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Miltefosine and antimonial drug susceptibility of Leishmania Viannia species and populations in regions of high transmission in Colombia.
PLoS Negl Trop Dis. 2014 May; 8(5):e2871.PN

Abstract

BACKGROUND

Pentavalent antimonials have been the first line treatment for dermal leishmaniasis in Colombia for over 30 years. Miltefosine is administered as second line treatment since 2005. The susceptibility of circulating populations of Leishmania to these drugs is unknown despite clinical evidence supporting the emergence of resistance.

METHODOLOGY/PRINCIPAL FINDINGS

In vitro susceptibility was determined for intracellular amastigotes of 245 clinical strains of the most prevalent Leishmania Viannia species in Colombia to miltefosine (HePC) and/or meglumine antimoniate (Sb(V)); 163, (80%) were evaluated for both drugs. Additionally, susceptibility to Sb(V) was examined in two cohorts of 85 L. V. panamensis strains isolated between 1980-1989 and 2000-2009 in the municipality of Tumaco. Susceptibility to each drug differed among strains of the same species and between species. Whereas 68% of L. V. braziliensis strains presented in vitro resistance to HePC, 69% were sensitive to Sb(V). Resistance to HePC and Sb(V) occurred respectively, in 20% y 21% of L. panamensis strains. Only 3% of L. V. guyanensis were resistant to HePC, and none to Sb(V). Drug susceptibility differed between geographic regions and time periods. Subpopulations having disparate susceptibility to Sb(V) were discerned among L. V. panamensis strains isolated during 1980-1990 in Tumaco where resistant strains belonged to zymodeme 2.3, and sensitive strains to zymodeme 2.2.

CONCLUSIONS/SIGNIFICANCE

Large scale evaluation of clinical strains of Leishmania Viannia species demonstrated species, population, geographic, and epidemiologic differences in susceptibility to meglumine antimoniate and miltefosine, and provided baseline information for monitoring susceptibility to these drugs. Sensitive and resistant clinical strains within each species, and zymodeme as a proxy marker of antimony susceptibility for L. V. panamensis, will be useful in deciphering factors involved in susceptibility and the distribution of sensitive and resistant populations.

Authors+Show Affiliations

Centro Internacional de Entrenamiento e Investigaciones Médicas (CIDEIM), Cali, Colombia.Centro Dermatológico Federico Lleras Acosta (CDFLLA), Bogotá, Colombia.Centro Dermatológico Federico Lleras Acosta (CDFLLA), Bogotá, Colombia.Centro Internacional de Entrenamiento e Investigaciones Médicas (CIDEIM), Cali, Colombia.Centro Dermatológico Federico Lleras Acosta (CDFLLA), Bogotá, Colombia.Centro Internacional de Entrenamiento e Investigaciones Médicas (CIDEIM), Cali, Colombia.Centro Internacional de Entrenamiento e Investigaciones Médicas (CIDEIM), Cali, Colombia.Centro Internacional de Entrenamiento e Investigaciones Médicas (CIDEIM), Cali, Colombia.

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

24853871

Citation

Fernández, Olga Lucía, et al. "Miltefosine and Antimonial Drug Susceptibility of Leishmania Viannia Species and Populations in Regions of High Transmission in Colombia." PLoS Neglected Tropical Diseases, vol. 8, no. 5, 2014, pp. e2871.
Fernández OL, Diaz-Toro Y, Ovalle C, et al. Miltefosine and antimonial drug susceptibility of Leishmania Viannia species and populations in regions of high transmission in Colombia. PLoS Negl Trop Dis. 2014;8(5):e2871.
Fernández, O. L., Diaz-Toro, Y., Ovalle, C., Valderrama, L., Muvdi, S., Rodríguez, I., Gomez, M. A., & Saravia, N. G. (2014). Miltefosine and antimonial drug susceptibility of Leishmania Viannia species and populations in regions of high transmission in Colombia. PLoS Neglected Tropical Diseases, 8(5), e2871. https://doi.org/10.1371/journal.pntd.0002871
Fernández OL, et al. Miltefosine and Antimonial Drug Susceptibility of Leishmania Viannia Species and Populations in Regions of High Transmission in Colombia. PLoS Negl Trop Dis. 2014;8(5):e2871. PubMed PMID: 24853871.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Miltefosine and antimonial drug susceptibility of Leishmania Viannia species and populations in regions of high transmission in Colombia. AU - Fernández,Olga Lucía, AU - Diaz-Toro,Yira, AU - Ovalle,Clemencia, AU - Valderrama,Liliana, AU - Muvdi,Sandra, AU - Rodríguez,Isabel, AU - Gomez,María Adelaida, AU - Saravia,Nancy Gore, Y1 - 2014/05/22/ PY - 2013/12/05/received PY - 2014/04/03/accepted PY - 2014/5/24/entrez PY - 2014/5/24/pubmed PY - 2015/6/2/medline SP - e2871 EP - e2871 JF - PLoS neglected tropical diseases JO - PLoS Negl Trop Dis VL - 8 IS - 5 N2 - BACKGROUND: Pentavalent antimonials have been the first line treatment for dermal leishmaniasis in Colombia for over 30 years. Miltefosine is administered as second line treatment since 2005. The susceptibility of circulating populations of Leishmania to these drugs is unknown despite clinical evidence supporting the emergence of resistance. METHODOLOGY/PRINCIPAL FINDINGS: In vitro susceptibility was determined for intracellular amastigotes of 245 clinical strains of the most prevalent Leishmania Viannia species in Colombia to miltefosine (HePC) and/or meglumine antimoniate (Sb(V)); 163, (80%) were evaluated for both drugs. Additionally, susceptibility to Sb(V) was examined in two cohorts of 85 L. V. panamensis strains isolated between 1980-1989 and 2000-2009 in the municipality of Tumaco. Susceptibility to each drug differed among strains of the same species and between species. Whereas 68% of L. V. braziliensis strains presented in vitro resistance to HePC, 69% were sensitive to Sb(V). Resistance to HePC and Sb(V) occurred respectively, in 20% y 21% of L. panamensis strains. Only 3% of L. V. guyanensis were resistant to HePC, and none to Sb(V). Drug susceptibility differed between geographic regions and time periods. Subpopulations having disparate susceptibility to Sb(V) were discerned among L. V. panamensis strains isolated during 1980-1990 in Tumaco where resistant strains belonged to zymodeme 2.3, and sensitive strains to zymodeme 2.2. CONCLUSIONS/SIGNIFICANCE: Large scale evaluation of clinical strains of Leishmania Viannia species demonstrated species, population, geographic, and epidemiologic differences in susceptibility to meglumine antimoniate and miltefosine, and provided baseline information for monitoring susceptibility to these drugs. Sensitive and resistant clinical strains within each species, and zymodeme as a proxy marker of antimony susceptibility for L. V. panamensis, will be useful in deciphering factors involved in susceptibility and the distribution of sensitive and resistant populations. SN - 1935-2735 UR - https://www.unboundmedicine.com/medline/citation/24853871/Miltefosine_and_antimonial_drug_susceptibility_of_Leishmania_Viannia_species_and_populations_in_regions_of_high_transmission_in_Colombia_ L2 - https://dx.plos.org/10.1371/journal.pntd.0002871 DB - PRIME DP - Unbound Medicine ER -