Poliovirus vaccination

Four months after the child’s presentation, both child and stepfather tested negative for cANCA. Although there is no evidence of WG in the stepson, there is an association between WG and the HLA B8 antigen which was inherited independently by both stepfather and stepson. cANCA is reported to be a highly specific and sensitive indicator of WGbut false-positive results do occur.4 WG has been reported in two related members of the same family presenting within two months of each other. Our finding of positive cANCA titres in two unrelated members of the same household, one of whom has WG, is further support of an environmental trigger for this disease. T G Barrett, C M

Taylor,

P Thomason

Children’s Hospital, Ladywood, Birmingham B16 8ET, UK

A

Pall, D Adu

Queen Elizabeth Hospital, Edgbaston, Birmingham

1

2

3

4

5

Jones D, Hopkinson N, Powell R. Autoantibodies in pet dogs owned by patients with systemic lupus erythematosis. Lancet 1992; 339: 1378-80. Katz P, Alling D, Haynes B, et al. Association of Wegener’s Granulomatosis with HLA-B8. Clin Immunol Immunopathol 1979; 14: 268-70. Nolle B, Specks U, Ludemann J, et al. Anticytoplasmic autoantibodies: their immunodiagnostic value in Wegener granulomatosis. Ann Intern Med 1989; 111: 28-40. Davenport A. ’False positive’ perinuclear and cytoplasmic antineutrophil cytoplasmic antibody results leading to misdiagnosis of Wegener’s granulomatosis and/or microscopic polyarteritis. Clin Nephrol 1992; 37: 124-30. Sewell R, Hamilton D. Time-associated Wegener’s granulomatosis in two members of a family. Nephrol Dial Transplant 1992; 7: 882.

standard methods.5 Unlike the other antigens, we demonstrated significant differences in poliovirus antibody titres between schedules (table). Only 1 child, in the accelerated schedule group, had antibody below detectable concentrations to type 3 poliovirus. Since the introduction of accelerated immunisation there has been an improvement in vaccine coveragewhich may balance the effect of a reduced immune response. Nevertheless, this finding emphasises the importance of ensuring that children receive a booster at pre-school age. An additional dose of OPV given at the time of measles-mumps-rubella vaccine, however, could also be used to boost antibody levels, as Moriniere suggests. This dose would require no extra visits and could be provided fairly cheaply. The benefits of such a policy must, however, be balanced against the extra risk of vaccineassociated poliomyelitis. The risk of paralysis is very small, especially after second and subsequent doses of OPV, and therefore a policy of including an extra booster of OPV is worthy of further consideration in the UK.

poliovirus with

Mary Ramsay, Norman Begg PHLS Communicable Disease Surveillance Centre, London NW9

David

Brown, Brian Megson

PHLS Virus Reference Division, London

1

CDC. Update: poliomyelitis outbreak-Netherlands, 1992. MMWR

2

Cameron SO, Carrington D, Patterson W. Could an outbreak of poliomyelitis occur in the UK? BMJ 1992; 304: 52. Department of Health. Immunisation against infectious disease. London: HM Stationary Office, 1990. Booy R, Aitken SJM, Taylor S, et al. Immunogenicity of combined diphtheria, tetanus and pertussis vaccine given at 2, 3 and 4 months versus 3, 5 and 9 months of age. Lancet 1992; 339: 507-10. White PMB, Green J. Prevalence of antibody to poliovirus in England and Wales 1984-1986. BMJ 1986; 293: 1153-55. White JM, Gillam SJ, Begg NT, Farrington CP. Vaccine coverage: recent trends and future prospects. BMJ 1992; 304: 682-84.

1992; 41: 917-18.

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Poliovirus vaccination 6

SIR-Moriniere and colleagues’ findings (June 19, p 1545) suggest that supplemental doses of poliovirus vaccine after primary immunisation in the developing world would improve levels of immunity to poliomyelitis. These workers do not suggest that such a strategy may be necessary in industrialised countries. A recent epidemic of poliomyelitis in the Netherlands’ and reports of poor levels of immunity in the UK, however, suggest that we should not be complacent.2 Since May, 1990, children in the UK have been immunised according to an accelerated schedule. Children are scheduled to receive combined diphtheria-tetanus-pertussis and oral poliovirus vaccines (OPV) at 2, 3, and 4 months of age, which are about the same ages as recommended in developing countries by the WHO expanded programme on immunisation.3 Studies comparing diphtheria, tetanus, and pertussis values after accelerated and prolonged immunisation have shown that, although immediate antibody response is lower after accelerated than after prolonged immunisation, there is little difference in antibody concentration at least 1 year after completion of primary immunisation (ref 4 and Ramsay et al, July 24, p 203). Serum samples collected from children aged 4 years who had been immunised with accelerated and prolonged schedules in 1985 were tested for neutralising antibody to

