy

3- Inactivated (killed) vaccines
- Organisms are killed or inactivated by heat or chemicals but remain antigenic.
- They are usually safe but less effective than live attenuated vaccines.
- The only absolute contraindication to their administration is a
severe local or general reaction to a previous dose.

4- Toxoids
- They are prepared by detoxifying the exotoxins of some bacteria rendering them
antigenic but not pathogenic.
Adjuvant (e.g. alum precipitation) is used to increase the
potency of vaccine.
- The antibodies produces in the body as a consequence of
toxoid administration neutralize the toxic moiety produced
during infection rather than act upon the organism itself.
- In general, toxoids are highly efficacious and safe
immunizing agents.

5- Polysaccharide and polypeptide (cellular fraction) vaccines
- They are prepared from extracted cellular fractions e.g.
meningococcal vaccine from the polysaccharide antigen of the
cell wall, the pneumococcal vaccine from the polysaccharide
contained in the capsule of the organism, and hepatitis B
polypeptide vaccine.
- Their efficacy and safety appear to be high.

6- Surface antigen (Recombinant protien) vaccines
- It is prepared by cloning HBsAg gene in yeast cells where it is
expressed. HBsAg produced is then used for vaccine
preparations.
- Their efficacy and safety also appear to be high.

Routes of Administration :
1- Deep subcutaneous or
intramuscular route (most vaccines)
2- Oral route (sabin vaccine, oral BCG vaccine,Cholera)
3- Intradermal route (BCG vaccine)
4- Scarification (small pox vaccine)
5- Intranasal route (live attenuated influenza vaccine)

Levels of effectiveness
1- Absolutely protective(100%): yellow fever vaccine.
2- Almost absolutely protective (99%): Variola, measles,
mumps, rubella vaccines, and diphtheria and tetanus toxoids.
3- Highly protective (80-95%): polio, BCG, Hepatitis B, and
pertussis vaccines.
4- Moderately protective (40-60%) TAB=typhoid-paratyphoid A
and B vaccine , cholera vaccine, and influenza killed vaccine.

1-Haemophilus influenzae type b vaccine =
‫لقاح‬‫من‬ ‫النزلية‬ ‫المستدمية‬‫النوع‬‫ب‬
2- Penta Vaccine = ‫الخماسى‬ ‫اللقاح‬
3- Triple Vaccine = ‫البكتيرى‬ ‫الثالثى‬ ‫المصل‬

• Polio, according to the CDC, is an incurable, "crippling and potentially deadly
infectious disease caused by a virus that spreads from person to person invading
the brain and spinal cord and causing paralysis."
• Poliovirus, the causative agent of poliomyelitis (commonly known as polio), is a
human entero virus and member of the family of , Picorna viridae
• RNA Virus
• 3 Serotypes of poliovirus, PV1, PV2, and PV3,

• The idea of a vaccine against polio was first introduced in 1910 as a result of
research by Simon Flexner, MD. In 1935 two teams tested a polio vaccine but
neither were successful and both teams infected and killed some test subjects
(the scientists, chimpanzees, human adults, and children). In 1951, Jonas Salk,
MD, and his team developed a method to cultivate polio virus in monkey kidney
tissue in order to be able to produce large amounts of the vaccine. On Apr. 12,
1955 the results of the Salk vaccine trials showed the vaccine was 80-90%
effective and the US government licensed the IPV (inactivated polio vaccine)
vaccine the same day.
• On Aug. 24, 1960, a polio vaccine (OPV; oral polio vaccine) created by Albert
Sabin, MD, was licensed for use in the US .
• Polio was declared eradicated in the Americas on Sep. 29, 1994 by the Pan
American Health Organization.
• An improved version of Jonas Salk’s IPV vaccine was phased in again in 1997,
because OPV had an increased risk of infecting children with the virus in the first
dose. In 2000 the transition to all-IPV vaccine schedule was complete.

