DR S G KASIConsultant pediatrician, Bengaluru

Member IAPCOI, 2011-12

VaccinationMotor-vehicle safetySafer workplacesControl of infectious diseasesDecline in deaths from coronary heart disease and

strokeSafer and healthier foodsHealthier mothers and babiesFamily planningFluoridation of drinking waterRecognition of tobacco use as health hazard

Ten Great Public Health Achievements-United States 1900-1999

20th CenturyAnnual Morbidity

2000(Provisional)

PercentDecrease

Comparison of 20th Century Annual Morbidity and Current Morbidity, Vaccine-Preventable Diseases

Diphtheria

Measles

Mumps

Pertussis

Polio (paralytic)

Rubella

Congenital Rubella

Syndrome

Tetanus

H. influenzae, type b and unknown (<5 yrs)

175,8

85

503,2

82

152,2

09

147,2

71

16,31

6

47,74

5

823

1,314

20,000

4

81

323

6,755

0

152

7

26

167

99.9

99.9

99.8

95.4

100

99.7

99.1

98.0

99.1

Source: CDC

VaccineNo of child vaccinated,

1985(%)

No of child vaccinated,

2010(%)

Percent increas

eMeasles 1 74 98.7%Polio 14 70 85.2%BCG 8 87 91.6%Hib No inf.Hepatitis B 0 37 100%Diphtheria 18 72 80%

Immunization coverage among 1-year-olds (%) in India

Ref: WHO. Available at URL: http://apps.who.int/ghodata/?vid=80100.

True:

Vaccines are Not Without Risk No vaccine is 100% safe No vaccine is 100% effectiveAll vaccines have possible side effects, most mild,

rarely severe

The risk of disease far outweighs the risk of vaccine

“The Cow Pock – or – the Wonderful Effects of the New Inoculation!”J. Gillray, 1802

Vaccine Concerns: As Old As Vaccines Themselves

Temporal Associations Between Vaccinations and Serious Illnesses Cause Public Concern

ArthritisAsthmaADDAutismBrain DamageCancerChronic Fatigue

SyndromeDiabetes

Gulf War Syndrome

Infantile SpasmsInflammatory

Bowel DiseaseMultiple SclerosisNeuroimmune

DysfunctionSudden Infant

Death Syndrome

Vaccines are generally given to healthy

people to prevent disease

Higher standard of safety is generally

expected of vaccines than of other medical

interventions

Public are intolerant to even minor of

adverse reactions related to products given to

healthy people, especially healthy babies.

An erroneous association or attributable risk can

undermine confidence in a vaccine and have

disastrous consequences for vaccine acceptance

and disease incidence.

The Vaccine safety balance

VACCINES HAVE TO BE SAFE

Prelicensure Vaccine Safety StudiesVaccine research and development is a carefully

controlled and very lengthy processVaccines are rigorously tested to ensure quality,

safety and efficacy at ALL stages of developmentPreclinical animal studies: immunogenicity and

SAFETYPhase I: assess SAFETY and obtain limited

immunogenicity and dosing data, adults, n= 10-50Phase II: assess COMMON REACTIONS and

obtain immunogenicity data in infants, n= 100-200Phase III: assess protective efficacy, identify

laboratory correlates of protection, ASSESS RARER REACTIONS, n depends on disease.

Phase IV surveillance: post licensure

Studies of new vaccines do not stop at point of licensure-The number of subjects in Phase I-III is too

small to detect rare eventsEven once a vaccine is in use, ongoing studies

are needed to detect RARER ADVERSE EVENTS

Vaccine Adverse Event Reporting System (VAERS)

Passive National reporting systemJointly administered by CDC and FDAReceives ~15,000 reports per yearDetects

new or rare eventsincreases in rates of known side effectspatient risk factors

Additional studies required to confirm VAERS signals

Does not assess causality

Large Linked DatabasesVSD: VSD is a network of 9 managed care

organizations across the United States. The combined population of these organizations is more than 9.8 million people.

