1
1130 mmol/1, and the serum calcium, phosphate, and magnesium were, respectively, 3.07, 0-88, and 0-85 mmol/1. The lithium was discontinued and carbimazole was prescribed. Although her symptoms improved, the hyperthyroidism recurred. 60 mg carbimazole daily was then given for three weeks, and in November, 1975, she was euthyroid. She showed no long-act- ing thyroid stimulator (L.A.T.S.) or L.A.T.S. protector, but she was still hypercalcxmic. A selenomethionine scan suggested a parathyroid adenoma in the left inferior gland, but her im- munoreactive parathyroid hormone was normal. No renal stones or evidence of osteitis fibrosa were found radiologically, but a single parathyroid adenoma was excised from the right inferior gland (Mr P. S. Boulter). Her serum calcium, phos- phate, and magnesium returned to normal, and the carbi- mazole was discontinued in September, 1976. She remains euthyroid, but she required more E.c.T. in April, 1977. I thank Dr L. S. Dirmikis for the L.A.T.s. assay, Dr J. L. H. O’Rior- dan for the parathyroid assay, and Dr J. Coleman for referring this case. St Luke’s Hospital, Guildford, Surrey GU1 3NT GERALD A. MACGREGOR TOXICITY OF PERTUSSIS VACCINE SIR,-The Ombudsman’s report, summarised in your Nov. 5 issue (p. 990), concludes that information about adverse reactions to pertussis vaccine was not conveyed to parents but that doctors, nurses, and health authorities were and are fully informed. Well informed about what? The report gives no indi- cation of what information about the nature, frequency, or im- plications of the adverse reactions was obtained or disclosed. The fact that an injection of pertussis vaccine may be fol- lowed by screaming fits, convulsions, apnaeic attacks, and other alarming symptoms has been on record for some time.1,2 A temporal relationship is not necessarily a causal one, so some experts prefer to regard these symptoms as fortuitous: the baby who has a convulsion, screams all night, or stops breathing a few hours after an injection was going to do so anyway, because of some pre-existing disturbance, recognised or unre- cognised.3 And it has to be acknowledged that, if 3 in a 1000 infants have convulsions independently of vaccination during the first year of life, the observed frequency (1:2500 to 1:10 000) of convulsions immediately after vaccination in that age-group4-6 might be attributable to chance. The position is entirely different if similar symptoms or aggravated symptoms recur after a second or third injection. The chance of recurrence, independently but within a day or two of injection, is very much lower, perhaps as low as one in several millions. In recurrences after vaccination the patterns observed (repeated convulsions, screaming like nothing else, loss of responsiveness to parents, paralytic or other motor dis- orders) suggest either a sudden intensification of a process already started at the time of the earlier injection or else a unique predisposition in a given child to react adversely to vaccine. I have records of 265 children who were reported to me as having reacted in this fashion to one or more injections of per- tussis vaccine. In 57 of these children, the main disturbance followed a second or subsequent injection. All but 2 are now mentally defective. In at least 70 there was evidence of predis- position to neurological disturbance in the form of a family history, birth trauma, or genetic or coincident disease, all of which are accepted contraindications to giving pertussis vac- cine. In all cases, medical information has been obtained inde- pendently of any submissions by their parents, and I am grate- 1. Madsen, T. J. Am med. Ass. 1933, 101, 187. 2. Miller, H. G., Stanton, J. B. Q. Jl Med. 1954, 23, 1. 3. Prensky, A. L. Dev. Med. Child Neurol. 1974, 16, 539. 4. Str&ouml;m, J. Br. med. J. 1967, iv, 320. 5. Ehrengut, W. Dt. med. Wschr. 1974, 99, 2273. 6. Lenard, H. G., Fest, U., Scholtz, W. Mschr. Kinderheilk, 1977, 125, 660. ful to many doctors all over the U.K. for patiently and carefully supplying me with detailed information from their records. In the past I have attempted to convey details of some of these cases to the Joint Committee on Immunisation and Vaccination of the D.H.S.S. More recently, by agreement with Sir Eric Scowen, the entire file of about 600 cases now held in the computer of the University of Glasgow has been made available to the Committee on the Safety of Medicines to enable them to prepare a confidential report for the Secretary of State. Between 1950 and 1973 I was on the whole convinced, as many people still are, that pertussis vaccine was reasonably, safe and effective. I was aware of reports to the contrary but discounted these because of "information" received from the D.H.S.S. and other health authorities in the U.K. and else- where. No "information" to the contrary reached me. Department of Community Medicine, University of Glasgow, Ruchill Hospital, Glasgow G20 9NB GORDON T. STEWART GROWTH-HORMONE DEFICIENCY IN CONGENITAL RUBELLA SiR,-Dr Preece and his colleagues (Oct. 22, p. 842) have made a significant contribution to helping us understand the extensive disorders that may be associated with congenital rubella. They report two cases of associated congenital rubella and alleged idiopathic growth-hormone deficiency. There is good evidence for growth-hormone deficiency in the first patient, and this report should make clinicians aware that congenital rubella and idiopathic growth-hormone deficiency may be associated. However, in the second case the diagnosis of growth-hormone deficiency is less certain. The patient had a peak serum-growth-hormone of 10-4 mi.u./1, 90 min after in- sulin. This response is compatible with a normal response in many laboratories. To prove growth-hormone deficiency in this patient, additional tests (preferably with the addition of propranolol) should have been done. Perhaps further data will be obtained, so that these two patients will stimulate investiga- tion of growth-hormone deficiency in other children with con- genital rubella and growth retardation Department of Pediatrics, University of Virginia School of Medicine, Charlottesville, Virginia 22901, U.S.A. ROBERT M. BLIZZARD RUBELLA VACCINE (HPV-77 DE5 STRAIN) FAILS TO SUSTAIN ANTIBODY TITRES SIR,-In our study of the persistence of immunity after measles, mumps, rubella, and oral poliovirus vaccination we have become concerned by the apparently high failure-rate of rubella vaccine. From children previously vaccinated at one suburban Minneapolis private clinic blood-samples were col- lected at a routine paediatric examination. Of the 119 vaccinees tested to date, 40 (33.6%) lacked detectable rubella immunity, having rubella hxmagglutination-inhibiting (H.I.) titres <8. In contrast, 13 children (10-9%) lacked measles antibodies (H.I. titres <2) and all had neutralising antibodies to poliovirus types 1-3. The rubella vaccine used was HPV-77 DEs; 69 children had received it in combination with measles and mumps, 13 were given it with mumps vaccine, and 37 received the rubella vac- cine alone. The median age at vaccination was 16 months (mode, 1 year) and the mean period from vaccination to serolo- gical testing was 5 years (median, 4-5 years). 26 (46%) of 56 children vaccinated when less than 15 months old had rubella H.I. titres <8, whereas 14 (22%) of 63 children vaccinated at 15 months or older were seronegative. These differences are statistically significant (corrected chi-square 7-2, P<0.01).

