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Doxycycline as a novel strategy against bancroftian filariasis-depletion of Wolbachia endosymbionts from Wuchereria bancrofti and stop of microfilaria production.

Identifieur interne : 000D12 ( Ncbi/Checkpoint ); précédent : 000D11; suivant : 000D13

Doxycycline as a novel strategy against bancroftian filariasis-depletion of Wolbachia endosymbionts from Wuchereria bancrofti and stop of microfilaria production.

Auteurs : Achim Hoerauf [Allemagne] ; Sabine Mand ; Kerstin Fischer ; Thomas Kruppa ; Yeboah Marfo-Debrekyei ; Alexander Yaw Debrah ; Kenneth M. Pfarr ; Ohene Adjei ; Dietrich W. Büttner

Source :

RBID : pubmed:12684759

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English descriptors

Abstract

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.

DOI: 10.1007/s00430-002-0174-6
PubMed: 12684759


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pubmed:12684759

Le document en format XML

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<term>Adult</term>
<term>Animals</term>
<term>Anti-Bacterial Agents (administration & dosage)</term>
<term>Anti-Bacterial Agents (pharmacology)</term>
<term>Anti-Bacterial Agents (therapeutic use)</term>
<term>Doxycycline (administration & dosage)</term>
<term>Doxycycline (pharmacology)</term>
<term>Doxycycline (therapeutic use)</term>
<term>Elephantiasis, Filarial (drug therapy)</term>
<term>Elephantiasis, Filarial (parasitology)</term>
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<term>Filaricides (administration & dosage)</term>
<term>Filaricides (pharmacology)</term>
<term>Filaricides (therapeutic use)</term>
<term>Ghana</term>
<term>Humans</term>
<term>Ivermectin (administration & dosage)</term>
<term>Ivermectin (pharmacology)</term>
<term>Ivermectin (therapeutic use)</term>
<term>Male</term>
<term>Microfilariae (drug effects)</term>
<term>Middle Aged</term>
<term>Parasitemia (drug therapy)</term>
<term>Symbiosis</term>
<term>Wolbachia (drug effects)</term>
<term>Wolbachia (growth & development)</term>
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<term>Adolescent</term>
<term>Adulte</term>
<term>Adulte d'âge moyen</term>
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<term>Antibactériens (administration et posologie)</term>
<term>Antibactériens (pharmacologie)</term>
<term>Antibactériens (usage thérapeutique)</term>
<term>Doxycycline (administration et posologie)</term>
<term>Doxycycline (pharmacologie)</term>
<term>Doxycycline (usage thérapeutique)</term>
<term>Femelle</term>
<term>Filaricides (administration et posologie)</term>
<term>Filaricides (pharmacologie)</term>
<term>Filaricides (usage thérapeutique)</term>
<term>Filariose lymphatique (parasitologie)</term>
<term>Filariose lymphatique (traitement médicamenteux)</term>
<term>Ghana</term>
<term>Humains</term>
<term>Ivermectine (administration et posologie)</term>
<term>Ivermectine (pharmacologie)</term>
<term>Ivermectine (usage thérapeutique)</term>
<term>Microfilaria ()</term>
<term>Mâle</term>
<term>Parasitémie (traitement médicamenteux)</term>
<term>Symbiose</term>
<term>Wolbachia ()</term>
<term>Wolbachia (croissance et développement)</term>
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<term>Filaricides</term>
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<term>Anti-Bacterial Agents</term>
<term>Doxycycline</term>
<term>Filaricides</term>
<term>Ivermectin</term>
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<keywords scheme="MESH" type="chemical" qualifier="therapeutic use" xml:lang="en">
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<term>Doxycycline</term>
<term>Filaricides</term>
<term>Ivermectin</term>
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<term>Doxycycline</term>
<term>Filaricides</term>
<term>Ivermectine</term>
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<term>Wuchereria bancrofti</term>
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<term>Filariose lymphatique</term>
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<div type="abstract" xml:lang="en">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.</div>
</front>
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