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Purpose: Leishmaniasis, caused by the parasite of the genus Leishmania, is a neglected tropical disease which is endemic in more than 60 countries. In South-East Asia, Brazil, and East Africa, it mainly occurs as kala-azar (visceral leishmaniasis, VL), and subsequently as post kala-azar dermal leishmaniasis (PKDL) in a smaller portion of cases. As stated per WHO roadmap, accessibility to accurate diagnostic methods is an essential step to achieve elimination. This study aimed to test the accuracy of a portable minoo device, a small battery-driven, multi-use fluorimeter operating with isothermal technology for molecular diagnosis of VL and PKDL. Methods: Fluorescence data measured by the device within 20 min are reported back to the mobile application (or app) via Bluetooth and onward via the internet to a backend. This allows anonymous analysis and storage of the test data. The test result is immediately returned to the app displaying it to the user. Results: The limit of detection was 11.2 genome copies (95% CI) as determined by screening a tenfold dilution range of whole Leishmania donovani genomes using isothermal recombinase polymerase amplification (RPA). Pathogens considered for differential diagnosis were tested and no cross-reactivity was observed. For its diagnostic performance, DNA extracted from 170 VL and PKDL cases, comprising peripheral blood samples (VL, n = 96) and skin biopsies (PKDL, n = 74) from India (n = 108) and Bangladesh (n = 62), was screened. Clinical sensitivity and specificity were 88% and 91%, respectively. Conclusion: Minoo devices can offer a convenient, cheaper alternative to other molecular diagnostics. Its easy handling makes it ideal for use in low-resource settings to identify parasite burden. [ABSTRACT FROM AUTHOR]

In a recent phase 2a clinical trial, the candidate leishmaniasis vaccine ChAd63-KH was shown to be safe and immunogenic in Sudanese patients with post kala-azar dermal leishmaniasis (PKDL). However, its value as a stand-alone therapeutic was unknown. To assess the therapeutic efficacy of ChAd63-KH, we conducted a randomized, double-blind, placebo-controlled phase 2b trial (ClinicalTrials.gov: NCT03969134). Primary outcomes were safety and efficacy (≥90% improvement in clinical disease). Secondary outcomes were change in severity grade and vaccine-induced immune response. 86 participants with uncomplicated PKDL of ≥6 month duration were randomized to receive ChAd63-KH (7.5 × 1010 viral particles, once by the intramuscular route) or placebo. 75 participants (87%) completed the trial as per protocol. No severe or serious adverse events were observed. At day 90 post-vaccination, 6/40 (15%) and 4/35 (11%) participants in the vaccine and placebo groups, respectively, showed ≥90% clinical improvement (risk ratio [RR] 1.31 [95% confidence interval (CI), 0.40–4.28], p = 0.742). There were also no significant differences in PKDL severity grade between study arms. Whole-blood transcriptomic analysis identified transcriptional modules associated with interferon responses and monocyte and dendritic cell activation. Thus, a single vaccination with ChAd63-KH showed no therapeutic efficacy in this subset of Sudanese patients with PKDL.

Post kala-azar dermal leishmaniasis (PKDL) is a skin disease that usually occurs among individuals with a past history of visceral leishmaniasis (VL). PKDL cases act as a reservoir of parasites and may play a significant role in disease transmission. Hence, prompt detection and complete treatment of PKDL cases are crucial for the control and elimination of VL. The purpose of this review was to highlight the barriers to effective control and prevention of VL/PKDL as well as potential solutions in India. Main obstacles are lack of knowledge about the disease and its vector, poor treatment-seeking behaviours, ineffective vector control measures, lack of confirmatory diagnostics in endemic areas, limited drug choices, treatment noncompliance among patients, drug resistance, and a lack of an adequate number of trained personnel in the health system. Therefore, in order to control and successfully eliminate VL in the Indian subcontinent, early detection of PKDL cases, improved diagnosis and treatment, raising awareness, and effective vector control mechanisms are necessary. [ABSTRACT FROM AUTHOR]

Visceral leishmaniasis (VL) is a severe and often fatal form of leishmaniasis caused by Leishmania donovani in the Indian sub-continent. Post Kala-azar Dermal Leishmaniasis (PKDL) is a late cutaneous manifestation of VL, typically occurring after apparent cure of VL, but sometimes even without a prior history of VL in India. PKDL serves as a significant yet neglected reservoir of infection and plays a crucial role in the transmission of the disease, posing a serious threat to the VL elimination program in the Indian sub-continent. Therefore, the eradication of PKDL should be a priority within the current VL elimination program aimed at achieving a goal of less than 1 case per 10,000 in the population at the district or sub-district levels of VL endemic areas. To accomplish this, a comprehensive understanding of the pathogenesis of PKDL is essential, as well as developing strategies for disease management. This review provides an overview of the current status of diagnosis and treatment options for PKDL, highlighting our current knowledge of the immune responses underlying disease development and progression. Additionally, the review discusses the impact of PKDL on elimination programs and propose strategies to overcome this challenge and achieve the goal of elimination. By addressing the diagnostic and therapeutic gaps, optimizing surveillance and control measures, and implementing effective intervention strategies, it is possible to mitigate the burden of PKDL and facilitate the successful elimination of VL in the Indian sub-continent. [ABSTRACT FROM AUTHOR]

Post kala‐azar dermal leishmaniasis (PKDL), a sequel of apparently cured visceral leishmaniasis (VL) presents with papulonodular (polymorphic) or hypopigmented lesions (macular) and is the proposed disease reservoir. As hypopigmentation appears consistently in PKDL, especially the macular form, this study aimed to delineate immune factors that singly or in combination could contribute towards this hypopigmentation. At lesional sites, the presence of melanocytes and CD8+ T‐cells was assessed by immunohistochemistry and mRNA expression of melanogenic markers (tyrosinase, tyrosinase‐related protein‐1 and MITF) by droplet digital PCR, while plasma levels of cytokines and chemokines were measured by a multiplex assay. In comparison with skin from healthy individuals, macular PKDL demonstrated a near total absence of Melan‐A+ cells at dermal sites, while the polymorphic cases demonstrated a 3.2‐fold decrease, along with a dramatic reduction in the expression of key enzymes related to the melanogenesis signalling pathway in both forms. The levels of circulating IFN‐γ, IL‐6, IL‐2, IL‐1β, TNF‐α and IFN‐γ‐inducible chemokines (CXCL9/10/11) were elevated and was accompanied by an increased lesional infiltration of CD8+ T‐cells. The proportion of CD8+ T‐cells correlated strongly with plasma levels of IFN‐γ (r = 0.8), IL‐6 (r = 0.9, p < 0.05), IL‐2 (r = 0.7), TNF‐α (r = 0.9, p < 0.05) and IL‐1β (r = 0.7), as also with CXCL9 (r = 0.5) and CXCL10 (r = 0.6). Taken together, the absence/reduction in Melan‐A suggested hypopigmentation in PKDL was associated with the destruction of melanocytes, following the impairment of the melanogenesis pathway. Furthermore, the presence of CD8+ T‐cells and an enhanced IFN‐γ‐associated immune milieu suggested the generation of a pro‐inflammatory landscape that facilitated melanocyte dysfunction/destruction. [ABSTRACT FROM AUTHOR]