GROWTH-HORMONE DEFICIENCY IN CONGENITAL RUBELLA

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mmol/1, and the serum calcium, phosphate, and magnesiumwere, respectively, 3.07, 0-88, and 0-85 mmol/1. The lithiumwas discontinued and carbimazole was prescribed. Althoughher symptoms improved, the hyperthyroidism recurred. 60 mgcarbimazole daily was then given for three weeks, and in

November, 1975, she was euthyroid. She showed no long-act-ing thyroid stimulator (L.A.T.S.) or L.A.T.S. protector, but shewas still hypercalcxmic. A selenomethionine scan suggested aparathyroid adenoma in the left inferior gland, but her im-munoreactive parathyroid hormone was normal. No renalstones or evidence of osteitis fibrosa were found radiologically,but a single parathyroid adenoma was excised from the rightinferior gland (Mr P. S. Boulter). Her serum calcium, phos-phate, and magnesium returned to normal, and the carbi-mazole was discontinued in September, 1976. She remains

euthyroid, but she required more E.c.T. in April, 1977.I thank Dr L. S. Dirmikis for the L.A.T.s. assay, Dr J. L. H. O’Rior-

dan for the parathyroid assay, and Dr J. Coleman for referring thiscase.

St Luke’s Hospital,Guildford, Surrey GU1 3NT GERALD A. MACGREGOR

TOXICITY OF PERTUSSIS VACCINE

SIR,-The Ombudsman’s report, summarised in your Nov.5 issue (p. 990), concludes that information about adversereactions to pertussis vaccine was not conveyed to parents butthat doctors, nurses, and health authorities were and are fullyinformed. Well informed about what? The report gives no indi-cation of what information about the nature, frequency, or im-plications of the adverse reactions was obtained or disclosed.The fact that an injection of pertussis vaccine may be fol-

lowed by screaming fits, convulsions, apnaeic attacks, andother alarming symptoms has been on record for some time.1,2A temporal relationship is not necessarily a causal one, so someexperts prefer to regard these symptoms as fortuitous: the babywho has a convulsion, screams all night, or stops breathing afew hours after an injection was going to do so anyway,because of some pre-existing disturbance, recognised or unre-cognised.3 And it has to be acknowledged that, if 3 in a 1000infants have convulsions independently of vaccination duringthe first year of life, the observed frequency (1:2500 to

1:10 000) of convulsions immediately after vaccination in thatage-group4-6 might be attributable to chance.The position is entirely different if similar symptoms or

aggravated symptoms recur after a second or third injection.The chance of recurrence, independently but within a day ortwo of injection, is very much lower, perhaps as low as one inseveral millions. In recurrences after vaccination the patternsobserved (repeated convulsions, screaming like nothing else,loss of responsiveness to parents, paralytic or other motor dis-orders) suggest either a sudden intensification of a processalready started at the time of the earlier injection or else aunique predisposition in a given child to react adversely tovaccine.

