| Article Access Statistics|
| Viewed||4060 |
| Printed||169 |
| Emailed||1 |
| PDF Downloaded||19 |
| Comments ||[Add] |
| Cited by others ||2 |
Click on image for details.
|Year : 2013 | Volume
| Issue : 3 | Page : 226-228
Development of post-kala-azar dermal leishmaniasis in AmBisome treated visceral leishmaniasis: A possible challenge to elimination program in India
VNR Das1, K Pandey1, D Singh2, C Forwood3, CS Lal4, P Das2
1 Department of Clinical Medicine, Rajendra Memorial Research Institute of Medical Sciences, Agamkuan, Patna, India
2 Department of Molecular Biology, Rajendra Memorial Research Institute of Medical Sciences, Agamkuan, Patna, India
3 Médecins Sans Frontières, Sadar Hospital, Vaishali, India
4 Department of Biochemistry, Rajendra Memorial Research Institute of Medical Sciences, Agamkuan, Patna, India
|Date of Submission||20-Nov-2012|
|Date of Decision||31-Jan-2013|
|Date of Acceptance||31-Jan-2013|
|Date of Web Publication||12-Sep-2013|
Department of Clinical Medicine, Rajendra Memorial Research Institute of Medical Sciences, Agamkuan, Patna
Source of Support: Médecins Sans Frontières-Spain (MSF) for drug procurement, Conflict of Interest: None
We report two cases, one male (33 years) and a female (14 years), that developed Post-Kala-azar Dermal Leishmaniasis (PKDL) after successful treatment for visceral leishmaniasis (VL) or Kala-azar with AmBisome, the lipid complex of Amphotericin B. Both cases presented with hypo-pigmented macular lesions all over the body. The patients responded well to AmBisome after treatment with three courses. This first ever case report from India indicates that possibly there is no effective drug for VL until date, which can prevent post-treatment development of PKDL.
Keywords: AmBisome, kala-azar, post-kala-azar dermal leishmaniasis, visceral leishmaniasis
|How to cite this article:|
Das V, Pandey K, Singh D, Forwood C, Lal C S, Das P. Development of post-kala-azar dermal leishmaniasis in AmBisome treated visceral leishmaniasis: A possible challenge to elimination program in India. J Postgrad Med 2013;59:226-8
|How to cite this URL:|
Das V, Pandey K, Singh D, Forwood C, Lal C S, Das P. Development of post-kala-azar dermal leishmaniasis in AmBisome treated visceral leishmaniasis: A possible challenge to elimination program in India. J Postgrad Med [serial online] 2013 [cited 2022 May 23];59:226-8. Available from: https://www.jpgmonline.com/text.asp?2013/59/3/226/118046
| :: Introduction|| |
Post-kala-azar dermal leishmaniasis (PKDL) is seen in India (5-15%), Sudan (>50%), Bangladesh, and Nepal after incomplete or partial treatment of visceral leishmaniasis (VL) cases with Sodium-Stibo-Gluconate (SSG).  Besides SSG, the development of PKDL has also been reported from VL cases treated with other anti-leishmanial drugs such as Pentamidine, Amphotericin B, Paromomycin and Miltefosine. PKDL is a dermatosis usually occurring as a sequel of VL or kala-azar (KA), caused by Leishmania donovani and characterized by macular, maculo-papular, and nodular skin lesions on the entire body. It is of considerable epidemiological importance, particularly in India because it acts as reservoir for transmission of the parasite through sandflies. In addition, the possibility exists that this could be one of the reasons for the massive epidemic of KA in Bihar in the 1970s. , The incubation period of PKDL after VL is usually 0-6 months in Sudan and 6 months to several years in India.  This first ever case series from India describes the development of PKDL after a full course of AmBisome, the lipid complex of Amphotericin B (given under direct supervision) that has the highest cure rate for VL and a favorable risk benefit profile. It is thus a matter of grave concern.
