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 infants, individuals with cancer, transplant recipients, those receiving immunosuppressive drugs or extensive antibiotic therapy, and persons with advanced 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. For a list of drugs and doses used to treat these diseases see Drugs for Parasitic Infections (2013).
ADME: absorption, distribution, metabolism, excretion
CDC: Centers for Disease Control and Prevention
CNS: central nervous system
CSF: cerebrospinal fluid
FDA: Food and Drug Administration
HAART: highly active antiretroviral therapy
HIV: human immunodeficiency virus
IND: investigational new drug
NADH: reduced (hydrogenated) nicotinamide adenine dinucleotide
NECT: nifurtimox-eflornithine combination therapy
PCP: Pneumocystis carini
PCR: polymerase chain reaction
PFOR: pyruvate-ferredoxin oxidoreductase
PJP: Pneumocystis jiroveci
WHO: World Health Organization
PROTOZOAL INFECTIONS OF HUMANS
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 (Petri 2014). Three morphologically identical but genetically distinct species of Entamoeba—E. histolytica, E. dispar, and E. moshkovskii—exist (Petri, 2014). In addition, Entamoeba bangladeshi was recently discovered in diarrheal samples and may be pathogenic (Royer et al., 2012). However, the major species that definitely requires treatment is E. histolytica, the third-leading cause of mortality by parasitic infection.
Humans are the only known hosts for these protozoa, which are transmitted by the fecal-oral route. Ingested E. histolytica cysts survive acid gastric contents and transform into trophozoites that reside in the large intestine (Petri, 2014). The outcome of E. histolytica infection is variable. 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). In a small proportion of patients, E. histolytica trophozoites invade through the colonic mucosa, reach the portal circulation, and travel to the liver, where they establish an amebic liver abscess (Haque et al., 2003). Both host and parasite factors influence the course and severity of the disease (Marie and ...