Challenges

**NOTE: This opportunity is only open to participants who registered for and attended the 2020 Grand Challenges Annual Meeting (virtual format).

<h2>THE OPPORTUNITY</h2>

The Grand Challenges Annual Meeting - held in <a href="https://grandchallenges.org/annual-meeting" target="_blank">11 countries</a> over the past 15 years and in a virtual format this year - fosters innovation and international collaboration to address the biggest challenges in global health and development. Our goal is to support a global community of problem solvers who work together to set an innovation agenda and do the breakthrough science to deliver on it. Recognizing the pressing global threat of COVID-19, this year's Annual Meeting will focus on how to accelerate transformational innovation for global health crises. The meeting will seek to facilitate collaboration among scientists, decision makers, and policymakers to discover, develop, and deploy the solutions needed to curb the COVID-19 pandemic, mitigate its impact, and prepare for future global health emergencies. Additionally, the meeting will explore how to harness the energy and lessons from COVID-19 to drive continued progress against a broad range of global health and development goals. Besides this Call-to-Action request for proposals from meeting participants, there are three public <a href="https://gcgh.grandchallenges.org/grant-opportunities" target="_blank">grant opportunities</a> addressing global health and development that are opening at the meeting.

<h2>THE CHALLENGE</h2>

The Call-to-Action provides an opportunity for Grand Challenges Annual Meeting participants to take action based on ideas they developed and people they met at the meeting. The <a href="https://gcgh.grandchallenges.org/grants/eyJzb3J0IjoiZGVzY2VuZGluZyIsInNvcnRGaWVsZCI6ImRhdGUiLCJudW1iZXJQZXJQYWdlIjoxMDAsInBhZ2VOdW1iZXIiOjB9/eyJ5ZWFycyI6W10sImNoYWxsZW5nZXMiOlsiMTI5Il0sInRlcm1zIjpbXSwiaW5pdGlhdGl2ZXMiOltdLCJsb2NhdGlvbnMiOltdfQ==" target="_blank">grants awarded</a> for the 2018 and 2019 Call-to-Action were for projects arising &nbsp;from diverse types of opportunities – as noted by applicants in their submitted proposals – to interact at the meeting and to bring together combinations of expertise and perspective to speed the impact of what would otherwise be separate work by individual investigators. We hope that interactive elements at this year's virtual meeting will still provide ways to catalyze collaborative grant applications and that the extra urgency of the meeting's focus this year will inspire projects with a goal and design that will yield a tangible solution to a key problem by the end of the grant.

Funding

Each meeting participant will have one opportunity to apply as the primary applicant for a USD $100,000 grant or a collaborative USD $200,000 grant, both with an 18-month grant duration. Collaborative awards require the participation of at least two meeting participants from different institutions. While restricted to one application as the primary applicant, meeting participants may participate as collaborators in multiple collaborative applications. Priority will be given to new or newly expanded collaborations, rather than to existing partners seeking new funding.

We will give highest priority to proposed projects that:

<ul>
	<li>Contribute to a network of creative people, anchored around the investigators and implementors who are closest to the problems in the countries most burdened by global health and development inequity and have the knowledge and perspective to direct the right approaches to the right parts of the problems to help ensure success – their collective action and directed energy is helping solve today's key problems in global health and development, while building a mechanism ready to solve tomorrow's</li>
	<li>Specifically address the meeting's goals and content around the response to the COVID-19 pandemic and beyond, noting that this funding opportunity is not designed to more broadly address COVID-19</li>
	<li>Are likely to yield a tangible answer to a question or solution to a problem within the grant term under the current and likely near-term constraints associated with the COVID-19 pandemic</li>
	<li>Are explicitly aligned with the content within the meeting's scientific tracks, noting that proposals will be reviewed based on their alignment with one primary track. Eligible scientific tracks for this Call-to-Action are listed below, and they include one separate scientific session (Novel Technologies for Global Health) as well as the entire Keystone Symposia Global Health Series conference overlapping with the Grand Challenges Annual Meeting. The Smart Farming Innovations track is not eligible, because it has its own separate <a href="https://gcgh.grandchallenges.org/grant-opportunities" target="_blank">request for proposals</a>.</li>
</ul>

Scientific tracks eligible for the Call-to-Action

<ul>
	<li>Addressing Challenges to Manage COVID-19: The Indian Experience - Addressing the need, the status, and the gaps that are unique to each solution and discussing the way forward for making all of these solutions accessible and affordable from an Indian perspective</li>
	<li>Applying a Translational Lens to Global Health - Exploring the use of translational tools in nutrition and COVID-19, including the challenges and opportunities from planning and executing clinical trials in a pandemic</li>
	<li>Global Partnerships &amp; Grand Challenges – Supporting local innovators solving local problems, helping build a critical mass of innovation champions linked through a global network to collectively address the most pressing global health and development challenges</li>
	<li>Leveraging Pathogen Genetic Sequencing - Sequencing SARS-CoV-2 during the COVID-19 pandemic, sequencing applied to epidemic and endemic pathogens, and building a suite of interoperable and open-source data analytics and visualization software packages for use in real-time epidemic and endemic disease control</li>
	<li>Optimizing Birth, Growth, and Development – Addressing the COVID-19 pandemic's direct and indirect effect on global health work around maternal, newborn, and child health, including pivoting resources during COVID-19, respiratory support in low- and middle-income countries, and studies of maternal (intrauterine) nutrition and fetal growth</li>
	<li>Repurposing Drugs for COVID-19: Approaches and Challenges – Exploring ongoing efforts to identify candidate drugs to repurpose for COVID-19 treatment and prophylaxis, including screening platforms and model systems</li>
	<li>Novel Technologies for Global Health – Showcasing development of the COVID-19 Cell Atlas and exploring the COVID-19 Human Tissue Atlas and a systems biology approach together with additional technologies</li>
	<li>Enabling Crop Analytics at Scale - Removing bottlenecks to large-scale collection, use, and sharing of ground truth data or processes for smallholder farmer applications</li>
	<li>Optimizing Nutrition for Maternal, Newborn, and Child Health (Keystone Symposia) – Emphasizing interdisciplinary research and connecting global nutrition and molecular nutrition experts</li>
</ul>

We will not consider funding approaches that:

<ul>
	<li>Are not explicitly aligned with the content within the meeting's scientific tracks eligible for this request for proposals that are listed above</li>
	<li>Are not accomplishable within the grant term under the current and likely near-term constraints associated with the COVID-19 pandemic</li>
</ul>

Note (added November 12, 2020): The Bill &amp; Melinda Gates Foundation will consider proposals targeting topics under the meeting scientific tracks and sessions listed in the request for proposals – the Radical Mental Health track and Leveraging Digital Technologies to Address Health Crises and Beyond track are not part of this particular request for proposals. Proposals submitted under the Global Partnerships &amp; Grand Challenges track should address one of the listed eligible meeting tracks or sessions and bring a specific focus on partnership.

Grand Challenges

**NOTE: This opportunity is only open to participants who registered for and attended the 2020 Grand Challenges Annual Meeting (virtual format).
<h2>THE OPPORTUNITY</h2>
The Grand Challenges Annual Meeting - held in <a href="https://grandchallenges.org/annual-meeting" target="_blank">11 countries</a> over the past 15 years and in a virtual format this year - fosters innovation and international collaboration to address the biggest challenges in global health and development. Our goal is to support a global community of problem solvers who work together to set an innovation agenda and do the breakthrough science to deliver on it. Recognizing the pressing global threat of COVID-19, this year's Annual Meeting will focus on how to accelerate transformational innovation for global health crises. The meeting will seek to facilitate collaboration among scientists, decision makers, and policymakers to discover, develop, and deploy the solutions needed to curb the COVID-19 pandemic, mitigate its impact, and prepare for future global health emergencies. Additionally, the meeting will explore how to harness the energy and lessons from COVID-19 to drive continued progress against a broad range of global health and development goals. Besides this Call-to-Action request for proposals from meeting participants, there are three public <a href="https://gcgh.grandchallenges.org/grant-opportunities" target="_blank">grant opportunities</a> addressing global health and development that are opening at the meeting.
<h2>THE CHALLENGE</h2>
The Call-to-Action provides an opportunity for Grand Challenges Annual Meeting participants to take action based on ideas they developed and people they met at the meeting. The <a href="https://gcgh.grandchallenges.org/grants/eyJzb3J0IjoiZGVzY2VuZGluZyIsInNvcnRGaWVsZCI6ImRhdGUiLCJudW1iZXJQZXJQYWdlIjoxMDAsInBhZ2VOdW1iZXIiOjB9/eyJ5ZWFycyI6W10sImNoYWxsZW5nZXMiOlsiMTI5Il0sInRlcm1zIjpbXSwiaW5pdGlhdGl2ZXMiOltdLCJsb2NhdGlvbnMiOltdfQ==" target="_blank">grants awarded</a> for the 2018 and 2019 Call-to-Action were for projects arising  from diverse types of opportunities – as noted by applicants in their submitted proposals – to interact at the meeting and to bring together combinations of expertise and perspective to speed the impact of what would otherwise be separate work by individual investigators. We hope that interactive elements at this year's virtual meeting will still provide ways to catalyze collaborative grant applications and that the extra urgency of the meeting's focus this year will inspire projects with a goal and design that will yield a tangible solution to a key problem by the end of the grant.
Funding
Each meeting participant will have one opportunity to apply as the primary applicant for a USD $100,000 grant or a collaborative USD $200,000 grant, both with an 18-month grant duration. Collaborative awards require the participation of at least two meeting participants from different institutions. While restricted to one application as the primary applicant, meeting participants may participate as collaborators in multiple collaborative applications. Priority will be given to new or newly expanded collaborations, rather than to existing partners seeking new funding.
We will give highest priority to proposed projects that:
<ul><li>Contribute to a network of creative people, anchored around the investigators and implementors who are closest to the problems in the countries most burdened by global health and development inequity and have the knowledge and perspective to direct the right approaches to the right parts of the problems to help ensure success – their collective action and directed energy is helping solve today's key problems in global health and development, while building a mechanism ready to solve tomorrow's</li>
<li>Specifically address the meeting's goals and content around the response to the COVID-19 pandemic and beyond, noting that this funding opportunity is not designed to more broadly address COVID-19</li>
<li>Are likely to yield a tangible answer to a question or solution to a problem within the grant term under the current and likely near-term constraints associated with the COVID-19 pandemic</li>
<li>Are explicitly aligned with the content within the meeting's scientific tracks, noting that proposals will be reviewed based on their alignment with one primary track. Eligible scientific tracks for this Call-to-Action are listed below, and they include one separate scientific session (Novel Technologies for Global Health) as well as the entire Keystone Symposia Global Health Series conference overlapping with the Grand Challenges Annual Meeting. The Smart Farming Innovations track is not eligible, because it has its own separate <a href="https://gcgh.grandchallenges.org/grant-opportunities" target="_blank">request for proposals</a>.</li>
</ul>Scientific tracks eligible for the Call-to-Action
<ul><li>Addressing Challenges to Manage COVID-19: The Indian Experience - Addressing the need, the status, and the gaps that are unique to each solution and discussing the way forward for making all of these solutions accessible and affordable from an Indian perspective</li>
<li>Applying a Translational Lens to Global Health - Exploring the use of translational tools in nutrition and COVID-19, including the challenges and opportunities from planning and executing clinical trials in a pandemic</li>
<li>Global Partnerships &amp; Grand Challenges – Supporting local innovators solving local problems, helping build a critical mass of innovation champions linked through a global network to collectively address the most pressing global health and development challenges</li>
<li>Leveraging Pathogen Genetic Sequencing - Sequencing SARS-CoV-2 during the COVID-19 pandemic, sequencing applied to epidemic and endemic pathogens, and building a suite of interoperable and open-source data analytics and visualization software packages for use in real-time epidemic and endemic disease control</li>
<li>Optimizing Birth, Growth, and Development – Addressing the COVID-19 pandemic's direct and indirect effect on global health work around maternal, newborn, and child health, including pivoting resources during COVID-19, respiratory support in low- and middle-income countries, and studies of maternal (intrauterine) nutrition and fetal growth</li>
<li>Repurposing Drugs for COVID-19: Approaches and Challenges – Exploring ongoing efforts to identify candidate drugs to repurpose for COVID-19 treatment and prophylaxis, including screening platforms and model systems</li>
<li>Novel Technologies for Global Health – Showcasing development of the COVID-19 Cell Atlas and exploring the COVID-19 Human Tissue Atlas and a systems biology approach together with additional technologies</li>
<li>Enabling Crop Analytics at Scale - Removing bottlenecks to large-scale collection, use, and sharing of ground truth data or processes for smallholder farmer applications</li>
<li>Optimizing Nutrition for Maternal, Newborn, and Child Health (Keystone Symposia) – Emphasizing interdisciplinary research and connecting global nutrition and molecular nutrition experts</li>
</ul>We will not consider funding approaches that:
<ul><li>Are not explicitly aligned with the content within the meeting's scientific tracks eligible for this request for proposals that are listed above</li>
<li>Are not accomplishable within the grant term under the current and likely near-term constraints associated with the COVID-19 pandemic</li>
</ul>Note (added November 12, 2020): The Bill &amp; Melinda Gates Foundation will consider proposals targeting topics under the meeting scientific tracks and sessions listed in the request for proposals – the Radical Mental Health track and Leveraging Digital Technologies to Address Health Crises and Beyond track are not part of this particular request for proposals. Proposals submitted under the Global Partnerships &amp; Grand Challenges track should address one of the listed eligible meeting tracks or sessions and bring a specific focus on partnership.

**NOTE: This opportunity is only open to participants who registered for and attended the 2020 Grand Challenges Annual Meeting (virtual format).

2020 Grand Challenges Annual Meeting Call-to-Action

<h2>THE OPPORTUNITY</h2>

Embracing the tradition of microbial fermentation to transform locally available foods into naturally vitamin-fortified, toxin-free, flavorful, and shelf-stable products could empower local communities to mitigate the impact of COVID-19 on supply chain/food security and improve the health and nutrition of mothers and children in the most vulnerable settings. Historical advances in food processing have largely employed strategies that involve supplementation with micronutrients and additives to improve nutritional content and stability, but these approaches require highly centralized supply chains.<a href="#_edn1" name="_ednref1" title="">1</a> In addition, chemical additives for preservation, flavor and texture purposes may have unintended consequences of contributing to compromised gut health and increased prevalence of metabolic disease (hypertension, diabetes, obesity).<a href="#_edn2" name="_ednref2" title="">2</a>

Fermentation is an ancient practice through which locally-sourced food substrates can be transformed naturally by environmentally occurring microbes. These processes are thought to be intricately intertwined with human biology, and it is hypothesized that our primate ancestors adapted to natural fermentation processes millions of years ago.<a href="#_edn3" name="_ednref3" title="">3</a> While many fermented foods (e.g., yogurt, cheese, coffee and alcohol) remain popular, certain types of fermentation are a dwindling art in many settings, representing a loss of cultural heritage and a natural way to improve the qualities of foods across several distinct axes<a href="#_edn4" name="_ednref4" title="">4</a>:

<ul>
	<li>Improve macro- and micro-nutrient quality and bioavailability (e.g., B vitamins)<a href="#_edn5" name="_ednref5" title="">5</a></li>
	<li>Remove anti-nutrients (mycotoxins; phytates, which decrease iron availability)<a href="#_edn6" name="_ednref6" title="">6</a></li>
	<li>Transform taste, flavor and texture<a href="#_edn7" name="_ednref7" title="">7</a></li>
	<li>Improve the preservation and stability of foods by excluding pathogens (through lowering pH, bacteriocin production, removing simple sugars)<a href="#_edn8" name="_ednref8" title="">8</a></li>
</ul>

Historical approaches of macronutrient supplementation and micronutrient fortification have been the basis for transformative global health nutrition interventions, ultimately saving millions of lives each year.<a href="#_edn9" name="_ednref9" title="">9</a> These approaches have also focused on pediatric populations, although recent work suggests that solutions targeting maternal nutrition may be even more impactful on pediatric health and have the important benefit of also improving maternal health.<a href="#_edn10" name="_ednref10" title="">10</a> Given limited access of nutritional interventions by the populations in greatest need<a href="#_edn11" name="_ednref11" title="">11</a> and formulations that are not optimized for gut and metabolic health,<a href="#_edn12" name="_ednref12" title="">12</a> malnutrition remains one of the most significant global health problems facing society today.

