EMINENCE

The challenge

The parasitic roundworm Onchocerca volvulus infects an estimated 20 million people, almost all of them in sub-Saharan Africa.  Spread by blackflies, Onchocerca infections can cause a range of symptoms, including blindness. This infection is commonly known as ‘river blindness’ because people living along watercourses are particularly vulnerable to infection, as this is where blackflies are most found.

Onchocerciasis has been targeted for elimination, and control currently relies primarily on mass drug administration with ivermectin. Although ivermectin kills microfilariae larvae, the stage of the Onchocerca life cycle when it is transmitted between people, it is much less active against adult worms, which can live for up to 20 years. It will therefore take more than a decade of mass drug administration campaigns to interrupt transmission. Onchocerciasis persists in several hotspots in Central and West Africa, where transmission intensity is high and ivermectin coverage is incomplete.

A further challenge is that mass drug administration with ivermectin cannot be used in areas where a second parasitic roundworm, Loa loa, is also present. Rapid killing of L. loa can trigger a potentially lethal physical reaction in the brain. Onchocerciasis hotspots in Gabon and large areas of other countries, covering 15 million people, are therefore excluded from ivermectin-based mass drug administration programmes. 

The project

Because of these challenges, the search is on for additional strategies to accelerate the elimination of onchocerciasis. The EMINENCE project is evaluating the use of moxidectin as an alternative to ivermectin in high-transmission areas and regions where L. loa coexists with O. volvulus.

Phase II and III trials have shown that moxidectin is more active than ivermectin against microfilariae. It also appears to have more impact on adult worms. Although licensed only for use in children over the age of 12 years, an EDCTP2-funded trial has demonstrated its suitability for use in younger children. 

This potential advantage needs to be confirmed in programmatic field trials, which is a core aim of the EMINENCE project. A phase IIIb trial is being organised to compare annual or biannual use of either moxidectin or ivermectin in hotspot areas of Cameroon. The trial will assess effects on parasite carriage, levels of Onchocerca antibodies, and the presence of Onchocerca in blackfly vectors; it will also compare effects on adult worms.

In addition, the project is evaluating the safety of moxidectin use in L. loa endemic areas in the Republic of Congo and Cameroon. A dose-finding phase II trial is underway, testing progressively higher doses of moxidectin in progressively heavier L. loa infections to identify the highest dose that could be used in campaigns.

Alongside these trials, the project team is gathering the views of key stakeholders, including health workers and community members, on the use of moxidectin. It will also carry out an economic analysis to highlight the financial implications of introducing moxidectin and generate materials to help countries introduce it into mass drug administration campaigns.

Impact

The EMINENCE project is a key step in the development of moxidectin as a potential agent for onchocerciasis control. It will:

• Reveal whether the superior performance of moxidectin over ivermectin is also seen in key sub-Saharan African locations.
• Demonstrate whether moxidectin can be used safely in Loa loa endemic areas.

If the benefits of moxidectin are confirmed, its introduction could extend the use of mass drug administration campaigns and accelerate the elimination of a common and debilitating neglected tropical disease having a major impact on health and quality of life across a swathe of sub-Saharan Africa.