A PROJECT ON TUBERCULOSIS

DIVYA KUMAR
19UPH038

A DISSRETATION REPORT
SUBMITTED IN PARTIAL FULFILMENT OF THE REQUIREMENTS
FOR THE DEGREE OF BACHELOR OF PHARMACY

SCHOOL OF PHARMACY & EMERGING SCIENCES,

BADDI UNIVERSITY OF EMERGING SCIENCES & TECHNOLOGY

2023
 DECLARATION

I Divya kumar hereby certify that I had been personally carried out the work depicted in
the thesis entitled, “A Review on Tuberculosis”, under the Supervision of Ms. Alka
Sharma (Assistant professor), during the academic session 2022 -2023. No part of the
thesis has been submitted for the award of any other degree or diploma prior to this date.

Date:
Place:

Signature

Divya kumar
19uph038

2
 CERTIFICATE
This is to certify that the work reported in the thesis entitled “A PROJECT ON
TABLET MANUFACTURING AND ITS TYPE”, has been carried out by
GULSHAN KUMAR under the supervision and guidance of Ms. Sheetal Sharma
(Assistant Professor) at School of Pharmacy and Emerging Sciences, Baddi
University of Emerging Sciences and Technology, Baddi, Solan, H.P., India, during
the academic session 2022 - 2023.

____________________ ___________________ ___________________

Signature of Supervisor Signature of HoD-SPES Signature of Dean-SPES
Ms. Sheetal Sharma Mr. Bhartendu Sharma Prof. (Dr.) Ravinesh Mishra
Assistant Professor HoD-SPES Dean-SPES

DATE: PLACE:
Baddi

3
 AKNOLDGEMENT

As begin to reflect onto the magnitude of this project, I am reminded of kindness, support and
affection to me by people who I am overwhelmed.

It is my privilege to thank Prof. (Dr.) Ravinesh Mishra (DEAN-SPES) and Mr.

Bhartendu Sharma (HoD-SPES) Baddi University of emerging science and technology,
for making available the requisite facilities for project.

Primarily I would thank God for being able to complete this project with success, and then I
would like to thank my project guide Ms. Alka Sharma (Assistant Professor), whose
valuable guidance has been the ones that helped me patch this project and make it full proof
success this suggestions and her instructions has served as the major contribution towards
the completion of the project, then I would like to thank my parents and friends who have
helped me with their valuable suggestions and guidance has been helpful in various phases
of the completion of the project, last but not the least I would thank my classmates who have
helped me a lot.

DIVYA KUMAR
19UPH038

TABLE OF CONTENT

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S.NO. CONTENT PAGE NO.

2 Introduction 7

3 Etiology 8

4 Epidemiology 8-9

5 Symptoms 9-12

6 Drug-resistance TB 12-13

7 How TB Spreads 13-14

8 Risk factor 14-15

9 Pathophysiology 15-17

10 Histopathology 17

11 History and Physical 17

12 Evaluation 17-20

13 Treatment / Management 20-23

14 Differential Diagnosis 23

15 Toxicity and Adverse Effect Management 23-24

16 Prognosis 24

17 Complication 24

18 Pearls and Other Issues 25

19 Enhancing Healthcare Team Outcomes 25-26

20 Conclusion 26-27

21 Reference 27-30

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1. Abstract
Tuberculosis (TB), which is caused by bacteria of the Mycobacterium tuberculosis complex,
is one of the oldest diseases known to affect humans and a major cause of death worldwide.
Tuberculosis continues to be a huge peril disease against the human population and
according to WHO, tuberculosis is a major killer of the human population after HIV/AIDS.
Tuberculosis is highly prevalent among the low socioeconomic section of the population and
marginalized sections of the community. In India, National strategic plan (2017-2025) has a
national goal of elimination of tuberculosis by 2025. It requires increased awareness and
understanding of Tuberculosis. In this review article history, taxonomy, epidemiology,
histology, immunology, pathogenesis and clinical features of both pulmonary tuberculosis
(PTB) and extra-pulmonary tuberculosis (EPTB) has been discussed. A great length of
detailed information regarding diagnostic modalities has been explained along with
diagnostic algorithm for PTB and EPTB. Treatment regimen for sensitive, drug resistant and
extensive drug resistant tuberculosis has been summarized along with newer drugs
recommended for multi drug resistant tuberculosis. This review article has been written after
extensive literature study in view of better understanding and to increase awareness
regarding tuberculosis, as a sincere effort that will help eliminate tuberculosis off the face of
the earth in near future.

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2. Introduction
Tuberculosis (TB) is an ancient human disease caused by Mycobacterium tuberculosis
which mainly affects the lungs, making pulmonary disease the most common presentation
(K Zaman, 2010) [1]. However, TB is a multi-systemic disease with a protean presentation.
The organ system most commonly affected includes the respiratory system, the
gastrointestinal (GI) system, the lymphoreticular system, the skin, the central nervous
system, the musculoskeletal system, the reproductive system, and the liver [2][3].

