Tuberculosis2

TuberculosisTuberculosis

Jiang LihongJiang Lihong

Tianjin Medical UniversityTianjin Medical University

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?

Diagnostic tests and Diagnostic tests and procedures the tuberculin procedures the tuberculin

testtest

The tuberculin testThe tuberculin test

• methodmethod

• assessmentassessment

• a negative reactiona negative reaction

• studies indicated when the tuberculin studies indicated when the tuberculin test is positivetest is positive

Who need to take the Who need to take the tuberculin testtuberculin test• People who have had close day-to-People who have had close day-to-

day contact with someone who has day contact with someone who has active TB diseaseactive TB disease

• people who has symptomspeople who has symptoms• people who have to be tested for a people who have to be tested for a

job or schooljob or school• people who have lowered immunitypeople who have lowered immunity

methodmethod

• OT: old tuberculinOT: old tuberculin

• PPD: purified protein derivative PPD: purified protein derivative tuberculintuberculin

• Standard dose of PPD tuberculin: 5 Standard dose of PPD tuberculin: 5 units 0.1ml of Tween stabilized units 0.1ml of Tween stabilized solution solution

tuberculin test is done on tuberculin test is done on childrenchildren

Site:volar surface of the forearm

Size:diameter 6-10mm

Within 48 to 72 hours, a positive TB skin test is marked by an area of reddish induration greater than 10 mm. It is the induration (firm bump) that is gently palpated that determines the size, not the area of redness. This reaction is slightly larger than the average positive test 17 mm in size. The positive reaction shown here was obtained with a TB skin test performed 20 years after the initial infection

• Figure A.Figure A.  6 hours after administration of tuberculin,   6 hours after administration of tuberculin, some reaction can be seen.  It is thought that this does some reaction can be seen.  It is thought that this does not reflect a specific reaction.not reflect a specific reaction.

• Figure B.Figure B.  After 24 hours a clear reaction is seen, but   After 24 hours a clear reaction is seen, but the demarcations are unclear.the demarcations are unclear.

• Figure C.Figure C.  After 48 hours a central induration is now   After 48 hours a central induration is now clearly present. It is thought to be the result of release clearly present. It is thought to be the result of release of cytokines by specified cells that activate the local of cytokines by specified cells that activate the local macrophages, resulting in the typical induration.macrophages, resulting in the typical induration.

• Figure D.Figure D.  After 72 hours the result can be read   After 72 hours the result can be read equally well.  The recommendation is to read the equally well.  The recommendation is to read the tuberculin test after 48 to 72 hours. tuberculin test after 48 to 72 hours.

AssessmentAssessment

• Site: volar surface of the forearmSite: volar surface of the forearm• time: 48 to 72 hourstime: 48 to 72 hours• assessment: assessment: • (1)erythema without induration and induration (1)erythema without induration and induration

less than 5 mm—negative(-)less than 5 mm—negative(-)• (3)induration greeter than 5 mm but less than (3)induration greeter than 5 mm but less than

10 mm—doubtful(+)10 mm—doubtful(+)• (4)induration greater than to 10 mm but less (4)induration greater than to 10 mm but less

than 20 mm—positive(++)than 20 mm—positive(++)• (5) induration greater than to 20 mm (+++)(5) induration greater than to 20 mm (+++)• (6)blister and necrosis—positive(++++)(6)blister and necrosis—positive(++++)

A negative reactionA negative reaction• A negative reaction to tuberculin A negative reaction to tuberculin

testing usually means that the testing usually means that the individual has never been infected individual has never been infected with the tubercle bacillus. However, with the tubercle bacillus. However, reaction may be falsely negative, reaction may be falsely negative, and it is important to recognize the and it is important to recognize the circumstance under which this may circumstance under which this may occuroccur

A negative reactionA negative reaction• (1)(1)individual has never been infected with individual has never been infected with

the tubercle bacillusthe tubercle bacillus

• (2)intercurrent disease (2)intercurrent disease

• (3)viral vaccines(3)viral vaccines

• (4)corticosteroids and immunosuppressive (4)corticosteroids and immunosuppressive agentsagents

• (5)celluar immune deficiency disease(5)celluar immune deficiency disease

A negative reactionA negative reaction

• (6)(6)Severe malnutritionSevere malnutrition

• (7)overwhelming tuberculous (7)overwhelming tuberculous infectioninfection

• (8)testing too early(8)testing too early

• (9)important testing material(9)important testing material

• (10)faulty technique(10)faulty technique

Studies indicated when the Studies indicated when the tuberculin test is positivetuberculin test is positive

• If a pulmonary infiltrative lesion is If a pulmonary infiltrative lesion is detected by radiography, gastric washing detected by radiography, gastric washing should be performed in an attempt to should be performed in an attempt to culture the tubercle bacillus.culture the tubercle bacillus.