Jonas Salk
October 28, 1914 – June 23, 1995
American
inactivated poliovirus vaccine (ipv) 1955

Albert Sabin
August 26, 1906 – March 3, 1993
Polish American
OPV (Oral Polio Vaccine) 1960

• The first polio vaccine was the inactivated polio
vaccine. It was developed by Jonas Salk and came
into use in 1955. The oral polio vaccine was developed
by Albert Sabin and came into commercial use in
1961. They are on the World Health Organization's List
of Essential Medicines, the most effective and safe
medicines needed in a health system. The wholesale
cost in the developing world is about US$0.25 per
dose for the oral form as of 2014. In the United States,
it costs between $25 and $50 for the inactivated form.

• Oral polio vaccine (OPV)
• OPV consists of a mixture of live attenuated poliovirus strains of each of the three
serotypes, selected by their ability to mimic the immune response following infection
with wild polioviruses, but with a significantly reduced incidence of spreading to the
central nervous system. 3 or more spaced doses of OPV are required to generate
adequate levels of seroconversion. The action of oral polio vaccine (OPV) is two-
pronged. OPV produces antibodies in the blood ('humoral' or serum immunity) to all
three types of poliovirus, and in the event of infection, this protects the individual
against polio paralysis by preventing the spread of poliovirus to the nervous system.
OPV strains also produce a local immune response in the lining ('mucous membrane') of
the intestines - the primary site for poliovirus multiplication. The antibodies produced
there inhibit the multiplication of subsequent infections of 'wild' (naturally occurring)
virus. This intestinal immune response to OPV is probably a reason why mass campaigns
with OPV have been shown to stop person-to-person transmission of wild poliovirus. In
very rare cases, the administration of OPV results in vaccine-associated paralysis
associated with a reversion of the vaccine strains to the more neurovirulent profile of
wild poliovirus. In a few instances, such vaccine strains have become both neurovirulent
and transmissible and have resulted in infectious poliomyelitis. Source:WHO

•Dose of Polio Vaccine :
• 1- OPV=Oral Polio Vaccine = Sabin ------ 2 Drops /orally
• 2- IPV =inactivated poliovirus vaccine =Salk ------ 0.5 cm / im
• Vaccine-associated paralytic polio =VAPP
• ranging from 1case per 700,000 to 1case per 3.4 million first doses

•BCG= Albert Calmette and Camille Guerin. They were two French scientists
who from 1905 had been working on developing a vaccine against TB. BCG is an
abbreviation of Bacillus Calmette-Guerin, meaning the bacilli of Calmette and
Guerin.
• Between 1905 and 1918, Calmette and Guerin carried out research into the
mechanisms of tuberculosis infection. They demonstrated that small doses of
injected and weakened animal bacilli could be used as a protective vaccine
against TB, in cattle and various species of monkey. So they then cultured the
bacillus, and found that successive culturing weakened the bacillus.
• Calmette and Guerin tried to produce ever more weakened strains of the bacillus
by successive sub culturing every three weeks. The research had to stop during
the first world war, but was resumed in 1918. By 1921 the tubercle bacillus had
been sub cultured 230 times, and it was so weakened that it was believed that it
could confer immunity without causing disease in humans.

•BCG Vaccine
• = Bacillus Calmette–Guérin
• first used medically in 1921
• 2004 the vaccine is given to about 100 million children per year globally
• BCG used in : 1- vaccination against tuberculosis
• 2- protective effects against some non-tuberculosis mycobacteria:
• -Leprosy: BCG has a protective effect against leprosy in the range of 20 to
80%.
• -Buruli ulcer: BCG may protect against or delay the onset of Buruli ulcer
• 3- Cancer immunotherapy in superficial forms of bladder cancer

Since the late 1970s, evidence has become available that
instillation of BCG into the bladder is an effective form of
immunotherapy in this disease. While the mechanism is unclear,
it appears a local immune reaction is mounted against the
tumor. Immunotherapy with BCG prevents recurrence in up to
67% of cases of superficial bladder cancer.
- Colorectal Cancer : The US biotech company Vaccinogen is
evaluating BCG as an adjuvant to autologous tumour cells used
as a cancer vaccine in stage II colon cancer.

