Oral administration of azithromycin ameliorates trypanosomosis in Trypanosoma congolense-infected mice

Abstract

Animal trypanosomosis is a devastating parasitic disease that is of economic importance to livestock production. The infection includes animal African trypanosomosis, surra, and dourine. The treatment is based solely on few compounds that were discovered decades ago and which are associated with severe toxicity. Furthermore, it is likely that the parasite has developed resistance towards them. Thus, there is an urgent need for new, accessible, and less toxic drugs. Azithromycin is an antibiotic with documented efficacy against Toxoplasma, Babesia, and Plasmodium. The current study investigated its effects against animal trypanosomes. An in vitro system was used to determine the trypanocidal effects of azithromycin against Trypanosoma congolense, Trypanosoma brucei brucei, and Trypanosoma evansi, and cytotoxicity in Madin-Darby bovine kidney (MDBK) and NIH 3T3 cells. Furthermore, the trypanocidal effects of azithromycin were investigated in T. congolense-infected mice. In vitro, azithromycin had an IC of 0.19 ± 0.17; 3.69 ± 2.26; 1.81 ± 1.82 μg/mL against T. congolense, T. b. brucei, and T. evansi, respectively. No cytotoxic effects were observed in MDBK and NIH 3T3 cells. The efficacy of orally administered azithromycin was investigated in short-term and long-term treatment protocols. Although the short-term treatment protocol showed no curative effects, the survival rate of the mice was significantly prolonged (p < 0.001) in comparison to the control group. The long-term treatment yielded satisfying curative effects with doses of 300 and 400 mg/kg achieving 80 and 100% survival, respectively. In conclusion, long-term oral azithromycin treatment has trypanocidal effects against T. congolense.

Metal nanoparticles restrict the growth of protozoan parasites

“…Parasite culture conditions were as previously reported [8]. Briefly, Trypanosoma congolense IL3000, a savannah-type strain isolated near the Kenya/Tanzania border in 1966, Trypanosoma evansi Tansui and T. b. brucei GUTat 3.1 were maintained in the bloodstream form (BSF) in HMI-9 medium [30] and propagated at 33 C (T. congolense) and 37 C (T. evansi and T. b. brucei) in the air.…”

“…The in vitro evaluation for anti-Trypanosoma activity was performed as previously described [8]. Briefly, T. congolense, T. b. brucei and T. evansi were seeded at 1 Â 10 5 , 1 Â 10 4 and 2 Â 10 4 cells/mL, respectively, in a Nunc TM 96-well optical bottom plate (Thermo Fisher Scientific, Pittsburgh, PA) and exposed to various concentrations of nanoparticles (0 to 10 lg/mL).…”

“…Trypanosoma infection is fatal if left untreated either in humans or animals. Chemotherapy is a major means of controlling the infection; however, the available treatment options have various shortcomings including limited efficacy, toxicity and the emergence of resistant strains of trypanosomes [2,8]. Melarsoprol, one of the few drugs effective against the second stage of the disease, is reported to cause encephalopathy in 10-15% of patients, and approximately 40% of these cases are fatal [9,10].…”

Therapeutic potential of the methanolic extract of Lepidium sativum seeds on mice infected with Trypanosoma evansi

“…Animal trypanosomiasis is catastrophic parasitic protozoan disease that is caused by Trypanosoma evansi , the most common and widespread trypanosome in domestic and wild animals (Desquesnes et al, 2013, Molefe et al, 2017). Trypanosoma evansi was the first mammalian trypanosome in the world to be described (by Evans in 1880); originally in the blood of camels and equines and later in the blood of a wide range of other hosts (Desquesnes et al, 2013).…”

“…Most of these, however, do not provide total control of the infection and are associated with high rates of disease recurrence, severe toxicity, severe side effects and sometimes mortality (Da Silva et al, 2008, Baldissera et al, 2017). In addition, the parasite has probably developed resistance towards these longstanding treatments (Steverding, 2010, Molefe et al, 2017). There is therefore an urgent need for new compounds as alternative and less toxic treatments.…”