Grand Challenges is a family of initiatives fostering innovation to solve key global health and development problems. Each initiative is an experiment in the use of challenges to focus innovation on making an impact. Individual challenges address some of the same problems, but from differing perspectives.
Iwnetim Abate and Loza Tadesse of SCIFRO Inc with Manu Prakash of Stanford University both in the U.S. will develop an education platform to inspire and equip African college students to solve local health problems through science using simple, inexpensive tools such as paper-based centrifuges and chemistry kits. Less than 8% of sub-Saharan Africans get to attend tertiary education, and there are limited options for pursuing a career in science. This means that even with the recent rise in inexpensive scientific equipment, many local problems of Africans remain unsolved. They will develop easy-to-follow pedagogy and teaching kits and use them to conduct a pilot study by holding a month-long summer workshop for 100 Ethiopian college students in Addis Ababa. The workshop will demystify the scientific process and motivate the students to begin tackling local projects, which will be monitored online. They will also invite 20 college instructors to participate and provide them with kits to distribute to their local schools and colleges.
Yasmin Chandani of inSupply Health Limited and Pratap Kumar of Health-E-net Limited both in Kenya will develop a simple digital health tool to support the maternal and child health supply chains for low-literate, nomadic communities spread sparsely across Kenya. Counties in semi-arid lands have poor maternal and child health indicators caused by vast distances, low literacy rates, no fixed health facilities, and no data on supply chains. To address this, they will develop software to combine paper-based methods with feature-phone cameras for community health workers to easily record data on stocks and supplies. The recorded data will be integrated into existing workflows to inform supply chain managers and support ordering and resupply decisions. They will perform a twelve-month pilot study in Turkana County that will involve training community health workers to use the tool, and they will evaluate its performance in accurately recording stocks dispensed and received during resupply. They will also collect qualitative feedback from health workers to help improve the tools design.
Rudolph Gleason of Georgia Tech Research Corporation in the U.S. and Abebbaw Fekadu of CDT-Africa in Ethiopia will develop a low-cost, wearable device that wirelessly monitors the vital signs of neonates in low-resource settings to help lower mortality rates. In Ethiopia, and many other regions, the leading causes of neonatal deaths are respiratory distress, infection, and asphyxia. However, the key warning signs of these conditions - temperature, heart rate, respiratory rate, and blood oxygen concentration - are difficult to monitor in low-resource settings that often lack sufficient technical resources and medical staff. They have built a first-generation device that they will test on 50 neonates over seven days in a hospital in Addis Ababa to assess its performance in the clinic and gather user feedback from nurses and parents. Using the results, they will employ a user-centered design approach and engage Ethiopian engineering students to improve the device design and perform a market analysis and cost assessments for local manufacturing.
Zaza Ndhlovu of the Africa Health Research Institute in South Africa and Fekadu Tafesse of Oregon Health & Science University (OHSU) will identify the molecular mechanisms enabling HIV to survive in humans to help develop new therapies to fully eradicate the disease. Potent antiretroviral therapies have rendered HIV a manageable chronic disease, but it is still incurable. Needing daily medication over a lifetime makes this approach ultimately expensive and also challenging to maintain in low-resource settings. The virus is thought to evade existing therapies by locating to lymph nodes where it is protected from being destroyed by CD8 T cells. CD8 T cells are banned from lymph nodes because they don't express the CXCR5 protein. They have discovered several epigenetic mechanisms that regulate CXCR5 levels. To follow up, they will screen 471 compounds that target epigenetic processes and may also upregulate CXCR5 in human primary CD8 T cells, and they will also test a known regulator of CXCR5 expression. Their results could lead to a gene therapy-based approach to cure HIV.
Mohlopheni Marakalala of the Africa Health Research Institute in South Africa and Eric Rubin of the Harvard TH Chan School of Public Health in the U.S. will use a genetic screening tool, Tn-seq, to identify the specific bacterial genes protecting Mycobacterium tuberculosis (MTB) from immune destruction that could be used to develop new therapeutic approaches to fight tuberculosis, which causes over 1.5 million deaths annually. BCG is the only approved tuberculosis vaccine, but its effect is limited, particularly in adults. This may be because BCG induces a memory-like innate immune response mediated by macrophages, so-called ‘trained immunity’, which the bacterium somehow evades. To find out how, they will use transposon-mediated mutagenesis to mutate every non-essential gene in MTB and use these mutant strains to infect BCG-trained monocytes isolated from vaccinated humans. The genes that enable MTB to survive under these conditions will then be identified by whole genome sequencing and validated using genetic and chemical approaches. This could ultimately lead to the development of targeted drugs to support BCG vaccinations.
