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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.

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Impact of S. Typhi Genome Structure Upon Survival in Water

Gemma LangridgeQuadram Institute BioscienceNorwich, United Kingdom
Grand Challenges Explorations
Salmonella Typhi
1 Nov 2019

Gemma Langridge of Quadram Institute Bioscience in the United Kingdom, along with co-investigators Aaron Jenkins of the University of Sydney in Australia and France Daigle of the University of Montreal in Canada, will collect different isolates of S. Typhi, which causes typhoid fever, to analyze genomic structure, growth, and gene expression to better understand how it can survive at low levels in water, and determine how it can be reactivated for monitoring. Typhoid fever is a potentially fatal disease associated with exposure to contaminated water. S. Typhi, the bacteria causing the disease, exist in water in a so-called viable-but-non-culturable (VBNC) state, which makes it difficult to monitor for control efforts. Their previous analyses have shown that the VBNC bacteria undergo structural rearrangements of their genomes and changes in gene expression, which may explain the reduced growth. They will analyze the correlation between genome structure and growth of different S. Typhi isolates using samples isolated from around 25 typhoid fever cases, and a further 75 stored isolates across the endemic region. Of these, a selection will be tested for their ability to enter a VBNC state and survive in water from areas of high and low typhoid incidence. One isolate that has entered VBNC with a defined structural genotype will be tested to establish the conditions most suitable for resuscitation.

Immonotherapy 'On-the-Go'

Hasan UludagRJH Biosciences Inc.Edmonton, Alberta, Canada
Grand Challenges Explorations
EmergingTechnologies
1 Nov 2019

Hasan Uludag of RJH Biosciences in Canada will develop an affordable immunotherapy system based on genome-integrating transposons that works inside the body for the treatment of a wide variety of diseases such as cancer and diabetes. Emerging immunotherapies offer promising treatment for many diseases, but they require genetic modification of immune cells outside the body, and are thus labor intensive and expensive, limiting their utility in developing countries. They will use engineered nanoparticles in a new approach to immunotherapy that modifies immune cells inside the body. The nanoparticles are derived from polymeric materials that can encapsulate nucleic acids and proteins and release them into host cells. These nanoparticles will be dispersed in a hydrogel matrix with immunostimulatory molecules to create a living bioreactor inside the host that will attract and genetically modify immune cells. They will select polymers for their ability to deliver DNA-based transposons (to facilitate integration into the host genome) to immune cells and to stably express a reporter gene. Optimal polymers will be transferred into mice and they will evaluate transfection efficiency into immune cells with a fluorescent reporter gene. Finally, they will test the therapeutic efficacy of their in situ immune cell engineering approach in a mouse leukemia model.

Improving Vaccination Awareness and Coverage in Somalia (IVACS)

Andrew SealUniversity College London, Institute for Global HealthLondon, United Kingdom
Grand Challenges Explorations
Immunization Demand
1 Nov 2019

Andrew Seal of the Institute for Global Health and Development in the United Kingdom will test whether traditional female social groups in Somalia can adopt a participatory learning and action (PLA) approach to improve vaccine knowledge and coverage in humanitarian settings. Vaccine-preventable diseases are prevalent in Somalia; measles is the leading cause of death in children under five, yet less than 40% of children are immunized. This is due in part to lack of knowledge about the benefits of vaccination. The PLA approach is based on the idea that sustainable social change is possible if teachers and learners engage in meaningful dialogue and share ideas and experiences. Abbay-Abbay groups, common throughout Somalia, are social groups of 10-20 women, led by an elected Khalifada (lead woman). They meet regularly and have a core interest in the challenges of child rearing, with most women having direct or indirect experience with losing a child to measles. They will recruit coordinators to support Abbay-Abbay leaders, providing information and facilitating learning around vaccinations. They will evaluate their approach for improving attitudes to vaccination and reducing the incidence of measles via a randomized cluster study.

