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What is TB?

  • ○scientific name: mycobacterium tuberculosis
  • ○acid fast, aerobic bacteria
  • ○grows rapidly - divides every 15-20 hours


How is TB spread?

  • ○droplets expelled when someone with active TB coughs, sneezes, speaks
  • ○TB NOT spread through:
    • ■shaking hands
    • ■sharing drinks
    • ■kissing
    • ■sharing toothbrushes
  • ○pulmonary TB most common


Pathogenesis of TB

  • •droplets with bacilli inhaled and travel to alveoli
  • •macrophages in alveoli ingest bacilli
    • •macrophages attract phagocytes to form a shell (granuloma) around bacilli
      • •most bacilli are destroyed or controlled - latent TB
      • •process can take up to 8 weeks
    • •some bacilli survive and multiply intracellularly
      • •they are released when macrophage dies - active TB
  • •disseminated through lymphatic system and bloodstream
  • •other immune cells, such as dendritic cells, may become involved
  • •extrapulmonary TB


Epidemiology: TB by the numbers


  • •in 1989, the CDC announced a goal of eradication of TB in the US by 2010
    • •Also part of the Millennium Development Goals
  • •Status of TB in the US per CDC reports:
    • •since 1992, incidence rates have ↓ by 3-10%/year
    • •9,565 total TB cases reported in 2013
      • •in 2014, total cases for ages 0-24 was 1421
    • •in 2013, 555 affected persons (0.2%) died from TB
  • •Worldwide, rates are quite higher:
    • •9.6 million new cases in 2014
      • •1.0 mil = children
    • •TB is listed as a leading cause of death
    • •in 2014, 1.5 million died worldwide from TB
      • •140,000 = children


Mapping TB: in the US


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For the Provider: Questions to ask to assess risk for TB

  • •where are you from?
    • •if not US: when do you move here?
  • •have you or someone you know ever had a positive PPD or TB test?
  • •have you or someone you know ever had TB? Been treated for TB?
  • •have you traveled outside of the US?
    • •If so, when, how long, where?*
  • •do you work/reside in a crowded place (jail or homeless shelter)?
  • •is there anyone at home who is immunocompromised?
  • *AAP guidelines say >1wk in high risk area puts individual at risk vs. WHO says >1mo


For the Provider: Questions to ask to assess risk for infection

  • •Are you (child) currently experiencing any of the following?:
    • •cough
    • •coughing up blood
    • •fever
    • •weight loss or failure to thrive
    • •tiredness/lethargy
    • •feeling sick
    • •night sweats
  • *However young children often do not show these symptoms


For the provider: •Other potentially helpful questions:

  • •have you (child) ever had the BCG vaccine?
  • •have you (child) ever had a chest x-ray? why and results?
  • •are/have you (child) taken medications?
  • •which medications? why?


High risk for TB


  • •close contact with person(s) with known/suspected TB
  • •foreign-born individuals from high risk countries: Africa, Asia, Latin America, Eastern Europe
  • •travel abroad
  • •individuals who reside or work in congregate settings: jail, homeless shelter
  • •health care workers
  • •immunocompromised patients
  • •certain populations including medically underserved, low-income, and those who abuse drugs/alcohol


Signs and Symptoms of Pulmonary TB (more common)

on ROS



  • ○a bad cough lasting 3+ weeks (dry or productive)
  • ○chest pain
  • ○coughing up blood or sputum
  • ○weakness/fatigue
  • ○loss of appetite
  • ○weight loss
  • ○chills
  • ○fever
  • ○night sweats


Signs and Symptoms of Pulmonary TB (more common)

on exam


  • ○VS: fever
  • ○LAD
  • ○actelectasis
  • ●*may have no symptoms!!*


What is Extrapulmonary TB?


  • ●less common than pulmonary TB but is common in pts with both HIV and TB
  • ●often disseminated through blood
  • ●if CNS involvement, can cause meningitis


Sx of extrapulmonary TB on ROS and exam


  • ○LAD (chronic or generalized)/lymphadenitis
  • ○malaise
  • ○headache
  • ○fever
  • ○personality changes
  • ○back pain
  • ○abdominal pain
  • ○vomiting or diarrhea
  • ○melena or blood in urine...