Visceral leishmaniasis (VL) is a severe and often fatal form of leishmaniasis caused by Leishmania donovani in the Indian sub-continent. Post Kala-azar Dermal Leishmaniasis (PKDL) is a late cutaneous manifestation of VL, typically occurring after apparent cure of VL, but sometimes even without a prior history of VL in India. PKDL serves as a significant yet neglected reservoir of infection and plays a crucial role in the transmission of the disease, posing a serious threat to the VL elimination program in the Indian sub-continent. Therefore, the eradication of PKDL should be a priority within the current VL elimination program aimed at achieving a goal of less than 1 case per 10,000 in the population at the district or sub-district levels of VL endemic areas. To accomplish this, a comprehensive understanding of the pathogenesis of PKDL is essential, as well as developing strategies for disease management. This review provides an overview of the current status of diagnosis and treatment options for PKDL, highlighting our current knowledge of the immune responses underlying disease development and progression. Additionally, the review discusses the impact of PKDL on elimination programs and propose strategies to overcome this challenge and achieve the goal of elimination. By addressing the diagnostic and therapeutic gaps, optimizing surveillance and control measures, and implementing effective intervention strategies, it is possible to mitigate the burden of PKDL and facilitate the successful elimination of VL in the Indian sub-continent.

• STAT1 ((Signal transducer and activator of transcription 1) serves as common factor upregulated in both VL and PKDL positive cases. • VLDLR (Very low density lipoprotein Receptor) exhibits significant suppression in PKDL and murine VL cases. • hsa-miR-30d-5p, hsa-miR-1226–3p, and hsa-miR-6891–3p regulates VLDLR for both VL and PKDL positive infection. Post Kala-azar dermal leishmaniasis (PKDL) arises as a significant dermal sequel following Visceral leishmaniasis (VL) caused by protozoan parasite Leishmania donovani (LD). PKDL acts as a significant constrain for VL elimination serving as a crucial reservoir for LD. PKDL patients exhibit depigmented macular and papular lesions on their skin, which results in social discrimination due to loss of natural skin color. Inflammatory reactions, prevalent in both VL and PKDL, potentially lead to tissue damage in areas harboring the parasite. Disruption of the immune-inflammasomal network not only facilitates LD persistence but also leads to the skin hypopigmentation seen in PKDL, impacting social well-being. Activation of inflammasomal markers like STAT1, NLRP1, NLRP3, AIM2, CASP11, and NLRP12 have been identified as a common host-defense mechanism across various Leishmania infections. Conversely, Leishmania modulates inflammasome activation to sustain its presence within the host. Nevertheless, in specific instances of Leishmania infection, inflammasome activation can worsen disease pathology by promoting parasite proliferation and persistence. This study encompasses recent transcriptomic analyses conducted between 2016 and 2023 on human and murine subjects afflicted with VL/PKDL, elucidating significant alterations in inflammasomal markers in both conditions. It offers a comprehensive understanding how these markers contribute in disease progression, drawing upon available literature for logical analysis. Furthermore, our analysis identifies validated miRNA network that could potentially disrupt this crucial immune-inflammasomal network, thereby offering a plausible explanation on how secreted LD-factors could enable membrane-bound LD, isolated from the host cytoplasm, to modulate cytoplasmic inflammasomal markers. Insights from this study could guide the development of host-directed therapeutics to impede transmission and address hypopigmentation, thereby mitigating the social stigma associated with PKDL. Schematic representation of key inflammasome related genes STAT1 and VLDLR, common between VL and PKDL positive cases from whole genome transcriptomics analysis of seven publicly available datasets and possible miRNAs networks regulating these inflammasomal markers. [Display omitted] [ABSTRACT FROM AUTHOR]

Post kala-azar dermal leishmaniasis (PKDL) is a mucocutaneous disease usually seen in apparently cured, inadequately treated or untreated cases of visceral leishmaniasis and is endemic to many parts of India, Nepal, Bangladesh, and eastern Africa (Sudan, Ethiopia, Kenya). The disease usually manifests as a variable combination of hypopigmented patches, erythematous succulent papulo-plaques, and nodular lesions on the face and upper body and sometimes extending on the extremities, genitalia, and tongue. Atypical morphology and presentations are not uncommon, especially in endemic areas, which include photosensitivity, verrucous, hypertrophic, xanthomatous, and ulcerative lesions. Recognition of spectrum of mucocutaneous changes helps physicians in early initiation of treatment and in reducing disease transmission in the community. The differential diagnosis depends on the pattern of manifestations, but lepromatous leprosy is the closest mimicker. Since PKDL does not cause significant morbidity, at least initially, but the affected patients continue to act as a reservoir of the disease, active case detection is required to identify cases early to control the disease transmission in the community.

Post-kala-azar dermal Leishmaniasis (PKDL) is one of the important neglected tropical diseases, which has a tremendous epidemiological significance, being the reservoir of kala-azar. Relapse and resistance to treatment along with the lack of a drug of choice and consensus treatment guideline pose a significant problem in the management of PKDL. The aim of this article was to review the available therapeutic options for PKDL, with special emphasis on their pharmaco-dynamics, pharmaco-kinetics, effectiveness, safety, tolerability, and cost factor. A comprehensive English language literature search was done for therapeutic options in PKDL across multiple databases (PubMed, EMBASE, MEDLINE, and Cochrane) for keywords (alone and in combination). MeSH as well as non-MeSH terms such as “Kala-azar,” “Leishmaniasis” AND “Treatment,” “Management,” “Antimony Sodium Gluconate,” “Meglumine Antimoniate,” “Amphotericin B,” “Paromomycin,” “Miltefosine” were taken into consideration. Among 576 relevant articles, 15 were deemed relevant to this review. These articles were evaluated using “Oxford Centre for Evidence-Based Medicine (OCEBM)” AND “strength of recommendation taxonomy” (SORT) with respect to the level of evidence and grade of recommendation. The review includes 15 studies. The use of sodium stibogluconate is being discouraged because of multiple documented reports of treatment failure. Liposomal amphotericin B is emerging as a favorable option, owing to its superiority in terms of effectiveness and safety profile. Miltesfosine is the drug of choice in India because of the ease of oral administration and minimal risk of toxicity. Isolated Paromomycin alone is not effective in PKDL; however, combination therapy with sodium stibogluconate is found to be safe and effective. Combination of amphotericin B and miltefosine is one of the excellent options. Immunotherapy with combination of alum-precipitated autoclaved Leishmania major (Alum/ALM) vaccine + Bacille Calmette-Gu´erin (BCG) has shown promising results. Kala-azar continues to haunt the tropical countries and PKDL being its reservoir is threatening its elimination. With the availability of drugs such as liposomal amphotericin B and miltefosine, apart from the advent of immunotherapy, the future of treatment of this condition looks promising.

