Digestive Chagas disease (DCD) is an enteric neuropathy caused by Trypanosoma cruzi infection. There is a lack of evidence on the mechanism of pathogenesis and rationales for treatment. We used a mouse model that recapitulates key clinical manifestations to study how infection dynamics shape DCD pathology, and the impact of treatment with the front-line drug benznidazole. Curative treatment at 6 weeks post-infection resulted in sustained recovery of GI transit function, whereas sub-curative treatment led to infection relapse and gradual return of DCD symptoms. Neuro-immune gene expression profiles shifted from chronic inflammation to a tissue repair signature after cure, accompanied by increased glial cell activity and regenerative neurogenesis in the myenteric neuronal plexus. Delaying treatment until 24 weeks post-infection led to a partial reversal of the DCD phenotype, suggesting the accumulation of permanent tissue damage over the course of chronic infection. Our study shows that murine DCD pathogenesis is sustained by chronic T. cruzi infection and is not an inevitable consequence of acute stage denervation. The risk that irreversible enteric neuromuscular tissue damage and dysfunction will develop highlights the importance of prompt diagnosis and treatment. Finally, these findings support the concept of treating asymptomatic T. cruzi infected individuals with benznidazole to prevent DCD development.

Yarra Bridge and Gardiners Creek viaduct together form a major elevated structure in the Melbourne CityLink toll-way: the busiest route in the Victorian freeway system. Originally constructed in the 1960s, they have been twice widened and modified extensively. The original structures recently required to be upgraded to withstand current and anticipated future loading. This paper discusses the viaduct's load rating by way of a combination of analytical assessment and observation of the structures' actual condition followed by the development of preferred strengthening concepts in conjunction with the contractor and asset owner. The methods used, including concrete infill, carbon-fibre strengthening and external post-tensioning, were designed to be flexible so they could be modified where ‘as-constructed’ details were found to differ from the original design drawings. Remedial works were also designed to be carried out below deck level, avoiding disruption to toll-way traffic while minimising the impact on stakeholders below.

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