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Unexplained cases of sudden infant death shortly after hexavalent vaccination

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B. Zinka at Ludwig-Maximilians-University of Munich
B. Zinka
E Rauch
E Rauch
E Rauch
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Andreas Buettner at Rostock University Medical Center
Andreas Buettner
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F Ruëff
F Ruëff
F Ruëff
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Vaccine 24 (2006) 5779–5780
Letter to the Editor
Unexplained cases of sudden infant death shortly after
hexavalent vaccination
Polyvalent vaccines like Hexavac®and Infanrix Hexa®
were developed to increase acceptance of vaccinations by
decreasing the number of necessary injections [1,2]. Com-
pared to their pentavalent predecessors, these hexavalent
vaccines additionally contain hepatitis B serum. They are
used for immunisation against diphtheria, pertussis, tetanus,
influenza, poliomyelitis and hepatitis B. Hexavac®and Infan-
rix Hexa®are available in European markets since October
2000. Until April 2003, approximately 3 million children
have been vaccinated in this way and about 9 million doses
were sold in the European union during this time [3]. Chil-
dren are to be vaccinated with these vaccines at the age of 2,
4, 6 and 12–14 months.
We report six cases of sudden infant death after hexavalent
vaccination that were autopsied and examined at the Munich
Institute of Legal Medicine from 2001 to 2004.
Among those investigated children, three were male and
three female, ageing between 4 and 17 months. Five chil-
dren had been vaccinated with Hexavac®, one with Infanrix
Hexa®during the past 48 h before death. Shortly after the
vaccination, three of the children developed symptoms like
tiredness, loss of appetite, fever up to 39 ◦C and insomnia.
All children were found dead without explanation 1–2 days
after the vaccination.
These children underwent a forensic post-mortem exam-
ination. They were assumed to be typical cases of SID
(sudden infant death) because there was no history of a
serious illness, and since all children died suddenly and
unexpectedly.
In addition to neuropathologic and histologic abnormal-
ities, all of these children showed an extraordinary brain
edema, which made them exceptional to other SID cases.
After the third of such extraordinary cases had been iden-
tified, we decided to further investigate the pathological
findings.
Abnormal neuropathologic findings were acute conges-
tion, defective blood–brain barrier, slight infiltration of the
leptomeninx by macrophages and lymphocytes, perivascu-
lar lymphocytic infiltration, diffuse infiltration of the pons,
mesencephalon and cortex by T-lymphocytes, microglia in
the hippocampus and pons, and in one case a necrosis in the
cerebellum.
In four cases, a slight infiltration of the liver by lympho-
cytes and eosinophile granulocytes was diagnosed, in two
cases also in the lung, and in one case in the spleen.
We were able to do histological examinations at the cuta-
neous injection site in one child and found an infiltration of
the cutaneous and subcutaneous layer by lymphocytes and
eosinophile granulocytes.
Three of these six cases could be investigated concerning
increased serum levels of mast cell tryptase and IgE. Mast
cell-tryptase concentration was slightly above normal in one,
and markedly elevated in the other two children (18, 100 and
108 ␮g/l). On the other hand, IgE levels were normal and
specific IgE against tetanus toxoid and latex could not be
detected.
Autopsy and all further investigations did not reveal other
serious abnormalities that could have lead to the deaths of the
children.
The neuropathological findings in the investigated cases
are unlikely to explain the deaths, since early post-vaccinal
encephalopathy is mostly associated with a congestive and
edematous brain without relevant inflammatory infiltration.
Post-vaccinal encephalopathies are mentioned especially in
relation with vaccinations against pertussis [4,5]. Such cases,
however, typically show clinical symptoms like somnolence,
convulsion, headache or paresis [4]. Such or similar symp-
toms could not be found in any of the examined cases.
Increased brain weights either which result from edema
or hyperemia, and in which clinical symptoms are lacking,
are described as “benign intracranial hypertension”, and are
reported mainly after DTP-vaccinations [6].
