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Achim Hoerauf - One of the best experts on this subject based on the ideXlab platform.
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macrofilaricidal activity after Doxycycline only treatment of onchocerca volvulus in an area of loa loa co endemicity a randomized controlled trial
PLOS Neglected Tropical Diseases, 2010Co-Authors: Joseph D Turner, Nicholas Tendongfor, Mathias E Esum, Kelly L Johnston, Stuart R Langley, Louise Ford, Brian Faragher, Sabine Specht, Sabine Mand, Achim HoeraufAbstract:BACKGROUND: The risk of severe adverse events following treatment of onchocerciasis with ivermectin in areas co-endemic with loiasis currently compromises the development of control programmes and the treatment of co-infected individuals. We therefore assessed whether Doxycycline treatment could be used without subsequent ivermectin administration to effectively deliver sustained effects on Onchocerca volvulus microfilaridermia and adult viability. Furthermore we assessed the safety of Doxycycline treatment prior to ivermectin administration in a subset of onchocerciasis individuals co-infected with low to moderate intensities of Loa loa microfilaraemia. METHODS: A double-blind, randomized, field trial was conducted of 6 weeks of Doxycycline (200 mg/day) alone, Doxycycline in combination with ivermectin (150 microg/kg) at +4 months or placebo matching Doxycycline + ivermectin at +4 months in 150 individuals infected with Onchocerca volvulus. A further 22 individuals infected with O. volvulus and low to moderate intensities of Loa loa infection were administered with a course of 6 weeks Doxycycline with ivermectin at +4 months. Treatment efficacy was determined at 4, 12 and 21 months after the start of Doxycycline treatment together with the frequency and severity of adverse events. RESULTS: One hundred and four (60.5%) participants completed all treatment allocations and follow up assessments over the 21-month trial period. At 12 months, Doxycycline/ivermectin treated individuals had lower levels of microfilaridermia and higher frequency of amicrofilaridermia compared with ivermectin or Doxycycline only groups. At 21 months, microfilaridermia in Doxycycline/ivermectin and Doxycycline only groups was significantly reduced compared to the ivermectin only group. 89% of the Doxycycline/ivermectin group and 67% of the Doxycycline only group were amicrofilaridermic, compared with 21% in the ivermectin only group. O. volvulus from Doxycycline groups were depleted of Wolbachia and all embryonic stages in utero. Notably, the viability of female adult worms was significantly reduced in Doxycycline treated groups and the macrofilaricidal and sterilising activity was unaffected by the addition of ivermectin. Treatment with Doxycycline was well tolerated and the incidence of adverse event to Doxycycline or ivermectin did not significantly deviate between treatment groups. CONCLUSIONS: A six-week course of Doxycycline delivers macrofilaricidal and sterilizing activities, which is not dependent upon co-administration of ivermectin. Doxycycline is well tolerated in patients co-infected with moderate intensities of L. loa microfilariae. Therefore, further trials are warranted to assess the safety and efficacy of Doxycycline-based interventions to treat onchocerciasis in individuals at risk of serious adverse reactions to standard treatments due to the co-occurrence of high intensities of L. loa parasitaemias. The development of an anti-wolbachial treatment regime compatible with MDA control programmes could offer an alternative to the control of onchocerciasis in areas of co-endemicity with loiasis and at risk of severe adverse reactions to ivermectin.
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wolbachia endobacteria depletion by Doxycycline as antifilarial therapy has macrofilaricidal activity in onchocerciasis a randomized placebo controlled study
Medical Microbiology and Immunology, 2008Co-Authors: Achim Hoerauf, Sabine Specht, Sabine Mand, Alexander Yaw Debrah, Yeboah Marfodebrekyei, Rolf Fimmers, Kenneth Pfarr, Marcelle Buttner, Peter Konadu, Claudio BandiAbstract:In a randomized, placebo-controlled trial in Ghana, 67 onchocerciasis patients received 200-mg/day Doxycycline for 4–6 weeks, followed by ivermectin (IVM) after 6 months. After 6–27 months, efficacy was evaluated by onchocercoma histology, PCR and microfilariae determination. Administration of Doxycycline resulted in endobacteria depletion and female worm sterilization. The 6-week treatment was macrofilaricidal, with >60% of the female worms found dead, despite the presence of new, Wolbachia-containing worms acquired after the administration of Doxycycline. Doxycycline may be developed as second-line drug for onchocerciasis, to be administered in areas without transmission, in foci with IVM resistance and in areas with Loa co-infections.
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macrofilaricidal effect of 4 weeks of treatment with Doxycycline on wuchereria bancrofti
Tropical Medicine & International Health, 2007Co-Authors: Sabine Mand, Alexander Yaw Debrah, Linda Batsa, Yeboah Marfodebrekyei, Kenneth Pfarr, Ohene Adjei, Dietrich W Buttner, Marcelle Buttner, Achim HoeraufAbstract:Summary Objective To evaluate the efficacy of Doxycycline as a macrofilaricidal agent against Wuchereria bancrofti. Method In the Western Region of Ghana, 18 patients infected with W. bancrofti were recruited and treated with 200 mg Doxycycline per day for 4 weeks. Seven untreated patients served as controls. Four months after Doxycycline treatment, all patients received 150 μg/kg ivermectin. Patients were monitored for Wolbachia and microfilaria loads, antigenaemia and filarial dance sign (FDS). Results Four months after Doxycycline treatment, cases had a significantly lower Wolbachia load than controls; and 24 months after treatment, microfilaraemia, antigenaemia and frequency of FDS were significantly lower in cases than controls. Most importantly, 4 weeks of Doxycycline killed 80% of macrofilariae, which is comparable with the results of a 6-week regimen. Circulating filarial antigenaemia and FDS were strongly correlated. Conclusion A 4-week regimen of Doxycycline seems sufficient to kill adult W. bancrofti and could be advantageous for the treatment of individual patients, e.g. in outpatient clinics. Activite macrofilaricide de la Doxycycline apres 4 semaines de traitement du Wuchereria bancrofti Objectif: Evaluer l’efficacite de la Doxycycline comme agent macrofilaricide contre Wuchereria bancrofti. Methode: Dans la region ouest du Ghana, 18 patients atteints du W. bancrofti ont ete recrutes et traites avec la Doxycycline a 200 mg par jour pendant quatre semaines et sept patients non traites