Active vs. Latent TB

  • •so far what we have discussed is active… recap:
    • •active infection with s/s present
    • •can spread disease
  • •Latent:
    • •TB is present but the immune system has fought off active infection
    • •no s/s to indicate its presence
    • •might only be picked up incidentally or if asked the right questions
    • •person is not infectious and cannot spread TB to others
    • •when the immune system can no longer fight off TB, latent stage → active infection


What is Reactivation TB?

Who is at risk?

  • •AKA chronic, secondary, or post-primary tuberculosis
  • •occurs in previously infected individual who had not fully healed
  • •can go undiagnosed for a long time (years)
  • •presents with similar symptoms but may have additional complications from long-term disease
  • •are at risk for reactivation if:
    • •immunocompromised or comorbid condition
    • •recent TB infection (within the past 2 years)
    • •was not treated properly for TB in the past


Image summary: TB

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Differentials for TB

  • •Depending on the presentation consider…:
  • •cancer
  • •GERD
  • •FUO
  • •Lymphadenopathy/lymphadenitis
  • •fibrotic lung disease
  • •anorexia nervosa
  • •other infections (pneumonia, CMV, histoplasmosis)
  • •other chronic conditions (diabetes, HIV, lupus)


Screening Tests for Tuberculosis


Tuberculin Skin Test (TST): describe how it's done and read

  • Standard method for children of all ages (birth and up):
  • •TB antigens = purified protein derivative (PPD)
  • •0.1mL intradermal injection
  • •6-10mm elevation of skin (a wheal)
  • •Read 48-72 hours after administration
  • •Measured in millimeters of INDURATION
  • •palpable, raised, hardened area/swelling,
  • •not erythema


Skin Test Interpretation in children

  • Positive results:
  • Induration of 5mm
    • •close contact with known or suspected people with TB disease
    • •suspected to have TB disease
    • •with immunosuppressive conditions/receiving immunosuppressive therapy
  • Induration of 10mm or more
    • •less than 4 years old
    • •with other medical conditions (ex. Hodgkin disease, lymphoma, DM)
    • •Recent immigrants, born from or travel to high-incidence countries
    • •Resident of/exposed to high risk congregate settings
  • Induration of 15mm or more
    • •age 4 and older with no known risk factors


TST: when might you see false positives or negatives

  • False positive may seen with:
    • •infection with nontuberculous mycobacteria
    • •improper administration
    • prior BCG vaccinations ONLY if child was vaccinated in the last 2-3 months. rare after a couple months.

  • False negative may be observed:
    • •In setting of recent TB exposure (within 8-10 weeks)= test 8012w after exposure
    • •Infants < 6 months old


What is Interferon-Gamma Release assay (IGRA)

types, advantages

  • •Blood test that measures immune system reactivity to Mycobacterium tuberculosis
  • •Types:
    • •QuantiFERON-TB Gold In-Tube test (QFT-GIT)
    • •T-SPOT - TB test
  • •Advantages:
    • •Single patient visit
    • •Result within 24 hours
    • •Recent BCG vaccination does not cause false positive results
  • •Preferred use for children > 5 yo
  • •Evidence for IGRA use in children is limited


What to do with positive results of TB tests? 

Is it recommended to do >1 test?

  • •TST or IGRA are used to screen for both TB disease or latent TB infection
  • •Positive results can mean latent or active TB infection
  • •Not recommended to do both tests
  • •Other evaluation/clinical evidence must follow to distinguish diagnosis


Chest Radiography – F/U Screening

What type of CXR to order

  • •Frontal and lateral chest radiography
    • •Confirms or rules out pulmonary/intrathoracic TB, if positive skin/blood test and/or asymptomatic


Chest Radiography: most commonfindings in children / adolescents with TB

  • •Most common positive finding in children with TB:
    • •Primary complex consisting of opacification with hilar or subcarinal lymphadenopathy, in the absence of notable parenchymal involvement
    • •Most are asymptomatic
  • •Adolescents with TB
    • •Typical adult disease findings
    • •Upper lobe infiltrates, pleural effusions, cavitation


Negative vs Positive Film Findings - Child

HILAR LAD in pic #2

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Negative vs Positive Film Findings -Adolescent

#2 is upper lobe infiltrates

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 Two main ways to obtain smear and culture for diagnosis:

