TuberculosisTuberculosis

Jiang LihongJiang Lihong

Tianjin Medical UniversityTianjin Medical University

tuberculosistuberculosis

• EtiologyEtiology

• EpidemiologyEpidemiology

• PathogenesisPathogenesis

• Clinical manifestationClinical manifestation

• Diagnostic tests and procedures the Diagnostic tests and procedures the tuberculin testtuberculin test

• TreatmentTreatment

INTRODUCTIONINTRODUCTION

• Chronic infectious disease Chronic infectious disease characterized by an extremely characterized by an extremely variable clinical coursevariable clinical course

• pathogen: mycobacterium pathogen: mycobacterium tuberculosis ; mycobacterium bovistuberculosis ; mycobacterium bovis

• Both the incidence and death rate of Both the incidence and death rate of tuberculosis have decreased tuberculosis have decreased dramatically since 1970. dramatically since 1970.

• Unfortunately, the number of new active Unfortunately, the number of new active cases has not decreased as rapidly as cases has not decreased as rapidly as the death rate, and the incidence has the death rate, and the incidence has increased during recent years.(?)increased during recent years.(?)

EtiologyEtiology• Non-spore forming, nonmotile, Non-spore forming, nonmotile,

pleiomorphic, weakly gram-positive, pleiomorphic, weakly gram-positive, curved rods about 2-4um longcurved rods about 2-4um long

• Appear beaded or clumped in stained Appear beaded or clumped in stained clinical specimens or culture mediaclinical specimens or culture media

• Grow best at 37-41Grow best at 37-41• grow slowly, their generation time being grow slowly, their generation time being

12-24 hr12-24 hr

tuberculosistuberculosis

tuberculosistuberculosis

tuberculosistuberculosis

•

EpidemiologyEpidemiology

WHO estimates that one third of the WHO estimates that one third of the world’s population are infected with M. world’s population are infected with M. tuberculosis. Tuberculosis is especially tuberculosis. Tuberculosis is especially

prevalent in populations undergoing the prevalent in populations undergoing the stresses of poor nutrition, over-crowding, stresses of poor nutrition, over-crowding,

inadequate health care, and inadequate health care, and displacement.displacement.

Infectious routeInfectious route

• Pulmonary route: cough, sneeze, Pulmonary route: cough, sneeze, speakspeak

• digestive route: milkdigestive route: milk

• others: skin, placenta et al.others: skin, placenta et al.

Spread of droplet nuclei from one individual to another. CDC. After droplet nuclei are inhaled, the bacteria are nonspecifically taken up by alveolar macrophages. However, the macrophages are not activated and are unable to destroy the intracellular organisms.  

• Facial infection of a Facial infection of a boy that boy that contracted bovine contracted bovine TB by drinking milk TB by drinking milk from an infected from an infected cow(1923)cow(1923)

Evidence suggests that Evidence suggests that differences in tuberculosis differences in tuberculosis

attack rates result from attack rates result from differences in socioeconomic differences in socioeconomic status and living conditions status and living conditions rather than racial factors.rather than racial factors.

•

ageage• Infant: develop progressive extension of Infant: develop progressive extension of

the initial lesion in the lung, miliary the initial lesion in the lung, miliary tuberculosis, tuberculosis meningitis(?)tuberculosis, tuberculosis meningitis(?)

• puberty and adult: chronic pulmonary puberty and adult: chronic pulmonary tuberculosistuberculosis

• adolescence girls develop chronic adolescence girls develop chronic pulmonary TB more commonly than boyspulmonary TB more commonly than boys

PathogenesisPathogenesis

• In the initial infection, tubercle bacilli In the initial infection, tubercle bacilli enter the lungs and establish a site. enter the lungs and establish a site. Although host defenses in the lung Although host defenses in the lung respond to the initial infection, some respond to the initial infection, some organisms reach regional lymph organisms reach regional lymph nodes through the lymphatics, and nodes through the lymphatics, and others reach distant organs via the others reach distant organs via the hematogenous route.hematogenous route.

Primary complexPrimary complex

• Pulmonary parenchymal lesion (initial Pulmonary parenchymal lesion (initial focus)focus)

• lymphangitislymphangitis

• hilar adenopathyhilar adenopathy

progressprogress

• Blood vessels or lymphatics: massive Blood vessels or lymphatics: massive hematogenous disseminationhematogenous dissemination

• bronchial lumen and bronchogenic bronchial lumen and bronchogenic dissemination: tuberculous dissemination: tuberculous bronchopneumonia bronchopneumonia

ghon complex in lung,gross. Note the subpleural granuloma at the right along with the granuloma in the hilar lymph node, typical findings for the Ghon complex of primary TB.

