TB Fulltext

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Background

Tuberculosis (TB), a multisystemic disease with myriad presentations and manifestations, is

the most common cause of infectious diseaserelated mortality worldwide. The World Health

Organiation (WHO) has estimated that ! billion people ha"e latent TB and that globally, in!##$, the disease %illed &.' million people.$ (*ee +pidemiology.)

lthough TB rates are decreasing in the -nited *tates, the disease is becoming more common

in many parts of the world. n addition, the pre"alence of drug/resistant TB is also increasing

worldwide. 0oinfection with the human immunodeficiency "irus (H1) has been an

important factor in the emergence and spread of resistance. && (*ee Treatment.)

Mycobacterium tuberculosis, a tubercle bacillus, is the causati"e agent of TB. t belongs to a

group of closely related organisms2includingM africanum,M bovis, andM microti2in the

M tuberculosiscomple3. (*ee +tiology.) n image of the bacterium is seen below.

-nder a high magnification of &445$3, this scanning electron

micrograph depicts some of the ultrastructural details seen in the cell wall configuration of a

number of 6ram/positi"e 7ycobacterium tuberculosis bacteria. s an obligate aerobic

organism, 7. tuberculosis can only sur"i"e in an en"ironment containing o3ygen. Thisbacterium ranges in length between !/5 microns, with a width between #.!/#.4 microns.

mage courtesy of the 0enters for 8isease 0ontrol and 9re"ention:8r. ;ay Butler.

The lungs are the most common site for the de"elopment of TB< =4> of patients with TB

present with pulmonary complaints. +3trapulmonary TB can occur as part of a primary or

late, generalied infection. (*ee 9athophysiology and 9resentation.)

The primary screening method for TB infection (acti"e or latent) is the 7antou3 tuberculin

s%in testwith purified protein deri"ati"e (998). n in "itro blood test based on interferon/

gamma release assay (6;) with antigens specific for 7 tuberculosis can also be used to

screen for latent TB infection. 9atients suspected of ha"ing TB should submit sputum for

acid/fast bacilli (?B) smear and culture. (*ee Wor%up.)

The usual treatment regimen for TB cases from fully susceptible M tuberculosisisolates

consists of @ months of multidrug therapy. +mpiric treatment starts with a 5/drug regimen of

isoniaid, rifampin, pyrainamide, and either ethambutol or streptomycin< this therapy is

subseAuently adusted according to susceptibility testing results and to3icity. 9regnant

women, children, H1/infected patients, and patients infected with drug/resistant strains

reAuire different regimens. (*ee Treatment and 7edication.)

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Caws "ary from state to state, but communicable/disease laws typically empower public

health officials to in"estigate suspected cases of TB, including potential contacts of persons

with TB. n addition, patients may be incarcerated for noncompliance with therapy.

Dew TB treatments are being de"eloped,&! and new TB "accines are under in"estigation.

(*ee +pidemiology and Treatment.)

Historical background

TB is an ancient disease. *igns of s%eletal TB (9ott disease) ha"e been found in remains from

+urope from Deolithic times (=### B0+), ancient +gypt (## B0+), and the pre/0olumbian

Dew World. TB was recognied as a contagious disease by the time of Hippocrates (5##

B0+), when it was termed EphthisisE (6ree% fromphthinein, to waste away). n +nglish,

pulmonary TB was long %nown by the term Fconsumption.G 6erman physician ;obert och

disco"ered and isolatedM tuberculosisin &==!.

The worldwide incidence of TB increased with population density and urban de"elopment, sothat by the ndustrial ;e"olution in +urope (&'4#), it was responsible for more than !4> of

adult deaths. n the early !#th century, TB was the leading cause of death in the -nited

*tates< during this period, howe"er, the incidence of TB began to decline because of "arious

factors, including the use of basic infection/control practices (eg, isolation).

