Studies of Adenovirus Type III Infection Treated with Methisazone and Trifluorothymidine ∗

Abstract

Adenovirus infection of man is common and some adenoviruses have been implicated as causative factors of cancer in animals. Some types of adenovirus produce sufficiently mild infections, however, so that volunteer studies with these agents appear relatively simple and risk free (1,2).

The testing of drugs on randomly occurring diseases is difficult, since a definite clinical diagnosis may not be possible until the disease is past. In addition, the variability of randomly occurring cases, except in very large epidemics, would require that very large numbers of people be tested with any new drug which is to be evaluated in order for such studies to be meaningful. Volunteer studies of induced infection appeared safer and more practical than the study of random cases as a method of drug evaluation, and adenovirus type III, passed only in human amnion cells, and isolated from a very mild local infection seemed an ideal agent to provide this test system.

Two drugs possess in vitro activity against adenovirus and seem reasonably safe for use in man. Methislazone (N-methylisatin-B-thiosemicarbazone) is of proven value in a variety of pox virus infections of man, clearly preventing smallpox in contacts and probably providing therapeutic benefit in the treatment of vaccinia gangrenosa (3-13). Recent studies of this drug in tissue culture indicate that it has some in vitro effect in suppressing adenovirus multiplication (14), and a broad experience with thousands of subjects provides detailed information as to its safety and toxicity (3-6). Trifluorothymidine (F₃TdR) is a potent and nontoxic antimetabolite of proven benefit in the experimental and clinical treatmcnt of herpes simplex infection in the eye when administered locally as drops (15,16). Since it suppresses and interferes with virus DNA synthesis, and drugs of this class have been shown to have activity against adenovirus in tissue culture (14) the topical administration of trifluorothymidine also seemed of possible clinical value.