Reasons why Tuberculosis has not been eradicated from the world by now

Developing new effective methods of diagnosis for early and accurate case detection, rapid commencement and adherence to effective treatment regimens and building the support framework for the patient and the community would be the key to fulfilling our goal of EndTB.

We, humans, as a species are driven by our curiosity, our irresistible urge to search out the unknown, explain the unexplainable. This nature is deeply rooted in our bones and carries us to where we are today. We, as a scientific community, have advanced tremendously especially in last hundred years. We have split the atom, put the people on the moon, sent our spacecrafts deep into the cosmos, cracked the code of DNA, synthesize the gene, found a cure for disease like HIV and eradicated the disease like Small Pox. But there is a disease that always eludes us and that disease is Tuberculosis (TB).

It was 24th March, 1882, when Dr, Robert Koch announced that he has identified the organism that causes TB. Mycobacterium tuberculosis is a nasty cylindrical shaped bacterium, responsible for causing one of the oldest known infections to the mankind. This discovery opened the gate to understanding this disease and its cure. In 1921, BCG vaccine developed by Albert Calmette and Camille Guerin, first used in humans. Another breakthrough came when in 1943 Selman Waksman, Elizabeth Bugie and Albert Schatz developed streptomycin. Today Isoniazid (1951), Pyrazinamide (1952), Ethambutol (1961) and Rifampin (1966), these 4 drugs regimen is still the most commonly used in the treatment of TB.1

Despite 100 years of vaccination and 80 years of chemotherapy, TB continues to be among us. According to World Health Organization (WHO), tuberculosis is leading cause of mortality due to an infection exceeding HIV. There are 10.4 million new cases and 1.8 million deaths from TB each year.2

So, what are the factors that makes TB such an enigma?

1. Infection and Disease: TB can persist in a human body in latent state. So, all the people who got infected, do not get the disease. Only about 10% infected people progress to active TB disease in their lifetime.

2. Diagnosis:DiagnosingapatientwithTBisanotherhorrorstory.Ononeside,there is traditional Ziehl- Neelsen staining method which we use in our most peripheral centers in India. On the other side, we have newer methods based on nucleic acid detection like GeneXpert and TrueNat. The problem is TB affects multiple organs in the body, we get multiple different kind of samples, from sputum, pleural fluid and bones to urine and genital fluid. So, the diagnostic yield of these testing methods changes depending on the sample site.

3. Grueling Treatment and Rampant Resistance: Although we have chemotherapy for TB for almost 80 years now, the real picture is far from promising. The widespread resistant to multiple drugs makes this a perfect nightmare. Treatment usually requires multiple drugs for a very long time. For example, in drug- sensitive TB (DS-TB), the treatment regimen consists of 4 drugs for 6 months and in Multiple drug- resistant TB (MDR-TB), the treatment regimen consistent of 6-7 drugs for 11-12 months. Now these are a lot of drugs for a long time for an infectious disease. There are grueling toxicities to these drugs. The treatment regimen requires periodic monitoring and modification. Sometimes we have to stop and rechallenge the drug in the patient. In India, not every doctor handling cases of TB on daily basis, is trained in managing treatment toxicity.3 This is one of the reasons for discontinuation of the treatment by the patient. No clear definition of the cure adds pain to management to this disease.

4. Disruption of Social and Financial Structure: There is still stigma associated with TB in India. It is still considered as a disease of the poor. This behavior withdraws the social support of the patient. Then there is loss of work-days and even unemployment. Overall, TB puts pressure on patient’s financial, occupational and social fabric

5. DevelopedvsDevelopingCountries:IthasbeenaundeniablefactthatTBismore common in Low- and Middle-Income countries (LMIC), where many people live below the poverty line. People in LMIC are more likely to live in overcrowded and poorly ventilated houses. They are more likely to suffer from micronutrient deficiencies, malnutrition and other diseases like HIV, DM, COPD, Silicosis. The healthcare system in these countries is overburdened with limited access. All these factors make a favorable environment for tuberculosis.

All above mentioned factors with an overburdened health system makes Tb a nightmare for a health professional in India. What we need is a community centered approach rather than a patient centered approach. Developing new effective methods of diagnosis for early and accurate case detection, rapid commencement and adherence to effective treatment regimens and building the support framework for the patient and the community would be the key to fulfilling our goal of EndTB.

References:

1. CDC.gov.in/tb 2. Bloom BR, Atun R, Cohen T, Dye C, Fraser H, Gomez GB, Knight G, Murray M, Nardell E, Rubin E, Salomon J, Vassall A, Volchenkov G, White R, Wilson D, Yadav P. Tuberculosis. In: Holmes KK, Bertozzi S, Bloom BR, Jha P, editors. Major Infectious

Diseases. 3rd ed. Washington (DC): The International Bank for Reconstruction and Development / The World Bank; 2017 Nov 3. Chapter 11. PMID: 30212088. 3. Sandhu GK, Tuberculosis: Current Situation and Overview of its Control Programs in India; J Glob Infect Dis. 2011 Apr-Jun; 3(2): 143–150. PMID: 21731301