Pediatric tuberculosis all you ever wanted to know
Download
1 / 66

Pediatric Tuberculosis: - PowerPoint PPT Presentation


  • 552 Views
  • Updated On :

Pediatric Tuberculosis: All You Ever Wanted to Know. Ann M. Loeffler, MD Pediatric Consultant Francis J. Curry National Tuberculosis Center Legacy Emanuel Children’s Hospital Portland, OR. No disclosures. Pediatric TB Epidemiology How to evaluate & treat children for TB

loader
I am the owner, or an agent authorized to act on behalf of the owner, of the copyrighted work described.
capcha
Download Presentation

PowerPoint Slideshow about 'Pediatric Tuberculosis: ' - arleen


An Image/Link below is provided (as is) to download presentation

Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author.While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server.


- - - - - - - - - - - - - - - - - - - - - - - - - - E N D - - - - - - - - - - - - - - - - - - - - - - - - - -
Presentation Transcript
Pediatric tuberculosis all you ever wanted to know l.jpg

Pediatric Tuberculosis: All You Ever Wanted to Know

Ann M. Loeffler, MD

Pediatric Consultant

Francis J. Curry National Tuberculosis Center

Legacy Emanuel Children’s Hospital

Portland, OR



Slide3 l.jpg

  • Pediatric TB Epidemiology

  • How to evaluate & treat children for TB

  • Use of IGRA tests in children

  • Tuberculin skin testing and BCG impact


Reported tb cases by age group united states 2006 l.jpg
Reported TB Cases by Age Group, United States, 2006

807 cases

<15 yrs

(6%)

>65 yrs

(19%)

15–24 yrs

(11%)

13,779

Total cases

25–44 yrs

(34%)

45–64 yrs

(29%)


Tuberculosis cases by ethnicity in the united states 2006 l.jpg
Tuberculosis cases by ethnicityin the United States – 2006

485 under 5 yrs

White Black Hispanic Asian

American Indian/Native American


California percent cases by age and ethnicity 2006 l.jpg
California: percent cases by age and ethnicity, 2006

n = 91


Interesting facts l.jpg
Interesting Facts

  • Around 25% of children with TB are diagnosed based on positive culture

  • 70% of < 15 year olds were started on four drug therapy in CA (93% for > 15 yr olds)

  • 7.9% drug resistance among < 5 year olds 1993-2007

    • 4% resistance among African American

    • 8% resistance among Whites / Hispanics

    • 12% resistance among Asians


Meron 4 months l.jpg
Meron 4 ½ months


Screening guidelines l.jpg
Screening guidelines

  • Do not screen every child with a TST

  • Screen every child at each well child visit with a questionnaire

  • Questions should relate to risk of TB infection

  • (Adults risk assessment is risk of progression to TB disease)

  • Skin test only children with risk factors


Screening guidelines10 l.jpg
Screening guidelines

  • Was your child born outside the US?

  • Has your child traveled outside the US?

  • Has your child been exposed to anyone with TB disease?

  • Does your child have close contact with anyone with a positive TB skin test?

  • Risk-assessment questions based on local epi.


Tb screening in children l.jpg
TB screening in children

  • There is no gold standard for diagnosing TB infection

  • Hard to measure sensitivity and specificity of tests

  • Tuberculin skin test (5TU of PPD by Mantoux method) is 80-96% sensitive

    • 10-20% of children with TB disease have TST (-)

    • Up to 4.5% remain negative during treatment

    • TST less often positive in infants, malnourished, HIV


Meron l.jpg
Meron

  • Meron has received a BCG at birth

  • Does BCG impact a TST ?

  • At what age?


Bcg and tst l.jpg
BCG and TST

  • Individuals who have received BCG vaccine are more likely to have a positive TST than those who have not

  • They come from areas with higher rates of TB

  • BCG efficacy 0 – 80%

    • Universally acknowledged to prevent disseminated disease in infants

  • Increased risk of TB disease with increasing TST size


Bcg and tst aap l.jpg
BCG and TST (AAP)

  • BCG impacts TST least:

    • Vaccine given at birth

    • If skin tested long after immunization

    • Without exposure to NTM

    • In populations with high TB prevalence

    • When vaccine has fewer viable bacilli

Pediatrics 2004;114;1175-1201 - see handout for table and references

http://www.pediatrics.org/cgi/content/full/114/4/S2/1175


Bcg tst guinea bissau l.jpg
BCG / TST Guinea-Bissau

Roth Vaccine 2005;23:3991-8


Time after bcg l.jpg
Time after BCG

Pediatrics 2004;114;1175-1201 - see handout for table and references


Mexican study 1 st and 6 th grades enrolled l.jpg
Mexican study 1st and 6th grades enrolled