Look back in medical records to see if a particular adverse event is more common among people who have received a particular vaccine

Rapid Cycle Analysis (RCA) to continuously look at information coming into VSD to see if the rate of certain health conditions is higher among vaccinated people

Clinical Immunization Safety Assessment NetworkCDC’s Clinical Immunization Safety Assessment

(CISA) Project was established in 2001 to address the unmet vaccine safety clinical research needs of the United States.

CISA is a national network of vaccine safety experts from the CDC’s Immunization Safety Office (ISO), seven medical research centers, and other partners, which provides a comprehensive vaccine safety public health service to the nation.

 CISA addresses vaccine safety issues, conducts high quality clinical research, and assesses complex clinical adverse events following vaccination.

Definition : AEFIAny untoward medical occurrence which

follows immunization and which does not necessarily have a causal relationship with the usage of the vaccine.

The adverse event may be any unfavourable or unintended sign, abnormal laboratory finding, symptom or disease

Causality assessment of adverse event following immunization (AEFI): user manual for the revised WHO classification.2013

What are Serious AEFIs? Any AEFI that has caused or has the potential to cause • Death, Hospitalization, Disability, Cluster (>2 or more cases) or where the Vaccine quality is suspicious

The private practitioners (including pediatricians) should use the ‘First Information Report’ (FIR) form for reporting serious AEFI cases to the district officials.

The pediatricians should help the investigation team in collection of all the related information.

Once an AEFI is reported from private sector, the DIO and district AEFI committee members would then investigate the reported AEFI case (PIR)

After all investigations are done and a conclusion arrived , the DIR is made.

Appendix 1 FIR : Page ½

Section A FIRST INFORMATION REPORT (FIR) (To be completed by the person reporting the AEFI and sent to MO - Immediately)

(Only for Serious Adverse Events Following Immunization) Serious AEFI category (Encircle): Death / Hospitalized / Cluster* / Disability

State District

Block/ Ward Village/ Urban Area

Address of the site:

Reported by (Name) : Today’s Date:

Designation:

Contact phone number (with STD Code) :

Patient Name

Age / Date of Birth Sex Male Female

Father / Husbands Name

Complete Address of the Case with landmarks (Street name, house number, village, block, Tehsil, PIN No., Telephone No. etc.)

P I N - P H O N E -

Date of Vaccination D D M M Y Y Y Y Time of Vaccination H H M M ( AM PM )

Name of recent Vaccine(s) given:

Date of first symptom D D M M Y Y Y Y Time of first symptom H H M M ( AM PM )

Current status (encircle) Death / Still Hospitalized / Recovered & Discharged / Left Against Medical Advice (LAMA)

Date of Death D D M M Y Y Y Y Time of Death H H M M ( AM PM )

Additional Information:

* use separate form for each case in a cluster Details of Hospitalization:

Hospitalization No/ Yes Date D D M M Y Y Y Y Time of Hospitalization

H H M M ( AM PM )

Name and Address of hospital:

Outcome (encircle) Death / Still Hospitalized / Recovered & Discharged / Left Against Medical Advice (LAMA)

If died, Date of Death D D M M Y Y Y Y Time of Death H H M M ( AM PM )

Post mortem done? (encircle) Yes**/ No / Planned on (date) ________

If Yes, Date__________ Time__________

Details of vaccine, diluents & Vitamin-A given to the patient (*In the doses administered column write the dose received by beneficiary like 1st, 2nd, 3rd, booster and any other)

Vaccine/Vit-A/ Diluent *Dose

Administered Name of Manufacturer

(in BLOCK Letters) Batch No.

Manufacturing Date

Expiry Date

BCG

BCG Diluent

DPT

OPV

Measles

Vaccine AEFI CausalityCausality is the relationship between two

events (the cause and the effect), where the second event is a consequence of the first

Causality assessment is the systematic review of data about an AEFI case; it aims to determine the likelihood of a causal association between the event and the vaccine(s) received.

Temporal vs. Causal Associations:Is Sequence Consequence?

A Exposure(Vaccine, Drug,Diet, OccupationOthers)?

