VHF Scan for Sep 02, 2016

News brief

Spain reports its first 2 cases of Crimean-Congo hemorrhagic fever

Spain has reported its first two cases of Crimean-Congo hemorrhagic fever (CCHF)—one of them fatal—a tick-borne viral disease that is found in eastern Europe, the Middle East, Africa, and much of Asia.

The fatal case involved a 62-year-old man who had had a tick bite and died in a Madrid hospital, according to yesterday's weekly communicable disease update from the European Centre for Disease Prevention and Control (ECDC). The other patient is an intensive care nurse who became infected while caring for the 62-year-old man; her condition was not described.

Medical authorities are assessing 200 people who had contact with the two patients, and some are being confined to their homes, the ECDC said.

Although Spain has not had any CCHF cases before, the CCHF virus was found in the country in 2010, according to the infectious disease blog Avian Flu Diary. The blog cited a 2012 report in Emerging Infectious Diseases that said the virus was found in red deer in Caceres, Spain, in 2010. It was closely related to CCHF viruses in Senegal and Mauritania in West Africa, suggesting that it could have been brought to Spain by migratory birds, the report said.

CCHF virus is carried by ixodid (hard) ticks, and many animals, including cattle, sheep, goats, and hares, serve as amplifying hosts, according to the US Centers for Disease Control and Prevention (CDC). Humans catch the disease through tick bites or contact with animal blood, and the virus can spread from person to person via body fluids.

CCHF has a sudden onset and severe symptoms and signs that can include uncontrolled bleeding, according to the CDC. In outbreaks, mortality rates in hospital patients have ranged from 9% to 50%.
Sep 1 ECDC report
Sep 2 Avian Flu Diary post
2012 Emerg Infect Dis report on CCHF virus
CDC information on CCHF

Ebola cluster traced to sexual transmission 15 months after man's illness

A cluster of Ebola cases in Guinea earlier this year has been traced to sexual transmission from a man who had recovered from the disease close to 15 months earlier, marking the longest known period of sexual transmissibility after recovery from the disease.

"Evidence for sexual transmission of the persisting EBOV in February 2016, about 470 days after onset of symptoms in the survivor, is compelling," says the report by an international team of researchers, published yesterday in Clinical Infectious Diseases.

The cluster involved 3 probable and 7 confirmed cases in Guinea, with 8 deaths, in February, March, and April of this year, the report says.

Genomic analysis of the viruses showed they were closely related to strains from West Africa's epidemic, but they were most closely related to a cluster dating to 2014 rather than to late 2015 strains. They matched most closely with the virus from a man who was admitted for treatment in Gueckedou, Guinea, in November 2014 and survived.

An epidemiologic investigation revealed that case-patient 1 from the 2016 cluster had intercourse with the Gueckedou Ebola survivor in late January 2016. Semen samples collected from the survivor on Mar 21 and Apr 9 tested positive for the virus. Genetic sequencing then revealed that his virus was identical to those in cases 4 and 5 of the new cluster, "supporting the epidemiologic evidence of sexual transmission." Additional sequencing and phylogenetic analysis indicated that the whole cluster was linked with the man.

The authors said their results suggest that Ebola virus persisted in the survivor for 531 days—from Oct 26, 2014, until Apr 9, 2016. (Another report from Liberia earlier this week noted that Ebola RNA was found in one survivor's semen 565 after his recovery, but it was not known if it represented viable virus.)

The longest previous case of viable Ebola virus persistence in semen, as indicated by likely transmission, was 179 days after illness onset, the researchers said, citing a 2015 report.

In other observations, the researchers said the virus harbored by the Ebola survivor evolved extremely slowly. Virus in blood collected Nov 3, 2014, differed from that in semen collected Mar 21, 2016, by just five mutations, indicating an evolution rate six times slower than the average rate seen in the West African epidemic.
Sep 1 Clin Infect Dis report
Related Aug 31 CIDRAP News item

ASP Scan (Weekly) for Sep 02, 2016

News brief

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


Four CRE cases reported in Wisconsin

Originally published Sep 1.

Investigators with the Centers for Disease Control and Prevention (CDC) today describe a small cluster of the worrisome "superbug" known as carbapenem-resistant Enterobacteriaceae (CRE) at two Wisconsin hospitals in Morbidity and Mortality Weekly Report (MMWR).

