Repeated high doses of avermectins cause prolonged sterilisation, but do not kill, Onchocerca ochengiadult worms in African cattle
Background Ivermectin (Mectizan™, Merck and CO. Inc.) is being widely used in the control of human onchocerciasis (Onchoverca volvulus) because of its potent effect on microfilariae. Human studies have suggested that, at the standard dose of 150 μg/kg an annual treatment schedule of ivermectin rever...
Ausführliche Beschreibung
Autor*in: |
deC Bronsvoort, Barend M [verfasserIn] Renz, Alfons [verfasserIn] Tchakouté, Virginia [verfasserIn] Tanya, Vincent N [verfasserIn] Ekale, David [verfasserIn] Trees, Alexander J [verfasserIn] |
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E-Artikel |
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Sprache: |
Englisch |
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2005 |
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Übergeordnetes Werk: |
Enthalten in: Filaria journal - [S.l.] : BioMed Central, 2002, 4(2005), 1 vom: 08. Aug. |
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Übergeordnetes Werk: |
volume:4 ; year:2005 ; number:1 ; day:08 ; month:08 |
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DOI / URN: |
10.1186/1475-2883-4-8 |
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Katalog-ID: |
SPR031808212 |
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245 | 1 | 0 | |a Repeated high doses of avermectins cause prolonged sterilisation, but do not kill, Onchocerca ochengiadult worms in African cattle |
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520 | |a Background Ivermectin (Mectizan™, Merck and CO. Inc.) is being widely used in the control of human onchocerciasis (Onchoverca volvulus) because of its potent effect on microfilariae. Human studies have suggested that, at the standard dose of 150 μg/kg an annual treatment schedule of ivermectin reversibly interferes with female worm fertility but is not macrofilaricidal. Because of the importance of determining whether ivermectin could be macrofilaricidal, the efficacy of high and prolonged doses of ivermectin and a related avermectin, doramectin, were investigated in cattle infected with O. ochengi. Methods Drugs with potential macrofilaricidal activity, were screened for the treatment of human onchocerciasis, using natural infections of O. ochengi in African cattle. Three groups of 3 cows were either treated at monthly intervals (7 treatments) with ivermectin ($ Ivomec^{®} $, Merck and Co. Inc.) at 500 μg/kg or doramectin ($ Dectamax^{®} $, Pfizer) at 500 μg/kg or not treated as controls. Intradermal nodules were removed at 6 monthly intervals and adult worms were examined for signs of drug activity. Results There was no significant decline in nodule diameter, the motility of male and female worms, nor in male and female viability as determined by the ability to reduce tetrazolium, compared with controls, at any time up to 24 months from the start of treatments (mpt). Embryogenesis, however, was abrogated by treatment, which was seen as an accumulation of dead and dying intra-uterine microfilariae (mf) persisting for up to 18 mpt. Skin mf densities in treated animals had fallen to zero by <3 mpt, but by 18 mpt small numbers of mf were found in the skin of some treated animals and a few female worms were starting to produce multi-cellular embryonic stages. Follow-up of the doramectin treated group at 36 mpt showed that mf densities had still only regained a small proportion of their pre-treatment levels. Conclusion These results have important implications for onchocerciasis control in the field. They suggest that ivermectin given at repeated high does may sterilise O. volvulus female worms for prolonged periods but is unlikely to kill them. This supports the view that control programmes may need to continue treatments with ivermectin for a period of decades and highlights the need to urgently identify new marcofiliaricidal compounds. | ||
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700 | 1 | |a Renz, Alfons |e verfasserin |4 aut | |
700 | 1 | |a Tchakouté, Virginia |e verfasserin |4 aut | |
700 | 1 | |a Tanya, Vincent N |e verfasserin |4 aut | |
700 | 1 | |a Ekale, David |e verfasserin |4 aut | |