At the moment, to our knowledge, there are no refer-
ence values available regarding mast cell-tryptase plasma
concentrations in children up to the age of 12 years. For
older children the 95.0 percentile is 11.4 ␮g/l. Increased
tryptase levels were repeatedly described in SID [7,8].It
is unlikely that our children had a predisposition for an
atopic diathesis, since mast cell-tryptase plasma concentra-
tions were increased while IgE levels were normal. The
increased tryptase levels and numbers of eosinophile granu-
locytes suggest that an anaphylactic reaction developed after
the vaccination. As time to death seems comparably long for
an acute anaphylactic reaction, a delayed immune reaction
has to be discussed.
Prior to the release of hexavalent sera (in the years
1994–2000), we observed only one child out of 198 cases
0264-410X/$ – see front matter © 2005 Elsevier Ltd. All rights reserved.
doi:10.1016/j.vaccine.2005.03.047
5780 Letter to the Editor / Vaccine 24 (2006) 5779–5780
with sudden unexplained infant death who died shortly after
vaccination (DTP). However, between 2001 and 2004 five of
such cases were identified in our institution among 74 chil-
dren with SID. This would indicate a 13-fold increase (the
local autopsy rate for infants is about 70%). A recent analysis
of all cases known to German authorities [9] showed death
rates that were to be expected statistically for the first day
after vaccination. As four of those 10 cases were autopsied at
Munich, although the Munich institute represents just 7.8%
of the German population, a real number of about 50 cases
might be expected, that is, 500% of the statistic figures to be
expected.
We reported these six cases to direct attention to a pos-
sibly serious vaccination side effect. So far, there is no
way to proof that these infant deaths are caused by vac-
cination. Therefore, the relation between the vaccinations
and the death of the children must remain uncertain. Nev-
ertheless, we feel that it is important to inform vaccinat-
ing physicians and pediatricians as well as parents about
such possibly fatal complications after application of hex-
avalent vaccines. Especially, physicians and pediatricians
should be also informed about the possibility of using pen-
tavalent vaccines, which seem to be associated with lesser
complications.
Finally, if broad use of hexavalent vaccines continues,
extensive studies are most likely required to assess or exclude
a relation between vaccination and death in infants.
References
[1] Liese JG, Stojanov S, Berut F, Minini P, Harzer E, Jow S, et al.
Large scale safety study of a liquid hexavalent vaccine (D-T-acP-IPV-
PRP-T-HBs) administered at246and12-14 months of age. Vaccine
2002;20:448–54.
[2] Mallet E, Fabre P, Pines E, Salomon H, Staub T, Sch¨
odel F, et
al. Immunogenicity and safety of a new liquid hexavalent combines
vaccine compared with separate administration of reference licensed
vaccines in infants. Pediatr Infect Dis J 2000;19:1119–27.
[3] Keller-Stanislawski B, L¨
ower J. Todesf¨
alle in zeitlichem Zusam-
menhang mit Sechsfachimpfung. Informationen f¨
ur medizinische
Fachkreise des Paul-Ehrlich-Instituts, Bundesamt f¨
ur Sera und Impf-
stoffe, 01.07.2003.
[4] Buchwald G. Postvakzinale Enzephalitis und postvakzinale
Enzephalopathie. Med Welt 1971:1697–701 [Heft 43].
[5] Steinmann L, Weiss A, Adelmann N, Lim N, Zuniga R, Oehlert J, et
al. Pertussis toxin is required for pertussis vaccines encephalopathy.
Proc Natl Acad Sci USA 1985;82:8733–6.
[6] Gross TP, Milstien JB, Kuritsky JN. Bulging fontanelle after
immunization with diphtheria–tetanus–pertussis vaccine and
diphtheria–tetanus vaccine. J Pediatr 1989;114(3):423–5.
[7] Edston E, Gidlund E, Wickman M, Ribbing H, van Hage-Hamsten
M. Increased mast cell tryptase in sudden infant death – anaphylaxis,
hypoxia or artefact. Clin Exp Allergy 1999;29:1648–54.
[8] Buckley MG, Variend S, Walls AF. Elevated serum concentrations
of ␤-tryptase, but not ␣-tryptase, in sudden infant death syndrome
(SIDS). An investigation of anaphylactic mechanisms. Clin Exp
Allergy 2001;31:1696–704.
