Dana G Mordue1, Gary P Wormser2. 1. Department of Microbiology and Immunology, New York Medical College, Valhalla. 2. Division of Infectious Diseases, New York Medical College, Valhalla.
Abstract
BACKGROUND: Tafenoquine (TQ) was recently approved by the US Food and Drug Administration for prophylaxis of malaria and, in addition, for eradication of the hepatic phase of the relevant Plasmodium species. In this study, we evaluated the efficacy of TQ for treatment of Babesia microti infection in mice with severe combined immunodeficiency (SCID). METHODS: SCID mice were infected with 1.1-1.5 × 108 B. microti-infected red blood cells by intraperitoneal injection. On day 3 or 4 postinfection, when parasitemia levels typically exceeded 10%, mice were treated with TQ vs vehicle alone, both administered by oral gavage. RESULTS: A single dose of TQ completely eliminated detectable parasites, with a >90% reduction in the level of parasitemia within just 4 days. Before elimination, a conspicuous phenotypic change in the parasite was observed. Although parasitologic cure was not achieved, there was no evidence for the development of drug resistance. CONCLUSIONS: This study suggests that TQ may be a highly useful drug to treat B. microti infection in patients. If further animal studies establish that a marked reduction in B. microti parasitemia can be reliably achieved with peak blood levels of TQ known to be well tolerated in humans, a clinical trial in patients should be considered.
BACKGROUND:Tafenoquine (TQ) was recently approved by the US Food and Drug Administration for prophylaxis of malaria and, in addition, for eradication of the hepatic phase of the relevant Plasmodium species. In this study, we evaluated the efficacy of TQ for treatment of Babesia microti infection in mice with severe combined immunodeficiency (SCID). METHODS:SCIDmice were infected with 1.1-1.5 × 108 B. microti-infected red blood cells by intraperitoneal injection. On day 3 or 4 postinfection, when parasitemia levels typically exceeded 10%, mice were treated with TQ vs vehicle alone, both administered by oral gavage. RESULTS: A single dose of TQ completely eliminated detectable parasites, with a >90% reduction in the level of parasitemia within just 4 days. Before elimination, a conspicuous phenotypic change in the parasite was observed. Although parasitologic cure was not achieved, there was no evidence for the development of drug resistance. CONCLUSIONS: This study suggests that TQ may be a highly useful drug to treat B. microti infection in patients. If further animal studies establish that a marked reduction in B. microti parasitemia can be reliably achieved with peak blood levels of TQ known to be well tolerated in humans, a clinical trial in patients should be considered.
Authors: Chau Vuong; Lisa H Xie; Brittney M J Potter; Jing Zhang; Ping Zhang; Dehui Duan; Christina K Nolan; Richard J Sciotti; Victor E Zottig; N P Dhammika Nanayakkara; Babu L Tekwani; Larry A Walker; Philip L Smith; Robert M Paris; Lisa T Read; Qigui Li; Brandon S Pybus; Jason C Sousa; Gregory A Reichard; Bryan Smith; Sean R Marcsisin Journal: Antimicrob Agents Chemother Date: 2015-04-13 Impact factor: 5.191
Authors: Gary P Wormser; Raymond J Dattwyler; Eugene D Shapiro; John J Halperin; Allen C Steere; Mark S Klempner; Peter J Krause; Johan S Bakken; Franc Strle; Gerold Stanek; Linda Bockenstedt; Durland Fish; J Stephen Dumler; Robert B Nadelman Journal: Clin Infect Dis Date: 2006-10-02 Impact factor: 9.079
Authors: Luis Carvalho; Juan Román Luque-Ortega; José Ignacio Manzano; Santiago Castanys; Luis Rivas; Francisco Gamarro Journal: Antimicrob Agents Chemother Date: 2010-09-13 Impact factor: 5.191
Authors: P J Krause; T Lepore; V K Sikand; J Gadbaw; G Burke; S R Telford; P Brassard; D Pearl; J Azlanzadeh; D Christianson; D McGrath; A Spielman Journal: N Engl J Med Date: 2000-11-16 Impact factor: 91.245
Authors: Erin E Milner; Jonathan Berman; Diana Caridha; Samuel P Dickson; Mark Hickman; Patricia J Lee; Sean R Marcsisin; Lisa T Read; Norma Roncal; Brian A Vesely; Lisa H Xie; Jing Zhang; Ping Zhang; Qigui Li Journal: Malar J Date: 2016-12-07 Impact factor: 2.979