Tuberculosis and its Advanced Therapy

Lecture Notes, 2018

25 Pages, Grade: A


List of Contents

1. Introduction

2. Epidemiology

3. Pathogenesis

4. Types of tuberculosis

5. Diagnosis

6. Management of tuberculosis

7. Treatment duration and comments

8. Isoniazid drug information

9. Rifampicin drug information

10. Pyrazinamide drug information

11. Ethambutol drug information

12. Streptomycin drug information


1. Introduction

Tuberculosis [TB] is an infectious disease that can affect any part of the body, mainly an infection of the lungs.

In Neo-Latin word, tuberculosis is termed as ‘TUBERCLE’ which means round nodule and ‘OSIS’ which means condition.

The causative organism for tuberculosis is Mycobacterium tuberculosis in human and Mycobacterium bovis in animals. Mycobacterium tuberculosis is small, aerobic, nonmotile bacillus[1]. The other causative organisms are Mycobacterium africanum and Mycobacterium microti. The non-mycobacterium genuses are Mycobacterium leprae, Mycobacterium avium, Mycobacterium asiaticum. The M.Tuberculosis complex consists of M.africanum, M.bovis, M.canetti, and M.microti.


Figure No-1: Classification of Tuberculosis[2]

illustration not visible in this excerpt

2. Epidemiology

According to WORLD HEALTH ORGANISATION (WHO), in 2012 they estimated around 8.6 million cases in which women were found approximately around 2.9. Most cases were found in Africa (27%) and Asia (58%), with a highest incidence in India (2.0-2.4 million), China (0.9-1.1 million); and total accounted the number of cases is 38%[3].

The incidence rate of TB was eventually declined from 1997-2001 but increased in 2001 due to more number of HIV infected patient’s cases in Africa. Later there was a reduction of 1.3% per year since 2002. The absolute numbers of cases were also decreasing, but this has begun in 2006.

The estimated prevalent cases in 2012 were around 12 million, corresponding to 169 cases per one lakh population[3]. TB prevalence is declining from the early 1990’s (before incidence started to decline). This is largely due to the introduction of DOTS strategy, which may have contributed to the reduction of chronic and cases which are untreated and duration of illness.

In 2012 TB mortality cases are estimated to be 1.3 million deaths including 320000 HIV associated cases. Since 1990 a drop of 45% TB mortality rate has been observed[4].

Figure No.2: Incidence, prevalence, and mortality of TB[4]

illustration not visible in this excerpt

The spread of tuberculosis can happen while coughing without covering mouth, crowded places with poor ventilation, spitting everywhere. From the area of damaged tissue, TB bacteria enter into the bloodstream which spreads throughout the body, set up many foci of infection; all appears tiny and white tubercles in the tissues[5].

Most important risk factor globally is HIV; 13% of people with TB are infected by the virus[6]. Chronic lung disease (CLD) is one of the risk factors. Silicosis increases the risk about 30-folds[7]. Cigarette smokers have nearly twice the risk of TB compared to nonsmokers[8].People with prolonged, frequent, or close contact with people with TB are at particularly high risk of becoming infected, with an estimated 22% infection rate[9].

The severe symptoms are a Persistent cough, Chest pain, Coughing with bloody sputum, Shortness of breath, Urine discoloration, Cloudy and reddish urine, Fever with chills and Fatigue.

3. Pathogenesis

Figure No-3: Pathogenesis of TB[10]

illustration not visible in this excerpt

4. Types of Tuberculosis

A. Pulmonary TB: If tuberculosis infection becomes active, it most commonly involves the lungs (about 90% of cases) [11, 12].

There are two types of pulmonary TB, one is Primary TB where the infection vary from inter-individual conditions and it applies who has not been infected formerly or immunized and another is Secondary TB where it doesn’t varies from inter-individual but it applies who has already been infected formerly.

B. Extrapulmonary TB: Around 15-20% of active cases, the infection spreads outside the lungs, causing other kinds of TB[13]. These collectively termed as "extrapulmonary tuberculosis"[14].

There are 10 different types of extra pulmonary TB; they are Lymph Node TB which is frequently seen in HIV infected patients with symptoms like swelling of lymph nodes commonly at cervical and supracervical.

Pleural TB which has involvement of pleura and penetration of tubercle bacilli into pleural space.

TB of Upper Airways involves larynx, pharynx, and epiglottis with symptoms like dysphasia and chronic productive cough.

Genitourinary TB occurs in the genitourinary tract with symptoms like urinary frequency, dysuria, and hematuria.

Skeletal TB involves the parts like spine, hip and knee with symptoms like pain in hip joints and knees, swelling of knees and trauma.

Gastrointestinal TB involves part of GI tract with symptoms like abdominal pain, diarrhea, and weight loss.

TB Meningitis and Tuberculoma which results from the spread of primary and secondary TB.

TB Pericarditis in which 1-8% of all TB cases spreads mainly from mediastinal or hilar nodes or from lungs.

Military Or Disseminated TB is producing lesions at different extrapulmonary sites due to the entry of infection into the pulmonary veins. "Disseminated Tuberculosis" is the most serious and widespread form of TB, which is also known as miliary tuberculosis[15]. About 10% of extra pulmonary cases include military TB[16].

Less Common Forms includes uveitis, panopthalmitis and painful hypersensitivity related phlyetenular conjunctivitis.

