Mutations in Theileria Annulata Cytochrome B Gene Associated with Buparvaquone Resistance in Cattle, Egypt

Abstract

Buparvaquone is now the principle medicinal drug utilized against tropical theileriosis. The current study was conducted to determine the potential association between the resistance against buparvaquone and the occurrence of mutations in the Cytochrome b (Cyto b) gene of Theileria annulata (T. annulata) in cattle under Egyptian conditions. We sequenced the Cyto b gene of T. annulata of 6 blood samples collected from 1 responding and 5 non-responding cattle to buparvaquone treatment. The analysis revealed that two mutations occurred in codons 253 and 262 within the quinol oxidation (Qo2) drug-binding site of the five resistant isolates. Two mutations in the Qo1 site were found together in the buparvaquone sensitive isolate only. Our findings suggest that the failure of buparvaquone therapy could be attributed to the presence of single or double point mutations at the Qo2 site of T. annulata Cyto b gene.

Selection of genotypes harbouring mutations in the cytochrome b gene of Theileria annulata is associated with resistance to buparvaquone

“…The use of buparvaquone, a hydroxynaphthoquinone antiprotozoal drug akin to parvaquone and atovaquone, remains the only therapeutic option for the treatment of tropical theileriosis since the late 1980s [7]. However, several reports have indicated an increase in the number of treatment failures [8][9][10][11]13], raising the possibility of Theileria annulata developing resistance to buparvaquone. Buparvaquone resistance has been associated with mutations in the Cyto b gene [9][10][11]13].…”

“…However, several reports have indicated an increase in the number of treatment failures [8][9][10][11]13], raising the possibility of Theileria annulata developing resistance to buparvaquone. Buparvaquone resistance has been associated with mutations in the Cyto b gene [9][10][11]13]. However, it is important to note that in previous studies, the selection response of resistant parasite populations under drug pressure was not examined.…”

“…and has been used for the treatment of the disease since the 1980s [ 7 ]. However, an increase in the rate of buparvaquone treatment failure has been reported in a number of countries, including Tunisia [ 8 , 9 ], Iran [ 10 ], Sudan [ 11 , 12 ] and Egypt [ 13 ]. Both the mode of action and the mechanism of resistance to buparvaquone are still not fully known.…”

“…The majority of previous studies investigating parasite resistance to anti-theilerial drugs have been conducted using blood samples from animals that are unresponsive to treatment with buparvaquone [ 10 , 11 , 13 ]. However, it is likely that these samples comprise a mixture of sensitive and resistant parasite populations, thus making it difficult to conclusively identify which parasite genotypes, and mutations in the Cyto b gene or TaPIN1 gene, are most strongly linked to buparvaquone resistance.…”

Seroprevalence and risk factors of tropical theileriosis in smallholder asymptomatic large ruminants in Egypt

“…In Egypt, there are 8.6 million cattle and buffaloes, 80% of them are owned by smallholder farmers (22). The detection and prevalence of T. annulata in cattle have been documented in other countries (23)(24)(25), including Egypt (26)(27)(28)(29)(30). However, there is little information about the detection and epidemiology of theileriosis in water buffaloes.…”