10-day melarsoprol treatment of "Trypanosoma brucei gambiense" sleeping sickness : from efficacy to effectiveness

Schmid, Caecilia. 10-day melarsoprol treatment of "Trypanosoma brucei gambiense" sleeping sickness : from efficacy to effectiveness. 2004, Doctoral Thesis, University of Basel, Faculty of Science.


Official URL: http://edoc.unibas.ch/diss/DissB_6961

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Treatment of human African trypanosomiasis (sleeping sickness) with the currently available drugs is unsatisfactory and new drugs and approaches are urgently needed. Despite being associated with severe adverse reactions and a long, complicated treatment schedule, melarsoprol (Arsobal®) is expected to remain the most used drug for the treatment of latestage sleeping sickness for the next decade because alternative treatments are too expensive and only at very preliminary stages of development. In the presented study, the overall effectiveness of an abridged application scheme of melarsoprol for the treatment of late-stage gambiense sleeping sickness was evaluated. In a first part, the long-term efficacy of the 10-day schedule was concluded based on the followup of the patients treated in a large-scale controlled clinical trial in Angola in 1998 (IMPAMEL I). In a second part, the overall effectiveness of this abridged treatment schedule was assessed in a multinational drug utilisation study (IMPAMEL II) that was executed under field conditions. Clinical effectiveness was shown by addressing specifically the usefulness in different settings, e.g. in different countries / centres and in children below 15 years of age. An economic appraisal was also done to assess the monetary benefit if switching from the standard treatment schedule to the short course of melarsoprol. 2800 patients from 16 different treatment centres ofAfrican countries endemic for T.b gambiense trypanosomiasis were treated with 10 daily doses of 2.2 mg melarsoprol/kg bodyweight on consecutive days. The short- and long-term efficacies of the 10-day schedule were good and comparable to the standard schedules found in the randomised, controlled clinical trial in Angola and in previous trials published in literature. However, poor follow-up is an inherent problem of sleeping sickness control and therefore highly variable attendance rates of the follow-up examinations could be anticipated. In our studies, they varied from acceptable in the controlled trial in Angola to rather low rates in many treatment centres of the multinational study. Highly variable outcomes were also found for the safety of the 10-day treatment schedule reported from the different treatment centres in the multinational evaluation. But nevertheless, the safety under field conditions proved to be well comparable to the findings of the clinical trial previously executed in Angola, the literature and the retrospective data from the participating treatment centres. No unexpected findings were reported. In addition, the tolerability and effectiveness of the abridged treatment schedule in children were assessed by reviewing all patients treated in the multinational study who were below the age of 15 years. There is evidence that the safety and efficacy profile of the 10-day schedule is similar in children and adults. The abridged treatment schedule was well tolerated by the children and we found only non-significant differences in the occurrence of
adverse events compared to adults. Some of these differences could be explained by higher
rates of concomitant parasitic diseases in children and the fact that some adverse events
cannot be separated from common signs and symptoms of the disease, especially in
younger children (e.g. headache). The cure rates were identical in the subpopulations.
We found the 10-day treatment schedule to be more cost-effective than the standard
treatment and a highly cost-effective treatment option for late-stage gambiense sleeping
sickness in areas with scarce resources. The costs of treatment (diagnosis, hospitalisation
and sleeping sickness specific treatment) were assessed in two rural treatment centres and
compared to the benefits of the 10-day treatment and of the standard treatments, measured
by the cost of treatment per DALY (disability-adjusted life-year) averted. The net benefit from
switching from the standard (26 to 30 days hospitalisation) to the 10-day treatment schedule
did reduce the costs per DALY averted by almost half of the costs calculated for the standard
schedules and represented a “good value for money” option in the control of sleeping
In addition, the 10-day schedule bears several advantages over the standard national
treatment schedules: It reduces treatment duration, hospitalisation time, and total drug
amount per patient, it is easier to implement in basic, rural treatment centres, and it
increases the treatment centres’ capacity.
Based on our findings and the experience of the sleeping sickness control programs in the
respective countries, the abridged protocol was recommended by the 27th ISCTRC in late
2003 as the standard schedule for melarsoprol treatment of late-stage sleeping sickness due
to T.b. gambiense. However, because of the different clinical nature and the high
parasitaemia, the use of the 10-day schedule against T.b. rhodesiense is strongly
discouraged until the necessary clinical evaluation will be conducted. Based on its simplified
implementation, the 10-day schedule offers straightforward adaptation for combination
therapy with other existing drugs, especially for melarsoprol refractory patients.
Advisors:Tanner, Marcel
Committee Members:Buscher, Philippe and Burri, Christian
Faculties and Departments:09 Associated Institutions > Swiss Tropical and Public Health Institute (Swiss TPH) > Former Units within Swiss TPH > Molecular Parasitology and Epidemiology (Beck)
UniBasel Contributors:Tanner, Marcel and Burri, Christian
Item Type:Thesis
Thesis Subtype:Doctoral Thesis
Thesis no:6961
Thesis status:Complete
Number of Pages:154
Identification Number:
edoc DOI:
Last Modified:22 Jan 2018 15:50
Deposited On:13 Feb 2009 15:00

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