Awarded Grants

Vinicius de Araujo Oliveira of Fiocruz in Brazil will develop a framework for the re-use of large clinical and administrative datasets to enable comparative analysis of COVID-19 vaccine safety and effectiveness in Brazil and in Pakistan, with colleagues at Shaukat Khanum Memorial Cancer Hospital and Research Centre there, to improve pandemic responses and promote data-driven evidence generation in the Global South. Monitoring vaccinations across different settings is crucial for containing pandemics. However, comparative analysis of large health datasets in different scenarios is challenging due to concerns around safety and reproducibility and the loss of the context in which the data was collected, which can affect research results. They will adapt data science standards and tools to different local health system scenarios and run individual and joint vaccine effectiveness analyses for the two countries to assess compatibility and reproducibility of the findings. They will also build a public data visualization dashboard for health managers and policymakers to monitor the pandemic, particularly in vulnerable populations.

Vincent Cubaka of Partners In Health in the U.S. will build robust data governance structures to enable the utilization of electronic medical records from multiple countries for research purposes to improve health. So-called FAIR (Findable, Accessible, Interoperable, Reusable) data principles enhance the value of personal medical records for research, and CARE principles were developed to protect the owners of these data. However, the rigidity of these principles can create conflicts, which can make it difficult, for example, to open access to datasets across different countries. To address this, for their current project studying the impact of COVID-19 on chronic care patients across four low- and middle-income countries, they will develop data governance structures and set-up a multi-country community oversight committee to enable full access by researchers to appropriately de-identified individual-level data on a suitable platform.

Wyckliff Omondi from the Ministry of Health in Kenya will integrate a neglected tropical disease (NTD) surveillance program into the national blood donation program as a more cost-effective mechanism to monitor lymphatic filariasis and other endemic NTDs in Kenya. Kenya is on course to eliminate lymphatic filariasis using mass drug administration programs. Certifying regions as disease-free requires careful post-treatment assessments. To support this, they will work with the Kenya National Blood Transfusion Service, which collects, tests, and distributes blood across the country, to collect small, normally discarded blood samples from regional centers and test them for lymphatic filariasis, dengue and chikungunya in their central laboratory. As well as supporting eradication efforts, this routine testing will provide an early warning system by identifying distribution patterns and prevalence of dengue and chikungunya, which have histories of outbreaks in coastal regions.

Ida Viktoria Kolte of Fiocruz in Brazil will employ metagenomic next generation sequencing (mNGS) for the analysis of sputum and blood samples from Indigenous patients to identify the causes of severe lung infection in the rural Amambai district. Brazil's one million Indigenous people suffer a disproportionate burden of infectious and respiratory diseases. Lung infections are challenging to diagnose because they can be caused by viral, bacterial and fungal pathogens and are often associated with co-infections. They will collect samples from 170 patients aged over 18 years presenting with symptoms of severe lung infection from five locations and subject them to next generation sequencing to identify the microorganisms present. They will also use implementation research to identify any cultural barriers that have restricted current diagnostic and therapeutic practices to help more effectively implement the new metagenomic next generation sequencing technology into clinical practice.

Jennifer Fitzpatrick of Zambart in Zambia will design and implement a one-step multiplex whole genome sequencing platform for the diagnosis of female genital schistosomiasis (FGS), sexually transmitted infections (STIs) and vaginal microbiome analysis in Zambia. FGS is caused by Schistosoma haematobium and affects around 56 million women in sub-Saharan Africa. Current diagnostic capabilities for STIs and FGS are inadequate and many patients are either incorrectly treated, overtreated or receive no treatment at all. They will use 525 self-taken vaginal swabs to develop the sequencing assay and follow-up with self-taken cervicovaginal swabs and S. haematobium eggs taken from up to 2,000 sexually active girls and women aged 15 to 50 for further development and implementation of the platform to enable the rapid identification of known and new pathogens. They will also characterize the cervicovaginal flora to gain insights into its role in sexual and reproductive health.

Elizabeth Batty of the University of Oxford in the United Kingdom will use metagenomic next generation sequencing to identify pathogens in patient samples that are negative by all other diagnostics, to better understand the causes of febrile illness in South and Southeast Asia. Although studies have identified a broad spectrum of pathogens underlying non-malarial febrile illness, the cause of fever remains unknown in more than half of patients. Febrile illness causes substantial morbidity and mortality, and correct diagnoses are needed to ensure that patients receive the appropriate treatments. They will collect samples in multiple healthcare centers in Bangladesh, Lao PDR and Thailand, and use multiplex PCR and serological tests that detect the most common causes of acute fever. Up to 300 samples that test negative using these approaches will be sent to the central Mahidol-Oxford Tropical Medicine Research Unit laboratories in Bangkok for metagenomic sequencing and bioinformatic analysis.

Marion Jourdan of Danone Nutricia Research in the Netherlands together with Michael Zimmermann of ETH Zürich in Switzerland will test an approach to enhance iron absorption from food in children in Kenya by providing them with live food-grade bacteria to release phytate-bound iron from popular foods such as cereal flour. Phytates bind strongly to iron and inhibit its absorption. Their previous work identified different bacterial strains containing phytases that could grow in milk, degrade phytates, and release nutritionally-relevant levels of free iron in vitro. They will test different strain combinations for their phytate-degrading activity under different conditions, such as in specific foods and in an environment mimicking the upper GI tract, and select the best one for producing a fermented food product. This will then be tested to assess its effect on iron absorption in a cohort of 22 iron-deficient Kenyan school-aged children.

Aida Badiane of the Universite Cheikh Anta Diop de Dakar in Senegal will use shotgun metagenomic next generation sequencing (mNGS) to identify the pathogens causing nosocomial infections in Senegal to improve diagnosis and treatment. Nosocomial infections (i.e., hospital-acquired) cause substantial mortality in Senegal but remain poorly understood. To create a more complete profile of the causative pathogens, they will apply shotgun mNGS to different types of clinical samples from 61 patients at LeDantec hospital to identify and quantify the pathogens. They will also identify the most suitable sample types for diagnosing the most common pathogens. The sequencing data will be analyzed and shared with clinicians, stakeholders and the global research community, and will help in the development of suitable diagnostic assays. This project will help implement sequencing technologies into the national healthcare system.

Innocent Semali of Hubert Kairuki Memorial University in Tanzania will design a more effective strategy for eliminating trachoma in the nomadic Maasai communities in Tanzania. Trachoma is a bacterial disease and a leading cause of blindness. Globally, there are around 84 million sufferers, mostly in sub-Saharan Africa. In Tanzania, the standard control strategy, which involves mass drug administration of azithromycin, eliminated trachoma from most districts. However, the strategy has largely failed in nomadic populations for unclear reasons. To identify those reasons, they will work towards building a partnership with a Maasai community and relevant stakeholders and use interviews and surveys to document their perceptions and behaviors around the standard trachoma interventions. This information will be used to understand the failure of the previous interventions and, together with the communities and stakeholders, to develop new strategies for testing in two villages using a mixed methods approach.

Haroon Hafeez of Shaukat Khanum Memorial Cancer Hospital and Research Centre in Pakistan will develop a framework for the re-use of large clinical and administrative datasets to enable comparative analysis of COVID-19 vaccine safety and effectiveness in Pakistan and in Brazil, with colleagues at Fiocruz there, to improve pandemic responses and promote data-driven evidence generation in the Global South. Monitoring vaccinations across different settings is crucial for containing pandemics. However, comparative analysis of large health datasets in different scenarios is challenging due to concerns around safety and reproducibility and the loss of the context in which the data was collected, which can affect research results. They will adapt data science standards and tools to different local health system scenarios and run individual and joint vaccine effectiveness analyses for the two countries to assess compatibility and reproducibility of the findings. They will also build a public data visualization dashboard for health managers and policymakers to monitor the pandemic, particularly in vulnerable populations.

Kanny Diallo of the Centre Suisse de Recherches Scientifiques en Côte d'Ivoire will use metagenomic sequencing to investigate the etiological diversity of meningitis in Mali, Guinea, and Côte d’Ivoire, three countries in the so-called African meningitis belt, to improve diagnosis and public health responses. The African meningitis belt stretches from Senegal to Ethiopia and has the highest burden of meningitis worldwide. Meningitis can be caused by many different types of pathogens (bacteria, virus, fungi, and parasites), which vary between countries. Although 35 meningitis-causing pathogens are detectable by current PCR-based techniques, over 80% of cases remain undiagnosed suggesting that other pathogens are involved. They will perform a prospective study by collecting 65 cerebrospinal fluid samples from children under 5 years old with suspected meningitis and apply an unbiased metagenomic approach to identify both known and unknown pathogens. Their results will also help inform the design of new vaccines.

Solomon Langat of the Kenya Medical Research Institute in Kenya will develop a targeted viral enrichment protocol to improve the sensitivity of metagenomic sequencing for detecting known and novel vector-borne and viral hemorrhagic fever viruses. Infectious disease outbreaks caused by arboviruses and other viral infectious pathogens are common, particularly in Kenya. Current methods for diagnosing these infections have limited sensitivity and only detect known pathogens. In contrast, high-throughput sequencing and metagenomics can broaden detection capabilities to unknown pathogens and is also a rapid approach for monitoring outbreaks in real time. However, background noise from host nucleic acids can limit its sensitivity. They will design broadly-targeting hybridization probes to capture entire families of viruses before sequencing to improve the sensitivity of detection and test them on confirmed positive and negative samples. They will also use their method on samples from the ongoing national arbovirus surveillance program.