5EQ, UK

SIR-In many developing countries, there remain large gaps in immunity, especially to types 1 and 3 polioviruses, despite giving the conventional three doses of OPV. Moriniere and colleagues have recommended one supplemental dose of OPV or of inactivated poliovirus vaccine of enhanced potency (IPV) to overcome this difficulty. In countries with high (about 90%) vaccination coverage with three doses of OPV, they recommend one dose of IPV, since the antibody responses to IPV are significantly greater than to OPV. To countries wishing to adopt the above schedule, I advise caution. The seroconversion index (SI) is the average of the seroconversion rates to the 3 types of polioviruses. In developed countries the SI after three doses of OPV is over 98. In Cote d’Ivoire the SI increased from 75 to only 82 in 6-month-old infants and from 83 to only 85 in 9-month-old infants as a result of the supplemental dose of OPV. Thus wide gaps in immunity persisted even after the supplementary dose, and therefore this dose cannot be recommended as a solution to the difficulty. Countries wishing to use only OPV in a schedule will have to give five doses of OPV per infant to achieve an SI of near 90%.’ Some countries may need 1 or 2 more doses, which may be given beyond infancy, to achieve an SI over 95%.2 Alternatively, OPV should be distributed in pulses to supplement the three dose schedules and to eliminate gaps in

immunity. *ttest for differences between schedules.

Table: Poliovirus antibody titres in 21 children schedule and 30 on prolonged schedule

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accelerated

The short-term evaluation of the response to one dose of IPV is inadequate to suggest that a single supplementary dose of IPV will overcome difficulties. After giving one supplemental dose of IPV to recipients of three doses of OPV, the SI increased from 78 to 94 in 6-month-old infants and from 85 to

96 in 9-month-old infants. Although the improvement seems impressive, it deserves careful scrutiny. In infants who remained seronegative despite three doses of OPV, one dose of IPV induced seroconversion rates of 80-81"" for type 1 and 67-78% for type 3. These seroconversion rates are very similar to those obtained in unvaccinated and seronegative infants given only one dose OfOPV.3 ’ Thus, the high seroconversion rates do not seem to be due to earlier sensitisation by OPV. Apart from the theory that the immunological memory induced by one dose of IPV may perhaps be sufficient for protection, there has not been any study showing that the immunity induced by one dose of IPV is either robust or longlasting. The vaccine efficacy of one dose of IPV was only 36"" and of two doses 89% in a study in Senegal.5 With present knowledge, we have to assume that the immunity induced by one dose of IPV will gradually wane and many children will become susceptible. As with all other inactivated viral and bacterial vaccines (except polysaccharide), IPV also needs at least two doses to ensure that immunity is protective as well as longlasting.

We thank Dr Akio Yamada, National Institute of scientific advice.

College Hospital, Vellore 632 004.

India

Health, Japan,

for

Harumi Sawada Department of Epidemiology, Hokkaido

Institute of Public Health.

Sapporo 060, Japan

Shoki Yano Department of Pharmaceutical Science, Hokkaido Institute of Public Health

Yogo Oka Oka Paediatric Clinic

Takehiro

Togashi

Department of Paediatrics. Hokkaido University

Yamada A, Takeuchi K, Tanabayashi K, Hishiyama M, Takahashi Y, Sugiura A. Differentiation of the mumps vaccine strains from the wild viruses by the nucleotide sequences of the P gene. Vaccine 1990; 8:

1

553-57.

Sanger F, Nicklen S, Coulson AR. DNA sequencing with chainterminating inhibitors. Proc Natl Acad Sci USA 1977; 74: 5463-67. Nakayama T, Oka S, Komase K, et al. The relationship between the mumps vaccine strain and parotitis after vaccination. J Infect Dis 1992;

2

T Jacob John Christian Medical

reported.1.35 The Ministry of Health and Welfare in Japan decided to discontinue the use of measles, mumps, and rubella vaccine in April, 1993.

mumps monovalent vaccine has been

3

165: 186-87.

