Pittsburgh Research Team Uses Rapid Diagnosis Technology to Tackle HIV Testing Problems

As associate medical director of clinical immunopathology at the University of Pittsburgh Medical Center, Sarah Wheeler has received many calls from clinicians about diagnostic testing in the hospital, including those dealing with human immunodeficiency virus.

However, one call made her realize the limits of modern medical technology.

“We received a call from (UPMC) Magee–Womens Hospital that a woman was in active labor with no prior medical history and no baseline infectious disease testing, and we didn’t have any tests that could provide us an accurate result for her HIV status that could be done rapidly,” said Wheeler, who is also an assistant professor of pathology at Pitt.

This isn’t an uncommon scenario, but it was the event that led to Wheeler and other Pitt researchers taking action. She, along with Michael Shurin, a fellow professor of pathology, and Alexander Star, professor of chemistry at Pitt, are creating a testing device that will be able to determine in one minute whether a patient is infected with HIV. Currently, early HIV screening takes 1,440 minutes — an entire day.

Michael Shurin, professor of pathology, is part of the team that created the HIV Detective, a device for giving a rapid diagnosis for HIV infection.
“We thought, ‘We should be able to do something better,’” Shurin said.

Shurin’s tenure in the clinical laboratory took him through the earliest tests for HIV, and he has seen the progress to date in these tests as helpful, but inadequate for the clinical situations he now faces as division director of clinical immunopathology. Building on his decade-long collaboration in cancer research with Star, Shurin started pulling together a team to tackle this problem.

The HIV Detective is the team’s solution to the need for early and rapid diagnosis of HIV. It is a testing platform that would fit in the palm of a hand and allows health care workers to gather a few drops of blood from a patient onto a sensor smaller than Roosevelt’s ear on the dime and provides an HIV screening result in one minute.

This leap forward in testing is possible due to another recent project from the Star laboratory, a working THC breath test.

The THC-detection technology hinges on carbon nanotubes, tiny tubes of carbon 100,000 times smaller than a human hair, which are capable of conducting electricity and monitoring molecular interactions.

“Think of it like wires connected to molecules,” said Star. “The detection is really fast.”

Using the same technology in the HIV Detective means the team members don’t have to wait for the lengthy and insensitive chemical reactions currently used in testing; they can get real-time results from HIV antigen-antibody binding. This allows for a fast and accurate test, as Star’s team has demonstrated with their successful breathalyzer test that also helps in diagnosing and monitoring Type 1 diabetes in patients.

The technology also would allow the team to make the HIV Detective device cost-efficient, which could benefit HIV patients in other countries who cannot afford access to testing. About 34 million people worldwide have the virus.

Patients are most infectious when they first contract HIV, but current rapid tests do not detect HIV in this acute stage — about two to four weeks in. According to the Centers for Disease Control and Prevention, of the 1.1 million people who have HIV in the U.S., about 20% remain unaware they have the virus during this stage because they show no symptoms.

It was this message that helped the HIV Detective team win a $100,000 grand prize from the 2019 Pitt Innovation Challenge (PInCh), hosted by Pitt’s Clinical and Translational Science Institute (CTSI). The prize money will enable the team to create a prototype and use it for clinical trials.

“Our ultimate goal is approval from the Food and Drug Administration, so it can be used across the country,” Wheeler said.

“The PInCh competition provides the opportunity for University teams to identify important medical and public health problems and address those problems with unique solutions,” said CTSI director Steven Reis, who also is associate vice chancellor for clinical research and health sciences, and a professor of medicine at Pitt. “This year’s winners — including HIV Detective — proved, once again, that through creative thinking by diverse research teams, discoveries can be applied to address real world health challenges.”

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FDA Allows Marketing of First Rapid Diagnostic Test for Detecting Ebola Virus Antigens

The U.S. Food and Drug Administration allowed marketing of a rapid diagnostic test (RDT) to detect Ebola virus antigens (proteins) in human blood from certain living individuals and samples from certain recently deceased individuals suspected to have died from Ebola (cadaveric oral fluid). The OraQuick Ebola Rapid Antigen Test is the first rapid diagnostic test the FDA has allowed to be marketed in the U.S. for the Ebola Virus Disease (EVD). The test provides a rapid, presumptive diagnosis that must be confirmed.