Evidence of TB has been reported in human remains dated thousands of years (Hershkovitz
et al., 2017, K Zaman 2010). For a human pathogen with no known environmental reservoir,
Mycobacterium tuberculosis has honed the art of survival and has persisted in human
communities from antiquity through modern time.

In the past few decades, there has been a concerted global effort to eradicate TB. These
efforts had yielded some positive dividends especially since 2000 when the World Health
Organization (WHO, 2017) estimated that the global incidence rate for tuberculosis has
fallen by 1.5% every year. Furthermore, mortality arising from tuberculosis has significantly
and steadily declined. The World Health Organization (WHO, 2016) reports a 22% drop in
global TB mortality from 2000 through 2015.

Despite the gains in tuberculosis control and the decline in both new cases and mortality, TB
still accounts for a huge burden of morbidity and mortality worldwide. The bulk of the
global burden of new infection and tuberculosis death is borne by developing countries with
6 countries, India, Indonesia, China, Nigeria, Pakistan, and South Africa, accounting for
60% of TB death in 2015, (WHO, 2017) [4].

Tuberculosis remains a significant cause of both illness and death in developed countries
especially among individuals with a suppressed immune system[5][6]. People with HIV are
particularly vulnerable to death due to tuberculosis. Tuberculosis accounted for 35% of
global mortality in individuals with HIV/AIDS in 2015. (W.H.O, 2017). Children are also

7
vulnerable, and tuberculosis was responsible for one million illnesses in children in 2015
according to the WHO.

3. Etiology
M. tuberculosis causes tuberculosis. M. tuberculosis is an alcohol and acid-fast bacillus. It is
part of a group of organisms classified as the M. tuberculosis complex. Other members of
this group are, Mycobacterium africanum, Mycobacterium bovis, and Mycobacterium
microti[1]. Most other mycobacteria organisms are classified as non-tuberculous or atypical
mycobacterial organisms.

M. tuberculosis is a non-spore forming, non-motile, obligate-aerobic, facultative,

catalasenegative, intracellular bacteria. The organism is neither gram-positive nor gram-
negative because of a very poor reaction with the Gram stain. Weakly positive cells can
sometimes be demonstrated on Gram stain, a phenomenon known as "ghost cells."

The organism has several unique features compared to other bacteria such as the presence of
several lipids in the cell wall including mycolic acid, cord factor, and Wax-D. The high lipid
content of the cell wall is thought to contribute to the following properties of M.
tuberculosis infection:

● Resistance to several antibiotics

● Difficulty staining with Gram stain and several other stains

● Ability to survive under extreme conditions such as extreme acidity or alkalinity, low oxygen
situation, and intracellular survival(within the macrophage)

The Ziehl-Neelsen stain is one of the most commonly used stains to diagnose T.B. The
sample is initially stained with carbol fuchsin (pink color stain), decolorized with acid-
alcohol, and then counter-stained with another stain (usually, blue-colored methylene blue).
A positive sample would retain the pink color of the original carbol fuchsin, hence the
designation, alcohol and acid-fast bacillus (AAFB)[7][8].

8
4. Epidemiology
Geographic Distribution
Tuberculosis is present globally. However; developing countries account for a
disproportionate share of tuberculosis disease burden. In addition to the six countries listed
above, several countries in Asia, Africa, Eastern Europe, and Latin and Central America
continue to have an unacceptably high burden of tuberculosis.
In more advanced countries, high burden tuberculosis is seen among recent arrivals from
tuberculosis-endemic zones, health care workers, and HIV-positive individuals. The use of
immunosuppressive agents such as long-term corticosteroid therapy has also been associated
with an increased risk.
More recently, the use of a monoclonal antibody targeting the inflammatory cytokine, tumor
necrotic factor alpha (TNF-alpha) has been associated with an increased risk. Antagonists of
this cytokine include several monoclonal antibodies (biologics) used for the treatment of
inflammatory disorders. Drugs in this category include infliximab, adalimumab, etanercept,
and golimumab. Patients using any of these medications should be monitored for
tuberculosis before and during the period of drug treatment[11].

Other Major Risk Factors

● Socioeconomic factors: Poverty, malnutrition, wars
● Immunosuppression: HIV/AIDS, chronic immunosuppressive therapy (steroids, monoclonal
antibodies against tumor necrotic factor), a poorly developed immune system (children, primary

immunodeficiency disorders)

● Occupational: Mining, construction workers, pneumoconiosis (silicosis)

Global impact of TB
TB occurs in every part of the world. In 2021, the largest number of new TB cases occurred
in the WHO South-East Asian Region, with 46% of new cases, followed by the WHO
African Region, with 23% of new cases and the WHO Western Pacific with 18%.

9
In 2020, 87% of new TB cases occurred in the 30 high TB burden countries. Eight countries
accounted for more than two thirds of the global total: India, Indonesia, China, the
Philippines, Pakistan, Nigeria, Bangladesh and the Democratic Republic of the Congo[9].