AI and InfraRed Spectroscopy to Accelerate Malaria Control

Fredros OkumuIfakara Health InstituteIfakara, Tanzania
Grand Challenges Explorations
EmergingTechnologies
1 Nov 2019

Fredos Okumu of the Ifakara Health Institute in Tanzania will develop technology to evaluate mosquito control interventions using a combination of artificial intelligence, infrared spectroscopy, and entomology. Malaria caused over 400,000 deaths in 2017, the majority in the developing world, and an effective way to control the disease is to target the mosquitoes that transmit it. Current tools cannot precisely measure mosquito age or life-expectancy, and are therefore unable to predict the impact of mosquito control interventions. The biochemical composition of the mosquito exoskeleton varies with species and age; as the types of chemical bonds change so does the amount of light absorbed in the mid-infrared region. This can be measured with mid-infrared spectroscopy (MIRS), and they will combine this with machine learning to measure the age of mosquito populations. Using a dataset collected from over 25,000 lab-raised mosquitoes, they have developed a supervised machine learning model that accurately predicts mosquito age and species. They will optimize this model to work also on wild mosquito populations, develop an online platform for real-time analysis of mosquito MIRS data, and test its ability to measure the effectiveness of malaria control interventions.

Monitoring Windborne Activities of Disease Vectors, Pathogens, and Pests

Tovi LehmannNational Institutes of HealthBethesda, Maryland, United States
Grand Challenges Explorations
EmergingTechnologies
1 Nov 2019

Tovi Lehmann of the National Institute of Health in the U.S. will establish cross-country networks of aerial sampling stations in Africa to monitor windborne movement of insects and pests, and evaluate risks to public health, food safety, and ecosystem stability. Vector-borne disease is among Africa's top health priorities, and control of the insect vectors is the primary target for prevention. They will use a unique aerial sampling program to collect airborne insects across Mali and Ghana, and identify insects and pathogens within them by molecular analysis. Sticky nets mounted on helium balloons have shown, in a pilot project, to collect diverse samples, more representative of area fauna than ground sampling protocols. The same project showed that mosquitoes frequently travel (and may spread disease) over hundreds of kilometers. Overnight aerial sampling will be conducted ten nights per month for six months, followed by insect taxonomic identification and RNA/DNA sequencing to identify insects and pathogens. Weather data will be collected from the sampling stations at both ground level and sampling altitude and combined with population data for statistical analysis and simulation of flight patterns. They will produce dynamic, species-specific maps of select insects and pathogens with putative sites of origin, routes and destinations, which will be used to evaluate risks to public health and food security.

S. Typhi Mechanisms of Temperature- and Microbiota-Dependent Environmental Persistence

Denise MonackStanford UniversityStanford, California, United States
Grand Challenges Explorations
Salmonella Typhi
1 Nov 2019

Denise Monack of Stanford University in the U.S. will use a genetic approach to identify the molecular mechanisms that enable the typhoid fever-causing bacterium S. Typhi to survive in aquatic environments and to rapidly adapt to transmission to humans. Annually, S. Typhi causes over 20 million infections and 200,000 deaths, mostly among populations that lack access to clean drinking water. Understanding how S. Typhi persists in water and then quickly adapts to its human host is critical for controlling transmission. Bacteria use various mechanisms to adapt to environmental changes, including so-called RNA thermometers (RNATs), which form secondary structures in mRNAs that can rapidly activate gene expression when temperatures change. They will use their established genetic screening approach to identify new RNATs in S. Typhi and validate their ability to promote bacterial persistence within aquatic microbial communities by generating mutants. They will also follow up on past work in which a bioinformatics approach identified new RNATs that may regulate the expression of the chitinase enzyme, which is used by the cholera-causing bacterium to bind to plankton and create a protective environmental niche. They will evaluate whether chitin is also important for S. Typhi persistence and transmission.

Community Theatre for Immunization

Chijioke KaduruCorona Management SystemsAbuja, Nigeria
Grand Challenges Explorations
Immunization Demand
1 Nov 2019

Chijioke Kaduru of Corona Management Systems in Nigeria will use a human-centered approach to develop a community theater production that showcases real stories to educate caregivers on the value of vaccinations and increase childhood vaccine coverage. Almost half of caregivers in Nigeria lack awareness of the value of vaccines, which has increased the incidence of childhood diseases. To address this, they will stimulate social change by showcasing aspects of immunization - identifying concerns and discussing potential solutions - in a community theater production based at the income and education level of caregivers. They will work with stakeholders including immunization teams, community health workers, women's groups, and religious leaders to develop the production. The cast will be made up of community members with real experiences, and performances will be held in public places, traditional meeting spaces, schools, and places of religious worship, and be recorded for future airing. By better engaging caregivers with their human-centered approach, they expect to generate a greater demand for immunization services.