700 | 1 | |a Trees, Alexander J |e verfasserin |4 aut | |
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10.1186/1475-2883-4-8 doi (DE-627)SPR031808212 (SPR)1475-2883-4-8-e DE-627 ger DE-627 rakwb eng 610 ASE deC Bronsvoort, Barend M verfasserin aut Repeated high doses of avermectins cause prolonged sterilisation, but do not kill, Onchocerca ochengiadult worms in African cattle 2005 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Background Ivermectin (Mectizan™, Merck and CO. Inc.) is being widely used in the control of human onchocerciasis (Onchoverca volvulus) because of its potent effect on microfilariae. Human studies have suggested that, at the standard dose of 150 μg/kg an annual treatment schedule of ivermectin reversibly interferes with female worm fertility but is not macrofilaricidal. Because of the importance of determining whether ivermectin could be macrofilaricidal, the efficacy of high and prolonged doses of ivermectin and a related avermectin, doramectin, were investigated in cattle infected with O. ochengi. Methods Drugs with potential macrofilaricidal activity, were screened for the treatment of human onchocerciasis, using natural infections of O. ochengi in African cattle. Three groups of 3 cows were either treated at monthly intervals (7 treatments) with ivermectin ($ Ivomec^{®} $, Merck and Co. Inc.) at 500 μg/kg or doramectin ($ Dectamax^{®} $, Pfizer) at 500 μg/kg or not treated as controls. Intradermal nodules were removed at 6 monthly intervals and adult worms were examined for signs of drug activity. Results There was no significant decline in nodule diameter, the motility of male and female worms, nor in male and female viability as determined by the ability to reduce tetrazolium, compared with controls, at any time up to 24 months from the start of treatments (mpt). Embryogenesis, however, was abrogated by treatment, which was seen as an accumulation of dead and dying intra-uterine microfilariae (mf) persisting for up to 18 mpt. Skin mf densities in treated animals had fallen to zero by <3 mpt, but by 18 mpt small numbers of mf were found in the skin of some treated animals and a few female worms were starting to produce multi-cellular embryonic stages. Follow-up of the doramectin treated group at 36 mpt showed that mf densities had still only regained a small proportion of their pre-treatment levels. Conclusion These results have important implications for onchocerciasis control in the field. They suggest that ivermectin given at repeated high does may sterilise O. volvulus female worms for prolonged periods but is unlikely to kill them. This supports the view that control programmes may need to continue treatments with ivermectin for a period of decades and highlights the need to urgently identify new marcofiliaricidal compounds. Adult Worm (dpeaa)DE-He213 Ivermectin (dpeaa)DE-He213 Female Worm (dpeaa)DE-He213 Onchocerciasis (dpeaa)DE-He213 Moxidectin (dpeaa)DE-He213 Renz, Alfons verfasserin aut Tchakouté, Virginia verfasserin aut Tanya, Vincent N verfasserin aut Ekale, David verfasserin aut Trees, Alexander J verfasserin aut Enthalten in Filaria journal [S.l.] : BioMed Central, 2002 4(2005), 1 vom: 08. Aug. (DE-627)356006263 (DE-600)2092309-0 1475-2883 nnns volume:4 year:2005 number:1 day:08 month:08 https://dx.doi.org/10.1186/1475-2883-4-8 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_2522 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 4 2005 1 08 08 |
spelling |
10.1186/1475-2883-4-8 doi (DE-627)SPR031808212 (SPR)1475-2883-4-8-e DE-627 ger DE-627 rakwb eng 610 ASE deC Bronsvoort, Barend M verfasserin aut Repeated high doses of avermectins cause prolonged sterilisation, but do not kill, Onchocerca ochengiadult worms in African cattle 2005 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Background Ivermectin (Mectizan™, Merck and CO. Inc.) is being widely used in the control of human onchocerciasis (Onchoverca volvulus) because of its potent effect on microfilariae. Human studies have suggested that, at the standard dose of 150 μg/kg an annual treatment schedule of ivermectin reversibly interferes with female worm fertility but is not macrofilaricidal. Because of the importance of determining whether ivermectin could be