• Side effects of BCG :
• 1- Very common side effect (affecting 9 out of 10 people):
• Hardness at the injection site, followed by a raised blister.
• 2- Uncommon side effects (affecting up to 1 in 100 people at each dose):
• Headache and a raised temperature (fever)
• An ulcer which develops from the blister at the injection site, two to six weeks
after injection. This may be painful and take several weeks or months to heal
fully.
• Swelling of lymph nodes in the armpit larger than 1 cm across
• An enlarged lymph node that becomes infected (lymphadenitis)
• 3- Rare side effects (affecting up to 1 in 1000 people at each dose):
• More severe skin reactions. These usually heal within a few weeks.
• Bone inflammation (osteitis or osteomyelitis)
• An abscess at the injection site

• As with any vaccine, medicine or food, there is a very small chance of an
immediate severe allergic reaction called anaphylaxis. Anaphylaxis is different
from less severe allergic reactions because it causes life-threatening breathing
and/or circulation problems. It is always serious but can be treated with
adrenaline. In the UK between 1997 and 2003 there were a total of 130 reports
of anaphylaxis following ALL immunisations, but all of these people survived.
Around 117 million doses of vaccines were given in the UK during this period,
making the overall rate around 1 in 900,000. Depending on the cause of the
reaction, and following expert guidance, the person may be able to have
vaccinations in the future.

Route of administration: intradermal
(0.05 mL dose for children under one
year)
(0.1 mL dose for recipients over one year)
Skin Thickness :
1- The Epidermis = 0.5 – 1.5
millimeter
2- The Dermis = 0.6 – 3.0
millimeters
3- The Subcutaneous Tissue =
Variable

Diphtheria, Tetanus, and Pertussis
Vaccines
DPT

• Tetanus Vaccine = Tetanus Toxoid = TT = inactive vaccine
• Tetanus vaccine, also known as tetanus toxoid (TT), is an inactive vaccine used to
prevent tetanus. During childhood 5 doses are recommended, with a 6th given
during adolescence . Additional doses every 10 years are recommended. After 3
doses almost everyone is initially immune. In those who are not up to date on
their tetanus immunization a booster should be given within 48 hours of an
injury. In those with high risk injuries who are not fully immunized tetanus
antitoxin may also be recommended. Making sure women who are pregnant are
up to date on their tetanus immunization and, if not, immunizing them can
prevent neonatal tetanus.
• The vaccine is very safe including during pregnancy and in those with HIV/AIDS.
Redness and pain at the site of injection occur in between 25% and 85% of
people. Fever, feeling tired, and minor muscles pains occur in less than 10% of
people. Severe allergic reactions occur in less than one in 100,000 people.

• A number of vaccine combinations include the tetanus vaccine such as DTaP and
Tdap which contain diphtheria, tetanus, and pertussis vaccine, and DT and Td
which contain diphtheria and tetanus vaccine. DTaP and DT are given to
children less than seven years old while Tdap and Td are given to those seven
years old and older. The lowercase d and p denote lower strengths of diphtheria
and pertussis vaccines.
• The tetanus vaccine was developed in 1924 and became available in the United
States in the 1940s. Its use resulted in a 95% decrease in the rate of tetanus. It
is on the World Health Organization's List of Essential Medicines, the most
effective and safe medicines needed in a health system. The wholesale cost in
the developing world is between 0.17 and 0.65 USD per dose as of 2014. In the
United States a course of tetanus vaccine is between 25 and 50 USD.

