Tuberculosis and BCG

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Tuberculosis and BCG Steve Graham Centre for International Child Health University of Melbourne Department of Paediatrics Royal Children s Hospital Melbourne Child Lung Health International Union Against Tuberculosis and Lung Disease Paris

Risk of TB disease following infection by age Adapted from Marais B, et al. Int J Tuberc Lung Dis 2004

Global TB Report, WHO 2013

Available approaches to prevent TB in children Improved case-finding and management BCG Contact screening and management Infection control Early identification and effective treatment of infectious TB cases will reduce the burden of child TB Neonatal BCG immunisation is used widely but efficacy is variable The main proven benefit of neonatal BCG is protection against severe disseminated forms of TB in children This has huge potential to reduce the burden of TB in children Focus is on individuals infected with TB that have greatest likelihood of developing active TB disease following infection this includes infants, young children and HIV-infected children of any age Widely recommended but uptake by families and implementation by NTP are poor Lack of awareness of risk for children attending health facilities with carers TB wards; TB clinics; HIV clinics

BCG protects against disseminated TB in children Summary Efficacy Miliary Tuberculosis 77% Summary Efficacy Tuberculous Meningitis 73% Trunz, et al. Lancet 2006

Child TB caseload in Malawi in 1998 Childhood TB caseload: Malawi 1998 Harries AD et al. Int J Tuberc Lung Dis 2002 Malawi NTP, 1998 Total caseload Total childhood 0-4 years 5-14 years numbers (proportion of childhood caseload) 22,982 proportion of total caseload 2,739 11.9% 1,615 (58.9%) 1,124 (41.1%) 7% 4.9% Smear-positive PTB Smear-negative PTB EPTB 127 (4.6%) 1,804 (65.9%) 808 (29.5%) 1.3% 21.3% 15.9%

Burden of child TB in PNG: 2005-6 Law I, Poka H, et al. Poster The Union Global Lung Health Conference 2008 Child TB accounts for 33% of total TB case-load Pulmonary TB Smear positive Smear negative Smear not done 1208 (61%) 18 138 1052 EPTB 769 (39%) Total 1977

Types of childhood EPTB disease Malawi NTP, 1998 PNG, 2005-6 EPTB cases 808 1097 Lymphadenitis Pleural effusion Spinal Pericarditis Abdominal Miliary Meningitis Bone disease Not indicated/others 331 (41%) 101 (12%) 83 (10%) 60 (7%) 39 (5%) 34 (4%) 30 (4%) 12 (1%) 118 (14.6%) 342 (31%) 94 (9%) 41 (4%) 12 (1%) 173 (16%) 64 (6%) 257 (23%) 15 (1%) 99 (9%) EPTB represented 30% and 39% of childhood TB cases in Malawi and PNG respectively.

Protective effect of BCG Stronger protective efficacy against disseminated disease than against pulmonary disease Primarily aims to protect against tuberculosis and has protective efficacy against leprosy Recent evidence suggests may also have some protective efficacy against infection when exposed Roy A, et al. BMJ 2014 Efficacy variable between populations and perhaps between strains used In high burden settings, routinely given to newborns Practice and coverage variable www.bcgatlas.org

Burden of TB in Australia Incidence 5-6 cases/100,000 population per year 85% of cases are overseas born majority present within 2 years of arriving in Australia Children < 2% TB caseload In 2005-9, there were only 5 cases of TB meningitis notified in Australia, which is equivalent to less than 1 per 20 million general population per year.

These outcomes meet the International Union Against TB and Lung Disease (IUATLD) criteria for low prevalence countries, in determining BCG policy, which are: average annual notification rate of pulmonary sputum smear positive cases of 5 per 100,000 or less in the preceding 3 years; OR average annual notification rate of TB meningitis in children under 5 years of less than 1 case per 10 million general population; OR an average annual risk of TB infection of 0.1% or less

Key recommendations BCG vaccination is not recommended for general use in the Australian population or for most health care workers (HCWs). BCG vaccination is contraindicated in HIV infected persons. BCG vaccination is recommended for: Aboriginal and Torres Strait Islander neonates in communities with a high incidence of TB; Neonates and children 5 years of age and under who will be travelling to or living in countries or areas with a high prevalence of TB (>50 per 100,000) for extended periods; BCG vaccination may be considered in the following: Children over 5 years of age who will be travelling to or living in countries or areas with a high prevalence of TB for extended periods; HCWs who may be at high risk of exposure to drug resistant TB.

Half of the world s 20 high burden TB countries are in the Asia-Pacific region

Contraindications to BCG vaccination patients with current or previous tuberculosis patients with a current febrile illness patients with skin conditions such as eczema or dermatitis patients who have had a previous live vaccination within the past four weeks patients with a history of a positive reaction to a Mantoux test people who are HIV infected, or are in a high risk group for HIV and have not been tested patients receiving immunosuppressive medication such as corticosteroids or cancer chemotherapy or with other conditions likely to suppress immunity.

Risk of BCG Very low risk from vaccine Local reaction +/- regional adenitis varies between strains Suppurative adenitis 0.03-0.5% Disseminated disease 0.3-0.4 per 1 million Increased risk of disseminated BCG in HIV-infected newborns 1% in pre-art era BCG IRIS with early ART

Thank you