Ph-Ch1: TB & TB Epidemiology

Tuberculosis

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Figure: Causative agent for Tuberculosis is Bacillus: Mycobacterium tuberculosis (M.tb)

Tuberculosis (TB) is a communicable disease that is a major cause of ill health.
TB is caused by the bacillus Mycobacterium tuberculosis (M.tb)
TB disease typically affects the lungs (pulmonary TB) (80%) but can also affect other parts of the body (extra pulmonary TB) (20%)
It spreads when people who are sick with TB expel bacteria into the air (for example by coughing, sneezing, shouting or singing)
It is one of the top 10 causes of death worldwide and the leading cause of death from a single infectious agent

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Global Burden of TB

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Globally, an estimated 11 million people fell ill with TB (incidence) in 2021.
Historically, it has been the top infectious disease killer. In 2021, there were an estimated 1.4 million TB deaths and an additional 187 000 deaths among HIV-positive people.
Three countries accounted for 42% of global cases in 2021: India (26%), the Russian Federation (8.5%) and Pakistan (7.9%).

Figure: Estimated TB incidence in 2021, for countries with at least 100 000 incident cases; Source: Global TB Report, 2022.

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Global tuberculosis report 2022.

TB is one of the top burdensome infectious diseases in India. It is estimated that, around 1/4th (26%) of the world's TB cases are in India, translating to about 30 Lakhs new TB cases emerging each year (TB incidence). Against this estimated incidence the National TB Elimination program reported around 19 lakh new and relapse cases in the year 2021.

An estimated 5 Lakhs deaths occur due to TB each year in the country, translating to about 1 case of TB death every one-two minutes. Compared to this, there are only about 60 thousand deaths due to HIV and about 77 deaths due to Malaria each year.

TB diagnosis and treatment services although provided free of cost in the public sector, the cost of accessing these services and related loss of wages drive the affected people with poverty (catastrophic costs). TB also has a huge impact on the world's and the country's economy because of loss of workdays (100 million workdays per year).

Assessment

Question	Answer 1	Answer 2	Answer 3	Answer 4	Correct answer	Correct explanation	Page id	Part of Pre-test	Part of Post-test
What is the estimated number of incident TB cases that emerge each year in India?	35 Lakh cases	26 Lakh Cases	26% of the Global Burden	19 Lakh Cases	2	The estimated number of new and relapse (incident) cases in India that emerge each year is about 26 Lakh		Yes	Yes
How many cases of deaths are estimated to be caused by TB in India	Approximately One death every 2-3 minutes	Approximately 5 Lakh deaths	60 Thousand deaths each year	1 and 2	4	In India it is estimated that there is around one death caused due to TB every one to two minutes, translating to about 5Lakh deaths each year in India		Yes	Yes

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TB Causative organism

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Figure Mycobacterium tuberculosis

TB is caused due to the infection by a bacterium called Mycobacterium tuberculosis.

Figure: Extra-Pulmonary Tuberculosis

It often affects the lungs, and in such cases it is called Pulmonary Tuberculosis. But, it can affect almost any part of the body (except the hair and the nails), in which it is known as Extra-Pulmonary Tuberculosis.

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Technical and Operational Guidelines for TB Control in India 2016

Mode of TB Transmission

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Tuberculosis is transmitted mainly through the air via droplet nuclei generated when a TB patient coughs or sneezes.

It is estimated that every sputum smear-positive patient spreads the infection to 10 – 15 persons annually, if untreated..

Figure: Transmission of TB bacteria through air via droplet

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Pathogenesis of TB

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Tuberculosis (TB) is an infectious, chronic, granulomatous disease caused by Mycobacterium tuberculosis. It usually involves the lungs but may affect any organ or tissue in the body.

The pathogenesis of TB in a previously unexposed immunocompetent individual is centred on the development of cell-mediated immunity. This confers resistance to the organism and results in the development of tissue hypersensitivity to tubercular antigens.

The pathologic features of TB, such as caseating granulomas and cavitation, result from the destructive tissue hypersensitivity that is part and parcel of the host immune response.

The sequence of events from inhalation of the infectious droplets to the containment of the primary focus of infection is as follows:

Figure: Pathogenesis of Tuberculosis

In many individuals, the stage 5 response (from above) halts the infection before significant tissue destruction or illness occur (Latent TB Infection). In other individuals with immune deficits due to age or immunosuppression, the infection progresses to stage 5, and the ongoing immune response results in caseation necrosis (Active TB Disease). The figure above provides more details on the progression of TB disease.

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TB Infection

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TB Infection (or previously known as Latent TB infection) is a stage in between uninfected and having active TB. In this stage the person has no symptoms and can only be identified using laboratory tests.
The vast majority of infected people may never develop TB disease. However, to achieve TB elimination, it is important to treat TB infection in people at risk of developing active TB disease.
It is a state of persistent immune response to stimulation by Mycobacterium tuberculosis antigens with no evidence of clinically manifested active TB.
There is no single acceptable/reliable test for direct identification of Mycobacterium tuberculosis infection in humans. Tuberculin Skin Test (TST) and Interferon-gamma release assay (IGRA) are commonly used tests for identifying TB infection.

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Progression to TB Disease

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After exposure to infective droplets containing M.TB, only a small proportion gets infected and further progresses to active TB disease.

Majority of those that get infected persist in a stage of clinical latency known as TB infection (previously known as Latent TB infection). They do not have TB disease and do not show any symptoms of TB and no evidence of any TB related changes on chest X-ray.
A small proportion of those with prior infection may progress to active TB disease due to various environmental/ agent/ host factors.

