dIn this study, we introduce a multilocus sequence typing (MLST) scheme, comprised of seven single-copy housekeeping genes, to genetically characterize Trichomonas vaginalis. Sixty-eight historical and recent isolates of T. vaginalis were sampled from the American Type Culture Collection and female patients at area health care facilities, respectively, to assess the usefulness of this typing method. Forty-three polymorphic nucleotide sites, 51 different alleles, and 60 sequence types were distinguished among the 68 isolates, revealing a diverse T. vaginalis population. Moreover, this discriminatory MLST scheme retains the ability to identify epidemiologically linked isolates such as those collected from sexual partners. Population genetic and phylogenetic analyses determined that T. vaginalis population structure is strongly influenced by recombination and is composed of two separate populations that may be nonclonal. MLST is useful for investigating the epidemiology, genetic diversity, and population structure of T. vaginalis.

Artemisinin compounds inhibit in vitro growth of cultured Trypanosoma cruzi and Trypanosoma brucei rhodesiense at concentrations in the low micromolar range. Artemisinin also inhibits calcium-dependent ATPase activity in T. cruzi membranes, suggesting a mode of action via membrane pumps. Artemisinins merit further investigation as chemotherapeutic options for these pathogens.Diseases caused by insect-borne trypanosomatid parasites are a significant and neglected public health problem worldwide. Chagas' disease, caused by infection with Trypanosoma cruzi, is a major agent of disease in Latin America, with 16 to 18 million infected individuals and an annual death toll of 50,000. It is also an emerging problem in the United States, where an estimated 100,000 infected individuals reside (16). Trypanosoma brucei subspp., the causative agents of human African trypanosomiasis or "sleeping sickness," infect 50,000 annually. Approximately 300,000 to 500,000 people have trypanosomiasis and will die if not treated (18). Current therapeutic options for Trypanosoma infections, benznidazole and nifurtimox for Chagas' disease treatment and suramin, pentamidine, melarsoprol, and eflornithine for treatment of sleeping sickness, are far from ideal (8,17). These drugs all suffer from one or more disadvantages-high cost, parenteral administration, long treatment courses (months), high clinical failure rates, or parasite drug resistance-and they elicit multiple, serious, and potentially fatal toxic side effects. New therapeutic alternatives are obviously desirable for treatment of these lifethreatening infections.Artemisinin is a sesquiterpene lactone isolated from Artemisia annua, an annual herb that has been used in traditional Chinese medicine for over 2,000 years (21). Artemisinin is hydrophobic, passes biological membranes easily, and is a potent antimalarial with effective 50% inhibitory concentrations (IC 50 values) ranging from 4.2 to 16.2 nM for different derivatives. Oral, parenteral, or rectal dosages achieve micromolar plasma concentrations (22). Artemisinin derivatives have been used to treat malaria cases around the world, and their extensive usage has not been associated with any significant toxicity (19). Artemisinin generates bioreactive radicals capable of intracellular damage, depolarizes mitochondrial membrane potential in yeast, and inhibits the Plasmodium falciparum endoplasmic reticulum calcium pump (SERCA), and artemisininresistant P. falciparum contains SERCA mutations (9,13,14,(20)(21)(22).Artemisinin compounds also show efficacy against Leishmania spp. of trypanosomatid parasites, achieving 50% killing at 750 nM for Leishmania major promastigotes, at 3 to 30 M for intracellular amastigote stages in macrophages, and at 1.4 to 382.9 M against Leishmania infantum promastigotes (1, 23). Artemether treatment (50 mg/kg of body weight/day) of footpad lesions in mice, by oral, intralesional, intramuscular, or intravenous administration, significantly reduces lesion size and L. major parasite numbers (23). Oral dih...

Amastigotes (tissue forms) of Leishmania donovani isolated from infected hamster spleens carried out several physiological activities (respiration, catabolism of energy substrates, and incorporation of precursors into macromolecules) optimally at pH 4.0 to 5.5. All metabolic activities that were examined decreased sharply above the optimal pH. Promastigotes (culture forms), on the other hand, carried out the same metabolic activities optimally at or near neutral pH. This adaptation to an acid environment may account in part for the unusual ability of amastigotes to survive and multiply within the acidic environment of the phagolysosomes in vivo.

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