2. Current international guidelines recommend 6–9 months of isoniazid (INH) preventive chemotherapy to prevent the development of active tuberculosis in children exposed to a susceptible strain of M. tuberculosis, but this treatment is dependent on good adherence Retrospective studies have indicated that adherence to unsupervised INH preventive chemotherapy is poor.

3. 1. to describe the outcome of screening in children ages <5 years with household exposure to an adult pulmonary tuberculosis index case 2. to determine the prevalence and possible risk factors of infection among children contacts 3. to determine the extent of adherence and outcome in children contacts to 6 months of unsupervised INH prophylaxis

4. Establishing a Target Population Creating a Research Design Data Analysis Tools A descriptive facility-based cross-sectional study Screening and treatment Setting: Three of national TB control program chest dispensaries (primary care facilities) in Alexandria City, Egypt. Subjects: During a 3-month period, facility-based tuberculosis treatment registers were used to prospectively identify all new adult (>15 years) pulmonary tuberculosis cases. All children <5 years old in household contact with index cases were identified and screened for tuberculosis. N = 252 fully screened child Setting: Three of national TB control program chest dispensaries (primary care facilities) in Alexandria City, Egypt. Subjects: During a 3-month period, facility-based tuberculosis treatment registers were used to prospectively identify all new adult (>15 years) pulmonary tuberculosis cases. All children <5 years old in household contact with index cases were identified and screened for tuberculosis. N = 252 fully screened child The child contacts were given unsupervised INH preventive chemotherapy once active tuberculosis was excluded. Preventive chemotherapy consisted of unsupervised INH monotherapy for 6 months with monthly collection of tablets from the clinic. Adherence to and outcome of preventive chemotherapy were prospectively monitored. Adherence was considered reasonable if tablets were collected for more than 4 months, poor if collection occurred for 2–4 months, and very poor if monthly tablets are collected once or twice only (treatment period <2 months). The child contacts were given unsupervised INH preventive chemotherapy once active tuberculosis was excluded. Preventive chemotherapy consisted of unsupervised INH monotherapy for 6 months with monthly collection of tablets from the clinic. Adherence to and outcome of preventive chemotherapy were prospectively monitored. Adherence was considered reasonable if tablets were collected for more than 4 months, poor if collection occurred for 2–4 months, and very poor if monthly tablets are collected once or twice only (treatment period <2 months). Interviewing format Transfer sheet Interviewing format Transfer sheet T h e d a t a w a s e n t e r e d, a n a l y z e d a n d t a b u l a t e d u s i n g S P S S ( v e r s i o n 1 8. 0 ). F r e q u e n c i e s w e r e c o m p u t e d c a t e g o r i a l v a r i a b l e s. P r o p o r t i o n s w e r e c o m p a r e d s i m u l t a n e o u s l y b y t h e c h i - s q u a r e d t e s t. F i s h e r e x a c t t e s t w a s u s e d w h e n t h e c h i - s q u a r e d - t e s t w a s n o t v a l i d. B i v a r i a t e a n a l y s i s o f t h e r i s k f a c t o r s f o r c o n t r a c t i n g a L a t e n t T B i n f e c t i o n w a s p e r f o r m e d u s i n g t h e o d d s r a t i o a n d i t s 9 5 % c o n f i d e n c e i n t e r v a l. A m u l t i v a r i a t e l o g i s t i c r e g r e s s i o n m o d e l w a s c o n s t r u c t e d t o c o n t r o l t h e c o n f o u n d e r s. T h e i n d e p e n d e n t v a r i a b l e s u s e d i n t h e l o g i s t i c m o d e l s w e r e a l l d i c h o t o m o u s. T h e l e v e l o f s i g n i f i c a n c e w a s s e t a t < 0. 0 5. T h e d a t a w a s e n t e r e d, a n a l y z e d a n d t a b u l a t e d u s i n g S P S S ( v e r s i o n 1 8. 0 ). F r e q u e n c i e s w e r e c o m p u t e d c a t e g o r i a l v a r i a b l e s. P r o p o r t i o n s w e r e c o m p a r e d s i m u l t a n e o u s l y b y t h e c h i - s q u a r e d t e s t. F i s h e r e x a c t t e s t w a s u s e d w h e n t h e c h i - s q u a r e d - t e s t w a s n o t v a l i d. B i v a r i a t e a n a l y s i s o f t h e r i s k f a c t o r s f o r c o n t r a c t i n g a L a t e n t T B i n f e c t i o n w a s p e r f o r m e d u s i n g t h e o d d s r a t i o a n d i t s 9 5 % c o n f i d e n c e i n t e r v a l. A m u l t i v a r i a t e l o g i s t i c r e g r e s s i o n m o d e l w a s c o n s t r u c t e d t o c o n t r o l t h e c o n f o u n d e r s. T h e i n d e p e n d e n t v a r i a b l e s u s e d i n t h e l o g i s t i c m o d e l s w e r e a l l d i c h o t o m o u s. T h e l e v e l o f s i g n i f i c a n c e w a s s e t a t < 0. 0 5.

