Chemosensitization of Trypanosoma congolense strains resistant to isometamidium chloride by tetracyclines and enrofloxacin

Autor: Niko Speybroeck, Hervé Sèna Vitouley, Tanguy Marcotty, Stanny Geerts, Dirk Berkvens, V. Delespaux, Peter Van den Bossche, Krisna Roy
Přispěvatelé: UCL - SSS/IRSS - Institut de recherche santé et société
Rok vydání: 2010
Předmět:
Veterinary medicine
EFFLUX
Trypanosoma congolense
Antibiotics
CATTLE
Drug Resistance
Drug resistance
Parasitemia
INCREASE
chemistry.chemical_compound
Mice
MULTIDRUG-RESISTANCE
Enrofloxacin
lcsh:Public aspects of medicine
Phenanthridines
Infectious Diseases
Treatment Outcome
Tetracyclines
Drug Therapy
Combination
Isometamidium chloride
medicine.drug
Fluoroquinolones
Research Article
Infectious Diseases/Tropical and Travel-Associated Diseases
lcsh:Arctic medicine. Tropical medicine
MOLECULAR TOOLS
Combination therapy
SSU-RDNA AMPLIFICATION
Tetracycline
medicine.drug_class
lcsh:RC955-962
INHIBITION
Antiprotozoal Agents
Oxytetracycline
Biology
DIAGNOSIS
medicine
Animals
DRUG-RESISTANCE
ANALOGS
Infectious Diseases/Antimicrobials and Drug Resistance
Public Health
Environmental and Occupational Health
Infectious Diseases/Protozoal Infections
Biology and Life Sciences
lcsh:RA1-1270
Survival Analysis
Multiple drug resistance
Disease Models
Animal
Trypanosomiasis
African
chemistry
Cattle
Zdroj: PLoS Neglected Tropical Diseases
PLoS Neglected Tropical Diseases, Vol. 4, no. 9, p. e828.1-e828.8 (2010)
PLoS Neglected Tropical Diseases, Vol 4, Iss 9, p e828 (2010)
PLOS NEGLECTED TROPICAL DISEASES
ISSN: 1935-2735
1935-2727
Popis: Background Because of the development of resistance in trypanosomes to trypanocidal drugs, the livelihood of millions of livestock keepers in sub-Saharan Africa is threatened now more than ever. The existing compounds have become virtually useless and pharmaceutical companies are not keen on investing in the development of new trypanocides. We may have found a breakthrough in the treatment of resistant trypanosomal infections, through the combination of the trypanocide isometamidium chloride (ISM) with two affordable veterinary antibiotics. Methodology/Principal Findings In a first experiment, groups of mice were inoculated with Trypanosoma congolense strains resistant to ISM and either left untreated or treated with (i) tetracycline, (ii) ISM or (iii) the combination of the antibiotic and the trypanocide. Survival analysis showed that there was a significant effect of treatment and resistance to treatment on the survival time. The groups treated with ISM (with or without antibiotic) survived significantly longer than the groups that were not treated with ISM (P
Author Summary African Animal Trypanosomiasis causes the death of 3 million head of cattle each year. The annual economic losses as a result of the disease are estimated to be 4.5 billion US dollars. Trypanosomes are transmitted by tsetse flies and can infect a wide range of hosts from wildlife to domestic animals. This study is dealing with Trypanosoma congolense, which is one of the very prevalent parasites affecting livestock of poor African rural communities, decreasing the milk and meat production but also reducing the fitness of cattle that is used as draught power. Infected animals can only be treated by three compounds, i.e., diminazene, isometamidium and ethidium. These three products have been in use for more than a half century and it is thus not surprising to observe treatment failures. In some areas, the trypanosomes circulating have developed resistance to the three drugs leaving the farmers with no further options. As pharmaceutical companies are not keen on investing efforts and money in the development of new veterinary drugs for this low-budget market, our idea was to render an old ineffective drug effective again by combining it with existing potentiating compounds that are available and affordable for the livestock keeper.
Databáze: OpenAIRE
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