News Scan for Dec 05, 2016

News brief

Researchers describe high-yield flu B vaccine virus production method

Researchers from the University of Wisconsin-Madison today described a new technique that could improve the production of influenza B vaccine viruses, consisting of a "backbone" for adding specific components to protect against both the Victoria and Yamagata lineages. They reported their findings today in Proceedings of the National Academy of Sciences.

The process is designed to grow vaccine viruses at high yield in mammalian cell culture rather than in eggs. The researchers developed the backbone after screening influenza B viruses for genetic mutations that were linked to improved replication. With the mutants as templates, they attached the influenza B surface protein genes that provoke and immune response.

They picked out the combinations that showed more vigorous growth in cell culture, highlighting two candidate backbones linked to higher amounts of vaccine viruses. The team also fleshed out the characteristics of each backbone that contributed to the higher yields and found that both were genetically stable.

Yoshihiro Kawaoka, DVM, PhD, who led the study, said in a UW-Madison press release that vaccine producers face several obstacles with efficiently making effective flu vaccines. Cell-culture–grown vaccine viruses are less likely to mutate compared with those grown in eggs, but flu viruses don't grow as well in cell culture compared with eggs, he said.

"It may still not be perfect, but it will at least be substantially better than current vaccines," he said. In 2015 Kawaoka's team created a high-yield influenza A virus candidate for cell-culture production. He said several companies and federal agencies have contacted him about the influenza A and influenza B backbones. He added that he is hopeful that vaccine manufacturers can use the systems in cell-culture systems already available in the United States and Japan.

The overarching goal is to develop more effective flu vaccines, Kawaoka said. "This is something we have to do."
Dec 5 Proc Natal Acad Sci abstract
Dec 5 University of Wisconsin press release
Sep 3, 2015, CIDRAP News scan "Experts devise potential high-yield flu vaccine approach"

African strain of Zika vaccine protects monkeys against Asian strain

A new study in PLoS Neglected Tropical Diseases showed that a Zika virus vaccine formulated with the East African Zika strain MR766 completely protected macaques against Asian lineage Zika virus, which is the one causing disease in the Americas. This finding suggests that immunity against one strain of the mosquito-borne virus is cross-protective against others.

The authors said their findings mean more possibilities for vaccine design and testing. "These data suggest that immunogen selection is unlikely to adversely affect the breadth of vaccine protection," the authors write.

Though the study challenged only three monkeys, it's the first work that shows cross-immunity between Zika virus strains. Like Japanese encephalitis and yellow fever, also flaviviruses, infection with one Zika strain offers protective heterologous immunity.

The authors also said that protection against detectable viremia from homologous and heterologous virus strains during the rechallenge suggests that "the immunologic barrier for complete protection may be comparatively low," which means that vaccine candidates could be efficacious even if they are not highly immunogenic.
Dec 2 PLoS Negl Trop Med study

CDC: 19 more cases of acute flaccid myelitis

The Centers for Disease Control and Prevention (CDC) today said 19 new cases of acute flaccid myelitis (AFM) have been diagnosed since its Nov 1 update, with three newly affected states. There are now 108 cases in 36 states.

While the AFM case count for 2016 is still lower than the 2014 case count (120), the CDC is concerned about the increase in cases in recent months. Last year, only 21 AFM cases were reported to the CDC.

Most people who contract AFM are children and suffer from polio-like illness and symptoms, including sudden limb weakness and spinal cord inflammation. The condition can also mimic West Nile Virus and meningitis.

States voluntarily report AFM cases to the CDC, making collecting data a challenge. And despite extensive testing, the CDC said the cause of AFM is still unknown, but likely to be related to other viral infections.
Dec 5 CDC update

PAHO reports only 305 new chikungunya cases

For the second update in a row, the Pan American Health Organization (PAHO) late last week reported low chikungunya numbers, with only 305 new cases.

Countries in the Americas, however, are well behind in their reporting to PAHO on the disease. The Dec 2 report is for epidemiologic week 48 of the year, but only six nations have reported on week 46 or more recently. Brazil, for example, which has logged about 80% of the cases so far in 2016 and noted 100,000 new cases in early November, has not reported since week 37.

