Paediatric

Tuberculosis
Updated February 2013
 Objective

•To describe the epidemiology of tuberculosis

•To understand how TB is diagnosed in children

•To be familiar with common chest xray findings of TB

infection

•To understand basic TB treatment

1
11/21/2013

Page 1

xxx00.#####.ppt 11/21/2013 9:52:20 AM

Summary
•There is high prevalence of TB in Tanzania

•Children with TB have higher rates of developing disease

and when they do the disease is more severe

•Skin testing and sputum testing are inaccurate in children

•Diagnosis of TB in children is largely historical

•If an adult at home has smear positive TB have high

suspicion to treat child for TB

•EFV is preferred for patients on ATB. For children who

cannot use EFV, use ABC or maximum dose NVP.

Page 2

xxx00.#####.ppt 11/21/2013 9:52:20 AM

Epidemiology
• Incidence of bacteriologic confirmed TB in
Tanzania is 354 per 100,000

• Compare with:
‐Kenya 288 per 100,000
‐Uganda 193 per 100,000
‐South Africa 993 per 100,000
‐United States 4 per 100,000

Source: The World Bank, 2011 stats

Page 3

xxx00.#####.ppt 11/21/2013 9:52:20 AM

Epidemiology

Page 4

xxx00.#####.ppt 11/21/2013 9:52:20 AM

Epidemiology

Page 5

xxx00.#####.ppt 11/21/2013 9:52:20 AM

Epidemiology of TB/HIV

 TB and HIV commonly co-exist

 Children with HIV infection are 5-10 times
more likely to develop TB disease than those
without HIV infection
 Children with dual infection of TB and HIV are
4 times more likely to die than those with TB
alone

11/21/2013
Page 6 6
xxx00.#####.ppt 11/21/2013 9:52:20 AM
Epidemiology of TB in Children

•Is most common between the ages of 1 and 4 years from

primary infection

•Secondary peak incidence in adolescents as combination of

primary and reactivation disease

•Young age puts children at high risk for infection, for

progression from infection to disease, and for spread of
disease to other parts of the body

•Most children with TB are smear negative and are not

infectious

Page 7

xxx00.#####.ppt 11/21/2013 9:52:20 AM

 Forms of Paediatric TB
•Pulmonary (usually primary)
‐Smear negative (majority)
Central Nervous System
‐Smear positive (in children >6 - Meningitis
years)
Lymphatics
•Extra pulmonary - Scrofula (of the neck)

‐Miliary TB (usually in children less Pleura

- TB pleurisy
than 3 years)
Disseminated
‐TB meningitis (usually in children - Miliary TB
less than 3 years)
Bones, joints or spine
‐TB lymphadenopathy (all ages) - Potts disease

‐TB effusions (pleural, pericardial

and peritoneal) Genitourinary
- Urogenital TB
‐Spinal TB (often school-aged
children)

Page 8

xxx00.#####.ppt 11/21/2013 9:52:20 AM

General TB Diagnostic
Approaches

 History and examination of the patient

 Laboratory examinations
 Bacteriologic confirmation is achieved in

only 30-40% of cases

 Chest X-ray (CXR) alone NOT reliable
For all patients with suspected EPTB, specimens should be sent for microscopy and, if
available, culture & histology (ISTC)

Page 9

xxx00.#####.ppt 11/21/2013 9:52:20 AM

Diagnosis

 Largely by history.
 Tuberculin testing (positive in 0-30%)
 Microbiologic diagnosis
 Smears of gastric aspirates, induced sputum, CSF
or other body fluids
 Cultures-more sensitive;

 Even if samples (sputum or gastic) are obtained,

disease is paucibacilliary and smears are low yield.
 Chest x-ray useful in PTB or miliary TB
 Histological diagnosis
10

Page 10

xxx00.#####.ppt 11/21/2013 9:52:20 AM

 Evaluation of Suspected Paediatric TB:
Signs and Symptoms
 Consider TB in any child with:
 History of unexplained weight loss or failure to grow
normally
 Unexpected fever, especially lasting longer than 2 weeks
 Chronic cough (more than 14 days in HIV negative, any
duration in HIV positive)
 Failure of response to appropriate antibiotic treatment of
presumed bacterial pneumonia or meningitis
 Contact with an adult or older child with smear-positive PTB
in the last 6 months-2 years. 50% of children who live with
TB infected adult, develop TB

Page 11

xxx00.#####.ppt 11/21/2013 9:52:20 AM

Evaluation of Suspected Pediatric TB:
Physical Exam
On exam:
 Appearance: Normal or Thin/wasted

