post - kala - azar dermal leishmaniasis ( pkdl ) is a dermal manifestation of leishmania donovani infection and often follows resolution of clinical visceral leishmaniasis ( vl ) .
however , it may also manifest without prior history of vl in a small minority of patients .
pkdl is characterized by macular , papular , or nodular lesions or a mixture of them .
it is quite common in sudan ( occurring in > 50% of patients with vl ) , where it may occur concurrently or follows immediately after an episode of vl and heals spontaneously in majority of patients , whereas in the indian subcontinent it occurs in 220% of patients , 6 months to several years after an episode of vl . in a recent trial
the prevalence of confirmed pkdl cases was 4.4 per 10 000 individuals and 7.8 if probable cases were also considered .
several treatment regimens have been recommended for the treatment of pkdl in india , for example , 120 days of parenteral sodium stibogluconate ( 20  mg / kg body weight )   or three courses of 20 daily infusions of amphotericin b with an interval of 20 days in between the courses .
these inordinately long parenteral regimens invariably lead to either nonacceptance or poor compliance . in the last decade two new antileishmanial compounds , miltefosine and paromomycin , have been approved for the treatment of vl in india .
there is a report about the efficacy of miltefosine at a higher dose 50  mg tid for 60 days ( with a need to extend to 90 days if required ) in small number of pkdl patients in bangladesh .
of all the antileishmanial drugs , paromomycin is considerably cheaper and is produced in india . in this study
the study was carried out at the kala - azar medical research center , muzaffarpur , the field site of the institute of medical sciences , banaras hindu university .
patients with pkdl were enrolled between october 2007 and august 2009 and followed for one year after treatment .
the study was approved by the institutional ethics committee , and written informed consent was taken from all enrolled patients and by the parents of patients of < 18 years of age .
patients of both sexes , aged more than 10 years , with skin lesions of pkdl ( nodules , papules , plaques , or macules ) identified by a qualified and trained doctor at kala - azar medical research center , muzaffarpur , with or without history of an episode of vl in the past , were included in the study .
taking into account the decreased slit - skin smear parasite and culture positivity in diagnosis of pkdl we did only pcr for making the diagnosis .
the immune - chromatographic rk39 strip test was performed in serum of all the patients . only pcr and k39 positive confirmed cases were included in the study .
patients with platelet count < 100000/mm , total leukocyte count ( tlc ) < 2500/mm and hemoglobin ( hb ) < 8.0  g/100  ml , hepatic enzymes > 3 times the upper limit of normal range , serum bilirubin > 2 times the upper limit of normal range , and serum creatinine or blood urea nitrogen ( bun ) above normal range were excluded from the study .
patients with any noncompensated or uncontrolled condition , such as active tuberculosis , malignant disease , severe malaria , hiv , or other major infectious diseases , lactation , pregnancy , or inadequate contraception in females of childbearing potential for the treatment period , were also excluded from the study .
once eligible for enrollment , patients were given daily paromomycin 11  mg / kg ( base ) intramuscularly for 45 days .
clinical parameters like vital signs were assessed daily , and hematological and biochemical assessments were done on days 15 , 30 , and 45 of treatment . for monitoring the adverse events , except nephrotoxicity , common toxicity criteria of national cancer institute were used .
if there was toxicity of grade 3 and above , the treatment was discontinued and the subject was removed from the study and offered rescue treatment .
nephrotoxicity was defined as an increase in serum creatinine that was either double the baseline levels or more than 2.0  mg per deciliter [ 177  mol per liter ] .
cure was defined as complete disappearance of skin lesion(s ) after treatment , as reported by the patient and assessed by the trained physician at 12-month followup .
those patients who failed treatment in the form of no response and increase in number and size of lesion at 1-year followup and those patients in whom treatment was stopped due to adverse events were offered rescue treatment with three 20-day courses of amphotericin b in doses of 1  mg / kg given 20 days apart .
comparison of means was done by using paired student 's t - test for paired data . a p value less than 0.05 ( < 0.05 ) was considered as statistically significant .
thirty - one patients with pkdl were included in the study out of which three patients did not give a history of a prior episode of vl .
