PAEDIATRIC TBJenny Handforth

June 2014

Overview

•Why is Paediatric TB important

•Epidemiology- know the patients

•Adult v child with TB - differences?

• Diagnostic challenges:

Why do you need to know about Paediatric TB?

• 1 million cases estimated globally each year (11%)

• 25-40% of all cases are children in high burden countries

• 4-7% in low burden countries

• Higher risk of severe disease and death in young children

• Indicator of effectiveness of TB control programmes

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Figure 1.1: Tuberculosis case reports and rates, UK, 2000-2012

Source: Enhanced Tuberculosis Surveillance (ETS), Enhanced Surveillance of Mycobacterial Infections (ESMI), Office for National Statistics (ONS)

Data as at July 2013                    

Prepared by: TB Section, Centre for Infectious Disease Surveillance and Control, Public Health England      

4 Tuberculosis in the UK: 2013 report

5 Tuberculosis in the UK: 2013 report

Figure 1.3. Three-year average tuberculosis case rates by local area*, UK, 2010-2012 *England – Local authorities, Wales and Scotland – Health

Boards, NI – data not available

Source: Enhanced Tuberculosis Surveillance (ETS), Enhanced Surveillance of Mycobacterial Infections (ESMI), Office for National Statistics (ONS)Data as at July 2013

Prepared by: TB Section, Centre for Infectious Disease Surveillance and Control, Public Health England

© Crown copyright and database rights 2013 Ordnance Survey 100016969

London

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6 Tuberculosis in the UK: 2013 report

Figure 1.4: Tuberculosis case reports and rates by region*, England, 2012

* HPA regionCI – 95% confidence intervals        Source: Enhanced Tuberculosis Surveillance (ETS), Office for National Statistics (ONS)  Data as at July 2013        Prepared by: TB Section, Centre for Infectious Disease Surveillance and Control, Public Health England

Figure 1.6: Tuberculosis case reports by place of birth and country, UK, 2012

Source: Enhanced Tuberculosis Surveillance (ETS), Enhanced Surveillance of Mycobacterial Infections (ESMI)

Data as at July 2013                    

Prepared by: TB Section, Centre for Infectious Disease Surveillance and Control, Public Health England      

7 Tuberculosis in the UK: 2013 report

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Figure 1.8: Non UK-born tuberculosis case reports by time since entry to the UK to tuberculosis diagnosis, UK, 2012

Source: Enhanced Tuberculosis Surveillance (ETS), Enhanced Surveillance of Mycobacterial Infections (ESMI)

Data as at July 2013                    

Prepared by: TB Section, Centre for Infectious Disease Surveillance and Control, Public Health England      

8 Tuberculosis in the UK: 2013 report

Figure 1.10: Tuberculosis case reports and rates by age group and place of birth, UK, 2012

Source: Enhanced Tuberculosis Surveillance (ETS), Enhanced Surveillance of Mycobacterial Infections (ESMI), Office for National Statistics (ONS)

Data as at July 2013                    

Prepared by: TB Section, Centre for Infectious Disease Surveillance and Control, Public Health England      

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9 Tuberculosis in the UK: 2013 report

Figure 1.11: Tuberculosis case reports and rates by age group and sex, UK, 2012

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10 Tuberculosis in the UK: 2013 report

Source: Enhanced Tuberculosis Surveillance (ETS), Enhanced Surveillance of Mycobacterial Infections (ESMI), Office for National Statistics (ONS)

Data as at July 2013                    

Prepared by: TB Section, Centre for Infectious Disease Surveillance and Control, Public Health England      

Figure 1.14: Child to adult ratio in notifications rate, UK, 2000-2012

The child-to-adult ratio is the ratio of the case notification rate in children under 15 years of age, to that in adults. A declining trend in the ratio suggests a decrease in ongoing transmission (European Centre for Disease Prevention and Control).

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Source: Enhanced Tuberculosis Surveillance (ETS), Enhanced Surveillance of Mycobacterial Infections (ESMI)

Data as at July 2013                    

Prepared by: TB Section, Centre for Infectious Disease Surveillance and Control, Public Health England      

11 Tuberculosis in the UK: 2013 report

Questions that must be asked...• Has this child been exposed to TB?