5. Symptoms
When TB germs survive and multiply in the lungs, it is called a TB infection. A TB infection may
be in one of three stages. Symptoms are different in each stage.
Primary TB infection. The first stage is called the primary infection. Immune system cells
find and capture the germs. The immune system may completely destroy the germs. But
some captured germs may still survive and multiply[9].
Most people don't have symptoms during a primary infection. Some people may get flu-like symptoms,
such as:
● Low fever.
● Tiredness.
● Cough.
Latent TB infection. Primary infection is usually followed by the stage called latent TB infection.
Immune system cells build a wall around lung tissue with TB germs. The germs can't do any more
harm if the immune system keeps them under control. But the germs survive. There are no
symptoms during latent TB infection.
Active TB disease. Active TB disease happens when the immune system can't control an
infection. Germs cause disease throughout the lungs or other parts of the body. Active TB
disease may happen right after primary infection. But it usually happens after months or
years of latent TB infection.
Symptoms of active TB disease in the lungs usually begin gradually and worsen over a few weeks.
They may include:
● Cough.
● Coughing up blood or mucus.
● Chest pain.
● Pain with breathing or coughing.
● Fever.
● Chills.

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● Night sweats.
● Weight loss.

11
  Not wanting to eat.
 Tiredness.
 Not feeling well in general.
Active TB disease outside the lungs. TB infection can spread from the lungs to other parts
of the body. This is called extrapulmonary tuberculosis. Symptoms vary depending on what
part of the body is infected. Common symptoms may include:
● Fever.
● Chills.
● Night sweats.
● Weight loss.
● Not wanting to eat.
● Tiredness.
● Not feeling well in general.
● Pain near the site of infection.
Active TB disease in the voice box is outside the lungs, but it has symptoms more like
disease in the lungs.
Common sites of active TB disease outside the lungs include:
● Kidneys.
● Liver.
● Fluid surrounding the brain and spinal cord.
● Heart muscles.
● Genitals.
● Lymph nodes.
● Bones and joints.
● Skin.
● Walls of blood vessels.
● Voice box, also called larynx.
Active TB disease in children. Symptoms of active TB disease in children vary. Typically,
symptoms by age may include the following:
● Teenagers. Symptoms are similar to adult symptoms.
● 1- to 12-year-olds. Younger children may have a fever that won't go away and
weight loss[12].

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 ● Infants.The baby doesn't grow or gain weight as expected. Also, a baby may have
symptoms from swelling in the fluid around the brain or spinal cord, including:
o Being sluggish or not active.
o Unusually fussy.
o Vomiting
o Poor feeding.
o Bulging soft spot on the head.
o Poor reflexes.

When to see a doctor

The symptoms of tuberculosis are similar to symptoms of many different illnesses. See your
health care provider if you have symptoms that don't improve with a few days of rest[16].
Get emergency care if you have:
● Chest pain.
● Sudden, severe headache.
● Confusion.
● Seizures.
● Difficulty breathing.
Get immediate or urgent care if you:
● Cough up blood.
● Have blood in your urine or stool.

6. Drug-resistant TB
Some forms of the TB bacteria have become drug resistant. This means that drugs that once
cured the disease no longer work.
This happens, in part, because of naturally occurring genetic changes in bacteria. A random
genetic change in a bacterium might give it some quality that makes it more likely to
survive the attack of an antibiotic. If it does survive, then it can multiply.
When antibiotic drugs aren't used correctly — or drugs fail to kill all the bacteria for
another reason — the conditions are ideal for more-resistant versions of the bacteria to get

13
established and multiply. If these bacteria are passed on to other people, a new drug-
resistant strain can grow over time[10].
Problems that can lead to such drug-resistant strains of bacteria include the following:
● People didn't follow directions for taking the drugs or stopped taking the
drugs.
● They weren't prescribed the right treatment plan.
● Drugs were not available.
● The drugs were of poor quality.
● The body didn't absorb the drugs as expected.

Multi-Drug Resistant Tuberculosis (MDR-TB) and Extremely Multi-

Drug
MDR-TB
● This refers to tuberculosis with strains of Mycobacterium which have developed resistance
to the classic anti-tuberculosis medications. TB is especially a problem among patients with
HIV/AIDS. Resistance to multiple anti-tuberculosis medications including at least the two
standard anti-tuberculous medications, Rifampicin or Isoniazid, is required to make a
diagnosis of MDR-TB.
● Seventy-five percent of MDR-TB is considered primary MDR-TB, caused by infection with
MDR-TB pathogens. The remaining 25% are acquired and occur when a patient develops
resistance to treatment for tuberculosis. Inappropriate treatment for tuberculosis because of
several factors such as antibiotic abuse; inadequate dosage; incomplete treatment is the
number one cause of acquired MDR-TB. XDR-T.B
● This is a more severe type of MDR-TB. Diagnosis requires resistance to at least four
antituberculous medications including resistance to Rifampicin, Isoniazid, and resistance to
any two of the newer anti-tuberculous medications. The newer medications implicated in
XDRTB are the fluoroquinolones (Levofloxacin and moxifloxacin) and the injectable
second-line aminoglycosides, Kanamycin, Capreomycin, and amikacin.
● The mechanism of developing XDR-TB is similar to the mechanism for developing
MDRTB.
● XDR -TB is an uncommon occurrence[19].

