Treatment of Uveitis with Pyrimethamine (Daraprim)

ALTHOUGH toxoplasmosis was suggested as a cause of congenital choroido- retinitis over 30 years ago, the definite importance of the organism in the acquired disease is still in doubt.The early observations of Janku (1923) and Torres (1927) attracted little attention until Wolf and Cowen (1937) isolated the parasite from a fatal human case.The frequent occurrence of retinitis in the neonatal cases has been confirmed by many authors-for example, Pinkerton and Weinman (1940) and Koch, Wolf, Cowen, and Paige (1943)-and with the development of serological methods, such as the cytoplasm modifying dye test of Sabin and Feldman (1948), it has been possible to assess the importance of the toxoplasma gondii in childhood cases of choroido-retinitis.Wilder (1952) suggested from a study of histological material that the parasite could be found in certain types of acquired adult choroiditis; her observations have been confirmed by Duke-Elder, Ashton, and Brihaye-Van Geertruyden (1953), and Jacobs and others (1954) have been able to isolate the parasite from an excised eye which had choroiditis.Unfortunately, these methods of diagnosis can only be used with eyes which have been removed, and any attempts to diagnose the disease by serological methods is complicated by the widespread occurrence of low titre antibodies in normal individuals, but attempt to assess the importance of the infection have been made, notably by Woods, Jacob, Word, and Cook (1954) and by Smith and Ashton (1955).These latter authors, from an analysis of 200 cases, found that a higher proportion of their patients showed antibodies than were present in the normal population.They con- cluded that, although titre levels were not diagnostic in individual cases, they did show a striking association between toxoplasma infection and pos- terior uveitis, and they suggested that one of the means of elucidating the exact nature of this relationship might be by means of the response to a specific chemotherapeutic agent.The most suitable agent for such a trial seemed to be pyrimethamine (Daraprimt (5-(p-chlorphenyl)-2:4-diamino-6-ethylpyrimidine), a drug first introduced for the treatment of malaria.Eyles and Coleman (1953) had first shown it to possess an antitoxoplasmic effect in experimental infections, and this had been confirmed by Summers (1953) and by Trevino, Varela,