the median duration of interval between treatment of vl and development of pkdl was two years . amongst the previously treated patients for vl ,
22 patients were treated with sodium stibogluconate ( ssg ) , 3 patients with amphotericin b and miltefosine each , and 1 patient with paromomycin . among the various forms of skin lesions
patients one had nodular lesion on face / chin with hypopigmented macular lesion over trunk , arms , and lower limb , and the other had hypopigmented macular and nodular lesions over the whole body .
one patient presented with erythematous lesion over face while one patient presented with nodular and erythematous lesion on face with hypopigmented macular lesion over the whole body .
pm was well tolerated by all patients without any significant derangement in hematological and biochemical parameter .
14 patients ( 45.2% ) complained of pain at injection site which was the most common side effect noted .
posttreatment clinical , biochemical , and hematological parameters were similar to the baseline values except slight improvement in the platelet count ( table 1 ) .
at one - year followup , out of 31 patients , 9 ( 37.5% ) were cured with complete disappearance of lesion while 15 ( 62.5% ) patients showed no improvement ; rather there was increase in lesion and appearance of nodular lesions in 11 patients .
all the patients who improved were having macular lesions . among three patients who had nodular lesions ,
pm is very effective in the treatment of vl with a cure rate of ~95% .
these results prompted us to use pm for the treatment of pkdl . since dose / duration of every antileishmanial drug in pkdl is 2 - 3 times that used for vl , we arbitrarily selected a regimen of pm for 45 days ( ~2 times of vl ) for the treatment of pkdl .
though 45 days of pm treatment did not result in any noticeable adverse event except the expected injection site pain , the cure rate with this relatively better tolerated regimen of pm was unfortunately far from satisfactory .
since these patients were admitted in the hospital for the entire duration of treatment , and pm injection was administered by nursing staff ; compliance was ensured . in india cure rates
are 6492% with ssg in doses of 20  mg / kg per day for 120 days .
ssg , being a toxic drug with high volume ( 1012  ml ) of intramuscular injections given in long regimen of 120 days , makes acceptance of this regimen very poor .
similarly 60 injections of amphotericin b given over 100 days pose a real threat of nephrotoxicity .
unfortunately , nearly every trial for pkdl consists of small number of patients with no randomization . clinical response may differ according to the type of lesions in pkdl ; nodules and papules disappear in 120 days , macules in 200 days .
thus it becomes imperative to follow these patients for a sufficiently long duration to see the long term effects of treatment .
though the cure rate was unacceptably low , it had noticeable activity and cured one - third of the patients .
future studies using paromomycin with another antileishmanial drug like miltefosine could yield successful short duration regimen for the treatment of pkdl and should be tested .
it is also important to know that the tolerance to the drug was excellent even though the drug was used for twice the duration of that used in vl .
the unresponsiveness of pm in pkdl which is very effective for treatment of vl highlights that there is a lot to be still discovered about the mechanism and pattern of response of pm against different manifestations of leishmaniasis .
 
 background . 
 post - kala - azar dermal leishmaniasis ( pkdl ) plays an important role in maintaining endemicity of visceral leishmaniasis and its transmission . 
 treatment regimens for pkdl are toxic and require 3 - 4 months of hospitalization . 
 these long and arduous regimens result in extensive noncompliance . 
 there is an urgent need to develop a safe , effective , and acceptable regimen for the treatment of pkdl . 
 paromomycin ( pm ) has been recently approved in india for treatment of visceral leishmaniasis ( vl ) ; hence we tested its efficacy in patients with pkdl . methods . in this exploratory study , 
 31 patients with pkdl aged 10 years and above were administered pm 11  mg / kg daily intramuscularly for 45  days and followed up for one year . results . 
 out of 31 patients , 7 patients were lost to followup at 1  year and 9 ( 37.5% ) got cured with complete disappearance of lesion , while 15 ( 62.5% ) showed no improvement by per protocol analysis . conclusion . 
 cure rate with 45 intramuscular injections of pm was unacceptably low though there was no serious side effect of the drug . 
 whether paromomycin can be used in multidrug therapy to shorten the duration of treatment should be the next logical step for investigation . 
1. Introduction
2. Material and Methodology
3. Results
4. Discussion