5. Diagnosis

1. Bacteriological test:-

a) Zeihl - Nielsen stain
b) Auramine stain ( fluorescence microscopy)

2. Sputum culture test:-

a) Lowenstein - Jensen solid medium - 4-18wks
b) Liquid medium - 8-14days
c) Agar medium - 7-14days

3. Radiography :- Chest x-ray [CXR]

4. Nucleic acid amplification:-

Species identification, several hours, Low sensitivity, high cost, most useful for the confirmation of tuberculosis in persons with AFB positive sputa

5. Tuberculin Skin Test:-

Injection into the skin of the lower arm

48-72 hours later checked for reaction

Diagnosis is done based on the size of the wheel Dose = 0.1ml contains 0.04ug tuberculin PPD Less than 6mm - negative

6mm or greater but less than 15mm - hypersensitive to tuberculin protein, may be due to previous TB infection, BCG or exposure to atypical mycobacterium

>= 15mm - strongly hypersensitive to tuberculin protein, suggestive of TB infection or disease

6. Other Biological Examinations:-

Cell count (lymphocytes)

Protein (pandy and Rivalta tests) - ascites, meningitis and pleural effusion Chest X-ray and sputum cultures for acid-fast bacilli are part of the initial evaluation[17]. Nucleic acid amplification and adenosine deaminase testing may allow rapid diagnosis of TB[18]. In Sarcoidosis, Hodgkin's lymphoma, malnutrition, and active tuberculosis the test may be falsely negative[19].

Prevention and control efforts of tuberculosis majorly depend on the infant’s vaccination, an exact diagnosis and appropriate treatment of active cases[20]. The preventive measures are you should keep mask to avoid exposure and take BCG vaccine prior and for regular medical follow up, BCG vaccine in children decreases the risk of the infection by 20% and the risk of infection turning into disease by 60%[21].Isolation of patient is necessary so that others will not get affected, ventilation is necessary never be in a dark room mostly natural sunlight is better, use UV germicidal irradiation.


[1]. Dolin, Gerald L Mandell, John E et al. Mandell, Douglas, and Bennett's principles and practice of infectious diseases. Philadelphia, PA. 2010, 7th edition, Churchill Livingstone-Elsevier. Chapter 250.


[3]. World Health Organization (WHO) Global Tuberculosis Report 2013. Geneva: 2013.

[4]. e2014070/

[5]. Crowley, Leonard V. An introduction to human disease: pathology and pathophysiology correlations. Sudbury, Mass. 2010, 8th edition. Jones and Bartlett. p. 374

[6]. World Health Organization (2011). The sixteenth global report on tuberculosis. Archived from the original (PDF) on 6 September 2012.

[7]. ATS/CDC Statement committee on Latent Tuberculosis Infection.Targeted tuberculin testing and treatment of latent tuberculosis infection. American Thoracic Society"2000. MMWR Recommendations and Reports. 49: p.1-51.

[8]. van Zyl Smit RN, Pai M, Yew WW, et al. Global lung health: the colliding epidemics of tuberculosis, tobacco smoking, HIV and COPD. European Respiratory Journal. 2010, 35 (1): 27–33.

[9]. Ahmed N, Hasnain S. Molecular epidemiology of tuberculosis in India: Moving forward with a systems biology approach". Tuberculosis. 2011. 91 (5): 407-3


[11]. Lawn SD, Zumla AI. Tuberculosis. Lancet. 2011, 378 (9785): 57–72.

[12]. Behera, D. Textbook of Pulmonary Medicine (2nd ed.). New Delhi: Jaypee Brothers Medical Publishers. 2010 p. 457. ISBN 978-81-8448-749-7. Archived from the original on 6 September 2015.

[13]. Jindal, editor-in-chief SK. Textbook of Pulmonary and Critical Care Medicine. New Delhi: Jaypee Brothers Medical Publishers. 2011. p. 549. ISBN 978-93-5025-073-0. Archived from the original on 7 September 2015

[14]. Golden MP, Vikram HR. Extrapulmonary tuberculosis: an overview. American Family Physician. 2005.72 (9): 1761-1768

[15]. Dolin Gerald L Mandell, John E Bennett, Raphael. Mandell, Douglas, and Bennett's principles and practice of infectious diseases (7th ed.). Philadelphia, PA:2010, 7th edition. Churchill Livingstone/Elsevier. pp. Chapter 250

[16]. Ghosh, Thomas M Habermann, Amit K. Mayo Clinic internal medicine: concise textbook. Rochester, MN: Mayo Clinic Scientific Press. 2008. p. 789. ISBN 978-1-4200-6749-1.

[17]. Escalante. In the clinic. Tuberculosis. Annals of Internal Medicine. 2009, 150 (11):2.

[18]. Bento J Silva As, Rodrigue F, Duarte R. Diagnostic tools in tuberculosis. Acta Medica Porguesa. 2011, 24(1):145-154.

[19]. Kumar V, Abbas Ak, Fausto N, Mitchell RN. Robbins Basic Pathology. Saunders Elsevier, 8th edition: 516-522.

[20]. Lawn SD, Zumla AI. Tuberculosis. Lancet. 2011, 378(9785):57-72

[21]. Roy A, Eisenunt M, Harris RJ, et al. Effect of BCG vaccination against Mycobacterium tuberculosis infection in children: systematic review and metaanalysis. BMJ. 349.

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Tuberculosis and its Advanced Therapy
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Tuberculosis, epidemiology, treatment, isoniazid, ethambutol, pyrazinamide, mechanism of action
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Dr. Sagar Pamu (Author), 2018, Tuberculosis and its Advanced Therapy, Munich, GRIN Verlag,


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