COVID-19, with disruption of supply chains and a predilection for individuals with metabolic diseases, has served to increase the urgency for identifying locally-sourceable health-promoting maternal nutrition solutions that treat undernutrition without increasing the risk of obesity, diabetes, and hypertension. Ironically, it may be that these new solutions already exist in the form of ancient traditions reevaluated and revalued through a next-generation and evidence-based lens.

<h2>THE CHALLENGE</h2>

Beyond many of the well-known examples of microbial fermentation, the vast majority of fermentation processes around the world remain uncharacterized and their potential human health benefits are unknown. These ancient practices may hold the key to impactful and locally targeted nutritional interventions that combine tradition and science to tackle malnutrition. Rigorous scientific evaluation has been limited and characterization to understand potential benefits could be pursued to validate and underscore the importance of preserving this cultural heritage.

What we are looking for

This call seeks to fund pilot studies that investigate the biological effect of traditional locally fermented foods on key microbiome, gut, and health biomarkers in local populations. The goal is to provide investigators in Sub-Saharan Africa and South Asia with the resources to build local capacity to investigate fermented foods as novel maternal nutrition interventions. In particular, sequencing technology – a transformative tool that has enabled in-depth investigation of microbial communities – will be provided to all investigators to democratize the ability to investigate foods and health effects, and build local capacity. Ultimately, the goal is to empower local communities to develop geography and culture specific interventions powered by fermentation, in country.

Proposals should specifically address the following core elements, but investigators are welcome to propose creative strategies and designs to accomplish the core goals of this call and account for local cultural traditions. In addition, it is expected that study design will be refined after award through a collaborative forum invovling other awardees and the foundation:

<ul>
	<li>Identification of a local (geographic/cultural) fermented food for study
	<ul>
		<li>Many foods may not be colloquially considered to be fermented, but any process that incorporates biotransformation by microbes is acceptable</li>
		<li>Living microbes were actively employed as a part of the fermentation process and final product consumed retains live organisms</li>
		<li>Fermentation may be driven by known organisms, e.g. bacterial Lactobacillus sp., fungal Aspergillus sp., or less studied food-borne organisms</li>
		<li>Must be plant-based (e.g., grain or staple crop). Plant-based fermented foods are a requirement due to lower cost of goods for scalability compared to animal-based foods</li>
		<li>Food with a cultural precedent in maternal nutrition are of high interest</li>
		<li>The food being investigated must be produced in compliance under all relevant local food manufacturing regulations and modern food safety practices</li>
	</ul>
	</li>
	<li>Pilot study design for longitudinal intervention study for understanding the effect of the fermented food in a naïve (no, or limited, fermented food consumption) population
	<ul>
		<li>The target population should be women of reproductive age, and a naive population not currently consuming or with limited consumption of the target fermented food to better understanding the biological effects of the food itself. Different subpopulations (urban vs. rural, various cultural groups, different sub-geographies within a country, etc.) with lower consumption of the target fermented food could be specifically targeted. If populations traditionally consuming fermented foods are considered, it would be important to undertake a baseline to understand the additive effect after consumption of "target foods".</li>
		<li>Longitudinal intervention studies are recommended, with small cohort sizes (20-30 participants) and sustained exposure to the fermented food (e.g., at least daily &gt;5 days) but ultimately the study design should be motivated by the end goal of characterizing the effects of the food on maternal nutrition through host (blood and fecal) and gut microbiome biomarkers.</li>
		<li>A template dietary questionnaire will be provided and can be customized to local foods and traditions</li>
		<li>Existing infrastructure that may improve ability to execute on the proposed study can and should be highlighted</li>
	</ul>
	</li>
	<li>Biological sample biobanking and characterization before and after food intervention
	<ul>
		<li>Fermented foods themselves (metagenomic analysis of fungal [ITS] and bacterial [16S] constituents), potentially across distinct batches and preparation methods</li>
		<li>Serial fecal samples from participants (metagenomic analysis; lipocalin-2, myeloperoxidase, and calprotectin of particular interest)</li>
		<li>Serial serum/blood samples from participants (Iron studies, B-vitamin analysis; lipocalin-2, IL-6 and CRP are of particular interest given the association of inflammation biomarkers with maternal nutrition and birth outcomes) <a href="#_edn13" name="_ednref13" title="">13</a></li>
		<li>Other characterization approaches of food (including effects of fermentation on the nutritional profile) or biological samples using conventional or existing techniques</li>
		<li>Proposals should specifically address existing laboratory infrastructure and capacity for integrating next generation sequencing into existing laboratory workflows (e.g. nucleic acid extraction, PCR, etc.)</li>
	</ul>
	</li>
</ul>

As a part of this 18 month Grand Challenges award, sequencing platforms (funded with up to USD $40K for sequencing technology out of this USD $200K award) and training will be provided to investigators to enable local sequence-based characterization of the fermented foods and microbiome effects. The output of this study will be pilot data evaluating the biological effect of traditional fermented foods on gut, microbiome and health axes in local populations. Any additional points on the sustainability of the intervention and the empowerment of local champions to continue the work, integrating with state and national level Maternal, Infant and Young Child Nutrition (MIYCN) programs would also be welcome.

What we will not consider funding 

<ul>
	<li>Investigators and institutions not located in Sub-Saharan Africa or South Asia</li>
	<li>Investigators not studying local foods (specific to the culture or geography)</li>
	<li>Investigators not investigating local populations</li>
	<li>Proposals that do not contain a human interventional study targeted towards women of reproductive age. No studies on child populations will be funded.</li>
	<li>Proposals not addressing all the stated study design criteria above</li>
	<li>Proposals that do not demonstrate a capacity to perform the research proposed; investigators should describe capacity for human studies, sample collection, processing and storage, including but not limited to:
	<ul>
		<li>Relevant approvals from local authorities/institutions/Government on the research methodology and sharing of data among collaborators, eventually for global access</li>
		<li>Data analysis and adherence to relevant local laws/ policies pertaining to data sharing, hosting and data protection.</li>
		<li>Secure handling of personally identifiable information data and research results</li>
		<li>Institutional Review Boards or equivalent human study regulation strategy</li>
		<li>Sample collection capacity/protocols and capacity for sample storage</li>
		<li>Ability to perform human biological sample characterization as proposed</li>
	</ul>
	</li>
</ul>

___________________________________

References

<a href="#_ednref1" name="_edn1" title="">[1]</a> <a href="https://www.fao.org/3/a-i3953e.pdf" target="_blank">https://www.fao.org/3/a-i3953e.pdf</a>

<a href="#_ednref2" name="_edn2" title="">[2]</a> <a href="https://www.nature.com/articles/nature14232/" target="_blank">https://www.nature.com/articles/nature14232/</a>

<a href="#_ednref3" name="_edn3" title="">[3]</a> <a href="https://www.pnas.org/content/112/2/458" target="_blank">https://www.pnas.org/content/112/2/458</a>

<a href="#_ednref4" name="_edn4" title="">[4]</a> <a href="https://www.sciencedirect.com/science/article/pii/S0958166919300990" target="_blank">https://www.sciencedirect.com/science/article/pii/S0958166919300990</a>

<a href="#_ednref5" name="_edn5" title="">[5]</a> <a href="https://academic.oup.com/advances/article/4/4/463/4259633" target="_blank">https://academic.oup.com/advances/article/4/4/463/4259633</a>

<a href="#_ednref6" name="_edn6" title="">[6]</a> <a href="https://www.sciencedirect.com/science/article/abs/pii/0963996994900965" target="_blank">https://www.sciencedirect.com/science/article/abs/pii/0963996994900965</a>

<a href="#_ednref7" name="_edn7" title="">[7]</a> <a href="https://ifst.onlinelibrary.wiley.com/doi/full/10.1046/j.1365-2621.1999.00245.x" target="_blank">https://ifst.onlinelibrary.wiley.com/doi/full/10.1046/j.1365-2621.1999.00245.x</a>

<a href="#_ednref8" name="_edn8" title="">[8]</a> <a href="https://www.karger.com/Article/Abstract/104752" target="_blank">https://www.karger.com/Article/Abstract/104752</a>

<a href="#_ednref9" name="_edn9" title="">[9]</a> <a href="https://link.springer.com/article/10.1186/2046-4053-2-67" target="_blank">https://link.springer.com/article/10.1186/2046-4053-2-67</a>

<a href="#_ednref10" name="_edn10" title="">[10]</a> <a href="https://academic.oup.com/ajcn/article/109/2/457/5307124" target="_blank">https://academic.oup.com/ajcn/article/109/2/457/5307124</a>

<a href="#_ednref11" name="_edn11" title="">[11]</a> <a href="https://www.who.int/maternal_child_adolescent/topics/child/malnutrition/en/" target="_blank">https://www.who.int/maternal_child_adolescent/topics/child/malnutrition/en/</a>

<a href="#_ednref12" name="_edn12" title="">[12]</a> <a href="https://science.sciencemag.org/content/365/6449/eaau4732" target="_blank">https://science.sciencemag.org/content/365/6449/eaau4732</a>

<a href="#_ednref13" name="_edn13" title="">[13]</a> <a href="https://pubmed.ncbi.nlm.nih.gov/28274163/" target="_blank">https://pubmed.ncbi.nlm.nih.gov/28274163/</a>

<h2>THE OPPORTUNITY</h2>
Embracing the tradition of microbial fermentation to transform locally available foods into naturally vitamin-fortified, toxin-free, flavorful, and shelf-stable products could empower local communities to mitigate the impact of COVID-19 on supply chain/food security and improve the health and nutrition of mothers and children in the most vulnerable settings. Historical advances in food processing have largely employed strategies that involve supplementation with micronutrients and additives to improve nutritional content and stability, but these approaches require highly centralized supply chains.<a href="#_edn1" name="_ednref1" title="" id="_ednref1">1</a> In addition, chemical additives for preservation, flavor and texture purposes may have unintended consequences of contributing to compromised gut health and increased prevalence of metabolic disease (hypertension, diabetes, obesity).<a href="#_edn2" name="_ednref2" title="" id="_ednref2">2</a>
Fermentation is an ancient practice through which locally-sourced food substrates can be transformed naturally by environmentally occurring microbes. These processes are thought to be intricately intertwined with human biology, and it is hypothesized that our primate ancestors adapted to natural fermentation processes millions of years ago.<a href="#_edn3" name="_ednref3" title="" id="_ednref3">3</a> While many fermented foods (e.g., yogurt, cheese, coffee and alcohol) remain popular, certain types of fermentation are a dwindling art in many settings, representing a loss of cultural heritage and a natural way to improve the qualities of foods across several distinct axes<a href="#_edn4" name="_ednref4" title="" id="_ednref4">4</a>:
<ul><li>Improve macro- and micro-nutrient quality and bioavailability (e.g., B vitamins)<a href="#_edn5" name="_ednref5" title="" id="_ednref5">5</a></li>
<li>Remove anti-nutrients (mycotoxins; phytates, which decrease iron availability)<a href="#_edn6" name="_ednref6" title="" id="_ednref6">6</a></li>
<li>Transform taste, flavor and texture<a href="#_edn7" name="_ednref7" title="" id="_ednref7">7</a></li>
<li>Improve the preservation and stability of foods by excluding pathogens (through lowering pH, bacteriocin production, removing simple sugars)<a href="#_edn8" name="_ednref8" title="" id="_ednref8">8</a></li>
</ul>Historical approaches of macronutrient supplementation and micronutrient fortification have been the basis for transformative global health nutrition interventions, ultimately saving millions of lives each year.<a href="#_edn9" name="_ednref9" title="" id="_ednref9">9</a> These approaches have also focused on pediatric populations, although recent work suggests that solutions targeting maternal nutrition may be even more impactful on pediatric health and have the important benefit of also improving maternal health.<a href="#_edn10" name="_ednref10" title="" id="_ednref10">10</a> Given limited access of nutritional interventions by the populations in greatest need<a href="#_edn11" name="_ednref11" title="" id="_ednref11">11</a> and formulations that are not optimized for gut and metabolic health,<a href="#_edn12" name="_ednref12" title="" id="_ednref12">12</a> malnutrition remains one of the most significant global health problems facing society today.
COVID-19, with disruption of supply chains and a predilection for individuals with metabolic diseases, has served to increase the urgency for identifying locally-sourceable health-promoting maternal nutrition solutions that treat undernutrition without increasing the risk of obesity, diabetes, and hypertension. Ironically, it may be that these new solutions already exist in the form of ancient traditions reevaluated and revalued through a next-generation and evidence-based lens.
<h2>THE CHALLENGE</h2>
Beyond many of the well-known examples of microbial fermentation, the vast majority of fermentation processes around the world remain uncharacterized and their potential human health benefits are unknown. These ancient practices may hold the key to impactful and locally targeted nutritional interventions that combine tradition and science to tackle malnutrition. Rigorous scientific evaluation has been limited and characterization to understand potential benefits could be pursued to validate and underscore the importance of preserving this cultural heritage.
What we are looking for
This call seeks to fund pilot studies that investigate the biological effect of traditional locally fermented foods on key microbiome, gut, and health biomarkers in local populations. The goal is to provide investigators in Sub-Saharan Africa and South Asia with the resources to build local capacity to investigate fermented foods as novel maternal nutrition interventions. In particular, sequencing technology – a transformative tool that has enabled in-depth investigation of microbial communities – will be provided to all investigators to democratize the ability to investigate foods and health effects, and build local capacity. Ultimately, the goal is to empower local communities to develop geography and culture specific interventions powered by fermentation, in country.
Proposals should specifically address the following core elements, but investigators are welcome to propose creative strategies and designs to accomplish the core goals of this call and account for local cultural traditions. In addition, it is expected that study design will be refined after award through a collaborative forum invovling other awardees and the foundation:
<ul><li>Identification of a local (geographic/cultural) fermented food for study
<ul><li>Many foods may not be colloquially considered to be fermented, but any process that incorporates biotransformation by microbes is acceptable</li>
<li>Living microbes were actively employed as a part of the fermentation process and final product consumed retains live organisms</li>
<li>Fermentation may be driven by known organisms, e.g. bacterial Lactobacillus sp., fungal Aspergillus sp., or less studied food-borne organisms</li>
<li>Must be plant-based (e.g., grain or staple crop). Plant-based fermented foods are a requirement due to lower cost of goods for scalability compared to animal-based foods</li>
<li>Food with a cultural precedent in maternal nutrition are of high interest</li>
<li>The food being investigated must be produced in compliance under all relevant local food manufacturing regulations and modern food safety practices</li>
</ul></li>
<li>Pilot study design for longitudinal intervention study for understanding the effect of the fermented food in a naïve (no, or limited, fermented food consumption) population
<ul><li>The target population should be women of reproductive age, and a naive population not currently consuming or with limited consumption of the target fermented food to better understanding the biological effects of the food itself. Different subpopulations (urban vs. rural, various cultural groups, different sub-geographies within a country, etc.) with lower consumption of the target fermented food could be specifically targeted. If populations traditionally consuming fermented foods are considered, it would be important to undertake a baseline to understand the additive effect after consumption of "target foods".</li>
<li>Longitudinal intervention studies are recommended, with small cohort sizes (20-30 participants) and sustained exposure to the fermented food (e.g., at least daily &gt;5 days) but ultimately the study design should be motivated by the end goal of characterizing the effects of the food on maternal nutrition through host (blood and fecal) and gut microbiome biomarkers.</li>
<li>A template dietary questionnaire will be provided and can be customized to local foods and traditions</li>
<li>Existing infrastructure that may improve ability to execute on the proposed study can and should be highlighted</li>
</ul></li>
<li>Biological sample biobanking and characterization before and after food intervention
<ul><li>Fermented foods themselves (metagenomic analysis of fungal [ITS] and bacterial [16S] constituents), potentially across distinct batches and preparation methods</li>
<li>Serial fecal samples from participants (metagenomic analysis; lipocalin-2, myeloperoxidase, and calprotectin of particular interest)</li>
<li>Serial serum/blood samples from participants (Iron studies, B-vitamin analysis; lipocalin-2, IL-6 and CRP are of particular interest given the association of inflammation biomarkers with maternal nutrition and birth outcomes) <a href="#_edn13" name="_ednref13" title="" id="_ednref13">13</a></li>
<li>Other characterization approaches of food (including effects of fermentation on the nutritional profile) or biological samples using conventional or existing techniques</li>
<li>Proposals should specifically address existing laboratory infrastructure and capacity for integrating next generation sequencing into existing laboratory workflows (e.g. nucleic acid extraction, PCR, etc.)</li>
</ul></li>
</ul>As a part of this 18 month Grand Challenges award, sequencing platforms (funded with up to USD $40K for sequencing technology out of this USD $200K award) and training will be provided to investigators to enable local sequence-based characterization of the fermented foods and microbiome effects. The output of this study will be pilot data evaluating the biological effect of traditional fermented foods on gut, microbiome and health axes in local populations. Any additional points on the sustainability of the intervention and the empowerment of local champions to continue the work, integrating with state and national level Maternal, Infant and Young Child Nutrition (MIYCN) programs would also be welcome.
What we will not consider funding 
<ul><li>Investigators and institutions not located in Sub-Saharan Africa or South Asia</li>
<li>Investigators not studying local foods (specific to the culture or geography)</li>
<li>Investigators not investigating local populations</li>
<li>Proposals that do not contain a human interventional study targeted towards women of reproductive age. No studies on child populations will be funded.</li>
<li>Proposals not addressing all the stated study design criteria above</li>
<li>Proposals that do not demonstrate a capacity to perform the research proposed; investigators should describe capacity for human studies, sample collection, processing and storage, including but not limited to:
<ul><li>Relevant approvals from local authorities/institutions/Government on the research methodology and sharing of data among collaborators, eventually for global access</li>
<li>Data analysis and adherence to relevant local laws/ policies pertaining to data sharing, hosting and data protection.</li>
<li>Secure handling of personally identifiable information data and research results</li>
<li>Institutional Review Boards or equivalent human study regulation strategy</li>
<li>Sample collection capacity/protocols and capacity for sample storage</li>
<li>Ability to perform human biological sample characterization as proposed</li>
</ul></li>
</ul>___________________________________
References
<a href="#_ednref1" name="_edn1" title="" id="_edn1">[1]</a> <a href="https://www.fao.org/3/a-i3953e.pdf" target="_blank">https://www.fao.org/3/a-i3953e.pdf</a>
<a href="#_ednref2" name="_edn2" title="" id="_edn2">[2]</a> <a href="https://www.nature.com/articles/nature14232/" target="_blank">https://www.nature.com/articles/nature14232/</a>
<a href="#_ednref3" name="_edn3" title="" id="_edn3">[3]</a> <a href="https://www.pnas.org/content/112/2/458" target="_blank">https://www.pnas.org/content/112/2/458</a>
<a href="#_ednref4" name="_edn4" title="" id="_edn4">[4]</a> <a href="https://www.sciencedirect.com/science/article/pii/S0958166919300990" target="_blank">https://www.sciencedirect.com/science/article/pii/S0958166919300990</a>
<a href="#_ednref5" name="_edn5" title="" id="_edn5">[5]</a> <a href="https://academic.oup.com/advances/article/4/4/463/4259633" target="_blank">https://academic.oup.com/advances/article/4/4/463/4259633</a>
<a href="#_ednref6" name="_edn6" title="" id="_edn6">[6]</a> <a href="https://www.sciencedirect.com/science/article/abs/pii/0963996994900965" target="_blank">https://www.sciencedirect.com/science/article/abs/pii/0963996994900965</a>
<a href="#_ednref7" name="_edn7" title="" id="_edn7">[7]</a> <a href="https://ifst.onlinelibrary.wiley.com/doi/full/10.1046/j.1365-2621.1999.00245.x" target="_blank">https://ifst.onlinelibrary.wiley.com/doi/full/10.1046/j.1365-2621.1999.00245.x</a>
<a href="#_ednref8" name="_edn8" title="" id="_edn8">[8]</a> <a href="https://www.karger.com/Article/Abstract/104752" target="_blank">https://www.karger.com/Article/Abstract/104752</a>
<a href="#_ednref9" name="_edn9" title="" id="_edn9">[9]</a> <a href="https://link.springer.com/article/10.1186/2046-4053-2-67" target="_blank">https://link.springer.com/article/10.1186/2046-4053-2-67</a>
<a href="#_ednref10" name="_edn10" title="" id="_edn10">[10]</a> <a href="https://academic.oup.com/ajcn/article/109/2/457/5307124" target="_blank">https://academic.oup.com/ajcn/article/109/2/457/5307124</a>
<a href="#_ednref11" name="_edn11" title="" id="_edn11">[11]</a> <a href="https://www.who.int/maternal_child_adolescent/topics/child/malnutrition/en/" target="_blank">https://www.who.int/maternal_child_adolescent/topics/child/malnutrition/en/</a>
<a href="#_ednref12" name="_edn12" title="" id="_edn12">[12]</a> <a href="https://science.sciencemag.org/content/365/6449/eaau4732" target="_blank">https://science.sciencemag.org/content/365/6449/eaau4732</a>
<a href="#_ednref13" name="_edn13" title="" id="_edn13">[13]</a> <a href="https://pubmed.ncbi.nlm.nih.gov/28274163/" target="_blank">https://pubmed.ncbi.nlm.nih.gov/28274163/</a>

