In 2020, the World Health Organization (WHO) estimated the global presence (prevalence) of tuberculosis (TB) at 10 million cases. A total of 1.5 million people died from TB in 2020. Newly diagnosed cases (incidence) decreased to 5.8 million in 2020 from 7.1 million in 2019. (This decrease occurred during the COVID-19 pandemic; it is thought that the pandemic lockdown resulted in decreased TB transmission rates, but delays in case notification due to pandemic disruptions remain under investigation.) "TB was second only to COVID-19 as a leading cause of death from a single infectious agent"1 (WHO, 2021, p. 28). Although new case numbers appear to be decreasing, the prevalence of TB disease remains high.
Tuberculosis, present in all countries, is curable and preventable according to the WHO. However, the emergence of drug-resistant tuberculosis strains in the recent past has sustained and even propelled the current TB public health crisis. As of the most recent WHO Global Tuberculosis Report 2021, India, Indonesia, and the Philippines make up >43% of cases of TB. (Europe and the Russian Federation, previously on the list of high TB burden countries, have met with success driven by a decline in new case incidence.) The burden of resistant TB strains will be covered later in this course.
The World Health Organization classifies drug-resistant TB into the following five categories:
1. Isoniazid-resistant TB
2. RR-TB (resistant to rifampin)
3. MDR-TB (multi-drug resistant TB; resistant to isoniazid and rifampin)
4. Pre-XDR-TB (pre-extensively drug-resistant TB; resistance to rifampicin plus any fluoroquinolone)
5. XDR-TB (extensively drug-resistant TB; resistant to rifampicin, plus any fluoroquinolone, plus at least one of the drugs bedaquiline or linezolid)
Note: The terminology, TDR-TB (totally drug-resistant TB) nomenclature is not well-defined and not currently recognized by WHO.
Approximately 3-4% of newly diagnosed cases are MDR-TB or RR-TB, while those previously treated have remained at 18-21%. In former Soviet Union countries, this percentage of drug resistance among previously treated is >50%.
XDR-TB has been reported by 123 WHO countries. Approximately 6.2% of MDR-TB cases have XDR-TB. A small proportion of cases falls into this category, mainly due to a lack of diagnostic capacity in low and lower-middle-income countries.
History of resistance:
- In 1992, an outbreak of MDR-TB in New York City was reported. After pubic health intervention and control, the overall incidence of TB began to subside in the United States (US). CDC data showed a consistent decline in both drug-susceptible and drug-resistant strains. However, reports for the US indicated a gradual increase in cases of MDR-TB in foreign-born patients.
- In 2010, the appearance of four cases of XDR-TB in the US caused concern, as the cases demonstrated resistance to first-line drugs and many of the second-line drugs (fluoroquinolones, capreomycin, amikacin, and kanamycin as reported by CDC). This number increased to 74 cumulative cases from 1993-2006. Note that XDR-TB is rare in the US, with only 1 case reported in 2020 (CDC).
- By 2011, India reported cases that were completely resistant to all available anti-tuberculosis drugs. Patient isolates were phenotypically resistant to the available first- and second-line anti-TB drugs, defined by their susceptibility tests (12-drug panel). Methods of diagnosis and susceptibility testing were inconsistent. In addition, many patients were co-infected with HIV.
The map to the right, presented with permission from the WHO, shows the estimated worldwide TB incidence in 2020.
In this course, the presentation of a brief history of tuberculosis and its developing resistance to anti-tuberculosis drugs is followed by cases and TB-resistance challenges from regions of India, Italy, and the US-Mexican border. The pathogenesis of TB disease in humans is diagrammed and a review of diagnostic laboratory methods, susceptibility testing, and methods of control are explored.