Post-kala-azar dermal leishmaniasis (PKDL) is a cutaneous sequel of visceral leishmaniasis (VL) or kala-azar and has become an entity of epidemiological significance by virtue of its ability to maintain the disease in circulation during inter-epidemic periods. PKDL has been identified as one of the epidemiological marker of “kala-azar elimination programme.” Data obtained in 2018 showed PKDL distribution primarily concentrated in 6 countries, which includes India, Sudan, south Sudan, Bangladesh, Ethiopia, and Nepal in decreasing order of case-burden. In India, PKDL cases are mainly found in 54 districts, of which 33 are in Bihar, 11 in West Bengal, 4 in Jharkhand, and 6 in Uttar Pradesh. In West Bengal the districts reporting cases of PKDL cases include Darjeeling, Uttar Dinajpur, Dakshin Dinajpur, Malda, and Murshidabad. The vulnerability on the young age is documented in various studies. The studies also highlights a male predominance of the disease but recent active surveillance suggested that macular form of PKDL shows female-predominance.It is recommended that along with passive case detection, active survey helps in early identification of cases, thus reducing disease transmission in the community. The Accelerated plan for Kala-azar elimination in 2017 introduced by Government of India with the goal to eliminate Kala-azar as a public health problem, targets to reduceing annual incidence

Post-kala-azar dermal leishmaniasis (PKDL) is a skin condition that occurs in a small percentage of people who have been cured of visceral leishmaniasis (VL), and contributes to transmission of VL. The rK39 rapid test cannot decisively diagnose PKDL due to presence of antileishmanial antibodies from past VL episodes. CL Detect™ Rapid Test, an in-vitro diagnostic test that detects Leishmania antigen peroxidoxin, was assessed for diagnosing PKDL. The CL Detect RDT had 73.3% sensitivity and 100% specificity in the study. The test can be used as a primary screening tool to monitor PKDL in endemic regions and identify active Leishmania infection., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

The various lesions seen in the clinical presentation of post kala-azar dermal leishmaniasis (PKDL) are reflected in the histopathology of the type of lesion biopsied. The cells that form the dermal infiltrate include lymphocytes, histiocytes, and plasma cells in varying proportions. The infiltrate, which is mild and confined to the superficial dermis in macular lesion becomes denser with the increasing severity of the lesion. Leishman–Donovan bodies (LDB) in general are rarely demonstrable in macules and somewhat infrequently in the rest, though at times they may be numerous; mucosal lesions offer a greater chance of visualizing LDB than biopsies from the skin. A characteristic histomorphology in nodules is prominent follicular plugging with a dense plasma cell-rich lymphohistiocytic dermal infiltrate that shows an abrupt cut-off in the lower dermis, an appearance highly suggestive of PKDL even in the absence of LDB. Russell bodies within plasma cells, vascular changes, and xanthoma-like hue have been seen in plaques from chronic PKDL. The histopathologic picture in some may also mimic that seen in tuberculoid and lepromatous leprosy, and other granulomatous dermatoses. In contrast to Indian PKDL, epithelioid cell granulomas with giant cells are more common in African PKDL, and vascular changes are rare though neuritis showing LDB has been described.

Post kala-azar dermal leishmaniasis (PKDL), a clinical sequela of visceral leishmaniasis (VL), plays a critical role in the anthroponotic transmission of VL, particularly in the Indian subcontinent (ISC). The early, accurate, and feasible diagnosis of PKDL is essential for the attainment and sustenance of VL elimination goal in ISC. PKDL poses a stumbling block for this goal, considering the heterogeneity presented with regard to time after cure of VL and onset of PKDL, chronicity, and clinical variations. In most of the endemic regions the diagnosis is based on clinical examination, previous history of VL, by ruling out other disorders, and by the response to treatment. The conventional microscopic examination involving the demonstration of Leishman–Donovan bodies (LDB) in macrophages is pathognomonic, however, the method faces constraints in terms of being invasive, less sensitive, technically demanding, and difficult to be applied in field conditions. Serological evidences are of limited use because antileishmanial antibodies remain positive for years after VL treatment. Molecular tools such as PCR, nested-PCR, Q-PCR overcome these constraints and have become increasingly popular due to their high sensitivity and specificity along with their applicability in diverse clinical samples. Molecular methods not only play a key role in early detection but also provide quantification and monitoring of treatment effectiveness. NCBI PubMed search tool was used for locating, selecting, and extracting research articles pertinent for this review article by using various related terminologies on the molecular diagnosis of leishmaniasis.

Kala-azar, commonly known as visceral leishmaniasis (VL), is a neglected tropical disease that has been targeted in South Asia for elimination by 2020. Presently, the Kala-azar Elimination Programme is aimed at identifying new low-endemic foci by active case detection, consolidating vector control measures, and decreasing potential reservoirs, of which Post Kala-azar Dermal Leishmaniasis (PKDL) is considered as the most important. PKDL is a skin condition that occurs after apparently successful treatment of VL and is characterized by hypopigmented patches (macular) or a mixture of papules, nodules, and/or macules (polymorphic). To achieve this goal of elimination, it is important to delineate the pathophysiology so that informed decisions can be made regarding the most appropriate and cost-effective approach. We reviewed the literature with regard to PKDL in Asia and Africa and interpreted the findings in establishing a potential correlation between the immune responses and pathophysiology. The overall histopathology indicated the presence of a dense, inflammatory cellular infiltrate, characterized by increased expression of alternatively activated CD68+ macrophages, CD8+ T cells showing features of exhaustion, CD20+ B cells, along with decreased CD1a+ dendritic cells. Accordingly, this review is an update on the overall immunopathology of PKDL, so as to provide a better understanding of host-parasite interactions and the immune responses generated which could translate into availability of markers that can be harnessed for assessment of disease progression and improvement of existing treatment modalities.