Grand Challenges seeks pilot studies that investigate the biological effect of traditional locally fermented foods on key microbiome, gut, and health biomarkers in local populations. The goal is to provide investigators in Sub-Saharan Africa and South Asia with the resources to build local capacity to investigate fermented foods as novel maternal nutrition interventions.

Integrating Tradition and Technology for Fermented Foods for Maternal Nutrition

<h2>THE OPPORTUNITY</h2>

At the Bill &amp; Melinda Gates Foundation, we believe that malaria eradication within a generation is possible. We recognize that in order to achieve this, National Malaria Control Programs (NMCPs) must be empowered to use timely, high-quality data to inform their malaria strategic planning, decision-making, program implementation, and evaluation. As we work to sustain the decline in incidence rates that have marked the last fifteen years of malaria control, this concept of data-to-action has never been more important.

Our vision for data-to-action, recently endorsed by WHO’s Malaria Policy Advisory Committee (MPAC), is one of stratification and sub-national tailoring. In the first step, multiple data sources – from geospatial to epidemiological data – are used to define district-level strata within a country. Next, additional data types are used as the input to mathematical models that output the optimal package of interventions that result in maximum malaria burden reduction within a given resource envelope. The success of stratification and sub-national tailoring is highly dependent on the underlying data, which may not always be complete, high-quality, and / or timely. We are therefore exploring new data streams that might improve our understanding of factors driving changes in malaria epidemiology or be used to optimize the choice of interventions modelled. One of these new data streams is serological, genetic, and / or genomic data which arises from malaria molecular surveillance.

Malaria Molecular Surveillance (MMS) is an umbrella term which describes the use of molecular biology approaches – from serology to genotyping to whole genome sequencing (WGS) – to interrogate parasite and / or vector populations in order to derive epidemiologically actionable information. MMS does not include research-oriented genetic and genomic investigations, such as studies using genomics to investigate parasite or mosquito biology. Rather, the emphasis is on analyses that can directly influence malaria control policy and practice. In addition to the laboratory techniques used, MMS also includes the bioinformatics tools and resources necessary to process, interpret, and share the resulting data.

<h2>THE CHALLENGE</h2>

Initial work in the MMS space focused on methods development and proof-of-concept pilot studies. Now, the tools and analyses are maturing, the infrastructure is in place, and the time-to-result is much shorter, meaning that MMS is beginning to influence program planning and execution. In elimination settings, genetics has been deployed in focused investigations of malaria importations. In higher-burden settings, MMS is being used to visualize the spatio-temporal spread of antimalarial drug resistance markers, influencing treatment guidelines, and to track the effect of different interventions on parasite genetic diversity as a surrogate measure of transmission intensity.

In June 2019, a WHO Technical Consultation on the role of parasite and vector genetic and genomic data in malaria surveillance (<a href="https://www.who.int/malaria/mpac/mpac-october2019-session7-report-consultation-on-genomics.pdf" target="_blank">workshop report</a>), stakeholders from MMS community – both on the research and programmatic sides – gathered with the goal of identifying those MMS use cases for which sufficient evidence exists to recommend routine use for malaria control and elimination, and those for which more upstream research is needed in order to generate a broader evidence base for future recommendations.

The list of use cases that are ready or near ready (marked with an asterisk*) for programmatic deployment includes:

<ul>
	<li>Detect drug resistance: monitor the prevalence/frequency of molecular markers of drug resistance to inform intervention selection, treatment guidelines, and surveillance</li>
	<li>Detect hrp2/3 deletions: monitor the prevalence/frequency of hrp2/3 deletion affecting RDT efficacy to inform diagnostic selection</li>
	<li>Assess drug resistance gene flow: determine the origins of drug resistance markers and monitor their spread within/among regions and parasite populations to inform containment strategies and regional policies around intervention selection, treatment guidelines, and surveillance*</li>
	<li>Predict emerging resistance: detect signatures of positive selection suggesting emerging resistance to inform intervention selection, treatment guidelines, and surveillance*</li>
	<li>Identify local transmission: identify focal areas of high transmission and clusters of infections to inform resource deployment*</li>
	<li>Distinguish local and imported cases: in elimination settings, classify cases as imported or otherwise for case investigation and elimination certification*</li>
	<li>Reconstruct transmission chains: elucidate contributing factors (e.g. seasonality, migrants, asymptomatic cases, and highly infectious individuals) to ongoing transmission patterns to inform intervention selection, resource deployment, surveillance, and case investigation*</li>
	<li>Determine connectivity of parasite populations: assess degree to which transmission is linked among regions due to linked parasite populations to inform program planning and resource deployment*</li>
	<li>Survey for allelic variation in target sites for gene drive: determine whether SNPs that would prevent CRISPR site recognition exist in wild populations to optimize gene drive release planning*</li>
</ul>

As MMS transitions from proof-of-concept work in academic institutions to operational reality in NMCPs, Ministries of Health, and National Public Health Institutes, the challenge lies in conducting the work in a way that engages country programs and malaria decision-makers and that empowers them to understand and use their data actively for programmatic decision-making.

The purpose of this call is therefore to identify new and innovative approaches to integrating malaria molecular surveillance into malaria surveillance and programmatic decision-making in malaria endemic countries. 

What we are looking for:

We are looking for innovative proposals that will use MMS data to enable NMCPs to inform their national and sub-national surveillance efforts, national strategic planning, and/or intervention implementation. These may include proposals that: create or expand laboratory, bioinformatics, and data interpretation capacity within NMCPs or at institutions closely affiliated with an NMCP; create or implement tools for communicating and sharing parasite and/or vector molecular surveillance data; and/or build relationships between groups with MMS capacity and NMCP partners. Proposals should target the use cases identified above that are ready or near-to-ready for programmatic deployment. We do not want respondents to be generating MMS data for research purposes; rather, the intent of this call is to support the application of MMS approaches to routine malaria surveillance and planning within NMCPs, Ministries of Health, or similar organizations.

While we welcome respondents from around the world, we are particularly interested in proposals from respondents working in high-burden malaria settings. All proposals must include a principal investigator or co-investigator from a malaria-endemic country.

Winning proposals should:

<ul>
	<li>Explain the rationale for and potential benefits of using MMS data in their setting</li>
	<li>Address one or more of the use cases outlined in the Challenge section above</li>
	<li>Include representation from the NMCP, Ministry of Health (MOH) representation, government agency or healthcare provider responsible for malaria control in the country / region</li>
	<li>Describe how MMS information arising from the project will be shared with the NMCP, MOH and other key stakeholders</li>
</ul>

A few examples of work that would be considered for funding:

<ul>
	<li>Implementing or scaling-up a laboratory assay for hrp2/3 deletion and / or antimalarial drug resistance marker surveillance in partnership with an NMCP</li>
	<li>Developing a web interface or reporting tool for communicating molecular data to stakeholders who do not have genomics / bioinformatics experience</li>
	<li>Creating a bioinformatics workflow for MMS data that goes from fastq file to a readable report summarizing the analysis results in a user-friendly way</li>
	<li>Developing and implementing a training program to familiarize NMCP staff with the use and interpretation of MMS data</li>
</ul>

We will not consider funding for:

<ul>
	<li>Proposals that do not include an investigator from a malaria-endemic country</li>
	<li>Proposals that do not include an explicit partnership with the NMCP, MOH or other authority responsible for malaria surveillance and control in the country / region</li>
	<li>Proposals that do not demonstrate how the results will immediately influence malaria decision-making by the relevant NMCP, MOH or other authority</li>
</ul>

