Miltefosine and Antimonial Drug Susceptibility of Leishmania Viannia Species and Populations in Regions of High Transmission in Colombia
Publication Date
May 22, 2014
Journal
PLOS Neglected Tropical Diseases
Authors
Olga Lucía Fernández, Yira Diaz Toro, Clemencia Ovalle, Liliana Valderrama, et al
Volume
8
Issue
5
Pages
e2871
DOI
https://dx.plos.org/10.1371/journal.pntd.0002871
Publisher URL
http://journals.plos.org/plosntds/article?id=10.1371%2Fjournal.pntd.0002871
PubMed
http://www.ncbi.nlm.nih.gov/pubmed/24853871
PubMed Central
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4031164
Europe PMC
http://europepmc.org/abstract/MED/24853871
Web of Science
000337735100052
Scopus
84901807655
Mendeley
http://www.mendeley.com/research/miltefosine-antimonial-drug-susceptibility-leishmania-viannia-species-populations-regions-high-trans
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Mendeley | Further Information

{"title"=>"Miltefosine and Antimonial Drug Susceptibility of Leishmania Viannia Species and Populations in Regions of High Transmission in Colombia", "type"=>"journal", "authors"=>[{"first_name"=>"Olga Lucía", "last_name"=>"Fernández", "scopus_author_id"=>"54958235500"}, {"first_name"=>"Yira", "last_name"=>"Diaz-Toro", "scopus_author_id"=>"55260131600"}, {"first_name"=>"Clemencia", "last_name"=>"Ovalle", "scopus_author_id"=>"17344236700"}, {"first_name"=>"Liliana", "last_name"=>"Valderrama", "scopus_author_id"=>"6701830781"}, {"first_name"=>"Sandra", "last_name"=>"Muvdi", "scopus_author_id"=>"55655398500"}, {"first_name"=>"Isabel", "last_name"=>"Rodríguez", "scopus_author_id"=>"23987236100"}, {"first_name"=>"María Adelaida", "last_name"=>"Gomez", "scopus_author_id"=>"10143098900"}, {"first_name"=>"Nancy Gore", "last_name"=>"Saravia", "scopus_author_id"=>"7004212910"}], "year"=>2014, "source"=>"PLoS Neglected Tropical Diseases", "identifiers"=>{"pmid"=>"24853871", "doi"=>"10.1371/journal.pntd.0002871", "sgr"=>"84901807655", "isbn"=>"1935-2735", "scopus"=>"2-s2.0-84901807655", "issn"=>"19352735", "pui"=>"373228471"}, "id"=>"f3bc41b3-24bd-3730-8e8b-8f69420fa2be", "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.\\n\\nMETHODOLOGY/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.\\n\\nCONCLUSIONS/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.", "link"=>"http://www.mendeley.com/research/miltefosine-antimonial-drug-susceptibility-leishmania-viannia-species-populations-regions-high-trans", "reader_count"=>54, "reader_count_by_academic_status"=>{"Unspecified"=>1, "Professor > Associate Professor"=>2, "Student > Doctoral Student"=>4, "Researcher"=>10, "Student > Ph. D. Student"=>11, "Student > Postgraduate"=>4, "Student > Master"=>12, "Student > Bachelor"=>7, "Professor"=>2, "Other"=>1}, "reader_count_by_user_role"=>{"Unspecified"=>1, "Professor > Associate Professor"=>2, "Student > Doctoral Student"=>4, "Researcher"=>10, "Student > Ph. D. Student"=>11, "Student > Postgraduate"=>4, "Student > Master"=>12, "Student > Bachelor"=>7, "Professor"=>2, "Other"=>1}, "reader_count_by_subject_area"=>{"Unspecified"=>2, "Biochemistry, Genetics and Molecular Biology"=>8, "Nursing and Health Professions"=>1, "Agricultural and Biological Sciences"=>16, "Medicine and Dentistry"=>17, "Veterinary Science and Veterinary Medicine"=>3, "Pharmacology, Toxicology and Pharmaceutical Science"=>1, "Chemistry"=>1, "Immunology and Microbiology"=>4, "Engineering"=>1}, "reader_count_by_subdiscipline"=>{"Engineering"=>{"Engineering"=>1}, "Medicine and Dentistry"=>{"Medicine