tuberculosis

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doi: 10.4037/ccn2009968 2009;29:34-43Crit Care Nurse Nancy A. KnechelTuberculosis: Pathophysiology, Clinical Features, and Diagnosis

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Tuberculosis has recentlyreemerged as a majorhealth concern. Eachyear, approximately 2million persons world-

wide die of tuberculosis and 9 mil-lion become infected.1 In the UnitedStates, approximately 14000 casesof tuberculosis were reported in 2006,a 3.2% decline from the previousyear; however, 20 states and theDistrict of Columbia had higherrates.2 The prevalence of tuberculo-sis is continuing to increase becauseof the increased number of patientsinfected with human immunodefi-ciency virus, bacterial resistance tomedications, increased internationaltravel and immigration from coun-

Tuberculosis: Pathophysiology,Clinical Features, and Diagnosis

CEContinuing Education

34 CRITICALCARENURSE Vol 29, No. 2, APRIL 2009 www.ccnonline.org

tries with high prevalence, and thegrowing numbers of the homelessand drug abusers.3 With 2 billionpersons, a third of the world popu-lation,1 estimated to be infectedwith mycobacteria, all nurses, regard-less of area of care, need to under-stand the pathophysiology, clinicalfeatures, and procedures for diagno-sis of tuberculosis. The vulnerabilityof hospitalized patients to tubercu-losis is often underrecognized becausethe infection is habitually considereda disease of the community. Mosthospitalized patients are in a subop-timal immune state, particularly inintensive care units, making exposureto tuberculosis even more seriousthan in the community. By under-standing the causative organism,pathophysiology, transmission, anddiagnostics of tuberculosis and theclinical manifestations in patients,critical care nurses will be betterprepared to recognize infection,prevent transmission, and treat thisincreasingly common disease.

Causative Organism Tuberculosis is an infection

caused by the rod-shaped,

Nancy A. Knechel, RN, MSN, ACNP

Clinical Article

PRIME POINTS

• The vulnerability of hospitalized patients to tuberculosis is oftenunderrecognized becausethe infection is habituallyconsidered a disease of thecommunity.

• Read the article to findout how to obtain a defin-itive diagnosis of tubercu-losis.

• Learn about tuberculosistest like the QuantiFERON-TB Gold test and how it isbeing used.

• Nurses should advocatefor prompt isolation ofpatients with suspected orconfirmed tuberculosis.

©2009 American Association of Critical-Care Nurses doi: 10.4037/ccn2009968

This article has been designated for CE credit. A closed-book, multiple-choice examination fol-lows this article, which tests your knowledge ofthe following objectives:

1. Identify 3 reasons why the prevalence oftuberculosis is continuing to increase

2. List at least 2 diagnostic tests for tuberculosis3. Describe 2 medically challenging physiological

characteristics of tuberculosis caused by thelipid barrier of mycobacteria.



www.ccnonline.org CRITICALCARENURSE Vol 29, No. 2, APRIL 2009 35

non–spore-forming, aerobic bacteriumMycobacterium tuberculosis.4 Mycobac-teria typically measure 0.5 μm by 3μm, are classified as acid-fast bacilli,and have a unique cell wall structurecrucial to their survival. The well-developed cell wall contains a con-siderable amount of a fatty acid,mycolic acid, covalently attached tothe underlying peptidoglycan-boundpolysaccharide arabinogalactan,providing an extraordinary lipidbarrier. This barrier is responsiblefor many of the medically challeng-ing physiological characteristics oftuberculosis, including resistance toantibiotics and host defense mecha-nisms. The composition and quantityof the cell wall components affectthe bacteria’s virulence and growthrate.5 The peptidoglycan polymerconfers cell wall rigidity and is justexternal to the bacterial cell mem-brane, another contributor to thepermeability barrier of mycobacte-ria. Another important componentof the cell wall is lipoarabinomannan,a carbohydrate structural antigen onthe outside of the organism that isimmunogenic and facilitates the sur-vival of mycobacteria within macro -phages.5,6 The cell wall is key to thesurvival of mycobacteria, and a morecomplete understanding of the biosyn-thetic pathways and gene functionsand the development of antibioticsto prevent formation of the cell wallare areas of great interest.6

TransmissionMycobacterium tuberculosis is

spread by small airborne droplets,called droplet nuclei, generated bythe coughing, sneezing, talking, orsinging of a person with pulmonaryor laryngeal tuberculosis. Theseminuscule droplets can remain air-borne for minutes to hours afterexpectoration.5 The number ofbacilli in the droplets, the virulenceof the bacilli, exposure of the bacillito UV light, degree of ventilation,and occasions for aerosolization allinfluence transmission.7 Introduc-tion of M tuberculosis into the lungsleads to infection of the respiratorysystem; however, the organisms canspread to other organs, such as thelymphatics, pleura, bones/joints,or meninges, and cause extrapul-monary tuberculosis.

PathophysiologyOnce inhaled, the infectious

droplets settle throughout the air-ways. The majority of the bacilli aretrapped in the upper parts of theairways where the mucus-secretinggoblet cells exist. The mucus pro-duced catches foreign substances,and the cilia on the surface of thecells constantly beat the mucus andits entrapped particles upward forremoval.8 This system provides thebody with an initial physical defensethat prevents infection in most per-sons exposed to tuberculosis.9