macrofilaricidal, the efficacy of high and prolonged doses of ivermectin and a related avermectin, doramectin, were investigated in cattle infected with O. ochengi. Methods Drugs with potential macrofilaricidal activity, were screened for the treatment of human onchocerciasis, using natural infections of O. ochengi in African cattle. Three groups of 3 cows were either treated at monthly intervals (7 treatments) with ivermectin ($ Ivomec^{®} $, Merck and Co. Inc.) at 500 μg/kg or doramectin ($ Dectamax^{®} $, Pfizer) at 500 μg/kg or not treated as controls. Intradermal nodules were removed at 6 monthly intervals and adult worms were examined for signs of drug activity. Results There was no significant decline in nodule diameter, the motility of male and female worms, nor in male and female viability as determined by the ability to reduce tetrazolium, compared with controls, at any time up to 24 months from the start of treatments (mpt). Embryogenesis, however, was abrogated by treatment, which was seen as an accumulation of dead and dying intra-uterine microfilariae (mf) persisting for up to 18 mpt. Skin mf densities in treated animals had fallen to zero by <3 mpt, but by 18 mpt small numbers of mf were found in the skin of some treated animals and a few female worms were starting to produce multi-cellular embryonic stages. Follow-up of the doramectin treated group at 36 mpt showed that mf densities had still only regained a small proportion of their pre-treatment levels. Conclusion These results have important implications for onchocerciasis control in the field. They suggest that ivermectin given at repeated high does may sterilise O. volvulus female worms for prolonged periods but is unlikely to kill them. This supports the view that control programmes may need to continue treatments with ivermectin for a period of decades and highlights the need to urgently identify new marcofiliaricidal compounds. Adult Worm (dpeaa)DE-He213 Ivermectin (dpeaa)DE-He213 Female Worm (dpeaa)DE-He213 Onchocerciasis (dpeaa)DE-He213 Moxidectin (dpeaa)DE-He213 Renz, Alfons verfasserin aut Tchakouté, Virginia verfasserin aut Tanya, Vincent N verfasserin aut Ekale, David verfasserin aut Trees, Alexander J verfasserin aut Enthalten in Filaria journal [S.l.] : BioMed Central, 2002 4(2005), 1 vom: 08. Aug. (DE-627)356006263 (DE-600)2092309-0 1475-2883 nnns volume:4 year:2005 number:1 day:08 month:08 https://dx.doi.org/10.1186/1475-2883-4-8 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_2522 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 4 2005 1 08 08 |
allfields_unstemmed |
10.1186/1475-2883-4-8 doi (DE-627)SPR031808212 (SPR)1475-2883-4-8-e DE-627 ger DE-627 rakwb eng 610 ASE deC Bronsvoort, Barend M verfasserin aut Repeated high doses of avermectins cause prolonged sterilisation, but do not kill, Onchocerca ochengiadult worms in African cattle 2005 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Background Ivermectin (Mectizan™, Merck and CO. Inc.) is being widely used in the control of human onchocerciasis (Onchoverca volvulus) because of its potent effect on microfilariae. Human studies have suggested that, at the standard dose of 150 μg/kg an annual treatment schedule of ivermectin reversibly interferes with female worm fertility but is not macrofilaricidal. Because of the importance of determining whether ivermectin could be macrofilaricidal, the efficacy of high and prolonged doses of ivermectin and a related avermectin, doramectin, were investigated in cattle infected with O. ochengi. Methods Drugs with potential macrofilaricidal activity, were screened for the treatment of human onchocerciasis, using natural infections of O. ochengi in African cattle. Three groups of 3 cows were either treated at monthly intervals (7 treatments) with ivermectin ($ Ivomec^{®} $, Merck and Co. Inc.) at 500 μg/kg or doramectin ($ Dectamax^{®} $, Pfizer) at 500 μg/kg or not treated as controls. Intradermal nodules were removed at 6 monthly intervals and adult worms were examined for signs of drug activity. Results There was no significant decline in nodule diameter, the motility of male and female worms, nor in male and female viability as determined by the ability to reduce tetrazolium, compared with controls, at