Name: Bumduuren Tuvshintulga
Affiliation: Obihiro University of Agriculture and Veterinary Medicine, Japan
Position: Foreign researcher
Term: April 2018 to July 2018
Host researcher: Dr. Ikuo Igarashi (English / Japanese)
Circumstances of application:
Human babesiosis, a malaria-like illness, is mainly caused by Babesia microti. This parasite is transmitted by Ixodid ticks. Although human babesiosis might develop subclinical symptoms to the host, immunocompromised individuals are very susceptible to B. microti infection. Only atovaquone is considered as a potent antibabesial agent, but clinical relapses link to atovaquone resistant B. microti. Therefore, novel chemotherapy is the most important measure against wild type and atovaquone-resistant B. microti in immunocompromised patients. Recently, we evaluated an antibiotic named clofazimine against B. microti in mice. Clofazimine showed a potent growth inhibitory effect on B. microti in immunocompetent mice (BALB/c), but it was not tested yet using an immunocompromised animal infected with wild type and atovaquone-resistant B. microti. Since, I have interested on evaluation of the growth inhibitory effect of clofazimine against wild type and atovaquone-resistant B. microti in immunocompromised mice (Icr-SCID). Therefore, I applied NRCPD position to conduct the proposed experiments.
Research activity in NRCPD:
In the results of the proposed study, 20 mg/kg clofazimine and atovaquone inhibited the growth of B. microti in BALB/c and SCID mice as well. However, atovaquone-treated parasite showed recurrence in all five SCID mice on day 2 post-treatment (1st line treatment), even these atovaquone-treated parasites were not inhibited by 2nd line treatment with 20 mg/kg atovaquone. In the sequencing analysis, two variants of point mutations in amino acid sequences of atovaquone-binding cytochrome b protein were determined from atovaquone-treated parasites as compared to that from wild type and CF-treated parasites after the 2nd line treatments. Next, these atovaquone-resistant parasites were highly inhibited by the 3rd line treatment with 20 mg/kg clofazimine. On the other hand, prolonged (54 days) treatment with 20 mg/kg clofazimine completely eliminated B. microti infection in SCID mice.
After the end of July, 2018, I am going to work on research study of establishment of stably expression of green fluorescent protein in Theileria equi, under supervision of Prof. Ikuo Igarashi. After that I will return back Mongolia. In Mongolia, I had been working as a researcher in the Institute of Veterinary Medicine before I came to Japan for graduate and postgraduate research studies. Therefore, I will continue to work in the Institute of Veterinary Medicine as a researcher. In the future, I would like to work on investigation, detection and isolation of B. microti in ticks and humans as well.