1 John TJ. Antibody response of infants in tropics to five doses of oral polio vaccine. BMJ 1976; i: 811-12. 2 John TJ. Immunisation against polioviruses in developing countries. Rev Med Virol (in press). 3 Salk J, Van Wezel AL, Stoeckel P, et al. Theoretical and practical considerations in the application of killed poliovirus vaccine for the control of paralytic poliomyelitis. Dev Biol Stand 1981; 47: 181-98. 4 Swartz TA, Ben-Porach E, Ben-Yshai Z, et al. A controlled trial with inactivated poliovaccine. Dev Biol Stand 1981; 47: 199-208. 5 Robertson SE, Traverso HP, Drucker JA, et al. Clinical efficacy of a new enhanced-potency inactivated poliovirus vaccine. Lancet 1988; i: 897-98.

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Forsey T, Mawn JA, Yates PJ, Bentley ML, Minor PD. Differentiation of vaccine and wild mumps viruses using the polymerase chain reaction and dideoxynucleotide sequencing. J Gen Virol 1990; 71: 987-90. Nishino Y. Parotid gland swelling after MMR immunization. J 1991; no 3513: 27-30 (in Japanese).

Low

Jpn Med

infectivity of tuberculosis

SIR-McFarland and

colleagues (July 10, p 112) report a for a person with pulmonary tuberculosis investigation who travelled on a transatlantic flight in December, 1992. Direct costs to the Minnesota Department of Health exceeded US$25 000 and no secondary cases were detected. In September, 1992, the department of public health in Sheffield Health Authority received notification of a case of highly-infectious pulmonary tuberculosis in a health-care worker. The diagnosis was made by a physician in Toronto, where the person had travelled 3 weeks earlier. We decided not to organise a contact investigation of fellow air travellers on a transatlantic flight for two reasons: because tuberculosis is a disease of low infectivity and prolonged, close exposure to a heavy inoculum is usually necessary for infection to take place; secondly, because such an exercise would have involved a worldwide search for over 300 fellow travellers. We had been told that a seating plan for the flight would not have been retained by the airline and therefore we would not be able to identify close casual contacts. We felt that such an exercise would be most unlikely to yield any secondary cases and would not be cost-effective. Subsequent investigation of 11 close contacts, 71 occupational contacts, and 378 possible patient contacts revealed no evidence of transmission. Two other recent contact investigations in Sheffield of 50 and 243 vulnerable casual contacts of highly infectious sources identified no secondary cases. Our experiences and those of McFarland and colleagues suggest that extensive investigations of casual contacts of highly infectious pulmonary tuberculosis may not be costeffective, even when contact has been made with those presumed to be vulnerable. Tuberculosis has rightly been given a high profile in the 1990s, but its basic epidemiology must not be forgotten when planning contact investigations.

contact

Transmission of Urabe mumps vaccine between siblings 91-year-old girl was diagnosed with acute parotitis fever, (37 TC pain and swelling in right parotid gland) on April 7, 1991. 19 days before onset, her 21-year-old sister had consulted the same paediatrician for parotid gland swelling with fever (38-5°C), which seemed due to measles, mumps, and rubella SIR-A

immunisation on Feb 26. The vaccine contained Urabe Am9 mumps strain. The 19 days between onsets suggests transmission of infectious mumps vaccine from the younger sister. To test this idea, a throat swab was taken from the patient on April 8 for isolation of the mumps virions on Vero cells. Furthermore, serum was collected on April 11 and May 11 for checking the immune response to viral antigens. Total RNA was prepared from the virus-infected Vero cells and a portion of P gene of the viral genome (223 basepairs) was reversetranscribed and amplified by polymerase chain reaction.’ The product was cloned into the SmaI site of pTZ 19R. Nucleotides in the insert were sequenced.2 The DNA sequence data can discriminate the Urabe Am9 strain from other vaccine strains such as Hoshino or Torii or the wild type of mumps virus.’ The DNA sequence of the swab-derived isolate showed A to G nucleotide substitution at nucleotide position 198, which is specific to the Urabe Am9 strain.’ The serum specimens showed more than a fourfold rise in HI titre (64 versus less than 16) to mumps virus. A similar increase in HI titre occurred in the vaccinated sister. There was no other outbreak of parotitis in the neighbourhood at or around the time of these cases. The parotid swelling of the sister was probably caused by Urabe Am9 mumps strain and then the mumps strain was transmitted to the patient. Isolation of mumps viruses from the individuals who received measles, mumps, and rubella or

Tony Baxter The Lodge, Bramwith Lane, South Bramwith, Nr Doncaster DN7 5SJ, UK

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