any time up to 24 months from the start of treatments (mpt). Embryogenesis, however, was abrogated by treatment, which was seen as an accumulation of dead and dying intra-uterine microfilariae (mf) persisting for up to 18 mpt. Skin mf densities in treated animals had fallen to zero by <3 mpt, but by 18 mpt small numbers of mf were found in the skin of some treated animals and a few female worms were starting to produce multi-cellular embryonic stages. Follow-up of the doramectin treated group at 36 mpt showed that mf densities had still only regained a small proportion of their pre-treatment levels. Conclusion These results have important implications for onchocerciasis control in the field. They suggest that ivermectin given at repeated high does may sterilise O. volvulus female worms for prolonged periods but is unlikely to kill them. This supports the view that control programmes may need to continue treatments with ivermectin for a period of decades and highlights the need to urgently identify new marcofiliaricidal compounds. Adult Worm (dpeaa)DE-He213 Ivermectin (dpeaa)DE-He213 Female Worm (dpeaa)DE-He213 Onchocerciasis (dpeaa)DE-He213 Moxidectin (dpeaa)DE-He213 Renz, Alfons verfasserin aut Tchakouté, Virginia verfasserin aut Tanya, Vincent N verfasserin aut Ekale, David verfasserin aut Trees, Alexander J verfasserin aut Enthalten in Filaria journal [S.l.] : BioMed Central, 2002 4(2005), 1 vom: 08. Aug. (DE-627)356006263 (DE-600)2092309-0 1475-2883 nnns volume:4 year:2005 number:1 day:08 month:08 https://dx.doi.org/10.1186/1475-2883-4-8 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_2522 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 4 2005 1 08 08 |
allfieldsGer |
10.1186/1475-2883-4-8 doi (DE-627)SPR031808212 (SPR)1475-2883-4-8-e DE-627 ger DE-627 rakwb eng 610 ASE deC Bronsvoort, Barend M verfasserin aut Repeated high doses of avermectins cause prolonged sterilisation, but do not kill, Onchocerca ochengiadult worms in African cattle 2005 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Background Ivermectin (Mectizan™, Merck and CO. Inc.) is being widely used in the control of human onchocerciasis (Onchoverca volvulus) because of its potent effect on microfilariae. Human studies have suggested that, at the standard dose of 150 μg/kg an annual treatment schedule of ivermectin reversibly interferes with female worm fertility but is not macrofilaricidal. Because of the importance of determining whether ivermectin could be macrofilaricidal, the efficacy of high and prolonged doses of ivermectin and a related avermectin, doramectin, were investigated in cattle infected with O. ochengi. Methods Drugs with potential macrofilaricidal activity, were screened for the treatment of human onchocerciasis, using natural infections of O. ochengi in African cattle. Three groups of 3 cows were either treated at monthly intervals (7 treatments) with ivermectin ($ Ivomec^{®} $, Merck and Co. Inc.) at 500 μg/kg or doramectin ($ Dectamax^{®} $, Pfizer) at 500 μg/kg or not treated as controls. Intradermal nodules were removed at 6 monthly intervals and adult worms were examined for signs of drug activity. Results There was no significant decline in nodule diameter, the motility of male and female worms, nor in male and female viability as determined by the ability to reduce tetrazolium, compared with controls, at any time up to 24 months from the start of treatments (mpt). Embryogenesis, however, was abrogated by treatment, which was seen as an accumulation of dead and dying intra-uterine microfilariae (mf) persisting for up to 18 mpt. Skin mf densities in treated animals had fallen to zero by <3 mpt, but by 18 mpt small numbers of mf were found in the skin of some treated animals and a few female worms were starting to produce multi-cellular embryonic stages. Follow-up of the doramectin treated group at 36 mpt showed that mf densities had still only regained a small proportion of their pre-treatment levels. Conclusion These results have important implications for onchocerciasis control in the field. They suggest that ivermectin given at repeated high does may sterilise O. volvulus female worms for prolonged periods but is unlikely to kill them. This supports the view that