11

Prevention of tuberculosis.Prevention of tuberculosis.

Targeted Tuberculin Skin TestingTargeted Tuberculin Skin Testing

Lecturer Lecturer MDMD, Ph.D. Furdela , Ph.D. Furdela Victoria Victoria

Assistant Assistant Professor,Professor, Pediatric Pediatrics s Department #2, Ternopil State Department #2, Ternopil State Medical University, UkraineMedical University, Ukraine

22

Tuberculosis Tuberculosis in Children and Adolescentsin Children and Adolescents

Epidemiology Epidemiology Public Health Aspects & TB ControlPublic Health Aspects & TB Control

• Targeted Tuberculin Skin TestingTargeted Tuberculin Skin Testing• Contact InvestigationsContact Investigations

BCG VaccineBCG Vaccine Treatment of Latent TB Infection and TB Treatment of Latent TB Infection and TB

DiseaseDisease

33

Global Epidemiology of TBGlobal Epidemiology of TB

Tuberculosis remains the leading infectious Tuberculosis remains the leading infectious disease in the worlddisease in the world• More than 40% of the world’s population (>2 More than 40% of the world’s population (>2

billion people) are infected with billion people) are infected with M. tuberculosisM. tuberculosis• In the 1990s:In the 1990s:

90 million new cases90 million new cases 30 million deaths30 million deaths

• Among children <15 years of age:Among children <15 years of age: Approximately 13 million casesApproximately 13 million cases 5 million deaths5 million deaths

44

Reported TB Cases Reported TB Cases United States, 1982-2003United States, 1982-2003

Year

1983 1987 1991 1995 1999 2003

No

. of

Ca

ses

12,000

16,000

20,000

24,000

28,000

55

Number of TB Cases inNumber of TB Cases inU.S.-born vs. Foreign-born Persons U.S.-born vs. Foreign-born Persons

United States, 1993-2003United States, 1993-2003

0

5000

10000

15000

20000

1993 1995 1997 1999 2001 2003

U.S.-born Foreign-born

No

. o

f C

ases

CDC

66

Trends in TB Cases in Foreign-born Trends in TB Cases in Foreign-born Persons, United States, 1986-2003Persons, United States, 1986-2003

0

2 000

4 000

6 000

8 000

10 000

86 87 88 89 90 91 92 93 94 95 96 97 98 990

10

20

30

40

50

60

No. of Cases Percentage of Total Cases

No. of Cases Percentage

00 01 02 03

CDC

77

Reported TB Cases by Age Group Reported TB Cases by Age Group United States, 2003United States, 2003

25 - 44 yrs (34%)

<15 yrs(6%)

15 - 24 yrs(11%)

45 - 64 yrs (29%)

65+ yrs (20%)

88

Summary of Epidemiology of TBSummary of Epidemiology of TB Cases and case rates are on the declineCases and case rates are on the decline Foreign born persons account for more than 50% of Foreign born persons account for more than 50% of

U.S. casesU.S. cases• New Jersey: 70%New Jersey: 70%

TB in children:TB in children:• Highest risk for disease:Highest risk for disease:

<5 years of age<5 years of age Foreign born childrenForeign born children

• 60% of cases develop within 18 months of arrival in U.S.60% of cases develop within 18 months of arrival in U.S.• Most common countries of birth: Mexico, Philippines, VietnamMost common countries of birth: Mexico, Philippines, Vietnam

Varies depending on immigration patterns, i.e., recent increases in Varies depending on immigration patterns, i.e., recent increases in case among children from Sub-Saharan Africa and Eastern Europecase among children from Sub-Saharan Africa and Eastern Europe

Racial and ethnic minoritiesRacial and ethnic minorities

99

Significance of Significance of Tuberculosis in ChildrenTuberculosis in Children

A case of tuberculosis in a child is A case of tuberculosis in a child is considered a “sentinel healthcare considered a “sentinel healthcare event” representing recent event” representing recent transmission of TB within the transmission of TB within the communitycommunity

