Pentavalent vaccine introduction in immunization programme in India

1. Introduction of Pentavalent Vaccine In
Routine Immunization

2. Contents:
Operational
Guidelines for Use of
Pentavalent Vaccine
Issues related to
Pentavalent vaccine

3. OperationalGuidelinesforUseof
PentavalentVaccine

5. 1. BACKGROUND
• 8.1 million cases of serious Hib diseases, and 371,000 deaths globally,
in the year 2000 (Watt et al, 2009).
• annually 2.4 to 3.0 million cases of Hib disease occurs in India
• 72,000 deaths due to Hib disease in 2009. (NTAGI subcommittee on
Hib, Watt et al )
• Total 1,726,000 under five death in 2009 (UNICEF, 2010) .
• Hib associated deaths are 4% [(72,000 / 1,726,000)*100] of all under 5
mortality.
• morbidity burden : 25-30% of Hib meningitis survivors suffering from
long term neurological sequalae (NTAGI Sub-committee, 2009).

6. 1. BACKGROUND
• Vaccines are the only public health tool.
• World Health Organization recommended in 2006 that Hib vaccines be
included in routine immunization programmes of all countries .
• Introduced in more than 150 countries.
• As a consequence, invasive Hib disease has been practically eliminated
in many industrialized countries, and its incidence has been
dramatically reduced in some parts of the developing world.

7. 2. THE DISEASE
• Gram-negative coccobacillus
• affects only humans
• six types of Haemophilus influenzae (a, b, c, d, e, and f),
• Haemophilus influenzae type b (Hib) bacteria accounts
for over 90% of serious Haemophilus influenzae
infections in children.
• Hib bacteria live in the nose and throat area.
2.1-What is Haemophilus influenzae ?

8. 2.2- Modes of transmission
• droplets of saliva when an infected individual coughs or
sneezes.
• Hib can also be spread when children share toys and
other objects that they have put in their mouth.
• The probability of transmission increases when children
spend prolonged periods of time together in settings
such as day-care or crèches.
• Children are often asymptomatic carriers of the Hib
bacteria showing no signs or symptoms but still can
infect others.

9. 2.3- Risk groups for Hib disease
• Children between the ages of 4 to 18 months of age
are most at risk (WHO, 2006).
• When the child reaches 2 or 3 months of age, the
level of maternal antibodies decreases and the risk
of Hib infection increases.
• Hib disease after the age of five years is considered
rare.

10. 2.4- Diseases caused by Hib infection
Bacterial meningitis:
• In the absence of vaccination, bacterial meningitis in children is most often caused by Hib. In
developing countries, as many as 40% of Hib cases result in death. Furthermore, 15% to 35%
of children who survive Hib meningitis are left with permanent neurological disabilities such
as mental retardation and hearing loss (NTAGI Sub-committee, 2009).
Inflammation of the lungs:
• In developing countries, Hib is a major cause of pneumonia (or acute lower respiratory
infection, ALRI) in children. It has been found that up to 20% of the severe bacterial
pneumonia cases are caused by Hib.
 In India, Hib is a leading cause of meningitis (40-50% of all cases ) and pneumonia (25- 30%
of all pneumonia cases) in children aged less than 5 years.
Other Hib infections include:
• Septicaemia: Presence of pathogenic bacteria in the blood.
• Septic arthritis: Inflammation of the joints.
• Osteomyelitis: Inflammation of the bones
• Epiglottitis: Inflammation of the larynx and pharynx. In the absence of appropriate and
immediate treatment, 50% of cases are fatal.

11. 2.5. Diagnosis of Hib infection
• The diagnosis of Hib disease can be made by bacterial culture,
Latex Agglutination Test or by Polymerase Chain Reaction
(PCR).
• In reality, it is very difficult to identify Hib in resource poor
settings.
• The culture needs to be done on sterile fluids like CSF or
blood. For CSF, a delicate procedure called a lumber puncture
(LP) must be done.
• The samples collected need to be stored and transported in
appropriate media while maintaining appropriate cold chain
to have any chances of culturing Hib bacteria.

12. 2.6- Treatment
• Treatment for Hib disease is not always effective
because some strains of Hib may be resistant to
antibiotics.
• Antibiotic resistance is a serious problem, which is
continuously increasing in developing countries,
including India.
• Immunization against Hib is a cost effective strategy
for disease prevention.

13. 3. HIB CONTAINING
PENTAVALENT VACCINE
• Hib vaccines are available in different formulations of liquid or
lyophilised (dried powder), stand alone (mono-valent) and
combination (DPT+Hib, DPT+HepB+Hib) forms.
• The formulation which will be provided in Universal
Immunization Programme (UIP) in India will be Liquid
Pentavalent vaccine (LPV).
• The vaccine will have 5 antigens (DPT+ HepB+ Hib) in a single
formulation.
3.1. Formulation

14. 3.2- Presentation
• The Liquid pentavalent vaccine (LPV) in the
UIP will be available in 10 dose presentation.

