Picture of CPG Cover

TB IN CHILDREN & PREGNANT WOMEN

by Dr. Suryati Adnan

Development group members

Dr. Suryati Adnan Consultant Infectious Disease Paediatrician Hospital Sultan Hj Ahmad Shah, Pahang Dr. Jeyaseelan P. Nachiappan Senior Consultant Infectious Disease Paediatrician Hospital Teluk Intan, Perak Dr. Jumeah Shamsuddin Maternal-Fetal Medicine Specialist DEMC Specialist Hospital, Selangor

CONTENTS
Update on current management of TB in children & pregnant women Latest antiTB regimens & dosages in children

Evidence-based management of BCG lymphadenitis LTBI & contact management in children

TB IN CHILDREN
TB in children is increasing in Malaysia

High risk of active disease in infants & children under 5 years of age Active TB usually develops within 2 years of infection but can be as short as a few weeks in infants

TBIS, 2011; WHO 2006

TB IN CHILDREN
PTB & lymph node TB - commonest presentations

Most children with PTB are sputum negative

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COMMON CLINICAL PRESENTATIONS OF TB IN CHILDREN Prolonged fever Failure to thrive Unresolved pneumonia Persistent lymphadenopathy

DIAGNOSTIC TESTS FOR ACTIVE TB

AFB smear & culture from clinical specimens

CXR - PTB, pleural, hilar LN disease

TST (Mantoux test) compounded by false positive/negative Other relevant diagnostic procedures and imagings for PTB and EPTB in children are similar to adults
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TST (MANTOUX TEST)

False positive Mantoux
BCG vaccination Non-TB mycobacterium infection

False negative Mantoux

Immunosuppression

RECOMMENDATION 18
Children suspected of PTB should have sputum examination, CXR & TST performed. (Grade C)
Gastric lavage/aspiration should be performed in infants & children who are unable to expectorate sputum. (Grade C)

TREATMENT FOR TB DISEASE IN CHILDREN

TB cases
New smear positive PTB New smear negative PTB Less severe EPTB Regimen* Intensive phase Continuation phase 2HRZ 4HR

Remarks
Ethambutol can be added in the intensive phase of suspected isoniazidresistance or extensive pulmonary disease cases.

Severe concomitant HIV disease Severe form of EPTB TB meningitis/ spine/bone

2HRZE 2HRZE

4HR 10HR

WHO , 2010; WHO, 2006

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TREATMENT FOR TB DISEASE IN CHILDREN

TB cases Previously treated smear positive PTB including relapse and treatment after interruption Regimen* Intensive phase Continuation phase 3HRZE 5HRE Remarks All attempt should be made to obtain culture & sensitivity result. In those highly suspicious of MDR-TB, refer to paediatrician with experience in TB management. Refer to paediatrician with experience in TB management. Refer to paediatrician with experience in TB management. WHO , 2010; WHO, 2006
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Treatment failure TB

MDR-TB

Individualised regimen

ANTI-TB DRUGS IN CHILDREN

Drug Isoniazid
Rifampicin Pyrazinamide Ethambutol

Dose (range) in mg/kg 10 (10 - 15)

15 (10 - 20) 35 (30 - 40) 20 (15 - 25)

Maximum dose 300 mg

600 mg 2g 1g

Pyridoxine 5 - 10 mg daily need to be added if isoniazid is prescribed.

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RECOMMENDATION 19
All children with TB should be given standardised treatment regimens & dosages according to the relevant diagnostic categories. (Grade C)

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LATENT TB INFECTION (LTBI) IN CHILDREN LTBI : infected with M.tuberculosis but patient is asymptomatic. Active TB disease : Symptomatic TB infection. Children younger than 5 years old with LTBI has 10 - 20% risk of developing active TB disease. (Horsburgh CR Jr, 2004)

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DIAGNOSTIC TESTS FOR LTBI IN CHILDREN LTBI is suspected in children exposed to active TB person For child contact: perform CXR & TST Sputum AFB smear is not required in asymptomatic child being investigated for LTBI Symptomatic child: examine & investigate for active TB & other diseases as indicated
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INTERFERON GAMMA RELEASE ASSAY IN CHILDREN The amount of Interferon Gamma (IFN-y) released is correlated directly with age (p<0.0001). (Lighter J et al., Pediatrics. 2009)

IGRA test is less likely to be positive in children < 2 years of age. The sensitivity of both IGRAs & TST are reduced in young or HIV-positive children.
(WHO, 2011)
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RECOMMENDATION 20
TST should be used as a standard test to diagnose LTBI in children. (Grade C) IGRA should not be used as a replacement for TST in diagnosing LTBI in children. (Grade C)

