Treatment of Bolivian Mucosal Leishmaniasis with Miltefosine

Soto, Jaime; Toledo, Julia; Valda, L.; Balderrama, Margarita; Rea, Irene Maeve; Parra, Rolando Sergio Llópiz; Ardiles, J Herrera; Soto, Paula; Gómez, Antonio López; Molleda, F.; Fuentelsaz, C.; Anders, G; Sindermann, H.; Engel, Jürgen; Berman, Jonathan

doi:10.1086/510588

Cited by 124 publications

(93 citation statements)

References 15 publications

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“…Considering that MF's efficacy against cutaneous leishmaniasis due to Leishmania (Viannia) species varies from 53% to 91%, 3,4,17,18 and in Brazil, MF was effective against L. (V.) braziliensis in 75% of patients, 1 it would be interesting to investigate whether clinical isolates from unresponsive patients presented low susceptibility to MF in vitro.…”

Section: 5mentioning

confidence: 99%

“…3,4 In Brazil, 70% success rates were observed in two MF clinical trials of cutaneous leishmaniasis due to L. (V.) braziliensis and Leishmania (V.) guyanensis.…”

mentioning

confidence: 99%

“…2 This oral drug has also been approved for the treatment of tegumentary leishmaniasis in Colombia, after the demonstration of equivalent efficacy to antimony, and in other countries in South America. 3 However, the response is heterogeneous in areas of high prevalence of L. (V.) braziliensis: for example, a clinical trial showed 83% efficacy for MF in cutaneous leishmaniasis in Bolivia, whereas a 53% cure rate was observed in Guatemala. 3,4 In Brazil, 70% success rates were observed in two MF clinical trials of cutaneous leishmaniasis due to L. (V.) braziliensis and Leishmania (V.) guyanensis.…”

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Susceptibility to Miltefosine in Brazilian Clinical Isolates of Leishmania (Viannia) braziliensis

Espada

Ribeiro‐Dias

Dorta

et al. 2017

The American Society of Tropical Medicine and Hygiene

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Abstract. Leishmania (Viannia) braziliensis is the main causative species of tegumentary leishmaniasis in Brazil. In this study, we evaluated the susceptibility of 16 clinical isolates of L. (V.) braziliensis from different regions of Brazil to miltefosine in vitro. Half-maximal inhibitory concentrations of miltefosine varied from 22.9 to 144.2 μM against promastigotes and from 0.3 to 4.2 μM against intracellular amastigotes. No significant differences were found between isolates of different geographical origins. A clear correlation between the EC 50 against promastigotes and amastigotes within each isolate was found. These findings contribute to the evaluation of miltefosine's potential and limitations for the treatment of tegumentary leishmaniasis in Brazil.Tegumentary leishmaniasis is a disease of importance in Brazil, where it is mainly caused by Leishmania (Viannia) braziliensis. The efficacy of the first-line drug, meglumine antimoniate, for the treatment of cutaneous leishmaniasis in areas of L. (V.) braziliensis predominance in Brazil can be as low as 53%.1 New therapeutic alternatives are highly desirable. Miltefosine (MF) (hexadecylphosphatidylcholine) was approved for the treatment of visceral leishmaniasis in India in 2002, where pentavalent antimony was already considered as ineffective due to widespread parasite resistance. 2This oral drug has also been approved for the treatment of tegumentary leishmaniasis in Colombia, after the demonstration of equivalent efficacy to antimony, and in other countries in South America.3 However, the response is heterogeneous in areas of high prevalence of L. (V.) braziliensis: for example, a clinical trial showed 83% efficacy for MF in cutaneous leishmaniasis in Bolivia, whereas a 53% cure rate was observed in Guatemala. 3,4 In Brazil, 70% success rates were observed in two MF clinical trials of cutaneous leishmaniasis due to L. (V.) braziliensis and Leishmania (V.) guyanensis. 1,5The aim of this work was to characterize the MF susceptibility of L. (V.) braziliensis clinical isolates from Brazilian patients with tegumentary leishmaniasis from two geographically distinct regions.Eight clinical isolates were obtained from lesion biopsies of patients with tegumentary leishmaniasis attending the Anuar Auad Tropical Diseases Hospital, Goiânia, Goiás, Brazil (Leishbank), 6 and eight isolates were obtained through needle aspiration of skin lesions from patients attending the health post of Corte de Pedra, Bahia, Brazil. After the isolation, cultures were frozen and recovered to perform this study. The isolates were typed by polymerase chain reaction of internal transcribed spacer of ribosomal DNA and hsp70 gene followed by restriction analysis using Hae III, as described. 7,8 The M2903 reference strain and 16 clinical isolates produced the expected profile for L. (V.) braziliensis (data not shown).The activity of MF against promastigotes was evaluated by the (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) (MTT) assay as previously described.9 Approximatel...

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Section: 5mentioning

confidence: 99%

“…3,4 In Brazil, 70% success rates were observed in two MF clinical trials of cutaneous leishmaniasis due to L. (V.) braziliensis and Leishmania (V.) guyanensis.…”

mentioning

confidence: 99%

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confidence: 99%

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Susceptibility to Miltefosine in Brazilian Clinical Isolates of Leishmania (Viannia) braziliensis

Espada

Ribeiro‐Dias

Dorta

et al. 2017

The American Society of Tropical Medicine and Hygiene

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“…69 Another drug that has been tested for its efficacy in treating CL in Bolivia is miltefosine, with reported cure rates of 88-91% and 58-83% for LCL and ML, respectively. 70,71 Several anecdotal reports describe the use of folk medicine to treat the leishmaniases in Bolivian communities, 72 and many local Bolivia plants have been found to have anti-leishmanial activity in vitro [72][73][74] and in vivo . 74 However, to date, there has been no controlled study to establish whether these plants have a potential application in clinical medicine.…”

Section: Disease Distribution Notification and Incidencementioning

confidence: 99%

Leishmaniases in Bolivia: Comprehensive Review and Current Status

García

Parrado²,

Rojas³

et al. 2009

The American Journal of Tropical Medicine and Hygiene

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Abstract. The leishmaniases are protozoan, zoonotic diseases transmitted to human and other mammal hosts by the bite of phlebotomine sandflies. Bolivia has the highest incidence of cutaneous leishmaniasis (CL) in Latin America (LA), with 33 cases per 100,000 population reported in 2006. CL is endemic in seven of the country's nine administrative departments. Visceral leishmaniasis (VL) is comparatively rare and is restricted to one single focus. Most CL cases are caused by Leishmania ( Viannia ) braziliensis (85% cases); VL is caused by L. (L.) infantum. Seven sandfly species are incriminated as vectors and Leishmania infections have been detected in several non-human mammal hosts. Transmission is associated with forest-related activities, but recently, cases of autochthonous, urban transmission were reported. Because most cases are caused by L. (V.) braziliensis, Bolivia reports the greatest ratio (i.e., up to 20% of all cases) of mucosal leishmaniasis to localized CL cases in LA. Per national guidelines, both CL and VL cases are microscopically diagnosed and treated with pentavalent antimony.

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“…However, because of considerably more serious side effects and related costs, amphotericin B has been considered as an alternative treatment [18,19]. However, topical application of drugs induces a more rapid healing due to a high drug concentration locally in the lesion and avoids the adverse effects of systemic therapies [12,20].…”

Section: Introductionmentioning

confidence: 99%