1. health and fitness
2. disease

TUBERCULOSIS
MICROBIOLOGY

Mycobacterium tuberculosis

Mycobacterium bovis: rare since pasturization of milk

Obligate aerobes, slow growing, tendancy to develop drug resistance

High lipid content in walls (mycolic acids) thus AFB (acid fast bacillus)

NOT picked up w/ gram stain: pus aspirate w/ -ve gram stain ........... Think TB

Person to person spread via air borne droplets from sputum smear +ve Pt

Intracellular survival allows it to be dormant for yrs

Air exchange is CRUCIAL to preventing spread in the ED

Tranmission is rare outdoor b/c of suceptibility to UV light

People are non-infectious after 2 weeks of treatment unless cultures stay positiv

Four phase of growth:
(1) Continous Rapid Growth
- extracellular pool in the cavitary form of pulmn TB
- oxygen tension is high, replication is fast, and #s are high
(2) Extracellular Slow Growth
- colony of m/os in caseous material
- growth rate in spurts and is relatively slow
- extracellular and are particularly sensitive to rifampin
(3) Intracellular
- inside the macrophage
- medium is acid and particularly sensitive to pyrazinamide
(4) Dormant, Non-Replicating
- areas thruout the host and may not replicate during a course of Rx
and therefore remain viable
- potential source of relapse when these organisms begin to replicate
after the Rx has been stopped
- No drugs are bacteriocidal against dormant m/os (must be
replicating for drugs to work)
EPIDEMIOLOGY

1/3 of world population Mantoux positive

Worst infectious disease world wide

Very high rates in the Inuit, northern Sask aboriginals, and imigrants (asian, vietnamese,
phillipino, mexican

Most cases are reactivation and most are pulmonary (characterized by upper lobe
disease b/c the m/o is a aerobe :. seeks out the highest O2 env – also renal cortex and
bone epiphysis)

Bimodal incidence: higher rates in young and old

HIV/AIDS: 800X the rates of TB; CD4 cells are very important on CMI for TB

Question: NAME 10 RISK FACTORS FOR TB
Known TB contact
HIV/AIDS
Elderly
Long term care (nursing homes, prison
IVDA
Homeless
Low income
Aboriginals
Chronic disease
Immunosuppressed
Immigrants: Asain, Mexican, Philipino, African

Question: NAME 10 RISK FACTORS FOR REACTIVATIO OF TB
TB infection within 2 years
HIV/AIDS
CRF
Head and neck cancer
IVDA
Diabetes
Corticosteroid therapy
Hematologic or immune diseases
CXR shows prior unRx TB
Immunosuppressive drugs
Low body weith
Intestinal bypass or gastrectomy
Chronic malabsorption syndrome
FOUR STAGES OF PATHOGENESIS

STAGE I

Alveolar macrophage phagocytosis

Bacillus either dies or overcomes the macrophage response

STAGE II

Bacillus replicates despite the macrophage response (including
monocytes)

Tubercle develops = primary focus of infection consisting of many bacilli
replicating within macrophages

The bacillus spreads via lymphatics to blood then to lymphnodes and
orgens

Spread to the lung predominates in the apices b/c it is an aeorbic
organism

STAGE III

CMI reaction by CD4 T cells limits growth

Granulomas develop = destruction of macrophages infected with bacilli

Delayed Type Hypersensitivity reaction withCD8 cytotoxic cells leads to
destruction and formation of CASEATING NECROTIC GRANULOMAS

Bacilli can survive for many years in caseated granlomasw

Immunocompetent: primary lesion walled off and disease arrested and the
only evidence of the infection is a +ve PPD (Primary TB is stage I-III)

Immunocompromised: weak CMI thus caseatious material expands; may
be calcified to form a Ghon Complex
Primary progressive TB = advancing pneumonia
Disseminated TB = lymphohematogenous spread of TB

STAGE IV

Months to decade later\

Decreased resistance leads to reactivation of dormatnt focus

Liquefaction of the tubercle leads to excellent growth medium

Reactivation of delayed hypersensitivity reaction leads to tissue
destruction, erosion through bornchi thus develops a caseating
bronchopneumonia
CLINICAL FEATURES

Two phases of infection
(1) Primary TB
- mild flu-like or asymptomatic
- infrequently may develop into Miliary TB
- disseminated blood infection
(2) Secondary TB
- usu due to reactivation (rarely due to a second infection)
- reactivation common when T cell immunity is impaired
- commonly located at lung apex
* Lung apex...............Secondary TB
* Whole lung.............Miliary TB
When to “Think TB”

- cough/sputum > 4wks
- wt loss
- night sweats
- unexplained fever > 1wk
- antibiotic unresponsive pneumonia
- the patient is: aboriginal, foreign born, inner city homeless, elderly, HIV +
- do NOT rely on CXR b/c it may be normal

