News Scan for Nov 11, 2016

News brief

More animal trial results for Zika vaccine, Florida's local cases grow

Researchers from the Wistar Institute and the Public Health Agency of Canada yesterday reported promising findings in mice and nonhuman primates for a DNA-based Zika vaccine developed by Inovio, GeneOne Life Sciences, and academic institutions.

All vaccinated animals were protected from Zika after experimental infection. Compared to unvaccinated animals, the vaccinated ones appeared to be protected against cerebral cortex and hippocampal degeneration. The team published its findings in npj Vaccines.

The new findings follow promising results published in February from a mouse study of Inovio's Zika vaccine, which is delivered through an electroporation delivery system.

In a press release, the Wistar Institute said the vaccine is currently being tested in two phase 1 human trials with the first results for one of them expected by the end of the year.
Nov 10 npj Vaccines abstract
Nov 10 Wistar Institute press release 

In other Zika developments, the Florida Department of Health (Florida Health) today reported two more locally acquired cases, both of them linked to the Miami Beach outbreak. Florida Health said one of the cases involves a patient from out-of-state.

The additional cases boost Florida's local infection total to 224.
Nov 11 Florida Health daily Zika update


Study reveals Chagas disease burden in south Texas

The prevalence of Chagas disease in Texas' Rio Grande Valley area is much greater than originally thought, as much as 23 times higher than earlier estimates, according to a study published yesterday by a team from the National School of Tropical Medicine at Baylor University.

After testing kissing bugs that spread the Trypanosoma cruzi parasites that are responsible for the disease and analyzing previously collected blood samples from coyotes, stray dogs, and humans from the Rio Grande Valley, scientists reported their disease burden estimate in Public Library of Science (PLoS) Neglected Tropical Diseases.

Chagas disease is a serious concern, because nearly a third of infected people can develop potentially fatal cardiomyopathy. It is predominantly found in high-poverty areas where substandard living conditions put people in contact with the insects that spread the disease.

Of 841 human blood samples researchers tested, 3 (0.4%) were positive for T cruzi, along with evidence that 8% of coyotes and 3.8% of stray dogs were infected. Of the kissing bugs they sampled, 56.5% were positive for the parasite. Based on the findings, they estimated that 4,600 people in the valley are infected with Chagas disease, with 1,300 of them at risk for cardiomyopathy.

Larger, more extensive seroprevalence studies are underway in the Rio Grande Valley to better assess the risk, according to the study. The authors wrote, "with up to 30% of infected individuals developing a potentially fatal cardiac disease, it is imperative that we identify and treat patients before heart disease occurs."
Nov 10 PLoS Negl Trop Dis report
Nov 10 PLoS
press release

Flu Scan for Nov 11, 2016

News brief

H7N9 avian flu sickens two in China

China is reporting two new H7N9 avian influenza infections, the first since July. The new cases potentially mark the start of the fifth wave of infections.

One of the patients is a 77-year-old woman who works as a farmer near the Jiangsu province city of Huzhou who bought poultry from a live market before she became ill, according to a statement today from Hong Kong's Centre for Health Protection (CHP). She is hospitalized in serious condition.

The other case involves an 89-year-old man from the city of Suzhou in Zhejiang province who is also listed in serious condition.

A CHP spokesman said in the statement, "As winter approaches, based on the seasonal pattern of avian influenza viruses, their activity in the Mainland is expected to increase. The public should avoid contact with poultry, birds and their droppings and should not visit live poultry markets and farms to prevent avian influenza."

Since the novel virus emerged in 2013, 809 cases have been reported, most of them from China, according to a case list kept by FluTrackers, an infectious disease news message board.
Nov 11 CHP statement
FluTrackers global H7N9 case list


Childhood exposures to influenza determine future immunity

For the last decade, scientists have wondered why novel influenza A viruses have attacked certain age groups at higher rates. Now, a new study published in Science explains that the first strain of influenza a young child is exposed to determines their future susceptibility to different novel avian influenza strains.