  • •Sputum sample
    • •Suggested for adolescents
      • •Difficult to obtain in young children = insufficient tussive force
    • •Sputum induction may be used
      • •Admin. aerosolized heated saline + salbuterol → suction
      • •Suggested safer than gastric aspiration
  • Gastric aspiration
    • •Primary method for young children
    • •Early morning gastric contents collected from fasting child
      • •3 samples on different days
  • •Lumbar puncture for Children <12 months old suspected of having pulmonary or extrapulmonary TB


Algorithm: what to do if suspicion for active pulmonary TB

  • If children < 4yo or high suspicion of active TB >>TREAT before getting back culture results 
    • -Younger children have risk for rapid disease progression
    • -Example = abnormal chest x-ray, positive TST, positive smear
  • If low suspicion is low >> wait for cultures before treating
    • -Example = abnormal chest x-ray, negative TST, negative smear
  • Graph source: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3068897/figure/F1/

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Diagnosis of Latent Tuberculosis Infection

•Asymptomatic/no physical findings

•Positive TST or IGRA

•Normal Chest radiography

→ Consider treatment for prevention


Treatment for Latent TB Infection: 1st line

  • •1st line: Isoniazid (INH)
    • •Daily for 6-9 months, well tolerated
    • •Monitor every 4-6 weeks for 3 months → every 2-3 months
      • •Assess for possible drug toxicity
      • •Side Effects: GI intolerance (n/v, abd pain), dark urine(color of coke), rash, fatigue, risk of hepatotoxicity
      • •Baseline or routine LFTs not recommended

The preferred regimen for children aged 2 to 11 years is 9 months of daily INH.

Isoniazid on an empty stomach, liquid option available


Treatment for Latent TB Infection: 2nd line

  • •2nd line: Isoniazid+Rifapentine (INH-RPT) OR Rifampin
    • •INH-RPT = Directly observed treatment for 2-17 yo, another regimen option for healthy patients > 12yo with risk for developing TB
    • Rifampin = daily for 4 months, for INH intolerance/resistant
    • •Side Effects: Nausea, anorexia, pruritis, orange discoloration of body fluids, hyperbilirubinemia
    • •Watch for drug interactions (ex. phenytoin >> increase levels; oral contraceptives à decrease blood levels)

INH-RPT = use if recent exposure to contagious TB, conversion from negative to positive on TST or IGRA, chest x-ray findings of healed pulmonary TB,

-Do not give under 2 yo

OCP drug interaction applies to both RPT and Rifampin à advices alternative contraceptive method


Diagnosis of Active TB Disease

  • •Clinical symptom(s) or asymptomatic
  • •History of contact or at high risk
  • •Positive TST or IGRA
  • •Abnormal Chest X-ray findings usually
  • •Positive sputum, possibly
  • → Needs treatment

Symptoms may include one or more of the following: fever, cough, chest pain, weight loss, night sweats, hemoptysis, fatigue, and decreased appetite.

Chest radiograph is usually abnormal. However, may be normal in persons with advanced immunosuppression or extrapulmonary disease.

The laboratory tests used to find TB in sputum are less likely to have a positive result in children because children are more likely to have TB disease caused by a smaller number of bacteria (paucibacillary disease). Also, difficult to collect sputum in younger children.

Smear positive in about 50% of patients


Treatment for Active TB Disease

  • → Most likely to refer to a specialist!
    • •For first 2 months (Initial phase):
      • •INH + Rifampin (RIF) + Ethambutol + Pyrazinamide daily
    • •4 or 7 month continuation phase
      • •INH + RIF daily
    • •Monitor monthly
      • •Disease progression, adherence, drug toxicity
    • •Sputum cultures monthly after initial phase until 2 consecutive negative cultures
    • •Follow up chest x-ray not necessary


Drug-Resistant Tuberculosis

what is it / when to suspect 

  • •Resistant to Isoniazid and Rifampin
  • •Suspect if…
    • •TB treatment failure à positive sputum smear/culture after 4 months of treatment OR drug susceptibility test
    • •TB in a region with known high drug-resistance rates
    • •Contact with drug-resistant TB


Drug-Resistant Tuberculosis

Dx and Tx

  • •Optimal tx for children is uncertain, but recommend Fluoroquinolone for tx
  • •Nucleic acid tests/assay for diagnosis:
    • •GeneXpert MTB/RIF, MTBDRplus, MTBDR
  • •Management difficult → Expert consultation important!