  • TB rate 28 / 100,000

  • TST rates increased by age (8% of 5-7y; 19% 14-16y)

  • Higher TST > 10 mm in BCG vaccinated – BUT few unvaccinated and increased risk with vaccination within 4 years and more than one vaccine

  • TST rates increased by degree of association with a TB case

  • 3 of 97 children with a positive TST developed TB disease within one year

Garcia-Sancho Int J of Epidem 2006;35:1447-54


Variability between regions l.jpg
Variability between regions

  • India

    • 16% TST > 10 mm in BCG scar neg

    • 8% TST > 10 mm in BCG scar pos

    • Larger studies of > 100,000 children agree

  • Korea, UK, USA, Japan BCG adversely impacts specificity of TST

  • Tropical countries may have more rapidly waning TST reaction ? Environmental NTM


Meron19 l.jpg
Meron

  • Evaluated in the adoption clinic

  • TST placed at 8 months of life

  • 12 mm induration

  • What do you do now?

  • ? IGRA test


Quantiferon qft l.jpg
QuantiFERON (QFT)

  • The QuantiFERON tests measure release of gamma-interferon from lymphocytes in whole blood stimulated by TB proteins

  • The original QFT stimulated the lymphocytes with PPD solution

  • QFT-Gold stimulates with lymphocytes with specific TB proteins (ESAT-6 and CFP10)

  • QFT-G In-tube has three proteins coating tube


Qft g or qft it l.jpg
QFT-G or QFT-IT

  • A handful of studies in children

  • Different study designs:

    • Evaluation of TB disease/contacts

      • assesses sensitivity of test

    • Evaluation of TB exposure by gradient in otherwise low risk individuals in low prevalence areas

      • Assesses specificity of the test

  • Variable results

    • QFT concordant with TST

    • QFT more specific than TST

    • QFT less sensitive than TST


India qft git tb suspects or contacts l.jpg
India QFT-GIT: TB suspects or contacts

  • TST 1 TU PPD RT23

  • 10 mm breakpoint

  • 92% BCG hx 82% scars

  • No QFT indeterminates

  • 11 children diagnosed as TB disease

    • TST 82% sens; QFT 64% sens

    • 8 children with laboratory confirmed TB

      • 3 of 8 were TST and QFT negative

Dogra J Infect 2007;54:267-76


India qft git tb suspects or contacts23 l.jpg
India QFT-GIT: TB suspects or contacts


Qft g in cambodian 5yrs contacts l.jpg
QFT-G in Cambodian < 5yrs contacts

  • Good correlation for both QFT and TST by smear / contagion

  • 5% indeterminate / 10 mm TST breakpoint 2.5TU

  • 195 evaluable children

    • 24% positive TST

    • 17 % positive QFT

  • 19 TB disease (no cultures or HIV serologies)

    • 79% positive TST

    • 53% positive QFT

Okada K Epidemiol Infect 2008;in press



Other studies l.jpg
Other studies

  • QFT-G in Australian contacts – poor agreement with TST more sensitive; high rates of inderminates; QFT pos for all 9 with TB disease (defined as TST pos)

    • Connell Thorax 2006;6:616-20

  • QFT-IT in Nigerian contacts

    • 74% QFT pos in contacts of smear pos (53% TST+)

      • Nakaoka Emerg Infect Dis 2006;12:1383-1388


  • Other qft studies l.jpg
    Other QFT studies

    • 2 newborns with miliary TB: positive QFT-G, neg TST

      • Connell CID 2006;42:e82-5

    • High risk South African school children screened by QFT-GIT and TST; 33.2% pos QFT and 43.5% pos by TST

      • Tsiouris Int J Tuberc Lung Dis 2006;10:939-41


    Other qft studies28 l.jpg
    Other QFT studies

    • QFT-G used to follow up exposed HS students with positive TST;

      • Higuchi Respirology 2007;12:88-92

    • QFT-2G 5 cases of dz QFT pos; 1 of 3 asymptomatic QFT pos developed TB

      • Mori J Japan Assoc Infect Dis 2005;79:937-44


    Elispot based tests l.jpg
    Elispot based tests

    • Enumerates reacting lymphocytes after PBMC are removed from whole blood

    • T-SPOT®.TB is licensed abroad and pending FDA approval


    Elispot pediatric studies l.jpg
    Elispot Pediatric Studies

    • South African Study of 260 TB suspects –

      • 83% sensitivity of Elispot vs. 63% of TST in confirmed or highly probable cases

