Grand Challenges Explorations Round 11
Solutions for onchocerciasis, lymphatic filariasis, soil-transmitted helminth infections (ascariasis, trichuriasis, and hookworm disease), and schistosomiasis
Neglected tropical diseases (NTDs) are a large and diverse group of diseases that disproportionately affect health and livelihood of the poor in the developing world and typically lack attention and funding for research and development. Although in recent decades there has been significant progress toward the elimination and even eradication of some neglected diseases, there is still an unmet need to discover, develop, and deliver tools and strategies to diagnose, treat and interrupt transmission of some neglected diseases.
In line with the London Declaration and the WHO Roadmap on NTDs, we have focused our efforts in this Explorations round on the elimination of lymphatic filariasis (LF, also known as elephantiasis) by 2020, and the control of onchocerciasis (river blindness), soil-transmitted helminthic (STH) infections (ascariasis, trichuriasis, and hookworm disease), and schistosomiasis. These diseases are typically controlled through whole-population mass drug administration campaigns. They are high on global disease burden studies and are in need of innovative and transformative approaches for detection, diagnosis, and treatment.
For more information on the specific diseases, please see the WHO descriptions of onchocerciasis, LF, STH and schistosomiasis.
Mass drug administration (MDA) campaigns form the bedrock of attempts to control or eliminate onchocerciasis, LF, STH infections and schistosomiasis. In these campaigns, whole populations are treated irrespective of disease status, based on prevalence at the community level. The current tools are deficient in a number of respects. Drugs for onchocerciasis and LF interrupt transmission by killing juvenile worms but do not kill adult worms, requiring multiple rounds of treatment before adult worms eventually die and transmission stops. Furthermore, these drugs cannot be used in areas where there is potential co-infection with another helminth, Loa loa, and no simple test for Loa loa infection exists (for more information, please see the WHO strategic direction for onchocerciasis research). We lack robust diagnostics and tools to determine when to stop MDA campaigns, and coordination among mapping, monitoring, treatment, and surveillance campaigns for multiple diseases.
We are looking for people from within and outside the NTD community who have ideas for new approaches or ways to apply existing technology from other sectors to address some of the key challenges associated with developing new tools or strategies to support the control and elimination targets for onchocerciasis, LF, STH, and schistosomiasis.
Some of the key challenges facing the development of drugs and diagnostics for these specific diseases are as follows:
Need for strategies that address multiple diseases: Many individuals are infected with more than one pathogen causing the NTDs described above. New strategies are needed to integrate mapping, treatment, monitoring, and surveillance of some combination of these diseases (onchocerciasis, LF, Loa loa, STH, and schistosomiasis) simultaneously.
Drug development is hampered by lack of robust and facile model systems: For the discovery of a macrofilaricide, greater access to the adult worms that cause onchocerciasis and LF, or a validated surrogate model, is needed. Current efficacy models are very time-consuming and require large quantities of drug candidate.
Need for development of new drugs to treat these NTDs: Effective, safe, inexpensive and tolerable medicines are needed to treat populations affected by onchocerciasis and LF. Since entire communities are frequently treated using an MDA schedule, new drugs must be safe and effective for children, pregnant women, and other populations at high risk for complications.
Need for diagnostics for mapping, treatment, monitoring and/or surveillance of these NTDs: For onchocerciasis and LF, diagnostics are needed to determine when adult worms have been killed and MDA can be discontinued. For areas where Loa loa is co-endemic with onchocerciasis, a diagnostic is needed to detect individuals who harbor high levels of Loa loa microfilariae. New point-of-care diagnostics are also needed for STH and schistosomiasis. For diagnostics to have the greatest impact, one test or diagnostic platform should simultaneously diagnose multiple diseases, samples must be easy to collect and transport, and tests must be either point-of-care or have the ability to be batched for high-throughput analysis at regional laboratory centers.
What We Are Looking For:
We aim to generate novel approaches to treatment and control of onchocerciasis, LF, STH, and schistosomiasis. We seek technologies and innovations to improve detection of viable adult worms, to develop drug treatments that are safe, effective, and affordable, and interventions that interrupt transmission, with the ultimate goal of ridding the world of these infectious diseases.
Proposals must (i) have a testable hypothesis, (ii) include an associated plan for how the idea would be tested or validated, and (iii) yield interpretable and unambiguous data in Phase I, in order to be considered for Phase II funding.
A few examples of what we will consider for funding:
Strategies for multiple diseases:
- Strategies that combine mapping, monitoring, and/or surveillance of one disease with treatment of another, or other combinations of approaches that apply to more than one of the diseases of interest;
- Innovative and efficient methods for scale up and increased coverage of mass drug administration to treat multiple neglected diseases (mentioned above) at once;
- Creative and scalable approaches that increase the efficiency and effectiveness of mapping, monitoring, treatment, and/or surveillance including xenomonitoring and more environmentally acceptable snail control methods;
- Innovative ideas on sourcing and studying macrofilaria, which differ significantly from the current method of sacrificing and dissecting animals that have naturally become infected to retrieve worm specimens;
- New facile rapid in vivo models that are predictive of activity in humans;
- Innovative approaches to discovery of macrofilaricidal agents, especially for onchocerciasis, suitable for delivery through mass drug administration, and for use in Loa loa infected regions of the world;
- Platforms for screening new drug candidates;
- Innovative approaches to drug development for onchocerciasis or LF that target factors in the host leading to elimination of parasites;
- One test or diagnostic platform to simultaneously diagnose multiple diseases mentioned above - using a single clinical sample;
- Diagnostics of viable adult worm infection in onchocerciasis and LF;
- Semi-quantitative diagnostic to assess Loa loa microfilariae burden to screen and treat in areas that are co-endemic for onchocerciasis and Loa loa.
We will not consider funding for:
- Ideas that are not directly relevant to developing countries;
- Ideas that address diseases other than those listed in this call (onchocerciasis, lymphatic filariasis, Loa loa, schistosomiasis, and only the following soil-transmitted helminthes: ascariasis, trichuriasis, and hookworm disease);
- Ideas that provide only incremental improvements to current diagnostics, drugs, or techniques;
- Approaches to drug discovery that are limited to screening compounds for activity against one isolated target unless the target is pharmacologically validated, or unless the compounds to be tested can be advanced rapidly into clinical development (i.e. without further optimization);
- Drug discovery that applies only to schistosomiasis or STH;
- Diagnostics for onchocerciasis and LF that do not identify or utilize biomarkers specific to adult worms, or biomarkers of exposure or very early infection;
- Discovery and development of vaccines;
- Strategies that focus solely on vector control methods;
- Approaches that only provide treatment or symptomatic relief without breaking the infective cycle of the parasite;
- Social or educational interventions, including approaches focused on hygiene, sanitation, or environmental decontamination that do not directly apply to MDA or surveillance;
- Solely infrastructure or capacity-building initiatives;
- Basic research without clear relevance to the goals of this topic.