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Author Correction: Short-Course, High-Dose Rifampicin Achieves Wolbachia Depletion Predictive of Curative Outcomes in Preclinical Models of Lymphatic Filariasis and Onchocerciasis
- Source :
- Scientific Reports, Scientific Reports, Vol 8, Iss 1, Pp 1-1 (2018)
- Publication Year :
- 2018
-
Abstract
- Lymphatic filariasis (LF) and onchocerciasis are priority neglected tropical diseases targeted for elimination. The only safe drug treatment with substantial curative activity against the filarial nematodes responsible for LF (Brugia malayi, Wuchereria bancrofti) or onchocerciasis (Onchocerca volvulus) is doxycycline. The target of doxycycline is the essential endosymbiont, Wolbachia. Four to six weeks doxycycline therapy achieves >90% depletion of Wolbachia in worm tissues leading to blockade of embryogenesis, adult sterility and premature death 18–24 months post-treatment. Long treatment length and contraindications in children and pregnancy are obstacles to implementing doxycycline as a public health strategy. Here we determine, via preclinical infection models of Brugia malayi or Onchocerca ochengi that elevated exposures of orally-administered rifampicin can lead to Wolbachia depletions from filariae more rapidly than those achieved by doxycycline. Dose escalation of rifampicin achieves >90% Wolbachia depletion in time periods of 7 days in B. malayi and 14 days in O. ochengi. Using pharmacokinetic-pharmacodynamic modelling and mouse-human bridging analysis, we conclude that clinically relevant dose elevations of rifampicin, which have recently been determined as safe in humans, could be administered as short courses to filariasis target populations with potential to reduce anti-Wolbachia curative therapy times to between one and two weeks.
- Subjects :
- DNA, Bacterial
0301 basic medicine
Science
030231 tropical medicine
Administration, Oral
Embryonic Development
Onchocerciasis
Bioinformatics
Article
Mice
03 medical and health sciences
Elephantiasis, Filarial
0302 clinical medicine
parasitic diseases
medicine
Animals
Humans
Wuchereria bancrofti
Short course
Author Correction
Brugia malayi
Filarioidea
Lymphatic filariasis
Multidisciplinary
biology
business.industry
qs_4
medicine.disease
biology.organism_classification
Anti-Bacterial Agents
Disease Models, Animal
Onchocerca volvulus
Treatment Outcome
030104 developmental biology
Medicine
Wolbachia
Rifampin
business
Rifampicin
medicine.drug
Subjects
Details
- ISSN :
- 20452322
- Volume :
- 8
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- Scientific reports
- Accession number :
- edsair.doi.dedup.....fee7d531500b2bcb751b7029747778d3