• Has the child been infected with TB?

• If yes does this child have Tb disease?

• Who has infected this child?

• …and answered!

3 scenarios for investigating TB in children1. Screening healthy children - screen for

TB risk factors

2. Known contact with infectious case - usually adult

3. Child with symptoms and/or signs of TB or abnormal CXR

- high index of suspicion required

Pathogenesis of TB in childhood

• Exposure to bacilli

from adult

• No infection • Primary complex

Dissemination to

lung apices,

meninges,bone

spine,nodes

• heals • progresses • Active disease• Dormant

TB disease (TB) or Latent TB (LTB)• TB: active M. tuberculosis in some part of child’s body

• May be asymptomatic• Abnormal CXR and/or abnormal clinical exam

• LTB: dormant M. tuberculosis• Clinical exam normal• X rays normal

• Diagnosis is made by• History• Clinical examination• CXR/imaging/microbiology

Risk of Disease following primary infectionMarais BJ et al. Int J Tuberc Lung Dis 2004;8:392-402

Disseminated TB

Pulmonary TB

No disease comments

< 1 years

10-20% 30-40% 50% High rates of morbidity & mortality

1-2 years

2-5% 10-20% 75-80% High rates of morbidity & mortality

2-5 years

0.5% 5% 95%

5-10 years

<0.5% 2% 98% Safe school years

>10 years

<0.5% 10-20% 80-90% Adult disease

Table 1.2: Tuberculosis case reports by site of disease, UK, 2012

Site of disease* Number of cases Percentage**

Pulmonary 4,563 52.1

Extra-thoracic lymph nodes 1,872 21.4

Intra-thoracic lymph nodes 946 10.8

Other extra-pulmonary 619 7.1

Pleural 651 7.4

Gastrointestinal 471 5.4

Bone – spine 394 4.5

Cryptic± 46 0.5

Miliary± 197 2.3

Bone – other 218 2.5

CNS – meningitis 187 2.1

Genitourinary 137 1.6

CNS – other 80 0.9

Laryngeal 16 0.2

Unknown extra-pulmonary 15 0.2

17 Tuberculosis in the UK: 2013 report

Source: Enhanced Tuberculosis Surveillance (ETS), Enhanced Surveillance of Mycobacterial Infections (ESMI)

Data as at July 2013                    

Prepared by: TB Section, Centre for Infectious Disease Surveillance and Control, Public Health England      

*With or without disease at another site **Percentage of cases with known sites of disease (8751)±For Scotland cases, this includes both cryptic and miliary site

CNS - Central Nervous System   Total percentage exceeds 100% due to infections at more than one site

Evaluation for TB

Medical history

Physical examination

Mantoux tuberculin skin test

IGRAs

Chest radiograph

Bacteriologic or histologic exam

Medical History

Symptoms of disease

History of TB exposure, infection, or disease

Past TB treatment

Demographic risk factors for TB

Medical conditions that increase risk for TB disease

Systemic Symptoms of TB

Fever

Cough

Chills

Night sweats

Appetite loss

Weight loss

Tiredness

Testing for TB Disease and Infection

Factors that May Affect the Skin Test Reaction

Type of Reaction Possible CauseFalse-positive Nontuberculous mycobacteria BCG vaccination

AnergyFalse-negative Recent TB infection Very young age (< 6 months old) Live-virus vaccination Overwhelming TB disease

Anergy

•Do not rule out diagnosis based on negative skin test result

•Consider anergy in persons with no reaction if

- HIV infected

- Overwhelming TB disease

- Severe or febrile illness

- Viral infections

- Live-virus vaccinations

- Immunosuppressive therapy.

•Anergy skin testing no longer routinely recommended

Interferon Gamma Release Assays (IGRAs)• Recommended in NICE guidelines• Quantiferon-TB gold and T-spot.TB• Incubate patients blood with M. tuberculosis specific antigens (ESAT 6 & CFP-10)

• Measure production of gamma interferon • More specific than TST• Cannot distinguish between active and latent TB• Expensive• Technically difficulties with sampling• Lack of data for children

Chest Radiograph

Abnormalities often seen in apical

or posterior segments of upper lobe or superior segments of lower lobeIn young children- can mimic pneumonia/effusionshilar lymphadenopathy

May have unusual appearance in

HIV-positive persons Cannot confirm diagnosis of TB

.

