Leishmaniasis impact and treatment access

Boer, Margriet den; Argaw, Daniel; Jannin, J.; Alvar, Jorge

doi:10.1111/j.1469-0691.2011.03635.x

Cited by 212 publications

(110 citation statements)

References 20 publications

Supporting

Mentioning

104

Contrasting

Unclassified

Order By: Relevance

“…However, following reports of high rates of toxicity of antimonials in HIV-infected individuals [18], liposomal amphotericin B has been recommended as the preferential first line treatment for this patient group [13], [19]. Although the cost of liposomal amphotericin B has undergone substantial reductions for low income countries, there remain issues of availability of this drug in the public sector in several resource-constrained settings in East-Africa [20], [21]. In Ethiopia, the country with the highest co-infection rate globally, liposomal amphotericin B is in short supply.…”

Section: Introductionmentioning

confidence: 99%

High Parasitological Failure Rate of Visceral Leishmaniasis to Sodium Stibogluconate among HIV Co-infected Adults in Ethiopia

et al. 2014

View full text Add to dashboard Cite

BackgroundAntimonials are still being used for visceral leishmaniasis (VL) treatment among HIV co-infected patients in East-Africa due to the shortage of alternative safer drugs like liposomal amphotericin B. Besides tolerability, emergence of resistance to antimonials is a major concern.ObjectivesThis study was aimed at assessing the clinical outcome of VL-HIV co-infected patients when treated with sodium stibogluconate (SSG).MethodsRetrospective patient record analysis of VL-HIV co-infected patients treated at a clinical trial site in north-west Ethiopia was done. Patients with parasitologically confirmed VL and HIV co-infection treated with SSG were included. The dose of SSG used was 20 mg Sb5 (pentavalent antimony)/kg and maximum of 850 mg Sb5 for 30 days. The clinical outcomes were defined based on the tissue aspiration results as cure or failure, and additionally the safety and mortality rates were computed.ResultsThe study included 57 patients treated with SSG and by the end of treatment only 43.9% of patients were cured. The parasitological treatment failure and the case fatality rate were 31.6% and 14.0% respectively. SSG was discontinued temporarily or permanently for 12 (21.1%) cases due to safety issues. High baseline parasite load (graded more than 4+) was significantly associated with treatment failure (odds ratio = 8.9, 95% confidence interval = .5-51.7).ConclusionSSG is not only unsafe, but also has low effectiveness for VL-HIV patients. Safe and effective alternative medications are very urgently needed. Drug sensitivity surveillance should be introduced in the region.

show abstract

Section: Introductionmentioning

confidence: 99%

High Parasitological Failure Rate of Visceral Leishmaniasis to Sodium Stibogluconate among HIV Co-infected Adults in Ethiopia

et al. 2014

View full text Add to dashboard Cite

show abstract

“…1 Within its sandfly insect vector, Leishmania replicate as motile flagellated procyclic promastigotes which differentiate, via several intermediate forms, into the infective metacyclic promastigotes that await transmission in the sandfly anterior midgut and mouthparts. Upon blood feeding, metacyclic promastigotes are released into the host and eventually make their way into macrophages, inside which the parasites differentiate into ovoid nonmotile amastigotes.…”