and Dentistry"=>17}, "Chemistry"=>{"Chemistry"=>1}, "Immunology and Microbiology"=>{"Immunology and Microbiology"=>4}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>16}, "Nursing and Health Professions"=>{"Nursing and Health Professions"=>1}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>8}, "Unspecified"=>{"Unspecified"=>2}, "Pharmacology, Toxicology and Pharmaceutical Science"=>{"Pharmacology, Toxicology and Pharmaceutical Science"=>1}, "Veterinary Science and Veterinary Medicine"=>{"Veterinary Science and Veterinary Medicine"=>3}}, "reader_count_by_country"=>{"Colombia"=>1, "Argentina"=>1, "Brazil"=>2, "Portugal"=>1}, "group_count"=>3}

Scopus | Further Information

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/1508000"], "description"=>"a<p>163 strains were evaluated for both drugs, plus 41 for Sb<sup>V</sup> only, and 41 for HePC only yielding a total of 204 strains for each drug and 245 for one or both drugs.</p>", "links"=>[], "tags"=>["Infectious diseases", "strains", "regions", "prevalence", "evaluated"], "article_id"=>1034445, "categories"=>["Biological Sciences"], "users"=>["Olga Lucía Fernández", "Yira Díaz-Toro", "Clemencia Ovalle", "Liliana Valderrama", "Sandra Muvdi", "Isabel Rodriguez", "María Adelaida Gómez", "Nancy Gore Saravia"], "doi"=>"https://dx.doi.org/10.1371/journal.pntd.0002871.t001", "stats"=>{"downloads"=>0, "page_views"=>7, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Species_distribution_of_L_Viannia_strains_from_regions_of_high_prevalence_evaluated_in_vitro_for_drug_susceptibility_a_/1034445", "title"=>"Species distribution of <i>L. Viannia</i> strains from regions of high prevalence evaluated <i>in vitro</i> for drug susceptibility<sup>a</sup>.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2014-05-22 03:20:35"}
  • {"files"=>["https://ndownloader.figshare.com/files/1507999"], "description"=>"<p>Children <7 years of age were more frequently infected with strains of <i>L. V. panamensis</i> pertaining to zymodeme 2.3, while farmers were more often infected by strains belonging to zymodeme 2.2. n = 280 (A), Chi-square test, <i>P</i><0.05. Distribution of <i>L. V. panamensis</i> strains belonging to zymodeme 2.2 (n = 181) and 2.3 (n = 149) by age of patients with cutaneous leishmaniasis from the Municipality of Tumaco, 1980–1989 (B and C).</p>", "links"=>[], "tags"=>["Infectious diseases", "municipality"], "article_id"=>1034444, "categories"=>["Biological Sciences"], "users"=>["Olga Lucía Fernández", "Yira Díaz-Toro", "Clemencia Ovalle", "Liliana Valderrama", "Sandra Muvdi", "Isabel Rodriguez", "María Adelaida Gómez", "Nancy Gore Saravia"], "doi"=>"https://dx.doi.org/10.1371/journal.pntd.0002871.g006", "stats"=>{"downloads"=>1, "page_views"=>10, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Association_of_zymodeme_age_and_occupation_in_the_Municipality_of_Tumaco_/1034444", "title"=>"Association of zymodeme, age and occupation in the Municipality of Tumaco.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-05-22 03:20:35"}
