The compound quinine was first extracted from cinchona bark in Paris in the 1820s by Pierre Joseph Pelletier and Joseph Bienaime Caventou. Cinchona bark was first exploited for its effectiveness in treating fever by the Jesuits in Peru in the 17th century (3).

Hans Andersag first synthesized Resochin, later called chloroquine, at the Bayer Company in Eberfeld, Germany in 1934. The synthesis resulted from the structural analysis of the quinine molecule and the localization of the antimalarial activity at the level of the oxyquinolinebenzene nucleus (9). It was initially rejected as being too toxic. Later, studies in the U.S. and Australia showed it to be the most effective schizontocide and the least toxic of 4-aminoquinoline derivatives against P. falciparum, vivax, and malaraie (8). Then in 1945, Chlorquine then became the standard recommendation for use in the suppression and treatment of malaria by the World Health Organization (8). The drug was mass distributed in salt as well as in tablet form in Brazil and other areas with high prevalences of malaria. USAID purchased over 137 million tablets for distribution in the early 1960s.

Resistance of the Plasmodium to chloroquine was first suspected by Ray and Sharma in 1956, approximately 11 years after its introduction. The first confirmed cases were in two Americans who returned from Colombia with chloroquine resistant P. falciparum strains. Their strains did respond to treatment with pyrimethamine and quinine. Shortly thereafter, the U.S. Army began to see rising incidence of malaria among troops in Vietnam who were being prophylaxed with chloroquine. Resistance was becoming a serious issue, raising the distubing possibility of reintroduction of malaria into countries where it had been eradicated decades before (8).