New Approaches in Model Systems, Diagnostics, and Drugs for Specific Neglected Tropical Diseases (Round 10)

Opportunity:

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) and of soil-transmitted helminthic (STH) infections (ascariasis, trichuriasis, and hookworm disease) . 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, and STH.

The Challenge:

Mass drug administration (MDA) campaigns form the bedrock of attempts to control or eliminate onchocerciasis, LF, and STH infections. 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, and therefore multiple rounds of treatment are required 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). Drugs used to treat STH are limited, and there is potential for resistance to emerge. We lack robust diagnostics and tools to determine when to stop MDA campaigns.

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 to support the control and elimination targets for lymphatic filariasis, onchocerciasis (river blindness) and soil-transmitted helminthic (STH) infections.

Some of the key challenges facing the development of drugs and diagnostics for these specific diseases are as follows:

• Drug development is hampered by lack of robust and facile model systems: For the discovery of a macrofilaricide, greater access to adult worms, 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, LF, and STH. Since entire communities are frequently treated using an MDA schedule, children, pregnant women, and other populations at high risk for complications, are likely to receive these drugs regularly.
• Need for diagnostics to detect the presence of viable adult worms in onchocerciasis, Loa loa, or lymphatic filariasis: For onchocerciasis, there is currently no method to determine when adult worms have been killed and MDA is no longer needed. In areas where Loa loa is co-endemic with onchocerciasis, MDA with ivermectin for treatment of onchocerciasis causes severe adverse effects in patients infected with Loa loa. Detection of individuals who harbor high levels of Loa loa infections would allow for targeted treatment of ivermectin avoiding these serious adverse events. A diagnostic test exists for adult worms in LF, but a new or improved test is needed.
• Need strategies to treat for multiple diseases: Many partnerships and programs are devoted to the control or elimination of a single neglected disease; however, people can be infected with more than one pathogen simultaneously. Since drugs currently donated by pharmaceutical partners are effective against several of these infections, major health gains as well as administrative efficiencies are achieved by coordinating efforts to address several diseases at once.

What We Are Looking For:

We aim to generate novel approaches to treatment and control of onchocerciasis, LF, and STH. 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. For example, a new macrofilaricide would reduce the number of cycles of mass drug administration required thus accelerating progress towards elimination of onchocerciasis and LF.

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:

• 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;
• Diagnostics of viable adult worm infection;
• 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;
• Innovative approaches to drug development that target factors in the host leading to elimination of parasites;
• New and innovative methods for mass drug administration and surveillance to manage and treat multiple of these neglected diseases at once;
• Innovative ways of treating STH infection, including probiotic methods.

We will not consider funding for:

• Ideas that are not directly relevant to developing countries;
• Ideas that are not applicable to the following diseases:
  • filarial diseases, specifically lymphatic filariasis and onchocerciasis, with the exception of strategies to detect Loa loa infection in areas co-endemic with onchocerciasis or
  • soil-transmitted helminthes, specifically ascariasis, trichuriasis, and hookworm disease;
• Approaches to treating STH that would be unique to one pathogen;
• Development of tools or strategies that apply only to schistosomiasis;
• Incremental improvements in current diagnostics or drugs;
• 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);
• Discovery and development of vaccines;
• Strategies that focus solely on vector control methods;
• Basic research without a clear relevance to the goals of this topic.