Screening and analysis of ocean samples also identified a possible missing link in how the RNA viruses evolved
An international team of scientists has used genetic screening and machine learning techniques to identify more than 5,500 previously unknown species of marine RNA viruses and is proposing five new phyla (biological groups) of viruses. The latter would double the number of RNA virus phyla to 10, one of which may be a missing link in the early evolution of the microbes.
Though the newly-discovered viruses are not currently associated with human disease—and therefore do not drive any current medical laboratory testing—for virologists and other microbiologists, “a fuller catalog of these organisms is now available to advance scientific understanding of how viruses evolve,” said Dark Daily Editor-in-Chief Robert Michel.
“While scientists have cataloged hundreds of thousands of DNA viruses in their natural ecosystems, RNA viruses have been relatively unstudied,” wrote four microbiologists from Ohio State University (OSU) who participated in the study in an article they penned for The Conversation.
The OSU study authors included:
Ahmed Zayed, PhD, research scientist, Dept. of Microbiology, OSU.
Matthew Sullivan, PhD, Professor of Microbiology and Director of the Center of Microbiome Science at OSU.
“RNA viruses are clearly important in our world, but we usually only study a tiny slice of them—the few hundred that harm humans, plants and animals,” explained Matthew Sullivan, PhD (above), Director, Center of Microbiome Science, in an OSU news story. Sullivan led the OSU research team. “We wanted to systematically study them on a very big scale and explore an environment no one had looked at deeply, and we got lucky because virtually every species was new, and many were really new,” he added. (Photo copyright: University of Ohio.)
RNA versus DNA Viruses
In contrast to the better-understood DNA virus, an RNA virus contains RNA instead of DNA as its genetic material, according to Samanthi Udayangani, PhD, in an article she penned for Difference Between. Examples of RNA viruses include:
One major difference, she explains, is that RNA viruses mutate at a higher rate than do DNA viruses.
The OSU scientists identified the new species by analyzing a database of RNA sequences from plankton collected during a series of ocean expeditions aboard a French schooner owned by the Tara Ocean Foundation.
“Plankton are any aquatic organisms that are too small to swim against the current,” the authors explained in The Conversation. “They’re a vital part of ocean food webs and are common hosts for RNA viruses.”
The team’s screening process focused on the RNA-dependent RNA polymerase (RdRp) gene, “which has evolved for billions of years in RNA viruses, and is absent from other viruses or cells,” according to the OSU news story.
“RdRp is supposed to be one of the most ancient genes—it existed before there was a need for DNA,” Zayed said.
The RdRp gene “codes for a particular protein that allows a virus to replicate its genetic material. It is the only protein that all RNA viruses share because it plays an essential role in how they propagate themselves. Each RNA virus, however, has small differences in the gene that codes for the protein that can help distinguish one type of virus from another,” the study authors explained.
The screening “ultimately identified over 44,000 genes that code for the virus protein,” they wrote.
Identifying Five New Phyla
The researchers then turned to machine learning to organize the sequences and identify their evolutionary connections based on similarities in the RdRp genes.
“The more similar two genes were, the more likely viruses with those genes were closely related,” they wrote.
The technique classified many of the sequences within the five previously known phyla of RNA viruses:
But the researchers also identified five new phyla—including two dubbed “Taraviricota” and “Arctiviricota”—that “were particularly abundant across vast oceanic regions,” they wrote. Taraviricota is named after the Tara expeditions and Arctiviricota gets its name from the Arctic Ocean.
They speculated that Taraviricota “might be the missing link in the evolution of RNA viruses that researchers have long sought, connecting two different known branches of RNA viruses that diverged in how they replicate.”
In addition to the five new phyla, the researchers are proposing at least 11 new classes of RNA viruses, according to the OSU story. The scientists plan to issue a formal proposal to the International Committee on Taxonomy of Viruses (ICTV), the body responsible for classification and naming of viruses.
Studying RNA Viruses Outside of Disease Environments
“As the COVID-19 pandemic has shown, RNA viruses can cause deadly diseases. But RNA viruses also play a vital role in ecosystems because they can infect a wide array of organisms, including microbes that influence environments and food webs at the chemical level,” wrote the four study authors in The Conversation. “Mapping out where in the world these RNA viruses live can help clarify how they affect the organisms driving many of the ecological processes that run our planet. Our study also provides improved tools that can help researchers catalog new viruses as genetic databases grow.”
