TB CPG Lecture

8/3/2019 TB CPG Lecture

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Tuberculosis in Infancyand Childhood


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Tuberculosis key facts

More than 2 billion individuals worldwide are infected withthe TB bacilli

Each person with TB disease can infect 10-15 people in ayear; 1 in 10 people will progress to TB disease in theirlifetime

In 2008, the global incidence was estimated at 139cases/100,000 population with 1.8 million deaths from TB

TB is the leading cause of deaths in people with HIV; 1 in 4people with HIV die due to TB

People with HIV are 20-30x more likely to develop TB than

those who do not have HIV In 2008, there were an estimated 500,000 new MDR-TB

cases worlwide; with 56% of cases in China, India and theRussian Federation


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What is the value of a history of contact in the diagnosis of TB?

The search for a history of exposure to an adult and oradolescent with tuberculous disease should be investigatedin the evaluation of a child suspected of TB

The risk of TB infection is associated with intensity of

contact and the number of bacilli in the sputum There is no evidence that a history of exposure to a case

with TB taken singly would be strongly predictive ofchildhood TB. However, when taken in conjunction withother clinical data, a history of contact of exposure to a

case of TB has a good positive predictive value Tuberculin skin test and chest x-ray should be done in a

child with a history of contact even if asymptomatic


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What are the clinical manifestations most suggestive of

childhood tuberculosis disease?

The following manifestations when taken together are suggestive ofTB: history of recent weight loss or failure to gain weight, cough andor wheezing > 2 weeks and prolonged, unexpected fever > 2 weeks

The combination of all these 3 taken collectively has a positivepredictive value of 73%

Diagnostic test most recently developed have not found a place inthe routine evaluation of children suspected or having TB, rather,clinical manifestations, skin test, chest x-ray and exposure to aninfectious adult remain as standard diagnostic methods

In addition to the signs and symptoms above, failure to respond toappropriate medications and failure to regain previous state ofhealth 2 weeks after an infection are also suggestive oftuberculusis disease

In the presence of any 3 of the 5 signs and symptoms, work up forTB disease is recommended


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What is a positive tuberculin skin test when used in the

diagnosis of childhood TB disease

An induration of more than or equal to 10mm isconsidered positive regardless of BCG statususing 5 TU PPD-S or 2TU RT23 Mantoux test readat 48-72 hours

An induration of more than or equal to 5mm isconsidered positive if any of the following arepresent: history of close contact with a known or

suspected infectious case of TB, clinical findingssuggestive of TB, chest x-ray suggestive of TB andimmunocompromised conditions


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What are the chest radiograph findings most suggestive

of childhood TB?

The most common chest radiograph finding in

childhood TB is lymphadenpathy found in the

hilar and paratracheal area

The most common parenchymal changes are

lobar opacification, airspace, consolidation,

segmental or lobar atelectasis, air trapping

and pleural effusion


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How can a diagnosis of childhood latent TB infection (LTBI) be

made?

The diagnosis of LTBI can be made in a child

with a tuberculin skin test of more than or

equal to 10mm but no clinical or chest x-ray

findings of TB disease or whose chest x-ray

shows evidence of healed infection

The primary objective of testing for latent PTB

is to identify children who are at increased riskfor developing tuberculous disease


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When is microbiologic diagnosis of childhood tuberculosis

recommended?

The diagnosis of childhood tuberculosis can be made withoutrecourse to microbiologic identification ofM. tuberculosis

The yield of microbiologic studies in children is low. Children < 10yrs have difficulty expectorating adequate sputum and also becausechildhood TB is paucibacillary

There are however, conditions where microscopy and culture arenecessary:

-when MDRTB is suspected in the absence of a culture-positive indexcase including treatment failure

-in cases when TB is strongly considered in a sick child but the

diagnosis cannot be made using other criteria Multiple specimen collection, at least 3, is important in children

who tend to have fewer bacilli


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What is the best clinical specimen to obtain for microbiologic

diagnosis?

In children 10 yrs and older sputum is the best

specimen to collect

In young children < 10 yrs, the use of gastric

aspirate as specimen of choice for smear and

culture recommended because of the

difficulty of obtaining adequate sputum

specimens. They swallow their sputum ratherthan expectorate.


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What is the value of new diagnostic tests for TB

The use of new diagnostic test, in view of theirlimitations and because of few studies in

children, high cost and limited local

availability, is limited to situations where

diagnosis is difficult or of urgency because of

rapid results


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How can a diagnosis of extrapulmonary TB be made?

To diagnose TB meningitis, CSF analysis isessential with a definitive diagnosis establishedby positive CSF culture. A positive PCR establishesthe diagnosis but a negative result does not rule

out TBM Lymph node aspiration and or biopsy with

cytology and culture establishes the diagnosis ofTB lymphadenitis

Plain radiographs, CT scan and or MRI can beutilized to diagnose TB of the spine. Biopsy iffeasible, may be done for confirmation


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Spectrum of TB Exposure, infection and disease

TB exposure TB Infection TB Disease

Exposure yes yes yes

Signs & Symptoms none none positive

Tuberculin Skin Test negative Positive (but

negative in many

children)

Positive(but

negative in many

children)

Chest X-ray negative negative may be positive

(negative or

unreliable)

Direct Sputum

Smear Microscopy

negative negative May be positive or

negative)

Other Diagnostics negative (may be positive) (may be positive)


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What is the optimal drug regimen for newly diagnosed PTB in

children?