According to the report, officials with the Wisconsin State Laboratory of Hygiene notified the Wisconsin Division of Public Health in June 2015 that five carbapenemase-producing CRE isolates had been identified among four inpatients at two hospitals in southeastern Wisconsin. They all contained the KPC gene, which codes for Klebsiella pneumoniae carbapemenase.

The KPC-CRE isolates were identified among 49 isolates obtained from 46 patients from February to May 2015. The median age of the four patients (two men and two women) was 65, and median hospitalization length was 83 days. All four patients had been intubated and undergone a tracheostomy.

Further investigation revealed that the five isolates exhibited a high degree of genetic relatedness but did not uncover how the bacteria traveled between the two facilities. Active surveillance conducted at the two hospitals in July 2015 identified no further cases. Site visits, reviews of infection prevention protocols, and interviews with infection prevention staff members, primary care providers, and patients found no breaches in recommended practices.

The authors of the report say the findings demonstrate the importance of routine hospital- and laboratory-based surveillance for the detection of healthcare-related CRE. In this case, staff at neither of the two hospitals was aware of the possibility of CRE transmission among their patients. The authors also say the use of molecular subtyping methods (like whole-genome sequencing) to determine the genetic similarities in the isolates was particularly valuable.
Sep 2 MMWR report


ASP intervention not found to improve outcomes in C diff patients

Originally published Sep 1.

A study today out of the University of Michigan has found a real-time antibiotic stewardship program (ASP) intervention in patients with Clostridium difficile infection (CDI) improved process measures but did not improve outcomes.

The study, published in the American Journal of Infection Control, details the results of what the authors call a "quasiexperimental" study of adult CDI patients before and after a real-time ASP review was initiated.

In the intervention group (285 patients), an ASP pharmacist was called in after diagnosis to review each case with the medical team and make recommendations on optimal treatment, antibiotic therapy and acid-suppressing therapy, and surgical/infectious disease consultation. In the control group (307 patients), CDI treatment was left to the discretion of the patient's primary medical team. Overall, ASP pharmacists provided treatment recommendations for 129 of the 285 patients in the intervention group.

The primary measurement of the study was a composite of several outcomes—including 30-day mortality, intensive care unit admission, surgery, and CDI recurrence. But process measures that may influence outcomes in CDI patients were also measured, with researchers looking at whether acid-suppressive therapy was reduced in CDI patients and whether patients with severe CDI received infectious disease consultation and appropriate and timely antibiotic therapy.

In the end, the researchers found that ASP intervention reduced unnecessary acid-suppressing therapy when compared with the control group. And patients with severe CDI who received ASP intervention were more likely to be treated with vancomycin, receive vancomycin therapy more quickly, and receive infectious disease consultation than the patients in the pre-intervention group. This finding is in line with previous studies on ASP intervention in CDI patients.

However, the investigators were not able to demonstrate a statistically significant improvement in primary clinical outcomes among the patients who received ASP intervention. Occurrence of primary composite outcome was 14.7% in the pre-intervention group and 12.3% in the intervention groups. The authors of the study say this may be due to the low baseline rates of these outcomes among the patients.

In conclusion, the authors say their findings, when added to previous literature on the topic, raise questions about whether ASP involvement in the conventional management of CDI is worthwhile, especially in institutions with low rates of CDI-attributable complications.
Sep 1 Am J Infect Control study


Study: Written reports help dentists reduce antibiotic prescribing

Originally published Aug 31.

A new UK study has found that dentists prescribe fewer antibiotics to their patients after receiving a report on their past prescribing habits.

According to the study, published yesterday in PLoS Medicine, dentists prescribe roughly 10% of the antibiotics dispensed in UK community pharmacies, often in the absence of clinical need. Using dental prescribing and treatment claim data routinely collected by the UK National Health Service (NHS), researchers with the RAPiD (Reducing Antibiotic Prescribing in Dentistry) trial set out to determine whether an individualized audit and feedback intervention could have an impact on prescribing habits.

The trial included 795 dental practices in Scotland, with 632 practices in an intervention group and 163 in a control group. The intervention group was further subdivided into two groups: one that received a line graph showing an individual dentist's monthly prescribing rate, and another that received a line graph with a written "behavior change" message containing national guidelines for dental antibiotic prescribing.

