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Abstract: Trypanocidal drug resistance is unanimously recognized as a threat for livestock production in regions where the prevalence of trypanosomosis is high. To assess the impact of the disease and the effect of drug resistance on the health of small ruminants, twelve Trypanosoma vivax isolates collected in 6 villages in the vicinity of Bobo Dioulasso (Burkina Faso) were injected into 12 groups of 5 Sahelian goats, two being treated with 3.5mg/kg body weight diminazene aceturate (DA), two with 0.5mg/kg body weight isometamidium chloride (ISM) and one left untreated as control. A monitoring was performed every 5days for 100days to evaluate the parasitaemia by buffy coat examination, the hematocrit and the body weight. Among the 12 groups, 6 were additionally monitored using a trypanosome specific 18S-PCR–RFLP every 5days from day 30 to day 100 to verify the complete clearance of the parasites from the blood of the hosts. In six groups of goats, trypanosomes disappeared completely after treatment, five groups showed relapses in at least one goat treated with ISM and one group showed relapses in one goat treated with DA and one with ISM. For the 6 groups that were screened both using microscopic examination and trypanosome specific 18S-PCR–RFLP, the following results were observed: for the groups treated with DA, no relapses by microscopic examination and 83.3% (10/12) using the 18S-PCR–RFLP. For the groups treated with ISM, 25% (3/12) relapses by microscopic examination and 83.3% with the 18S-PCR–RFLP (10/12). The evolution of the PCV and the weight during the observation period from relapsing (either by microscopical examination or by 18S-PCR–RFLP diagnosis) and non relapsing animals were compared. The relative average PCV in goats that relapsed microscopically, decreased significantly more than in non-relapsing goats. This difference was not significant when relapses were detected using the trypanosome specific 18S-PCR–RFLP. This indicates that only the animals with the highest parasitaemia suffered from the infection. Relapses after treatment where the host controls the parasitaemia to a level below the sensitivity of the microscopical examination do not affect body weight nor PCV. [Copyright &y& Elsevier]

This article discusses the development and evaluation of a PCR-RFLP test for the detection of trypanocidal drug resistance in Trypanosoma congolense, a parasite that causes animal African trypanosomiasis (AAT) in sub-Saharan Africa. AAT affects livestock production and endangers the food supply of rural communities. The test, which detects a single point mutation in the parasite's DNA, was found to be more sensitive than the gold standard test. The use of blood spots or buffy coats on filter paper for sample collection and storage was also explored, offering logistical and economic advantages for large-scale surveys. [Extracted from the article]

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<0.01). The group treated with the combination trypanocide/antibiotic survived significantly longer than the group treated with ISM (P<0.01). In a second experiment, groups of cattle were inoculated with the same resistant trypanosome strain and treated with (i) ISM, (ii) ISM associated with oxytetracycline or (iii) ISM associated with enrofloxacine. All animals treated with ISM became parasitaemic. In the groups treated with ISM-oxytetracycline and ISM-enrofloxacine, 50% of the animals were cured. Animals from the groups treated with a combination trypanocide/antibiotic presented a significantly longer prepatent period than animals treated with ISM (p<0.001). The impact of the disease on the haematocrit was low in all ISM treated groups. Yet, it was lower in the groups treated with the combination trypanocide/antibiotic (p<0.01). Conclusions/Significance: After optimization of the administration protocol, this new therapeutic combination could constitute a promising treatment for livestock infected with drug resistant T. congolense. 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. [ABSTRACT FROM AUTHOR]

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<0.01). The group treated with the combination trypanocide/antibiotic survived significantly longer than the group treated with ISM (P<0.01). In a second experiment, groups of cattle were inoculated with the same resistant trypanosome strain and treated with (i) ISM, (ii) ISM associated with oxytetracycline or (iii) ISM associated with enrofloxacine. All animals treated with ISM became parasitaemic. In the groups treated with ISMoxytetracycline and ISM-enrofloxacine, 50% of the animals were cured. Animals from the groups treated with a combination trypanocide/antibiotic presented a significantly longer prepatent period than animals treated with ISM (p<0.001). The impact of the disease on the haematocrit was low in all ISM treated groups. Yet, it was lower in the groups treated with the combination trypanocide/antibiotic (p<0.01). Conclusions/Significance: After optimization of the administration protocol, this new therapeutic combination could constitute a promising treatment for livestock infected with drug resistant T. congolense. [ABSTRACT FROM AUTHOR]