Grand Challenges Explorations

<h2>THE OPPORTUNITY</h2>
At the Bill &amp; Melinda Gates Foundation, we believe that malaria eradication within a generation is possible. We recognize that in order to achieve this, National Malaria Control Programs (NMCPs) must be empowered to use timely, high-quality data to inform their malaria strategic planning, decision-making, program implementation, and evaluation. As we work to sustain the decline in incidence rates that have marked the last fifteen years of malaria control, this concept of data-to-action has never been more important.
Our vision for data-to-action, recently endorsed by WHO’s Malaria Policy Advisory Committee (MPAC), is one of stratification and sub-national tailoring. In the first step, multiple data sources – from geospatial to epidemiological data – are used to define district-level strata within a country. Next, additional data types are used as the input to mathematical models that output the optimal package of interventions that result in maximum malaria burden reduction within a given resource envelope. The success of stratification and sub-national tailoring is highly dependent on the underlying data, which may not always be complete, high-quality, and / or timely. We are therefore exploring new data streams that might improve our understanding of factors driving changes in malaria epidemiology or be used to optimize the choice of interventions modelled. One of these new data streams is serological, genetic, and / or genomic data which arises from malaria molecular surveillance.
Malaria Molecular Surveillance (MMS) is an umbrella term which describes the use of molecular biology approaches – from serology to genotyping to whole genome sequencing (WGS) – to interrogate parasite and / or vector populations in order to derive epidemiologically actionable information. MMS does not include research-oriented genetic and genomic investigations, such as studies using genomics to investigate parasite or mosquito biology. Rather, the emphasis is on analyses that can directly influence malaria control policy and practice. In addition to the laboratory techniques used, MMS also includes the bioinformatics tools and resources necessary to process, interpret, and share the resulting data.
<h2>THE CHALLENGE</h2>
Initial work in the MMS space focused on methods development and proof-of-concept pilot studies. Now, the tools and analyses are maturing, the infrastructure is in place, and the time-to-result is much shorter, meaning that MMS is beginning to influence program planning and execution. In elimination settings, genetics has been deployed in focused investigations of malaria importations. In higher-burden settings, MMS is being used to visualize the spatio-temporal spread of antimalarial drug resistance markers, influencing treatment guidelines, and to track the effect of different interventions on parasite genetic diversity as a surrogate measure of transmission intensity.
In June 2019, a WHO Technical Consultation on the role of parasite and vector genetic and genomic data in malaria surveillance (<a href="https://www.who.int/malaria/mpac/mpac-october2019-session7-report-consultation-on-genomics.pdf" target="_blank">workshop report</a>), stakeholders from MMS community – both on the research and programmatic sides – gathered with the goal of identifying those MMS use cases for which sufficient evidence exists to recommend routine use for malaria control and elimination, and those for which more upstream research is needed in order to generate a broader evidence base for future recommendations.
The list of use cases that are ready or near ready (marked with an asterisk*) for programmatic deployment includes:
<ul><li>Detect drug resistance: monitor the prevalence/frequency of molecular markers of drug resistance to inform intervention selection, treatment guidelines, and surveillance</li>
<li>Detect hrp2/3 deletions: monitor the prevalence/frequency of hrp2/3 deletion affecting RDT efficacy to inform diagnostic selection</li>
<li>Assess drug resistance gene flow: determine the origins of drug resistance markers and monitor their spread within/among regions and parasite populations to inform containment strategies and regional policies around intervention selection, treatment guidelines, and surveillance*</li>
<li>Predict emerging resistance: detect signatures of positive selection suggesting emerging resistance to inform intervention selection, treatment guidelines, and surveillance*</li>
<li>Identify local transmission: identify focal areas of high transmission and clusters of infections to inform resource deployment*</li>
<li>Distinguish local and imported cases: in elimination settings, classify cases as imported or otherwise for case investigation and elimination certification*</li>
<li>Reconstruct transmission chains: elucidate contributing factors (e.g. seasonality, migrants, asymptomatic cases, and highly infectious individuals) to ongoing transmission patterns to inform intervention selection, resource deployment, surveillance, and case investigation*</li>
<li>Determine connectivity of parasite populations: assess degree to which transmission is linked among regions due to linked parasite populations to inform program planning and resource deployment*</li>
<li>Survey for allelic variation in target sites for gene drive: determine whether SNPs that would prevent CRISPR site recognition exist in wild populations to optimize gene drive release planning*</li>
</ul>As MMS transitions from proof-of-concept work in academic institutions to operational reality in NMCPs, Ministries of Health, and National Public Health Institutes, the challenge lies in conducting the work in a way that engages country programs and malaria decision-makers and that empowers them to understand and use their data actively for programmatic decision-making.
The purpose of this call is therefore to identify new and innovative approaches to integrating malaria molecular surveillance into malaria surveillance and programmatic decision-making in malaria endemic countries. 
What we are looking for:
We are looking for innovative proposals that will use MMS data to enable NMCPs to inform their national and sub-national surveillance efforts, national strategic planning, and/or intervention implementation. These may include proposals that: create or expand laboratory, bioinformatics, and data interpretation capacity within NMCPs or at institutions closely affiliated with an NMCP; create or implement tools for communicating and sharing parasite and/or vector molecular surveillance data; and/or build relationships between groups with MMS capacity and NMCP partners. Proposals should target the use cases identified above that are ready or near-to-ready for programmatic deployment. We do not want respondents to be generating MMS data for research purposes; rather, the intent of this call is to support the application of MMS approaches to routine malaria surveillance and planning within NMCPs, Ministries of Health, or similar organizations.
While we welcome respondents from around the world, we are particularly interested in proposals from respondents working in high-burden malaria settings. All proposals must include a principal investigator or co-investigator from a malaria-endemic country.
Winning proposals should:
<ul><li>Explain the rationale for and potential benefits of using MMS data in their setting</li>
<li>Address one or more of the use cases outlined in the Challenge section above</li>
<li>Include representation from the NMCP, Ministry of Health (MOH) representation, government agency or healthcare provider responsible for malaria control in the country / region</li>
<li>Describe how MMS information arising from the project will be shared with the NMCP, MOH and other key stakeholders</li>
</ul>A few examples of work that would be considered for funding:
<ul><li>Implementing or scaling-up a laboratory assay for hrp2/3 deletion and / or antimalarial drug resistance marker surveillance in partnership with an NMCP</li>
<li>Developing a web interface or reporting tool for communicating molecular data to stakeholders who do not have genomics / bioinformatics experience</li>
<li>Creating a bioinformatics workflow for MMS data that goes from fastq file to a readable report summarizing the analysis results in a user-friendly way</li>
<li>Developing and implementing a training program to familiarize NMCP staff with the use and interpretation of MMS data</li>
</ul>We will not consider funding for:
<ul><li>Proposals that do not include an investigator from a malaria-endemic country</li>
<li>Proposals that do not include an explicit partnership with the NMCP, MOH or other authority responsible for malaria surveillance and control in the country / region</li>
<li>Proposals that do not demonstrate how the results will immediately influence malaria decision-making by the relevant NMCP, MOH or other authority</li>
</ul>

Grand Challenges Explorations seeks new and innovative approaches to integrating molecular surveillance into malaria surveillance and programmatic decision-making in malaria endemic countries. Malaria molecular surveillance encompasses the use of molecular biology approaches to interrogate parasite or vector populations to derive epidemiologically actionable information.

New Approaches to Integrating Molecular Surveillance into Malaria Control Programs (Round 26)

Note: Please see the request for proposals document with additional background as a PDF file on the right.
<h2>Summary</h2>
Smart Farming Innovations for Small-Scale Producers Request for Proposals (RFP) seeks Smart Farming solutions that leverage digital technology innovations that have the potential to drive positive impact for smallscale producer (SSP) entrepreneurs delivered through bundled farmer services and enabled by scalable digital and data platforms (<a href="#Fig1" id="_Fig1">Figure 1</a>). Solutions should address one or more challenges faced by smallscale crop and livestock producers in one or more areas of agricultural advisory, farm management decision support, input supply, finance, insurance, market access and linkages. Solutions should use human-centered design to elucidate the barriers that prevent SSPs from improving productivity, profitability and income – then propose Smart Farming solutions that can help elevate smallscale production entrepreneurs. Some of the fundamental challenges to address include: 1) low productivity driven by lack of access to information and services; climate change, weather variability and pest and disease outbreaks; 2) lack of access to tailored financial and insurance products, and 3) lack of access to and choice of market and offtake options. Additionally, solutions will need to consider barriers to adoption of digital farmer services, such as low language and digital literacy, the high relative cost of services and devices and, in particular, gender gaps and other potential downsides of digital solutions (e.g. the growing digital divide).
<img alt="" height="406" src="https://stage-drupal.grandchallenges.org/sites/default/files/images/farming-digital-technologies-diagram.jpg" width="414" />
<a href="#_Fig1" id="Fig1">Figure 1</a>. Smart Farming Innovations for SSPs
Awards: There are two grant types – Seed Grants and Scale-Up Grants – each with its own requirements. Applicants can only apply for one of these grant types must select which level for which they are applying (proposal should not be submitted for both grant types).
Seed Grants – Up to USD 250,000 to be implemented up to 12 months. Seed Grants are proposals for Smart Farming solutions that can demonstrate potential in meeting the following criteria:
<ul><li>Leveraging digital technology innovations with the potential to scale, for example, utilizing a proven technology that has been applied in agriculture in another geography; transferring a technology from another sector such as health, infrastructure or finance; sourcing an entirely new technology;</li>
<li>Show potential to improve SSP incomes, productivity and ability to adapt to climate change;</li>
<li>Address barriers to scaled adoption of digital services, such as access, affordability and language and digital literacy. This includes addressing women's access to digital services and closing the digital divide between those who have access and marginalized populations who do not;</li>
<li>Have the potential to be bundled with multiple farmer-facing services into an integrated solution;</li>
<li>Are enabled by robust digital and data technology platforms and services;</li>
<li>Provide fit-for-purpose solutions (e.g. developed using human-centered design) for SSP enterprises who seek to sell a portion of production to markets;</li>
<li>Show potential to be scaled using a sustainable business model and are affordable and able to provide positive return on investment at a smallholder farm level through successful pilots, scaling partners, or higher volume production driving down prices.</li>
</ul>Scale-Up Grants – Up to USD 1,500,000 to be implemented up to 24 months. Scale-Up Grants are proposals with demonstrated ability and sufficient evidence to have positive impact. In addition to the criteria listed above for Seed Grants, Scale-Up Grants must also:
<ul><li>Leverage digital technology innovations with demonstrated readiness to scale and proven ability to bundle with other services;</li>
<li>Meet all criteria regarding technology innovations, scalable platforms, and sustainable bundled service delivery models;</li>
<li>Demonstrate that additional funding will enable value capture by SSPs or other value chain actors and sustainable and viable service delivery models over the long term.</li>
<li>Please upload a separate document – 1 additional page maximum – that describes your partner consortium in more detail, including the various partners' capabilities, and additional evidence of value add, income, productivity, women's empowerment and long-term sustainability of the solution.</li>
</ul>Consortiums: To increase the probability that projects funded through this RFP will continue after the initial project completion and evolve into a continuing global public good or sustained solution, applicants are encouraged to consider of a range of partners to form a consortium. This investment will prioritize those who partner with organizations interested in Smart Farming in low- and middle-income countries (LMICs) as long-term opportunities. There are several types of organizations we envisage being part of consortia submitting proposals: Enterprise Technology Platforms (Big-Tech), Enterprise Agriculture (Big-Ag), Ag-Tech Startups (Ag-Tech + Farm-Tech), Research Organizations (R&amp;D), national and international NGOs and farmer-based organizations (Implementors), Government and International Organizations.
Geographies: While we primarily seek solutions applicable to the LMICs listed below and favor those forming local partnerships. Other geographies will be considered if a strong case is made for doing so.
<ul><li>Africa: Kenya, Uganda, Ethiopia, Tanzania, Rwanda, Ghana, Senegal, Mali, Burkina Faso, Malawi, Zambia, Mozambique, Nigeria</li>
<li>Asia: India (Bihar, Odisha, Uttar Pradesh, Andhra Pradesh), Bangladesh</li>
</ul>

Grand Challenges seeks innovative digital solutions with potential to scale and integrate with bundled farmer services. Solutions should address one or more challenges facing small scale crop and livestock producer entrepreneurs in the areas of agricultural advisory, input supply, finance, insurance, market access, and decision support tools.

Smart Farming Innovations for Small-Scale Producers

Balance the Equation is the first-ever Grand Challenge focused on U.S. education. The Bill &amp; Melinda Gates Foundation is seeking to disrupt the deeply imbalanced system against this generation – and previous generations – of Black, Latino, English Learners (ELs), and students experiencing poverty in the United States, who we will refer to as priority students, as it relates to their Algebra 1 experience in 7th, 8th, or 9th grade, in-class or online.

Balance the Equation - A Grand Challenge for Algebra 1

<h2>THE OPPORTUNITY</h2>

Fundamental changes in menstrual health and hygiene (MHH) products are needed to meet the needs of women and girls in low and middle income countries (LMIC) who face challenges with regard to their overall menstrual health and to managing their menstrual periods with dignity. Women and girls in LMIC face significant challenges barriers related to MHH from menarche to menopause. Current literature, while limited, shows an association between inadequate access to MHH products and poorer physical and mental health outcomes.<a href="#_ftn1" name="_ftnref1" title="">[1]</a> <a href="#_ftn2" name="_ftnref2" title="">[2]</a> In Ethiopia, for example, only 28% of women and girls reported having "everything they need" to manage their menstruation. Globally, based on data collected from 8 countries in PMA2020 (Performance Monitoring for Action, 2020), it is estimated that 528 million women and girls are lacking what they need for basic MHH care. Challenges can range from social stigma, lack of clean water for basic hygiene, and ineffective, inadequate, or expensive products.<a href="#_ftn3" name="_ftnref3" title="">[3]</a> For example, many women and girls face limited economic resources to purchase supplies that best meet their needs. In addition, girls face inadequate or poor water and sanitation facilities at school, lack of privacy and lengthy travel to and from schools, which increases the likelihood of leaks/stains. Lack of access to MHH products that are context-appropriate, affordable and sustainable can have tangible biological and social impact. Additionally, limited access to MHH products leads to diminished dignity and respect and increased discrimination and stigma for many women and girls in LMIC across their reproductive life.

Key characteristics of MHH products for women and girls include effectiveness, safety, discretion, sustainability, and affordability. Currently available products (e.g., disposable pads, reusable pads, tampons, and menstrual cups) all involve trade-offs among one or more of these desired characteristics and attributes. For example, menstrual cups are discreet but expensive and difficult to use; disposable pads are discreet but create a lot of waste that is particularly problematic in LMICs. Additionally, lack of access to clean water limits the utility of reusable products (e.g., menstrual cups) for many women. As a result, some women and girls turn to inadequate and potentially harmful homemade alternatives such as goatskin, cow patties, or cloths in many settings. In India for example, 88% of women and girls use homemade alternative products to manage MHH.

While a multi-pronged approach to address dignified menstrual health is broadly necessary, one key need is innovation in materials science and transformative product development to better meet user needs. This Grand Challenge opportunity is focused exclusively on the product innovation domain. To date, changes in this field have been largely incremental - often focusing on increasing access through pricing or making current products with biodegradable materials. Disruptive innovation in this space has the potential to shift the current market structure and thus improve reach to poor and vulnerable populations. To be most impactful, significant changes in science and technology require mitigation of environmental impact with the aspirational goal to create zero waste and move toward a circular economy (defined as an economic system aimed at eliminating waste and the reuse, sharing, repair, refurbishment, remanufacturing, and recycling of resources).

<h2>THE CHALLENGE</h2>

We seek fundamentally transformative and innovative ideas to support the design and development of new MHH products that meet key criteria of being responsive to user needs - particularly in LMIC context; with priority focus on safety, unobtrusiveness, effectiveness (no leaking), cultural acceptability, and sustainability. While there are a number of challenges related to access to current products, reducing stigma, and shifting social norms, this opportunity is specifically focused on driving transformative innovation in the product development domain. We are particularly seeking new technologies, including those potentially used in adjacent fields such as materials science, that could be adapted to innovative MHH products. We fully recognize that technology alone does not automatically improve people's lives. Thus, these creative solutions must be contextually grounded and designed in response to the needs and preferences of women and girls living in LMIC and designed particularly with the future in mind.

Proposals should include how they will address the following criteria:

<ul>
	<li>Innovation: We are seeking radical transformation of existing MHH products, including leveraging materials science and other product innovations.</li>
	<li>Discretion: The ability to use a product without it being detected is of high importance to women and girls, specifically during: wear (e.g., no blood leaking and staining clothes), cleaning (e.g., for reusable products, washing product can be kept discreet and is feasible in the absence of clean water supply), and disposal (e.g., for disposable products, does not leave conspicuous waste). Other considerations include safety (e.g., obviating the need to access public sanitation facilities at night). Finally, functionality over the life course depends upon adaptability to times of irregular and sometimes heavy bleeding, including perimenarche, postpartum, and perimenopause.</li>
	<li>Sustainability: Current MHH products either require access to clean water to clean (e.g., menstrual cup) or result in waste (e.g., disposable pad). A transformative product would neither require neither clean water nor result in waste.</li>
</ul>

Note: Given the foundation's target geographies and populations, a MHH product needs to be affordable for a woman throughout her reproductive years. This criterion will need to be weighed carefully against the prior criteria. While striving for a low cost of goods sold (COGS), we also recognize that affordability can be addressed through multiple levers including market dynamics and scaled production.

The following will not be considered for funding:

<ul>
	<li>Basic research in materials science or product design that does not address the criteria as outlined above</li>
	<li>Proposals only focusing on innovative new materials science without a clear path toward developing an MHH prototype manufacturing process</li>
	<li>Proposals where there is no clear path forward to scale</li>
	<li>Proposals focused on current MHH product delivery and education, as opposed to a technological solution for innovations in new products</li>
	<li>Proposals that focus on incremental change of existing products</li>
	<li>Proposals focused on other aspects of MHH, including infrastructure/systems for addressing access to existing products, water and sanitation improvements or shifting social norms around stigmatization.</li>
</ul>

_____________________________

<a href="#_ftnref1" name="_ftn1" title="">[1]</a>&nbsp;<a href="https://www.unfpa.org/news/menstruation-not-girls-or-womens-issue-%E2%80%93-its-human-rights-issue" title="https://www.unfpa.org/news/menstruation-not-girls-or-womens-issue-its-human-rights-issue">https://www.unfpa.org/news/menstruation-not-girls-or-womens-issue-its-human-rights-issue</a>

<a href="#_ftnref2" name="_ftn2" title="">[2]</a> Hennegan J, et al. Women’s and girls‘ experiences of menstruation in low- and middle-income countries: A systematic review and qualitative metasynthesis. PloS Med. 2019; 16:e1002803.

<a href="#_ftnref3" name="_ftn3" title="">[3]</a> Kuhlmann AS, Henry K, Wall LL. Menstrual Hygiene Management in Resource-Poor Countries. Obstet Gynecol Surv. 2017;72:356-76.

