Download - Primary Tuberculosis 1
PRIMARY TUBERCULOSISPRIMARY TUBERCULOSISDR.MUHAMMAD FAROOQUE
M.B.,B.S. D.T.C.D.IN THE NAME OF ALLAH,THE MOST GRACIOUS,THE MOST MERCIFUL
PRIMARY TUBERCULOSISPRIMARY TUBERCULOSIS
DR. MUHAMMAD FAROOQUE
MB BS DTCD
WHAT IS TUBERCULOSIS?WHAT IS TUBERCULOSIS?
Chronic, granulomatous, infectious, communicable, Multisystem, curable disease.
Epidemiology: Global Threat• One in three humans infected with TB (19-41%)• 8 million new cases of active TB each year• 3 million deaths/year (24 million/year all causes)• #1 cause of infection-related deaths worldwide• 1993 WHO: global public health emergency• One death every 15 seconds.
2 MILLION PEOPLE DIE EVERY YEAR EQUAL TO 20 SUCH STADIUMS
HISTORY OF TBHISTORY OF TB
A DISEASE OF GREAT ANTIQUITY. EVIDENCE IN VERTEBRAE OF NEOLITHIC MAN
IN EUROPE, EGYPTIAN MUMMIES DATING POSSIBLY AS
EARLY AS 3700BC. IN 17TH & 18TH CENTURIES IN EUROPE 25% OF
ADULTS DEATHS DUE TO TB NAMED AS WHITE PLAGUE.
CAUSE OF DEATH FOR MILLION OF MILLIONS OF PEOPLE INCLuDING MANY RENOWNED PERSONS.
KING TUTANKHAMENEGYPTIAN PHARAOH
BARUCH SPINOSADUTCH PHILOSOPHER
SIMON BOLIVERVENEZUELAN REVOLUTIONARY LEADER
JOHN KEATSENGLISH POET
EDGAR ALLAN POEAMERICAN WRITER,POET
FREDERIC CHOPINPOLISH COMPOSER , PIANIST
ROBERT LOUIS STEVENSONSCOTISH WRITER
ANTON CHEKHOVRUSSIAN WRITER
FRANZ KAFKACZECH NOVELIST
ELEANOR ROOSEVELT AMERICAN HUMANIYARIAN/FIRST LADY
EUGENE ONEILLAMERICAN PLAYWRIGHT
GEORGE ORWELLENGLISH NOVELIST/ESSAYIST
REASONS FOR INCREASING INCIDENCEREASONS FOR INCREASING INCIDENCE POVERTY. POPULATION INCREASE. LACK OF ACCESS TO HEALTH CARE. LACK OF KNOWLEDGE. CIVIL UNREST. INEFFECTIVE TB CONTROL PROGRAMS. SOCIAL DEPRIVATION (HOMELESS,IV DRUG
ABUSER) HIV. DRUG RESISTANCE IMMIGRATION FROM HIGH PREVALENCE
AREAS.
TUBERCULOSIS WAS A KILLER TUBERCULOSIS WAS A KILLER AND IT REMAINS A KILLER AND IT REMAINS A KILLER
DISEASE EVEN TODAYDISEASE EVEN TODAY..• Causative organism is just
• 2-4micrometer long &• 0.2-0.5micrometer wide.
SITE-SPECIFIC MYCOBACTERIAL DISEASE.
MAJOR LESS COMMON
PULMONARY M.TUBERCULOSIS M.BOVIS M.XENOPI MAC
M.KANSASII
M.MALMOENSE
LYMPH NODE M.TUBERCULOSIS
MYCOBACTERIUM AVIUM COMPLEX (M.SCROFULACEUM,M.INTRACELLULARE & M.AVIUM)
M.MALMOENSE
M.BOVIS, M.FORTUITUM M.CHELONEI.
SOFT TISSUE/SKIN
M.LEPRAE
M.ULCERANS
M.TUBERCULOSIS
M.MARINUM
M.FORTUITUM M.CHELONEI.
DISSEMINATED(SEEN IN IMMUNODEFICENY STATES)
MAC(HIV-ASSOCIATED)
M.HAEMOPHILUM BCG
M.GENAVENSAE
M.FORTUITUM M.CHELONEI.
.
