Tuberculosis

Department of Internal Medicine

By Dr. Abraham B.(R1)
Mekelle university
Jan 2025

1
 Learning objectives
• Definition
• Epidemiology
• Classification
• Clinical Manifestation
• Diagnosis of tuberculosis
• Basic principle in the management of
tuberculosis, monitoring treatment and drug
side effect plus tuberculosis treatment for
special scenario

2
 Definition

• Tuberculosis is an airborne communicable

disease caused by the members of
M.tuberculosis complex.
• Mycobacterium Tuberculous complex:
 M.Tuberculosis
 M.Bovis
 M.Africanum
 M.Microti
 M.Canetti

3
 Cont,d…
• Tuberculosis (TB), the oldest diseases known to
affect humans
• Tuberculosis is an airborne communicable disease
caused by bacteria from Mycobacterium
tuberculosis complex
-is mainly transmitted to a susceptible person by
inhalation of droplet nuclei containing M.
tuberculosis.
• If properly treated, drug-susceptible strains is
curable in virtually all cases
• If untreated, fatal within 5 years in 50–65% of
cases 4
 Epidemilogy
 According to the global TB report ,2022 10.6 million
people are estimated to have follen ill with TB in 2021.
 Globaly an estimated 3.6% of new TB cases and 18% of
previously treated TB cases were having MDR/RR-TB in
2021.
 Over all total of 450,000 incident MDR/RR-TB cases were
estimated to be emerged in 2021.
 Ethiopia is among the 30 High TB, TB-HIV and MDR-TB
Burden Countries, with annual estimated TB incidence of
119/100,000 populations and death rate of 16/100,000
populations in 2021.
 An estimated 1.1% of new TB cases and 7.5% of previously
treated TB cases had drug resistant TB in 2021 and an
estimated 1800 MDR/RR-TB cases emerging in 2021.
5
 Etiologic agent….
• Mycobacteria belong to:
– Family Mycobacteriaceae
– Order Actinomycetales
– Species belonging to the M. tuberculosis
complex important agent of human disease
is M. tuberculosis
– M. tuberculosis
• Rod-shaped, non spore-forming, thin aerobic bacterium
measuring 0.5 m by 3µm
• Acid-fast bacilli(AFB)mycolic acid

6
7
 Natural History of Disease

• With treatment
– Proper chemotherapy very high chance of being cured
– Improper use of anti-TB drugs chronic infectious cases and
MDR
• Without treatment
– Often fatal
– 5-year mortality rate among sputum smear–positive cases
was 50 to 65%.
– Spontaneous recovery: 10 – 20%
– Chronic, progressive TB: 20-30 %

8
 Contd…
From Exposure to Infection
– Transmission “TB droplet nuclei” aerosolized by
coughing, sneezing, or speaking
– Important determinant for transmission are:
• Intimacy and duration of contact with index case
• Degree of infectiousness of the case
– Cavitary pulmonary disease, laryngeal TB and
produce sputum highly infectious
– Sputum smear–negative/culture-positive TB are
less infectious
– Culture-negative pulmonary TB and extrapulmonary
TB are non infectious
• Shared environment

9
Contd…
From Infection to Disease
– Depends on
• The immunity of the person eg HIV
infection…….
• Age
– Primary vs post primary tuberculosis
– Dormant vs active tuberculosis

10
 Latent and Active TB

 Latent tuberculosis infection (LTBI) .

-refers to the stage where by the immune system of the person halt
the multiplication of the bacilli and tissue damage, and hence, no
symptoms presents
 Active TB disease - refers to the conditions whereby the
person with TB infection starts to present with clinical
presentation of TB that requires full course multi-drug
chemotherapy. It may present as:
-Primary TB: occurs in 5-10% of case when active TB develops
immediately after infection usually within 1-2 years after exposure.
-Common in children and other immunosuppressed individuals
-Post-primary/secondary TB: refers to active TB that is a result of
reactivation of endogenous latent foci, which remained dormant since
the initial infection.

