Tuberculosis is caused by bacteria belonging to the Mycobacterium tuberculosis complex. It usually affects the lungs and can spread to other organs if untreated. The most common causative agent is M. tuberculosis. Transmission typically occurs through airborne droplets produced by patients with infectious pulmonary TB. Common symptoms include cough, fever, night sweats and weight loss. While curable with proper treatment, tuberculosis remains a major global health problem especially in developing countries.

1. Dr. Mukesh Sah, MD
United Kingdom
TUBERCULOSIS
Dr.Mukesh Sah

2. TUBERCULOSIS:
 Caused by bacteria belonging to the
Mycobacterium tuberculosis complex
 The disease usually affects the lungs; up to 1/3 of
patients have disease involving other organs
 If untreated, the disease may be fatal within 5
years in more than half of cases
 Transmission usually takes place through the
airborne spread of droplet nuclei produced by
patients with infectious PTB
Dr.Mukesh Sah

3. ETIOLOGIC AGENT:
 M. tuberculosis- the most frequent and important agent of
human disease
 M. bovis- the bovine tubercle bacillus, an important cause
of TB transmitted by unpasteurized milk and currently the
cause of a small percentage of cases in developing
countries
 M. africanum- isolated from cases in West, Central and
East Africa
 M. microti- the “vole” bacillus, a less virulent and rarely
encountered organism
 M. canettii- a very rare isolate in African cases
Dr.Mukesh Sah

4. ETIOLOGIC AGENT:
 M. tuberculosis is a rod-shaped, non-spore-forming
thin aerobic bacterium measuring 0.5um x 3um
 Neutral on Gram’s staining
 ACID FASTNESS: due mainly to the organism’s high
content of MYCOLIC ACIDS and other cell wall lipids
 LIPOARABINOMANNAN:
 A molecule in the mycobacterial cell wall
 Involved in the pathogen-host interaction and facilitates
survival within macrophages
Dr.Mukesh Sah

5. EPIDEMIOLOGY:
 More than 3.8 million new cases of TB- all forms
(pulmonary and extrapulmonary), 90% of them from
developing countries- were reported to the WHO in
2001
 It is estimated that 1.8million deaths from TB occurred
in 2000, 98% of them in developing countries
FROM EXPOSURE to INFECTION:
 M. tuberculosis is most commonly transmitted from a
patient with infectious PTB to other persons by droplet
nuclei, which are aerosolized by coughing, sneezing or
speaking
 The tiny droplets dry rapidly; the smallest (< 10 um in
diameter) may remain suspended in the air for several
hours and may gain access to the terminal air passages
when inhaled
Dr.Mukesh Sah

6. EPIDEMIOLOGY:
 Important determinants of transmission:
 (1) The probability of contact with a case of TB
 (2) The intimacy and duration of the contact
 (3) The degree of infectiousness of the case
 (4) The shared environment of the contact
 Several studies of close contacts have clearly demonstrated that
TB patients whose sputum contains AFB visible by microscopy
play the greatest role in the spread of infection
 Patients with sputum smear-negative/culture-positive TB are less
infectious
 Those with culture-negative pulmonary disease and
extrapulmonary TB are essentially non-infectious
 Up to 20 contacts may be infected by each AFB-positive case
before detection in high-prevalence settings
 Crowding in poorly ventilated rooms is one of the most
important factors in the transmission of tubercle bacilli,
since it increases the intensity of contact with a case
Dr.Mukesh Sah

7. EPIDEMIOLOGY:
FROM INFECTION to DISEASE:
 The risk of developing disease after being infected
depends on endogenous factors such as the following:
 (1) an individual’s innate susceptibility to the disease
 (2) the level of function of cell-mediated immunity
 PRIMARY TUBERCULOSIS
 clinical illness following infection and is common in children up
to 4 years of age
 Although this form may be severe and disseminated, it is
usually not transmissible
 SECONDARY (POSTPRIMARY) TUBERCULOSIS
 Dormant bacilli persisting for years after infection before
reactivating to produce clinical illness
Dr.Mukesh Sah

8. EPIDEMIOLOGY:
 AGE is an important determinant of the risk of disease
after infection
 Among infected persons, the incidence of TB is highest during
late adolescence and early adulthood
 The incidence among women peaks at 25 to 34 years of age
 In this age group rates among women are usually higher than those
among men, while at older ages the opposite is true
 The risk may increase in the elderly because of waning
immunity and co-morbidity
 The most potent risk factor for TB among infected
individuals is HIV co-infection, which suppresses
cellular immunity
 The risk that latent M. tuberculosis infection will proceed to
active disease is directly related to the patient’s degree of
immunosuppression
Dr.Mukesh Sah