History

Asymptomatic unless advanced

Cytokine effects: anorexia, fatigue, weak, wt loss, fevers, chills,
headachee

Fevers in afternoon and sweats at night is classsic

Chronic cough is the MC pulmonary symptoms

Hemopytsis can be absent, mild, or massive

Dyspnea and pleuritic chest pain can occur

Peds: hilar lymphadenopathy noted on CXR for resp symptoms; may have
wheezing, atelectasis, pneumonia, or query foreign body

Elderly often only have chronic cough and FTT

HIV typically present with extrapulmonary manifestations

ASK about risk factors

Physical Exam

Pneumonia findings

D’Espeine’s sign of mediastinal lymphadenopathy

Erythema Nodosum

Keratoconjunctitive: unilateral eye inflammation

General: wasting, fever, pale, thin

How common is reactivation?

Immunocompetent: 5% per lifetime

HIV/AIDS: 10% per year
Q: NAME 15 COMPLICATIONS OF TB

Pulmonary

Pneumothorax: increases with cavitating lesion

Pleural effusions

Empyema: rare, late in dz, more common with immunosuppressed

Superinfection: aspergillus fungal ball superinfection

Hemoptyis: mild or massive

Endobronchial spread
MC complication of cavitary dz
Seen as 5-10 mm poorly defined nodules in dependant
lung zones which may collasce into parenchymal
consolication (galloping consolidation)

Airway spread
Cavitation drains into broncheal treat where the infection
spread throughout the airway
Bronchietasis, bronchial stenosis, lobar atelectaisis,
tracheal TB, laryngeal TB

Extra-Pulmonary (think MSK, GI, GU, Neuro, Renal, ID, Hem)

Lymphadenitis

Pericarditis

Osteomyelitis

Septic arthritis

Renal TB

Scrotal mass, prostatitis, epididymitis, orchitits

Endometritis, oopharitis, cervicitis, vaginitis, PID

Diseminated (Miliary) TB: multisystem disease

Meningitis

Brain abscess

Spinal abscess

Peritonitis

GI TB: abdo pain, obstruction, hemorrhage, peritonitis
CXR IN THE TB PATIENT

General

CXR is an important screening tool in the ED as we won’t have definitive
tests

Classic findings = upper lobe cavitary infiltrates but there are MANY

Normal CXR is 99% sensitive (immunocompetent pt)

Normal CXR is 85% sensitive in HIV patients

Primary TB

Pneumonic infiltrate with hilar or mediastinal lymph nodes is very
suggestive ( any age);

Infiltrates: homgenous, single lobe (may look like regular pneumonia with
lymphadenopathy being the only clue of TB)

Lymphadenopathy is the main finding in kids; unilateral is most
common

Massive adenopathy with airway collapse and atelectasis is common in
young kids







Pleural effusion: moderate to large size
Miliar TB: 1-3mm innumerable non-calcified nodules throughout lungs
Tuberculomas: well defined nodular lesion of the lung (healed primary TB)
Ghon focus: healed primary TB that shows on CXR as calcified scar
Ranke complex: Ghon complex associated with calcified hilar lymph
nodes

Progressive primary TB: extending consolidation with secondary foci often
in the upper lobes
Post Primary TB

Upper lung infiltrate (aerobes) with or without cavitation

Fibrosis and cavitation are common

Bilateral upper lobe infiltrates is VERY suggestive of TB

Fibroproductive lesions: reticular nodular opacification that is seen after
the primary infection is taken over by reactive fibrosis
Irregular and angular in contour, strands extending toward
the hilum, calcification common
This pattern is very suggestive of TB
Miscellaneous

CXR changes over MONTHS can determine active vs inactive TB

Cavitating lung lesions should make you think TB U.P.O.

Cavitations can heal and leave Bullae

HIV: primary TB CXR changes are common but post-primary are not
DIAGNOSIS = Mantoux + CXR + Sputum
Skin Testing


Only tool available for detecting LATENT TB INFECTION

Principle: TB infection produces sensitivity to certain antigens (purifiedc
protein derivative = PPD)

Ttype IV rxn or delayed type hypersensitivity reaction (T cells) means you
are infected w/ the bug somewhere (granuloma)

PPD will be +ve 3-8 weeks after initial infection

How to read: read at 48-72 hrs and measure maximum diameter of
palpable induration (NOT erythema)

(+) test means that you are infected but does NOT neccessarily mean that
you have active disease

(+) ve test = 5 mm, 10 mm, 15 mm of induration depending on risks!

