SSCP analysis of the P2 purine transporter TcoAT1 gene of Trypanosoma congolense leads to a simple PCR-RFLP test allowing the rapid identification of diminazene resistant stocks

Delespaux, V.; Chitanga, Simbarashe; Geysen, Dirk; Goethals, A.; Bossche, Peter Van Den; Geerts, S.

doi:10.1016/j.actatropica.2006.10.001

Cited by 43 publications

(45 citation statements)

References 21 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…This suggests that the purine salvage system based on P2 transport is also involved in the development of resistance to DA in this species. However, contrary to what is observed for the putative ABC transporter involved in ISM resistance [24], heterozygous strains were not observed (N=26 homozygous) [45]. To elucidate the recessive or dominant character of the mutation, the sensitivity to DA of a strain that is heterozygous for the mutation should be characterized.…”

Section: Resistance To Diminazene Aceturate By a P2-type Purine Transmentioning

confidence: 88%

“…A putative P2-type purine transporter TcoAT1 in T. congolense was identified by reciprocal blasting of the TbAT1 gene of T. brucei and a conserved Val306 to Ile306 permutation in this gene was observed in T. congolense strains that show resistance to DA [45]. This suggests that the purine salvage system based on P2 transport is also involved in the development of resistance to DA in this species.…”

Section: Resistance To Diminazene Aceturate By a P2-type Purine Transmentioning

confidence: 97%

“…Recently, the analysis of the P2-type purine transporter TcoAT1 of T. congolense by SSCP led to a simple BclI-PCR-RFLP test enabling the rapid identification of DA-resistant stocks [45]. This test is based on a single nucleotide permutation (G to A) observed in the DA-resistant strains that can be easily detected through BclI restriction of the amplicon.…”

Section: Pcr-rflp and Allele-specific Pcr For The Detection Of Da Resmentioning

confidence: 99%

“…BclI-PCR-RFLP was validated using 26 T. congolense strains [45]. A correct identification was obtained with 14 strains that were identified as sensitive at 20 mg kg −1 of DA, with nine being identified as resistant at 20 mg kg −1 in the standardized mouse test.…”

Section: Correlation With In Vivo Testsmentioning

confidence: 99%

See 3 more Smart Citations

Molecular tools for the rapid detection of drug resistance in animal trypanosomes

Delespaux

Geysen

Bossche

et al. 2008

Trends in Parasitology

104

View full text Add to dashboard Cite

There are currently 17 African countries in which animal trypanocidal drug resistance has been reported. Largescale surveys were carried out in only ten of them. The lack of baseline information is mainly due to the fact that the methods currently available for the detection of drug resistance are laborious, expensive and time consuming. In this review the mechanisms involved in resistance to isometamidium and diminazene will be discussed, together with some new molecular detection tools that have been developed recently enabling faster diagnosis of drug resistance than conventional laboratory or field tests. African animal trypanosomiasis and drug resistanceTsetse fly-transmitted trypanosomiasis is an important constraint to livestock development in sub-Saharan Africa with estimated annual losses owing to the direct and indirect effects of the disease running into billions of dollars. Approximately 9 million km 2 of sub-Saharan Africa, representing about one-third of the total land, is affected by tsetse flies [1]. Within this region, some 46-62 million head of cattle and other livestock species are at risk of the disease [2]. Trypanosomiasis is controlled either by controlling the vector or by controlling the parasite, or a combination of both. Over the years, a large arsenal of vector-control tools has been developed. Nevertheless, the control of animal trypanosomiasis in often poor rural communities has and will continue to rely heavily on the use of trypanocidal drugs. This is not surprising considering the private nature (i.e. the easy, individual, nonconcerted use) of such treatments and the difficulties in maintaining cleared areas in the absence of barriers to re-invasion of tsetse flies. Only a small group of chemoprophylactic and chemotherapeutic trypanocidal compounds are currently in use and new compounds are unlikely to become available in the near future [3]. Geerts and Holmes [4] estimated that in Africa 35 million doses of veterinary trypanocidal drugs are administered each year with isometamidium chloride (ISM), ethidium bromide (EtBr) and diminazene aceturate (DA) estimated to represent 40%, 26% and 33%, respectively, of the total trypanocidal drug market by value [5]. ISM is mainly used as a prophylactic drug and provides on average 3 months' protection (2-22 weeks) against trypanosome infection. DA has only therapeutic properties and EtBr has limited prophylactic properties and is mainly used as a therapeutic agent [6]. Considering the well known mutagenic properties of EtBr, this drug should ideally be removed from the drug market, but in practice it is still widely used in many countries. Removing this drug from the market would not jeopardize the treatment of animal trypanosomiasis because it can be replaced either by DA for curative purposes or by ISM for prophylactic purposes. When trypanosomes are resistant to ISM, EtBr will be ineffective as cross-resistance is observed between the two drugs [7]. As a result of inappropriate trypanocidal drug-use practices, there is growing co...

show abstract

Section: Resistance To Diminazene Aceturate By a P2-type Purine Transmentioning

confidence: 88%

Section: Resistance To Diminazene Aceturate By a P2-type Purine Transmentioning

confidence: 97%

Section: Pcr-rflp and Allele-specific Pcr For The Detection Of Da Resmentioning

confidence: 99%

Section: Correlation With In Vivo Testsmentioning

confidence: 99%

See 2 more Smart Citations

Molecular tools for the rapid detection of drug resistance in animal trypanosomes

Delespaux

Geysen

Bossche

et al. 2008

Trends in Parasitology

104

View full text Add to dashboard Cite

show abstract

“…The availability of a reliable and sensitive molecular tool that allows the rapid screening for diminazene aceturate (DA) resistance (Delespaux et al, 2006) and the availability of a large number of T. congolense strains isolated from cattle in 1996 and 2003 in the same geographic area of Eastern Zambia made it possible to determine the spread of DA resistance in a geographically confined area during this period.…”

Section: Introductionmentioning

confidence: 99%