Ghon complex in lung,closer view,gross. On closer inspection,caseous tan necrotic tissue is seen to constitute the granulomas in this gross appearance of a Ghon complex. Most patients with primary TB are asymptomatic, and the granulomas resolve

Cavitary tuberculosis in lung, florid, gross. .

Cavitary tuberculosis in lung, closer view,gross. The caseous necrosis is extensive, and cavitation is prominent. Such patients can be highly contagious

Miliary tuberculosis in lung, gross. The small millet seed sized granulomas in this lung are typical for miliary Tuberculosis

Miliary tuberculosis in lung, closer view,gross. Miliary tuberculosis, as seen here, typically occurs when resistance to mycobacterial infection is poor.

Clinical manifestationsClinical manifestations

Without clinical manifestationWithout clinical manifestation

ranging over a broad ranging over a broad spectrum of intensityspectrum of intensity

Tuberculosis affects many Tuberculosis affects many parts of the bodyparts of the body

•

Common findingsCommon findings

• FeverFever

• malaisemalaise

• anorexiaanorexia

• weight lossweight loss

• night sweatsnight sweats

• coughcough

Initial (primary) tuberculosisInitial (primary) tuberculosis

• In the initial pulmonary infection host In the initial pulmonary infection host defenses are usually able to limit the defenses are usually able to limit the infection after it has caused a small infection after it has caused a small parenchymal lesion, lymphangitis, hilar parenchymal lesion, lymphangitis, hilar adenopathy, and subsequent minimal adenopathy, and subsequent minimal hematogenous dissemination.hematogenous dissemination.

• In the 2-10In the 2-10 weeks required for weeks required for development of tuberculin development of tuberculin hypersensitivity, the child may not appear hypersensitivity, the child may not appear ill.ill.

Initial (primary) tuberculosisInitial (primary) tuberculosis

• With development of tuberculin With development of tuberculin hypersensitivity, there may be fever hypersensitivity, there may be fever and positive tuberculin test.and positive tuberculin test.

• X-ray: infant: infiltrative lesion and X-ray: infant: infiltrative lesion and enlargement of hilar nodes; old enlargement of hilar nodes; old children: often normal children: often normal

Initial (primary ) Initial (primary ) tuberculosistuberculosis• The child, usually an infant, who is unable The child, usually an infant, who is unable

to limit spread of the parenchymal lesion to limit spread of the parenchymal lesion develops a progressive initial focus. develops a progressive initial focus.

• There may be persistent fever, malaise, There may be persistent fever, malaise, anorexia, pallor, anemia,weakness,weight anorexia, pallor, anemia,weakness,weight lossloss

• However, extensive tuberculosis lesion However, extensive tuberculosis lesion often produce minimal abnormal physical often produce minimal abnormal physical findings.findings.

Initial (primary ) Initial (primary ) tuberculosistuberculosis

• In initial tuberculosis, hilar glandular In initial tuberculosis, hilar glandular involvement is constant.involvement is constant.

• With the passage of time the nodes With the passage of time the nodes generally decrease in size, residual generally decrease in size, residual calcification being the only calcification being the only permanent evidence of involvement.permanent evidence of involvement.

Initial (primary ) Initial (primary ) tuberculosistuberculosis

• Clinical manifestation of bronchial Clinical manifestation of bronchial involvement depend on the degree involvement depend on the degree to which air exchange is to which air exchange is embarrassed.embarrassed.

• Expiratory wheezing, emphysema, Expiratory wheezing, emphysema, atelectasis, bronchiectasisatelectasis, bronchiectasis

Previous primary Previous primary tuberculosistuberculosis• Both the peripheral Both the peripheral

lung nodule(arrow lung nodule(arrow 1) and the hilar 1) and the hilar lymphnode(arrow lymphnode(arrow 2), which have 2), which have been infected with been infected with tuberculosis , have tuberculosis , have calcified.calcified.

Cavitary pulmonary Cavitary pulmonary tuberculosistuberculosis

tuberculosistuberculosis• This radiograph This radiograph

shows a patient shows a patient with typical with typical radiographic radiographic findings of findings of tuberculosis.tuberculosis.

• This is a chest This is a chest radiograph taken radiograph taken after therapy of a after therapy of a patient with patient with tuberculosis.tuberculosis.

Reinfetion(chronic) Reinfetion(chronic) pulmonarypulmonary• Endogenous/exogenousEndogenous/exogenous

• differs from initial form: apex of the lung, differs from initial form: apex of the lung, cavitation, little or no hilar glandular cavitation, little or no hilar glandular enlargementenlargement

• fever, malaise, anorexia, weight loss, fever, malaise, anorexia, weight loss, anemia, cough, chest painanemia, cough, chest pain

• Hemoptysis does not occur as commonly Hemoptysis does not occur as commonly in children as in adults.in children as in adults.

