In summary, we have further promoted the concept that FhGST-S1 clearly demonstrates key host-parasite roles in synthesising PGs and stimulating PG release from host innate immune cells. In addition we have shown FhGST-S1 to be a key protein for detoxification, which may well be involved in TCBZ response. In line with current vaccine development theory we have shown FhGST-S1 to have multi-functional roles in the liver fluke physiology. Furthermore, we have shown FhGST-S1 to be expressed across ontogenic stages, localised to the fluke surface, and to the egg, both characteristics vital for vaccine development and success. Whilst no protection from fluke burden was seen in trials, the inclusion of rFhGST-S1 as a multivalent vaccine component should be investigated. However, it is important to fully characterise the host immune response during the early stages post-infection to better understand the mechanism mediating an effective host response. This will be essential to improve any future vaccine formulation. [36, 51, [68] [69] [70] [71] Table 2 Refs. Figure S1 Multiple sequence alignment and neighbourjoining phylogenetic tree across seven species-independent classes of GSTs. A) Alignment of the sigma class GSTs of trematodes shows the extent of identity and similarity across this class of GSTs. Boxed residues indicate complete identity between all sequences. Residues shaded in grey indicate conserved residues. B) Neighbour-joining tree placing mammalian and trematode GSTs within the same broad Sigma class. A distinct separation of clusters within this Sigma class is observed as with the recently reclassified 'Nu' class of GSTs from nematodes [49] . Sequences were aligned via the ClustalW program [29] in BioEdit Sequence Alignment Editor version 7.0.5.2. [30] . Phylogenetic neighbourjoining bootstrap trees were produced and viewed within TREE-VIEW [33] . Key to sequences in 1a and 1b. Author Contributions Discriminating Active from Latent Tuberculosis in Patients Presenting to Community Clinics BACKGROUND: Because of the high global prevalence of latent TB infection (LTBI), a key challenge in endemic settings is distinguishing patients with active TB from patients with overlapping clinical symptoms without active TB but with co-existing LTBI. Current methods are insufficiently accurate. Plasma proteomic fingerprinting can resolve this difficulty by providing a molecular snapshot defining disease state that can be used to develop point-of-care diagnostics. METHODS: Plasma and clinical data were obtained prospectively from patients attending community TB clinics in Peru and from household contacts. Plasma was subjected to high-throughput proteomic profiling by mass spectrometry. Statistical pattern recognition methods were used to define mass spectral patterns that distinguished patients with active TB from symptomatic controls with or without LTBI. RESULTS: 156 patients with active TB and 110 symptomatic controls (patients with respiratory symptoms without active TB) were investigated. Active TB patients were distinguishable from undifferentiated symptomatic controls with accuracy of 87% (sensitivity 84%, specificity 90%), from symptomatic controls with LTBI (accuracy of 87%, sensitivity 89%, specificity 82%) and from symptomatic controls without LTBI (accuracy 90%, sensitivity 90%, specificity 92%). CONCLUSIONS: We show that active TB can be distinguished accurately from LTBI in symptomatic clinic attenders using a plasma proteomic fingerprint. Translation of biomarkers derived from this study into a robust and affordable point-of-care format will have significant implications for recognition and control of active TB in high prevalence settings. Tuberculosis is the leading bacterial cause of death worldwide, with an estimated 8.8 million new cases of active disease and 1.6 million deaths per year [1] . Much of the burden of disease lies in the developing world, where annual incidence can reach 700 per 100,000 in certain regions [1] . New and unrecognised cases drive the epidemic, with transmission usually occurring before the index case is diagnosed. Multi-drug resistant cases and HIV co-infection further complicate control efforts [2] . Pulmonary TB is the most frequent clinical and transmissible manifestation of active disease. Rapid diagnosis and treatment are critical in the prevention of transmission.