Tuberculosis (TB) is a disease that typically affects the lungs caused by the bacterial species, Mycobacterium tuberculosis. Other potential areas of infection include brain, spine, and kidney. (CDC, 2016). TB continues to top the charts as one of the leading infectious diseases resulting in death. On a global scale, the WHO reported in 2019 about 10 million people fell ill and 1.4 million died from TB. To add to the severity, there is an increasing rise of multi-drug resistant TB (MDR-TB) strains. Such cases cannot be treated with preferential antimicrobial first-line drugs (namely isoniazid and rifampin) and instead must be treated with medications of greater toxicity to the patient and less effectiveness on treating the infection itself; referred to as second-line drugs (Tiberi, 2021; WHO, 2020; CDC, 2017). The WHO’s 2020 global TB Report claimed that there were an estimated 500,000 cases of MDR-TB in 2019, where only 186,722 cases were actually diagnosed. Only 57% of the diagnosed cases had a positive treatment outcome. In addition, further resistant strains referred to as extensively drug-resistant TB (XDR TB) and totally-drug resistant TB (TDR-TB) have been seen where most or if not all first and second line medications for TB are powerless (Tiberi, 2021; Velayati, 2013).
Interestingly, infection by M. tuberculosis does not necessarily lead to sickness. Such condition is referred to as latent TB infection (LTBI). At this stage, the body’s immune system is able to effectively keep the infection at bay and contain is pathogenic qualities. Much of the time people with LTBI are asymptomatic and thus aware they even have the condition to begin with. The CDC estimates that 13 million people in the US alone have LTBI. However, in the event that the infection surpasses the immune systems capabilities, the infection “reawakens” and TB disease results where without treatment can be fatal. This can occur either within week of initial infection or after years (CDC, 2020). Signs and symptoms of TB include: a cough lasting longer than 3 weeks, chest pain, sudden weightless, fever, chills, lack of appetite, night sweats, and coughing of blood or sputum (sputum refers to a phlegm like substance residing within in the lungs as a result of infection). Only TB can be spread through respiratory droplets to others individuals, LTBI cannot. Respiratory droplet secretion can result from coughing, sneezing, and speaking (and yes that includes singing aloud your favorite Taylor Swift song when it comes on the radio. No shame. Although, I do suppose those are more likely to be private concerts) (CDC, 2016). Individuals with weakened immune systems, chronic health conditions, babies/young children, those living with HIV/AIDS, in hospital settings, and populations in Asia and Africa are at higher risk for developing TB (American Lung Association, 2020).
Unfortunately, with the given COVID-19 pandemic, research and statistical projections are revealing how the it has negatively impacted TB cases globally; regarding its connection to decreased abilities and resources for both preventative and treatment care. In addition, it is predicted that TB incidences and mortality rates will increase by 5-15% in next five years. Such equates to an additional hundreds of thousands lives lost due to TB alone (McQuaid et al., 2021). The WHO’s 2021 Global TB Report points that TB related deaths have not increased in decades. Much of the projected increases are the direct result of a decrease in reported and diagnosed TB cases amidst the chaos the pandemic has had on health care systems globally (see figure below). Such poses a large threat in that the more cases that go unreported the larger the risk of spread; increasing cases, death toll, and drug-resistant strains prevalence. Specific factors that which has brought this decline include: service providers facing lack of necessary equipment and capacity, TB patients inability to access TB services due to fear of COVID-19 infection, stigma, lockdowns, reduction of facility operating hours, and reductions in the ability to pay for TB treatment expenses. In addition, countries of high TB prevalence have been having to reassign funds and personnel from national TB programs and reallocate towards COVID-19 relief measures (McQuaid et al., 2021). Furthermore, research regarding improvements for MDR-TB and treatment for LTBI have seen various levels of disruption, delaying future goals in reductions of TB outlined in the WHO’s END-TB Strategy back in 2015.
As of today, there are 10 drugs U.S. Food and Drug Administration (FDA) approved for treating TB disease. Treatment involves taking several of these medications for 6 to 9 months. The lengthy treatment period and combination therapy poses risks for individuals such that they may fail to complete their treatment. This increases the chance for resistant strains to develop. For typical drug sensitive strains (DS-TB), the first-line medications used are isoniazid, rifampin, ethambutol, and pyrazinamide. On the other hand, drug-resistant strains where treatment regimens are not 100% effective, can have negative implications on the body as mentioned earlier (CDC, 2016). Fortunately, despite the setbacks, there has still been progress regarding new TB treatment regimens. A scientific article from 2020 highlights such progress noting of the current 5 ongoing clinical trials and 17 observational studies looking into shorter treatment regimens for DS-TB and MDR-TB respectively. Specifically, for the DS-TB trials, evidence points to higher-dose rifampin as key to shorter regimens. In addition, animal models show promising insight in using medications such as Clofazimine and Linezolid (both of which are used for MDR-TB) as another way to shorten treatment time for DS-TB. In reference to improved MDR-TB treatments, the WHO recommended a new treatment in December of 2019 that is FDA approved consisting of bedaquiline, pretomanid, and linezolid for 6 – 9 months. Such was based of the trial NCT02333799 (Nix-TB) where participants included those with MDR-TB and XDR-TB. Although this is not necessarily a shorter regimen; these widen the scope of potential treatment options for this increasing drug resistant strain prevalence, especially given the onset of XDR-TB and TDR-TB strains. One trial in particular, NCT02754765 (endTB), is evaluating the safety and efficacy of five, new, completely oral, and shortened regimen for MDR-TB. An oral regimen is advantageous for its ability to be taken anywhere. Such results are expected sometime this year.
In summary, tuberculosis disease sees no boundaries and therefore a global problem. COVID-19 put a damper on the progress towards its eradication and as result, cases are back on the rise. Much of the severity lies in rise of drug resistant strains of TB, namely MDR-TB. However, with increased efforts towards prevention strategies and continuing to develop new medications, there is still potential future where TB’s grasp on mankind will be weakened substantially or even all together.
A MicroByte 