  • {"files"=>["https://ndownloader.figshare.com/files/1507996"], "description"=>"<p>Reduction of parasite burden at the discriminatory concentration of Sb<sup>V</sup> (A and C) and HePC (B and D) for <i>L. V. panamensis</i> and <i>L. V. braziliensis</i> strains from Pacific, Andean, Orinoquía and Amazon regions. Because of the lower frequency of <i>L. V. panamensis</i> in regions east of the Andes mountain range, <i>L. V. panamensis</i> strains are combined for Orinoquía and Amazon regions. Qualitative classification of susceptibility is defined by the cutoff thresholds (dotted horizontal line) and indeterminate ranges are illustrated by gray shading. K-W for <i>L. V. panamensis</i> and HePC, <i>P</i> = 0.0012 and Dunn procedure, * <i>P</i><0.05: Compared with Orinoquía and Amazon regions.</p>", "links"=>[], "tags"=>["Infectious diseases", "meglumine", "antimoniate", "miltefosine", "geographic"], "article_id"=>1034441, "categories"=>["Biological Sciences"], "users"=>["Olga Lucía Fernández", "Yira Díaz-Toro", "Clemencia Ovalle", "Liliana Valderrama", "Sandra Muvdi", "Isabel Rodriguez", "María Adelaida Gómez", "Nancy Gore Saravia"], "doi"=>"https://dx.doi.org/10.1371/journal.pntd.0002871.g003", "stats"=>{"downloads"=>0, "page_views"=>24, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Susceptibility_of_L_V_panamensis_and_L_V_braziliensis_to_meglumine_antimoniate_and_miltefosine_by_geographic_region_/1034441", "title"=>"Susceptibility of <i>L. V. panamensis</i> and <i>L. V. braziliensis</i> to meglumine antimoniate and miltefosine by geographic region.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-05-22 03:20:35"}
  • {"files"=>["https://ndownloader.figshare.com/files/1507995"], "description"=>"<p>Map of major natural geographic regions of Colombia (A). Susceptibility expressed as reduction of parasite burden at the discriminatory concentration of Sb<sup>V</sup> (B) and HePC (C) in clinical strains of <i>L. V. panamensis, L. V. braziliensis</i> and <i>L. V. guyanensis.</i> Distributions of % reduction of parasite burden represent the median and the interquartile range. Qualitative classification of susceptibility is defined by the cutoff thresholds (dotted horizontal line) and indeterminate ranges are illustrated by gray shading. K-W for Sb<sup>V</sup>: <i>P</i> = 0.012 and K-W for HePC: <i>P</i><0.0001. * Dunn's multiple comparison test <i>P</i><0.05.</p>", "links"=>[], "tags"=>["Infectious diseases", "geographic", "regions", "meglumine", "antimoniate"], "article_id"=>1034440, "categories"=>["Biological Sciences"], "users"=>["Olga Lucía Fernández", "Yira Díaz-Toro", "Clemencia Ovalle", "Liliana Valderrama", "Sandra Muvdi", "Isabel Rodriguez", "María Adelaida Gómez", "Nancy Gore Saravia"], "doi"=>"https://dx.doi.org/10.1371/journal.pntd.0002871.g002", "stats"=>{"downloads"=>0, "page_views"=>6, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Susceptibility_of_Leishmania_Viannia_species_from_major_natural_geographic_regions_to_meglumine_antimoniate_and_miltefosine_/1034440", "title"=>"Susceptibility of <i>Leishmania Viannia</i> species from major natural geographic regions to meglumine antimoniate and miltefosine.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-05-22 03:20:35"}
  • {"files"=>["https://ndownloader.figshare.com/files/1508001", "https://ndownloader.figshare.com/files/1508002", "https://ndownloader.figshare.com/files/1508003"], "description"=>"<div><p>Background</p><p>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 <i>Leishmania</i> to these drugs is unknown despite clinical evidence supporting the emergence of resistance.