Researchers said that people born before 1968 were more likely to be exposed to H1 or H2 influenza strains in childhood, making them less susceptible to H5N1, which in in the same virus group. Younger people, however, were more likely to first contract a flu from the H3 subtype viruses, and are less susceptible to H7N9 avian influenza—both are in a second virus group. That's because flu groups contain subtypes that offer cross-strain immunity. In other words, if a person was exposed to an H1 strain in childhood, they have an imprint that helps them fend off avian H5 for life, resulting in a 75% reduced risk of severe illness and an 80% reduced risk of death.

To model this, the authors looked at flu trends from 1918 to 2015 in China, Egypt, Cambodia, Indonesia, Thailand, and Vietnam. The most deadly influenza illnesses occurred when a cohort was exposed to a mismatched avian strain. Thus birth year, and not age, is the most important risk factor for establishing risk for severe disease outcomes.

"For any country with suitable contact and demographic data, the methods shown here can provide rolling estimates of which age groups would be at highest risk for severe disease should particular novel HA subtypes emerge. Such projections could guide cohort- or region-specific prevention, preparation, or control," the authors concluded.
Nov 11 Science study


H5N8 strikes ducks and turkeys in Switzerland, Austria

Today the World Organization for Animal Health (OIE) reported that H5N8 was found in ducks near Kreuzlingen, Switzerland. Kreuzlingen is a village on Lake Constance. The OIE also confirmed that that waterfowl on the Austrian side of the lake had also died from the highly pathogenic avian flu.

According to OIE’s Swiss report, three tufted ducks were found dead in Lake Constance on Nov 4, and virus sequencing showed H5N8, the same H5 clade that's been found in India, Hungary, Austria, Croatia, Poland, Germany, Denmark, and the Netherlands. In their Austrian report, the OIE said 10 ducks on the Austrian shores of Lake Constance also died on Nov 7.

H5N8 targets migratory birds and waterfowl, as well as poultry. Though the virus has not known to threaten human health, it can devastate poultry farms. According to Avian Flu Diary, an infectious disease blog, Austrian officials are now reporting that H5N8 has been confirmed in a flock of free-range turkeys in Vorarlberg, a state near Lake Constance. Last week, 9,000 turkeys in Hungary also died from H5N8.

In other H5 news, South Korea has confirmed H5N6 in the excrement of wild birds. The government report was shared by FluTrackers, an infectious disease news message board. The feces were collected on Oct 28 by a research team from Konkuk University. This is the first time high-path avian flu has been reported in South Korea this winter.
Nov 11 OIE Swiss report
Nov 11 OIE Austrian report
Nov 11 Avian Flu Diary post
Nov 11 FluTrackers post

ASP News Scan for Nov 11, 2016

News brief

Our weekly wrap-up of antimicrobial stewardship & antimicrobial resistance scans

How monitoring resistance gene frequency can help combat AMR

Originally published by CIDRAP News on Nov 10.

A paper published yesterday in Open Biology argues that monitoring resistance gene frequency might be a better way to track and combat antimicrobial resistance (AMR) and could enable swifter, more accurate treatment of patients with bacterial infections.

To date, management of AMR has focused on tracking the rise of drug-resistant pathogens. But the authors of the paper argue that while such surveillance is essential, it only documents that end stage of the resistance process and ignores the root cause of AMR—the development and spread of genes that confer resistance to organisms. In addition, limiting the measurement of pathogenic organisms to the clinical setting ignores the reservoir of resistance genes available to pathogens in the wider environment.

Therefore, lead author Carolyn Michael, PhD, et al propose directly monitoring the entire genetic resistance resource available to microbes and measuring and analyzing the frequency of resistance-providing genes in both clinical and non-clinical environments, including shopping centers, transportation hubs, and sewage treatment centers. Doing so, they argue, will allow for better estimates of the changing scope of the AMR problem.

"Doing this will let us see rising numbers of resistance genes before they get to a pathogen and also keep an eye on the different types of resistance genes already in pathogens," Michael says in a University of Technology Sydney news release.

