1. TB IN CHILDREN & PREGNANT WOMEN
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CPG Cover
TB IN CHILDREN & PREGNANT WOMEN by
Dr. Suryati Adnan &
Dr. Jumeah Shamsuddin

2. LEARNING OBJECTIVES
To update current management of TB in children & pregnant women
To highlight latest antiTB regimens & dosages in children
To address evidence-based management of BCG lymphadenitis
To strengthen LTBI & contact management in children

3. 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
TBIS, 2011; WHO 2006
Data from TBIS 2011 showed TB in children is increasing in Malaysia.
History of contact is a strong factor to suspect TB in a symptomatic child
Infants & young children under 5 years are at higher risk of developing active disease
Active TB usually develops within 2 years of infection but the time lag can be as short as a few weeks in infants

4. TB IN CHILDREN PTB & lymph node TB - commonest presentations
PTB & LN TB are the commonest presentations of TB in children
Most children with PTB are sputum negative

5. COMMON CLINICAL PRESENTATIONS OF TB IN CHILDREN
Prolonged fever
Failure to thrive
Unresolved pneumonia
Persistent lymphadenopathy
Symptoms of TB in children are usually non-specific
The common clinical presentations are : Prolonged fever , FTT, unresolved pneumonia & persistent LN , which may be the presenting features of by many other illnesses.
Hence, other chronic diseases must be ruled out especially if there is no history of contact

6. 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 & imagings for PTB & EPTB in children are similar to adults
The diagnostic tests for active TB in children are similar to adults . AFB smear & culture from clinical specimens, sputum , LN bx etc must be taken : For infants & young children who are unable to expectorate sputum , Gastric lavage or gastric aspiration should be performed .
for better diagnostic yield, it should be done following standard protocols .
Others: CT , MRI , scopes etc.

7. TST (MANTOUX TEST) False positive Mantoux False negative Mantoux
BCG vaccination
Non-TB mycobacterium infection
False negative Mantoux
Immunosuppression
False negative results may be seen in those who have compromised immune system like severe malnutrition, premature infants, intercurrent viral illness, TB meningitis or disseminated disease
Immunocompetent children with TB: 10%

8. 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)

9. TREATMENT FOR TB DISEASE IN CHILDREN
TB cases
Regimen*
Remarks
Intensive phase
Continuation phase
New smear positive PTB
New smear negative PTB
Less severe EPTB
2HRZ
4HR
Ethambutol can be added in the intensive phase of suspected isoniazid-resistance or extensive pulmonary disease cases.
Severe concomitant HIV disease
2HRZE
Severe form of EPTB
TB meningitis/ spine/bone
10HR
*Direct observation of drug ingestion is recommended especially during the initial phase of treatment & whenever possible during the continuation phase.
WHO , 2010; WHO, 2006

10. TREATMENT FOR TB DISEASE IN CHILDREN
TB cases
Regimen*
Remarks
Intensive phase
Continuation phase
Previously treated smear positive PTB including relapse & treatment after interruption
3HRZE
5HRE
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.
Treatment failure TB
Refer to paediatrician with experience in TB management.
MDR-TB
Individualised regimen
*Direct observation of drug ingestion is recommended especially during the initial phase of treatment & whenever possible during the continuation phase.
WHO , 2010; WHO, 2006

11. ANTITB DRUGS IN CHILDREN
Dose (range) in mg/kg
Maximum dose
Isoniazid
10 ( )
300 mg
Rifampicin
15 ( )
600 mg
Pyrazinamide
35 ( )
2 g
Ethambutol
20 ( )
1 g
Take note that the dosages of antiTB drugs in children are higher than previously recommended.
The doses previously were extrapolated from adult pharmacokinetic studies, recent data showed that the doses did not achieve adequate desired serum level.
Optic neuritis was a concern with ethmabutol, a SR showed that ethambutol can be used safely in children. (Donald PR et al., Int J Tuberc Lung Dis. 2006)
Pyridoxine mg daily need to be added if isoniazid is prescribed.

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

13. 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 % risk of developing active TB disease. (Horsburgh C et al., N Engl J Med, 2004)

14. 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
CXR & TST should be done for all child contacts.
Symptomatic child must be thoroughly examined & investigated for active TB & other diseases as indicated

15. INTERFERON GAMMA RELEASE ASSAY (IGRA) 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)
Both positive IGRA & TST responses are strongly associated with increasing likelihood of TB. However, children ≤12 months of age are more likely to have positive TST results rather than IGRA.
WHO states that the sensitivity of both IGRAs & TST are reduced in young or HIV-positive children. (WHO, 2011)

16. 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)

17. 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
6-month of isoniazid for children with LTBI is recommended by WHO,however studies of LTBI in adults showed that 12-month was better than 6-month treatment of INH in reducing the number of active TB cases i.e. 75% & 65% respectively. However, the 6-month isoniazid is recommended considering the problem of adherence & hepatoxic effects of longer duration of isoniazid.
In a cross-sectional study on LTBI in children, 3-month isoniazid plus rifampin (3HR) regimen had a low failure rate of 0.85%.
Short course 3HR & 4HR had equal minor side effects as 9H which did not warrant discontinuation or modification of treatment
NICE guideline recommends either regimen
US: 9H

18. 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)
There is no retrievable evidence of treatment for LTBI in HIV-infected children. Hence, we follow WHO recommendation of 6-months isoniazid therapy.

