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


METHODS
In 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.


RESULTS
Seventy 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).


CONCLUSIONS
Relapse rate in PKDL following miltefosine treatment has increased substantially, indicating the need of introducing alternate drugs/ combination therapy with miltefosine.
Dermatology Department, Safdarjung Hospital and Vardhman Mahavir Medical College (VMMC), New Delhi, India.
V
V
Ramesh
National Institute of Pathology (ICMR), Safdarjung Hospital Campus, New Delhi, India.
Ruchi
R
Singh
National Institute of Pathology (ICMR), Safdarjung Hospital Campus, New Delhi, India.
Kumar
K
Avishek
National Institute of Pathology (ICMR), Safdarjung Hospital Campus, New Delhi, India.
Aditya
A
Verma
National Institute of Pathology (ICMR), Safdarjung Hospital Campus, New Delhi, India.
Deepak Kumar
DK
Deep
National Institute of Pathology (ICMR), Safdarjung Hospital Campus, New Delhi, India.
Sandeep
S
Verma
National Institute of Pathology (ICMR), Safdarjung Hospital Campus, New Delhi, India.
Poonam
P
Salotra
D000328:Adult; D000981:Antiprotozoal Agents / Q000008:administration & dosage*; D002648:Child; D005260:Female; D006651:Histocytochemistry; D006801:Humans; D007194:India; D016773:Leishmaniasis, Cutaneous / Q000188:drug therapy* / Q000469:parasitology / Q000473:pathology; D007898:Leishmaniasis, Visceral / Q000150:complications*; D008297:Male; D008875:Middle Aged; D059208:Parasite Load; D010767:Phosphorylcholine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D060888:Real-Time Polymerase Chain Reaction; D012008:Recurrence; D016896:Treatment Outcome; D055815:Young Adult
D000981:Antiprotozoal Agents; D010767:Phosphorylcholine; C039128:miltefosine