Addressing the gaps: Childhood TB

25 March 2017

Laura Brandt, MD, FAAP

Clinical Services Director

International Training and Education Center for Health

(I-TECH)

Overview

• Epidemiology of child TB

• Prevention gap, barriers

• Diagnosis gap, barriers

• Approach to diagnosis

• The way forward

World TB Day 2017

0

100

200

300

400

500

1990

1992

1994

1996

1998

2000

2002

2004

2006

2008

2010

2012

Rat

e (p

er 1

00,0

00)

Trends of Prevalence, Mortality and

Incidence in the African Region: 1990-2013

Source: Global Tuberculosis Report 2014

TB Prevalence TB Mortality

TB Incidence TB/HIV Incidence

4

0

5,000

10,000

15,000

20,000

25,000

30,000

35,000

40,000

45,000

2006 2007 2008 2009 2010 2011 2012

0-4 Years 5-14 years

5

TB cases: 0-4 years and 5-14 years African Region 2006 - 2012

Global Child TB Burden What % of total TB

cases in SSA are

children?

6%

10-12%

15-20%

>20%

• Estimated 1 million

children <15 yrs with

TB (2015)* o 1/3 notified

• 210,000 died*

• >7.5 million infected * o <7% receive prophylaxis

*WHO Global Tuberculosis

Report 2016

10%

Greatest burden

<2 years old

TB in children • A leading cause of morbidity and

mortality in children

• It is preventable and usually curable

• Proportion of child deaths due to TB

(compared to other infections)

increasing

• Cannot reduce childhood mortality

(MDG 4) without addressing child TB

Current TB disease prevention

policies in Namibia 1. BCG vaccination at birth, helps prevent

disseminated disease in very young: well

implemented?

2. Provide one course of isoniazid preventive therapy

(IPT) to all PLHIV: implemented somewhat

3. Provide (additional) IPT to all immuno-

compromised persons of any age following proven

close contact with an infectious TB case: poorly

implemented

4. Provide IPT to ALL children <5 years old following

proven close contact with an infectious TB case:

very poorly implemented

The Policy – Practice Gap

MoHSS Policy: IPT

GLs

TB prevented

in child with TB contact

X

Barriers to implementation of IPT in <5 year olds

• Perceived inability to rule out active TB

o Symptom-based screening safe and feasible

(CXR of little value in asymptomatic children)

• Perceived fear of creating drug resistance

o Risk of acquiring DR is low if screening adhered to

o No elevated risk of DR observed in studies

o Pauci-bacillary disease, rarely transmit infection,

risk to community irrelevant

• Poor adherence with prolonged IPT

o Good adherence is possible

o Short-course IPT with dual drug regimens under

investigation

Risk of TB disease after infection by age (pre-tx era)

Adapted from Marais B, et al. Int J Tuberc Lung Dis 2004,8:392-402

50%

20%

Age-sex distribution: new and relapse TB cases, Namibia, 2016

0

200

400

600

800

1000

1200

1400

0-04 5-15 15-24 25-34 35-44 45-54 55-64 65+

Nu

mb

er o

f C

ases

Age Groups

Male Female

12

NTLP report, 2017

The Diagnosis Gap

0

5

10

15

20

25

*Namibia 2016 **SSA est. %

Children <15 years: % of total TB burden

*NTLP 2016 report

**Seddon,JA, D.Shingadia.2014.Infect Drug Resist.7:153-165

We diagnose

<half!

≥20%

9.5%

Myths and Mis-perceptions

• TB is a disease of adolescents and

adults, not of small children

oNot true!

• Child TB not a public health problem

because it is usually non-infectious

oNot true! Child TB means there is ongoing

TB transmission in the community, and this

is a problem!

o Infected children of today are reservoirs

for tomorrow’s TB patients

Myths and Mis-perceptions (2)

• Very difficult to diagnose TB especially

in young children o Not true! It may be difficult to CONFIRM, but

one can usually make a diagnosis

The Policy – Practice Gap

MoHSS Paediatric TB

diagnosis and

treatment GLs

Child diagnosed with and cured of

TB

X

Where will we find the lost children with TB?

• In households of patients with TB

o Are we missing opportunities to prevent or diagnose?

• Presenting to primary health care with signs and

symptoms of common childhood illness, e.g. cough,

weight loss, and malnutrition

o Are we remembering to think of TB, ask the right questions

and examine for clues?

• Presenting ill to secondary and tertiary health care

o Are we remembering to think of TB, ask the right questions

and evaluate comprehensively?

Diagnosis can be

challenging

BUT

is diagnosis always

“difficult”?

Case: 18 month old boy • Presents to PHC clinic with cough

• On examination: T=38˚C, weight: 8.8 kg (WFA z-

score= -2), RR=36, lungs clear

What else do you want to know?

• When did cough start? persistent? worsening?

o “long time”, more than a week ago, not getting better

• Appetite?

o not eating well

• Previous weights?

o Growth chart shows a drop from 9.5 kg (-1 z-score) 3 months previously

Case: 18 month old boy(2) • Anyone at home or who looks after the child

diagnosed with TB?

• No

• Anyone at home or anyone who looks after child

coughing?

o Yes, father has been coughing some weeks but is too busy

to get it checked

• HIV status?

o Mother RT negative when pregnant, not tested since

Clinical diagnosis?

