Corallopyronin A for short-course anti-wolbachial, macrofilaricidal treatment of filarial infections.
Current efforts to eliminate the neglected tropical diseases onchocerciasis and lymphatic filariasis, caused by the filarial nematodes Onchocerca volvulus and Wuchereria bancrofti or Brugia spp., respectively, are hampered by lack of a short-course macrofilaricidal-adult-worm killing-treatment. Anti...
Published in: | PLOS Neglected Tropical Diseases |
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ftdoajarticles:oai:doaj.org/article:d4370a71cad149209e66761eb918df85 2023-05-15T15:11:56+02:00 Corallopyronin A for short-course anti-wolbachial, macrofilaricidal treatment of filarial infections. Andrea Schiefer Marc P Hübner Anna Krome Christine Lämmer Alexandra Ehrens Tilman Aden Marianne Koschel Helene Neufeld Lillibeth Chaverra-Muñoz Rolf Jansen Stefan Kehraus Gabriele M König Domen Pogorevc Rolf Müller Marc Stadler Stephan Hüttel Thomas Hesterkamp Karl Wagner Kenneth Pfarr Achim Hoerauf 2020-12-01T00:00:00Z https://doi.org/10.1371/journal.pntd.0008930 https://doaj.org/article/d4370a71cad149209e66761eb918df85 EN eng Public Library of Science (PLoS) https://doi.org/10.1371/journal.pntd.0008930 https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0008930 https://doaj.org/article/d4370a71cad149209e66761eb918df85 PLoS Neglected Tropical Diseases, Vol 14, Iss 12, p e0008930 (2020) Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 article 2020 ftdoajarticles https://doi.org/10.1371/journal.pntd.0008930 2022-12-31T00:23:08Z Current efforts to eliminate the neglected tropical diseases onchocerciasis and lymphatic filariasis, caused by the filarial nematodes Onchocerca volvulus and Wuchereria bancrofti or Brugia spp., respectively, are hampered by lack of a short-course macrofilaricidal-adult-worm killing-treatment. Anti-wolbachial antibiotics, e.g. doxycycline, target the essential Wolbachia endosymbionts of filariae and are a safe prototype adult-worm-sterilizing and macrofilaricidal regimen, in contrast to standard treatments with ivermectin or diethylcarbamazine, which mainly target the microfilariae. However, treatment regimens of 4-5 weeks necessary for doxycycline and contraindications limit its use. Therefore, we tested the preclinical anti-Wolbachia drug candidate Corallopyronin A (CorA) for in vivo efficacy during initial and chronic filarial infections in the Litomosoides sigmodontis rodent model. CorA treatment for 14 days beginning immediately after infection cleared >90% of Wolbachia endosymbionts from filariae and prevented development into adult worms. CorA treatment of patently infected microfilaremic gerbils for 14 days with 30 mg/kg twice a day (BID) achieved a sustained reduction of >99% of Wolbachia endosymbionts from adult filariae and microfilariae, followed by complete inhibition of filarial embryogenesis resulting in clearance of microfilariae. Combined treatment of CorA and albendazole, a drug currently co-administered during mass drug administrations and previously shown to enhance efficacy of anti-Wolbachia drugs, achieved microfilarial clearance after 7 days of treatment at a lower BID dose of 10 mg/kg CorA, a Human Equivalent Dose of 1.4 mg/kg. Importantly, this combination led to a significant reduction in the adult worm burden, which has not yet been published with other anti-Wolbachia candidates tested in this model. In summary, CorA is a preclinical candidate for filariasis, which significantly reduces treatment times required to achieve sustained Wolbachia depletion, clearance of ... Article in Journal/Newspaper Arctic Directory of Open Access Journals: DOAJ Articles Arctic Cora ENVELOPE(-60.317,-60.317,-62.467,-62.467) PLOS Neglected Tropical Diseases 14 12 e0008930 |
institution |
Open Polar |
collection |
Directory of Open Access Journals: DOAJ Articles |
op_collection_id |
ftdoajarticles |
language |
English |
topic |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
spellingShingle |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 Andrea Schiefer Marc P Hübner Anna Krome Christine Lämmer Alexandra Ehrens Tilman Aden Marianne Koschel Helene Neufeld Lillibeth Chaverra-Muñoz Rolf Jansen Stefan Kehraus Gabriele M König Domen Pogorevc Rolf Müller Marc Stadler Stephan Hüttel Thomas Hesterkamp Karl Wagner Kenneth Pfarr Achim Hoerauf Corallopyronin A for short-course anti-wolbachial, macrofilaricidal treatment of filarial infections. |