<h2>THE OPPORTUNITY</h2>
Fundamental changes in menstrual health and hygiene (MHH) products are needed to meet the needs of women and girls in low and middle income countries (LMIC) who face challenges with regard to their overall menstrual health and to managing their menstrual periods with dignity. Women and girls in LMIC face significant challenges barriers related to MHH from menarche to menopause. Current literature, while limited, shows an association between inadequate access to MHH products and poorer physical and mental health outcomes.<a href="#Note1">1, </a><a href="#Note2">2</a> In Ethiopia, for example, only 28% of women and girls reported having "everything they need" to manage their menstruation. Globally, based on data collected from 8 countries in PMA2020 (Performance Monitoring for Action, 2020), it is estimated that 528 million women and girls are lacking what they need for basic MHH care. Challenges can range from social stigma, lack of clean water for basic hygiene, and ineffective, inadequate, or expensive products.<a href="#Note3">3</a> For example, many women and girls face limited economic resources to purchase supplies that best meet their needs. In addition, girls face inadequate or poor water and sanitation facilities at school, lack of privacy and lengthy travel to and from schools, which increases the likelihood of leaks/stains. Lack of access to MHH products that are context-appropriate, affordable and sustainable can have tangible biological and social impact. Additionally, limited access to MHH products leads to diminished dignity and respect and increased discrimination and stigma for many women and girls in LMIC across their reproductive life.
Key characteristics of MHH products for women and girls include effectiveness, safety, discretion, sustainability, and affordability. Currently available products (e.g., disposable pads, reusable pads, tampons, and menstrual cups) all involve trade-offs among one or more of these desired characteristics and attributes. For example, menstrual cups are discreet but expensive and difficult to use; disposable pads are discreet but create a lot of waste that is particularly problematic in LMICs. Additionally, lack of access to clean water limits the utility of reusable products (e.g., menstrual cups) for many women. As a result, some women and girls turn to inadequate and potentially harmful homemade alternatives such as goatskin, cow patties, or cloths in many settings. In India for example, 88% of women and girls use homemade alternative products to manage MHH.
While a multi-pronged approach to address dignified menstrual health is broadly necessary, one key need is innovation in materials science and transformative product development to better meet user needs. This Grand Challenge opportunity is focused exclusively on the product innovation domain. To date, changes in this field have been largely incremental - often focusing on increasing access through pricing or making current products with biodegradable materials. Disruptive innovation in this space has the potential to shift the current market structure and thus improve reach to poor and vulnerable populations. To be most impactful, significant changes in science and technology require mitigation of environmental impact with the aspirational goal to create zero waste and move toward a circular economy (defined as an economic system aimed at eliminating waste and the reuse, sharing, repair, refurbishment, remanufacturing, and recycling of resources).
<h2>THE CHALLENGE</h2>
We seek fundamentally transformative and innovative ideas to support the design and development of new MHH products that meet key criteria of being responsive to user needs - particularly in LMIC context; with priority focus on safety, unobtrusiveness, effectiveness (no leaking), cultural acceptability, and sustainability. While there are a number of challenges related to access to current products, reducing stigma, and shifting social norms, this opportunity is specifically focused on driving transformative innovation in the product development domain. We are particularly seeking new technologies, including those potentially used in adjacent fields such as materials science, that could be adapted to innovative MHH products. We fully recognize that technology alone does not automatically improve people's lives. Thus, these creative solutions must be contextually grounded and designed in response to the needs and preferences of women and girls living in LMIC and designed particularly with the future in mind.
Proposals should include how they will address the following criteria:
<ul><li>Innovation: We are seeking radical transformation of existing MHH products, including leveraging materials science and other product innovations.</li>
<li>Discretion: The ability to use a product without it being detected is of high importance to women and girls, specifically during: wear (e.g., no blood leaking and staining clothes), cleaning (e.g., for reusable products, washing product can be kept discreet and is feasible in the absence of clean water supply), and disposal (e.g., for disposable products, does not leave conspicuous waste). Other considerations include safety (e.g., obviating the need to access public sanitation facilities at night). Finally, functionality over the life course depends upon adaptability to times of irregular and sometimes heavy bleeding, including perimenarche, postpartum, and perimenopause.</li>
<li>Sustainability: Current MHH products either require access to clean water to clean (e.g., menstrual cup) or result in waste (e.g., disposable pad). A transformative product would neither require neither clean water nor result in waste.</li>
</ul>Note: Given the foundation's target geographies and populations, a MHH product needs to be affordable for a woman throughout her reproductive years. This criterion will need to be weighed carefully against the prior criteria. While striving for a low cost of goods sold (COGS), we also recognize that affordability can be addressed through multiple levers including market dynamics and scaled production.
The following will not be considered for funding:
<ul><li>Basic research in materials science or product design that does not address the criteria as outlined above</li>
<li>Proposals only focusing on innovative new materials science without a clear path toward developing an MHH prototype manufacturing process</li>
<li>Proposals where there is no clear path forward to scale</li>
<li>Proposals focused on current MHH product delivery and education, as opposed to a technological solution for innovations in new products</li>
<li>Proposals that focus on incremental change of existing products</li>
<li>Proposals focused on other aspects of MHH, including infrastructure/systems for addressing access to existing products, water and sanitation improvements or shifting social norms around stigmatization.</li>
</ul>_____________________________
<a>1</a><a href="https://www.unfpa.org/news/menstruation-not-girls-or-womens-issue-%E2%80%93-its-human-rights-issue#" target="_blank"> https://www.unfpa.org/news/menstruation-not-girls-or-womens-issue-%E2%80%93-its-human-rights-issue#</a>
<a>2</a>Hennegan J, et al. Women’s and girls‘ experiences of menstruation in low- and middle-income countries: A systematic review and qualitative metasynthesis. PloS Med. 2019; 16:e1002803.
<a>3</a>Kuhlmann AS, Henry K, Wall LL. Menstrual Hygiene Management in Resource-Poor Countries. Obstet Gynecol Surv. 2017;72:356-76.

Grand Challenges Explorations seeks transformative and innovative ideas to support the design and development of a new menstrual health and hygiene product that meets key criteria of being responsive to user needs, focusing on discreetness, affordability, and sustainability. Truly disruptive technologies harnessing materials science will be prioritized. Solutions must be designed in response to the needs and preferences of women and girls living in low- and middle-income countries and designed particularly with the future in mind.

Innovations in Materials Science for a Transformative Menstrual Health and Hygiene Product (Round 25)

<h2>BACKGROUND</h2>

Cesarean section (CS) is a life-saving procedure for mother and newborn. However, too often c-section is not available, is provided without adequate quality, or is provided when not medically indicated - all dimensions that lead to maternal and newborn mortality and morbidity. We see an opportunity to nurture the field to identify and demonstrate feasibility of interventions to address challenges related to safe, timely, and appropriate cesarean section in low and middle income countries.

<h2>THE CHALLENGE</h2>

We invite proposals for interventions to address the following challenges related to the cesarean section:

<ol>
	<li>Increasing access to cesarean section where it is currently inadequate</li>
	<li>Increasing quality and safety of cesarean section to reduce iatrogenic harm to both mothers and newborns</li>
	<li>Reducing rates of non-medically indicated cesarean section.</li>
</ol>

Interventions addressing more than one challenge (e.g. quality and access) are encouraged. In some geographies all three of these challenges exist simultaneously, at different times for different populations; in other geographies only one or two of these challenges predominate. Applications should clearly state which of these three challenges is being targeted and provide clear rationale for why the intervention is likely to address the challenge. We are particularly interested in geographies with high fertility and weak health systems that will face challenges to ensure the provision of safe c-sections can keep pace with medical need, and we will thus consider applications proposing activities to be implemented in Sub-Saharan Africa or South Asia (India, Pakistan, Bangladesh).

Grant Funding Levels

We seek to make Seed Grants to generate proof of concept of novel interventions together with Validation Grants to generate further evidence of feasibility at a larger scale for existing interventions.

<ul>
	<li>Seed Grants of $100K for up to 24 months: These grants are intended to provide proof of concept of an intervention that is entirely novel at small scale (e.g., single facility or district). Applicants should conduct a literature review to verify that the proposed intervention has no documented evidence; documentation of the methods and outcomes of this review must be provided in the application. These grants should demonstrate the feasibility of a novel intervention and its impact on one or more of the c-section challenges identified in this call for applications.</li>
	<li>Validation Grants of $300K for up to 24 months: These grants are intended to demonstrate the feasibility of a single intervention or a combination of interventions at the scalable unit <a href="#_ftn1" id="_ftnref1">[1]</a> of a health system. Validation grants must replicate, confirm or more rigorously test one intervention - or multiple interventions - that have previously demonstrated proof of concept at a smaller scale. Given the complexity of the problem, we acknowledge that multi-component interventions are required, and we eoncourage applications exploring these.</li>
</ul>

What We Are Looking For:

All applications should:

<ul>
	<li>Focus on health service or delivery innovation. This call for applications excludes development of new medical devices and non-interventional analysis of data</li>
	<li>Describe how the intervention will be tailored to the epidemiology and health system where it will be implemented</li>
	<li>Ensure that women and newborns receive care that respects and preserves their dignity, including informed consent<a href="#_ftn2" id="_ftnref2" name="_ftnref2">[2]</a></li>
	<li>Include participation from institutions based in South Asia and sub-Saharan Africa; applications led by institutions from these geographies are encouraged</li>
	<li>Propose interventions that align with the attributes of scalable health innovations<a href="#_ftn3" id="_ftnref3" name="_ftnref3">[3]</a></li>
	<li>Report impact on c-section rates disaggregated by Robson classification<a href="#_ftn4" id="_ftnref4" name="_ftnref4">[4]</a>, and safety with indicators such as case fatality rates and rates of post-operative complication</li>
	<li>Propose activities to be implemented in a country in Sub-Saharan Africa or South Asia (India, Pakistan, Bangladesh).</li>
</ul>

A few of the many options we will consider include (but are not limited to): clinical team huddles for improving quality of CS; interventions to improve immediate breastfeeding and bonding among mother-infant pairs after CS; interventions to improve communication between patient and care team; restructuring labor wards to facilitate latent phase labor management; adjustments to financial incentives related to CS; policy and liability reform.

We will not consider funding for approaches that have been widely used and evaluated in LMIC settings to scale up access to cesarean section (e.g., task shifting); activities to improve quality of care that already have extensive evidence of effectiveness; emergency transport interventions; mass media campaigns; or development of new tools for surgery, anesthesia, or patient monitoring.

Collaboration

This request for proposals seeks to create a consortium of individually funded projects that will benefit from sharing information between projects. We expect that such sharing will help to ensure that the goals of the innovative approaches in individual projects are ultimately integrated with each other, thereby increasing the chances that the programs will be greater than the sum of their parts. Furthermore, we expect that sharing experimental methods, data, and resources will ultimately improve the ability to compare and validate local research findings and to develop interventions and products. We expect to bring together all grantees after 18-24 months to share what they have learned in their work and to discuss how to accelerate progress with these lessons.

<drupal-media data-align="center" data-entity-type="media" data-entity-uuid="6e3e1e63-035c-4e42-93c0-8ddc90679019"></drupal-media>

Figure 1. Framework for considering cesarean section

________________________________

<a href="#_ftnref1" id="_ftn1">[1]</a><a href="https://implementationscience.biomedcentral.com/articles/10.1186/s13012-016-0374-x" target="_blank">Barker P, Reid A, Schall M. A Framework for scaling up health interventions: lessons learned from large scale improvement initiatives in Africa. Implementation Science. 2016</a>.

<a href="#_ftnref2" name="_ftn2" title="">[2]</a><a href="https://www.who.int/maternal_child_adolescent/documents/improving-maternal-newborn-care-quality/en/" target="_blank">WHO. Standards for Improving Quality of Maternal and Newborn Care in Health Facilities. 2016.</a>

<a href="#_ftnref3" name="_ftn3" title="">[3]</a><a href="https://www.sciencedirect.com/science/article/pii/S0277953614006133" target="_blank">Spicer et al. "Scaling-up is a craft not a science: Catalysing scale-up of health innovations…" Social Science and Medicine. 2014"</a>

<a href="#_ftnref4" name="_ftn4" title="">[4]</a><a href="https://www.who.int/reproductivehealth/publications/maternal_perinatal_health/robson-classification/en/" target="_blank">WHO. Robson Classification: Implementation Manual. 2017</a>

<h2>BACKGROUND</h2>
Cesarean section (CS) is a life-saving procedure for mother and newborn. However, too often c-section is not available, is provided without adequate quality, or is provided when not medically indicated - all dimensions that lead to maternal and newborn mortality and morbidity. We see an opportunity to nurture the field to identify and demonstrate feasibility of interventions to address challenges related to safe, timely, and appropriate cesarean section in low and middle income countries.
<h2>THE CHALLENGE</h2>
We invite proposals for interventions to address the following challenges related to the cesarean section:
<ol><li>Increasing access to cesarean section where it is currently inadequate</li>
<li>Increasing quality and safety of cesarean section to reduce iatrogenic harm to both mothers and newborns</li>
<li>Reducing rates of non-medically indicated cesarean section.</li>
</ol>Interventions addressing more than one challenge (e.g. quality and access) are encouraged. In some geographies all three of these challenges exist simultaneously, at different times for different populations; in other geographies only one or two of these challenges predominate. Applications should clearly state which of these three challenges is being targeted and provide clear rationale for why the intervention is likely to address the challenge. We are particularly interested in geographies with high fertility and weak health systems that will face challenges to ensure the provision of safe c-sections can keep pace with medical need, and we will thus consider applications proposing activities to be implemented in Sub-Saharan Africa or South Asia (India, Pakistan, Bangladesh).
Grant Funding Levels
We seek to make Seed Grants to generate proof of concept of novel interventions together with Validation Grants to generate further evidence of feasibility at a larger scale for existing interventions.
<ul><li>Seed Grants of $100K for up to 24 months: These grants are intended to provide proof of concept of an intervention that is entirely novel at small scale (e.g., single facility or district). Applicants should conduct a literature review to verify that the proposed intervention has no documented evidence; documentation of the methods and outcomes of this review must be provided in the application. These grants should demonstrate the feasibility of a novel intervention and its impact on one or more of the c-section challenges identified in this call for applications.</li>
<li>Validation Grants of $300K for up to 24 months: These grants are intended to demonstrate the feasibility of a single intervention or a combination of interventions at the scalable unit<a href="#Note1">1</a> of a health system. Validation grants must replicate, confirm or more rigorously test one intervention - or multiple interventions - that have previously demonstrated proof of concept at a smaller scale. Given the complexity of the problem, we acknowledge that multi-component interventions are required, and we eoncourage applications exploring these.</li>
</ul>What We Are Looking For:
All applications should:
<ul><li>Focus on health service or delivery innovation. This call for applications excludes development of new medical devices and non-interventional analysis of data</li>
<li>Describe how the intervention will be tailored to the epidemiology and health system where it will be implemented</li>
<li>Ensure that women and newborns receive care that respects and preserves their dignity, including informed consent<a href="#Note2">2</a></li>
<li>Include participation from institutions based in South Asia and sub-Saharan Africa; applications led by institutions from these geographies are encouraged</li>
<li>Propose interventions that align with the attributes of scalable health innovations<a href="#Note3">3</a></li>
<li>Report impact on c-section rates disaggregated by Robson classification<a href="#Note4">4</a>, and safety with indicators such as case fatality rates and rates of post-operative complication</li>
<li>Propose activities to be implemented in a country in Sub-Saharan Africa or South Asia (India, Pakistan, Bangladesh).</li>
</ul>A few of the many options we will consider include (but are not limited to): clinical team huddles for improving quality of CS; interventions to improve immediate breastfeeding and bonding among mother-infant pairs after CS; interventions to improve communication between patient and care team; restructuring labor wards to facilitate latent phase labor management; adjustments to financial incentives related to CS; policy and liability reform.
We will not consider funding for approaches that have been widely used and evaluated in LMIC settings to scale up access to cesarean section (e.g., task shifting); activities to improve quality of care that already have extensive evidence of effectiveness; emergency transport interventions; mass media campaigns; or development of new tools for surgery, anesthesia, or patient monitoring.
Collaboration
This request for proposals seeks to create a consortium of individually funded projects that will benefit from sharing information between projects. We expect that such sharing will help to ensure that the goals of the innovative approaches in individual projects are ultimately integrated with each other, thereby increasing the chances that the programs will be greater than the sum of their parts. Furthermore, we expect that sharing experimental methods, data, and resources will ultimately improve the ability to compare and validate local research findings and to develop interventions and products. We expect to bring together all grantees after 18-24 months to share what they have learned in their work and to discuss how to accelerate progress with these lessons.
<a href="https://gcgh.grandchallenges.org/sites/default/files/C-Section_Chart_Square.jpg" target="_parent"><img alt="" src="https://gcgh.grandchallenges.org/sites/default/files/C-Section_Chart_Square.jpg" /></a> 
Figure 1. Framework for considering cesarean section
________________________________
<a name="#Note1" id="#Note1">1</a><a href="https://implementationscience.biomedcentral.com/articles/10.1186/s13012-016-0374-x" target="_blank">Barker P, Reid A, Schall M. A Framework for scaling up health interventions: lessons learned from large scale improvement initiatives in Africa. Implementation Science. 2016</a>.
<a name="#Note2" id="#Note2">2</a><a href="https://www.who.int/maternal_child_adolescent/documents/improving-maternal-newborn-care-quality/en/" target="_blank">WHO. Standards for Improving Quality of Maternal and Newborn Care in Health Facilities. 2016.</a>
<a name="#Note3" id="#Note3">3</a><a href="https://www.sciencedirect.com/science/article/pii/S0277953614006133" target="_blank">Spicer et al. "Scaling-up is a craft not a science: Catalysing scale-up of health innovations…" Social Science and Medicine. 2014"</a>
<a name="#Note4" id="#Note4">4</a><a href="https://www.who.int/reproductivehealth/publications/maternal_perinatal_health/robson-classification/en/" target="_blank">WHO. Robson Classification: Implementation Manual. 2017</a>

Grand Challenges seeks ideas for interventions to address the following challenges related to cesarean section: 1) increasing access to cesarean section where it is currently inadequate, 2) increasing quality and safety of cesarean section to reduce iatrogenic harm to both mothers and newborns, 3) reducing rates of non-medically indicated cesarean section. Proposed activities should be implemented in Sub-Saharan Africa or South Asia (India, Pakistan, Bangladesh).