Special routines required for people getting repeat tests (do test twice)
Sputum = Gold Standard for Dx


3 morning specimens are the best samples; observed collection is best

Can be induced with nebs or gastric washings (children)

Fiberoptics with BAL or biopsy may be needed if sputum can’t be done or
suspicion remains despite -ve sputum

Testing of Sputum
Direct microscopy = Acid Fast Bacillus Stain: most rapid,
relatively insensitive unless TB is active; does not r/o TB;
three morning sputum samples helps increase yeild
Culture: MORE sensitive than AFB staining

Other Testing

PCR is being developed




Mycobacterium TB direct test, Tuberculosteric acid test, detection of
adenosine deaminase activity and serologic testing are all being
developed
Midstream urine for GU TB
Blood cultures also important (esp. w/ HIV)
Lymph nodes sent to micro for culture and pathology for cytology
DIFFERENTIAL DIAGNOSIS AND COMPLICATIONS

Pulmonary TB

Bacterial pneumonia: more systemic effects, shorter duration, less
lymphadenopathy, wbc count changes, responds to abx

Fungal infections: histo, coccidio, blastomyocsis, other mycobacterium

HIV patient with pneumonia: PCP, fungi, etc, differential is extensive,
needs bronchoscopy for dx

Q: name causes of cavitary lung lesions
TB
Staph pyogenes
Klebsiella pneumonia
Bronchogenic carcinoma
Pulmonary infarction
Wegener’s granulomatosis
Upper lobe bullous emphysema
Upper lobe neurofibromas

Differential of predominantly upper lobe infiltrates
TB (calcification suggests TB)
Atypical myocobacteria
Ankylosing spondylitis
Silicosis
Collagen vasc dz
Lymphomas
Actinomyces
Extrinsic alveolitis
Aspergillosis
Sarcoidosis

Lymphadenitis

TB lymphadenitis = scrofula

MC form of extrapulmonary TB (EPTB)

Enlarged painless, red, firm mass in region of lymph nodes

Cervical chains or supraclavicular fossa are most common

Skin inflammation in later stages, may have fistula or sinus tract

Ddx: lymphoma, cancer, fungus, cat scratch, sarcoid, reactive, bacterial,
etc

Lymph node biopsy is or FNA is diagnostic

THINK OF with persistent lymph nodes that don’t resolve w/ abx course

Pleural Effusion

Thought to represent hypersensitivity rxn to TB Ags in pleural space

Skin test initially -ve

Usu straw colored effusion, unilateral and Parenchymal abnormalities in
50%

Culture +ve in minority

Pleural Bx for culture and histology establishes the Dx








Rx = TB Rx
Bone and Joint infections

Spinal TB = Pott’s disease is the most common (60%)

Has been described in almost any joint

Majority have prior hx of TB or concurent pulmonary TB

CXR may be normal in up to ½

lesion: paraspinal abscess skips vertebral bodies
Renal dz

Parenchymal tuberculomas, granulomas

Scarring and obstruction anywhere along urinary tract

CRF, stones, pyelo, HTN

Sterile pyuria is Classic
Genital

Male: TB is on ddx of orchitis, prostatitis, epididymitis

Female: TB is on ddx of vaginitis, cerviticitis, endometritis, oophoritis
Multisystem dz

Miliar tb = massive dissemination of TB that leads to systemic illness

More common in immunocompromised with recent or remote infection

Most common in elderly and immunusuppressed with AIDS etc

Fever, anorexia, weight loss

Multiple presentations

Miliary TB pattern on CXR only in 50%

Definitive dx: liver bx, BM bx, lymph node bx, pulmonary bx
TB meningitis

Occurs from rupture of a tubercle into the subarachnoid space (not blood
spread)

Insidious onset w/ progressive headache, fever, lethargy, mild neck
stiffness

No response to conventional treatment

Seizure, focal neurological findings, and papilledema common

Strokes common bc/ of associated vasculitis: aneuryms, thrombosis,
hemorrhage

TB accumulates at base of brain :. cranial nerve palsies common

Hyponatremia from SIADH common

CT may show tuberculomas

Elderly, homeless, immunosuppressed, poor living conditions ------- Think
TB

Sensitivity of AFB culture on one LP is 35%; increases to 90% with repeat
LP
Other CNS effects

Spinal meningitis

Incracranial abscess
GI

Pain

Obstruction

Bleeding

Peritonitis: spread from a lymph node to the peritoneum; paracentesis
AFB staining and culture only positive in 30%; biopsy may be required for
dx
TREATMENT




ED Management

Most important is to consider dx and isolate appropriately

Most emergent is massive hemoptysis: intubate,
bronchoscopy/angiography/surgery to stop hemorrhage

Severely ill: treat on spec if you have reason to suspect TB as it will not
preclude diagnosis

Ideal environment for treatment: at home antibiotics with household
member receiving prophylaxis