B Disease

Time

•Direct and only cause?•One of multiple potential causes?•Co-factor/indirect cause, trigger?•Coincidental?

NATIONAL AEFI GUIDELINES IN INDIA

Some Case Studies…..RotaShield and IntussusceptionMMR and AutismThiomersal in vaccines and adverse

neurodevelopmental outcomeMultiple vaccines and overload of immune

systemDTwP and encephalopathyPentavalent vaccine in India

Case Study – 1 Rotavirus Vaccine and

Intussusception

First rotavirus vaccine (Rotashield) licensed by FDA in August 1998 for prevention of rotavirus gastroenteritis in infantsPre-licensure data for Intussusception (IS)

5 cases in 10,054 vaccines 1 cases in 4633 placebo recipients Difference in rates not statistically significant Lack of apparent association between IS and wild-

type rotavirus infectionPhase 4 study commitment at licensurePackage insert: IS included as potential AEIS prospectively added as term in VAERS

database

29

Case Study 1 (cont.)• VAERS reports Sept 98 – Feb 99: 10 IS cases,

temporal clustering after 1st dose and within 7 days after vaccination provided signal

• July 1999*– 15 IS cases reported to VAERS, 12 within 7 days

after vaccination• ~1.5 million doses administered 8/98-6/1/99• 14-16 cases would be expected in week after

vaccination by chance alone – Population-based studies suggested higher IS

rates after vaccination (not statistically significant) – CDC and AAP recommended temporary suspension

of use

*MMWR July 16, 1999; 48:577-58130

Case Study 1 (cont.)October 1999

Population-based studies: elevated risk of IS after vaccination*

ACIP withdrew its recommendation for vaccination

Wyeth voluntarily withdrew vaccineWhat was attributable risk?

Consensus estimate ~1/10,000**Did vaccine “trigger IS but result in no net

increase?*** *MMWR September 3, 2004;53:786-789 **Pediatrics 2002;110:e67-73 ***Lancet 2004;363:1547-50

31

How did this impact next rotavirus vaccine?To evaluate an IS risk of 1/10000, study size

had to be atleast 40000Both Rotateq and Rotarix had study sizes of

60000-70000Pre-licensure studies: no increased risk of IS.Post-licensure surveillance: VAERS,

manufacturer’s phase 4 study (44,000 infants) and CDC’s VSD study (90,000 infants)

Very slight increase in risk of IS in some post licensure studies, however significant cost benefit ratio in favor.

Combined annual excess of 96 cases of IS in Mexico (1 per 51,000 infants) & Brazil (1 per 68,000 infants) and 5 deaths due to intussusception was attributable to RV1.

However, RV1 prevented approximately 80,000 hospitalizations and 1300 deaths from diarrhea each year in these two countries. 1

1. N Engl J Med 2011; 364:2283-2292

Case Study – 2MMR vaccine & Autism

The origin of the controversy !

Wakefield’s theory was supported by studies that identified measles virus nucleic acid sequences in the blood cells and intestinal tissue of some children who had experienced severe behavioral regression

A similar investigation with a larger sample failed to reveal persistence of measles virus nucleic acids in the peripheral blood of children with autism-spectrum disorder

Results of several large population and ecologic-based studies have failed to provide any support for Wakefield’s theory

Retrospective cohort study of all children born in Denmark

between 1991 and 1998

537,303 children, 82% vaccinated with MMR vaccine

Same incidence of autism

No clustering of cases related to vaccine

The “Denmark” Study

Madsen KM, et al. N Engl J Med 2002;347:1477- 1482

The Science …………..After a review of multiple ( 18) well conducted

studiesThe Institute of Medicine (IOM) in a report on

vaccine safety has stated that “the committee concludes that the evidence favors rejection of a causal relationship between MMR vaccine and autism”

Feb, 2009, the U.S. Court of Federal Claims dismissed ~4,900 cases involved the National Vaccine Injury Compensation Program

Thiomersal and Vaccines:Thimerosal has been used as a preservative in

vaccines since the 1930sSome concern regarding mercury exposure and

adverse neurodevelopmental outcomeIn 1999, the US FDA estimated that infants who

were immunized according to the recommended schedule might have received amounts of ethylmercury that exceed EPA limits for exposure to methylmercury.

