Household-contact investigation plus standard passive case finding was more effective than standard passive case finding alone for the detection of tuberculosis in a high-prevalence setting at 2 years. (Funded by the Australian National Health and Medical Research Council; ACT2 Australian New Zealand Clinical Trials Registry number, ACTRN12610000600044 .).

Patients treated for tuberculosis had a markedly elevated risk of death, particularly in the post-treatment period. Interventions to reduce tuberculosis mortality must enhance the early detection of drug-resistance, improve treatment effectiveness, and address non-communicable diseases.

Background Active case finding is recommended as an important strategy to control tuberculosis, particularly in low-income and middle-income countries with a high prevalence of the disease. However, the costs and costeffectiveness of active case finding are unclear due to the absence of evidence from randomised trials. We assessed the costs and cost-effectiveness of an active case finding strategy in Vietnam, where there is a high prevalence of tuberculosis. MethodsWe conducted an economic evaluation alongside the Active Case Finding in Tuberculosis (ACT2) trial-a pragmatic cluster-randomised controlled trial in 70 districts across eight provinces of Vietnam. Patients aged 15 years and older with smear-positive pulmonary tuberculosis were recruited to the trial if they lived with one or more other household members. Household contacts were verbally invited to the clinic by the index patient with tuberculosis. ACT2 compared a combination of active and passive case finding with usual care (passive case finding) of household contacts of patients with tuberculosis from a health system perspective. Clustering occurred at the district and household level. Districts were the unit of randomisation, and we used minimisation to ensure balance of intervention and control districts within each province. In the intervention group, participants were invited to attend screening at baseline, 6 months, 12 months, and 24 months. We determined health-care costs with a standardised national costing survey and reported results in 2017 $US. The primary outcome of our study was disability-adjusted life years (DALYs) averted over a 24-month period. ACT2 was registered prospectively with the Australian and New Zealand Clinical Trials Registry, number ACTRN126.100.00600044.

Background Abnormal DNA methylation may be important in germ cell tumour (GCT) aetiology, as germ cells undergo complete epigenetic reprogramming during development. GCTs show differences in global and promoter methylation patterns by histologic subtype. We conducted an epigenome-wide study to identify methylation differences by GCT histology. Methods Using the Illumina HumanMethylation450K array we measured methylation in 154 paediatric GCTs (21 germinomas/seminomas/dysgerminoma, 70 yolk sac tumours [YST], 9 teratomas, and 54 mixed histology tumours). We identified differentially methylated regions (DMRs) between GCT histologies by comparing methylation beta values. Results We identified 8,481 DMRs (FWER < 0.05). Unsupervised hierarchical clustering of individual probes within DMRs resulted in four high level clusters closely corresponding to tumour histology. Clusters corresponding to age, location, sex and FFPE status were not observed within these DMRs. Germinomas displayed lower levels of methylation across the DMRs relative to the other histologic subtypes. Pathway analysis on the top 10% of genes with differential methylation in germinomas/seminomas/dysgerminoma compared to YST suggested angiogenesis and immune cell-related pathways displayed decreased methylation in germinomas/seminomas/dysgerminoma relative to YST. Conclusions Paediatric GCT histologies have differential methylation patterns. The genes that are differentially methylated may provide insights into GCT aetiology including the timing of GCT initiation.