TUBERCULOSIS

DR KWAGHE BARKA VANDI

CONSULTANT ANATOMIC PATHOLOGIST

DEPARTMENT OF HISTOPATHOLOGY JUTH

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OUTLINE

• INTRODUCTION
• AETIOLOGY
• EPIDEMIOLOGY
• PATHOGENESIS
• SITES OF INFECTIONS
• CLINICAL FEATURES
• DIAGNOSIS
• WORLD TUBERCULOSIS DAY

INTRODUCTION

• TUBERCULOSIS IS AN ANCIENT SCOURGE

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• HAS PLAGUED HUMANKIND THROUGHOUT KNOWN HISTORY AND HUMAN PREHISTORY

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• IT IS A SERIOUS CHRONIC PULMONARY AND SYSTEMIC DISEASE CAUSED MOST OFTEN BY M. TUBERCULOSIS

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INTRODUCTION

• MYCOBACTERIUM TUBERCULOSIS MAY HAVE KILLED MORE PERSONS THAN ANY OTHER MICROBIAL PATHOGEN

AETIOLOGY

• ON MARCH 24, 1882, DR. ROBERT KOCH ANNOUNCED THE DISCOVERY OF MYCOBACTERIUM TUBERCULOSIS, THE BACTERIA THAT CAUSE TUBERCULOSIS (TB)

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• THE GENUS MYCOBACTERIUM ARE SLENDER, AEROBIC RODS THAT GROW IN STRAIGHT OR BRANCHING CHAINS

AETIOLOGY

• MYCOBACTERIA HAVE A UNIQUE WAXY CELL WALL COMPOSED OF UNUSUAL GLYCOLIPIDS AND LIPIDS INCLUDING MYCOLIC ACID

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• THESE MAKES THEM ACID-FAST, MEANING THEY RETAIN STAINS EVEN ON TREATMENT WITH A MIXTURE OF ACID AND ALCOHOL.

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• THEY ARE WEAKLY GRAM POSITIVE

EPIDEMIOLOGY

• ACCORDING TO THE WHO, TUBERCULOSIS IS ESTIMATED TO AFFECT MORE THAN A BILLION INDIVIDUALS WORLDWIDE

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• THERE ARE 8 - 10 MILLION NEW CASES AND 1.6 MILLION DEATHS EACH YEAR

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• 13% OF THE PEOPLE WHO DEVELOPED TUBERCULOSIS IN 2011 WERE HIV-POSITIVE.

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EPIDEMIOLOGY

• TUBERCULOSIS IS THE SECOND-MOST COMMON CAUSE OF DEATH FROM INFECTIOUS DISEASE IN THE WORLD

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• IT IS MORE COMMON IN DEVELOPING COUNTRIES

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• ABOUT 80% OF THE POPULATION IN MANY ASIAN AND AFRICAN COUNTRIES TEST POSITIVE IN TUBERCULIN TESTS

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• 5–10% OF THE US POPULATION TEST POSITIVE

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EPIDEMIOLOGY

• IT FLOURISHES WHERE THERE IS POVERTY, CROWDING, AND CHRONIC DEBILITATING ILLNESSES

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• THE MAJOR SOURCE OF TRANSMISSION IS HUMANS WITH ACTIVE PULMONARY TUBERCULOSIS

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• HUMANS ARE THE ONLY RESERVOIR FOR M. TUBERCULOSIS

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EPIDEMIOLOGY

• PEOPLE WITH ACTIVE PULMONARY TUBERCULOSIS RELEASE MYCOBACTERIA PRESENT IN THEIR SPUTUM INTO THE ENVIROMENT

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• OROPHARYNGEAL AND INTESTINAL TUBERCULOSIS CAN BE CONTRACTED BY DRINKING MILK CONTAMINATED WITH MYCOBACTERIUM BOVIS

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PATHOGENESIS

• M. TUBERCULOSIS ENTERS MACROPHAGES BY PHAGOCYTOSIS MEDIATED BY SEVERAL RECEPTORS EXPRESSED ON THE PHAGOCYTE

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• INCLUDING MANNOSE BINDING LECTIN AND CR3

