There have been several news reports that the world's first dengue vaccine will be available next year. However, the latest clinical trials show that the vaccine only provides a protection of around 50 per cent for DENV-2 and DENV-1, which are commonly found in Singapore.
DENV-1 accounts for 90 per cent of infections locally as a large population lacks the immunity against this particular dengue virus serotype. Until a vaccine that can offer higher protection becomes available, it is crucial to find a suitable treatment for dengue fever, as there is presently none available world-wide.
The good news is that a team of Singapore General Hospital (SGH) and Duke-NUS Graduate Medical School (Duke-NUS) researchers are now a step closer to finding a treatment for dengue fever. In the CELADEN study completed last year, the team found that Celgosivir, a medicine derived from a naturally occurring compound found in the seeds of the Moreton Bay Chestnut tree, is generally safe and well-tolerated by patients affected with the dengue virus.
Participants recruited for the study were admitted to SGH for five days, during which time they received either the placebo or Celgosivir. They continued to be followed up on days 7, 10 and 15 at the outpatient clinics where clinical histories and blood were taken. A physical examination of the patient was also done during these sessions.
"We found that the drug regimen in our CELADEN study was well-tolerated. And because dengue virus is cleared from the blood within three to five days and fever subsides in the same period, a regimen with more frequent dosing will be tested in the next phase of our trial to see its therapeutic effect," said Dr Jenny Low, Senior Consultant, Department of Infectious Diseases, SGH, and Principal Investigator of the study.
"Prior work conducted at Duke-NUS has demonstrated that dose regimen is an important factor in mediating the antiviral effects of Celgosivir," said Professor Subhash Vasudevan, Emerging Infectious Diseases Program at Duke-NUS.
The findings of the study were published in Lancet Infectious Diseases on 28 May 2014.
Moving to the next phase of the study, SingHealth and Duke-NUS have signed an exclusive licensing agreement with 60 Degrees Pharmaceuticals to evaluate the efficacy and safety of an alternate dosing regimen as well as combination drug treatments in dengue patients. The NUS Industry Liaison Office, which is part of NUS Enterprise, took the lead in coordinating and facilitating this multi-party collaboration and the license negotiation.
"Other viral diseases such as hepatitis C and HIV required combination regimens to demonstrate clinical benefit. This may also be the case for dengue. To that end, 60P has also entered into a collaboration agreement with NUS earlier in March 2014 to investigate the utility of drug combinations in animal models. This agreement builds on prior collaborations between the parties to evaluate the antiviral effects of other approved drugs," said Mr Geoff Dow, CEO, 60P.
Dengue fever is an acute febrile illness transmitted by mosquitoes, which affects half the world's population. There are 96 million symptomatic infections, 500,0000 hospitalisations and 25,000 deaths per year attributed to the disease. The economic burden is $12 billion. In Singapore, as elsewhere, the incidence of the disease has continued to increase despite aggressive control measures.
- Jenny G Low, Cynthia Sung, Limin Wijaya, Yuan Wei, Abhay P S Rathore, Satoru Watanabe, Boon Hian Tan, Liying Toh, Lian Tee Chua, Yan'an Hou, Angelia Chow, Shiqin Howe, Wing Ki Chan, Kah Hin Tan, Jasmine S Chung, Benjamin P Cherng, David C Lye, Paul A Tambayah, Lee Ching Ng, John Connolly, Martin L Hibberd, Yee Sin Leo, Yin Bun Cheung, Eng Eong Ooi, Subhash G Vasudevan. Efficacy and safety of celgosivir in patients with dengue fever (CELADEN): a phase 1b, randomised, double-blind, placebo-controlled, proof-of-concept trial. The Lancet Infectious Diseases, 2014; 14 (8): 706 DOI: 10.1016/S1473-3099(14)70730-3
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