Improving Access to and Use of Safe and Appropriate Cesarean Section

<h2>THE OPPORTUNITY</h2>

Countries rely on both routine health systems and campaign-based delivery to extend the reach of important health products. Many programs, including immunization, neglected tropical diseases, nutrition, malaria, and polio regularly rely on such campaigns to support accelerated disease control, make progress towards elimination/eradication goals, and achieve large scale health impact.

Campaign-based delivery of health interventions is typically time-limited, intermittent, and implemented at-scale. All countries utilize health campaigns in some capacity - such as for outbreak response - and campaigns have been shown to be an effective way of driving health impact. For example, Vitamin A supplementation is estimated to reduce risk of all-cause child mortality by 12%. <a href="#_ftn1" id="_ftnref1" name="_ftnref1">[1]</a> Measles campaigns are estimated to reach 66% of "zero-dose" children who are not otherwise immunized by routine health systems. <a href="#_ftn2" id="_ftnref2" name="_ftnref2">[2]</a>

Still, the performance of campaigns is variable, and campaigns often do not realize their potential impact. For example, only 47% of the measles campaigns and 38% of vitamin A campaigns reached their intended coverage targets.<a href="#_ftn3" id="_ftnref3" name="_ftnref3">[3]</a>&nbsp;Campaign evaluations may also show they consistently miss a subset of populations - most often the most vulnerable - resulting in reduced equity of the health intervention. Although many campaigns experiment with or implement innovations to increase effectiveness, these innovations are rarely systematically evaluated, iterated upon, and disseminated.

Quality planning is a key enabler of effective campaign implementation and is critical to support campaign performance. More specifically, microplanning, which specifically addresses the detailed, delivery-level planning required to reach intended populations with a health intervention, is recognized as a critical driver of campaign success. Planning and microplanning can be used as a tool to identify and reach the most vulnerable populations (e.g., high-risk and unreached populations).

We believe there is opportunity to dramatically&nbsp;improve the way health campaigns that deliver health products or services realize impact, including through improved planning/microplanning. These campaigns will achieve higher coverage of target populations, better identify and reach high-risk/unreached populations, and efficiently use campaign resources.

<h2>THE CHALLENGE</h2>

We are seeking innovative solutions that accelerate the improvement of coverage, reach, efficiency, and effectiveness of mass health campaigns that deliver health products or services in low-and middle-income countries, specifically through improved planning/microplanning and focus on unreached populations.

Specifically, we are looking for innovations in approaches, practices, or tools that dramatically improve the&nbsp;planning/microplanning that will lead to improved effectiveness of campaigns. We are also looking for innovative tools and technologies to more effectively identify and reach the most vulnerable populations when countries are designing and implementing mass campaigns.

In order to contribute to the development and spread of campaign "best practices", a solution should be applicable to campaigns beyond the context in which it is originally tested (e.g., applicable in&nbsp;multiple&nbsp;lower- to middle-incomes countries and/or applicable&nbsp;across multiple types of health campaigns&nbsp;such as immunization, NTDs, malaria, or nutrition).

We are especially interested in novel approaches that draw on innovation from large-scale delivery models outside of the health sector, which may include interventions used in the private sector.

Successful proposals should consider the following:

Planning and microplanning: This includes the planning processes - led by governments and often supported by partners - at the national, sub-national, facility, or community levels. Overall planning supports the mobilization of information and resources needed to conduct the campaign, and&nbsp;<a href="https://www.who.int/polio-transition/documents-resources/best-practices-microplanning.pdf?ua=1" target="_blank">microplanning</a>&nbsp;specifically addresses the detailed, delivery-level planning required to reach intended populations with the health intervention. Innovations might include/consider:

<ul>
	<li>Interactive or adaptive microplans that better incorporate past or real-time data (e.g. based on prior campaign performance or operational monitoring data) to guide planning and implementation.</li>
	<li>Increased automation of microplans (e.g. updating, adapting microplans for other platforms).</li>
	<li>Modeling and analytics to test, identify, and recommend more effective implementation approaches (e.g. modeling to identify optimal location of campaign fixed sites and outreach posts in order to improve community access).</li>
	<li>Novel or nontraditional information or data sources to improve the accuracy of planning (e.g. geospatial data to improve population estimation or location and more accurately plan for and target campaign delivery).</li>
	<li>Technologies for developing and using community maps or populations that can help campaigns to better reach their intended age groups or sub-populations.</li>
	<li>Novel approaches to understanding the effectiveness of campaign planning and implementation while campaigns are ongoing or during post-campaign evaluations.</li>
</ul>

Identifying and reaching high-risk or unreached populations: This includes innovative approaches to better understand, identify, and reach un/underserved communities and unreached or "zero-dose" children. This wil likely include novel tools, technologies, and methodologies to more effectively identify and reach high-risk or unreached populations at a subnational level (e.g. approaches to leverage data, maps, or other information to support campaign planning, appropriate use of targeted or sub-national campaigns, and post-campaign assessments).

Criteria for success include solutions that:

<ul>
	<li>Are transformative, novel, or innovative. These interventions will significantly change the way in which campaigns are planned, conducted, or evaluated by proposing new ways of working, leveraging lessons from other sectors, or increasing transparency and effectiveness.</li>
	<li>Could be used by various health campaigns beyond the campaign in which the innovation is originally conceptualized or tested, such as for immunization (measles, yellow fever, meningitis, etc.), neglected tropical diseases (trachoma, onchocerciasis, schistosomiasis etc.), nutrition (vitamin A, deworming), malaria (bed net distribution, seasonal malaria chemoprophylaxis), and polio.</li>
	<li>Could be used in various low- and middle-income countries beyond the country in which the innovation is originally conceptualized or tested.</li>
	<li>Can be designed, tested, and scaled as a "best practice".</li>
	<li>Can be applied in low- and middle-income countries.</li>
	<li>Are cost effective.</li>
</ul>

We will not consider funding for:

<ul>
	<li>Proposals that are not innovative; proposals that only offer incremental / non-transformative improvements (e.g., use of mobile data collection instead of paper-based collection) with no clear link to dramatically improved campaign effectiveness; proposals that repeat conventional approaches without novel application.</li>
	<li>Proposals addressing one specific health need/campaign platform, rather than an innovation that would improve health campaigns in general.</li>
	<li>Proposals focused on educational campaigns or are not specifically focused on campaign-based delivery of health goods and services. Interventions that are better classified as technical assistance or campaign implementation (e.g., focused on the delivery or improvement of a single campaign).</li>
	<li>Proposals focused on improving access to existing tools or technologies or seeking to apply existing tools in ways that do not transform the current practices used for campaign-based delivery.</li>
	<li>Proposals where the solution is to leverage one health campaign for co-delivery of other goods or services (e.g., using a NTD campaign to deliver vaccine reminders).</li>
	<li>Approaches not directly relevant to low-income settings and that do not clearly consider the local context of available financial systems and infrastructure for resource poor health settings (e.g., using expensive devices; require government issued IDs where few people have them; require hospital deliveries in settings where this is not the norm).</li>
	<li>Secondary analysis of existing studies or systematic reviews unless there is a clear way in which the analysis can be scaled and will fundamentally change practice.</li>
	<li>Approaches that circumvent the public sector completely.</li>
	<li>Approaches which would require a donor’s long-term financial support to sustain.</li>
	<li>Approaches that are clinic based.</li>
</ul>

_________________________

<a href="#_ftnref1" name="_ftn1" title="">[1]</a>Imdad et al. Vitamin A supplementation for preventing morbidity and mortality in children from six months to five years of age. Cochrane Database of Systematic Reviews, 2017.

<a href="#_ftnref2" name="_ftn2" title="">[2]</a>Portnoy et al. Impact of measles supplementary immunization activities on reaching children missed by routine programs. Vaccine, 2018; In this use, "zero-dose" refers to children with no prior dose of measles vaccine. “Zero-dose” can also refer to children who have not received their first dose of other key vaccines.

<a href="#_ftnref3" name="_ftn3" title="">[3]</a>Internal analysis of WHO PCT Databank and GHO data (accessed September 2019).

<h2>THE OPPORTUNITY</h2>
Countries rely on both routine health systems and campaign-based delivery to extend the reach of important health products. Many programs, including immunization, neglected tropical diseases, nutrition, malaria, and polio regularly rely on such campaigns to support accelerated disease control, make progress towards elimination/eradication goals, and achieve large scale health impact.
Campaign-based delivery of health interventions is typically time-limited, intermittent, and implemented at-scale. All countries utilize health campaigns in some capacity - such as for outbreak response - and campaigns have been shown to be an effective way of driving health impact. For example, Vitamin A supplementation is estimated to reduce risk of all-cause child mortality by 12%.<a href="#Note1">1</a> Measles campaigns are estimated to reach 66% of "zero-dose" children who are not otherwise immunized by routine health systems.<a href="#Note2">2</a>
Still, the performance of campaigns is variable, and campaigns often do not realize their potential impact. For example, only 47% of the measles campaigns and 38% of vitamin A campaigns reached their intended coverage targets.<a href="#Note3">3</a> Campaign evaluations may also show they consistently miss a subset of populations - most often the most vulnerable - resulting in reduced equity of the health intervention. Although many campaigns experiment with or implement innovations to increase effectiveness, these innovations are rarely systematically evaluated, iterated upon, and disseminated.
Quality planning is a key enabler of effective campaign implementation and is critical to support campaign performance. More specifically, microplanning, which specifically addresses the detailed, delivery-level planning required to reach intended populations with a health intervention, is recognized as a critical driver of campaign success. Planning and microplanning can be used as a tool to identify and reach the most vulnerable populations (e.g., high-risk and unreached populations).
We believe there is opportunity to dramatically improve the way health campaigns that deliver health products or services realize impact, including through improved planning/microplanning. These campaigns will achieve higher coverage of target populations, better identify and reach high-risk/unreached populations, and efficiently use campaign resources.
<h2>THE CHALLENGE</h2>
We are seeking innovative solutions that accelerate the improvement of coverage, reach, efficiency, and effectiveness of mass health campaigns that deliver health products or services in low-and middle-income countries, specifically through improved planning/microplanning and focus on unreached populations.
Specifically, we are looking for innovations in approaches, practices, or tools that dramatically improve the planning/microplanning that will lead to improved effectiveness of campaigns. We are also looking for innovative tools and technologies to more effectively identify and reach the most vulnerable populations when countries are designing and implementing mass campaigns.
In order to contribute to the development and spread of campaign "best practices", a solution should be applicable to campaigns beyond the context in which it is originally tested (e.g., applicable in multiple lower- to middle-incomes countries and/or applicable across multiple types of health campaigns such as immunization, NTDs, malaria, or nutrition).
We are especially interested in novel approaches that draw on innovation from large-scale delivery models outside of the health sector, which may include interventions used in the private sector.
Successful proposals should consider the following:
Planning and microplanning: This includes the planning processes - led by governments and often supported by partners - at the national, sub-national, facility, or community levels. Overall planning supports the mobilization of information and resources needed to conduct the campaign, and <a href="https://www.who.int/polio-transition/documents-resources/best-practices-microplanning.pdf?ua=1" target="_blank">microplanning</a> specifically addresses the detailed, delivery-level planning required to reach intended populations with the health intervention. Innovations might include/consider:
<ul><li>Interactive or adaptive microplans that better incorporate past or real-time data (e.g. based on prior campaign performance or operational monitoring data) to guide planning and implementation.</li>
<li>Increased automation of microplans (e.g. updating, adapting microplans for other platforms).</li>
<li>Modeling and analytics to test, identify, and recommend more effective implementation approaches (e.g. modeling to identify optimal location of campaign fixed sites and outreach posts in order to improve community access).</li>
<li>Novel or nontraditional information or data sources to improve the accuracy of planning (e.g. geospatial data to improve population estimation or location and more accurately plan for and target campaign delivery).</li>
<li>Technologies for developing and using community maps or populations that can help campaigns to better reach their intended age groups or sub-populations.</li>
<li>Novel approaches to understanding the effectiveness of campaign planning and implementation while campaigns are ongoing or during post-campaign evaluations.</li>
</ul>Identifying and reaching high-risk or unreached populations: This includes innovative approaches to better understand, identify, and reach un/underserved communities and unreached or "zero-dose" children. This wil likely include novel tools, technologies, and methodologies to more effectively identify and reach high-risk or unreached populations at a subnational level (e.g. approaches to leverage data, maps, or other information to support campaign planning, appropriate use of targeted or sub-national campaigns, and post-campaign assessments).
Criteria for success include solutions that:
<ul><li>Are transformative, novel, or innovative. These interventions will significantly change the way in which campaigns are planned, conducted, or evaluated by proposing new ways of working, leveraging lessons from other sectors, or increasing transparency and effectiveness.</li>
<li>Could be used by various health campaigns beyond the campaign in which the innovation is originally conceptualized or tested, such as for immunization (measles, yellow fever, meningitis, etc.), neglected tropical diseases (trachoma, onchocerciasis, schistosomiasis etc.), nutrition (vitamin A, deworming), malaria (bed net distribution, seasonal malaria chemoprophylaxis), and polio.</li>
<li>Could be used in various low- and middle-income countries beyond the country in which the innovation is originally conceptualized or tested.</li>
<li>Can be designed, tested, and scaled as a "best practice".</li>
<li>Can be applied in low- and middle-income countries.</li>
<li>Are cost effective.</li>
</ul>We will not consider funding for:
<ul><li>Proposals that are not innovative; proposals that only offer incremental / non-transformative improvements (e.g., use of mobile data collection instead of paper-based collection) with no clear link to dramatically improved campaign effectiveness; proposals that repeat conventional approaches without novel application.</li>
<li>Proposals addressing one specific health need/campaign platform, rather than an innovation that would improve health campaigns in general.</li>
<li>Proposals focused on educational campaigns or are not specifically focused on campaign-based delivery of health goods and services. Interventions that are better classified as technical assistance or campaign implementation (e.g., focused on the delivery or improvement of a single campaign).</li>
<li>Proposals focused on improving access to existing tools or technologies or seeking to apply existing tools in ways that do not transform the current practices used for campaign-based delivery.</li>
<li>Proposals where the solution is to leverage one health campaign for co-delivery of other goods or services (e.g., using a NTD campaign to deliver vaccine reminders).</li>
<li>Approaches not directly relevant to low-income settings and that do not clearly consider the local context of available financial systems and infrastructure for resource poor health settings (e.g., using expensive devices; require government issued IDs where few people have them; require hospital deliveries in settings where this is not the norm).</li>
<li>Secondary analysis of existing studies or systematic reviews unless there is a clear way in which the analysis can be scaled and will fundamentally change practice.</li>
<li>Approaches that circumvent the public sector completely.</li>
<li>Approaches which would require a donor’s long-term financial support to sustain.</li>
<li>Approaches that are clinic based.</li>
</ul>_________________________
<a name="#Note1" id="#Note1">1</a>Imdad et al. Vitamin A supplementation for preventing morbidity and mortality in children from six months to five years of age. Cochrane Database of Systematic Reviews, 2017.
<a name="#Note2" id="#Note2">2</a>Portnoy et al. Impact of measles supplementary immunization activities on reaching children missed by routine programs. Vaccine, 2018; In this use, "zero-dose" refers to children with no prior dose of measles vaccine. “Zero-dose” can also refer to children who have not received their first dose of other key vaccines.
<a name="#Note3" id="#Note3">3</a>Internal analysis of WHO PCT Databank and GHO data (accessed September 2019).

