Filariasis: new drugs and new opportunities for lymphatic filariasis and onchocerciasis

@article{Hoerauf2008FilariasisND,
  title={Filariasis: new drugs and new opportunities for lymphatic filariasis and onchocerciasis},
  author={Achim Hoerauf},
  journal={Current Opinion in Infectious Diseases},
  year={2008},
  volume={21},
  pages={673–681}
}
  • A. Hoerauf
  • Published 1 December 2008
  • Medicine
  • Current Opinion in Infectious Diseases
Purpose of review Chemotherapy against onchocerciasis and lymphatic filariasis has been discussed mainly within the framework of mass drug administration with diethylcarbamazine, ivermectin and albendazole. Although strong reductions in infection prevalence were achieved, the regimes for these drugs do not fully cover needs of individual patients who seek treatment because of symptoms. Chemotherapy against filarial Wolbachia endosymbionts with doxycycline showed higher antiparasitic efficacy in… 
Chemotherapy of filariasis – established strategies and new developments
TLDR
Current treatment options and current research approaches for optimization of anti-helminthic therapy are summarized and reviewed, including the exploration of optimized delivery strategies of ivermectin and albendazole, the discovery and development of new antibiotics for antiwolbachial chemotherapy and macrofilaricidal antihelminethics.
Macrofilaricidal Activity in Wuchereria bancrofti after 2 Weeks Treatment with a Combination of Rifampicin plus Doxycycline
TLDR
A pilot study with a combination of 2-week doxycycline and rifampicin demonstrates moderate macrofilaricidal activity against W. bancrofti.
Current perspective of new anti-Wolbachial and direct-acting macrofilaricidal drugs as treatment strategies for human filariasis
TLDR
Within a collaboration of the non-profit organizations Drugs for Neglected Diseases initiative (DNDi), the Bill & Melinda Gates Foundation, and partners from academia and industry, several new promising macrofilaricidal drug candidates were identified, which will be discussed in this review.
Elimination of lymphatic filariasis: do we have the drugs to complete the job?
TLDR
Alternative and effective MDA regimens and strategies will be needed if the GPELF is to achieve the goals of global elimination of lymphatic filariasis by 2020.
Macrofilaricidal activity and amelioration of lymphatic pathology in bancroftian filariasis after 3 weeks of doxycycline followed by single-dose diethylcarbamazine.
TLDR
The beneficial effects of doxycycline on lymphatic dilation is confirmed and adds to the existing evidence that doxy cycline, in addition to being macrofilaricidal, may be used to prevent or reverse lymphatic pathology.
Doxycycline depletes Wolbachia and kills adult worms of Wuchereria bancrofti
TLDR
This scoping review argues that doxycycline is by far the most promising of the current anti wolbachial drugs under investigation and is relatively safe and does not generate adverse effects associated with rapid killing of worms as with some MDA drugs.
Anti-Wolbachia drug discovery and development: safe macrofilaricides for onchocerciasis and lymphatic filariasis
TLDR
The primary goal of the anti-Wolbachia (A·WOL) consortium is to find drugs and regimens that reduce the period of treatment from weeks to days (7 days or less), and to finding drugs which would be safe in excluded target populations (pregnancy and children).
In vivo efficacy of the boron-pleuromutilin AN11251 against Wolbachia of the rodent filarial nematode Litomosoides sigmodontis
TLDR
Results indicate that AN11251 is superior to doxycycline and comparable to high-dose rifampicin in the L. sigmodontis mouse model, allowing treatment regimens as short as 10–14 days, and represents a promising pre-clinical candidate that could be further evaluated and developed as potential clinical candidate for human lymphatic filariasis and onchocerciasis.
Current Evidence on the Use of Antifilarial Agents in the Management of Bancroftian Filariasis
TLDR
This narrative review summarizes the current evidence for drug management of bancroftian filariasis and shows that doxycycline therapy against Wolbachia, an endosymbiotic bacterium of the parasite, is capable of reducing microfilaria rates and adult worm activity.
...
...

References

SHOWING 1-10 OF 76 REFERENCES
Antibiotic therapy in murine filariasis (Litomosoides sigmodontis): comparative effects of doxycycline and rifampicin on Wolbachia and filarial viability
TLDR
The combination of antirickettsial drugs could be used as a suitable tool to explore the minimum duration of therapy required for the depletion of Wolbachia in parasitized hosts subsequent to the onset of patency in human and animal filariasis and the prevention of adverse reactions in human infections.
Efficacy of 2- and 4-week rifampicin treatment on the Wolbachia of Onchocerca volvulus
TLDR
Embryogenesis and microfilariae production were reduced after 4 weeks rifampicin treatment, rendering rifampsicin an antibiotic with anti-wolbachial efficacy in human onchocerciasis.
Strategies and tools for the control/elimination of lymphatic filariasis.
TLDR
New approaches to disease control, based on preventing bacterial superinfection, can now halt or even reverse the lymphoedema and elephantiasis sequelae of filarial infection.
Doxycycline treatment of Brugia malayi-infected persons reduces microfilaremia and adverse reactions after diethylcarbamazine and albendazole treatment.
  • T. Supali, Y. Djuardi, E. Sartono
  • Medicine
    Clinical infectious diseases : an official publication of the Infectious Diseases Society of America
  • 2008
TLDR
A 6-week course of doxycycline, either alone or in combination with diethylcarbamazine-albendazole, leads to a decrease in microfilaremia and reduces adverse reactions to antifilarial treatment in B. malayi-infected persons.
Albendazole for lymphatic filariasis.
TLDR
There is insufficient evidence to confirm or refute that albendazole co-administered with DEC or ivermectin is more effective than DEC oriver mectin alone in clearing microfilariae or killing adult worms.
Doxycycline Reduces Plasma VEGF-C/sVEGFR-3 and Improves Pathology in Lymphatic Filariasis
TLDR
A 6-wk regimen of antifilarial treatment with doxycycline against W. bancrofti showed a strong macrofilaricidal activity and reduction in plasma levels of VEGF-C/sVEGFR-3, the latter being associated with amelioration of supratesticular dilated lymphatic vessels and with an improvement of pathology in lymphatic filariasis patients.
Treatment strategies underpinning the global programme to eliminate lymphatic filariasis
TLDR
The evidence for the efficacy and safety of these two-drug regimens underpinning the global strategy for elimination of LF are reviewed, and recommendations for future developments in chemotherapy for LF are made, focusing on unresolved issues.
...
...