Occurrence of multiple drug resistance in <i>Trypanosoma brucei rhodesiense</i> isolated from sleeping sickness patients

Abstract

The occurrence of cross-resistance among melarsoprol-resistant Trypanosoma brucei rhodesiense isolates was investigated in this study. The isolates, T. b. rhodesiense KETRI 237, 2538, 1992, 2709, 2694 and 3530, had been obtained from sleeping sickness patients in Kenya and Uganda between 1960 and 1985. Five groups consisting of six mice each were inoculated intraperitoneally with 105 parasites of each isolate, and 24 h later treated with either melarsoprol, homidium chloride, diminazene aceturate or isometamidium chloride. The control group comprised infected but untreated mice. The mice were monitored for cure for a period of 60 days post-treatment. The mean prepatent period in the control mice was 5 days while the mean survival period was 22 days. Five of the stabilates, KETRI 237, 2538, 2709, 2694, and 3530, were confirmed to be melarsoprol resistant. Cross-resistance was observed, with the majority of the isolates being resistant to homidium chloride (5/6) and diminazene aceturate (5/6), but all were sensitive to isometamidium chloride (6/6). However T. b. rhodesiense KETRI 1992, which was previously considered as melarsoprol resistant, was sensitive to all the drugs tested. In conclusion, our study has revealed the existence of cross-resistance among the melarsoprol resistant isolates which could only be cured by isometamidium.

Differential virulence of Trypanosoma brucei rhodesiense isolates does not influence the outcome of treatment with anti-trypanosomal drugs in the mouse model

“…In a study by Sokolova et al [46], these authors observed that resistance to nifurtimox did not compromise parasite virulence. This is despite previous studies reporting that drug resistant trypanosome have reduced virulence [47,48].…”

“…The twelve T.b. rhodesiense clones were placed into four classes of virulence based on the survival of 60% or more of the infected mice as follows: very-acute (0-15 days), acute (16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30), sub-acute (31)(32)(33)(34)(35)(36)(37)(38)(39)(40)(41)(42)(43)(44)(45) and chronic classes (46)(47)(48)(49)(50)(51)(52)(53)(54)(55)(56)(57)(58)(59)(60). Each mouse's survival time was determined on the basis of a � 25% decline in PCV and consistently high parasitaemia levels of 1x10 9 /ml for at least two consecutive days as previously described [27].…”

The lymphatic system favours survival of a uniqueT. bruceipopulation, and its invasion results in major host pathology

“…brucei infection. Other directions that have been explored under the lymph node-T. brucei umbrella include lymph node pathology (Barrowman and Roos, 1979;Morrison et al, 1981), lymph node invasion and its importance for tissue distribution (Alfituri et al, 2020a(Alfituri et al, , 2020bRudin et al, 1984), and diverse variant antigen types present across the host body (Turner et al, 1986).…”