control programmes may need to continue treatments with ivermectin for a period of decades and highlights the need to urgently identify new marcofiliaricidal compounds. Adult Worm (dpeaa)DE-He213 Ivermectin (dpeaa)DE-He213 Female Worm (dpeaa)DE-He213 Onchocerciasis (dpeaa)DE-He213 Moxidectin (dpeaa)DE-He213 Renz, Alfons verfasserin aut Tchakouté, Virginia verfasserin aut Tanya, Vincent N verfasserin aut Ekale, David verfasserin aut Trees, Alexander J verfasserin aut Enthalten in Filaria journal [S.l.] : BioMed Central, 2002 4(2005), 1 vom: 08. Aug. (DE-627)356006263 (DE-600)2092309-0 1475-2883 nnns volume:4 year:2005 number:1 day:08 month:08 https://dx.doi.org/10.1186/1475-2883-4-8 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_2522 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 4 2005 1 08 08 |
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10.1186/1475-2883-4-8 doi (DE-627)SPR031808212 (SPR)1475-2883-4-8-e DE-627 ger DE-627 rakwb eng 610 ASE deC Bronsvoort, Barend M verfasserin aut Repeated high doses of avermectins cause prolonged sterilisation, but do not kill, Onchocerca ochengiadult worms in African cattle 2005 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Background Ivermectin (Mectizan™, Merck and CO. Inc.) is being widely used in the control of human onchocerciasis (Onchoverca volvulus) because of its potent effect on microfilariae. Human studies have suggested that, at the standard dose of 150 μg/kg an annual treatment schedule of ivermectin reversibly interferes with female worm fertility but is not macrofilaricidal. Because of the importance of determining whether ivermectin could be macrofilaricidal, the efficacy of high and prolonged doses of ivermectin and a related avermectin, doramectin, were investigated in cattle infected with O. ochengi. Methods Drugs with potential macrofilaricidal activity, were screened for the treatment of human onchocerciasis, using natural infections of O. ochengi in African cattle. Three groups of 3 cows were either treated at monthly intervals (7 treatments) with ivermectin ($ Ivomec^{®} $, Merck and Co. Inc.) at 500 μg/kg or doramectin ($ Dectamax^{®} $, Pfizer) at 500 μg/kg or not treated as controls. Intradermal nodules were removed at 6 monthly intervals and adult worms were examined for signs of drug activity. Results There was no significant decline in nodule diameter, the motility of male and female worms, nor in male and female viability as determined by the ability to reduce tetrazolium, compared with controls, at any time up to 24 months from the start of treatments (mpt). Embryogenesis, however, was abrogated by treatment, which was seen as an accumulation of dead and dying intra-uterine microfilariae (mf) persisting for up to 18 mpt. Skin mf densities in treated animals had fallen to zero by <3 mpt, but by 18 mpt small numbers of mf were found in the skin of some treated animals and a few female worms were starting to produce multi-cellular embryonic stages. Follow-up of the doramectin treated group at 36 mpt showed that mf densities had still only regained a small proportion of their pre-treatment levels. Conclusion These results have important implications for onchocerciasis control in the field. They suggest that ivermectin given at repeated high does may sterilise O. volvulus female worms for prolonged periods but is unlikely to kill them. This supports the view that control programmes may need to continue treatments with ivermectin for a period of decades and highlights the need to urgently identify new marcofiliaricidal compounds. Adult Worm (dpeaa)DE-He213 Ivermectin (dpeaa)DE-He213 Female Worm (dpeaa)DE-He213 Onchocerciasis (dpeaa)DE-He213 Moxidectin (dpeaa)DE-He213 Renz, Alfons verfasserin aut Tchakouté, Virginia verfasserin aut Tanya, Vincent N verfasserin aut Ekale, David verfasserin aut Trees, Alexander J verfasserin aut Enthalten in Filaria journal [S.l.] : BioMed Central, 2002 4(2005), 1 vom: 08. Aug. (DE-627)356006263 (DE-600)2092309-0 1475-2883 nnns volume:4 year:2005 number:1 day:08 month:08 https://dx.doi.org/10.1186/1475-2883-4-8 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_2522 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 4 2005 1 08 08 |