11
RISK FACTORS/ CONDITIONS FOR DEVELOPING ACTIVE TB
13
 Pathogenesis

• Inhalation and deposition in the lungs of

the tubercle bacillus leads to one of four
possible outcomes:
Immediate clearance of the organism
Chronic or latent infection
 Rapidly progressive disease (or primary
disease)
Post primary TB many years after the
infection (reactivation disease)
14
 Clinical Manifestations
• TB anatomically classified as PTB, EPT or both

• Before HIV 80-90% of all new cases of TB were

limited to the lungs
• In HIV era < 70% are pulmonary

• In HIV 2/3(~60% ) TB may have both pulmonary

and extrapulmonary TB or extrapulmonary TB alone

15
 Cont,d….

Pulmonary Tuberculosis
•A persistent and progressive cough, often
accompanied by non-specific systemic symptoms
such as fever, night sweats or loss of weight, is the
commonest presentation of pulmonary tuberculosis.
• A history of household/close contact with a
person with infectious TB, and presence of
documented recent weight loss may indicate the
presence of TB in such patients to warrant
investigation.
 Pulmonary TB
• Category: primary and post primary(secondary or
adult type)

1-Primary Disease: [ child type]

– Occur: initial infection with tubercle bacilli
– Epidemiology: children “in high burden areas”
– Clinically: asymptomatic or with fever and/or chest pain
• Young children with immature CMI and immunocompromized patients
– Lung involvement:
• Initially middle and lower lung

17
 Contd…
2-Postprimary (Adult-Type) Disease
– Reactivation or secondary TB
– Result from endogenous reactivation of distant latent
infection or recent infection (primary infection or reinfection)
– Lung involvement:
• Apical and posterior segments of the upper lobes &
superior segment of lower lobe.

• Ranges: small infiltrates to extensive cavitary disease

18
Con,t

19
Contd…
• Clinical manifestation:
– Early disease
• Sign and symptom non specific
• Diurnal fever and night sweats due to defervesence, weight loss,
anorexia, general malaise, and weakness
– Cough develop late 90%
• Initially nonproductive and morning
• Later
– Purulent sputum, sometimes with blood streaking
– Hemoptysis 20-30%
– Massive hemoptysis
» Rupture of a dilated vessel in a cavity (Rasmussen's
aneurysm)

– Pleuritic chest pain: subpleural parenchymal

lesions or pleural disease
– Dyspnea and ARDS  rare

20
 Extrapulmonary TB
• Virtually all organ systems may be affected
• Incidence
– Immuncompetent 10-15%
– Immunocompromized (HIV/AIDS) upto 60%

• Order of frequency
– 1st -Lymph nodes
– 2nd -Pleura
– 3rd -Genitourinary tract
– 4th -Bones and joints
– 5th –CNS (meningitis and tuberculoma)
– 6th -Peritoneum
– 7th -Pericardium
21
 1-Lymph Node TB (Tuberculous Lymphadenitis)

• caused by lymphatic spread of the organism

• Involvement of the lymph nodes is commoner in children and
in person in the later stages of HIV infection.
• Slowly developing painless Cervical Lymph node enlargement
(regardless of HIV infection) is the commonest sites of
involvement, though axillary and intra-abdominal lymph nodes
may be affected
Clinical presentations
• Initially cervical lymph nodes are firm and discrete, but later
they become matted together and become fluctuant.
• The overlying skin may breakdown with the formation of
abscesses and chronic discharging sinuses, which heal with
scarring.

22
Cont,d….

23
2. Tuberculous pleurisy
• Tuberculous is the commonest cause of a
unilateral pleural effusion.
•It is also the commonest form of HIV-related
extra-pulmonary disease.
•Management of tuberculous pleural effusion should
aim at starting TB treatment promptly and
determining the HIV-status of the patient.
 Con’d…
Clinical features:
 Presentation is most often acute with a non-
productive cough, chest pain, shortness of
breath and high temperature.
 Findings on clinical examination may include:
- Tracheal and mediastinal shift away from the
side of the effusion
- Decreased air entry
- Stony dullness on percussion on the side of the
effusion
 Contd…
• 3-Genitourinary TB
– Accounts 15%