ont servis de controles. Quatre mois apres le traitement a la Doxycycline, tous les patients ont recu 150 mg/kg d’ivermectine. Les patients ont ete suivis pour les taux de Wolbachia et de microfilaire, l’antigenemie et le signe de la danse filariale (FDS). Resultats: Quatre mois apres le traitement a la Doxycycline, les cas avaient un taux de Wolbachia significativement plus faible que les controles et 24 mois apres le traitement, la microfilaremie, l’antigenemie et la frequence du FDS etaient sensiblement plus faibles chez les cas que chez les controles. De facon plus importante, quatre semaines de Doxycycline avaient comme consequence un effet macrofilaricide de 80%, ce qui est comparable aux resultats d’un regime de six semaines. L’antigenemie filariale circulante et le FDS etaient fortement associes. Conclusion: Un regime de quatre semaines de Doxycycline semble suffisant pour obtenir une activite macrofilaricide sur W. bancrofti et pourrait etre avantageux dans le traitement individuel des patients, par exemple dans des cliniques de patients ambulants. Actividad macrofilaricida despues de 4 semanas del tratamiento con doxyciclina de Wuchereria bancrofti Objetivo: Evaluar la eficacia de la doxiciclina como agente macrofilaricida frente a Wuchereria bancrofti. Metodo: En la region de Ghana occidental, se reclutaron 18 pacientes infectados con W. bancrofti y fueron tratados con 200 mg de doxiciclina por dia durante cuatro semanas. Siete pacientes no tratados sirvieron como controles. Cuatro meses despues del tratamiento con doxiciclina, todos los pacientes recibieron 150μg/kg de ivermectina. Los pacientes fueron monitorizados para cargas de Wolbachia y microfilaria, antigenemia, y signos de movimiento filarial (filarial dance signs - FDS). Resultados: Cuatro meses despues del tratamiento con doxiciclina, los casos tenian una carga de Wolbachia significativamente menor que los controles. Veinticuatro meses despues del tratamiento, la microfilaremia, antigenemia, y la frecuencia de FDS eran significativamente menores en los casos que en los controles. Mas importante aun, cuatro semanas de doxiciclina tuvieron un efecto macrofilaricida del 80%, lo cual es comparable con los resultados de un regimen de seis semanas. La antigenemia filarial circulante (AFC) y FDS estaban altamente correlacionadas. Conclusion: Un regimen de cuatro semanas de doxiciclina parece ser suficiente para alcanzar una actividad macrofilaricida frente a W. bancrofti, y podria ser ventajoso para el tratamiento de pacientes individuales, por ejemplo en consulta externa.
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macrofilaricidal activity after Doxycycline treatment of wuchereria bancrofti a double blind randomised placebo controlled trial
The Lancet, 2005Co-Authors: Mark J Taylor, Joseph D Turner, Sabine Mand, Achim Hoerauf, Williams H Makunde, Helen F McgarryAbstract:Summary Background Wolbachia endosymbionts of filarial nematodes are vital for larval development and adult-worm fertility and viability. This essential dependency on the bacterium for survival of the parasites has provided a new approach to treat filariasis with antibiotics. We used this strategy to investigate the effects of Doxycycline treatment on the major cause of lymphatic filariasis, Wuchereria bancrofti . Methods We undertook a double-blind, randomised, placebo-controlled field trial of Doxycycline (200 mg per day) for 8 weeks in 72 individuals infected with W bancrofti from Kimang'a village, Pangani, Tanzania. Participants were randomly assigned by block randomisation to receive capsules of Doxycycline (n=34) or placebo (n=38). We assessed treatment efficacy by monitoring microfilaraemia, antigenaemia, and ultrasound detection of adult worms. Follow-up assessments were done at 5, 8, 11, and 14 months after the start of treatment. Analysis was per protocol. Findings One person from the Doxycycline group died from HIV infection. Five (Doxycycline) and 11 (placebo) individuals were absent at the time of ultrasound analysis. Doxycycline treatment almost completely eliminated microfilaraemia at 8–14 months' follow-up (for all timepoints p Interpretation An 8-week course of Doxycycline is a safe and well-tolerated treatment for lymphatic filariasis with significant activity against adult worms and microfilaraemia.
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Doxycycline in the treatment of human onchocerciasis kinetics of wolbachia endobacteria reduction and of inhibition of embryogenesis in female onchocerca worms
Microbes and Infection, 2003Co-Authors: Achim Hoerauf, Sabine Mand, Yeboah Marfodebrekyei, Mark J Taylor, Ohene Adjei, Marcelle Buttner, Lars Volkmann, Dietrich W ButtnerAbstract:Recently, experts have warned that mass treatment with ivermectin alone may not interrupt the transmission of Onchocerca. Hence, additional drugs are needed, such as antibiotics acting on symbiotic endobacteria of the filariae, the causative agents of onchocerciasis. Based on animal experiments, human onchocerciasis was treated with Doxycycline, and preliminary observations published in 2001 in The Lancet showed sterility in female worms by depletion and marked reduction in symbiotic Wolbachia endobacteria from the filariae. Here, a detailed kinetic analysis of the features of the worms, following administration or not of Doxycycline to the patients is reported. Sixty-three onchocerciasis patients in Ghana were treated with 100 mg Doxycycline daily for 6 weeks and 2 or 6 months later with ivermectin. Onchocercomas were extirpated 2, 6, 11 and 18 months after the onset of treatment and the filariae were examined by immunohistology and PCR. The analysis showed: (i) progressive depletion of Wolbachia from adult worms and microfilariae by Doxycycline over a period of 6 months; (ii) inhibition of embryogenesis by Doxycycline after 6 months with respect to all embryo stages followed by decline in microfilariae after 11 months; (iii) reduction in spermatozoa in the female genital tract by Doxycycline, whereas spermiogenesis was only partly reduced after 11 and 18 months; (iv) no relevant macro- or microfilaricidal activity; (v) depletion/marked reduction in endobacteria and inhibition of embryogenesis were sustained until 18 months after Doxycycline and 12 months after co-administration of ivermectin; (vi) no severe adverse side effects were seen. Due to its long-lasting inhibition of embryogenesis, Doxycycline presents an additional strategy for the treatment of onchocerciasis and control of Onchocerca microfilariae transmission. Extension of the existing registration will not require much time or high cost. Treatment of individual patients can be considered immediately.
Sabine Mand - One of the best experts on this subject based on the ideXlab platform.