1010

Children <15 years with TBChildren <15 years with TBby Site of Diseaseby Site of Disease

Extrapulmonary20%

Pulmonary

75%

Pulmonary & Extrapulmonary

5%

1111

Children <15 years with TB:Children <15 years with TB:Extrapulmonary DiseaseExtrapulmonary Disease

5

636

86

12 MiliaryLymphaticPleuraMeningealBone/JointOther

1212

TB Control In the TB Control In the UnitedUnited States States

Identification of new cases of TBIdentification of new cases of TB• Initiation of appropriate treatmentInitiation of appropriate treatment• Directly observed therapyDirectly observed therapy

Contact InvestigationsContact Investigations• Identify persons at risk for infectionIdentify persons at risk for infection

Targeted tuberculin testing Targeted tuberculin testing • Identifies persons at high risk for TB who Identifies persons at high risk for TB who

would benefit by treatment of LTBIwould benefit by treatment of LTBI• Treatment of latent TB infection (LTBI)Treatment of latent TB infection (LTBI)

1313

Mantoux Tuberculin Skin TestMantoux Tuberculin Skin Test Specificity of the test varies depending on the Specificity of the test varies depending on the

prevalence of LTBI and the frequency of cross-prevalence of LTBI and the frequency of cross-reactions to the PPD antigen in a given population reactions to the PPD antigen in a given population

In a population with relatively high frequency In a population with relatively high frequency cross-reactions the specificity of the PPD is <95% cross-reactions the specificity of the PPD is <95% • Decreases the positive predictive value of positive test Decreases the positive predictive value of positive test

in a low risk populationin a low risk population• If the specificity is 90% in a low risk population with a If the specificity is 90% in a low risk population with a

prevalence of LTBI of 1%:prevalence of LTBI of 1%: Positive predictive value of TST: 8%Positive predictive value of TST: 8% 92% of positives are false positives92% of positives are false positives

• As prevalence of LTBI increases the PPV increases As prevalence of LTBI increases the PPV increases

1414

Mantoux Mantoux tuberculin skin testtuberculin skin test

1515

AAP Recommendations: AAP Recommendations: Targeted Tuberculin Skin TestingTargeted Tuberculin Skin Testing

Risk of exposure to TB should be assessed Risk of exposure to TB should be assessed at routine healthcare evaluationsat routine healthcare evaluations

Only children with an increased risk of Only children with an increased risk of acquiring TB infection or disease should acquiring TB infection or disease should be considered for testingbe considered for testing

Frequency of testing should be according Frequency of testing should be according to the degree of risk of acquiring infectionto the degree of risk of acquiring infection

““Screening” is an Screening” is an inefficientinefficient way to control way to control tuberculosis tuberculosis

1616

Targeted Tuberculin Testing Targeted Tuberculin Testing Risk-Assessment QuestionnaireRisk-Assessment Questionnaire

Was your child born outside the United States? Was your child born outside the United States? • Africa, Asia, Eastern Europe, Latin AmericaAfrica, Asia, Eastern Europe, Latin America

Has your child traveled outside the United States? Has your child traveled outside the United States? >>1 1 weekweek

Has your child been exposed to anyone with TB Has your child been exposed to anyone with TB disease? TB or LTBI, nature of contactdisease? TB or LTBI, nature of contact

Does your child have close contact with a person who Does your child have close contact with a person who has a positive TB skin test?has a positive TB skin test?

1717

Targeted Tuberculin Testing Targeted Tuberculin Testing Risk-Assessment QuestionnaireRisk-Assessment Questionnaire

Depending on local epidemiology and priorities other Depending on local epidemiology and priorities other possible questions include:possible questions include:• Does your child spend time with anyone who has Does your child spend time with anyone who has

been in jail or a shelter, uses illegal drugs or has HIV?been in jail or a shelter, uses illegal drugs or has HIV?• Has your child had raw milk or eaten unpasteurized Has your child had raw milk or eaten unpasteurized

cheese?cheese?• Is there a household member born outside the U.S.?Is there a household member born outside the U.S.?• Is there a household member who has traveled Is there a household member who has traveled

outside the U.S.?outside the U.S.?