Resurgence of TB

The -* 0enters for 8isease 0ontrol and 9re"ention (080) has been recording detailed

epidemiologic information on TB since &$4I. Beginning in &$=4, a resurgence of TB was

noted. The increase was obser"ed primarily in ethnic minorities and especially in personsinfected with H1. TB control programs were re"amped and strengthened across the -nited

*tates, and rates again began to fall. (*ee +pidemiology.)

s an 8* (acAuired immunodeficiency syndrome)related opportunistic infection, TB is

associated with H1 infections, with dual infections being freAuently noted. 6lobally,

coinfection with H1 is highest in *outh frica, ndia, and Digeria. 9ersons with 8* are

!#/5# times more li%ely than immunocompetent persons to de"elop acti"e TB.&I

0orrespondingly, TB is the leading cause of mortality among persons infected with H1.&5

Worldwide, TB is most common in frica, the West 9acific, and +astern +urope. These

regions are plagued with factors that contribute to the spread of TB, including the presence oflimited resources, H1 infection, and multidrug/resistant (78;) TB. (*ee +pidemiology.)

Drug-resistant TB

78;/TB is defined as resistance to isoniaid and rifampin, which are the ! most effecti"e

first/line drugs for TB. n !##@, an international sur"ey found that !#> ofM tuberculosis

isolates were 78;.&5 rare type of 78;/TB, called e3tensi"ely drug/resistant TB (J8;/

TB), is resistant to isoniaid, rifampin, any fluoroAuinolone, and at least one of I inectable

second/line drugs (ie, ami%acin, %anamycin, or capreomycin).$ J8;/TB resistant to all anti/

TB drugs tested has been reported in taly, ran, and ndia.&4

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7ultiple factors contribute to the drug resistance ofM tuberculosis,including incomplete and

inadeAuate treatment or adherence to treatment, logistical issues, "irulence of the organism,

multidrug transporters, host genetic factors, and H1 infection. study from *outh frica

found high genotypic di"ersity and geographic distribution of J8;/TB isolates, suggesting

that acAuisition of resistance, rather than transmission, accounts for between @I> and '4> of

J8;/TB cases.&@

Statistics

n a !##= report by the WHO, the proportion of TB cases in which the patient was resistant to

at least & antituberculosis drug "aried widely among different regions of the world, ranging

from #> to o"er 4#>< the proportion of 78;/TB cases ranged from #> to o"er !#>. The

WHO calculated that the global population/weighted proportion of 78;/TB was !.$> in

new TB cases, &4.I> in pre"iously treated patients, and 4.I> in all TB cases.&'

n the -nited *tates, the percentage of 78;/TB cases has increased slowly, from #.$> of the

total number of reported TB cases in !##= to &.I> of cases in !#&&. lthough the percentageof -*/born patients with primary 78;/TB has remained below &> since &$$', the

proportion of cases in which the patient was foreign born increased from !4.I> in &$$I to

=!.'> in !#&&.&=

J8;/TB is becoming increasingly significant.&' ccording to the -* Dational TB

*ur"eillance *ystem (DT**), between &$$I and !##@ a total of 5$ cases (I> of e"aluable

78;/TB cases) met the re"ised case definition for J8;/TB. The largest number of J8;/

TB cases was found in Dew Kor% 0ity and 0alifornia.

Cure rate

The cure rate in persons with 78;/TB is 4#/@#>, compared with $4/$'> for persons with

drug/susceptible TB.&5 The estimated cure rate for J8;/TB is I#/4#>.$ n people who are

also infected with H1, 78;/TB and J8;/TB often produce fulminant and fatal disease in e3posed health/care wor%ers.

Global surveillance and treatment of TB

s pre"iously stated, multidrug resistance has been dri"en by poor compliance with TB

therapies,resulting in difficulties in controlling the disease. 0onseAuently, a threat of globalpandemic occurred in the late &$=#s and early &$$#s. ;eacting to these signals, the WHO

de"eloped a plan to try to identify '#> of the worldLs cases of TB and to completely treat at

least =4> of these cases by the year !###.

Out of these goals were born maor TB sur"eillance programs and the concept of directly

obser"ed therapy (8OT), which reAuires a third party to witness compliance with

pharmacotherapy. With worldwide efforts, global detection of smear/positi"e cases rose from

&&> (&$$&) to 54> (!##I), with '&/=$> of those cases undergoing complete treatment.

