Leishmaniasis and poverty

Alvar, Jorge; Yactayo, Sergio; Bern, Caryn

doi:10.1016/j.pt.2006.09.004

Cited by 647 publications

(556 citation statements)

References 44 publications

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“…It is one of the most neglected diseases worldwide, distributed especially in tropical and subtropical areas, and it has strong and complex associations with poverty (Alvar et al, 2006). Leishmania parasites cause three forms of leishmaniases (cutaneous, mucocutaneous and visceral leishmaniasis) depending on the infecting species.…”

Section: Introductionmentioning

confidence: 99%

Development of a loop-mediated isothermal amplification method for rapid mass-screening of sand flies for Leishmania infection

et al. 2014

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Entomological monitoring of Leishmania infection in leishmaniasis endemic areas offers epidemiologic advantages for predicting the risk and expansion of the disease, as well as evaluation of the effectiveness of control programs. In this study, we developed a highly sensitive loop-mediated isothermal amplification (LAMP) method for the mass screening of sand flies for Leishmania infection based on the 18S rRNA gene. The LAMP technique could detect 0.01 parasites, which was more sensitive than classical PCR. The method was robust and could amplify the target DNA within 1 hr from a crude sand fly template without DNA purification. Amplicon

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Section: Introductionmentioning

confidence: 99%

Development of a loop-mediated isothermal amplification method for rapid mass-screening of sand flies for Leishmania infection

et al. 2014

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“…It is a significant cause 56 of morbidity and mortality in developing countries, and affects about 2 million people per year 57 mostly in tropical and subtropical regions (Alvar et al, 2006). Leishmaniasis is also an important 58 public health and veterinary concern in Mediterranean countries (Dujardin, 2006).…”

Section: Introduction 54mentioning

confidence: 99%

6-Br-5methylindirubin-3′oxime (5-Me-6-BIO) targeting the leishmanial glycogen synthase kinase-3 (GSK-3) short form affects cell-cycle progression and induces apoptosis-like death: Exploitation of GSK-3 for treating leishmaniasis

Xingi

Smirlis

Myrianthopoulos

et al. 2009

International Journal for Parasitology

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Indirubins known to target mammalian cyclin-dependent kinases (CDKs) and glycogen synthase kinase (GSK-3) were tested for their antileishmanial activity. 6-Br-indirubin-3'-oxime (6-BIO), 6-Br-indirubin-3'acetoxime and 6-Br-5methylindirubin-3'oxime (5-Me-6-BIO) were the most potent inhibitors of L. donovani promastigote and amastigote growth (IC50 values ≤ 1.2 μM). Since the 6-Br substitution on the indirubin backbone greatly enhances the selectivity for mammalian GSK-3 over CDKs, we identified the leishmanial GSK-3 homologues, a short (LdGSK-3s) and a long one, focusing on LdGSK-3s which is closer to human GSK-3β for further studies. Kinase assays showed that 5-Me-6-BIO inhibited LdGSK-3s more potently than CRK3 (the CDK1 homologue in Leishmania), while 6-BIO was more selective for CRK3. Promastigotes treated with 5-Me-6-BIO accumulated in the S and G2/M cell-cycle phases and underwent apoptosis-like death.Interestingly, these phenotypes were completely reversed in parasites over-expressing LdGSK-3s.This finding strongly supports that LdGSK-3s is a) the intracellular target of 5-Me-6-BIO and b) involved in cell-cycle control and in pathways leading to apoptosis-like death. 6-BIO treatment induced a G2/M arrest, consistent with inhibition of CRK3, and apoptosis-like death. These effects were partially reversed in parasites over-expressing suggesting that in vivo 6-BIO may also target LdGSK-3s. Molecular docking of 5-Me-6-BIO in CRK3 and 6-BIO in human and LdGSK-3s active sites predict the existence of functional/structural differences that are sufficient to explain the observed difference in their affinity. In conclusion, LdGSK-3s is validated as a potential drug target in Leishmania and could be exploited for the development of selective indirubin-based leishmanicidals. AUTHOR AGREEMENT FORMManuscript title: "5-Me-6-BIO targeting the leishmanial GSK-3 short form affects cell-cycle progression and induces apoptosis-like death: exploitation of GSK-3 for treating leishmaniasis" Authors: Evangelia Xingi, Despina Smirlis , Vassilios Myrianthopoulos , Prokopios Magiatis, Karen M. Grant, Laurent Meijer, Emmanuel Mikros, Alexios-Leandros Skaltsounis and Ketty Soteriadou We, the undersigned, acknowledge that we have read the above manuscript and accept responsibility for its contents. We confirm this manuscript has not been published previously and if accepted in the International Journal for Parasitology will not be published elsewhere without the approval of the Editor-in-Chief. We also confirm there are no financial or other relationships that might lead to a conflict of interest.[If a financial or other relationship exists that might lead to a conflict of interest, please provide that information here.][If this letter is being submitted at revision and if there have been any changes in authors added to/deleted from the paper or if the order of author citation has changed since the original submission, please include a statement acknowledging those changes, before each author (including authors deleted fro...

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“…Visceral leishmaniasis (VL), caused by the protozoan parasites Leishmania donovani and L. infantum, is one of the most important of the neglected tropical diseases, with approximately 500,000 new cases and 70,000 deaths reported per annum (7,8). Pentavalent antimonial drugs remain a first-line therapy for VL in most parts of the world, although increasing drug resistance now limits their use in India.…”

Section: Introductionmentioning

confidence: 99%

Inhibition of receptor tyrosine kinases restores immunocompetence and improves immune-dependent chemotherapy against experimental leishmaniasis in mice

Dalton¹,

Maroof²,

Owens³

et al. 2010

J. Clin. Invest.

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Receptor tyrosine kinases are involved in multiple cellular processes, and drugs that inhibit their action are used in the clinic to treat several types of cancer. However, the value of receptor tyrosine kinase inhibitors (RTKIs) for treating infectious disease has yet to be explored. Here, we have shown in mice that administration of the broad-spectrum RTKI sunitinib maleate (Sm) blocked the vascular remodeling and progressive splenomegaly associated with experimental visceral leishmaniasis. Furthermore, Sm treatment restored the integrity of the splenic microarchitecture. Although restoration of splenic architecture was accompanied by an increase in the frequency of IFN-γ + CD4 + T cells, Sm treatment alone was insufficient to cause a reduction in tissue parasite burden. However, preconditioning by short-term Sm treatment proved to be successful as an adjunct therapy, increasing the frequency of IFN-γ + and IFN-γ + TNF + CD4 + T cells, enhancing NO production by splenic macrophages, and providing dose-sparing effects when combined with a first-line immune-dependent anti-leishmanial drug. We propose, therefore, that RTKIs may prove clinically useful as agents to restore immune competence before the administration of chemo-or immunotherapeutic drugs in the treatment of visceral leishmaniasis or other diseases involving lymphoid tissue remodeling, including cancer.

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Leishmaniasis and poverty

Cited by 647 publications

References 44 publications

Development of a loop-mediated isothermal amplification method for rapid mass-screening of sand flies for Leishmania infection

Development of a loop-mediated isothermal amplification method for rapid mass-screening of sand flies for Leishmania infection

6-Br-5methylindirubin-3′oxime (5-Me-6-BIO) targeting the leishmanial glycogen synthase kinase-3 (GSK-3) short form affects cell-cycle progression and induces apoptosis-like death: Exploitation of GSK-3 for treating leishmaniasis

Inhibition of receptor tyrosine kinases restores immunocompetence and improves immune-dependent chemotherapy against experimental leishmaniasis in mice

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