Immunization for ChildrenImmunization for Childrenรศ.นพ.ภพ โกศลารักษ์

ภาควชิากมุารเวชศาสตร์

คณะแพทยศาสตร์

มหาวทิยาลยัขอนแก่น

Pediatric vaccination

• Basic knowledge

• Pitfalls in EPI vaccines

• Optional vaccines

• Questions and Answers

Host Defense Mechanism• Physicoanatomical barrier

• Phagocytosis– Circulating phagocytosis e.g. PMN

– Fixed phagocytosis e.g. macrophage

• reticuloendothelial system

• Humoral factors– Complement and properdin system

– Humoral immunity e.g. immunoglobulin

• Cell-mediated immunity

Immunization

• Passive immunization: immunoglobulin

• Active immunization: vaccination

Vaccine• Live attenuated : BCG, OPV, MMR, Var, Oty

• Killed : pertussis, JE, Rabies, HAV

• Toxoid : diphtheria, tetanus

• Subunit (recombinant) : HBV, Influenza, Acel-P

• Polysaccharide : Pnc, Meningococcal, Ty

• Conjugated polysaccharide : Hib, Pnc, Meningo

Vaccine: route

• Oral: OPV, Oral typhoid

• Intramuscular: HBV, HAV, DTP, Rabies, Hib, Influenza, Typhoid

• Subcutaneous: MMR, Varicella, JE, Ty, Hib, Influenza

• Intradermal: BCG, Rabies

Injection Site • Vaccines should not be injected on the hip area

• Infants and young children: antero-lateral of mid-thigh

• Older children: deltoid

Vaccination - aims

• Short term

: Prevention – individual, risk group• Long term

: Eradication

: Smallpox, Polio, Measles, HBV

Vaccination• Mimic natural infection• Low adverse events• Protection

: antibody, antitoxin, CMIR: short term – killed vaccine: long term – attenuated vaccine

Pitfalls in EPI vaccines

• Vaccine schedule• Adverse reaction• Vaccine information system

EPI Schedule for Thai ChildrenEPI Schedule for Thai Children

Birth 1M 2M 4M 6M 9M 18M 4-6Y

BCG

HBV1 HBV2 HBV3

DTP1 DTP2 DTP3

OPV1 OPV2 OPV3

DTP4 DTP5

OPV4 OPV5

MMR1

JE1,2, 3, (4)

MMR2

ThendT q 10 yrs

Rate of ReactogenicityRate of Reactogenicity

0102030405060708090

100

BCG Hib HBV M/MMR OPV T/DT DTP

Local Fever other systemic

Perc

ent

Arthus’ ReactionArthus’ Reaction

BCG LymphadenitisBCG Lymphadenitis

BCG Complications

BCG should not be given at buttock or hip:

- irritation from diaper- contamination with urine/stool- difficult to examine scar

Multiple BCG Does Not Confer Better Immunity

More Local Reaction from Repeated BCG

MOPH no longer give second BCG unless there is no document of BCG at birth and no scar

Urticaria Following JE Vaccine

Next dose can be given in those experienced Non-immediate reaction

But need careful observation post vaccination!

อตัราความครอบคลุมโดยเฉลี่ยของวคัซีนในงานสร้างเสริม

ภมูิคุม้กนัโรคในประเทศไทย

วคัซีน ร้อยละ

บีซีจี 99

คอตีบ-บาดทะยกั-ไอกรน (ดีทีพี) ครั้งที่ 3 98

โปลิโอ ครั้งที่ 3 98

ตบัอกัเสบบี ครั้งที่ 3 96

หดั 96

บาดทะยกัในหญิงมีครรภ ์(2 ครั้งหรือกระตุน้) 93

ไขส้มองอกัเสบครั้งที่ 2 87

จากการสาํรวจดว้ยวธิี cluster survey โดยกรมควบคุมโรค พ.ศ.2546

Impact of Vaccination

Impact of Vaccination

Tetanus Cases Reported in ThailandTetanus Cases Reported in Thailand

0

5

10

15

20

25

Case/100,000

Death%

Pertussis Cases Reported in ThailandPertussis Cases Reported in Thailand

0

2

4

6

8

10

12

Case/100,000

Death%

Measles Cases Reported in ThailandMeasles Cases Reported in Thailand

0

20

40

60

80

100

Case/100,000

Death%

EncephalitisEncephalitis

0

5

10

15

20

25

30

Case/100,000

Death%

2010 Optional Immunization Schedule for Thai Children

2M 4M 6M 9M 12M 18M 4-6Y 11-12Y

VZV1

Hib1 Hib2 Hib3

HAV1,2*

DTaP1 DTaP2 DTaP4DTaP3 DTaP5/Tdap

IPV1 IPV2 IPV3 (IPV4) Tdap then dT

q10y

HPV1,2,3

Rota1 Rota2 (Rota3)

PCV7-1

PCV7-2

(PCV7-3)

Yearly Influenza Vaccine

PCV7-4Live JE 1,2

VZV2

IPV5(Hib4)

* Optional schedule for healthy infants: 2+1 (2, 4, 12-15 m)

* PIDST Recommendation 2010

Optional vaccines

• Increase immunogenicity in infant: conjugated vaccine: H. influenzae B, PCV, Meningococcus

• Less adverse event: IPV, acellular pertussis, rotavirus

• New vaccines: HPV, rotavirus: Varicella, HAV

Pichichero M. Consultant for Pediatricians 2005;June:263-7.