The US PHA and AAP urged vaccine manufacturers to remove thimerosal from all infant vaccines as soon as practical

Almost all childhood vaccines in USA, Europe and Australia are thimerosal free.

California Estimated Prevalence of Autism and Estimated Mercury Exposure in Vaccines

From Stehr-Green P et al. Am J Prev Med 2003; 25:101-106

All Mercury is Not the SameMercury in any form has not been linked to

autism

Major toxicity – methyl Hg

Ethyl mercury – shorter ½ lifeLess associated with neurotoxicity

Children who were enrolled in an efficacy trial of pertussis vaccines in 1992–1993 were contacted in 2003.

N= 1043, 2 groups, Gp1: TM= 62.5mcg, Gp2: TM= 137.5mcg

Results: Among the 24 neuropsychological outcomes that were evaluated, only 2 were significantly associated with thimerosal exposure.

Conclusion: The few associations found between thimerosal exposure and neuropsychological development might be attributable to chance. The associations found were based on small differences in mean test scores, and their clinical relevance remains to be determined.

Alberto Eugenio Tozzi, MD at al. Pediatrics 2009;123:475–482

A case-control study was conducted in 3 managed care organizations (MCOs) of 256 children with ASD and 752 controls matched by birth year, gender, and MCO.

Adjusted OR Prenatal: 1.12 (0.83–1.51)Birth-1 month: 0.88 (0.62–1.26) Birth- 7 months: 0.60 (0.36–0.99) Birth- 20 months: 0.60 (0.32– 0.97) Conclusion: Prenatal and early-life exposure

to ethylmercury from thimerosal-containing vaccines and immunoglobulin preparations was not related to increased risk of ASDs.

Cristofer S. Price, ScM et al. Pediatrics 2010;126:656–664

1047 children enrolled,7 - 10 years age and administered standardized tests assessing 42 neuropsychological outcomes.( ASD excluded)

Association between current neuropsychological performance and exposure to mercury during the prenatal period, the neonatal period , and the first 7 months of life.

Among the 42 neuropsychological outcomes, we detected only a few significant associations with exposure to mercury from thimerosal. The detected associations were small and almost equally divided between positive and negative effects.

Conclusion……Our study does not support a causal

association between early exposure to mercury from thimerosal-containing vaccines and immune globulins and deficits in neuropsychological functioning at the age of 7 to 10 years.

William W. Thompson et al. n engl j med 357;13 september 27, 2007

Institute of MedicineImmunization Safety Review Vaccines and Autism†

The Committee concludes that the evidence favors rejection of a causal relationship between 1) thimerosal-containing vaccines and autism and 2) MMR vaccine and autism

In the absence of experimental or human evidence that vaccination (either the MMR vaccine or the preservative thimerosal) affects metabolic, developmental, immune, or other physiological or molecular mechanisms that are causally related to the development of autism, the Committee concludes that the hypotheses generated to date are theoretical only

†† Immunization Safety Review Committee, Institute of Medicine, National Academies Press, 2004

Thiomersal and Vaccines: WHO-GAVACSUpon review of the current epidemiologic

evidence and phamacokinetic profile of thiomersal, the Global Advisory Committee on Vaccine Safety concluded that there is currently no evidence of mercury toxicity in infants, children, or adults exposed to thiomersal in vaccines.

DTwP: Reactogenicity- SeriousProlonged inconsolable crying lasting for

more than three hours--- 0.3% Hyporesponsive-hypotonic reactions---

1/1750 immunizationsBrief tonic clonic seizures in association with

high fever--- 1/1750 immunizationsVery high fever > 40.5degC(104 deg F)---

0.3%Cody CL, Baraff LJ, Cherry JD, et al. Nature and rates of adverse reactions

associated with DTP and DT immunizations in infants and children. Pediatrics 1981; 68:650-60.

