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Chemosensitization of Trypanosoma congolense strains resistant to isometamidium chloride by tetracyclines and enrofloxacin
Because of the development of resistance in trypanosomes to trypanocidal drugs, the livelihood of millions of livestock keepers in sub-Saharan Africa is threatened now more than ever. The existing compounds have become virtually useless and pharmaceutical companies are not keen on investing in the d...
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| Published in: | PLoS neglected tropical diseases 2010-09, Vol.4 (9), p.e828-e828 |
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| creator | Delespaux, Vincent Vitouley, Hervé Sèna Marcotty, Tanguy Speybroeck, Niko Berkvens, Dirk Roy, Krisna Geerts, Stanny Van den Bossche, Peter |
| description | Because of the development of resistance in trypanosomes to trypanocidal drugs, the livelihood of millions of livestock keepers in sub-Saharan Africa is threatened now more than ever. The existing compounds have become virtually useless and pharmaceutical companies are not keen on investing in the development of new trypanocides. We may have found a breakthrough in the treatment of resistant trypanosomal infections, through the combination of the trypanocide isometamidium chloride (ISM) with two affordable veterinary antibiotics.
In a first experiment, groups of mice were inoculated with Trypanosoma congolense strains resistant to ISM and either left untreated or treated with (i) tetracycline, (ii) ISM or (iii) the combination of the antibiotic and the trypanocide. Survival analysis showed that there was a significant effect of treatment and resistance to treatment on the survival time. The groups treated with ISM (with or without antibiotic) survived significantly longer than the groups that were not treated with ISM (P |
| doi_str_mv | 10.1371/journal.pntd.0000828 |
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In a first experiment, groups of mice were inoculated with Trypanosoma congolense strains resistant to ISM and either left untreated or treated with (i) tetracycline, (ii) ISM or (iii) the combination of the antibiotic and the trypanocide. Survival analysis showed that there was a significant effect of treatment and resistance to treatment on the survival time. The groups treated with ISM (with or without antibiotic) survived significantly longer than the groups that were not treated with ISM (P<0.01). The group treated with the combination trypanocide/antibiotic survived significantly longer than the group treated with ISM (P<0.01). In a second experiment, groups of cattle were inoculated with the same resistant trypanosome strain and treated with (i) ISM, (ii) ISM associated with oxytetracycline or (iii) ISM associated with enrofloxacine. All animals treated with ISM became parasitaemic. In the groups treated with ISM-oxytetracycline and ISM-enrofloxacine, 50% of the animals were cured. Animals from the groups treated with a combination trypanocide/antibiotic presented a significantly longer prepatent period than animals treated with ISM (p<0.001). The impact of the disease on the haematocrit was low in all ISM treated groups. Yet, it was lower in the groups treated with the combination trypanocide/antibiotic (p<0.01).
After optimization of the administration protocol, this new therapeutic combination could constitute a promising treatment for livestock infected with drug resistant T. congolense.</description><identifier>ISSN: 1935-2735</identifier><identifier>ISSN: 1935-2727</identifier><identifier>EISSN: 1935-2735</identifier><identifier>DOI: 10.1371/journal.pntd.0000828</identifier><identifier>PMID: 20927189</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Animals ; Antibiotics ; Antiprotozoal Agents - administration & dosage ; Antiprotozoal Agents - pharmacology ; Cattle ; Disease Models, Animal ; Drug dosages ; Drug resistance ; Drug Resistance - drug effects ; Drug Therapy, Combination - methods ; Experiments ; Fluoroquinolones - administration & dosage ; Fluoroquinolones - pharmacology ; Glossina ; Infectious Diseases/Antimicrobials and Drug Resistance ; Infectious Diseases/Protozoal Infections ; Infectious Diseases/Tropical and Travel-Associated