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Doxycycline improves filarial lymphedema independent of active filarial infection a randomized controlled trial
Clinical Infectious Diseases, 2012Co-Authors: Sabine Mand, Sabine Specht, Alexander Yaw Debrah, Ute Klarmann, Linda Batsa, Yeboah Marfodebrekyei, Alexander Kwarteng, Aurea Beldadomene, Rolf Fimmers, Mark J TaylorAbstract:BACKGROUND The aim of this study was to determine whether improvement of filarial lymphedema (LE) by Doxycycline is restricted to patients with ongoing infection (positive for circulating filarial antigen [CFA]), or whether the majority of CFA-negative patients with LE would also show a reduction in LE severity. METHODS One hundred sixty-two Ghanaian participants with LE stage 1-5 (Dreyer) were randomized blockwise into 2 groups (CFA positive or negative) and allocated to 3 treatment arms of 6 weeks: (1) amoxicillin (1000 mg/d), (2) Doxycycline (200 mg/d), or (3) placebo matching Doxycycline. All groups received standard hygiene morbidity management. The primary outcome was reduction of LE stages. Secondary outcomes included frequency of acute attacks and ultrasonographic assessment of skin thickness at the ankles. Parameters were assessed before treatment and after 3, 12, and 24 months. RESULTS Doxycycline-treated patients with LE stage 2-3 showed significant reductions in LE severity after 12 and 24 months, regardless of CFA status. Improvement was observed in 43.9% of Doxycycline-treated patients, compared with only 3.2% and 5.6% in the amoxicillin and placebo arms, respectively. Skin thickness was correlated with LE stage improvement. Both Doxycycline and amoxicillin were able to reduce acute dermatolymphangioadenitis attacks. CONCLUSIONS Doxycycline treatment improves mild to moderate LE independent of ongoing infection. This finding expands the benefits of Doxycycline to the entire population of patients suffering from LE. Patients with LE stage 1-3 should benefit from a 6-week course of Doxycycline every other year or yearly, which should be considered as an improved tool to manage morbidity in filarial LE.
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macrofilaricidal activity after Doxycycline only treatment of onchocerca volvulus in an area of loa loa co endemicity a randomized controlled trial
PLOS Neglected Tropical Diseases, 2010Co-Authors: Joseph D Turner, Nicholas Tendongfor, Mathias E Esum, Kelly L Johnston, Stuart R Langley, Louise Ford, Brian Faragher, Sabine Specht, Sabine Mand, Achim HoeraufAbstract:BACKGROUND: The risk of severe adverse events following treatment of onchocerciasis with ivermectin in areas co-endemic with loiasis currently compromises the development of control programmes and the treatment of co-infected individuals. We therefore assessed whether Doxycycline treatment could be used without subsequent ivermectin administration to effectively deliver sustained effects on Onchocerca volvulus microfilaridermia and adult viability. Furthermore we assessed the safety of Doxycycline treatment prior to ivermectin administration in a subset of onchocerciasis individuals co-infected with low to moderate intensities of Loa loa microfilaraemia. METHODS: A double-blind, randomized, field trial was conducted of 6 weeks of Doxycycline (200 mg/day) alone, Doxycycline in combination with ivermectin (150 microg/kg) at +4 months or placebo matching Doxycycline + ivermectin at +4 months in 150 individuals infected with Onchocerca volvulus. A further 22 individuals infected with O. volvulus and low to moderate intensities of Loa loa infection were administered with a course of 6 weeks Doxycycline with ivermectin at +4 months. Treatment efficacy was determined at 4, 12 and 21 months after the start of Doxycycline treatment together with the frequency and severity of adverse events. RESULTS: One hundred and four (60.5%) participants completed all treatment allocations and follow up assessments over the 21-month trial period. At 12 months, Doxycycline/ivermectin treated individuals had lower levels of microfilaridermia and higher frequency of amicrofilaridermia compared with ivermectin or Doxycycline only groups. At 21 months, microfilaridermia in Doxycycline/ivermectin and Doxycycline only groups was significantly reduced compared to the ivermectin only group. 89% of the Doxycycline/ivermectin group and 67% of the Doxycycline only group were amicrofilaridermic, compared with 21% in the ivermectin only group. O. volvulus from Doxycycline groups were depleted of Wolbachia and all embryonic stages in utero. Notably, the viability of female adult worms was significantly reduced in Doxycycline treated groups and the macrofilaricidal and sterilising activity was unaffected by the addition of ivermectin. Treatment with Doxycycline was well tolerated and the incidence of adverse event to Doxycycline or ivermectin did not significantly deviate between treatment groups. CONCLUSIONS: A six-week course of Doxycycline delivers macrofilaricidal and sterilizing activities, which is not dependent upon co-administration of ivermectin. Doxycycline is well tolerated in patients co-infected with moderate intensities of L. loa microfilariae. Therefore, further trials are warranted to assess the safety and efficacy of Doxycycline-based interventions to treat onchocerciasis in individuals at risk of serious adverse reactions to standard treatments due to the co-occurrence of high intensities of L. loa parasitaemias. The development of an anti-wolbachial treatment regime compatible with MDA control programmes could offer an alternative to the control of onchocerciasis in areas of co-endemicity with loiasis and at risk of severe adverse reactions to ivermectin.
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wolbachia endobacteria depletion by Doxycycline as antifilarial therapy has macrofilaricidal activity in onchocerciasis a randomized placebo controlled study
Medical Microbiology and Immunology, 2008Co-Authors: Achim Hoerauf, Sabine Specht, Sabine Mand, Alexander Yaw Debrah, Yeboah Marfodebrekyei, Rolf Fimmers, Kenneth Pfarr, Marcelle Buttner, Peter Konadu, Claudio BandiAbstract:In a randomized, placebo-controlled trial in Ghana, 67 onchocerciasis patients received 200-mg/day Doxycycline for 4–6 weeks, followed by ivermectin (IVM) after 6 months. After 6–27 months, efficacy was evaluated by onchocercoma histology, PCR and microfilariae determination. Administration of Doxycycline resulted in endobacteria depletion and female worm sterilization. The 6-week treatment was macrofilaricidal, with >60% of the female worms found dead, despite the presence of new, Wolbachia-containing worms acquired after the administration of Doxycycline. Doxycycline may be developed as second-line drug for onchocerciasis, to be administered in areas without transmission, in foci with IVM resistance and in areas with Loa co-infections.