Grand Challenges Explorations seeks innovative solutions that accelerate the improvement of coverage, reach, efficiency, and effectiveness of campaign-based delivery of health interventions.

Innovations for Improving the Impact of Health Campaigns (Round 25)

"That's the idea behind Grand Challenges - to focus bright scientists on the problems of the poorest, take some risks, and deliver results." Bill Gates

"Family planning and access to contraception - including information, supplies, and services - is an issue that I am passionate about, and it has become one of my personal priorities at the foundation. 
I believe it's one of the most urgent issues of our time." Melinda Gates

<h2>Background</h2>

Family planning is one of the most cost-effective ways to reduce maternal, infant and child mortality and contributes to the empowerment of women and families, as well as the expansion of opportunities for economic development. In recent decades, there have been tremendous improvements in the reproductive health of women in low resource settings. Global efforts have substantially accelerated progress toward the goal of reaching 120 million additional users of contraception by 2020 in the world’s poorest countries, an achievement well worth celebrating. Nonetheless, it is estimated that over 214 million women in developing countries have an unmet need for modern contraception.

While current contraceptive methods for women include exceptionally safe and effective options, not all methods are suitable for or acceptable to all women at all stages of their reproductive lives, and concerns about undesirable side effects remain a significant barrier to greater uptake and continued use of existing methods. As a result, women who desire to avoid pregnancy often find themselves without viable options that meet their needs. In particular, changes in uterine bleeding patterns are associated with use of hormonal contraceptive methods and copper intrauterine devices and, combined with access challenges and social or religious norms related to contraceptive use or menstrual bleeding, contribute to high discontinuation rates for these methods (up to 40% in the first year of use). While the concept of developing a non-hormonal pharmaceutical contraceptive with an improved tolerability profile as a suitable alternative has been promoted through research efforts and publications, a focused discovery effort has not been systematically pursued.

<h2>THE CHALLENGE</h2>

The Bill &amp; Melinda Gates Foundation is committed to a long-term vision of expanding contraceptive options for the most vulnerable women in low-resource settings through development of new methods that better align with women’s preferences. Contraceptive product innovation will be required to achieve this goal. Specifically, the emphasis for this work is on developing safe and effective non-hormonal contraceptive agents with both improved overall tolerability and a side effect profile differentiated from hormonal methods. This emphasis is based on an understanding that overall tolerability of and side effects from hormonal methods present real and meaningful barriers to women realizing their reproductive intentions.

This vision demands establishment of a strong research foundation upon which to build a robust pipeline of product candidates, recognizing that the attrition rate of products in preclinical and clinical development will likely be substantial due to the high bar for safety and efficacy. In order to establish a set of critical reproductive biology and early stage discovery capabilities, insource novel ideas from other areas of science, and improve the knowledge base needed to support such an effort, the foundation is launching the "Accelerating Discovery for Non-Hormonal Contraceptives" Grand Challenge in 2020. The goal of this Grand Challenge is to identify new approaches and concepts directed at the characterization of novel contraceptive drug targets, the identification of active contraceptive compounds useful for target validation and proof-of-principle studies, and the development of novel and impactful research tools with the potential to revolutionize the field of contraceptive R&amp;D.

The ultimate outcome driving the foundation’s investment in this area is the discovery new drug candidates that i) provide safe and effective contraception, ii) do not rely on systemic administration of reproductive steroid hormones or act through perturbation of sex steroid pathways, and iii) are suitable and appropriate for deployment in a low resource setting. The focus of this Grand Challenge is on broadly enhancing the research ecosystem for contraceptive discovery and advancing novel and bold ideas that can accelerate drug discovery in this field. We do not expect that novel contraceptive product candidates ready for entry into preclinical development will be identified in this early stage of funding. We anticipate, however, that projects funded through this Grand Challenge will identify new drug discovery approaches and technologies that have yet to be effectively applied to contraceptive R&amp;D. We expect to engage a broad range of expertise across disciplines in a collaborative and coordinated research program. It is anticipated, but not guaranteed, that success in these efforts would justify additional investment in a broader drug discovery effort by the Bill &amp; Melinda Gates Foundation, with the goal of developing innovative non-hormonal contraceptive methods to better serve the needs of women.

Approach

As approaches to discovery of new drugs for other indications have become increasingly sophisticated, these advances have not been applied to field of contraceptives. As a result, critical technical barriers continue to hamper progress and limit our ability to effectively identify novel contraceptive agents. These barriers include, but are not limited to:

<ul>
	<li>The inability to appropriately replicate in the laboratory a number of complex multi-cellular reproductive processes for the purposes of compound screening (e.g. ovulation);</li>
	<li>Poor understanding of contraceptive drug targets associated with key fertility pathways, and a lack of validated and scalable approaches to validate and assay potential targets;</li>
	<li>Lack of appropriate medium- to high-throughput phenotypic screening methodologies for identifying compounds capable of exerting a specific and potent contraceptive effect;</li>
	<li>Lack of appropriate in vitro and in vivo preclinical assays and biomarkers to assess i) the efficacy of agents targeting novel contraceptive mechanisms and ii) the potential side effects of novel agents.</li>
</ul>

It is our belief that these challenges can be addressed, and that doing so will create substantial new opportunities for contraceptive drug discovery. We seek to leverage advances in other areas of reproductive biology, both basic and applied, and emerging technologies in drug discovery to establish a suite of capabilities that can support a robust drug discovery program. It is not our intention to establish fully integrated end-to-end drug discovery capabilities with individual institutions through this program, but rather to fund a network of researchers, with each bringing a unique approach, and facilitate interactions between partners to maximize impact. Applicants should keep this in mind when articulating a project plan and focus on the key strengths that their expertise, approach, and technology can provide. Proposals should be aligned with one or more of the funding focus areas outlined below.

We are looking for proposals that:

<ul>
	<li>Engage scientists across a variety of disciplines, including those new to the field of contraceptive R&amp;D;</li>
	<li>Demonstrate innovative thinking by applying or incorporating concepts, methods or technologies not currently being used for contraceptive discovery;</li>
	<li>Present concepts and strategies that are "off the beaten track", significantly radical in conception, and daring in premise;</li>
</ul>

We will NOT consider funding for:

<ul>
	<li>Proposals focused on development of male contraceptives, including work on sperm-based approaches that could only feasibly be applied as vaginal methods;</li>
	<li>Proposals targeting the endometrium for the prevention on embryo implantation;</li>
	<li>Proposals on novel drug delivery systems for contraception;</li>
	<li>Discovery of adjunct or complementary molecules intended for co-delivery with hormonal contraceptive regimens;</li>
	<li>Basic studies of human reproductive biology without a clear connection to enabling non-hormonal contraceptive discovery;</li>
	<li>Pre-clinical or clinical development of advanced leads and candidates;</li>
	<li>Social science, marketing, or acceptability studies related to contraceptive use and uptake.</li>
</ul>

Awardees through this Grand Challenge may have the opportunity to access other Gates Foundation-funded resources, technology platforms, and grantee networks to help support their projects, facilitated by their Gates Foundation Program Officer. Applicants should, as completely as possible, describe what the proposed project will deliver within the scope of the application and the potential path forward, even if that encompasses activities that are beyond the scope of the current funding opportunity. Applicants invited to submit full proposals following LOI review (see the Review Process as detailed in the Rules and Guidelines) should expect to include critical milestones and relevant go/no-go decisions for the proposed project.

Funding Focus Areas:

<ol>
	<li>Biological Assay Development

	Many aspects of female reproduction remain challenging to replicate or model in a tractable, physiologically relevant, and highly reproducible fashion, but such tools and models will be fundamentally important to identifying and profiling contraceptive drug targets and contraceptive compounds. A better toolset of in vitro assays is needed that can recapitulate oocyte and follicle development, follicle selection, follicular rupture/ovulation, corpus luteum formation, cumulus-oocyte complex dynamics, and fertilization, including peri-fertilization events. New models should focus on assay tractability as well as establishing physiological relevance and modeling closely relevant features of the in vivo environment. Applicants seeking to develop such systems should clearly describe the planned approach and how this would improve upon existing methods. Including approaches to validate with human samples or human genetics/genomic information would be viewed favorably. Proposals should include a discussion on how assays will be standardized, validated, and scaled, including where possible the use of genetic or chemical probes as positive controls to demonstrate biologically relevant outcomes following assay perturbation.
	</li>
	<li>Drug Target Identification and Validation
	In the past two decades, target-based drug discovery approaches have become increasingly sophisticated and powerful, but further and complementary approaches are needed to sustain a pipeline of potential drug targets and enhance our understanding of target biology. Emphasis will be placed on unbiased approaches to identify potential contraceptive drug targets. These may include (but are not limited to):

	<ul>
		<li>RNAi- or CRISPR-based methods utilizing a robust and relevant biological assay,</li>
		<li>chemical genomics or proteomics linking probe compound activity to specific drug targets or pathways,</li>
		<li>analyses of human infertility as a pathway to identify relevant drug targets, or</li>
		<li>artificial intelligence-enabled approaches to target identification.</li>
	</ul>

	 
	Target characterization and validation efforts should focus on the determination of whether any particular gene that is critical for a reproductive process is vulnerable to inhibition by a small molecule inhibitor (using, for example, tunable knockdown or inducible degradation techniques), can likely be safely modulated by such an inhibitor (including assessment of roles in somatic tissue and activity of closely related homologs), and is likely to provide the desired contraceptive effect at realistic levels of inhibition (as opposed to complete loss-of-function). Applicants should clearly describe the critical assays, methods, or approaches they are proposing to underpin this work, and describe how such approaches will yield compelling and relevant data that could be used to support entry of identified targets into target-based drug discovery activities.
	</li>
	<li>Chemical genomics, probe generation, pilot screening
	The availability of active compounds that interfere with key steps in fertility would open up many avenues for further biological exploration and target validation, but methods for screening small compound libraries for chemical probe discovery are currently limited. Applications will be considered that propose small pilot-scale screening in complex systems for the purposes of identifying active compounds interfering with key reproductive functions. Applicants must detail how screening systems will be developed, tested, and validated in a format suitable for testing compounds, and should detail the type and source of chemical libraries that would be utilized. Biologically-informed hypotheses may be proposed to select mechanism- or target class-focused libraries as a starting point. We will not consider applications for screening of a single proposed target, but mechanism-focused approaches that interrogate multiple targets involved in a key reproductive process would be considered. Applicants must then describe an approach to deduce the specific targets of compounds identified in cell-based screens and demonstrate concordance between target-based activity and functional activity in validated in vitro systems.
	</li>
	<li>Contraceptive Antibodies
	While the cost and practicality of antibody-based therapeutics has historically been a challenge, particularly for application in a low resource setting, new advances in antibody half-life extension and cost-effective production open up the possibility that antibodies may be a more tractable option in the future, particularly if used in an "on demand" contraceptive modality. Moreover, this may allow consideration of targets that would otherwise not be amenable to small molecule inhibitors and may provide an enhanced safety window. Applications focused on contraceptive antibodies should clearly articulate the data supporting the validation of the proposed antigen target, the methods to be used for antibody identification, and the assays to be used relevant to determination of antibody function.

	(Note: the foundation is not accepting applications based on contraceptive immunization as an intervention modality, though such approaches could be applied experimentally for target validation.)
	</li>
	<li>Translational Science/Preclinical Evaluation Tools
	In addition to target and hit discovery activities, downstream aspects of drug and product development require early consideration to ensure the appropriate tools and data are in place once advanced leads and candidates are identified. We would consider funding for projects aimed at the following issues:

	<ul>
		<li>Identifying candidate biomarkers of efficacy for non-hormonal contraceptive mechanisms-of-action, including biochemical or imaging markers, that can be applied to preclinical in vivo models and, ideally, that could be applicable for validation in human clinical studies.</li>
		<li>Improving our understanding and prediction of reproductive tract and reproductive tissue pharmacokinetics to assist in building PK/PD models and enable early dose selection and safety risk evaluation.</li>
		<li>Improved and tractable in vivo models for contraceptive efficacy that overcome limitations of existing rodent and primate models.</li>
		<li>Innovative methods for early assessment of safety, toxicity, and side effect risk, with particular emphasis on the potential for endocrine disruption and bleeding side effects.</li>
	</ul>
	</li>
</ol>

There are clear thematic overlaps in the focus areas described above, and we would be happy to receive proposals that are directed at multiple focus areas, so long as the application demonstrates strength in all related areas of proposed work.

Award

This Grand Challenges request for proposals intends to fund individual awards of up to USD $2 million and for up to 3 years, based on the scope of the proposed project. The proposed budget must realistically reflect the technical work and project deliverables within a 3-year timeframe; in some cases, a smaller budget may be justified to establish initial proof-of-concept. Budgets and scope may be negotiated with applicants as part of the review process to ensure the foundation’s ability to fund a robust and balanced portfolio with existing available budget (see the Review Process as detailed in the Rules and Guidelines).

Successful award recipients may have the opportunity to apply for additional funding at the end of the grant period, based on technical success, portfolio fit, and continued strategic alignment with the foundation’s priorities. We reserve the right to determine eligibility for subsequent funding for this call based on these criteria.

