This document provides an overview of tuberculosis (TB), a disease caused by mycobacteria, primarily affecting humans and transmitted through airborne droplets. It discusses the disease's epidemiology, pathogenesis, clinical features, and connections to HIV, highlighting the complexities in diagnosing and managing the infection. The text also addresses the various forms of TB, including primary, secondary, and extrapulmonary TB, along with diagnostic approaches and treatment options.

1. Tuberculosis
Dr. Mutaz Ibrahim M. Nur

2. • A disease caused by mycobacteria and can
involve many different organs.
• Mycobacteria are slender, aerobic rods (bacilli)
• A waxy cell wall composed of mycolic acid
• Acid fast (AAFB)
• Weakly positive with Gram stain

3. Tuberculosis
• M. tuberculosis
• The reservoir of infection is humans with
active tuberculosis
• Oropharyngeal and intestinal tuberculosis
• M. bovis from infected cows milk

4. Geographical distribution

5. Epidemiology
• After HIV, tuberculosis is the leading infectious cause
of death in the world
• Poverty, crowding, and chronic debilitating illness
– Diabetes mellitus,
– Hodgkin's lymphoma,
– Chronic lung disease (particularly silicosis),
– Chronic renal failure,
– Malnutrition,
• Alcoholism, and Immunosuppression
• HIV and M. tuberculosis

6. • Infection Vs Disease
• Person-to-person transmission
• Airborne droplets of organisms from an active case
to a susceptible host
• Primary tuberculosis: usually asymptomatic
• Fibrosis and calcification.
• Organisms may remain dormant for decades.
• Reactivation to produce communicable and
potentially life-threatening disease (secondary)

7. • Infection is followed by delayed
hypersensitivity to M. tuberculosis antigens.
• The Tuberculin test.
• 2 to 4 weeks after infection, intracutaneous
injection of purified protein derivative of M.
tuberculosis (PPD) induces a visible and
palpable induration that peaks in 48 to 72
hours.

8. • A positive test does not differentiate between infection and
disease.
• False-negative
– Viral infections,
– Sarcoidosis,
– Malnutrition,
– Hodgkin disease,
– Immunosuppression, and
– Overwhelming active tuberculous disease.
• False-positive reactions may result from infection by
atypical mycobacteria.

9. Pathogenesis
• Immunocompetent Vs immunocompromised
host.
• Sensitisation Vs 1st
encounter
• Cell-mediated immunity
• The effector cells that mediate immunity also
mediate hypersensitivity and tissue
destruction
• Caseating granulomas and cavitation

11. • The issue of hypersensitivity and immunity to
the organism!!
• Loss of hypersensitivity (tuberculin negativity
in a previously tuberculin-positive individual)
may be a sign that resistance to the organism
is lost.

12. Pathogenesis
• Macrophages
• Early in infection, the bacilli replicate
unchecked
• Later, the T-helper response stimulates
macrophages to contain the proliferation of
the bacteria.

13. Pathogenesis
• M. tuberculosis enters macrophages
• Replicates within them
• Early in primary tuberculosis (<3 weeks) in the
nonsensitized individual there is proliferation of
bacteria in the alveolar macrophages and
airspaces
• Bacteremia and seeding of multiple sites.
• However, most patients at this stage are
asymptomatic or have a mild flulike illness.

14. Pathogenesis
• About 3 weeks after infection, a TH1 response
against M. tuberculosis is mounted
• Macrophages become bactericidal
• Mature TH1 cells, in lymph nodes and in the
lung, produce IFN-γ
• The TH1 response also leads to the formation
of granulomas and caseous necrosis

15. Pathogenesis
• This response contains the bacteria
• In some people, the infection progresses and
the ongoing immune response results in tissue
destruction due to caseation and cavitation

16. To summarize
• Immunity to M. tuberculosis is mediated by TH1 cells,
which stimulate macrophages to kill the bacteria.
• This immune response comes at the cost of
hypersensitivity and the accompanying tissue
destruction.
• Reactivation or re-exposure in a previously sensitized
host results in rapid mobilization of a defensive
reaction but also increased tissue necrosis.

17. Clinical Features

18. Primary tuberculosis
• Unexposed, and therefore unsensitized, person
• Clinically significant in only 5%
• Loss of immunity (elderly and profoundly
immunosuppressed ) may result in the
development of primary TB more than once
(i.e. Loss of sensitization)
• The source of the organism is exogenous

19. Primary tuberculosis
• Primary pulmonary TB.
• Primary intestinal TB.

20. Primary tuberculosis
• Latent disease in most of the cases.
• Some progress (progressive primary
tuberculosis ):
• Resembles an acute bacterial pneumonia
• Lower and middle lobe consolidation (not
apical), hilar adenopathy, and pleural effusion
• Cavitation is rare

21. Clinical Features

22. Primary tuberculosis
• Lymphohematogenous dissemination
• Tuberculous meningitis and miliary
tuberculosis (may also follow pregression of
secondary TB)

