Background: 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. However, this is dependent on good adherence and retrospective studies have indicated that adherence to unsupervised INH preventive chemotherapy is poor. Aim: To prospectively document adherence to six months of unsupervised INH monotherapy and outcome in children with household exposure to an adult pulmonary tuberculosis index case. Methods: From February 2003 to January 2005 in two suburbs of Cape Town, South Africa, all children ,5 years old in household contact with an adult pulmonary tuberculosis index case were screened for tuberculosis and given unsupervised INH preventive chemotherapy once active tuberculosis was excluded. Adherence and outcome were monitored. Results: In total, 217 index cases from 185 households were identified; 274 children ,5 years old experienced household exposure, of whom 229 (84%) were fully evaluated. Thirty eight children were treated for tuberculosis and 180 received preventive chemotherapy. Of the children who received preventive chemotherapy, 36/180 (20%) completed >5 months of unsupervised INH monotherapy. During the subsequent surveillance period six children developed tuberculosis: two received no preventive chemotherapy, and four had very poor adherence. Conclusion: Adherence to six months of unsupervised INH preventive chemotherapy was poor. Strategies to improve adherence, such as using shorter duration multidrug regimens and/or supervision of preventive treatment require further evaluation, particularly in children who are at high risk to progress to disease following exposure.

Background: There is a growing interest in the use of F-18 FDG PET-CT to monitor tuberculosis (TB) treatment response. Tuberculosis lung lesions are often complex and diffuse, with dynamic changes during treatment and persisting metabolic activity after apparent clinical cure. This poses a challenge in quantifying scan-based markers of burden of disease and disease activity. We used semi-automated, whole lung quantification of lung lesions to analyse serial FDG PET-CT scans from the Catalysis TB Treatment Response Cohort to identify characteristics that best correlated with clinical and microbiological outcomes.Results: Quantified scan metrics were already associated with clinical outcomes at diagnosis and 1 month after treatment, with further improved accuracy to differentiate clinical outcomes after standard treatment duration (month 6). A high cavity volume showed the strongest association with a risk of treatment failure (AUC 0.81 to predict failure at diagnosis), while a suboptimal reduction of the total glycolytic activity in lung lesions during treatment had the strongest association with recurrent disease (AUC 0.8 to predict pooled unfavourable outcomes). During the first year after TB treatment lesion burden reduced; but for many patients, there were continued dynamic changes of individual lesions. Conclusions: Quantification of FDG PET-CT images better characterised TB treatment outcomes than qualitative scan patterns and robustly measured the burden of disease. In future, validated metrics may be used to stratify patients and help evaluate the effectiveness of TB treatment modalities.

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