topic_facet |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
description |
Current efforts to eliminate the neglected tropical diseases onchocerciasis and lymphatic filariasis, caused by the filarial nematodes Onchocerca volvulus and Wuchereria bancrofti or Brugia spp., respectively, are hampered by lack of a short-course macrofilaricidal-adult-worm killing-treatment. Anti-wolbachial antibiotics, e.g. doxycycline, target the essential Wolbachia endosymbionts of filariae and are a safe prototype adult-worm-sterilizing and macrofilaricidal regimen, in contrast to standard treatments with ivermectin or diethylcarbamazine, which mainly target the microfilariae. However, treatment regimens of 4-5 weeks necessary for doxycycline and contraindications limit its use. Therefore, we tested the preclinical anti-Wolbachia drug candidate Corallopyronin A (CorA) for in vivo efficacy during initial and chronic filarial infections in the Litomosoides sigmodontis rodent model. CorA treatment for 14 days beginning immediately after infection cleared >90% of Wolbachia endosymbionts from filariae and prevented development into adult worms. CorA treatment of patently infected microfilaremic gerbils for 14 days with 30 mg/kg twice a day (BID) achieved a sustained reduction of >99% of Wolbachia endosymbionts from adult filariae and microfilariae, followed by complete inhibition of filarial embryogenesis resulting in clearance of microfilariae. Combined treatment of CorA and albendazole, a drug currently co-administered during mass drug administrations and previously shown to enhance efficacy of anti-Wolbachia drugs, achieved microfilarial clearance after 7 days of treatment at a lower BID dose of 10 mg/kg CorA, a Human Equivalent Dose of 1.4 mg/kg. Importantly, this combination led to a significant reduction in the adult worm burden, which has not yet been published with other anti-Wolbachia candidates tested in this model. In summary, CorA is a preclinical candidate for filariasis, which significantly reduces treatment times required to achieve sustained Wolbachia depletion, clearance of ... |
format |
Article in Journal/Newspaper |
author |
Andrea Schiefer Marc P Hübner Anna Krome Christine Lämmer Alexandra Ehrens Tilman Aden Marianne Koschel Helene Neufeld Lillibeth Chaverra-Muñoz Rolf Jansen Stefan Kehraus Gabriele M König Domen Pogorevc Rolf Müller Marc Stadler Stephan Hüttel Thomas Hesterkamp Karl Wagner Kenneth Pfarr Achim Hoerauf |
author_facet |
Andrea Schiefer Marc P Hübner Anna Krome Christine Lämmer Alexandra Ehrens Tilman Aden Marianne Koschel Helene Neufeld Lillibeth Chaverra-Muñoz Rolf Jansen Stefan Kehraus Gabriele M König Domen Pogorevc Rolf Müller Marc Stadler Stephan Hüttel Thomas Hesterkamp Karl Wagner Kenneth Pfarr Achim Hoerauf |
author_sort |
Andrea Schiefer |
title |
Corallopyronin A for short-course anti-wolbachial, macrofilaricidal treatment of filarial infections. |
title_short |
Corallopyronin A for short-course anti-wolbachial, macrofilaricidal treatment of filarial infections. |
title_full |
Corallopyronin A for short-course anti-wolbachial, macrofilaricidal treatment of filarial infections. |
title_fullStr |
Corallopyronin A for short-course anti-wolbachial, macrofilaricidal treatment of filarial infections. |
title_full_unstemmed |
Corallopyronin A for short-course anti-wolbachial, macrofilaricidal treatment of filarial infections. |
title_sort |
corallopyronin a for short-course anti-wolbachial, macrofilaricidal treatment of filarial infections. |
publisher |
Public Library of Science (PLoS) |
publishDate |
2020 |
url |
https://doi.org/10.1371/journal.pntd.0008930 https://doaj.org/article/d4370a71cad149209e66761eb918df85 |
long_lat |
ENVELOPE(-60.317,-60.317,-62.467,-62.467) |
geographic |
Arctic Cora |
geographic_facet |
Arctic Cora |
genre |
Arctic |
genre_facet |
Arctic |
op_source |
PLoS Neglected Tropical Diseases, Vol 14, Iss 12, p e0008930 (2020) |
op_relation |
https://doi.org/10.1371/journal.pntd.0008930 https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0008930 https://doaj.org/article/d4370a71cad149209e66761eb918df85 |
op_doi |
https://doi.org/10.1371/journal.pntd.0008930 |
container_title |
PLOS Neglected Tropical Diseases |
container_volume |
14 |
container_issue |
12 |
container_start_page |
e0008930 |
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1766342698849009664 |