|Chloroquine (CQ), a medication used to prevent and treat malaria by killing the malaria parasites living inside red blood cells, can make the TB bacteria Mycobacterium tuberculosis (Mtb) more susceptible to other antimalarial drugs / Photo by: Oxana Zaytseva via 123RF|
Chloroquine (CQ), a medication used to prevent and treat malaria by killing the malaria parasites living inside red blood cells, can make the TB bacteria Mycobacterium tuberculosis (Mtb) more susceptible to other antimalarial drugs. In turn, the drug can help fight drug-resistant tuberculosis. This is according to a study conducted by the Indian Institute of Science and the Tata Institute of Fundamental Research published by the interdisciplinary medical journal Science Translational Medicine.
Chloroquine, a Potential Drug for Drug-Resistant TB Patients
Authors Richa Mishra from the Department of Microbiology and Cell Biology of Bangalore-based Indian Institute of Science and their team found that CQ can provide a shorter and new therapy option for people with tuberculosis. Despite advances in science, medicine, and technology, TB is still one of the top 10 causes of death worldwide, according to the World Health Organization (WHO). In 2018, 10 million people were diagnosed with TB and 1.5 million died from the diseases, including the 251,000 among people with human immunodeficiency virus (HIV). Multidrug-resistant TB remains a health security threat and a public health crisis, the organization added.
Medical research platform Medical Xpress said that one of the reasons why TB still kills a million people every year is the manner of its treatment. It often requires a patient to take antibiotics for six months for a full recovery. It is a long period, making many patients prefer to stop taking their medicines, resulting in relapse or the TB bacteria ending up becoming more drug-resistant.
Why Fighting TB Is Difficult
The Indian researchers mentioned that fighting tuberculosis is difficult because the bacteria increase the level of acidity in the location where they are situated. As a result, it makes it challenging for the white blood cell macrophages to absorb them as well as for the antibacterial agents to work against the bacteria. The function of macrophages in the body is to get rid and destroy the unwanted particles in the body. It uses the process of phagocytosis, which means “eat cell.”
The recent study revealed that giving patients CQ tends to reduce the acidity level in the immune cells and around the tuberculosis bacteria. During their experiments, they use guinea pigs and mice. They added that giving patients with chloroquine reduced their TB treatment to possibly four months or shorter and there had been no adverse effects on the test subjects. They believe that it can be tested on humans too.
“Coadministration of chloroquine improved isoniazid treatment outcomes in both mouse and guinea pig models of Mtb infection,” their study reads. They concluded that their approach may be beneficial to patients infected with both TB and HIV. The American Lung Association even mentioned that people with weakened immune systems, particularly those with HIV or AIDS, and children below 5 years old are at greater risk for developing TB disease.
In an interview with the environment and science magazine Down to Earth, lead researcher Amit Singh explained that the TB bacteria that are tolerant to drugs is hiding in the macrophages. He added that the macrophages have slightly more acidic level pH and such acidity serves as the signal for the bacteria to start an adaptation program so that it can tolerate the oxidative stress of the drug. However, if the acidic pH will not be allowed in the macrophages, it could interfere with the adaptation of the bacteria and the anti TB drug will continue to be sensitive.
|The Indian researchers mentioned that fighting tuberculosis is difficult because the bacteria increase the level of acidity in the location where they are situated / Photo by: Katarzyna Białasiewicz via 123RF|
Is It Safe for TB Patients Without Malarial Infection?
When asked about the safety of administering the drug to patients without malarial infection, the lead researcher pointed out that CQ has a long history of safe usage on people. In their experiments, they also used only 10-20 fold lower compared to what is currently being used in treating malaria.
Based on the Global Health Observatory data repository of the WHO, countries with high estimated mortality rate of TB cases, excluding HIV, per 100,000 population in 2017 are as follows: India (31.0), Kenya (50.0), Democratic Republic of the Congo (60.0), Nigeria (63.0), Central African Republic (68.0), United Republic of Tanzania (47.0), Angola (67.0), Namibia (30.0), South Africa (39.0), Mozambique (73.0), Madagascar (52.0), Zambia (30.0), Kenya (50.0), Somalia (69.0|), Cameroon (320.0), Indonesia (40.0), Myanmar (51.0), Bangladesh (36.0), and Papua New Guinea (53.0).
On the other hand, countries with low estimated mortality rate of TB cases per 100,000 population in the same year are as follows: Canada (0.3), United States (0.2), Spain (0.5), Norway (0.2), Sweden (0.3), Finland (0.5), Belarus (0.8), Germany (0.4), France (0.6), United Kingdom (0.5), Ireland (0.5), Czech (0.4), Turkey (0.5), Kazakhstan (0.9), Syria (0.3), Israel (0.2), Egypt (0.4), Jordan (0.3), and Oman (0.5), among others.
Management consulting organization Stratagem Market Insights also said that the key players in the global chloroquine market will be ARTECEF, Fishman Chemical, and the Uniprix pharmacy company.
Curing and treating drug-resistant tuberculosis is complicated. The in-vivo research conducted by Mishra and the team may help combat the disease from first-line anti-TB drug-resistant to multidrug-resistant TB. If their results will be translated into positive results for human subjects, it will be a significant milestone not only in India but the world as a whole.