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610 ASE Repeated high doses of avermectins cause prolonged sterilisation, but do not kill, Onchocerca ochengiadult worms in African cattle Adult Worm (dpeaa)DE-He213 Ivermectin (dpeaa)DE-He213 Female Worm (dpeaa)DE-He213 Onchocerciasis (dpeaa)DE-He213 Moxidectin (dpeaa)DE-He213 |
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repeated high doses of avermectins cause prolonged sterilisation, but do not kill, onchocerca ochengiadult worms in african cattle |
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Repeated high doses of avermectins cause prolonged sterilisation, but do not kill, Onchocerca ochengiadult worms in African cattle |
abstract |
Background Ivermectin (Mectizan™, Merck and CO. Inc.) is being widely used in the control of human onchocerciasis (Onchoverca volvulus) because of its potent effect on microfilariae. Human studies have suggested that, at the standard dose of 150 μg/kg an annual treatment schedule of ivermectin reversibly interferes with female worm fertility but is not macrofilaricidal. Because of the importance of determining whether ivermectin could be macrofilaricidal, the efficacy of high and prolonged doses of ivermectin and a related avermectin, doramectin, were investigated in cattle infected with O. ochengi. Methods Drugs with potential macrofilaricidal activity, were screened for the treatment of human onchocerciasis, using natural infections of O. ochengi in African cattle. Three groups of 3 cows were either treated at monthly intervals (7 treatments) with ivermectin ($ Ivomec^{®} $, Merck and Co. Inc.) at 500 μg/kg or doramectin ($ Dectamax^{®} $, Pfizer) at 500 μg/kg or not treated as controls. Intradermal nodules were removed at 6 monthly intervals and adult worms were examined for signs of drug activity. Results There was no significant decline in nodule diameter, the motility of male and female worms, nor in male and female viability as determined by the ability to reduce tetrazolium, compared with controls, at any time up to 24 months from the start of treatments (mpt). Embryogenesis, however, was abrogated by treatment, which was seen as an accumulation of dead and dying intra-uterine microfilariae (mf) persisting for up to 18 mpt. Skin mf densities in treated animals had fallen to zero by <3 mpt, but by 18 mpt small numbers of mf were found in the skin of some treated animals and a few female worms were starting to produce multi-cellular embryonic stages. Follow-up of the doramectin treated group at 36 mpt showed that mf densities had still only regained a small proportion of their pre-treatment levels. Conclusion These results have important implications for onchocerciasis control in the field. They suggest that ivermectin given at repeated high does may sterilise O. volvulus female worms for prolonged periods but is unlikely to kill them. This supports the view that control programmes may need to continue treatments with ivermectin for a period of decades and highlights the need to urgently identify new marcofiliaricidal compounds. |
abstractGer |
Background Ivermectin (Mectizan™, Merck and CO. Inc.) is being widely used in the control of human onchocerciasis (Onchoverca volvulus) because of its potent effect on microfilariae. Human studies have suggested that, at the standard dose of 150 μg/kg an annual treatment schedule of ivermectin reversibly interferes with female worm fertility but is not macrofilaricidal. Because of the importance of determining whether ivermectin could be macrofilaricidal, the efficacy of high and prolonged doses of ivermectin and a related avermectin, doramectin, were investigated in cattle infected with O. ochengi. Methods Drugs with potential macrofilaricidal activity, were screened for the treatment of human onchocerciasis, using natural infections of O. ochengi in African cattle. Three groups of 3 cows were either treated at monthly intervals (7 treatments) with ivermectin ($ Ivomec^{®} $, Merck and Co. Inc.) at 500 μg/kg or doramectin ($ Dectamax^{®} $, Pfizer) at 500 μg/kg or not treated as controls. Intradermal nodules were removed at 6 monthly intervals and adult worms were examined for signs of drug activity. Results There was no significant decline in nodule