• members of the family and other close members of the family and other close contacts should evaluated with a careful contacts should evaluated with a careful history, a physical examination, a chest history, a physical examination, a chest radiograph, and /or a tuberculin test. radiograph, and /or a tuberculin test.

Identification of the tubercle Identification of the tubercle bacillus by smear or culturebacillus by smear or culture

• SputumSputum

• gastric washinggastric washing

• CSFCSF

sputumsputum

• If the child with pulmonary infections If the child with pulmonary infections is producing sputum, this may be is producing sputum, this may be cultured. If not, an aerosol-induced cultured. If not, an aerosol-induced sputum may prove useful in the child sputum may prove useful in the child old enough to cooperate.old enough to cooperate.

Gastric washingsGastric washings

• In a child of any age gastric washing In a child of any age gastric washing can be obtained or examination. can be obtained or examination. Before breakfast the stomach is Before breakfast the stomach is lavaged with sterile water, the lavaged with sterile water, the washing are aspirated and cultures washing are aspirated and cultures are then performed. are then performed.

CSFCSF• When the tuberculous meningitis is When the tuberculous meningitis is

suspected, the centrifuged sediment suspected, the centrifuged sediment of the cerebrospinal fluid should be of the cerebrospinal fluid should be examined for tubercle bacilli. T he examined for tubercle bacilli. T he cerebrospinal fluid should be cerebrospinal fluid should be cultured and treatment should be cultured and treatment should be instituted immediately on clinical instituted immediately on clinical grounds. grounds.

Radiographic studiesRadiographic studies• Radiographic studies may support the Radiographic studies may support the

opinion that the child has pulmonary or opinion that the child has pulmonary or osseous TB.However, similar radiographic osseous TB.However, similar radiographic findings are present in other diseases. findings are present in other diseases. Therefore caution should be exercised Therefore caution should be exercised interpretation of X-ray studies, and the interpretation of X-ray studies, and the diagnosis should not be made on this diagnosis should not be made on this evidence alone.evidence alone.

PCRPCR

• Polymerase chain reaction allows Polymerase chain reaction allows detection of M. Tuberculosis DNA. detection of M. Tuberculosis DNA. This is generally performed on This is generally performed on sputum samples.sputum samples.

What does having TB What does having TB infection mean?infection mean?

• Having TB infection means that the Having TB infection means that the TB germs are in the body but they TB germs are in the body but they are in an inactive state.are in an inactive state.

Inactive TB germs can't hurt you now ...

What is TB disease?What is TB disease?

• It is possible to get TB disease It is possible to get TB disease shortly after the germs enter the shortly after the germs enter the body if body defenses are weak.body if body defenses are weak.

• It is possible that the inactive TB It is possible that the inactive TB germs become active when body germs become active when body defenses are weakened.defenses are weakened.

... when body defenses are weakened, inactive TB germs become active and break out

casecase

Tuberculin testTuberculin test

Tuberculosis from sputumTuberculosis from sputum

Chest x-rayChest x-ray

Chest x-rayChest x-ray

treatmenttreatment

• General careGeneral care

• chemotherapychemotherapy

• immunizationimmunization

General careGeneral care• Patients with asymptomatic initial infection can be Patients with asymptomatic initial infection can be

managed as outpatients and require no restriction of managed as outpatients and require no restriction of activity. They should receive all immunizations, including activity. They should receive all immunizations, including rubeola vaccine.rubeola vaccine.

• Those with complications should be hospitalized until Those with complications should be hospitalized until afebrile and until their condition has stabilized to the point afebrile and until their condition has stabilized to the point where home care is possible.where home care is possible.

