Detection of Dengue Virus in Acutely Febrile Children in Kenya

The burden of dengue virus in Kenya is unknown, and is likely grossly underestimated due to febrile illnesses,often being presumptively treated as malaria , which is endemic. Additionally, Dengue fever can be fatal if left improperly treated especially in children who have lesser-developed immune systems. The objective of this ongoing study is to determine the incidence of dengue fever as the etiology of fever in febrile children in Western Kenya. In this ongoing study, children ages ≤17 presenting with febrile illness to our recruitment sites, had serum samples drawn for testing. For the purposes of the current study, RNA extracted from a subset of these samples (n=19) was reverse transcribed into cDNA and then tested for the presence of dengue virus by PCR followed by agarose gel electrophoresis. For positive samples, use of a sequential PCR reaction with dengue serotype-specific primer sets then enabled determination of the viral serotypes circulating in this population. Our preliminary data confirms the presence of dengue virus as a possible etiology of fever in children in Kenya with 2 out of the original 19 patient samples testing positive for DENV. Therefore, the data from the samples reports a Dengue infection rate of 10.5%. This preliminary data from our ongoing study at this time is too small to accurately determine the incidence of acute DENV infections in children with fever in Kenya; however, identification of DENV in the serum of acutely febrile children suggests that DENV is likely an important cause of fevers in Kenyan children

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