Decline in Clinical Efficacy of Oral Miltefosine in Treatment of Post Kala-azar Dermal Leishmaniasis (PKDL) in India

Abstract

BackgroundRecent studies have shown significant decline in the final cure rate after miltefosine treatment in visceral leishmaniasis. This study evaluates the efficacy of miltefosine in the treatment of post kala-azar dermal leishmaniasis (PKDL) patients recruited over a period of 5 years with 18 months of follow-up.MethodologyIn this study 86 confirmed cases of PKDL were treated with two different dosage regimens of miltefosine (Regimen I- 50mg twice daily for 90 days and Regimen II- 50 mg thrice for 60 days) and the clinical outcome assessed monthly. Cure/relapse was ascertained by clinical and histopathological examination, and measuring parasite burden by quantitative real-time PCR. In vitro susceptibility of parasites towards miltefosine was estimated at both promastigote and amastigote stages.ResultsSeventy three of eighty six patients completed the treatment and achieved clinical cure. Approximately 4% (3/73) patients relapsed by the end of 12 months follow-up, while a total of 15% (11/73) relapsed by the end of 18 months. Relapse rate was significantly higher in regimen II (31%) compared to regimen I (10.5%)(P<0.005). Parasite load at the pre-treatment stage was significantly higher (P<0.005) in cases that relapsed compared to the cases that remained cured. In vitro susceptibility towards miltefosine of parasites isolated after relapse was significantly lower (>2 fold) in comparison with the pre-treatment isolates (P<0.005).ConclusionRelapse rate in PKDL following miltefosine treatment has increased substantially, indicating the need of introducing alternate drugs/ combination therapy with miltefosine.

To evaluate efficacy and safety of amphotericin B in two different doses in the treatment of post kala-azar dermal leishmaniasis (PKDL)

“…Recently a study by Ramesh et. al reported that the efficacy of miltefosine is decreasing substantially in the treatment of PKDL with a cure rate of 85% [29]. A Similar trend of decrement had been found in the treatment of VL with miltefosine, the final cure rate dropped from 94% (phase III trial during 1999–2000) to about 90% [30].…”

Severe post-kala-azar dermal leishmaniasis successfully treated with miltefosine in an Ethiopian HIV patient

“…Here, we document a case of severe PKDL in an Ethiopian HIV patient successfully treated with miltefosine. The treatment duration of 28 days was shorter than that of up to 90 days reported in India (Ramesh et al, 2015). As miltefosine may be teratogenic, it is contraindicated during pregnancy, and women of reproductive age must use effective contraception during and for three months after treatment (Dorlo et al, 2012).…”

“…Reports from the Indian subcontinent show declining efficacy of miltefosine monotherapy and increasing treatment failure (Rijal et al, 2013;Ramesh et al, 2015). Therefore, research is needed on miltefosine in combination therapy (either with Liposomal amphotericin B or paromomycin), in order to reduce treatment duration, increase efficacy, and reduce the risk for the development of resistance (Drugs for Neglected Diseases Initiative, 2018).…”

Visceral Leishmaniasis

“…It has been demonstrated that in 2015 the efficacy of miltefosine has declined. Paromomycin has been shown to be effective against PKDL [7]. Amphotericin B is effective in the treatment of PKDL and several courses, where gaps between the two courses are required.…”