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Haemophilus Influenzae type b meningitis after three doses of vaccine
Haemophilus Influenzae type b meningitis after three doses of vaccine SIR-It has been reported that over 100 000 children have received polyribosylribitol phosphate-tetanus protein
conjugate vaccine (PRP-T) against Haemophilus influenzae type b (Hib) and that no cases of Hib disease have been reported in infants who have received more than one dose.1 Thus we consider it important to record a Gambian child who received three doses of PRP-T during infancy and yet subsequently developed Hib meningitis. A female Gambian infant was enrolled in a study to evaluate the effect of mixing PRP-T with diphtheria-pertusis-tetanus vaccine (DPT) before administration. This child was randomised to receive PRP-T and DPT by separate injections given into opposite anterolateral thighs on the same day. The vaccine used was Act-HIB (Pasteur Merieux, lot number S2190). Each dose was administered by a doctor (AH) at 2, 3, and 4 months of age. Fingerprick blood samples were collected at 3 and 4 months of age and 6 weeks after the third dose of vaccine. On Aug 4,1992, at 15 months of age, the child presented to our hospital with a 1 day history of fever and diarrhoea, having had two convulsions. Her temperature was 39°C and she had a stiff neck and a bulging fontanelle. There were no localising neurological signs. Her cerebrospinal fluid (CSF) was cloudy with 1845 x 106 white cells/L, gram stain revealed many gram-negative bacilli, and latex agglutination test was positive for Hib antigen. Culture of both blood and CSF yielded H influenzae type b which was (3-lactamase negative and sensitive to ampicillin and chloramphenicol. She was treated with intravenous and oral chloramphenicol and made an uneventful recovery. At follow-up 2 months later she was quite well with no neurological signs. She was well nourished (95 kg), had had no other serious infections, and showed no signs of an immunological,disorder. VDRL, HIV-1, and HIV-2 tests were normal. PRP antibody concentrations were measured by radioimmunoassay2 and calibrated agaimt US FDA standard serum (lot 1983). The results were as follows:
immunoglobulin concentrations were measured on Oct 25,1992. Total IgG was 442 mg/dL (normal range 290-1300), total IgA was 35 mg/dL (40-140), and total IgM was 220 mg/dL (50-200). Peripheral blood white cell count was 47 x 106fL and
Total
T-cell subsets were within normal limits. It is possible that this child had a high level of passively acquired maternal antibody that impaired her response to PRP-T and later to Hib disease. In some studies with Hib conjugate vaccines high pre-existing antibody levels inhibited anti-PRP responses.3.4 In recent studies of Gambian infants 15 of 295 (5%) unvaccinated infants had PRP antibody concentrations above 1 g/mL at 2 months of age. This seems
likely than the second possibility which is that, after initially responding to the PRP-T vaccine, the child mounted a poor response to subsequent doses and to the disease. Whatever the mechanism, her antibody response after the third dose was below that associated with short-term protection (0-15 gg/mL), she later developed invasive Hib disease, and 2 months after the episode she still had no detectable Hib antibody. Despite this she remains a healthy child with no signs of an immunological disorder.
more
794
It appears that this child is unable to respond normally to PRP. A high maternal antibody level and/or PRP-T vaccination might have contributed to her poor response. We believe that she may be at risk for further episodes of invasive Hib disease and we have taken steps to re-vaccinate her with a different conjugate vaccine. E K Mulholland, A Hoestermann, R O Suara, R A Adegbola, G Siber, C Thompson, B M Greenwood Medical Research Council Laboratories,
Fajara, PO Box 273, Banjul, The Gambia
Fritzell B, Plotkin S. Efficacy and safety of a Haemophilus influenzae type b capsular polysaccharide-tetanus protein conjugate vaccine. J Pediatr 1992; 121: 355-62. 2 O’Reilly RJ, Anderson P, Ingram DL, Peter G, Smith DH. Circulating polyribophosphate in Haemophilus influenzae type b meningitis: correlation with clinical course and antibody response. J Clin Invest 1975; 56: 1012-22. 3 Claesson BA, Schneerson R, Robbins JB, et al. Protective levels of serum antibodies stimulated in infants by two injections of Haemophilus influenzae type b capsular polysaccharide-tetanus toxoid conjugate. J Pediatr 1989; 114: 97-100. 4 Daum RS, Siber GR, Ballanco GA, Sood SK. Serum anticapsular antibody response in the first week after immunization of adults and infants with the Haemophilus influenzae type b-Neisseria meningitidis outer membrane protein complex conjugate vaccine. J Infect Dis 1991; 164: 1154-59. 1
Ischaemic neurological deficit after