9. RISK FACTORS for ACTIVE TB
among INFECTED PERSONS:
Dr.Mukesh Sah

10. NATURAL HISTORY of
DISEASE:
 Studies conducted before the advent of
chemotherapy showed that untreated TB is often fatal
 About 1/3 of patients died within 1 year after
diagnosis, and ½ died within 5 years
 5-year mortality among sputum smear-positive cases
was 65%
 Of the survivors at 5 years, ~60% had undergone
spontaneous remission, while the remainder were still
excreting tubercle bacilli
Dr.Mukesh Sah

11. PATHOGENESIS and
IMMUNITY:
 The interaction of M. tuberculosis with the human host
begins when droplet nuclei containing microorganisms
from infectious patients are inhaled
 < 10% of inhaled bacilli reach the alveoli where nonspecifically
activated macrophages ingest them
 Genes thought to confer virulence to M. tuberculosis:
 (1) katG- encodes for catalase, an enzyme protective against
oxidative stress
 (2) rpoV- the main sigma factor initiating transcription of
several genes
 *** Defects in katG and rpoV result in loss of virulence
 (3) erp gene- encodes a protein required for multiplication of
bacilli
 NRAMP1
 The human homologue cloned to chromosome 2q,may have a
role in determining susceptibility to TB, as suggested by a
study among West Africans
Dr.Mukesh Sah

12. PATHOGENESIS and
IMMUNITY:
 In the initial stage of host-bacterium interaction:
 1. The host’s macrophages contain bacillary
multiplication by producing proteolytic enzymes
 2. The bacilli begin to multiply
 If the bacilli multiply, their growth quickly kills the
macrophages, which lyse
 Non-activated monocytes attracted from the bloodstream to
the site by various chemotactic factors ingest the bacilli
released from the lysed macrophages
 These initial stages of infection are usually
asymptomatic
Dr.Mukesh Sah

13. PATHOGENESIS and
IMMUNITY:
2-4 weeks after infection, 2 additional host responses to
M. tuberculosis develop:
 (1) TISSUE-DAMAGING RESPONSE
 The result of a delayed-type hypersensitivity (DTH) reaction to
various bacillary antigens
 Destroys non-activated macrophages that contain multiplying
bacilli
 (2) MACROPHAGE-ACTIVATING RESPONSE
 A cell-mediated phenomenon resulting in the activation of
macrophages that are capable of killing and digesting tubercle
bacilli
 Although both responses inhibit mycobacterial growth,
it is the balance between the 2 that determines the
form of TB that will subsequently develop
Dr.Mukesh Sah

14. PATHOGENESIS and
IMMUNITY:
 TUBERCLES:
 Granulomatous lesions that form at the site of primary lesion
 These lesions consist of lymphocytes and activated macrophages
(epithelioid and giant cells)
 The tissue-damaging response not only destroys macrophages
but also produces early solid necrosis in the center of the tubercle
 The growth of M. tuberculosis is inhibited within the necrotic
environment by low oxygen tension and low pH
 CASEOUS NECROSIS:
 The activated macrophages aggregate around the lesion’s center
and effectively neutralize tubercle bacilli via cell-mediated
immunity
 The necrotic material resembles soft cheese
 CALCIFICATION:
 Even when healing takes place, viable bacilli may remain
dormant within macrophages or in the necrotic material and these
“healed” lesions in the lung parenchyma and hilar lymph nodes
may later undergo calcification
Dr.Mukesh Sah

15. PATHOGENESIS and
IMMUNITY:
 In a minority of patients, the macrophage-activating
response is weak, and mycobacterial growth can be
inhibited only by intensified DTH reactions, which lead to
TISSUE DESTRUCTION:
 The lesions enlarge and the surrounding tissue is
progressively damaged
 At the center of the lesion, the caseous material liquefies
 Bronchial walls and blood vessels are invaded and destroyed
 Cavities are formed
 The liquefied caseous material, containing large numbers
of bacilli, is drained through bronchi
 Within the cavity, tubercle bacilli multiply and spread into
the airways and the environment through expectorated
sputum
Dr.Mukesh Sah