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TREATMENT OF LTBI IN CHILDREN Active TB must be ruled out before starting LTBI treatment. Therapeutic regimens: Isoniazid: 6 months Isoniazid plus rifampicin : 3 months
WHO,2006 Panickar JR et al., Eur Respir J., 2007 Spyridis NP et al ., Clin Infect Dis., 2007.
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RECOMMENDATION 21
Non-HIV infected children with LTBI should be treated with 6-month of isoniazid or 3-month of isoniazid plus rifampicin. (Grade C)

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MANAGEMENT OF CHILD TB CONTACT

BCG LYMPHADENITIS
Develop 2 - 4 months after vaccination Usually self-limiting No evidence of benefit from medical therapy.
Erythromycin, isoniazid and rifampicin

Suppuration can occur in 30 - 80% If LN >3 cm & fluctuant: needle aspiration surgical excision (if recurring)
Banani SA et al., Arch Dis Child., 1994 Goraya JS et al., Postgrad Med J., 2002
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RECOMMENDATION 22
Medical therapy should not be offered routinely in BCG lymphadenitis. (Grade C)

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CONGENITAL & PERINATAL TB Congenital TB is rare Active maternal TB during delivery: take samples or biopsy for MTB culture & HPE Perinatal TB infection is suspected when infant does not respond to standard treatment
Coulter JB et al., Ann Trop Paediatr., 2011 Whittaker et al., Early Hum Dev., 2008 Smith KC et al., Curr Opin Infect Dis., 2002
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MANAGEMENT OF NEWBORNS Defer BCG at birth & perform full TB investigations if: mother diagnosed <2 mths before delivery or did not receive adequate treatment mother is sputum positive just before delivery the newborn is symptomatic Treat as active TB if indicated
WHO, 1998
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MANAGEMENT OF NEWBORNS INH as prophylaxis: 2 regimens a) INH for 6 mths b) INH for 3 mths & followed by mantoux test: o <5 mm - stop INH, give BCG o 5 mm - complete INH for 6 mths, give BCG Any symptoms suggestive of TB disease: repeat TB work up, treat as TB
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PROPHYLAXIS FOR INFANTS OF MATERNAL TB

RECOMMENDATION 23
BCG should not be given to babies on prophylactic TB treatment. (Grade C) Prophylactic TB treatment should be given to babies born to mothers with active PTB except those diagnosed more than 2 months before delivery who have documented smear negative before delivery. (Grade C)
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TB IN PREGNANCY & LACTATION Increased risk of maternal & perinatal morbidity First-line antiTB drugs are safe in pregnancy & breastfeeding Streptomycin: avoid during pregnancy risk of foetal ototoxicity
Ormerod P, Thorax, 2001
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TB IN PREGNANCY & LACTATION Breastfeeding should be continued Surgical mask should be used if the mother is still infectious Pyridoxine should be given to mothers taking isoniazid Infant-mother separation is considered if the mother has MDR-TB or is non-compliant to treatment
Ormerod P, Thorax, 2001
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ORAL CONTRACEPTIVE PILLS & ANTITB DRUGS Rifamycin (rifampicin & rifabutin) reduces the efficacy of both combined oral contraceptives & progesterone-only pills

Alternative contraceptive method should be used during & for 1 month after stopping rifamycins
NZMoH; 2010

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RECOMMENDATION 24
All women of child bearing age suspected of TB should be asked about current or planned pregnancy. (Grade C) First-line antiTB drugs except streptomycin can safely be used in pregnancy. (Grade C) First-line antiTB drugs can safely be used in breastfeeding. (Grade C) Pyridoxine supplementation should be given to all pregnant and breastfeeding women taking isoniazid. (Grade C) Patient on rifampicin should use alternative contraception methods other than oral contraceptives and progesteroneonly pills. (Grade C)

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TAKE HOME MESSAGES TB IN CHILDREN Children <5years old have high risk of developing active TB disease Defer BCG in newborns at risk of perinatal TB until INH completed. TST and CXR should be performed in all child contacts . BCG lymphadenitis does not require antibiotic.
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TAKE HOME MESSAGES MATERNAL TB First-line antiTB drugs are safe in pregnancy & lactation. Streptomycin must be avoided in pregnancy. Rifamycins reduce the efficacy of OCPs.

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THANK YOU
drsuryati_adnan@phg.moh.gov.my jaynachi@gmail.com jumeah70@yahoo.com

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