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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Orapan Sripichai of the National Institute of Health of Thailand in Thailand will engage a national network of laboratories for the genomic surveillance of Salmonella, involving sequencing clinical isolates to characterize strains, virulence factors and mechanisms of antimicrobial resistance. Salmonella infection is prevalent in Thailand and can be life-threatening. The emergence of multidrug-resistant Salmonella strains in Southeast Asia is an additional major concern. They will collect approximately 1,500 clinical isolates from 77 provincial hospitals across Thailand over one year, and train local laboratory scientists and bioinformaticians to produce and analyze genomics data. The data will be uploaded to a standard repository in the National Center for Biotechnology Information (NCBI) and will help to guide prevention and control measures.
Rifky Waluyajati Rachman of the West Java Provincial Health Laboratory in Indonesia will employ targeted next-generation sequencing (NGS) to support genomic surveillance of drug-resistant tuberculosis (TB) in Indonesia. Indonesia has the second highest number of TB cases globally and a growing burden of largely undetected multidrug-resistant TB, yet no drug resistance surveillance in place. They will perform targeted NGS on over 5,000 positive sputum samples to more accurately estimate drug-resistant TB prevalence. They will also conduct whole genome sequencing at the community level to understand transmission patterns and help guide public health interventions. To build capacity, they will provide tailored training on the experimental, bioinformatic, public health, and epidemiological aspects of infectious disease surveillance. They will also establish a public center of expertise for pathogen surveillance in West Java, which has a population of 48 million.
Jacqueline Weyer of the National Institute for Communicable Diseases in South Africa and Jinal Bhiman of Wits Health Consortium (Pty) Ltd also in South Africa will leverage a rapid monoclonal antibody (mAb) isolation and screening pipeline to develop diagnostics that differentiate between pathogens to support epidemic responses. Africa’s burden of many zoonoses and vector-borne diseases (VBD), such as Lassa fever and yellow fever, remains largely unknown, mainly due to diagnostic costs and limited access to reagents. They will leverage an existing screening pipeline, with infrastructure established by the Global Immunology and Immune Sequencing for Epidemic Response - South Africa (GIISER-SA) project, using a mouse model as a more readily available source of pathogen-specific B cells to identify mAbs that detect three ebolavirus species. These mAbs will be tested for sensitivity and specificity using patient samples and can be used to develop immunoassays, including rapid lateral flow assays, which are important for rapid, field-based diagnosis.
Anne Lee of Brigham and Women's Hospital in the U.S. and Yasir Shafiq of Aga Khan University in Pakistan will develop geospatial models to predict risks of undernutrition among adolescent girls and pregnant and lactating women in settings affected by conflict, climate and COVID-19 to help target interventions. Globally, around 30–40 million pregnant women and 50 million adolescent girls are underweight. Risks of undernutrition have recently been amplified by numerous armed conflicts, climatic shocks such as flooding and the COVID-19 pandemic. However, real-time data shortages prevent interventions, such as balanced energy-protein supplements, from reaching the highest-risk groups. Using Bayesian Hierarchical Spatial modeling, they will develop geospatial models for countries vulnerable to conflict and climate change, such as Ethiopia and Yemen. By incorporating socio-demographic and economic indicators, and climate-related and conflict-related shocks from national databases, they can estimate risks based on exposure and predict outcomes, such as undernutrition and anemia.
Margaret Kasaro and Soumya Benhabbour of the University of North Carolina at Chapel Hill in the U.S. will evaluate 3D-printed intravaginal ring (IVR) prototypes in Zambia to identify the design most acceptable to women for long-term use against unplanned pregnancy and HIV infection. In Zambia, HIV prevalence remains particularly high among women, and 41% of pregnancies are unplanned. IVRs are an effective, well-tolerated, and women-controlled contraceptive and HIV-preventative; however, their performance has suffered in large-scale clinical trials because of poor adherence. They have exploited a state-of-the-art 3D-printing process to rapidly engineer IVRs in a cost-effective, single-step process enabling the controlled release of multiple drugs for HIV prevention and contraception. They will recruit around 16 women, aged 18–45 from Kampala Health Centre, and use focus groups to evaluate their views on the proposed 90-day timeframe of use for four different IVR prototypes to guide the final design.