DTwP: Reactogenicity- RareRisk of severe neurologic illness and

permanent brain damage.Infantile SpasmsReye’s syndromeSIDSChronic neurological damage

The WC-Pertussis vaccine controversyThe controversy was first ignited by a study

published in 1974 suggesting neurological complications associated with the WC-pertussis vaccine

Reports of post-vaccine febrile seizures added fuel to the fire

WC-pertussis vaccine coverage plummeted in many developed countries

These countries quickly experienced widespread pertussis epidemics

M. KULENKAMPFF,*et al. Archives of Disease in Childhood, 1974, 49, 46. Brown NJ et al. Curr. Opin. Neurol. 20, 181–187 (2007). Romanus V, Pediatr. Infect. Dis. J. 6, 364–371 (1984).

NCES Study: Original report.The National Childhood Encephalopathy Study,

conducted in Great Britain from 1976 to 1979All children between 2-35 months admitted

with an acute neurological illness were studied for association with DPT vaccine

Outcome was assessed at 15 days and 12-18 months

1182 patients, 2 million DPT dosesIt was estimated that acute encephalopathy

with permanent brain damage occurred at the widely quoted rate of 1 per 310,000 doses

Miller DL, Ross EM, Alderslade R et al: Pertussis immunization and serious acute neurological illness in children. Br Med J 1981; 282: 1595-1599.

NCES Study: Follow up reportThree of the seven children originally reported

as impaired after vaccination had in fact been healthy.

Viral encephalitis confirmed by means of culture or autopsy in two

Reye's syndrome in oneviral encephalitis diagnosed on the basis of

abnormalities of the CSF but not confirmed in the laboratory in one.

Amended form: the results of the NCES showed no increase in the risk of death or permanent neurologic damage in previously healthy recipients of DPT vaccine.

DPT and neurol illnesses:Why the association??Coincidental manifestation of a previously

hidden condition, such as brain malformation;Triggering of an event that was destined to

occur, such as infantile spasmsCoincidental acute processes, such as viral

encephalitis or Reye's syndromeProvocation of febrile convulsions in a child

with a genetically determined low threshold for convulsions

Provocation of febrile convulsions in a child with underlying disease or epilepsy

A close temporal association must not be accepted as indicative of a

cause-and-effect relation, despite the powerful urge to do so.

The number of vaccinations over the last century has steadily increased…

Offit et al. Pediatrics. 2002.

But the total number of proteins and polysaccharides in the vaccines has diminished dramatically

Year Vaccines Antigens

1900 1 200

1960 5 3217

1980 7 3041

2000 11 123-126

2010 12 133-135

Each infant would have the theoretical capacity to respond to about 10 000 vaccines at any one time

If 11 vaccines were given to infants at one time, then about 0.1% of the immune system would be “used up.”

Because naive B- and T-cells are constantly replenished, a vaccine never really “uses up” a fraction of the immune system.

Children respond to multiple vaccines given at the same time in a manner similar to individual vaccines

Vaccines do not increase the risk of other infections

Available data suggest that multiple vaccines DO NOT

overwhelm the immune system

How many antigens is the infant exposed to naturally? At birth colonisation with genital tract flora

occurs (about 18 species) At birth colonisation with faecal flora occurs

(about 400 species) Breast milk contains around 8 species of

microbe. Each species have around 3-6x1000 different

proteins Therefore infants are exposed to >1000000

different proteins naturally

The Pentavalent Vaccine in IndiaIn 2008, the National Technical Advisory Group on

Immunization (NTAGI) in India met to discuss the introduction of Hib vaccine in the Universal Immunization Program (UIP).

Hib diseases burden is sufficiently high in India to warrant prevention by vaccination.

Hib vaccines have been demonstrated to be safe, both globally and in India

Hib vaccines have been shown to be extremely efficacious in all settings where they have been used

Hib vaccine fits into the UIP immunization scheduleNTAGI recommended the inclusion of Hib vaccine in

the UIP.

