Treatment of visceral leishmaniasis: model-based analyses on the spread of antimony-resistant L. donovani in Bihar, India.
<h4>Background</h4>Pentavalent antimonials have been the mainstay of antileishmanial therapy for decades, but increasing failure rates under antimonial treatment have challenged further use of these drugs in the Indian subcontinent. Experimental evidence has suggested that parasites whic...
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Public Library of Science (PLoS)
2012-01-01
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| Series: | PLoS Neglected Tropical Diseases |
| Online Access: | https://journals.plos.org/plosntds/article/file?id=10.1371/journal.pntd.0001973&type=printable |
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| author | Anette Stauch Hans-Peter Duerr Jean-Claude Dujardin Manu Vanaerschot Shyam Sundar Martin Eichner |
| author_facet | Anette Stauch Hans-Peter Duerr Jean-Claude Dujardin Manu Vanaerschot Shyam Sundar Martin Eichner |
| author_sort | Anette Stauch |
| collection | DOAJ |
| description | <h4>Background</h4>Pentavalent antimonials have been the mainstay of antileishmanial therapy for decades, but increasing failure rates under antimonial treatment have challenged further use of these drugs in the Indian subcontinent. Experimental evidence has suggested that parasites which are resistant against antimonials have superior survival skills than sensitive ones even in the absence of antimonial treatment.<h4>Methods and findings</h4>We use simulation studies based on a mathematical L. donovani transmission model to identify parameters which can explain why treatment failure rates under antimonial treatment increased up to 65% in Bihar between 1980 and 1997. Model analyses suggest that resistance to treatment alone cannot explain the observed treatment failure rates. We explore two hypotheses referring to an increased fitness of antimony-resistant parasites: the additional fitness is (i) disease-related, by causing more clinical cases (higher pathogenicity) or more severe disease (higher virulence), or (ii) is transmission-related, by increasing the transmissibility from sand flies to humans or vice versa.<h4>Conclusions</h4>Both hypotheses can potentially explain the Bihar observations. However, increased transmissibility as an explanation appears more plausible because it can occur in the background of asymptomatically transmitted infection whereas disease-related factors would most probably be observable. Irrespective of the cause of fitness, parasites with a higher fitness will finally replace sensitive parasites, even if antimonials are replaced by another drug. |
| format | Article |
| id | doaj-art-62ec8d86c62842f5bb5b0aabce23e483 |
| institution | OA Journals |
| issn | 1935-2727 1935-2735 |
| language | English |
| publishDate | 2012-01-01 |
| publisher | Public Library of Science (PLoS) |
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| series | PLoS Neglected Tropical Diseases |
| spelling | doaj-art-62ec8d86c62842f5bb5b0aabce23e4832025-08-20T02:15:25ZengPublic Library of Science (PLoS)PLoS Neglected Tropical Diseases1935-27271935-27352012-01-01612e197310.1371/journal.pntd.0001973Treatment of visceral leishmaniasis: model-based analyses on the spread of antimony-resistant L. donovani in Bihar, India.Anette StauchHans-Peter DuerrJean-Claude DujardinManu VanaerschotShyam SundarMartin Eichner<h4>Background</h4>Pentavalent antimonials have been the mainstay of antileishmanial therapy for decades, but increasing failure rates under antimonial treatment have challenged further use of these drugs in the Indian subcontinent. Experimental evidence has suggested that parasites which are resistant against antimonials have superior survival skills than sensitive ones even in the absence of antimonial treatment.<h4>Methods and findings</h4>We use simulation studies based on a mathematical L. donovani transmission model to identify parameters which can explain why treatment failure rates under antimonial treatment increased up to 65% in Bihar between 1980 and 1997. Model analyses suggest that resistance to treatment alone cannot explain the observed treatment failure rates. We explore two hypotheses referring to an increased fitness of antimony-resistant parasites: the additional fitness is (i) disease-related, by causing more clinical cases (higher pathogenicity) or more severe disease (higher virulence), or (ii) is transmission-related, by increasing the transmissibility from sand flies to humans or vice versa.<h4>Conclusions</h4>Both hypotheses can potentially explain the Bihar observations. However, increased transmissibility as an explanation appears more plausible because it can occur in the background of asymptomatically transmitted infection whereas disease-related factors would most probably be observable. Irrespective of the cause of fitness, parasites with a higher fitness will finally replace sensitive parasites, even if antimonials are replaced by another drug.https://journals.plos.org/plosntds/article/file?id=10.1371/journal.pntd.0001973&type=printable |
| spellingShingle | Anette Stauch Hans-Peter Duerr Jean-Claude Dujardin Manu Vanaerschot Shyam Sundar Martin Eichner Treatment of visceral leishmaniasis: model-based analyses on the spread of antimony-resistant L. donovani in Bihar, India. PLoS Neglected Tropical Diseases |
| title | Treatment of visceral leishmaniasis: model-based analyses on the spread of antimony-resistant L. donovani in Bihar, India. |
| title_full | Treatment of visceral leishmaniasis: model-based analyses on the spread of antimony-resistant L. donovani in Bihar, India. |
| title_fullStr | Treatment of visceral leishmaniasis: model-based analyses on the spread of antimony-resistant L. donovani in Bihar, India. |
| title_full_unstemmed | Treatment of visceral leishmaniasis: model-based analyses on the spread of antimony-resistant L. donovani in Bihar, India. |
| title_short | Treatment of visceral leishmaniasis: model-based analyses on the spread of antimony-resistant L. donovani in Bihar, India. |
| title_sort | treatment of visceral leishmaniasis model based analyses on the spread of antimony resistant l donovani in bihar india |
| url | https://journals.plos.org/plosntds/article/file?id=10.1371/journal.pntd.0001973&type=printable |
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