Bacteria in droplets that bypassthe mucociliary system and reach thealveoli are quickly surrounded andengulfed by alveolar macrophages,7,8

the most abundant immune effectorcells present in alveolar spaces.10

These macrophages, the next line ofhost defense, are part of the innateimmune system and provide anopportunity for the body to destroythe invading mycobacteria and pre-vent infection.11 Macrophages arereadily available phagocytic cells thatcombat many pathogens withoutrequiring previous exposure to thepathogens. Several mechanisms andmacrophage receptors are involvedin uptake of the mycobacteria.11 Themycobacterial lipoarabinomannan isa key ligand for a macrophage recep-tor.12 The complement system alsoplays a role in the phagocytosis ofthe bacteria.13 The complement pro-tein C3 binds to the cell wall andenhances recognition of the mycobac-teria by macrophages. Opsonizationby C3 is rapid, even in the air spacesof a host with no previous exposureto M tuberculosis.14 The subsequentphagocytosis by macrophages initi-ates a cascade of events that resultsin either successful control of theinfection, followed by latent tuber-culosis, or progression to active dis-ease, called primary progressivetuberculosis.8 The outcome is essen-tially determined by the quality ofthe host defenses and the balancethat occurs between host defensesand the invading mycobacteria.11,15

After being ingested by macro-phages, the mycobacteria continueto multiply slowly,8 with bacterialcell division occurring every 25 to 32hours.4,7 Regardless of whether theinfection becomes controlled or pro-gresses, initial development involves

Nancy Knechel received a BSN from the University of Maryland, Baltimore, in 2003 andthen worked in an emergency department in Sacramento, California. She received an MSNfrom the University of Pennsylvania in the acute care nurse practitioner program and nowworks at University of California, San Diego Medical Center, in the Division of Trauma.Corresponding author: Nancy A. Knechel, RN, MSN, ACNP, University of California, San Diego Medical Center,200 W Arbor Dr, #8896, San Diego, CA 92103-8896 (e-mail: [email protected]).

To purchase electronic or print reprints, contact The InnoVision Group, 101 Columbia, Aliso Viejo, CA 92656.Phone, (800) 899-1712 or (949) 362-2050 (ext 532); fax, (949) 362-2049; e-mail, [email protected].

Author



production of proteolytic enzymesand cytokines by macrophages in anattempt to degrade the bacteria.11,12

Released cytokines attract T lym-phocytes to the site, the cells thatconstitute cell-mediated immunity.Macrophages then present myco -bacterial antigens on their surfaceto the T cells.11 This initial immuneprocess continues for 2 to 12 weeks;the microorganisms continue to growuntil they reach sufficient numbersto fully elicit the cell-mediatedimmune response, which can bedetected by a skin test.4,8,11

For persons with intact cell-mediated immunity, the next defen-sive step is formation of granulomasaround the M tuberculosis organisms16

(Figure 1). These nodular-typelesions form from an accumulationof activated T lymphocytes andmacrophages, which creates a micro-environment that limits replicationand the spread of the mycobacte-ria.8,12 This environment destroysmacro phages and produces earlysolid necrosis at the center of thelesion; however, the bacilli are ableto adapt to survive.18 In fact, Mtuberculosis organisms can changetheir phenotypic expression, such asprotein regulation, to enhance sur-vival.13 By 2 or 3 weeks, the necroticenvironment resembles soft cheese,often referred to caseous necrosis,and is characterized by low oxygenlevels, low pH, and limited nutri-ents. This condition restricts fur-ther growth and establishes latency.Lesions in persons with an adequateimmune system generally undergofibrosis and calcification, success-fully controlling the infection sothat the bacilli are contained in thedormant, healed lesions.18 Lesionsin persons with less effective immune

systems progress to primary pro-gressive tuberculosis.4,8,13,18

For less immunocompetent per-sons, granuloma formation is initi-ated yet ultimately is unsuccessfulin containing the bacilli. The necrotictissue undergoes liquefaction, andthe fibrous wall loses structuralintegrity. The semiliquid necroticmaterial can then drain into abronchus or nearby blood vessel,leaving an air-filled cavity at theoriginal site. In patients infectedwith M tuberculosis, droplets can be

coughed up from the bronchus andinfect other persons. If dischargeinto a vessel occurs, occurrence ofextrapulmonary tuberculosis is likely.Bacilli can also drain into the lym-phatic system and collect in the tra-cheobronchial lymph nodes of theaffected lung, where the organismscan form new caseous granulomas.18

Clinical ManifestationsAs the cellular processes occur,

tuberculosis may develop differentlyin each patient, according to the


Figure 1 Pathophysiology of tuberculosis: inhalation of bacilli (A), containment in agranuloma (B), and breakdown of the granuloma in less immunocompetent individu-als (C).Images courtesy of Centers for Disease Control and Prevention.17

Droplet nuclei withbacilli are inhaled,enter the lung, anddeposit in alveoli.

Macrophages and T lymphocytes acttogether to try to contain the infection byforming granulomas.

In weaker immune systems, the wall losesintegrity and the bacilliare able to escape andspread to other alveolior other organs.

A

B

C




status of the patient’s immune sys-tem. Stages include latency, primarydisease, primary progressive disease,and extrapulmonary disease. Eachstage has different clinical manifes-tations (Table 1).

Latent TuberculosisMycobacterium tuberculosis

organisms can be enclosed, as previ-ously described, but are difficult tocompletely eliminate.15 Persons withlatent tuberculosis have no signs orsymptoms of the disease, do not feelsick, and are not infectious.19 How-ever, viable bacilli can persist in thenecrotic material for years or even alifetime,9 and if the immune systemlater becomes compromised, as itdoes in many critically ill patients,the disease can be reactivated.