Jurriaan de Steenwinkel of the Erasmus Medical Center Rotterdam in the Netherlands together with Eric Nuermberger of Johns Hopkins University in the U.S. will combine expertise to develop a robust, preclinical mouse model of latent tuberculosis (TB) together with a molecular assay for measuring candidate drug activity to boost drug development. Reducing latent TB infections is essential to meet the goal of the World Health Organization’s End TB Strategy but current drugs have limited effect and measuring the activity of candidate compounds in latent infections is challenging. Successfully developing new drugs also requires improved preclinical models that identify drug candidates more likely to be effective in the clinic. They will combine their paucibacillary murine TB model with their first-in-class RS ratio assay, which quantifies rRNA synthesis in the causative Mycobacterium tuberculosis, and test its value for identifying new drugs that can more rapidly and effectively cure patients also with latent infections.

Yoke-Fun Chan of the University of Malaya in Malaysia will deploy metagenomic next generation sequencing to identify regional, rare and novel pathogens associated with neuroinfection in Malaysia. Neuroinfection can be caused by many different pathogens and around 60-80% of cases remain undiagnosed. Malaysia is a hotspot for viruses associated with encephalitis and an ideal location for establishing global pathogen surveillance. They will sequence around 300 archived cerebrospinal fluid and blood samples, and samples from prospectively recruited pediatric and adult patients with suspected neuroinfection at several medical centers to identify the causative pathogens. They will also establish a standardized metagenomics protocol for neuroinfection. The data will help clarify the epidemiology of neuroinfections in Malaysia and pave the way to implement metagenomic next generation sequencing for routine, real-time diagnosis of many infectious diseases to support public health decision-making.

Volga Ana Iñiguez Rojas of the Fundación para el Desarrollo de la Ecología in Bolivia will use metagenomic next generation sequencing to determine the diversity of viruses circulating in wild and domestic mammals and humans in two highly contrasting regions in Bolivia: The Amazon and the Andean Highlands. Emerging infectious diseases from zoonotic pathogens are a major public health threat. Bolivia is a hotspot for zoonotic diseases because of its highly diverse mammalian species and extensive deforestation. They will strengthen laboratory capacities with metagenomic next generation sequencing tools to identify circulating viruses in key mammalian species and people at high risk for exposure, namely Indigenous communities and wildlife center personnel. Data from 1,250 mammals and 390 humans and an overall risk assessment of human spillover potential will be shared across sectors together with training activities to promote coordinated action.

Karifa Kourouma of the Centre National de Formation et de Recherche en Santé Rurale (CNFRSR) de Maferinyah in Guinea will integrate metagenomic sequencing into an existing viral hemorrhagic fever surveillance platform in Guinea to enable identification of a broad range of known and unknown infectious pathogens. Guinea is a hotspot for viral hemorrhagic fevers such as Ebola and dengue. The current platform uses PCR-based diagnostics but these lack sensitivity and can only detect a handful of known viruses. Metagenomic sequencing can identify a much broader range of pathogens as well as unknown pathogens enabling earlier detection of outbreaks. They will leverage an existing biobank of plasma and serum samples from patients with viral hemorrhagic fever and test the ability of metagenomic sequencing to identify known and unknown pathogens. They will also implement their approach into the existing platform for ongoing sequencing of new patient samples.

Rakhi Dandona of the Public Health Foundation of India will examine gender disparities in national health programs in India by harnessing existing large-scale gender-specific data for disease burden and their risk factors from the Global Burden of Disease Study to help address gender-based health inequities in India. Males and females are affected differently by many diseases. The researchers will examine three national health programs in India covering various age-groups, specifically adolescent health, the elderly, and mental health, for gender-specific disease and risk estimates to assess where more focus is needed on girls and women. This would facilitate gender-specific health interventions within the existing national health programs and identify potential new programs to achieve better health outcomes for women and girls.

Victor Tunje Jeza of the Technical University of Mombasa in Kenya will apply metagenomic next generation sequencing to identify the etiology of febrile illness not associated with malaria, chikungunya or dengue in coastal and Western Kenya, to help design more effective interventions for prevention and treatment. Febrile illnesses are caused by diverse pathogens and are common among children in the coastal and western regions, where malaria is also endemic. Standard treatment of febrile patients testing negative for malaria is generally broad-spectrum antibiotics, which may be ineffective and favors the development of drug resistance. They will sequence 350 archived febrile patient serum samples from two previous NIH-funded cohort studies and 100 prospectively collected serum samples to characterize and compare the pathogens causing local febrile illness in the different regions and identify any that are newly emerging or re-emerging.

Rajpal S. Kashyap of the Central India Institute of Medical Sciences in India will use metagenomic next generation sequencing (mNGS) to investigate the etiology of undiagnosed meningoencephalitis cases in tertiary care hospitals in India. Meningoencephalitis is a central nervous system disease associated with substantial morbidity and mortality in India. Up to 75% of cases remain undiagnosed because current tests are unable to identify the wide range of causative pathogens. In contrast, mNGS approaches are far more sensitive and have been successfully used to diagnose otherwise undiagnosed cases of encephalitis, thereby improving patient outcomes. They will investigate the value of mNGS as a diagnostic tool in difficult-to-diagnose meningoencephalitis cases with unknown etiology in a tertiary care hospital setting. This will reveal the diversity of causative pathogens, which will help develop more effective treatments and support policy making and antimicrobial stewardship.

Luc Samison of Centre d'Infectiologie Charles Mérieux - University of Antananarivo in Madagascar will support more responsive and resilient antimicrobial resistance (AMR) surveillance systems in Madagascar and Burkina Faso by building a data science center for the electronic collection, analysis and dissemination of data. They will develop and refine data collection tools and sharing processes to promote multi-disciplinary collaborations and strengthen data governance and standards. These will be applied to detecting multi-drug resistant Escherichia coli and Enterobacteriaceae in several settings including pregnant women, hospitalized patients, chickens and surface water. They will also develop new tools and processes to provide stakeholders with strategic AMR indicators in real-time to support decision-making. This project will also support data-centered health research on AMR surveillance and can be applied to a range of pathogen surveillance settings in other low- and middle-income countries.

Munyaradzi Musvosvi of the University of Cape Town in South Africa will determine whether a valuable biomarker of tuberculosis (TB) can be measured in small volumes of blood collected by finger-prick together with an automated, low-cost processing approach to accelerate diagnoses in low-resource settings. Individuals with TB have higher levels of a specific activation marker on the surface of some of their T cells, which could be a valuable diagnostic target. However, current methods to measure levels requires trained health and laboratory professionals to draw the blood, perform the assay, and analyze the results. As a more practical approach for resource-limited settings, they will test whether the biomarker can be reliably measured in low volumes of blood. They will also develop a microfluidic device to automatically process blood samples for flow cytometry analysis, and novel staining reagents as an alternative to expensive antibodies.

Rachel Chikwamba of the Council for Scientific and Industrial Research in South Africa together with Kerry Love of Sunflower Therapeutics in the U.S. will establish local manufacturing capacity in South Africa to increase access to protein-based biologic drugs including antibodies and vaccines, which are used for treating many different diseases. Access to biologics is unevenly distributed across the globe, and the conventional manufacturing practices are expensive and require substantial physical space and operational know-how. They have established low-cost, automated and modular manufacturing systems that can be easily adapted to different biologics and changing market needs. They will determine current local and regional needs and capabilities associated with biologics, identify five initial products for development, and produce business models for commercialization that can be used as a roadmap for the successful local deployment of their biologics manufacturing technology.

Sana Syed of the University of Virginia in the U.S. together with Imran Nisar of Aga Khan University in Pakistan will utilize metabolic modeling of patient-derived ‘omics data from pre-existing maternal and pediatric cohorts to identify new biomarkers and therapeutic targets for environmental enteropathy (EE), which is associated with impaired childhood growth and development and vaccine responses. They will leverage a computational, flux-balance analysis-based approach to analyze large transcriptomic and proteomic datasets from pregnant mothers and infants with EE to identify disease-associated metabolic signatures. The signatures derived from pregnant mothers might precede the development of EE and reveal pharmaceutical targets for prevention. They will also develop a duodenal enteroid cell culture model derived from biopsies of children with EE to test whether the identified infant-derived metabolic signatures can be disrupted with existing pharmacological agents as potential new treatments.

Chijioke Kaduru of Corona Management Systems in Nigeria will strengthen malaria mathematical modeling capability and capacity in Nigeria by building a fellowship program for field epidemiologists and current doctorate students in epidemiology. The program will be embedded within the Nigeria Field Epidemiology Training Program (NFETP), which is managed and coordinated by the Nigeria Centre for Disease Control. The NFETP serves to strengthen and coordinate Nigeria’s ability to respond to public health events through training public health leaders in interventional epidemiology and developing institutionalized and sustainable public health workforce capacity, and its graduates participate in priority disease control programs, including for malaria and neglected tropical diseases. The new fellowship program is expected to increase the number of Ph.D. level-trained mathematical modelers with malaria expertise based in Nigeria and localize modeling expertise to support the National Malaria Elimination Program.

Adriana Bonomo of Fiocruz in Brazil together with Penny Moore of the National Institute for Communicable Diseases in South Africa will identify solutions for combating new SARS-CoV-2 variants by developing an in vitro assay to predict new variants and identifying broad specificity antibodies for use as new drugs and diagnostics. Despite the success of vaccines and antibody therapies, the continual emergence of new viral variants, which thwart our immune defenses and therapies, remains a major challenge of the pandemic. They will develop a virus training assay by culturing existing variants with hyper-immune sera from infected individuals in South Africa and Brazil to drive selection of new mutations and identify potential new variants. They will also isolate new monoclonal antibodies directed to conserved cleavage sites of the viral spike protein, which are essential for it to infect cells, that could be used as treatments to block infection by a wide range of variants.

