Old dog, New Tricks? Assessing the Potential of Integrating Focal Vector Suppression with Drug Cure to Control and Eliminate River Blindness

By Louise Hamill

Onchocerciasis, also known as river blindness, is one of the vector-borne neglected tropical diseases (NTDs); in this case, transmitted by many different species of black fly. The majority of infections (99%) occur in sub-Saharan Africa. The disease was previously also found in South America but is now thankfully close to total elimination; with only a few isolated, extremely remote areas still to be verified disease-free. The aim for Africa is to achieve continent-wide interruption of transmission by 2025.  Current control of river blindness in Africa, which, as well as blindness, leads to debilitating, disfiguring skin pathology, is based upon the mass delivery of ivermectin to entire populations in endemic areas. Ivermectin kills microfilariae in the skin, but has no significant effects on adult worms. This necessitates repeated rounds of ivermectin mass delivery for a period of 12 – 15 years, with sustained high coverage of the at-risk population essential for successful disease control and eventual elimination.

This approach has had notable successes in several areas, led by the efforts of the African Programme for Onchocerciasis Control (APOC). However in other areas, the impact of sustained delivery of ivermectin for fifteen years, and in some areas more than two decades, has yet to result in the predicted interruption of transmission. Furthermore, where the eye worm Loa loa and onchocerciasis occur together, mass delivery of ivermectin cannot be easily rolled out. Ivermectin causes unwanted side effects, and in rare cases death, in individuals infected with L. loa as the drug rapidly kills this parasite. L. loa is common in large swathes of West and Central Africa, allowing onchocerciasis to endure in these areas, where many people are still infected and transmission of both pathogens is actively taking place, despite ongoing control efforts. Clearly there is no one-size-fits-all approach to curtail river blindness, and there is a need to seek alternative strategies to ivermectin-based control in areas where river blindness and L. loa overlap.

In the nineteen seventies and eighties the WHO onchocerciasis control programme, OCP, ran an extremely successful vector control strategy against onchocerciasis in savannah areas of West Africa. This programme relied exclusively on aerial application of larvicide to kill black fly larval as they resided in rivers and streams. It is estimated this past use of vector control prevented 600,000 cases of blindness and prevented 40 million people being infected. The scale of this undertaking, including the huge financial cost and human resource needed, means that the use of mass vector elimination as a tool for onchocerciasis control is very much consigned to the history books. Before turning the page completely on this chapter of onchocerciasis control, are there any lessons to be learnt from this “old dog”?

The COUNTDOWN meeting on Focal black fly Control in Cameroon

This is exactly the question we set out to debate when COUNTDOWN convened a technical advisory panel at the Liverpool School of Tropical Medicine on 22nd of July 2016. Although mass vector control is out of the question, is there any way in which short-term, localised approaches can be used to augment and complement existing strategies?

Vector Meeting

Attendees at the COUNTDOWN meeting on Focal Black fly Control, from Left to Right: Professor Graham Matthews, Professor Rory Post, Dr Frank Walsh, Didier Bakajika, Dr John B. Davies, Dr Louise Hamill, Dr Hans Dobson, Dr Joseph Turner, Professor María-Gloria Basáñez, Professor Mark Taylor, Isobel Routledge, Professor Russell Stothard, Professor Robert Cheke. Not pictured; Professor Janet Hemingway, Dr Lisa Reimer.

Previous work in South West Cameroon by members of the COUNTDOWN consortium indicates that ten years of ivermectin delivery in our study area has not had the expected impact on disease prevalence. The average community-level of skin microfilaria prevalence stands at 52.7 percent, with the infection intense even in children under ten years of age. Additional work in South West Cameroon found current adherence to ivermectin mass delivery by local residents is not adequate to achieve onchocerciasis control. This is an area where alternative and complementary strategies are urgently needed.

The COUNTDOWN consortium has proposed that larvicidal treatment of vector breeding sites at the same time as testing and treating the human population with doxycycline could offer a complementary onchocerciasis control strategy. This two-pronged approach, it is hoped, will have a greater impact on disease transmission than using either technique in isolation. Doxycycline targets “friendly” bacteria living within the adult onchocerciasis worms, resulting in a significant shortening of their lifespans and giving doxycycline a very different mode of action to ivermectin. Since L. loa does not harbour the same bacteria, individuals co-infected with L. loa who take doxycycline will not suffer the same side effects as can happen with ivermectin. From the evidence above, it is clear to see ivermectin mass delivery has not had the desired impact on disease prevalence over the past ten years in this area of South West Cameroon; could targeted vector suppression jump start the path to onchocerciasis control?

At the meeting, debate revolved around the factors influencing choice of larvicide; when, how often & for how long the larvicide should be applied; the most suitable sampling methods to monitor impact of the larviciding on adult and larval black fly; and how best to undertake monitoring of the impact of insecticide application on non-target organisms. The optimal timing of any vector suppression to best amplify the impact of the community test-and-treat strategy is crucial. The way ahead is far from straight forward, highlighting the importance of rigorously assessing the evidence and our proposed strategy in this way. Although the use of localised vector control against black flies is not a new proposal, there is little information on how this could be implemented against free-living black fly larvae.

Where next?

The control and elimination of NTDs in Africa has repeatedly been in the post-millennium development goals policy spotlight, with (among others) the WHO roadmap to elimination, the London Declaration on NTDs and recently the launch of the Expanded Special Programme for Elimination of NTDS (ESPEN). Similar to the situation for lymphatic filariasis, scale-up of mass delivery of ivermectin will not be enough to achieve the London Declaration 2020 targets for onchocerciasis control and elimination. The use of both doxycycline and focal vector suppression are separately recommended by WHO and APOC as alternative onchocerciasis control strategies, to accelerate progress towards onchocerciasis control, however as relatively new control strategies evidence on their implementation is scarce and evidence on integrated, dual-strategy implementation is wholly absent. The specific contexts in which these tools could be successfully implemented together are unclear.  Going forward with our onchocerciasis work in Cameroon, COUNTDOWN’s focus is consolidation of the evidence gathered at the vector control meeting to assess the possibility of implementing localised vector suppression as an adjunct to existing and alternative control and elimination strategies. This will bridge vital evidence gaps and provide clarity on if and where these techniques can be used, and the optimal conditions in which to implement them.

 

 

 

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