• REPLICATION TAKES PLACE IN MACROPHAGES BY INHIBITING MATURATION OF PHAGOSOME AND FORMATION OF PHAGOLYSOSOME

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PATHOGENESIS

• THIS OCCURS DURING THE FIRST 3 WEEKS OF INFECTION IN PRIMARY TUBERCULOSIS (IN NONSENSITIZED INDIVIDUALS)

PATHOGENESIS

PATHOGENESIS

• MYCOBACTERIA PROLIFERATE IN THE PULMONARY ALVEOLAR MACROPHAGES AND AIR SPACES, RESULTING IN BACTEREMIA AND SEEDING OF MULTIPLE SITES

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• MULTIPLE PATHOGEN ASSOCIATED MOLECULAR PATTERNS OF M. TUBERCULOSIS, INCLUDING LIPOPROTEINS AND GLYCOLIPIDS, ARE RECOGNIZED BY THE INNATE IMMUNE RECEPTORS E.G. TOLL-LIKE RECEPTORS SUCH AS TLR2

PATHOGENESIS

• THIS INITIATES AND ENHANCES THE INNATE AND ADAPTIVE IMMUNE RESPONSES TO M. TUBERCULOSIS AT 3 WEEKS POST INFECTION

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• STIMULATION OF TLR2 BY MYCOBACTERIAL LIGANDS PROMOTES PRODUCTION OF IL-12 BY ANTIGEN PRESENTING CELLS (APC, DENTRITIC CELLS AND MACROPHAGES)

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• NAIVE CD4₊ T-CELLS RECOGNIZE PEPTIDES DISPLAYED BY APC AND THE IL-12 SECRETED BY THEM

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PATHOGENESIS

• THIS INDUCES THE DIFFERENTIATION OF NAIVE CD4₊ T-CELLS INTO T_H1 SUBSET

• THESE TH1 CELLS SECRETE IFN-Ƴ WHICH ACTIVATES MACROPHAGES

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• THESE CLASSICALLY ACTIVATED MACROPHAGES ARE ALTERED IN SEVERAL WAYS:-

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PATHOGENESIS

• 1. THEIR ABILITY TO PHAGOCYTOSE AND KILL MICROORGANISMS IS MARKEDLY AUGMENTED BY MATURATION OF PHAGOLYSOSOME IN INFECTED MACROPHAGES

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• 2. STIMULATION OF INDUCIBLE NITRIC OXIDE SYNTHASE

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PATHOGENESIS

• 3. EXPRESS MORE CLASS II MHC MOLECULES ON THEIR SURFACES

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• 4. THEY SECRETE TNF, IL-1 AND CHEMOKINES WHICH PROMOTES INFLAMMATION

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PATHOGENESIS

• 5. STIMULATES THE FORMATION OF GRANULOMA AND CASEOUS NECROSIS

• 6. MACROPHAGES ACTIVATED BY INF-Ƴ ARE TRANSFORMED INTO EPITHELIOID CELLS WHICH AGGREGATE TO FORM GRANULOMAS

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• 7. SOME EPITHELIOID CELLS FUSE TO FORM GIANT CELLS (LANGHAN TYPE)

PATHOGENESIS

SITES OF INFECTION

• LUNGS/PULMONARY TUBERCULOSIS

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• LYMPH NODES/LYMPHADENITIS

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• GASTROINTESTINAL

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• ADRENAL GLANDS/RENAL

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• CNS/ TB MENINGITIS

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SITES OF INFECTION

• OSTEO-ARTICULAR…E.G. OTEOMYELITIS/POTT DISEASE

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• CUTANEOUS/SKIN

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• CARDIAC

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• GENITO-URINARY

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CLINICAL FEATURES

• SYSTEMIC SYMPTOMS ARE RELATED TO CYTOKINES RELEASED BY ACTIVATED MACROPHAGES (E.G., TNF AND IL-1)

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• INCLUDE; MALAISE, ANOREXIA, CACHEXIA, AND FEVER.

