Liposomal amphotericin B is more effective in polymorphic lesions of post kala-azar dermal leishmaniasis

Abstract

Background: Post kala-azar dermal leishmaniasis (PKDL) is thought to be the reservoir of infection for visceral leishmaniasis in South Asia. The development of strategies for the diagnosis and treatment of PKDL are important for the implementation of the visceral leishmaniasis elimination program. Aims: Liposomal amphotericin B (L-AMB) has been an overwhelming success in the treatment of visceral leishmaniasis. However, the empirical three-week regimen of L-AMB proposed for PKDL was shown to be inadequate, especially in the macular variant. This study aimed to delineate response of the different variants of PKDL to L-AMB. Methods: Skin biopsies were collected from PKDL cases at disease presentation and upon completion of treatment with L-AMB. Parasite DNA was detected by Internal Transcribed Spacer-1 PCR (ITS-1 PCR) and quantified by amplification of parasite kDNA. CD68 + macrophages were estimated in tissue sections by immunohistochemistry. Results: Treatment with L-AMB decreased the parasite load by 97% in polymorphic cases but only by 45% in macular cases. The median parasite load (89965 vs 5445 parasites/μg of genomic DNA) as well as infiltration by CD68+ cells before treatment was much greater in the polymorphic cases. Limitations: Although monitoring of the parasite load for 12 months post-treatment would have been ideal, this was not possible owing to logistical issues as well as the invasive nature of biopsy collection procedure. Conclusion: A dramatic decrease in the parasite burden was noted in patients with polymorphic lesions. Although patients with macular disease also had a decrease in parasite burden, this was not as marked as in the polymorphic cases. There was also a significantly greater infiltration of CD68 + macrophages in polymorphic PKDL before therapy.

IgG3 and IL10 are effective biomarkers for monitoring therapeutic effectiveness in Post Kala-Azar Dermal Leishmaniasis

“…Miltefosine impacted substantially upon all antibody subclasses especially in the polymorphic form, and accounted for the decrease in IgG ( Fig 2Aii ) as also IgG1, IgG2 and IgG3 ( Fig 2D–2F ). This was in agreement with the parasite load wherein Miltefosine caused a dramatic decline in parasite load, more so in the polymorphic form [ 13 , 14 ]. Miltefosine mediates its leishmanicidal activity directly via parasite apoptosis [ 40 ] and indirectly by its immunomodulatory ability to skew macrophages towards a M2 phenotype, accompanied by a decrease in circulating levels of IL-10, TGF-β and IL-4 [ 24 ] which in this study translated into a decrease in the levels of Immunoglobulins ( Fig 3 ).…”

“…for 3 weeks [ 11 , 12 ]. The chemotherapeutic efficacy of Miltefosine vs. LAmB was assessed by quantifying the parasite load in skin biopsies [ 13 ] wherein irrespective of the lesional type, patients following treatment with Miltefosine showed an absence of parasite DNA that was sustained up to at least 6 months; however, with LAmB there was parasite persistence suggesting treatment inadequacy [ 13 , 14 ]. In resource limited settings, quantification of parasite load using nucleic acid based detection methods is not always feasible, endorsing the need to validate alternatives e.g.…”

Post kala-azar dermal leishmaniasis in the Indian sub-continent: challenges and strategies for elimination

“…However, concerns were raised regarding the potential emergence of hypokalemia-induced rhabdomyolysis associated with its usage ( 44 ). The effectiveness of AmBisome in treating different types of lesions in Indian PKDL patients has been studied, and it has been observed that the response to treatment can vary depending on the lesion type ( 45 ). The study found that patients with polymorphic lesions showed a more pronounced decrease in parasite burden following treatment with AmBisome compared to patients with macular lesions.…”

Histological findings associated with treatment response in cutaneous leishmaniasis: a clinicopathological correlation study

“…9 While primary drug resistance is a growing concern, 10 host immune responses and the severity of clinical symptoms are also likely contributing factors to the variable treatment response. 7,11 Furthermore, severe pain at the injection site and the economic burden of reaching a secondary/tertiary hospital at regular intervals over several weeks affect treatment compliance. 12 Detailed observations of clinicopathology, along with the treatment response, may reveal correlations with the healing process in patients.…”

“…A patient's response to treatment and the time required for complete healing of the cutaneous lesion(s) depend on multiple factors 9 . While primary drug resistance is a growing concern, 10 host immune responses and the severity of clinical symptoms are also likely contributing factors to the variable treatment response 7,11 . Furthermore, severe pain at the injection site and the economic burden of reaching a secondary/tertiary hospital at regular intervals over several weeks affect treatment compliance 12 …”