Abstract
BackgroundHigh frequency of relapse in miltefosine-treated visceral leishmaniasis (VL) patients in India and Nepal followed up for twelve months.ObjectiveTo identify epidemiological and clinical risk factors for relapse of VL in patients recently treated with standard dosing of miltefosine in India and Nepal.DesignProspective 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.ResultsWe 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.ConclusionsYoung 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.
Highlights
IntroductionVisceral leishmaniasis (VL) is a systemic parasitic disease that is caused by the Leishmania donovani species complex and is typically fatal unless treated
Young age and male gender were associated with increased risk of visceral leishmaniasis (VL) relapse after miltefosine, suggesting that the mechanism of relapse is mainly host-related i.e. immunological factors and/or drug exposure
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
Summary
Visceral leishmaniasis (VL) is a systemic parasitic disease that is caused by the Leishmania donovani species complex and is typically fatal unless treated. Some VL patients develop post-kala azar dermal leishmaniasis (PKDL) years after being successfully treated, and others relapse with clinical VL, usually within months after the end of treatment. Close monitoring of the treatment performance under programme conditions would be appropriate, which implies verifying if patients are effectively cured In practice this requires a clinical check-up of all treated VL patients at (various) time point(s) after the end of their treatment, since cure in VL is a clinical concept, Early treatment outcomes Initial cure: Non-response: Defaulter: Side-effects related switch: Death: Late treatment outcomes Definite cure: Relapse: Lost to follow-up: Death: Treatment completed, clinical improvement (absence of fever, regression of enlarged spleen+return of appetite and/or gain in body weight). High frequency of relapse in miltefosine-treated visceral leishmaniasis (VL) patients in India and Nepal followed up for twelve months
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