Flowchart of children included in the study.

<p>Flowchart of children included in the study.</p

Median IFN-γ U/ml in all three Quantiferon TB Gold In-Tube tubes in children and adults.

<p>Comparison of median IFN-γ values in the three QFT tubes in children and adults according to diagnostic TB classificaiton. There were significantly lower levels* (p<0.05) in all subgroups of children compared to adults, except in the positive control where median levels in children with confirmed and not TB were not significantly different to levels in adults.</p><p>Wilcoxon’s rank-sum test used to test difference between median IFN-γ in children and adults.</p><p>IQR: interquartile range.</p

Characteristics of study population.

†<p>HIV test result available for 209 children, weight-for-age Z-score data available for 188 children, history of contact data available for 208 children (reported contact to case of TB in last 2 years), 1 child with confirmed TB did not have follow-up data (follow-up status defined as health status of child 6 months after inclusion into study).</p>*<p>Clinical TB in children defined as active TB diagnosed by local physician based on clinical examination, CXR and TST. Clinical TB in adults defined as active TB diagnosed by local physician, all included adults had positive Ziehl-Neelsen smear microscopy as well as either positive culture and/or positive fluorescence microscopy.</p

Risk factors association with positive QFT result in adults.

<p>Risk factor analysis using logistic regression analysis found lower odds of a positive QFT result in HIV infected adults.</p><p>OR: odds ratio from univariable analysis.</p><p>Adj. OR: adjusted odds ratio adjusted for age, sex, HIV infection and BMI.</p>*<p>Odds ratio calculated as per year increase in age.</p>†<p>p-value for the odds ratios.</p

Summary of recruitment and diagnostic classification of children.

<p>* Children without follow-up data were excluded since they could not be classified according to the TB classifications. However one child had culture confirmed TB and could therefore be classified without follow-up data. ** The first 61 QFT results were excluded, when the initial QFT analysis showed very poor response in all the QFT tubes, including the mitogen. This was attributed to incorrect storage in a room reaching temperatures above 30°C. Subsequent tubes were all stored at 5–10°C.</p

Risk factors association with positive QFT results in children.

<p>Risk factor analysis using logistic regression analysis found no association between known risk factors and a positive QFT result in children.</p><p>OR: unadjusted odds ratio from univariable analysis.</p><p>Adj OR: adjusted odds ratio, adjusted for age, sex, HIV, z-score and contact TB case.</p>†<p>p-value for the odds ratios.</p>*<p>Compares living with a case of smear positive TB case to those reporting no contact at all.</p

Risk factors association with indeterminate QFT result in adults.

<p>Risk factor analysis using logistic regression analysis found no association between suspected risk factors and an indeterminate QFT result in adults.</p><p>OR: odds ratio from univariable analysis.</p><p>Adj. OR: adjusted odds ratio adjusted for age, sex, HIV infection and BMI.</p>*<p>Odds ratio calculated as per year increase in age.</p>**<p>Logistic regression analysis not possible for association between BMI and indeterminate result, since there are no indeterminate results in those with BMI ≥18.5.</p>†<p>p-value for the odds ratios.</p

Sensitivity of Quantiferon TB Gold In-Tube test and Tuberculin Skin test in children and adults.

<p>Sensitivity of QFT and TST according to TB status in children and adults, showing low sensitivity of both T-cell based test in children, irrespective of TB classification, compared to adults with confirmed TB.</p>*<p>Sensitivity analysis of QFT excludes indeterminate results.</p>†<p>Difference between sensitivity in QFT and TST tested using two-sample test of proportion.</p

Childhood mortality according to Quantiferon TB Gold In-Tube result.

<p>Childhood mortality recorded during admission and at 6 month follow-up, according to QFT results. Children who did not attend scheduled follow-up at 6 months were traced and follow-up visits were conducted in their homes within 7–12 months of inclusion. Both the mortality during admission and the overall mortality in children with an indeterminate QFT result was significantly higher than in children with a determinate QFT result, p<0.001. * One of 154 children with a determinate QFT result did not have follow-up data.</p

Geospatial distribution of <i>Mycobacterium tuberculosis</i> genotypes in Africa

<div><p>Objective</p><p>To investigate the distribution of <i>Mycobacterium tuberculosis</i> genotypes across Africa.</p><p>Methods</p><p>The SITVIT2 global repository and PUBMED were searched for spoligotype and published genotype data respectively, of <i>M</i>. <i>tuberculosis</i> from Africa. <i>M</i>. <i>tuberculosis</i> lineages in Africa were described and compared across regions and with those from 7 European and 6 South-Asian countries. Further analysis of the major lineages and sub-lineages using Principal Component analysis (PCA) and hierarchical cluster analysis were done to describe clustering by geographical regions. Evolutionary relationships were assessed using phylogenetic tree analysis.</p><p>Results</p><p>A total of 14727 isolates from 35 African countries were included in the analysis and of these 13607 were assigned to one of 10 major lineages, whilst 1120 were unknown. There were differences in geographical distribution of major lineages and their sub-lineages with regional clustering. Southern African countries were grouped based on high prevalence of LAM11-ZWE strains; strains which have an origin in Portugal. The grouping of North African countries was due to the high percentage of LAM9 strains, which have an origin in the Eastern Mediterranean region. East African countries were grouped based on Central Asian (CAS) and East-African Indian (EAI) strain lineage possibly reflecting historic sea trade with Asia, while West African Countries were grouped based on Cameroon lineage of unknown origin. A high percentage of the Haarlem lineage isolates were observed in the Central African Republic, Guinea, Gambia and Tunisia, however, a mixed distribution prevented close clustering.</p><p>Conclusions</p><p>This study highlighted that the TB epidemic in Africa is driven by regional epidemics characterized by genetically distinct lineages of <i>M</i>. <i>tuberculosis</i>. <i>M</i>. <i>tuberculosis</i> in these regions may have been introduced from either Europe or Asia and has spread through pastoralism, mining and war. The vast array of genotypes and their associated phenotypes should be considered when designing future vaccines, diagnostics and anti-TB drugs.</p></div