•MYCOBACTERIA
•FIRST DESCRIBED BY ROBERT KOCH IN 1882
•ACID ALCOHOL FAST•AEROBIC OR MICROAEROPHILIC•NON-SPORE FORMING•NON MOTILE•CAN REMAIN DORMANT IN TISSUES AND PERSIST FOR MANY YEARS•FACULTATIVE INTRACELLULAR PARASITE USUALLY OF MACROPHAGES•HAS SLOW GENERATION TIME 15-20HR•MICROSCOPICALLY LOOKS LIKE BENT RODS.
TRANSMISSIONTRANSMISSION
AIREBORNEBY DROPLET NULEUS1 DROPLET NUCLEUS CONTAINS
AROUND 3AFBMOST EFFECTIVELLY INFECTIVE
D.N. HAS DIAMETER OF 5MICROMETER.
INFECTIVITY OF THE PATIENT.
• Smear positivity.• Frequency and duration of cough.• Physical and chemical characteristics of
sputum,,,,tenaceous sp; more infectious than watery.
• Pt; without ATT ,,,sputum more infectious.• 1-2 weeks after effective ATT ,risk of
transmission is minimal.
ROUTE OF TRANSMISSIONROUTE OF TRANSMISSIONAIRBORNE BY DROPLET NUCLEUSAIRBORNE BY DROPLET NUCLEUS
HOW DROPLET NUCLEI HOW DROPLET NUCLEI ARE PRODUCED & SPREADARE PRODUCED & SPREAD
Any respiratory manoeuvres generate droplet nuclei due to evaporation of small respiratory droplets.
COUGHING….1bout =3000 D.N.SINGING…….1minute =3000 D.N.SPEAKING…..5minutes talk=3000 D.N.SPITTINGSNEEZING=affects till 10 feet.
JOURNEY OF DROPLET JOURNEY OF DROPLET NUCLEUSNUCLEUS
Once they are generated and released in air, the organism can remain viable for extended period of time.
If inhaled by other human being ,will produce infection.
May be eliminated by radiation from sun,infinite dilution.
WHO IS AT RISK?WHO IS AT RISK?
PATIENT-RELATED
•Age. (children>young)•First-generation immigrants from high prevelnce countries•Close contacts of patients with smear positive pulmonary TB•CXR evidence of self-healed TB•Primary infection <1year
ASSOCIATED DISEASES
HIV, Silicosis, DM(IDDM), Immunocompromised, CRF,
Malignancy(leukemia,)
GIT Diseases associated with malnutition,.Gastectomy,Jejuno-ileal bypass,ca pancreas, malabsorption
PREVENTION OF TRANSMISSION PREVENTION OF TRANSMISSION (especially in hospital setting)(especially in hospital setting)
o EARLY CASE FINDINGo EARLY START OF TREATMENTo ISOLATION OF POSITIVE CASES o HIV POSITIVE STAFF SHOULD AVOID TO WORK IN
TB WARDSo ISOLATION ROOMS ---WELL VENTILATED, +
NEGATIVE SUCTION OF AIR EXHAUST FOLLOWED BY TREATMENT OF AIR
o USE OF HIGH EFFICIENCY PARTICULATE AIR FILTER RESPIRATORS,MASKS LIKE N95
TIME TABLE FOR TB.TIME TABLE FOR TB.TIME FROM INFECTION MANIFESTATION
3-8 weeks
3-6 months (3-12M)
Upto 3 Years
From 3 year onward (1-5 Yr)
Around 8 years (average5-15)
PRIMARY COMPLEX
TST POSITIVE
Meningeal,Miliary,Pleural dis.