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macrofilaricidal effect of 4 weeks of treatment with Doxycycline on wuchereria bancrofti
Tropical Medicine & International Health, 2007Co-Authors: Sabine Mand, Alexander Yaw Debrah, Linda Batsa, Yeboah Marfodebrekyei, Kenneth Pfarr, Ohene Adjei, Dietrich W Buttner, Marcelle Buttner, Achim HoeraufAbstract:Summary Objective To evaluate the efficacy of Doxycycline as a macrofilaricidal agent against Wuchereria bancrofti. Method In the Western Region of Ghana, 18 patients infected with W. bancrofti were recruited and treated with 200 mg Doxycycline per day for 4 weeks. Seven untreated patients served as controls. Four months after Doxycycline treatment, all patients received 150 μg/kg ivermectin. Patients were monitored for Wolbachia and microfilaria loads, antigenaemia and filarial dance sign (FDS). Results Four months after Doxycycline treatment, cases had a significantly lower Wolbachia load than controls; and 24 months after treatment, microfilaraemia, antigenaemia and frequency of FDS were significantly lower in cases than controls. Most importantly, 4 weeks of Doxycycline killed 80% of macrofilariae, which is comparable with the results of a 6-week regimen. Circulating filarial antigenaemia and FDS were strongly correlated. Conclusion A 4-week regimen of Doxycycline seems sufficient to kill adult W. bancrofti and could be advantageous for the treatment of individual patients, e.g. in outpatient clinics. Activite macrofilaricide de la Doxycycline apres 4 semaines de traitement du Wuchereria bancrofti Objectif: Evaluer l’efficacite de la Doxycycline comme agent macrofilaricide contre Wuchereria bancrofti. Methode: Dans la region ouest du Ghana, 18 patients atteints du W. bancrofti ont ete recrutes et traites avec la Doxycycline a 200 mg par jour pendant quatre semaines et sept patients non traites ont servis de controles. Quatre mois apres le traitement a la Doxycycline, tous les patients ont recu 150 mg/kg d’ivermectine. Les patients ont ete suivis pour les taux de Wolbachia et de microfilaire, l’antigenemie et le signe de la danse filariale (FDS). Resultats: Quatre mois apres le traitement a la Doxycycline, les cas avaient un taux de Wolbachia significativement plus faible que les controles et 24 mois apres le traitement, la microfilaremie, l’antigenemie et la frequence du FDS etaient sensiblement plus faibles chez les cas que chez les controles. De facon plus importante, quatre semaines de Doxycycline avaient comme consequence un effet macrofilaricide de 80%, ce qui est comparable aux resultats d’un regime de six semaines. L’antigenemie filariale circulante et le FDS etaient fortement associes. Conclusion: Un regime de quatre semaines de Doxycycline semble suffisant pour obtenir une activite macrofilaricide sur W. bancrofti et pourrait etre avantageux dans le traitement individuel des patients, par exemple dans des cliniques de patients ambulants. Actividad macrofilaricida despues de 4 semanas del tratamiento con doxyciclina de Wuchereria bancrofti Objetivo: Evaluar la eficacia de la doxiciclina como agente macrofilaricida frente a Wuchereria bancrofti. Metodo: En la region de Ghana occidental, se reclutaron 18 pacientes infectados con W. bancrofti y fueron tratados con 200 mg de doxiciclina por dia durante cuatro semanas. Siete pacientes no tratados sirvieron como controles. Cuatro meses despues del tratamiento con doxiciclina, todos los pacientes recibieron 150μg/kg de ivermectina. Los pacientes fueron monitorizados para cargas de Wolbachia y microfilaria, antigenemia, y signos de movimiento filarial (filarial dance signs - FDS). Resultados: Cuatro meses despues del tratamiento con doxiciclina, los casos tenian una carga de Wolbachia significativamente menor que los controles. Veinticuatro meses despues del tratamiento, la microfilaremia, antigenemia, y la frecuencia de FDS eran significativamente menores en los casos que en los controles. Mas importante aun, cuatro semanas de doxiciclina tuvieron un efecto macrofilaricida del 80%, lo cual es comparable con los resultados de un regimen de seis semanas. La antigenemia filarial circulante (AFC) y FDS estaban altamente correlacionadas. Conclusion: Un regimen de cuatro semanas de doxiciclina parece ser suficiente para alcanzar una actividad macrofilaricida frente a W. bancrofti, y podria ser ventajoso para el tratamiento de pacientes individuales, por ejemplo en consulta externa.
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macrofilaricidal activity after Doxycycline treatment of wuchereria bancrofti a double blind randomised placebo controlled trial
The Lancet, 2005Co-Authors: Mark J Taylor, Joseph D Turner, Sabine Mand, Achim Hoerauf, Williams H Makunde, Helen F McgarryAbstract:Summary Background Wolbachia endosymbionts of filarial nematodes are vital for larval development and adult-worm fertility and viability. This essential dependency on the bacterium for survival of the parasites has provided a new approach to treat filariasis with antibiotics. We used this strategy to investigate the effects of Doxycycline treatment on the major cause of lymphatic filariasis, Wuchereria bancrofti . Methods We undertook a double-blind, randomised, placebo-controlled field trial of Doxycycline (200 mg per day) for 8 weeks in 72 individuals infected with W bancrofti from Kimang'a village, Pangani, Tanzania. Participants were randomly assigned by block randomisation to receive capsules of Doxycycline (n=34) or placebo (n=38). We assessed treatment efficacy by monitoring microfilaraemia, antigenaemia, and ultrasound detection of adult worms. Follow-up assessments were done at 5, 8, 11, and 14 months after the start of treatment. Analysis was per protocol. Findings One person from the Doxycycline group died from HIV infection. Five (Doxycycline) and 11 (placebo) individuals were absent at the time of ultrasound analysis. Doxycycline treatment almost completely eliminated microfilaraemia at 8–14 months' follow-up (for all timepoints p Interpretation An 8-week course of Doxycycline is a safe and well-tolerated treatment for lymphatic filariasis with significant activity against adult worms and microfilaraemia.
Alexander Yaw Debrah - One of the best experts on this subject based on the ideXlab platform.