Although coinfection with humanimmunodeficiency virus is the mostnotable cause for progression toactive disease, other factors, suchas uncontrolled diabetes mellitus,sepsis, renal failure, malnutrition,smoking, chemotherapy, organtransplantation, and long-term cor-ticosteroid usage, that can triggerreactivation of a remote infectionare more common in the criticalcare setting.8,19 Additionally, persons65 years or older have a dispropor-tionately higher rate of disease thanany does other age group,20 oftenbecause of diminishing immunityand reactivation of disease.21

Primary DiseasePrimary pulmonary tuberculosis

is often asymptomatic, so that the

results of diagnostic tests (Table 2)are the only evidence of the disease.Although primary disease essentiallyexists subclinically, some self-limitingfindings might be noticed in anassessment. Associated paratracheallymphadenopathy may occur becausethe bacilli spread from the lungsthrough the lymphatic system. Ifthe primary lesion enlarges, pleuraleffusion is a distinguishing finding.This effusion develops because thebacilli infiltrate the pleural spacefrom an adjacent area. The effusionmay remain small and resolve spon-taneously, or it may become largeenough to induce symptoms suchas fever, pleuritic chest pain, anddyspnea. Dyspnea is due to poorgas exchange in the areas of affectedlung tissue. Dullness to percussion

Table 1 Differences in the stages of tuberculosis

Early infection

Immune system fights infection

Infection generally proceeds without signs or symptoms

Patients may have fever, paratracheal lymphadenopathy,or dyspnea

Infection may be only subclinicaland may not advance to activedisease

Early primary progressive(active)

Immune system does not controlinitial infection

Inflammation of tissues ensues

Patients often have nonspecificsigns or symptoms (eg, fatigue,weight loss, fever)

Nonproductive cough develops

Diagnosis can be difficult: findingson chest radiographs may benormal and sputum smears maybe negative for mycobacteria

Late primary progressive(active)

Cough becomes productive

More signs and symptomsas disease progresses

Patients experience pro-gressive weight loss,rales, anemia

Findings on chest radio -graph are normal

Diagnosis is via cultures ofsputum

Latent

Mycobacteria persist in thebody

No signs or symptoms occur

Patients do not feel sick

Patients are susceptible toreactivation of disease

Granulomatous lesions calcifyand become fibrotic, becomeapparent on chest radiographs

Infection can reappear whenimmunosuppression occurs

Table 2 Diagnostic tests for identifying tuberculosis

Variable

Purpose of testor study

Time requiredfor results

Sputum smear

Detect acid-fast bacilli

<24 hours

Sputum culture

Identify Mycobacteriumtuberculosis

3-6 weeks with solidmedia, 4-14 days withhigh-pressure liquid chromatography

Polymerasechain reaction

Identify Mtuberculosis

Hours

Tuberculin skin test

Detect exposureto mycobacteria

48-72 hours

QuantiFERON-TB test

Measure immunereactivity to Mtuberculosis

12-24 hours

Chest radiography

Visualize lobarinfiltrates withcavitation

Minutes



and a lack of breath sounds are phys-ical findings indicative of a pleuraleffusion because excess fluid hasentered the pleural space.7

Primary Progressive TuberculosisActive tuberculosis develops in

only 5% to 10% of persons exposedto M tuberculosis. When a patientprogresses to active tuberculosis,early signs and symptoms are oftennonspecific. Manifestations ofteninclude progressive fatigue, malaise,weight loss, and a low-grade feveraccompanied by chills and nightsweats.22 Wasting, a classic featureof tuberculosis, is due to the lack ofappetite and the altered metabolismassociated with the inflammatoryand immune responses. Wastinginvolves the loss of both fat and leantissue; the decreased muscle masscontributes to the fatigue.23 Fingerclubbing, a late sign of poor oxygena-tion, may occur; however, it doesnot indicate the extent of disease.24

A cough eventually develops inmost patients. Although the coughmay initially be nonproductive, itadvances to a productive cough ofpurulent sputum. The sputum mayalso be streaked with blood. Hemop-ty sis can be due to destruction of apatent vessel located in the wall ofthe cavity, the rupture of a dilatedvessel in a cavity, or the formationof an aspergilloma in an old cavity.The inflamed parenchyma may causepleuritic chest pain. Extensive diseasemay lead to dyspnea or orthopneabecause the increased interstitialvolume leads to a decrease in lungdiffusion capacity. Although manypatients with active disease havefew physical findings, rales may bedetected over involved areas duringinspiration, particularly after a

cough. Hematologic studies mightreveal anemia, which is the cause ofthe weakness and fatigue. Leukocy-tosis may also occur because of thelarge increase in the number ofleukocytes, or white blood cells, inresponse to the infection.7

Extrapulmonary TuberculosisAlthough the pulmonary system

is the most common location fortuberculosis, extrapulmonary diseaseoccurs in more than 20% of immuno-competent patients, and the risk forextrapulmonary disease increaseswith immunosuppression.20 Themost serious location is the centralnervous system, where infectionmay result in meningitis or space-occupying tuberculomas. If nottreated, tubercular meningitis isfatal in most cases, making rapiddetection of the mycobacteria essen-tial.8 Headaches and change in men-tal status after possible exposure totuberculosis or in high risk groupsshould prompt consideration of thisdisease as a differential diagnosis.Another fatal form of extrapulmonarytuberculosis is infection of the blood-

stream by mycobacteria; this formof the disease is called disseminatedor miliary tuberculosis. The bacillican then spread throughout thebody, leading to multiorgan involve-ment.25 Miliary tuberculosis pro-gresses rapidly and can be difficultto diagnose because of its systemicand nonspecific signs and symp-toms, such as fever, weight loss, andweakness.7 Lymphatic tuberculosisis the most common extrapulmonarytuberculosis, and cervical adenopa-thy occurs most often. Other possi-ble locations include bones, joints,pleura, and genitourinary system.20

Laboratory and DiagnosticStudies

Active tuberculosis may be con-sidered as a possible diagnosis whenfindings on a chest radiograph of apatient being evaluated for respira-tory symptoms are abnormal, asoccurs in most patients with pul-monary tuberculosis. The radiographsmay show the characteristic find-ings of infiltrates with cavitation inthe upper and middle lobes of thelungs21 (Figure 2). However, specific


