MF3 - Tuberculosis

7/30/2019 MF3 - Tuberculosis

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Tuberculosis

By:

Laurence Gerard A. Aberia

06.22.2013


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Case of JZ

36 y/o unmarried man from RI

Recently released from state prison

Does carpentry for a living

Lives with a distant cousin in abungalow


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Case of JZ

Complained of the ff at the ER:

1.)Hemoptysis secondary to persistent

coughing over the last month

2.) Pain during exhalation and inhalation

3.) Fatigue

4.) Decreased appetite


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Introduction

Tuberculosis (TB) is caused by bacteria of theMycobacterium tuberculosis complex

Lungs are usually affected although other

organs may be involved as well

One of the oldest diseases known to affecthumans

Remains to be one of the major causes ofdeath worldwide


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Etiology

M. tuberculosis is a rod-shaped, non-spore-forming,thin aerobic bacteriummeasuring 0.5 m by 3 m.

Acid-fast bacilli

Complete genomesequence ofM. tuberculosiscomprises 4043 genesencoding 3993 proteins and50 genes encoding RNAs

High guanine + cytosinecontent (65.6%) is indicativeof an aerobic lifestyle.


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Epidemiology

More than 2B (1/3 of world pop.) areestimated to be infected with TB

Most cases come from developing countriesin Asia, Africa, and in the Middle East

Global incidence peaked around 2003 and

now appears to be declining slowly

In 20108.8M ill; 1.4M died


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Epidemiology

Commonlytransmitted bydroplet nuclei whichare aerosolized by

coughing, sneezing,or speaking

There may be as

many as 3000infectious nuclei percough


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Epidemiology

Determinants of transmission:

1.) Probability of contact

2.) Intimacy & duration of contact3.) Degree of infectiousness

4.) Shared environment


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Epidemiology

Pts whose sputum contains AFB visible bymicroscopy are the most likely to transmitthe infection

Most infectious pts: pts who have cavitarypulmonary disease, and pts who havelaryngeal TB

Pts with extrapulmonary disease arenonifectious


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Epidemiology

The risk of developing disease depends largely on theindividuals innate immunologic and nonimmunologicdefenses

Clinical illness directly following infection: Primary TB

common among children & immunocompromisedpersons

Primary TB is not generally associated with high-leveltransmissibility despite its severity

Dormant bacilli: Secondary TB / Postprimary TB

Secondary TB is more infectious b/c of frequentcavitation


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Pathogenesis and Immunity

Inhalation of nuclei containing microorganismfrom infectious pt: signals the interaction ofM.tuberculosis with the human host

Complex series of events happen that ensurethe survival of the bacilli within thephagosomes

If the bacilli are successful in arrestingphagosome maturation, replication begins


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What makes TB so dangerous?

C N C

Coalesce

Necrosis

Cavity


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Clinical Manifestations

TB may be classified as:

Pulmonary

Extrapulmonary

Both pulmonary and extrapulmonary


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Pulmonary TB

Primary Disease Occurs soon after the

initial infection withtubercle bacilli

Middle and lower lungzones are involved

Lesions formed are

peripheral

May progress rapidly toclinical illness

Postprimary Disease Results from endogenous

reactivation of latentinfection

Localized to the apicaland posterior segmentsof the upper lobe

A.K.A: Adult-type

Reactivation

Secondary TB


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Extrapulmonary TB

In order of frequency, theextrapulmonary sites most commonlyinvolved in tuberculosis are:

Lymph nodes Pleura

Genitourinary tract

Bones & Joints

Meninges Peritoneum

Pericardium


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Extrapulmonary TB: Lymph-Node

Presents as painless swelling of thelymph nodes, most commonly atposterior cervical and supraclavicular

sitesscrofula (lymphadenitis)

Most common type of EPTB

Frequent among HIV-infected patients


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Extrapulmonary TB: Pleura

Result from either:

contiguous spread of parenchymal

inflammation

accompanying postprimary disease,

actual penetration by tubercle bacilli into

the pleural space


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Extrapulmonary TB: Upper Airways

A complication of advanced cavitarypulmonary tuberculosis

may involve the larynx, pharynx, andepiglottis

Symptoms include: hoarseness, dysphonia, and dysphagia

productive cough


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Extrapulmonary TB: Genitourinary

involve any portion of the genitourinarytract

Common presentations: urinaryfrequency, dysuria, nocturia, hematuria,and flank or abdominal pain

