Introduction of Pentavalent Vaccine In Routine Immunization

Contents:

Operational Guidelines for Use of Pentavalent Vaccine

Issues related to Pentavalent vaccine

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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).

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.

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 influenzaeinfections in children.

• Hib bacteria live in the nose and throat area.

2.1-What is Haemophilus influenzae ?

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 Hibbacteria showing no signs or symptoms but still can infect others.

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.

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.

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.

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.

3. HIB CONTAININGPENTAVALENT 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

3.2- Presentation

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

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.

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

3.5. Age group for vaccination

• Hib containing pentavalent vaccine is indicated in children from the age of 6 weeks up to 12 months.

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.

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

3.7. Dosage and route:

• The dose of pentavalent vaccine is 0.5 ml.

• The mode of administration of pentavalentvaccine 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.

3.8. Inter-changeability of the vaccines

• Liquid pentavalent vaccines from different manufacturers can be used to complete the immunization schedule of an infant.

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.

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.

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.

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.

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 & HepBvaccines will be given as combination pentavalentvaccine 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.

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.

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Issues:

Issues related to pentavalent vaccine

• Safety

• Efficacy

• Cost effectiveness

• Feasibility

• Changes in Hib epidemiology following use of Hib

vaccines

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.

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

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

CHANGES IN HIB EPIDEMIOLOGY AFTER INTRODUCTION OF HIB VACCINE

Issues related to pentavalent vaccine

CHANGES IN HIB EPIDEMIOLOGY

Issues related to pentavalent vaccine

Current Epidemiology and Trends in Invasive Haemophilus influenzaeDisease—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

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)

CHANGES IN HIB EPIDEMIOLOGY

Issues related to pentavalent vaccine

Invasive Haemophilus influenzae in British Columbia: non-Hib and non-typeablestrains 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

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

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. influenzaeinfection, particularly by nontypeable strains.

AEFI

Minor reactions which are not AEFI

Adrenaline can be repeated 3 times after every 5 min.

Hydrocortisone and Antihistaminic can be used.

Nebulised Salbutamol for respiratory difficulties.

Anaphylaxis:

District AEFI (Adverse Event Following Immunization) teams in

Delhi State:

District Chairman Convener MemberWestDelhi Administration Dispensary Building, A-2, Paschim Vihar, New Delhi-110063.

CDMO (West)Dr.Dharamparkash.,off: 25255021, 25287217,(fax-25281388)

Addl.CDMO (West)Dr. Neelam BhartiMob. 9968186393

HOD-PediatricsGuru Gobind Singh Hospital Raghubir Nagar Delhi-110027Ph.25988532

South-WestDelhi Administration Dispensary Building, Sector-2, Dwarka, New Delhi-75.

CDMO(South West)Dr. Jerath(CDMO) (SWD)Mob. 9891499941Dr. R.C.Milli. mob.9868279193. Off. & fax-25089596

Addl.CDMO(South West)Dr. KalpanaMob. 9810420569

HOD-Pediatrics25494337, 25494331Deen Dayal Upadhya Hospital Hari Nagar Delhi-110064

North DistrictDelhi Administration Dispensary Building, Gulabi Bagh, Delhi-110007

CDMO (North)Dr.Archana, mob.9999360639Office: 23646687 fax.23646687

Addl.CDMO (North)Dr.V.S.HarnejaMob:981052305Office: 23646687fax.23646687

Dr.Ritu ChopraHOD, Pediatrics Aruna Asaf Ali Hospital Ph.No.20211297Mob.9718994110

North-WestDelhi Administration Dispensary Building, Sector-13, Rohini, Delhi-110085

CDMO (North West)Dr. Renu SethMob. 9871317639off.27861592,27861464,(fax-27861592)

Addl.CDMO (North-West)Dr. Renu AggarwalMob. 9871317639

HOD Pediatrics Dr.Tarun Kumar: Mob.9810582484Ph.27636780Babu Jagjiwan Ram Hospital, E Block, Jahangir Puri, Delhi -33

District Chairman Convener MemberSouthDelhi 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 PawarMob. 9958039393Dr. Jyoti SachdevaMob. 9968675865

HOD-PediatricsMalviya Nagar Hospital, Malviya Nagar, Delhi

Central/NewDelhiDelhi 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.SethiPh. Ph. 23232400, 23381912 (Extn. 4440)Mob.9868809133grsethi56@gmail.comLok Nayak Jai Parkash Hospital, JLN Marg, New Delhi – 110002

EastDelhi Administration Dispensary Building, A-Block, Near Jain Mandir, Surajmal Vihar, Delhi-110092

CDMO (East)Dr.R.P.Midha, Mob. 9811031656off: 22378314, (fax-22374842)

Addl.CDMO (East)Dr.Sanjeev SharmaPh.22374791Mob. 9968214936

Dr.Navin Kumar, HOD-PediatricsMob. 9953593973Lal Bahadur Shastri Hospital Khichripur Delhi-110091

North-EastDelhi Administration Dispensary Building, A-14, G-1, DilshadGarden, Delhi-110095.

CDMO (North East)Dr. G.P.Sinha, Mob. 9968295551off: 22583568,22135083 (fax-22116203)

Addl.CDMO (North East)Dr.Krishan DevMob. 9868244710

Dr.Sunil Gomber, Professor PediatricsPh. 22581730 (Extn.501)Mob. 9810654564sunilgomber@hotmail.comGuru Teg Bahadur Hospital, Shadhara Delhi-110095