At the start of trial, the rate of antibiotics prescribed per 100 NHS treatment claims was 8.3 in the control group and 8.5 in the intervention group. After 12 months, the researchers found that both groups were prescribing fewer antibiotics. But the drop in the prescribing rate in the intervention group—from 8.5 to 7.5—was 5.7% greater than it was for the control group. And the subset of dentists who received a written message saw their prescribing rate drop by an additional 6%.

The authors of the study wrote that the findings are significant because they indicate that a "relatively straightforward, low-cost public health and patient safety intervention" could help the entire healthcare system address antimicrobial resistance.
Aug 30 PLoS Med study


Review outlines economic incentives for antibiotic development

Originally published Aug 31.

Limited commercial returns are considered a primary factor in why pharmaceutical companies are not investing in antibiotic development. That's why a "constellation of economic incentives" will be needed to promote antibacterial drug development going forward, according to an article published yesterday in Clinical Infectious Diseases.

The article, written by members of the Trans-Atlantic Task Force on Antimicrobial Resistance (TATFAR), is a review of the various economic incentives identified in policy documents, peer-reviewed publications, organization proposals, and government-sponsored reviews that have addressed the question of how to spur new antibiotic development. In October 2015, TATFAR agreed to make an informed recommendation on a package of economic incentives to be considered and implemented in the future.

In those documents, the authors found a consensus around the idea that economic incentives must contain both "push and pull" mechanisms that will guarantee return on investment. Push incentives include subsidies (in the form of grants, public-private partnerships, and tax credits) to fund early-stage development of antimicrobials, which is often risky and expensive. The idea is to provide incentives to academic institutions and companies by providing up-front money for research and development.

Pull incentives, on the other hand, are meant to encourage antibacterial drug development by promising a substantial financial reward to companies that successfully develop new antibiotics. Examples include large milestone or prize payments, patent buy-outs, advanced market commitments, and extended market exclusivity.

Pull incentives, the authors found, will be most successful if they rely on a "de-linkage" model that would remove the motivation for pharmaceutical companies to market and oversell their product. Negating the need for high product sales, they argue, would ensure that new antibiotics are not overused, thereby linking new antibiotic development to conservation and stewardship.

Finally, the authors found widespread agreement that global coordination will be needed to administer the funding of these incentive programs. 
Aug 30 Clin Infect Dis literature review


Growing polymyxin resistance reported in CRE in Brazil

Originally published Aug 31.

Brazilian researchers are reporting increasing resistance to polymyxin antibiotics in clinical Klebsiella Pneumoniae strains that are already resistant to carbapenem antibiotics.

In a letter to Emerging Infectious Diseases, the researchers report on an analysis of more than 3,000 K pneumoniae isolates recovered from patients at 10 private tertiary-care hospitals in Sao Paulo from January 2011 to December 2015.

The analysis showed a dramatic increase in carbapenem resistance in the K pneumoniae isolates—from 6.8% in 2011 to 35.5% in 2015. And among the carbapenem-resistant K pneumoniae isolates, polymyxin resistance rose from 0% in 2011 to 27.1% in 2015. Polymyxin resistance among carbapenem-susceptible K pneumoniae isolates also rose, from 0.7% in 2011 to 3.9% in 2015.

The authors said the findings are worrisome because carbapenem-resistant Enterobacteriaceae (CRE) are more deadly than carbapenem-susceptible strains, and carbapenem-resistant K pneumoniae bacteria are endemic in Brazil. Furthermore, most resistant infections are treated with polymyxins.
Aug 30 Emerg Infect Dis letter


UN experts warn antibiotic resistance will put mothers, infants at risk

Originally published Aug 30.

Every year, more than 30,000 women and 400,000 newborns die from infections that occur shortly after a woman has given birth. And those numbers will likely grow as rising drug resistance renders antibiotics less effective.

That's the central message in a commentary yesterday by Anthony Costello, MD, WHO director of maternal, newborn, child, and adolescent health, and Stefan S. Peterson, MD, PhD, MPH, UNICEF chief of health. The global health experts write that overuse of antibiotics in humans, along with "needless use" in animals, has created a "recipe for disaster" by accelerating the process in which exposed microbes build resistance.