Figure 2 Chest radiographs in pulmonary tuberculosis. A, Infiltrates in left lung. B,Bilateral advanced pulmonary tuberculosis and cavitation in apical area of right lung.Images courtesy of Centers for Disease Control and Prevention.26

BA




groups of patients, such as theelderly and patients with advancedinfection by human immunodefi-ciency virus, may not have thesetypical findings. Compared withother patients, both groups havethe classic cavitation less oftenand may have lower-lobe infil-trates as a prominent finding.7,21

Although abnormal findings on achest radiograph may suggesttuberculosis, they are not diagnos-tic for the disease.19

Traditionally, the first laboratorytest used to detect active tuberculosisin a patient with abnormal findingson chest radiographs is examinationof a sputum smear for the presenceof acid-fast bacilli (Table 2). Also,because the bacilli have entered thesputum, the patient is infectious toothers. According to the Centers forDisease Control and Prevention,19 3sputum specimens should be usedfor detection of pulmonary tubercu-losis, with specimens collected in themorning on consecutive days. How-ever, recently, investigators havequestioned the need for 3 speci-mens. Leonard et al27 concludedthat examination of 2 specimensis just as sensitive.

For the test, sputum is smearedon a slide, stained, dried, and thentreated with alcohol. Any bacillithat are present will remain redbecause they will not destain. Thetest is not specific for tuberculosis,because other mycobacteria givethe same results, but it does providea quick method to determine if res-piratory precautions should bemaintained while more definitivetesting is performed. Results ofsputum smears should be availablewithin 24 hours of the specimencollection.19

DiagnosisThe Standard

Definitive diagnosis of tubercu-losis requires the identification ofM tuberculosis in a culture of a diag-nostic specimen. The most frequentsample used from a patient with apersistent and productive cough issputum. Because most mycobacteriagrow slowly, 3 to 6 weeks may berequired for detectable growth onsolid media. However, a newer,alternative method in which high-performance liquid chromatogra-phy is used to isolate and differenti-ate cell wall mycolic acids providesconfirmation of the disease in 4 to14 days.19 Conventionally, 3 sputumsamples were also used for culturediagnosis, but the use of 2 specimens,as mentioned earlier for smears,also applies for cultures.27

After medications are started,the effectiveness of the therapy isassessed by obtaining sputum sam-ples for smears. Once again, the tra-ditional requirement of 3 sputumsmears negative for M tuberculosismay be unnecessary when deter-mining if respiratory isolation canbe discontinued.28 A patient is con-sidered to have achieved cultureconversion when a culture is nega-tive for the mycobacteria after asuccession of cultures have beenpositive; culture conversion is themost important objective evalua-tion of response to treatment.19

AlternativesUnfortunately, not all patients

with tuberculosis can be detectedby culture of sputum specimens, asituation that can lead to delayedor missed diagnosis.20,29 Addition-ally, many critically ill patients havetrouble producing the necessary

material from the lungs and insteadproduce saliva or nasopharyngealdischarge. For patients who havedifficulty generating sputum, inhala-tion of an aerosol of normal salinecan be used to induce sputum forcollection.4,7,19 However, if sputumspecimens are still inadequate, orthe index of suspicion for tuberculo-sis is still high despite cultures nega-tive for M tuberculosis, alternativeapproaches are available.

Bronchoscopy with bronchialwashings or bronchoalveolar lavagecan provide sputum for diagnosis.19

In bronchial washing, a fiberopticbronchoscope is inserted into thelungs, and fluid is squirted in andthen collected, essentially washingout a sample of cells and secretionsfrom the alveolar and bronchial air-spaces. Aliquots obtained from sub-sequent lavages constitutebronchoalveolar lavage specimens.30

In patients with involvement ofintrathoracic lymph nodes, as indi-cated by adenopathy suggestive oftuberculosis, who have sputumsmears negative for M tuberculosis,culture of specimens collected bytransbronchial needle aspirationcan be used to accurately andimmediately diagnose the disease.With this technique, specimens arecollected by inserting a 19-gaugeflexible histology needle through abronchoscopy tube; patients aresedated but conscious, and com-puted tomography scans are usedfor guidance.31

Technological AdvancementsNewer diagnostic techniques for

faster detection of M tuberculosisinclude nucleic acid amplificationtests. In these tests, molecular biol-ogy methods are used to amplify



DNA and RNA, facilitating rapiddetection of microorganisms; thetests have been approved by theFood and Drug Administration.32

One method is the polymerasechain reaction assay, which can beused to differentiate M tuberculosisfrom other mycobacteria on thebasis of genetic information andprovides results within hours.Although the test can provide rapidconfirmation of M tuberculosis insputum specimens positive for acid-fast bacilli, it has limitations, includ-ing high cost, low sensitivity, andlow availability. A polymerase chainreaction assay positive for M tuber-culosis in conjunction with a sputumsmear positive for the organismindicates true tuberculosis, but in apatient with a sputum smear nega-tive for the organism, the positivepolymerase chain reaction assayshould be considered carefullyalong with clinical indicators. Theresults of these assays can not berelied on as the sole guide for isola-tion or therapy.33

Diagnosing LatencyOnce patients recover from a

primary M tuberculosis infection and

the infection becomes latent, spu-tum specimens are negative for theorganisms, and findings on chestradiographs are typically normal.These patients also do not havesigns or symptoms of infection, andthey are not infectious to others.Tuberculin skin testing is the mostcommon method used to screen forlatent M tuberculosis.3

