Scientists at LSTM have proven that targeting an essential bacterial symbiont, Wolbachia, with a course of antibiotics cures patients of their parasitic worms and improves disease pathology. This discovery in 1999 offers superior efficacy compared to existing anti-filarial drugs delivering prophylaxis, transmission blocking, safe macrofilaricidal activity and improved case management therapy. This approach has been endorsed by WHO elimination programmes for onchocerciasis, (Onchocerciasis Elimination Programme for the Americas, OEPA) and lymphatic filariasis (Global Programme to Eliminate Lymphatic Filariasis, GELF). The Centre for Disease Control (CDC), also recommends this new strategy for elimination and morbidity management.
Underpinning research
LSTM is studying the filarial parasites which cause elephantiasis (Wuchereria bancrofti and Brugia malayi) and river blindness (Onchocerca volvulus) since 1993. Both of these diseases are part of a recent focus on neglected tropical diseases (NTDs), recognizing that about a billion more people are at risk and millions are infected with NTDs.
LSTM has made significant progress discovering a previously unexpected role of Wolbachia bacterial symbionts as drivers of filarial disease, essential contributors to the biology of filarial nematodes, and as a target for treatment through antibiotic therapy. The antibiotic doxycycline can be used to treat patients with fewer adverse effects than existing therapies such as ivermectin. New drugs are still needed to reduce the treatment course and are being developed in partnership with industry.
The breakthrough stimulated the formation of the 'Anti-Wolbachia' (A·WOL I) consortium in 2007 and A·WOL II in 2013, to search for new drugs active against Wolbachia. The consortium consists of internationally recognised researchers in the UK, Germany, Africa and USA and collaborates with pharmaceutical companies.
The new anti-wolbachial therapy provides an alternative to the treatment for onchocerciasis and lymphatic filariasis in areas co-endemic with loiasis. Previous anti-macrofilarial treatments have resulted in the rapid kill of L. loa microfilariae but at the risk of severe complications resulting in encephalopathy, coma and death. However, by using antibacterial drugs these severe adverse events are avoided because L. loa microfilariae do not have Wolbachia symbionts. This has potential to overcome a major barrier to the implementation of mass drug administration (MDA) programmes.
Findings by A·WOL of 6 and 8 week courses of doxycycline have been reported as a safe and well tolerated treatment for lymphatic filariasis with significant activity against adult worms and microfilaraemia, treatment improves mild to moderate lymphodema independent of on-going infection. This benefit expands to the entire population of patients suffering from lymphodema. Doxycycline is able to kill the adult worms, making doxycycline the first drug already approved for human use that controls the parasite and the quality of life of persons with pathology.
To test whether a 6-week course of treatment was deliverable through community-directed MDA approaches, in 2007 a community trial of treatment with doxycycline was carried out in two health districts in Cameroon, co-endemic for O. volvulus and L. loa. With 17,519 eligible subjects, the therapeutic coverage was 73.8% with 97.5% compliance, encouraging the feasibility of using doxycycline community-directed delivery in restricted populations of this size. The evaluation of the effectiveness of this delivery of doxycycline showed significant improvements over standard strategies, even up to four years after delivery, which is not dependent upon co-administration of ivermectin. These findings show that a multi-week course of treatment is not a barrier to community-delivery of MDA in restricted populations of this size and supports its implementation to complement existing control strategies for onchocerciasis.
Details of impact
LSTM research findings changed WHO and the CDC strategies, treatment guidelines and recommendations.
Policy impact
One objective of the A∙WOL programme is to promote advocacy of A∙WOL’s outcomes by interfacing with CNTD (currently FPSU - ed) and external scientific advisors to facilitate dialogue, representation and engagement with control programmes: the African Programme for Onchocerciasis Control (APOC), OEPA and GPELF, stakeholder meetings and NTD community forums.
The membership of the A∙WOL Consortium and the External Scientific Advisory Committee (ESAC) in particular is ideally equipped through its excellent networks to promote the findings and practical opportunities the A∙WOL project provides.
Commercial impact
The breakthrough of anti-wolbachial therapy stimulated the creation of both product discovery and development pipelines at LSTM to identify new antibiotics which target Wolbachia and could be used to combat onchocerciasis and lymphatic filariasis.
For more information on this impact case study including research references; key research grants and sources to corroborate the impact please click here.
This impact case study was part of LSTM’s joint submission with University of Liverpool to REF2014.