Antimicrobial Resistance Scan for Sep 22, 2016

News brief

Alliance forms to ensure accountability in AMR fight

A collection of public health and infectious disease groups are banding together to ensure that the United Nations (UN), national governments, and other international bodies live up to their promise to tackle antimicrobial resistance (AMR).

The overarching aim of the Conscience of Antimicrobial Resistance Action (CARA) will be to hold the UN—including its subsidiary organizations, the World Health Organization (WHO), Food and Agriculture Organization (FAO), and the World Organization for Animal Health (OIE)—accountable for ensuring that countries live up to their commitments to create national action plans to reduce AMR. Those action plans are one of the key features of a political declaration on AMR that was adopted by UN member states yesterday.

In a press release, the alliance said its goals would include improving the surveillance of antibiotic use and resistance; helping define "appropriate antimicrobial use" and using this definition to guide stewardship efforts; ensuring universal access to antibiotics, especially in low-income countries; reinforcing judicious use of antimicrobials in agriculture; and supporting the development of new antimicrobials, diagnostic tests, and vaccines. CARA said it also plans to adopt clear, quantitative targets for meeting those goals and reporting on progress.

The nine founding members of the alliance are the Center for Disease Dynamics, Economics & Policy, the British Society for Antimicrobial Chemotherapy, the Antibiotic Resistance Action Center, the Center for Global Development, the German Center for Infection Research, the Pew Charitable Trusts, the Norwegian Institute of Public Health, the World Alliance Against Antibiotic Resistance, and the Center for Infectious Disease Research and Policy (publisher of CIDRAP News) at the University of Minnesota. The group plans to add partners from other sectors and countries.
Sep 20 CARA press release

Powerful new resistance mechanism found in Campylobacter

Researchers in China have identified the emergence of a new mechanism that enhances resistance to multiple classes of antibiotics in Campylobacter bacteria.

The new mechanism is a variant of CmeABC, an efflux pump that confers multidrug resistance in Campylobacter. Efflux pumps are considered an important mechanism for antibiotic resistance; they help protect bacterial organisms by pushing antimicrobials and other toxins out of cells.

In the study, published this week in mBio, researchers characterized the variant—which they've coined RE-CmeABC—as a "super" efflux pump that is much more potent. It desensitizes Campylobacter to multiple classes of antibiotics, and it confers high levels of resistance to fluoroquinolones, which are the primary class of antibiotic used in Campylobacter infections. It also promotes the emergence of fluoroquinolone-resistant mutants under selection pressure.

The researchers said RE-CmeABC is especially prevalent in C jejuni and is emergent in chickens and pigs in China, the likely result of extensive use of antimicrobials in Chinese agriculture. In addition, their analysis found that RE-CmeABC can spread to other types of bacteria through horizontal gene transfer. They concluded that it will probably continue to spread in clinical isolates.

"Thus, enhanced efforts are needed to prevent its further dissemination," they wrote.

Campylobacter bacteria, particularly C jejuni, are the most common cause of diarrheal illness in humans. Infections usually result from consuming undercooked or contaminated poultry, unpasteurized milk, or contaminated water. Drug-resistant Campylobacter is listed as a serious antibiotic resistance threat by the US Centers for Disease Control and Prevention.
Sep 20 mBio study

News Scan for Sep 22, 2016

News brief

WHO: More evidence of camel-MERS link in recent Saudi cases

Yesterday the World Health Organization (WHO) described five recent cases of MERS-CoV in Saudi Arabia, providing more evidence of the risk that camel contact poses in transmitting the disease.

The five cases of MERS-CoV (Middle East respiratory syndrome coronavirus) were documented between Aug 23 and Sep 11. Three of the cases involved direct contact with camels. Both a 55-year-old Saudi man from Arar city, and a 40-year-old expatriate man from Al Hofuf reported drinking raw camel milk in the 14 days before symptom onset. The man from Arar is in stable condition, while the other man is in critical condition and on mechanical ventilation.

A 65-year-old man from Riyadh also was diagnosed as having MERS after he had contact with camels. He remains in stable condition.

Another case was described in a 43-year-old Saudi man from Huraymila, who was a household contact of another MERS patient. He has no co-morbidities and is in stable condition. Finally, a 69-year-old Saudi man from Taif city is in stable condition after contracting the disease. He has no known risk factors.

According to the WHO, since September of 2012 there have been 1,806 laboratory-confirmed cases of MERS-CoV, including at least 643 related deaths.
Sep 21 WHO update

First in new malaria drug class shows promise in human trial

A trial of a new class of malaria drug called KAF156 in humans showed activity against both types of malaria parasites, Plasmodium falciparum and Plasmodium vivax, including those that were resistant to artemisinin, researchers reported yesterday in the New England Journal of Medicine.

New malaria drugs are urgently needed to battle the emergence of drug-resistant malaria parasites, and the new drug, if cleared, would be used as a combination treatment, part of a strategy to curb resistance. KAF156 is the first in a new class of drugs called imidazolopiperazines, and though scientists are still characterizing how it works, they think it may target a previously unknown Plasmodium falciparum gene. Novartis is part of the team that developed and supported the drug, along with support from the Wellcome Trust, the Singapore Economic Development Board, and the Medicines for Malaria Venture.