7. How TB Spreads
TB bacteria spread through the air from one person to another. When a person with TB
disease of the lungs or throat coughs, speaks, or sings, TB bacteria can get into the air.
People nearby may breathe in these bacteria and become infected.

14
TB is NOT spread by
● shaking someone’s hand
● sharing food or drink
● touching bed linens or toilet seats
● sharing toothbrushes
● kissing

When a person breathes in TB bacteria, the bacteria can settle in the lungs and begin to
grow. From there, they can move through the blood to other parts of the body, such as the
kidney, spine, and brain.
TB disease in the lungs or throat can be infectious. This means that the bacteria can spread
to other people. TB in other parts of the body, such as the kidney or spine, is usually not
infectious.
People with TB disease are most likely to spread it to people they spend time with every
day.
This includes family members, friends, and co-workers or schoolmates[19].

8. Risk factors
Anyone can get tuberculosis, but certain factors increase the risk of getting an infection.
Other factors increase the risk of an infection becoming active TB disease.
The Centers for Disease Control and Prevention recommends a TB test for people who have
an increased risk of TB infection or active TB disease. Talk to your health care provider if
you have one or more of the following risk factors.
Risk of TB infection
Certain living or working conditions make it easier for the disease to pass from one person
to another. These conditions increase the risk of getting a TB infection:
● Living with someone with active TB disease.
● Living or traveling in a country where TB is common, including several countries in
Latin America, Africa, Asia and the Pacific Islands.
● Living or working in places where people live close together, such as prisons, nursing
homes and shelters for homeless people.
● Living in a community identified as being at high risk of tuberculosis.
● Working in health care and treating people with a high risk of TB.

15
Risk of active TB disease
A weakened immune system increases the risk of a TB infection becoming active TB
disease.
Conditions or treatments that weaken the immune system include:
● HIV/AIDS.
● Diabetes.
● Severe kidney disease.
● Cancers of the head, neck and blood.
● Malnutrition or low body weight.
● Cancer treatment, such as chemotherapy.
● Drugs to prevent rejection of transplanted organs.
● Long-term use of prescription steroids.
● Use of unlawful injected drugs.
● Misuse of alcohol.
● Smoking and using other tobacco products.
Age and active TB disease
The risk of a TB infection becoming active TB disease changes with age.
● Under 5 years of age. Until children reach age 5, they have high risk of a TB
infection becoming active TB disease. The risk is greater for children under age
2. Tuberculosis in this age group often leads to serious disease in the fluid
surrounding the brain and spinal column, called meningitis.
● Age 15 to 25. People in this age group have an increased risk of developing
more-severe active TB disease in the lungs.
● Age 65 and older. The immune system weakens during older age. Older adults
have a greater risk of active TB disease. Also, the disease may be more difficult
to treat[13][14][15].

9. Pathophysiology
Although, usually a lung infection, tuberculosis is a multi-system disease with protean
manifestation. The principal mode of spread is through the inhalation of infected
aerosolized droplets.
The body's ability to effectively limit or eliminate the infective inoculum is determined by
the immune status of the individual, genetic factors, and whether it is a primary or
secondary exposure to the organism. Additionally, M. tuberculosis possesses several
virulence factors that make it difficult for alveolar macrophages to eliminate the organism

16
from an infected individual. The virulence factors include the high mycolic acid content of
the bacteria's outer capsule, which makes phagocytosis to be more difficult for alveolar
macrophages. Furthermore, some of the other constituents of the cell wall such as the cord
factor may directly damage alveolar macrophages. Several studies have shown that
mycobacteria tuberculosis prevents the formation of an effective phagolysosome, hence,
preventing or limiting the elimination of the organisms.
The first contact of the Mycobacterium organism with a host leads to manifestations known
as primary tuberculosis. This primary TB is usually localized to the middle portion of the
lungs, and this is known as the Ghon focus of primary TB. In most infected individuals, the
Ghon focus enters a state of latency. This state is known as latent tuberculosis.
Latent tuberculosis is capable of being reactivated after immunosuppression in the host. A
small proportion of people would develop an active disease following first exposure. Such
cases are referred to as primary progressive tuberculosis. Primary progressive tuberculosis
is seen in children, malnourished people, people with immunosuppression, and individuals
on long-term steroid use.
Most people who develop tuberculosis, do so after a long period of latency (usually several
years after initial primary infection). This is known as secondary tuberculosis. Secondary
tuberculosis usually occurs because of reactivation of latent tuberculosis infection. The
lesions of secondary tuberculosis are in the lung apices. A smaller proportion of people who
develop secondary tuberculosis do so after getting infected a second time (re-infection). The
lesions of secondary tuberculosis are similar for both reactivation and reinfection in terms
of location (at the lung apices), and the presence of cavitation enables a distinction from
primary progressive tuberculosis which tends to be in the middle lung zones and lacks
marked tissue damage or cavitation[24].
Type-IV Hypersensitivity and Caseating Granuloma
Tuberculosis is a classic example of a cell-mediated delayed type IV hypersensitivity
reaction.
Delayed Hypersensitivity Reaction: By stimulating the immune cells (the helper
TLymphocyte, CD4+ cells), Mycobacterium tuberculosis induces the recruitment and
activation of tissue macrophages. This process is enhanced and sustained by the production
of cytokines, especially interferon gamma.

