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

BACKGROUND: Post kala-azar dermal leishmaniasis (PKDL) is a skin disorder that usually occurs among patients with a past history of visceral leishmaniasis (VL). Cases are also reported without a history of VL. There is no satisfactory treatment regimen available at present. We aimed to compare the efficacy and safety of amphotericin B in two different doses (0.5mg/kg vs 1mg/kg) in a prospective randomized trial in 50 PKDL patients. METHODS: In this open label study 50 patients with PKDL, aged between 5-60 years were randomized in two groups. Group A received amphotericin B in the dose of 0.5 mg/kg in 5% dextrose, daily for 20 infusions for 3 courses at an interval of 15 days between each course and Group B received amphotericin B in the dose of 1mg/kg in 5% dextrose on alternate days, 20 infusions for 3 courses an interval of 15 days between each course and followed up for one year. RESULTS: A total of 50 patients were enrolled, 25 in each of group A and group B. Two patients lost to follow up and three patients withdrew consent due to adverse events. The initial cure rate was 92% in group A and 88% in group B by intention to treat analysis and final cure rate by per protocol analysis was 95.65% and 95.45% in group A and group B respectively. Two patients each from either group relapsed. Nephrotoxicity was the most common adverse event occurring in both the groups. CONCLUSION: The lower dose appears to have fewer adverse events however, nephrotoxicity remains a problem in both regimens. The 0.5mg/kg regimen may be considered instead of the higher dosage however safer treatments remain critical for PKDL treatment.

Repeated training of accredited social health activists (ASHAs) for improved detection of visceral leishmaniasis cases in Bihar, India.

Accredited Social Health Activists (ASHAs) are incentive-based, female health workers responsible for a village of 1000 population and living in the same community and render valuable services towards maternal and child health care, polio elimination program and other health care-related activities including visceral leishmaniasis (VL). One of the major health concerns is that cases remain in the endemic villages for weeks without treatment causing increased likelihood to treatment failure and disease transmission in the community. To address this problem, we have begun a training program for ASHAs to enhance early detection of potential VL cases and referring them to their local Primary Health Centers (PHCs) for diagnosis and treatment. The result of this training showed increased referral rate to PHCs for diagnosis and treatment. Encouraged with the results from a single training session, we determined in the present study whether repeated training of ASHAs resulted in an a further increase in VL case referral to the local PHCs. After two training sessions, VL referrals by ASHAs increased to 46% as compared to 28% after a single training session in this cohort and a baseline of 7% before training. ASHA training is an effective way to conduct active case detection of VL cases and should be repeated once a year.

Comparative evaluation of PCR and imprint smear microscopy analyses of skin biopsy specimens in diagnosis of macular, papular, and mixed papulo-nodular lesions of post-kala-azar dermal leishmaniasis.

Diagnosis of post-kala-azar dermal leishmaniasis (PKDL), particularly the macular form, is difficult when based on microscopy. This study compared the results of nested PCR (91.9% positive samples) with imprint smear microscopy (70.9% positive samples) for 62 PKDL samples. We found that nested PCR, which indicated 87.5% positivity for the macular lesions, compared to 41.6% positivity by imprint smear microscopy, is an efficient method for early diagnosis of PKDL.

Microalbuminuria and glomerular filtration rate in paediatric visceral leishmaniasis.

Visceral leishmaniasis, caused by Leishmania donovani, is a serious form of leishmaniasis and fatal if untreated. Nearly half of the VL cases are children. There are very few studies of renal function in pediatric visceral leishmaniasis. The aim of this study was to evaluate renal dysfunction by studying glomerular filtration rate (GFR), microalbuminuria, and microscopic examination of urine. Laboratory analysis was performed on blood and urine samples of 40 parasitologically confirmed pediatric VL cases. Laboratory data of urine examination showed albuminuria in 10% (4/40), white blood cells in 20% (8/40), hematuria in 10% (4/40), microalbuminuria in 37.5% (15/40), and decreased GFR in 27.5% (11/40). Renal involvement was manifested in most of the pediatric VL cases. These findings may help clinicians in decision making for safe and suitable antileishmanial treatment particularly in childhood VL.

Evaluation of rK-39 strip test using urine for diagnosis of visceral leishmaniasis in an endemic region of India.

The definitive diagnosis of visceral leishmaniasis (VL) requires invasive procedures for demonstration of parasites in tissue smear or culture. These procedures need expertise and laboratory supports and cannot be performed in the field. The aim of the present study was to evaluate the existing rK-39 immunochromatographic nitrocellulose strips test (ICT) with some modification in human urine for diagnosis of VL. The test was performed on both sera and urine samples on the same 786 subjects (365 confirmed VL and 421 control subjects). The sensitivity of the rK-39 ICT in serum was 100%, whereas the specificity was 93.8%, 100%, and 96.2% in healthy controls from endemic, non-endemic, and other infectious diseases, respectively. However, in urine samples, the test showed 96.1% sensitivity and 100% specificity. Considering sensitivity and feasibility of the test in the field, rK-39 ICT using urine samples can be an alternative to conventional invasive VL diagnosis.