"That's the idea behind Grand Challenges - to focus bright scientists on the problems of the poorest, take some risks, and deliver results." Bill Gates
"Family planning and access to contraception - including information, supplies, and services - is an issue that I am passionate about, and it has become one of my personal priorities at the foundation. 
I believe it's one of the most urgent issues of our time." Melinda Gates
<h2>Background</h2>
Family planning is one of the most cost-effective ways to reduce maternal, infant and child mortality and contributes to the empowerment of women and families, as well as the expansion of opportunities for economic development. In recent decades, there have been tremendous improvements in the reproductive health of women in low resource settings. Global efforts have substantially accelerated progress toward the goal of reaching 120 million additional users of contraception by 2020 in the world’s poorest countries, an achievement well worth celebrating. Nonetheless, it is estimated that over 214 million women in developing countries have an unmet need for modern contraception.
While current contraceptive methods for women include exceptionally safe and effective options, not all methods are suitable for or acceptable to all women at all stages of their reproductive lives, and concerns about undesirable side effects remain a significant barrier to greater uptake and continued use of existing methods. As a result, women who desire to avoid pregnancy often find themselves without viable options that meet their needs. In particular, changes in uterine bleeding patterns are associated with use of hormonal contraceptive methods and copper intrauterine devices and, combined with access challenges and social or religious norms related to contraceptive use or menstrual bleeding, contribute to high discontinuation rates for these methods (up to 40% in the first year of use). While the concept of developing a non-hormonal pharmaceutical contraceptive with an improved tolerability profile as a suitable alternative has been promoted through research efforts and publications, a focused discovery effort has not been systematically pursued.
<h2>THE CHALLENGE</h2>
The Bill &amp; Melinda Gates Foundation is committed to a long-term vision of expanding contraceptive options for the most vulnerable women in low-resource settings through development of new methods that better align with women’s preferences. Contraceptive product innovation will be required to achieve this goal. Specifically, the emphasis for this work is on developing safe and effective non-hormonal contraceptive agents with both improved overall tolerability and a side effect profile differentiated from hormonal methods. This emphasis is based on an understanding that overall tolerability of and side effects from hormonal methods present real and meaningful barriers to women realizing their reproductive intentions.
This vision demands establishment of a strong research foundation upon which to build a robust pipeline of product candidates, recognizing that the attrition rate of products in preclinical and clinical development will likely be substantial due to the high bar for safety and efficacy. In order to establish a set of critical reproductive biology and early stage discovery capabilities, in-source novel ideas from other areas of science, and improve the knowledge base needed to support such an effort, the foundation is launching the "Accelerating Discovery for Non-Hormonal Contraceptives" Grand Challenge in 2020. The goal of this Grand Challenge is to identify new approaches and concepts directed at the characterization of novel contraceptive drug targets, the identification of active contraceptive compounds useful for target validation and proof-of-principle studies, and the development of novel and impactful research tools with the potential to revolutionize the field of contraceptive R&amp;D.
The ultimate outcome driving the foundation’s investment in this area is the discovery new drug candidates that i) provide safe and effective contraception, ii) do not rely on systemic administration of reproductive steroid hormones or act through perturbation of sex steroid pathways, and iii) are suitable and appropriate for deployment in a low resource setting. The focus of this Grand Challenge is on broadly enhancing the research ecosystem for contraceptive discovery and advancing novel and bold ideas that can accelerate drug discovery in this field. We do not expect that novel contraceptive product candidates ready for entry into preclinical development will be identified in this early stage of funding. We anticipate, however, that projects funded through this Grand Challenge will identify new drug discovery approaches and technologies that have yet to be effectively applied to contraceptive R&amp;D. We expect to engage a broad range of expertise across disciplines in a collaborative and coordinated research program. It is anticipated, but not guaranteed, that success in these efforts would justify additional investment in a broader drug discovery effort by the Bill &amp; Melinda Gates Foundation, with the goal of developing innovative non-hormonal contraceptive methods to better serve the needs of women.
Approach
As approaches to discovery of new drugs for other indications have become increasingly sophisticated, these advances have not been applied to field of contraceptives. As a result, critical technical barriers continue to hamper progress and limit our ability to effectively identify novel contraceptive agents. These barriers include, but are not limited to:
<ul><li>The inability to appropriately replicate in the laboratory a number of complex multi-cellular reproductive processes for the purposes of compound screening (e.g. ovulation);</li>
<li>Poor understanding of contraceptive drug targets associated with key fertility pathways, and a lack of validated and scalable approaches to validate and assay potential targets;</li>
<li>Lack of appropriate medium- to high-throughput phenotypic screening methodologies for identifying compounds capable of exerting a specific and potent contraceptive effect;</li>
<li>Lack of appropriate in vitro and in vivo preclinical assays and biomarkers to assess i) the efficacy of agents targeting novel contraceptive mechanisms and ii) the potential side effects of novel agents.</li>
</ul>It is our belief that these challenges can be addressed, and that doing so will create substantial new opportunities for contraceptive drug discovery. We seek to leverage advances in other areas of reproductive biology, both basic and applied, and emerging technologies in drug discovery to establish a suite of capabilities that can support a robust drug discovery program. It is not our intention to establish fully integrated end-to-end drug discovery capabilities with individual institutions through this program, but rather to fund a network of researchers, with each bringing a unique approach, and facilitate interactions between partners to maximize impact. Applicants should keep this in mind when articulating a project plan and focus on the key strengths that their expertise, approach, and technology can provide. Proposals should be aligned with one or more of the funding focus areas outlined below.
We are looking for proposals that:
<ul><li>Engage scientists across a variety of disciplines, including those new to the field of contraceptive R&amp;D;</li>
<li>Demonstrate innovative thinking by applying or incorporating concepts, methods or technologies not currently being used for contraceptive discovery;</li>
<li>Present concepts and strategies that are "off the beaten track", significantly radical in conception, and daring in premise;</li>
</ul>We will NOT consider funding for:
<ul><li>Proposals focused on development of male contraceptives, including work on sperm-based approaches that could only feasibly be applied as vaginal methods;</li>
<li>Proposals targeting the endometrium for the prevention on embryo implantation;</li>
<li>Proposals on novel drug delivery systems for contraception;</li>
<li>Discovery of adjunct or complementary molecules intended for co-delivery with hormonal contraceptive regimens;</li>
<li>Basic studies of human reproductive biology without a clear connection to enabling non-hormonal contraceptive discovery;</li>
<li>Pre-clinical or clinical development of advanced leads and candidates;</li>
<li>Social science, marketing, or acceptability studies related to contraceptive use and uptake.</li>
</ul>Awardees through this Grand Challenge may have the opportunity to access other Gates Foundation-funded resources, technology platforms, and grantee networks to help support their projects, facilitated by their Gates Foundation Program Officer. Applicants should, as completely as possible, describe what the proposed project will deliver within the scope of the application and the potential path forward, even if that encompasses activities that are beyond the scope of the current funding opportunity. Applicants invited to submit full proposals following LOI review (see the Review Process as detailed in the Rules and Guidelines) should expect to include critical milestones and relevant go/no-go decisions for the proposed project.
Funding Focus Areas:
<ol><li>Biological Assay Development
Many aspects of female reproduction remain challenging to replicate or model in a tractable, physiologically relevant, and highly reproducible fashion, but such tools and models will be fundamentally important to identifying and profiling contraceptive drug targets and contraceptive compounds. A better toolset of in vitro assays is needed that can recapitulate oocyte and follicle development, follicle selection, follicular rupture/ovulation, corpus luteum formation, cumulus-oocyte complex dynamics, and fertilization, including peri-fertilization events. New models should focus on assay tractability as well as establishing physiological relevance and modeling closely relevant features of the in vivo environment. Applicants seeking to develop such systems should clearly describe the planned approach and how this would improve upon existing methods. Including approaches to validate with human samples or human genetics/genomic information would be viewed favorably. Proposals should include a discussion on how assays will be standardized, validated, and scaled, including where possible the use of genetic or chemical probes as positive controls to demonstrate biologically relevant outcomes following assay perturbation.
</li>
<li>Drug Target Identification and Validation
In the past two decades, target-based drug discovery approaches have become increasingly sophisticated and powerful, but further and complementary approaches are needed to sustain a pipeline of potential drug targets and enhance our understanding of target biology. Emphasis will be placed on unbiased approaches to identify potential contraceptive drug targets. These may include (but are not limited to):
<ul><li>RNAi- or CRISPR-based methods utilizing a robust and relevant biological assay,</li>
<li>chemical genomics or proteomics linking probe compound activity to specific drug targets or pathways,</li>
<li>analyses of human infertility as a pathway to identify relevant drug targets, or</li>
<li>artificial intelligence-enabled approaches to target identification.</li>
</ul>
	Target characterization and validation efforts should focus on the determination of whether any particular gene that is critical for a reproductive process is vulnerable to inhibition by a small molecule inhibitor (using, for example, tunable knockdown or inducible degradation techniques), can likely be safely modulated by such an inhibitor (including assessment of roles in somatic tissue and activity of closely related homologs), and is likely to provide the desired contraceptive effect at realistic levels of inhibition (as opposed to complete loss-of-function). Applicants should clearly describe the critical assays, methods, or approaches they are proposing to underpin this work, and describe how such approaches will yield compelling and relevant data that could be used to support entry of identified targets into target-based drug discovery activities.
</li>
<li>Chemical genomics, probe generation, pilot screening
The availability of active compounds that interfere with key steps in fertility would open up many avenues for further biological exploration and target validation, but methods for screening small compound libraries for chemical probe discovery are currently limited. Applications will be considered that propose small pilot-scale screening in complex systems for the purposes of identifying active compounds interfering with key reproductive functions. Applicants must detail how screening systems will be developed, tested, and validated in a format suitable for testing compounds, and should detail the type and source of chemical libraries that would be utilized. Biologically-informed hypotheses may be proposed to select mechanism- or target class-focused libraries as a starting point. We will not consider applications for screening of a single proposed target, but mechanism-focused approaches that interrogate multiple targets involved in a key reproductive process would be considered. Applicants must then describe an approach to deduce the specific targets of compounds identified in cell-based screens and demonstrate concordance between target-based activity and functional activity in validated in vitro systems.
</li>
<li>Contraceptive Antibodies
While the cost and practicality of antibody-based therapeutics has historically been a challenge, particularly for application in a low resource setting, new advances in antibody half-life extension and cost-effective production open up the possibility that antibodies may be a more tractable option in the future, particularly if used in an "on demand" contraceptive modality. Moreover, this may allow consideration of targets that would otherwise not be amenable to small molecule inhibitors and may provide an enhanced safety window. Applications focused on contraceptive antibodies should clearly articulate the data supporting the validation of the proposed antigen target, the methods to be used for antibody identification, and the assays to be used relevant to determination of antibody function.
(Note: the foundation is not accepting applications based on contraceptive immunization as an intervention modality, though such approaches could be applied experimentally for target validation.)
</li>
<li>Translational Science/Preclinical Evaluation Tools
In addition to target and hit discovery activities, downstream aspects of drug and product development require early consideration to ensure the appropriate tools and data are in place once advanced leads and candidates are identified. We would consider funding for projects aimed at the following issues:
<ul><li>Identifying candidate biomarkers of efficacy for non-hormonal contraceptive mechanisms-of-action, including biochemical or imaging markers, that can be applied to preclinical in vivo models and, ideally, that could be applicable for validation in human clinical studies.</li>
<li>Improving our understanding and prediction of reproductive tract and reproductive tissue pharmacokinetics to assist in building PK/PD models and enable early dose selection and safety risk evaluation.</li>
<li>Improved and tractable in vivo models for contraceptive efficacy that overcome limitations of existing rodent and primate models.</li>
<li>Innovative methods for early assessment of safety, toxicity, and side effect risk, with particular emphasis on the potential for endocrine disruption and bleeding side effects.</li>
</ul></li>
</ol>There are clear thematic overlaps in the focus areas described above, and we would be happy to receive proposals that are directed at multiple focus areas, so long as the application demonstrates strength in all related areas of proposed work.
Award
This Grand Challenges request for proposals intends to fund individual awards of up to USD $2 million and for up to 3 years, based on the scope of the proposed project. The proposed budget must realistically reflect the technical work and project deliverables within a 3-year timeframe; in some cases, a smaller budget may be justified to establish initial proof-of-concept. Budgets and scope may be negotiated with applicants as part of the review process to ensure the foundation’s ability to fund a robust and balanced portfolio with existing available budget (see the Review Process as detailed in the Rules and Guidelines).
Successful award recipients may have the opportunity to apply for additional funding at the end of the grant period, based on technical success, portfolio fit, and continued strategic alignment with the foundation’s priorities. We reserve the right to determine eligibility for subsequent funding for this call based on these criteria.

Grand Challenges seeks new approaches and concepts for the characterization of contraceptive drug targets, the identification of active contraceptive compounds, and the development of novel and impactful research tools with the potential to revolutionize the field of contraceptive R&amp;D. We seek to leverage advances in reproductive biology, both basic and applied, and emerging technologies in drug discovery to establish a suite of capabilities that can support drug discovery in this challenging area.

Accelerating Discovery for Non-Hormonal Contraceptives

The <a href="https://www.aasciences.africa/" target="_blank">African Academy of Sciences (AAS)</a>, the <a href="https://www.bmbf.de/en/index.html" target="_blank">German Federal Ministry of Education and Research</a> (Bundesministerium für Bildung und Forschung, BMBF) and the <a href="http://www.gatesfoundation.org" target="_blank">Bill &amp; Melinda Gates Foundation</a> have come together in a transformative partnership to support African investigators to accelerate MNCH targets towards the Sustainable Development Goals (SDGs) for health.

The first initiative of the partnership is to launch a new Grand Challenge: Focusing on top priorities for MNCH in Africa – solutions to meet the Sustainable Development Goal 3 targets for maternal, neonatal and child health.

This challenge focuses on the top priorities for MNCH in Africa 2019 and aligns with the findings of the MNCH research prioritization using The Child Health and Nutrition Research Initiative (CHNRI) process conducted in 2019 in Africa. CHNRI uses the principles of wisdom of the crowds to systematically collect and transparently score research options against important criteria in a particular field. In a three-stage democratic process lasting 7 months, the MNCH expert convening 2019, aggregated thoughts from MNCH experts working in Africa and showed that there is a need to concentrate on four areas of importance in MNCH that remain a grand challenge for Africa. These are:

<ul>
	<li>better health during pregnancy</li>
	<li>better care at birth</li>
	<li>better post-birth care for women and their newborns</li>
	<li>better hospital care of sick newborns</li>
</ul>

The aggregated research priorities are across the spectrum of health research and in all four domains of description (epidemiology), discovery (new interventions), development (improvement of existing interventions), and delivery (implementation research, including health systems).

This is, therefore, a call for proposals looking for big, bold, innovative ideas that can have the greatest impact on African maternal and neonatal health with the potential for future sustainability and scaling.

Grand Challenges Africa

The <a href="https://www.aasciences.africa/" target="_blank">African Academy of Sciences (AAS)</a>, the <a href="https://www.bmbf.de/en/index.html" target="_blank">German Federal Ministry of Education and Research</a> (Bundesministerium für Bildung und Forschung, BMBF) and the <a href="http://www.gatesfoundation.org" target="_blank">Bill &amp; Melinda Gates Foundation</a> have come together in a transformative partnership to support African investigators to accelerate MNCH targets towards the Sustainable Development Goals (SDGs) for health.
The first initiative of the partnership is to launch a new Grand Challenge: Focusing on top priorities for MNCH in Africa – solutions to meet the Sustainable Development Goal 3 targets for maternal, neonatal and child health.
This challenge focuses on the top priorities for MNCH in Africa 2019 and aligns with the findings of the MNCH research prioritization using The Child Health and Nutrition Research Initiative (CHNRI) process conducted in 2019 in Africa. CHNRI uses the principles of wisdom of the crowds to systematically collect and transparently score research options against important criteria in a particular field. In a three-stage democratic process lasting 7 months, the MNCH expert convening 2019, aggregated thoughts from MNCH experts working in Africa and showed that there is a need to concentrate on four areas of importance in MNCH that remain a grand challenge for Africa. These are:
<ul><li>better health during pregnancy</li>
<li>better care at birth</li>
<li>better post-birth care for women and their newborns</li>
<li>better hospital care of sick newborns</li>
</ul>The aggregated research priorities are across the spectrum of health research and in all four domains of description (epidemiology), discovery (new interventions), development (improvement of existing interventions), and delivery (implementation research, including health systems).
This is, therefore, a call for proposals looking for big, bold, innovative ideas that can have the greatest impact on African maternal and neonatal health with the potential for future sustainability and scaling.

The <a href="https://www.aasciences.africa/" target="_blank">African Academy of Sciences (AAS)</a>, the <a href="https://www.bmbf.de/en/index.html" target="_blank">German Federal Ministry of Education and Research</a> (Bundesministerium für Bildung und Forschung, BMBF) and the <a href="http://www.gatesfoundation.org" target="_blank">Bill &amp; Melinda Gates Foundation</a> have come together in a transformative partnership to support African investigators to accelerate MNCH targets towards the Sustainable Development Goals (SDGs) for health.

Challenges

2020 Grand Challenges Annual Meeting Call-to-Action

Integrating Tradition and Technology for Fermented Foods for Maternal Nutrition

New Approaches to Integrating Molecular Surveillance into Malaria Control Programs (Round 26)

Smart Farming Innovations for Small-Scale Producers

Balance the Equation - A Grand Challenge for Algebra 1

Innovations in Materials Science for a Transformative Menstrual Health and Hygiene Product (Round 25)

Improving Access to and Use of Safe and Appropriate Cesarean Section

Innovations for Improving the Impact of Health Campaigns (Round 25)

Accelerating Discovery for Non-Hormonal Contraceptives

Top Priorities for Maternal, Neonatal, and Child Health in Africa

Great ideas come from everywhere.

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View the Grand Challenges partnership network

Great ideas come from everywhere.