Effect of inadvertent intradermal administration of high dose percutaneous BCG vaccine

BMJ 1996;312:1205 (11 May)

Papers

Effect of inadvertent intradermal administration of high dose percutaneous BCG vaccine

M M Miles, senior clinical medical officer,^a R J Shaw, consultant respiratory physician ^b

^a Parkside Health (Community Trust), London W9 3XZ, ^b Chest and Allergy Clinic, St Mary's Hospital, London W2 1NY

Correspondence to: Dr Shaw.

In the United Kingdom it is recommended that all children receiveBCG vaccination to prevent development of tuberculosis.¹ ² Thestandard route of administration is intradermal. In neonatesa 10 times more potent percutaneous preparation is used, a smallvolume being injected to a depth of 2 mm with a modified Heafgun. The two preparations have similar packaging and labellingand so may easily be confused.³ We report the outcome of inadvertentintradermal administration of the stronger percutaneous productand define the relation between the development of skin lesionsand the dose of vaccine.

Subjects, methods, and results

Thirty two school children aged 11-14 received 0.1 ml of BCGvaccine intradermally at a routine school immunisation session.Nineteen received the preparation for percutaneous administration,which contains 50-250 million colony forming units per ml. Thirteenreceived the correct preparation, which contains 8-26 millioncolony forming units per ml (Evans Medical, Leatherhead, England).The error occurred because of the similar packaging and labellingof the two products. All parents and children were informedof the error and all agreed to a period of close observation.All observations were performed by the same observer (MMM).The study was not blind since a component of the consultationwas to discuss any concerns with children and parents.

The area of induration increased progressively and was significantlygreater in the group who had received the percutaneous vaccineintradermally (fig 1). Mean diameters were 0.96 cm (range 0.8-1.3,P<0.02 by Student's t test) at two weeks, 1.15 cm (0.9-1.5,P<0.01) at three weeks, and 1.23 cm (1.0-1.6, P<0.01)at six weeks; the mean diameter had decreased to 0.91 (0.6-2.2)cm by 15 weeks. By contrast, the mean diameter of the indurationin those receiving the correct intradermal vaccine was 0.83cm (0.7-0.9) at two weeks, 0.83 cm (0.6-1.1) at three weeks,and 0.77 cm (0.5-1.1) at six weeks.

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Fig1--Mean (SE) diameters of skin lesions after intradermal BCGvaccine and percutaneous vaccine given intradermally

The sequence of symptoms was itchiness, soreness, and discharge.These were similar in both groups, although discharge was morecommon at six weeks in the group given the percutaneous vaccine(nine out of 15 children v one out of 10 children). Ten of the15 children given the percutaneous vaccine were examined at28 weeks. They complained of no symptoms, and mature scars hadformed (mean diameter 1.2 cm (range 0.8-2.0)).

Comment

This study emphasises the requirement for clear packaging andlabelling of drugs. If subjects inadvertently receive the percutaneousBCG vaccine intradermally they may, however, be reassured thatthe lesion will resolve over a few months without treatment.Although the lesions were sometimes painful, the indurationwas larger, and discharge was more common after six weeks whenthe high dose preparation was given intradermally. The lesionshad started to resolve at 15 weeks.

The results also suggest a clear dose-response relation in vivobetween the size of the inflammatory response and the dose ofvaccine. We do not know whether there is a relation betweenthe size of the inflammatory response and the protective effectof BCG or the size of the scar.

Funding: Parkside Health (Community Trust).

Conflict of interest: None.