• The patients with chronic tuberculosis is contagious only so The patients with chronic tuberculosis is contagious only so long as the sputum is positive for M. tuberculosis and long as the sputum is positive for M. tuberculosis and significant coughing is present.significant coughing is present.

chemotherapychemotherapy

Asymptomatic tuberculin-Asymptomatic tuberculin-positive children and positive children and adolescentsadolescents

• IsoniazidIsoniazid• period:12 momthsperiod:12 momths• dosage: 10-20mg/kg/24hr(max300mg)dosage: 10-20mg/kg/24hr(max300mg)• toxic effects: hepatotoxicity(rare in toxic effects: hepatotoxicity(rare in

children), peripheral neuritis(reported only children), peripheral neuritis(reported only in association with accidental poisoning), in association with accidental poisoning), toxic encephalopathy(rare and probably toxic encephalopathy(rare and probably reversible with withdrawal of the drug)reversible with withdrawal of the drug)

Children and adolescents with Children and adolescents with

symptomatic tuberculosissymptomatic tuberculosis • Combined therapy with isoniazid and Combined therapy with isoniazid and

rifampinrifampin

• rifampin: 10-20mg/kg(max600mg); rifampin: 10-20mg/kg(max600mg);

• toxic effects:transient abnormalities of toxic effects:transient abnormalities of liver function, nausea and vomiting, an liver function, nausea and vomiting, an orange-red color may be noted in orange-red color may be noted in secretionssecretions

Short-course chemotherapyShort-course chemotherapy

• Period: 6-9monthsPeriod: 6-9months

• isoniazid and rifampin at usual daily isoniazid and rifampin at usual daily doses for 1 monthdoses for 1 month

• isonizid and rifanpin twice weekly for isonizid and rifanpin twice weekly for 8 months8 months

Other drugsOther drugs• Pyrazinamide: Pyrazinamide:

15-30mg/kg/24hr(potentially hepatotoxic)15-30mg/kg/24hr(potentially hepatotoxic)

• streptomycin: 20-40mg/kg(potentially streptomycin: 20-40mg/kg(potentially nephrotoxic)nephrotoxic)

• ethambutol, ethionamide, para-ethambutol, ethionamide, para-aminosalicylic acid, capreomycin, aminosalicylic acid, capreomycin, kanamycin, cycloserinekanamycin, cycloserine

•

drugdrug Dosage(kg/Dosage(kg/d)d)

methomethodd

Main adverse Main adverse reactionreaction

INHINH 10mg(≤30010mg(≤300mg/d)mg/d)

po (im, po (im, iv)iv)

Hepatotoxicity,periphHepatotoxicity,peripheralneuritis,hyperseneralneuritis,hypersensitivity,feversitivity,fever

RFPRFP 10mg(≤45010mg(≤450mg/d)mg/d)

popo Hepatotoxicity,nauseHepatotoxicity,nausea,vomita,vomit

SMSM 20-30mg20-30mg

(≤750mg/d)(≤750mg/d)imim Nephrotoxic,hyperseNephrotoxic,hyperse

nsitivity,fevernsitivity,fever

PZAPZA 20-30mg20-30mg

(≤750mg/d)(≤750mg/d)popo Hepatotoxic,hyperuriHepatotoxic,hyperuri

cemia,arthralgia,cemia,arthralgia,

EMBEMB 15-25mg15-25mg popo Optic neuritisOptic neuritis

ETHETH 10-15mg10-15mg popo As same as INHAs same as INH

corticosteroidcorticosteroid

• Actual or impeding cerebrospinal Actual or impeding cerebrospinal fluid block in tuberculous meningitis fluid block in tuberculous meningitis

• respiratory distress in tuberculous respiratory distress in tuberculous endobronchitisendobronchitis

immunizationimmunization• BCG: bacille calmette guerinBCG: bacille calmette guerin

• Indicated only when contact with active Indicated only when contact with active tuberculosis cannot be avoided in the tuberculosis cannot be avoided in the family or community.family or community.

• Should not be given to individuals with Should not be given to individuals with comprised immune status caused by comprised immune status caused by underlying disease or immunosuppressive underlying disease or immunosuppressive drug therapy.drug therapy.

• Two French scientists Albert Two French scientists Albert Calmette and Camille Guerin Calmette and Camille Guerin developed a vaccine against developed a vaccine against tuberculosis from an attenuated tuberculosis from an attenuated form of the bovine bacillus in form of the bovine bacillus in 1921. BCG stands for Bacillus-1921. BCG stands for Bacillus-Calmette‑Guerin. It is the only Calmette‑Guerin. It is the only vaccine we have for the vaccine we have for the prevention of TB. It should be prevention of TB. It should be given to children at birth. BCG given to children at birth. BCG protects children from meningial protects children from meningial and milliary TB.and milliary TB.

questionquestion

• How to assess tuberculin testHow to assess tuberculin test

• what dose a negative reaction mean?what dose a negative reaction mean?

• Short-course treatment: drug; Short-course treatment: drug; dosagedosage

• how to immunize?how to immunize?

thanksthanks