News Scan for Apr 10, 2017

African Zika circulation
Chikungunya spike
Carbapenem-resistant E cloacae
Resistant Klebsiella
Ebola studies
Pneumonia and sedatives

Tests reveal Zika circulating in Africa for more than 20 years

Zika virus has been silently circulating in West Africa for more than two decades, according to a study of 387 blood samples collected from 1992 to 2016, researchers from Harvard University, Nigeria, and Senegal reported in the Journal of Infectious Diseases.

The virus was first identified in 1947 but wasn't linked with known epidemics until 2007 and hadn't been linked to neurologic disease before 2015.

Given the need to better characterize Zika prevalence in regions where the mosquito vector is present, the study team looked at blood or serum samples from febrile patients (who had HIV or malaria) from three different study groups in Senegal and Nigeria. They screened all of the samples for Zika immunoglobulin M (IgM) antibodies and found a 6.2% Zika seroprevalence. Samples that were positive Zika antibodies were also screened for dengue virus. All positive Zika samples were negative for dengue virus IgM. Of the Zika-positive samples, 70% were from female patients, in line with the percentage of female study participants.

The Zika envelope protein gene was amplified from four samples. Phylogenetic analysis showed that the Zika viruses were from the African lineages, with three clustering with viruses collected from Nigerian mosquitoes and one most closely related from mosquito Zika viruses collected from Ivory Coast.

The researchers said the findings also show, in addition to the fact that Zika has been circulating in Africa for many years, that infections occur alongside other illnesses, highlighting the need for better tests to distinguish Zika from febrile infections.
Apr 8 J Infect Dis abstract


PAHO reports 7,000-case chikungunya jump fueled by infections in Brazil

The Pan American Health Organization (PAHO) reported 7,342 new chikungunya cases and 5 new related deaths late last week, driven almost entirely by new infections in Brazil.

In the previous weeks, the Americas reported 207 and 526 new cases, but 4 weeks ago countries logged 7,091 new cases—again attributed in large part to infections in Brazil. The case count for 2017 has now reached 20,319, PAHO said in its Apr 7 update.

Brazil, reporting on 3 weeks' of catch-up data, noted 7,231 new cases and 17,525 for the year, or 86% of the total. Peru had the second-largest increase, with 61 new infections and only 411 total cases for 2017. The five new chikungunya-related deaths are all in Brazil, bringing the country's—and region's—total to six fatalities.

Many nations, however, have not reported on their chikungunya situation for weeks. Even Brazil is not up to date, as its data are current only through week 10 of the year, even though the PAHO report covers cases through week 14.

The chikungunya outbreak began in late 2013 on the Caribbean island of St. Martin and has now sickened at least 2,407,346 people.
Apr 7 PAHO update


Study finds rising carbapenem resistance in Enterobacter cloacae

New data from the Veteran's Health Administration (VHA) suggests rising carbapenem resistance in Enterobacter cloacae, researchers report in Emerging Infectious Diseases.

Carbapenem-resistant Klebsiella pneumoniae emerged as an epidemic in US healthcare settings over a decade ago, but it's not the only Enterobacteriaceae species that has exhibited resistance to carabapenems, and recent outbreaks of E cloacae harboring K pneumoniae carbapenemase (KPC) have raised concerns about carbapenem resistance in E cloacae complex (E cloacae, E asburiae, E kobei, E hormaechei, E xiafangensis). Using clinical and microbiologic data from the VHA network, researchers set out to observe national trends of carbapenem resistance and nonsusceptibility in K pneumoniae and E cloacae complex during the past decade.

For the study, the researchers identified 128,431 K pneumoniae and 38,219 E cloacae complex isolates from 140 VA facilities in 40 states and tested them for susceptibility to carbapenems. The data showed that carbapenem-resistant K pneumoniae and E cloacae complex both spread beyond the eastern United States from 2006-2015, with carbapenem-resistant E cloacae centered in the Southwest and Pacific Coast by 2014-2015.

But while carbapenem resistance and nonsusceptibility rates among K pneumoniae isolates remained steady over the decade (over 1% resistance and 3%-4% nonsusceptibility), rates of resistance and nonsusceptibility increased in E cloacae complex, with more than 4% of isolates showing nonsusceptibility to carbapenems and 2.5% showing resistance in 2014-2015.

These results, the authors write, indicate that a "second epidemic of carbapenem-resistant E cloacae complex appears to be unfolding." Although the genetic background is not well defined, they hypothesize that carbapenem-resistant E cloacae complex "contains genotypes with epidemic potential associated with increasing rates of carbapenem resistance observed at the VHA."