Crowdsourcing to Rebuild Chinese Caregiver Trust in Childhood Vaccines

Joseph TuckerLondon School of Hygiene and Tropical MedicineLondon, United Kingdom
Grand Challenges Explorations
Immunization Demand
1 Nov 2019

Joseph Tucker of the London School of Hygiene and Tropical Medicine in the United Kingdom will hold a national crowdsourcing contest to develop a social media-based intervention to improve confidence in childhood vaccines and boost coverage in China. Expert-driven strategies have been launched to promote vaccination coverage in China, but have had limited effect. As an alternative approach, they will apply crowdsourcing to tap into the knowledge of individuals to design a more effective, online intervention. They will open the contest with a call for new ideas that use text, images, and videos to promote vaccinations; enable online evaluation of those ideas by crowd and expert judges; and assemble a steering committee of health experts to produce the finalists. The final content of the intervention will be developed by the finalists in an intensive 'designathon' event. They will test the new intervention in select community health centers in three cities in China and analyze its ability to improve confidence in vaccinations.

Immunization Strategies for Working Mothers

Olukemi AmoduCollege of Medicine, University of IbadanIbadan, Nigeria
Grand Challenges Explorations
Immunization Demand
1 Nov 2019

Olukemi Amodu, Mofeyisara Omobowale and Folakemi Amodu of the University of Ibadan College of Medicine in Nigeria will develop a three-part intervention to provide more convenient and accessible vaccinations for children of working mothers to increase the timeliness and completion of childhood vaccinations. Despite education campaigns, the demand for childhood vaccination in Nigeria is low, partly because working mothers have limited time to attend vaccination clinics. The three-part intervention comprises priority and more convenient immunization services at existing clinics, mobile vaccine clinics for the many mothers who work long hours in the marketplace, and a smartphone-based application to send vaccine reminders. They will test their approach in the city of Ibadan by setting up mobile clinics at three market places to provide weekly vaccination services and education counseling for mothers in their own shops. These mothers will also be supported with a savings program (VaccoSavings) to help them track money saved to pay for vaccines not paid for by the government. They will also enable mothers working in the formal sector to book vaccine appointments at more convenient times at a child welfare center where they will be attended to promptly. All mothers with smartphones will be supported by the VaccApp application to track vaccine schedules and provide automatic reminders. The impact of these combined strategies on the demand for vaccinations will be evaluated after one year.

S. Typhi Survival and Gene Acquisition in Biofilm Communities

Windy TannerUniversity of UtahSalt Lake City, Utah, United States
Grand Challenges Explorations
Salmonella Typhi
1 Nov 2019

Windy Tanner and Jim VanDerslice of the University of Utah in the U.S., together with colleagues from Mehran University of Engineering and Technology in Pakistan, will analyze water samples to determine the conditions that promote the survival of the typhoid fever causing bacterium Salmonella Typhi, and they will use metagenomic deconvolution to identify any gene exchange from other microbial species that may produce drug-resistant strains. S. Typhi is responsible for over 100,000 deaths each year, mostly in the developing world where fecal contamination of food and drinking water is common. The emergence of drug-resistant strains has limited the available treatment options. Biofilms are environmental niches with complex microbial communities and are ubiquitous in the environments where S. Typhi is commonly found. They will sample water and biofilms from a variety of these environments along the fecal-drinking water transmission route in the Sindh province of Pakistan and test for the presence of S. Typhi using qPCR and culture methods. They will also evaluate whether specific organisms stabilize and protect S. Typhi in these biofilms and could cause resistance gene exchange.

Does Phage Predation Shape Typhoid Ecology in Urban Water?

Jason AndrewsStanford UniversityStanford, California, United States
Grand Challenges Explorations
Salmonella Typhi
1 Nov 2019

Jason Andrews of Stanford University in the U.S. will study the association between the typhoid fever-causing bacterium Salmonella Typhi and its bacteriophage in both aquatic environments and the human gastrointestinal tract to see if they influence geographic and seasonal disease outbreaks in Bangladesh. The ecology and evolution of many know bacterial pathogens including V. cholerae are affected by the viruses (bacteriophage) that infect them. Indeed, seasonal cholera epidemics are inversely correlated with phage prevalence in water. They will study this relationship in S. Typhi, which contaminates half of city water supplies in Bangladesh. They will generate a library of local phage strains infecting S. Typhi and use a computational approach to identify indicator S. Typhi strains that may be susceptible to these phage, which they will then test experimentally. They will also characterize the abundance and strains of phage in municipal water supplies, and in stool samples from typhoid cases, and compare these with clinical cases of typhoid to determine if they shape temporal and spatial patterns of typhoid.

