PAEDIATRIC TB Jenny 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

Figure 1.1: Tuberculosis case reports and rates, UK, 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, *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 London

6 Tuberculosis in the UK: 2013 report Figure 1.4: Tuberculosis case reports and rates by region*, England, 2012 * HPA region CI – 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

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 9 Tuberculosis in the UK: 2013 report

Figure 1.11: Tuberculosis case reports and rates by age group and sex, UK, 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, 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). 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 children 1. 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 healsprogresses Dissemination to lung apices, meninges,bone spine,nodes 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 infection Marais BJ et al. Int J Tuberc Lung Dis 2004;8: 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, 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 Cause False-positive Nontuberculous mycobacteria BCG vaccination Anergy False-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 lobe In young children- can mimic pneumonia/effusions hilar 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 *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

NHS Evidence Tuberculosis topic page Visit NHS Evidence for the best available evidence on tuberculosis diagnosis, treatment and management

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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?