This remarkable study, which was partially funded by the US National Science Foundation, will be most intriguing to virologists and microbiologists. However, clinical laboratories also should be interested in the fact that the catalog of known viruses has just expanded by 5,500 types of RNA viruses.
While working to increase turn-around-times for STAT tests, Florida’s first coronavirus patient arrived, requiring SMH’s clinical laboratory team to adapt its plans
Despite the COVID-19 pandemic, the clinical laboratory team at 839-bed Sarasota Memorial Hospital, part of the Sarasota Memorial Health Care System (SMH) in Sarasota, Fla., not only implemented a new automated microbiology system, it also installed a new mass spectrometry analyzer, along with new instruments to support large volumes of SARS-CoV-2 testing.
How SMH’s microbiology laboratory team accomplished this while shelter-in-place directives in Florida caused many patients to stop visiting emergency departments and physicians’ offices—and as hospitals and medical laboratory facilities restricted access to staff and essential personnel—provides useful lessons for pathologists and clinical laboratory managers.
“Florida reported its first positive SARS-CoV-2 infection on March 2, marking the beginning of an outbreak that continues today,” he noted, adding, “This created the need to support the hospital in identifying infected patients in Sarasota County by having the microbiology lab acquire and set up more instruments. Also, the micro lab needed space for a new mass spectrometry analyzer to speed up pathogen identification this year.
In the same TDR interview, Olevia Fulkert, Microbiology Technical Supervisor at SMH said the microbiology lab had to reconfigure its layout to be prepared for the new COPAN system. “Our team had to arrange space for these new instruments, while protecting the space needed for the microbiology automation.”
“The WASPLab (above) literally went right into the middle of the busiest area of our lab,” said SMH’s Director of Laboratory Services, Harold Vore, MS, MT. “That’s the room we call COVID central, because that’s where we process all SARS-CoV-2 specimens.” SMH’s medical laboratory team began this implementation in the early months of the COVID-19 pandemic and relied on Lean processes to accomplish its goals. (Photo copyright: Sarasota Memorial Health Care System.)
Return of the ‘Snowbirds’
In August, SMH’s microbiology laboratory staff was busy validating the WASPLab instruments so the lab would be ready to process patient specimens when Florida’s snowbirds—out-of-state residents who arrive for the winter—return to Sarasota.
Vore knew several elements would be required for SMH’s microbiology automation project to succeed:
He had to assure the microbiology lab’s staff that adding automation would not cause any loss of jobs.
Timing of the implementation was critical, because lab test volume rises in the winter when tourists and part-time residents return.
Lean methods would be important because lab staff was familiar with them and they would help the vendor to arrange the physical layout and workflow to optimize productivity, reduce errors, and decrease turnaround times.
Vore needed documentation that showed automating the microbiology lab met and exceeded the return-on-investment projections he and his lab team used to persuade health system administrators of its value.
According to Vore, to date the installation has gone smoothly. “The staff in the microbiology lab has been phenomenal,” he commented. “They have continued to do what they always do, while at the same time we’re installing this large new system right in their midst.
“And they did not complain. In fact, they were eager to make progress in improving production,” he continued. “That attitude is common among our laboratory staff, because we saw the same thing happen when we automated our core lab.”
Increasing Microbiology Lab Capacity without Increasing Staff
Vore estimates automation will expand SMH’s microbiology laboratory capacity by up to 40%. “We measure that 40% in terms of the number of plates our techs can read per day with the WASPLab versus how we did it manually with our existing staff,” he explained. “We may still need to increase some staff. But even without adding staff, we thought we could move the peg further down the road in terms of throughput and improve our turnaround time too.
“We cannot make bacteria grow any faster and yet our specimen volume continues to increase,” he noted. “That makes automating microbiology the right strategy. Also, if we hadn’t automated the core lab starting in 2015, we might not have been able to handle the increased volume that we saw last year and this year’s additional surge in COVID-19 tests.”
How Lean Helped with the Implementation
Workflow in microbiology has traditionally been mostly manual. Therefore, combining Lean and automation can generate substantial benefits for a lab. “By definition, the design of the WASPLab is Lean,” Vore explained. “By that I mean the person who touches each specimen the least wins. That’s why the WASPLab is designed the way it is. Once we load a specimen in the front end, theoretically, no one needs to touch those plates until the testing is complete.”