The authors suggest integration of susceptibility testing with molecular characterization at the VHA could help clarify the changing epidemiology of carbapenem-resistant Enterobacteriaceae in the United States.
Apr 7 Emerg Infect Dis research letter

Tigecycline- and carbapenem-resistant K pneumoniae in Taiwan

A Taiwanese study has found a high mortality rate in patients with tigecycline- and carbapenem-resistant Klebsiella pneumoniae, researchers report in PLoS One.

In the study, researchers with Taiwan's National Defense Medical Center collected clinical isolates of carbapenem nonsusceptible K pneumoniae isolates from 21 hospitals across the country from January 2012 through December 2014. They were looking to explore the clinical characteristics and outcome of carbapenem-resistant K pneumoniae that is also resistant to tigecycline, one of the few remaining antibiotic options for treatment of carbapenem-resistant bacterial infections. They also wanted to determine the mechanisms of resistance.

Overall, 1,093 isolates were collected, and 16 of those were identified as tigecycline- and carbapenem-resistant K pneumoniae. The patients were, for the most part, critically ill, with 10 suffering from urinary tract infections. Other infections included pneumonia (2), biliary tract infections (2), bacteremia (1), and peritonitis (1). The 30-day mortality of the 16 patients was 44%, with a much higher mortality rate in the non-urinary tract infection patients (83% vs. 20%). Comparison with a case control group showed that the mortality for tigecycline-susceptible carbapenem-resistant K pneumonia infection was 31%.

Pulsed-field gel electrophoresis and multilocus sequence typing revealed no dominant clone or sequence type among the isolates, and quantitative real-time polymerase chain reaction analysis identified over-expression of both the efflux pump genes acrB and oqxB in seven of the isolates and oqxB in another seven. But because overexpression of these genes was not detected in two of the isolates, the researchers believe other factors may be involved in mediating tigecycline resistance.

Given how difficult the infections are to treat, the authors conclude that "efforts are urgently needed to improve the knowledge of the epidemiological status of tigecycline resistance accompanied by carbapenem resistance in order to tackle its spread."
Apr 7 PLoS One research article


New compendium on Ebola addresses vaccines, outbreak control

The journal Philosophical Transactions of the Royal Society B: Biological Sciences published a 15-article theme issue on West Africa's 2013-2016 Ebola outbreak today. In an introduction to the special issue, journal editors said this is the first compendium that addresses the largest Ebola epidemic in history, and contains the first review of Ebola vaccine candidates.

The development of a vaccine is the most important outcome from the research conducted during the outbreak, the editors said, but the issue also contains studies on death rates, asymptomatic infections, transmission risk, and outbreak control. Despite having 3 years to conduct studies on the virus, the editors said there was a paucity of data collected on disease interventions and prophylactic vaccine candidate use.

"The impact of this epidemic on individuals, healthcare, societies and economies was profound and will last many years beyond the end of the epidemic," the editors said in the introduction to the issue. "Looking forward, we sincerely hope that recommendations will be enacted and will translate into tangible solutions."
Apr 10 PTRSB issue


Study links sedatives to pneumonia in Alzheimer's patients

Commonly used sedatives called benzodiazepines are associated with an increased risk of pneumonia when prescribed to people who have Alzheimer's disease, according to a study published in CMAJ (Canadian Medical Association Journal) that was designed to show only a link, not whether the drugs were the cause of pneumonia.

Dementia, of which 60% to 70% of cases involve Alzheimer's, is a risk factor for pneumonia, and many people with dementia take benzodiazepines and non-benzodiazepines called Z-drugs, both sedatives, according to a CMAJ news release.

To determine a possible link, Finnish researchers looked at data from national registries on 49,484 adults with Alzheimer's from 2005 to 2011 in Finland. The mean age of participants was 80, and 62.7% were women. The investigators matched 5,232 patients taking benzodiazepines and 3,269 patients taking Z-drugs with the 40,983 not taking either drug.

They found that benzodiazepines were linked to a 28% increased risk of pneumonia in patients with Alzheimer disease, with the risk highest (doubled) during the first 30 days of treatment. The association between Z-drug use and pneumonia, in contrast, was not statistically significant. (But the authors did not conclude Z-drugs were safer, because the study did not address that.)

The results are consistent with studies that have found an increased risk of pneumonia in patients of all ages taking benzodiazepines, according to the CMAJ release. The authors suggest that the sedative nature of benzodiazepines may increase the risk of pneumonia by increasing the aspiration of saliva or food into the lungs.

"Benefits and risks of the use of benzodiazepines should be carefully considered for patients with Alzheimer disease and include risk of pneumonia," the authors conclude.
Apr 10 CMAJ abstract
Apr 10 CMAJ press release

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