1818

AAP Recommendations: AAP Recommendations: Tuberculin Skin TestingTuberculin Skin Testing

Children for whom Children for whom immediate TSTimmediate TST is indicated: is indicated:

• Contacts of persons with confirmed or suspected Contacts of persons with confirmed or suspected infectious tuberculosis (contact investigation)infectious tuberculosis (contact investigation)

• Children with CXR or clinical findings suggesting TBChildren with CXR or clinical findings suggesting TB• Children immigrating from endemic countries (e.g., Children immigrating from endemic countries (e.g.,

Asia, Middle East, Africa, Latin America)Asia, Middle East, Africa, Latin America)• Children with histories of travel to endemic countries Children with histories of travel to endemic countries

and/or significant contact with indigenous persons from and/or significant contact with indigenous persons from such countries such countries

1919

AAP Recommendations: AAP Recommendations: Tuberculin Skin TestingTuberculin Skin Testing

Children who should have an Children who should have an annual TSTannual TST::

•Children with HIV infectionChildren with HIV infection

• Incarcerated adolescentsIncarcerated adolescents

2020

AAP Recommendations: AAP Recommendations: Tuberculin Skin TestingTuberculin Skin Testing

Some experts recommend that these children should Some experts recommend that these children should be tested be tested every 2-3 yearsevery 2-3 years::• Children exposed to the following persons:Children exposed to the following persons:

HIV-infectedHIV-infected Homeless Homeless Residents of nursing homesResidents of nursing homes Institutionalized or incarcerated adolescents or Institutionalized or incarcerated adolescents or

adultsadults Users of illicit drugsUsers of illicit drugs Migrant farm workersMigrant farm workers

• Foster children with exposure to adults in the Foster children with exposure to adults in the preceding high risk groupspreceding high risk groups

2121

AAP Recommendations: AAP Recommendations: Tuberculin Skin TestingTuberculin Skin Testing

Children who should be considered for TST at Children who should be considered for TST at 4-6 and 11-16 4-6 and 11-16 years of ageyears of age::

• Children whose parents immigrated (with unknown TST Children whose parents immigrated (with unknown TST status) from regions of the world with high prevalence of status) from regions of the world with high prevalence of tuberculosistuberculosis

• Children with continued potential exposure by travel to Children with continued potential exposure by travel to endemic areas and/or household contact with persons endemic areas and/or household contact with persons from endemic areas (with unknown TST status)from endemic areas (with unknown TST status)

2222

Administering the Tuberculin Skin TestAdministering the Tuberculin Skin Test

Inject intradermally 0.1 ml of 5 Inject intradermally 0.1 ml of 5 TU PPD tuberculinTU PPD tuberculin

Produce wheal 6mm to 10mm in Produce wheal 6mm to 10mm in diameterdiameter

Placed and read by Placed and read by experienced health experienced health professionalsprofessionals

2323

Reading the Tuberculin Skin TestReading the Tuberculin Skin Test

Read reaction 48-72 hours after injectionRead reaction 48-72 hours after injection

Measure only indurationMeasure only induration

Record reaction in millimetersRecord reaction in millimeters

2424

Positive TST in Children:Positive TST in Children:Definitions Definitions

Takes into account the following:Takes into account the following:

• Risk of infection (exposure)Risk of infection (exposure)• Risk of progression to diseaseRisk of progression to disease

Immune statusImmune status AgeAge

2525

Positive TST Results: Positive TST Results: Infants, Children, and AdolescentsInfants, Children, and Adolescents

TST considered positive at TST considered positive at >>5 mm induration when:5 mm induration when:• In close contact with known or suspected contagious In close contact with known or suspected contagious

cases of tuberculosiscases of tuberculosis• Suspected to have tuberculosis disease:Suspected to have tuberculosis disease:

