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Pediatric Tuberculosis Update . Dr. George McSherry. Audio Conference July 27, 2005. Tuberculosis in Children and Adolescents 2005. Epidemiology Public Health Aspects & TB Control Targeted Tuberculin Skin Testing Contact Investigations BCG Vaccine

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Pediatric tuberculosis update

Pediatric Tuberculosis Update

Dr. George McSherry

Audio Conference July 27, 2005


Tuberculosis in children and adolescents 2005
Tuberculosis in Children and Adolescents 2005

  • Epidemiology

  • Public Health Aspects & TB Control

    • Targeted Tuberculin Skin Testing

    • Contact Investigations

  • BCG Vaccine

  • Treatment of Latent TB Infection and TB Disease


Global epidemiology of tb
Global Epidemiology of TB

  • Tuberculosis remains the leading infectious disease in the world

    • More than 40% of the world’s population (>2 billion people) are infected with M. tuberculosis

    • In the 1990s:

      • 90 million new cases

      • 30 million deaths

    • Among children <15 years of age:

      • Approximately 13 million cases

      • 5 million deaths


Reported tb cases united states 1982 2003
Reported TB Cases United States, 1982-2003

28,000

24,000

No. of Cases

20,000

16,000

12,000

1983

1987

1991

1995

1999

2003

Year


Number of tb cases in u s born vs foreign born persons united states 1993 2003
Number of TB Cases inU.S.-born vs. Foreign-born Persons United States, 1993-2003

No. of Cases

CDC


Trends in tb cases in foreign born persons united states 1986 2003
Trends in TB Cases in Foreign-born Persons, United States, 1986-2003

No. of Cases

Percentage

00

01

02

03

CDC


Percentage of tb cases among foreign born persons united states
Percentage of TB Cases Among Foreign-born Persons, United States

1993

2003

DC

DC

>50%

25% - 49%

<25%


Countries of birth for foreign born persons reported with tb united states new jersey 2003
Countries of Birth for Foreign-born StatesPersons Reported with TB: United States (New Jersey), 2003

Mexico*

26% (9%)

Other

Countries

36% (52%)

Philippines*

12% (11%)

S. Korea

2% (2%)

Haiti

3% (5%)

Viet Nam*

8% (2%)

China

5% (1%)

Peru (9.4%)

Ecuador (8.1%)

India

8% (17%)


Pediatric tuberculosis update

Pediatric TB case rates by race/ethnicity, 1993-2001 States

Nelson, L. J. et al. Pediatrics 2004;114:333-341


Reported tb cases by age group united states 2003
Reported TB Cases by Age Group StatesUnited States, 2003

<15 yrs

(6%)

65+ yrs

(20%)

15 - 24 yrs

(11%)

25 - 44 yrs

(34%)

45 - 64 yrs

(29%)



Pediatric tuberculosis update

TB case rates by age group, 1993-2001 <15 Years

Nelson, L. J. et al. Pediatrics 2004;114:333-341


Summary of epidemiology of tb
Summary of Epidemiology of TB <15 Years

  • Cases and case rates are on the decline

  • Foreign born persons account for more than 50% of U.S. cases

    • New Jersey: 70%

  • TB in children:

    • Highest risk for disease:

      • <5 years of age

      • Foreign born children

        • 60% of cases develop within 18 months of arrival in U.S.

        • Most common countries of birth: Mexico, Philippines, Vietnam

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

      • Racial and ethnic minorities


Significance of tuberculosis in children
Significance of <15 YearsTuberculosis in Children

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


Children 15 years with tb by site of disease
Children <15 years with TB <15 Yearsby Site of Disease


Children 15 years with tb extrapulmonary disease
Children <15 years with TB: <15 YearsExtrapulmonary Disease


Tb control in the united states
TB Control In the <15 YearsUnited States

  • Identification of new cases of TB

    • Initiation of appropriate treatment

    • Directly observed therapy

  • Contact Investigations

    • Identify persons at risk for infection

  • Targeted tuberculin testing

    • Identifies persons at high risk for TB who would benefit by treatment of LTBI

    • Treatment of latent TB infection (LTBI)


Mantoux tuberculin skin test
Mantoux Tuberculin Skin Test <15 Years

  • Specificity of the test varies depending on the prevalence of LTBI and the frequency of cross-reactions to the PPD antigen in a given population