15. 3.3- Storage volume
• The storage volume of Hib vaccine in 10 dose
vials is approximately the same as currently
used DPT or HepB vaccine in similar
presentation.
• Hence, there would not be any additional cold
chain space requirement, while introducing
pentavalent vaccine.

16. 3.4- Storage temperature
• Pentavalent vaccine should be stored at
temperature of 2-8 degree Celsius, in the basket of
ILR and should never be frozen.
• Conditioned ice packs should be used during
transportation to prevent freezing

17. 3.5. Age group for vaccination
• Hib containing pentavalent vaccine is indicated in
children from the age of 6 weeks up to 12 months.

18. 3.6. Vaccination schedule
• During the initial months of Pentavalent vaccine
introduction, only those children who are coming for
the first dose of DPT will be administered
Pentavalent vaccine. (Phasing In)
• Infants who have already received either their first
or second doses of DPT & Hep B (i.e., DPT/HepB 1 or
DPT/HepB 2) will complete the schedule with DPT &
Hep B only.

19. Immunization Schedule in Delhi
AGE Old Schedule New Schedule
At birth BCG, OPV-0, Hep B -birth dose BCG, OPV-0, Hep B -birth dose
6 Weeks OPV, DPT, Hep B (1st dose) OPV, Pentavalent (1st dose)
10 Weeks OPV, DPT, Hep B (2nd dose) OPV, Pentavalent (2nd dose)
14 Weeks OPV, DPT, Hep B (3rd dose) OPV, Pentavalent (3rd dose)
9 months Measles Measles
15-18 months MMR MMR
16-24 months OPV, DPT booster-1 OPV, DPT booster-1
2 years Typhoid Typhoid
5 years DPT booster-2 DPT booster-2

20. 3.7. Dosage and route:
• The dose of pentavalent vaccine is 0.5 ml.
• The mode of administration of pentavalent
vaccine is the same as DPT vaccine
• Pentavalent vaccine is used directly from the
vial and given by intramuscular injection in the
antero-lateral aspect of the mid thigh in
infants.

21. 3.8. Inter-changeability of the vaccines
• Liquid pentavalent vaccines from different
manufacturers can be used to complete the
immunization schedule of an infant.

22. 3.9- Adverse events following immunization
• Hib vaccine has not been associated with any serious adverse
effects.
• Redness, swelling and pain at the site of injection may occur in as
many as 25% of those who have been vaccinated.
• Such reactions usually start within 1 day after immunization and
last for 1–3 days (WHO 2009, Govt. of India, 2010).
• Less commonly, children may develop fever or can become
irritable for a short period.
• When the Hib vaccine is given at the same time or as a
combination vaccine with DPT, such as with pentavalent vaccine,
the rate of AEFI is not any higher than when DPT is given alone.

23. 3.10. Contraindications:
Severe allergic reactions
• Although rare, an individual may have had a severe
allergic reaction to a component of the vaccine
following a previous dose of Hib/pentavalent vaccine.
In such an event, subsequent doses are contraindicated
and should not be given.
Persons with moderate or severe acute illness
• Children with moderate or severe acute illness should
not be administered pentavalent vaccine until their
condition improves. The minor illnesses, however, such
as upper respiratory infections (URI) is not a
contraindication to vaccination.

24. 3.11. effectiveness
• All Hib containing vaccines (i.e., pentavalent vaccine) are safe
and efficacious.
• They provide 85 to 95% protection after completion of the
schedule.
• The vaccination reduces nasopharyngeal colonization – or
carriage – of the organism, leading to substantially greater
reduction in disease transmission and incidence than can be
directly attributed to the effects of the vaccine.
• This indirect effect on herd immunity has been demonstrated
in several postintroduction effectiveness studies.

25. 3.12. Long term protection and booster dose
• In general, the Hib vaccine provides protection for at
least 15 years. Current scientific evidence suggests
that protection is life long.
• In the case where serum antibodies wane, an
anamnestic response of antibody production
triggered by memory B cells and memory T4 cells
often occurs following re-exposure to the vaccine.
• A booster dose is not recommended.

26. 3.13 Continuation of HepB birth dose and DPT boosters:
• Following the introduction of pentavalent vaccine,
at the age of 6, 10 and 14 weeks, the DPT & HepB
vaccines will be given as combination pentavalent
vaccine However, HepB vaccine will be continued to
be used for the birth dose (with in 24hrs).
• Similarly, the booster doses of DPT vaccines (at 16-
24 months & at 5-6 years)will continue to be given
as stand alone formulations.

27. 3.14 - Open Vial Policy:
• These open vials should be kept in proper cold
chain and with date of opening of the vial
mentioned.
• This open vial should not be used after one
month of its opening.