The tuberculin skin test is per-formed by intradermally injecting0.1 mL of intermediate-strengthpurified protein derivative (PPD) thatcontains 5 tuberculin units. After 48to 72 hours, the injection site is exam-ined for induration but not redness(Figure 3, Table 3). Although thetest is useful because the PPD elicitsa skin reaction via cell-mediatedimmunity when injected in patientspreviously infected with mycobacte-ria, it is limited because it is not spe-cific for the species of mycobacteria.Many proteins in the PPD productare highly conserved in variousspecies of mycobacteria. Also, thetest is of limited value in patientswith active tuberculosis because ofits low sensitivity and specificity.False-negatives can occur in patientswho are immunocompromised or

malnourished, because these patientscannot mount an immune responseto the injection, and in 20% to 25%of patients who have active tubercu-losis, because there is a time lag of2 to 10 weeks between infection andthe T-lymphocyte response requiredfor a positive skin reaction. False-positives can occur in patients whohave infections caused by mycobac-teria other than M tuberculosis orwho have been given BCG vaccine.35

The tuberculin skin test wasthe only test available to detect latenttuberculosis until an interferon-release assay, called QuantiFERON-TBtest, was approved by the Food andDrug Administration in 2001. Then,in 2005, a new interferon-assay,called QuantiFERON-TB Gold wasapproved and is intended to replacethe QuantiFERON-TB test, which isno longer commercially available. Inboth tests, the cell-mediated reactiv-ity to M tuberculosis is determinedby incubating whole blood with anantigen and then using an enzyme-linked immunosorbent assay tomeasure the amount of interferon-γreleased from white blood cells. Inthe QuantiFERON-TB Gold test, 2synthetic antigenic proteins specific


Figure 3 Measuring induration, noterythema, in a tuberculin skin test.Image courtesy of Centers for Disease Controland Prevention.34

Table 3 Positive tuberculin skin tests

Diameter of induration

≥5

≥10

≥15

Considered positive for

Persons at high risk for tuberculosis:Patients with chronic diseases (eg, infection with human

immunodeficiency virus)Persons with recent exposure to tuberculosisPatients with findings on radiographs suggestive of

tuberculosisEmployees of hospitals and long-term care facilities

Persons at risk for tuberculosis:Injectable drug usersPersons in close living conditionsPersons born in countries with high prevalence of

tuberculosis

Persons who do not belong to either of the other groups




in PPD are used rather than a PPDadmixture, making this test moresensitive than its predecessor.QuantiFERON-TB Gold providesresults in less than 24 hours andcan be used to detect both activeand latent tuberculosis. The resultsof the QuantiFERON-TB Gold testare similar to those of the tuberculinskin test, and the Centers for DiseaseControl and Prevention now recom-mend that the QuantiFERON-TBGold test be used in all instances inwhich the tuberculin skin test for-merly would have been used.32

Implications for CriticalCare Nurses

With the reemergence of tuber-culosis, being well informed aboutthis disease is more important thanbefore. Tuberculosis can be difficultto diagnose promptly, resulting indelayed isolation of patients andpotential spread of the disease.Detection of extrapulmonary tuber-culosis is generally even more diffi-cult because this type is often lessfamiliar to clinicians.7 Nurses playan important role in recognizingthe clinical signs and symptoms oftuberculosis, a situation that placesthem in a position for early recogni-tion of the disease, leading to diag-nosis and early isolation to preventtransmission. Importantly, diagno-sis may be based on clinical mani-festations even without a culturepositive for M tuberculosis.19 Nursesare also in a position to optimizenutrition, educate, provide emotionalsupport, and prepare patients andpatients’ families for discharge fromthe hospital.

Nearly every type of health caresetting has been implicated in thetransmission of M tuberculosis.9 The

emergency department can play avital role in control because it is apoint of entry into the hospital.However, because of the nonspe-cific signs and symptoms and datedscreening protocols, initial detectionof tuberculosis is still missed inemergency department triage.36

Consequently, a patient with tuber-culosis can be discharged into thecommunity or admitted to the hos-pital without any intervention.Patients admitted because of traumamay also escape screening for tuber-culosis, because the focus is almostentirely on injuries. Often traumapatients are admitted to an intensivecare unit, where other patients areparticularly susceptible to any infec-tion. Intubated patients are compro-mised directly from the pulmonarystandpoint and lack normal upperairway defenses that protect the lungsfrom bacteria. Many nosocomialtuberculosis outbreaks have beenreported,36 emphasizing that nursesand other health care personnelshould remember that even hospital-ized patients may have tuberculosis.

IsolationBecause nurses play a key role in

detecting tuberculosis, they shouldadvocate for prompt isolation ofpatients with suspected or confirmedM tuberculosis infection (Figure 4).Nurses should be familiar with theisolation precautions that must beimplemented. Patients with suspectedtuberculosis should be placed in anegative-pressure room, and appro-priate particulate respiratory masks(N-95/high-efficiency particulate airfilters) should be readily availableoutside the door for anyone enteringthe room.37 The number of visitorsshould be minimized, and children

should be discouraged from visiting.Patients should be instructed tocover their nose and mouth with atissue when sneezing or coughing.Additionally, they should wear amask when leaving the room, andnonurgent procedures should bepostponed until the infectious phasehas passed.

Patients receiving mechanicalventilation should also be kept in anegative-pressure room, and respi-ratory masks should still be usedby anyone who enters the room. Aclosed-system endotracheal suctioncatheter should be used for suction-ing whenever feasible. In order tohelp reduce the risk of contaminat-ing ventilation equipment or releaseof M tuberculosis organisms into theroom air, a bacterial filter should beplaced on the endotracheal tube oron the expiratory side of the ventila-tion circuit. Good oral care andstrict adherence to suctioning infec-tion control practices should be apriority, because ventilator-associatedpneumonia is already a predominantnosocomial infection and wouldpose an enhanced threat to a patientwith tuberculosis.

