PUDJI LESTARI (2011) PERAN KONDISI LINGKUNGAN RUMAH, STATUS GIZI, STATUS BESI, RESPONS IMUN DAN POLIMORFISME NRAMP1 TERHADAP PROBABILITAS KEJADIAN SAKIT PADA ANAK KONTAK TUBERKULOSIS. Disertasi thesis, UNIVERSITAS AIRLANGGA.

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Abstract

Indonesia is one of the countries with the largest tuberculosis (TB) cases in the world. In endemic area, TB in children account for 12-20% from all TB cases. Children living with active TB adult cases are at higher risk for infection and disease development. Identifying children with latent infection of TB may be of potential use. Environmental factors play significant roles and host responses to mycobacterium are essential. This research aimed to explore environmental factors, including humidity and number of people living in the same house, and host factors, including nutrition status iron status, and genetic background of variation in NRAMP gene which play role in disease development. In a cross-sectional study design, children living with active TB adult for at least 8 weeks were recruited. Clinical and radiological examinations were conducted. Tuberculin skin test (TST), Interferon Gamma Release Assay (IGRA), and ELISPOT were examined. Mycobacterial 16S rRNA in cell was studied. Of 56 index cases with active TB adult who lived in a low socio economic condition, 73 contact TB children were recruited. These children were examined for chest radiology and TST/IGRA/ELISPOT. These children were classified as sick when they showed clinical signs (42.4%), indicating they had TB disease, or otherwise classified as not sick (57.6%). After adjusting with TST/IGRA/ELISPOT, morbidity rate is 43.8% to 53.4%. Surprisingly, all mycobacterial 16S rRNA examination in a subset randomized of 43 samples showed positive results, suggesting that all contact TB children were infected with M.tuberculosis. Environmental conditions of the house played roles in disease development i.e humidity and the number of people living in the same house. Shared bedroom and the density of M.tuberculosis in the sputum were, however, not confirmed with higher risk for developing of TB disease. Nutritional status was generally poor, however, the iron status was within normal range. Anemia in these children was only found in 2 of 73 (2.7%). Of 50 sub sample examined, no helminthes infection was found. NRAMP1 polymorphisms in D543N and 3 UTR showed no significant different between sick and not sick groups. Result on Interferon gamma concentration in serum showed the highest concentration on sick group, while Interleukin-10 remain stable between groups. To predict whether contact TB children can develop TB later in the life time, a model had been developed using multiple regression analyses. The predictive value of TB disease using parameters such as weight to age, the number of member in house and positive TST test, resulted in a predictive value of 75,3% with determinant coefficient (pseudo R) 46,7%. This study has showed for the first time that in contact with open case for 8 weeks, 100% children are infected (using 16S rRNA examination). Nutrition status, number of people living in the same house and positive tuberculin test are predictor for disease development. TB assessment in children is essential to prevent new TB cases later in adult.

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