Approach to TB in the emergency department

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8espite the importance of early isolation of patients with acti"e TB, a standardied triage

protocol with acceptable sensiti"ities has yet to be de"eloped.&$ 7oran et al demonstrated

that among patients with acti"e TB in the emergency department (+8), TB was often

unsuspected, and isolation measures were not used.!# The difficulty in establishing such a

protocol only highlights the importance of the emergency physicianMs role in the prompt

identification and isolation of acti"e TB.

large percentage of +8 patients are at increased ris% for ha"ing acti"e TB, including

homeless:shelter/dwelling patients, tra"elers from endemic areas, immunocompromised

patients, health/care wor%ers, and incarcerated patients. Therefore, emergency physicians

must consider the management and treatment of TB as a critical public health measure in the

pre"ention of a new epidemic.!&

?or high/ris% cases, prehospital wor%ers can assist in identifying household contacts who may

also be infected or who may be at high ris% of becoming infected.

9rehospital wor%ers should be aware that any case of acti"e TB in a young child indicatesdisease in & or more adults with close contact, usually within the same household. TB in a

child is a sentinel e"ent indicating recent transmission.

Etrapulmonary involvement in TB

+3trapulmonary in"ol"ement occurs in one fifth of all TB cases< @#> of patients with

e3trapulmonary manifestations of TB ha"e no e"idence of pulmonary infection on chest

radiographs or in sputum cultures.

!utaneous TB

The incidence of cutaneous TB appears low. n areas such as ndia or 0hina, where TB

pre"alence is high, cutaneous manifestations of TB (o"ert infection or the presence of

tuberculids) ha"e been found in less than #.&> of indi"iduals seen in dermatology clinics.

"cular TB

TB can affect any structure in the eye and typically presents as a granulomatous process.

eratitis, iridocyclitis, intermediate u"eitis, retinitis, scleritis, and orbital abscess are within

the spectrum of ocular disease. 0horoidal tubercles and choroiditis are the most common

ocular presentations of TB. dne3al or orbital disease may be seen with preauricularlymphadenopathy. Because of the wide "ariability in the disease process, presenting

complaints will "ary.

7ost often, patients will complain of blurry "ision that may or may not be associated with

pain and red eye. n the rare case of orbital disease, proptosis, double "ision, or e3traocular

muscle motility restriction may be the presenting complaint. 9reseptal cellulitis in children

with spontaneous draining fistula may also occur. n cases of both pulmonary and

e3trapulmonary TB, there may be ocular findings without ocular complaints.

n patients with confirmed acti"e pulmonary or acti"e, nonocular e3trapulmonary TB, ocular

incidence ranges from &.5/4.'5>. n H1 patients, the incidence of ocular TB may be higher,with a reported pre"alence of from !.=/&&.5>.

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#atient education

9atient information on TB can be found at the following sitesN

080 Tuberculosis (TB)

World Health Organiation Tuberculosis

?or patient education information, see thenfections 0enter, as well as Tuberculosis.

#athophysiology

nfection withM tuberculosisresults most commonly through e3posure of the lungs or

mucous membranes to infected aerosols. 8roplets in these aerosols are &/4 m in diameter< in

a person with acti"e pulmonary TB, a single cough can generate I### infecti"e droplets, with

as few as bacilli needed to initiate infection.

When inhaled, droplet nuclei are deposited within the terminal airspaces of the lung. The

organisms grow for !/&! wee%s, until they reach ##/,### in number, which is sufficient

to elicit a cellular immune response that can be detected by a reaction to the tuberculin s%in

test.

7ycobacteria are highly antigenic, and they promote a "igorous, nonspecific immune

response. Their antigenicity is due to multiple cell wall constituents, including glycoproteins,

phospholipids, and wa3 8, which acti"ate Cangerhans cells, lymphocytes, and

polymorphonuclear leu%ocytes

When a person is infected withM tuberculosis, the infection can ta%e & of a "ariety of paths,

most of which do not lead to actual TB. The infection may be cleared by the host immune

system or suppressed into an inacti"e form called latent tuberculosis infection (CTB), with

resistant hosts controlling mycobacterial growth at distant foci before the de"elopment of

acti"e disease. 9atients with CTB cannot spread TB.