16. PATHOGENESIS and
IMMUNITY:
2 Types of cells are essential in cell-mediated immunity against M.
tuberculosis:
 (1) MACROPHAGES – directly phagocytize tubercle bacilli and
secrete the following cytokines:
 A. INTERLEUKIN (IL)-1 – contributes to fever
 B. INTERLEUKIN (IL)-6 – contributes to hyperglobulinemia
 C. TUMOR NECROSIS FACTOR (TNF)- α – contributes to the
killing of mycobacteria, the formation of granulomas, and a
number of systemic effects (fever and weight loss)
 (2) T CELLS (mainly CD4+ lymphocytes) – also produce
cytokines
 A. TH1- promote cell-mediated immunity; participate in MHC
Class II-restricted killing of cell infected with M. tuberculosis
 (a) INTERFERON (IFN)-γ – induce release of nitric oxide
 (b) INTERLEUKIN (IL)-2
 B. TH2 – produce IL-4, IL-5 and IL-10 and promote humoral
immunity
Dr.Mukesh Sah

17. PATHOGENESIS and
IMMUNITY:
 Coincident with the appearance of immunity, DTH to
M. tuberculosis develops
 This reactivity is the basis of the PPD skin test, which is
used primarily for the detection of M. tuberculosis
infection in persons without symptoms
 The cellular mechanism responsible for PPD reactivity
are related mainly to previously sensitized CD4+
lymphocytes, which are attracted to the skin-test site
where they proliferate and produce cytokines
 While DTH is associated with protective immunity
(PPD-positive persons being less susceptible to a
new M. tuberculosis infection than PPD-negative
persons), it by no means guarantees protection
against reactivation
Dr.Mukesh Sah

18. I. PULMONARY
TUBERCULOSIS:
A. PRIMARY DISEASE:
 Often seen in children and is frequently localized to the middle
and lower lung zones
 The lesion forming after infection is usually peripheral and
accompanied by hilar or paratracheal lymphadenopathy
 In the majority of cases, the lesion heals spontaneously and may
later be evident as a small calcified nodule (GHON LESION)
 CLINICAL MANIFESTATIONS:
 In children and persons with impaired immunity (malnutrition, HIV
infection), primary PTB may progress rapidly to clinical illness
 Pleural effusion- results from penetration of bacillli into the pleural
space from an adjacent subpleural focus
 Progressive primary tuberculosis- the primary site rapidly enlarges,
its central portion undergo necrosis, and acute cavitation develops
 Hilar or mediastinal lymphadenopathy – due to the spread of bacilli
from the lung parenchyma through lymphatic vessels
 Hematogenous dissemination into various organs producing
granulomatous lesions
 Although healing frequently takes place, immunocompromised persons
may develop miliary TB and/or tubeculous meningitis
Dr.Mukesh Sah

19. I. PULMONARY
TUBERCULOSIS:
B. POSTPRIMARY DISEASE:
 Also called adult-type, reactivation or secondary TB
 Results from endogenous reactivation of latent infection and is
usually localized to the apical and posterior segments of the
upper lobes, as well as the superior segments of the lower lobes,
where the high oxygen concentration favors mycobacterial
growth
 CLINICAL MANIFESTATIONS:
 Early in the course of the disease: fever, night sweats, weight
loss, anorexia, malaise and weakness
 Cough- initially non-productive and subsequently accompanied
by the production of purulent sputum, sometimes with blood
streaking
 Hemoptysis- results from erosion of a fully patent vessel located
in the wall of a cavity, or due to rupture of a dilated vessel in a
cavity (Rasmussen’s aneurysm), or from aspergilloma formation
in an old cavity
 Pleuritic chest pain, dyspnea and (occasionally) ARDS
 The most common hematologic findings are mild anemia and
Dr.Mukesh Sah

20. II. EXTRAPULMONARY
TUBERCULOSIS:
In order of frequency, the extrapulmonary sites
most commonly involved in TB are:
 (1) lymph nodes
 (2) pleura
 (3) genitourinary tract
 (4) bones and joints
 (5) meninges
 (6) peritoneum
 (7) pericardium
Dr.Mukesh Sah

21. LYMPH NODE TUBERCULOSIS
(Tuberculous Lymphadenitis):
 25% of all cases of extrapulmonary TB
 Particularly frequent among HIV-infected patients
 Due largely to M. tuberculosis
 Present as painless swelling of the lymph nodes, most
commonly at cervical and supraclavicular sites
(SCROFULA)
 Diagnosis is established by FNA or surgical biopsy
 (+) AFB in up to 50%
 (+) cultures in 70-80%
 Histologic examination shows granulomatous lesions
Dr.Mukesh Sah

22. PLEURAL TUBERCULOSIS:
Common in primary TB and results from penetration of
tubercle bacilli into the pleural space
 Depending on the extent of reactivity, the effusion may
be small, remain unnoticed, and resolve spontaneously
or may be sufficiently large to cause symptoms (fever,
pleuritic chest pain, dyspnea)
 PE of pleural effusion: dullness to percussion and
absence of breath sounds
 Thoracentesis- required to ascertain the nature of the
effusion
 Fluid may be straw colored or hemorrhagic
 EXUDATE:
 (1) protein concentration > 50% of that in serum
 (2) normal to low glucose concentration
 (3) pH < 7.2
 (4) detectable WBCs (500 – 2500/ uL)
Dr.Mukesh Sah