Seth Bloom of Massachusetts General Hospital in the U.S. together with Sinaye Ngcapu of the Center for the AIDS Programme of Research (CAPRISA) in South Africa will investigate how bacterial vaginosis (BV) and non-Lactobacillus-dominated vaginal microbiota elevate the risk of contracting HIV-1 to help develop preventative therapies. South Africa has high rates of BV and microbiota-associated vaginal HIV transmission but the underlying mechanisms are unknown, which makes it difficult to prevent. The researchers will combine samples from South African cohorts with innovative in vitro assays to test their hypothesis that bacterially-produced putrescine, which is a BV-associated metabolite, in the cervicovaginal mucosa enhances HIV risk by increasing the post-translational modification and thereby activation of a molecule involved in promoting HIV protein production. They will also test existing inhibitors of this pathway as novel, pre-clinical HIV prevention candidates to establish the groundwork for a clinical trial.

Penny Moore of the National Institute for Communicable Diseases in South Africa together with Adriana Bonomo of Fiocruz in Brazil will identify solutions for combating new SARS-CoV-2 variants by developing an in vitro assay to predict new variants and identifying broad specificity antibodies for use as new drugs and diagnostics. Despite the success of vaccines and antibody therapies, the continual emergence of new viral variants, which thwart our immune defenses and therapies, remains a major challenge of the pandemic. They will develop a virus training assay by culturing existing variants with hyper-immune sera from infected individuals in South Africa and Brazil to drive selection of new mutations and identify potential new variants. They will also isolate new monoclonal antibodies directed to conserved cleavage sites of the viral spike protein, which are essential for it to infect cells, that could be used as treatments to block infection by a wide range of variants.

Wilfred Ndifon of the African Institute for Mathematical Sciences - Next Einstein Initiative Foundation in Rwanda together with Luc Djogbénou from the Université d'Abomey-Calavi, Benin, and Jeanine Condo from the University of Rwanda, will collaborate with academic institutions, operational partners and national malaria control programs (NMCPs) from Benin, Rwanda, Senegal, Burkina Faso, Mozambique, Côte d'Ivoire, Switzerland, Australia, Kenya and Ghana to create a sustainable ecosystem of mathematical modelers, translational specialists, and decision-makers to support malaria interventions in Africa. They will develop curricula in modeling, epidemiology, and infectious disease biology for MSc and PhD students. They will also bridge the gap between academic modeling and the operational needs of NMCPs across English, French and Portuguese-speaking countries by developing targeted training for researchers and NMCP staff. This cultural shift in educational approaches is designed to teach the language of data scientists while focusing research on providing data-driven evidence relevant for policy making.

Xiao-Guang Chen, Zetian Lai and Chunmei Wang of Southern Medical University in China and their international partner Guiyun Yan of the University of California, Irvine in the U.S. will develop new traps that are more attractive to malaria vectors. They will incorporate the new traps with infrared vector detection, automatic recording and wireless transmission technologies, and test the efficacy of the new trap and the automated malaria vector surveillance apparatus both in the laboratory and in the field. This novel, real-time malaria vector surveillance tool can help efficiently monitor biting behavior, population abundance and transmission dynamics of malaria vectors, and tremendously enhance malaria transmission surveillance and facilitate the evaluation of new vector control measures targeting outdoor malaria vectors.

Zhang Dongjing, Zheng Xiaoying, Wu Yu and Wang Gang of Sun Yat-sen University in China together with their international partners Badria El-Sayed, Tellal Ageep, Ammar Hassan and Mohamed Korti all from the National Centre for Research in Sudan, and Jeremy Bouyer, Maiga Hamidou, Hanano Yamada and Adly Abdalla of Insect Pest Control Laboratory in Austria will develop highly specific and environmentally friendly Sterile Insect Technique (SIT) to control outdoor Anopheles mosquitoes. Once the feasibility evaluation is passed, the results will form a systematic technical package of SIT to control Anopheles stephensi and provide the scientific basis and technical support for subsequent field trials of SIT to control this outdoor malaria vector in African countries such as Sudan or other Asian countries.

Weiguo Fang of Zhejiang University and Guoding Zhu of Jiangsu Institute of Parasitic Diseases in China together with their international partner Abdoulaye Diabaté of Institut de Recherche en Sciences de La Santé in Burkina Faso, by referring to the widely used small farmer-operated factories for production of entomopathogenic fungal spores in China, will develop a spore production technology for the transgenic Metarhizium strain, which is cost-effective, of low technological bar and can be easily implemented in low-and middle-income countries and regions. A novel bifunctional device will also be provided for outdoor mosquito control. Currently, mycoinsecticides and their release devices are only suitable for indoor mosquito control.

GuoXiong Peng, Yuxian Xia, Yueqing Cao and ZhengBo He of Chongqing University in China together with their international partner Raymond J. St. Leger of the University of Maryland in the U.S. will screen mosquitocidal fungal strains from China and abroad for high-yield virulent and stable production strains against larvae and adults, test the safety of the production strains, optimize solid fermentation medium, fermentation process and the components and proportion in the formulation to develop oil-based fungal mosquitocides for outdoor application. This will help address issues including mosquito resistance and environmental pollution caused by massive use of chemical insecticides.

Biao Jiang, Jianhua Yao, Ping Xing, Jia Li and Wanjun Wang of the Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences together with their international partners Ole Skovmand and Sérgio Sousa both of Landcent (Europe) B.V. in The Netherlands will utilize in silico screening to discover mosquito insecticide or repellent compounds in traditional Chinese medicine. At least one safe, environmentally friendly and efficient novel mosquito insecticide or repellent insecticide is expected to be obtained, which will then be used to further develop outdoor vector control technology or products. The development of such mosquito insecticides or repellent compounds will help address insecticide resistance issues and accelerate the global malaria elimination process.

Sibao Wang of the Institute for Biological Sciences, Chinese Academy of Sciences and Duoquan Wang from the China CDC together with their international partners Abdoulaye Diabaté of Institut de Recherche en Sciences de La Santé in Burkina Faso and Marcelo Jacobs-Lorena of Johns Hopkins University in the U.S. will develop procedures to efficiently introduce a specific bacterium into field mosquitoes in order to evaluate effectiveness of the bacterium spread through mosquito populations and to block parasite transmission in a more realistic setting. Introducing anti-Plasmodial symbiotic bacteria into mosquito populations can potentially transform mosquitoes into ineffective vectors. This unconventional approach has already shown promise in the laboratory.

Damazo Kadengye of the African Population and Health Research Center in Kenya will establish a functional Learning Health System to promote the exploration of population health data from multiple sources to improve public health responses to infectious diseases in sub-Saharan Africa. Utilizing the data revolution to generate new knowledge is crucial for achieving global health targets, but there is a lack of suitable tools and limited access to data from different sources. They will integrate multiple large HIV/AIDS datasets from 11 longitudinal population cohorts in East Africa and develop an organizational architecture that enhances data discoverability and promotes responsible open data sharing, supporting collaborations between healthcare professionals, policy makers and researchers. They will also train scientists to produce data-based evidence using data science tools and predictive statistical models and to work with policy makers at local and national levels.

Yaw Asare Afrane of the University of Ghana will build malaria modeling capacity in West Africa by training a critical mass of modeling scientists across multiple career stages to work closely with national malaria control programs (NMCPs). They will strengthen infrastructure and faculty in existing laboratories, provide technical training and support, and promote modeling as a PhD program in universities. They will also develop mathematical modeling curricula in malaria and NTDs in multiple languages and adapted for each country, which will be freely available online. In addition, they will build an anglo-franco-lusophone West African consortium of modelers, epidemiologists, parasitologists, and NMCPs, to share expertise and support NMCP priorities, and ultimately to sustain reductions in malaria burden.

Sheetal Silal of the University of Cape Town in South Africa will establish the Malaria Modeling and Analytics: Leaders in Africa (MMALA) program to promote the training and career development of a critical mass of African malaria modelers that can support decision making of national malaria control programs (NMCPs). They will increase the number of PhD-trained mathematical modelers with malaria expertise in sub-Saharan Africa institutions, and foster relationships with NCMPs from Angola, Botswana, Eswatini, Mozambique, Namibia, South Africa, Zambia, Zimbabwe, Benin, Cameroon, and Ghana including providing literacy training workshops. Twelve PhD candidates will be selected and provided with complementary coursework, research skills development, and secondment opportunities at their local NMCPs. They will also hold regional and central events to help build networks and share expertise across this cohort of modelers and develop an open web resource for malaria.

Peter van Heusden of the University of the Western Cape in South Africa together with Placide Mbala of the Institut National de Récherche Biomedicale in the DRC will establish in-house pathogen sequencing capabilities at a research institute in the DRC to enable rapid responses to meningitis outbreaks and improve patient outcomes. Despite the success of vaccines, meningitis outbreaks caused by diverse bacterial species still cause substantial fatalities across Africa. Diagnosis of the latest outbreak in the DRC was delayed for several months because samples had to be transported out of the country for genomic sequencing. They will leverage a field-portable sequencer with bioinformatics processor to build a platform with a user-friendly interface for use in a low-infrastructure setting. They will also train local scientists to extract DNA from patient samples, run the sequencer, and interpret the results so that they can provide rapid surveillance of meningitis-causing pathogens directly in the DRC.