Tetanus Antitoxin:
Therapeutic action
– Neutralisation of tetanus toxin. Tetanus antiserum provides temporary passive immunity against tetanus
for 2 weeks.
Indications
– Prevention of tetanus in wound management, in patients non immunised or incompletely immunised or
in patients whose immunisation status is unknown, in combination with tetanus vaccine
– Treatment of clinical tetanus
Dosage and duration
– Prevention of tetanus
Tetanus antiserum is administered in the event of tetanus-prone wounds, e.g. wounds with fracture, deep
penetrating wounds, bite wounds, wounds containing foreign bodies, wounds contaminated with soil,
infected wounds, extensive tissue damage (contusions, burns).
Child and adult: 1500 IU single dose; 3000 IU if more than 24 hours has elapsed
It is administered as soon as possible after injury, along with the tetanus vaccine, in a separate syringe and
injection site.
– Treatment of tetanus
Neonate: 1500 IU single dose
Child and adult: 10 000 IU single dose

Human Tetanus Immunoglobulin = HTIG
Therapeutic action
– Neutralisation of tetanus toxin. HTIG provides passive immunization against tetanus for 3 to 4 weeks.
Indications
– Prevention of tetanus in wound management, in patients non immunised or incompletely immunised or in
patients whose immunisation status is unknown, in combination with tetanus vaccine
– Treatment of clinical tetanus
Forms and strengths, route of administration
– Solution for injection, in 250 IU (250 IU/ml, 1 ml) or 500 IU (250 IU/ml, 2 ml) ampoule or single-dose syringe, for
IM injection. DO NOT ADMINISTER BY IV ROUTE.
Dosage and duration
– Prevention of tetanus
HTIG is administered in the event of tetanus-prone wounds, e.g. wounds with fracture, deep penetrating wounds,
bite wounds, wounds containing foreign bodies, wounds contaminated with soil, infected wounds, extensive tissue
damage (contusions, burns).
Child and adult: 250 IU single dose; 500 IU if more than 24 hours has elapsed
HTIG should be administered as soon as possible after injury, along with the tetanus vaccine, in a separate syringe
and injection site.
– Treatment of tetanus
Neonate, child and adult: 500 IU single dose, to be injected into 2 different sites

Dose of DPT Vaccine:
0.5 ml/ IM at 2,4,6,18 months age
Common side effects of DTP :
1-injection site reactions (redness, warmth, swelling, tenderness, itching, pain,
hives, and rash)
2-fever (up to about 1 child in 4)
3-drowsiness
4-fretfulness
5-vomiting (up to about 1 child in 50)
6-weight loss (anorexia)
7-persistent crying
8-rarely Convulsions (jerking or staring) (about 1 child out of 14,000)

Persistent Inconsolable Screaming :
- Inconsolable continuous cry for 3 hours or longer
accompanied by high pitched screaming
-DPT, Pertussis
- Settles within a day, analgesics may help.

• From 1956 to 1960, before the availability of a vaccine, an average of 542 000
cases of measles were reported each year in the US, along with an average of 450
measles-related deaths, 4000 encephalitis cases (often with permanent brain
damage), and 150 000 respiratory complications.
• The measles vaccine was licensed in 1963 and the measles, mumps, rubella
(MMR) vaccine was licensed in 1971. For the years between 1987 and 2000, the
number dropped to 28 730 cases of measles in children younger than 5 years of
age; 97 died, 43 contracted encephalitis, and 2480 contracted pneumonia. Since
1997, there has been less than 1 case per million population in the US. The
global burden of measles in 1999 was an estimated 873 000 deaths that were
reduced through a world-wide vaccination campaign to an estimated 164 000
deaths in 2008.