23. PLEURAL TUBERCULOSIS:
 Needle biopsy is often required for diagnosis and reveals
granulomas and/or yields a (+) culture in 70% of cases
 Responds well to chemotherapy and may resolve
spontaneously; the usefulness of glucocorticoids is debatable
 TUBERCULOUS EMPYEMA:
 A less common complication
 Results from the rupture of a cavity with delivery of a large
number of organisms into the pleural space, or of a
bronchopleural fistula from a pulmonary lesion
 CXR: pyopneumothorax with an air-fluid level
 The effusion is purulent and thick and contains large numbers of
lymphocytes, with (+) acid-fast smear and (+) culture of pleural
fluid
 Surgical drainage is required as adjunct to chemotherapy
 May result in severe pleural fibrosis and restrictive lung disease
Dr.Mukesh Sah

24. TUBERCULOSIS of the UPPER
AIRWAYS:
 Always a complication of advanced cavitary
pulmonary TB
 Involves the larynx, pharynx and epiglottis
 SYMPTOMS:
 Hoarseness
 Dysphagia
 Chronic productive cough
 DIAGNOSIS:
 Acid-fast smear of the sputum
 Biopsy
Dr.Mukesh Sah

25. GENITOURINARY
TUBERCULOSIS:
 15% of cases of extrapulmonary TB
 Due to hematogenous seeding following primary infection
 Local symptoms: frequency, dysuria, hematuria, flank pain
 The documentation of culture-negative pyuria in acidic urine
raises the suspicion of TB
 Culture of 3 morning urine specimen yields a definite diagnosis
(90%)
 GENITAL TB:
 Diagnosed more commonly in females and affects the fallopian
tubes and endometrium
 Symptoms: infertility, pelvic pain, menstrual abnormalities
 Diagnosis: requires biopsy or culture of specimen obtained by
D&C
 In males, TB preferentially affects the epididymis, producing a
slightly tender mass that may drain externally through a fistulous
tract, orchitis or prostatitis
 GUT TB responds well to chemotherapy
Dr.Mukesh Sah

26. SKELETAL TUBERCULOSIS:
 PATHOGENESIS:
 Reactivation of hematogenous foci
 Spread from adjacent paravertebral lymph nodes
 WEIGHT-BEARING JOINTS (spine, hips, knees) are
affected most commonly
 CLINICAL MANIFESTATIONS:
 SPINAL TB (POTT’S DISEASE or TUBERCULOUS
SPONDYLITIS)
 Involves 2 or more adjacent vertebral bodies
 Most common site in children: upper thoracic spine
 Adults: lower thoracic and upper lumbar vertebrae
Dr.Mukesh Sah

27. SKELETAL TUBERCULOSIS:
 CLINICAL MANIFESTATIONS:
 KYPHOSIS (GIBBUS)- due to collapse of vertebral bodies
with advanced disease
 PSOAS ABSCESS- paravertebral “cold” abscesses in the
lower spine which reach the inguinal ligament
 PARAPLEGIA- a catastrophic complication of Pott’s disease
usually due to an abscess or a lesion compressing the spinal
cord
 PARAPARESIS- a medical emergency due to a large
abscess that requires drainage
 Skeletal TB responds to chemotherapy but severe cases
may require surgery
Dr.Mukesh Sah

28. TUBERCULOUS MENINGITIS and
TUBERCULOMA:
 Seen most often in young children but also develops in adults
infected with HIV
 TUBERCULOUS MENINGITIS:
 Results from the hematogenous spread of primary or postprimary
pulmonary disease or from the rupture of a subependymal
tubercle into the subarachnoid space
 CLINICAL MANIFESTATIONS:
 Typically evolves over 1-2 weeks
 Headache, mental changes or as confusion, lethargy, altered sensorium
and neck rigidity
 Paresis of cranial nerves (ocular nerves in particular) is a frequent finding,
and involvement of cerebral arteries may produce focal ischemia
 Hydrocephalus
 DIAGNOSIS:
 Lumbar puncture is the cornerstone for diagnosis
 CSF:
 High leukocyte count (predominance of neutrophils in the early stage
then lymphocytes)
 Protein content of 1-8 g/L (100 to 800 mg/dL)
 Low glucose concentration
Dr.Mukesh Sah