In addition, Michael and her colleagues write, understanding the rise and fall of resistance genes in the environment can guide both local and global antimicrobial stewardship efforts by helping clinicians know which antimicrobials are likely to be ineffective. And that, in turn, could lead to better treatment.
Nov 9 Open Biology
Nov 9 University Technology Syndey
news release

Study finds plasmids can accelerate evolution of antibiotic resistance
Originally published by CIDRAP News on Nov 9.     

A study published Monday in Nature Ecology and Evolution suggests plasmids may play more of a role in spreading and facilitating antibiotic resistance than previously thought.

Plasmids, which are mobile pieces of DNA, have long been known to spread resistance by facilitating the horizontal transfer of antibiotic-resistant genes between bacteria. An example of how plasmids work is found in MCR-1, a colistin-resistance gene that was identified in Escherichia coli bacteria in China and has since been found in more than 30 countries. But what is less clear is the role that plasmids play as catalysts in gene evolution.

To explore that question, researchers from the University of Oxford used a novel experimental model to determine whether bacteria carrying antibiotic resistance genes on plasmids have evolutionary advantages over bacteria that have resistance genes on chromosomes. The model involved creating strains of E Coli with a beta-lactamase gene on either the chromosome or a multi-copy plasmid, then exposing the strains to increasing concentrations of the antibiotic ceftazidime.

What the researchers found was that beyond facilitating horizontal gene transfer, the plasmid accelerated the development of ceftazidime resistance in the E coli strains by facilitating the evolution of novel variants of the gene, increasing the rate of appearance of those variants, and then amplifying the effects through greater gene expression.

"Our paper demonstrates that plasmids can also act as evolutionary catalysts that accelerate the evolution of new forms of resistance," senior author Craig MacLean, PhD, an associate professor in the department of zoology at Oxford, said in a university press release. "This occurs because bacteria usually carry more than one copy of a plasmid, which allows resistance genes carried by plasmids to rapidly evolve new functions—in this case, the ability to degrade an antibiotic. Additionally, plasmids automatically amplify the number of copies of these new and improved resistance genes."

MacLean and his colleagues say their findings have general implications for the "evolution of antibiotic resistance, adaptation and innovation in bacteria," and argue that they highlight the importance of developing new drugs that can block plasmid replication.
Nov 7 Nature Ecology and Evolution study
Nov 8 University of Oxford press release

FDA advisory panel recommends new antibiotic for approval
Originally published by CIDRAP News on Nov 8.

An advisory panel to the US Food and Drug Administration (FDA) voted on Nov 3 to recommend a new antibiotic to treat community-acquired pneumonia (CABP), despite concerns over liver toxicity.

In a 7-6 vote, members of the FDA's Antimicrobial Drugs Advisory Committee recommended approval of the drug solithromycin, a macrolide antibiotic that has activity against macrolide-resistant CABP pathogens. But while the panel voted unanimously (13-0) that there was substantial evidence of solithromycin's efficacy, and that the drug works as well as moxifloxacin in patients with CABP, they also voted 12-1 that the risk of hepatoxicity has not been adequately characterized.

Reuters reports that clinical trials of solithromycin showed greater number of patients taking the drug developed elevated liver enzymes than those taking moxifloxacin, a possible sign of underlying liver damage. But there were no cases of acute liver injury. The panel recommended that drug maker Cempra Inc. be required to conduct additional studies on potential liver damage after the drug is approved.

"We appreciate the meaningful discussion from today's panel. Their supportive view and thoughtful comments on approaches to ensuring appropriate use are consistent with Cempra’s commitment to make solithromycin available to the right patients for a five to seven day course of an oral and/or IV macrolide as monotherapy for CABP," Cempra president and CEO Prabhavathi Fernandes PhD, said in a company press release.

Cempra argues that new antibiotics for the treatment of CABP are much needed, as rates of pneumococcal resistance to macrolides can exceed 50%.

The FDA is not bound by the advisory panel's recommendations.
Nov 4 Cempra Inc. press release
Nov 4 Reuters story


Study finds limiting use of '4C' antibiotics can reduce C diff infection rates
Originally published by CIDRAP News on Nov 8.

