Sample-to-Answer Rapid, Multiplexed and PCR-Free Detection of Arboviral Fever Diseases in Resource Limited Settings

Arthropod-borne viruses (arboviruses) comprise many of the most important ‘emerging pathogens’ due to their geographic spread and their increasing impact on vulnerable human populations. Arboviral diseases are poised to become more common with globalization. We have demonstrated high seroprevalence for flaviviruses in multiple regions with marked regional variability and have documented the occurrence of many unrecognized human arboviral infections.

Diagnostics are lacking at health care centers making accurate diagnosis of these infections impossible. The similarity of symptoms to other illnesses means that effective diagnosis will work best if diagnostic systems are able to simultaneously check for the presence of multiple possible infectious agents in a rapid fashion at point of care settings. Despite significant effort in developing new diagnostic technologies, there is strong evidence showing that current front-line diagnostic approaches do not always correctly identify arboviral diseases. Without accurate diagnostics, arbovirus outbreaks are detected late, and sporadic cases go undetected, leading to delayed response to outbreaks, ineffective effort to prevent further disease spread, and substantial introduction risk to naïve countries. There is urgent need for easy-to-operate and rapidly deployable clinical diagnostics tools that can provide sample-to-answer manner.

This research program will lead to field deployable rapid assays for detection of three high-impact biodefense pathogens: dengue virus strains 1 through 4 (DENV1-4); zika virus (ZIVK); and chikungunya virus (CHIKV). The integrated diagnostic platform will utilize a novel surrogate approach, and open source robotics technology. The system will be designed to initiate diagnosis from serum/plasma/blood and provide a sample-to answer diagnostic within less than 35 minutes. This collaborative interdisciplinary program will build upon ongoing field surveillance of arboviral infections in Grenada, extending application of our novel approach to development of a clinical platform for low-risk successful technology to the diagnosis of biodefense arboviral pathogens in humans from ongoing Grenadian surveillance programs in the validation phase of this application. Collaborative work for this NIH/NIAID R01 project involves integration of biosensor engineering (Yanik Group), molecular virology (Pinsky Group), and infectious diseases epidemiology (LaBeaud Group) to build and field-test our novel point-of-care viral diagnostic platform with Windward Islands Research and Education Foundation (WINDREF) and St. George’s University teams. Our proposed work is innovative, as it is using a novel approach to solve a long-standing problem, rapid and accurate arboviral diagnosis in health care settings. Once this project is successfully completed, our collaborations will ensure that project findings are realized in policy and prevention efforts at all levels and will translate into effective intervention platforms.

PI: Ali Ahmet Yanik, Desiree LaBeaud, Ben Pinsky

Funding provided by the National Institute of Health. 12/2020 – 11/2021.


Animal-Sourced Foods as a Global Risk for Rift Valley Fever Disease Spread and Emergence in Urban Areas

Rift Valley Fever is a mosquito-transmitted zoonotic virus that can also be transmitted to humans directly from infective livestock. Risk factors associated with human exposure include herding and slaughtering livestock and assisting animal births. Consuming raw meat and milk are also thought to be potential risk factors; however very little field data on the infectious nature of meat and milk exists which underscores a major gap regarding worldwide RVFV emergence prevention and control, particularly in urban areas. To date, there have not been any outbreaks of RVFV in urban areas. However, the world is becoming increasingly urban and RVFV has proven to be a highly adaptable virus since it has spread from its origin in Kenya. Our research investigates the potential for RVFV emergence in new areas through a complex mobilization of animal products. We will link testing results of animal products to the origin location and explore high-risk areas for potential introduction to urban centers using participatory mapping techniques. By testing animal products entering large urban tertiary marketplaces from different regions of Kenya, we will disentangle the relationships between animal sourced foods and RVFV risk. Additionally, our pooling methods in the laboratory could provide a potentially paradigm shifting sampling framework for the way we currently detect new RVFV outbreaks and conduct animal surveillance.

 As the world becomes increasingly urban, congested areas have an increased demand for animal source foods, different vector distributions driven by land use change, and significant inequalities within a small geographical area, making them hotspots for disease and prime locations to study animal-sourced food safety. This project builds on previous documented human RVFV seropositivity and uses a One health approach to investigate this newly discovered urban burden of RVFV in humans and new risk factors associated with urban transmission.

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