The Crisis of Increasing Drug-Resistance in the Tuberculosis Pandemic

Drug-Resistant TB

About every 22 seconds, someone dies from Tuberculosis. As the deadliest bacterial infection worldwide, Tuberculosis causes or contributes to 1-1.5 million deaths per year, recently surpassing HIV as the deadliest single infectious agent. Around ten million people become sick with Tuberculosis each year, with about ¼ of the world’s population having a TB infection. While Tuberculosis is a treatable and preventable disease, most infections are latent and undiagnosed, further exacerbating the challenges of this pandemic.

By some estimates, the number of deaths per year cited above may be notably low for several reasons: (1) many cases go undiagnosed; (2) TB deaths often occur in areas that lack medical facilities and therefore remain unreported; (3) active TB infections often coincide with HIV infections, diabetes, or other factors that cause the patient to be immunocompromised, so Tuberculosis is not always recognized as a primary or contributing factor.
Over five percent of infections involve drug-resistant strains. While overall TB infections have been decreasing in recent years, the rate of drug-resistant strains has increased. From 2018 to 2019, the rate of drug-resistant TB infections increased by approximately 10%. Despite the ongoing development of new TB treatments, the growing rate of drug-resistance remains one of the greatest current health crises, and it is likely to continue getting worse in the coming years. Rapid and accurate diagnosis of antibiotic resistance is critical, not only to the health of each patient but also the global response to this pandemic.

Types of Antibiotic-Resistant Tuberculosis

Mono-resistance: resistance to a single first-line anti-TB drug.

Poly-resistance: resistance to multiple first-line anti-TB drugs, other than both isoniazid and rifampicin.

Multidrug resistance (MDR): resistance to at least both isoniazid and rifampicin, the most effective first-line antibiotics currently approved. Survival rates for multi-drug resistant TB drops to around 50%.

Extensive drug resistance (XDR): resistance to any fluoroquinolone, plus at least one second-line injectable drugs (capreomycin, kanamycin, or amikacin), in addition to isoniazid and rifampicin resistance. Survival rates for XDR TB fall below 30%.

Rifampicin resistance (RR): any resistance to rifampicin, including mono-resistance, poly-resistance, MDR, or XDR, as detected by phenotypic or genotypic methods, such as molecular assays.

Drug resistance is on the rise for several reasons, including improper or incomplete antibiotic usage and delayed diagnosis.

The Need for Accurate Diagnosis

Tuberculosis presents several diagnostic challenges. Tuberculosis patients often encounter long diagnostic delays, both in the detection of TB and the identification of drug resistance, increasing the severity, mortality, and transmission.
As a respiratory infection, Tuberculosis has overlapping symptomologies with several pathogens. In its early stages, Tuberculosis typically presents with non-specific, non-incapacitating symptoms that may be easily attributed to other pathogens. The index of suspicion is often low enough that care providers forgo testing, especially in areas where TB is not endemic. Latent and early-stage active infections frequently go undiagnosed, allowing carriers to unknowingly infect others. As noted above, almost ¼ of the world’s population has a TB infection.

Diagnostic delays are not the only impediments to the treatment of drug-resistant strains. The second-line drugs (including levofloxacin, moxifloxacin, bedaquiline, delamanid, linezolid, and pretomanid) can be difficult to source in certain regions, in addition to having higher toxicity and longer treatment courses—more than two years in some cases. Because of the increase in drug-resistant Tuberculosis infections and the unique treatments required, the ability to quickly identify drug resistance genotypically is critical for proper treatment. Accurate diagnosis is essential for the effective treatment of this persistent—yet treatable—pathogen.

Microbiologics Controls

Microbiologics simplifies QC for MTB/RIF assays with IVD controls. The Rifampicin-Resistant Mycobacterium tuberculosis Positive Control Panel and Rifampicin-Resistant Mycobacterium tuberculosis Negative Control are designed to make quality control testing of molecular assays fast, reliable, and affordable.

Sources

Nathavitharana, Ruvandhi R. “Stamping out Tuberculosis: The Importance of Diagnostic Innovation and Effective Implementation.” Annals of the American Thoracic Society. May 2019. https://www.atsjournals.org/doi/full/10.1513/AnnalsATS.201902-173ED.


“Tuberculosis.” The World Health Organization. https://www.who.int/health-topics/tuberculosis.


“Tuberculosis (TB).” Center for Disease Control. https://www.cdc.gov/tb/default.htm.

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