Endemic in all of Africa, the Balkans, the Middle East, and in Asia, Crimean-Congo hemorrhagic fever is a disease caused by a tick-borne virus. Its symptoms can include fever, muscle pains, headache, vomiting, diarrhea, and even bleeding into the skin. Found across the Southern Hemisphere, Zika virus is spread by the bite of an infected mosquito and can cause rash, fever, conjunctivitis, muscle and joint pain, malaise, and headache. In pregnant women, the virus can even cause miscarriages, stillborn babies, or babies born with birth defects. Reported around the world and across North America, Tularemia, or “rabbit fever,” is caused by a bacterium that is passed from infected rodents and rats or the bite of a tick or deer fly to humans, causing skin ulcers and swollen lymph glands. Though diseases like these and others are often discovered as outbreaks, some are becoming more prevalent due to factors like climate change and global travel. Diseases that used to be limited to a local endemic can now more easily cross borders and leap continents, causing a possible global pandemic. Field-forward diagnostic devices can meet the need for detection and diagnoses of these diseases in areas of the world where access to modern medical facilities may be limited.
Considerations for Device Development Diagnostic tools that were previously the size of a refrigerator can now be carried in the palm of one’s hand, making them quite literally handheld. When taking these devices out of the controlled environment of a laboratory or other clinical setting and making them portable to remote environments, there are several factors that must be considered to ensure their operational effectiveness.
Durability – Extreme environmental conditions can impact a device’s functionality, so that must be factored into its design. It must be able to operate reliably in a wide range of hot, cold, windy, and dusty environmental conditions. Too, because these devices are carried into remote areas, they must be rugged enough to withstand being tossed into a backpack, bounced around on a motorbike, or even accidentally dropped.
Power source – A device needs to run on an unlimited power source, as electricity and even solar can present a challenge in remote locations, so battery operated is often the best choice.
User-friendliness – Devices must be user-friendly for individuals without specialized training and in environments that are not controlled.
Maintain operation – The device must be operational without Wi-Fi access or other communication connection, as it likely will not be available.
Materials use – Any reagents and consumables being used must possess all these same qualities and be usable without cold storage, which is nearly impossible in a remote environment. Materials that are usually frozen must be converted for use in not only ambient temperatures, but also in weather extremes. This may warrant lyophilizing, or freeze-drying, necessary reagents.
Sample-to-Answer Time – When working in a remote environment, field operations mean mobile operations, so researchers don’t have the luxury of time to wait for a result. There are also usually a limited number of devices, so time to result in that situation directly correlates with the number of tests that can be run.
When developed with these considerations factored in, field-forward diagnostic devices can successfully be deployed to remote regions around the world, increasing access to care. From remote settings in Africa, South America, and anywhere else there is a public health emergency or combat zone, field-forward devices change where detection and diagnostics can take place by expanding the testing bandwidth. Even in rural areas of highly developed countries, they improve public health by putting these devices into the hands of people most in need.
Even in settings that do have access to sequencing capabilities, a backlog of samples may prevent samples from being run in a timely manner. During the COVID-19 pandemic, we developed genotyping assays that could be run on a mobile platform. This helped screen patient samples to triage and prioritize which samples should then be sequenced, taking pressure off the healthcare system when it was flooded with specimens and caring for more patients than normal. You can read more about this work at “Development, testing and validation of a SARS-CoV-2 multiplex panel for detection of the five major variants of concern on a portable PCR platform” from Frontiersin.org.
Applications in Animal Agriculture It is believed that the 1918-1919 influenza (H1N1) pandemic originated in pigs and spread to humans, resulting in “up to 50 million deaths, including some 675,000 deaths in the United States alone.” Since then, swine also were proposed as “mixing vessel,” intermediary hosts between birds and humans during the 1957 Asian and 1968 Hong Kong pandemics. Today, diseases like H5N1 are spreading among wild birds and mammals, as well as poultry and dairy cow populations, having a devastating impact on production and food prices.
For domesticated animal populations, rather than a time-consuming process of testing individual animals for the virus, the health of the herd can be assessed through sentinel testing. In some cases, this can be conducted through aerosol or stool collection. In a swine operation, samples can also be collected from chew ropes. After collection, these materials are tested for the presence of the virus, providing an indication of the herd’s health.
Choosing the right matrix for diagnostics and detection is critical. In diagnostics, blood is common, but can be difficult to get from individual animals. Diagnosis of upper respiratory infections relies upon nasopharyngeal swabs. Saliva has become more and more common because it’s very easy to collect and noninvasive. In disease detection, the possibilities are nearly endless. Our research scientists have worked with everything from bits of tissue to teeth from deceased cattle. When searching for a bacterium like anthrax, researchers collect anything and everything they can, including soil and water samples.
Use of Biomarkers in Field-Forward Detection Genetics-based diagnostics rely upon direct detection of the pathogen’s DNA and RNA. Conversely, sampling for biomarkers relies upon an indication, also called a marker, such as a protein marker or an mRNA marker, indicating that the disease is present without direct detection.
Rather than determining exactly what disease has been found, the non-specificity of biomarkers can be a positive aspect, as they can be more universal. For example, it may not matter to a clinician exactly what disease is present; rather, they may be more interested in whether the disease is bacterial, viral, or fungal so they can begin treatment with antibiotics, antivirals, or antifungals. Using bacterial sepsis as an example, there is often less than one bacterial cell per milliliter of blood, which makes genetics-based diagnostics exceedingly difficult. By using biomarker-based diagnostics instead, field researchers can find the host response to that bacterium being present, which can be prevalent at much higher levels than the bacteria itself. Having a potentially higher sensitivity also often translates to earlier diagnosis, possibly before symptoms are even present.
Using artificial intelligence (AI) and machine learning, the detection of biomarkers provides a wealth of information that can be pieced together to understand what specific markers mean and what diseases may be present in an environment. Too, that data can help answer not only what diseases are present, but how bad they are, and what treatments are best.
By creating field-forward tools that are small, durable, user-friendly, and can be brought into remote communities around the world, we can democratize diagnostics and detection.
GETTING STARTED AT MRIGLOBAL Contact MRIGlobal for further information about our work with infectious diseases. Through a multidisciplinary approach, we provide scientific and subject matter expertise for the development of medical countermeasures research against specific threats, while expanding and accelerating the delivery of high quality clinical diagnostic products.
To discuss how we can help your project be successful, contact us today.
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