I have records of 265 children who were reported to me ashaving reacted in this fashion to one or more injections of per-tussis vaccine. In 57 of these children, the main disturbancefollowed a second or subsequent injection. All but 2 are nowmentally defective. In at least 70 there was evidence of predis-position to neurological disturbance in the form of a familyhistory, birth trauma, or genetic or coincident disease, all ofwhich are accepted contraindications to giving pertussis vac-cine. In all cases, medical information has been obtained inde-

pendently of any submissions by their parents, and I am grate-

1. Madsen, T. J. Am med. Ass. 1933, 101, 187.2. Miller, H. G., Stanton, J. B. Q. Jl Med. 1954, 23, 1.3. Prensky, A. L. Dev. Med. Child Neurol. 1974, 16, 539.4. Str&ouml;m, J. Br. med. J. 1967, iv, 320.5. Ehrengut, W. Dt. med. Wschr. 1974, 99, 2273.6. Lenard, H. G., Fest, U., Scholtz, W. Mschr. Kinderheilk, 1977, 125, 660.

ful to many doctors all over the U.K. for patiently andcarefully supplying me with detailed information from theirrecords. In the past I have attempted to convey details of someof these cases to the Joint Committee on Immunisation andVaccination of the D.H.S.S. More recently, by agreement withSir Eric Scowen, the entire file of about 600 cases now heldin the computer of the University of Glasgow has been madeavailable to the Committee on the Safety of Medicines toenable them to prepare a confidential report for the Secretaryof State.

Between 1950 and 1973 I was on the whole convinced, asmany people still are, that pertussis vaccine was reasonably,safe and effective. I was aware of reports to the contrary butdiscounted these because of "information" received from theD.H.S.S. and other health authorities in the U.K. and else-where. No "information" to the contrary reached me.

Department of Community Medicine,University of Glasgow,Ruchill Hospital,Glasgow G20 9NB GORDON T. STEWART

GROWTH-HORMONE DEFICIENCY INCONGENITAL RUBELLA

SiR,-Dr Preece and his colleagues (Oct. 22, p. 842) havemade a significant contribution to helping us understand theextensive disorders that may be associated with congenitalrubella. They report two cases of associated congenital rubellaand alleged idiopathic growth-hormone deficiency.

There is good evidence for growth-hormone deficiency in thefirst patient, and this report should make clinicians aware thatcongenital rubella and idiopathic growth-hormone deficiencymay be associated. However, in the second case the diagnosisof growth-hormone deficiency is less certain. The patient hada peak serum-growth-hormone of 10-4 mi.u./1, 90 min after in-sulin. This response is compatible with a normal response inmany laboratories. To prove growth-hormone deficiency inthis patient, additional tests (preferably with the addition ofpropranolol) should have been done. Perhaps further data willbe obtained, so that these two patients will stimulate investiga-tion of growth-hormone deficiency in other children with con-genital rubella and growth retardation

Department of Pediatrics,University of Virginia

School of Medicine,Charlottesville, Virginia 22901, U.S.A. ROBERT M. BLIZZARD

RUBELLA VACCINE (HPV-77 DE5 STRAIN) FAILS TOSUSTAIN ANTIBODY TITRES

SIR,-In our study of the persistence of immunity aftermeasles, mumps, rubella, and oral poliovirus vaccination wehave become concerned by the apparently high failure-rate ofrubella vaccine. From children previously vaccinated at onesuburban Minneapolis private clinic blood-samples were col-lected at a routine paediatric examination. Of the 119 vaccineestested to date, 40 (33.6%) lacked detectable rubella immunity,having rubella hxmagglutination-inhibiting (H.I.) titres <8. In

contrast, 13 children (10-9%) lacked measles antibodies (H.I.titres <2) and all had neutralising antibodies to poliovirustypes 1-3.The rubella vaccine used was HPV-77 DEs; 69 children had

received it in combination with measles and mumps, 13 were

given it with mumps vaccine, and 37 received the rubella vac-cine alone. The median age at vaccination was 16 months

(mode, 1 year) and the mean period from vaccination to serolo-gical testing was 5 years (median, 4-5 years). 26 (46%) of 56children vaccinated when less than 15 months old had rubellaH.I. titres <8, whereas 14 (22%) of 63 children vaccinated at15 months or older were seronegative. These differences arestatistically significant (corrected chi-square 7-2, P<0.01).