Visceral leishmaniasis (VL) is a deadly neglected tropical disease caused by a parasite Leishmania donovani and spread by female sand flies Phlebotomus argentipes. There is conflicting evidence regarding the role of insecticide-treated nets (ITNs) on the prevention of VL. Numerous studies demonstrated the effectiveness of ITNs. However, KalaNet, a large trial in Nepal and India did not support those findings. The purpose of this paper is to gain insight into the situation by mathematical modelling. We expand a mathematical model of VL transmission based on the KalaNet trial and incorporate the use of ITNs explicitly into the model. One of the major contributions of this work is that we calibrate the model based on the available epidemiological data, generally independent of the KalaNet trial. We validate the model on data collected during the KalaNet trial. We conclude that in order to eliminate VL, the ITN usage would have to stay above 96%. This is higher than the 91% ITNs use at the end of the trial which may explain why the trial did not show a positive effect from ITNs. At the same time, our model indicates that asymptomatic individuals play a crucial role in VL transmission.

Leishmaniasis is a neglected tropical disease that affects 12 million people worldwide. The disease has high morbidity and mortality rates and is prevalent in over 80 countries, leaving more than 300 million people at risk of infection. Of all of the manifestations of this disease, cutaneous leishmaniasis (CL) is the most common form and it presents as ulcerating skin lesions that can self-heal or become chronic, leading to disfiguring scars. This review focuses on the different pathologies and disease manifestations of CL, as well as their varying degrees of severity. In particular, this review will discuss self-healing localized cutaneous leishmaniasis (LCL), leishmaniasis recidivans (LR), mucocutaneous leishmaniasis (MCL), anergic diffuse cutaneous leishmaniasis (ADCL), disseminated leishmaniasis (DL), and Post Kala-azar Dermal Leishmaniasis (PKDL), which is a cutaneous manifestation observed in some visceral leishmaniasis (VL) patients after successful treatment. The different clinical manifestations of CL are determined by a variety of factors including the species of the parasites and the host’s immune response. Specifically, the balance between the pro and anti-inflammatory mediators plays a vital role in the clinical presentation and outcome of the disease. Depending upon the immune response, Leishmania infection can also transition from one form of the disease to another. In this review, different forms of cutaneous Leishmania infections and their immunology are described.

Leishmaniasis is a neglected tropical disease that affects 12 million people worldwide. The disease has high morbidity and mortality rates and is prevalent in over 80 countries, leaving more than 300 million people at risk of infection. Of all of the manifestations of this disease, cutaneous leishmaniasis (CL) is the most common form and it presents as ulcerating skin lesions that can self-heal or become chronic, leading to disfiguring scars. This review focuses on the different pathologies and disease manifestations of CL, as well as their varying degrees of severity. In particular, this review will discuss self-healing localized cutaneous leishmaniasis (LCL), leishmaniasis recidivans (LR), mucocutaneous leishmaniasis (MCL), anergic diffuse cutaneous leishmaniasis (ADCL), disseminated leishmaniasis (DL), and Post Kala-azar Dermal Leishmaniasis (PKDL), which is a cutaneous manifestation observed in some visceral leishmaniasis (VL) patients after successful treatment. The different clinical manifestations of CL are determined by a variety of factors including the species of the parasites and the host's immune response. Specifically, the balance between the pro and anti-inflammatory mediators plays a vital role in the clinical presentation and outcome of the disease. Depending upon the immune response, Leishmania infection can also transition from one form of the disease to another. In this review, different forms of cutaneous Leishmania infections and their immunology are described. [ABSTRACT FROM AUTHOR]

Post-kala-azar dermal Leishmaniasis (PKDL) is one of the important neglected tropical diseases, which has a tremendous epidemiological significance, being the reservoir of kala-azar. Relapse and resistance to treatment along with the lack of a drug of choice and consensus treatment guideline pose a significant problem in the management of PKDL. The aim of this article was to review the available therapeutic options for PKDL, with special emphasis on their pharmaco-dynamics, pharmaco-kinetics, effectiveness, safety, tolerability, and cost factor. A comprehensive English language literature search was done for therapeutic options in PKDL across multiple databases (PubMed, EMBASE, MEDLINE, and Cochrane) for keywords (alone and in combination). MeSH as well as non-MeSH terms such as "Kala-azar," "Leishmaniasis" AND "Treatment," "Management," "Antimony Sodium Gluconate," "Meglumine Antimoniate," "Amphotericin B," "Paromomycin," "Miltefosine" were taken into consideration. Among 576 relevant articles, 15 were deemed relevant to this review. These articles were evaluated using "Oxford Centre for Evidence-Based Medicine (OCEBM)" AND "strength of recommendation taxonomy" (SORT) with respect to the level of evidence and grade of recommendation. The review includes 15 studies. The use of sodium stibogluconate is being discouraged because of multiple documented reports of treatment failure. Liposomal amphotericin B is emerging as a favorable option, owing to its superiority in terms of effectiveness and safety profile. Miltesfosine is the drug of choice in India because of the ease of oral administration and minimal risk of toxicity. Isolated Paromomycin alone is not effective in PKDL; however, combination therapy with sodium stibogluconate is found to be safe and effective. Combination of amphotericin B and miltefosine is one of the excellent options. Immunotherapy with combination of alum-precipitated autoclaved Leishmania major (Alum/ALM) vaccine + Bacille Calmette-Gu´erin (BCG) has shown promising results. Kala-azar continues to haunt the tropical countries and PKDL being its reservoir is threatening its elimination. With the availability of drugs such as liposomal amphotericin B and miltefosine, apart from the advent of immunotherapy, the future of treatment of this condition looks promising. [ABSTRACT FROM AUTHOR]

Post kala-azar dermal leishmaniasis (PKDL) is a mucocutaneous disease usually seen in apparently cured, inadequately treated or untreated cases of visceral leishmaniasis and is endemic to many parts of India, Nepal, Bangladesh, and eastern Africa (Sudan, Ethiopia, Kenya). The disease usually manifests as a variable combination of hypopigmented patches, erythematous succulent papulo-plaques, and nodular lesions on the face and upper body and sometimes extending on the extremities, genitalia, and tongue. Atypical morphology and presentations are not uncommon, especially in endemic areas, which include photosensitivity, verrucous, hypertrophic, xanthomatous, and ulcerative lesions. Recognition of spectrum of mucocutaneous changes helps physicians in early initiation of treatment and in reducing disease transmission in the community. The differential diagnosis depends on the pattern of manifestations, but lepromatous leprosy is the closest mimicker. Since PKDL does not cause significant morbidity, at least initially, but the affected patients continue to act as a reservoir of the disease, active case detection is required to identify cases early to control the disease transmission in the community. [ABSTRACT FROM AUTHOR]