  • In a population with relatively high frequency cross-reactions the specificity of the PPD is <95%

    • Decreases the positive predictive value of positive test in a low risk population

    • If the specificity is 90% in a low risk population with a prevalence of LTBI of 1%:

      • Positive predictive value of TST: 8%

      • 92% of positives are false positives

    • As prevalence of LTBI increases the PPV increases

Huebner RE. Clin Infect Dis 1993;17:968


Aap recommendations targeted tuberculin skin testing
AAP Recommendations: <15 YearsTargeted Tuberculin Skin Testing

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

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

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

  • “Screening” is an inefficient way to control tuberculosis


Targeted tuberculin testing risk assessment questionnaire
Targeted Tuberculin Testing <15 YearsRisk-Assessment Questionnaire

  • Was your child born outside the United States?

    • Africa, Asia, Eastern Europe, Latin America

  • Has your child traveled outside the United States? >1 week

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

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

Pediatrics 2004;114:1175, supplement


Targeted tuberculin testing risk assessment questionnaire1
Targeted Tuberculin Testing <15 YearsRisk-Assessment Questionnaire

  • Depending on local epidemiology and priorities other possible questions include:

    • Does your child spend time with anyone who has been in jail or a shelter, uses illegal drugs or has HIV?

    • Has your child had raw milk or eaten unpasteurized cheese?

    • Is there a household member born outside the U.S.?

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

Pediatrics 2004;114:1175, supplement


Aap recommendations tuberculin skin testing
AAP <15 YearsRecommendations: Tuberculin Skin Testing

  • Children for whom immediate TST is indicated:

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

    • Children with CXR or clinical findings suggesting TB

    • Children immigrating from endemic countries (e.g., Asia, Middle East, Africa, Latin America)

    • Children with histories of travel to endemic countries and/or significant contact with indigenous persons from such countries

Red Book 2003


Aap recommendations tuberculin skin testing1
AAP Recommendations: <15 YearsTuberculin Skin Testing

  • Children who should have an annual TST:

    • Children with HIV infection

    • Incarcerated adolescents

Red Book 2003


Aap recommendations tuberculin skin testing2
AAP Recommendations: <15 YearsTuberculin Skin Testing

  • Some experts recommend that these children should be tested every 2-3 years:

    • Children exposed to the following persons:

      • HIV-infected

      • Homeless

      • Residents of nursing homes

      • Institutionalized or incarcerated adolescents or adults

      • Users of illicit drugs

      • Migrant farm workers

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


Aap recommendations tuberculin skin testing3
AAP Recommendations: <15 YearsTuberculin Skin Testing

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

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

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


Administering the tuberculin skin test
Administering the Tuberculin Skin Test <15 Years

  • Inject intradermally 0.1 ml of 5 TU PPD tuberculin

  • Produce wheal 6mm to 10mm in diameter

  • Placed and read by experienced health professionals


Reading the tuberculin skin test
Reading the Tuberculin Skin Test <15 Years

  • Read reaction 48-72 hours after injection

  • Measure only induration

  • Record reaction in millimeters


Parental reading of tuberculin skin testing
Parental Reading of Tuberculin Skin Testing <15 Years

  • TST was placed on 37 children from different families

    • Parents were instructed verbally about

      • The importance of the test

      • When and how to read induration

        • Given written instructions

        • Had the date stamped on their hands

    • Site was marked with permanent marker and a bracelet with the reading date was placed on the child’s hand

  • Results: 36/37 returned for reading

    • Only 22% of families (8/36) were able to both read and document skin test results appropriately

Cheng TL, PIDJ 1996


Positive tst in children definitions
Positive TST in Children: <15 YearsDefinitions

  • Takes into account the following:

    • Risk of infection (exposure)

    • Risk of progression to disease

      • Immune status

      • Age


Positive tst results infants children and adolescents
Positive TST Results: <15 YearsInfants, Children, and Adolescents

  • TST considered positive at >5 mm induration when:

    • In close contact with known or suspected contagious cases of tuberculosis

    • Suspected to have tuberculosis disease:

      • CXR consistent with active or previously active tuberculosis

      • Clinical evidence of tuberculosis

    • Receiving immunosuppressive therapy

    • With immunosuppressive conditions

    • With HIV infection


Positive tst results infants children and adolescents1
Positive TST Results: <15 YearsInfants, Children, and Adolescents