“Today’s marketing authorization provides another important tool in the effort to fight Ebola, which continues to be a priority of the U.S. Government, especially as we work with our partners, including the World Health Organization, to help address the current Ebola outbreak in the Democratic Republic of Congo (DRC),” said Acting FDA Commissioner Ned Sharpless, M.D. “The current outbreak in the DRC has already killed thousands and the outbreaks in West Africa that began in 2014 tragically killed more than 11,000. Investigational vaccines and therapeutics have shown promising results, but one of the most important tools in stopping these outbreaks is quickly diagnosing patients and supporting safe and dignified burials. This marketing authorization may provide additional assurances to health care professionals seeking to use these types of rapid diagnostics. The ability to use this test to promptly make a presumptive Ebola diagnosis could help providers to more quickly isolate patients and begin treatments that can be potentially life-saving. Additionally, this device could be used to support safe and dignified burials while helping to reduce the risk of transmission during those burials.”

EVD, which is caused by the Ebola virus, is a severe, often fatal disease in humans that can spread through direct contact with blood or body fluids or objects contaminated with body fluids, as well as from the bodies of those who have died from the virus. EVD has led to several large outbreaks in Africa, including the West African Ebola epidemic that began in 2014 and was the largest outbreak of EVD in recorded history, and the ongoing outbreak in the DRC, which is currently the second largest outbreak. Extensive efforts are underway by the Ministry of Health in the DRC to contain the current outbreak with support from the World Health Organization, the U.S. government, and other partners. These measures include campaigns to promote good hygiene, large-scale vaccination campaigns, specialized Ebola treatment centers where those infected or exposed to the virus can receive investigational therapeutics, and comprehensive efforts to trace and prevent the spread of EVD through vaccination campaigns, monitoring for symptoms, diagnostic testing, and implementation of infection prevention and control measures, such as safe and dignified burial procedures.

During the 2014 outbreak, the Secretary of the Department of Health and Human Services declared that circumstances exist justifying the authorization of emergency use of in vitro diagnostics for detection of Ebola virus. At the time, the FDA worked with CDC and test developers to make diagnostic tests, including the OraQuick Ebola Test, available through the Emergency Use Authorization (EUA) pathway. This pathway allows the FDA to temporarily authorize the use of unapproved medical products to address a public health emergency when specific conditions are met, including that there are no adequate, approved and available alternatives to the product for diagnosing, preventing, or treating the disease or condition. The FDA has authorized a number of diagnostic tests for EVD under the EUA pathway to assist with the public health response. Today’s marketing authorization of the first EVD presumptive rapid diagnostic test for Ebola virus antigens through the De Novo review pathway reflects the ongoing collaboration between the U.S. Government and test developers to gather additional data on EUA products.

For the OraQuick Ebola Test submission, the FDA reviewed data from multiple clinical studies of blood samples and cadaveric oral fluid from the 2014 West African outbreak and from a variety of analytical studies. Based on these data, the FDA determined that general and special controls were necessary to provide a reasonable assurance of the safety and effectiveness of the OraQuick Ebola Test when intended to identify antigens associated with Ebola virus in blood from symptomatic patients and oral fluid of cadavers. The amount of Ebola virus when patients have severe symptoms of EVD is usually high; however, the amount of virus in samples taken early after infection when symptoms are not present yet or taken early during the course of EVD when symptoms are mild can be very low. The studies demonstrated the importance of testing only symptomatic individuals so that the amount of virus is high enough to be detectable by this test. Therefore, the OraQuick Ebola Test is intended for use in patients suspected of and with signs or symptoms consistent with EVD, and when the patient meets the CDC’s Ebola virus epidemiological criteria, such as history of residence in or travel to a geographic region with active EVD transmission at the time of travel. The OraQuick Ebola Test is not intended to be used for general Ebola infection screening (e.g., airport screening) or testing of individuals at risk of exposure without observable signs of infection.

