Scientists Simplifying Science

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Last week March 24th was observed as World Tuberculosis day. The World Health Organisation (WHO) has been marking this day since 1997, to not only generate awareness and to mobilise activity by government and public health organisations, but also inspire efforts among researchers and local communities towards ending tuberculosis/TB – billed as one of the top infectious diseases in the world. With anti-TB drugs available since 1948, it is hard to believe that this disease has proven to be a formidable nemesis with alarmingly high mortality rates in the modern world.

Tuberculosis is caused by Mycobacterium tuberculosis, a bacteria characterised by the special architecture of its mycolic acid-containing cell wall. On inhalation by a susceptible human, the bacteria travel to the lungs where it is ingested by the immune cells called macrophages as a normal protocol of the human body’s defence mechanism against foreign substances. This bacterium is capable of manipulating the human host’s cellular immune response to its own advantage and persist in the form of calcified granuloma/lesion bodies containing macrophage ingested bacteria surrounded and restricted at the site by macrophages and T cells. The bacteria can remain dormant in the lungs for years or decades and in 5-10% of the infected individuals undergo TB-reactivation triggered by a number of pre-disposing factors, mainly lowered immunity. Apart from other biological factors, the vulnerable group is characterised by individuals with organ transplants, kidney dialysis, HIV-infection, etc. Socio-economic factors like poverty, drug abuse, homelessness and depression also form characteristics of the at risk population.

Said to have originated in the horn of Africa and earlier known as ‘consumption’, TB has come a long way to evolving and diverging along with the human race, to becoming a world pandemic claiming ~1.4 million victims in 2014.

Figure: Lienhardt C. et al, Nat Rev Microbiol, 2012;10(6):407-416

The WHO lists countries with high incidence of TB cases as High Burden Countries (HBC)s, which are further classified as

1) TB, when the infection can be completely cured by a 6 month treatment which consists of a 6 month long course involving antimicrobial drugs like rifampicin, isoniazid, pyrazinamide, ethambutol and streptomycin

2) MDR-TB (multiple-drug resistant TB), where the infection is resistant to at least two of the most powerful anti-TB drugs – rifampicin and isoniazid. Resistance to yet more drugs is a dangerous manifestation and is termed as XDR-TB/’extensive resistance to anti-TB drugs’, which is sadly on the rise. The causes for a treatable resistance to manifest into a drug resistance is mainly due to discontinuous treatment due to irregular medical supplies, ignorance and poverty. This is currently an area where action is required, esp. regarding diagnosis in children.

3) TB/HIV, where HIV co-infection complicates an active or latent TB condition. Neither infections make an individual prone to the other, but once co-infected there is a rapid acceleration in the progression of both diseases, hence doubling the fatality rate. This condition requires treatment with anti-TB drugs and anti- retroviral therapy

Given that the bacterial spread is mainly air-borne from human to human (cough, sneeze etc.), and human migration becomes more common with easier travelling options and accessibility, TB is no longer a tropical disease. In fact, the WHO puts the number of infected individuals (latent carriers included) as 2 billion or 1/3 of the world population. Yet, there seems to be a higher concentration of TB cases within certain countries – 80% of TB cases are concentrated in just 22 countries, and India figures as one of them (http://stoptb.org/countries/tbdata.asp).

TB in India

It is not known why some individuals are resistant to TB, however being malnourished/immunocompromised does pose to be a risk factor. Much has been written about the causes of TB and why it is prevalent especially among the poor and the undernourished. But in India, it is not uncommon to hear of TB occurrences in unexpected or non-impoverished circumstances. Coupled with the rising number of MDR-TB and XDR-TB, this presents an alarming situation and could be a great setback to a developing economy.

In an endeavour to control TB by 2030 (2050 for India), the WHO has published a detailed country-wise TB profile for helping one understand the magnitude of the problem as well as the steps being taken to control TB by the global funding bodies as well as local government expenditure. The report for India suggests that there is more streamlined reporting of TB occurrences now due to mandatory national web-based reporting since 2012. The recent list drawn up for 2016-2022 is a matter of concern points out that India along with Indonesia and China accounts for 43% of global cases (23% individually). where one sees a drop in domestic funding in WHO 2015 TB reports.

Source: http://www.who.int/tb

India is a signatory to the World Health Assembly which endorses the ‘End TB strategy‘ and aims for 50 % reduction in incidence and 75% reduction in TB related deaths by 2025, the ultimate goal being complete eradication of TB. Due to its alignment with poverty- a socio-economical problem, TB proves somewhat complicated to understand and hence difficult to address. Prof Soumya Swaminathan, Director General of Indian Council of Medical Research has been spearheading a movement to bring about awareness about India’s struggle with paediatric and MDR-TB and has previously stated that rising numbers of TB cases are a blot on India’s growth story with the burden disproportionately borne by the poor. Hence elimination of TB does boil down to a great extent, on eradication of poverty.

Meanwhile with the impeding launch of the new drug Bedaquiline, the intense awareness being created by media and the support system provided by various community lead programs show some promise. We plan to shed more light on this issue in the future and hence stay tuned to hear more about Prof Swaminathan’s work and opinions on the current policies regarding TB drugs and whether a TB-free India an achievable target. Do not forget to follow us on Twitter for updates about the tweetchat,

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About the Author: Kartika Shetty, Ph.D. is a biophysicist specialising in protein-protein and protein-ligand interactions. Her recent focus is drug discovery and development for targeting lymphomas, along with her fellow researchers at the Institute of Cancer Research, London. Kartika is a member/editor of the ClubSciWri team and is an avid science quiz enthusiast. An alumnus of the Indian Institute of Science, she has been involved in participating and hosting in quiz events in and around the IISc campus (for reasons unknown, now is restricted to pub quizzes, since moving to the UK ! ).

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