 Temperature: Normal or elevated

 Fluid on one side of chest

 Enlarged non-tender lymph nodes or lymph node abscess
especially on neck
 Signs of meningitis, especially when developed over several
days and spinal fluid contains mostly lymphocytes and elevated
protein
 Abdomen: masses or ascites
 Bone/joints: swelling, effusion, angulation of the spine
Page 12

xxx00.#####.ppt 11/21/2013 9:52:20 AM

Pulmonary TB X-Ray Findings

Page 13

xxx00.#####.ppt 11/21/2013 9:52:20 AM

Normal Chest Xray

Page 14

xxx00.#####.ppt 11/21/2013 9:52:20 AM

 Normal Chest Xray

• Young children
may have a normal
widened
mediastinum due
to thymic shadow.
They also have
larger cardiac
silhouette.

Page 15

xxx00.#####.ppt 11/21/2013 9:52:20 AM

Pulmonary TB X-Ray Findings

Hilary
lymphadenopathy

Page 16

xxx00.#####.ppt 11/21/2013 9:52:20 AM

Pulmonary TB X-Ray Findings

Page 17

xxx00.#####.ppt 11/21/2013 9:52:20 AM

 Pulmonary TB X-Ray Findings

Left paratracheal lymph gland enlargement Hilar lymph gland enlargement with infiltration
seldom occurs in isolation in tuberculosis. It is usually into the surrounding lung tissue.
accompanied by hilar lymph gland enlargement.

Page 18

xxx00.#####.ppt 11/21/2013 9:52:20 AM

Pulmonary TB X-Ray Findings

Page 19

xxx00.#####.ppt 11/21/2013 9:52:20 AM

Pulmonary TB X-Ray Findings

Compression of left
main bronchus by hilar
lympadenopathy
causing ball valve
phenomenon and left
lung hyperexpansion

Page 20

xxx00.#####.ppt 11/21/2013 9:52:20 AM

Pleural effusion in a child with TB

Page 21

xxx00.#####.ppt 11/21/2013 9:52:20 AM

Milliary TB

Page 22

xxx00.#####.ppt 11/21/2013 9:52:20 AM

TB Pulmonary Cavities

Page 23

xxx00.#####.ppt 11/21/2013 9:52:20 AM

TB Pericardial Effusion

Page 24

xxx00.#####.ppt 11/21/2013 9:52:20 AM

 Tuberculin Skin Test (TST)

•Also called the Mantoux or PPD (Purified Protein

Derivative) test
‐Indicates mycobacterial infection but NOT necessarily the
presence of TB disease
‐Used in children
‐Should be performed by trained personnel
‐Read TST result 48 – 72 hours later by measuring the size
of induration

© 2010 Baylor College of Medicine

Page 25

xxx00.#####.ppt 11/21/2013 9:52:20 AM

Tuberculin Skin Test (TST)

Page 26

xxx00.#####.ppt 11/21/2013 9:52:20 AM

Tuberculin Skin Test (TST)

Page 27

xxx00.#####.ppt 11/21/2013 9:52:20 AM

Interpretation of TST Results
Patient Characteristic Positive TST Result

HIV-infected > 5 mm diameter induration

Severely malnourished (marasmus or > 5 mm diameter induration

kwashiorkor)

Contact to a case of infectious TB > 5 mm diameter induration

(smear positive)

All other children (regardless of > 10 mm diameter induration

whether they have received a BCG
vaccination or not)

NOTE: A negative TST does not rule out TB.

Page 28

xxx00.#####.ppt 11/21/2013 9:52:20 AM

TST False Positive and False Negative
Results
 False positives from:
 BCG (Bacille Calmette-Guérin) vaccination
 Infection with non-tuberculosis mycobacterium
 Improper administration or interpretation
 False negatives from:
 Incorrect administration or interpretation of the TST
 Age less than 6 months
 Severe malnutrition
 Advanced HIV disease
 Immune suppression by other diseases or medication
 Viral illness or recent live virus immunizations
 Overwhelming TB disease

Page 29

xxx00.#####.ppt 11/21/2013 9:52:20 AM

Score Chart for Diagnosis of
TB in Children
 The score chart should be used in all child TB suspects in whom
bacteriologic confirmation has not been successful
• A score of 7 or higher is highly suggestive of TB
• However, no pediatric scoring system has been well validated in children
(especially in HIV-infected children)

Page 30

xxx00.#####.ppt 11/21/2013 9:52:20 AM

Score Chart for Diagnosis of TB in Children
SCORE IF SIGN OR SYMPTOM IS PRESENT
0 1 2 3 4 Score
GENERAL FEATURES
Duration of Less than 2 2-4 weeks More than 4 weeks
illness weeks
Failure to thrive Weight gain No weight gain or Weight loss
or weight loss weight faltering