CXR consistent with active or previously active CXR consistent with active or previously active tuberculosistuberculosis

Clinical evidence of tuberculosisClinical evidence of tuberculosis• Receiving immunosuppressive therapyReceiving immunosuppressive therapy• With immunosuppressive conditionsWith immunosuppressive conditions

• With HIV infectionWith HIV infection

2626

Positive TST Results: Positive TST Results: Infants, Children, and AdolescentsInfants, Children, and Adolescents

TST considered positive at TST considered positive at >>10 mm10 mm induration in children:induration in children:• At increased risk of disseminated disease:At increased risk of disseminated disease:

Young age: <4 years of ageYoung age: <4 years of age Other medical conditions: Hodgkin disease, lymphoma, Other medical conditions: Hodgkin disease, lymphoma,

diabetes mellitus, chronic renal failure, malnutritiondiabetes mellitus, chronic renal failure, malnutrition• With increased exposure to tuberculosis diseaseWith increased exposure to tuberculosis disease

Born or whose parents were born in high-prevalence Born or whose parents were born in high-prevalence regions of the worldregions of the world

Frequently exposed to adults who are HIV-infected, Frequently exposed to adults who are HIV-infected, homeless, users of illicit drugs, residents of nursing homeless, users of illicit drugs, residents of nursing homes, incarcerated or institutionalized persons, homes, incarcerated or institutionalized persons, migrant farm workersmigrant farm workers

Travel and exposure to high-prevalence regions of the Travel and exposure to high-prevalence regions of the worldworld

2727

Positive TST Results: Positive TST Results: Infants, Children, and Adolescents Infants, Children, and Adolescents

TST considered positive at TST considered positive at >>15 mm15 mm indurationinduration::

• In children In children >>4 years of age without any risk factors4 years of age without any risk factors

2828

Evaluation of the ChildEvaluation of the Child with a Positive TST with a Positive TST

Evaluation of all children with a Evaluation of all children with a positive TST should include:positive TST should include:•A careful historyA careful history

Household investigation Household investigation

•Physical examinationPhysical examination•Chest radiographs (PA & lateral)Chest radiographs (PA & lateral)

2929

Treatment of Treatment of Latent Tuberculosis Infection in ChildrenLatent Tuberculosis Infection in Children

INH 10 mg/kg (max., 300 mg) PO daily for 270 dosesINH 10 mg/kg (max., 300 mg) PO daily for 270 doses Alternative: Twice weekly directly observed (DOT) INH 20-40 Alternative: Twice weekly directly observed (DOT) INH 20-40

mg/kg (max., 900 mg) PO for 72 dosesmg/kg (max., 900 mg) PO for 72 doses Monitor index case isolate sensitivitiesMonitor index case isolate sensitivities Hepatotoxicity from INH is rare in children:Hepatotoxicity from INH is rare in children:

• A monthly assessment for clinical evidence of A monthly assessment for clinical evidence of hepatotoxicity should be made: loss of appetite or weight, hepatotoxicity should be made: loss of appetite or weight, nausea, vomiting, abdominal pain, jaundicenausea, vomiting, abdominal pain, jaundice

• Routine monitoring of LFTs is not indicatedRoutine monitoring of LFTs is not indicated

3030

Tuberculosis Control in the Tuberculosis Control in the United StatesUnited States

Contact InvestigationsContact Investigations

“ “The most reliable TB control program is based upon The most reliable TB control program is based upon aggressive and expedient contact investigations, aggressive and expedient contact investigations, rather than routine screening of large populations rather than routine screening of large populations with low risk.”with low risk.”

Can be complex, require experience and often a lot Can be complex, require experience and often a lot of detective work.of detective work.