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Doxycycline improves filarial lymphedema independent of active filarial infection a randomized controlled trial
Clinical Infectious Diseases, 2012Co-Authors: Sabine Mand, Sabine Specht, Alexander Yaw Debrah, Ute Klarmann, Linda Batsa, Yeboah Marfodebrekyei, Alexander Kwarteng, Aurea Beldadomene, Rolf Fimmers, Mark J TaylorAbstract:BACKGROUND The aim of this study was to determine whether improvement of filarial lymphedema (LE) by Doxycycline is restricted to patients with ongoing infection (positive for circulating filarial antigen [CFA]), or whether the majority of CFA-negative patients with LE would also show a reduction in LE severity. METHODS One hundred sixty-two Ghanaian participants with LE stage 1-5 (Dreyer) were randomized blockwise into 2 groups (CFA positive or negative) and allocated to 3 treatment arms of 6 weeks: (1) amoxicillin (1000 mg/d), (2) Doxycycline (200 mg/d), or (3) placebo matching Doxycycline. All groups received standard hygiene morbidity management. The primary outcome was reduction of LE stages. Secondary outcomes included frequency of acute attacks and ultrasonographic assessment of skin thickness at the ankles. Parameters were assessed before treatment and after 3, 12, and 24 months. RESULTS Doxycycline-treated patients with LE stage 2-3 showed significant reductions in LE severity after 12 and 24 months, regardless of CFA status. Improvement was observed in 43.9% of Doxycycline-treated patients, compared with only 3.2% and 5.6% in the amoxicillin and placebo arms, respectively. Skin thickness was correlated with LE stage improvement. Both Doxycycline and amoxicillin were able to reduce acute dermatolymphangioadenitis attacks. CONCLUSIONS Doxycycline treatment improves mild to moderate LE independent of ongoing infection. This finding expands the benefits of Doxycycline to the entire population of patients suffering from LE. Patients with LE stage 1-3 should benefit from a 6-week course of Doxycycline every other year or yearly, which should be considered as an improved tool to manage morbidity in filarial LE.
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wolbachia endobacteria depletion by Doxycycline as antifilarial therapy has macrofilaricidal activity in onchocerciasis a randomized placebo controlled study
Medical Microbiology and Immunology, 2008Co-Authors: Achim Hoerauf, Sabine Specht, Sabine Mand, Alexander Yaw Debrah, Yeboah Marfodebrekyei, Rolf Fimmers, Kenneth Pfarr, Marcelle Buttner, Peter Konadu, Claudio BandiAbstract:In a randomized, placebo-controlled trial in Ghana, 67 onchocerciasis patients received 200-mg/day Doxycycline for 4–6 weeks, followed by ivermectin (IVM) after 6 months. After 6–27 months, efficacy was evaluated by onchocercoma histology, PCR and microfilariae determination. Administration of Doxycycline resulted in endobacteria depletion and female worm sterilization. The 6-week treatment was macrofilaricidal, with >60% of the female worms found dead, despite the presence of new, Wolbachia-containing worms acquired after the administration of Doxycycline. Doxycycline may be developed as second-line drug for onchocerciasis, to be administered in areas without transmission, in foci with IVM resistance and in areas with Loa co-infections.
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macrofilaricidal effect of 4 weeks of treatment with Doxycycline on wuchereria bancrofti
Tropical Medicine & International Health, 2007Co-Authors: Sabine Mand, Alexander Yaw Debrah, Linda Batsa, Yeboah Marfodebrekyei, Kenneth Pfarr, Ohene Adjei, Dietrich W Buttner, Marcelle Buttner, Achim HoeraufAbstract:Summary Objective To evaluate the efficacy of Doxycycline as a macrofilaricidal agent against Wuchereria bancrofti. Method In the Western Region of Ghana, 18 patients infected with W. bancrofti were recruited and treated with 200 mg Doxycycline per day for 4 weeks. Seven untreated patients served as controls. Four months after Doxycycline treatment, all patients received 150 μg/kg ivermectin. Patients were monitored for Wolbachia and microfilaria loads, antigenaemia and filarial dance sign (FDS). Results Four months after Doxycycline treatment, cases had a significantly lower Wolbachia load than controls; and 24 months after treatment, microfilaraemia, antigenaemia and frequency of FDS were significantly lower in cases than controls. Most importantly, 4 weeks of Doxycycline killed 80% of macrofilariae, which is comparable with the results of a 6-week regimen. Circulating filarial antigenaemia and FDS were strongly correlated. Conclusion A 4-week regimen of Doxycycline seems sufficient to kill adult W. bancrofti and could be advantageous for the treatment of individual patients, e.g. in outpatient clinics. Activite macrofilaricide de la Doxycycline apres 4 semaines de traitement du Wuchereria bancrofti Objectif: Evaluer l’efficacite de la Doxycycline comme agent macrofilaricide contre Wuchereria bancrofti. Methode: Dans la region ouest du Ghana, 18 patients atteints du W. bancrofti ont ete recrutes et traites avec la Doxycycline a 200 mg par jour pendant quatre semaines et sept patients non traites ont servis de controles. Quatre mois apres le traitement a la Doxycycline, tous les patients ont recu 150 mg/kg d’ivermectine. Les patients ont ete suivis pour les taux de Wolbachia et de microfilaire, l’antigenemie et le signe de la danse filariale (FDS). Resultats: Quatre mois apres le traitement a la Doxycycline, les cas avaient un taux de Wolbachia significativement plus faible que les controles et 24 mois apres le traitement, la microfilaremie, l’antigenemie et la frequence du FDS etaient sensiblement plus faibles chez les cas que chez les controles. De facon plus importante, quatre semaines de Doxycycline avaient comme consequence un effet macrofilaricide de 80%, ce qui est comparable aux resultats d’un regime de six semaines. L’antigenemie filariale circulante et le FDS etaient fortement associes. Conclusion: Un regime de quatre semaines de Doxycycline semble suffisant pour obtenir une activite macrofilaricide sur W. bancrofti et pourrait etre avantageux dans le traitement individuel des patients, par exemple dans des cliniques de patients ambulants. Actividad macrofilaricida despues de 4 semanas del tratamiento con doxyciclina de Wuchereria bancrofti Objetivo: Evaluar la eficacia de la doxiciclina como agente macrofilaricida frente a Wuchereria bancrofti. Metodo: En la region de Ghana occidental, se reclutaron 18 pacientes infectados con W. bancrofti y fueron tratados con 200 mg de doxiciclina por dia durante cuatro semanas. Siete pacientes no tratados sirvieron como controles. Cuatro meses despues del tratamiento con doxiciclina, todos los pacientes recibieron 150μg/kg de ivermectina. Los pacientes fueron monitorizados para cargas de Wolbachia y microfilaria, antigenemia, y signos de movimiento filarial (filarial dance signs - FDS). Resultados: Cuatro meses despues del tratamiento con doxiciclina, los casos tenian una carga de Wolbachia significativamente menor que los controles. Veinticuatro meses despues del tratamiento, la microfilaremia, antigenemia, y la frecuencia de FDS eran significativamente menores en los casos que en los controles. Mas importante aun, cuatro semanas de doxiciclina tuvieron un efecto macrofilaricida del 80%, lo cual es comparable con los resultados de un regimen de seis semanas. La antigenemia filarial circulante (AFC) y FDS estaban altamente correlacionadas. Conclusion: Un regimen de cuatro semanas de doxiciclina parece ser suficiente para alcanzar una actividad macrofilaricida frente a W. bancrofti, y podria ser ventajoso para el tratamiento de pacientes individuales, por ejemplo en consulta externa.