Post-kala-azar dermal leishmaniasis (PKDL) is a cutaneous sequel of visceral leishmaniasis (VL) or kala-azar and has become an entity of epidemiological significance by virtue of its ability to maintain the disease in circulation during inter-epidemic periods. PKDL has been identified as one of the epidemiological marker of "kala-azar elimination programme." Data obtained in 2018 showed PKDL distribution primarily concentrated in 6 countries, which includes India, Sudan, south Sudan, Bangladesh, Ethiopia, and Nepal in decreasing order of case-burden. In India, PKDL cases are mainly found in 54 districts, of which 33 are in Bihar, 11 in West Bengal, 4 in Jharkhand, and 6 in Uttar Pradesh. In West Bengal the districts reporting cases of PKDL cases include Darjeeling, Uttar Dinajpur, Dakshin Dinajpur, Malda, and Murshidabad. The vulnerability on the young age is documented in various studies. The studies also highlights a male predominance of the disease but recent active surveillance suggested that macular form of PKDL shows female-predominance. It is recommended that along with passive case detection, active survey helps in early identification of cases, thus reducing disease transmission in the community. The Accelerated plan for Kala-azar elimination in 2017 introduced by Government of India with the goal to eliminate Kala-azar as a public health problem, targets to reduceing annual incidence <1/10,000. Leishmania donovani is the established causative agent, but others like L. tropica or L. infantum may occasionally lead to the disease, especially with HIV-co-infection. Dermal tropism of the parasite has been attributed to overexpression of parasite surface receptors (like gp 63, gp46). Various host factors are also identified to contribute to the development of the disease, including high pretreatment IL 10 and parasite level, inadequate dose and duration of treatment, malnutrition, immuno-suppression, decreased interferon-gamma receptor 1 gene, etc. PKDL is mostly concentrated in the plains below an altitude of 600 mts which is attributed to the environment conducive for the vector sand fly (Phlebotumus). Risk factors are also linked to the habitat of the sand fly. Keeping these things in mind "Integrated vector control" is adopted under National vector borne disease control programme as one of the strategies to bring down the disease burden. [ABSTRACT FROM AUTHOR]

Post kala-azar dermal leishmaniasis (PKDL), a clinical sequela of visceral leishmaniasis (VL), plays a critical role in the anthroponotic transmission of VL, particularly in the Indian subcontinent (ISC). The early, accurate, and feasible diagnosis of PKDL is essential for the attainment and sustenance of VL elimination goal in ISC. PKDL poses a stumbling block for this goal, considering the heterogeneity presented with regard to time after cure of VL and onset of PKDL, chronicity, and clinical variations. In most of the endemic regions the diagnosis is based on clinical examination, previous history of VL, by ruling out other disorders, and by the response to treatment. The conventional microscopic examination involving the demonstration of Leishman–Donovan bodies (LDB) in macrophages is pathognomonic, however, the method faces constraints in terms of being invasive, less sensitive, technically demanding, and difficult to be applied in field conditions. Serological evidences are of limited use because antileishmanial antibodies remain positive for years after VL treatment. Molecular tools such as PCR, nested-PCR, Q-PCR overcome these constraints and have become increasingly popular due to their high sensitivity and specificity along with their applicability in diverse clinical samples. Molecular methods not only play a key role in early detection but also provide quantification and monitoring of treatment effectiveness. NCBI PubMed search tool was used for locating, selecting, and extracting research articles pertinent for this review article by using various related terminologies on the molecular diagnosis of leishmaniasis. [ABSTRACT FROM AUTHOR]

The various lesions seen in the clinical presentation of post kala-azar dermal leishmaniasis (PKDL) are reflected in the histopathology of the type of lesion biopsied. The cells that form the dermal infiltrate include lymphocytes, histiocytes, and plasma cells in varying proportions. The infiltrate, which is mild and confined to the superficial dermis in macular lesion becomes denser with the increasing severity of the lesion. Leishman–Donovan bodies (LDB) in general are rarely demonstrable in macules and somewhat infrequently in the rest, though at times they may be numerous; mucosal lesions offer a greater chance of visualizing LDB than biopsies from the skin. A characteristic histomorphology in nodules is prominent follicular plugging with a dense plasma cell-rich lymphohistiocytic dermal infiltrate that shows an abrupt cut-off in the lower dermis, an appearance highly suggestive of PKDL even in the absence of LDB. Russell bodies within plasma cells, vascular changes, and xanthoma-like hue have been seen in plaques from chronic PKDL. The histopathologic picture in some may also mimic that seen in tuberculoid and lepromatous leprosy, and other granulomatous dermatoses. In contrast to Indian PKDL, epithelioid cell granulomas with giant cells are more common in African PKDL, and vascular changes are rare though neuritis showing LDB has been described. [ABSTRACT FROM AUTHOR]

Kala-azar, commonly known as visceral leishmaniasis (VL), is a neglected tropical disease that has been targeted in South Asia for elimination by 2020. Presently, the Kala-azar Elimination Programme is aimed at identifying new low-endemic foci by active case detection, consolidating vector control measures, and decreasing potential reservoirs, of which Post Kala-azar Dermal Leishmaniasis (PKDL) is considered as the most important. PKDL is a skin condition that occurs after apparently successful treatment of VL and is characterized by hypopigmented patches (macular) or a mixture of papules, nodules, and/or macules (polymorphic). To achieve this goal of elimination, it is important to delineate the pathophysiology so that informed decisions can be made regarding the most appropriate and cost-effective approach. We reviewed the literature with regard to PKDL in Asia and Africa and interpreted the findings in establishing a potential correlation between the immune responses and pathophysiology. The overall histopathology indicated the presence of a dense, inflammatory cellular infiltrate, characterized by increased expression of alternatively activated CD68+ macrophages, CD8+ T cells showing features of exhaustion, CD20+ B cells, along with decreased CD1a+ dendritic cells. Accordingly, this review is an update on the overall immunopathology of PKDL, so as to provide a better understanding of host-parasite interactions and the immune responses generated which could translate into availability of markers that can be harnessed for assessment of disease progression and improvement of existing treatment modalities. [ABSTRACT FROM AUTHOR]

Elimination of visceral leishmaniasis is a priority programme in Indian subcontinent. The World Health Organization has set a new target to eliminate kala-azar by the year 2020 as previous target elimination year (2015) has passed. The elimination programme has successfully curbed the rate of infection in endemic regions; however, there are still few challenges in its route. The current drug control regime is extremely limited and comprises only two (amphotericin B and miltefosine) drugs, which are also susceptible for parasites resistance. Moreover, these drugs do not produce sterile cure, and cured patients may develop post kala-azar dermal leishmaniasis even after a decade of cure leaving behind a potent source of parasitic reservoirs for further disease transmission. A significant proportion of endemic population remain seropositive but aymptomatic for many years without any clinical symptom that serve as latent parasitic reservoirs. The lack of tools to identify live parasites in asymptomatic infections and there association in disease transmission, parameters of sterile cure along with post kala-azar dermal leishmaniasis progression remain a major threat in its elimination. In this review, we discuss the potential of host immune inhibitory mechanisms to identify immune correlates of protective immunity to understand the mystery of asymptomatic infections, sterile cure and post kala azar dermal leishmaniasis.