Diseases ; Livestock ; Mice ; Parasitemia - drug therapy ; Parasitemia - parasitology ; Pharmaceutical industry ; Phenanthridines - administration & dosage ; Phenanthridines - pharmacology ; Rural areas ; Rural development ; Survival Analysis ; Tetracyclines - administration & dosage ; Tetracyclines - pharmacology ; Treatment Outcome ; Tropical diseases ; Trypanosoma ; Trypanosoma congolense ; Trypanosoma congolense - drug effects ; Trypanosomiasis, African - drug therapy ; Trypanosomiasis, African - parasitology</subject><ispartof>PLoS neglected tropical diseases, 2010-09, Vol.4 (9), p.e828-e828</ispartof><rights>2010 Delespaux et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited: Delespaux V, Vitouley HS, Marcotty T, Speybroeck N, Berkvens D, et al. (2010) Chemosensitization of Trypanosoma congolense Strains Resistant to Isometamidium Chloride by Tetracyclines and Enrofloxacin. PLoS Negl Trop Dis 4(9): e828. doi:10.1371/journal.pntd.0000828</rights><rights>Delespaux et al. 2010</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c623t-ab25d6e1f2ef4befa8e7aa2651c7333c69184d2b90fb1773c80c0855cad357203</citedby><cites>FETCH-LOGICAL-c623t-ab25d6e1f2ef4befa8e7aa2651c7333c69184d2b90fb1773c80c0855cad357203</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.proquest.com/docview/1288113424/fulltextPDF?pq-origsite=primo$$EPDF$$P50$$Gproquest$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.proquest.com/docview/1288113424?pq-origsite=primo$$EHTML$$P50$$Gproquest$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,885,25753,27924,27925,37012,37013,44590,53791,53793,75126</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/20927189$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Kita, Kiyoshi</contributor><creatorcontrib>Delespaux, Vincent</creatorcontrib><creatorcontrib>Vitouley, Hervé Sèna</creatorcontrib><creatorcontrib>Marcotty, Tanguy</creatorcontrib><creatorcontrib>Speybroeck, Niko</creatorcontrib><creatorcontrib>Berkvens, Dirk</creatorcontrib><creatorcontrib>Roy, Krisna</creatorcontrib><creatorcontrib>Geerts, Stanny</creatorcontrib><creatorcontrib>Van den Bossche, Peter</creatorcontrib><title>Chemosensitization of Trypanosoma congolense strains resistant to isometamidium chloride by tetracyclines and enrofloxacin</title><title>PLoS neglected tropical diseases</title><addtitle>PLoS Negl Trop Dis</addtitle><description>Because of the development of resistance in trypanosomes to trypanocidal drugs, the livelihood of millions of livestock keepers in sub-Saharan Africa is threatened now more than ever. The existing compounds have become virtually useless and pharmaceutical companies are not keen on investing in the development of new trypanocides. We may have found a breakthrough in the treatment of resistant trypanosomal infections, through the combination of the trypanocide isometamidium chloride (ISM) with two affordable veterinary antibiotics.
In a first experiment, groups of mice were inoculated with Trypanosoma congolense strains resistant to ISM and either left untreated or treated with (i) tetracycline, (ii) ISM or (iii) the combination of the antibiotic and the trypanocide. Survival analysis showed that there was a significant effect of treatment and resistance to treatment on the survival time. The groups treated with ISM (with or without antibiotic) survived significantly longer than the groups that were not treated with ISM (P<0.01). The group treated with the combination trypanocide/antibiotic survived significantly longer than the group treated with ISM (P<0.01). In a second experiment, groups of cattle were inoculated with the same resistant trypanosome strain and treated with (i) ISM, (ii) ISM associated with oxytetracycline or (iii) ISM associated with enrofloxacine. All animals treated with ISM became parasitaemic. In the groups treated with ISM-oxytetracycline and ISM-enrofloxacine, 50% of the animals were cured. Animals from the groups treated with a combination trypanocide/antibiotic presented a significantly longer prepatent period than animals treated with ISM (p<0.001). The impact of the disease on the haematocrit was low in all ISM treated groups. Yet, it was lower in the groups treated with the combination trypanocide/antibiotic (p<0.01).