The OraQuick Ebola Test may also be used in recently deceased individuals (cadaveric oral fluid) with epidemiological risk factors (including geographic locations with high prevalence of EVD) suspected to have died of EVD to inform decisions on safe handling of cadavers to prevent disease transmission.

Negative results do not rule out Ebola virus infection. The definitive identification of EVD requires additional testing and confirmation procedures (such as by a more sensitive but less rapid polymerase chain reaction test) and in consultation with public health and/or other authorities to whom reporting is required.

The OraQuick Ebola Test was reviewed under the De Novo premarket review pathway, a regulatory pathway for low-to-moderate-risk devices of a new type. Along with this marketing authorization, the FDA is establishing criteria, called special controls, that determine the requirements for demonstrating accuracy, reliability and effectiveness of tests intended to identify Ebola virus antigens. These special controls, when met along with general controls, provide a reasonable assurance of safety and effectiveness for tests of this type. This action also creates a new regulatory classification, which means that subsequent devices of the same type with the same intended use may go through the FDA’s 510(k) pathway, whereby devices can obtain clearance by demonstrating substantial equivalence to a predicate device.

The OraQuick Ebola Test was granted Breakthrough Device designation, meaning the FDA provided intensive interaction and guidance to the company on efficient device development, to expedite evidence generation and the agency’s review of the device. To qualify for such designation, a device must provide for more effective treatment or diagnosis of a life-threatening or irreversibly debilitating disease or condition, and meet one of the following criteria: the device must represent a breakthrough technology; there must be no approved or cleared alternatives; the device must offer significant advantages over existing approved or cleared alternatives; or the availability of the device is in the best interest of patients.

The FDA granted marketing authorization of the OraQuick Ebola Test to OraSure Technologies, Inc.

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Microfluidic Device for Rapid Lyme Disease Diagnosis

Researchers at Columbia University have developed a microfluidic device that can diagnose Lyme disease in as little as 15 minutes. The device is particularly accurate in identifying antibody biomarkers that are present during early stage Lyme disease, raising hopes that it could be useful in detecting cases of early infection in a doctor’s office, leading to timely treatment.

Lyme disease, which is spread by infected ticks, is incredibly common. Approximately 300,000 Americans are diagnosed with the disease each year, and if left untreated it can result in serious neurological and cardiac symptoms. The disease is difficult to spot, as many of the early symptoms are similar to those found with other conditions.

Diagnosing and treating the disease early is important in achieving good patient outcomes, but the current diagnostic tests require both an ELISA and a western blot, which are cumbersome, take a while to perform, and require trained laboratory specialists. Moreover, the accuracy of these tests in identifying early cases of Lyme disease is quite poor.

Zoomed photo of fluid moving through a small channel in the new microfluidic chip.
To address these issues, the Columbia researchers developed a point-of-care microfluidic test for Lyme disease, which a doctor could use in their office, and which can provide a diagnosis within just 15 minutes.

“Our findings are the first to demonstrate that Lyme disease diagnosis can be carried out in a microfluidic format that can provide rapid quantitative results,” said Sam Sia, a researcher involved in the study. “This means that our test could easily be used directly in a doctor’s office, obviating having to send the samples out to a laboratory that needs at least a couple of hours, if not days, to get test results.”

The new assay detects three biomarkers of Lyme disease in patient samples, and demonstrates greater sensitivity than traditional Lyme detection assays. Excitingly, the device also appears to be better at detecting early stage Lyme disease and can detect antibodies that are present in the blood in the first few weeks after someone contracts Lyme disease.

“While the assay will require more refinement and testing before it can be approved for widespread use as a test for Lyme disease, our results are very exciting,” said Siddarth Arumugam, another researcher involved in the study. “It will help so many people if we can develop a single, rapid, multiplexed diagnostic test to identify Lyme disease stage that can be used in doctors’ offices.”

Reference: A Multiplexed Serologic Test for Diagnosis of Lyme Disease for Point-of-Care Use

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