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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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Intracellular Survival of S. Typhi in Environmental Acanthamoeba

Dilip AbrahamChristian Medical College, VelloreVellore, Tamil Nadu, India
Grand Challenges Explorations
Salmonella Typhi
1 Nov 2019

Dilip Abraham of Christian Medical College in India will analyze water samples from peri-urban and rural areas in India to study whether and how the typhoid fever-causing bacterium S. Typhi survives by living inside the common amoebae, Acanthamoeba. Acanthamoeba spp. are known to internalize S. Typhi, and may provide an intracellular environmental niche and extend survival of the bacteria. They will collect samples from drinking water sources and sewage lines in peri-urban and rural sites in Southern India. From these samples, they will recover Acanthamoeba and detect any internalized S. Typhi by culture and PCR. Whole genome sequencing will be used to conduct comparative genomic analysis of intracellular S. Typhi to identify any major virulence markers that promote its ability to be internalized by and remain viable within Acanthamoeba. This would help explain why persistence of S. Typhi in the environment can lead to sporadic outbreaks, and allow officials to plan preventative strategies beyond vaccines for the control and elimination of typhoid.

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.

Determining the 'Environmental Typhoid Mary', and Conditions that Favour Perisistence

Andrew GreenhillFederation University AustraliaBallarat, Victoria, Australia
Grand Challenges Explorations
Salmonella Typhi
1 Nov 2019

Andrew Greenhill of Federation University Australia in Australia, along with partners at the Papua New Guinea Institute of Medical Research, will use advanced environmental microbiology methods to study microbial community dynamics associated with survival of the typhoid fever-causing bacterium Salmonella Typhi in aquatic environments in Papua New Guinea. "Typhoid Mary" Mallon was an Irish-American cook, written into infectious disease folklore as the first asymptomatic carrier of S. Typhi. More than eighty years after her death, little is still known about how the bacteria persists in environmental niches such as contaminated water, which is a major route of disease transmission. They will collect and filter water samples from streams in areas where the disease is common over an eight-month period covering both wet and dry seasons and analyze the microbial communities within by qPCR. This will be combined with physiochemical parameters of the water (temperature, stream height, photosynthetic activity) collected using DIMPP - a low-cost, late-stage prototype suitable for use in low-resource environments - to build network models. These models will be used to identify mathematical connections between environmental factors, aquatic populations, and the presence of antibiotic resistance genes. These connections could be used to develop an early warning system for impending outbreaks.

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.

Toward a Permanent Influenza Vaccine: Design of Hemagglutinin Antigen Analogs and Vaccination Protocols by Structural Modeling, Atom-Based Simulations, Machine Learning, and Experiments

Martin KarplusHarvard UniversityCambridge, Massachusetts, United States
Grand Challenges
Influenza Vaccine
29 Aug 2019

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