GIT,Bone & Joint,L/N disease
Post prim;Dis due to reactivation or reinfection
Genito-Urinary & Skin Lesion
TSTTST
Screening for TB “ppd” the Mantoux Tuberculin Skin Test• Delayed-type
hypersensitivity reaction• Induration not erythema• Most common TB test
– Best supportive data– Established thresholds
• Not ideal test– False positive results– False negative results– Poor follow-up compliance
Screening for TB Anergy
• Inability to react to TST• Impaired immune response to delayed-type
hypersensitivity reaction (Type IV)• Most common with highest risk groups
– prolonged corticosteroids– recent immunomodulators– current chemotherapy– HIV infection
Screening for TB Boost Phenomenon / Two-Step Testing
• Initial TST false negative• Occurs following long latency between
infection and testing – “hibernating” immune response
• TST reactivates immune response – subsequent tests positive
• Common, ~20%• 2 step testing recommended for high risk
– TST repeated in 2 weeks
Tuberculin Skin TestPositive Result
≥ 5 mm induration
• HIV infection
• Recent contact active TB
• CXR c/w prior TB (fibrotic changes)
• Immunosuppressive therapy – Organ transplant recipients– Corticosteroids (>15mg prednisone/day)– TNF-α antagonists
Tuberculin Skin TestPositive Result
≥ 10 mm induration• Converters (>10mm change within 2 years)• Recent immigrants from endemic region• High risk settings • Targeted chronic medical disorders
Health care workersChronic care facilityPrisoners and prison workersHomeless and homeless shelter workers
Diabetes MellitusESRDLeukemia/lymphomaHead, neck, lung cancerSilicosisGastrectomy≤ 90% ideal body weight
Tuberculin Skin TestPositive Result
≥ 15 mm induration
• All others
• Avoid testing in this group
• High false positive rate
Tuberculin Skin TestFalse Positive Results
• Nontuberculosis mycobacteria
– NTMB, MOTT
– Typically < 10 mm
• BCG administration
– Positive ppd for 5-10 years
• Reading erythema instead of induration
Tuberculin Skin TestFalse Negative Results
• Reading erythema instead of induration• Immunocompromised / Anergy• Inappropriate test administration/reading• Recent infection (2-12 wks to convert TST)• Extremes of age• Boost phenomenon• Live viral immunization (measles, smallpox)• Overwhelming active TB infection
A negative ppd DOES NOT rule-out active disease
SKIN TESTING IN TB
HEAF METHOD MANTOUX TESTMULTIPUNCTURE METHOD.
READ AT 3-7 DAYS.
GRADE 1:4– 6 PAPULES.
GRADE 2: CONFLUENT.FORMING RING.
GRADE 3:CENTRAL INDURATION
GRADE 4: > 10 MM INDURATION
SINGLE PRICK TEST.
READ AT 2-4 DAYS.
POSITIVE IF INDURATION 5-14 MM(=HEAF GRADE 2)
>15 MM =HEAF GRADE 3-4
Bacillus Calmette-Guerin Vaccine“BCG”
• Live vaccine from M. bovis strain• Used in highly endemic regions• Limited efficacy in preventing TB• Reduces mortality a/w TB meningitis among
children• Results in positive TST• ppd reaction and efficacy wane over time
Screening for TB Boost Phenomenon / Two-Step Testing
• Initial TST false negative• Occurs following long latency between
infection and testing – “hibernating” immune response
• TST reactivates immune response – subsequent tests positive
• Common, ~20%• 2 step testing recommended for high risk
– TST repeated in 2 weeks
PRIMARY PULMONARY PRIMARY PULMONARY TUBERCULOSIS.TUBERCULOSIS.
•THE FIRST INFECTION WITH THE TUBERCLE BACILLUS IS
KNOWN AS PRIMARY TUBERCULOSIS.
•IT USUALLY INCLUDES INITIAL LESION AND DRAINING LYMPH
NODES.
PRIMARY TBPRIMARY TBORGANS INVOLVEDORGANS INVOLVED
LUNGSTONSILS INTESTINESKIN
---
Prim;Pulm;TB.Prim;Pulm;TB.
LUNGS ARE MOST COMMON SITE OF INFECTION.
ALL LOBAR SEGMENTS ARE AT EQUAL RISK OF BEING SEEDED BY INHALED INFECTED DROPLETS.
25% OF CASES MAY BE MORE THAN ONE PRIMARY FOCUS.
DIFFERENCE B/W INFECTION & DIFFERENCE B/W INFECTION & DISEASEDISEASE
INFECTION MEANS THAT MTB IS IN THE BODY BUT IMMUNE
SYSTEM IS KEEPING THE BACTERIA UNDER CONTROL.
DIFF;B/W TB infection DISEASE
MTB +ve +ve
TST +ve +ve
CXR -ve +ve
Sputum D/S -ve +ve
Sputum C/S -ve +ve
S/S -ve +ve
Infectivity -ve +ve
Defined as TB case
NO YES
FATE OF INFECTIONFATE OF INFECTION
Most prim;infection heals with or without calcification of primary complex.