Antibiotic resistance, they say, will have a major impact on newborns, who lack fully developed immune systems and are therefore more susceptible to infections they might pick up from their mother or from the hospital. Even more at risk will be children born in low-income countries, where healthcare facilities often lack basic sanitary conditions and lifesaving antibiotics are scarce.

"More children in Africa die from a lack of access to antibiotics than from antibiotic-resistant infections," Costello and Peterson write. "Indeed, many still die from infections, such as bacterial pneumonia, that should be easily treatable."

To solve this problem of "access and excess" and save the lives of infants and mothers, Costello and Peterson write, healthcare providers need to begin by stopping the spread of infection and negating the need for antibiotics. This means that all healthcare facilities must have running water and basic sanitation, and that staff must follow good hygiene practices. They also recommend implementing policies to discharge mothers and newborns from the hospital sooner, in order to reduce exposure to infectious microbes.

And lastly, healthcare providers should use antibiotics only when they can confirm that they are absolutely needed. "Simply put, those who need lifesaving antibiotics must get them, and those who do not must not," they write.
Aug 29 WHO commentary


MCR-1 found for the first time on the Arabian Peninsula

Originally published Aug 29.

An international team of researchers is reporting the first case of the colistin-resistance gene MCR-1 on the Arabian Peninsula.

In a study published in the International Journal of Infectious Diseases, the researchers reported that out of 75 colistin-resistant Enterobacteriaceae strains isolated from clinical cases in Bahrain, Kuwait, Oman, Saudi Arabia, and the United Arab Emirates, 4 Escherichia  coli isolates were found to harbor the MCR-1 gene on mobile pieces of DNA known as plasmids. Two of the isolates were from blood samples; the two others were from urine and a bed sore.

The researchers noted that the plasmids on the four isolates all carried various genes that confer resistance to carbapenem and beta-lactam antibiotics, with one of the isolates expressing high levels of carbapenem resistance. Besides colistin—which is considered an antibiotic of last resort—all four strains were uniformly resistant to third-generation cephalosporins, tetracycline, trimetoprime/sulfamethoxasole and gentamicin.

The researchers also said that one of the plasmids identified is the first found in a human E coliisolate to carry both MCR-1 and resistance genes to other classes of antibiotics. The findings are a concern because they suggest antibiotics commonly used in humans could facilitate the spread of MCR-1-carrying bacteria.

The MCR-1 gene was first identified in China in 2015, when researchers detected its presence in E colisamples from food, food animals, and humans. Since then, it's been found in bacteria in more than 30 countries.
Aug 26 Int J Infect Dis study 


British scientists warn about drug-resistant fungal infections

Originally published Aug 29.

UK scientists say that fungal infections are becoming increasingly resistant to the drugs used to treat them and warn that deaths will likely increase with rising resistance.

Fungi can cause a host of illnesses, from minor skin infections such as ringworm to more dangerous conditions like valley fever. While many of these conditions can be treated easily, fungal infections become more of a threat when they occur in people with compromised immune systems, like cancer patients, HIV patients, and premature babies. They're also a bigger problem in developing nations.

The Guardian reports that UK doctors are becoming increasingly alarmed about rising resistance to a class of antifungal agents known as azoles, which are used to treat a variety of fungal infections. Fungal resistance is similar to antibiotic resistance, but experts say it may be even more worrisome because there are far fewer drugs to treat fungal infections than there are antibiotics to treat bacterial infections.

"We cannot afford to lose the few drugs we have—particularly as very little funding is being made available for research into fungi and fungal infections," said Adilia Warris, MD, co-director of the Centre for Medical Mycology at Aberdeen University.

Warris and other experts said the widespread use of fungicides on agricultural crops is one of the factors in rising fungal resistance.

Fungal infections take more than 1.3 million lives each year globally, according to Rutgers University scientists.
Aug 26 Guardian story
Dec 23, 2013 Rutgers news release "Attacking fungal infection, one of world's major killers"

News Scan for Sep 02, 2016

News brief

Officials report 25 cases of meningitis C in Southern California

Local and US health officials today reported that 25 people in Southern California have contracted meningitis C, most of them men who have sex with men (MSM).