19. MANAGEMENT OF CHILD TB CONTACT
Mantoux test may be negative in children who are malnourished & immunocompromised.
Contact tracing & investigations in children are to be done within six weeks of diagnosis of the index patient.
Source: World Health Organization. Guidance for national tuberculosis programmes on the management of tuberculosis in children. Geneva: WHO; 2006

20. CXR IN CHILD CONTACT CXR is important:-
TST is not specific & sensitive enough
Need to exclude active TB
Suboptimal clinical assessment
Some areas have high TB burden e.g. OA population, immigrants etc.
high degree of exposure
language barrier
CXR IS IMPORTANT TO EXCLUDE ACTIVE PTB
TST is not specific & sensitive enough to be the sole determinant of LTBI or active TB in children
History taking (exposure & s/s of active TB) & physical examination may be done suboptimally by inexperienced health staff or face communication barrier. These are important factors to decide diagnosis of LTBI or active TB

21. CXR IN CHILD CONTACT CXR can be omitted:-
If the health staff are able to exclude active
TB  
Adequate history & physical examination
Considering the risk factors of
severity of exposure
age of the child
disease burden in community
logistics for follow-up for 2 years     

22. BCG LYMPHADENITIS Develop 2 - 4 months after vaccination
Usually self-limiting
No evidence of benefit from medical therapy
Erythromycin, isoniazid & rifampicin
Suppuration can occur in %
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
BCG lymphadenitis tends to occur months after vaccination & suppuration can occur in % of lymphadenitis.
It is normally self-limiting, medical therapy has no evidence of benefit.
Medical therapy such as erythromycin, isoniazid and rifampicin have been used, but no
proper trials have shown that it can reduce suppuration or shorten duration of healing.123, level III
Surgical intervention, aspiration or excision is advised if the node is >3 cm in diameter, fluctuant & the overlying skin is inflammed; needle aspiration reduces rate of spontaneous rupture. Surgical excision is curative & reduces healing time when aspiration fails or if multiple nodes are involved.
I&D is not recommended.

23. RECOMMENDATION 22
Medical therapy should not be offered routinely in BCG lymphadenitis. (Grade C)

24. 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
Congenital TB is a rare complication of in-utero tuberculosis infection.
If maternal TB is suspected during delivery, obtain placenta/vaginal/endometrial samples or biopsy for MTB culture and histopathological examination.
Perinatal TB infection should be considered in all infants with sepsis, pneumonia unresponsive to standard antimicrobial treatment.

25. 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

26. MANAGEMENT OF NEWBORNS
INH as prophylaxis: 2 regimens
INH for 6 mths
INH for 3 mths & followed by mantoux test:
<5 mm - stop INH, give BCG
≥5 mm - complete INH for 6 mths, give BCG
Any symptoms suggestive of TB disease: repeat TB work up, treat as TB
After active TB is ruled out, babies at risk of infection from their mothers should be given isoniazid preventive therapy.

27. PROPHYLAXIS FOR INFANTS OF MATERNAL TB
For infants of mothers diagnosed after delivery , exclude active TB from examination & Ix , even if all are negatives, commence prophylactic therapy : INH for 6 m or INH+rifampicin for 3 mth , in view of very close contact. If BCG was given less than 2 mths before therapy , the baby must be reimmunised.

28. 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)

29. 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
TB in pregnancy is associated with increased risk of maternal & perinatal morbidity such as prematurity, SGA/LBW, etc.
First-line antiTB i.e. INH, rifampicin, ethambutol & pyrazinamide are safe in pregnancy & BF.
Streptomycin: avoid during pregnancy due to risk of foetal ototoxicity.

30. 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

31. ORAL CONTRACEPTIVE PILLS (OCPs) & 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
MOH NZ, 2010

32. 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 & breastfeeding women taking isoniazid. (Grade C)
Patient on rifampicin should use alternative contraception methods other than oral contraceptives & progesterone-only pills. (Grade C)

33. 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 & CXR should be performed in all child TB contacts.
BCG lymphadenitis does not require antibiotic.

34. 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.

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