[9] Kriess R, Toschke AM, Straßburger K, Kundi M, Kalies H, Nennstiel
U, et al. Sudden and unexpected deaths after the administration of
hexavalent vaccines (DTPa-IPV-HBV-Hib): Is there a signal? Eur J
Pediatr 2005;164(2):61–9.
B. Zinka ∗
E. Rauch
A. Buettner
R. Penning
Institut f¨ur Rechtsmedizin der Universit¨at M¨unchen
Institute of Legal Medicine, Frauenlobstrasse 7a
D-80337 M¨unchen, Germany
F. R u ¨
eff
Klinik und Poliklinik f¨ur Dermatologie und Allergologie
der Universit¨at M¨unchen-Innenstadt, Frauenlobstrasse 9
80337 M¨unchen, Germany
∗Corresponding author. Tel.: +49 89 5160 5163
fax: +49 89 5160 5144
E-mail address: Bettina.Zinka@med.uni-muenchen.de
(B. Zinka)
Available online 10 May 2005
... That same year, scientists associated with the Institute of Forensic Medicine in Munich, Germany (Zinka et al.) [54] reported that 6 children "were found dead without explanation" 1-2 days after hexavalent vaccination. The children underwent a forensic post-mortem examination: "In addition to neuropathological and histologic abnormalities, all of these children showed an extraordinary brain edema…. ...
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Bulging fontanelle after immunization with diphtheria-tetanus-pertussis vaccine and diphtheria-tetanus vaccine
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  • Apr 1989
  • J Pediatr
A propos de 9 cas de bombement de la fontanelle apres vaccination DT ou DTC, et bien qu'une relation de cause a effet ne puisse encore etre affirmee, les praticiens devraient etre avertis de ce phenomene et communiquer les cas qu'ils pourraient eventuellement rencontrer
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Increased mast cell tryptase in sudden infant death - Anaphylaxis, hypoxia or artefact?
Article
  • Dec 1999
Increased concentrations of mast cell tryptase in post mortem blood have frequently been observed in sudden infant deaths but the cause of this has not yet been clarified. The aim was to evaluate factors (immunological, morphological and anamnestic data) behind the observed increase in mast cell tryptase in sudden infant deaths with elevated tryptase. Mast cell tryptase and total immunoglobulin (Ig) E were measured in post mortem sera from 44 infants younger than 1.5 years. Radioallergosorbent tests were performed for possible allergens (mixture for relevant food allergens, Phadiatop and latex). IgG subclasses, IgM, and complement factors (C3, C4 and factor B) were measured with radial immunodiffusion. Mast cells, labelled with antibodies against mast cell tryptase, were counted in the lungs and heart. The circumstances of death and medical history of the deceased infant and family were obtained through police and hospital records. In 40% of the SIDS cases tryptase was elevated (>10 microg/L). Total IgE in serum was increased in 33% compared with clinical reference values but showed no association with mast cell tryptase. RAST tests were positive in three cases. In one of these cases both tryptase and total IgE were elevated. The only variable that was associated with high tryptase values was prone position at death (P < or = 0.05 ). Allergy or asthma in the family were alleged in 50% of the cases, but was not associated with elevated tryptase or IgE. Children with elevated total IgE also displayed high concentrations of IgG1 and IgG2. Infants who died in the spring had significantly higher IgE than the others (P < or = 0.05). The results do not support the hypothesis that the elevated tryptase concentrations in sudden infant death are caused by allergy. The association between prone position at death and elevated tryptase could hypothetically be explained by mast cell degranulation due to, for example, a hypoxic stimulus in these infants.
