News Scan for Sep 14, 2016

News brief

Report notes multidrug-resistant CRE after combo treatment

Investigators from the University of Pittsburgh yesterday reported 3 cases of ceftazidime-avibactam resistance after 37 patients who had carbapenem-resistant Enterobacteriaceae (CRE) infections were treated with the combination, according to a case series in Clinical Infectious Diseases.

The scientists reported a 59% success rate (22/37), with 9 deaths, 4 recurrent CRE infections, and 2 patients with no clinical improvement. Microbiologic failure, defined as isolation of CRE after 7 or more days of ceftazidime-avibactam therapy, occurred in 10 of the 37 patients (27%), with 5 patients having recurrent CRE at 30 days and 4 at 90 days and 1 patient having urinary colonization with CRE.

Of those 10 patients, ceftazidime-avibactam resistance was detected in 3. Ceftazidime is a third-generation cephalosporin, and avibactam is a beta-lactamase inhibitor.

An accompanying commentary by Brad Spellberg, MD, of the University of Southern California and Robert Bonomo, MD, of Case Western Reserve University in Cleveland, said the fact that the resistance developed after only 10 to 19 days of ceftazidime-avibactam therapy is especially worrisome.

"It is important not to draw firm conclusions from an uncontrolled, retrospective case series," the commentary authors wrote. "Nevertheless, this is a very important study, as it is the first meaningful clinical evaluation of the efficacy of ceftazidime-avibactam when treating CRE infections, and among a fairly large number of patients with CRE. The results are quite concerning. Mortality continues to be high, and resistance seems to emerge rapidly."
Sep 13 Clin Infect Dis abstract
Sep 13 Clin Infect Dis commentary

Pair of studies underscore benefits of prenatal Tdap vaccination

Immunization with the tetanus, diphtheria, and pertussis (Tdap) vaccine during roughly the third pregnancy trimester was more effective than postpartum vaccination at preventing pertussis in babies in their first weeks of life, according to a retrospective cohort study of California mothers. Researchers based at the California Department of Public Health, using California Immunization Registry data from 2013 through 2014, reported their findings yesterday in Clinical Infectious Diseases.

Among the state's live births during those 2 years, 74,791 women had a record of Tdap vaccination during pregnancy or within 14 days of birth. After excluding mothers who delivered babies at less than 27 weeks' gestation or weighing less than 500 grams, the team included 74,504 for the study—58% who were vaccinated during pregnancy and 42% who were vaccinated postpartum.

Of the women vaccinated during pregnancy, 77% received Tdap during the recommended period of 27 to 36 weeks gestation. Of women vaccinated after delivery, most received Tdap within the first 2 days, most likely during hospitalization.

Tdap received during the recommended 27-to-36-week period was 85% more effective than postpartum vaccination at preventing pertussis in babies younger than 8 weeks old. The researchers said the findings underscore the importance of providing Tdap to pregnant women during prenatal visits at the earliest opportunity from 27 to 36 weeks' gestation.
Sep 13 Clin Infect Dis abstract

In other Tdap research, a group including two authors of the above study found that babies with pertussis who were born to mothers who were vaccinated during pregnancy had less severe disease compared with unvaccinated mothers. The findings from the retrospective cohort study also appeared yesterday in Clinical Infectious Diseases.

From Jan 1, 2011, through Dec 31, 2015, 752 pertussis infections were reported in California babies younger than 63 days old. Of 420 babies with complete maternal vaccination information, 49 mothers (12%) got Tdap during pregnancy, with the rest unvaccinated or vaccinated after delivery. Of 18 moms vaccinated during the third trimester, 14 received it during the recommended 27-to-36-week window.

Overall vaccine effectiveness (VE) for preventing hospitalization was 72%, and after adjusting for infants' chronological and gestational age, as well as babies' receipt of diphtheria-tetanus-acellular pertussis (DTaP) vaccination, VE was 58%. None of the babies born to vaccinated mothers were intubated or died.

Babies born to mothers who were vaccinated during pregnancy had a significantly lower risk of hospitalization (RR 0.5; 95% confidence interval [CI] 0.4-0.6) or intensive care unit admission (RR 0.8, 95% CI 0.7-0.9). Among infants who were hospitalized, those born to vaccinated moms had shorter hospitalizations (median 3 versus 6 days).

The researchers said their findings are the first known study to show that prenatal Tdap vaccination cuts disease severity in infected infants, adding that the results emphasize how critical the vaccination strategy is for reducing pertussis illnesses and deaths.
Sep 13 Clin Infect Dis abstract

Study shows novel screen-and-treat malaria approach not effective

A novel approach that is one of the main interventions to protect pregnant women in sub-Saharan Africa from malaria does not work any better than a simpler approach, according to a study yesterday in PLoS Medicine.

The novel strategy—in which pregnant women are screened every 4 to 6 weeks for malaria with rapid diagnostic testing and treated with dihydroartemisinin-piperaquine (DP) only if they test positive—does not lower the risk of poor pregnancy outcomes compared with treating all pregnant women with sulfadoxine-pyrimethamine (SP) at the same 4- to 6-week office visits, an international team of researcher found. The novel treatment approach was devised in response to increased resistance of the malaria parasite to SP, which in some areas has topped 90%. The World Health Organization recommends SP for pregnant women.

