News Scan for May 10, 2016

News brief

Policy draft, risk-benefit analysis posted ahead of NSABB meeting

Ahead of its upcoming meeting, the National Science Advisory Board for Biosecurity (NSABB) has posted a draft of a working group's recommendations to guide federal officials in evaluating proposed gain-of-function (GOF) studies on H5N1 flu and other dangerous pathogens, and an outside company tasked with crafting a risk-benefit analysis of GOF research has posted its final report.

The two items are key parts of efforts to reach common ground on controversial GOF studies and are part of the Obama Administration's October 2014 charge to the NSABB to come up with ways to guide the federal funding policies for that type of research.

The research evaluation recommendations, posted May 6, were first discussed at the NSABB's January meeting, and again in March at a symposium hosted by the National Academies. The group said the draft is intended as a deliberative document, which could be finalized during the NSABB's upcoming full meeting on May 24, which will be live-streamed on the Web. The group will also discuss its next steps for guiding US government policies on GOF studies.

In a related development, Gryphon Scientific, a life sciences group hired to conduct the GOF risk-benefit analysis, posted its final report on its Web site. It released its first draft in December 2015. The company finalized the document in April after the March National Academies symposium.

"GOF" refers to experiments that enhance the pathogenicity, transmissibility, or host range of a pathogen with the aim of advancing scientific understanding.
May 6 NSABB GOF research evaluation recommendations draft report
April Gryphon GOF risk-benefit final report

PAHO reports almost 1,000 new chikungunya cases in the Americas

The Pan American Health Organization (PAHO) late last week reported 996 new suspected and confirmed cases of chikungunya, bringing the 2016 total to 83,599 cases.

Colombia had the largest increase. The country's 571 new cases brought its 2016 total to 13,029, according to the May 6 update. Venezuela was next with 316 new cases and 2,396 total. Many countries did not report cases last week and have not for many weeks.

In the previous week, PAHO reported 28,317 new cases, mostly in Brazil. No new deaths were reported last week, keeping that number at 12 for the year, all in Brazil.

The outbreak was first reported in December 2013 on St. Martin in the Caribbean with the first recorded cases of the disease in the Americas. Since then PAHO has reported 1,963,145 suspected or confirmed cases, including 279 fatalities.
May 6 PAHO update

Study: Aggressive treatment greatly lowers risk of recurrent MDR-TB

In patients with multidrug-resistant tuberculosis (MDR-TB), aggressive treatment regimens with long continuation after conversion can greatly lower the risk of recurrence, say the results of a study published May 8 in Clinical Infectious Diseases.

The authors, from several institutions in Russia and in Boston, retrospectively analyzed the cases of 399 MDR-TB patients in Tomsk, Russia, whose illnesses were successfully treated (ie, cured or treatment completed) from Sept10, 2000, through Nov 1, 2004.

Outcomes in patients receiving long, aggressive regimens were compared with outcomes in patients receiving other treatment regimens. Long, aggressive treatment means five or more drugs judged likely to be effective, including a second-line injectable agent and a fluoroquinolone, in the intensive phase (ie, for at least 6 months after sputum culture conversion) and four or more drugs in a continuation phase of at least 18 months post-conversion.

Over a 42.4-month median duration of follow-up, there were 27 recurrences. After adjusting for risk factors for recurrence such as age, sex, presence of diabetes, extensive pulmonary involvement, and other confounding factors, patients receiving the long, aggressive regimens had a 78% reduction in disease recurrence (hazard ratio, 0.22 [95% confidence interval, 0.05-0.92] for those receiving regimens other than the long aggressive one).

Further research by means of controlled trials is needed to determine such factors as the importance of duration of continuation of treatment and the potential contribution of all drugs available for TB treatment, the authors say.

They conclude, "Our study adds to a growing body of evidence that individualized aggressive regimens improve treatment outcomes for MDR-TB, particularly among populations where previous exposure to second-line drugs is common.
May 8 Clin Infect Dis study abstract

Avian Flu Scan for May 10, 2016

News brief

Novel avian flu subtype H3N6 found co-circulating with H3 and H5 viruses

A novel avian flu subtype, H3N6, was found co-circulating with other viruses on duck farms in China's Hunan province, according to a May 6 study in Scientific Reports.

Researchers analyzed 10 avian flu strains isolated from domestic ducks, geese, and duck pond water from 2014 to 2015 on farms in Hunan's Wugang city. Avian flu viruses H3N2, H3N8, and H5N6 were found co-circulating in domestic ducks, along with a new subtype, H3N6, which likely derived from H5N6. The new virus possesses a neuraminadase deletion that makes it unique compared with other H3 subtypes, the authors said.

All four subtypes replicated efficiently in mammal cells, including Madin-Darby Canine Kidney (MDCK) epithelial cells, though the H3 viruses grew to higher titers compared with H5N6 in the first 12 hours, followed by a drop in viral load 72 hours after infection. The viruses were also found to replicate well in adenocarcinomic human alveolar basal epithelial (A459) cells.

The H3 viruses and H5N9 also demonstrated low pathogenicity in mice. H3N2 and H3N8 caused high viral titers in the lungs and nasal turbinates of infected mice, while H3N6 and H5N6 were able to replicate effectively only in the lungs. None of the four subtypes caused murine disease or death, the authors said.

Given the occurrence of novel subtypes produced by gene reassortment of co-circulating avian flu viruses, the authors recommended improving biosecurity measures on Chinese poultry farms to reduce the possibility of avian flu outbreaks and interspecies transmission.
May 6 Sci Rep study

Researchers say genetic traits may influence human susceptibility to H7N9

Chinese scientists have identified 64 human genetic peculiarities that they think may affect susceptibility to infection with the H7N9 avian flu virus, according to a report yesterday in Scientific Reports.

The authors hypothesized that genetic characteristics may influence both susceptibility to H7N9 infection and the severity of illness, since relatively few of the many people exposed to poultry during H7N9 outbreaks have contracted the infection.

The team took blood samples from 18 confirmed H7N9 patients, 6 of whom had fatal cases. They extracted the DNA and sequenced the portions of it that encode proteins (exons). This led to the identification of 64 single-nucleotide polymorphisms (SNPs) in 21 genes that were more common in the H7N9 patients than in the general population.

"These mutations were found in genes encoding proteins responsible for multiple key host defense mechanisms, including cytokine production, airway epithelium barrier function and pathogen associated molecular pattern signaling pathway," suggesting that the SNPs may affect susceptibility to H7N9, the report says.

Some of the 21 genes have previously been identified as linked to H7N9 susceptibility, the authors said. For example, an earlier study indicated that dysfunction of a gene called IFITM3 is associated with increased cytokine production during H7N9 infection and is correlated with mortality.

The team acknowledged that their sample was small and that the findings need to be confirmed by further studies, which they are working on.

"Further investigations into the function of these genes in host susceptibility may help identify individuals who are at high risk for infection," they concluded. "In addition, translational research into the function of the genes identified in this study may provide new potential therapeutic targets for influenza virus infection."
May 9 Sci Rep article