PKDL—A Silent Parasite Pool for Transmission of Leishmaniasis in Kala-azar Endemic Areas of Malda District, West Bengal, India

Ganguly, Shirshendu; Saha, Pabitra; Chatterjee, Moytrey; Roy, Surajit; Ghosh, Tamal; Guha, Subhasish Kamal; Kundu, Prabir Kumar; Bera, Dilip Kumar; Basu, Nandita; Maji, Ardhendu Kumar

doi:10.1371/journal.pntd.0004138

Cited by 34 publications

(29 citation statements)

References 34 publications

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“…The cumulative incidence of a PKDL relapse following PKDL treatment ranged from 0–12.5% [ 9 , 92 ]. Two of the 9 (22%) PKDL patients detected in a house to house survey were relapsed cases of PKDL [ 88 ].…”

Section: Resultsmentioning

confidence: 99%

“…Two of the 9 (22%) PKDL patients detected in a house to house survey were relapsed cases of PKDL [ 88 ]. There was no correlation between the miltefosine dosage used for treating PKDL and PKDL relapse [ 92 ]. However, the proportion of PKDL relapse following a 3mo PKDL treatment with miltefosine was significantly higher (43%) compared to PKDL patients treated with 4mo of miltefosine [ 121 ].…”

Section: Resultsmentioning

confidence: 99%

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Transmission Dynamics of Visceral Leishmaniasis in the Indian Subcontinent – A Systematic Literature Review

et al. 2016

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BackgroundAs Bangladesh, India and Nepal progress towards visceral leishmaniasis (VL) elimination, it is important to understand the role of asymptomatic Leishmania infection (ALI), VL treatment relapse and post kala-azar dermal leishmaniasis (PKDL) in transmission.Methodology/ Principal FindingWe reviewed evidence systematically on ALI, relapse and PKDL. We searched multiple databases to include studies on burden, risk factors, biomarkers, natural history, and infectiveness of ALI, PKDL and relapse. After screening 292 papers, 98 were included covering the years 1942 through 2016. ALI, PKDL and relapse studies lacked a reference standard and appropriate biomarker. The prevalence of ALI was 4–17-fold that of VL. The risk of ALI was higher in VL case contacts. Most infections remained asymptomatic or resolved spontaneously. The proportion of ALI that progressed to VL disease within a year was 1.5–23%, and was higher amongst those with high antibody titres. The natural history of PKDL showed variability; 3.8–28.6% had no past history of VL treatment. The infectiveness of PKDL was 32–53%. The risk of VL relapse was higher with HIV co-infection. Modelling studies predicted a range of scenarios. One model predicted VL elimination was unlikely in the long term with early diagnosis. Another model estimated that ALI contributed to 82% of the overall transmission, VL to 10% and PKDL to 8%. Another model predicted that VL cases were the main driver for transmission. Different models predicted VL elimination if the sandfly density was reduced by 67% by killing the sandfly or by 79% by reducing their breeding sites, or with 4–6y of optimal IRS or 10y of sub-optimal IRS and only in low endemic setting.Conclusion/ SignificanceThere is a need for xenodiagnostic and longitudinal studies to understand the potential of ALI and PKDL as reservoirs of infection.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Transmission Dynamics of Visceral Leishmaniasis in the Indian Subcontinent – A Systematic Literature Review

et al. 2016

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“…The major limitation of this study is that we performed RPA and qPCR assay with DNA extracted by three different DNA Extraction methods using different skin biopsies. This might have generated some variance, and an over-or underestimation of the performance of any of the methods, as the parasites are not evenly distributed in the lesions of PKDL patients (5). The skin biopsy procedure is invasive and requires surgical set-up and this limits the ability to collect multiple biopsies without negatively impacting patient participation and use as an active field-based case detection method.…”

Section: Discussionmentioning

confidence: 99%

“…For unknown reasons the incidence of PKDL cases with different types of lesions varies across L. donovani endemic regions (2). In Sudan, 50-60% of treated VL patients develop PKDL within 6 months, whereas, in Indian Subcontinent, PKDL is reported to develop in 5-10% VL patients within 2-4 years after treatment (3)(4)(5). Surprisingly, the incidence rate of PKDL increases two fold within 5 years of completion of VL treatment (6).…”

Section: Introductionmentioning

confidence: 99%

Evaluation of rapid extraction methods coupled with Recombinase polymerase amplification assay for point-of-need diagnosis of Post-kala-azar-dermal leishmaniasis