– Due to hematogenous seeding

– Local sx- dysuria, hematuria, frequency, flank pain

– Culture -ve pyuria---→ TB

– IVP

– Calcification and ureteral strictures →hydronephrosis and

renal damage---RF

26
 Contd…
• 4-Skeletal TB
– Bone and joint TB account 10%
– Pathogenesis:
• Hematogenous or from adjacent LN
– Frequency: most weight bearing joint
• Hips in 13% and knees in 10%
– Diagnosis: synovial fluid aspiration, culture or tissue biopsy
• Spinal TB(Pott's disease or tuberculous spondylitis) in 40%
– Two or more adjacent vertebral bodies
– Site
» Lower thoracic and upper lumbar vertebrae adult
» Thoracic spine children
– Features: kyphosis (gibbus), paravertebral "cold" abscess (chest
mass, psoas abscess), paraplegia
– Diagnosis: -CT, MRI
-Aspiration of the abscess or bone biopsy confirms

27
 Contd…
• 5-CNS TB: Tuberculous Meningitis and
Tuberculoma
– Accounts for 5%
– Commonly seen: children and HIV positives

Tuberculous meningitis
• Pathogenesis:
– Hematogenous spread of primary or postprimary
pulmonary TB
• Positive radiography 50%
• Clinical
– Evolve in 1-2 weeks “subacute meningitis” headache and slight
mental changes after a prodrome of weeks of low-grade fever,
malaise, anorexia, and irritability
– Complications
» Involve base of the brain “basal meningitis” ocular nerves
paresis in particular
» Focal ischemic(vasculitis) involvement of cerebral arteries
» Coma hydrocephalus and intracranial hypertension 28
Cont…
Diagnosis
• Lumbar puncture(CSF analysis)
• Leukocytosis with lymphocytic predominance
• Protein content of 1–8 g/L (100–800 mg/dL)
• Low glucose concentration
• AFB positive in third, yield increase with repetition
• Culture 80% “gold standard”
• Not treated uniformly fatal
• Neurologic squeal are documented in 25% of treated cases
• Corticosteroid treatment

29
Contd…
Tuberculoma
• Brain or spinal involvement
• Clinically:
– One or more space-occupying lesions
– Brain: causes seizures and focal signs
• Diagnosis:
– CT or MRI reveals contrast-enhanced ring lesions
– Biopsy is necessary to establish the diagnosis

30
 6. Gastrointestinal TB

• Uncommon, account 3.5%

• Common site: terminal ileum and the cecum

• Source-swallowing sputum, unpasteurized milk, hematogenous
• Common- cecum/ileum
• Clinical picture -depends on the organ
o Hepatobilliary -jaundice,hepatomegaly
o Spleen -Splenomegaly
o Abdominal pain, diarrea,constipation
o Hematochezia
o Fever, weight loss, night sweat, anal fistula
o Ascites(peritonitis),lymph node
DX- Abd U/S,C/T,MRI / peritoneal fluid analysis-Cell count, AFB ,culture,
peritoneal biopsy
–
31
 Contd…
• 7-Pericardial TB (Tuberculous Pericarditis)
– Generally not common: elderly and HIV positives
– Pathogenesis
• Adjacent mediastinal or hilar lymph nodes or to hematogenous
spread
– Clinically
• Subacute to chronic
• Dyspnea, fever, dull retrosternal pain, and a pericardial friction rub
• Feature of cardiac tamponade
– Diagnosis
• High index “pericardial effusion” with
– High-risk population: HIV, high prevalence area
– Evidence of previous TB in other organs
– If echocardiography, CT, or MRI shows effusion and thickness
across the pericardial space

32
Contd…
8. Miliary or Disseminated TB
– Miliary TB is due to hematogenous spread of tubercle
bacilli
• Yellowish granulomas 1–2 mm in diameter that resemble millet seeds
• Children: from primary
• Adult: either recent infection or reactivation of old disseminated foci
– Clinical manifestations
• Nonspecific (Fever, night sweats, anorexia, weakness, and weight loss)
• Commonly: Hepatomegaly, splenomegaly, and lymphadenopathy
– Eye examination choroidal tubercles, pathognomonic of miliary
TB, in up to 30% of cases
– Meningismus occurs in <10% of cases
– meningism a condition in which there are signs of
meningeal irritation suggesting meningitis, but where
there is no pathological change in the cerebrospinalfluid

