News Scan for Oct 04, 2013

Norovirus vaccine tested
Promising antiviral compounds
MDR-TB treatment completion

Norovirus vaccine reduced symptoms in challenge study

A vaccine targeting two common norovirus strains reduced vomiting and diarrhea and prevented severe illness in a small clinical challenge study, researchers reported today at the IDWeek conference in San Francisco.

The vaccine was tested in 98 volunteers who agreed to drink water containing the virus; 50 of them received the intramuscular vaccine and 48 received a placebo injection, according to a press release from the Infectious Diseases Society of America (IDSA), one of the meeting sponsors.

Norovirus infections numbered 26 (52%) in the vaccine group and 29 (60%) in the placebo group. Ten vaccinees (20%) had vomiting or diarrhea of any severity, versus 20 (42%) of the placebo recipients, a significant 52% reduction (P =.028), according to an e-mailed press release from Takeda Pharmaceuticals, sponsor of the trial.

Also, there were no cases of severe vomiting and/or diarrhea in the vaccine group, versus four in the placebo group (0% vs 8.3%; P =.054), Takeda reported.

"Like rotavirus vaccine, protection increases as severity increases, and that's what you want a vaccine to do," said lead author David I. Bernstein, MD, MA, professor of pediatrics at Children's Hospital Medical Center in Cincinnati, at an IDWeek press teleconference today.

The number of volunteers with any gastroenteritis symptoms was also lower in the vaccine group, but the difference was not significant, the Takeda statement said.

The vaccine uses virus-like particles to target norovirus genotypes GII.4 and GI.1. Bernstein said GII.4 currently causes about 60% of cases and GI.1 causes another 10% to 20%.

He said that if the vaccine works well in further trials, it could be used in specific groups, such as the elderly, people in day care settings, those going on a cruise, and nursing home residents.
Oct 28, 2010, CIDRAP News story about earlier norovirus vaccine trial


New antiviral class shows promise in early tests

Researchers have identified novel compounds that block a key step in flu virus replication, which could lead to new antiviral medications, according to a press release today from Rutgers University, where a team identified the new agents.

The new class of inhibitors targets cap-snatching endonuclease activity of viral polymerase. The group first reported its findings in an advance issue of ACS Chemical Biology.

The investigators used high-resolution crystallography of the 2009 H1N1 virus to visualize the structure of an enzyme, which they used to screen binding compounds. Researchers screened 800 small molecule fragments that bind to metal ions in the enzyme.

Eddy Arnold, PhD, professor of chemistry and chemical biology at Rutgers, said in the release that the enzyme the team targeted steals material from human cells to disguise the invading flu viruses, a process known as cap-snatching. "What we're doing is by blocking or inhibiting this enzyme is to interfere with the flu's ability to disguise itself," he said.

The hydroxypyridinone compounds showed antiviral activity against the 2009 H1N1 virus in Madin-Darby canine kidney (MDCK) cells. Researchers reported that the compounds also show promise against H5N1 avian influenza and the H7N9 virus that recently sparked an outbreak in China.

Arnold said that Rutgers researchers have been trying to create other antiviral drugs besides oseltamivir (Tamiflu), which is currently the gold standard for treating flu and a key tool for use in an influenza pandemic but isn't useful against resistant flu strains. He noted that the team's work on the new antiviral is based on an approach used to develop HIV drugs.

So far work on the new compounds is at the proof-of-principle stage, he said. "It's not trivial to go from this point to actually delivering a drug, but we're optimistic—this class of inhibitors has all the right characteristics."
Oct 4 Rutgers University press release
Aug 26 ACS Chem Biol abstract


UK MDR-TB treatment-completion rate falls below WHO targets

About 71% of UK patients who were diagnosed as having multidrug-resistant tuberculosis (MDR-TB) completed treatment in 2 years or more, but the rate falls below World Health Organization (WHO) and UK targets, a study yesterday in Eurosurveillance found.

UK researchers analyzed data from all MDR-TB patients in England, Wales, and Northern Ireland from 2004 through 2007. Of the 204 patients, 144 (70.6%) completed treatments in 24 months or more, 14 (6.9%) stopped treatment, 14 (6.9%) died, 16 (7.8%) were lost to follow up, 1 (0.5%) relapsed, and 9 (4.4%) were transferred overseas. UK guidelines recommend at least 18 months of treatment.

The rate of treatment completion is below the WHO target of 75% and the UK goal of 85% but above the European Union target of 70%, the authors note. They said that a previously published study showed a 72.1% rate of completed treatment in 2010.

The scientists found that treatment with a fluoroquinolone or bacteriostatic drug was independently associated with successful treatment outcome.

The authors conclude, "The UK should consider adopting individualised regimens based on WHO recommended drugs, taking into account drug sensitivities."
Oct 3 Eurosurveillance report

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