Hematogenous spread …via lymphatic.. seeding of tubercle bacilli to other parts of lungs as well as other organs.
Infection usually contained at pulm. & extra pulm;sites.
Potential for reactivation of infection at all sites is present
RISK OF PROGRESSION OF RISK OF PROGRESSION OF
INFECTION TO DISEASEINFECTION TO DISEASE.. Once infected, stays infected for many
years,probably for life. Approx.90% Do Not develop TUBERCULOSIS
(asymptomatic,but INFECTED POSITIVE TST. Infected individuals can develop TB disease at
any time. Chance of dvlping dis;is greatest shortly after
infection and then steadily lessens as time goes by.
The most important trigger is weakening of immune resistance.
NATURAL HISTORY OF NATURAL HISTORY OF
UNTREATED TBUNTREATED TB..Without treatment,after 5 years::::50%
of pulm. TB pts;will be dead.25% self-cured by there strong immune
response.25% will remain ill with
chronic,infectious TB.
50% Dead
25% CURED25% chronic
STAGES OF DISEASESTAGES OF DISEASEPATHOLOGYPATHOLOGY
STAGE 1STAGE 1DROPLET NUCLEI INHALED…DROPLET NUCLEI INHALED…
REACH ALVEOLI.---VASODILATION—INFLUX OF PMN & REACH ALVEOLI.---VASODILATION—INFLUX OF PMN & MACROPHAGESMACROPHAGES
STAGES OF DISEASESTAGES OF DISEASEPATHOLOGY PATHOLOGY
Stage 2Stage 2
7-21 days..MTB multiplies within a group of phagocytic cells”macrophages”which are not activated to kill AFB.
Macrophages from blood travel to alveoli. These new macrophages engulf MTB.
These macrophages remains unable to destroy these MTB as they are not activated….RESULT.. Macrophages burst.
Stages of diseaseStages of diseasePATHOLOGYPATHOLOGY
STAGE 3STAGE 3
Lymphocytes begins to infiltrate. T-cells recognise MTB. These T-LYMPHOCYTES liberate
cytokines including gamma –interferon. IFN can activate the macrophages to
become capable of destroying MTB. TST becomes POSITIVE. Activated macrophages release IL-1,TNF.
Stages of diseaseStages of diseasePATHOLOGYPATHOLOGY
STAGE 3 CONTD;STAGE 3 CONTD; Tubercle Formation Begins.
Macrophages develop pale foamy cytoplasm & crowd togather as epitheliod cells to form the tubercle.
Some mono nuclear cells fuse to form MULINUCLEATED OR LANGHANS GIANT CELL.
Centre of tubercle is characterized by Caseation Necrosis.
MTB can not multiply with in these tubercle because of low PH & ANOXIC environment.
MTB can persist for long time.
Stages of diseaseStages of diseasePATHOLOGYPATHOLOGY
Stage 4Stage 4 Surrounding the Tubercle many
macrophages are present in different states.ACTIVATED,POORLY
ACTIVATED,& UNACTIVATED. MTB uses these unactivated & poorly
activated macrophages to replicate and hence TUBERCLE grows.
Growing tubercle invade surrounding structure Artery, Bronchus
STAGES OF DISEASESTAGES OF DISEASEPATHOLOGYPATHOLOGY
STAGE 5STAGE 5
Casseous centres of tubercle liquify. It is conducive to MTB growth. Now org; rapidly multiply extracellularly. After some time----walls of nearby bronchi
become Necrotic & Rupture…Cavity formation takes place.
MTB spill into other airways …spread to other parts of lung.
Pathology of TB.Pathology of TB.
PRIMARY INFECTION IS USUALLY EVIDENT AS A SUBPLEURAL TUBERCLE CALLED AS GHON FOCUS
IT MAY BE IN ANY LUNG ZONE
GHON FOCUS + DRAINING HILAR L/N
PRIMARY OR GHON FOCUS PRIMARY OR GHON COMPLEX
OUTCOME OF PRIMARY INFECTIONOUTCOME OF PRIMARY INFECTION
NO CLINICAL DISEASE; POSITIVE TST; USUAL OUT COME =90% OF CASES.