MMR and autism
Autistic spectrum disorder represents a continuum of cognitive and neurobehavioral disorders
including autism. The prevalence of autism varies considerably with case ascertainment, ranging
from 0.7 – 21.1 per 10 000 children (median 5.2 per 10 000) while the prevalence of autistic
spectrum disorder is estimated to be 1 - 6 per 1000. Eleven epidemiological studies
(representing the most recent studies, mostly in the last 4 years) were reviewed in detail, taking
into consideration study design (including ecologic, case control, case-crossover and cohort
studies) and limitations. The review concluded that existing studies do not show evidence of an
association between the risk of autism or autistic disorders and MMR vaccine. Three laboratory
studies were also reviewed. It was concluded that the alleged persistence of measles vaccine
virus in the gastrointestinal tract of children with autism and inflammatory bowel disease
requires further investigation through independent studies before the laboratory findings of the
published studies, which have serious limitations, can be considered confirmed.
Based on the extensive review presented, GACVS concluded that no evidence exists of a causal
association between MMR vaccine and autism or autistic disorders. The Committee believes the
matter is likely to be clarified by a better understanding of the causes of autism. GACVS also
concluded that there is no evidence to support the routine use of monovalent measles, mumps
and rubella vaccines over the combined vaccine, a strategy which would put children at
increased risk of incomplete immunization. Thus, GACVS recommends that there should be no
change in current vaccination practices with MMR.
Source : http://www.who.int/vaccine_safety/committee/topics/mmr
GACVS=Global Advisory Committee on Vaccine Safety

Complications of Typhoid Fever

Typhoid vaccines
There are 2 vaccines to prevent typhoid.
1- One is an inactivated (killed) vaccine gotten as a shot.
2- The other is a live, attenuated (weakened) vaccine which is taken orally

• Rotavirus is the most common cause of diarrhoeal disease among infants and
young children. It is a genus of double-stranded RNA viruses in the family
Reoviridae. Nearly every child in the world is infected with rotavirus at least once
by the age of five. Immunity develops with each infection, so subsequent
infections are less severe; adults are rarely affected. There are 9 species of this
virus, referred to as A, B, C, D, E, F, G, H and I. Rotavirus A, the most common
species, causes more than 90% of rotavirus infections in humans.
• The virus is transmitted by the faecal-oral route. It infects and damages the cells
that line the small intestine and causes gastroenteritis (which is often called
"stomach flu" despite having no relation to influenza). Although rotavirus was
discovered in 1973 by Ruth Bishop and her colleagues by electron micrograph
images and accounts for approximately one third of hospitalisations for severe
diarrhoea in infants and children, its importance has historically been
underestimated within the public health community, particularly in developing
countries. In addition to its impact on human health, rotavirus also infects
animals, and is a pathogen of livestock.

• Rotaviral enteritis is usually an easily managed disease of childhood, but in 2013,
rotavirus caused 37 percent of deaths of children from diarrhoea and 215,000
deaths worldwide, and almost two million more become severely ill. Most of
these deaths occurred in developing countries. In the United States, before
initiation of the rotavirus vaccination programme, rotavirus caused about 2.7
million cases of severe gastroenteritis in children, almost 60,000 hospitalisations,
and around 37 deaths each year. Following rotavirus vaccine introduction in the
United States, hospitalisation rates have fallen significantly. Public health
campaigns to combat rotavirus focus on providing oral rehydration therapy for
infected children and vaccination to prevent the disease. The incidence and
severity of rotavirus infections has declined significantly in countries that have
added rotavirus vaccine to their routine childhood immunisation policies.