| :: Case Report|| |
A 33-year-old male patient (case 1) and a 14-year-old female patient (case 2), presented with hypo-pigmented patches all over the body. Both the patients reported to out-patient-clinic of Rajendra Memorial Research Institute of Medical Sciences in October 2009 and May 2009 respectively. Clinical examination revealed hypo-pigmented macular lesions without scale, non-tender and non-ulcerative. Sensation was intact and there was no thickness of the ulnar nerve. Macular patches were more marked on the face and upper arm in case 1 and face and upper trunk in case 2 [Figure 1]a and [Figure 2]a. Systemic examination did not reveal any abnormalities such as anemia, dehydration, hepatosplenomegaly, and lymphadenopathy.
|Figure 1: (a) Showing macular lesions over back and arms pretreatment. (b) Disappearance of macular lesions post treatment|
Click here to view
|Figure 2: (a) Showing macular lesions on the back of neck and arms before treatment. (b) Disappearance of the lesions post treatment|
Click here to view
The retrospective documentary workup for a past history of VL confirmed that both the patients indeed had clinical signs and symptoms of VL. After screening with rK-39 rapid immunochromatographic test (ICT) and confirmation by demonstration of L. donovani bodies in splenic aspirates, they were treated with AmBisome ® (Gilead Sciences, Inc. San Dimas, CA) 20 mg/kg body weight in four divided doses on 1 st , 2 nd , 5 th and 10 th day of treatment in June 2008 and December 2007, respectively. At the end of treatment (EOT) examination on Day 10, both were clinically cured. During the 3-month and 6-month follow-up, they had no signs and symptoms of VL or PKDL. Case 2 was lost to 6-month follow-up. However, in between 6-15 months, and 3-12 months of EOT respectively, case 1 and case 2 developed skin lesions on face that spread subsequently to the entire whole body.
The microscopic examination of imprint skin smear of the PKDL lesions showed presence of L. donovani bodies in macrophage in case 1; case 2 was found negative for L. donovani bodies. However, after 3 months, case 2 re-visited the clinic with progressive lesions and PKDL was confirmed parasitologically in skin imprint smear this time. The rK-39 ICT and polymerase chain reaction (PCR) from blood as well as skin snip was also positive for L. donovani. The hematological and biochemical parameters were found within the normal range or non-clinically significant [Table 1]. Enzyme linked immunosorbent assay for Human Immunodeficiency Virus-I was found non-reactive in both the cases. Both were treated with AmBisome ® 2.5 mg/kg body weight/day for 20 days for three courses at 15 days interval. The patients responded well to treatment, all the macular lesions disappeared and L. donovani bodies were not demonstrable from skin snip lesions [Figure 1]b and [Figure 2]b. PCR from blood and skin snip were also negative. The patients were followed-up to 2 years without any relapse.
|Table 1: Baseline hematological and biochemical parameters of case 1 and case 2|
Click here to view
| :: Discussion|| |
This is probably the first report of PKDL after successful treatment for VL with AmBisome in India. Traditionally it has been thought that PKDL occurs in VL cases after partial, incomplete, irregular or even full course of SSG treatment. In some cases, PKDL may develop even without past history of VL, 10-20% in the Indian context. A study from India revealed that extensive use of Amphotericin B for treatment of VL may decrease incidence of PKDL.  Miltefosine, an oral drug, has been introduced as first line of drug at pilot level under KA elimination program by Govt. of India, but unfortunately development of PKDL after treatment with Miltefosine has also been reported.  In a comparative study of AmBisome and SSG, conducted in Sudan on 26 VL subjects, no significant differences in terms of clinical and laboratory parameters were observed between the two regimens, but 3 patients (out of 16) and 1 patient (out of 10) developed PKDL in the SSG and AmBisome group respectively.  Demonstration of L. donovani bodies in the slit skin smear or by culture of the skin tissue is considered to be the gold standard for diagnosis of PKDL.  Amongst the molecular diagnostic tools, PCR has proved to be more promising technique. 