    • Elispot even more superior in children < 3 yrs, HIV infected and malnourished

    • 31% of children with “not TB” (defined as TST neg) were Elispot positive

    • No inderminates

      • Lieberschuetz Lancet 2004;364:2196-203


    Elispot pediatric studies31 l.jpg
    Elispot Pediatric Studies

    • 70 South African TB suspects evaluated with Elispot

      • 83% positive Elispot for definite TB

      • Increased responses after 1 month of treatment

        • One child with culture pos TB remained negative

      • Decreasing response at 3 and 6 months

        Nichol CID 2005;40:1301-8


    Other elispot studies l.jpg
    Other Elispot studies

    • TST neg newborn exposed to mother with MDR-TB. Elispot serially positive – baby eventually developed disease

      • Richeldi Pediatrics 2007;119:e1-5

    • TSpot and QFT-GIT compared in German children with cx pos TB, NTM or other respiratory diseases. TSpot 98% specific, QFT 100% specific and TST 58%

      • Detjen CID 2007;45:322-8


    Other elispot studies33 l.jpg
    Other Elispot studies

    • 535 students exposed in UK school tested by Elispot and TST. Elispot positive more closely related to exposure; TST more positive in BCG vaccinated

      • Ewer Lancet 2003;361:1168-73


    Other elispot studies34 l.jpg
    Other Elispot Studies

    • Turkish study – 979 child contacts

      • 13 diagnosed with TB (11 +TST, 12+ Elispot)

      • Increasing Elispot positive with age, child of source, more than one source in household

      • BCG found to protective against infection and dz

      • More infection and disease in BCG unvaccinated

        • Soysal Lancet 2005;366:1443-51


    Slide35 l.jpg

    • Elispot in Gambian child contacts

      • Hill Pediatrics 2006;117:1542-8

    • Review of Tcell-based diagnosis in children

      • Lalvani Current Opinion Infect Dis 2007;20:264-71

    • Review: new approaches and emerging technologies in the diagnosis of childhood TB

      • Marais Paediatric Resp Rev 2007;8:124-133


    Back to meron l.jpg
    Back to Meron

    • Would a negative IGRA test rule out TB infection or disease?

    • How cautious do you want to be?

    • i.e. How risk averse are you?

    • I err on the side of evaluating and treating BCG vaccinated children with TST > 10 mm.


    Evaluation of a positive tst l.jpg
    Evaluation of a positive TST

    • History and physical:

      • History reveals that Meron has had serial respiratory illnesses in the orphanage

      • She is small for her age

    • Chest radiograph – 2 views

      • Alert the radiologist that you are evaluating for TB


    Chest radiographs l.jpg
    Chest radiographs

    Characteristic: Adults Children

    Location: Apical Anywhere

    (25% multilobar)

    Adenopathy: Rare Usual (30-90%)

    (except HIV)

    Cavitation: Common Rare (except adolescents)

    Signs and symptoms: Consistent Relative paucity


    Slide39 l.jpg

    Positive TB skin test

    Clinically and radiographically

    Abnormal

    Normal

    Consistent

    with TB

    More consistent with other diagnosis

    Treat for LTBI

    Collect cultures and

    start 4 drug TB therapy

    Patient very stable?

    NO

    YES

    TB still possible?

    Other diagnosis confirmed,

    Course inconsistent with TB

    Consider culture

    collection

    (NO INH!!!)

    Treat other

    diagnosis

    Reassess weekly

    *** Cultures only help if they are positive*


    Meron s radiograph l.jpg
    Meron’s radiograph

    • Frontal view is fairly unremarkable

    • Lateral view shows likely lymphadenopathy

    • Chest radiographic changes which are more impressive than the history and physical are more likely to be caused by TB

    • What now?


    Laboratory testing l.jpg
    Laboratory testing

    • No routine lab testing for LTBI patients

    • International adoptees are screened for Hepatitis, syphilis, HIV, parasites, lead, etc.

    • All TB patients should be tested for HIV

    • Specimens for microbiologic testing should be collected on all patients. If I have a very strong source case, I may collect only one.


    Bacteriologic diagnosis l.jpg
    Bacteriologic diagnosis

    • Sputum can rarely be collected from children

    • Can try sputum induction in older children

      • Zar Lancet 2005;365:130-4

    • Bronchoalveolar lavage is invasive, expensive and should be reserved for situations where the diagnosis is in question


    Bacteriologic diagnosis45 l.jpg
    Bacteriologic diagnosis

    • Gastric aspirates

      • people swallow mucus in their sleep

      • collect gastric contents before the stomach empties

      • www.nationaltbcenter.edu

        • Pediatric on-line course: resources


    Gastric aspirate yield l.jpg
    Gastric aspirate yield

    • Literature for 3 gastric aspirates: 40%

    • Nearly 100% yield for <3 month olds

      • smear rarely positive after 3 months

    • First specimen is the very highest yield

    • Higher yield for pulmonary vs. LAD

    • A negative culture does not rule out TB


    Back to meron49 l.jpg
    Back to Meron

    • 2 gastric aspirates collected

    • Adoption labs showed transaminase elevation

    • Started on TB therapy

      after ALT normalized

    • How many drugs?


