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Cross-resistance associated with development of resistance to isometamidium in a clone of Trypanosoma congolense
A S Peregrine1, M A Gray, S K Moloo
1International Livestock Research Institute, Nairobi, Kenya. aperegrine@ovcnet.uoguelph.ca
Abstract:
Resistance to isometamidium was increased 94-fold in a clone of Trypanosoma congolense (clone IL 1180) by repeated subcurative treatment of infected mice for 11 months. This was associated with 3.4-, 33-, and 4.2-fold increases in resistance to diminazene, homidium, and quinapyramine, respectively. Both T. congolense IL 1180 and the resistant derivative were able to undergo cyclical development in Glossina morsitans centralis tsetse flies, producing hypopharyngeal infection rates of 40.0 and 39.8%, respectively.
Insights
Repeated treatment with isometamidium significantly increased resistance in Trypanosoma congolense, a parasite causing significant livestock disease. This drug resistance also extended to other trypanocidal drugs, impacting treatment options.
Area of Science:
- Veterinary Parasitology
- Drug Resistance Studies
- Molecular Biology
Background:
- Trypanosomiasis remains a major threat to livestock in Africa.
- Isometamidium is a key drug for treating trypanosomiasis.
- Emergence of drug resistance in Trypanosoma parasites is a significant concern for disease control.
Purpose of the Study:
- To investigate the development of resistance to isometamidium in Trypanosoma congolense.
- To assess cross-resistance to other trypanocidal drugs.
- To evaluate the impact of drug resistance on parasite infectivity in tsetse flies.
Main Methods:
- In vivo selection of Trypanosoma congolense (clone IL 1180) through repeated subcurative treatment of infected mice over 11 months.
- Phenotypic drug resistance assays for isometamidium, diminazene, homidium, and quinapyramine.
- Cyclical development and transmission studies in Glossina morsitans centralis tsetse flies.
Main Results:
- A 94-fold increase in resistance to isometamidium was achieved in the selected T. congolense clone.
- Associated increases in resistance were observed for diminazene (3.4-fold), homidium (33-fold), and quinapyramine (4.2-fold).
- Both the original and resistant clones maintained the ability to infect tsetse flies, with similar hypopharyngeal infection rates (40.0% and 39.8%).
Conclusions:
- Subcurative isometamidium treatment can rapidly induce high-level resistance in Trypanosoma congolense.
- This resistance is associated with cross-resistance to multiple trypanocidal drugs.
- Drug-resistant Trypanosoma congolense can still be efficiently transmitted by tsetse flies, posing a significant challenge for trypanosomiasis control.