Tuberculous pleurisyTuberculous pleurisy• Cultures of the pleural fluid are often Cultures of the pleural fluid are often

negative for tubercle bacillinegative for tubercle bacilli• tuberculin test is importanttuberculin test is important• X-ray/pleural biopsyX-ray/pleural biopsy• Clinical manifestation vary according to Clinical manifestation vary according to

extent of the effusion and nature of the extent of the effusion and nature of the underlying pulmonary lesion. The effusion underlying pulmonary lesion. The effusion often develops about a year or so after the often develops about a year or so after the primary infectionprimary infection

Tuberculous pleurisyTuberculous pleurisy• Low to high fever, shortness of breath, Low to high fever, shortness of breath,

chest pain on deep inspiration, and chest pain on deep inspiration, and diminished breath sounddiminished breath sound

• Tuberculin skin test is positive in only 70-Tuberculin skin test is positive in only 70-80% of case80% of case

• Prognosis is excellent but radiographic Prognosis is excellent but radiographic resolution often takes monthsresolution often takes months

Pleural fluidPleural fluid• Yellow, only occasionally tinged with Yellow, only occasionally tinged with

bloodblood• Specific gravity is usually 1.012-Specific gravity is usually 1.012-

1.025, the protein is usually 2-4g/dl, 1.025, the protein is usually 2-4g/dl, and the glucose may be lowand the glucose may be low

• Several hundred to several thousand Several hundred to several thousand white blood cells/mmwhite blood cells/mm³³

Miliary tuberculosisMiliary tuberculosis• A massive hematogenous dissemination A massive hematogenous dissemination

produce miliary tuberculosis.produce miliary tuberculosis.• Infant and young childrenInfant and young children• 6 to 12 months after the primary 6 to 12 months after the primary

tuberculosistuberculosis• Often develops without antecedent Often develops without antecedent

evidence of tuberculous disease ;less evidence of tuberculous disease ;less commonly it follows a known infection.commonly it follows a known infection.

Miliary tuberculosisMiliary tuberculosis

• clinical manifestation: early: clinical manifestation: early: irritability, anorexia, fever, malaise; irritability, anorexia, fever, malaise; developing: fever, prostration, weight developing: fever, prostration, weight loss, spleen, liver,peripheral loss, spleen, liver,peripheral lymphnodes enlargelymphnodes enlarge

• diagnosis: tuberculin test, X-diagnosis: tuberculin test, X-ray(snowstorm appearance)ray(snowstorm appearance)

Tuberculous meningitisTuberculous meningitis

• Tuberculous meningitis is one of the Tuberculous meningitis is one of the most serious complications of most serious complications of tuberculosis. It usually develops tuberculosis. It usually develops within a year after initial infection. within a year after initial infection. Meningitis may occur as a Meningitis may occur as a complication of miliary tuberculosis.complication of miliary tuberculosis.

Tuberculous meningitisTuberculous meningitis

Three stages:Three stages:

• The prodromal stage of invasion with The prodromal stage of invasion with nonspecific symptomsnonspecific symptoms

• the stage of clear-cut meningeal the stage of clear-cut meningeal manifestationsmanifestations

• the terminal stage of paralysis, the terminal stage of paralysis, coma, and deathcoma, and death

Tuberculous meningitisTuberculous meningitis• The brain stem is often the site of The brain stem is often the site of

greatest involvement, which greatest involvement, which accounts for the frequently accounts for the frequently associated dysfunction of cranial associated dysfunction of cranial nerves III,VI,VII. The exudate also nerves III,VI,VII. The exudate also interferes with the normal flow of interferes with the normal flow of CSF in and out of the venticular CSF in and out of the venticular system, leading to a communicating system, leading to a communicating hydrocephalus.hydrocephalus.

First (prodromal) stageFirst (prodromal) stage

• Diagnosis remains in doubt for 1 to 2 Diagnosis remains in doubt for 1 to 2 weeksweeks

• nonspecific symptoms: irritable nonspecific symptoms: irritable disposition, drowsiness, restless disposition, drowsiness, restless sleep, loss of appetite, constipation, sleep, loss of appetite, constipation, abdominal pain, low-grade fever, abdominal pain, low-grade fever, headache, vomitingheadache, vomiting

Secondary(meningeal ) Secondary(meningeal ) stagestage• Signs of meningeal irritation: stiff neck and Signs of meningeal irritation: stiff neck and

back, positive Kerning and Bruzinski signs, back, positive Kerning and Bruzinski signs, bulging of the anterior fontanel, bulging of the anterior fontanel, exaggeration of deep tendon reflexesexaggeration of deep tendon reflexes

• sensorium is clouded, temperature sensorium is clouded, temperature increases,vomiting becomes more increases,vomiting becomes more frequentfrequent

Second(meningeal) stageSecond(meningeal) stage

• Eye-grounds: papilledema, Eye-grounds: papilledema, peripherally located choroidal peripherally located choroidal tuberclestubercles

• cranial nerve palsiescranial nerve palsies

• lasts 7 to 10 dayslasts 7 to 10 days

• irregular respiration developsirregular respiration develops

Third (terminal) stageThird (terminal) stage

• Stupor progresses to coma.Stupor progresses to coma.