The lungs are the most common site for the de"elopment of TB< =4> of patients with TB

present with pulmonary complaints. +3trapulmonary TB can occur as part of a primary or

late, generalied infection. n e3trapulmonary location may also ser"e as a reacti"ation site),

followed by Hispanics (!$>) and non/Hispanic blac%s:frican mericans (&4>). Howe"er,

blac%s:frican mericans represented I$> of TB cases in -*/born persons.&=

There were 4!$ deaths from TB in !##$, the most recent year for which these data are

a"ailable.

&nternational statistics

6lobally, more than & in I indi"iduals is infected with TB.I= ccording to the WHO, there

were =.= million incident cases of TB worldwide in !#, with &.& million deaths from TB

among H1/negati"e persons and an additional #.I4 million deaths from H1/associated TB.

n !##$, almost million children were orphaned as a result of parental deaths caused by

TB.I$

O"erall, the WHO noted the followingI$ N

The absolute number of TB cases has been falling since !##@ (rather than rising

slowly, as indicated in pre"ious global reports)

TB incidence rates ha"e been falling since !##! (! years earlier than pre"iously

suggested)

+stimates of the number of deaths from TB each year ha"e been re"ised downwards

The 4 countries with the highest number of incident cases in !# were ndia, 0hina, *outh

frica, ndonesia, and 9a%istan. ndia alone accounted for an estimated !@> of all TB cases

worldwide, and 0hina and ndia together accounted for I=>.I$

Race-related demographics

n !#&&, only &@> of TB cases in the -* occurred in non/Hispanic whites< =5> occurred in

racial and ethnic minorities, as follows&= N

Hispanics / !$>

sians / I#>

Don/Hispanic blac%s:frican mericans / !I>

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merican ndians:nati"e las%ans / &>

Dati"e Hawaiians:other 9acific slanders &>

Howe"er, race is not clearly an independent ris% factor, as foreign/born persons account for

''> of TB cases among Hispanics and $@> of TB cases among sians, but only !$> of TBcases among blac%s. This s%ewed distribution is most li%ely due to socioeconomic factors.

%e-related demographics

8espite the fact that TB rates ha"e declined in both se3es in the -nited *tates, certain

differences e3ist. TB rates in women ha"e declined with age, but in men, rates ha"e increased

with age. n addition, men are more li%ely than women to ha"e a positi"e tuberculin s%in test

result. The reason for these differences may be social, rather than biologic, in nature.

The estimated se3 pre"alence for TB "aries by source, from no se3 pre"alence to a male/to/female ratio in the -nited *tates of !N&.

Age-related demographics

Higher rates of TB infection are seen in young, nonwhite adults (pea% incidence, !4/5# y)

than in white adults. n addition, white adults manifest the disease later (pea% incidence, age

'# y) than do nonwhite persons.

n the -nited *tates, more than @#> of TB cases occur in persons aged !4/@5 years< howe"er,

the age/specific ris% is highest in persons older than @4 years. I$ TB is uncommon in children

aged 4/&4 years.

#rognosis

?ull resolution is generally e3pected with few complications in cases of non/78;/ and non/

J8;/TB, when the drug regimen is completed. mong published studies in"ol"ing 8OT

treatment of TB, the rate of recurrence ranges from #/&5>. 5# n countries with low TB rates,

recurrences usually occur within &! months of treatment completion and are due to relapse. 5&

n countries with higher TB rates, most recurrences after appropriate treatment are probably

due to reinfection rather than relapse.5!

9oor prognostic mar%ers include e3trapulmonary in"ol"ement, an immunocompromisedstate, older age, and a history of pre"ious treatment. n a prospecti"e study of &$$ patients

with TB in 7alawi, &! (@>) died. ;is% factors for dying were reduced baseline TD?/P

response to stimulation (with heat/%illedM tuberculosis), low body mass inde3, and ele"ated

respiratory rate at TB diagnosis.5I

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This radiograph shows a patient with typical radiographic fndings otuberculosis.

This is a chest radiograph taken ater therapy was administered to a patient withtuberculosis.

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This posteroanterior chest radiograph shows right upper lobe consolidation withminimal volume loss (elevated horizontal fssure) and a cavity in a 43yearoldman who presented with cough and ever.

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