Estimating disease burden of rotavirus in floodwater through traffic in the urban areas: A case study of Can Tho city, Vietnam

Microbial pathogens in urban floodwaters pose risks to human health, potentially causing diseases such as diarrhea. However, the disease burden related to urban traffic exposure from citizens passing through floodwaters is not easily quantified and therefore not included in many studies. Notably, this problem has received little attention in low-to-middle-income countries, with frequent flood events and the heavy diarrheal disease burden. This article calculates the infection risks and disease burden, considering traffic associated with exposure to floodwater contaminated with rotavirus for the first time in Ninh Kieu District, Can Tho city. Can Tho city in the Vietnamese Mekong Delta is well known to have many flood events every year, with many diarrheal cases during the flood season. The methodology comprises two steps. First, we applied quantitative microbial risk assessment that proposes the inclusion of exposure to traffic due to rotavirus in floodwater. Second, the disease burden was expressed in disability-adjusted life years (DALYs). The exposed groups are child pedestrians, adult pedestrians, motorcyclists, and cyclists. We used video footage to monitor the traffic. The results show that total DALYs per flood event were 1.35 × 104 for 63,390 exposed people (i.e., 2129 DALYs per 10,000 cases). Motorcyclists are the strongest contributors to the DALYs (95%), followed by cyclists (2.8%), adult pedestrians (2%), and child pedestrians (0.2%). The population in Ninh Kieu District may suffer from waterborne diseases through traffic activities during flooding times. Our approach can be applied in other areas worldwide and helps identify main risk groups and focus areas for interventions.Hydraulic Structures and Flood RiskUrban Desig

Sparsentan in patients with IgA nephropathy: a prespecified interim analysis from a randomised, double-blind, active-controlled clinical trial

Background: Sparsentan is a novel, non-immunosuppressive, single-molecule, dual endothelin and angiotensin receptor antagonist being examined in an ongoing phase 3 trial in adults with IgA nephropathy. We report the prespecified interim analysis of the primary proteinuria efficacy endpoint, and safety. Methods: PROTECT is an international, randomised, double-blind, active-controlled study, being conducted in 134 clinical practice sites in 18 countries. The study examines sparsentan versus irbesartan in adults (aged ≥18 years) with biopsy-proven IgA nephropathy and proteinuria of 1·0 g/day or higher despite maximised renin-angiotensin system inhibitor treatment for at least 12 weeks. Participants were randomly assigned in a 1:1 ratio to receive sparsentan 400 mg once daily or irbesartan 300 mg once daily, stratified by estimated glomerular filtration rate at screening (30 to 1·75 g/day). The primary efficacy endpoint was change from baseline to week 36 in urine protein-creatinine ratio based on a 24-h urine sample, assessed using mixed model repeated measures. Treatment-emergent adverse events (TEAEs) were safety endpoints. All endpoints were examined in all participants who received at least one dose of randomised treatment. The study is ongoing and is registered with ClinicalTrials.gov, NCT03762850. Findings: Between Dec 20, 2018, and May 26, 2021, 404 participants were randomly assigned to sparsentan (n=202) or irbesartan (n=202) and received treatment. At week 36, the geometric least squares mean percent change from baseline in urine protein-creatinine ratio was statistically significantly greater in the sparsentan group (-49·8%) than the irbesartan group (-15·1%), resulting in a between-group relative reduction of 41% (least squares mean ratio=0·59; 95% CI 0·51-0·69; p<0·0001). TEAEs with sparsentan were similar to irbesartan. There were no cases of severe oedema, heart failure, hepatotoxicity, or oedema-related discontinuations. Bodyweight changes from baseline were not different between the sparsentan and irbesartan groups. Interpretation: Once-daily treatment with sparsentan produced meaningful reduction in proteinuria compared with irbesartan in adults with IgA nephropathy. Safety of sparsentan was similar to irbesartan. Future analyses after completion of the 2-year double-blind period will show whether these beneficial effects translate into a long-term nephroprotective potential of sparsentan. Funding: Travere Therapeutics