INTRODUCTION

Humans have been plagued by malarial parasites for centuries and reference to maladies associated with malaria may be found in antiquities over the past 5,000 years (1). For much of this time the cause of the intermittent chills and fevers, splenomegaly, and mortality associated with malaria was unknown. However, with consistent identification of the brownish black pigment (hemozoin) found during autopsies of malaria victims from the early 1700s on, scientific discovery methodically began to dissect malarial parasites from the various secret hiding places of their complex life cycle. Alphonse Laveran first observed the tiny ring-stage parasites of the malaria blood-stage infection in 1880 (1), and Ronald Ross would reveal that the female anopheline mosquito was responsible for malaria transmission in 1897 (1). During the late 1800s and ending in 1922 individual discoveries illustrated that malaria in humans was caused by four distinct species of Plasmodium – P. falciparum, P. vivax, P. malariae, and P. ovale (2), and that fevers resulting from infection by these parasites would soon find their way into successful, albeit unorthodox, treatment of neurosyphilis.

The era of malaria therapy, launched in earnest by Julius Wagner von Jauregg in 1917 (3), paved the way for important advances in malaria research as observations resulting from thousands of treated patients provided the opportunity to study early stages of infection, development of immunity and characteristics of the immune response, and the efficacy of various antimalarial drugs (4).