This case report series alerts to the atypical manifestations of dermal leishmaniasis in an area endemic for post kala-azar dermal leishmaniasis, the sequel to visceral leishmaniasis. We have reported two cases with multiple skin lesions, wherein the rK39 strip test, polymerase chain reaction and parasite load confirmed the presence of Leishmania parasites. The causative parasite was identified as Leishmania major by restriction fragment length polymorphism of the ribosomal DNA Internal Transcribed Spacer-1, overruling the clinical suspicion of post kala-azar dermal leishmaniasis. The third case presented with fever and extensive hypopigmented patches in the upper extremities; parasites were identified in blood and skin by polymerase chain reaction and typed by restriction fragment length polymorphism as Leishmania donovani, establishing this as a case of visceral leishmaniasis concomitant with dermal leishmaniasis, secondary to dissemination of viscerotropic L. donovani. The present case series emphasizes the importance of molecular tools to identify the Leishmania species in order to ensure appropriate treatment. [ABSTRACT FROM AUTHOR]

Post Kala-azar Dermal Leishmaniasis (PKDL), a sequel of apparently cured Visceral Leishmaniasis presents in South Asia with papulonodular (polymorphic) or hypomelanotic lesions (macular). Till date, the polymorphic variant was considered predominant, constituting 85–90%. However, following active-case surveillance, the proportion of macular PKDL has increased substantially to nearly 50%, necessitating an in-depth analysis of this variant. Accordingly, this study aimed to delineate the cellular infiltrate in macular vis-à-vis polymorphic PKDL. To study the overall histopathology, hematoxylin and eosin staining was performed on lesional sections and phenotyping by immunohistochemistry done in terms of dendritic cells (CD1a), macrophages (CD68), HLA-DR, T-cells (CD8, CD4), B-cells (CD20) and Ki67 along with assessment of the status of circulating homing markers CCL2, CCL7 and CXCL13. In polymorphic cases (n = 20), the cellular infiltration was substantial, whereas in macular lesions (n = 20) it was mild and patchy with relative sparing of the reticular dermis. Although parasite DNA was identified in both variants by ITS-1 PCR, the parasite load was significantly higher in the polymorphic variant and Leishman-Donovan bodies were notably minimally present in macular cases. Both variants demonstrated a decrease in CD1a+ dendritic cells, HLA-DR expression and CD4+ T-cells. In macular cases, the proportion of CD68+ macrophages, CD8+ T-cells and CD20+ B-cells was 4.6 fold, 17.0 fold and 1.6 fold lower than polymorphic cases. The absence of Ki67 positivity and increased levels of chemoattractants suggested dermal homing of these cellular subsets. Taken together, as compared to the polymorphic variant, patients with macular PKDL demonstrated a lower parasite load along with a lesser degree of cellular infiltration, suggesting differences in host-pathogen interactions, which in turn can impact on their disease transmitting potential and responses to chemotherapy. Image 1 • Comparative analysis of immunopathology of polymorphic vs. macular PKDL. • Dense lymphohistiocytic infiltrate in polymorphic PKDL. • Mild and patchy cellular infiltration in macular PKDL with minimal Leishman Donovan bodies. • Decreased presence of CD1a, HLA-DR and CD4+ T-cells in both variants. • The presence of CD8+, CD68+and CD20+ cells in polymorphic>>>macular PKDL. [ABSTRACT FROM AUTHOR]

An 18 year-old-girl, a resident of Buxar District of Bihar State, India, presented with hypopigmented rash on face of six months duration. Superficial sensations were intact. There was history of being treated for prolonged fever two years ago, for about three weeks. Based on history, clinical and microscopic examination, she was diagnosed to have post kala-azar dermal leishmaniasis. Treatment with parenteral sodium stibogluconate was initiated, to which she responded satisfactorily. This case highlights the classical lesions of Indian type of PKDL and reiterates the fact that sodium stibogluconate should still be considered first line therapy as it is a cheap, yet efficacious drug.

Elimination of visceral leishmaniasis is a priority programme in Indian subcontinent. The World Health Organization has set a new target to eliminate kala-azar by the year 2020 as previous target elimination year (2015) has passed. The elimination programme has successfully curbed the rate of infection in endemic regions; however, there are still few challenges in its route. The current drug control regime is extremely limited and comprises only two (amphotericin B and miltefosine) drugs, which are also susceptible for parasites resistance. Moreover, these drugs do not produce sterile cure, and cured patients may develop post kala-azar dermal leishmaniasis even after a decade of cure leaving behind a potent source of parasitic reservoirs for further disease transmission. A significant proportion of endemic population remain seropositive but aymptomatic for many years without any clinical symptom that serve as latent parasitic reservoirs. The lack of tools to identify live parasites in asymptomatic infections and there association in disease transmission, parameters of sterile cure along with post kala-azar dermal leishmaniasis progression remain a major threat in its elimination. In this review, we discuss the potential of host immune inhibitory mechanisms to identify immune correlates of protective immunity to understand the mystery of asymptomatic infections, sterile cure and post kala azar dermal leishmaniasis. [ABSTRACT FROM AUTHOR]

Purpose: Leishmania, the causative organisms for leishmaniasis, reside in host macrophages and survive by modulating the microbicidal pathways via attenuation of the oxidative burst and/or suppression of cell-mediated immunity. As post kala-azar dermal leishmaniasis (PKDL), the dermal sequela of visceral leishmaniasis, has no animal model, the underlying mechanism(s) that nullify the microbicidal effector mechanisms remain poorly understood. This study was aimed at assessing the status of dipeptidyl peptidase CD26, a co-stimulatory molecule that is essential for T-cell signal activation. Methods: The frequency/expression of CD26 and CD45RO/RA was evaluated by flow cytometry, while levels of soluble CD26 (sCD26), CXCL-10, RANTES, IL-10 and TGF-β along with adenosine deaminase (ADA) activity were measured using ELISA. Results: In patients with PKDL vis-à-vis healthy individuals, there was a significant decrease in the frequency and expression of CD26 on CD3CD8 T-cells, which was accompanied by a significant lowering of plasma levels of sCD26. Furthermore, these patients showed a significant decrease in the frequency of CD45RO/CD8 T-cells, concomitant with a significant increase in the proportion of CD45RA/CD8 T-cells. This could collectively translate into reduced formation of the immunological synapse of CD26, CD45RO, and ADA, and lead to an attenuation of the Th1 responses. The decreased levels of CD26 and sCD26 correlated negatively with raised levels of Th2 cytokines, IL-10, and TGF-β along with the lesional parasite load, indicating disease specificity. Conclusions: Taken together, the decreased expression and secretion of CD26 in patients with PKDL resulted in impairment of the CD26-ADA interaction, and thereby possibly contributed to T-cell unresponsiveness, emphasizing the need to develop immunomodulatory therapies against PKDL and by extension, the leishmaniases. [ABSTRACT FROM AUTHOR]

