Why advances in point-of-care TB diagnostics determine the future of the AIDS crisis
by Mariel Selbovitz, MPH
TB—one of the greatest killers and what appears to be the most persistent of our public health threats—still lacks effective widespread utility of rapid point-of-care diagnostics to quickly and accurately diagnosis TB infection. With the continual spread of HIV worldwide driving susceptibility to TB as well as drug-resistant strains of TB becoming more prevalent, identifying new capacities to address the disease needs to become an essential priority for this next Congressional session. TB Biosciences is one of a very small number of diagnostic companies going out on a limb to address this disparity, which continues to cost the lives of millions each year.
Sessions at AIDS 2014 provided a sobering look at the stark realities of what malingering public policy around advances in TB diagnosis and treatment will result in. TB is the number-one killer of people living with HIV in the developing world. It is costing governments hundreds of millions of dollars each year in lost revenue in taxes and GDP growth and exacerbating the toll of the AIDS crisis. We have effective treatment, but diagnostics continue to lag behind. During sequestration and austerity, federal funding is still hard for small biotechnology companies to secure despite the overwhelming demand.
Two of the founders of OraSure Technologies, maker of the OraQuick rapid HIV test, have reunited to make a rapid, point-of-care tuberculosis test. TB Biosciences is in an advanced stage of development and looking forward to regulatory submission. Like many companies developing diagnostics, the current economic environment makes raising capital difficult. Dr. Sam Niedbala, CEO of TB Biosciences, concurs, stating that “TB as an infection is complicated and challenging. Coupled with the perception that the problem is only in the developing world adds another level of difficulty to developing solutions.”
TB Biosciences has been collaborating with researchers and clinicians at Lehigh University and NYU School of Medicine to develop its technology for a cost-effective, rapid point-of-care TB diagnostic with a sensitivity (a high sensitivity means there are a low percentage of false negative results) and specificity (a high specificity means there are a low percentage of false positive results) of greater than ninety percent, increasing healthcare workers’ ability to detect and therefore treat active TB infection. TB Biosciences received a Phase II STTR grant from the NIH in 2013 to further develop their technology, which is based on a diverse group of small proteins present in active TB infection that was discovered by examining the genome of the TB bacteria. The company’s technology is based on patented novel proteins and derived synthetic peptides combined in multiplexed diagnostic platform. The one drawback of this new diagnostic is that it does not detect latent TB infection.
TB Biosciences’ test is being evaluated as a reliable and rapid serological test for active TB infection in countries where the disease is endemic and in high-risk populations including in homeless shelters and prisons, and among immigrants and returning veterans from countries with endemic TB. There are over twenty-five peer-reviewed publications supporting TB Biosciences’ approach, almost all of which were led by Suman Laal, PhD, Director, AIDS International Training and Research Program, Research Microbiologist, Manhattan Veterans Affairs Medical Center, NYU Medical Center, whose research is focused on immunology/immunology and molecular biology of mycobacteria and opportunistic infection in HIV disease.
There are other platforms receiving significant support, but none address the challenges of bringing a serologic test for active TB to market. TB in immune-compromised people is traditionally diagnosed by a combination of a sputum test and chest X-ray, but the low sensitivity and specificity is problematic and the sputum smear microscopy test does not work well in patients with HIV.
We are on the verge of another epidemic of plague proportions with the rise and increasing incidence of multidrug resistant (MDR) and extensively drug resistant (XDR) TB. Tuberculosis diagnosis remains a challenge among HIV patients, as it often requires advanced and expensive technologies. Stable TB case detection and rising TB drug resistance are in part the consequence of historically neglected laboratory capacities and services and a lack of effective new TB diagnostic tools. The World Health Organization stated in their report, entitled “Towards universal access to diagnosis and treatment of multidrug-resistant and extensively drug-resistant tuberculosis by 2015 of the Xpert MDR TB rapid diagnostic assay,” about the most promising of new MDR TB diagnostic: “Although the Xpert MTB/RIF [Mycobacterium tuberculosis/rifampicin resistance] test introduced in 2010 may bring diagnosis closer to patients, it is not a point-of-care assay, and the need for increased research investment into novel rapid tests therefore remains.”
In December 2010, the WHO endorsed the Xpert MTB/RIF test for use in endemic countries to identify cases of TB, MDR-TB, and TB/HIV co-infection. The Xpert MTB/RIF system is a rapid, point-of-care automated, cartridge-based nucleic amplification sputum diagnostic that simultaneously tests for infection and resistance to RIF. It detects DNA sequences of mycobacterium tuberculosis bacteria and RIF resistance via PCR and identification of all known clinically relevant resistance mutations in the TB genome, with results available in ninety minutes. The diagnostic was developed in partnership with Cepheid, Inc., Foundation for Innovation New Diagnostics (FIND), University of Medicine and Dentistry of New Jersey, with support from the NIH.
The urgent need for a rapid, point-of-care TB diagnostic is no longer elusive with the development of TB Biosciences technology. Extensive testing of this point-of-care diagnostic should be made a priority in order to offer a possible solution to the long standing TB diagnosis dilemma.
While the treatment of regular, MDR, and XDR-TB remains a challenge of paramount importance, diagnostics are at the crux of our ability to address any contemporary pandemic infectious disease. Scientific conference after conference exhibit the demand from doctors caring for people living with HIV in resource-poor settings for an effective, rapid point-of-care rapid diagnostic for TB. However, it appears there is virtually no emphasis on developing these tests, only the realization that they are desperately needed. While the hype around HIV eradication efforts enthusiastically reaches new heights of infeasibility, innovations in TB diagnostics continue to want for the definitive support necessary to save lives and stabilize the most affected regions. That is a shame that leaders of the Global Fund to Fight HIV/AIDS, TB and Malaria, the Congressional HIV/AIDS Caucus, Congressional Biomedical Research Caucus, Office of National AIDS Policy, UNAIDS, The Gates Foundation—and all of us—are going to have to bear. As austerity measures and sequestration continue to take their toll on public research programs, a mandate is desperately needed that we prioritize the most cost-effective, near-term opportunities we have and pursue them before our next accounting at the XXI International AIDS Conference (AIDS 2016) in South Africa.
Mariel Selbovitz, MPH, serves as the Chair of the Cornell ACTG Community Advisory Board and has authored over thirty abstracts and articles.