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Doxycycline as a novel strategy against bancroftian filariasis depletion of wolbachia endosymbionts from wuchereria bancrofti and stop of microfilaria production
Medical Microbiology and Immunology, 2003Co-Authors: Achim Hoerauf, Sabine Mand, Alexander Yaw Debrah, Yeboah Marfodebrekyei, Kerstin Fischer, Thomas Kruppa, Kenneth Pfarr, Ohene Adjei, Dietrich W ButtnerAbstract:Chemotherapy of onchocerciasis by Doxycycline, which targets symbiotic Wolbachia endobacteria, has been shown to result in a long-term sterility of adult female worms and corresponding absence of microfilariae. It represents an additional chemotherapeutic approach. The aim of this study was to determine whether a similar regimen would also show efficacy against Wuchereria bancrofti. Ghanaian individuals (n=93) with lymphatic filariasis and a minimum microfilaremia of 40 microfilariae/ml were included in a treatment study consisting of four arms: (1) Doxycycline 200 mg/day for 6 weeks; (2) Doxycycline as in (1), followed by a single dose of ivermectin after 4 months; (3) ivermectin only; or (4) no treatment during observation period of 1 year (ivermectin at the end of the study). Doxycycline treatment resulted in a 96% loss of Wolbachia, as determined by real time PCR from microfilariae. After 12 months, Doxycycline had led to a 99% reduction of microfilaremia when given alone, and to a complete amicrofilaremia together with ivermectin. In contrast, after ivermectin treatment alone a significant presence of microfilariae remained (9% compared to pretreatment), as known from other studies. This study shows that Doxycycline is also effective in depleting Wolbachia from W. bancrofti. It is likely that the mechanism of Doxycycline is similar to that in other filarial species, i.e., a predominant blockade of embryogenesis, leading to a decline of microfilariae according to their half-life. This could render Doxycycline treatment an additional tool for the treatment of microfilaria-associated diseases in bancroftian filariasis, such as tropical pulmonary eosinophilia and microfiluria.
Yeboah Marfodebrekyei - One of the best experts on this subject based on the ideXlab platform.
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Doxycycline improves filarial lymphedema independent of active filarial infection a randomized controlled trial
Clinical Infectious Diseases, 2012Co-Authors: Sabine Mand, Sabine Specht, Alexander Yaw Debrah, Ute Klarmann, Linda Batsa, Yeboah Marfodebrekyei, Alexander Kwarteng, Aurea Beldadomene, Rolf Fimmers, Mark J TaylorAbstract:BACKGROUND The aim of this study was to determine whether improvement of filarial lymphedema (LE) by Doxycycline is restricted to patients with ongoing infection (positive for circulating filarial antigen [CFA]), or whether the majority of CFA-negative patients with LE would also show a reduction in LE severity. METHODS One hundred sixty-two Ghanaian participants with LE stage 1-5 (Dreyer) were randomized blockwise into 2 groups (CFA positive or negative) and allocated to 3 treatment arms of 6 weeks: (1) amoxicillin (1000 mg/d), (2) Doxycycline (200 mg/d), or (3) placebo matching Doxycycline. All groups received standard hygiene morbidity management. The primary outcome was reduction of LE stages. Secondary outcomes included frequency of acute attacks and ultrasonographic assessment of skin thickness at the ankles. Parameters were assessed before treatment and after 3, 12, and 24 months. RESULTS Doxycycline-treated patients with LE stage 2-3 showed significant reductions in LE severity after 12 and 24 months, regardless of CFA status. Improvement was observed in 43.9% of Doxycycline-treated patients, compared with only 3.2% and 5.6% in the amoxicillin and placebo arms, respectively. Skin thickness was correlated with LE stage improvement. Both Doxycycline and amoxicillin were able to reduce acute dermatolymphangioadenitis attacks. CONCLUSIONS Doxycycline treatment improves mild to moderate LE independent of ongoing infection. This finding expands the benefits of Doxycycline to the entire population of patients suffering from LE. Patients with LE stage 1-3 should benefit from a 6-week course of Doxycycline every other year or yearly, which should be considered as an improved tool to manage morbidity in filarial LE.
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wolbachia endobacteria depletion by Doxycycline as antifilarial therapy has macrofilaricidal activity in onchocerciasis a randomized placebo controlled study
Medical Microbiology and Immunology, 2008Co-Authors: Achim Hoerauf, Sabine Specht, Sabine Mand, Alexander Yaw Debrah, Yeboah Marfodebrekyei, Rolf Fimmers, Kenneth Pfarr, Marcelle Buttner, Peter Konadu, Claudio BandiAbstract:In a randomized, placebo-controlled trial in Ghana, 67 onchocerciasis patients received 200-mg/day Doxycycline for 4–6 weeks, followed by ivermectin (IVM) after 6 months. After 6–27 months, efficacy was evaluated by onchocercoma histology, PCR and microfilariae determination. Administration of Doxycycline resulted in endobacteria depletion and female worm sterilization. The 6-week treatment was macrofilaricidal, with >60% of the female worms found dead, despite the presence of new, Wolbachia-containing worms acquired after the administration of Doxycycline. Doxycycline may be developed as second-line drug for onchocerciasis, to be administered in areas without transmission, in foci with IVM resistance and in areas with Loa co-infections.