“That’s the ideal we’re trying to reach,” he added. “At the moment, we still need to pull the plates to, as we say, ‘pick them.’ But we just introduced a way to improve that part of the process.
Adding Mass Spectrometry
“Along with the microbiology automation, we now read specimens digitally and we tell the machine to take a certain plate off so we can spot it,” Vore continued. “To speed up that process, we got some additional funding and bought a mass spec analyzer that uses MALDI-TOF to identify pathogens. Now we get the boost from the WASPLab, and we also use mass spec to cut six hours off our first read,” Vore added.
“The WASPLab and the mass spec give us higher quality incubation and better harvest of pathogens. Once we spot the plate, the mass spec can identify the pathogen in about two minutes,” he said.
“After going live with the mass spectrometry in August, we’ve made huge progress versus the normal process, where we would plate the specimen manually under a hood and then put the specimen in the incubator and pull it out to read 24 hours later,” he said.
“That whole step-by-step process to identify the pathogen could take 48 hours,” he continued. “But now we can move to a 24-hour, seven-day-a-week operation, where we can do first-in-first-out of pathogens in about 18 hours. That cuts six hours off the time to do the first plate read. Then we can spot it and get a result from the mass spec in two minutes. The impact for patient care can be tremendous.
“In a recent case, for example, we had to identify a specimen from an infant and used the mass spec to identify salmonella in two minutes,” Vore noted. “Normally that would take at least a day or more. That’s what I mean about making tremendous impact on patient care by using automation in microbiology.”
Clearly, this would be a challenging project for any medical laboratory to complete during the best of times, let alone during the early months of the COVID-19 pandemic. But through determination, the use of Lean, and a positive approach, SMH’s microbiology lab team implemented the first WASPLab in the state of Florida. And it will improve SMH’s ability to care for patients for years to come.
Researchers believe new findings about genetic changes in C. difficile are a sign that it is becoming more difficult to eradicate
Hospital infection control teams, microbiologists, and clinical laboratory professionals soon may be battling a strain of Clostridium difficile (C. difficile) that is even more resistant to disinfectants and other forms of infection control.
A WSI news release states the researchers “identified genetic changes in the newly-emerging species that allow it to thrive on the Western sugar-rich diet, evade common hospital disinfectants, and spread easily.”
Microbiologists and infectious disease doctors know full well that this means the battle to control HAIs is far from won.
“C. difficile is currently forming a new species with one group specialized to spread in hospital environments. This emerging species has existed for thousands of years, but this is the first time anyone has studied C. difficile genomics in this way to identify it. This particular [bacterium] was primed to take advantage of modern healthcare practices and human diets,” said Nitin Kumar, PhD (above), in the news release. (Photo copyright: Wellcome Sanger Institute.)
Genomic Study Finds New Species of Bacteria Thrive in
Western Hospitals
In the published paper, Nitin Kumar, PhD, Senior Bioinformatician at the Wellcome Sanger Institute and Joint First Author of the study, described a need to better understand the formation of the new bacterial species. To do so, the researchers first collected and cultured 906 strains of C. difficile from humans, animals, and the environment. Next, they sequenced each DNA strain. Then, they compared and analyzed all genomes.
The researchers found that “about 70% of the strain collected specifically from hospital patients shared many notable characteristics,” the New York Post (NYPost) reported.
Hospital medical laboratory leaders will be intrigued by the
researchers’ conclusion that C. difficile is dividing into two separate
species. The new type—dubbed C. difficile clade A—seems to be targeting
sugar-laden foods common in Western diets and easily spreads in hospital
environments, the study notes.
“It’s not uncommon for bacteria to evolve, but this time we actually see what factors are responsible for the evolution,” Kumar told Live Science.
New C. Difficile Loves Sugar, Spreads
Researchers found changes in the DNA and ability of the C.
difficile clade A to metabolize
simple sugars. Common hospital fare, such as “the pudding cups and instant
mashed potatoes that define hospital dining are prime targets for these strains”,
the NYPost explained.
Indeed, C. difficile clade A does have a sweet tooth. It was associated with infection in mice that were put on a sugary “Western” diet, according to the Daily Mail, which reported the researchers found that “tougher” spores enabled the bacteria to fight disinfectants and were, therefore, likely to spread in healthcare environments and among patients.