29. TUBERCULOUS MENINGITIS and
TUBERCULOMA:
 CT or MRI may show hydrocephalus and abnormal
enhancement of basal cisterns or ependyma
 TREATMENT:
 The disease responds to chemotherapy; however, neurologic
sequelae are documented in 25% of treated cases
 If unrecognized, tuberculous meningitis is fatal
 Glucocorticoids (Dexamethasone 12 mg/d for 4-6 weeks)
enhance the chances of survival and reduce the frequency of
neurologic sequelae
 TUBERCULOMA:
 An uncommon manifestation of TB presenting as 1 or
more space-occupying lesions and usually causes
seizures and focal signs
 CT or MRI reveals contrast-enhanced ring lesions, but
biopsy is necessary to establish the diagnosis
Dr.Mukesh Sah

30. GASTROINTESTINAL
TUBERCULOSIS:
 Any portion of the GIT may be affected
 Various pathogenic mechanisms are involved:
 (1) swallowing of sputum with direct seeding
 (2) hematogenous spread
 (3) ingestion of milk from cows affected by bovine TB (rare)
 TERMINAL ILEUM and CECUM- sites most commonly involved
 SYMPTOMS: abdominal pain, diarrhea, obstruction,
hematochezia, a palpable mass in the abdomen, fever, weight
loss and night sweats
 DIAGNOSIS: As surgery is required in most cases, the diagnosis
can be established by histologic examination and culture of
specimens obtained intraoperatively
 TUBERCULOUS PERITONITIS:
 Follows either the direct spread of tubercle bacilli from ruptured
lymph nodes and intraabdominal organs or hematogenous
seeding
 Nonspecific abdominal pain, fever and ascites
 DIAGNOSIS:
 Paracentesis reveals EXUDATIVE fluid (high protein content,
leukocytosis with lymphocytic predominance
Dr.Mukesh Sah

31. PERICARDIAL TUBERCULOSIS
(Tuberculous Pericarditis) :
 Often a disease of the elderly in countries with low TB prevalence and in
HIV-infected patients
 Usually due to:
 (1) direct progression of a primary focus within the pericardium
 (2) reactivation of a latent focus
 (3) rupture of an adjacent lymph node
 CLINICAL MANIFESTATIONS:
 Onset may be subacute or acute (fever, dull retrosternal pain, friction rub)
 Effusion eventually develops and cardiovascular symptoms and signs of
cardiac tamponade may ultimately appear
 DIAGNOSIS:
 Pericardiocentesis under echocardiographic guidance
 The effusion is EXUDATIVE in nature
 Culture of the fluid reveals M. tuberculosis (30%), while biopsy has a
higher yield
 COMPLICATIONS: chronic constrictive pericarditis with thickening of
the pericardium, fibrosis and calcification
 TREATMENT: Prednisone 20 to 60mg/d for up to 6 weeks
Dr.Mukesh Sah

32. MILIARY or DISSEMINATED
TUBERCULOSIS:
 Miliary TB is due to hematogenous spread of tubercle bacilli
 Lesions are usually yellowish granulomas 1-2 mm in diameter
that resemble millet seeds (thus the term miliary, coined by 13th
century pathologists)
 CLINICAL MANIFESTATIONS: nonspecific and protean,
depending on the predominant site of involvement
 PE: hepatomegaly, splenomegaly, lymphadenopathy, and eye
examination may reveal CHOROIDAL TUBERCLES which are
pathognomonic of miliary TB (30%)
 DIAGNOSIS:
 CXR: miliary reticulonodular pattern, large infiltrates, interstitial
infiltrates (HIV), pleural effusion
 Sputum smear is (-) in 80% of cases
 Hematologic abnormalities
 Elevated alkaline phosphatase levels
 BAL and transbronchial biopsy are most likely to permit
bacteriologic confirmation, and granulomas are evident in liver or
bone marrow biopsy specimens
Dr.Mukesh Sah

33. MILIARY or DISSEMINATED
TUBERCULOSIS:
 CRYPTIC MILIARY TUBERCULOSIS:
 A rare presentation seen in the elderly which has a
chronic course
 Characterized by mild intermittent fever, anemia, and
ultimately, meningeal involvement preceding death
 NONREACTIVE MILIARY TUBERCULOSIS:
 An acute septicemic form which occurs very rarely
 Due to massive hematogenous dissemination of tubercle
bacilli
 Pancytopenia is common
 At postmortem examination, multiple necrotic but non-
granulomatous (“nonreactive”) lesions are detected
Dr.Mukesh Sah