3131

Tuberculosis Exposure in Children Tuberculosis Exposure in Children History, PE, TST, CXR done History, PE, TST, CXR done

• CXR is done regardless of TST resultCXR is done regardless of TST result IFIF::

• Asymptomatic and physical examination is normalAsymptomatic and physical examination is normal• TST is negativeTST is negative• Chest X-ray is normalChest X-ray is normal

AND IF <4 years of age STARTAND IF <4 years of age START: Isoniazid (INH) 10 : Isoniazid (INH) 10

mg/kg (max., 300 mg) PO once dailymg/kg (max., 300 mg) PO once daily

3232

Tuberculosis Exposure in ChildrenTuberculosis Exposure in Children

Why is INH given even if there is no evidence of Why is INH given even if there is no evidence of infection or disease at initial visit:infection or disease at initial visit:• May already be infectedMay already be infected• Infection more likely to progress to diseaseInfection more likely to progress to disease• Infants and younger children are more likely to have Infants and younger children are more likely to have

disseminated disease or meningitisdisseminated disease or meningitis TST repeated 12 weeks after contact broken with TST repeated 12 weeks after contact broken with

infectious adult:infectious adult:• If TST (-), discontinue INHIf TST (-), discontinue INH• If TST (+), re-evaluate child and treat accordinglyIf TST (+), re-evaluate child and treat accordingly

3333

Prevention of Tuberculosis in Children: Prevention of Tuberculosis in Children: Missed Opportunities Missed Opportunities

Failure to find and appropriately manage adult Failure to find and appropriately manage adult source cases (Case finding)source cases (Case finding)

Delay in reporting the initial diagnosis of TBDelay in reporting the initial diagnosis of TB Contact investigation interview failureContact investigation interview failure Delay in evaluation of exposed childrenDelay in evaluation of exposed children Failure to completely evaluate exposed childrenFailure to completely evaluate exposed children Failure to prescribe prophylactic INHFailure to prescribe prophylactic INH Failure to maintain a contact under surveillanceFailure to maintain a contact under surveillance LTBI diagnosed; treatment not prescribedLTBI diagnosed; treatment not prescribed Failure to complete treatment for LTBI (Adherence)Failure to complete treatment for LTBI (Adherence)

3434

BCG Vaccine BCG Vaccine and Tuberculin Skin Testingand Tuberculin Skin Testing

History of a BCG is never a contraindication to tuberculin History of a BCG is never a contraindication to tuberculin skin testingskin testing

No reliable method of distinguishing (+) TSTs due to BCG No reliable method of distinguishing (+) TSTs due to BCG from those caused by infection with from those caused by infection with M. tuberculosisM. tuberculosis

Therefore, management of children with a history of BCG Therefore, management of children with a history of BCG and a (+) PPD includes:and a (+) PPD includes:• Diagnostic evaluation including a chest radiographDiagnostic evaluation including a chest radiograph• Appropriate treatmentAppropriate treatment

3535

BCG – Fantasy and FactBCG – Fantasy and Fact

BCG protects against getting TB BCG protects against getting TB infectioninfection

BCG provides lifetime protection against BCG provides lifetime protection against developing active TBdeveloping active TB

BCG causes the tuberculin skin test (TST) BCG causes the tuberculin skin test (TST) to be positive for lifeto be positive for life

In a BCG-vaccinated person, a positive In a BCG-vaccinated person, a positive TST is most likely due to BCGTST is most likely due to BCG

A positive TST in a person of any age A positive TST in a person of any age from any country is most likely due to from any country is most likely due to BCG, not TB infectionBCG, not TB infection

There is no need for a BCG-vaccinated There is no need for a BCG-vaccinated person with a positive TST to be treatedperson with a positive TST to be treated

•BCG will not protect against becoming infected with TB

•BCG protects against severe complications of TB disease in young children, but provides little or no protection in adolescents and adults

•BCG causes the TST to be positive for a few years and then the TST reaction becomes much weaker. Generally, no reaction is present after 5 years.

•There is no way to tell whether a positive TST is due to BCG or to TB infection

•A positive TST in an adolescent or adult from a TB high-burden country is almost always due to TB infection, not BCG

•Persons with a positive TST from TB high-burden countries are at high risk of developing active TB and should be treated

FACTFANTASY