NutritionAdequate nutrition is an impor-

tant feature though all stages ofinfection. Malnutrition appears toincrease the risk for tuberculosis;persons with low body mass indexare greatly more at risk for tubercu-losis than are those with a highindex.38 Additionally, among patientsunderweight at the time of diagno-sis, those who increase their weightby 5% during the first 2 months oftreatment have significantly lessrelapse than do patients who gainless than 5%.38 Nurses should take



particular note of underweighttuberculosis patients, recognizingthat being underweight is a riskfactor for relapse and encouragingaggressive nutritional support.39

Also, because functional recoveryoften lags behind microbiologicalcure, the aim of nutritional inter-vention should be to restore leantissue.23,39 Nurses should also encour-age patients to engage in physical

activity to counter the loss of musclemass and subsequent fatigue. Advo-cating for a nutritionist and physicaltherapist to evaluate a patient withtuberculosis to make patient-specificrecommendations would be anappropriate action for nurses.

Emotional Support and EducationIn addition to the direct respon-

sibilities of nursing, many nurses

are also a key source of emotionalsupport for patients and patients’families during times of illness.Perceived emotional support fromnursing staff can improve adherenceto therapy. Many patients with tuber-culosis experience feelings of guiltand face stigma, and patients’ fam-ily members often fear associatingwith the patients.40 Nurses can pro-vide education to patients andpatients’ families about transmis-sion and treatment to help reducemisconceptions and can elicit con-versations to communicate con-cerns. Encouragement combinedwith education can affect a patient’sadherence to therapy, as well asimprove the patient’s mood andperception of the illness.

ConclusionsTuberculosis has reemerged as a

major public health concern and isthe second deadliest infectious dis-ease worldwide. Understanding thepathophysiology of this contagiousairborne disease, from the primaryinfection to primary progressive(active) disease or latency, is impor-tant. Understanding the pathophys-iology will help critical care nursesbe aware of the causes of the classicsigns and symptoms for tuberculo-sis. Many different diagnostic testscan be used to evaluate a patientwith suspected tuberculosis, and thestage or progression of the diseasemarkedly affects the results. Even incritical care, each nurse has an


Figure 4 A general plan-of-care algorithm for a patient who may have tuberculosis.

Patient recently admitted throughemergency department or trauma

bay

Long-term patient, immunocompro-mised patient, or patient with risk

factors for tuberculosis

Smear positive for mycobacteria: continue isolation

Smear negative for mycobacteria:remove patient from isolation

Sputum culture

If findings on chest radiograph equivocalfor tuberculosis and skin test or

QuantiFERON test positive for tuberculosis,patient may have latent tuberculosis

Patient may have tuberculosis andmay not have been screened for the

disease when admitted

Patient is vulnerable to tuberculosisfrom newly admitted patients or

hospital outbreaks

If possible, inquire about history of or exposure to tuberculosis

Sputum culture positivefor Mycobacterium

tuberculosis

Sputum culturenegative for Mtuberculosis

Look for signs and symptomsof reactivation of disease

during hospitalization

Maintain isolationprecautions,

optimize nutrition,educate patient,provide support

Remove patientfrom isolation

Patient has signs and/or symptoms suggestive of tuberculosis

Isolate patient and advocate for screening: chest radiograph

1. Skin test with purified protein derivative or QuantiFERON-TB Gold test2. Sputum smear

d•tmoreTo read more about tuberculosis, read “ThePursuit of Healthcare” by Christopher W.Bryan-Brown and Kathleen Dracup in theAmerican Journal of Critical Care, 2004;13:368-370. Available at www.ajcconline.org.

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opportunity to contribute to thecontrol of tuberculosis by learningabout the signs and symptoms ofthe disease, risk factors specific tocritical care patients, and the appro-priate actions to take should such acase occur. The more nurses knowabout tuberculosis, the more they cancontribute to minimizing its trans-mission, making early diagnoses, andpreventing increases in morbidityand mortality due to this disease. CCN

Financial DisclosuresNone reported.

References1. Centers for Disease Control and Prevention.

World TB day—March 24, 2007. MMWRMorb Mortal Wkly Rep. 2007;56(11):245.

2. Centers for Disease Control and Preven-tion. Trends in tuberculosis incidence,United States, 2006. MMWR Morb MortalWkly Rep. 2007;56(11):245-250.

3. Goldrick BA. Once dismissed, still rampant:tuberculosis, the second deadliest infec-tious disease worldwide. Am J Nurs. 2004;104(9):68-70.

4. Porth CM. Alterations in respiratory func-tion: respiratory tract infections, neoplasms,and childhood disorders. In: Porth CM,Kunert MP. Pathophysiology: Concepts ofAltered Health States. Philadelphia, PA: Lip-pincott Williams & Wilkins; 2002:615-619.

5. Lee RB, Li W, Chatterjee D, Lee RE. Rapidstructural characterization of the arabino-galactan and lipoarabinomannan in livemycobacterial cells using 2D and 3DHR-MAS NMR: structural changes in thearabinan due to ethambutol treatment andgene mutation are observed. Glycobiology.2005;15(2):139-151.

6. Joe M, Bai Y, Nacario RC, Lowary TL. Syn-thesis of the docosanasaccharide arabinandomain of mycobacterial arabinogalactanand a proposed octadecasaccharide biosyn-thetic precursor. J Am Chem Soc. 2007;129(32):9885-9901.

7. American Thoracic Society and Centers forDisease Control and Prevention. Diagnosticstandards and classification of tuberculosisin adults and children. Am J Respir Crit CareMed. 2000;161(4 pt 1):1376-1395.

8. Frieden TR, Sterling TR, Munsiff SS, WattCJ, Dye C. Tuberculosis. Lancet. 2003;362:887-899.

9. Jensen PA, Lambert LA, Iademarco MF,Ridzon R; Centers for Disease Control andPrevention. Guidelines for preventing thetransmission of Mycobacterium tuberculosisin health-care settings, 2005. MMWRRecomm Rep. 2005;54(RR-17):1-141.