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macrofilaricidal effect of 4 weeks of treatment with Doxycycline on wuchereria bancrofti
Tropical Medicine & International Health, 2007Co-Authors: Sabine Mand, Alexander Yaw Debrah, Linda Batsa, Yeboah Marfodebrekyei, Kenneth Pfarr, Ohene Adjei, Dietrich W Buttner, Marcelle Buttner, Achim HoeraufAbstract:Summary Objective To evaluate the efficacy of Doxycycline as a macrofilaricidal agent against Wuchereria bancrofti. Method In the Western Region of Ghana, 18 patients infected with W. bancrofti were recruited and treated with 200 mg Doxycycline per day for 4 weeks. Seven untreated patients served as controls. Four months after Doxycycline treatment, all patients received 150 μg/kg ivermectin. Patients were monitored for Wolbachia and microfilaria loads, antigenaemia and filarial dance sign (FDS). Results Four months after Doxycycline treatment, cases had a significantly lower Wolbachia load than controls; and 24 months after treatment, microfilaraemia, antigenaemia and frequency of FDS were significantly lower in cases than controls. Most importantly, 4 weeks of Doxycycline killed 80% of macrofilariae, which is comparable with the results of a 6-week regimen. Circulating filarial antigenaemia and FDS were strongly correlated. Conclusion A 4-week regimen of Doxycycline seems sufficient to kill adult W. bancrofti and could be advantageous for the treatment of individual patients, e.g. in outpatient clinics. Activite macrofilaricide de la Doxycycline apres 4 semaines de traitement du Wuchereria bancrofti Objectif: Evaluer l’efficacite de la Doxycycline comme agent macrofilaricide contre Wuchereria bancrofti. Methode: Dans la region ouest du Ghana, 18 patients atteints du W. bancrofti ont ete recrutes et traites avec la Doxycycline a 200 mg par jour pendant quatre semaines et sept patients non traites ont servis de controles. Quatre mois apres le traitement a la Doxycycline, tous les patients ont recu 150 mg/kg d’ivermectine. Les patients ont ete suivis pour les taux de Wolbachia et de microfilaire, l’antigenemie et le signe de la danse filariale (FDS). Resultats: Quatre mois apres le traitement a la Doxycycline, les cas avaient un taux de Wolbachia significativement plus faible que les controles et 24 mois apres le traitement, la microfilaremie, l’antigenemie et la frequence du FDS etaient sensiblement plus faibles chez les cas que chez les controles. De facon plus importante, quatre semaines de Doxycycline avaient comme consequence un effet macrofilaricide de 80%, ce qui est comparable aux resultats d’un regime de six semaines. L’antigenemie filariale circulante et le FDS etaient fortement associes. Conclusion: Un regime de quatre semaines de Doxycycline semble suffisant pour obtenir une activite macrofilaricide sur W. bancrofti et pourrait etre avantageux dans le traitement individuel des patients, par exemple dans des cliniques de patients ambulants. Actividad macrofilaricida despues de 4 semanas del tratamiento con doxyciclina de Wuchereria bancrofti Objetivo: Evaluar la eficacia de la doxiciclina como agente macrofilaricida frente a Wuchereria bancrofti. Metodo: En la region de Ghana occidental, se reclutaron 18 pacientes infectados con W. bancrofti y fueron tratados con 200 mg de doxiciclina por dia durante cuatro semanas. Siete pacientes no tratados sirvieron como controles. Cuatro meses despues del tratamiento con doxiciclina, todos los pacientes recibieron 150μg/kg de ivermectina. Los pacientes fueron monitorizados para cargas de Wolbachia y microfilaria, antigenemia, y signos de movimiento filarial (filarial dance signs - FDS). Resultados: Cuatro meses despues del tratamiento con doxiciclina, los casos tenian una carga de Wolbachia significativamente menor que los controles. Veinticuatro meses despues del tratamiento, la microfilaremia, antigenemia, y la frecuencia de FDS eran significativamente menores en los casos que en los controles. Mas importante aun, cuatro semanas de doxiciclina tuvieron un efecto macrofilaricida del 80%, lo cual es comparable con los resultados de un regimen de seis semanas. La antigenemia filarial circulante (AFC) y FDS estaban altamente correlacionadas. Conclusion: Un regimen de cuatro semanas de doxiciclina parece ser suficiente para alcanzar una actividad macrofilaricida frente a W. bancrofti, y podria ser ventajoso para el tratamiento de pacientes individuales, por ejemplo en consulta externa.
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Doxycycline in the treatment of human onchocerciasis kinetics of wolbachia endobacteria reduction and of inhibition of embryogenesis in female onchocerca worms
Microbes and Infection, 2003Co-Authors: Achim Hoerauf, Sabine Mand, Yeboah Marfodebrekyei, Mark J Taylor, Ohene Adjei, Marcelle Buttner, Lars Volkmann, Dietrich W ButtnerAbstract:Recently, experts have warned that mass treatment with ivermectin alone may not interrupt the transmission of Onchocerca. Hence, additional drugs are needed, such as antibiotics acting on symbiotic endobacteria of the filariae, the causative agents of onchocerciasis. Based on animal experiments, human onchocerciasis was treated with Doxycycline, and preliminary observations published in 2001 in The Lancet showed sterility in female worms by depletion and marked reduction in symbiotic Wolbachia endobacteria from the filariae. Here, a detailed kinetic analysis of the features of the worms, following administration or not of Doxycycline to the patients is reported. Sixty-three onchocerciasis patients in Ghana were treated with 100 mg Doxycycline daily for 6 weeks and 2 or 6 months later with ivermectin. Onchocercomas were extirpated 2, 6, 11 and 18 months after the onset of treatment and the filariae were examined by immunohistology and PCR. The analysis showed: (i) progressive depletion of Wolbachia from adult worms and microfilariae by Doxycycline over a period of 6 months; (ii) inhibition of embryogenesis by Doxycycline after 6 months with respect to all embryo stages followed by decline in microfilariae after 11 months; (iii) reduction in spermatozoa in the female genital tract by Doxycycline, whereas spermiogenesis was only partly reduced after 11 and 18 months; (iv) no relevant macro- or microfilaricidal activity; (v) depletion/marked reduction in endobacteria and inhibition of embryogenesis were sustained until 18 months after Doxycycline and 12 months after co-administration of ivermectin; (vi) no severe adverse side effects were seen. Due to its long-lasting inhibition of embryogenesis, Doxycycline presents an additional strategy for the treatment of onchocerciasis and control of Onchocerca microfilariae transmission. Extension of the existing registration will not require much time or high cost. Treatment of individual patients can be considered immediately.
