Monitoring drug resistance in leishmaniasis

Croft, Simon L.

doi:10.1046/j.1365-3156.2001.00754.x

Cited by 100 publications

(78 citation statements)

References 54 publications

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“…It should be performed preferably in vitro using the amastigote-macrophage model, which evaluate the resistance of L. donovani isolates to antimonials (Croft, 2001).…”

Section: Discussionmentioning

confidence: 99%

Treatment of visceral leishmaniasis in south-eastern Nepal: decreasing efficacy of sodium stibogluconate and need for a policy to limit further decline

Rijal

Chappuis

Singh

et al. 2003

Transactions of the Royal Society of Tropical Medicine and Hygi

117

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Sodium stibogluconate (SSG) is the first-line therapy for visceral leishmaniasis (VL) in south-eastern Nepal. Recent studies from the neighbouring state of Bihar, India, have shown a dramatic fall in cure rates with treatment failure occurring in up to 65% of VL patients treated with SSG. A prospective study was conducted at a tertiary-level hospital located in south-eastern Nepal from July 1999 to January 2001. Parasitologically proven kala-azar patients with no previous history of treatment for VL were treated with SSG 20 mg/kg/d for 30 d which was extended to 40 d in those with persistent positive parasitology. Of the 110 patients who completed SSG therapy and were assessed at 1 and 6 months, definite cure was achieved in 99 patients (90%) and SSG failure occurred in 11 patients (10%). Except for the presence of hepatomegaly and a lower platelet count there was no clinical or laboratory baseline characteristic associated with treatment failure. A significantly lower cure rate (76%, P= 0.03) was observed in patients from the district of Saptari, which borders the antimony-resistant VL areas of Bihar. The efficacy of SSG as a first-line treatment for VL in south-eastern Nepal was still satisfactory, except for the patients living closer to the antimony-resistant VL areas of India. These findings indicate that the spread of resistance to antimonials is already taking place in Nepal and that a policy to control further spread should be urgently implemented.

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“…It should be performed preferably in vitro using the amastigote-macrophage model, which evaluate the resistance of L. donovani isolates to antimonials (Croft, 2001).…”

Section: Discussionmentioning

confidence: 99%

Treatment of visceral leishmaniasis in south-eastern Nepal: decreasing efficacy of sodium stibogluconate and need for a policy to limit further decline

Rijal

Chappuis

Singh

et al. 2003

Transactions of the Royal Society of Tropical Medicine and Hygi

117

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“…In view of the lack of safe drugs and the serious secondary effects caused by available chemotherapy (2), there is a need for new drugs for the treatment of leishmaniasis infections. Therefore, the discovery of novel classes of inhibitors can be an important step which contributes to overcoming the drug resistance of Leishmania (3).…”

Section: Introductionmentioning

confidence: 99%

Aurapten, a coumarin with growth inhibition against Leishmania major promastigotes

Napolitano

Silva

Ellena

et al. 2004

Braz J Med Biol Res

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Several natural compounds have been identified for the treatment of leishmaniasis. Among them are some alkaloids, chalcones, lactones, tetralones, and saponins. The new compound reported here, 7-geranyloxycoumarin, called aurapten, belongs to the chemical class of the coumarins and has a molecular weight of 298.37. The compund was extracted from the Rutaceae species Esenbeckia febrifuga and was purified from a hexane extract starting from 407.7 g of dried leaves and followed by four silica gel chromatographic fractionation steps using different solvents as the mobile phase. The resulting compound (47 mg) of shows significant growth inhibition with an LD 50 of 30 µM against the tropical parasite Leishmania major, which causes severe clinical manifestations in humans and is endemic in the tropical and subtropical regions. In the present study, we investigated the atomic structure of aurapten in order to determine the existence of common structural motifs that might be related to other coumarins and potentially to other identified inhibitors of Leishmania growth and viability. This compound has a comparable inhibitory activity of other isolated molecules. The aurapten is a planar molecule constituted of an aromatic system with electron delocalization. A hydrophobic side chain consisting of ten carbon atoms with two double bonds and negative density has been identified and may be relevant for further compound synthesis.

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“…Indeed, 024-032. factors that are linked to the host (e.g., immunosuppression or malnutrition), the drug itself (e.g., drug batch or counterfeit drugs), the Leishmania species, the practitioner or the patient (e.g., incomplete treatment follow-up) will also play a role in parasite drug resistance and treatment failure [4,9,10]. In most parts of the world, the frequency of parasite antimony resistance linked to treatment failure is unknown [4,9,10]. This information should be crucial to address the risk of selection and transmission of drug-resistant parasites, particularly in areas where antimony is the only chemotherapeutic alternative.…”

Section: Introductionmentioning

confidence: 99%

Leishmania antimony resistance/ susceptibility in Algerian foci

Eddaikra¹,

Aït-Oudhia²,

Oury³

et al. 2017

Open J Trop Med

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024-032. Medical Group AbstractAlgeria is one of the most endemic countries for cutaneous and visceral forms of leishmaniosis. Strikingly, with more than 21,000 annual cases of cutaneous leishmaniosis recorded in 2010, the disease has a major public health impact. For all forms of leishmaniosis, the fi rst line treatment relies on antimonial containing drug i.e., Glucantime®, developed during the 1950's. As early as 1986, antimonial treatment failure was reported during cutaneous leishmaniosis treatment. Linked to this therapeutic failure, Leishmania strains displaying a low susceptibility towards antimonials were isolated. Nevertheless, in Algeria, antimonial formulations still remain the fi rst line drug for all clinical forms of leishmaniosis. Therefore, an urgent need of knowledge on the baseline antimony susceptibility status of parasites strains in Algeria is required. These pieces of knowledge will shed light not only on the prevalence of antimony resistance in this area but also on underlying factors triggering this drug resistance in natural populations. Here, we performed a review of the literature on what is known about epidemiology, treatment failure, and antimony-resistance, in Algeria. We bring information on underlying mechanisms acting in antimony resistant parasites and discuss their potential to be used for diagnostic purpose. This analysis will help to set up protocols aiming at detecting antimony resistant strains in Algeria and to test the risk of transmission, two steps that are essential to defi ne public health policy in Algeria.

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Monitoring drug resistance in leishmaniasis

Cited by 100 publications

References 54 publications

Treatment of visceral leishmaniasis in south-eastern Nepal: decreasing efficacy of sodium stibogluconate and need for a policy to limit further decline

Treatment of visceral leishmaniasis in south-eastern Nepal: decreasing efficacy of sodium stibogluconate and need for a policy to limit further decline

Aurapten, a coumarin with growth inhibition against Leishmania major promastigotes

Leishmania antimony resistance/ susceptibility in Algerian foci

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