• Rotavirus vaccine
• Two brands of Rotavirus Vaccine are available :
• 1- RotaTeq 3 Doses at 2,4,6 Months
• 2- Rotarix 2 Doses at 2,4 Months

Rotavirus vaccine Risks :
- Babies might become irritable, or have mild, temporary
diarrhea or vomiting after getting a dose of rotavirus vaccine
-There is also a small risk of intussusception from
rotavirus vaccination, usually within a week after the 1st
or 2nd vaccine dose. This additional risk is estimated to
range from about 1 in 20,000 to 1 in 100,000 US infants
who get rotavirus vaccine.
- severe allergic reaction

• Human papillomavirus = HPV
• DNA virus from the papillomavirus family, of which over 170 types are known.
More than 40 types are transmitted through sexual contact , increase the risk of
cancer of the cervix, vulva, vagina, penis, anus, mouth, or throat. Nearly all
cervical cancer is due to HPV with two types, HPV16 and HPV18, accounting for
70% of cases. Between 60% and 90% of the other cancers mentioned above are
also linked to HPV. HPV6 and HPV11 are common causes of genital warts and
laryngeal papillomatosis.

• In March 1918 an international influenza pandemic broke out, that led to the
deaths of 50 million people worldwide

Seasonal Influenza
600,000,000 case per year and 500,000 died due to complications of influenza
• Causes annual epidemics
• Is highly infectious with a 1–5 day incubation period
• Severity of illness depends on prior influenza virus
immune experience, health, and age
• May cause no symptoms in 30–50% of those infected by the virus
• Symptomatic disease: abrupt onset of fever muscle
aches, sore throat, cough and headache
• Many school days (and caregiver work days) lost
• Can trigger life-threatening complications:
In an average year, 114,000 hospitalizations and
approximately20,000 deaths in the USA
• The most common vaccine preventable disease in the USA

• Influenza Virus Infections
• Influenza A
• • Moderate to severe illness
• • Affects all age groups
• • Infects animals and humans
• • Associated with seasonal epidemics
• • Associated with pandemics
• Influenza B
• • Similar illness
• • Primarily affects children
• • Infects humans only
• • Aspirin-associated Reye’s Syndrome*
• Influenza C
• • Similar illness
• • Infects primarily pigs
• • Humans infected sporadically
• *An illness in children of encephalopathy and fatty
• degeneration of the liver, often fatal.

• Influenza Complications
• Most common among
• • Older adults
• • Those with chronic health problems such as asthma,
• lung disease (including smoking), obesity
• • Children younger than 5 years of age (especially
• younger than 2)
• • Pregnant women
• Complications
• • Bacterial pneumonia, sinusitis, otitis media
• • Encephalitis in children
• • Rhabdomyelitis in adults (rare)

• Indications for Influenza Vaccine
• Although influenza virus vaccines are currently recommended only for those infants
(older than 6 months of age) considered at "high risk," there is an increasing swell of
interest in "routine" universal immunization of infants and children.
• This is based on 2 features. First, during influenza virus seasons there are large numbers
of infants admitted to hospital with fevers of unknown origin which are shown to be
due to influenza virus. Additionally, there is the epidemiologic observation that
preschool- and school-age children acquiring acute influenza virus infections bring the
agent home and infect adults and others with whom they have contact. Those who are
advocating for universal pediatric immunization with influenza vaccines do so on the
basis of reducing hospital admissions for fevers of unknown origin and diminishing the
transmission of virus to adults.
• Current recommendations, however, are only for infants "at high risk" such as those
with asthma, cystic fibrosis, other chronic pulmonary disease, cardiac disease with
congestive failure, immunosuppression, sickle cell disease, chronic renal disease,
diabetes, or other chronic metabolic disease, as well as patients who may be receiving
chronic aspirin therapy (in order to avoid Reye's syndrome).
• Vaccine is given in 2 doses to children under 8 years of age if they have not previously
received the vaccine. A new influenza virus vaccine administered by nasal spray is
rapidly approaching licensure in this country and would greatly facilitate the
administration of vaccine to infants and children, as well as adults.