• THE FEVER IS LOW GRADE AND REMITTENT (APPEARING EACH LATE AFTERNOON AND THEN SUBSIDING), AND NIGHT SWEATS OCCUR.

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PULMONARY TUBERCULOSIS

THERE ARE TWO PATHOPHYSOLOGICAL TYPES OF CLINICAL TUBERCULOSIS:-

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1. PRIMARY (IN NON-SENSITIZED INDIVIDUALS)

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• SECONDARY (IN SENSITIZED INDIVIDUALS)

PRIMARY PULMONARY TUBERCULOSIS

• OCCURS IN 5% OF NEWLY INFECTED PEOPLE

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• THE SOURCE OF INFECTION IS EXOGENOUS

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• IN MOST PEOPLE THIS IS CONTAINED, BUT IN SOME IT IS PROGRESSIVE

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• IT RESEMBLES AN ACUTE BACTERIAL PNEUMONIA WITH LOBAR CONSOLIDATION, HILAR ADENOPATHY AND PLEURAL EFFUSSION

MILIARY TUBERCULOSIS

MILIARY PULMONARY DISEASE

• ORGANISMS DRAINING THROUGH LYMPHATICS MAY ENTER THE VENOUS BLOOD AND CIRCULATE BACK TO THE LUNG

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• GIVING MICROSCOPIC OR SMALL, VISIBLE LESIONS (2-MM), FOCI OF YELLOW-WHITE CONSOLIDATIONSCATTERED THROUGH THE LUNG PARENCHYMA

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MILIARY TUBERCULOSIS

• LATER CONSOLIDATION OF LARGE REGIONS OR EVEN WHOLE LOBES OF THE LUNG WILL BE INVOVLED

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• WITH PROGRESSIVE PULMONARY TUBERCULOSIS, THE PLEURAL CAVITY IS INVARIABLY INVOLVED, AND SEROUS PLEURAL EFFUSIONS, TUBERCULOUS EMPYEMA, OR OBLITERATIVE FIBROUS PLEURITIS MAY DEVELOP

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MILIARY TUBERCULOSIS

SYSTEMIC MILIARY TUBERCULOSIS

• OCCURS WHEN BACTERIA DISSEMINATE THROUGH THE SYSTEMIC ARTERIAL SYSTEM

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• MILIARY TUBERCULOSIS IS MOST PROMINENT IN THE LIVER, BONE MARROW, SPLEEN, ADRENALS, MENINGES, KIDNEYS, FALLOPIAN TUBES, AND EPIDIDYMIS, BUT COULD INVOLVE ANY ORGAN

MILIARY TUBERCULOSIS

SECONDARY PULMONARY TUBERCULOSIS

• THIS MAY FOLLOW SHORTLY AFTER PRIMARY TUBERCULOSIS

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• MOST OFTEN YEARS AFTER INITIAL INFECTION BY REACTIVATION OF LATENT INFECTION OR BY EXOGENOUS RE-INFECTION

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• CHARACTERIZED MOSTLY BY CAVITATIONS IN THE APEX OF UPPER LOBES AND EROSION OF CAVITIES INTO AIRWAYS (ASSMAN FOCUS)

SECONDARY PULMONARY TUBERCULOSIS

• WITH PROGRESSIVE PULMONARY INVOLVEMENT, THERE IS INCREASING AMOUNTS OF SPUTUM, AT FIRST MUCOID AND LATER PURULENT

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• SOME DEGREE OF HEMOPTYSIS IS PRESENT IN ABOUT HALF OF ALL CASES OF PULMONARY TUBERCULOSIS

