World Tuberculosis Day Is March 24: 6 Questions for a 20-Year Veteran of TB Testing

According to the US Centers for Disease Control and Prevention (CDC), 2 billion people—or one-quarter of the world’s population—may be infected with tuberculosis (TB), a contagious and sometimes deadly infection most often caused by the bacterium Mycobacterium tuberculosis. While the disease is rampant in other parts of the world, the US is not immune. In 2023, there were nearly 10,000 new cases reported in this country, up roughly 16% from 2022.

In recognition of World Tuberculosis Day this March 24, we sat down with Kimberlee Musser, PhD, chief of bacterial disease, Wadsworth Center, New York State Department of Health (NYDOH), and asked her six questions about tackling this ancient disease in a modern world.

What drew you to work in TB testing?

My career in public health started as an APHL Emerging Infectious Diseases postdoc fellow, and for the last 20 years I have been involved in Mycobacterium tuberculosis testing at the Wadsworth Center. At the time when I was asked to take this testing on, molecular diagnostic development was wide open, which was exciting. That, coupled with the reality that molecular diagnostics, if sensitive and specific, could have a major impact on how quickly we could detect the disease and predict drug resistance for Mycobacterium tuberculosis, drew me to this work.

I will also say that contributing to TB diagnostics has been one of the most fulfilling aspects of my public health career. This work takes quite a village, and there are many who have been essential to our success, including CDC and APHL, past and current Wadsworth Center leaders and team members and our New York State and New York City TB Control colleagues.

TB is often thought of as a disease of the past, yet we still have outbreaks in this country today. Why?

We have made some incredible strides in combating TB disease in the US. What was once more than 26,000 cases per year in the 1990s turned to a steady decline until 2020, when closer to 7,000 cases were identified. However, since the COVID-19 pandemic [when cases may have gone undiagnosed and healthcare resources were diverted elsewhere] there has been some ground lost in this fight to eliminate TB. While outbreaks are rare (thanks to the dedicated epidemiologists, laboratorians and others in local, state and national positions focused on TB case finding, treatment and control), there are occasional outbreaks that go undetected.

Can you explain how TB testing is conducted?

Testing for Mycobacterium tuberculosis and members of the Mycobacterium tuberculosis complex (MTBC, a genetically similar group of bacteria that can cause tuberculosis)—as well as the detection of drug resistance—is complicated by the slow growth of these organisms. Our lab at the Wadsworth Center has offered a clinical whole genome sequencing, or WGS, test for use on culture positive samples. This test provides a complete, accurate genome sequence in less than a week that can be analyzed by a bioinformatic pipeline. Ours was developed with our bioinformatician, Pascal Lapierre, working together with our team—Vincent Escuyer, Tanya Halse, Joseph Shea, Michelle Dickinson and myself—to refine the analysis and reporting. While we still need to wait for a culture, this testing saves a great deal of time when it comes to drug susceptibility testing on MTBC culture-positive samples. It is also highly comprehensive, detecting important mutations in the TB genome associated with drug resistance.

We now also have a clinical targeted next generation sequencing test, or tNGS, that provides results on an important set of these mutations directly on the PCR-positive specimen, allowing even more rapid testing. This test was developed and validated by our team and an amazing APHL-CDC Public Health Laboratory Fellow, Shannon Murphy, along with our advanced molecular detection scientist Carol Smith, who is funded through CDC’s Epidemiology and Laboratory Capacity Program. We also have newer tNGS assays in development as well.

How do you think laboratory work such as yours is impacting the surveillance of TB?

By performing WGS for MTBC on all TB cases, we not only utilize the genome for drug susceptibility analysis, but we also utilize the genome to compare to the other 8,000 TB genomes from cases in our database. Weekly, we provide this surveillance analysis of the nearest neighbor genomes from cases that are within 10 mutations (over the 4.4 million base pairs) to our NY State and NY City TB Control epidemiologists to provide rapid TB surveillance data. Importantly, the US has a critically important program focused on WGS of MTBC for national surveillance. Since 2018, CDC has worked with the National TB Molecular Surveillance Center to perform WGS on all US cases with MTBC. New York State also contributes sequence data to this national surveillance program.

What do you wish the average person knew about TB?

That TB disease, although not a major issue in the US, is considered the world’s most deadly infectious disease, causing 1.2 million deaths annually and claiming 3,500 deaths every day. Also critically important is making sure that people with TB are on the most appropriate treatment regimens, and that they stay on the regimen for the full course so that subpopulations of their MTBC infection don’t become drug-resistant and much more difficult and costly to treat.

What do you think the future of this ancient disease is? What advances are being made? Where will we be in 10, 20 years?

I am very hopeful that newer molecular diagnostics that can provide drug-susceptibility testing on specimens (rather than isolates) will be available in many more settings and will lead to better and faster treatment of TB cases. I am also hopeful that newer drugs and drug regimens will continue to be available for TB cases with drug-resistant MTBC, and that these treatments will become available globally to all people with TB in need of these treatments. Maintaining testing and surveillance activities is critically important to combating TB disease and ensuring effective treatments.