34. HIV-Associated
TUBERCULOSIS:
 TB is an important opportunistic disease among HIV-
infected persons
 TB can appear at any stage of HIV infection, and its
presentation varies with the stage
 The diagnosis of TB may be unusually difficult due to
the following:
 (1)Sputum smears may be positive less frequently
among TB patients with HIV infection
 (2) Radiographic findings are atypical (e.g., lower zone
infiltrates without cavity formation)
 (3) There is a lack of classic granuloma formation in the
late stages
 (4) Negative results in PPD skin tests
 Extrapulmonary TB is common, and the most
common forms are lymphatic, disseminated, pleural
and pericardial
Dr.Mukesh Sah

35. DIAGNOSIS:
1. AFB MICROSCOPY:
 For patients with suspected PTB, 2 sputum specimens,
preferably collected early in the morning, should be
submitted to the laboratory for AFB smear and
mycobacteriology culture
2. MYCOBACTERIAL CULTURE:
 Definitive diagnosis depends on the isolation and
identification of M. tuberculosis from a sputum specimen
obtained from a patient with productive cough
 Specimens may be inoculated onto egg- or agar-based
medium (e.g., Lowenstein-Jensen or Middlebrook 7H10)
and incubated at 37 C under 5% CO2
 4-8 weeks may be required before growth is detected
Dr.Mukesh Sah

36. DIAGNOSIS:
3. NUCLEIC ACID AMPLIFICATION:
 These systems permit the diagnosis of TB in as little a
several hours
 Applicability is limited by low sensitivity (lower than
culture, but higher than AFB smear microscopy) and
high cost
 At present, these tests are most useful for the rapid
confirmation of TB in persons with AFB-positive sputa
4. DRUG SUSCEPTIBILTY TESTING:
 In general, the initial isolate of M. tuberculosis should be
tested for susceptibilty to isoniazid, rifampicin and
ethambutol
 Expanded susceptibility testing is mandatory when
resistance to 1 or more of anti-TB drugs is found, or if
the patient either fails to respond to initial therapy or has
a relapse after the completion of treatment
Dr.Mukesh Sah

37. DIAGNOSIS:
 5. RADIOGRAPHIC PROCEDURES:
 The initial suspicion of PTB is often based on abnormal chest
radiographic findings in a patient with respiratory symptoms
 The “classic” picture is that of upper lobe disease with infiltrates
and cavities
 6. PPD SKIN TESTING and DIAGNOSIS of LATENT TB
INFECTION:
 Most widely used in screening for M. tuberculosis infection
 Positive reactions are obtained when patients have been infected
with M. tuberculosis but do not have active disease and when
persons have been sensitized by non-tuberculous bacteria or
Bacille Calmett-Guerin (BCG) vaccination
 In the absence of a history of BCG vaccination, a positive skin
test may provide additional support for the diagnosis of TB in
culture-negative cases
 7. CYTOKINE RELEASE ASSAYS:
 QuantiFERON TB TEST- recommended for screening for latent
TB infection in populations at low to moderate risk of TB
Dr.Mukesh Sah

38. TREATMENT:
RECOMMENDED DOSAGE for INITIAL
TREATMENT of TUBERCULOSIS in ADULTS:
DRUG DAILY DOSE 3x
WEEKLY DOSE
ISONIAZID 5mg/kg, max 300mg 15 mg/kg,
max 900mg
RIFAMPICIN 10mg/kg, max 600mg 10mg/kg, max
600 mg
PYRAZINAMIDE 20-25mg/kg 30-40mg/kg, max
3g
max 2g
Dr.Mukesh Sah

39. TREATMENT:
 SECOND-LINE DRUGS:
 Injectable drugs: Streptomycin, Kanamycin,
Amikacin, Capreomycin
 Oral agents: Ethionamide, Cycloserine, PAS,
Fluoroquinolones (Levofloxacin, Gatifloxacin,
Moxifloxacin)
 THIRD-LINE AGENTS:
 Clofazimine, Amithiozone, Amoxicillin/Clavulanic
acid, Linezolid
Dr.Mukesh Sah

40. TREATMENT:
Short-course regimens are divided into:
 (1) INITIAL (Bactericidal) PHASE:
 During this phase, the majority of the tubercle bacilli are killed,
symptoms resolve, and the patient becomes non-infectious
 2 months of isoniazid, rifampicin, pyrazinamide and
ethambutol
 (2) CONTINUATION (Sterilizing) PHASE:
 This phase is required to eliminate persisting mycobacteria
and prevent relapse
 4 months of isoniazid and rifampin
 To prevent isoniazid-related neuropathy, PYRIDOXINE
(10-25 mg/d) should be added to the regimen given to
persons at high risk of vitamin B6 deficiency (e.g.,
alcoholics; malnourished persons; pregnant and lactating
women; patients with CRF, DM, HIV infection or AIDS)
Dr.Mukesh Sah