PolysaccharideConjugate Property

NoYesLack of hyporesponsiveness

NoYesBooster effect

NoYesPersistence of protection

NoYesHerd immunity

NoYesReduction of nasopharyngeal carriage of bacteria

NoYesImmune memory

NoYesT-cell-dependent immune response(response by children < 2 yo)

Comparison of Polysaccharide and Conjugate Vaccines

Rosenberg N.M. NEJM 2001;345(14):1042-53.

Principle of Polysaccharide-Protein Conjugate VaccinePrinciple of Polysaccharide-Protein Conjugate Vaccine

WHO. 2004 Global Immunization Data. Available at: http://www.who.int/immunization_monitoring/data/GlobalImmunizationData.pdf. Accessed July 11, 2008.

Pneumococcal disease

Measles Rotavirus Hib Pertussis Tetanus Other* Meningococcus

*Polio, diphtheria, yellow fever

Estim

ated

num

ber o

f dea

ths

(WH

O 2

002)

Global PerspectiveVaccine-Preventable Deaths (WHO)

Global PerspectiveVaccine-Preventable Deaths (WHO)

0

500,000

1,000,000

1,500,000

2,000,000

All agesChildren < 5 years

Streptococcus pneumoniae is the leading cause of vaccine-preventable deaths globally

IPD( Invasive Pneumococcal Disease )

Atkinson W, et al, eds. Epidemiology and Prevention of Vaccine-Preventable Diseases. CDC Pink Book. 11th ed. Washington DC: Public Health Foundation; 2009:217-230. 30

Seve

rity

of D

isea

seMeningitis

Bacteremia

Acute otitis media

Bacteremic pneumonia

Pneumonia

IPD

Coverage of Invasive Pneumococcal Isolates by PCV in Thai Children 2000-2005

Collaborative study: Siriraj, NIH, Chula, Bhumipol, QSNICH

0

20

40

60

80

100

7 - valent 9 - valent 11 - valent 13 - valent

<1 yo

<2 yo

<5 yo

Cover by:

%

N=11571 69

74 7476 76 7476 7785 86 88

Wanatpreeya Phongsamart, et al. Vaccine 2007; 25:1275-80

Paper PCV7 PCV10 PCV13 Years N** Method

Phongsamart W, et al. Vaccine 2007;25:1275-1280 1

73.9% 77.4% 87.8%2000-2005

(4 institutes in BKK+NIH)

115 Sterile sites

Baggett HC, et al. CID 2009;48:S65-742 79% 84% 95%

May05-June07(Sa Kaeo, Nakorn

phanom)19 Blood

Cultures

Srifeungfung S, et al. Vaccine 2010; 28:3440-34443

70.3% 70.3% 81.2%

Jan 06-Feb 09(4 tertiary care public hosp, 6 private and 4 public hosp)

106(64+42)

Sterile site and Non

Sterile site

Rhodes J, et al. 7th

ISPPD.*4 73% 75% 88% 1998-2008(>50 Hosp.) 223 Normally

sterile sites

Dejsirilert S, et al. 7th

ISPPD.*5 74% 80% 92%

1998-2008 (33 Hosp. in

1998-2004, 60 Hosp. in 2005-

2008)

113 Sterile sites

* Poster presentation 7th ISPPD, Mar 10, Tel aviv, Israel, ** Isolates from children < 5 years old

Serotype Coverage by 7-, 10-, 13-valent PCV of Normal Sterile Sites in Thai Children < 5 Years Old

Summary of PCV CoveragePCV7: 62‐79%  PCV10: 70‐84%PCV13: 81‐95%

, 70%, 80%, 90%

Recommended Schedule for PCV7Age (m) Primary series Booster Total

doses2-6 * 3 doses, 2 m apart 12-15 m 47-11 2 doses, 2 m apart 12 m 312-23 2 doses, > 2 m apart - 224-59• Healthy children

• High risk children<3 prior doses

>3 prior doses

1 dose

1 dose, > 2 m from recent dose

1 dose, > 2 m from recent dose

-

1 dose, 2 m later

-

1

2

1

AAP. Pediatrics 2000;106:362-6.* PIDST Recommendation 2010

* Optional schedule for healthy infants: 2+1 (2, 4, 12-15 m)

1997

1998

1999

2000

2001

2002

2003

2004

2005

0

50

100

150

200

250<112-4

Year

IPD

rat

e / 1

00 0

00

http://www.cdc.gov/ncidod/dbmd/abcs/survreports.htm

PCV7

Impact on Invasive Pneumococcal Diseases

Centers for Disease Control and Prevention. MMWR 2005;54:893-7.