Chowdhury

Ghosh

Khan

et al. 2019

Preprint

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Introduction Post kala-azar dermal leishmaniasis (PKDL) usually develops as sequelae of visceral leishmaniasis (VL) and can manifest in multiple dermatological forms. Since PKDL patients harbor Leishmania donovani parasites and can potentially trigger inter-epidemic transmission of the disease, the success of kala-azar elimination programme could be jeopardized by these cases. Although several molecular methods with promising diagnostic efficacy have been developed to detect PKDL cases, albeit complicated and expensive DNA extraction methods limit their application in resource poor settings. To address this, in comparison to a reference DNA extraction method (Qiagen), we evaluated two rapid DNA extraction methods and determined their impact on the detection of the parasite DNA using our newly developed recombinase polymerase amplification (RPA) assay.Methods Thirty suspected PKDL cases were enrolled after diagnosis by clinical examination and a positive rk39 strip test. DNA was extracted from three skin biopsy samples using either a spin column-based method (Qiagen) or one of two rapid DNA extraction methods, (Boil & Spin (B&S) and SpeedXtract (SE)). RPA and qPCR were subsequently performed with the extracted samples to detect L. donovani DNA.Results Using DNA extracted by Qiagen method, the qPCR and RPA assays exhibited sensitivities of 86.7% and 93.3% respectively. In contrast, the sensitivity of RPA assay dropped to 76.7% and 63.3%, respectively, when the B&S and SE rapid extraction methods were performed. Despite this compromised sensitivity, B&S-RPA technique yielded an excellent agreement with both Q-qPCR (k = 0.828) and Q-RPA (k =0.831) techniques. Moreover, SE-RPA showed good agreement with Q-qPCR (k = 0.755), Q-RPA (k =0.692) and B&S-RPA (k =0.635) assays. As expected, with all of the three DNA extraction methods, both qPCR and RPA assay showed absolute specificity.Conclusions This study finding substantiates the superior diagnostic efficacy of Qiagen DNA extraction method over B&S and SE method in detecting LD DNA through RPA assay from skin biopsy of PKDL patients. To apply these rapid DNA extraction methods in resource-constrained settings, further methodological refinement is warranted to improve DNA yield and purity through rigorous experiments.

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“…In India, on the other hand, PKDL occurs in 5 to 10% of former VL patients, manifests two to three years after their recuperation, and in general requires treatment [59]. In both cases, the patients-even though completely cured from VL-may play a role in the transmission of the disease [60].…”

Section: Pathologymentioning

confidence: 99%

Epidemiological, Biological and Clinical Aspects of Leishmaniasis with Special Emphasis on Busi Yasi in Suriname

Mans¹,

Kent²,

Hu³

et al. 2017

J Clin Exp Dermatol Res

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The parasitic disease leishmaniasis is caused by protozoa of the genus Leishmania which are transmitted by sand fly vectors of the genus Phlebotomus in the Old World and Lutzomyia in the New World. Transmission can either be anthroponotic (human to human) or zoonotic through mammalian reservoirs such as dogs and rodents. Leishmaniasis has three principal clinical manifestations, namely cutaneous leishmaniasis (CL), mucocutaneous leishmaniasis (MCL), and visceral leishmaniasis (VL). The cutaneous form characteristically causes skin ulcers, the mucocutaneous form manifests as lesions of skin, mouth, and nose, and the (potentially lethal) visceral form affects the internal organs such as spleen and liver and also invades the bone marrow. Leishmaniasis is endemic in about ninety-eight countries and the diverse types of the disease occur in different regions of the world. CL is most common in Afghanistan, Algeria, Pakistan, Iran, Brazil, and Colombia; MCL is mainly restricted to countries of the Amazon Basin; and VL is most frequently seen in the Indian sub-continent, the Horn of Africa (Sudan and Ethiopia), and Brazil. The current global prevalence is estimated at about 12 million, and each year, the disease in one of its forms makes about 2 million new victims and claims up to 50,000 fatalities. This paper presents epidemiological, biological, and clinical aspects of leishmaniasis throughout the world; then focuses on the disease in the Republic of Suriname (South America); addresses in more detail the species of Leishmania parasites in that country; and concludes with potential future directions to improve our understanding of leishmaniasis in Suriname.

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PKDL—A Silent Parasite Pool for Transmission of Leishmaniasis in Kala-azar Endemic Areas of Malda District, West Bengal, India

Cited by 34 publications

References 34 publications

Transmission Dynamics of Visceral Leishmaniasis in the Indian Subcontinent – A Systematic Literature Review

Transmission Dynamics of Visceral Leishmaniasis in the Indian Subcontinent – A Systematic Literature Review

Evaluation of rapid extraction methods coupled with Recombinase polymerase amplification assay for point-of-need diagnosis of Post-kala-azar-dermal leishmaniasis

Epidemiological, Biological and Clinical Aspects of Leishmaniasis with Special Emphasis on Busi Yasi in Suriname

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