33
Contd…

– Chest radiography
• Miliary infiltrate
• Normal: early, HIV infected
• Other interstitial/nodular infiltrate, pleural effusion
– Sputum smear microscopy is negative in 80% of cases
– Hematologic abnormalities
• Anemia with leukopenia, lymphopenia, neutrophilic leukocytosis
and leukemoid reactions, and polycythemia
– TST may be negative in up to half of cases
– Bronchoalveolar lavage and transbronchial biopsy are
more likely to provide bacteriologic confirmation

34
Con,t

35
 Diagnosis
• The key to the diagnosis of TB is a high index of
suspicion
• Clinical symptoms
– General non-specific systemic symptoms:
• weight loss, fatigue, malaise, fever, night sweating, anorexia
– Organ specific symptoms

• Case definition:
– TB suspect: any person with cough of two weeks or more
– A case of TB: a definite case of TB or health care provide
decide to treat as TB with full course
– A definite/proven case of TB: one sputum smear positive
or culture positive for MTB

36
 Contd….
• Diagnostic method
– Bacteriologic method
1. Direct light microscopy/conventional microscopy
• Sputum microscopy: 2 sputum sample “national Ethiopia guideline”
• Smear Microscopy-it is cheap, simple, produces rapid &
reliable results:Two staining methods can be used to identify
acid-fast bacilli:
-Ziel-Neelsen staining (ZN) - has low sensitivity (40-60%)
and requires 5,000-10,000 bacilli per ml of sputum to get positive
results
-Fluorescent auramine staining (LED FM)
-requires less time for slide reading and has additional 10%
sensitivity over ZN microscopy to identify bacillus

37
Contd…
2 . Culture
-Gold standard technique
– Can detect a minimum of 10-100 bacilli per ml of sputum.
– sensitivity=80%,specificity=98%

– Culture with DST MDR

3. Molecular test
-Gene Xpert MTB/RIF
– Rapid DNA test for TB
– Indicated: high burden with MDRTB and TB/HIV
– Useful for diagnosis of TB in children and extrapulmonary

38
Contd….

– Histo-pathologic diagnosis
• FNAC: from accessible mass
• Aspiration of effusion
• Biopsy: serous membrane, body tissue, skin, endometrium
…….

– Radiographic examination

39
40
Contd…
• Classification of
tuberculosis – History of previous
– Anatomical site: treatment
• Pulmonary • New patient
• Extrapulmonary • Relapse
• Treatment failure
– Bacteriological result: • Return after default
• Smear positive • Transfer in
• Smear negative – HIV status of the patient
• Extrapulmonary • Smear positive
• Smear negative
• Extrapulmonary

41
 Treatment of tuberculosis
• Aim of TB treatment:
– To cure patient and restore quality of life
– To prevent death from active TB or its late effect
– To prevent relapse of TB
– To prevent development and transmission of drug
resistance
– To decrease TB transmission to others

• Anti- TB drugs
– Appropriate combination of drugs
– Prescribe proper dosage of drugs
– Taken regularly by patient
– Taken for sufficient period of time

42
 Contd….
• Chemotherapeutic drugs for TB are:
First line “Ethiopia”
• Rifampicin(R)
• Isoniazide(H)
• Pyrazinamide(Z)
• Ethambutol(E)
• Streptomycin(S)
– FDC: RHZE, RHZ, RH, EH
– Drug available as lose form: E, H and S

• Monitoring: DOTs

43
Contd…
• Phase of therapy
– Intensive(initial) phase
• New case: four drug 8weeks
• Aim: to make patient non infectious(2-3weeks)

– Continuation phase
• New case: 2 drugs for 4 months

44
46
 Drug-Resistant TB
• Mono drug resistant
– Resistance to INH or RIF but not both
• Polydrug resistant
– Resistance to antiTB drugs other than INH and RIF
• Multidrug resistant(MDR)
– Resistance to both INH and RIF but not to second line
antiTB drugs
• XDR
– Resistant to all fluoroquinolones and to at least one of
three second-line injectable agents (amikacin,
kanamycin, and capreomycin)

47
 REFFERENCES

• Harrison principle of Internal medicine 21ST

Edtion
• UPToDate 2024
• Ethiopia National guideline TB/Leprosy 2021

48
Thank You

49