LUNGS/CHEST X-RAY

LUNGS/GROSS

GHON COMPLEX

GHON COMPLEX

LUNGS/GROSS

CAVITATORY TUBERCULOSIS

MILIARY TUBERCULOSIS

GRANULOMA WITH CENTRAL NECROSIS

GRANULOMA

GRANULOMA

EXTRAPULMONARY TUBERCULOSIS

• CNS TB MAY PRESENT WITH MENINGITIS OR INTRACRANIAL TUBERCULOMAS

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• ABDOMINAL TB INCLUDES TB PERITONITIS AND TB OF THE GI TRACT

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EXTRAPULMONARY TUBERCULOSIS

• DISSEMINATED TB; MOST COMMONLY INVOLVED ORGANS (IN ORDER) ARE LUNGS, LIVER, SPLEEN, KIDNEYS, AND BONE MARROW

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• POTT DISEASE IS A PRESENTATION OF EXTRAPULMONARY TUBERCULOSIS WHEREBY DISEASE IS SEEN IN THE SPINAL VERTEBRAE

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GIBBUS IN POTT DISEAESE

POTT DISEASE

DIAGNOSIS

• TUBERCULOSIS IS DIAGNOSED BY FINDING MYCOBACTERIUM TUBERCULOSIS BACTERIA IN A CLINICAL SPECIMEN TAKEN FROM THE PATIENT

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• ACID-FAST BACILLI (AFB) SMEAR

ZIEHL NEELSEN STAIN (ACID-FAST STAIN)

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• BACTERIOLOGICAL CULTURE TESTS

LOWENSTEIN-JENSEN MEDIA

• BACTEC RADIOMETRIC CULTURE SYSTEM FOR BACTERIA (9-16DAYS)

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DIAGNOSIS

• MYCOBACTERIAL CULTURE, WHICH HAS THE HIGHEST SENSITIVITY FOR DIAGNOSING AND CONFIRMING ACTIVE TB, REQUIRES 2 TO 6 WEEKS FOR INTERPRETATION

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• WHILE OTHER INVESTIGATIONS MAY STRONGLY SUGGEST TUBERCULOSIS AS THE DIAGNOSIS, THEY CANNOT CONFIRM IT.

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DIAGNOSIS

• A COMPLETE MEDICAL EVALUATION FOR TUBERCULOSIS (TB) MUST INCLUDE A MEDICAL HISTORY, A PHYSICAL EXAMINATION, A CHEST X-RAY AND MICROBIOLOGICAL EXAMINATION OF SPUTUM OR SOME OTHER APPROPRIATE SAMPLES

• IT MAY ALSO INCLUDE A TUBERCULIN SKIN TEST, OTHER SCANS AND X-RAYS,

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• SURGICAL BIOPSY FOR HISTOLOGY

HIV /AIDS AND TB

• ALL STAGES OF HIV INFECTION ARE ASSOCIATED WITH AN INCREASED RISK OF TUBERCULOSIS.

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• HIV-POSITIVE PEOPLE HAVE AN INCREASED FREQUENCY OF FALSE-NEGATIVE SPUTUM SMEARS AND TUBERCULIN TESTS (THE LATTER SOMETIMES REFERRED TO AS “ANERGY”)

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• THERE IS ABSENCE OF CHARACTERISTIC GRANULOMAS IN TISSUES, PARTICULARLY IN THE LATE STAGES OF HIV.

WORLD TB DAY

• 24^TH OF MARCH EACH YEAR.

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• IT COMMEMORATES THE DAY IN 1882 WHEN DR ROBERT KOCH ASTOUNDED THE SCIENTIFIC COMMUNITY BY ANNOUNCING THAT HE HAD DISCOVERED THE CAUSE OF TUBERCULOSIS

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• THE TB BACILLUS

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WORLD TB DAY

THE EVENT WAS INTENDED TO EDUCATE THE PUBLIC ABOUT:-

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• 1. THE DEVASTATING HEALTH AND ECONOMIC CONSEQUENCES OF TB.

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• 2. ITS EFFECTS ON DEVELOPING COUNTRIES, AND ITS CONTINUED TRAGIC IMPACT ON GLOBAL HEALTH.

WORLD TB DAY

• UNTIL TB IS CONTROLLED, THE WORLD TB DAY WON’T BE A CELEBRATION.

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• BUT A VALUABLE OPPORTUNITY TO EDUCATE THE PUBLIC ABOUT THE DEVASTATION CAUSED BY TB AND HOW SPREAD AND HOW IT CAN BE STOPPED.

THANK YOU

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