Chapter 50: Antiparasitic Agents and Resistance

INTRODUCTION

Parasites have been with us throughout human history, and the use of natural remedies to treat these infections date to ancient times. Indigenous people of the Amazon first used quinine-containing extracts of cinchona tree bark to treat malarious patients hundreds of years ago. In China, a recipe for malaria treatment using Qinghaosu tea was recorded by Ge Hong centuries earlier. Based on what we now know about the chemistry of these natural products, both remedies had a firm biochemical basis for their effectiveness. European investigators worked on creating new (and often highly toxic) treatments in the second half of the 19th century. By 1930, chemically synthesized drugs had been marketed for the treatment of malaria, trypanosomiasis, and schistosomiasis.

In spite of the introduction and explosive increase in the number and variety of antibiotics, antiparasitic medications have lagged far behind. Most antibacterials are ineffective against parasites, which share eukaryotic characteristics of their hosts. Because of the lack of safer alternatives, chemotherapeutics synthesized in the preantibiotic era remained critical elements of the parasitologist's therapeutic armamentarium until very recently. Most required prolonged or parenteral administration, the effectiveness of many was restricted to particular disease stages, and the toxicity of a few mandated that use be limited to very severe or life-threatening conditions. With time, and at a pace much slower than that seen for the antibacterial agents, newer antiparasitics were developed that overcame many of these problems. Their numbers are still limited, and only recently have their safety and efficacy begun to match those of their antibacterial equivalents.

Antiparasitic drug use and development has been shaped to a significant degree by the concentration of parasitic diseases in impoverished areas of the world. Community-based public health measures aimed at interrupting pathogen transmission, such as provision of sanitary facilities, clean water supplies, and insecticide-treated bed nets are often beyond the means of tightly constrained local budgets. Consequently, the major burden of mitigating the impact of parasitic illnesses in endemic areas often falls on clinical officers or community health workers who, operating in remote and relatively under-resourced conditions, must examine, diagnose, and treat sick patients with whom they have only fleeting contact. Given these realities, optimal therapy for parasitic infections requires drugs that are effective in a single dose, easily administered, safe enough to be dispensed with limited medical supervision, sufficiently inexpensive to be widely used, and at low risk of accelerating drug resistance. Few such agents exist. Pharmaceutical companies, faced with the enormous costs of drug development and approval, have been reluctant to expend capital they are unlikely to recover. Public–private partnerships, cofinanced and operated by philanthropic organizations, industry, and academia, provide an exciting new model that may yield the next wave of effective treatment for parasitic infections. Until the international community provides the resources ...