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      Macrofilaricidal Activity in Wuchereria bancrofti after 2 Weeks Treatment with a Combination of Rifampicin plus Doxycycline

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          Abstract

          Infection with the filarial nematode Wuchereria bancrofti can lead to lymphedema, hydrocele, and elephantiasis. Since adult worms cause pathology in lymphatic filariasis (LF), it is imperative to discover macrofilaricidal drugs for the treatment of the infection. Endosymbiotic Wolbachia in filariae have emerged as a new target for antibiotics which can lead to macrofilaricidal effects. In Ghana, a pilot study was carried out with 39 LF-infected men; 12 were treated with 200 mg doxycycline/day for 4 weeks, 16 were treated with a combination of 200 mg doxycycline/day + 10 mg/kg/day rifampicin for 2 weeks, and 11 patients received placebo. Patients were monitored for Wolbachia and microfilaria loads, antigenaemia, and filarial dance sign (FDS). Both 4-week doxycycline and the 2-week combination treatment reduced Wolbachia load significantly. At 18 months posttreatment, four-week doxycycline resulted in 100% adult worm loss, and the 2-week combination treatment resulted in a 50% adult worm loss. In conclusion, this pilot study with a combination of 2-week doxycycline and rifampicin demonstrates moderate macrofilaricidal activity against W. bancrofti.

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          Lymphatic filariasis and onchocerciasis.

          Mark Taylor, Achim Hoerauf, Moses J. Bockarie (2010)
          Lymphatic filariasis and onchocerciasis are parasitic helminth diseases that constitute a serious public health issue in tropical regions. The filarial nematodes that cause these diseases are transmitted by blood-feeding insects and produce chronic and long-term infection through suppression of host immunity. Disease pathogenesis is linked to host inflammation invoked by the death of the parasite, causing hydrocoele, lymphoedema, and elephantiasis in lymphatic filariasis, and skin disease and blindness in onchocerciasis. Most filarial species that infect people co-exist in mutualistic symbiosis with Wolbachia bacteria, which are essential for growth, development, and survival of their nematode hosts. These endosymbionts contribute to inflammatory disease pathogenesis and are a target for doxycycline therapy, which delivers macrofilaricidal activity, improves pathological outcomes, and is effective as monotherapy. Drugs to treat filariasis include diethylcarbamazine, ivermectin, and albendazole, which are used mostly in combination to reduce microfilariae in blood (lymphatic filariasis) and skin (onchocerciasis). Global programmes for control and elimination have been developed to provide sustained delivery of drugs to affected communities to interrupt transmission of disease and ultimately eliminate this burden on public health. Copyright © 2010 Elsevier Ltd. All rights reserved.
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            Strategies and tools for the control/elimination of lymphatic filariasis.

            Camilla Ottesen, Amir Karam, Charles B. Duke … (1996)
            Lymphatic filariasis infects 120 million people in 73 countries worldwide and continues to be a worsening problem, especially in Africa and the Indian subcontinent. Elephantiasis, lymphoedema, and genital pathology afflict 44 million men, women and children; another 76 million have parasites in their blood and hidden internal damage to their lymphatic and renal systems. In the past, tools and strategies for the control of the condition were inadequate, but over the last 10 years dramatic research advances have led to new understanding about the severity and impact of the disease, new diagnostic and monitoring tools, and, most importantly, new treatment tools and control strategies. The new strategy aims both at transmission control through community-wide (mass) treatment programmes and at disease control through individual patient management. Annual single-dose co-administration of two drugs (ivermectin + diethylcarbamazine (DEC) or albendazole) reduces blood microfilariae by 99% for a full year; even a single dose of one drug (ivermectin or DEC) administered annually can result in 90% reductions; field studies confirm that such reduction of microfilarial loads and prevalence can interrupt transmission. New approaches to disease control, based on preventing bacterial superinfection, can now halt or even reverse the lymphoedema and elephantiasis sequelae of filarial infection. Recognizing these remarkable technical advances, the successes of recent control programmes, and the biological factors favouring elimination of this infection, the Fiftieth World Health Assembly recently called on WHO and its Member States to establish as a priority the global elimination of lymphatic filariasis as a public health problem.
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              Macrofilaricidal activity after doxycycline treatment of Wuchereria bancrofti: a double-blind, randomised placebo-controlled trial.

              Mark Taylor, Williams H. Makunde, Helen McGarry … (2015)
              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. 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. 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<0.001). Ultrasonography detected adult worms in only six (22%) of 27 individuals treated with doxycycline compared with 24 (88%) of 27 with placebo at 14 months after the start of treatment (p<0.0001). At the same timepoint, filarial antigenaemia in the doxycycline group fell to about half of that before treatment (p=0.015). Adverse events were few and mild. 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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                Author and article information

                Journal
                Journal ID (nlm-ta): J Parasitol Res
                Journal ID (publisher-id): JPR
                Title: Journal of Parasitology Research
                Publisher: Hindawi Publishing Corporation
                ISSN (Print): 2090-0023
                ISSN (Electronic): 2090-0031
                Publication date (Print): 2011
                Publication date (Electronic): 22 May 2011
                Volume: 2011
                Electronic Location Identifier: 201617
                Affiliations
                1Faculty of Allied Health Sciences, Kwame Nkrumah University of Science and Technology, UPO, PMB, Kumasi, Ghana
                2Kumasi Centre for Collaborative Research in Tropical Medicine (KCCR), Kwame Nkrumah University of Science and Technology, UPO, PMB, Kumasi, Ghana
                3Institute for Medical Microbiology, Immunology and Parasitology, University Clinic Bonn, Sigmund-Freud-Stra βe 25, D-53105 Bonn, Germany
                4School of Medical Sciences, Kwame Nkrumah University of Science and Technology, UPO, PMB, Kumasi, Ghana
                Author notes

                Academic Editor: C. Genchi

                Article
                DOI: 10.1155/2011/201617
                PMC ID: 3112504
                PubMed ID: 21687646
                SO-VID: c71494a8-959c-4b95-83a0-0a064c450eae
                Copyright © Copyright © 2011 Alexander Yaw Debrah et al.
                License:

                This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                Date received : 6 December 2010
                Date accepted : 2 March 2011
                Categories
                Subject: Research Article

                ScienceOpen disciplines: Parasitology
                Data availability:
                ScienceOpen disciplines: Parasitology

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