“The new C. difficile produces spores that are more
resistant and have increased sporulation
and host colonization capacity when glucose or fructose is available for
metabolism. Thus, we report the formation of an emerging C. difficile
species, selected for metabolizing simple dietary sugars and producing high
levels or resistant spores, that is adapted for healthcare-mediated
transmission,” the researchers wrote in Nature Genetics.
Bacteria Pose Risk to Patients
The findings about the new strains of C. difficile bacteria
now taking hold in provider settings are important because hospitalized
patients are among those likely to develop life-threatening diarrhea due to
infection. In particular, people being treated with antibiotics are vulnerable
to hospital-acquired infections, because the drugs eliminate normal gut
bacteria that control the spread of C. difficile bacteria, the
researchers explained.
According to the Centers for Disease Control and Prevention (CDC), C. difficile causes about a half-million infections in patients annually and 15,000 of those infections lead to deaths in the US each year.
New Hospital Foods and Disinfectants Needed
The WSI/LSHTM study suggests hospital representatives should
serve low-sugar diets to patients and purchase stronger disinfectants.
“We show that strains of C. difficile bacteria have continued to evolve in response to modern diets and healthcare systems and reveal that focusing on diet and looking for new disinfectants could help in the fight against this bacteria,” said Trevor Lawley, PhD, Senior Author and Group Leader of the Lawley Lab at the Wellcome Sanger Institute, in the news release.
Microbiologists, infectious disease physicians, and their
associates in nutrition and environmental services can help by understanding
and watching development of the new C. difficile species and offering
possible therapies and approaches toward prevention.
Meanwhile, clinical laboratories and microbiology labs will
want to keep up with research into these new forms of C. difficile, so
that they can identify the strains of this bacteria that are more resistant to
disinfectants and other infection control methods.
The UE study sheds light on the types of bacteria in
wastewater that goes down hospital pipes to sewage treatment plants. The study
also revealed that not all infectious agents are killed after passing through
waste treatment plants. Some bacteria with antimicrobial (or antibiotic)
resistance survive to enter local food sources.
The scientists concluded that the amount of AMR genes found
in hospital wastewater was linked to patients’ length-of-stays and consumption
of antimicrobial resistant bacteria while in the hospital.
In a paper the University of Edinburgh published on medRxiv, the researchers wrote: “There was a higher abundance of antimicrobial-resistance genes in the hospital wastewater samples when compared to Seafield community sewage works … Sewage treatment does not completely eradicate antimicrobial-resistance genes and thus antimicrobial-resistance genes can enter the food chain through water and the use of [processed] sewage sludge in agriculture. As hospital wastewater contains inpatient bodily waste, we hypothesized that it could be used as a representation of inpatient community carriage of antimicrobial resistance and as such may be a useful surveillance tool.”
Additionally, they wrote, “Using metagenomics to identify
the full range of AMR genes in hospital wastewater could represent a useful
surveillance tool to monitor hospital AMR gene outflow and guide environmental
policy on AMR.”
Antimicrobial stewardship programs are becoming increasingly critical to preventing the spread of AMR bacteria. “By having those programs, [there are] documented cases of decreased antibiotic resistance within organisms causing these infections,” Paul Fey, PhD, of the University of Nebraska Medical Center, told MedPage Today. “This is another indicator of how all hospitals need to implement stewardship programs to have a good handle on decreasing antibiotic use.” [Photo copyright: University of Nebraska.]
Don’t Waste the Wastewater
Antibiotic resistance occurs when bacteria change in response to medications to prevent and treat bacterial infections, according to a World Health Organization (WHO) fact sheet. The CDC estimates that more than 23,000 people die annually from two million antibiotic-resistance infections.
Wastewater, the UE scientists suggest, should not go to
waste. It could be leveraged to improve hospitals’ detection of patients with antimicrobial
resistance, as well as to boost environment antimicrobial-resistance polices.
They used metagenomics (the study of genetic material
relative to environmental samples) to compare the antimicrobial-resistance
genes in hospital wastewater against wastewater from community sewage
points.
The UE researchers:
First collected samples over a 24-hour period from various areas in a tertiary hospital;
They then obtained community sewage samples from various locations around Seafield, Scotland;
Antimicrobial-resistance genes increased with longer length of patient stays, which “likely reflects transmission amongst hospital inpatients,” researchers noted.