17
Two main changes involving macrophages occur during this process namely, the formation
of multinucleated giant cells and the formation of epithelioid cells. Giant cells are
aggregates of macrophages that are fused together and functions to optimize phagocytosis.
The aggregation of giant cells surrounding the Mycobacterium particle and the surrounding
lymphocytes and other cells is known as a granuloma.
Epithelioid cells are macrophages that have undergone a change in shape and have
developed the ability for cytokine synthesis. Epithelioid cells are modified macrophages
and have a flattened (spindle-like shape) as opposed to the globular shape characteristic of
normal

18
macrophages. Epithelioid cells often coalesce together to form giant cells in a tuberculoid
granuloma.
In addition to interferon-gamma (IFN-gamma), the following cytokines play important roles
in the formation of a tuberculosis granuloma, Interleukin-4 (IL-4), Interleukin-6 (IL-6), and
tumor necrotic factor-alpha (TNF-alpha).
The appearance of the granuloma in tuberculosis has been described as caseous or cheese-
like on gross examination. This is principally explained by the rich mycolic acid content of
the mycobacterium cell wall. Because of this unique quality, the term caseous or caseating
necrosis has been used to describe granulomatous necrosis caused by mycobacteria
tuberculosis.
Histologically, caseous necrosis would present as a central area of uniform eosinophilia on
routine hematoxylin and eosin stain[18].

10. Histopathology
The granuloma is the diagnostic histopathological hallmark of tuberculosis.
The defining features of the granuloma of tuberculosis are:
● Caseation or caseous necrosis demonstrable as a region of central eosinophilia.
● Multinucleated giant cells[25]

11. History and Physical

A chronic cough, hemoptysis, weight loss, low-grade fever, and night sweats are some of the
most common physical findings in pulmonary tuberculosis.
Secondary tuberculosis differs in clinical presentation from the primary progressive disease.
In secondary disease, the tissue reaction and hypersensitivity are more severe, and patients
usually form cavities in the upper portion of the lungs.
Pulmonary or systemic dissemination of the tubercles may be seen in active disease, and this
may manifest as miliary tuberculosis characterized by millet-shaped lesions on chest x-ray.
Disseminated tuberculosis may also be seen in the spine, the central nervous system, or the
bowel[17].

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12. Evaluation
Screening Tests
Tuberculin skin testing: Mantoux test (skin testing with PPD)
The Mantoux reaction following the injection of a dose of PPD (purified protein derivative)
is the traditional screening test for exposure to Tuberculosis. The result is interpreted taking
into consideration the patient's overall risk of exposure. Patients are classified into 3 groups
based on the risk of exposure with three corresponding cut-off points. The 3 major groups
used are discussed below.
Low Risk
● Individuals with minimal probability of exposure are considered to have a positive
Mantoux test only if there is very significant induration following intradermal
injection of PPD. The cut-off point for this group of people (with minimal risk of
exposure) is taken to be 15 mm.
Intermediate Risk
● Individuals with intermediate probability are considered positive if the induration is
greater than 10 mm.
High Risk
● Individuals with a high risk of a probability of exposure are considered positive if the
induration is greater than 5 mm.
Examples of Patients in the Different Risk Categories
● Low Risk/Low Probability: Patients with no known risk of exposure to TB. Example:
No history of travel, military service, HIV-negative, no contact with a chronic cough
patient, no occupational exposure, no history of steroids. Not a resident of a
TBendemic region.
● Intermediate Risk/Probability: Residents of TB-endemic countries (Latin America, Sub
-Sahara Africa, Asia), workers or residents of shelters, Medical or microbiology
department personnel.
● High Risk/Probability: HIV-positive patient, a patient with evidence of the previous
TB such as the healed scar on an x-ray), contact with chronic cough patients. Note that
a Mantoux test indicates exposure or latent tuberculosis. However, this test lacks
specificity, and patients would require subsequent visits for interpreting the results as
well as chest x-ray for confirmation. Although relatively sensitive, the Mantoux

