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Encephalitis in a 13-year-old boy following 17D yellow fever vaccine
Journal of Infection (I99 o) zi, ~o5-Io6
CASE REPORT E n c e p h a l i t i s in a 13-year-old boy f o l l o w i n g I7D y e l l o w fever vaccine B. D. Schoub,*~ C.J. Dommann,* S. Johnson,* C. Downier and P. L. Patelt * National Institute for Virology and Department of Virology, University of the Witwatersrand and t Private Physicians, Durban, South Africa Accepted for publication 7 February ~99o
Summary We report a case of encephalitis following yellow fever vaccine in a healthy 13 yearold-boy. This is the first reported case in a child older than 3 years of age and the second over the age of 9 months, before which time the vaccine is contraindicated for routine immunisation.
Introduction Yellow fever immunisation is a statutory r e q u i r e m e n t for travellers to a n u m b e r of tropical countries in the world including those on the African continent. E n d e m i c yellow fever does not occur in the R e p u b l i c of South Africa or in the neighbouring countries; however, the National Institute for Virology manufactures some 2oo ooo doses of vaccine annually for inoculation of travellers, especially to tropical Africa. T h e vaccine is administered t h r o u g h the offices of the Regional Directors of H e a l t h and identification of vaccinial complications has been maintained by means of a questionnaire since the vaccine was first distributed some 4o years ago. T o date only a few cases of relatively trivial side effects have been n o t e d - - m i l d hypersensitivity reactions to egg protein, pain in the arm etc. W e report here the first serious reaction, encephalitis, reported to us following inoculation with locally made yellow fever vaccine. Only I7 other cases of post-vaccine encephalitis have been reported to the W o r l d H e a l t h Organization, the oldest in a child of 3 years of age. 1
Case report T h e patient, a I 3 - y e a r - o l d healthy Indian boy, was inoculated with I 7 D yellow fever vaccine p r e p a r e d at the National Institute for Virology (see below) on 5 M a y I989. O n e week later he was admitted to hospital following a grand mal seizure at school. H e had high fever b u t no neck stiffness. L a t e r that day he had two m o r e convulsions and developed a left sixth cranial nerve paralysis, b u t no other central nervous system signs. T h e fever continued during the following day, and he complained of severe headache and exhibited signs of cerebral irritation. H i s C S F was clear and colourless and u n d e r a Address for correspondence: Professor B. D. Schouh, National Institute for Virology, Private Bag X4, Sandringham 213I, South Africa. oi63-4453/9o/o4oio5 +o2 $o2.oo/o
© ~99o The British Society for the Study of Infection
lO6
B. D. SCHOUB E T A L .
pressure of 200 mm. It contained no cells and the chemistry was normal. T h e brain scan confirmed encephalitis with decreased tissue attenuation in the right frontal lobe involving mainly the white matter and h y p o d e n s e areas in the right posterior parietal region. T h e E E G record was markedly abnormal in keeping with diffuse cerebral disturbance affecting the right m o r e than the left side. T h e patient made an uneventful recovery after I month. Yellow fever vaccine
T h e yellow fever vaccine used was prepared at the National Institute for Virology from a secondary seed lot of I 7 D strain derived from Rockefeller F o u n d a t i o n batch 176o. T h e secondary seed batch used had been safety tested in nine seronegative rhesus monkeys w h o all seroconverted. N o n e developed encephalitis or paralysis following intracerebral inoculation. In addition toxicity testing in guinea-pigs and sterility testing were negative. Except for the case described here no other complications in h u m a n vaccinees have been reported to the National Institute for Virology. Discussion
Neurological complications following immunisation with I 7 D yellow fever vaccine are very rare. Only 17 cases of encephalitis have been reported following tens o f millions of immunisations carried out for over 40 years. T h e W o r l d Health Organization requirements for yellow fever vaccine make provision for neurovirulence testing of seed virus in rhesus m o n k e y s and this is strictly adhered to in the p r o d u c t i o n of the local vaccine. Nevertheless, as a precautionary measure, children u n d e r the age of 9 m o n t h s should not routinely be i m m u n i s e d as I6 of the I7 cases reported occurred in infants of 7 m o n t h s and younger. T h e only fatality, however, occurred in a child 3 years of age. 2 Neurological complications with the very m u c h less frequently used Dakar vaccine strain are somewhat more frequent than with the 17D strain. 3 Because of financial restrictions further confirmatory tests were not carried out on this case of post-yellow fever vaccine encephalitis. H o w e v e r , the findings of a clear, colourless, acellular cerebrospinal fluid together with the temporal association of clinical signs and s y m p t o m s of encephalitis 7 days after receiving the vaccine are highly suggestive of a causal relationship. This case is thus the first one in a child older than 3 years to be reported and only the second in one b e y o n d the age when routine immunisation is contraindicated. Clearly these two isolated case reports should not affect the current r e c o m m e n d a t i o n s for yellow fever immunisation b u t public health officials do need to be cognisant of the possibility of encephalitis, even in older children. References
I. World Health Organization I986. Immunisation practice. In: Prevention and Control of Yellow Fever in Africa, pp. 58-64, Wlto Geneva, 1986. 2. Joint Statement. Fatal viral encephalitis following I7D yellow laver vaccine inoculation: Report of a case in a 3-year-old child. J A M A 1966; x98:671-672. 3. Diop Mar I, Niang I, Gutcheney A et al. Enc6phalites cons6cutives h la vaccination antiamarile (d'aprbs 248 cas observ6s ~ Dakar en 1965). Ann Pediatr 1967; I 4 : I 8 I - I 9 I.