</p><p>Methodology/Principal Findings</p><p><i>In vitro</i> susceptibility was determined for intracellular amastigotes of 245 clinical strains of the most prevalent <i>Leishmania Viannia</i> species in Colombia to miltefosine (HePC) and/or meglumine antimoniate (Sb<sup>V</sup>); 163, (80%) were evaluated for both drugs. Additionally, susceptibility to Sb<sup>V</sup> was examined in two cohorts of 85 <i>L. V. panamensis</i> 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 <i>L. V. braziliensis</i> strains presented <i>in vitro</i> resistance to HePC, 69% were sensitive to Sb<sup>V</sup>. Resistance to HePC and Sb<sup>V</sup> occurred respectively, in 20% y 21% of <i>L. panamensis</i> strains. Only 3% of <i>L. V. guyanensis</i> were resistant to HePC, and none to Sb<sup>V</sup>. Drug susceptibility differed between geographic regions and time periods. Subpopulations having disparate susceptibility to Sb<sup>V</sup> were discerned among <i>L. V. panamensis</i> strains isolated during 1980–1990 in Tumaco where resistant strains belonged to zymodeme 2.3, and sensitive strains to zymodeme 2.2.</p><p>Conclusions/Significance</p><p>Large scale evaluation of clinical strains of <i>Leishmania Viannia</i> 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 <i>L. V. panamensis,</i> will be useful in deciphering factors involved in susceptibility and the distribution of sensitive and resistant populations.</p></div>", "links"=>[], "tags"=>["Infectious diseases", "miltefosine", "antimonial", "susceptibility", "populations", "regions", "colombia"], "article_id"=>1034446, "categories"=>["Biological Sciences"], "users"=>["Olga Lucía Fernández", "Yira Díaz-Toro", "Clemencia Ovalle", "Liliana Valderrama", "Sandra Muvdi", "Isabel Rodriguez", "María Adelaida Gómez", "Nancy Gore Saravia"], "doi"=>["https://dx.doi.org/10.1371/journal.pntd.0002871.s001", "https://dx.doi.org/10.1371/journal.pntd.0002871.s002", "https://dx.doi.org/10.1371/journal.pntd.0002871.s003"], "stats"=>{"downloads"=>0, "page_views"=>12, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/Miltefosine_and_Antimonial_Drug_Susceptibility_of_Leishmania_Viannia_Species_and_Populations_in_Regions_of_High_Transmission_in_Colombia/1034446", "title"=>"Miltefosine and Antimonial Drug Susceptibility of <i>Leishmania Viannia</i> Species and Populations in Regions of High Transmission in Colombia", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2014-05-22 03:20:35"}
  • {"files"=>["https://ndownloader.figshare.com/files/1507998"], "description"=>"<p>The relationship between genetic diversity, zymodeme, drug susceptibility and geographic distribution was examined based on an unrooted neighbor joining tree generated from the distances calculated for microsatellite data. Strains included <i>L. V. panamensis</i> isolated from patients in the Municipality of Tumaco, Nariño pertaining to zymodemes 2.3 (n = 10) and 2.2 (n = 10), <i>L. V. panamensis</i> strains from the Pacific coast region not typed by isoenzyme analysis, and <i>L. V. guyanensis</i> strains isolated from patients from Andean (n = 9) and Amazon regions (n = 8). Range of susceptibility to antimony at 32 µg Sb<sup>V</sup>/ml is shown for the genetically discriminated groups of strains. ND* Zymodeme not determined.</p>", "links"=>[], "tags"=>["Infectious diseases"], "article_id"=>1034443, "categories"=>["Biological Sciences"], "users"=>["Olga Lucía Fernández", "Yira Díaz-Toro", "Clemencia Ovalle", "Liliana Valderrama", "Sandra Muvdi", "Isabel Rodriguez", "María Adelaida Gómez", "Nancy Gore Saravia"], "doi"=>"https://dx.doi.org/10.1371/journal.pntd.0002871.g005", "stats"=>{"downloads"=>0, "page_views"=>10, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Analysis_of_genetic_diversity_of_L_V_panamensis_and_L_V_guyanensis_strains_/1034443", "title"=>"Analysis of genetic diversity of <i>L. V. panamensis</i> and <i>L. V. guyanensis</i> strains.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-05-22 03:20:35"}