Hib burden in India:0.5-2.6% of all hospital admissions were

attributable to bacterial meningitis, including Hib25% (range: 14-35%) of bacterial meningitis was

attributable to Hib in IndiaCFR: Hib meningitis- 20-29%, invasive Hib

disease- 16%23-40% have neurological sequealae13-19% of pneumonia are due to HibWHO estimated the burden of Hib disease in

India in the year 2000 to be about 2.4 million cases and 72,000 deaths in children <5 years of age, accounting for approximately 4% of all child deaths in India

Incidence of Hib meningitis in India (Minz, IJMR, 2008)

Prospective surveillance in <5yo from 1997-99 in 5 admin areas of Vellore, Tamil Nadu

Incidence of Hib meningitis:7.1/100,000 in <5yo32/100,000 in 0-11 mos19/100,000 in 0-23 mos

Provides 1st minimal estimates of Hib incidence in IndiaSimilar to incidence in Europe pre vaccine useDocumented areas where they might have missed cases,

i.e. meningitis deaths that never reached hospital, very low lumbar puncture rates in one of the study hospitals, additional cases picked up by commercial latex test that could not be done on all the specimens.

Regional Hib Disease BurdenSri Lanka: Prospective surveillance found Hib

meningitis incidence of 20.1 cases/100,000 in children <5 yrs in 2004 (95% CI 14.5 – 27)1

Mongolia: Prospective active surveillance from 2002-04 in children 2 mo.-5 yrs.2

Hib meningitis incidence 28/100,000 Adjusted incidence was 40/100,000 (adjusting for cases

without complete CSF information and culture negative, probable bacterial cases)

Pakistan: <1yr: 38.1/100,000, <5yr: 7.6/100,000

1 Batuwanthudawe, unpublished data; 2 Watt, unpublished data3 Zaidi AKM. Eastern Mediterranean Health Journal (in press).

Naturally acquired anti-Hib antibodies in Indian infants. Ind Ped Vol 34, 1997,Pg 9-15

5% 7%

21%

-30%

-20%

-10%

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20%

30%

40%

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Clinical Pneumonia

Severe Pneumonia

CXR+ Pneumonia

Proportion of pneumonia prevented by Hib vaccine

Post Introduction Experience showing Hib Vaccine Efficacy* in Developing Countries(95% CI)

Gambiaall Hib diseaseVE: 95% (67-100%)**^ (Adegbola, 2005)

MalawiHib meningitisVE: 92% (72-98%)(Daza, 2006)

UgandaHib meningitisVE: 93% (CI 69-99%)(Lewis, 2008)

Kenyaall Hib diseaseVE: 88% (73-96%)(Cowgill, 2006) *VE= Vaccine Efficacy or Vaccine Effectiveness

**At least 3 doses Gambia, other studies at least two doses<36 months Gambia, other studies <5 years

PakistanHib Vaccine Assessment(Zaidi, in progress)

BangladeshHib Vaccine Assessment

Preventable fraction due to Hib Vaccine in Bangladesh

Community controls

(%)

Hospital controls(%)

PNEUMONIAWHO Radiologist

17 ( -10 to 38)34 ( 6 – 53)

35 (13 – 52)44 ( 20 – 65)

MENINGITIS 89 ( 28 – 100) 93 ( 53 – 100)

Baqui et al. Pediatric Infectious Disease Journal: July 2007 - Volume 26 - Issue 7 - pp 565-571

How cost effective is Hib vaccine in India??With a price of US $2.00 per dose of pentavalent

vaccine, the cost per DALY averted will be US $26In 2007, the GDP per capita in India was US $785.Hence, the costs per DALY averted from Hib

vaccine is estimated to be considerably less than the GDP per capita and according to WHO benchmarks, the vaccine is therefore considered “highly cost-effective”.

INDIAN PEDIATRICS VOL 46, 2009, 945-954

GOI’s Pentavalent Introduction Plan2011: LPV introduced in

Tamil Nadu and Kerala2013: LPV introduced in

Karnataka, Haryana, Puducherry, Goa, and Gujarat and Jammu and Kashmir.

