Name: Leonardo J. M. Carvalho
Affiliation: Oswaldo Cruz Foundation (Fiocruz), Rio de Janeiro, Brazil
Position: Professor
Term: May to July 2019
Host researcher: Dr. Naoaki Yokoyama (English / Japanese)
Circumstances of application:
Leonardo Carvalho was a JICA kenshuin in the first longterm course (ObiCAP course) offered by NRCPD in 1995-1996, working under the guidance of Profs Hideyuki Nagasawa and Ikuo Igarashi on the host immune response to Neospora caninum. During the XIX ICTMM in Brisbane in 2016, he met with Igarashi sensei, who suggested him to apply for the NRCPD foreigner visiting researcher program, which he did in 2019 having as host researcher Yokoyama sensei, leader of the Babesia group.
Babesiosis represents a veterinary and medical threat, and there is an increasing need for novel therapeutic drugs to effectively target this diverse group of parasites. There is particular interest on this subject in Brazil, which hosts the largest commercial cattle herd in the World (over 200 million heads) and it is the largest World exporter of cattle meat. Artemisinin-based combination therapies (ACT) have been successfully implemented worldwide for malaria, a human disease caused by a related apicomplexan parasite, Plasmodium. We asked whether ACTs would be effective against Babesia in vitro and in vivo. Therefore, the objective of this project was to evaluate the chemosensitivity in vitro of Babesia bovis, and in vivo of B. microti, to the antimalarial drugs mefloquine, tafenoquine, primaquine, lumefantrine and methylene blue, alone or in combination with artesunate.
Research activity in NRCPD:
Four different antimalarial drugs (artesunate, mefloquine, tafenoquine, primaquine) showed in vitro activity against Babesia bovis in the range of 9-30 µM, whereas methylene blue showed the most potent activity (0.2 µM) and lumefantrine showed no activity up to 200 µM. When combined with artesunate, tafenoquine and primaquine showed improved activity (2-3-fold increase) and mefloquine had a striking 20-fold increase in activity. However, mefloquine (50 mg/kg), whether alone or in combination with artesunate, showed no activity against B. microti in vivo. On the other hand, tafenoquine (10 mg/kg, base), combined or not with artesunate, induced rapid clearance of parasites by microscopy after three doses. However, microscopy-negative mice remained PCR-positive for more than two weeks after the last tafenoquine dose. Tafenoquine, and most likely other 8-aminoquinoline compounds, are a promising class of chemicals to be further developed for the treatment of babesiosis.
Future prospects:
A manuscript is being prepared to be submitted to a parasitology journal.
The work performed during the three months of the visiting researcher program set the basis for a potential collaboration between NRCPD and Fiocruz, which is under discussion. For this purpose, Yokoyama sensei will be visiting Fiocruz still in 2019.