In vitro Sensitivity of Naegleria fowleri to Qinghaosu and Dihydroqinghaosu

Abstract

Primary amebic meningoencephalitis (PAM) is a rare but rapidly fatal infection caused by Naegleria fowleri, a free-living ameba. Victims of PAM, usually previously healthy children and young adults, contract the disease by swimming in warm stagnant freshwater ponds and other bodies of water contaminated with Naegleria fowleri. The amebae reach the meninges via the nasal passages (John, 1982, Annual Review of Microbiology 36: 101-123; Martinez, 1985, Freeliving amebas: Natural history, prevention, diagnosis, pathology, and treatment of disease, CRC Press, Boca Raton, Florida, 156 p.). Although N. fowleri is susceptible to a number of antimicrobial agents in vitro (Jamieson, 1975, Journal of Clinical Pathology 28: 446-449; Duma and Finley, 1976, Antimicrobial Agents and Chemotherapy 10: 370-376; Thong et al., 1977, Lancet ii: 876), no reliable therapy exists. The only 3 well-documented survivors of the disease have all been treated with regimens that included amphotericin B (Apley et al., 1970, British Medical Journal 1: 596-599; Carter, 1972, Transactions of the Royal Society of Tropical Medicine and Hygiene 66: 193-213; Seidel et al., 1982, New England Journal of Medicine 306: 346-348). However, there have been numerous cases where prompt institution of similar therapy has not cured victims of this disease (Carter, 1972, loc. cit.; Stevens et al., 1981, Journal of Infectious Diseases 143: 193-199; Seidel, 1982, New England Journal of Medicine 306: 1296 [letter]). Qinghaosu (QHS, artemisinin) is a naturally occurring sesquiterpene lactone whose structure includes a peroxide ring (Fig. 1). QHS is extracted from Artemisia annua, a Chinese herb that has been used for centuries in traditional med-