Charles Wondji of the Centre for Research in Infectious Diseases in Cameroon will establish the African Consortium in Modeling for Effective Vector Control (ACoMVeC) together with seven research institutes across the continent, bringing together African scientists and northern partners in the U.S. and United Kingdom to help improve malaria control. They will train 15 PhD level modelers at both French- and English-speaking African universities in transmission dynamics modeling, coding compartmental models using R or Python, statistical methods, understanding uncertainty, and using models for policy. These modelers will investigate several independent projects including modelling the impact of insecticide resistance on malaria transmission. They will also set up technical advisory groups to help national malaria control programs identify key operational research projects for modeling and effectively leverage modeling approaches to facilitate decision making.

Nicole Stoffel of the University of Oxford in the United Kingdom together with Pattanee Winichagoon of Mahidol University in Thailand will perform a double-blind randomized controlled trial to test whether providing iron-fortified food to iron-deficient women in Thailand improves their immune response to vaccination. Vaccines underperform in low- and middle-income countries, which may be caused by poor nutrition. Iron deficiency is common, and iron may play a key role in adaptive immunity and vaccine response. Preliminary data from their earlier study in Kenya showed that women given intravenous iron one week before a vaccine produced significantly more antibodies. To translate this to low-resource settings, they will perform a trial of 180 women in northeastern Thailand and provide half of them with a wheat-flour-based baked snack fortified with iron for forty days and test its effect on their immune response to two vaccine types: an intramuscular influenza vaccine and an oral typhoid vaccine.

Nitin Baliga of the Institute for Systems Biology in the U.S. together with Google Applied Science will combine systems biology with machine learning and artificial intelligence to accelerate the discovery of more effective and affordable treatments for tuberculosis. Tuberculosis kills 1.5 million people annually, but developing novel treatments is expensive using current methods and complicated by the different physiological states and sub-populations of the causative Mycobacterium tuberculosis. To address this, they will use a new modelling approach that leverages transcriptome data and a novel algorithm to identify more robust protein targets that are valid across bacterial states and populations. These targets will then be screened using DNA-encoded small molecule libraries (DELs), which is lower-cost than traditional high-throughput screens. Screening results will be used to train a machine learning model to identify small molecule compounds with favorable drug-like properties and high probabilities of inhibiting the target. The anti-bacterial activity of selected compounds will then be tested experimentally.

Lye McKinnon of the University of Manitoba in Canada together with Ali Ssetaala of the Uganda Virus Research Institute in Uganda will determine whether nasal mucosal immune responses induced by COVID-19 vaccines and natural infection can help prevent infection and transmission. Although COVID-19 mRNA vaccines effectively prevent severe disease, they are less effective at preventing transmission, which is critical for protecting vulnerable populations particularly against emerging, highly transmissible variants. Boosting nasal immunity may locally inhibit replication of the SARS-CoV-2 virus and thereby limit both infection and transmission. To test this, they will perform a two-site longitudinal study in Winnipeg, Canada and Kampala/Entebbe, Uganda of fully vaccinated individuals with and without breakthrough Omicron infections to determine whether existing nasal immunity is protective. They will also test whether Omicron breakthrough boosts virus-specific IgA and T cell responses in the nasal mucosa, which may further protect against transmission. The results may strengthen the case for nasal-delivered vaccines to better contain the COVID-19 pandemic.

Sergio Chicumbe and colleagues at the Instituto Nacional de Saúde in Mozambique together with the Ministry of Health and other stakeholders will create a plan for strengthening the national surveillance and response systems established during the COVID-19 pandemic and expanding them to multiple diseases. During the pandemic, they built systems that spanned the public and private sectors to ensure rapid testing and data collection country-wide, as well as data reporting in real-time. Their proposal will involve integrating this system with existing surveillance systems such as the countrywide mortality surveillance for action, which registers births and deaths. The proposal will also link laboratory data with individual data collected by public health officials, while ensuring confidentiality, to produce more valuable datasets for public health and emergency response. They will also provide training to strengthen analytical capabilities and establish a data-to-action framework to support decision-making.

Mohamed Alex Vandi and colleagues at the Ministry of Health and Sanitation in Sierra Leone together with Umar N’jai of the University of Sierra Leone will develop a plan to strengthen and integrate the national capacity for disease surveillance in Sierra Leone to better prevent, detect and respond to diseases and public health emergencies. Sierra Leone has a fragile healthcare system, and increasing coordination, human resources, infrastructure and reporting tools would make it less susceptible to epidemic threats. The plan will involve strengthening the existing disease surveillance systems for human, animal and environmental health by integrating them and enabling data sharing and interoperability, and enhancing data quality and integrity. They will also plan the production of early warning systems, which will involve building and integrating a national mortality surveillance platform, and the development of a national protocol for ongoing surveillance of cases of acute febrile illnesses and viral hemorrhagic fevers, many of which remain undiagnosed.

Aamer Ikram and colleagues at the National Institutes of Health in Pakistan will develop a plan for an upgraded and integrated disease surveillance system that detects, reports, investigates and responds to multiple public health threats from communicable diseases like cholera and natural disasters such as floods. The current disease surveillance systems in Pakistan are fragmented and there is no central repository of health information. This hampers data-driven decision-making, which is needed to prevent the spread of disease. They will develop a costed action plan and conduct a feasibility analysis for integrating multiple disease surveillance and response data streams through application programming interfaces (APIs), which will result in national patient registries. This will also involve building and training machine learning models to link different data sets, and developing and implementing artificial intelligence technology with visualization tools to improve data analysis and forecasting.

Alex Riolexus Ario and colleagues at the Uganda National Institute of Public Health will develop a plan that transforms disease surveillance in Uganda by upgrading it to an integrated, real-time, digitized national disease surveillance system that works across the human, animal and environment sectors. Uganda is located in the eco-rich Congo basin and the filovirus and meningitis belts, which increase the risk of infectious disease outbreaks and natural disasters. While electronic tools and reporting are available, they have limited coverage, use, and interoperability across sectors. Their proposal will bring together relevant stakeholders to develop objectives, strategies and activities, as well as costing and roadmaps. The plan will involve multiple collaborators in activities including linking the Civil Registration and Vital Statistics system with case-based surveillance to determine disease burdens. It will also involve further digitizing laboratory data, and integrating and ensuring interoperability of the multiple surveillance data reporting platforms currently used by the different sectors.

Sanjeev Kumar of The Goat Trust in India will develop animated mobile applications that provide information on improving productivity, veterinary and financial services, and markets for women goat herders in the Indian states of Uttar Pradesh and Bihar to increase their income. These women work in remote regions with limited support, and many are illiterate. They will develop simple applications with health, nutrition, animal husbandry, a marketplace, and management components, and integrate value-chain players such as products and services suppliers. In health, they will develop a decision support tool to help farmers identify diseases using 141 symptoms and to select the most suitable treatment in consultation with vets. For the marketplace, farmers will be able to order quality products and pay directly. There will also be a web-based platform for goat sales. They will develop the applications in consultation with farmers and other stakeholders, and perform pilot testing.

Esther Muiruri of Equity Group Foundation in Kenya will expand their Equity Online-Agriculture platform to provide information on agricultural best practices, including smart-farming innovations, as well as access to financing and markets to initially 200,000, and subsequently up to two million, small-scale farmers in Kenya to improve their productivity and income. They will build the platform to digitally disseminate agricultural information such as soil testing and pest and disease control, which will improve timely planting and crop and livestock management. They will also build in training in financial literacy targeted towards women, who make up the majority of agricultural workers, and access to financial support and tailored insurance products by implementing e-vouchers and loans, digital wallets and a credit scoring system. Market information and direct contacts with potential buyers will also be provided through an online platform.

Shafiq-ul Islam of ACME AI in Bangladesh will produce a smartphone-based system that uses computer vision and machine learning to accurately estimate the weight of cows and goats to help smallholder livestock farmers in rural Bangladesh maximize productivity and profits. Accurately determining livestock weight is challenging for these farmers but critical for determining the right amounts of food and medicines. They will develop a machine learning model and mobile application that uses the smartphone’s camera to process distance, height, and depth information and calculate the weight of the animal to within >90% accuracy. They will test three different business cases, including combining the computer vision-based weighing system with products and service providers, and evaluate the impact on food and medicine purchases, and animal growth and quality, which are directly linked with income.

Mukhlid Yousif of Wits Health Consortium in South Africa will sequence SARS-CoV-2 in sewage samples collected periodically from 40 wastewater treatment facilities across South Africa for the early detection of potentially dangerous variants to inform public health policies. Genome sequencing using sewage samples can monitor the molecular epidemiology and diversity of circulating SARS-CoV-2 variants, and also identify new variants even before they can be detected in the clinic. They will collect a total of 528 wastewater samples over a twelve-month period and process them for sequencing to identify novel mutations or mutations that are unique to variants-of-concern, especially those not yet reported in Africa. They will also compare these data with sequences of SARS-CoV-2 variants from local COVID-19 patients to support interpretation of wastewater sequencing results. Results will be immediately published online and communicated to provincial and national COVID incident management teams.

Francine Ntoumi of the Fondation Congolaise pour la Recherche Medicale in the Republic of Congo will set-up a national SARS-CoV-2 genomic surveillance system by increasing sequencing capacity to monitor viral variants-of-concern and determine the impact of vaccines on disease transmission to inform public health decisions. They will perform a cohort study by collecting oropharyngeal samples from patients at COVID-19 testing centers in the two largest cities, which account for 80% of the country’s new infections, and sequence around 60 SARS-CoV-2-positive samples per month to determine the prevalence of variants. These will be combined with existing COVID-19 epidemiological and clinical data to determine the virulence, transmissibility, and symptoms associated with new and existing viral variants-of-concern. They will also analyze blood samples from vaccinated and unvaccinated COVID-19 patients to evaluate their immune responses and combine these with socio-demographic and clinical data to determine vaccine effectiveness.