The study involved 1,873 pregnant women in Malawi from Jul 21, 2011, to Mar 18, 2013. The prevalence of adverse birth outcomes varied little between the two groups, from 29.9% in the screen-and-treat group to 28.8% in the SP group.

In addition, the prevalence of malaria at delivery was higher in the screen-and-treat group, at 48.7%, compared with 40.8% in the SP group.

The results, however, may not hold true in all areas because the risk of malaria transmission and level of drug resistance varies by location, according to a Public Library of Science (PLoS) news release. In addition, the study did not probe the effects of using monthly DP without screening.
Sep 13 PLoS Med study
Sep 13 PLoS news release

WHO: No major health events at the Hajj, flu levels lower

No major disease outbreaks or other public health threats surfaced during the Hajj pilgrimage that just concluded in Saudi Arabia, which drew about 2 million people, the World Health Organization (WHO) said today after wrapping up its mission in the country to support the health ministry.

Before the event, the Saudi Ministry of Health (MOH) and the WHO did a risk assessment of health hazards that could crop up during the pilgrimage, and the MOH undertook several preventive measures in, for example, infection prevention, risk communication, and how to avoid heat illness.

Early findings point to a decline in flu morbidity and mortality compared with last year's Hajj, the WHO said. It added that the downturn could be related to the MOH decision to require flu vaccination for pilgrims and that some countries vaccinated their travelers based on Saudi Arabia's health requirement.

"No cases of Middle East respiratory syndrome coronavirus (MERS-CoV) have been reported so far among pilgrims," the WHO said. "Of 344 samples collected and tested by the national public health laboratory, none was found to be positive for MERS-CoV."
Sep 14 WHO statement

Flu Scan for Sep 14, 2016

News brief

Outbreak H5N2 viruses from 2015 show increased adaptation to chickens

The highly pathogenic H5N2 avian flu virus strain that caused outbreaks in poultry flocks across the United States is better adapted to chickens than a precursor H5N2 virus and is highly adapted to wild ducks, according to a new study by US Department of Agriculture (USDA) scientists published in Virology.

The researchers inoculated chickens and mallard ducks with one of 4 outbreak H5N2 viruses, 3 from affected turkey farms in Minnesota, South Dakota, and Arkansas, and 1 from a chicken outbreak in Iowa. They found that 3 of the viruses were better adapted to chickens compared with a wild-type H5N2 strain isolated from a norther pintail duck in Oregon in 2014.

But they also found that transmission of these four poultry isolates was not increased compared with the wild-type strain except in the case of the Minnesota isolate, which is at odds with what happened in the 2015 outbreaks: fairly rapid farm-to-farm spread of the disease. The USDA authors say a number of factors could be at play in this discrepancy, such as environmental factors, secondary infections, and the physiological stress of egg-laying.

"So although we see indications of increased adaptation to chickens," the authors wrote, "the viruses are still in transition to being fully chicken-adapted viruses."

In the mallard experiments, the team found the poultry viruses highly adapted. Also, two of the poultry isolates had a similar high infectivity as the pintail H5N2 virus, while the other two had a lower rate. The investigators also found that the H5N2 poultry isolate from Minnesota occasionally caused deaths in the ducks at high doses.

"This increased virulence in mallards was unexpected since this virus showed increased adaptation to chickens," the researchers wrote. "However, previous experiments have shown great variability in virulence in ducks."
Sep 12 Virology study

Protein Sciences awarded BARDA grant for pandemic vaccine

Protein Sciences announced that it has received a contract from the Biomedical Advanced Research and Development Authority (BARDA) to enlist the company's proprietary cell-based flu vaccine platform in making pandemic vaccine, according to a Sep 7 press release.

The company, of Meriden, Conn., said the contract will cover preparation of the starting materials to prepare for multiple potential pandemics. The preparations could shave a month or more off the time when Protein Sciences would have a vaccine available, the company said. It added that the contract is worth up to $610 million through 2021 if BARDA, part of the US Department of Health and Human Services (HHS), exercises all its options.

Manon Cox, PhD, MBA, Protein Sciences president and chief executive officer, said in the statement, "We are very pleased to extend our relationship with BARDA and support them in their mission to provide 'More, Faster, Better' vaccines in the face of a pandemic."

Protein Sciences' recombinant protein-based cell-culture flu vaccine platform , already used to make the seasonal flu vaccine Flublok, is the only vaccine made without using egg-based technology. It doesn't require infectious flu virus, antibiotics, preservatives, or adjuvants. In 2009 the company won a BARDA contract for late-stage development.

A 2012 analysis of the flu vaccine landscape found that alternative platforms such as cell culture likely shorten production time and are less vulnerable to contamination, but added that flu vaccines that continue to target the hemagglutinin head of the virus have limited capacity to boost effectiveness or provide broad durable protection against a range of flu viruses.
Sep 7 Protein Sciences press release
Oct 2012 flu vaccine analysis "The Compelling Need for Game-Changing Influenza Vaccines"