Section: Introductionmentioning

confidence: 99%

Glycosome turnover inLeishmania majoris mediated by autophagy

et al. 2014

View full text Add to dashboard Cite

Abbreviations: ATG, autophagy-related; GFP, green fluorescent protein; mC, mCherry fluorescent protein; MVT, multivesicular tubule; RFP, red fluorescent protein; TEM, transmission electron microscopy.Autophagy is a central process behind the cellular remodeling that occurs during differentiation of Leishmania, yet the cargo of the protozoan parasite's autophagosome is unknown. We have identified glycosomes, peroxisome-like organelles that uniquely compartmentalize glycolytic and other metabolic enzymes in Leishmania and other kinetoplastid parasitic protozoa, as autophagosome cargo. It has been proposed that the number of glycosomes and their content change during the Leishmania life cycle as a key adaptation to the different environments encountered. Quantification of RFP-SQL-labeled glycosomes showed that promastigotes of L. major possess »20 glycosomes per cell, whereas amastigotes contain »10. Glycosome numbers were significantly greater in promastigotes and amastigotes of autophagy-defective L. major Datg5 mutants, implicating autophagy in glycosome homeostasis and providing a partial explanation for the previously observed growth and virulence defects of these mutants. Use of GFP-ATG8 to label autophagosomes showed glycosomes to be cargo in »15% of them; glycosome-containing autophagosomes were trafficked to the lysosome for degradation. The number of autophagosomes increased 10-fold during differentiation, yet the percentage of glycosome-containing autophagosomes remained constant. This indicates that increased turnover of glycosomes was due to an overall increase in autophagy, rather than an upregulation of autophagosomes containing this cargo. Mitophagy of the single mitochondrion was not observed in L. major during normal growth or differentiation; however, mitochondrial remnants resulting from stress-induced fragmentation colocalized with autophagosomes and lysosomes, indicating that autophagy is used to recycle these damaged organelles. These data show that autophagy in Leishmania has a central role not only in maintaining cellular homeostasis and recycling damaged organelles but crucially in the adaptation to environmental change through the turnover of glycosomes.

show abstract

“…Unaffordable costs and poor supply of these drugs in countries where leishmaniasis is endemic limit access to the drugs for the majority of affected patients because of the widespread occurrence leishmaniasis predominantly among the poorest social strata. All of these drugs have disadvantages in terms of toxicity, efficacy, price, or treatment regimen (2)(3)(4). Given these downsides in the existing treatments for VL, a new orally available and inexpensive antileishmanial drug is needed.…”

mentioning

confidence: 99%

Preclinical Studies Evaluating Subacute Toxicity and Therapeutic Efficacy of LQB-118 in Experimental Visceral Leishmaniasis

Cunha-Júnior

Martins

Canto‐Cavalheiro

et al. 2016

Antimicrob Agents Chemother

View full text Add to dashboard Cite

e Visceral leishmaniasis (VL) is the most severe form of leishmaniasis and is the second major cause of death by parasites, after malaria. The arsenal of drugs against leishmaniasis is small, and each has a disadvantage in terms of toxicity, efficacy, price, or treatment regimen. Our group has focused on studying new drug candidates as alternatives to current treatments. The pterocarpanquinone LQB-118 was designed and synthesized based on molecular hybridization, and it exhibited antiprotozoal and antileukemic cell line activities. Our previous work demonstrated that LQB-118 was an effective treatment for experimental cutaneous leishmaniasis. In this study, we observed that treatment with 10 mg/kg of body weight/day LQB-118 orally inhibited the development of hepatosplenomegaly with a 99% reduction in parasite load. An in vivo toxicological analysis showed no change in the clinical, biochemical, or hematological parameters. Histologically, all of the analyzed organs were normal, with the exception of the liver, where focal points of necrosis with leukocytic infiltration were observed at treatment doses 5 times higher than the therapeutic dose; however, these changes were not accompanied by an increase in transaminases. Our findings indicate that LQB-118 is effective at treating different clinical forms of leishmaniasis and presents no relevant signs of toxicity at therapeutic doses; thus, this framework is demonstrated suitable for developing promising drug candidates for the oral treatment of leishmaniasis.

show abstract

Leishmaniasis impact and treatment access

Cited by 212 publications

References 20 publications

High Parasitological Failure Rate of Visceral Leishmaniasis to Sodium Stibogluconate among HIV Co-infected Adults in Ethiopia

High Parasitological Failure Rate of Visceral Leishmaniasis to Sodium Stibogluconate among HIV Co-infected Adults in Ethiopia

Glycosome turnover inLeishmania majoris mediated by autophagy

Preclinical Studies Evaluating Subacute Toxicity and Therapeutic Efficacy of LQB-118 in Experimental Visceral Leishmaniasis

Contact Info

Product

Resources

About