TB contact None Reported (but no Smear positive

documentation), (with documentation)
reported smear
negative or EPTB
TST Negative, Positive
not done

Malnutrition not Present

improved after 4
weeks therapy
Unexplained Positive
fever not
responding to
appropriate
therapy

Page 31

xxx00.#####.ppt 11/21/2013 9:52:20 AM

Score Chart for Diagnosis of TB in Children (2)

0 1 2 3 4 Score
LOCAL FEATURES
Painless, enlarged Any non- Positive
lymph nodes cervical cervical lymph
lymph nodes
nodes
Swelling of bones or Positive
joints

Unexplained ascites or Positive

abdominal mass

CNS findings: Positive

Meningitis, lethargy,
irritability and other
behavior changes
Angle deformity of the Positive
spine

TOTAL SCORE

Page 32

xxx00.#####.ppt 11/21/2013 9:52:20 AM

Score Chart for Diagnosis of TB in Children (2)

0 1 2 3 4 Score
LOCAL FEATURES
Painless, enlarged Any non- Positive
lymph nodes cervical cervical lymph
lymph nodes
nodes
Swelling of bones or Positive
joints

Unexplained ascites or Positive

abdominal mass

CNS findings: Positive

Meningitis, lethargy,
irritability and other
behavior changes
Angle deformity of the Positive
spine

TOTAL SCORE

Page 33

xxx00.#####.ppt 11/21/2013 9:52:20 AM

Interpretation of
Paediatric Score Chart

≥ 7 points

High likelihood of TB:

REFER for TB Treatment

Page 34

xxx00.#####.ppt 11/21/2013 9:52:20 AM

 Differential Diagnosis of PTB

•Bacterial pneumonia

•Lymphoid interstitial pneumonitis (LIP) or Chronic

Lung Disease

•Pneumocystis pneumonia (PCP)

•Viral pneumonia

Page 35

xxx00.#####.ppt 11/21/2013 9:52:20 AM

Recommended Regimens for Children with TB in Tanzania
Recommended Regimens for
Children with TB in Tanzania
TB disease category Recommended regimen
Intensive phase Continuation phase

All forms of pulmonary TB 2RHZE 4RH

and extra pulmonary TB
except TB meningitis,
military TB and TB of the
spine/bones/joints
TB meningitis, military TB 2RHZE 10RH
and TB of the
spine/bones/joints
Previously treated smear 3RHZE, Use streptomycin in 5RHE
positive pulmonary TB the first 2months only
(Relapse. Treatment failure, when susceptibility is
return after default confirmed.
MDR-TB Refer to MDR treatment guideline

Page 36

xxx00.#####.ppt 11/21/2013 9:52:20 AM

Drug dosing for the treatment of
tuberculosis in children

Page 37

xxx00.#####.ppt 11/21/2013 9:52:20 AM

Comparing Paediatric and Adult
Fixed Dose Combinations (FDC)
Adults Children
Initial: RHZE Initial: RHZ
RMP 150 mg RMP 60 mg
INH 75 mg INH 30 mg
PZA 400 mg PZA 150 mg
EMB 275 mg -
Continuation: RH Continuation: RH
RMP 150 mg RMP 60 mg
INH 75 mg INH 30 mg

Page 38

xxx00.#####.ppt 11/21/2013 9:52:20 AM

Weight-based dosing of Anti-TB Medicines
using Pediatric Formulations (2-20kg)

Intensive Phase Continuation Phase

(2 months) (4 months)
RHZ (pediatric) Ethambutol RH (pediatric)
Weight (kg) 60/30/150 100 mg 60/30
2 - 2.9 kg 1/2 tablet 1/2 tablet 1/2 tablet
3 - 3.9 kg 1 tablet 1/2 tablet 1 tablet
4 - 5.9 kg 1 tablet 1 tablet 1 tablet
6 - 7.9 kg 1.5 tablets 1.5 tablets 1.5 tablets
8 - 10.9 kg 2 tablets 2 tablets 2 tablets
11 - 13.9 kg 3 tablets 2 tablets 3 tablets
14 - 19.9kg 4 tablets 3 tablets 4 tablets

Page 39

xxx00.#####.ppt 11/21/2013 9:52:20 AM

Weight-based dosing of Anti-TB Medicines
using Adult FDC formulations (> 5 kg)