10. Korf JE, Pynaert G, Tournoy K, et al.Macrophage reprogramming by mycolicacid promotes a tolerogenic response inexperimental asthma. Am J Respir Crit CareMed. 2006;174(2):152-160.

11. van Crevel R, Ottenhoff THM, van der MeerJWM. Innate immunity to Mycobacteriumtuberculosis. Clin Microbiol Rev. 2002;15:294-309.

12. Nicod LP. Immunology of tuberculosis.Swiss Med Wkly. 2007;137(25-26):357-362.

13. Li Y, Petrofsky M, Bermudez LE. Mycobac-terium tuberculosis uptake by recipienthost macrophages is influenced by environ-mental conditions in the granuloma of theinfectious individual and is associated withimpaired production of interleukin-12 andtumor necrosis factor alpha. Infect Immun.2002;70:6223-6230.

14. Ferguson JS, Weis JJ, Martin JL, SchlesingerLS. Complement protein C3 binding toMycobacterium tuberculosis is initiated bythe classical pathway in human bronchoalve-olar lavage fluid. Infect Immun. 2004;72:2564-2573.

15. Goyot-Revol V, Innes JA, Hackforth S,Hinks T, Lalvani A. Regulatory T cells areexpanded in blood and disease sites inpatients with tuberculosis. Am J Resp CritCare Med. 2006;173:803-810.

16. Rosenkrands I, Slayden RA, Crawford J, et al.Hypoxic response of Mycobacteria tubercu-losis studied by metabolic labeling and pro-teome analysis of cellular and extracellularproteins. J Bacteriol. 2002;184:3485-3491.

17. Transmission and pathogenesis of tubercu-losis: TB disease [self-study module]. Cen-ters for Disease Control and PreventionWeb site. http://www2.cdc.gov/phtn/tbmodules/modules1-5/m1/con6a.htm.Accessed January 29, 2009.

18. Dheda, K, Booth H, Huggett JF, et al. Lungremodeling in pulmonary tuberculosis. JInfect Dis. 2005;192:1201-1210.

19. Interactive core curriculum on tuberculo-sis. Centers for Disease Control and Pre-vention Web site. http://www.cdc.gov/tb/webcourses/CoreCurr/TB_Course/Menu/frameset_internet.htm. Accessed January28, 2009.

20. Surveillance reports: reported tuberculosis inthe United States, 2005. Centers for DiseaseControl and Prevention Web site. http://www.cdc.gov/tb/surv/surv2005/default.htm.Published September 2006. Last reviewedMay 18, 2008. Accessed January 28, 2009.

21. Thrupp L, Bradley S, Smith P, Simor A,Gantz N, et al. Tuberculosis prevention andcontrol in long-term-care facilities for olderadults. Infect Control Hosp Epidemiol. 2004;25:1097-1108.

22. TB elimination: the difference between latentTB infection and active TB disease. Centersfor Disease Control and Prevention Web site.http://cdc.gov/tb/pubs/tbfactsheets/LTBIandActiveTB.pdf. Updated October 7,2008. Accessed January 28, 2009.

23. Paton NI, Chua YK, Earnest A, Chee CB.Randomized controlled trial of nutritionalsupplementation in patients with newlydiagnosed tuberculosis and wasting. Am JClin Nutr. 2004;80:450-465.

24. Ddungu H, Johnson JL, Smieja M, Mayanja-Kizza H. Digital clubbing in tuberculosis—relationship to HIV infection, extent ofdisease and hypoalbuminemia. BMC InfectDis. 2006;6:45.

25. Wang JY, Hsueh PR, Wang SK, et al. Dissem-

inated tuberculosis: a 10-year experience in amedical center. Medicine (Baltimore). 2007;86(1):39-46.

26. Vaccines and preventable diseases: tubercu-losis photos. Centers for Disease Controland Prevention Web site. http://www.cdc.gov/vaccines/vpd-vac/tb/photos.htm. Lastmodified September 11, 2007. Accessed Jan-uary 29, 2009.

27. Leonard MK, Osterholt D, Kourbatova EV,et al. How many sputum specimens are nec-essary to diagnose pulmonary tuberculosis?Am J Infect Control. 2005;33(1):58-61.

28. Bryan CS, Rapp DJ, Brown CA. Discontinu-ation of respiratory isolation for possibletuberculosis: do two negative sputumsmear results suffice? Infect Control HospEpidemiol. 2006;27:515-516.

29. Jafari C, Ernst M, Kalsdorf B, et al. Rapiddiagnosis of smear-negative tuberculosis bybronchoalveolar lavage enzyme-linkedimmunospot. Am J Respir Crit Care Med.2006;174:1048-1054.

30. Rutgers SR, Timens W, Kauffmann HF, et al.Comparison of induced sputum withbronchial wash, bronchoalveolar lavageand bronchial biopsies in COPD. Eur RespirJ. 2000;15:109-115.

31. Bilaceroglu S, Gunel O, Eris N, Cagirici U,Mehta AC. Transbronchial needle aspira-tion in diagnosing intrathoracic tuberculo-sis lymphadenitis. Chest. 2004;126:259-267.

32. Mazurek GH, Jereb J, Lobue P, et al; Divisionof Tuberculosis Elimination, National Centerfor HIV, STD, and TB Prevention, Centersfor Disease Control and Prevention (CDC).Guidelines for using the QuantiFERON-TBgold test for detecting Mycobacteriumtuberculosis infection, United States [pub-lished correction appears in MMWR MorbMortal Wkly Rep. 2005:54(50):1288]. MMWRRecomm Rep. 2005;54(RR-15):49-55.