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Alternative regimens

A daily intensive phase followed by three

times weekly continuation phase

(2HRZE/4H3R3), provided that each dose is

directly observed

Three times weekly dosing throughout

therapy (2H3R3Z3E3/4H3R3), provided that

every dose is directly observed and the

patient dose does not have HIV nor living in anHIV-prevalent setting


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Adjunctive Therapy

Patients with complicated forms of TB( TB meningitis,endobronchial TB and TB pericarditis) have been shown to

benefit from the addition of steroids to the anti-TB drug

regimen

Corticosteroids are recommended in all cases of TB meningitis Prednisone 2mkd x 4 weeks, for most seriouslly ill children the

dose may be increased to 4mkd (maximum dose of

60mg/day)

The dose of prednisone should be gradually tapered over one-to-two weeks before finally being discontinued


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Is BCG recommended to be administered to Filipino infants at birth?

BCG vaccination induces artificial primary

immunity to TB for prevention of subsequentillness caused by virulent bacilli

The exposure to certain varieties of mycobacteriacan give rise to a cell-mediated response which

opposes the protective effect of subsequent BCGvaccination. If interfence with the response toBCG occurs this way, one method to avoid this isto vaccinate early in life, before exposure to these

mycobacteria. This reason is in support of ourrecommendation to administer BCG vaccinationat birth


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Tuberculosis in Special Situation

TB in Pregnancy and Lactation

TB in pregnancy should be treated without delay HREZ constitute the standard treatment for pregnant

women

Streptomycin and other aminoglycosides should be

avoided Pyridoxine (25mg/day) is recommended for those

taking Isoniazid

Treatment options include 2HRZE/4HR or 2HRE/7HR

Breasfeeding is encouraged because only minimalamounts of the drug are excreted in breast milk

Mothers with LTBI should be treated with INH x 9months without delay


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Newborns of Tuberculous Mothers

Newborn whose mother has LTBI-after birth the infant should not be separated

from the asymptomatic tuberculin positive

mother with a negative chest xray but shouldbe given BCG


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Newborn whose mother has TB disease

The mother who has current TB disease but has

undergone treatment for 2 weeks or more ispresumed to be no longer contagious at the timeof delivery

Possibility of congenital TB should be ruled out

The newborn should be given INH x 3 mos thenshould undergo TST

If TST is negative, INH should be discontinued

If TST is positive and the baby remainsasymptomatic with a negative Cxray, preventivetherapy with INH should be completed for 9 mos


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Separation is recommended for a mother who hascurrent TB disease but has not received treatment

The infant should receive INH, rifampicin can be given

to INH-resistant maternal TB isolate The placenta should be sent for AFB stain and TB

culture and sensitivity and should be histologicallyexamined for granulomata

If initial TST turns out negative, test should be repeatedafter 3 months

If TST turns out positive but CXray negative, INH orRifampicin should be continued for 6 mos

If the TST and Cxray of the mother are negative and shehas completed her treatment, BCG should beadministered to the infant while INH or Rifampicinshould be discontinued


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If the mother has extrapulmonary disease

such as TB meningitis, miliary, bone or joint

TB, the infant must be monitored closely for

possible congenital tuberculosis

A newborn with congenital TB should be given

quadruple Anti-TB drugs x 2mos(HRZS) + HR x

4-7 mos

If congenital TB is ruled out, preventive

therapy should be given, similar to cases of

newborns whose mother has TB disease


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Tuberculosis in Children with Liver Impairment

INH could be removed in the initial drug regimenand REZ be given for 6-9 mos

In the treatment regimen without PZA, HRE mustbe given for two months, followed by 7 monthsof HR for a total of 9 mos

In advanced cases of severe liver disease, onlyrifampicin can be used with ethambutol,fluoroquinolone, cycloserine and other injectableagents for 12 to 18 mos

For severe and unstable liver disease;streptomycin, ethambutol, fluoroquinolones, andother second line drug


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TB in Children with Drug-Induced Hepatitis

Hepatotoxic 1st

line drugs should be discontinuedor modified depending on the level of AST

Drug-induced liver injury- AST level 3or more

times than the upper limit of the normal in the

presence of symptoms or 5x more than the upper

limit in the absence of any symptoms

AST of < 5x more than normal is mild toxicity; AST

of 5-10x more than normal is moderate; and alevel of 10x more than normal is severe


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Rifampicin should be started first

If there is no increase in AST after 1 week, INHmay be restarted

PZA will be restarted 1 week after INH if AST is

not increasing

If symptoms recur or AST increases, the last

drug added must be stopped

If hepatitis is severe, PZA must bediscontinued and replaced by ethambutol or

INH and rifampicin be continued x 9 mos


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TB in Children with Renal Impairment

The recommended initial TB treatment regimen for

patients with renal failure or severe renal insufficiencyis 2mos of HRZE followed by 4mos of HR

A longer dosing interval of PZA and EMB 3x a week isrecommended

If streptomycin must be used, the dosage is 15mg/kg,2-3x/week, to a maximum of 1 gram per dose, andserum levels of the drug should be monitored

In severe renal impairment with creatinine clearance

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