The possibility of an “X” factor. The first documented drug resistance of human malaria

Abstract

Sweeney A. W. 1996. The possibility of an “X” factor. The first documented drug resistance of human malaria. International Journal for Parasitology 26: 1035–1061. Malaria was the major cause of casualties among allied forces in the South West Pacific campaigns during 1942 and 1943, despite the suppressive use of quinine and later atebrin. Clinical experiments undertaken at the Land Headquarters Medical Research Unit of the Australian Army in Cairns, under the direction of Neil Hamilton Fairley, demonstrated that atebrin was able to provide complete protection against vivax and falciparum malaria. Fairley presented the experimental results to army commanders in a specially convened conference at Atherton, Queensland, in June 1944 and persuaded the army that the solution to the malaria problem was for men to take 1 tablet (100 mg) of atebrin each day with unvarying regularity while in a malarious area and for 4 weeks afterwards. Subsequently, rigid atebrin discipline was adopted and the incidence of the disease amongst Australian soldiers in New Guinea during 1945 fell to the lowest levels ever recorded to that time by non-immune troops operating for extended periods in highly endemic malarious areas. The one exception to this unprecedented achievement was during the Aitape-Wewak campaign when an epidemic of falciparum malaria developed despite the use of suppressive atebrin. An investigation of this epidemic, involving chemotherapeutic experiments of malaria derived from specially selected patients evacuated to Cairns, showed that some of the parasites were resistant to atebrin. This paper provides an account of how the epidemic was dealt with by commanders in the field; how suspected atebrin-resistant cases came to light; and how these cases were dealt with experimentally. The emergence and spread of drug-resistant falciparum malaria has since become a key factor limiting man's endeavour to combat the disease. The investigation of the Aitape-Wewak epidemic involved the first systematic field and laboratory studies on the resistance of human malaria to any drug. From the scientific point-of-view, it broke new ground and covered uncharted territory which had not been explored previously by other workers. These observations formed the solid foundations on which later advances in this field subsequently have developed.