DNA Polymorphism Assay Distinguishes Isolates of<i>Leishmania donovani</i>That Cause Kala-Azar from Those That Cause Post-Kala-Azar Dermal Leishmaniasis in Humans

Gannavaram, Sreenivas; Raju, B. V. Subba; Singh, Ruchi; Selvapandiyan, Angamuthu; Duncan, Robert C.; Sarkar, Debdeep; Nakhasi, Hira L.; Salotra, Poonam

doi:10.1128/jcm.42.4.1739-1741.2004

Cited by 28 publications

(24 citation statements)

References 20 publications

(19 reference statements)

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“…An informed consent based on the guidelines of the Ethical Committee, Safdarjung Hospital, New Delhi, was obtained from the patients. L. donovani isolates were prepared from bone marrow aspirates of VL patients, as described elsewhere (Sreenivas et al 2004a). All the isolates were characterised as L. donovani, on the basis of reaction with species-specific monoclonal antibody and/ or polymerase chain reaction (Sreenivas et al 2004b).…”

Section: Methodsmentioning

confidence: 99%

Biomarkers of antimony resistance: need for expression analysis of multiple genes to distinguish resistance phenotype in clinical isolates of Leishmania donovani

et al. 2012

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Resistance to antimony is a major cause of failure to therapy in a large proportion of visceral leishmaniasis cases. Methods to distinguish resistant and sensitive parasite are urgently needed as the standard in vitro intracellular drug susceptibility assays are cumbersome and time consuming. Differential expression profiling studies have led to the identification of several antimony resistance-associated genes; however, their efficacy as a potential biomarker for monitoring antimony resistance remains imprecise. We analysed the expression of eight genes [antimony metabolism-associated genes - multidrug resistance protein A (MRPA), γ-glutamylcysteine synthetase (γ-GCS) and aquaporin-1 (AQP1) - and genes identified by proteome/transcriptome profiling—heat shock protein 83, mitogen-activated protein kinase 1 and histones H1, H2A and H4) in antimony-resistant (n=10) and antimony-sensitive (n=4) clinical isolates of Leishmania donovani by quantitative real-time PCR, in comparison with a lab-generated resistant and a standard sensitive isolate. We observed a significant differential expression of MRPA, histone H1 (p<0.01), γ-GCS, HSP83 (p<0.005) and histone H2A and H4 (p<0.0001) in a group of sodium antimony gluconate-resistant isolates compared to sensitive isolates. Preferential AQP1 expression was observed in all the sensitive isolates (p<0.0001). Overall, expression profile in field isolates for all the genes studied showed altered expression in majority of isolates, while in some, the expression was static. All the isolates showed a mosaic of expression pattern of the genes analysed indicating constellation of genes contributes towards the drug susceptibility of parasite. As none of the genes exhibit an absolute correlation with phenotype, targeted expression analysis of a set of genes should be considered as biomarker for distinguishing the antimony-resistant and antimony-sensitive parasite.

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Section: Methodsmentioning

confidence: 99%

Biomarkers of antimony resistance: need for expression analysis of multiple genes to distinguish resistance phenotype in clinical isolates of Leishmania donovani

et al. 2012

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“…Such parasite strains may be differentiated by the use of genetic tags [54,55]. Recent developments have even indicated that some genes are significantly overexpressed among isolates from patients with PKDL compared with those obtained from cases of visceral leishmaniasis [56].…”

Section: Parasite Strains As Determinants Of Clinical and Therapeuticmentioning

confidence: 99%

Recent developments leading toward a paradigm switch in the diagnostic and therapeutic approach to human leishmaniasis

Schriefer

Wilson

Carvalho

2008

Current Opinion in Infectious Diseases

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Purpose of review To identify recent papers showing how human and parasite genetics influence leishmaniasis, and how understanding of the immunopathology may be utilized in immunotherapy for these diseases. Recent findings Progress has been made in recent years showing the complexity within populations of Leishmania spp. and indicating that different strains lead to diverse clinical pictures and responses to treatment. Thus detection of parasite genetic tags for the precise identification of infecting strains, and for predictive diagnosis of clinical and therapeutic fates seems now possible. Host genetic loci involved in disease outcome have been detected, which may also be explored for better case management. These developments in diagnosis will demand expanding the therapeutic arsenal to take their expected effect. This is starting to be fulfilled by immunotherapies successfully employed to treat cases refractory to standard first line drugs, as the result of a more profound comprehension of the immunopathology of the leishmaniases. Summary The knowledge mounting has already helped explain why different patients present different forms of leishmaniasis and respond differently to treatment, and may be on the verge of catalyzing a major change in the already over a century old paradigm of diagnosing and managing these patients.

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“…Studies of molecular DNA markers of parasites from mucosal lesions of leishmaniasis and from blood samples of patients with kalaazar have shown they represent different strains of L. donovani 13 . A similar study of genetic polymorphisms distinguishes L. donovani strain responsible for kala-azar from that in PKDL 21 .…”

Section: Discussionmentioning

confidence: 99%

“…Finally, keeping similarity to reports of different strains of L. donovani responsible for cutaneous and mucosal lesions in patients from Sudan and India 13,21 , genetic studies of strains of L. (L.) chagasi that affect the skin could be interesting to distinguish them of those that only affect internal organs in VL, mainly for the possibility of prediction of mucosal compromising. In this report it was possible to show similarity, using enzymatic digestion with HaeIII, of a 120 bp DNA fragment amplified from skin lesion from this patient with aids-VL co-infection and from blood sample collected from another patient with VL.…”

Section: Discussionmentioning

confidence: 99%

L. (L.) chagasi in aids and visceral leishmaniasis (kala-azar) co-infection

Roselino

Chociay

Costa

et al. 2008

Rev. Inst. Med. trop. S. Paulo

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SUMMARYConcomitant skin lesions in visceral leishmaniasis (VL) or kala-azar are rare, being more common the description of postkala-azar dermal leishmaniasis occurring post treatment of kala-azar. Skin lesions caused by Leishmania donovani are frequently seen in the aids-VL co-infection. In Brazil cutaneous or mucosal forms of tegumentary leishmaniasis concomitant with aids are more commonly registered. Here we present a case of aids-VL co-infection, with unusual cutaneous and digestive compromising attributed to L. (L.) chagasi, with special attention to ecthymatous aspect of the lesion, allied to the absence of parasite on the histological skin biopsy.

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DNA Polymorphism Assay Distinguishes Isolates ofLeishmania donovaniThat Cause Kala-Azar from Those That Cause Post-Kala-Azar Dermal Leishmaniasis in Humans

Cited by 28 publications

References 20 publications

Biomarkers of antimony resistance: need for expression analysis of multiple genes to distinguish resistance phenotype in clinical isolates of Leishmania donovani

Biomarkers of antimony resistance: need for expression analysis of multiple genes to distinguish resistance phenotype in clinical isolates of Leishmania donovani

Recent developments leading toward a paradigm switch in the diagnostic and therapeutic approach to human leishmaniasis

L. (L.) chagasi in aids and visceral leishmaniasis (kala-azar) co-infection

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