diameter, the motility of male and female worms, nor in male and female viability as determined by the ability to reduce tetrazolium, compared with controls, at any time up to 24 months from the start of treatments (mpt). Embryogenesis, however, was abrogated by treatment, which was seen as an accumulation of dead and dying intra-uterine microfilariae (mf) persisting for up to 18 mpt. Skin mf densities in treated animals had fallen to zero by <3 mpt, but by 18 mpt small numbers of mf were found in the skin of some treated animals and a few female worms were starting to produce multi-cellular embryonic stages. Follow-up of the doramectin treated group at 36 mpt showed that mf densities had still only regained a small proportion of their pre-treatment levels. Conclusion These results have important implications for onchocerciasis control in the field. They suggest that ivermectin given at repeated high does may sterilise O. volvulus female worms for prolonged periods but is unlikely to kill them. This supports the view that control programmes may need to continue treatments with ivermectin for a period of decades and highlights the need to urgently identify new marcofiliaricidal compounds. |
abstract_unstemmed |
Background Ivermectin (Mectizan™, Merck and CO. Inc.) is being widely used in the control of human onchocerciasis (Onchoverca volvulus) because of its potent effect on microfilariae. Human studies have suggested that, at the standard dose of 150 μg/kg an annual treatment schedule of ivermectin reversibly interferes with female worm fertility but is not macrofilaricidal. Because of the importance of determining whether ivermectin could be macrofilaricidal, the efficacy of high and prolonged doses of ivermectin and a related avermectin, doramectin, were investigated in cattle infected with O. ochengi. Methods Drugs with potential macrofilaricidal activity, were screened for the treatment of human onchocerciasis, using natural infections of O. ochengi in African cattle. Three groups of 3 cows were either treated at monthly intervals (7 treatments) with ivermectin ($ Ivomec^{®} $, Merck and Co. Inc.) at 500 μg/kg or doramectin ($ Dectamax^{®} $, Pfizer) at 500 μg/kg or not treated as controls. Intradermal nodules were removed at 6 monthly intervals and adult worms were examined for signs of drug activity. Results There was no significant decline in nodule diameter, the motility of male and female worms, nor in male and female viability as determined by the ability to reduce tetrazolium, compared with controls, at any time up to 24 months from the start of treatments (mpt). Embryogenesis, however, was abrogated by treatment, which was seen as an accumulation of dead and dying intra-uterine microfilariae (mf) persisting for up to 18 mpt. Skin mf densities in treated animals had fallen to zero by <3 mpt, but by 18 mpt small numbers of mf were found in the skin of some treated animals and a few female worms were starting to produce multi-cellular embryonic stages. Follow-up of the doramectin treated group at 36 mpt showed that mf densities had still only regained a small proportion of their pre-treatment levels. Conclusion These results have important implications for onchocerciasis control in the field. They suggest that ivermectin given at repeated high does may sterilise O. volvulus female worms for prolonged periods but is unlikely to kill them. This supports the view that control programmes may need to continue treatments with ivermectin for a period of decades and highlights the need to urgently identify new marcofiliaricidal compounds. |
collection_details |
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container_issue |
1 |
title_short |
Repeated high doses of avermectins cause prolonged sterilisation, but do not kill, Onchocerca ochengiadult worms in African cattle |
url |
https://dx.doi.org/10.1186/1475-2883-4-8 |
remote_bool |
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author2 |
Renz, Alfons Tchakouté, Virginia Tanya, Vincent N Ekale, David Trees, Alexander J |
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doi_str |
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up_date |
2024-07-04T01:19:51.973Z |
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