• Pupils become dilated and fixedPupils become dilated and fixed

• corneal reflex is absentcorneal reflex is absent

• deep tendon reflexes disappeardeep tendon reflexes disappear

• emaciation and scaphoid abdomen emaciation and scaphoid abdomen are notableare notable

• Irregular respiration developsIrregular respiration develops

CT OR MRICT OR MRI

• may be normal during early stages of may be normal during early stages of the disease . As disease progresses, the disease . As disease progresses, basilar enhancement, and basilar enhancement, and communicating hydrocephalus with communicating hydrocephalus with signs of cerebral edema or early signs of cerebral edema or early focal ischemia are the most common focal ischemia are the most common findings.findings.

• Some small children with tuberculous Some small children with tuberculous meningitis may have one or several meningitis may have one or several clinically silent tuberculomas, clinically silent tuberculomas, occuring most often in the cerebral occuring most often in the cerebral cortex or thalamic regions.cortex or thalamic regions.

CSFCSF

• Leukocyte count usually ranges from Leukocyte count usually ranges from 10 to 500 cells/mm10 to 500 cells/mm³³, , glucose is glucose is typically less than 40mg/dl but rarely typically less than 40mg/dl but rarely goes below 20mg/dl, protein level is goes below 20mg/dl, protein level is elevated and may be markedly high elevated and may be markedly high secondary to hydrocephalus and secondary to hydrocephalus and spinal block.spinal block.

Tuberculous lymphadenitisTuberculous lymphadenitis

• Cervical glandular involvement is the Cervical glandular involvement is the most common formmost common form

• diagnosis involves differentiation diagnosis involves differentiation from disordersfrom disorders

• a positive tuberculin test points a positive tuberculin test points toward,but does not provetoward,but does not prove

• biopsy and culturebiopsy and culture

18 18 year-old woman presented with a several month history of year-old woman presented with a several month history of progressive swelling of the left side of her neck. Biopsy of the neck progressive swelling of the left side of her neck. Biopsy of the neck node was positive for acid-fast bacillinode was positive for acid-fast bacilli

Skeletal tuberculosisSkeletal tuberculosis

• Tuberculosis osteomyelitis involves Tuberculosis osteomyelitis involves mainly the thoracic and lumbar mainly the thoracic and lumbar vertebrae followed by knee and hip. vertebrae followed by knee and hip. There is extensive necrosis and bony There is extensive necrosis and bony destruction with compressed destruction with compressed fractures and extension to soft fractures and extension to soft tissues, including psoas tissues, including psoas “cold”abscess.“cold”abscess.

Gastrointestinal tuberculosisGastrointestinal tuberculosis

• This is uncommon today because routine This is uncommon today because routine pasteurisation of milk has elimated M. pasteurisation of milk has elimated M. bovis infections. However, M. Tuberculosis bovis infections. However, M. Tuberculosis organisms coughed up in sputum may be organisms coughed up in sputum may be swallowed into GI tract. The classic lesions swallowed into GI tract. The classic lesions are circumferential ulcerations with are circumferential ulcerations with stricture of small intestine. stricture of small intestine.

QuestionsQuestions• Pathogen of TBPathogen of TB• what is primary complex?what is primary complex?• Clinical manifestations especially Clinical manifestations especially

tuberculous meningitistuberculous meningitis• When the patient has miliary When the patient has miliary

tuberculosis, what is the typical chest tuberculosis, what is the typical chest x-ray manifestation?x-ray manifestation?

Quiz( fifteen minutes)Quiz( fifteen minutes)

• Definition: 1. Immunologic system Definition: 1. Immunologic system • 2.Brudzinski sign 2.Brudzinski sign • Fill the blanks:1. ____ is the most abundant Fill the blanks:1. ____ is the most abundant

Ig of the body.Ig of the body.• 2.Causative organism of acute bacterial 2.Causative organism of acute bacterial

meningitis are ______, ________ and _____.meningitis are ______, ________ and _____.• Questions:1. Classification of PIDQuestions:1. Classification of PID• 2. Principals of antimicrobial therapy for 2. Principals of antimicrobial therapy for

acute bacterial meningitisacute bacterial meningitis

Thank you!Thank you!