Tuberculosis (TB) is a deadly disease caused by Mycobacterium tuberculosis. A resurgence of TB was observed in the United States during 1985-1992; however, the annual TB rate has declined steadily. In 2013, the incidence rate of TB in the US was 3 cases in 100000 and a decrease of 4.2% was registered as compared to 2012. However, the foreign-born and racial minority populations are disproportionately affected by TB in the United States. The disparity in the TB incidence rates among US born persons, foreign born persons, whites and racial/ethnic minority populations makes it impossible to completely eliminate TB from the United States. Strategies for decreasing the import of TB into the US need to be implemented and international partnerships should be worked out to strengthen the control of TB in the countries with higher incidence rates. Continued collaborative measures are required globally to reduce the incidence of TB.
Human-immunodeficiency virus (HIV) contributes to the TB pandemic in the US because the chances of progression of TB infection to TB disease increase with the increase in immune-suppression in the HIV infection or AIDS. However, the number of TB cases with HIV infection has decreased in 2013 as compared to 2012. To address the issue of TB-HIV co-infection, new guidelines have been issued by the Centers for Disease Control and Prevention (CDC) recommending that all new patients of TB should be routinely tested for HIV. Awareness programs are being run by the CDC to educate the health care providers about HIV-TB co-infection (Centers for Disease Control and Prevention CDC, 2014).
The need of new anti-TB drugs was also emphasized as many HIV-infected people were found to have extensively drug-resistant TB. Several investigational studies are underway to discover wonder drugs for TB. Some of the drugs belonging to different chemical classes are TMC-207, OPC 67683, SQ109, PA824, moxifloxacin, and gatifloxacin. These drugs are being tested in humans and preliminary trials have been completed with moxifloxacin. These trials aimed at shortening the regimen for TB. Another drug, SQ109, is under clinical trials for TB and is expected to be a broad spectrum drug that can act against bacteria, fungi and parasites. This drug is claimed to evade resistance by targeting multiple pathways in the pathogen. This drug is being developed by the chemists of the University of Illinois and is said to target multiple pathogens ranging from yeast to malaria.
Drug resistance is major public health problem and often results from the mutation of the target protein (to which the drug binds) of the pathogen. Hence, to decrease the probability of drug resistance, the drug molecules may be designed such that they have multiple targets (instead of only one). The development of SQ109 is based on the above hypothesis and it is expected to be a multifunctional drug. Originally, SQ109 was known to block a protein involved in cell was synthesis of Mycobacterim tuberculosis. However, when it was tested against other bacteria and fungi, it showed promising results and research is underway to identify other targets of this molecule.
Owing to its chemical structure, SQ109 is thought to bind with some enzymes and antiparasitic drug targets. It was found to block proteins involved in critical functions in bacteria, fungi and parasites, but not humans. Studies involving the mechanism of action of SQ109 concluded that this molecule inhibited two enzymes involved in energy generation as well as it made the cell membrane permeable.
Scientists are keen to synthesize other chemical analogs of SQ109, so that a library of molecules may be generated for testing against TB and other parasitic infections. The newly synthesized molecules are expected to be more effective and/or less toxic. One of the synthesized molecules was found to be five times more active than the parent molecule SQ109 against the TB bacilli. The efficiency of SQ109 is now being tested against other diseases viz. Chaga’s disease, leishmaniasis and sleeping sickness (University of Illinois at Urbana-Champaign, 2014).
In the era of drug resistance, the generation of multi-drug resistant superbugs is on the rise. Hence, the antibiotic development researchers should focus on the multiple-target drugs. The drugs like SQ109 may further be studied and its analogs may be designed to increase the effectiveness or address the resistance issues. Overall decline in TB will only be possible with improved case management, intensified outreach, testing of populations at high risk and discovery of new treatments & diagnostics for TB.
References
Centers for Disease Control and Prevention (CDC). (2014, March 21). Trends in Tuberculosis Incidence – United States, 2013. MMWR Weekly. Retrieved May 14, 2012 from http://www.cdc.gov/mmwr/preview/mmwrhtml/mm6311a2.htm