The Routine Immunization Buddy System (RIBS)

Itoro AtaSolina Center for International Development and ResearchAbuja, Nigeria
Grand Challenges Explorations
Immunization Demand
1 Nov 2019

Itoro Ata of the Solina Center for International Development and Research in Nigeria will implement a program to support unemployed mothers in Nigeria by linking education on the importance of vaccinations with vocational skills education and training to improve immunization coverage. Many rural areas in Nigeria have consistently low rates of routine immunization and large populations of unemployed, stay-at-home mothers whose children are at risk of vaccine-preventable disease. They will create a direct link between community health systems and economic empowerment programs focused on vocational skill development by creating the Routine Immunization Buddy System (RIBS). Mothers in the program will be placed in small support groups and paired with another woman within the group. The lead woman of each group will be trained by community health workers to provide practical information on vaccines using a teaching tool called Hannun Rigakafi (the immunization hand). Women in the RIBS groups will also be taught about possible work options, such as farming, and offered associated tools and training. Pairing education on vaccines with vocational training should help boost the confidence of the mothers and better motivate them to complete the five routine childhood immunizations for their children. The program will be piloted in the Kaduna state of Nigeria and evaluated for improving vaccination knowledge and demand.

SALUBONG: Building Vaccine Confidence in the Philippines

Shannon McMahonUniversity of HeidelbergHeidelberg, Germany
Grand Challenges Explorations
Immunization Demand
1 Nov 2019

Shannon McMahon of the Heidelberg Institute of Global Health in Germany and Mark Donal Reñosa of the Research Institute for Tropical Medicine in the Philippines will create and test an intervention based on narrative and imagery to re-establish trust in vaccinations in Western Visayas, Philippines. Confidence in the safety of vaccines has recently dropped in the Philippines, exacerbated by controversy with a dengue vaccine in 2017. The country is now facing a measles outbreak, with a 3000% increase in cases in some areas. They will develop Salubong, a program named for an important Filipino term, to improve confidence in vaccines. It is a word that means to welcome someone into one’s life. An intervention of this name is implicitly rooted in understanding and compassion, rather than in blunt scientific logic, and is expected to be effective at encouraging wary families to reconsider their views. Also an acronym for its own development, Salubong will be developed through Share Appraising (focus groups with parents and community members), Life Stories and Uncovering (in depth interviews with parents and storyboard and think-aloud exercises), Bridging and Optimizing (presentation of the results to community health workers) and Navigating and Gaining (testing of the model in urban and rural areas with measles outbreaks).

A Malaria Mosquito Gut On-a-Chip

Pietro AlanoIstituto Superiore di SanitàRome, Italy
Grand Challenges Explorations
EmergingTechnologies
1 Nov 2019

Pietro Alano of the Instituto Superiore de Sanità in Italy will develop a biochip that mimics the midgut of the Anopheles mosquito and can be used to more easily and quickly test candidate anti-malarial compounds for blocking transmission of the causative Plasmodium parasite. Malaria is a potentially fatal infection caused by parasites transmitted between humans through the bites of infected mosquitoes. When a mosquito bites an infected person, immature Plasmodium gametocytes enter the mosquito and transform into an invasive ookinete stage in its midgut. They then traverse the gut wall to the external gut lumen, where they enter their parasite stage. To eliminate malaria, compounds are needed that block the transmission of Plasmodium. However, current methods to evaluate the candidate transmission-blocking drugs or vaccines that are under development are slow and involve feeding malaria-infected blood to mosquitoes, which is potentially dangerous. As an alternative, they will create a biochip to reproduce the mosquito midgut environment that can support the development of parasites, and develop a bioluminescent antibody-based technique to count successfully traversing ookinetes. They will test the performance of the biochip using known anti-transmission drugs.

