FW: Hib Vaccine and Diabetes

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http://www.bmj.com/cgi/content/full/319/7217/1133

BMJ 1999;319:1133 ( 23 October )

Letters

Association between type 1 diabetes and Hib vaccine

Causal relation is likely

More research is still needed

Causal relation is likely

EDITOR We initiated and funded a collaborative study

with Tuomilehto on the

effect of the Haemophilus influenzae type b vaccine

on type 1 diabetes and

found that the data support a causal relation (paper

submitted for

publication). Furthermore, the potential risk of the

vaccine exceeds the

potential benefit. We compared a group that received

four doses of the

vaccine, a group that received one dose, and a group

that was not

vaccinated. The cumulative incidence of diabetes per

100 000 in the three

groups receiving four, one, and no doses of the

vaccine was 261, 237, and

207 at age 7 and 398, 376, and 340 at age 10

respectively.

Karvonen et al's analysis is not rational, and their

conclusion is not

supported by our data.1 Their calculations of

relative risk are also

misleadingly low, and we urge readers to check them.

Most researchers would

compare the group who received four doses with the

group that was not

vaccinated or the two vaccinated groups with the

group that was not

vaccinated. The results of both comparisons reach

significance. The

cumulative difference in cases of type 1 diabetes

per100 000 between those

receiving four doses and those who were not

vaccinated is 54 cases (P=0.013)

at 7 years and 58 cases at 10 years (P=0.029; single

tail Fisher test). The

relative risk is 1.26 at 7 years. The cumulative

difference between those

receiving four doses or one dose of the vaccine and

those who were not

vaccinated is 42 cases (P=0.016) at 7 years and 47

cases at 10 years

(P=0.028).

The rise in diabetes, just one potential adverse

effect, exceeds the benefit

of the vaccine, which has been estimated to prevent

seven deaths and 7-26

cases of severe disability per 100 000 children

immunised.2 Even the

difference in cases of diabetes between the groups

receiving four doses and

one dose exceeds the mean expected benefit. Temporal

changes in the

incidence of diabetes do not explain the differences

since there were an

extra 31 cases of type 1 diabetes per 100 000

children aged 5-10, and the

incidence of diabetes in this group had been stable

for about 10 years

before this.3 Furthermore, sharp rises in diabetes

have been recorded in the

United States4 and the United Kingdom5 after the

introduction of the

haemophilus vaccine.

Public health officials want to avoid scaring the

public, but they risk

depriving damaged children of compensation. Denials

of safety issues may

erode public confidence, especially since diabetes

induced by the vaccine

may be avoided by starting vaccination a few weeks

earlier.

J Barthelow Classen, president.

Classen Immunotherapies, 6517 Montrose Avenue,

Baltimore, MD 21212, USA

Classen@...

C Classen, infectious disease physician.

Division of Infectious Diseases, LDS Hospital, Salt

Lake City, UT, USA

a Competing interests: Methods used in the authors'

research (including

methods of testing vaccines for the induction of

diabetes and methods of

giving vaccines without inducing diabetes) are

covered by patents owned by

Classen Immunotherapies. Dr Classen holds

shares in Classen

Immunotherapies; Dr Classen owns no shares in

the company, receives no

funding from it, and has no financial ties to it or

this research.

1. Karvonen M, Cepaitis Z, Tuomilehto J. Association

between type 1 diabetes

and Haemophilus influenzae type b vaccination: birth

cohort study. BMJ 1999;

318: 1169-1172[Abstract/Full Text]. (1 May.)

2. Peltola H, Kayhty H, Sivonen A, Makela H.

Hemophilus influenza type B

capsular polysaccharide vaccine in children: a

double blind field study of

100 000 vaccinees 3 months to 5 years of age in

Finland. Pediatrics 1977;

60: 730-737[Abstract].

3. Tuomilehto J, Virtala E, Karvonen M, Lounamen R,

Pitkaniemi J, Reunanen

A, et al. Increase in incidence of insulin-dependent

diabetes mellitus among

children in Finland. Int J Epidemiol 1995; 24:

984-992[Medline].

4. Dokheel TM. An epidemic of childhood diabetes in

the United States.

Diabetes Care 1993; 16: 1606-1611[Medline].

5. Gardner S, Bingley PJ, Sawtell PA, Weeks S, Gale

EA. Rising incidence of

insulin dependent diabetes in children under 5 years

in Oxford region: time

trend analysis. BMJ 1997; 315: 713-716[Abstract/Full

Text].

More research is still needed

EDITOR I read Classen and Classen's comments in the

eBMJ1 [edited letter

printed here, above] on the paper by Karvonen et

al.2 Classen and Classen

question the way that the data in the paper were

analysed and presented.

They highlight the fact that in table 2 the relative

risk of type 1 diabetes

was only compared between cohorts 1 and 3 (those who

did not receive any

Haemophilus influenzae type b vaccine and those who

received the vaccine at

24 months only) and cohorts 2 and 3 (those who

received four doses of the

vaccine from 3 months and those who received the

vaccine at 24 months only).

Why did Karvonen et al not give a comparison between

cohorts 1 and 2 (those

who did not receive any vaccine and those who

received four doses from 3

months)?

Furthermore, in figure 1 of this paper (cumulative

incidence of type 1

diabetes per 100 000 person years in Finnish

children aged 10 or under) only

the data for cohorts 2 and 3 were plotted. Why were

the data for cohort 1

excluded? Could it be that including the data for

cohort 1 on the graph

would have allowed a more direct visual comparison

between cohorts 1 and 2

to be made? And would this have then made it more

difficult for Karvonen et

al to convince casual observers that there is no

link between the

introduction of H influenzae type b vaccine and an

increase in the incidence

of type 1 diabetes?

The greatest increase in type 1 diabetes has

occurred in children aged under

4 (fig 2),2 which coincides with the period when H

influenzae type b vaccine

was introduced in the mid-1980s. This should raise

our suspicions as to

whether the vaccine could be responsible for this

increase. Karvonen et al

have dismissed the data as not being significant;

however, the impact on the

lives of a further 58 cases per 100 000 children at

the age of 10 who will

have to learn how to deal with a lifelong chronic

disease such as type 1

diabetes should not be trivialised.

Further research would do well to focus on the

incidence of type 1 diabetes

before and after the introduction of H influenzae

type b vaccination

programmes in other countries, such as Australia,

the United States, and the

United Kingdom.

Heidi White, hospital pharmacist.

Lyell McEwin Health Service, Vale, South

Australia, Australia

rebel1@...

1. Electronic responses. Association between type 1

diabetes and Haemophilus

influenzae type b vaccination: birth cohort study.

eBMJ 1999;318

www.bmj.com/cgi/content/full/318/7192/1169#responses

(accessed 7 May 1999).

2. Karvonen M, Cepaitis Z, Tuomilehto J. Association

between type 1 diabetes

and Haemophilus influenzae type b vaccination: birth

cohort study. BMJ 1999;

318: 1169-1172[Abstract/Full Text]. (1 May.)

b Competing interests: None declared.

Other related articles in BMJ:

PAPERS

Association between type 1 diabetes and Haemophilus

influenzae type b

vaccination: birth cohort study.

Marjatta Karvonen, Zygimantas Cepaitis, and Jaakko

Tuomilehto

BMJ 1999 318: 1169-1172. [Abstract] [Full text]