Aida Sadikh Badiane of the Universite Cheikh Anta Diop de Dakar in Senegal will use a metabolomics platform to identify cervicovaginal metabolites and inflammatory mediators associated with high-risk human papillomavirus (HPV) infection, which cause the majority of cervical cancer cases, in Senegalese women. Cervical cancer is the leading cause of cancer deaths in women in sub-Saharan Africa. Metabolic and immune markers could enable more effective diagnoses for these diseases than the current methods used in low-resource settings. They will perform a prospective, cross-sectional study on a cohort of 385 women using an untargeted metabolomics platform to identify molecules within the cervicovaginal microenvironment that are predictive of infection and cancer risk. They will also use Luminex assays to evaluate inflammatory molecules and other markers associated with infection, and sequence the L1-HPV gene in the samples to better track the genotypes in Senegal.
Pragya Yadav of the Indian Council of Medical Research - National Institute of Virology in India will strengthen genomic and epidemiological surveillance in different locations across India to enhance preparedness against high-risk viral diseases. With India's extreme geo-climatic diversity, it is under constant threat of emerging and reemerging viral infections. They will enhance surveillance of endemic diseases in India, including Zika and Dengue, by establishing a network of seven laboratories and training staff in molecular diagnostic techniques, including sequencing, data analysis, and biosafety. They will also select surveillance sites for collecting samples and expand next-generation sequencing capacity to identify variants.
Simon Kariuki of the Kenya Medical Research Institute in Kenya will use an antibody platform to characterize children's immune responses to the new malaria vaccine to determine the impact of any accompanying infections. The WHO recently approved a new malaria vaccine that will mainly be deployed in sub-Saharan Africa. During its development, HIV-infected children were found to mount weaker immune responses. Helminth infections, which are prevalent in sub-Saharan Africa, are also suspected to negatively impact vaccine efficacy. To test this, they will use an antibody-dynamics platform to assess the impact of helminths and other current or prior parasitic, bacterial, and viral infections on humoral and cellular immune responses following the 4th dose of the new malaria vaccine in two- to three-year-old children at six hospitals in western Kenya. This will help design more effective deployment strategies such as deworming before vaccination.
Senjuti Saha of the Child Health Research Foundation in Bangladesh will use a single-cell analytics platform to track the immune responses of babies before and after receiving a pneumococcal conjugate vaccine to determine the impact of various factors, including nutritional status and seasonality, on vaccine efficacy. Vaccines have successfully reduced childhood morbidity and mortality; however, their efficacy can be influenced by host factors and extrinsic factors through unknown cellular mechanisms. They will recruit 50 newborns in a rural district north of Dhaka and collect blood and nasopharyngeal swabs before, during and after a routine vaccination series. They will extract peripheral blood mononuclear cells and use them to perform single-cell RNA sequencing to identify cell subtypes and link differential vaccine responses to factors including gestational age, nutritional status and sex.
Yasir Shafiq of Aga Khan University in Pakistan and Anne Lee of Brigham and Women's Hospital in the U.S. will develop geospatial models to predict risks of undernutrition among adolescent girls and pregnant and lactating women in settings affected by conflict, climate and COVID-19 to help target interventions. Globally, around 30–40 million pregnant women and 50 million adolescent girls are underweight. Risks of undernutrition have recently been amplified by numerous armed conflicts, climatic shocks such as flooding and the COVID-19 pandemic. However, real-time data shortages prevent interventions, such as balanced energy-protein supplements, from reaching the highest-risk groups. Using Bayesian Hierarchical Spatial modeling, they will develop geospatial models for countries vulnerable to conflict and climate change, such as Ethiopia and Yemen. By incorporating socio-demographic and economic indicators, and climate-related and conflict-related shocks from national databases, they can estimate risks based on exposure and predict outcomes, such as undernutrition and anemia.