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Tuberculosis and Youth Keith W. Wilson BA MD PhD CCFP Sept 2011 Outline • • • • • • What is TB? TB Facts TB in Children TB Control TB Prevention Conclusions What is TB? What is TB? • Mycobacterium tuberculosis – Discovered in 1882 by Robert Koch (18431910), German Physician • M. tuberculosis accounted for 1 in 7 deaths in Europe at that time (about 1:3 for young productive adults) • Acid-Fast Bacillus Classic Features of TB • TB can affect any organ system: bone, kidney, CNS; 80% are pulmonary • Active disease presentation: – persistent cough > 3 weeks duration – +/-haemoptysis, decreased appetite, weight loss, general weakness, night sweats • Active disease atypical presentation: diminished clinical signs, much more common in HIV-infected TB Transmission • Spread through the air • Enters through the lungs • Person with untreated pulmonary TB disease can infect 10-15 people each year TB Infection vs. TB Disease • TB infection – organism is present, but dormant, cannot infect others • TB disease (active TB) – person is sick and can transmit disease to others if in lungs • Lifetime risk of developing (active) TB disease if TB infected but HIV neg: 10% • Annual risk of developing TB disease if coinfected with HIV: 10% When does TB Infection become Disease? • Most likely in first two years after infection • If person becomes immunocompromised – HIV – Cancer – Chemotherapy – Poorly controlled diabetes – malnutrition TB Facts TB Facts • 2 billion people (1/3 of the world’s population) are infected with TB bacilli • 1 in 10 people infected with TB bacilli will become ill with active TB • TB is a disease of poverty; mostly affecting young adults during their most productive years • Death due to TB is mostly found in developing countries with nearly half occurring in Asia Source: World Health Organization 2007 TB Facts • In 2009 – 1.7 million people died from TB (4600 deaths per day) – 9.4 million new cases of TB (80% of these were in 22 countries) • Global incendence rate fell to 137 cases per 100,000 in 2009 • Highest level of people successfully treated was 86% achieved in 2008 Source: World Health Organization 2010 Estimated TB Incidence 2009 TB is a Worldwide Problem Source: World Health Organization 2010 TB in Children TB in Children • Estimated 1 million children worldwide with TB – 75% of these occur in the 22 high-burden countries – In low-burden countries, childhood TB constitutes about 5% of the caseload, compared to 20-40% in high-burden countries • Estimated 130,000 deaths per year in children worldwide – High correlation with socioeconomic status, nutritional status & immunosuppression Source: Swaminathan S, Rekha B (2010) Canadian Context • Most cases of paediatric cases of TB in Canada are found in: – Aboriginal children – Foreign-born children – Canadian-born children of foreign-born parents Source: Canadian Tuberculosis Standards, 6th Edition (2007) TB in Canada Source: Canadian Tuberculosis Standards, 6th Edition (2007) TB in Canada Adapted from: Tuberculosis in Canada 2009 – Pre-Release (2010) TB in Canadian Children Adapted from: Tuberculosis in Canada 2009 – Pre-Release (2010) TB in Canadian Children Adapted from: Tuberculosis in Canada 2009 – Pre-Release (2010) Challenges to TB Control • Three major challenges exist in TB control unique to children: – TB diagnosis in children is difficult – TB in children is considered a sentinel/recent event – Increased risk of latent TB infection (LTBI) Source: Canadian Tuberculosis Standards, 6th Edition (2007) TB Diagnosis in Children • A Major Challenge! – Less than 15% cases are smear positive and culture yields are only 30-40% – In non-endemic countries, without bacteriologic confirmation, triad of: • Close contact with infectious index case • Positive tuberculin skin test • Presence of suggestive abnormalities on CXR Source: Swaminathan S, Rekha B (2010) TB Diagnosis in Children • Clinical Presentation – Most children are asymptomatic at presentation, typically identified as a contact by public health – Later found to have abnormal chest xrays – Older children and adolescents are more likely to manifest adult presentation (fever, night sweats and weight loss) TB Diagnosis in Children • Pulmonary parenchymal disease: most common manifestation at 60-80% cases • Extra-pulmonary manifestations: – – – – – Lymphadenopathy (67%) CNS involvement (13%) Pleural involvement (6%) Miliary and/or disseminated (5%) Skeletal (4%) Source: Swaminathan S, Rekha B (2010) Complications in Children • Parenchymal lesions may enlarge and caseate • Nodes may enlarge and compress or erode through a bronchus (causing wheeze, pneumonia or atelectasis) • Subclinical bacteraemia which seeds distant sites (apices of lungs, lymph nodes and CNS) • The above is most common in < 5yo Source: Canadian Tuberculosis Standards, 6th Edition (2007) Diagnostic Tools • Tuberculin skin test (TST) remains standard tool • Interferon-Gamma Release Assays (IGRA) – can be helpful, particularly in those previously immunized with BCG vaccine – However immature immune response in infants and young children pose a challenge • Chest Xrays – Difficulty in interpretation remains • CT Scan – Not routinely recommended Source: Canadian Tuberculosis Standards, 6th Edition (2007) Diagnostic Tools • Others – Gastric aspirates: people swallow mucus in their sleep – Sputum Induction: sometimes useful in older children – Cultures: Nucleic acid amplificiation tests/PCR (but limited in paucibacillary disease) Source: Paediatr Child Health 2003; 8(3): 162-172 TB Screening • Targeted TB Screening in Children – Contacts of known cases of active TB – Children with suspected active TB disease – Children with known risk factors for progression of infection to disease – Children travelling or residing for 3+ months in an area with a high incidence of TB – Children who arrived in Canada from countries with high TB incidence within past 2 years Source: Paediatr Child Health 2010; 15(8): 529-33 TB Control Priorities of TB Control • Completion of treatment is paramount! • Treating non-pulmonary cases and those with infection, without active disease are of lesser public health importance! (unless you are a child!) • A poor TB program worse than no TB program— bad programs breed resistance! • These priorities hold regardless of HIV status! TB Control • Directly Observed Treatment, Short-course (DOTS) – Once diagnosed, community works observe and record patients swallowing their full course of TB medications – Usual medications include isoniazid, rifampicin, pyrazinadmide, streptomycin and ethambutol – A six-month supply of medications costs $11 USD per patient: one of the most cost-effective of all health interventions – Completion of all prescribed medications reduces the incidence of resistance DOTS Strategy 1. Political commitment with increased and sustained funding 2. Case detection through quality-assured bacteriology 3. Standardized treatment with supervision and patient support 4. Effective drug supply and management system 5. Monitoring and evaluation system, and impact measurement DOTS Effectiveness • 26 million TB patients have been treated under DOTS since 1995 • 187 countries have adopted DOTS – Many need to expand DOTS services however • Dissemination through WHO and STOPTB programmes Turning the corner? Millions of new cases per year 4 Rest of world 3 Africa 2 1 E Europe 0 1990 1995 2000 2005 TB Prevention TB Prevention • • • • Contact Tracing Screening Vaccines – BCG Treating LTBI Contact Tracing • Childhood case likely to be recent infection – Rigourous search of index case – Child as index case unlikely to be particularly contagious • All exposed children should be identified and risk ascertained – Children <5yo with neg TST and neg CXR should consider taking “window” preventive therapy (8 weeks – as it may take that long for the exposed to convert their TST to positive) Latent TB Infection • Latent TB Infection (LTBI) – A few bacilli sequestered “somewhere” – Walled off by host defenses – Not clinically detected – Positive test: TST or IGRA Future Dilemmas • MDR/XDR-TB is in Canada – unclear how many cases are paediatric • Co-infection with HIV • Difficult to overcome the overall burden of TB without considering the Social Determinants of Health Concluding Remarks Source: CMAJ (2011); 183(7): 741 In Summary • Children are not just ‘little adults’ when it comes to TB • TB is challenging to diagnose in the paediatric population • New tools on the horizon will help combat TB in children • We have a long way to go in Canada to overcome the burden of TB in our most vulnerable populations – get involved in advocacy! Thank you Questions? Dr Keith W Wilson [email protected]