TAK-003
TAK-003 or DENVax is a recombinant chimeric vaccine with DENV1, DENV3, and DENV4 components on a dengue virus type 2 (DENV2) backbone originally developed at Mahidol University in Bangkok and now funded by Inviragen (DENVax) and Takeda (TAK-003). Phase I and II trials were conducted in the United States, Colombia, Puerto Rico, Singapore and Thailand. Based on the 18-month data published in the journal Lancet Infectious Diseases, indicated that TAK-003 produced sustained antibody responses against all four virus strains, regardless of previous dengue exposure and dosing schedule.Data from the phase III trial, which began in September 2016, show that TAK-003 was efficacious against symptomatic dengue. TAK-003 appears to not lack efficacy in seronegative people or potentially cause them harm, unlike CYD-TDV. The data appear to show only moderate efficacy in other dengue serotypes than DENV2.In March 2021, the European Medicines Agency accepted the filing package for TAK-003 intended for markets outside of the EU. In development
TV-003/005
TV-003/005 is a tetravalent admixture of monovalent vaccines, that was developed by NIAID, that were tested separately for safety and immunogenicity. The vaccine passed Phase I trials and Phase II studies in US, Thailand, Bangladesh, India and Brazil.NIH has conducted Phase I and Phase II studies in over 1000 participants in the US.
In 20 patients (12 and 8 probands, respectively), missense mutations (R672H; MIM *160270.0001 and R672C; MIM *160270.0002) caused substitution of arg672, an embryonic myosin residue retained post-embryonically. Of the remaining 6 patients in whom they found mutations, 3 had missense private de novo (E498G; MIM *160270.0006 and Y583S) or familial mutations (V825D; MIM *160270.0004); 3 other patients with sporadic expression had de novo mutations (T178I; MIM *160270.0003), which was also found in DA2B; 2 patients had no recognized mutations. Diagnosis
Freeman–Sheldon syndrome is a type of distal arthrogryposis, related to distal arthrogryposis type 1 (DA1). In 1996, more strict criteria for the diagnosis of Freeman–Sheldon syndrome were drawn up, assigning Freeman–Sheldon syndrome as distal arthrogryposis type 2A (DA2A).On the whole, DA1 is the least severe; DA2B is more severe with additional features that respond less favourably to therapy. DA2A (Freeman–Sheldon syndrome) is the most severe of the three, with more abnormalities and greater resistance to therapy.Freeman–Sheldon syndrome has been described as a type of congenital myopathy.In March 2006, Stevenson et al. published strict diagnostic criteria for distal arthrogryposis type 2A (DA2A) or Freeman–Sheldon syndrome. These included two or more features of distal arthrogryposis: microstomia, whistling-face, nasolabial creases, and H-shaped chin dimple. Management
Surgical and anesthetic considerations
Patients must have early consultation with craniofacial and orthopaedic surgeons, when craniofacial, clubfoot, or hand correction is indicated to improve function or aesthetics. Operative measures should be pursued cautiously, with avoidance of radical measures and careful consideration of the abnormal muscle physiology in Freeman–Sheldon syndrome.