The report covers 2 weeks, as the agency's previous update was on Nov 18 and detailed 231 new cases. Countries and territories in the Americas this year have now reported 441,611 suspected, confirmed, and imported cases.

Colombia saw the largest increase, with 106 new cases and 19,384 for the year. Mexico, Costa Rica, and El Salvador reported increases ranging from 50 to 62 new cases, and the United States had 20 new imported cases. PAHO reported no new chikungunya-related deaths last week, leaving that figure at 135.

The outbreak started in late 2013 on the Caribbean island of St. Martin, and has now sickened 2,320,051 people.
Dec 2 PAHO update

Stewardship / Resistance Scan for Dec 05, 2016

News brief

Study documents country variations in pediatric antibiotic prescribing

An analysis of antibiotic prescribing in outpatient pediatric settings in three European countries—Italy, the Netherlands, and the United Kingdom—showed varied usage patterns that might be helpful for evaluating and modifying current antibiotic stewardship programs, according to a study in the latest issue of the Pediatric Infectious Disease Journal.

Researchers based their retrospective cohort study on prescribing information from electronic health records from 2001 to 2010, covering more than 2 million children. The databases include records for Italian children up to age 14 and for the Netherlands and the United Kingdom up to age 18. The team also looked at two newly proposed pediatric-specific quality indicators: the proportion of amoxicillin users (amoxicillin index) and the ratio between amoxicillin and broad-spectrum antibiotics (A/B ratio).

For all three countries, antibiotic use was highest in the first years of life.

Prevalence of antibiotic prescribing was highest in Italy at 52.0%, followed by the United Kingdom at 36.2%, and the Netherlands at 18.0%. UK clinicians showed a slight reduction in global and amoxicillin use over time, with low prescribing of broad-spectrum antibiotics. In the Netherlands, antibiotic prescribing is low and stable, but levels of broad-spectrum antibiotics are progressively increasing. Meanwhile, in Italian pediatric settings, patterns were dominated by broad-spectrum antibiotics.

The investigators noted that two pediatric quality indicators easily showed the patterns and that the total antibiotic prevalence indicators may both be useful for gauging national programs and making future improvements.
December Pediatr Infect Dis J abstract

Study: MDR-TB in Shanghai gaining resistance as it spreads

A study in The Lancet Infectious Diseases indicates that multidrug-resistant tuberculosis (MDR-TB) strains in the largest city in China are largely being transmitted from person to person, and that many of those strains are becoming more resistant during transmission.

In the population-based, retrospective observational study, Chinese researchers performed genotyping and whole-genome sequencing of isolates from 7,892 patients in Shanghai who tested positive for TB from 2009 to 2012. They also measured strain diversity within and between genomically clustered isolates. The authors of the study say it's the first population-based study to combine genomics with detailed epidemiologic data to identify MDR-TB transmission pathways in a region in China, the country with the second-most MDR-TB cases worldwide.

It is commonly believed, the authors note, that most cases of MDR-TB result from inadequate treatment. But while many cases of MDR-TB strains are due to person-to-person transmission of MDR strains, few studies have provided evidence of transmission of MDR-TB at the population level. Understanding the causes and transmission patterns of MDR-TB is considered crucial for efforts to reduce the disease.

The findings suggest that transmission is common. Overall, the researchers found that 367 of the 7,892 patients (5%) had MDR-TB. They also found that nearly a third of the 324 MDR strains identified were in 38 genomic clusters that differed by 12 or fewer single nucleotide polymorphisms, which indicates recent transmission, and that transmission of MDR strains accounted for 73% of MDR-TB cases overall. Residential communities and related public facilities were the most common transmission settings.

Furthermore, transmission network analysis showed that 87% of the clusters acquired additional drug-resistance mutations during transmission.

"Transmission of MDR strains of tuberculosis has a substantial role in the burden of MDR tuberculosis in China," the authors write. "Interventions, such as early detection of cases, infection control, and evidence-based treatment, are urgently needed to stem the epidemic."
Dec 2 Lancet Infect Dis study