28. IssuesrelatedtoPentavalent
Vaccine
Issues:

29. Issues related to pentavalent vaccine
• Safety
• Efficacy
• Cost effectiveness
• Feasibility
• Changes in Hib epidemiology following use of Hib
vaccines

30. Issues related to pentavalent vaccine
Storage volume & Presentation:
• A phase III randomized, controlled study to assess and
compare the immunogenicity and tolerability of
single and multi-dose vials of DTwP-Hib, a fully liquid
quadravalent vaccine and their comparison with
TETRAct-Hib vaccine in Indian infants aged 6–14
weeks. Vaccine Vol 29, 48, 8 Nov 2011, 8773-79
• Postvaccination, geometric mean titres for each
component did not differ significantly between the
single dose vial and multi dose vial subgroups and
among the two study groups.

31.  Immunogenicity and safety of an indigenously manufactured
reconstituted pentavalent (DTwP-HBV+Hib) vaccine in comparison
with a foreign competitor following primary and booster
immunization in Indian children Vaccine Vol 7, 4 2011,451 – 57
• Post-primary immunization, 100% seroprotection was noted for Diphtheria,
Tetanus, Hepatitis B and PRP-Hib components in both the vaccine groups
• For pertussis, response was 96.1% in SIIL and 95.4% in GSK group.
• The overall safety profile as well as persistence of antibodies against all vaccine
components up to the time of booster immunization was comparable between the
SIIL and GSK groups.
Immunogenicity and safety
Issues related to pentavalent vaccine

32. Immunogenicity and safety
 Fully liquid DTaP5-IPV-Hib + PCV7 compared with DTaP3-
IPV/Hib + PCV7. Vaccine Volume 29, Issue 43, 6 October 2011, Pages
7370-78
• Immunogenicity and safety of a Haemophilus influenzae B
(Hib)–hepatitis B vaccine with a modified process hepatitis
B component administered with concomitant
pneumococcal conjugate vaccine to infants.
• Mean annual incidence of H. influenzae infection was 1.62
cases per 100 000 population;(redn of 92%)
• Small increases in the incidence of serotypes a, e, and f
were observed during 1989–2008.
Issues related to pentavalent vaccine

33. CHANGES IN HIB EPIDEMIOLOGY AFTER
INTRODUCTION OF HIB VACCINE
Issues related to pentavalent vaccine

34. CHANGES IN HIB EPIDEMIOLOGY
Issues related to pentavalent vaccine
 Current Epidemiology and Trends in Invasive Haemophilus influenzae
Disease—United States, 1989–2008. Clin Infect Dis. (2011) 53 (12): 1230-1236
• For children < 5 years, a 95% reduction IN INCIDENCE from 37.18/
100,000 children in 1989 to 3.09/100,000 children

35. CHANGES IN HIB EPIDEMIOLOGY
Issues related to pentavalent vaccine
•Large increases in the incidence of
infection caused by non-b types and
nontypeable strains were observed
•The largest increase in incidence
was observed for serotype f (0.06
cases per 100 000 population in 1989
to 0.25 cases per 100 000 population
in 2008; 317% increase)

36. CHANGES IN HIB EPIDEMIOLOGY
Issues related to pentavalent vaccine
Invasive Haemophilus influenzae in British Columbia: non-Hib and non-typeable
strains causing disease in children and adults. International Journal of Infectious
Diseases Volume 15, Issue 3, March 2011, Pages e167-e173
•98 isolates in 2008-09
•66% were caused by non-typeable strains, followed by serotypes b
(12%), a (10%), f (10%), and e (1%).
•Serotypes b and f and non-typeable strains caused disease mainly in
adults over 18 years of age
•Serotype a caused disease mainly in children under the age of 2 years

37. CHANGES IN HIB EPIDEMIOLOGY
Issues related to pentavalent vaccine
Changes in serotype distribution of Haemophilus influenzae meningitis isolates
identified through laboratory-based surveillance following routine childhood
vaccination against H. influenzae type b in Brazil.
•Hib accounted for 98% of H. influenzae meningitis isolates received during 1990–1999
versus 59% during 2000–2008
•Non-b serotypes increased from 1% to 19%
•Higher proportions of non-b serotypes and NTHi than Hib were isolated from blood

38. CHANGES IN HIB EPIDEMIOLOGY
Issues related to pentavalent vaccine
4 important conclusions…
1. A shift in the distribution of capsular serotypes of invasive H. influenzae disease
has occurred, with nontypeable strains replacing type b strains as the most
common blood- stream isolates.
2. Shift in the peak age incidence: The most common disease manifestation of
invasive H. influenzae infection is bacteremia caused by nontypeable strains in
adults
3. Infections caused by encapsulated non-type b serotypes, especially serotypes a
and f, have been observed in selected geographic regions.
4. Selected studies suggest an increasing incidence of invasive H. influenzae
infection, particularly by nontypeable strains.