Important to get smear/culture after 2 months of TB treatment (active) to assess if treatment is working/ risk of drug resistance à result should be negative by 2 months, if not get drug susceptivility


Bacille Calmette-Guerin (BCG) Vaccine

what is it, what does it protect against?

  • •Vaccine to prevent TB and other mycobacterial infections
    • •Meningitis and disseminated TB (Military)
  • •Protects against extrapulmonary, but not latent pulmonary


Bacille Calmette-Guerin (BCG) Vaccine

when is it recommended in US, efficacy, implications for TB screening

  • •U.S.A. = recommended only for immune-competent children with high risk of exposure
  • •Efficacy depends on extent of prior exposure & age
    • •No exposure = more benefit
    • •Less effective with age
  • •May cause false positive TST 2-3 months after vaccination
  • •At risk children should still get screened/tested even if vaccinated by BCG


Other Vaccines to be aware of in screening for TB

  • •Vaccination with live viruses (ex. Measles) can interfere with TST reactions >> suppress (+) results
    • •Skin testing must be given…
      • •Same day as the live-virus vaccination (OR)
      • •4-6 weeks after vaccine administration (OR)
      • •One month after smallpox vaccination
    • •Effect of live-virus vaccination on IGRA has not been studied


Recommendations for screening and tx in adolescent mothers: nursing or pregnant

  • Adolescent mothers - nursing or pregnant
    • •Pregnancy: Screen and treat if at high risk for latent to active
      • •Tx choice: Isoniazid + pyridoxine supplement
    • Should have pretreatment LFT test, first 2 months
      • •No BCG vaccination with pregnancy
    • •Breastfeeding: not contraindicated if treated w/ first line agents
      • •Do not breastfeed if treating for drug-resistant TB


Recommendations for screening and tx in HIV infected or immunosuppressed

  • •Important test: Sputum samples, lymph node aspiration if needed, Xpert MTB/RIF assay for rapid diagnosis
  • •Positive if TST is >5mm, more likely to be negative w/ low CD4


Recommendations for screening in international adoptees

  • •Initial screening 2 weeks after arrival – screening, TST and HIV testing performed
  •   >>If negative TST = recommend repeat TST/IGRA 3 months after initial TST
  • •Follow up visit 6 months after initial visit, unless earlier visit warranted
  • •If child has symptoms, sputum tests required (even if TST/IGRA and chest x-ray negative)
  • •If known HIV infection, chest x-ray AND sputum tests required
  • •If treated, DOT = Directly Observed Therapy >> provider watches child swallow or take each dose of medication, 6 months to complete
  • ? of overestimation of latent tb in international adoptees. More w/TST than IGRS - recommend getting IGRA if TST +


Monitoring and future surveillance if + TST

  • •Patients with documented positive TST should not repeat the skin test
    • •Repeat testing has no clinical utility for assessing effectiveness of treatment
  • •Ongoing potential TB exposure + positive TBT history → should get baseline chest x-ray
  • •Recommend screening for HIV if positive latent or active TB


When to report...

  • •Must contact and report to local or state TB control program if...
    • •In contact with a positive TB disease
    • •Child had contact with someone with TB disease
    • •Do not need to report latent TB infection


Community resource for kids w/TB

  • The Winchester Chest Clinic - YNHH
    • •Only specialized pediatric tuberculosis outpatient clinic in Connecticut
    • •Dr. Robert Baltimore
    • •Located at 789 Howard Avenue, New Haven


Key points for exam

  • Key points for Tuberculosis
  • World wide risks and high risk populations in US.
  • Epidemiology and pathophysiology
  • Unique factors about TB in children
    • Risks
    • Transmission
    • Presentation
  • Screening recommendations for children
    • Risk levels
    • Types of screening TST, IGRA
    • Timing of screening
      • From possible exposure (2-10 weeks)
      • Relationship to immunizations especially MMR
    • Facts about BCG
    • Interpretation of screening
  • Latent and active disease
    • Definitions
    • Approaches to distinguishing
      • Risk assessment
      • CXR findings
    • Risks of LTBI and active
    • Management
    • Public health ramifications