sclerotherapy SiR-Van der Plan and colleagues (Feb 12, p 428) describe a reversible ischaemic neurological deficit after sclerotherapy of varicose veins with polidocanol. They suggest that activated haemostasis by sclerotherapy resulted in ischaemic brain injury. We favour an alternative explanation-that sclerotherapy included local thrombosis, the neurological deficit being due to paradoxical embolism. Patent foramen ovale with the possibility of paradoxical embolism is frequent in young patients with stroke1.2 and cannot be "excluded by transthoracic ultrasound"; that calls for transoesophageal or contrast echocardiography.3 A 2-day neurological deficit is usually accompanied by an ischaemic lesion in the brain; a negative computed tomography scan 5 days after the event does not exclude an ischaemic lesion, which might have been demonstrated by the more sensitive magnetic resonance imaging.5 The "activation of the coagulation system with reactive fibrinolysis", demonstrated 2 days after the onset of the neurological deficit, is no strong argument against a thromboembolic cause. The observed changes in haemostasis can also accompany local thrombosis at the injection site or thromboembolism to the brain. Before "activation of haemostasis" due to sclerotherapy is accepted as the most probable cause of neurological deficit in a young patient, alternative diagnoses, such as paradoxical embolism, should be excluded. The prognosis and treatment will be different. Peter Trenkwalder, Helmut Lydtin Department of Internal Medicine, Stamberg Hospital, Ludwig Maximilian University of Munich, D-82319 Starnberg, Germany
1
2 3 4
5
Lachet Ph, Mas JL, Lascault G, et al. Prevalence of patent foramen ovale in patients with stroke. N Engl J Med 1988; 318: 1148-52. Webster MWI, Smith HJ, Sharpe DN, et al. Patent foramen ovale in young stroke patients. Lancet 1988; ii: 11-12. Matsuzaki M, Toma Y, Kusukava R. Clinical application of transoesophageal echocardiography. Circulation 1990; 82: 709-22. Conti RC. Embolic stroke: are we missing the source in many young patients? Clin Cardiol 1993; 16: 83-84. Edelman RR, Warach S. Magnetic resonance imaging I. N Engl J Med
1993; 328: 708-16.
conjugate vaccine (PRP-T) against Haemophilus influenzae type b (Hib) and that no cases of Hib disease have been reported in infants who have received more than one dose.1 Thus we consider it important to record a Gambian child who received three doses of PRP-T during infancy and yet subsequently developed Hib meningitis. A female Gambian infant was enrolled in a study to evaluate the effect of mixing PRP-T with diphtheria-pertusis-tetanus vaccine (DPT) before administration. This child was randomised to receive PRP-T and DPT by separate injections given into opposite anterolateral thighs on the same day. The vaccine used was Act-HIB (Pasteur Merieux, lot number S2190). Each dose was administered by a doctor (AH) at 2, 3, and 4 months of age. Fingerprick blood samples were collected at 3 and 4 months of age and 6 weeks after the third dose of vaccine. On Aug 4,1992, at 15 months of age, the child presented to our hospital with a 1 day history of fever and diarrhoea, having had two convulsions. Her temperature was 39°C and she had a stiff neck and a bulging fontanelle. There were no localising neurological signs. Her cerebrospinal fluid (CSF) was cloudy with 1845 x 106 white cells/L, gram stain revealed many gram-negative bacilli, and latex agglutination test was positive for Hib antigen. Culture of both blood and CSF yielded H influenzae type b which was (3-lactamase negative and sensitive to ampicillin and chloramphenicol. She was treated with intravenous and oral chloramphenicol and made an uneventful recovery. At follow-up 2 months later she was quite well with no neurological signs. She was well nourished (95 kg), had had no other serious infections, and showed no signs of an immunological,disorder. VDRL, HIV-1, and HIV-2 tests were normal. PRP antibody concentrations were measured by radioimmunoassay2 and calibrated agaimt US FDA standard serum (lot 1983). The results were as follows:
immunoglobulin concentrations were measured on Oct 25,1992. Total IgG was 442 mg/dL (normal range 290-1300), total IgA was 35 mg/dL (40-140), and total IgM was 220 mg/dL (50-200). Peripheral blood white cell count was 47 x 106fL and
Total
T-cell subsets were within normal limits. It is possible that this child had a high level of passively acquired maternal antibody that impaired her response to PRP-T and later to Hib disease. In some studies with Hib conjugate vaccines high pre-existing antibody levels inhibited anti-PRP responses.3.4 In recent studies of Gambian infants 15 of 295 (5%) unvaccinated infants had PRP antibody concentrations above 1 g/mL at 2 months of age. This seems
likely than the second possibility which is that, after initially responding to the PRP-T vaccine, the child mounted a poor response to subsequent doses and to the disease. Whatever the mechanism, her antibody response after the third dose was below that associated with short-term protection (0-15 gg/mL), she later developed invasive Hib disease, and 2 months after the episode she still had no detectable Hib antibody. Despite this she remains a healthy child with no signs of an immunological disorder.
