ArticlePLoS neglected tropical diseases2018
Combinations of registered drugs reduce treatment times required to deplete Wolbachia in the Litomosoides sigmodontis mouse model.
Article in PLoS neglected tropical diseases, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed.
- Assessing the efficacy of high-dose rifampicin plus albendazole against onchocerciasis.PLoS neglected tropical diseases · 2026Trial
- Comparison of 6-Week Doxycycline vs 6-Week Rifampicin or 3 Weeks of Doxycycline Plus Rifampicin in the Treatment of Onchocerciasis: A Randomized, Placebo-Controlled, Double-Blind, Phase 2 Trial.Open forum infectious diseases · 2026Article
- Systematic modeling predicts synergistic and safe drug combinations for parasitic diseases.PLoS neglected tropical diseases · 2026Article
- Host environment shapes filarial parasite fitness and Wolbachia endosymbionts dynamics.PLoS pathogens · 2025Article
- The pipeline for drugs for control and elimination of neglected tropical diseases: 2. Oral anti-infective drugs and drug combinations for off-label use.Parasites & vectors · 2023Review
- Programmed cell death pathways as targets for developing antifilarial drugs: Lessons from the recent findings.Journal of cellular and molecular medicine · 2023Review
- Toward novel treatment against filariasis: Insight into genome-wide co-evolutionary analysis of filarial nematodes andFrontiers in microbiology · 2023Article
- Discovery of Substituted Di(pyridin-2-yl)-1,2,4-thiadiazol-5-amines as Novel Macrofilaricidal Compounds for the Treatment of Human Filarial Infections.Journal of medicinal chemistry · 2022Article
- A qPCR to quantify Wolbachia from few Onchocerca volvulus microfilariae as a surrogate for adult worm histology in clinical trials of antiwolbachial drugs.Parasitology research · 2022Article
- The filarial and the antibiotics: Single or combination therapy using antibiotics for filariasis.Frontiers in cellular and infection microbiology · 2022Review
- Human filariasis-contributions of the Litomosoides sigmodontis and Acanthocheilonema viteae animal model.Parasitology research · 2021Review
- Onchocerciasis drug development: from preclinical models to humans.Parasitology research · 2021Review
- Molecular Docking Simulation Studies Identifies Potential Natural Product Derived-Antiwolbachial Compounds as Filaricides against Onchocerciasis.Biomedicines · 2021Article
- Corallopyronin A for short-course anti-wolbachial, macrofilaricidal treatment of filarial infections.PLoS neglected tropical diseases · 2020Article
- In vivo efficacy of the boron-pleuromutilin AN11251 against Wolbachia of the rodent filarial nematode Litomosoides sigmodontis.PLoS neglected tropical diseases · 2020Article
- Quantitative methods for assessing local and bodywide contributions to Wolbachia titer in maternal germline cells of Drosophila.BMC microbiology · 2019Article
- Advances in Antiwolbachial Drug Discovery for Treatment of Parasitic Filarial Worm Infections.Tropical medicine and infectious disease · 2019Review
- Boron-Pleuromutilins as Anti- Wolbachia Agents with Potential for Treatment of Onchocerciasis and Lymphatic Filariasis.Journal of medicinal chemistry · 2019Article
- Discovery of ABBV-4083, a novel analog of Tylosin A that has potent anti-Wolbachia and anti-filarial activity.PLoS neglected tropical diseases · 2019Article
- Macrofilaricidal efficacy of single and repeated oral and subcutaneous doses of flubendazole in Litomosoides sigmodontis infected jirds.PLoS neglected tropical diseases · 2019Article
Corrections and comments
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Authors and funding
11 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Filarial parasites can be targeted by antibiotic treatment due to their unique endosymbiotic relationship with Wolbachia bacteria. This finding has led to successful treatment strategies in both, human onchocerciasis and lymphatic filariasis. A 4-6 week treatment course using doxycycline results in long-term sterility and safe macrofilaricidal activity in humans. However, current treatment times and doxycycline contraindications in children and pregnant women preclude widespread administration of doxycycline in public health control programs; therefore, the search for shorter anti-wolbachial regimens is a focus of ongoing research. We have established an in vivo model for compound screening, using mice infected with Litomosoides sigmodontis. We could show that gold standard doxycycline treatment did not only deplete Wolbachia, it also resulted in a larval arrest. In this model, combinations of registered antibiotics were tested for their anti-wolbachial activity. Administration of rifamycins in combination with doxycycline for 7 days successfully depleted Wolbachia by > 2 log (>99% reduction) and thus resulted in a significant reduction of the treatment duration. Using a triple combination of a tetracycline (doxycycline or minocycline), a rifamycin and a fluoroquinolone (moxifloxacin) led to an even greater shortening of the treatment time. Testing all double combinations that could be derived from the triple combinations revealed that the combination of rifapentine (15mg/kg) and moxifloxacin (2 x 200mg/kg) showed the strongest reduction of treatment time in intraperitoneal and also oral administration routes. The rifapentine plus moxifloxacin combination was equivalent to the triple combination with additional doxycycline (>99% Wolbachia reduction). These investigations suggest that it is possible to shorten anti-wolbachial treatment times with combination treatments in order to achieve the target product profile (TPP) requirements for macrofilaricidal drugs of no more than 7-10 days of treatment.
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