  • TST considered positive at >10 mminduration in children:

    • At increased risk of disseminated disease:

      • Young age: <4 years of age

      • Other medical conditions: Hodgkin disease, lymphoma, diabetes mellitus, chronic renal failure, malnutrition

    • With increased exposure to tuberculosis disease

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

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

      • Travel and exposure to high-prevalence regions of the world


Positive tst results infants children and adolescents2
Positive TST Results: <15 YearsInfants, Children, and Adolescents

  • TST considered positive at >15 mminduration:

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


Evaluation of the child with a positive tst
Evaluation of the Child <15 Years with a Positive TST

  • Evaluation of all children with a positive TST should include:

    • A careful history

      • Household investigation

    • Physical examination

    • Chest radiographs (PA & lateral)


Treatment of latent tuberculosis infection in children
Treatment of <15 YearsLatent Tuberculosis Infection in Children

  • INH 10 mg/kg (max., 300 mg) PO daily for 270 doses

  • Alternative: Twice weekly directly observed (DOT) INH 20-40 mg/kg (max., 900 mg) PO for 72 doses

  • Monitor index case isolate sensitivities

  • Hepatotoxicity from INH is rare in children:

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

    • Routine monitoring of LFTs is not indicated


Tuberculosis control in the united states
Tuberculosis Control in the <15 YearsUnited States

  • Contact Investigations

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

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


Concentric circle approach to contact tracing
Concentric-Circle Approach to Contact Tracing <15 Years

Home

Environment

Casual

Close

Index

Case

Leisure

Environment

Work/School

Environment

Adapted from Etkind S., Veen J., In Reichman-Hershfield:

Tuberculosis: A Comprehensive International Approach, 2000


Presenting patient ppt index case
Presenting Patient (Ppt.) <15 Years(Index case)

  • 6/14/04 (Monday): 39 year-old female was admitted to a suburban New Jersey hospital with complaints of fever, decreased appetite, 23 lb weight loss, cough X 1-3 months, night sweats

  • Chest radiographs were done


Presenting patient index case
Presenting Patient (Index case) <15 Years

  • 6/17 (Thursday): First sputum was obtained for AFB studies; AFB smear reported as (4+); AFB subsequently confirmed as M. tuberculosis

  • 6/19 (Saturday): Treatment initiated with INH, RIF, PZA, & ethambutol

  • 6/21 (Monday): Presumptive case of TB reported by telephone to local health department

    • Included in the report: Place of employment - a Daycare Center (DCC)

    • Same day: Health department nurse contacted TB controller for the county


Contact investigation initiated
Contact Investigation Initiated <15 Years

  • 6/21 (Monday): Maintaining confidentiality, TB controller calls asst. dir. of DCC to schedule CI management meeting and on-site assessment; asst. dir. volunteers that Ppt. is her aunt (“I know who this is…”):

    • Secretarial volunteer 1-2 hrs/week

    • Works at desk doing paperwork, filing

    • Little or no contact with children in the daycare

  • Asst. dir. also reveals that she has 6 mo. old infant, exposed to Ppt. socially on weekends (10 hrs/wk):

    • “Does not attend daycare”

    • “Diagnosed with pneumonia 4 weeks ago”

      • TB controller arranges with local health department to have TST placed that day on the infant; CXR scheduled

      • In subsequent TB Q & A sessions with other parents it is learned that infant was at daycare regularly


Contact investigation cont
Contact Investigation, cont. <15 Years

  • 6/22: First of 4 interviews of Ppt. by 3 different interviewers is held in hospital

    • Infectious period: 3/17-6/14/04 (Contact broken)

    • May have spent more time daycare (2-3 hrs/day) than originally described by niece

    • Not much contact with children

  • 6/23: On-site assessment of DCC conducted by TB controller:

    • High priority contacts: 35

      • 30 children attend: All <4 years of age

      • 5 staff members: Adults and adolescents

    • Daycare is in a church basement



Contact investigation cont1
Contact Investigation, cont. <15 Years

  • 6/23: Field visit by PHR to home of social contacts reveals a second 6 mo. old infant previously identified by Ppt. during an interview:

    • Significant social contact

    • History of pneumonia 3 weeks prior

    • PHR & TB controller consult with PNP and infant is referred to ER for evaluation

    • Chest radiographs are done


Contact investigation initial results household and social contacts
Contact Investigation, Initial Results: <15 YearsHousehold and Social Contacts


Contact investigation cont2
Contact Investigation, cont. <15 Years

  • Continuing assessment and DCC parent notification

  • 6/29 & 6/30: TSTs placed, CXRs done

  • 6 extra clinic sessions, including 3 done at local health department

  • Multiple meetings by TB Center staff with DCC staff; follow-up interviews of Ppt.