  • {"files"=>["https://ndownloader.figshare.com/files/1507997"], "description"=>"<p>Distribution and median susceptibility of clinical strains from the Rosario River and Mira River foci during the decades 1980–1989 and 2000–2009. K-W, <i>P</i><0.0001 and Dunn procedure (A). Comparison of susceptibility of strains pertaining to zymodeme 2.3 and zymodeme 2.2 isolated during 1980–1989 from the Rosario River and Mira River foci to Sb<sup>V</sup> (B and C). Qualitative classification of susceptibility is defined by the cutoff thresholds (dotted horizontal line) and indeterminate ranges are illustrated by gray shading. Mann-Whitney, <i>P</i><0.0001.</p>", "links"=>[], "tags"=>["Infectious diseases", "strains", "meglumine", "antimoniate", "endemic", "foci", "tumaco", "susceptibility"], "article_id"=>1034442, "categories"=>["Biological Sciences"], "users"=>["Olga Lucía Fernández", "Yira Díaz-Toro", "Clemencia Ovalle", "Liliana Valderrama", "Sandra Muvdi", "Isabel Rodriguez", "María Adelaida Gómez", "Nancy Gore Saravia"], "doi"=>"https://dx.doi.org/10.1371/journal.pntd.0002871.g004", "stats"=>{"downloads"=>4, "page_views"=>8, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Susceptibility_of_L_V_panamensis_strains_to_meglumine_antimoniate_in_endemic_foci_of_Tumaco_and_association_of_drug_susceptibility_with_zymodeme_/1034442", "title"=>"Susceptibility of <i>L. V. panamensis</i> strains to meglumine antimoniate in endemic foci of Tumaco and association of drug susceptibility with zymodeme.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-05-22 03:20:35"}
  • {"files"=>["https://ndownloader.figshare.com/files/1507992"], "description"=>"<p>Reduction of parasite burden at the discriminatory concentration of anti-leishmanial drugs for clinical strains of <i>L. V. panamensis</i>, <i>L. V. braziliensis</i> and <i>L. V. guyanensis</i>. The cutoff thresholds (dotted horizontal line) of <41% reduction of parasite burden by Sb<sup>V</sup> (A) and <50% reduction of parasite burden by HePC (B), and indeterminate zones (gray region) were defined based on previously described ROC curves as reduction of parasite burden between 35% and 48% for Sb<sup>V</sup> and 44% and 56% for HePC (Fernandez O, et al 2012).<sup> a</sup> Strains presenting <i>in vitro</i> resistance. Kruskal-Wallis (K-W) for Sb<sup>V</sup>: <i>P</i> = 0.0009 and K-W for HePC: <i>P</i><0.0001. * Dunn's multiple comparison test <i>P</i><0.05: Compared with <i>L. V. braziliensis</i>.</p>", "links"=>[], "tags"=>["Infectious diseases", "colombia", "meglumine", "antimoniate"], "article_id"=>1034437, "categories"=>["Biological Sciences"], "users"=>["Olga Lucía Fernández", "Yira Díaz-Toro", "Clemencia Ovalle", "Liliana Valderrama", "Sandra Muvdi", "Isabel Rodriguez", "María Adelaida Gómez", "Nancy Gore Saravia"], "doi"=>"https://dx.doi.org/10.1371/journal.pntd.0002871.g001", "stats"=>{"downloads"=>1, "page_views"=>12, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Susceptibility_of_L_Viannia_species_in_Colombia_to_meglumine_antimoniate_and_miltefosine_/1034437", "title"=>"Susceptibility of <i>L. Viannia</i> species in Colombia to meglumine antimoniate and miltefosine.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-05-22 03:20:35"}

PMC Usage Stats | Further Information

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Relative Metric

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