Background: Patients with Post kala-azar dermal leishmaniasis (PKDL) are considered a reservoir of Leishmania donovani. It is imperative to identify and treat them early for control of visceral leishmaniasis (VL), a current priority in the Indian subcontinent. We explored trends in clinico-epidemiological features of PKDL cases over last two decades, for improving management of the disease.Methods: Clinically suspected cases were diagnosed with rK39 strip test followed by parasitological confirmation by microscopy and/or PCR/qPCR in skin tissue/slit aspirates. Patients were treated with antimonials till 2008 and subsequently with miltefosine.Results: The study indicated higher incidence of PKDL cases in areas of high endemicity for VL, with 20 % cases reporting no history of VL. Approximately 26 % cases of PKDL were initially misdiagnosed at primary health centers. Duration between onset of PKDL and diagnosis was above 12 months in 80 % cases. Diagnostic sensitivity was 32-36 % with microscopy and 96-100 % with PCR/qPCR. Compliance to treatment was over 85 % with miltefosine while 15 % with antimonials. Relapse rate with miltefosine was up to 13.2 %.Conclusions: PKDL patients tend to delay reporting and are often misdiagnosed. Confirmatory diagnosis using minimally invasive skin slit aspirate samples would help overcome such issues. There was a paradigm shift in compliance with miltefosine; however, increasing relapse rate indicated the need for newer therapies with oral formulations. [ABSTRACT FROM AUTHOR]

Background We assessed the feasibility and results of active case detection (ACD) of visceral leishmaniasis (VL), post kala-azar dermal leishmaniasis (PKDL) and other febrile diseases as well as of bednet impregnation for vector control. Methods Fever camps were organized and analyzed in twelve VL endemic villages in Bangladesh, India, and Nepal. VL, PKDL, tuberculosis, malaria and leprosy were screened among the febrile patients attending the camps, and existing bednets were impregnated with a slow release insecticide. Results Among the camp attendees one new VL case and two PKDL cases were detected in Bangladesh and one VL case in Nepal. Among suspected tuberculosis cases two were positive in India but none in the other countries. In India, two leprosy cases were found. No malaria cases were detected. Bednet impregnation coverage during fever camps was more than 80% in the three countries. Bednet impregnation led to a reduction of sandfly densities after 2 weeks by 86% and 32%, and after 4 weeks by 95% and 12% in India and Nepal respectively. The additional costs for the control programmes seem to be reasonable. Conclusion It is feasible to combine ACD camps for VL and PKDL along with other febrile diseases, and vector control with bednet impregnation. [ABSTRACT FROM AUTHOR]

Rarely, post-kala-azar dermal leishmaniasis (PKDL) may coexist with visceral leishmaniasis (VL). The concomitant PKDL and VL are referred to as Para-kala-azar dermal Leishmaniasis. We report a case of Para kala-azar dermal leishmaniasis in a chronic Hepatitis-B virus-infected patient who presented with an abdominal lump and multiple maculopapular skin lesions and is resistant to sodium stibogluconate but successfully treated with liposomal Amphotericin-B., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Moniruzzaman et al.)

Post kala-azar dermal leishmaniasis (PKDL) is a skin complication resulting from infection with Leishmania donovani (LD) parasite. It mostly affects individuals who have previously suffered from visceral leishmaniasis (VL) caused by LD. In some cases, PKDL develops among people infected with LD, but do not show any symptoms of VL. Clinical presentation includes hypopigmented macules/papules/nodules or polymorphic lesions (combination of two or more lesions). Except for skin lesions, PKDL patients are generally healthy and usually do not seek medical care. These patients play an important role in interepidemic transmission of the infection and subsequent VL outbreak. Therefore, proper diagnosis and treatment of PKDL patients is important for the control of VL in endemic countries, especially in the Indian subcontinent where VL is anthroponotic. Here, we report the challenges in the estimation of PKDL burden, its diagnosis, and treatment, and suggest possible solutions based on recent literature, reports, published manuals, and web-based information. [ABSTRACT FROM AUTHOR]

Post kala-azar dermal leishmaniasis (PKDL) is a neglected complication of visceral leishmaniasis (VL)–a deadly, infectious disease that claims approximately 20,000 to 40,000 lives every year. PKDL is thought to be a reservoir for transmission of VL, thus, adequate control of PKDL plays a key role in the ongoing effort to eliminate VL. Over the past few years, several expert meetings have recommended that a greater focus on PKDL was needed, especially in South Asia. This report summarizes the Post Kala-Azar Dermal Leishmaniasis Consortium Meeting held in New Delhi, India, 27-29 June 2012. The PKDL Consortium is committed to promote and facilitate activities that lead to better understanding of all aspects of PKDL that are needed for improved clinical management and to achieve control of PKDL and VL. Fifty clinicians, scientists, policy makers, and advocates came together to discuss issues relating to PKDL epidemiology, diagnosis, pathogenesis, clinical presentation, treatment, and control. Colleagues who were unable to attend participated during drafting of the consortium meeting report. [ABSTRACT FROM AUTHOR]

Abstract: Post kala-azar dermal leishmaniasis (PKDL), a dermal sequel of visceral leishmaniasis presents with macular or polymorphic lesions. As immunological variations between these two forms have not been delineated, we evaluated levels of antileishmanial total Ig, IgG and its subclasses, IgM, IgE, IgG avidity, cytokines IL-10, IL-4, IL-13 and expression of CD19. The levels of Ig and IgG in polymorphic PKDL were higher than macular PKDL, while significant curtailment in levels of Ig, IgM and IgG following treatment was evident only in polymorphic PKDL. With regard to IgG subclasses, IgG1 and IgG3 were significantly raised in polymorphic PKDL, whereas in macular PKDL only IgG1 was elevated; treatment decreased levels of IgG1, IgG2 and IgG3 only in polymorphic PKDL; IgE levels were raised in both groups but no marked alterations occurred following treatment. The avidity of IgG was higher in polymorphic PKDL and correlated with duration of disease. IL-10 was higher in polymorphic PKDL and decreased significantly after treatment, whereas in macular PKDL IL-4 predominated. Taken together, in PKDL the humoral immune response was greater in the polymorphic variant than the macular form suggesting that serological markers may have a role in monitoring polymorphic PKDL. [Copyright &y& Elsevier]