Fidele Ntie-Kang, a computational chemist at the Department of Chemistry, University of Buea in Cameroon, will establish a state-of-the-art drug discovery regional center for Central Africa that utilizes natural products from across the continent to identify new antiviral drugs suitable for resource-limited regions. Dr. Ntie-Kang is a pioneer in harnessing the diverse African flora for drug discovery purposes. His research group is building an online natural products database, which contains compounds isolated from plants, fungi, corals and bacterial species growing in Africa. He will set up a unique team of synthetic organic chemists, natural product chemists, computational chemists, microbiologists, biochemists and artificial intelligence experts, and build an open access pan-African library of naturally occurring compounds and a cloud-based computing platform. The team will combine virtual and in vitro screening techniques to identify natural compounds targeting the SARS-CoV-2 spike protein and the HIV Vpu protein, as well as promoting HIV latency-reversal. They will also train students to expand research capacity, and transfer the knowledge and technology developed during the project to other research institutes.

Annettee Nakimuli, Associate Professor of Obstetrics and Gynaecology and Dean of the School of Medicine at Makerere University in Uganda, will identify predictors of adverse pregnancy outcomes in Ugandan women with a focus on Great Obstetrical Syndromes (GOS), such as pre-eclampsia, to help develop context-relevant interventions for prevention and treatment. Dr. Nakimuli is an internationally-recognized research leader in maternal health for Africa. She performed the first genetic case-control study on pre-eclampsia among indigenous Africans, and identified different biological factors to those found in European studies, which helps explain the higher incidence. Building on her experience setting up cohort studies, she will prospectively collect biological samples and clinical data from a large cohort of 4,000 women throughout their pregnancies at Kawempe and Mulago Hospitals in Kampala to identify predictive biomarkers, and establish a biobank and database to facilitate future research. She will also implement artificial intelligence for data analysis to identify relevant socio-epidemiological, clinical, and biological features that contribute to the development of Great Obstetrical Syndromes.

Yaw Bediako, Founder and Chief Executive Officer of Yemaachi Biotech and researcher at the West African Centre for Cell Biology and Infectious Pathogens in Ghana, will bring together African biotech and academia with the Francis Crick Institute to provide important insights into how vaccines can be designed to work more optimally among African people. The African continent has the highest infectious disease burden in the world but almost no capacity for vaccine development or testing. Instead, most vaccines are tested in healthy Caucasian adults in high income countries, and many have lower efficacy among African populations. Dr. Bediako studies immune function in African populations and is devoted to building research capacity in Africa. He developed and successfully deployed the first national SARS-CoV-2 variant tracker on the continent, which displayed the distribution of viral variants in real-time. He will perform a prospective cohort study, and use molecular, cellular, and data-analysis approaches to investigate if the cellular and humoral immune responses to the AstraZeneca COVID-19 vaccine differ between Ghanaian and UK populations, and identify the effect of host genetic diversity on vaccine response. These data will support more rational vaccine design among African populations.

Abdoulaye Djimde, President of the Pathogens genomic Diversity Network Africa (PDNA), will work to better prepare Africa to fight infectious diseases and tackle those of the future. Dr. Djimde’s research group uses molecular and genetic approaches to study malaria, and their results have supported policy decision-making in Mali and the West Africa sub-region. His work on anti-malarial resistance led to a change in first-line therapy, and his group also serves as a training ground for many scientists in Africa. Recognizing the importance of collaborative research across the continent for studying infectious diseases, he established PDNA, which is an African-led research network spanning sixteen countries. PDNA investigates the genetic diversity of human pathogens to inform disease control and elimination strategies. He will set up a PDNA Pathogens Genomics Institute in Mali equipped with genetic and molecular epidemiology infrastructure. The Institute will train the next generation of scientists, and study the emergence and spread of malaria, SARS-CoV-2, and anti-microbial resistance, and identify novel pathogens. They will also focus on engagement with communities and health policy makers across the member countries to support public health on the continent.

Isabella Oyier, Associate Professor and Head of Bioscience at the KEMRI-Wellcome Trust Research Programme in Kenya, will establish a national malaria molecular surveillance platform that is integrated into the Division of National Malaria Programme (DNMP) to directly translate research into policy. The malaria burden in Africa is no longer declining due to the emergence of new variants that are undetectable by standard diagnostics and resistant to the frontline antimalarial drug. Dr. Oyier, a leader in malaria molecular epidemiology, is committed to eradicating malaria in Africa. She pursues a collaborative approach by sharing resources across laboratories and partnering with key stakeholders to ensure research impacts policy. This approach enabled her to make critical contributions to the genomics surveillance and testing efforts during the COVID-19 pandemic in Kenya. She will establish a national data repository and a working group to develop a sustainable next-generation sequencing platform that can be easily implemented across malaria-endemic regions where sentinel health facilities will be established to collect samples. She will also build user-friendly bioinformatics pipelines to examine parasite genetic diversity and the distribution of resistance markers, and to present actionable data for policy decision-making.

Mainga Hamaluba, Head of Clinical Research at the KEMRI-Wellcome Trust Research Programme in Kenya, will develop a pragmatic adaptive trial platform to evaluate key interventions for improving child survival in East Africa in real-life routine practice conditions as a faster and lower-cost alternative to traditional randomized controlled trials. Dr. Hamaluba has led a wide-range of complex clinical trials, including oversight of a complement of COVID-19 prevention and vaccine trials. She will use newborn care and hypoxic-ischaemic encephalopathy (HIE; also known as birth asphyxia) as a case study for the platform. HIE is the leading cause of admission in a network of Newborn Units in Kenya and causes severe neurological disabilities in survivors. Leveraging an existing and unique clinical surveillance framework and biobank at her institute, she will conduct a pragmatic platform adaptive randomized controlled trial of three licensed treatments to evaluate their effect on newborn survival. She will also establish procedures to increase the speed, rigor, and adaptability of regulatory approval protocols for clinical trials, and focus on training and mentorship of local healthcare workers in clinical research.

Iruka Okeke, Professor of Pharmaceutical Microbiology at the College of Medicine, University of Ibadan in Nigeria, will develop sequence-based methods and leverage genomics data to jumpstart the development of diagnostics and vaccines for neglected bacterial pathogens in African settings. Professor Okeke has devoted her career to studying neglected enteric bacteria that can cause potentially fatal bloodstream and diarrheal infections. She recognizes the power of genomics approaches to improve surveillance and better define pathogen virulence. She has been developing lower-cost and simpler methods to traditional culture-based techniques for detecting difficult-to-culture bacterial pathogens directly from blood samples in minimally-equipped laboratories. These methods incorporate nanopore sequencing together with target enrichment by the CRISPR-Cas9 system for rapid, direct-from-specimen diagnosis and genomic surveillance. She will adapt these methods for identifying a range of pathogens directly from stool, urine, and other clinical samples. She will also grow a community of experts to support this project by training African scientists in molecular science and bioinformatics.

Jesse Gitaka of Mount Kenya University in Kenya in collaboration with David Anderson of Burnet Institute in Australia, will develop a diagnostic device for iron deficiency anemia that is suitable for resource-limited settings. Iron deficiency anemia can cause maternal death, prematurity and stunting. Current diagnostic tests require expensive equipment or are not specific enough to distinguish between the different causes of anemia. They will develop a device that detects the low levels of hemoglobin found in immature red blood cells, called reticulocytes. The device will use magnetic beads and microfluidics to physically separate reticulocytes from whole blood, and then absorbance to measure the red color of hemoglobin and thereby determine levels. They will use samples from healthy donors to develop algorithms that can calculate the amount of hemoglobin per reticulocyte to provide an accurate diagnosis.

Collen Masimirembwa, Professor and founding President and Chief Scientific Officer of the African Institute of Biomedical Science and Technology (AiBST), Zimbabwe, will generate a research and innovation ecosystem, including training scientists and establishing centers of excellence in genomic medicine research, for the sustainable development of genomic and pharmaceutical medicine capability in Africa. Dr. Masimirembwa is on a mission to achieve world-class drug discovery and development capability in Africa. In 2002, he founded AiBST in Zimbabwe, and over the last ten years has organized a series of drug discovery and development courses across the continent to introduce the subjects and contextualize them for Africa. He will establish three centers of excellence in Zimbabwe, Kenya, and Nigeria to help launch an R&D biotechnology industry in Africa by forging partnerships with relevant stakeholders and training industry-focused scientists. He will also perform a prospective, multi-center clinical trial across several countries to determine the effectiveness of pharmacogenetic testing in reducing the incidence of adverse drug reactions and increasing treatment efficacy in African populations.

Jo-Ann Passmore, Associate Professor of the University of Cape Town in South Africa, will pilot the formation of the vaginal microbiome research consortium in Africa (VMRC4Africa) by establishing a network of researchers and centers of excellence for conducting research and clinical trials to promote women’s health across the continent. Dr. Passmore uses immune biomarkers and microbial-based approaches to study HIV and HPV pathogenesis and prevention in African women. Her work identified genital tract inflammation as a major predictor of HIV risk and pathogenesis, and revealed that inflammation reduces the efficacy of the anti-retroviral drug tenofovir, which is used to treat HIV. Her laboratory is a South African center of excellence in HIV prevention and she is committed to nurture and mentor young African researchers. She will establish the necessary infrastructure for African researchers to document the changing composition of the vaginal microbiota, beginning with South African and Kenyan women. They will use sequencing and build a biorepository to help identify health-promoting <em>Lactobacillus</em>-dominated microbiota in different geographic regions. These could be co-formulated into live biotherapeutic products to treat genital tract inflammation for women globally.

