Host Immune Response to Mosquito-Transmitted Chikungunya Virus Differs from That Elicited by Needle Inoculated Virus

Mosquito-borne diseases are a worldwide public health threat. Mosquitoes transmit viruses or parasites during feeding, along with salivary proteins that modulate host responses to facilitate both blood feeding and pathogen transmission. Understanding these earliest events in mosquito transmission of arboviruses by mosquitoes is essential for development and assessment of rational vaccine and treatment strategies. In this report, we compared host immune responses to chikungunya virus (CHIKV) transmission by (1) mosquito bite, or (2) by needle inoculation.Differential cytokine expression was measured using quantitative real-time RT-PCR, at sites of uninfected mosquito bites, CHIKV-infected mosquito bites, and needle-inoculated CHIKV. Both uninfected and CHIKV infected mosquitoes polarized host cytokine response to a TH2 profile. Compared to uninfected mosquito bites, expression of IL-4 induced by CHIKV-infected mosquitoes were 150 fold and 527.1 fold higher at 3 hours post feeding (hpf) and 6 hpf, respectively. A significant suppression of TH1 cytokines and TLR-3 was also observed. These significant differences may result from variation in the composition of uninfected and CHIKV-infected mosquito saliva. Needle injected CHIKV induced a robust interferon-gamma, no detectable IL-4, and a significant up-regulation of TLR-3.This report describes the first analysis of cutaneous cytokines in mice bitten by CHIKV-infected mosquitoes. Our data demonstrate contrasting immune activation in the response to CHIKV infection by mosquito bite or needle inoculation. The significant role of mosquito saliva in these earliest events of CHIKV transmission and infection are highlighted

Aortic valve cusp repair does not affect durability of modified aortic valve reimplantation for tricuspid aortic valvesCentral MessagePerspective

Objective: During aortic valve reimplantation, cusp repair may be needed to produce a competent valve. We investigated whether the need for aortic valve cusp repair affects aortic valve reimplantation durability. Methods: Patients with tricuspid aortic valves who underwent aortic valve reimplantation from January 2002 to January 2020 at a single center were retrospectively analyzed. Propensity matching was used to compare outcomes between patients who did and did not require aortic valve cusp repair. Results: Cusp repair was performed in 181 of 756 patients (24%). Patients who required cusp repair were more often male, were older, had more aortic valve regurgitation, and less often had connective tissue disease. Patients who underwent cusp repair had longer aortic clamp time (124 ± 43 minutes vs 107 ± 36 minutes, P = .001). In-hospital outcomes were similar between groups and with no operative deaths. A total of 98.3% of patients with cusp repair and 99.3% of patients without cusp repair had mild or less aortic regurgitation at discharge. The median follow-up was 3.9 and 3.2 years for the cusp repair and no cusp repair groups, respectively. At 10 years, estimated prevalence of moderate or more aortic regurgitation was 12% for patients with cusp repair and 7.0% for patients without cusp repair (P = .30). Mean aortic valve gradients were 6.2 mm Hg and 8.0 mm Hg, respectively (P = .01). Ten-year freedom from reoperation was 99% versus 99% (P = .64) in the matched cohort and 97% versus 97%, respectively (P = .30), in the unmatched cohort. Survival at 10 years was 98% after cusp repair and 93% without cusp repair (P = .05). Conclusions: Aortic valve reimplantation for patients with tricuspid aortic valves has excellent long-term results. Need for aortic valve cusp repair does not affect long-term outcomes and should not deter surgeons from performing valve-sparing surgery