S. Typhi in Water and Role of Microbial Partners

France DaigleUniversité de MontréalMontreal, Quebec, Canada
Grand Challenges Explorations
Salmonella Typhi
1 Nov 2019

France Daigle of the University of Montreal in Canada will identify the microorganisms that enable the survival of the typhoid fever-causing bacterium, Salmonella enterica serovar Typhi, at low levels in water, and thereby enhances disease spread. Typhoid fever spreads through contaminated food and water, and results in over 125,000 deaths annually worldwide. S. Typhi are so-called auxotrophic bacteria because they rely on an external source of the essential amino acids that they need to grow. Microbial interactions may provide nutrients and also increase bacterial fitness and support persistence by protecting them from the environment, thereby increasing the rate of disease transmission. They will assemble a microbial community in water consisting of three components: one protozoan (from a group known to promote bacterial survival); a defined consortium of bacteria representative of the human fecal microbiota; and fluorescently-tagged S. Typhi. They will evaluate the ability of S. Typhi to grow in these microcosms, and how they grow, such as in biofilms or inside the protozoa. They will also determine whether these persistent S. Typhi are better able to infect and survive in human cells. Finally, water samples from an endemic region in East Africa will be analyzed for the presence of S. Typhi and identified beneficial microbial partners using quantitative PCR.

Genome Sequencing of S. Typhi in Protistan Reservoirs

Andrew JacksonUniversity of LiverpoolLiverpool, United Kingdom
Grand Challenges Explorations
Salmonella Typhi
1 Nov 2019

Andrew Jackson of the University of Liverpool in the United Kingdom will determine whether the amoeba, Acanthamoeba, which is commonly found in water and soil, acts as a host for Salmonella Typhi bacteria, which cause typhoid fever, to support growth and disease spread in Malawi. Typhoid fever is a systemic, potentially fatal illness, usually contracted by consuming contaminated drinking water. An estimated 11-21 million cases occur worldwide each year. Acanthamoeba is known as the 'Trojan Horse' of the microbial world for its ability to host a number of human pathogens, including S. Typhi. It is speculated that Acanthamoeba acts as an environmental reservoir to facilitate the survival of S. Typhi, and perhaps other human pathogens. They will prove the widespread presence of Acanthamoeba-Salmonella associations directly by using single-cell DNA sequencing. Individual amoeba will be isolated from water and soil samples from typhoid hotspots in Malawi using fluorescence-activated cell sorting. Total DNA in each amoeba will be sequenced in order to identify carriage of S. Typhi strains. Single nucleotide polymorphism analysis will be used to compare these with bacteria in local clinical isolates to determine the role of Acanthamoeba in disease transmission.

On-Demand, Cell-Free Biomanufacturing of Conjugate Vaccines

Matthew DeLisaCornell UniversityIthaca, New York, United States
Grand Challenges Explorations
EmergingTechnologies
1 Nov 2019

Matthew DeLisa of Cornell University in the U.S. will create a cell-free synthetic biology platform for low-income settings that produces thermostable polysaccharide-based conjugate vaccines against diarrheal pathogens upon the addition of water to a single tube. Half-a-million children under age five die each year from diarrhea and dysentery, the majority in low- and middle-income countries. Two major causes of bacterial diarrhea are enterotoxigenic E. coli (ETEC) and Shigella strains. Conjugate vaccines combine multiple antigens into one vaccine to increase its activity. However, they require a complex manufacturing process, living cells, and refrigerated storage, which limit their application in developing countries. They will develop the materials and methods for manufacturing thermostable anti-diarrheal vaccines in single tubes that only require the addition of water just ahead of administration. The tubes will contain a plasmid that can express an FDA-approved carrier protein, along with selected O-antigen-polysaccharides from ETEC or Shigella strains, and an enzyme that can conjugate the two via glycosylation, all within a freeze-dried pellet. Following development, they will test the safety, scalability and portability of the vaccines, and characterize their ability to generate effective antibodies that can kill the bacteria. The system is expected to reduce conjugate vaccine costs, and its modular nature will facilitate expansion to other vaccine-preventable diseases.

Overcome Hysteresis Effect by Social Network Targeting

Feng FuDartmouth CollegeHanover, New Hampshire, United States
Grand Challenges Explorations
Immunization Demand
1 Nov 2019

Feng Fu of Dartmouth College in the U.S. will use social networks to promote positive attitudes and overcome negative views of vaccinations and thereby increase demand. The success of vaccinations has led to steep declines in the incidence of many serious diseases. However, this has decreased the perception of disease risk and thereby lowered vaccination coverage as parents concerns switch to other factors, such as cost and the perceived risk of the vaccination itself, which are fueled via social media channels. These current low vaccination rates exhibit so-called hysteresis whereby the past concerns about safety or necessity prevent the rates from increasing even when the concerns have been disproven. To overcome this, they will use computer modeling approaches to test the ability of targeting social networks to leverage social "contagion" (i.e., spread) of positive attitudes to vaccine knowledge. They will use a healthcare intervention dataset from a network of rural villages in Honduras to model how one or more health-related behaviors or beliefs of an individual affects the group to simulate the social contagion process related to vaccines. They will also evaluate the potential positive impact of influential individuals who publicly support vaccination. The results will be used to develop social network targeting algorithms to increase the demand for vaccination. Their modeling results will be validated using the real data from the village networks.