Intensive Phase Continuation Phase

(2 months) (4 months)
RHZE (adult) RH (adult)
Weight (kg) 150/75/400/275 150/75
Use pediatric formulation if
5 - 9.9 kg 1/2 tablet available, or 1/2 tablet
Use pediatric formulation if
10 - 14.9 kg 1 tablet available, or 1 tablet
Use pediatric formulation
15 - 19.9 kg 1.5 tablets available, or 1.5 tablets
20 - 24.9 kg 2 tablets 2 tablets
25 - 29.9 kg 2.5 tablets 2.5 tablets
30 - 40 kg 3 tablets 3 tablets
> 40 kg 4 tablets 4 tablets

Page 40

xxx00.#####.ppt 11/21/2013 9:52:20 AM

 Steroid Use in Pediatric TB

•Corticosteroids generally indicated when treating children

with:
‐ TB meningitis
‐ Severe miliary / disseminated TB
‐ Pericardial effusion
‐ Pleural TB with massive effusions
‐ Pulmonary TB with mediastinal lymph nodes obstructing airways

•Prescribe: Prednisolone 1-2mg/kg/day up to 4mg/kg (max

dose 60mg/day) for 4-6 weeks, followed by 2 week taper

Page 41

xxx00.#####.ppt 11/21/2013 9:52:20 AM

 TB/HIV CO TREATMENT
•Many interactions between rifampicin and HIV medications
‐ Interacts with NNRTIs (specifically NVP)
‐ Interacts with PIs (specifically LPV)
‐ Avoid nevirapine and PIs if child taking rifampicin.
‐ If can’t avoid, adjust doses accordingly

•EFV is preferred NNRTI to be used if child is taking

rifampicin

•Rifampicin effects on ART metabolism can last 2 weeks after

its discontinuation
‐ Therefore continue ART dose adjustments for 2 weeks
Page 42

xxx00.#####.ppt 11/21/2013 9:52:20 AM

 TB/HIV COTREATMENT

• NVP should be used at maximum dose (i.e.

200mg/m2) twice daily. On ART initiation

•Do not use NVP lead-in dosing since it will lead to

sub-therapeutic NVP levels.

Page 43

xxx00.#####.ppt 11/21/2013 9:52:20 AM

NVP Dosing Table for Children on ATT
Goal: Maximize Nevirapine to 200mg/m2/dose due to Rifampicin
effects
Pediatric Duovir N (AZT/3TC/NVP)

Weight (kg) 60/30/50 mg Amount NVP syrup (10mg/ml) to add

PM
Twice Daily Dose AM
0
3-3.9 1 0
0
4-4.9 1 1ml
1.5ml
5-5.9 1 1.5ml
0
6-6.9 1.5 0
0
7-7.9 1.5 1ml
1.5ml
8-8.9 1.5 1.5ml
2ml
9-9.9 1.5 2ml
0
10-10.9 2 0

Page 44

xxx00.#####.ppt 11/21/2013 9:52:20 AM

 TB/HIV COTREATMENT

• For children on a LPV/r (lopinavir boosted with

ritonavir) regimen, consider adding RTV in a 1:1
ratio to achieve a fully therapeutic dose of LPV.

Page 45

xxx00.#####.ppt 11/21/2013 9:52:20 AM

When to Start ART:
In children <3
years,<10kg
Start ART soon after TB AZT + 3TC + NVP
treatment (between 2 AZT +3TC+ ABC
and 8 weeks following
start of TB treatment)

In children
>3years,>10kg
AZT + 3TC + EFV

Page 46

xxx00.#####.ppt 11/21/2013 9:52:20 AM

 Isoniazid Prophylactic Treatment

Children eligible for IPT include

-Neonate whose mother is diagnosed with PTB
-Under 5 years old and have had contact with an adult
with infectious TB after active Tb has been excluded
regardless of HIV status
-HIV-infected > 1 year of age after active Tb has been
excluded regardless of history of contact
 Prophylactic dose: INH 10-15mg/kg/day for 6/12

Page 47

xxx00.#####.ppt 11/21/2013 9:52:20 AM

Summary
•There is high prevalence of TB in Tanzania

•Children with TB have higher rates of developing disease

and when they do the disease is more severe

•Skin testing and sputum testing are inaccurate in children

•Diagnosis of TB in children is largely historical

•If an adult at home has smear positive TB have high

suspicion to treat child for TB

•EFV is preferred for patients on ATB. For children who

cannot use EFV, use ABC or maximum dose NVP.

Page 48

xxx00.#####.ppt 11/21/2013 9:52:20 AM

Asante. Swali?

Page 49

xxx00.#####.ppt 11/21/2013 9:52:20 AM

TB Pathophysiology Review

Page 50

xxx00.#####.ppt 11/21/2013 9:52:20 AM

 Page 51

xxx00.#####.ppt 11/21/2013 9:52:20 AM