more
794
It appears that this child is unable to respond normally to PRP. A high maternal antibody level and/or PRP-T vaccination might have contributed to her poor response. We believe that she may be at risk for further episodes of invasive Hib disease and we have taken steps to re-vaccinate her with a different conjugate vaccine. E K Mulholland, A Hoestermann, R O Suara, R A Adegbola, G Siber, C Thompson, B M Greenwood Medical Research Council Laboratories,
Fajara, PO Box 273, Banjul, The Gambia
Fritzell B, Plotkin S. Efficacy and safety of a Haemophilus influenzae type b capsular polysaccharide-tetanus protein conjugate vaccine. J Pediatr 1992; 121: 355-62. 2 O’Reilly RJ, Anderson P, Ingram DL, Peter G, Smith DH. Circulating polyribophosphate in Haemophilus influenzae type b meningitis: correlation with clinical course and antibody response. J Clin Invest 1975; 56: 1012-22. 3 Claesson BA, Schneerson R, Robbins JB, et al. Protective levels of serum antibodies stimulated in infants by two injections of Haemophilus influenzae type b capsular polysaccharide-tetanus toxoid conjugate. J Pediatr 1989; 114: 97-100. 4 Daum RS, Siber GR, Ballanco GA, Sood SK. Serum anticapsular antibody response in the first week after immunization of adults and infants with the Haemophilus influenzae type b-Neisseria meningitidis outer membrane protein complex conjugate vaccine. J Infect Dis 1991; 164: 1154-59. 1
Ischaemic neurological deficit after
sclerotherapy SiR-Van der Plan and colleagues (Feb 12, p 428) describe a reversible ischaemic neurological deficit after sclerotherapy of varicose veins with polidocanol. They suggest that activated haemostasis by sclerotherapy resulted in ischaemic brain injury. We favour an alternative explanation-that sclerotherapy included local thrombosis, the neurological deficit being due to paradoxical embolism. Patent foramen ovale with the possibility of paradoxical embolism is frequent in young patients with stroke1.2 and cannot be "excluded by transthoracic ultrasound"; that calls for transoesophageal or contrast echocardiography.3 A 2-day neurological deficit is usually accompanied by an ischaemic lesion in the brain; a negative computed tomography scan 5 days after the event does not exclude an ischaemic lesion, which might have been demonstrated by the more sensitive magnetic resonance imaging.5 The "activation of the coagulation system with reactive fibrinolysis", demonstrated 2 days after the onset of the neurological deficit, is no strong argument against a thromboembolic cause. The observed changes in haemostasis can also accompany local thrombosis at the injection site or thromboembolism to the brain. Before "activation of haemostasis" due to sclerotherapy is accepted as the most probable cause of neurological deficit in a young patient, alternative diagnoses, such as paradoxical embolism, should be excluded. The prognosis and treatment will be different. Peter Trenkwalder, Helmut Lydtin Department of Internal Medicine, Stamberg Hospital, Ludwig Maximilian University of Munich, D-82319 Starnberg, Germany
1
2 3 4
5
Lachet Ph, Mas JL, Lascault G, et al. Prevalence of patent foramen ovale in patients with stroke. N Engl J Med 1988; 318: 1148-52. Webster MWI, Smith HJ, Sharpe DN, et al. Patent foramen ovale in young stroke patients. Lancet 1988; ii: 11-12. Matsuzaki M, Toma Y, Kusukava R. Clinical application of transoesophageal echocardiography. Circulation 1990; 82: 709-22. Conti RC. Embolic stroke: are we missing the source in many young patients? Clin Cardiol 1993; 16: 83-84. Edelman RR, Warach S. Magnetic resonance imaging I. N Engl J Med
1993; 328: 708-16.