Key message: ask the right questions - probe for a contact, check growth

Approach to TB diagnosis in children

• Careful history o TB contact (incl. household member with a

chronic cough), progressive, unremitting cough, fever, reduced playfulness, activity and appetite; no response to antibiotics

• Clinical examination o including growth assessment,

lymphadenopathy, chest exam (normal, adventitious sounds, wheeze)

o <2 months: pneumonia (can be acute), sepsis, HSmegaly

Growth faltering

Weight loss

Compare current with previous

weights

TB lymphadenopathy • Commonest form of EPTB in children

• Often 2-10 years old

• Commonest LN site: cervical

• Visibly large (>2 x 2 cm)

o painless and asymmetrical

o often multiple, can be discreet or matted

• Persistent (>1 month), not responsive to antibiotics

• Sinus and discharge may develop

Approach to TB diagnosis in children (2)

• Supportive investigations

o TST - less important if a positive exposure history

• 48-88% sensitivity; if HIV+,18-60% sensitive

o Chest X-ray

o Investigations relevant for suspected PTB or EPTB

• Bacteriological confirmation whenever

possible

• HIV testing

o Consider or rule out other HIV-related diagnoses

o Allows dual management, better outcomes

CXR abnormalities suggestive of TB

• Enlarged hilar lymph nodes

• Opacification

• Miliary mottling

• Cavitation (esp. in older children)

• Pleural or pericardial effusion (esp. in older

children)

Freely available on-line, google: diagnostic atlas Gie

http://www.theunion.org/index.php/en/component/flexicontent/items/item/110-diagnostic-atlas-of-

intrathoracic-tuberculosis-in-children

Diagnostic atlas of intrathoracic tuberculosis in children: a guide for low-income countries

2003, Robert Gie, IUATLD

Features for TB diagnosis

• chronic symptoms

• malnutrition

• tuberculin skin test

• CXR findings

Impact of HIV

• less specific

• less specific

• less sensitive

• less specific

Adapted from IUATLD/WHO, Management of Child TB training

Impact of HIV on clinical diagnosis of TB

Definitive diagnosis • Xpert MTB/RIF (Circular 1/2017), LPA,

culture • Sputum

o Challenge: some children unable to expectorate: • gastric aspirate • induced sputum

o Challenge: paucibacillary disease results in lower sensitivity

• EPTB specimens o LN FNA, biopsy o CSF/ascitic fluid taps

Sputum induction with inhaled hypertonic saline • How does it work?

o Interstitial fluid moves into airways (osmosis)

o Stimulates cough reflex, helps mobilise secretions

• Process: (utilise infection precautions)

o Pre-treatment with an inhaled bronchodilator

o Nebulisation with hypertonic (5%) saline x 15

minutes

o Chest physiotherapy

o Sample collection (expectoration or NP/OP

suctioning)

Sputum induction with inhaled hypertonic saline (2) • Target group: unable to voluntarily

expectorate

o SA study* found sputum induction successful in

142/149 (95%) of children with median age 9

months old with pneumonia (youngest 1 month

old)

• Staff training essential

*Zar,HJ et al. 2000.Arch Dis Child;82:305–308

Treatment • “Same old” anti-TB treatment first line

medications, but increased dosage per kg

to account for increased metabolism in

children already in 2012 TB GL

• Second line medications lagging behind

adults. . . but under study

Current treatment regimen

Body

weight

Intensive phase - 2 months

Current [RHZ]

“Pediatric”

(R60/H30/Z150)

No. tablets /

sachets

Add.

H100

No.

tablets

E100

No.

tablets /

sachets

E400

No.

tablets

6.5-7.4 kg 1½ ½ 1½

7.5-9.9 kg 2 ½ 1½

10-12.9 kg 2½ ½ 2

13-14.9 kg 3 1 3

15-19.9 kg 4 1 3

20-24.9 kg 5 1 1

New treatment regimen

Body weight

Intensive phase - 2 months Continuation phase

New RHZ

Pediatric

(R75/H50/Z150)

No. tablets

E100

No. tablets

New RH Paediatric

(R75/H50)

No. tablets

4-7 kg 1 1 1

8-11 kg 2 2 2

12-15 kg 3 2 3

16-24 kg 4 4 or one

adult E400

4

When 25+ kg, use adult formulations

Building the momentum for change. . .

Way forward:

How can we close the gaps? • Trace and screen every child contact of every

index case

• Strengthen TB symptom screening of all HIV (+)

children

• Integrate TB training into MCH, primary health care

and other courses

• Integrate TB screening and diagnosis into child

health SOPs/guidelines/GP visits, e.g., growth

monitoring, evaluation of fever or respiratory

infections

• Do appropriate investigations (clinical, supportive,

definitive)

• Advocate for child-friendly medications

Key points • We have the GLs, let’s implement them - do

something about the child TB prevention and

diagnosis gaps!

• Prevention with IPT saves lives

o Trace every child contact of every index TB case

• Child TB is underdiagnosed leading to too many

preventable deaths

• Diagnosis is not always difficult

o Always think of TB in primary care when child presents with

faltering growth, any cough, fever, lymphadenopathy

o Try to confirm diagnosis but not required to start TB treatment

o Use sputum induction method liberally

Thank you!