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Large scale safety study of a liquid hexavalent vaccine (D-T-acP–IPV–PRP∼T–HBs) administered at 2, 4, 6 and 12–14 months of age
Article
  • Dec 2001
  • VACCINE
A study was conducted to assess the safety of a new, liquid hexavalent vaccine (Hexavac, Aventis Pasteur MSD, Lyon, France) in a large population of 1783 children in Germany vaccinated at 2, 4, 6 and 12-14 months of age. Immediate reactions, local and systemic reactions, and serious adverse events (SAEs) were monitored. The frequencies of redness > or = 2 cm and swelling > or = 2 cm were 6.7 and 7.1% after all doses of the primary series combined and 13.4 and 12.0% following the booster dose, respectively. Transient swelling of the entire thigh was reported in seven infants after all doses of the primary series (0.1%) and in four children after the booster dose (0.2%). The most frequent systemic adverse events within 3 days after vaccination were irritability (19.3% after primary series and 13.2% after booster) and fever > or = 38.0 degrees C (15.4% after primary series and 28.5% after booster). Fever above 40.0 degrees C was reported in 0.1% of the infants post-primary series and in 0.9% of the children after the booster immunization. Only 3 of 144 SAE were considered to be vaccine related and were seen to resolve spontaneously and without sequelae. The liquid hexavalent vaccine was generally well tolerated when given to children as a primary immunization series at 2, 4 and 6 months and as a booster dose at 12-14 months.
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Elevated serum concentrations of β-tryptase, but not α-tryptase, in Sudden Infant Death Syndrome (SIDS). An investigation of anaphylactic mechanisms
Article
  • Dec 2001
Sudden Infant Death Syndrome, (SIDS) or cot death, remains the most common category of post-perinatal death in the UK. By definition, the cause of death is unknown, but a long-standing theory is that some of these deaths could be the result of anaphylaxis. To investigate the potential contribution of anaphylactic mechanisms to deaths in infancy by determining relative levels of alpha- and beta-tryptases and both total and allergen-specific IgE in sera from groups of infants whose deaths were attributed to SIDS or to other causes. Serum samples were collected at the time of post-mortem examination from infants whose death was classed as SIDS (n = 40) and from a comparison group in which cause of death had been established (n = 32). Serum tryptase concentrations were measured with a radioimmunoassay with monoclonal antibody G5 which detects primarily beta-tryptase or an ELISA with antibody AA5 which has equal sensitivity for alpha- and beta-tryptases. Levels of total IgE and IgE specific for casein, beta-lactoglobulin, house dust mite and moulds were determined. Analysis of the results of the two assays for tryptase indicated that levels of the beta-like tryptase (the form secreted on anaphylactic degranulation) were significantly higher in serum from infants with SIDS compared with those whose death was explained. There was no evidence for an increase in serum levels of alpha-tryptase (the variant secreted constitutively from mast cells). Total levels of serum IgE did not differ between the two groups and, reflecting the low circulating IgE concentrations in infancy, an elevation in IgE specific for the panel of allergens was not detected. In a proportion of SIDS victims there may be increased serum levels of beta-like tryptase, a marker for anaphylaxis. The failure to detect an increase in alpha-tryptase would suggest that mast cell hyperplasia is not a feature of cot death. The nature of the inciting agents remains unclear, but anaphylaxis deserves serious consideration as a possible cause of sudden death in infancy.
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Sudden and unexpected deaths after the administration of hexavalent vaccines (DTPa-IPV-HBV-Hib): Is there a signal?
  • Jan 2005
  • Eur J Pediatr
  • 61-69
  • R Kriess
  • A M Toschke
  • K Straßburger
  • M Kundi
  • H Kalies
  • U Nennstiel
Kriess R, Toschke AM, Straßburger K, Kundi M, Kalies H, Nennstiel U, et al. Sudden and unexpected deaths after the administration of hexavalent vaccines (DTPa-IPV-HBV-Hib): Is there a signal? Eur J Pediatr 2005;164(2):61-9.
Todesfä in zeitlichem Zusam-menhang mit Sechsfachimpfung. Informationen fü medizinische Fachkreise des Paul-Ehrlich-Instituts, Bundesamt fü Sera und Impf-stoffe, 01
  • Jan 2003
  • 07
  • Keller
  • B Stanislawski
  • Lö
Keller-Stanislawski B, Lö J. Todesfä in zeitlichem Zusam-menhang mit Sechsfachimpfung. Informationen fü medizinische Fachkreise des Paul-Ehrlich-Instituts, Bundesamt fü Sera und Impf-stoffe, 01.07.2003.