20
 reaction is not very specific and may give false-positive reactions in individuals who
have been exposed to the BCG-vaccine.
Interferon release assays (IGRA, Quantiferon Assays)
This is a tuberculosis screening test that is more specific and equally as sensitive as the
Mantoux test. This test assays for the level of the inflammatory cytokine, especially
interferon gamma.
The advantages of Quantiferon, especially in those with prior vaccination with BCG
vaccine, include, the test requires a single blood draw, obviating the need for repeat visits to
interpret results. Furthermore, additional investigations such as HIV screening could be
performed (after patient consent) on the same blood draw.
Quantiferon's disadvantages include cost and the technical expertise required to perform the
test.
Screening in Immunocompromised Patients
Immunocompromised patients may show lower levels of reaction to PPD or falsenegative
Mantoux because of cutaneous anergy.
A high level of suspicion should be entertained when reviewing negative screening tests for
tuberculosis in HIV-positive individuals. The Significance of Screening
A positive screening test indicates exposure to tuberculosis and a high chance of developing
active tuberculosis in the future. Tuberculosis incidence in patients with positive Mantoux
test averages between 2% to 10% without treatment.
Patients with a positive test should have a chest x-ray as a minimum diagnostic test. In some
cases, these patients should have additional tests. Patients meeting the criteria for latent
tuberculosis should receive prophylaxis with isoniazid.
Screening Questionnaires for Resource-Poor Settings
Several screening questionnaires have been validated to enable healthcare workers working
in remote and resource-poor environments screen for tuberculosis.
These questionnaires make use of an algorithm that combines several clinical signs and
symptoms of tuberculosis. Some of the commonly used symptoms are:
● Chronic cough
● Weight loss
● Fever and night sweats
● History of contact

21
 ● HIV status
● Blood in sputum
Several studies have confirmed the utility of using several criteria rather than a focus on
only chronic cough or weight loss.

Confirmatory and Diagnostic Tests

1. A chest x-ray is indicated to rule out or rule in the presence of active disease in all
screening test positive cases.
2. Acid Fast Staining-Ziehl-Neelsen
3. Culture
4. Nuclear Amplification and Gene-Based Tests: These represent a new generation of
diagnostic tools for tuberculosis. These tests enable identification of the bacteria or
bacteria particles making use of DNA-based molecular techniques. Examples are
Genexpert and DR-MTB.
The new molecular-based techniques are faster and enable rapid diagnosis with high
precision. Confirmation of TB could be made in hours rather than the days or weeks it takes
to wait for a standard culture. This is very important, especially among
immunocompromised hosts where there is a high rate of false-negative results. Some
molecular-based tests such as GeneXpert and DR-MTB also allow for the identification of
multidrug resistant tuberculosis[27][29][32].

13. Treatment / Management

Latent Tuberculosis
2020 LTBI treatment guidelines include the NTCA- and CDC-recommended treatment
regimens that comprise three preferred rifamycin-based regimens and two alternative
monotherapy regimens with daily isoniazid. These are only recommended for persons
infected with Mycobacterium tuberculosis that is presumed to be susceptible to isoniazid or
rifampin. A regimen of 3 months of once-weekly isoniazid plus rifapentine is a preferred
regimen that is strongly recommended for children aged more than 2 years and adults.
Another option is 4 months of daily rifampin for HIV-negative adults and children of all
ages. Three months of daily isoniazid plus rifampin is a preferred treatment that is

22
conditionally recommended for adults and children of all ages and for patients with HIV.
Regimens of 6 or 9 months of daily isoniazid are alternative recommended regimens.

Treatment of Active Infection

Treatment of confirmed TB requires a combination of drugs. Combination therapy is always
indicated, and monotherapy should never be used for tuberculosis. The most common
regimen for TB includes the following anti-TB medications:
First-Line Medications, Group 1
● Isoniazid -
Adults (maximum): 5 mg/kg (300 mg) daily; 15 mg/kg (900 mg) once, twice, or
three times weekly.
Children (maximum): 10-15 mg/kg (300 mg) daily; 20--30 mg/kg (900 mg) twice
weekly.
Preparations- Tablets (50 mg, 100 mg, 300 mg); syrup (50 mg/5 ml); aqueous
solution (100 mg/ml) for IV or IM injection.
● Rifampicin -
Adults (maximum): 10 mg/kg (600 mg) once daily, twice weekly, or three times
weekly.
Children (maximum): 10-20 mg/kg (600 mg) once daily or twice weekly.
Preparations- Capsules (150 mg, 300 mg)
● Rifabutin-
Adults (maximum): 5 mg/kg (300 mg) daily, twice, or three times weekly. When
rifabutin is used with efavirenz the dose of rifabutin should be increased to 450--600
mg either daily or intermittently.
Children (maximum): Appropriate dosing for children is unknown.
Preparations- Capsules (150 mg) for oral administration.
● RIfapentine -
Adults (maximum): 10 mg/kg (600 mg), once weekly (continuation phase of
treatment)
Children: The drug is not approved for use in children.
Preparation- Tablet (150 mg, film-coated).