Arrow points to cavity in patient's right upper lobe

Specimen Collection

Obtain 3 sputum specimens for smear examination and culture

Persons unable to cough up sputum, induce

sputum, bronchoscopy or gastric aspiration

Consider lymph node biopsy

Notoriously difficult to achieve in children

AFB smear

AFB (shown in red) are tubercle bacilli

Cultures

•Use to confirm diagnosis of TB

•Culture all specimens, even if smear negative

•Results in 4 to 14 days when liquid medium systems used

Colonies of M. tuberculosis growing on media

Treatment

• Doses weight adjusted• TB disease• 6 months of isoniazid & rifampicin

• Pyrazinamide and ethambutol for first 2 months

• CNS- total 12 months plus dexamethasone at start

• Latent TB• 3 months of isoniazid and rifampicin

• Or• 6 months isoniazid

Things to consider• Baseline LFTS• Eye check up• HIV testing

Young Children with TB• Differ from Adults with TB:• Signs/symptoms• Generally not infectious• Pattern of progression to disease • Response to treatment• Side effects• Don’t forget parent!

Adolescents with TB• Differ from young children:• Signs/symptoms• Delay in diagnosis• Adherence issues• Side effect profile• May be infectious!

Monitoring Patients

Establish rapport with patient and emphasize

Benefits of treatment

Importance of adherence to treatment regimen

Possible adverse side effects of regimen

Establishment of optimal follow-up plan

Monitoring Patients (cont.)

At least monthly, evaluate for

Adherence to prescribed regimen

Signs and symptoms of active TB disease

Signs and symptoms of hepatitis

Preventing and Controlling TB

Three priority strategies:

Identify and treat all persons with TB disease

Identify contacts to persons with infectious TB; evaluate and offer therapy

Test high-risk groups for LTBI; offer therapy as appropriate

Table 2.1: Number and proportion of tuberculosis cases with drug resistance by age group, UK, 2012

Tuberculosis in the UK: 2013 report 36

n % n % n %

0-14 10 9.7 10 9.7 7 6.8 103

15-44 240 7.2 264 7.9 65 2.0 3,333

45-65 77 7.6 78 7.7 8 0.8 1012

65+ 24 3.4 27 3.8 1 0.1 703

Age Group

Isoniazid Resistant to any Multi-drug

Total**resistant first line drug* resistant

*First line drugs - isoniazid, rifampicin, ethambutol and pyrazinamide**First line drugs – isoniazid, rifampicin, ethambutol and pyrazinamide**Culture confirmed cases with drug susceptibility results for at least isoniazid and rifampicin

Source: Enhanced Tuberculosis Surveillance (ETS), Enhanced Surveillance of Mycobacterial Infections (ESMI)

Data as at July 2013                    

Prepared by: TB Section, Centre for Infectious Disease Surveillance and Control, Public Health England      

Table 4.1: Treatment outcome at 12 months for tuberculosis cases, UK, 2011*

Tuberculosis in the UK: 2013 report 37

* Excludes MDR-TB and RMP-resistant TB cases. Not evaluated includes missing, unknown and transferred out

Source: Enhanced Tuberculosis Surveillance (ETS), Enhanced Surveillance of Mycobacterial Infections (ESMI)

Data as at July 2013                    

Prepared by: TB Section, Centre for Infectious Disease Surveillance and Control, Public Health England      

Treatment outcome n %

Completed 7,302 82.9

Died 434 4.9

Lost to follow-up 435 4.9

Still on treatment 289 3.3

Stopped 88 1.0

Not evaluated 257 2.9

Total 8,805 100

NHS Evidence

NHS Evidence Tuberculosis

topic page

Visit NHS Evidence for the best available

evidence on tuberculosis

diagnosis, treatment and management

Find out more

• www.nice.org.uk/guidance/CG117

Take home messages• Think about TB• TB is a family disease• Ask about risk factors• TB contacts• BCG Hx• Travel history• IGRA can be useful, but a negative IGRA does not exclude TB

• Liaise with TB nurses/doctors• TB therapy requires a lot of support• TB should be managed by specialists-discuss/refer early

Questions?