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Infektiologie Update 2018: 26. Jahrestagung der Paul-Ehrlich-Gesellschaft für Chemotherapie (PEG)

Paul-Ehrlich-Gesellschaft für Chemotherapie (PEG)

04. - 06.10.2018, Wien, Österreich

Doxycycline therapy for improvement of lymphedema of filarial and non-filarial origin

Meeting Abstract

  • J. M. Kuepper - Institute for Medical Microbiology, Immunology and Parasitology (IMMIP), University Hospital Bonn, Germany
  • U. Mwingira - National Institute for Medical Research (NIMR), Tanzania
  • S. Wanji - Public Health and Entomology, Department of Microbiology and Parasitology, University of Buea, Cameroon
  • I. Kroidl - Department for Infectious Diseases & Tropical Medicine, Hospital of the Ludwig-Maximilians-University (LMU), Munich, Germany
  • L. Batsa-Debrah - Kumasi Centre for Collaborative Research in Tropical Medicine (KCCR), Kumasi, Ghana
  • A. Ngenya - National Institute for Medical Research (NIMR), Tanzania
  • J. A. Njouendou - Public Health and Entomology, Department of Microbiology and Parasitology, University of Buea, Cameroon
  • U. Klarmann-Schulz - Institute for Medical Microbiology, Immunology and Parasitology (IMMIP), University Hospital Bonn, Germany; German Center for Infection Research (DZIF), Partner Site Bonn-Cologne, Bonn, Germany
  • A. Y. Debrah - German Center for Infection Research (DZIF), Partner Site Bonn-Cologne, Bonn, Germany; Faculty of Allied Health Sciences, Kwame Nkrumah University of Science and Technology (KNUST), Kumasi, Ghana
  • A. Hoerauf - Institute for Medical Microbiology, Immunology and Parasitology (IMMIP), University Hospital Bonn, Germany; German Center for Infection Research (DZIF), Partner Site Bonn-Cologne, Bonn, Germany

Infektiologie Update 2018. 26. Jahrestagung der Paul-Ehrlich-Gesellschaft für Chemotherapie (PEG). Wien, 04.-06.10.2018. Düsseldorf: German Medical Science GMS Publishing House; 2018. Doc18peg26

doi: 10.3205/18peg26, urn:nbn:de:0183-18peg264

Published: October 8, 2018

© 2018 Kuepper et al.
This is an Open Access article distributed under the terms of the Creative Commons Attribution 4.0 License. See license information at http://creativecommons.org/licenses/by/4.0/.


Outline

Text

Lymphedema (LE) can have various origins of which one is the infection with filarial worms like Wuchereria bancrofti. A previous study showed that a 6-week treatment with 200 mg doxycycline (DOX) did not only exert macro- and microfilaricidal effects but also improved the lymphedema in lymphatic filariasis (LF) patients [1]. We designed three multi-national interventional randomized double-blind placebo-controlled phase II clinical trials to confirm and expand these findings.

The three LEDoxy trials, funded by the TAKeOFF project (by BMBF), take place in Ghana (ISRCTN14042737), Tanzania (ISRCTN65756724) and Cameroon (ISRCTN11881662). Three additional study sites, Mali (NCT02927496), Sri Lanka (NCT02929134) and India (NCT02929121), are funded by the USAID and are conducted in collaboration with the NTD Support Center (Taskforce for Global Health, Atlanta, USA). The trials in Ghana and Tanzania as well as the three USAID funded studies focus on the efficacy of 200 mg DOX for 6 weeks compared to placebo in LF patients. These LF trials are separated in a confirmatory phase II trial including patients with LE stage 1–3 and a pilot trial which will investigate whether also patients with LE stages 4-6 can profit from treatment with DOX 200 mg.

Additionally, the trials in Ghana and Tanzania include a treatment arms with only 100 mg DOX daily which will be compared against placebo and DOX 200 mg. 100 mg DOX is widely used in malaria prophylaxis and against other infections. A previous RCT has shown that the macrofilaricidal effect of 100 mg DOX in LF is as good as the 200 mg dose [2]. A dose reduction would lead to less, if any, side effects and reduced costs for health care providers.

The trial in Cameroon is aimed to expand the previous findings from Mand et al. to podoconiosis (Podo) LE. The original study found that the positive effects on lymphedema in LF were independent of the infection status. Therefore it is possible that DOX can also exert its effects in lymphedema of other origins like Podo LE which is caused by irritant red clay soil. Patients with a LE Stage 2–4 will be included to investigate whether 200 mg DOX can also halt or improve progression of non-filarial LE.

The overall aim of our studies is to confirm the previous findings on multi-national level and thereby expanding the therapeutic options for LE patients. The treatment of lymphatic filariasis is mainly based on the elimination of the parasite but leaves the pathology behind. Establishing DOX to improve lymphedema of filarial and also non-filarial origin in international guidelines (e.g. WHO) for morbidity management could greatly improve the life of affected patients.


References

1.
Mand S, Debrah AY, Klarmann U, et al. Doxycycline Improves Filarial Lymphedema Independent of Active Filarial Infection: A Randomized Controlled Trial. Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America. 2012;55(5):621-630. DOI: 10.1093/cid/cis486 External link
2.
Klarmann U, Debrah AY, Mand S, Batsa L, Specht S, Pfarr K, Kwarteng A, Fimmers R, Taylor M, Adjei O, Hoerauf A. Shortening the Timeframe and Dosage of Anti-Wolbachia Therapy: Doxycycline Alone Versus Doxycycline Plus Rifampicin in Their Efficacy Against Lymphatic Filariasis; A Randomized, Double-Blind, Placebo-Controlled Trial [ASTMH abstract No. 522]. Am J Trop Med Hyg. 2012 Nov; 87(5 Suppl 1):157. DOI: 10.4269/ajtmh.2012.87.150 External link