23. Secondary tuberculosis
• In a previously sensitized host
• Reactivation
• Usually many decades after initial infection
• Weakened host resistance
• Exogenous reinfection

24. Secondary tuberculosis
• Reactivation is more common in low-
prevalence areas, while reinfection plays an
important role in regions of high prevalence

25. Secondary tuberculosis
• Apex of the upper lobes of one or both lungs
• High oxygen tension promotes growth of the
bacteria
• Pre-existence of hypersensitivity
• Prompt and marked tissue response
• Localisation of infection

26. Secondary tuberculosis
• Lymph nodes are less prominently involved
• Cavitation; results in
• Dissemination of mycobacteria along the
airways
• Source of infection when the patient coughs
up

27. Secondary tuberculosis
• Localized secondary tuberculosis may be
asymptomatic, or
• Insidious onset
• Malaise, anorexia, weight loss,
• Fever: low grade and remittent (appearing late
each afternoon and then subsiding), and
• Night sweats
• Sputum, at first mucoid and later purulent

28. • Hemoptysis
• Pleuritic pain
• Differential diagnosis??!!

29. Extrapulmonary TB
• Reactivation of dormant bacilli
• The GIT: ileocaecal, ascites
• The kidneys
• The epididymis
• Salpingitis, tubal abscesses and infertility in
females.
• Tuberculous meningitis and tuberculomas in
the CNS

30. Extrapulmonary TB
• Septic arthritis and osteomyelitis
• Potts disease of the spine and cold abscesses.
• Lupus vulgaris (TB of the skin)
• Constrictive pericarditis
• Adrenal TB, causing Addison’s disease.

31. Extrapulmonary TB
Tuberculous lymphadentitis
• Is common
• Hilar and paratracheal lymph nodes are the most
common.
• Initially the nodes are firm and discrete
• Later they become matted and can suppurate with
sinus formation.
• Scrofula =massive cervical lymph node
enlargement with discharging sinuses.

32. TB and HIV infection
• Stage of HIV infection
• Usual secondary TB
• More advanced immunosuppression (CD4+
<200 cells/mm3
): a clinical picture that
resembles progressive primary tuberculosis
(lower and middle lobe consolidation, hilar
lymphadenopathy, and noncavitary disease).
• Extrapulmonary involvement

33. TB and HIV infection
• Sputum-smear negativity for acid-fast bacilli
• False-negative PPD
• Lack of characteristic granulomas in tissues

34. Morphology

35. Primary Tuberculosis
• Pulmonary
• Intestinal; now rare
• Midzonal sub-pleural
• Ghon focus (inflammatory consolidation)
• Central caseous necrosis
• Drain to the regional nodes, which also often
caseate
• Ghon complex (the primary complex)

36. Ghon complex

37. Primary Tuberculosis
• In 95% of cases the Ghon complex undergoes
fibrosis and calcification; and despite seeding
of other organs, no lesions develop.

38. Primary Tuberculosis
• Granulomas
• Caseating and noncaseating.
• Tubercles (microscopic)
• Coalese to become macroscopically visible
• Immunocompromised people do not form the
characteristic granulomas

39. A granuloma with central necrosis

40. A higher magnification of the previous
photomicrograph

41. Epithelioid macrophages and a Langhan’s
giant cell

42. Numerous bacilli within and outside
macrophages (ZN stain)

43. Secondary Tuberculosis
• Initially, a small focus of consolidation close to
the apical pleura
• Central caseation and peripheral fibrosis
• Healing with fibrosis either spontaneously or
after therapy, or
• Progression and extension along several
different pathways

44. Secondary Tuberculosis
Progressive pulmonary tuberculosis
• The elderly and immunosuppressed
• Erosion into a bronchus (=cavity)
• Erosion of blood vessels (=hemoptysis)
• Healing by fibrosis distorts the pulmonary
architecture
• Spread by direct expansion, dissemination through
airways, lymphatic channels, or the vascular
system

45. Progressive pulmonary tuberculosis

46. TB with cavitation

47. Secondary Tuberculosis
• Miliary pulmonary disease
– Through lymphatics into venous return to the right
side of the heart and thence into the pulmonary
arteries
• Pleural effusions, tuberculous empyema, or
pleural fibrosis may develop
• Systemic miliary tuberculosis
– Liver, bone marrow, spleen, adrenals, meninges,
kidneys, fallopian tubes, and epididymis

48. Miliary TB spleen

49. Diagnosis
• History
• Physical examination
• Radiographic findings of consolidation or
cavitation in the apices of the lungs

50. Diagnosis
• Acid-fast smears (ZN) and cultures of the sputum
• Conventional cultures Vs liquid media-based culture
• Testing of drug susceptibility
• PCR is more rapid
• Multidrug resistance and implications on therapy
and prognosis
• Bacilli are easy to find early (exudative and caseous
phases)
• Become sparse later (fibrocalcific stages)

51. • Treatment
• Prevention and control
• Contact tracing
• Prophylaxis
• BCG vaccination