Two of the cases, which occurred from Mar 4 to Aug 11, have proved fatal, according to a report in Morbidity and Mortality Weekly Report (MMWR) by scientists from the US Centers for Disease Control and Prevention (CDC) and from California. Twenty-four of the cases were caused by serogroup C Neisseria meningitidis and one by N meningitidis of an undetermined serogroup.

Of the 25 patients, 23 (92%) were male, 20 of whom self-identified as MSM. Among the MSM, 8 (40%) reported Hispanic ethnicity, consistent with the proportion of Hispanic people in in Los Angeles County, the city of Long Beach, and Orange County, where the cases have occurred. The median age of the patients is 32 (range, 17 to 74 years).

The estimated attack rate among MSM in the affected region is 6.4 cases per 100,000, which is more than 50 times the incidence of meningococcal disease among all US men in 2015, the report said. Clusters of meningitis C in MSM were confirmed in New York City in 2010 to 2013, in Los Angeles County in 2012 to 2014, in Chicago in 2015 and this year, in Berlin in 2012 and 2013, and in Paris in 2014, the authors noted.

In response to the current outbreak, local health departments on Jul 26 recommended the four-strain meningococcal vaccine, MenACWY, for all MSM regardless of risk behaviors, because no risk groups have yet been identified in the current outbreak. That step expanded recommendations that were in place that focused on certain risk groups.

The most recent update from the California Department of Public Health (CDPH) on the outbreak, on Aug 3, listed 22 cases. The CDPH this week also highlighted an outbreak of Shigella infections in MSM in Southern California.
Sep 2 MMWR report
Aug 3 CDPH meningitis C update
Aug 29 CDPH Shigella notice


New group established to overcome epidemic vaccine barriers

A new alliance to finance and coordinate the development of new vaccines to curb infectious disease epidemics—the Coalition for Epidemic Preparedness Innovations (CEPI)—has been formally established, and its Web site launched today.

John-Arne Rottingen, MD, PhD, CEPI's interim chief executive officer, said in the group's newsletter today that stakeholders met in London Aug 30 to weigh in on the business plan and its ongoing work.

He said CEPI is anticipating a more formal launch at the World Economic Forum in Davos, Switzerland, in January.

At an earlier meeting the interim board elected as its chair Vijay Raghavan, PhD, who is with the biotechnology department at the Indian Ministry of Science and Technology. It elected Peter Piot, MD, PhD, director of the London School of Hygiene and Tropical Medicine, as its vice chair.

According to the CEPI Web site, the group's work is targeted to overcoming barriers to developing vaccines against new disease threats with a new funding model. It noted that developing a safe and effective vaccine against an emerging disease can take more than 10 years because of unique challenges that more commercially viable vaccines don't face  and because of regulatory hurdles. CEPI adds that outbreaks often hit developing countries the hardest.

The alliance includes governments, industry, academia, philanthropists, intergovernmental groups such as the World Health Organization, and nongovernmental organizations. The five founding partners are the Norwegian and Indian governments, Wellcome Trust, the Bill and Melinda Gates Foundation, and the World Economic Forum.
CEPI Web site


CDC, FDA investigating hepatitis A in frozen strawberries

Yesterday both the CDC and the Food and Drug Administration (FDA) said they were investigating a multistate hepatitis A outbreak linked to frozen strawberries imported from Egypt.

As of today, 70 people in seven states have contracted the foodborne illness, with 32 people requiring hospitalization. There have been no deaths. The outbreak total is 1 more than news media reported yesterday before the CDC update.

According to the FDA, "Nearly all ill people interviewed report eating smoothies containing strawberries at Tropical Smoothie locations in a limited geographic area." Tropical Smoothie Cafes stopped making smoothies with imported strawberries on Aug 8.

The CDC said the outbreak is tied to restaurants in four states: Virginia, West Virginia, Maryland, and North Carolina. People from other states reporting illness said they recently visited a Tropical Smoothie in one of those states.

In epidemiologic interviews conducted by the CDC, 97% of people who fell ill (68) reported visiting Tropical Smoothie in the month before they got sick, and all 70 interviewed said their smoothies contained strawberries.

At this time, the FDA said it has no reason to believe there is an ongoing risk of contracting hepatitis A at Tropical Smoothie Cafes.
Sep 1 CDC announcement
Sep 1 FDA announcement

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