41. RECOMMENDED
ANTITUBERCULOSIS TREATMENT
REGIMENS:
Dr.Mukesh Sah

42. MONITORING TREATMENT
RESPONSE:
 SPUTUM CULTURE:
 Patients with pulmonary disease should have their sputum
examined monthly until cultures become negative
 Patients with cavitary disease who do not achieve sputum
culture conversion by 2 months require extended treatment
 When sputum cultures remain positive at > 3months,
treatment failure and drug resistance should be suspected
 AFB SMEAR EXAMINATION:
 AFB smear examination should be undertaken at 2, 5 and 6
months
 Smears positive after 5months are indicative of treatment
failure
 Monitoring of the response to treatment during
chemotherapyby serial chest radiographs is not
recommended, as radiographic changes may lag behind
bacteriologic response and are not highly sensitive
Dr.Mukesh Sah

43. MONITORING DRUG TOXICITY:
 HEPATITIS :
 The most common adverse reaction of significance
 Patients should be educated about the signs and
symptoms of drug-induced hepatitis (e.g., dark urine,
loss of appetite)
 All adult patients should undergo baseline assessment
of liver function (e.g., serum aminotransferases and
bilirubin)
 For patients with symptomatic hepatitis and those with
marked (5-6-fold) elevations in serum levels of aspartate
aminotransferase, treatment should be stopped and
drugs reintroduced one at a time after liver function has
returned to normal
 HYPERSENSITIVITY REACTIONS:
 Usually require the discontinuation of all drugs and
rechallenge to determine which agent is the culprit
Dr.Mukesh Sah

44. MONITORING DRUG TOXICITY:
 HYPERURICEMIA and ARTHRALGIA:
 Caused by pyrazinamide; can be managed by the administration
of acetylsalicylic acid
 If gouty arthritis develops, pyrazinamide treatment should be
stopped
 AUTOIMMUNE THROMBOCYTOPENIA:
 Secondary to rifampin therapy; patients should not receive the
drug thereafter
 OPTIC NEURITIS:
 Due to ethambutol treatment; indication for permanent
discontinuation of the drug
 Other common manifestations of drug intolerance, such as
PRURITUS and GASTROINTESTINAL UPSET, can generally be
managed without the interruption of therapy
Dr.Mukesh Sah

45. TREATMENT FAILURE and
RELAPSE:
 TREATMENT FAILURE :
 suspected when sputum cultures remain positive after 3
months or when AFB smears remain positive after 5 months
 The isolate should be tested for susceptibility to 1st- and 2nd-
line agents
 When the results of susceptibility testing are expected to become
available within a few weeks, changes in the regimen can be
postponed at that time
 If the patient’s clinical condition is deteriorating, an earlier change in
regimen may be indicated
 The cardinal rule is to add more than 1 drug at a time to a failing
regimen; at least 2 and preferably 3 drugs to which the bacilli are likely
to be susceptible should be added, along with isoniazid and rifampin
 TREATMENT RELAPSE:
 It is prudent to begin the treatment of all relapses with all first-
line drugs pending the results of susceptibility testing
Dr.Mukesh Sah

46. HIV-Associated TUBERCULOSIS:
3 Important considerations relevant to TB treatment in HIV-infected
patients:
 (1) AN INCREASED FREQUENCY OF PARADOXICAL REACTIONS
 PARADOXICAL REACTIONS – exacerbations in symptoms, signs and
laboratory or radiographic manifestations of TB associated with the
administration of HAART regimens
 The first priority in the management of a possible paradoxical reaction is
to ensure that the clinical syndrome does not represent a failure of TB
treatment or the development of another infection
 Mild paradoxical reactions can be managed with symptom-based
treatment; glucocorticoids have been used for more severe cases
 (2) DRUG INTERACTIONS BETWEEN HAART AND RIFAMYCINS
 Rifampin, a potent inducer of enzymes of the cytochrome P450 system,
lowers the serum levels of many HIV protease inhibitors and some
mononucleoside reverse transcriptase inhibitors, drugs used in HAART
regimens; Rifabutin has been recommended in place of rifampin
 (3) DEVELOPMENT OF RIFAMPIN MONORESISTANCE WITH
WIDELY SPACED INTERMITTENT TREATMENT
 Patients with advance immunosuppression (CD4+ cell counts <100) are
prone to treatment failure and relapse with rifampin-resistant organisms
when treated with “highly intermittent” (i.e., once- or twice-weekly)
rifamycin-containing regimens
Dr.Mukesh Sah