Next in AP, Assam, Bihar, Chhattisgarh, Jharkhand, MP , Punjab, Rajasthan, WB and Uttarakhand.

Followed by national roll out

National roll out to follow

States where pentavalent vaccine with Hib will be introduced

Pentavalent vaccine in SrilankaIntroduced in 2008, Crucell vaccineWithin 3 months, 4 reports of deaths and 24

reports of suspected hypotonic hyporesponsive episodes (HHE), initial lot suspended

Next lot: 1 death, vaccine suspended, DTwP+HBV resumed

The reporting rate of HHE following the pentavalent vaccine (14.9 cases per 100 000 doses) was found to be well within the reported estimates of HHE following wP containing vaccines (21–250)cases per 100 000 doses).”

After a comprehensive investigation and review, reintroduced in 2010, up to 2012, another 14 deaths reported. 6 of 19 infant deaths were found at autopsy to have severe congenital heart disease.

Infants with CHD receive vaccine under close medical supervision

No further vaccine related deaths reported

Pentavalent vaccine in BhutanIntroduced in Sept 2009Identification of 5 cases with encephalopathy

and/or meningo‐encephalitis shortly after pentavalent vaccination prompted the authorities to suspend vaccination on 23 October 2009.

Following a similar investigative process, the vaccine was reintroduced in 2011

Pentavalent vaccine in VietnamIntroduced in June 2010Upto May 2013, a total of 43 serious AEFI cases

were investigated, including 27 fatalities. Vaccination suspended

The overall reporting rate of deaths after vaccination is approximately 1.8 per million doses.

After reviewing clinical, epidemiological and vaccine quality issues vaccination was resumed in October 2013

Pentavalent vaccine in India:54 deaths so far (as of Jan 2014)

STATE No of serious AEFI

No of deaths reported

Kerala 102 16

Tamil Nadu 23 8

Delhi 7 3

Goa 14 2

Gujarat 3 1

Harayana 7 2

J&K 19 12

Karnataka 12 6

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http://www.sunday-guardian.com/news/pentavalent-caused-54-children-deaths

Pentavalent vaccine: Some commentsVaccine introduction was accompanied with

very thorough training of health care staff about the benefits and risks of the vaccine.

In Sri Lanka and Bhutan, discontinuation and resumption of pentavalent vaccine use did not significantly modify the pattern of serious AEFI reports.

Incomplete clinical information significantly complicated the causality assessment.

Additional clinical information allowed another cause of death to be identified

Vaccines and SIDS;There was insufficient clinical information to allow

the cause of death to be ascertained, including the possibility of sudden infant death syndrome (SIDS).

The diagnosis of SIDS requires clinical information and a thorough post‐mortem examination (as described in the Brighton Collaboration case definition) that is not available in many instances.

As peak incidence of SIDS occurs in early infancy, a close temporal relationship between SIDS and receipt of pentavalent vaccine is expected by simple chance.

Legitimate increased attention to AEFI can pose new challenges to national decision‐makers.

‘‘Falsehood flies and the truth comes limping along after; so that when men come to be undeceived it is too late: the jest is over and the tale has had its effect.’’ Jonathan Swift

Rate Ratio of Autism and Autism Spectrum Disorders (ASD) by Exposure to Thimerosal in Vaccines†

Thimerosal in vaccines

Person-Years No Autism Other ASD

None 1,660,159 303 1.00 1.00

1 dose (25µg Hg)

169,920 181.01

(0.6-1.71)0.95

(0.66-1.37)

2 doses (75µg Hg)

447,973 330.70

(0.46-1.09)1.20

(0.92-1.56)

3 doses (125µg Hg)

602,113 530.96

(0.63-1.47)1.13

(0.84-1.51)

Trend per 25µg

0.98 (0.90-1.06)

1.03 (0.98-1.09)

†JAMA 2003; 290: 1763-1766Schedule 5 weeks, 9 weeks, 10 months, in Denmark