After optimization of the administration protocol, this new therapeutic combination could constitute a promising treatment for livestock infected with drug resistant T. congolense.</description><subject>Animals</subject><subject>Antibiotics</subject><subject>Antiprotozoal Agents - administration & dosage</subject><subject>Antiprotozoal Agents - pharmacology</subject><subject>Cattle</subject><subject>Disease Models, Animal</subject><subject>Drug dosages</subject><subject>Drug resistance</subject><subject>Drug Resistance - drug effects</subject><subject>Drug Therapy, Combination - methods</subject><subject>Experiments</subject><subject>Fluoroquinolones - administration & dosage</subject><subject>Fluoroquinolones - pharmacology</subject><subject>Glossina</subject><subject>Infectious Diseases/Antimicrobials and Drug Resistance</subject><subject>Infectious Diseases/Protozoal Infections</subject><subject>Infectious Diseases/Tropical and Travel-Associated Diseases</subject><subject>Livestock</subject><subject>Mice</subject><subject>Parasitemia - drug therapy</subject><subject>Parasitemia - parasitology</subject><subject>Pharmaceutical industry</subject><subject>Phenanthridines - administration & dosage</subject><subject>Phenanthridines - pharmacology</subject><subject>Rural areas</subject><subject>Rural development</subject><subject>Survival Analysis</subject><subject>Tetracyclines - administration & dosage</subject><subject>Tetracyclines - pharmacology</subject><subject>Treatment Outcome</subject><subject>Tropical diseases</subject><subject>Trypanosoma</subject><subject>Trypanosoma congolense</subject><subject>Trypanosoma congolense - drug effects</subject><subject>Trypanosomiasis, African - drug therapy</subject><subject>Trypanosomiasis, African - parasitology</subject><issn>1935-2735</issn><issn>1935-2727</issn><issn>1935-2735</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2010</creationdate><recordtype>article</recordtype><sourceid>PIMPY</sourceid><sourceid>DOA</sourceid><recordid>eNqFkltrFDEcxQdRbK1-A9GADz7tmstkJnkRZPFSKPhSn8N_ctnNkknWJFvcfnpn3WlpRTAvCcnvnCSH0zSvCV4S1pMP27TPEcJyF6tZ4mkIKp4050QyvqA9408frM-aF6VsMeaSC_K8OaNY0p4Ied7crjZ2TMXG4qu_hepTRMmh63zYQUwljYB0iusUJsKiUjP4WFC2xZcKsaKakJ8oW2H0xu9HpDchZW8sGg6o2onXBx18tAVBNMjGnFxIv0D7-LJ55iAU-2qeL5ofXz5fr74trr5_vVx9ulrojrK6gIFy01niqHXtYB0I2wPQjhPdM8Z0J4loDR0kdgPpe6YF1lhwrsEw3lPMLpq3J99dSEXNsRVFqBCEsJa2E3F5IkyCrdplP0I-qARe_dlIea0gV6-DVZjgwfFBGjbI1lICmEkC0BrnsOiZmLw-zrfth9EabeOUQXhk-vgk-o1apxtFZdtJTCaD97NBTj_3tlQ1-qJtCBBt2hclmOwkw1T8l-x5PwXSdscI3v1F_juG9kTpnErJ1t2_mmB17NydSh07p-bOTbI3D398L7orGfsNtzjYyg</recordid><startdate>20100928</startdate><enddate>20100928</enddate><creator>Delespaux, Vincent</creator><creator>Vitouley, Hervé Sèna</creator><creator>Marcotty, Tanguy</creator><creator>Speybroeck, Niko</creator><creator>Berkvens, Dirk</creator><creator>Roy, Krisna</creator><creator>Geerts, Stanny</creator><creator>Van den Bossche, Peter</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7QL</scope><scope>7SS</scope><scope>7T2</scope><scope>7T7</scope><scope>7U9</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8C1</scope><scope>8FD</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BENPR</scope><scope>C1K</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>F1W</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>H94</scope><scope>H95</scope><scope>H97</scope><scope>K9.</scope><scope>L.G</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>P64</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope></search><sort><creationdate>20100928</creationdate><title>Chemosensitization of Trypanosoma congolense strains resistant to isometamidium chloride by tetracyclines and enrofloxacin</title><author>Delespaux, Vincent ; Vitouley, Hervé Sèna ; Marcotty, Tanguy ; Speybroeck, Niko ; Berkvens, Dirk ; Roy, Krisna ; Geerts, Stanny ; Van den Bossche, Peter</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c623t-ab25d6e1f2ef4befa8e7aa2651c7333c69184d2b90fb1773c80c0855cad357203</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2010</creationdate><topic>Animals</topic><topic>Antibiotics</topic><topic>Antiprotozoal Agents - 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Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PLoS neglected tropical diseases</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Delespaux, Vincent</au><au>Vitouley, Hervé Sèna</au><au>Marcotty, Tanguy</au><au>Speybroeck, Niko</au><au>Berkvens, Dirk</au><au>Roy, Krisna</au><au>Geerts, Stanny</au><au>Van den Bossche, Peter</au><au>Kita, Kiyoshi</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Chemosensitization of Trypanosoma congolense strains resistant to isometamidium chloride by tetracyclines and enrofloxacin</atitle><jtitle>PLoS neglected tropical diseases</jtitle><addtitle>PLoS Negl Trop Dis</addtitle><date>2010-09-28</date><risdate>2010</risdate><volume>4</volume><issue>9</issue><spage>e828</spage><epage>e828</epage><pages>e828-e828</pages><issn>1935-2735</issn><issn>1935-2727</issn><eissn>1935-2735</eissn><abstract>Because of the development of resistance in trypanosomes to trypanocidal drugs, the livelihood of millions of livestock keepers in sub-Saharan Africa is threatened now more than ever. The existing compounds have become virtually useless and pharmaceutical companies are not keen on investing in the development of new trypanocides. We may have found a breakthrough in the treatment of resistant trypanosomal infections, through the combination of the trypanocide isometamidium chloride (ISM) with two affordable veterinary antibiotics.
