Coun%ng sick children: es%ma%ng the global incidence of childhood tuberculosis

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1 Coun%ng sick children: es%ma%ng the global incidence of childhood tuberculosis Helen E. Jenkins Brigham and Women s Hospital / Harvard Medical School, Boston, USA

2 Children.

3 Coun%ng sick children: es%ma%ng the global incidence of childhood tuberculosis Helen E. Jenkins Brigham and Women s Hospital / Harvard Medical School, Boston, USA

4 Tuberculosis Infec%ous disease caused by a bacterium, usually infec%ng the lungs (pulmonary) One third of global popula%on infected Annually: 8-9 million develop TB disease, 1 million deaths, 450,000 develop MDR- TB disease Treatment lasts 6 months or 18/24 months for MDR- TB TB diagnosis: sputum smear microscopy, culture etc are focused on pulmonary TB

5 Childhood TB and MDR- TB We currently have the perfect recipe to make children with TB invisible: 1. Childhood TB presents differently from in adults 2. Smear microscopy has been priori%sed Massive under- diagnosis in children WHO es%mates assume under detec%on in children equal to that in adults (current es%mate=530,000) We know nothing about the number of children with MDR- TB (current es%mate=???)

6 Accoun%ng for under diagnosis with smear microscopy ~50-60% ~10% Murray, Styblo, Rouillon. BIUATLD 1990

7 Scaling up smear posi%ve no%fica%on data 151 countries + + Percentage of TB!! $ $ S S 1 1 cases that are in # # " p & p & children P = P = = " 1 % 1 %! +! $ +! + $! (( S (( S i i # " p & )+ # " p & )+ S pt # # i i i % " i % " i age groups S + =smear posi%ve no%fica%ons p i =propor%on,, $ $ of TB cases that are smear posi%ve in the ith age group Assume no%fica%ons (S + ) without error Each p i is average of two numbers with associated standard error, assume normal distribu%on, draw 1000 %mes for each p i to get 1000 es%mates of P for each country S + p pt & ) % pt p pt & ) %

8 How did we do this? TB incidence in children MDR- TB incidence in children Smear + no%fica%ons by age Murray et al Percentage of TB cases that are in children = World Health Organiza%on data or es%mates, by country

9 Can we es%mate propor%on of all cases that are in children? Donald P. Childhood TB: Out of control? Curr Opinion Pulm Med 2002

10 Es%ma%ng the percentage of incident TB occurring in children Use TB incidence es%mates from WHO Method of es%ma%on varies by country Confidence intervals provided, assume normal distribu%on with SE equal to the largest of the two from the CI Logis%c regression, produces 1000 median lines Model then produces 1000 es%mates for each country of percentage

11 Logis%c regression using our scaled- up TB incidence es%mates shows exponen&al increase consistent with Donald 2002

12 How did we do this? TB incidence in children MDR- TB incidence in children Smear + no%fica%ons by age Murray et al Donald 2002 TB incidence x UN popn es%mates Percentage of TB cases that are in children Percentage of TB cases that are in children for all countries = World Health Organiza%on data or es%mates, by country

13 Es%ma%ng the risk of MDR- TB in child TB cases Proportion of all childhood TB cases with MDR-TB 0.4 Systema%c review resul%ng in 31 papers quan%fying the risk of MDR in child TB cases and 0.3 adult treatment- naïve TB cases Linear regression, random effect for country Y= X Proportion of treatment-naive adult TB cases with MDR-TB Jenkins et al. Lancet 2014

14 How did we do this? TB incidence in children MDR- TB incidence in children Smear + no%fica%ons by age Murray et al Percentage of TB cases that are in children Donald 2002 TB incidence x UN popn es%mates Percentage of TB cases that are in children for all countries Systema%c review Rela%onship between MDR risk in adults and MDR risk in children MDR risk in adults MDR risk in children x childhood TB = World Health Organiza%on data or es%mates, by country

15 Limita%ons Poten&al biases / issues: Any biases in the WHO es%mates / models will be perpetuated in our method Bias introduced by our highly non- linear method devised a simple sensi%vity test for this Incorrect specifica%on of model to predict percentage of TB cases amongst children Incorrect percentage of TB cases that are smear posi%ve by age ra%o of children to adults incorrect Incorrect rela%onship between MDR risk in children and adults. Generalisable to all countries?

16 Incident cases of TB disease and MDR- TB disease in children 999,792 (95% CI: 937,877 1,055,414) child TB cases, 31,948 (95% CI: 25,594 38,663) have MDR- TB Jenkins et al. Lancet 2014

17 Acknowledgements Ted Cohen (Brigham and Women s Hospital) Mercedes Becerra, Ari Tolman, Courtney Yuen, Salmaan Keshavjee (Harvard Medical School) Marcello Pagano (Harvard School of Public Health) Carlos Perez- Velez (University of Arizona, College of Medicine) Funding: MIDAS (NIH Award Number U54GM088558) NIAID (NIH Award Number K01AI102944)

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