Richard Njouom from the Centre Pasteur du Cameroun in Cameroon will establish a genomic surveillance network across the country to routinely track circulating SARS CoV-2 strains and identify novel variants for informing health authorities. They will use an existing national network of six COVID-19 molecular testing laboratories for collecting samples. Around 1,200 samples will be screened using a commercial SARS-CoV-2 mutation panel over the course of 12 months to identify existing viral variants-of-concern and variants-of-interest. They will also set up a sequencing platform to sequence the spike protein of the virus to identify new variants, as well as for generating 240 whole SARS CoV-2 genome sequences to monitor viral evolution and identify markers of disease severity or increased transmissibility. Policy briefs will be used to inform the health authorities of circulating variants.

Nicki Tiffin, Professor at the University of the Western Cape, South Africa, will build an online platform – the African Data and Biospecimen Exchange – to facilitate equitable, ethical, and transparent data and biospecimen sharing on the continent, and promote research collaborations to improve health. Sharing biospecimens and data such as human genomics and pathogen sequencing data for use by other scientists is critical to sustain research in Africa. However current barriers that preclude sharing include high costs, the need for specialized formatting, and legal limitations for sensitive data. Dr. Tiffin has worked extensively across multiple health research domains, built research networks and collaborators across Africa, and is passionate about the effective use of health data in scientific research. She will build a platform for uploading standardized resource meta-data to reduce overhead costs, and provide practical guidance and online templates for sharing sensitive datasets. She will undertake a consultative process with domain experts to produce the design and functionality of the platform.

Pontiano Kaleebu of the Uganda Virus Research Institute in Uganda will expand their genome surveillance platform to monitor the circulation of SARS-CoV-2 variants in Uganda to help inform timely public health decisions and the development of diagnostics and vaccines. They will obtain geographically-representative COVID-19 patient samples for genomic sequencing, as well as samples from strategic sites including points of entry, where several variants have emerged. They are also collecting blood samples and nasopharyngeal swabs from patients, some of whom have been vaccinated, to determine their ability to neutralize viral variants and to produce monoclonal antibodies for potential use as diagnostics or for vaccine design. The methods and capacity established during this project will also be used for immunological surveillance of other infectious diseases.

Moses Obimbo Madadi, Clinician-Scientist and Associate Professor at the University of Nairobi, Kenya, will form a coalition of researchers and develop tools to study the vaginal microbiome and metabolites during pregnancy to help identify predictive biomarkers and intervention strategies for improving pregnancy outcomes in Kenya. Africa carries a high burden of severe pregnancy complications such as stillbirths and neonatal deaths. To address this, Dr. Madadi is leveraging his broad experience in clinical, basic, and epidemiological research to establish a unique niche of translational research to support the health of women in Kenya and around the world. He will perform a prospective cohort study at four hospitals in Nairobi by collecting clinical data and vaginal samples from over 1200 pregnant women. He will use next-generation sequencing to analyze microbial communities, and metabolomic profiling to identify predictive and diagnostic signatures of adverse pregnancy outcomes. These data will be used to develop artificial intelligence-assisted prediction models that could be used as valuable screening tools to identify at-risk pregnancies for early interventions.

Anita Ghansah, Senior Research Fellow at the Noguchi Memorial Institute for Medical Research at the University of Ghana, will build a cost-efficient malaria molecular surveillance system with high spatial and temporal resolution that covers the entire country. Dr. Ghansah is an internationally-trained genetic epidemiologist. Recognizing the power of genomics and bioinformatics approaches for bolstering malaria surveillance in Ghana, she has been a pioneer of bioinformatics training in the country. She introduced expertise for genotyping molecular markers of drug resistance, which led to a change in the national policy on first-line treatment of malaria. She will build the relevant personnel and infrastructure capacity for this project, and lead a research team and staff effort to rapidly monitor key molecular markers of drug and diagnostic resistance in blood samples from malaria patients using high-throughput sequencing and bioinformatics approaches. This will produce country-wide, near real-time surveillance data to better inform the control and elimination efforts of the National Malaria Control Program of Ghana.

Vincent Okungu, Researcher at the University of Nairobi in Kenya, will develop sustainable financing models to boost domestic funding for research and development (R&D) in East Africa. R&D is routinely underfunded in Africa, with the continent producing around 2% of the research output yet accounting for 15% of the global population. Dr. Okungu is a senior health economist whose passion is to see the development of resilient health systems in Africa. He has directed several health sector projects, including a national strategy for non-communicable diseases, together with the Ministry of Health, to guide resource mobilization and investments in Rwanda. He will investigate R&D financing by governments in two study countries, Kenya and Rwanda, and design creative approaches to motivate policymakers to increase budgets, as well as identifying high impact health programs such as vaccine development that could attract investments from public and private sources. He will also leverage knowledge from other sectors to learn how best to mobilize domestic finances for R&D and explore new sources of tax revenues. He aims to establish a mechanism for financing at least one priority R&D project agreed upon by public and private stakeholders in Kenya and Rwanda.

Ify Aniebo, Senior Research Scientist and Principal Investigator at the Health Strategy and Delivery Foundation in Nigeria, will integrate molecular and genomics data for tracking drug resistance and disease transmission to strengthen malaria elimination efforts in Nigeria, which has one of the highest global burdens. Dr. Aniebo is a molecular geneticist working on malaria drug resistance, and is acknowledged as one of her country’s top young health leaders. She is also devoted to empowering the next generation of African females into the sciences. To achieve her goal of eradicating malaria, she has created partnerships with scientists and policy makers within and outside Nigeria. Leveraging these partnerships, including Nigeria’s National Malaria Elimination Program, she will conduct a cross-sectional survey in households across the country and collect around 10,000 blood samples from children aged 6-59 months during the wet season when there is high malaria transmission. These samples will be subjected to next generation sequencing to investigate the prevalence and genetic diversity of the malaria pathogen across different regions, and the presence of drug resistance. She will also build a reporting tool and dashboard to present the data and directly support decision making.

Fitsum Girma Tadesse of the Armauer Hansen Research Institute in Ethiopia will establish the Ethiopian Malaria Genomic Epidemiology Network (EMAGEN) by bringing together key public health, biomedical, and biotechnology institutions in Ethiopia to build malaria molecular surveillance capacity and renew elimination efforts. Eliminating malaria requires an urgent shift to more quantitative methods that can more accurately and rapidly track disease transmission and drug resistance, and better target interventions. They will develop a framework for building capacity and integrating it into the national malaria control and elimination strategy, produce next generation sequencing and bioinformatics protocols that will be used to monitor anti-malaria drug resistance, and train personnel in genomics and bioinformatics. They will also develop a simple, interactive web interface to effectively communicate results to diverse stakeholders.

Christian Happi of Redeemer's University in Nigeria will assess the impact and risks of emerging SARS-CoV-2 virus variants in Africa, which are threatening vaccination efforts. They will produce viral pseudotypes using genomic sequences of around ten SARS-CoV-2 variants-of-concern that are dominant in Africa. These pseudotypes will be used in high-throughput neutralization assays with Vero cells in the presence of serum samples taken from over 400 vaccinated or previously-infected Nigerians, which contain many different types of antibodies, to evaluate their ability to neutralize the viral variants. This will reveal how well protected the population is against viral variants, and inform vaccine and immunization strategies. The serum samples that strongly protect against a range of SARS-CoV-2 variants will be subjected to single-cell immunoglobulin gene sequencing to identify neutralizing monoclonal antibodies for designing more effective vaccines.

Sikhulile Moyo of the Botswana Harvard AIDS Institute will expand the country’s genomic surveillance capacity to identify circulating SARS-CoV-2 variants and track their transmission routes and dynamics to inform the public pandemic response. Botswana has one of the highest global burdens of HIV and the associated immunosuppression may prolong SARS CoV-2 replication thereby increasing the probability of viral mutation and emergence of new variants. However, there is insufficient sequencing capacity to track these variants. They will increase national capacity by improving infrastructure, optimizing workflows, and providing training, as well as establishing a sampling framework and surveillance strategy. This will enable the temporal and spatial monitoring of circulating SARS-CoV-2 viral lineages across Botswana. They will also identify any associations between circulating viral variants and HIV infection, and study the risk of infection to specific SARS-CoV-2 variants among vaccinated people.

Atsbeha Gebreegziabxier Weldemariam of the Ethiopian Public Health Institute (EPHI) together with colleagues at the Armauer Hansen Research Institute, both in Ethiopia, will boost the country’s sequencing capacity to establish routine SARS-CoV-2 genomic surveillance and monitor the emergence and impact of new variants to better inform public policy. Over 1,000 SARS-CoV-2 positive samples will be collected across 14 hospitals and laboratories over a period of ten months and subjected to next generation sequencing and bioinformatics analyses to identify any new variants. They will then test the efficacy of existing diagnostic assays for detecting these different variants. New genomic data will be promptly uploaded to public repositories, and a web-based platform will be developed to rapidly communicate research findings to relevant stakeholders, including the Ethiopian Ministry of Health, so that results can be readily translated into public health policy.

Iruka Okeke of the University of Ibadan in Nigeria will use academic sequencing resources to expand the genomic surveillance framework of Nigeria’s Centre for Disease Control for the rapid detection of newly-evolved or imported viral variants to inform national vaccination strategies. Nigeria’s SARS-CoV-2 sequencing needs currently surpass its capacity. To address this, they will repurpose existing academic sequencing and bioinformatics resources and expertise for SARS-CoV-2 genomic surveillance, and share the data with the national and global communities in near real-time. They will also pilot an approach to more efficiently monitor the existence and spread of viral variants and viral breakthrough strains by sequencing SARS-CoV-2 positive samples from around 180 health workers, who have greater exposure and better access to vaccines.

