Point mutations in the Theileria annulata cytochrome b gene is associated with buparvaquone treatment failure

In Vitro Screening of the Open-Source Medicines for Malaria Venture Malaria Box Reveals Novel Compounds with Profound Activities against Theileria annulata Schizonts

“…More recently, the first cases of treatment failures due to resistant parasite populations were reported (13). These treatment failures were shown to be associated with mutations in the Theileria cytochrome b gene encoding the ubiquinone reductase of the respiratory chain (14,15). Another potential target of BPQ is Theileria prolyl isomerase (TaPIN1), since mutations in the gene were demonstrated in BPQ-resistant cell lines (16).…”

Isolation, cloning and sequence analysis of lactate dehydrogenase gene from Theileria annulata may lead to design of new antitheilerial drugs

“…It was reported that buparvaquone and parvaquone have been the only available drugs for the treatment of tropical theileriosis to date and possibly for several more years (Mhadhbi et al 2010). The second case was reported from Fars Province, southern Iran (Sharifiyazdi et al 2012). In this study seven out of eight animals were reported to have died despite single (five cases) and double (two cases) injection of buparvaquone (2.5 mg/kg) as a result of the occurrence of resistance to buparvaquone treatment.…”

“…Parvaquone (McHardy and Morgan, 1985) and buparvaquone have been effectively used since their discovery in the treat-ment of Theileria infections in cattle in subsequent years without the development of any resistance to these drugs. However, resistance to buparvaquone has been recently reported for the first time in the literature (Mhadhbi et al 2010) and this has very recently been followed by a new case (Sharifiyazdi et al 2012). The first study was conducted in a farm located in Tunisia.…”

“…In this study seven out of eight animals were reported to have died despite single (five cases) and double (two cases) injection of buparvaquone (2.5 mg/kg) as a result of the occurrence of resistance to buparvaquone treatment. Resistance was explained by point mutations in the mitochondrial cytochrome b gene in the parasite (Sharifiyazdi et al 2012). This emphasizes the need for the design of new anti-theilerial drugs that will have different modes of action then the currently available drugs.…”

Molecular Modeling, Structural Analysis and Evaluation of 1-Deoxy-D-Xylulose-5-Phosphate Reductoisomerase (DXR) as a Putative Drug Target For Theileria Parva

“…On the other hand, the factors limiting the wide use of this treatment are the high costs of the acaricides that are utilized for tick control (8) and the rapid resistance development against a wide variety of these (9,10), as well as the absence of an efficient vaccine against T. parva that is proven to be safe (4). Moreover, in 2010, resistance to buparvaquone has been observed as well (11); this was followed by a new report in the year 2012 caused by point mutation mitochondrial cytochrome b gene in the parasite (12,13). Considering these factors, the development of an efficient and affordable anti-theilerial agent in a different mode of action that can be used safely is vital.…”