A rare case of Visceral leishmaniasis with multiple relapse and multi-drug unresponsive: successfully treated with combination therapy.

CASE: We report a 32-year old relapse case of Visceral leishmaniasis, treated with Paromomycin who belonged from a endemic zone of Bihar state, India. After confirmation, he was treated with Amphotericin B, followed by Liposomal Amphotericin B in full course and even in higher dose. But after each therapy, the patient either did not responded or relapsed after treatment. Ultimately, the patient was successfully treated with combination therapy of Liposomal amphotericin B and Miltefosine without any relapse. CONCLUSION: The multi-drug unresponsive Visceral leishmaniasis cases could pose a major threat to treatment strategy in the elimination program. In such situation, combination therapy seems to be a better approach that needs to be explored.

A controlled, randomized nonblinded clinical trial to assess the efficacy of amphotericin B deoxycholate as compared to pentamidine for the treatment of antimony unresponsive visceral leishmaniasis cases in Bihar, India.

BACKGROUND: There is significant variation in Amphotericin B (AMB) efficacy and relapses in antimony unresponsive visceral leishmaniasis (VL) cases over a period of time (10-15 years). Keeping in mind the above mentioned view this study was undertaken with an objective to assess the magnitude of cure and relapse rates of AMB in the treatment of antimony unresponsive VL cases. METHODS: In a controlled, randomized nonblinded clinical trial, we evaluated the cure and relapse rate of Amphotericin B deoxycholate as compared to pentamidine. A total of 82 sodium stibogluconate (SSG) unresponsive and parasitologically confirmed VL cases were included in this study and randomized into two groups, test (Amphotericin B) and control (Pentamidine). Both the groups were treated with recommended dosages (as per World Health Organization guidelines) of respective medicines. All the patients were followed up on 1st, 2nd, and 6th month after end of treatment. RESULTS: Apparent cure rate in the Amphotericin B group was found to be 95% (39/41) compared with 83% (34/41) in the Pentamidine group, which shows significant statistical difference (p = 0.05). The ultimate cure rate was found 92% (38/41) in the Amphotericin B group compared to 73% (30/41) in the Pentamidine group, which shows a significant statistical difference (Yates corrected chi-square = 4.42, p = 0.04). Similarly, significant statistical difference was observed in the relapse rate of the Amphotericin group compared to the Pentamidine group (p = 0.03). CONCLUSIONS: AMB may still be the drug of choice in the management of resistant VL cases in Bihar, India. This is due to its consistent apparent cure rate (95%), low relapse rate (2.5%), and cost effectiveness compared with other available antileishmanial drugs. It is a safe drug even in case of pregnancy. Efforts should be taken to form a future strategy so that this drug and coming newer drugs do not meet a similar fate as has happened to SSG and pentamidine over a span of 10-15 years.

Short report: Development of post-kala-azar dermal leishmaniasis (PKDL) in miltefosine-treated visceral leishmaniasis.

We report two cases of post-kala-azar dermal leishmaniasis (PKDL), which had subsequently developed after successful treatment of visceral leishmaniasis with miltefosine. Both patients had maculo-nodular lesions all over the body, and they were diagnosed as PKDL by parasitologic examination for Leishmania donovani bodies in a skin snip of lesions. Patients were put on amphotericin B and responded very well for nodular lesions with one course of treatment. However, longer duration of the treatment is needed for total clearance of macular lesions from body surface in PKDL cases. This is the first case report of PKDL in India, which developed after successful treatment of visceral leishmaniasis with miltefosine.

Phase 4 trial of miltefosine for the treatment of Indian visceral leishmaniasis.

BACKGROUND: Visceral leishmaniasis (VL) is a major public health problem in Bihar, accounting for 90% of all cases in India. Development of high levels of resistance to various existing drugs necessitated the search for alternative orally administered drugs. Hospital-based studies have shown that oral miltefosine is a highly effective treatment for VL both in adults and in children. METHODS: An open, single-arm trial was designed to investigate the feasibility of treatment of VL patients with miltefosine in field conditions in 13 centers in Bihar. RESULTS: The phase 4 study was conducted among 1132 adult and pediatric VL patients. Compliance was good, with 1084 (95.5%) patients completing the full 28-day treatment course. Nine hundred and seventy-one (85.8%) patients returned for the final cure assessment at 6 months after treatment. The final cure rate was 82% by intention to treat analysis and 95% by per protocol analysis (similar to the 94% cure rate in hospitalized patients). Treatment-related adverse events of common toxicity criteria grade 3 occurred in ~3% of patients, including gastrointestinal toxicity and rise in aspertate amino transferase, alanine amino transferase, or serum creatinine levels, similar to previous clinical experience. CONCLUSION: This study supports the use of miltefosine in an outpatient setting in an area where VL is endemic.