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- Ostyn, Bart, et al.
(författare)
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Failure of miltefosine treatment for visceral leishmaniasis in children and men in South-East Asia.
- 2014
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 9:6, s. e100220-
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: High frequency of relapse in miltefosine-treated visceral leishmaniasis (VL) patients in India and Nepal followed up for twelve months.OBJECTIVE: To identify epidemiological and clinical risk factors for relapse of VL in patients recently treated with standard dosing of miltefosine in India and Nepal.DESIGN: Prospective observational study in three Primary Health Centers and one reference center in Muzaffarpur district, Bihar, India; and two zonal hospitals and a university hospital in South-east Nepal; records of all consenting patients diagnosed with VL and treated with miltefosine according to the current treatment guidelines of the Kala azar elimination program between 2009 and 2011.RESULTS: We compared the clinical records of 78 cases of relapse with those of 775 patients who had no record of subsequent relapse. Relapse was 2 times more common amongst male patients (IRR 2.14, 95% CI 1.27-3.61), and 2 to 3 times more frequent in the age groups below 15 compared to the over 25 year olds (age 10 to 14: IRR 2.53; 95% CI 1.37-4.65 and Age 2 to 9: IRR 3.19; 95% CI 1.77-5.77). History of earlier VL episodes, or specific clinical features at time of diagnosis such as duration of symptoms or spleen size were no predictors of relapse.CONCLUSIONS: Young age and male gender were associated with increased risk of VL relapse after miltefosine, suggesting that the mechanism of relapse is mainly host-related i.e. immunological factors and/or drug exposure (pharmacokinetics). The observed decrease in efficacy of miltefosine may be explained by the inclusion of younger patients compared to the earlier clinical trials, rather than by a decreased susceptibility of the parasite to miltefosine. Our findings highlight the importance of proper clinical trials in children, including pharmacokinetics, to determine the safety, efficacy, drug exposure and therapeutic response of new drugs in this age group.
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| 2. |
- Uranw, Surendra, et al.
(författare)
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Adherence to miltefosine treatment for visceral leishmaniasis under routine conditions in Nepal.
- 2013
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Ingår i: Tropical medicine & international health. - : Wiley. - 1360-2276 .- 1365-3156. ; 18:2, s. 179-87
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To assess patient adherence to unsupervised single-drug miltefosine treatment for visceral leishmaniasis and to identify the factors influencing adherence.METHODS: This is a prospective cohort study of 171 patients with Visceral leishmaniasis (VL) in three healthcare settings in Nepal. Adherence was assessed through pill count, checking of treatment cards and adherence questionnaires, as well as miltefosine concentration measurements at the end of treatment. Poor adherence was defined as less than 90% of required capsules taken.RESULTS: Patient adherence to miltefosine was 83%. Predictors of adherence were being the male sex (OR = 2.60, 95% CI 1.02-6.67) and knowing the duration of treatment (OR = 3.05, 95% CI 1.16-8.04). Adherence was also better for patients who were literate and knew the side effects of treatment. Gastrointestinal side effects and negligence after the resolution of clinical symptoms of VL were the main reasons for poor adherence. Poor adherence was associated (though not statistically significant) with future relapse.CONCLUSION: Effective counselling during the treatment, a short take-home message on VL and on side effects and action of miltefosine, and follow-up visits are the best way to prevent poor adherence. Single end-of-treatment measurements of miltefosine concentrations as objective assessment of adherence would only be useful in addition to the subjective assessments when substantial doses of miltefosine have been missed.
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