Justin Lessler of the International Vaccine Access Center, Baltimore of the Johns Hopkins University Bloomberg School of Public Health in the U.S. and Anthony Ahumibe of Nigeria Centre for Disease Control in Nigeria will launch a West African disease surveillance network for cholera to leverage local pathogen genome sequencing efforts for disease control and ultimately elimination. New genome sequencing technologies at substantially decreased costs have opened up the opportunity for laboratories in low-resource settings to monitor local disease by sequencing the genomes of the causative pathogens, which is critical for understanding disease epidemiology and guiding control efforts. However, these laboratories often lack the ability to analyze complex sequencing data. To address this, they will hold sequencing training workshops; provide equipment, reagents, and ongoing bioinformatic support; and establish a cross-country peer network using online collaborative tools. In addition, in response to the COVID-19 pandemic, support for SARS-CoV-2 sequencing will be provided to selected sites in the disease surveillance network.
Lemu Golassa of Addis Ababa University in Ethiopia and Laurent Dembele of University of Science, Techniques and Technology of Bamako in Mali will analyze the malaria-causing parasite Plasmodium vivax to identify molecules that enable it to transform into a dormant hypnozoite form in the liver, which is thought to be the key obstacle to malaria elimination. In many regions, P. vivax has become the dominant species causing malaria, resisting eradication due to this dormant liver stage of infection where it is resistant to most existing drugs and still a major cause of disease. Understanding how P. vivax forms hypnozoites could help develop more effective malaria drugs. They will isolate P. vivax from human blood and use cultured liver cells to evaluate their ability to form hypnozoites. Transcriptional profiling on these different isolates should reveal the molecular markers that enable P. vivax to form hypnozoites, which could be used as drug targets.
Clare Wenham of the London School of Economics and Political Science in the United Kingdom and colleagues will study whether considering gender in the design and operation of mosquito-control programs can help them to sustainably eliminate vector-borne diseases such as Zika. Brazil has eliminated disease-causing mosquitoes several times, but they keep returning. Data from Africa have shown that malaria control programs purposefully involving women have longer-lasting effects, which may translate to other countries and for other diseases. To test this, they will analyze how women impact vector control programs, as well as how they are specifically affected by them, by conducting fieldwork, including interviewing local community health workers and vector control agents, and analyzing existing data. This evidence will be used to produce a gender-mainstreamed vector control policy for piloting to test whether gender is a valuable determinant of the success of disease-control programs.
Lyle McKinnon of the University of Manitoba in Canada and Nicola Mulder of the University of Cape Town in South Africa will study the cause of bacterial vaginosis, which is linked to reproductive health complications and increased risk of HIV, to help identify new treatments. Bacterial vaginosis (BV) is characterized by harmful vaginal populations of anaerobic bacteria, often recurs, and is more common in Black and Latina women, suggesting that there could be a genetic component involved. Indeed, their previous genome-wide association study in South African women identified two human genetic variants associated with BV. These genes are involved in the epithelial-to-mesenchymal transition whereby epithelial cells lose their adhesion properties to become more like mesenchymal cells. To test whether this process is key to BV, and can thus be used to develop new treatments, they will expand their genome-wide association study and use in vitro cell models to analyze the role of the epithelial-to-mesenchymal transition in promoting the growth of harmful types of bacteria.
Sunday Ekesi of the International Centre of Insect Physiology and Ecology in Kenya and Josh Tewskbury of Future Earth in the U.S. will model the effects of climate change on major food crops and their insect pests to better forecast crop yields and inform intervention strategies. The changing climate will likely have a multitude of effects on both insect-pest populations, by affecting their size and activity, and on crop physiology, which together will affect yield. They will dissect these complex interactions focusing on maize, which is the main staple food in Kenya, and a major maize-pest, and use a phytotron (enclosed research greenhouse) to evaluate the effects of the current climate, and a range of projected climates, on insect feeding rates and crop levels. These data will then be used in a process-based dynamic modelling approach to develop robust mathematical models that can make accurate predictions on crop loss caused by the climate.