Contraindications and precautions to receiving influenza vaccine
Influenza vaccination is contraindicated for individuals who have had documented
anaphylaxis to any ingredient in the vaccine except egg, or a previous dose of
inactivated influenza vaccine. These individuals should not receive the vaccine.
Influenza vaccination may be contraindicated or need to be delayed for people
receiving some new cancer treatments
The immune-stimulant actions of:
atezolizumab (Tecentriq®)
ipilimumab (Yervoy®)
nivolumab (Opdivo®)
pembrolizumab (Keytruda®)
on the immune system increase a person’s risk of developing autoimmune
conditions. It is not known whether receipt of an influenza vaccine whilst receiving
these treatments or for up to six months after treatment increases a theoretical
risk of triggering the occurrence of these side effects.

• Dose :
• Immunization Against Otitis Media
• Schedule: 1 dose (0.5 mL) IM at 2*, 4, 6, & 12 months old (*may be given as early as 6 weeks
old)
• 7-11 months old: 2 doses 4 weeks apart; 3rd dose at least 2 months later, after 12 month
• 12-23 months old: 2 doses, 2 months apart
• 2-9 years old: 1 dose
• Immunization Against S. Pneumoniae
• 1 dose (0.5 mL) IM at 2*, 4, 6, & 12 months old (*may be given as early as 6 weeks old)
• 7-12 months old: 2 doses 4 weeks apart; 3rd dose at least 2 months later, after 12 month
• 12-24 months old: 2 doses, 2 months apart
• 2-9 years old: 1 dose

• The splenectomized patient should be vaccinated to decrease the risk of
overwhelming postsplenectomy
• sepsis (OPSS) due to organisms such as Streptococcus pneumoniae, Haemophilus
influenzae type B, and Neisseria meningitidis. Patients should be educated prior
to discharge on the risk of OPSS and their immunocompromised state. An
understanding of the need for prompt medical attention should be instilled in
such patients to reduce the morbidity and mortality of postsplenectomy
infection.
• 1- Elective splenectomy patients should be vaccinated at least 14 days prior to
the operation.
• 2- Non-elective splenectomy patients should be vaccinated on or after
postoperative day 14.
• 3- Asplenic patients should be revaccinated at the appropriate time interval for
each vaccine.

There are at least 12 types of N. meningitidis, called “serogroups.” Serogroups A, B,
C, W, and Y cause most meningococcal disease.
People at Risk :
- Infants younger than one year old
- Adolescents and young adults 16 through 23 years old
- People with certain medical conditions that affect the immune system
- Microbiologists who routinely work with isolates of N. meningitidis
- People at risk because of an outbreak in their community

• Rabies
• around 59 000 die of rabies each year and nearly half of whom are children.
• Rabies is caused by RNA viruses in the family Rhabdoviridae, genus
lyssavirus. Virus is transmitted in the saliva of rabid animals after a bite or
through contamination of an open wound or mucous membrane. The
predominant reservoir of rabies in India, with most cases occurring in dogs
and rarely in cats. The incubation period (1–3 months but ranges from
days to years) is long enough to render immunization a highly effective
strategy for post exposure prophylaxis (Post EP), which is an emergency.
Key interventions for rabies control include vaccination for high-risk
individuals, surveillance of human cases, post-exposure prophylaxis
following animal bites, vaccination and/or culling of the canine population
and other animal reservoirs. In India, especially animal rabies is common
and education of children to avoid contact with stray or wild animals is of
primary importance.

Haemophilus influenzae type B Vaccine

• The oral Cholera vaccines are generally of 2 forms: inactivated and attenuated.
• Inactivated oral vaccines provide protection in 52 percent of cases the first year
following vaccination and in 62 percent of cases the second year. Two variants of
the inactivated oral vaccine currently are in use: WC-rBS and BivWC. WC-rBS
(marketed as "Dukoral") is a monovalent inactivated vaccine containing killed
whole cells of V. cholerae O1 plus additional recombinant cholera toxin B subunit.
BivWC (marketed as "Shanchol" and "mORCVAX") is a bivalent inactivated vaccine
containing killed whole cells of V. cholerae O1 and V. cholerae O139. mORCVAX is
only available in Vietnam.
• A live, attenuated oral vaccine (CVD 103-HgR or Vaxchora), derived from a
serogroup O1 classical Inaba strain, was approved by the US FDA in 2016.
• Injectable Cholera Vaccine
• Although rarely in use, the injected cholera vaccines are effective for people living
where cholera is common. They offer some degree of protection for up to two
years after a single shot, and for three to four years with annual booster. They
reduce the risk of death from cholera by 50 percent in the first year after
vaccination.