The phase 2 study enrolled adults from five centers in Thailand and Vietnam from March to August 2013 and compared two dosing schedules: 400 mg taken once daily for 3 days and a single 800 mg dose. The multiple-dose group included 21 participants who sought treatment for malaria, 11 with P vivax, and 10 with P falciparum. The single-dose group contained 22 patients, all with P falciparum.

Symptoms resolved and parasites cleared quickly in the subjects, faster than for several other drugs including mefloquine, slightly slower than for artemisinin, and significantly slower than for cipargamin, an experimental drug that offers the fastest known clearance. Adverse events, mainly vomiting and nausea, were more common in the single-dose group.

Thierry Diagana, PhD, who leads the Novartis Institute for Tropical Diseases, said in a company press release that KAF156 has the potential to be a game-changing treatment for malaria. "It acts against the two main parasites responsible for the majority of malaria deaths and against the blood and liver stages of the parasite's lifecycle."
Sep 21 N Engl J Med abstract
Sep 22 Novartis press release

CDC snapshot of summer flu reveals a few recent outbreaks, novel flu cases

In an overview today of flu activity over the summer, the US Centers for Disease for Control and Prevention (CDC) said levels were low overall, but starting in late August it began receiving reports of a few localized outbreaks fueled by influenza A H3N2.

The report, published in the latest issue of Morbidity and Mortality Weekly Report, also describes antigenic and genetic analysis of recently circulating flu strains, which helps experts monitor which ones are dominating and how closely circulating strains so far match the ones included in this year's seasonal flu vaccines.

From May 22 through Sep 10, all three strains circulated, but since July, influenza A was detected more often, with 84% of them H3N2. Over the same time period, 20 novel influenza A viruses were detected, up from 6 cases reported last year. Two involved variant H1N2 and 18 H3N2v. Both H1N2v case-patients had contact with pigs before they got sick and all of the H3N2v cases were reported in August in people who were exposed to pigs at fairs.

Antigenic testing found that recent 2009 H1N1 viruses closely match the upcoming season's component for that strain. Genetic sequencing found the 6B.1 subgroup predominated.

For the H3N2 virus, antigenic testing of recent strains found that almost 84% were similar to the cell-propagated virus representing the vaccine component, with a smaller proportion similar to the egg-propagated virus representing the vaccine strain. Recent influenza B viruses also were a close match with the vaccine strains.

The CDC said it's not possible to predict which strain will dominate during flu season or how effective the vaccine will be. However, it added that monitoring since February hasn't detected any significant antigenic changes, such as drift, which caused problems with vaccine protection during the 2014-2015 flu season.

The 2015-2016 flu season started later and saw lower levels of activity compared to the last few flu seasons, with 2009 H1N1 as the dominant strain.
Sep 22 MMWR report

Taiwan reports H5N2 outbreak; Netherlands notes no H5N8 in wild birds

In new H5 avian flu developments, officials in Taiwan report H5N2 in poultry, researchers note a lack of H5N8 in wild birds in the Netherlands, and H5N5 has been confirmed in an Antarctic penguin.

The outbreak in Taiwan affected a backyard flock in Hsinchu County in the north more than a month ago, according to a report posted by the World Organization for Animal Health (OIE) yesterday. Of 508 susceptible birds, 114 died from H5N8 and the remaining 394 were culled to prevent disease spread. Taiwan has reported a number of H5N2 outbreaks this year.
Sep 21 OIE report

Dutch researchers stepped up surveillance for highly pathogenic avian influenza (HPAI) H5N8 in wild birds after the strain was reported in sporadic outbreaks in Europe starting in late 2014. In a study today in Eurosurveillance, they report on results of sampling from Feb 21, 2015, to Jan 31, 2016.

The investigators detected only 1 H5N8-positive sample among 7,337—in a Eurasian wigeon that was sampled on Feb 25, 2015. They also report, "Antibodies specific for HPAI H5 clade 2.3.4.4 were absent in wild bird sera obtained before 2014 and present in sera collected during and after the HPAI H5N8 emergence in Europe, with antibody incidence declining after the 2014/15 winter."

The authors conclude, "Our results indicate that the HPAI H5N8 virus has not continued to circulate extensively in wild bird populations since the 2014/15 winter and that independent maintenance of the virus in these populations appears unlikely."
Sep 22 Eurosurveill study

Finally, avian flu has been detected in penguins in Antarctica on an island where the disease was previously undetected and in two species in which it had not been reported, according to a letter yesterday in Emerging Infectious Diseases. A virus from one of the birds was found to be H5N5.

Last year and this year, Chilean and US scientists collected samples from nine location on the Antarctic Peninsula, obtaining 138 blood samples from Adelie penguins and 513 cloacal swabs from Adelie, chinstrap, and gentoo penguins. Polymerase chain reaction identified avian flu viruses in 21 samples (8 from chinstraps and 13 from gentoos) on Aitcho Island, an avian flu first for both the island and those species.

Genetic sequencing of a virus from one of the chinstrap penguins determined that it was H5N5.
Sep 21 Emerg Infect Dis letter