Charles Sande of the African Research Collaboration for Health (ARCH) in Kenya will build on their existing SARS-CoV-2 genomic surveillance work covering the six counties of Coastal Kenya to identify new SARS-CoV-2 variants and evaluate their sensitivity to existing vaccines. Daily naso- and oropharyngeal samples from suspected COVID 19 cases will be processed for PCR testing and genome sequencing to identify any new SARS-CoV-2 variants. They will then evaluate the potential impact of these new variants on the Kenyan population by measuring the neutralizing activity of antibody-containing plasma obtained from a cohort of vaccinated adults. Using established channels, they will rapidly communicate their results to local and national health ministries, and across the African continent, to inform pandemic control strategies. Selected samples will be preserved for future monoclonal antibody development to target new variants.

Khurshid Talukder from the Centre for Woman and Child Health in Bangladesh will scale-up their proven approach using a package of 11 service interventions, including antenatal counselling and supportive care during labor, to reduce the cesarean section rate across Bangladesh. Bangladesh has an unnecessarily high cesarean section rate, which can have severe short and long-term health consequences for the mother and child. They developed a multi-service intervention to reduce the rate in their own hospital from 65% to 42% over two years. They will hold workshops at six other large maternity units for tailoring the intervention package to local needs, and train managers and maternity personnel to effectively deliver it in their clinics over an 18-month period. They will evaluate the effect of their approach on reducing cesarean section rates.

Mary Glover-Amengor of the Food Research Institute in Ghana will investigate whether drinking soymilk-burkina, a Ghanaian indigenous fermented milk and millet beverage (smoothie), improves the nutritional status and gut health of women of reproductive age living in the Volta and Oti regions of Ghana. They will produce the soymilk-burkina and test it for bacterial and fungal content and consumer acceptability. They will also recruit 30 pregnant and non-pregnant women and perform a randomized controlled trial to test the effect of daily consumption of 330ml soymilk-burkina over six months. Monthly blood and fecal samples will be collected during trial, and two months after, to analyze nutritional status, inflammation biomarkers and parasites. The gut microbiome will also be analyzed using culture-based assays and next generation sequencing.

Laeticia Celine Toe of Institut de Recherches en Sciences de la Santé in Burkina Faso will evaluate the nutritional content of traditionally-fermented millet porridge and its effects on gut health and inflammation in women of reproductive age in rural Burkina Faso. Maternal undernutrition affects child survival and is a major problem in sub-Saharan Africa and south Asia. This could be addressed by enhancing the nutritional content of common foods, which can be done by fermentation. They will provide a selection of households with locally-produced millet grain for fermenting, and collect samples every five days to evaluate the nutritional and microbial contents. They will also recruit a cohort of 30 women, including 15 pregnant women, to assess the effects of daily fermented millet porridge consumption on fecal microbiota composition, fatty acid levels, and inflammatory markers.

Peter Quashie of the University of Ghana, West African Centre for Cell Biology of Infectious Pathogens in Ghana will determine the impact of SARS-CoV-2 viral variants and their susceptibility to neutralization by vaccine-induced and naturally-acquired immunity to better manage pandemic control in Ghana. They will evaluate over 600 existing plasma samples taken at multiple timepoints from both vaccinated and unvaccinated COVID-19 patients with associated SARS-CoV-2 sequencing data to identify the viral variants, and additional samples as new variants emerge. They will use ELISA and Luminex assays to screen these samples for anti-viral antibodies. Positive samples will then be used in neutralization assays to measure their ability to protect against different viral variants. Plasma with strong broad or selective neutralization activity will be processed for single cell sequencing to identify monoclonal antibodies for potential therapeutic use. Their pipeline can also be applied to other viral outbreaks such as HIV or Ebola.

Manoja Kumar Das of the INCLEN Trust International in India will determine the optimal dose of traditional fermented rice-water (pakhala/torani) to improve the nutritional status and the gut and vaginal microbiomes in women of reproductive age in Odisha, India, to promote maternal health. They will provide different rice types and fermentation protocols for households to prepare torani and also prepare it in the laboratory and evaluate its stability and nutritional and microbial content. A prospective cohort study will be performed to determine the minimum daily dose needed to improve the diversity of the gut microbiota in eight to ten adult females. This will then be used in a pilot test with 200 adult reproductive-age women to evaluate the effects of a daily dose over six months on gut and vaginal microbiome diversity, nutritional profiles, and inflammatory markers.

Syed Asad Ali and colleagues of Aga Khan University in Pakistan will perform a clinical trial to test whether traditional fermented pickles (achars) reduce gut inflammation and promote healthy bacterial growth in women of reproductive age from the poor rural Matiari district in Pakistan, to help reduce rates of childhood stunting. Key drivers of childhood stunting are poor maternal health and nutrition, which could be improved by regular ingestion of fermented foods, although this has never been tested in a real-life setting. They will recruit 210 women of reproductive age and provide different types of locally-produced achar for consumption at home one-to-two times per day over a period of eight weeks. They will collect blood and fecal samples at four, eight, and 12 weeks, and test them for nutritional and inflammatory markers, and perform metagenomic analyses of a subgroup of samples to evaluate the composition of their microbiomes.

Heather Jaspan of the University of Cape Town in South Africa will conduct a randomized controlled trial of post-partum South African mothers to determine whether unpasteurized mageu is more nutritious and promotes a healthier gut microbiome than pasteurized mageu, which is more commonly consumed. Mageu is a common grain-based fermented porridge used as a weaning food in infants and as an energy drink in adults. It is generally produced in pasteurized form, which may inactive the live bacteria that can boost health. They will locally manufacture a live-culture grain-based fermented mageu and use it to conduct a pilot trial with 30 women. The women will receive either store-bought mageu or live-culture mageu for daily consumption over six weeks. They will collect fecal samples to measure microbial diversity, which is a marker of gut health, and host and inflammatory biomarkers between women consuming pasteurized versus unpasteurized mageu.

Yilan Ye from Tsinghua University in China will develop a small, self-adhesive menstrual product based on the suction cups of octopuses that can be fixed securely but reversibly inside the vaginal opening to block the flow of blood and enable its convenient disposal. They will design it specifically for women and girls in low- and middle-income countries by ensuring it is low-cost, re-usable, safe to apply, and does not require sanitation facilities. They will experiment with different commercialized, biocompatible thermoplastic polyurethanes (TPUs) as the raw materials to produce the adhesive polymers. They will first test these polymers for their ability to be strongly, reversibly and repeatedly stuck to the surface of porcine livers and hearts as surrogates that mimic the moist and irregular skin surface inside the vagina. Finally, they will develop an inject mold to manufacture a prototype for human testing that also contains a soft valve for convenient release.

Andrew Boulle and colleagues at the Western Cape Government Health Department and the University of Cape Town in South Africa will use a data science approach applied to anonymized COVID-19 health data from the government health department including over one million tests and 60,000 hospital admissions, to study the clinical epidemiology and evolution of a new variant of SARS-CoV-2 that emerged in South Africa and the impact on patients with existing health conditions. They will conduct a case-control study to determine the clinical severity of the variant and use a cross-sectional design to explore the evolution of viral load. They will also analyze the impact of COVID-19 on pregnancy by evaluating birth weight and other birth outcomes, such as still births, and use death registries to determine mortality rates in patients with HIV, TB, and diabetes.

Xiaofan Liu at the City University of Hong Kong in China and colleagues will reconstruct COVID-19 transmission chains between individuals in communities and households using statistical methods applied to existing datasets to more reliably estimate COVID-19 transmission characteristics, such as reproduction rates, that are critical for planning effective control measures. Currently, transmission characteristics are estimated using aggregated-level data, which leads to inaccuracies. Ideally, data on how COVID-19 is transmitted between individuals are needed. They will curate an existing collection of datasets containing over 40,000 COVID-19 cases in five Asian countries with person-to-person transmission evidence to reconstruct transmission chains. They will then apply statistical tests and an analytical methodology called regression analysis to identify the most important transmission risk factors, which may include virus strain, transmission media, population density, and climate conditions.

Luis Felipe Reyes at the Universidad de La Sabana in Colombia and colleagues will develop a standardized strategy for researchers to better utilize the ISARIC-COVID-19 dataset, which consists of over 520,000 hospitalized patients from more than 62 countries, and identify the causes and health impacts of severe complications. The dataset is particularly valuable because it covers varying standards-of-care around the world and could be used to study the geographic and time-based variability of the disease. The team will develop a standardized strategy to reformat and clean the ISARIC-COVID-19 dataset by producing data descriptors and reference codes and use this strategy to identify the risk factors and clinical characteristics of COVID-19 complications, such as cardiovascular complications, which are a major contributor to long-term morbidity and mortality, in order that vulnerable patients can be better treated.

Fernando Bozza at Fiocruz in Brazil and colleagues will quantify the real-world value of COVID-19 vaccines in Brazil for protecting individuals from severe disease and for protecting the entire population from being infected. Knowing how effective vaccination is, and how durable the response in the real world is, particularly in low- and middle-income countries, it is critical for ending the pandemic. They will determine the effectiveness of the vaccine for protecting individuals using an approach called test-negative design together with statistical and machine learning approaches to compare the severity of respiratory disease in COVID-19 patients from 43 hospitals. At the population level, they will perform an ecological study, and use regression analysis accounting for inequities to vaccine access, to measure the effect of vaccinations on COVID-19 cases, hospitalizations, and deaths.