Tuberculosis exposure in children
Tuberculosis Exposure in Children <15 Years

  • History, PE, TST, CXR done

    • CXR is done regardless of TST result

  • IF:

    • Asymptomatic and physical examination is normal

    • TST is negative

    • Chest X-ray is normal

  • AND IF <4 years of age START: Isoniazid (INH) 10 mg/kg (max., 300 mg) PO once daily


Tuberculosis exposure in children1
Tuberculosis Exposure in Children <15 Years

  • Why is INH given even if there is no evidence of infection or disease at initial visit:

    • May already be infected

    • Infection more likely to progress to disease

    • Infants and younger children are more likely to have disseminated disease or meningitis

  • TST repeated 12 weeks after contact broken with infectious adult:

    • If TST (-), discontinue INH

    • If TST (+), re-evaluate child and treat accordingly




Contact investigation results totals after initial testing
Contact Investigation Results: Totals Contacts After Initial Testing


Prevention of tuberculosis in children missed opportunities
Prevention of Tuberculosis in Children: Missed Opportunities

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

  • Delay in reporting the initial diagnosis of TB

  • Contact investigation interview failure

  • Delay in evaluation of exposed children

  • Failure to completely evaluate exposed children

  • Failure to prescribe prophylactic INH

  • Failure to maintain a contact under surveillance

  • LTBI diagnosed; treatment not prescribed

  • Failure to complete treatment for LTBI (Adherence)


Observations on private pediatrician involvement in contact investigations
Observations on Private Pediatrician Involvement in Contact Investigations

  • 6 of 30 (20%) of the exposed children were initially evaluated in conjunction with their pediatricians:

    • TSTs read by pediatricians were reported in at least one case as negative, i.e.: Not in millimeters

    • TSTs 0.0 (zero) mm:

      • H & PE, CXR done: None

    • TSTs 0.0 (zero) mm + CXR (-):

      • H & PE done: None

    • INH prescribed for prophylaxis for 6 contacts <4 yrs of age: None

    • In each case TCs made to assure proper evaluation were followed by a referral to TB Center for the evaluation


Importance of pediatric radiologic expertise
Importance of InvestigationsPediatric Radiologic Expertise

  • 7 of 30 (23%) chest X-rays taken during the initial investigation either needed to be repeated or were misinterpreted

    • In 5 cases the technique used yielded poor quality films

      • Repeats done at the same institution as the initial films, even when requests were made for a specific technique, did not address the question the initial films raised

    • In 2 cases, CXRs with evidence of disease were read as normal


Contact investigation lessons
Contact Investigation: Lessons Investigations

  • Importance of on-site assessment

  • Critical to provide follow-up TB interviews of Ppts. to allow for:

    • Clarification of previously collected contact information

    • Collection of additional information

    • Provision of additional TB education

    • Different interviewers if no contacts identified, rapport is an issue

  • Despite the rapidity of the contact investigation 9 cases of TB disease occurred in young children

    • Children develop disease soon after infection so it is imperative to move quickly

  • Pediatricians are generally not familiar with standard evaluations of children exposed to tuberculosis and use of INH in such situations

  • Radiologic expertise with young children is important:

    • In this CI, 7/30 CXRs either needed to be repeated or were interpreted incorrectly


Bcg vaccine and tuberculin skin testing
BCG Vaccine Investigationsand Tuberculin Skin Testing

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

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

  • Therefore, management of children with a history of BCG and a (+) PPD includes:

    • Diagnostic evaluation including a chest radiograph

    • Appropriate treatment


Bcg fantasy and fact
BCG – Fantasy and Fact Investigations

FANTASY

FACT

  • 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

  • BCG protects against getting TB infection

  • BCG provides lifetime protection against developing active TB

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

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

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

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


Pediatric tuberculosis update

INFORMATION LINE Investigations

1 • 800 • 4 TB DOCS1 • 800 • 482 • 3627www.umdnj.edu/ntbcweb