    National guidelines l.jpg
    National Guidelines

    “Many experts prefer to treat children with three (rather than

    four) drugs in the initial phase because the bacillary population

    is low, because many infants and children cannot tolerate

    the pill burden required with four oral drugs, and because of

    the difficulty in performing visual acuity tests in young children who are being treated with EMB.

    In children suspected or known to have been infected with an M. tuberculosis strain that is fully susceptible, the initial phase should consist of INH, RIF, and PZA.”


    National guidelines51 l.jpg
    National Guidelines

    “When epidemiologic circumstances suggest an increased risk of drug-resistant organisms being present, EMB can be used safely in a dose of about 15–20 mg/kg per day, even in children too young for routine eye testing.”


    Ats risks l.jpg
    ATS risks

    • Exposure to a person who has known drug-resistant tuberculosis

    • Exposure to a person with active tuberculosis who has had prior treatment for tuberculosis (treatment failure or relapse) and whose susceptibility test results are not known

    • Exposure to persons with active tuberculosis from areas in which there is a high prevalence of drug resistance

    • Exposure to persons who continue to have positive sputum smears after 2 months of combination chemotherapy

    • Travel in an area of high prevalence of drug resistance


    Meron53 l.jpg
    Meron

    • Meron was treated with a four drug treatment regimen by DOT

    • The second of her gastric aspirates grew Mtb

    • Resistant to INH and RIF, sensitive to PZA, EMB, SM

      • BUT – purity plates also grew MAC

    • What do you do now?


    Same principles as adults l.jpg
    Same principles as adults:

    • Collect cultures again if possible before changing regimen to look for emergence of drug resistance

    • Use all first line drugs available (unless previously used and associated with a failing regimen)

    • Use an injectable drug (streptomycin, amikacin, capreomycin, kanamycin) by Broviac

    • Use a fluoroquinolone

    • Use additional second line drugs to have 4 – 6 drugs in the regimen


    Mdr tb in children l.jpg
    MDR-TB in children

    • Screening labs:

      • CBC, CMP, TSH for ethionamide, cycloserine, audiology and vision

    • See www.nationaltbcenter.edu/drtb for drug doses

    • Meron’s baseline hearing screen showed high frequency hearing loss (adoption paperwork indicated previous receipt of gentamicin)


    Hearing loss in mdr tb l.jpg
    Hearing Loss in MDR-TB

    • Sometimes inevitable

    • Can sometimes use intermittent therapy to prevent worsening

    • Streptomycin associated with less hearing loss

    • Generally linked to total dose


    Meron57 l.jpg
    Meron

    • Received four months of aminoglycoside (BARE minimum)

    • Is thrilled to have her Broviac out

    • Has two negative gastric aspirates on therapy

    • Has gained many pounds

    • Repeat chest radiograph is essentially normal


    Meron61 l.jpg
    Meron

    I will treat her with another 14 months of pyrazinamide , ethambutol, ethionamide and levofloxacin (Vitamin B6) by DOT

    Monitoring growth & development, musculoskeletal, vision, etc.


    Conclusions l.jpg
    Conclusions

    • Pediatric TB is declining in the US – half of the cases of 1992

    • 25% of cases are treated without benefit of culture results (some are treated based on source case susceptibility)

    • Many in CA are treated with three drugs

    • ? Number of failures – 2 cases in AL experience


    Conclusions63 l.jpg
    Conclusions

    • BCG has variable protection

    • BCG has variable impact on TST reaction

      • Likely has less impact in high prevalence / tropical countries

    • IGRA tests are imperfect –

      • QFT tests are easier to perform – seem to have more indeterminate results

      • Elispot tests may be more sensitive for diagnosing TB Dz in children


    Conclusions64 l.jpg
    Conclusions

    • TB screening should be done by questionnaire

    • Only those with risks of exposure should undergo skin testing (or IGRA screening)

    • Patients with suspicion of TB disease should undergo 2 view chest radiography

    • If findings are more consistent with another disease, consider deferring treatment for a few weeks


    Conclusions65 l.jpg
    Conclusions

    • I prefer four drugs for TB disease in children

    • I find them to be very well tolerated

    • The biggest trick is getting the kids to take the drugs

    • www.nationaltbcenter.edu/pediatric_tb

    • www.nationaltbcenter.edu/drtb



    ad