Drug resistance in the Swedish/Norwegian BCG strain.

When a BCG strain is maintained by serial subcultures for several years, a change in its genetic properties may occur spontaneously. Such a change occurred in a strain maintained in the Norwegian State BCG Laboratory for 11 years. When received from Sweden in 1953, the strain was sensitive to the main tuberculostatics. However, in 1964, by mere chance, it was found to have become resistant to isoniazid. An examination of extant samples from the batches of freeze-dried vaccine produced during the period 1953-64 enabled the time and speed of the change to be determined. Although an alteration in drug sensitivity may not be harmful, it could cause a loss in the protective potency of a vaccine in man. It was to safeguard against this danger that the system of serial subcultures was discontinued and the seed lot system adopted, in accordance with WHO requirements.