Leveraging Food Distribution Networks to Increase Knowledge

Jessica CraigCenter for Disease Dynamics, Economics & PolicyWashington, District of Columbia, United States
Grand Challenges Explorations
Immunization Demand
1 Nov 2019

Jessica Craig of the Center for Disease Dynamics, Economics and Policy in the U.S. will use existing food distribution networks in low-income countries to publicize the importance of vaccination and inform caregivers when, where, and how to access local vaccine services by printing them on food labels, food and water carrying tools, and receipts. They will test whether their approach can improve vaccination rates using one rural and one urban area each in Kenya and in the Central African Republic. They will map their food distribution systems and health service clinics and consult local healthcare workers on the design of vaccine information materials to reach both literate and illiterate populations. They will evaluate the number of caregivers interacting with the materials using surveys in clinics, as well as the change in vaccination rate before and after a six-month period with materials in circulation. The approach is relatively simple and cost-effective because it leverages an existing network with a wide audience, and requires no additional work from frontline healthcare workers. It is also adaptable to any setting with a food distribution network, and can be expanded to deliver other types of health information.

Improving Frontline Worker and Caregiver Skills in Vaccination Pain Management

Caroline AuraUniversity of NairobiNairobi, Kenya
Grand Challenges Explorations
Immunization Demand
1 Nov 2019

Caroline Aura from the University of Nairobi in Kenya will teach frontline health workers and caregivers new skills so they can apply simple techniques such as swaddling and rocking to lessen the pain and distress of infants during injections to improve vaccination rates. Vaccination rates are still too low in many low-resource settings, which may be due in part to the discomfort they cause infants. This in turn makes caregivers reluctant to obtain all the recommended vaccinations for their children. Methods exist to reduce the associated pain of injections, but health workers lack the knowledge and skills to implement them. To test their approach, they will recruit vaccinators and community health workers at four rural immunization centers and use seminars and workshops to teach them pain-relieving techniques, including using specific positions and making soothing sounds. They will also develop audio-visual training tools and illustrative guides to help teach the techniques to parents for them to use at home as well. All healthy children under 12 months old visiting the centers for a vaccination will also receive one of the pain relief techniques. They will evaluate the ability of the health workers to manage pain, the level of distress of the infants, and the experience of the caregivers.

S. Typhi and Protozoa in Contaminated Water in Zimbabwe

Robert KingsleyQuadram Institute BioscienceNorwich, United Kingdom
Grand Challenges Explorations
Salmonella Typhi
1 Nov 2019

Robert Kingsley of the Quadram Institute Bioscience in the United Kingdom will locate the typhoid fever-causing bacteria S. Typhi in water reservoirs in Harare, Zimbabwe, and identify any associated protozoa species present in the water that may be supporting disease spread. Typhoid fever is endemic in Zimbabwe, with several major outbreaks reported in the last decade. The bacteria persist in unclean aquatic environments, possibly supported by protozoa, and are transmitted to humans through ingestion of contaminated drinking water. They will detect S. Typhi in sewage effluent and low-quality drinking water in hotspots of typhoid transmission by enrichment culture and PCR, and use whole genome sequencing to establish the phylogenetic relationship between these bacteria and clinical typhoid isolates in the same city. They will also amplify 18S rDNA from the sewage and drinking water samples to characterize the microbial community in water and define the protozoa population. These data will help identify potential synergistic interactions between S. Typhi and other microbes to inform prevention strategies.