39. AEFI

43. Minor reactions which are not AEFI

44. Adrenaline can be repeated 3 times after every 5 min.
Hydrocortisone and Antihistaminic can be used.
Nebulised Salbutamol for respiratory difficulties.
Anaphylaxis:

45. District AEFI (Adverse Event
Following Immunization) teams in
Delhi State:

46. District Chairman Convener Member
West
Delhi Administration
Dispensary Building, A-
2, Paschim Vihar, New
Delhi-110063.
CDMO (West)
Dr.Dharamparkash.,
off: 25255021, 25287217,
(fax-25281388)
Addl.CDMO (West)
Dr. Neelam Bharti
Mob. 9968186393
HOD-Pediatrics
Guru Gobind Singh Hospital
Raghubir Nagar Delhi-110027
Ph.25988532
South-West
Delhi Administration
Dispensary Building,
Sector-2, Dwarka, New
Delhi-75.
CDMO(South West)
Dr. Jerath
(CDMO) (SWD)
Mob. 9891499941
Dr.
R.C.Milli. mob.9868279193.
Off. & fax-25089596
Addl.CDMO(South West)
Dr. Kalpana
Mob. 9810420569
HOD-Pediatrics
25494337, 25494331
Deen Dayal Upadhya Hospital
Hari Nagar Delhi-110064
North District
Delhi Administration
Dispensary Building,
Gulabi Bagh, Delhi-
110007
CDMO (North)
Dr.Archana, mob.9999360639
Office: 23646687 fax.23646687
Addl.CDMO (North)
Dr.V.S.Harneja
Mob:981052305
Office: 23646687
fax.23646687
Dr.Ritu Chopra
HOD, Pediatrics Aruna Asaf Ali
Hospital Ph.No.20211297
Mob.9718994110
North-West
Delhi Administration
Dispensary Building,
Sector-13, Rohini,
Delhi-110085
CDMO (North West)
Dr. Renu Seth
Mob. 9871317639
off.27861592,
27861464,
(fax-27861592)
Addl.CDMO (North-West)
Dr. Renu Aggarwal
Mob. 9871317639
HOD Pediatrics Dr.Tarun Kumar:
Mob.9810582484
Ph.27636780
Babu Jagjiwan Ram Hospital, E
Block, Jahangir Puri, Delhi -33

47. District Chairman Convener Member
South
Delhi Administration
Dispensary Building,
Begumpur Village,
Near Malviya Nagar,
New Delhi-110017.
CDMO (South)
Dr. Meera Hajela,
mob.9871325444, off.2663339,
26693026,
26691939,26692389, (fax-
26683339)
Nodal Officer/Addl.CDMO (South)
Dr. Poonam Pawar
Mob. 9958039393
Dr. Jyoti Sachdeva
Mob. 9968675865
HOD-Pediatrics
Malviya Nagar Hospital,
Malviya Nagar, Delhi
Central/NewDelhi
Delhi Administration
Dispensary Building,
Bagichi Allaudin, Gali
no-4, Nabi Karim,
Pahar Ganj, Delhi-
110055
CDMO (Central)
Dr. Ashok
Khurana mob.9868842299,
off.23616835,
23557817, (fax-23516693)
Addl.CDMO (Central)
Dr.K.J.S. Bansal, mob. 9868110801
Dr.(Prof.) G.R.Sethi
Ph. Ph. 23232400, 23381912
(Extn. 4440)
Mob.9868809133
grsethi56@gmail.com
Lok Nayak Jai Parkash Hospital,
JLN Marg, New Delhi – 110002
East
Delhi Administration
Dispensary Building, A-
Block, Near Jain
Mandir, Surajmal Vihar,
Delhi-110092
CDMO (East)
Dr.R.P.Midha, Mob.
9811031656
off: 22378314, (fax-22374842)
Addl.CDMO (East)
Dr.Sanjeev Sharma
Ph.22374791
Mob. 9968214936
Dr.Navin Kumar, HOD-
Pediatrics
Mob. 9953593973
Lal Bahadur Shastri Hospital
Khichripur Delhi-110091
North-East
Delhi Administration
Dispensary Building, A-
14, G-1, Dilshad
Garden, Delhi-110095.
CDMO (North East)
Dr. G.P.Sinha, Mob.
9968295551
off: 22583568,
22135083 (fax-22116203)
Addl.CDMO (North East)
Dr.Krishan Dev
Mob. 9868244710
Dr.Sunil Gomber, Professor
Pediatrics
Ph. 22581730 (Extn.501)
Mob. 9810654564
sunilgomber@hotmail.com
Guru Teg Bahadur Hospital,
Shadhara Delhi-110095