23
 ● Pyrazinamide -
Adults: 20-25 mg/kg perday.
Children (maximum): 15-30 mg/kg (2.0 g) daily; 50 mg/kg twice weekly (2.0 g).
Preparations- Tablets (500 mg).

● Ethambutol -
Adults: 15-20 mg/kg per day.
Children (maximum): 15-20 mg/kg per day (2.5 g); 50 mg/kg twice weekly (2.5 g).
The drug can be used safely in older children but should be used with caution in
children in whom visual acuity cannot be monitored (generally less than 5 years of
age) (66). In younger children, EMB can be used if there is a concern with resistance
to INH or RIF.
Preparations- Tablets (100 mg, 400 mg) for oral administration.
Isoniazid and Rifampicin follow a 4-drug regimen (usually including Isoniazid, Rifampicin,
Ethambutol, and Pyrazinamide) for 2 months or six months. Vitamin B6 is always given
with Isoniazid to prevent neural damage (neuropathies).
Several other antimicrobials are effective against tuberculosis including the following
categories:
Second-Line Anti-tuberculosis Drugs, Group 2
Injectables aminoglycosides and injectable polypeptides.
Injectable aminoglycosides
● Amikacin
● Kanamycin
● Streptomycin
Injectable polypeptides
● Capreomycin
● Viomycin
Second-Line Anti-Tuberculosis Drugs, Group 3,
Oral and Injectable
Fluoroquinolones
● Levofloxacin
● Moxifloxacin

24
 ● Ofloxacin
● Gatifloxacin
Second-Line Anti-tuberculosis Drugs, Group 4
● Para-aminosalicylic acid
● Cycloserine

● Terizidone
● Ethionamide
● Prothionamide
● Thioacetazone
● Linezolid
Third-Line Anti-Tuberculosis Drugs, Group 5
These are medications with variable but unproven efficacy against TB. They are used for
total drug-resistant TB as drugs of last resort.
● Clofazimine
● Linezolid
● Amoxicillin/clavulanic acid
● Imipenem/cilastatin
● Clarithromycin
MDR-TB, XDR-TB
Multi-drug resistant TB is becoming increasingly common.
The combination of first-line and second-line medications is used at high doses to treat this
condition.
Bedaquiline
On December 28, 2012, the United States Food and Drug Administration Agency (FDA),
approved Bedaquiline as a drug for treating MDR-TB. This is the first FDA approval for an
anti-TB medication in 40 years. While showing remarkable promise in drug-resistant
tuberculosis, cost remains a big obstacle to delivering this drug to the people most affected
by
MDR-TB.
Clinical and Laboratory Monitoring
Liver function test is required for all patients taking isoniazid. Other monitoring in TB
includes monitoring for retinopathies for patients on ethambutol[22][23].

25
14. Differential Diagnosis
Tuberculosis is a great mimic and should be considered in the differential diagnosis of
several systemic disorders. The following is a non-exhaustive list of conditions to be
strongly considered when evaluating the possibility of pulmonary tuberculosis[17].
● Pneumonia
● Malignancy
● Non-tuberculous mycobacterium
● Fungal infection
● Histoplasmosis
● Sarcoidosis

15. Toxicity and Adverse Effect Management

Side Effect associated with most commonly used anti-TB drugs
1)Isoniazid-
Asymptomatic elevation of aminotransferases (10-20%), clinical hepatitis (0.6%), peripheral
neurotoxicity, hypersensitivity.
2)Rifampin-
Pruritis, nausea & vomiting, flulike symptoms, hepatotoxicity, orange discoloration of
bodily fluid.
3)Rifabutin-
Neutropenia, uveitis (0.01%), polyarthralgias, hepatotoxicity (1%))
4)Rifapentine-
Similar to rifampin
5)Pyrazinamide-
Hepatotoxicity (1%), nausea & vomiting, polyarthralgias (40%), acute gouty arthritis, rash
and photosensitive dermatitis
6)Ethambutol-
Retrobulbar neuritis (18%)
One of the most important aspects of tuberculosis treatment is close follow-up and
monitoring for these side effects. Most of these side effects can be managed by either close

26
monitoring or adjusting the dose. In some cases, the medication needs to be discontinued
and second-line therapy should be considered if other alternatives are not available[31].

16. Prognosis
The majority of patients with a diagnosis of TB have a good outcome. This is mainly
because of effective treatment. Without treatment mortality rate for tuberculosis is more than
50%. The following group of patients is more susceptible to worse outcomes or death
following TB infection:
● Extremes of age, elderly, infants, and young children
● Delay in receiving treatment
● Radiologic evidence of extensive spread.
● Severe respiratory compromise requiring mechanical ventilation
● Immunosuppression
● Multidrug Resistance (MDR) Tuberculosis[20].

17. Complications
Most patients have a relatively benign course. Complications are more frequently seen in
patients with the risk factors mentioned above. Some of the complications associated with
tuberculosis are:
● Extensive lung destruction
● Damage to cervical sympathetic ganglia leading to Horner's syndrome.
● Acute respiratory distress syndrome
● Milliary spread (disseminated tuberculosis)including TB meningitis.
● Empyema
● Pneumothorax
● Systemic amyloidosis[26].