5. Results 1: Tuberculosis screening results in children < 5 years old in household contact with an adult pulmonary tuberculosis index case No. (%)Variable TST results (mean positive TST: 18 ± 1.9 mm) 136 (54.0) TST positive ( 10 mm induration) Tuberculosis treatment 217 (86.1) Isoniazid preventive chemotherapy 2 (0.8) No preventive therapy (received Isoniazid within the preceding year) 33 (13.1)Treated for tuberculosis disease

6. Results 2: Possible factors affecting risk of TB infection among children in household contact with adult patients Crude odds ratio (95% CI) P value TST- negative children (n=116 TST- positive children (n=136) TotalRisk factor %No.% 6.7 (2.2 - 13.8) *0.00040.54783.1113160Child age, < 3 years 7.3 (2.5 – 12.9) * 0.00018.12188.2120141Child gender, boy 4.0 (2.2 - 7.2) *0.0006.9824.33341Severe malnutrition 2.1 (1.2 - 3.7) * 0.0141.7210.31416Absence of BCG scar 5.2 (1.8 - 8.6) * 0.00045.75395.6130183 Contact with sputum positive adult 0.7 (0.3 – 2.7)0.38153.46249.367129 Source case age, (15-40 years) 3.8 (1.7 – 6.5) *0.02810.31247.16476 Source case relation to the child, Mother 1.2 (0.8 – 4.6)0.06261.27174.3101172 Source case symptom duration > 3 months 5.9 (1.9 – 7.6) * 0.0008.12165.489110 The number of individuals per household > 6 6.7 (1.5 - 9.7) *0.00025.02986.8118147 Exposure to environmental tobacco smoke

7. Results 3: Radiographic disease manifestations identified in child tuberculosis contacts (n = 252) No. (%)Tuberculosis disease manifestation 211 (83.7)No tuberculosis 14 (5.6)Uncertain tuberculosis 6 of 14 (42.9) Treated as tuberculosis a 27 (10.7)Certain tuberculosis 22 (8.7) Uncomplicated lymph node disease Complicated lymph node disease 2 (7.4) Parenchymal consolidation 1 (3.7) Airway compression 1 (3.7) Lung cavity 1 (3.7) Pleural effusion

8. Results 4: Adherence to anti-tuberculosis treatment and preventive chemotherapy, and outcome according to preventive chemotherapy adherence (n = 252) ReasonablePoorVery poorNot given Treatment regimen No. (%) 29 (90.6)3 (9.4)1 (3.1)0 TB treatment (n = 32) 36 (16.6)13 (6.0)112 (51.6)56 (25.8) Preventive chemotherapy INH (n = 217) Outcome 0 (0.0) 4/112 (3.6)4/56 (7.1) Preventive chemotherapy group developed TB within 6 months

9. Results 5: Parent / Caregiver reported reasons for poor adherence of child contact (n=125) to INH preventive chemotherapy

10. The prevalence of tuberculosis infection and clinical disease among children in household contact with adult patients is high, and risk is significantly increased due to child contact, index patients, and environmental factors. Adherence to 6 months of unsupervised INH preventive chemotherapy was very poor. Prevention and early detection of pediatric cases are essential tasks in TB control. Findings of the present work confirm the importance of contact investigation in identifying new TB cases and providing chemoprophylaxis in young children based on the high risk of infection. It emphasizes the need to develop chemoprophylaxis strategies with improved adherence, such as short duration multidrug supervised regimens, particularly in children who are at high risk of infection and disease progression following exposure.

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