Pts may be asymptomatic

Female > Male


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Extrapulmonary TB: Skeletal

In bone and joint disease, spread fromadjacent paravertebral lymph nodes

Weight bearing joints are mostcommonly affected


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Clinical ManifestationsExtrapulmonaryTB: Meningitis and Tuberculoma

Results from the hematogenous spread ofprimary or postprimary pulmonarydisease or from the rupture of asubependymal tubercle into the

subarachnoid space

Paresis of cranial nerves

Lumbar puncture is the cornerstone ofdiagnosis


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Extrapulmonary TB: Gastrointestinal

Uncommon

Various pathogenetic mechanisms are

involved: Swallowing of sputum with direct seeding Hematogenous spread Ingestion of milk from cows affected by

bovine tuberculosis

Ileum and Cecum are the most commonsites involved


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Extrapulmonary TB: Pericardial

Often a disease of the elderly andthose with HIV

Due to direct progression of a primaryfocus within the pericardium, toreactivation of a latent focus, or torupture of an adjacent subcarinallymph node


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Clinical ManifestationsExtrapulmonaryTB: Miliary/Disseminated

Due to hematogenous spread oftubercle bacilli

Lesions: yellowish granulomas thatresemble millet seeds

Eye examination may reveal choroidal

tubercles

Rare presentation seen in the elderly:cryptic miliary TB, which has a chronic

course involvement preceding death


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Extrapulmonary TB: HIV associated

Common occurrence among HIVpatients

A new tuberculosis infection acquiredby an HIV-infected individual mayevolve to active disease in a matter of

weeks rather than months or years


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Diagnosis of TB

The diagnosis is first entertained whenthe chest radiograph of a patient isabnormal


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Diagnosis of TBAFB Microscopy

Based on the finding of AFB onmicroscopic examination of adiagnostic specimen, such as a smear

of expectorated sputum or of tissue


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Diagnosis of TBMycobacterial

Culture

Specimens may be inoculated ontoegg or agar-based medium andincubated at 37*C

48 weeks before growth is detected


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Diagnosis of TBNucleic Acid

Amplification

Permit the diagnosis of tuberculosis inas little as several hours, with highspecificity and sensitivity approaching

that of culture

most useful for the rapid confirmation

of tuberculosis in persons with AFB-positive specimens


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Diagnosis of TBDrug

Susceptibility Testing

Initial isolate ofM. tuberculosis shouldbe tested for susceptibility to isoniazid,rifampin, and ethambutol

Conducted directly (with the clinicalspecimen) or indirectly (with

mycobacterial cultures) on solid orliquid medium


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Diagnosis of TBRadiographic

Procedures

Abnormal chest radiographs

The classic picture is that of upper lobe

disease with infiltrates and cavities

CT for questionable findings on plain

chest radiography

MRI for intracranial TB


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Diagnosis of TBTuberculin Skin

Testing

Used in screening for latent TB infection

Positive result: firm red bump at the sitew/in 2 days

How its done: Injection of small amount of TB protein on

the top layer of the skin on inner forearm


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Management

Two aims of TB treatment:

1.) Interrupt TB transmission by rendering pts

nonifectious

2.) Prevent morbidity and death by curing

pts with TB


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Management

Four major drugs are considered the first-line agents for the treatment of TB:1.) isoniazid2.) rifampin

3.) pyrazinamide4.) ethambutol

Well absorbed after oral administration

69 months regimen


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Management

isoniazid, rifampin, pyrazinamide, andethambutol were chosen on the basisof their:

1.) bactericidal activity

2.) sterilizing activity

3.) low rate of induction of drugresistance


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Management

Bacteriologic evaluation is thepreferred method of monitoring theresponse to treatment for TB

Pts with pulmonary disorders: sputumexamination until it becomes negative

Pts with extrapulmonary tuberculosis:difficult and often not feasible


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Management

Some strains of TB that becomeresistant to drugs arise by spontaneouspoint mutations in the mycobacterial

genome

Drug resistant TB: occurs at a low, but

predictable rate


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Management

During treatment, pt should bemonitored fordrug toxicity

Common adverse effect: hepatitis

Hypersensitive reactions usually requirethe discontinuation of all drugs


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Management

Treatment failure: suspected when aptssputum culture remains positiveafter3 months, or if AFB smears remain

positive after 5 months

The mycobacterial strains infecting pts

who experience relapse afterapparent successful treatment are lesslikely to have acquired drug resistance


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Management

Best way to prevent TB: diagnose andisolate infectious cases rapidly andadminister treatment until pts are

rendered noninfectious


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