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Doxycycline as a novel strategy against bancroftian filariasis depletion of wolbachia endosymbionts from wuchereria bancrofti and stop of microfilaria production
Medical Microbiology and Immunology, 2003Co-Authors: Achim Hoerauf, Sabine Mand, Alexander Yaw Debrah, Yeboah Marfodebrekyei, Kerstin Fischer, Thomas Kruppa, Kenneth Pfarr, Ohene Adjei, Dietrich W ButtnerAbstract:Chemotherapy of onchocerciasis by Doxycycline, which targets symbiotic Wolbachia endobacteria, has been shown to result in a long-term sterility of adult female worms and corresponding absence of microfilariae. It represents an additional chemotherapeutic approach. The aim of this study was to determine whether a similar regimen would also show efficacy against Wuchereria bancrofti. Ghanaian individuals (n=93) with lymphatic filariasis and a minimum microfilaremia of 40 microfilariae/ml were included in a treatment study consisting of four arms: (1) Doxycycline 200 mg/day for 6 weeks; (2) Doxycycline as in (1), followed by a single dose of ivermectin after 4 months; (3) ivermectin only; or (4) no treatment during observation period of 1 year (ivermectin at the end of the study). Doxycycline treatment resulted in a 96% loss of Wolbachia, as determined by real time PCR from microfilariae. After 12 months, Doxycycline had led to a 99% reduction of microfilaremia when given alone, and to a complete amicrofilaremia together with ivermectin. In contrast, after ivermectin treatment alone a significant presence of microfilariae remained (9% compared to pretreatment), as known from other studies. This study shows that Doxycycline is also effective in depleting Wolbachia from W. bancrofti. It is likely that the mechanism of Doxycycline is similar to that in other filarial species, i.e., a predominant blockade of embryogenesis, leading to a decline of microfilariae according to their half-life. This could render Doxycycline treatment an additional tool for the treatment of microfilaria-associated diseases in bancroftian filariasis, such as tropical pulmonary eosinophilia and microfiluria.
Ada W Y Chung - One of the best experts on this subject based on the ideXlab platform.
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effectiveness of combination of losartan potassium and Doxycycline versus single drug treatments in the secondary prevention of thoracic aortic aneurysm in marfan syndrome
The Journal of Thoracic and Cardiovascular Surgery, 2010Co-Authors: H Clarice H Yang, Cornelis Van Breemen, Elliott Chum, Ada W Y ChungAbstract:Objective Losartan potassium (INN losartan), an antihypertensive drug, has been shown to prevent thoracic aortic aneurysm in Marfan syndrome through the inhibition of transforming growth factor β. Recently we reported that Doxycycline, a nonspecific inhibitor of matrix metalloproteinases 2 and 9, normalized aortic vasomotor function and suppressed aneurysm growth. We hypothesized that a combination of losartan potassium and Doxycycline would offer better secondary prevention treatment than would single-drug therapy to manage thoracic aortic aneurysm. Methods A well-characterized mouse model of Marfan syndrome (Fbn1 C1039G/+ ) was used. At 4 months of age, when aneurysm had established, mice (n = 15/group) were given Doxycycline alone (0.24 g/L), losartan potassium alone (0.6 g/L), or combined (0.12-g/L Doxycycline and 0.3-g/L losartan potassium) in drinking water. Littermate Fbn1 +/+ mice served as control. Thoracic aortas at 6 and 9 months were studied. Results At 9 months, aortic diameter in untreated group was increased by 40% relative to control. Losartan potassium or Doxycycline reduced aortic diameter by 10% to 16% versus untreated aortas. Losartan potassium and Doxycycline combined completely prevented thoracic aortic aneurysm and improved elastic fiber organization, also downregulating matrix metalloproteinases 2 and 9 and transforming growth factor β and normalizing aortic contractile and relaxation functions to control values. Conclusions Neither losartan potassium nor Doxycycline alone completely restored vascular integrity and cell function when given during delayed treatment, indicating the importance of timed pharmacologic intervention. Combined, however, they synergistically offered better aneurysm-suppressing effects than did single-drug medication in the secondary prevention of thoracic aortic aneurysm.
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long term Doxycycline is more effective than atenolol to prevent thoracic aortic aneurysm in marfan syndrome through the inhibition of matrix metalloproteinase 2 and 9
Circulation Research, 2008Co-Authors: Ada W Y Chung, H Clarice H Yang, Marek W Radomski, Cornelis Van BreemenAbstract:β-Blockers, eg, atenolol, are the cornerstone therapy for thoracic aortic aneurysm (TAA) in patients with Marfan syndrome; however, continued aortic dilatation has been reported. We have demonstrated that matrix metalloproteinase (MMP)-2 and -9 were upregulated during progression of TAA in Marfan syndrome, accompanied with degenerated elastic fibers and vasomotor dysfunction. We hypothesized that Doxycycline, a nonspecific inhibitor of MMPs, would ameliorate TAA by attenuating elastic fiber degeneration and improving vasomotor function. A well-characterized mouse model of Marfan syndrome (Fbn1 C1039G/+ ) was used. Mice were untreated (n=40), given Doxycycline (0.24g/L, n=30), or given atenolol (0.5g/L, n=30) in drinking water at 6 weeks of age. The Fbn1 +/+ mice served as control (n=40). At 3, 6, and 9 months, aortic segments from the ascending, arch, and descending portions were used to obtain the “average” value of the whole thoracic aorta. TAA was prevented in the Doxycycline group, whereas mild aneurysm was evident in the atenolol group. Doxycycline improved elastic fiber integrity, normalized aortic stiffness, and prevented vessel weakening. The impairment of vasocontraction and endothelium-dependent relaxation in the untreated and atenolol groups were improved by Doxycycline. The upregulation of transforming growth factor-β in the Marfan aorta was suppressed by Doxycycline. Doxycycline augmented expression ratios of tissue inhibitors of MMP to MMPs. Intraperitoneally injected neutralizing antibodies against MMP-2 and -9 yielded similar effects to Doxycycline. We concluded that long-term treatment with Doxycycline, through the inhibition of MMP-2 and -9, is more effective than atenolol in preventing TAA in Marfan syndrome by preserving elastic fiber integrity, normalizing vasomotor function, and reducing transforming growth factor-β activation.