Maria Yury Ichihara and colleagues at the Centre for Data and Knowledge Integration for Health (Cidacs) at Fiocruz in Brazil will create a social disparities index to measure inequalities relevant to the COVID-19 pandemic, such as unequal access to healthcare, to identify regions that are more vulnerable to infection and to better focus prevention efforts. In Brazil, markers of inequality are associated with COVID-19 morbidity and mortality. They will develop the index of available COVID-19 surveillance data, hosted on the Cidacs platform, and build a public data visualization dashboard to share the index and patterns of COVID-19 incidence and mortality with the broader community. This will enable health managers and policymakers to monitor the pandemic situation in the most vulnerable populations and target social and health interventions.

Kirsty Le Doare and colleagues at the MRC/UVRI & LSHTM Uganda Research Unit and Makarere University John's Hopkins University in Uganda will develop a model using data collected in real-time to identify the risk factors for adverse pregnancy and infant outcomes caused by the COVID-19 pandemic that can be used to rapidly inform interventions. Lockdowns can severely impact women giving birth and access to maternal, neonatal, and child healthcare. They will apply a Bayesian multivariate network meta-analysis, (a methodology that simultaneously analyses multiple outcomes and multiple treatments, allowing more studies to contribute towards each outcome and treatment comparison) to electronic medical records, leveraging existing data on the effect of the lockdown on antenatal and delivery services for over 30,000 pregnancies, vaccination data, and information on COVID-19 infection in pregnancy and infancy. They will also build a user-friendly data dashboard to support decision-making on infection prevention and control at the Ministry of Health.

Juliane Foseca de Oliveira and colleagues at Fiocruz in Brazil will develop mathematical and statistical methods to model COVID-19 infection transmission, prevention and control across populations in Brazil to better inform local intervention efforts. Social and economic inequalities are known to shape the spread of diseases, therefore the team will integrate existing health data together with social and economic determinants for 5,570 Brazilian cities, as well as assessing data on the effects of the mitigation strategies and social mobility patterns. These data will be used to develop and apply statistical analyses and nonlinear mathematical modelling to forecast disease evolution and outcomes that consider the specific socio-economic conditions, which influence transmission rates. The results will be presented on a user-friendly surveillance platform that can be used by local governments and communities to identify the most effective control methods for their region.

Dale Barnhart and colleagues at Harvard Medical School in the U.S. and Partners in Health of Haiti, Malawi, Mexico, and Rwanda will determine how the COVID-19 pandemic has impacted health care provision and utilization for patients with HIV, heart disease, and diabetes, and the health outcomes of these patients, in all four countries. They will pool existing electronic medical data on chronic care patients collected from up to 30 health facilities in each country and create a harmonized database to identify the impacts of COVID-19 and any successful strategies used to improve care. They will also develop a predictive model to identify which patient populations are most at risk from care disruption during the pandemic, which can help prioritize clinical and geographic areas that need interventions. Finally, they will develop data visualization tools to facilitate the communication and interpretation of the data by chronic care managers across the four different countries.

Carl Marincowitz and colleagues at the University of Sheffield in the United Kingdom and the University of Cape Town in South Africa will develop a risk assessment tool to help emergency clinicians quickly decide whether a patient with suspected COVID-19 needs emergency care or can be safely treated at home to avoid overburdening hospitals particularly in low- and middle- income countries (LMICs). They will use existing data to which they have access on 50,000 patients with suspected COVID-19 infection who sought emergency care in the United Kingdom, South Africa, and Sudan to develop prediction models for specific COVID-19 related outcomes in all income settings. These prediction models will be used to develop risk stratification tools, which enable providers to identify the right level of care and services for distinct subgroups of patients. These will be developed with input from patient and clinical stakeholders. The team will test the performance of their risk assessment tools for identifying high-risk patients with existing triage methods.

Janine Aucamp of North-West University in South Africa will produce a novel drug screening platform for malaria by building a physiologically-relevant in vitro tissue model of the sinusoidal space of the human liver, which supports the development of liver-stage malaria parasites (sporozoites). Artemisinin-based combination therapies are first-line treatments for malaria but their efficacy suffers from the development of resistance, thus alternative approaches are needed. One approach is to block parasite development in the liver, which can prevent the establishment and symptomatic onset of malaria. They will build three different three-dimensional micro-bioreactor liver models and evaluate how well they can be infected by Plasmodium falciparum sporozoites compared to two-dimensional cultures. They will then test the value of the most promising model for identifying anti-malarial drugs first using two approved drugs and subsequently by screening novel drugs.

Grace Mugumbate of Chinhoyi University of Technology in Zimbabwe will develop new anti-malarial drugs by using a chemogenomics approach for ligand-based and structure-based virtual screening to identify compounds that selectively bind to heat shock proteins of the malaria parasite, Plasmodium falciparum. P. falciparum heat shock proteins are essential for parasite growth and survival, and represent a valuable new target for developing safe and effective anti-malarials. They will use existing chemical and genomic data to produce three-dimensional structures of several heat shock proteins for performing the virtual screens. Machine learning approaches will be used to identify binding ligands and inhibitors that will be validated using enzymatic assays in vitro. Promising hits will then be subjected to structure-based optimization to identify active compounds as leads for further development.

Erick Strauss of Stellenbosch University in South Africa will develop a small molecule inhibitor of an enzyme that helps pathogenic bacteria evade the host immune system and potentially become resistant to antibiotics as a novel treatment for methicillin-resistant S. aureus (MRSA), which is a major public health concern. They discovered a bacterial enzyme, MerA, that neutralizes an anti-microbial compound secreted by immune cells. This prolongs the survival of the bacteria in the host, giving them time to develop mutations that could render them less susceptible to antibiotics. They have identified two different chemical scaffolds that occupy the active site of MerA and will employ a new inhibitor discovery strategy that combines parallel synthesis with an X-ray structure-based binding screen to identify promising MerA inhibitor leads. These leads will be evaluated by in vitro and ex vivo assays for further development.

Lyn-Marie Birkholtz of the University of Pretoria in South Africa will identify gametocytocidal
compounds that specifically prevent human-to-mosquito transmission of gametocytes and block gamete and oocyst formation in mosquitoes as a complementary strategy to help eliminate malaria. Traditionally, anti-malarial compounds have been developed to target asexual blood-stage parasites. However, also blocking parasite transmission is critical for eradication. They developed a platform that can screen multiple sexual stages of the parasite and recently used it to identify ten hit compounds from the Medicines for Malaria Venture (MMV) Pandemic Response Box (PRB), most of which have not previously been tested against malaria-causing parasites. They will validate those hits, optimize them, and analyze their structure-activity-relationship (SAR) and their potential mode of action to identify at least one chemotype as an early lead candidate for further development.

Laurent Dembele of the Université des Sciences, des Techniques et des Technologies de Bamako in Mali will use their cell-based ex vivo phenotypic drug assay to identify approved anti-malarial drugs that are effective also against the neglected malaria-causing pathogen Plasmodium malariae, which has become widespread in sub-Saharan Africa. To eliminate malaria, treatments should be effective for all circulating malaria pathogens. However, current artemisinin-based combination therapies (ACTs) are largely designed to target the historically more prevalent P. falciparum species. They will recruit around 400 patients with uncomplicated malaria in Faladje to determine the P. malariae malaria burden. They will also evaluate the ability of a panel of anti-malarial compounds to destroy cultured P. malariae together with P. falciparum to help guide treatment strategies.

Fortunate Mokoena of North West University in South Africa will couple molecular docking approaches with in vitro and in vivo validation to identify novel inhibitors of Trypanosoma brucei and Plasmodium falciparum, the causative agents of the lethal diseases, African trypanosomiasis and malaria, respectively. Current drugs targeting these pathogens have limited efficacy due to the development of resistance and can cause severe side effects. They will identify a new group of drugs that specifically target parasitic molecular chaperone proteins, specifically heat shock protein 90 (Hsp90), which is an ATPase that helps correctly fold newly synthesized proteins. They will computationally model the structures of Hsp90 from both T. brucei and P. falciparum and prepare a three-dimensional database of inhibitors for virtual screening. The top 30 candidate inhibitors that selectively bind parasitic Hsp90 will be subjected to geometry optimization and induced fit molecular docking, followed by evaluation of their parasite killing activity in vivo.

Elizabeth Kigondu of the Kenya Medical Research Institute will identify natural products that block the resistance mechanism developed by tuberculosis-causing bacteria against existing anti-mycobacterial drugs to help more effectively treat tuberculosis. Tuberculosis (TB) is a highly prevalent and severe disease that has been exacerbated by the emergence of multi-drug resistant TB for which only limited treatments are available. Efflux pumps play a critical role in mycobacterial resistance to two drugs, spectinomycin and rifampicin. They will identify natural products and their derivatives that block these efflux pumps by first searching databases for analogs to published efflux pump inhibitors, and then performing virtual docking experiments to identify those that bind. These will then be tested in drug combinations with spectinomycin and rifampicin for synergistic cytotoxicity and anti-mycobacterial activity.

Gabriel Mashabela of the South African Medical Research Council will develop novel tuberculosis drugs derived from South African medicinal plants by utilizing CRISPR genome editing technology to produce Mycobacterium deficient in essential metabolic enzymes that can be used to screen natural products. Although the majority of approved drugs are of natural origin, most drug-screening approaches use synthetic libraries, which lack diversity. However, natural products contain very low concentrations of bioactive compounds making them difficult to use in traditional drug screens. To address this, they will use CRISPR to reduce the levels of a selection of essential metabolic enzymes, without removing them completely, so that lower levels of bioactive compounds are needed. They will prepare extracts from 100 plants with anti-mycobacterial activity, and perform whole cell screening to identify those with killing activity against the different Mycobacterium mutants. These can then be further optimized for drug development.