Figure: Flow chart for TB disease progression

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Understanding delayed T-Cell Priming, Lung Recruitment, and AirwayLuminal T-Cell Responses in Host defence against Pulmonary Tuberculosis

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TB Infection Vs Active TB Disease

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TB Infection	Active TB Disease
May not have any signs & symptoms	Has sign and symptoms such as cough for more than two weeks, fever, weight loss and blood in sputum
Has dormant, contained bacteria is the body	Has active, multiplying bacteria in the body
Doesn't spread TB bacteria to others	May spread TB bacteria to others
Chest X-ray usually normal	Lesion in Chest X- ray (usually)
May advance to active TB. It is estimated that the lifetime risk of an individual with TB infection for progression to active TB is 5–10%.	Needs treatment for TB disease

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Technical and Operational Guidelines for TB Control in India 2016

Determinants of TB Disease

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Determinants are any characteristics that affect the health of a patient.

Biological Determinants	Behavioral Determinants	Socio Economic Determinants	Occupational Determinants
People living with HIV(PL HIV) History of contact with a case of TB People with underlying medical conditions like Diabetes, Kidney disease, Cancer etc. Existing lung disease Old age	Use of tobacco and alcohol Malnutrition	Person in contact with TB infected patient Person living in areas with poor ventilation & over crowding Poverty and Malnutrition Homeless	Mining work Quarry work(Silicosis) Construction work Migrant worker Daily wagers

Vulnerable Population for Tuberculosis

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TB can affect anyone but it is more prevalent in some communities which are vulnerable to TB disease due to various factors which are mentioned below:

Increased exposure of TB due to where they live or work

prisoners
slum dwellers
miners
hospital visitors
healthcare workers

Limited access to Quality TB services

Migrant workers
Women in settings with gender disparity,
Children
Physically challenged
Transgender population
Tribal and population living in hard to reach areas
Refugees or internally displaced people
Illegal miners and undocumented migrants

Increased risk because of biological or behavioural factors that compromise immune functions in people who:

People who live with HIV
have diabetes or silicosis
undergo immunosuppressive therapy
are undernourished
use tobacco
suffer from alcohol use disorders.
inject drugs

Prevention of TB

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As TB is an airborne infection, TB bacteria are released into the air when someone with infectious TB coughs or sneezes. The risk of infection can be reduced by taking simple precautions:

Figure: Measures for control and prevention of tuberculosis

TB Preventive Treatment(TPT) also has a very important role in prevention of TB. Presently, household contacts of sputum-positive TB patients are given TPT upon confirmation of TB infection and ruling our active Tuberculosis.

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Technical and Operational Guidelines for TB Control in India 2016

Chemotherapy and its implication in TB control

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Chemotherapy for TB is the use of an anti-TB drugs to kill, or prevent the replication of, TB mycobacteria in the patient’s body. Effective anti-TB chemotherapy renders the patient non-contagious and cures the patient, thereby interrupting the chain of transmission. Mortality rates of TB range from 50-80% in untreated smear-positive individuals and drop to lower than 5% under chemotherapy.

Most of the bacteria are killed during the first 8 weeks of treatment; however, there are persistent organisms that require longer treatment. TB disease must be treated for at least 6 months and in some cases even longer. The use of multi-drug therapy reduces the incidence of drug-resistant cases and increases the overall effectiveness of treatment.

If treatment is interrupted, any surviving bacteria may cause the patient to later become ill and infectious again, potentially with drug-resistant disease.

How infectious are tuberculosis patients under chemotherapy?

Under effective chemotherapy, there is a substantial decline in infectiousness in two weeks time, and may not be a major source of risk to any contacts. This decline is indicated by the rapid fall in the number of viable organisms in the sputum, and reduced frequency of coughing.

Types of Chemotherapy in TB

Preventive Chemotherapy: Regimen for healthy but TB infected persons with a high risk of developing TB, in order to prevent them from developing TB.
Standard Chemotherapy: Two-phased chemotherapy for an average of 6-8 months based on the combination of at least four major drugs (HRZE) given for 2 months during the initial intensive phase of treatment and followed by a combination of at least 2 drugs given for at least 4 months during the continuation phase of treatment.
Chemotherapy for Drug-resistant TB: Two-phased chemotherapy varying from 9 - 24 months in patients having demonstrated resistance to drugs used in standard chemotherapy. The regimen varies with the drug to which the resistance is present, however, each regimen contains a mix of second-line anti-TB drugs including injectables.

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Assessment

Question	Answer 1	Answer 2	Answer 3	Answer 4	Correct answer	Correct explanation	Page id	Part of Pre-test	Part of Post-test
Which type of chemotherapy regimen of anti-TB drugs is used for infected persons with a high risk of developing TB who have no signs or symptoms of active disease, in order to prevent them from developing TB?	First-line anti-TB drugs	Preventive Chemotherapy	Standard Chemotherapy	Chemotherapy for Drug Resistant-TB	2	Preventive chemotherapy regimen of anti-TB drugs is used for infected persons with a high risk of developing TB who have no signs or symptoms of active disease, in order to prevent them from developing TB.		Yes	Yes

TB Notification rate

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TB notification rate is the number of TB cases notified over a specified time period for a specified population, usually per lakh. It indicates how many cases have been diagnosed and informed to the National TB Elimination Program.

It is mostly calculated annually, and the calculation formula is as follows:

Figure: Deriving the Annualized TB Case Notification Rate

The National TB Elimination Program calculates TB notification rates based on TB cases notified using the digital surveillance system called Nikshay. Each state/district is provided with an annual target for TB case notification, the progress of which is measured periodically to understand efforts taken for the detection of TB cases.

Example

If the number of TB patients diagnosed in District X one year is 1000, and the mid-year population of District X is 10,00,000, then the annualized TB case notification rate is calculated as follows:

100 cases/100 000/year

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