Background: Active case detection (ACD) significantly contributes to early detection and treatment of visceral leishmaniasis (VL) and post kala-azar dermal leishmaniasis (PKDL) cases and is cost effective. This paper evaluates the performance and feasibility of adapting ACD strategies into national programs for VL elimination in Bangladesh, India and Nepal. Methods: The camp search and index case search strategies were piloted in 2010-11 by national programs in high and moderate endemic districts / sub-districts respectively. Researchers independently assessed the performance and feasibility of these strategies through direct observation of activities and review of records. Program costs were estimated using an ingredients costing method. Results: Altogether 48 camps (Bangladesh-27, India-19, Nepal-2) and 81 index case searches (India-36, Nepal-45) were conducted by the health services across 50 health center areas (Bangladesh-4 Upazillas, India-9 PHCs, Nepal-37 VDCs). The mean number of new case detected per camp was 1.3 and it varied from 0.32 in India to 2.0 in Bangladesh. The cost (excluding training costs) of detecting one new VL case per camp varied from USD 22 in Bangladesh, USD 199 in Nepal to USD 320 in India. The camp search strategy detected a substantive number of new PKDL cases. The major challenges faced by the programs were inadequate preparation, time and resources spent on promoting camp awareness through IEC activities in the community. Incorrectly diagnosed splenic enlargement at camps probably due to poor clinical examination skills resulted in a high proportion of patients being subjected to rK39 testing. Conclusion: National programs can adapt ACD strategies for detection of new VL/PKDL cases. However adequate time and resources are required for training, planning and strengthening referral services to overcome challenges faced by the programs in conducting ACD. [ABSTRACT FROM AUTHOR]

Background: Post kala-azar dermal leishmaniasis (PKDL) is a cutaneous form of disease that develops at variable times after individuals have received treatment for clinical visceral leishmaniasis (VL). The study aimed to investigate the possible role of interleukin 10 (IL-10) and development of PKDL. Methods: 77 families composed of 41 complete case-parent trios and 36 case-parent pairs from the Masalit ethnic group were genotyped for 3 IL10 promoter polymorphisms: -1082A/G, -819C/T and -592C/A. Results: Single point analysis using the transmission disequilibrium test showed no evidence of association between any of these IL10 promoter single nucleotide polymorphisms (SNPs) and development of PKDL. Haplotype analysis performed using TRANSMIT showed borderline significance between PKDL and the haplotype AA across -592C/A and -1082A/G (p = 0.053). Haplotypes GCC (0.33) and ATA (0.30) were the common haplotypes in this Sudanese population. Allele frequencies for the 3 SNPs differed significantly in Sudan compared to other African (Gambian, Malawian, YRI) populations. Conclusion: There is no evidence for an association between 3 SNPs in the IL10 gene promoter and susceptibility to PKDL in the Masalit ethnic group in Sudan, although some evidence for haplotype association was observed. Copyright © 2009 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background & objectives: Of the two reservoirs of infection of kala-azar Le., patients of kala-azar and post kala-azar dermal leishmaniasis (PKDL), PKDL provides easy access for the sandfly to pick up the parasites. In the last epidemic of 1977 in India, the importance of PKDL as a potential cause of increase in number of kala-azar cases was ignored. During recent years, we found an increase in the cases of kalaazar whereas cases of PKDL were decreasing in Bihar. We undertook this study to find out reasons for this phenomenon. Methods: These three different settings were selected to study the trends of the disease. (i) Cases of PKDL registered in the Dermatology Department of Patna Medical College Hospital (PMCH), one of the largest and oldest teaching hospital in Bihar, between 1970 and 2005; (ii) Rajendra Memorial Research Institute of Medical Sciences, Patna (RMRIMS), a research institute exclusively devoted to kala-azar (2000 and 2005); and (iii) interviews with two leading dermatologists of Patna selected by lottery on the incidence of PKDL and possible causes of its decrease, if any. The number of eases of kala-azar (visceral leishmaniasis, VL) from Bihar was studied from Malaria Departments of the Government of Bihar and Government of India, the two nodal departments dealing with the kala-azar. Results: Analysis of data from Dermatology Department of PMCH showed increase in number of cases of PKDL from two in 1970 to 12 in 1976, a year before the first epidemic of kala-azar in 1977 with 100,000 cases. Kala-azar cases decreased to 11,120 in 1982 due to control measures taken between 1977- 1979 but cases of PKDL reached 28 and kept on increasing. During 1950 to 1977, low dose and short duration regimen of sodium antimony gluconate (SAG) was mainly used in the treatment of kala-azar. Between 1977-1991 increasing incidence of unresponsiveness to SAG, led to the usage of longer duration and higher dose regimen of SAG, more use of amphotericin B (AMB) for SAG resistant cases and also as a first line drug for kala-azar and PKDL. The number of kala-azar cases started decreasing after control measures taken during 1992-1994 but cases of PKDL continued decreasing. The effect of control measures on the incidence of kala-azar was visible upto 2002, but decrease in number of PKDL cases continued. In 2005 the number of PKDL cases was 14 but number of kala-azar cases reached 21,177 in Bihar. In the interview, the two dermatologists also opined that PKDL was decreasing due to increased use of amphotericin B in the treatment of kala-azar. Trend analysis done on the data of PMCH and RMRIMS showed that PKDL will decrease in coming years and kala-azar will increase. Interpretation & conclusion: Incidence of PKDL decreased in PMCH and RMRIMS and also suggested by two dermatologists that extensive use of amphotericin B in the treatment of kala-azar might be responsible for decrease in number of cases of PKDL. [ABSTRACT FROM AUTHOR]

Background: Post-kala-azar dermal leishmaniasis follows an attack of visceral leishmaniasis and is caused by the same organism, i.e. Leishmania donovani.Methods: In the present study, biopsy specimens from hypopigmented macules, nodules or plaques of 25 patients clinically diagnosed as PKDL were evaluated for epidermal and dermal changes and for the presence or absence of Leishmania donovani bodies (LDBs).Results: The hypopigmented macules showed a patchy perivascular and periappendageal infiltrate with no demonstrable LDBs in any of the biopsies. In the nodular and plaque lesions, the infiltrate was diffuse, beneath an atrophic epidermis (74%) and follicular plugging (95.6%) was seen in most biopsies. The infiltrate consisted of lymphocytes, histiocytes and plasma cells in decreasing order of presence. LDBs could be demonstrated in only 10 (43.5%) biopsy specimens from nodular and plaque lesions and were never numerous.Conclusions: Histopathological features of PKDL are elucidated and discussed. [ABSTRACT FROM AUTHOR]