2. HYPERSENSITIVITY REACTIONS ERYTHEMA NODOSUM PHLYCTENULAR CONJUNCTIVITIS
DACTYLITIS
3. PULM. AND PLEURAL COMPLICATIONS TB PNEUMONIA,
LOBAR COLLAPSE, PL EFFUSION
DISSEMINATED DISEASE .
LYMPHADENOPATHY (USUALLY CERVICAL) . MENINGITIS,
PERICARDITIS, MILIARY DISEASE.
Clinical Features of Prim; Clinical Features of Prim; Pulm:TBPulm:TB
Asymptomatic ….A great majority especially adults.
Brief febrile illness. At the time of tuberculin conversion.
Occasionally,typical prim;Tb may occur in elderly people who have lost their tuberculin sensitivity.
Clinical Features of Primary Clinical Features of Primary Pulmonary TB.Pulmonary TB.
In few cases with more severe infection or low host resistance,the child may be unwell,with anorexia,failure to gain weight.
Cough(if L/N or Granulation tissue impinge on Bronchial wall.)
Wheeze_+ Sputum….rare in children. Crepts. Other signs according to complications.
FEATURES OF PRIMARY TB
INFECTION (4-8 WEEKS)
INFLUENZA LIKE ILLNESS
TST CONVERSION
PRIMARY COMPLEX
DISEASE
LYMPHADENOPATHY COLLAPSE CONSOLIDATION
OBSTRUCTIVE EMPHYSEMA CAVITATION
PL EFFUSION ENDOBRONCHIAL LESION MILIARY MENINGITIS PERICARDITIS
HYPERSENSITIVITY
ERYTHEMA NODOSUM
PHLECTENULAR CONJUNCTIVITIS DACTILITIS
Radiological featuresRadiological features
In adults CXR changes(lung component of prim complex) + at time of TST conversion (7-30%)
In children –CXR---- Hilar >Paratracheal or Both OR B/L Hilar Lymphadenopathy & Parenchymal lesion.
Segmental or lobar consolidation or obstructive emphysema on CXR.
Radiological abnormality may persist upto 6 months ater diagnosis.But complete resolution after 2 year.
Calcification may occur
Diagnosis of primary pulmonary Diagnosis of primary pulmonary TuberculosisTuberculosis
• HISTORY: contact +,vague ill health,brief febrile illness,cough,anorexia,wheeze, crepts,
• TST +ve• CXR changes unilateral or bilateral Hilar,
Paratracheal L/N, parenchymal lesion,consolidation,collapse,
• SPUTUM rarely produced in children• GASTRIC WASHING for AFB Staining (rarely
positive)• Gastric washing for AFB C/S (POSITIVE IN 20-
25% CASES)• PCR. (Mycobacterial DNA amplification
techniques)
COMPLICATIONS OF PRIMARY TBCOMPLICATIONS OF PRIMARY TB
COLLAPSE/CONSOLIDATION BRONCHIECTASIS OBSTRUCTIVE EMPHYSEMA BRONCHOLITH ERYTHEMA NODOSUM PHLYCTENULAR CONJUNCTIVITIS PLEURAL EFFUSION MILIARY TUBERCULOSIS
COLLAPSE/CONSOLIDATIONCOLLAPSE/CONSOLIDATION
• Ass e enlarged tuberculous L/N.at hilum.• Middle lobe is most often affected.• Radiological appearances are due to: • 1 collapse..• 2 inflammatory exudation..• 3 caseous pneumonia
COLLAPSE/CONSOLIDATIONCOLLAPSE/CONSOLIDATIONclinical presentationclinical presentation
WheezeCoughDullnessDiminished air entryBronchial breathingCreptsAsphyxia in children +-resulting in death
BronchiectasisBronchiectasis
Abnormal and permanently dilated airways.Cause in prim TB—distension of airways
by mucus,caseous tissue or sec;infection beyond a bronchial stenosis.
Obstructive emphysemaObstructive emphysema
Commoner in childrenA valve action results due to bronchus
compression,with air being admitted to a portion of lung on inspiration but unable to escape on expiration
This results in distention of a segment or a lobe.
BroncholithBroncholith
Calcification in a primary focus or L/N may be extruded into a bronchus as broncholith.