The best way to administer drugs is Directly Observed Therapy (DOT)

Two weeks of treatment with make the patient “non-infectious”

TB requires long periods of treatment (6-9 months)

Extrapulmonary TB usually requires even long treatment (>12 months)

ID and public health should be involved with treatment decisions

Surgery: localized disease that is multi-drug resistant should be
REMOVED

Drugs: ID and pulmonary will decide treatment; we need to know that
multiple drugs are indicated, for long periods of time, and their
complications

Corticosteroids are used for TB pericarditis

Pregnancy is not a contraindictation to treatment: INH, rifampin,
ethambutol + supplemental pyridoxime

Prophylaxis is used in some HIV +ve patients (INH alone)

Multi drug resistant TB is VERY serious and all efforts to prevent spread
should be made as treatment is very difficult
TB drugs

P
Pyrazinamide

I
Isoniazid

R
Rifampin

E
Ethambutol

S
Streptomycin
Side effects Summary

PYR - hepatitis, inc uric acid, arthralgia (serum sickness)

INH - hepatitis, paresthesia

RIF - hepatitis, flu like illness, birth ctrl

ETH - retrobulbar neuritis – check eyes

STREPT - vertigo, tinitis and ototoxicity, renal failure
* all can give rash, fever, N + V
* hepatitis most important, stop if symptomatic (RUQ pain)
Pyrazinamide

Hepatitis and hepatoxicity is the main problem;

Increased uric acid

Serum sickness, arthralgias can occur

Isoniazid







Hepatitis: 2%, increases with age
Polyneuropathy: increases with higher doses, decreased if pyridoxime
used
Net effect of INH = prevents the activation of pyridoxime (vit B6) to its active
form thus decreased GABA synthesis
Seizures occur because of lack of GABA (main inhibitory neurotransmitter)
Mortality may be 20% after acute large ingestion
Main problem is severe, prolonged, refractory seizures
Lactic acidosis and AGMA also occurs
Prolonged coma also occurs
PYRIDOXIME IS THE ANTIDOTE OF CHOICE (B6);
Mainstay of treatment as it attempts overcome pyridoxime inhibition by INH
Rapidly terminates seizures, corrects acidosis, and improves LOC
Dose of pyridoxime = dose of INH ingested (GRAM FOR GRAM)
Empiric dosing = 5 gm in adults, 70 mg/kg in peds










BCG vaccine

Bacille Calmette Guerin

Immunoprophylaxis

live attenuated M. bovis strain stimulates an immune response which
should cross react with Mycobacterium tuberculosis

Liver vaccine thus CONTRAINDICATED in AIDS

Efficacy is largely debatable

Europe used BCG vaccination for workers

Precludes the use of serial skin testing for surveillance

Indication: skin test -ve infants and kids who cannot take INH and have
ongoing exposure to untreated or inadequately treated active TB patient

doesn’t work very well
Isolation and Prevention of spread

Patient who you consider the dx should be in a negative pressure room

Surgical masks should be placed on the patient

Surgical masks are not adequate for health care workers

N-95 masks are convenient but not 100% protective

Respiratorys are the best and are indicated during intubation,
bronchoscopy or sputum induction
ED managament after Inadevertent Exposure of staff

EXAM QUESTION!!!!!!!!!!!!

See Box 129-8
TB testing program

Skin testing surveillance is mandatory in high risk env of ED

Treat if you turn positive!
TB in the HIV +ve PATIENT







the major opportunist w/ HIV (PCP not transmissable, MAC not curable)
HIV is the major factor affecting reactivation of previous TB exposure
- 10% per year reactivation
- 10% per lifetime reactivation in general population
occurs early in the disease (CD4 <200-500)
HIV immunosuppression may prevent immune response thus a -ve mantoux
signs and symptoms are nonspecific (wt loss, cough)
+ve sputum
- could be typical (Mycobacterium tuberculosis) or atypical (MAC =
Mycobacterium intracellurae)
- atypical is non-infectious but difficult to treat
- approach = assume typical and change when cultures come back
compare
EARLY IN DISEASE
- mantoux +ve 50-80%
- good response to Rx
- cavitation more frequent
- CXR typical
- 90% pulmonary
LATE IN DISEASE
- mantoux +ve <40%
- good response to Rx
- CXR less typical
- increased extrapulmonary involvement




>1 infection is very common therefore send culture for everything (TB,PCP, MAC)
treatment
- same except more problems w/ s/es b/c of polypharmacy
surveillence
- screen all HIV +ve Pts for TB; ask about previous contacts; test sputum
prevention
- mantoux >5mm + NO s/s ........................................ Prophylaxis with 2 drugs
DOT for 6mnths (if actual disease is ruled out)
- do not give BCG