Routine use of PCV in 2000

Pneumococcal Disease Burden in ThailandA prospective study of meningitis in Lampang and Phisanulok:

Population < 5 yo = 105,269N Rate/105<5yo

Potential meningitis (LP) 598 568Probable meningitis 28 26Laboratory confirmed 7 6.7

Hib 4 3.8 (1.0-9.7)

N.meningitidis 2 <3S.pneumoniae 1 (+1 pos H/C) <3

ATB detected in CSF 20/455 (4.4%)

Rerks-Ngarm S. Vaccine 2004;22:975-83.

Bacterial Meningitis in Thai Children Etiology and Mortality (N=618)

Bacterial Meningitis in Thai Children Etiology and Mortality (N=618)

Chotpitayasunondh C. Southeast Asian J Trop Med Public Health 1994;25:107-115.

%

Hib S.pneumo N.mening Salmonella Others0

5

10

15

20

25

30

35

40Proportion Mortality

Rotavirus

Pathogenesis Rotaviruses adhere to the GI tract epithelia

(jejunal mucosa)

Atrophy of the villi of the gut

* *

Loss of absorptive area

Flux of water and electrolytes

NSP4 viral enterotoxin

Enteric nervous system activation

VOMITING AND

diarrhoea

*Rotavirus infection in an animal model of infection. Photographs are from an experimentally infected calf. Reproduced with permission from Zuckerman et al, eds. Principles and Practice of Clinical Virology. 2nd ed. London: John Wiley & Sons; 1990:182.

Micrographs courtesy of Dr. Graham Hall, Berkshire, UK.

Epidemiology- Global Perspective

Bacteria

Unknown Rotavirus

Calicivirus

Rotavirus

Escherichia coli

Parasites

Otherbacteria

Developed Countries

Adenovirus

CalicivirusAstrovirusAdenovirus

Astrovirus

Unknown

Less Developed Countries

From Kapikian AZ, Chanock RM. Rotaviruses. In: Fields Virology 3rd ed 1996; 1659. Philadelphia, PA: Lippincott-Raven.

Distribution of pathogens reported to cause endemic/epidemic gastroenteritis & infantile vomiting & diarrhea

Estimated global burden of rotavirus disease

24 million outpatient visits

114 million domiciliary episodes

1 : 205

1 : 50

EventRisk of Particular Event

611,000 deaths

2.4 million inpatient visits

1 : 5

1 : 1

Rotavirus- Burden of Disease

Glass R, et al. Lancet 2006; 368: 323–332.

Rotavirus Disease Burden in ThailandRotavirus Disease Burden in Thailand

56,000 rotavirus diarrhea inpatient visit

131,000 rotavirus diarrhea health care visit

586,000 Rotavirus diarrhea episode

4.8 million diarrhea episodes(in children < 5 yo)

1 : 85

1 : 36

1 : 8

1 : 1

Risk Events

Jiraphongsa C et al. JID 2005: 192 (suppl 1)May be underestimated!

2001-3, of the 1095 stools from hospitalized

diarrhea, rotavirus positive in 838 (43%)

0

5

10

15

20

0 10 20 30 40 50 60 70

RotaShield™ RIX4414/placebo

Occurrence of Definite IS Cases Compared with RotaShield-associated Cases

V = VaccineP = Placebo

VP P

P PV V

VVP

VP P

Dose one

Dose two

V PVP P

P P P

IS cases

IS cases

75 83

107 145

VP

P P

1. Murphy TV, et al. N Engl J Med 2001;344(8):56472. 2. Vesikari T, et al. 23rd Annual Meeting of the European Society for PaediatricInfectious DiseasesESPID, Valencia, Spain, 1820 May 2005.

0

5

10

15

20

0 10 20 30 40 50 60 70

Recommendation for Use of Rotavirus Vaccines

Pentavelent (HBRV) Monovalent (HRV)

Route Oral OralAge of 1st dose 6-12 week > 6 weekGeneral schedule 2, 4, 6 mo 2, 4 moInterval of dose 4-10 week >4 weeksAge of last dose 32 week 24 weeksConcurrent OPV not mention 14 d apart for 1st doseOther concurrent vac OK OKBreast feeding OK OKContraindication Immunocommpromised, age out-of-range

allergic to vaccine/component, Ac illness

Rotavirus vaccine

• high protection against severe RVGE

– 85%–100% efficacy against all rotavirus GE-

related hospitalizations

Efficacy

Children’s Vaccine Initiative’s “Ideal Vaccine”

Children’s Vaccine Initiative’s “Ideal Vaccine”

• Oral• 1 - 2 doses• Early in life• Well tolerated

• Efficacious 100%• Safe• Can be administered:

- According to local schedule- With other vaccines

• Heat Stable• Affordable

The current vaccines: 2-3 doses Expensive Efficacy 70-90% Heat sensitive Interfered by OPV

World Health Forum 1992; 13 (1):93

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