33. Michos AG, Daikos GL, Tzanetou K, et al.Detection of Mycobacterium tuberculosisDNA in respiratory and nonrespiratoryspecimens by the Amplicor MTB PCR.Diagn Microbiol Infect Dis. 2006;54:121-126.

34. Mantoux tuberculin skin test. Centers forDisease Control and Prevention Web site.http://www.cdc.gov/tb/pubs/Posters/images/Mantoux_wallchart.PDF.Accessed January 29, 2009.

35. Anderson ST, Williams AJ, Brown JR, et al.Transmission of Mycobacterium tuberculo-sis undetected by tuberculin skin testing. AmJ Respir Crit Care Med. 2006;173:1038-1042.

36. Sokolove PE, Lee BS, Krawczky JA, BanosPT, Gregson AL. Implementation of anemergency department triage procedure forthe detection and isolation of patients withactive pulmonary tuberculosis. Ann InternMed. 2000;35:327-336.

37. Toth A, Fackelmann J, Pigott W, TolomeoO. Tuberculosis prevention and treatment.Can Nurse. 2004;100(9):27-30.

38. Khan A, Sterling TR, Reves R, et al. Lack ofweight gain and relapse risk in a largetuberculosis treatment trial. Am J Respir CritCare Med. 2006;174:344-348.

39. Schwenk A, Hodgson L, Wright A, et al.Nutritional partitioning during treatmentof tuberculosis: gain in body fat but not inprotein mass. Am J Clin Nutr. 2004;79:1006-1012.

40. Chalco K, Wu DY, Mestanza L, et al. Nursesas providers of emotional support topatients with MDR-TB. Int Nurs Rev. 2006;53(4):253-260.

eLettersNow that you’ve read the article, create or contributeto an online discussion about this topic using eLetters.Just visit www.ccnonline.org and click “Respondto This Article” in either the full-text or PDF viewof the article.



CE Test Test ID C0923: Tuberculosis: Pathophysiology, Clinical Features, and DiagnosisLearning objectives: 1. Identify 3 reasons why the prevalence of tuberculosis is continuing to increase 2. List at least 2 diagnostic tests for tuberculosis 3. Describe 2 medically challenging physiological characteristics of tuberculosis caused by the lipid barrier of mycobacteria

Program evaluationYes No

Objective 1 was met � �Objective 2 was met � �Objective 3 was met � �Content was relevant to my

nursing practice � �My expectations were met � �This method of CE is effective

for this content � �The level of difficulty of this test was: � easy � medium � difficult

To complete this program, it took me hours/minutes.

Test answers: Mark only one box for your answer to each question. You may photocopy this form.

1. How many people worldwide become infected with tubercu-losis each year?a. 2 million c. 14 millionb. 9 million d. 20 million

2. How many people in the world are estimated to be infectedwith mycobacteria?a. 9 billion c. 20 billionb. 14 billion d. 2 billion

3. What makes an intensive care unit patient’s tuberculosis exposure more serious than community exposure?a. A suboptimal immune stateb. Mycobacteria infectionc. Resistant bacteria infectiond. Advanced pneumonia

4. Tuberculosis is an infection caused by what rod shaped,non–spore-forming aerobic bacterium?a. Aspergilliusb. Mycobacteriumc. Enterococcusd. Streptococcus

5. Which of the following is a challenge created by the lipid bar-rier of Mycobacterium tuberculosis?a. Resistance to antibioticsb. Immune responsec. Physical defensed. Misdiagnosis

6. M tuberculosis is spread by which of the following?a. Skin contact with bacteriumb. Ingestion of bacteriac. Airborne dropletsd. Infection by blood stream

7. After being ingested by macrophages, the myocobacteria continue tomultiply slowly with bacteria cell division occurring how often?a. Every 20 to 32 hours c. Every 25 to 32 hoursb. Every 25 to 30 hours d. Every 20 to 30 hours

8.The initial immune process continues for how long?a. 2 to 10 weeks c. 2 to 12 weeksb. 4 to 12 weeks d. 4 to 10 weeks

9. Which of the following is the necrotic environment that is character-ized by low oxygen levels, low ph, and limited nutrients?a. Caseous necrosisb. Frontal necrosisc. Immune necrosisd.Fibrotic necrosis

10. What age group has a disproportionately higher rate of diseasethan any other age group?a. 50 years and olderb. 35 years and olderc. 40 years and olderd. 65 year and older

11. Why are the results of primary pulmonary tuberculosis diagnostictest often the only evidence of disease?a. Because primary tuberculosis is not diagnosedb. Because primary tuberculosis is misdiagnosedc. Because primary tuberculosis exists subclinicallyd.Because primary tuberculosis is asymptomatic

12. Upon diagnosing an abnormal chest radiograph, the first laboratorytest used to detect tuberculosis will examine which of the following?a. Sputum smear for acid-fast bacillib. Bronchoscopy findingsc. Purified protein derivative testd.Sputum culture

For faster processing, takethis CE test online atwww.ccnonline.org

(“CE Articles in this issue”)or mail this entire page to:

AACN, 101 Columbia Aliso Viejo, CA 92656.

Test ID: C0923 Form expires: April 1, 2011 Contact hours: 1.0 Fee: AACN members, $0; nonmembers, $10 Passing score: 9 correct (75%) Category: A, Synergy CERP ATest writer: Brenda Hardin-Wike, RN, CNS, MSN, CCNS

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SignatureThe American Association of Critical-Care Nurses is accredited as a provider of continuing nursing education by the American Nurses Credentialing Center’s Commission on Accreditation.

AACN has been approved as a provider of continuing education in nursing by the State Boards of Nursing of Alabama (#ABNP0062), California (#01036), and Louisiana (#ABN12). AACN programming meets the standards for most other states requiring mandatory continuing education credit for relicensure.

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