Erythema nodosumErythema nodosum• A manifestation of hypersensitivity reaction.due to
vasculitis in deep dermis & skin fat.• Tender,dusky-red nodular lesions on anterior
surface of legs>ant surface of thighs,>extensor surface of forearms>face.breast.
• 5-20 mm diameter nodule• Illdefined margin• Resolve over a week or two.• Red>purple>brown• Recurrent crops• Ass with fever positive TST recurrent crops of
lesions may occur.
Phlyctenular conjunctivitisPhlyctenular conjunctivitis
Reflects hypersensitivity to the tubercle bacilli. Usually seen in first year of infection. Common in children. Usually in one eye. Begin with LACRIMATION,IRRITATION,or
PHOTOPHOBIA. 1-3 mm shiny yellowish or grey bleb @ the
limbus,with a sheaf of dilated vessels running out toward it from edge of conjunctival sac.
Pleural effusionPleural effusion
MAY BE SEEN IN CHILDREN,5-12 YEARS. SMALL TRANSIENT USUALLY OCCURS 3-6 MONTHS AFTER
INFECTION. SYMPTOMS MALAISE,FEVER,PLEURIYIC
PAIN
Miliary TBMiliary TB
Result of acute diffuse dissemination of tubercle bacilli via blood-stream.
Form of severe infection Symptoms—fever, night sweats, anorexia, wt;loss,
dry cough, Signs-------hepatosplenomegaly, chest normal to
crepts, Fundoscopy –choroidal tbercles (5-10%) CXR—1-2 mm millet seeds shadow through lung
feild
CRYPTIC MILIARY TBCRYPTIC MILIARY TB
• AGE > 60 YEARS• INTERMITTENT LOW GRADE FEVER (PUO)
• UNEXPLAINED WEIGHT LOSS• GENERAL DEBILITY• HEPATOSPLENOMEGALY (25-50 % )• NORMAL CXR• BLOOD DYSCRASIAS; LEUKAMOID
REACTION, PANCYTOPENIA• NEGATIVE TST• CONFIRMATION BY BIOPSY OF LIVER OR
BONE MARROW.
TB MENINGITISTB MENINGITIS OCCURS SHORTLY AFTER A PRIM;
INFECTION IN CHILDHOOD OR AS PART OF MILIARY TB
USUAL LOCAL SOURCE OF INFECTION IS A CASEOUS FOCUS IN THE MENINGES OR BRAIN ADJ; TO CSF PATHWAY.
BRAIN COVERED BY A GREENISH ,GELATINOUS EXUDATE, ESPECIALLY AROUND THE BASE
NUMEROUS SCATTERED TUBERCLES + ON MENINGES.
SYMPTOMS OF TBMSYMPTOMS OF TBM
HEADACHEVOMITINGLOW-GRADE FEVERLASSITUDEDEPRESSIONCONFUSIONBEHAVIORAL CHANGES
SIGNS OF TBMSIGNS OF TBM
MENINGISM + -OCULOMOTOR PALSIESPAPILLOEDEMADEPRESSION OF CONSCIOUS LEVELFOCAL HEMISPHERE SIGNS
INVESTIGATIONS FOR TBM.INVESTIGATIONS FOR TBM.
ROUTINE INCLUDING CXR CSF RE (INCREASED PRESSURE,USUALLY CLEAR
BUT WHEN ALLOWED TO STAND A FINE CLOT “SPIDER WEB” MAY FORM)
CSF CHEMISTRY (INC PROTEINS & DEC.GLUCOSE.
CSF SMEAR AFB -+ CT BRAIN ( HYDROENCEPHALUS,MENINGEAL
ENHANCEMENT, TUBERCULOMA )
TB IN HIVTB IN HIV
MORE LIKELY INFECTION AFTER EXPOSURE.
USUALLY PROGRESSIVE PRIMARY DISEASE AFTER INFECTION.
REACTIVATION OF LATENT INFECTION.
REINFECTION WITH NEW STRAIN.REDUCED SMEAR-POS RATES IN PTB.
TB IN HIV TB IN HIV
LESS CAVITATION.ATYPICAL CXR APPEARANCES.MORE DISSEMINATED DISEASE.MORE EXTRA PULM; INFECTION.MORE RISK OF ADVERSE DRUG
REACTIONS.
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