The treatment of PKDL is no less difficult. Resistance has emerged to SSG, which used to be a very potent drug for treatment of VL and the cure rate in the endemic districts of Bihar is as low as 30-40%.  Moreover, its prolonged administration, as is required in PKDL, can limit its use particularly in view of cardio-toxicity and arthritis. Repeated courses of Amphotericin B have been found to be superior to SSG for treatment of PKDL that too for a lesser duration as well.  AmBisome has the highest cure rate against VL with minimum toxicity until date. This first ever case report from India describing development of PKDL in AmBisome treated VL cases indicates that possibly there is no really fully effective drug for VL until date, that can prevent post-development of PKDL.
PKDL has only cosmetic significance as far as the patient is concerned. Post-treatment monitoring under VL elimination program needs a close attention with special emphasis on detection and treatment of PKDL cases as early as possible. Moreover, an extensive study may be undertaken to estimate anti-leishmanial drug-wise variation, if any, in the rate of PKDL development after VL and understand the underlying pathological process as this can impact the disease elimination significantly.
| :: References|| |
|1.||Zijlstra EE, el-Hassan AM. Leishmaniasis in Sudan. Post kala-azar dermal leishmaniasis. Trans R Soc Trop Med Hyg 2001;95:S59-76. |
|2.||Dutta M, Ghosh TK. Review of current status of Leishmaniasis epidemiology. In: The Indo-UK Workshop on leishmaniasis. New Delhi: Indian Council of medical research; 1983. p. 97-102. |
|3.||World Health Organization (WHO). Disease control a decade of health development in South-East Asia 1968-1977. South-East Asia regional publication series No. 7. New Delhi: WHO; 1978. p. 233 |
|4.||Thakur CP, Kumar A, Mitra G, Thakur S, Sinha PK, Das P, et al. Impact of amphotericin-B in the treatment of kala-azar on the incidence of PKDL in Bihar, India. Indian J Med Res 2008;128:38-44. |
|5.||Das VN, Pandey K, Verma N, Lal CS, Bimal S, Topno RK, et al. Short report: Development of post-kala-azar dermal leishmaniasis (PKDL) in miltefosine-treated visceral leishmaniasis. Am J Trop Med Hyg 2009;80:336-8. |
|6.||Khalil EA, Hashim FA, Ali MS, Ghalib HW, Zijlstra EE, El Hag IA, et al. Comparative study of liposomal amphotericin B (AmBisome) and sodium stibogluconate in the treatment of Kala-Azar in the Sudan. E Afr Med J 1998;75:481-4. |
|7.||Sharma MC, Gupta AK, Verma N, Das VN, Saran R, Kar SK. Demonstration of Leishmania parasites in skin lesions of Indian post kala-azar dermal leishmaniasis (PKDL) cases. J Commun Dis 2000;32:67-8. |
|8.||Salotra P, Singh R. Challenges in the diagnosis of post kala-azar dermal leishmaniasis. Indian J Med Res 2006;123:295-310. |
|9.||Das VN, Ranjan A, Bimal S, Siddique NA, Pandey K, Kumar N, et al. Magnitude of unresponsiveness to sodium stibogluconate in the treatment of visceral leishmaniasis in Bihar. Natl Med J India 2005;18:131-3. |
|10.||Thakur CP, Narain S, Kumar N, Hassan SM, Jha DK, Kumar A. Amphotericin B is superior to sodium antimony gluconate in the treatment of Indian post-kala-azar dermal leishmaniasis. Ann Trop Med Parasitol 1997;91:611-6. |
[Figure 1], [Figure 2]
|This article has been cited by|
||An In-depth Proteomic Map of Leishmania donovani Isolate from Post Kala-azar Dermal Leishmaniasis (PKDL) Patient
| ||Chinmayee Bar Routaray, Avishek Kumar, Shyam Sundar, Gajanan Sathe, Harsh Pawar, Kalpana Pai |
| ||Acta Parasitologica. 2022; |
|[Pubmed] | [DOI]|
||Systematic Review of Host-Mediated Activity of Miltefosine in Leishmaniasis through Immunomodulation
| ||Semra Palic, Patrick Bhairosing, Jos H. Beijnen, Thomas P. C. Dorlo |
| ||Antimicrobial Agents and Chemotherapy. 2019; 63(7) |
|[Pubmed] | [DOI]|