CASE REPORT E n c e p h a l i t i s in a 13-year-old boy f o l l o w i n g I7D y e l l o w fever vaccine B. D. Schoub,*~ C.J. Dommann,* S. Johnson,* C. Downier and P. L. Patelt * National Institute for Virology and Department of Virology, University of the Witwatersrand and t Private Physicians, Durban, South Africa Accepted for publication 7 February ~99o
Summary We report a case of encephalitis following yellow fever vaccine in a healthy 13 yearold-boy. This is the first reported case in a child older than 3 years of age and the second over the age of 9 months, before which time the vaccine is contraindicated for routine immunisation.
Introduction Yellow fever immunisation is a statutory r e q u i r e m e n t for travellers to a n u m b e r of tropical countries in the world including those on the African continent. E n d e m i c yellow fever does not occur in the R e p u b l i c of South Africa or in the neighbouring countries; however, the National Institute for Virology manufactures some 2oo ooo doses of vaccine annually for inoculation of travellers, especially to tropical Africa. T h e vaccine is administered t h r o u g h the offices of the Regional Directors of H e a l t h and identification of vaccinial complications has been maintained by means of a questionnaire since the vaccine was first distributed some 4o years ago. T o date only a few cases of relatively trivial side effects have been n o t e d - - m i l d hypersensitivity reactions to egg protein, pain in the arm etc. W e report here the first serious reaction, encephalitis, reported to us following inoculation with locally made yellow fever vaccine. Only I7 other cases of post-vaccine encephalitis have been reported to the W o r l d H e a l t h Organization, the oldest in a child of 3 years of age. 1
Case report T h e patient, a I 3 - y e a r - o l d healthy Indian boy, was inoculated with I 7 D yellow fever vaccine p r e p a r e d at the National Institute for Virology (see below) on 5 M a y I989. O n e week later he was admitted to hospital following a grand mal seizure at school. H e had high fever b u t no neck stiffness. L a t e r that day he had two m o r e convulsions and developed a left sixth cranial nerve paralysis, b u t no other central nervous system signs. T h e fever continued during the following day, and he complained of severe headache and exhibited signs of cerebral irritation. H i s C S F was clear and colourless and u n d e r a Address for correspondence: Professor B. D. Schouh, National Institute for Virology, Private Bag X4, Sandringham 213I, South Africa. oi63-4453/9o/o4oio5 +o2 $o2.oo/o
© ~99o The British Society for the Study of Infection
lO6
B. D. SCHOUB E T A L .
pressure of 200 mm. It contained no cells and the chemistry was normal. T h e brain scan confirmed encephalitis with decreased tissue attenuation in the right frontal lobe involving mainly the white matter and h y p o d e n s e areas in the right posterior parietal region. T h e E E G record was markedly abnormal in keeping with diffuse cerebral disturbance affecting the right m o r e than the left side. T h e patient made an uneventful recovery after I month. Yellow fever vaccine
T h e yellow fever vaccine used was prepared at the National Institute for Virology from a secondary seed lot of I 7 D strain derived from Rockefeller F o u n d a t i o n batch 176o. T h e secondary seed batch used had been safety tested in nine seronegative rhesus monkeys w h o all seroconverted. N o n e developed encephalitis or paralysis following intracerebral inoculation. In addition toxicity testing in guinea-pigs and sterility testing were negative. Except for the case described here no other complications in h u m a n vaccinees have been reported to the National Institute for Virology. Discussion
Neurological complications following immunisation with I 7 D yellow fever vaccine are very rare. Only 17 cases of encephalitis have been reported following tens o f millions of immunisations carried out for over 40 years. T h e W o r l d Health Organization requirements for yellow fever vaccine make provision for neurovirulence testing of seed virus in rhesus m o n k e y s and this is strictly adhered to in the p r o d u c t i o n of the local vaccine. Nevertheless, as a precautionary measure, children u n d e r the age of 9 m o n t h s should not routinely be i m m u n i s e d as I6 of the I7 cases reported occurred in infants of 7 m o n t h s and younger. T h e only fatality, however, occurred in a child 3 years of age. 2 Neurological complications with the very m u c h less frequently used Dakar vaccine strain are somewhat more frequent than with the 17D strain. 3 Because of financial restrictions further confirmatory tests were not carried out on this case of post-yellow fever vaccine encephalitis. H o w e v e r , the findings of a clear, colourless, acellular cerebrospinal fluid together with the temporal association of clinical signs and s y m p t o m s of encephalitis 7 days after receiving the vaccine are highly suggestive of a causal relationship. This case is thus the first one in a child older than 3 years to be reported and only the second in one b e y o n d the age when routine immunisation is contraindicated. Clearly these two isolated case reports should not affect the current r e c o m m e n d a t i o n s for yellow fever immunisation b u t public health officials do need to be cognisant of the possibility of encephalitis, even in older children. References
I. World Health Organization I986. Immunisation practice. In: Prevention and Control of Yellow Fever in Africa, pp. 58-64, Wlto Geneva, 1986. 2. Joint Statement. Fatal viral encephalitis following I7D yellow laver vaccine inoculation: Report of a case in a 3-year-old child. J A M A 1966; x98:671-672. 3. Diop Mar I, Niang I, Gutcheney A et al. Enc6phalites cons6cutives h la vaccination antiamarile (d'aprbs 248 cas observ6s ~ Dakar en 1965). Ann Pediatr 1967; I 4 : I 8 I - I 9 I.