18. Pearls and Other Issues

Tuberculosis is a preventable and treatable infectious disease. Having said that, it's still one
of the major contributors to morbidity and mortality in developing countries where we are
still struggling to provide adequate access to care. Other challenges include lack of

27
awareness, delayed diagnosis, poor accessibility to medication and vaccination as well as
medication adherence. DOTS (Direct Observed Therapy) proposed by WHO has been very
effective in recent years to improve adherence to the treatment in tuberculosis patients. [9]
[10] Also, vaccination drive in developing countries has played a bigger role in decreasing
the prevalence of this infection. The preventive effect of BCG vaccination is controversial
but many studies have identified vaccination as a very important tool in the fight against
tuberculosis and we need to keep our focus on childhood vaccination especially in
developing countries.[11] WHO and other health organizations have to continue their
investment in developing strategy and research until we eradicate this disease from the
world map. New antituberculosis drugs need to be developed to shorten or otherwise
simplify the treatment of tuberculosis caused by drug-susceptible organisms, to improve
treatment of drugresistant tuberculosis, and to provide more efficient and effective treatment
of latent tuberculosis infection[33].

19. Enhancing Healthcare Team Outcomes

A team approach involving nurses, clinicians, and technicians will lead to the best
outcomes in treating patients with tuberculosis[21].

Granuloma of Tuberculosis. Arrows pointed at multi-nucleated giant cells.

Contributed By Dr. Rotimi Adigun (with permission from Kingston General Hospital)

28
20. Conclusion
Tuberculosis (TB) is a disease caused by the bacterium Mycobacterium tuberculosis. It
primarily affects the lungs but can also affect other organs and systems in the body. TB has
been present in human populations for thousands of years and has persisted through time.
Efforts to control and eradicate TB have shown positive results since the year 2000. The
global incidence rate of TB has been declining by 1.5% per year, and TB-related mortality
has significantly decreased by 22% between 2000 and 2015. However, TB still remains a
major global health burden, particularly in developing countries. Six countries, namely
India, Indonesia, China, Nigeria, Pakistan, and South Africa, accounted for 60% of TB
deaths in 2015.
TB is not limited to developing countries and can also affect individuals in developed
countries, especially those with weakened immune systems, such as people with HIV/AIDS.
In 2015, TB accounted for 35% of global mortality in individuals with HIV/AIDS. Children
are also vulnerable to TB, with one million cases reported in 2015.
Mycobacterium tuberculosis, the causative agent of TB, is a unique bacterium with various
features that contribute to its survival and persistence. It has a high lipid content in its cell
wall, making it resistant to antibiotics and difficult to stain with certain dyes. It can survive
under extreme conditions and is capable of intracellular survival within macrophages.

29
TB is diagnosed using various methods, including the Ziehl-Neelsen stain, which is a
commonly used staining technique to identify acid-fast bacilli (AFB). This stain helps in the
detection of TB bacteria in samples.
The global distribution of TB shows that it is present worldwide, but developing countries
bear the highest burden. In 2020, the WHO South-East Asian Region had the highest
number of new TB cases (46%), followed by the WHO African Region (23%) and the WHO
Western Pacific Region (18%). Several countries in Asia, Africa, Eastern Europe, and Latin
and Central America still have a high burden of TB.
TB can be transmitted through the air when a person with TB disease in the lungs or throat
coughs, speaks, or sings. It is not spread by casual contact like shaking hands or sharing
food. People with active TB disease are more likely to spread the infection to those they
spend time with regularly.
The symptoms of TB vary depending on the stage of the infection. In the primary stage,
most people don't have symptoms, but some may experience flu-like symptoms. During the
latent stage, there are no symptoms. Active TB disease can cause symptoms such as cough,
chest pain, fever, weight loss, and fatigue. TB can also affect other parts of the body, leading
to symptoms specific to the affected organ or system.
Drug-resistant TB is a growing concern, where the TB bacteria have developed resistance to
the drugs used to treat the infection. Multi-drug resistant tuberculosis (MDR-TB) is defined
as resistance to at least two standard anti-tuberculosis medications, while extensively
drugresistant TB (XDR-TB) is a more severe form with resistance to additional drugs. The
development of drug resistance is often due to factors such as incorrect use of medications,
poor treatment plans, or inadequate drug supply.
Certain risk factors increase the likelihood of acquiring a TB infection or developing active
TB disease. These include close contact with someone with active TB, living or traveling in
countries where TB is common, working in high-risk environments, and having a weakened
immune system due to conditions like HIV/AIDS or certain medications.
In summary, TB is a persistent global health burden, particularly affecting developing
countries. Efforts to control and eradicate TB have shown progress, but drug-resistant strains
pose a challenge. Increased awareness, early

30
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