A new study out of Scotland suggests that limiting the use of antibiotics associated with Clostridium difficile infection risk can reduce C difficile infection rates in hospital and community populations.

The study, published Nov 4 in the Lancet Infectious Diseases, was an observational and quasi-experimental time-series analysis that aimed to measure the impact of an antibiotic stewardship program (ASP) in northeast Scotland that emphasized reduction in hospital and community use of antibiotics linked to C difficile infection. The antibiotics—known as the 4Cs—included ciprofloxacin/fluoroquinolones, co-amoxiclav, clindamycin, and cephalosporins. After implementation, use of the 4C antibiotics was reduced by 50% in hospitals and the community.

Other infection control and prevention measures in the ASP included a hand-hygiene campaign, national auditing and inspections of hospital environment cleanliness, and reduced inappropriate use of proton-pump inhibitors. The total effect of interventions, which were initiated in 2009, was defined as the difference between the C difficile infection burden with the ASP and projected scenarios without stewardship.

From 1997 to 2012, investigators identified 4,885 cases of hospital-onset C difficile and 1,625 cases of community-onset C difficile. Controlling for multiple cofounders, the authors estimated that after implementation of the ASP, C difficile infection prevalence fell by 68% in hospitals and 45% in the community compared to projected scenarios without the ASP. Further analysis indicated that declines in C difficile could be explained by the removal of antibiotic selection pressure favoring multidrug-resistant ribotypes R001 and R027, which have been associated with higher incidence and more severe disease. No significant effects from other measures of the ASP were identified.

"Our study adds to existing evidence that antibiotic stewardship might be an effective tool for the control of C difficile infection in both hospitals and the community," the authors wrote.
Nov 4 Lancet Infect Dis study
Nov 4 Lancet Infect Dis commentary

Studies identify genetic markers for drug-resistant malaria

Originally published by CIDRAP News on Nov 7.

Two papers published last week in The Lancet Infectious Diseases describe the identification of molecular markers associated with drug resistance in Plasmodium falciparum malaria.

The two papers were genome-wide association studies of Cambodian strains of P falciparum that were looking to find molecular markers for resistance to piperaquine, a drug that is used in artemisinin combination therapies. As malaria in the Greater Mekong subregion becomes increasingly resistant to artemisinin and the partner drugs that are used to treat the P falciparum parasite—which accounts for most malaria cases and deaths—molecular markers are urgently needed to help public health officials monitor the spread of resistance and recommend alternative treatments.

In addition to Cambodia, artemisinin resistance has been detected in Laos, Myanmar, Thailand, and Vietnam.

In one study, led by researchers from the National Institute of Allergy and Infectious Diseases (NIAID) and the UK's Wellcome Trust Sanger Institute, investigators compared the complete genomes of 297 parasites isolated from Cambodian malaria patients to a reference malaria parasite genome and identified two genetic markers—amplifications of the exo-E425G and plasmepsin 2 and 3 genes—associated with the parasites' ability to resist piperaquine. The researchers believe that the amplification of the plasmepsin 2 and 3 genes may play a functional role in enabling parasites to resist piperaquine.

In the other study, researchers from the Institut Pasteur in Cambodia did a gene-wide association study on 31 malaria strains to define the resistant in-vitro phenotype. They found that an increased plasmepin 2 gene copy number was strongly associated with dihydroartemisinin-piperaquine treatment failure.

"The converging results of these studies make plasmepsin 2–3 amplification a robust marker for piperaquine resistance in the region," an accompanying commentary notes. "P falciparum transfected with multicopy plasmepsin 2–3 will be an invaluable tool to explore underlying resistance mechanisms."

Information about the distribution of these drug resistance markers, a press release from NIAID explains, is being used by officials in Cambodia and neighboring countries to determine the spread of piperaquine resistance and help guide treatment approaches.
Nov 3 Lancet Infect Dis study
Nov 3 Lancet Infect Dis
Nov 3 Lancet Infect Dis
press release

This week's top reads