In a first experiment, groups of mice were inoculated with Trypanosoma congolense strains resistant to ISM and either left untreated or treated with (i) tetracycline, (ii) ISM or (iii) the combination of the antibiotic and the trypanocide. Survival analysis showed that there was a significant effect of treatment and resistance to treatment on the survival time. The groups treated with ISM (with or without antibiotic) survived significantly longer than the groups that were not treated with ISM (P<0.01). The group treated with the combination trypanocide/antibiotic survived significantly longer than the group treated with ISM (P<0.01). In a second experiment, groups of cattle were inoculated with the same resistant trypanosome strain and treated with (i) ISM, (ii) ISM associated with oxytetracycline or (iii) ISM associated with enrofloxacine. All animals treated with ISM became parasitaemic. In the groups treated with ISM-oxytetracycline and ISM-enrofloxacine, 50% of the animals were cured. Animals from the groups treated with a combination trypanocide/antibiotic presented a significantly longer prepatent period than animals treated with ISM (p<0.001). The impact of the disease on the haematocrit was low in all ISM treated groups. Yet, it was lower in the groups treated with the combination trypanocide/antibiotic (p<0.01).
After optimization of the administration protocol, this new therapeutic combination could constitute a promising treatment for livestock infected with drug resistant T. congolense.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>20927189</pmid><doi>10.1371/journal.pntd.0000828</doi><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1935-2735 |
| ispartof | PLoS neglected tropical diseases, 2010-09, Vol.4 (9), p.e828-e828 |
| issn | 1935-2735 1935-2727 1935-2735 |
| language | eng |
| recordid | cdi_plos_journals_1288113424 |
| source | Publicly Available Content Database (Proquest) (PQ_SDU_P3); PubMed Central |
| subjects | Animals Antibiotics Antiprotozoal Agents - administration & dosage Antiprotozoal Agents - pharmacology Cattle Disease Models, Animal Drug dosages Drug resistance Drug Resistance - drug effects Drug Therapy, Combination - methods Experiments Fluoroquinolones - administration & dosage Fluoroquinolones - pharmacology Glossina Infectious Diseases/Antimicrobials and Drug Resistance Infectious Diseases/Protozoal Infections Infectious Diseases/Tropical and Travel-Associated Diseases Livestock Mice Parasitemia - drug therapy Parasitemia - parasitology Pharmaceutical industry Phenanthridines - administration & dosage Phenanthridines - pharmacology Rural areas Rural development Survival Analysis Tetracyclines - administration & dosage Tetracyclines - pharmacology Treatment Outcome Tropical diseases Trypanosoma Trypanosoma congolense Trypanosoma congolense - drug effects Trypanosomiasis, African - drug therapy Trypanosomiasis, African - parasitology |
| title | Chemosensitization of Trypanosoma congolense strains resistant to isometamidium chloride by tetracyclines and enrofloxacin |
| url | http://sfxeu10.hosted.exlibrisgroup.com/loughborough?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-27T19%3A17%3A32IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Chemosensitization%20of%20Trypanosoma%20congolense%20strains%20resistant%20to%20isometamidium%20chloride%20by%20tetracyclines%20and%20enrofloxacin&rft.jtitle=PLoS%20neglected%20tropical%20diseases&rft.au=Delespaux,%20Vincent&rft.date=2010-09-28&rft.volume=4&rft.issue=9&rft.spage=e828&rft.epage=e828&rft.pages=e828-e828&rft.issn=1935-2735&rft.eissn=1935-2735&rft_id=info:doi/10.1371/journal.pntd.0000828&rft_dat=%3Cproquest_plos_%3E2893335381%3C/proquest_plos_%3E%3Cgrp_id%3Ecdi_FETCH-LOGICAL-c623t-ab25d6e1f2ef4befa8e7aa2651c7333c69184d2b90fb1773c80c0855cad357203%3C/grp_id%3E%3Coa%3E%3C/oa%3E%3Curl%3E%3C/url%3E&rft_id=info:oai/&rft_pqid=1288113424&rft_id=info:pmid/20927189&rfr_iscdi=true |