Mobile Solutions for Mobile Populations: Closing the Gap

Ernest DarhokBroadReachCape Town, South Africa
Grand Challenges Explorations
Immunization Demand
1 Nov 2019

Ernest Darhok of Broadreach in South Africa will use mobile technology to improve access to child immunization services for populations living on the Kenya-Uganda border and help ensure all children are fully vaccinated. Refugee populations living in cross-border settings and migrant communities are particularly difficult to cover because of limited access, poor coordination across borders, and lack of efficient tracking. They have been using a human-centered approach to understand what these populations need to vaccinate their children, and have pilot tested the use of near-field communication cards with an immunization application that holds a child’s vaccination and health data for caregivers, which they can also use to plan more convenient appointments. This card can then be viewed and updated by health workers on both sides of the border using a mobile system. They will extend this pilot study to a wider population in Kenya and Uganda to evaluate the effect on vaccination rates against polio, and apply machine learning methods to better forecast vaccination needs at cross-border facilities to avoid stocks running out. They will obtain user feedback at all stages to help improve their approach.

Missed Opportunities for Vaccination Equity (MOVE)

Anita ShetJohns Hopkins University Bloomberg School of Public HealthBaltimore, Maryland, United States
Grand Challenges Explorations
Immunization Demand
1 Nov 2019

Anita Shet of Johns Hopkins School of Public Health in the U.S. will seek to increase childhood vaccination coverage in India and Nigeria by identifying opportunities for catch-up vaccinations when under-vaccinated children are hospitalized. Of the three million people who die each year from vaccine-preventable diseases, about half are children under the age of five, many of whom live in areas where vaccinations are available, but inequitably distributed. Inadequately vaccinated children frequently become sick and are hospitalized, yet most leave the hospital without receiving catch-up vaccines because of physical and policy barriers, or perceived contraindications. They will engage stakeholders, including hospital policy makers and community workers to launch MOVE (Missed Opportunities for Vaccine Equity) to identify and correct missed opportunities for vaccination by using child hospital visits to provide vaccine education and access. MOVE has three components: inpatient in-reach, where MOVE staff check immunization records and inform hospital personnel of missing vaccines; immunization service linkage to inpatient care, which ensures that vaccines are available and provides a vaccination schedule at discharge; and community outreach to provide follow-up reminders and education. They will modify an immunization application and reminder tool to record the data and maintain a cloud-based registry, and test their approach in two large community hospitals in India and Nigeria.

Community-Championed Social Norms Marketing

Amos KahwaDamax Solutions Company LtdDar es Salaam, Tanzania
Grand Challenges Explorations
Immunization Demand
1 Nov 2019

Amos Kahwa of Damax Solutions Company Ltd. in Tanzania will use human-centered design principles to develop a community-supported, social marketing approach that breaks down misconceptions and psychosocial barriers to immunization in developing countries and thereby increases demand. Research has identified several causes of the current low demand for vaccinations including misconceptions about safety, inadequate knowledge of schedules, and negative experiences at clinics. Current approaches designed to increase demand such as better education and incentives have had a limited effect. As an alternative, they propose to directly target the misperceptions and societal influences and empower the communities to help. They will first consult with community members and local government to gain further insight into the drivers of low demand that will be used to design a prototype package of interventions in collaboration with the local community. They will perform several rounds of testing and refining this package, and they will evaluate its ability to improve perceptions and social norms towards vaccinations and ultimately to improve demand.

Addressing Preeclampsia with Nanomedicine and Bioengineering

Marnie WinterUniversity of South AustraliaAdelaide,, South Australia, Australia
Grand Challenges Explorations
EmergingTechnologies
1 Nov 2019

Marnie Winter of the University of South Australia, together with Tina Bianco-Miotto, Claire Roberts, and Clare Whitehead of the University of Adelaide in Australia and the University of Toronto in Canada, will develop and test short-interfering RNAs (siRNA) high-density lipoprotein (HDL) nanocarriers for the treatment of preeclampsia. Globally, ten million women develop preeclampsia during pregnancy each year, which results in the deaths of 76,000 women and 500,000 babies; 99% of these are in developing countries. Most current treatments focus on treating the symptoms (high blood pressure and proteinuria) rather than the molecular causes. Some of the causative molecules, such as the angiogenesis inhibitor sFlt1, can be blocked by specific siRNAs, but the challenge is targeting the siRNAs to the right cells in the body. HDL delivery systems for this purpose are effective and safe, and both siRNAs and HDLs are stable at room temperature, important for therapies in resource-poor areas. They will optimize the formulation of their HDL nanocarrier manufacturing platform, and characterize siRNA loading, carrier stability, size, cellular uptake, and silencing ability in 2D culture. Further, they will bioengineer an ex-vivo placenta model that fully recapitulates the structural and phenotypic complexity of a preeclamptic placenta and use it to evaluate tissue penetration and silencing abilities of the siRNA-nanocarrier complex.

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