Fey suggests that further research into using sequencing
technology to monitor patients is warranted.
“I think that monitoring each patient and sequencing their
bowel flora is more likely where we’ll be able to see if there’s a significant
carriage of antibiotic-resistant organisms,” Fey told MedPage Today. “In
five years or so, sequencing could become so cheap that we could monitor every
patient like that.”
Fey was not involved in the University of Edinburgh
research.
Given the rate at which AMR bacteria spreads, finding antibiotic-resistance
genes in hospital wastewater may not be all that surprising. Still, the University
of Edinburgh study could lead to cost-effective ways to test the genes of
bacteria, which then could enable researchers to explore different sources of
infection and determine how bacteria move through the environment.
And, perhaps most important, the study suggests clinical
laboratories have many opportunities to help eliminate infections and slow
antibiotic resistance. Microbiologists can help move their organizations forward
too, along with infection control colleagues.
Contrary to CMS and Joint Commission programs implemented in 2017 to reduce them, incidents of hospital-acquired infections have risen for the past few years
Nevertheless, a recent Leapfrog Group report indicates hospitals are finding it increasingly difficult to remove infections all together. This has many healthcare leaders concerned.
The report, which was analyzed by Castlight Health, states that the number of hospitals reporting zero infections has declined significantly since 2015, according to a news release. According to the Leapfrog Group’s report:
Two million people acquire HAIs every year;
90,000 people die annually from HAIs;
HAI costs range from $1,000 to $50,000 depending on the infection.
Hospitals spend $28 to $45 billion annually on HAI costs, Healthcare Finance reported.
“I think it’s far too easy to let something slip, so it’s clear that there really needs to be a renewed focus on getting back to zero. We do still see some hospitals that are getting to zero, so it’s clearly possible,” Erica Mobley (above), Leapfrog Group’s Director of Operations, told Fierce Healthcare. (Photo copyright: LinkedIn.)
Regressing Instead of Progressing Toward Total HAI Elimination
Leapfrog Group’s report is based on 2017 hospital survey data submitted by 2,000 providers. The data indicates that in just two years the number of hospitals reporting zero HAIs dropped by up to 50%. The reported HAIs include:
Central line-associated bloodstream infections (CLABSI) occurring in Intensive Care and other units: 12.7% of hospitals reporting zero CLABSI infections in 2017, down from 25% in 2015;
The remaining infection measures studied by Leapfrog Group had less dramatic decreases over the same time period, according to Fierce Healthcare. Nevertheless, they are significant. They include:
Surgical site infections (SSI) following colon surgery: 19% zero infections compared to 23% previously;
Clostridium difficile (C. difficile) inpatient infections: 3% zero inpatient infections in 2017, compared to 5% in 2015.
Joint Commission Studies Antimicrobial Program Progress
Hospitals have revised their antimicrobial programs, which originally operated on a “top-down” structure, to programs that include clinicians from throughout entire provider organizations;
Health information technology (HIT) can enable real-time opportunities to launch antimicrobial therapy and treat patients; and,
Some barriers exist in getting resources to integrate technology and analyze data.
“These programs used expansion of personnel to amplify the antimicrobial stewardship programs’ impact and integrated IT resources into daily workflow to improve efficiency,” the researchers wrote. “Hospital antimicrobial stewardship programs can reduce inappropriate antimicrobial use, length of stay, C. difficile infection, rates of resistant infections, and cost.”
What Do CMS and Joint Commission Expect?
According to Contagion, while the Joint Commission program is part of medication management, CMS places its requirements for the antimicrobial stewardship program under “infection prevention.”
CMS requirements for an antimicrobial stewardship program include:
Developing antimicrobial stewardship program policies and procedures;
Implementing hospital-wide efforts;
Involving antimicrobial stakeholders for focus on antimicrobial use and bacterial resistance;
Setting evidence-based antimicrobial use goals; and,
Reducing effects of antimicrobial use in areas of C. difficile infections and antibiotic resistance.
Leapfrog Group’s data about fewer hospitals reporting zero infections offers opportunities for hospital laboratory microbiology professionals to get involved with hospital-wide antimicrobial program teams and processes and help their hospitals progress back to zero HAIs. Clinical laboratories, both hospital-based and independent, also have opportunities to contribute to improving the antimicrobial stewardship efforts of the physicians who refer them specimens.