Contraindications to Children
Vaccination

Dental Caries Vaccine
Development of a vaccine for tooth decay has been under
investigation for more than 50 years. In 1972, a caries
vaccine was said to be in animal testing in England, and that
it would have begun human testing soon.
Clinical trials have indicated that a mucosal immune response
to Streptococcus mutans crucial antigens can influence the pathogenesis
of dental caries.

Antiserum
Antiserum is human or nonhuman blood serum containing polyclonal antibodies
and is used to pass on passive immunity to many diseases. For example, passive
antibody transfusion from a previous human survivor (convalescent serum) used to
be the only known effective treatment for Ebola infection (but with little success
rate).
Antisera are widely used in diagnostic virology laboratories. The most common use
of antiserum in humans is as antitoxin or antivenom, to treat envenomation.

Vaccines under Research :
271Vaccines in Development
Respiratory Syncytial Virus
Malaria
Bilhareziasis
Hepatitis C
HIV
Cancer
Ebola Virus

• Websites:
• 1- www.immunize.org
• 2- www.cdc.gov/vaccines
• 3- www.who.int/topics/vaccines
• 4- www.nhs.uk/conditions/vaccinations
• 5- www.immunise.health.gov.au
• 6- www.cdc.gov/vaccines/acip
• 7- www.wikipedia.org
• 8- www.britannica.com
• 9- www.pathmicro.med.sc.edu
• 10- www.mpi-magdeburg.mpg.de
• 11- www.sc.edu
• 12- www.niaid.nih.gov
• 13- The Green Book’, www.dh.gov.uk
• 14- www.immunisation.nhs.uk
• 15- www.hps.scot.nhs.uk
• 16- www.immunisationscotland.org.uk
• 17- www.uvig.org
• 18- www.hpa.org.uk

• References :
• • 1. 3nd ed. Geneva: WHO; 2009. World Health Organization ganization (WHO)
• Unicef, World Bank. State of the world's vaccines and immunization.
• • 2. Geneva: WHO; 2012. Mar, [accessed on May 30, 2012]. World Health
• Organization. Global immunization data 2011. Available from:
• www.who.int/hpvcentre/Global_Immunization_Data.pdf .
• • 3. Fenner F, Henderson DA, Arita I, Jezek Z, Ladnyi ID. Geneva: World Health
• Organization; 1988. Smallpox and its eradication; pp. 369–71.
• • 4. New Delhi: Government of India and UNICEF; 2010. United Nations
• International Children's Fund. Coverage evaluation survey: all India report 2009.
• Basu RN, Jezek Z, Ward NA. New Delhi, India: World Health
• 5.Organization, South-East Asia Regional Office; 1979. The
• eradication of smallpox from India.

• • 6. Bhattacharya S, Harrison M, Worboys M. Hyderabad: Orient
• Longman; 2006. Fractured states: Smallpox, public health and
• vaccination policy in British India, 1800-1947.
• • 7. Bazin H. San Diego: Academic Press; 2000. The eradication of
• smallpox: Edward Jenner and the first and only eradication of a
• human infectious disease.
• 8•Janes Kuby, 2007, Vaccines, Immunology, W.H. Freeman and
• Company, Newyork, sixth Edition, Pg. 413- 428.
• 9•Satyanarayana U. , 2010, Vacines, Biotechnolgy, BOOK’ S AND
• ALLIED (P) Ltd, Kolkata, sixth edition, Pg. 211 -212.

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