47. DRUG-RESISTANT
TUBERCULOSIS:
 DRUG-RESISTANT TUBERCULOSIS:
 The result of MONOTHERAPY- i.e., the failure of the health
care provider to prescribe at least 2 drugs to which tubercle
bacilli are susceptible or of the patient to take properly
prescribed therapy
 PRIMARY DRUG RESISTANCE- resistance in a strain
infecting a patient who has not previously been treated
 ACQUIRED RESISTANCE – develops during treatment
with an inappropriate regimen
 Drug-resistant TB can be prevented by adherence to the
principles of sound therapy: the inclusion of at least 2
bactericidal drugs to which the organism is susceptible and
the verification that patients complete the prescribed
course.
Dr.Mukesh Sah

48. SPECIAL CLINICAL
SITUATIONS:
PEDIATRIC PATIENTS:
 The American Academy of Pediatrics recommends
that children with bone and joint TB, tuberculous
meningitis, or miliary TB receive 9-12 months of
treatment
RENAL DISEASE:
 Patients with CRF should not receive
aminoglycosides and should receive ethambutol only
if serum levels can be monitored
 Isoniazid, rifampin and pyrazinamide may be given in
the usual doses in cases of mild to moderate renal
failure, but the dosages of isoniazid and pyrazinamide
should be reduced for all patients with severe renal
failure except those undergoing dialysis
Dr.Mukesh Sah

49. SPECIAL CLINICAL
SITUATIONS:
LIVER DISEASE:
 Patients with severe hepatic disease may be treated with
ethambutol and streptomycin, and if required, with isoniazid and
rifampin under close supervision
 The use of pyrazinamide in patients with liver failiure should be
avoided
PREGNANCY:
 The regimen of choice for pregnant women is 9months of
treatment with isoniazid and rifampin supplemented by
ethambutol for the 1st 2months
 When required, pyrazinamide may be given, although there are
no data concerning its safety in pregnancy
 Streptomycin is contraindicated because it is known to cause 8th
cranial nerve damage in the fetus
 Treatment for TB is not a contraindication to breastfeeding
Dr.Mukesh Sah

50. PREVENTION:
BCG VACCINATION:
 BCG vaccine is recommended for routine use at birth in
countries with high TB prevalence
 The local tissue response begins 2-3weeks after
vaccination, with scar formation and healing within 3
months
TREATMENT of LATENT TB INFECTION:
 In most cases, candidates for treatment of latent TB of
persons are identified by PPD skin testing of persons in
defined high-risk groups
 For skin testing, 5 tuberculin units of polysorbate-stabilized
PPD should be injected intradermally into the volar surface
of the forearm (Mantoux method)
 Reactions are read at 48-72 hours as the transverse
diameter in mm of induration
Dr.Mukesh Sah

51. TUBERCULIN REACTION SIZE:
Dr.Mukesh Sah

52. REVISED DRUG REGIMENS for
TREATMENT of LTBI in ADULTS:
Dr.Mukesh Sah

53. BASICS of CONTROL:
 The highest priority in any TB control program is the
prompt detection of cases and the provision of short-
course therapy to all TB patients under proper case
management conditions, including directly observed
therapy, with emphasis on the cure of sputum smear-
positive cases
 In low-prevalence countries with adequate resources,
screening of high risk groups (immigrants from high-
prevalence countries and HIV-seropositive persons) is
recommended
 Identification of active cases of TB should be followed by
treatment
 PPD-positive high-risk persons should be treated for latent
infection
Dr.Mukesh Sah

54. BASICS of CONTROL:
 Measures to limit transmission include:
 (1) respiratory isolation of persons with suspected
TB until they are proven to be non-infectious (i.e.,
by sputum AFB smear negativity)
 (2) proper ventilation in rooms of patients with
infectious TB
 (3) use of UV lights in areas of increased risk of TB
transmission
 (4) periodic screening of personnel who may come
into contact with known or unsuspected cases of TB
Dr.Mukesh Sah

55. BASICS of CONTROL:
In high-prevalence countries, TB control programs should be
based on the following key elements defining the DOTS
strategy provided by the WHO:
 (1) political commitment by the government to sustained
TB control
 (2) case detection through microscopic examination of
sputum from patients who present to health care facilities
with cough of > 2-3 weeks’ duration
 (3) administration of standard short-course chemotherapy
to all sputum smear-positive patients under proper case
management conditions, including direct observation of
drug ingestion
 (4) establishment and maintenance of a system of regular
drug supply
 (5) establishment and maintenance of an effective
surveillance and monitoring system that allows
assessment of treatment outcomes (e.g., cure, completion
of treatment without bacteriologic proof of cure, death,
Dr.Mukesh Sah