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Humans host a wide variety of protozoal parasites that can be transmitted by insect vectors, directly from other mammalian reservoirs, or from one person to another. The immune system plays a crucial role in protecting against the pathological consequences of many protozoal infections. Thus, opportunistic infections with protozoa are prominent in patients with suppressed or underdeveloped immune systems, such as infants, individuals with cancer, transplant recipients, those receiving immunosuppressive drugs or extensive antibiotic therapy, and persons with advanced human immunodeficiency virus (HIV) infection. Because effective vaccines are unavailable, chemotherapy has been the only practical way to both treat infected individuals and reduce transmission. Satisfactory agents for treating important protozoal infections such as African trypanosomiasis (sleeping sickness) and chronic Chagas disease still are lacking. Many effective antiprotozoal drugs are toxic at therapeutic doses; this problem is exacerbated by increasing drug resistance (McCarthy et al., 2020). For a list of drugs and doses used to treat these diseases, see Kimberlin et al. (2018) and McCarthy et al. (2020).



AUC: area under the curve

CDC: U.S. Centers for Disease Control and Prevention

CSF: cerebrospinal fluid

DFMO: α-D,L-difluoromethylornithine

FDA: U.S. Food and Drug Administration

GI: gastrointestinal

HAT: Human African trypanosomiasis

HIV: human immunodeficiency virus

NECT: nifurtimox-eflornithine combination therapy

NTR: nitroreductase

PFOR: pyruvate-ferredoxin oxidoreductase

WBC: white blood cell

WHO: World Health Organization



Amebiasis affects about 10% of the world’s population, causing invasive disease in about 50 million people and death in about 100,000 of these annually (Stanley, 2003). Amebiasis is seen most commonly among individuals living in poverty, crowded conditions, and areas with poor sanitation. Multiple morphologically identical but genetically distinct species of Entamoeba—such as E. histolytica, E. dispar, E. bangladeshi, and E. moshkovskii—exist (Petri et al., 2020). However, the major species that requires treatment is E. histolytica, a leading cause of mortality by parasitic infection (World Health Organization [WHO], 2020a).

Humans are the only known hosts for these protozoa, which are transmitted by the fecal-oral route. Ingested E. histolytica cysts survive acidic gastric contents and transform into trophozoites that reside in the large intestine (Petri et al., 2020). The outcome of E. histolytica infection is variable; both host and parasite factors influence the course and severity of the disease (Marie and Petri, 2014). Many individuals remain asymptomatic but excrete the infectious cyst form, making them a source for further infections. In other individuals, E. histolytica trophozoites invade into the colonic mucosa with resulting colitis and bloody diarrhea (amebic dysentery). This bloody diarrhea may result from a phenomenon termed trogocytosis (“trogo” means “nibble”), where the parasite acquires required nutrients by “nibbling” on human cells (Ralston and Petri, 2011). In a small proportion of patients, E. ...

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