Tracing the start of COVID-19 in GA

At a time when COVID-19 appears to be receding in much of Georgia, it’s worth revisiting the start of the pandemic in early 2020. Emory virologist Anne Piantadosi and colleagues have a paper in Viral Evolution on the earliest SARS-CoV-2 genetic sequences detected in Georgia. Analyzing relationships between those virus sequences and samples from other states and countries can give us an idea about where the first COVID-19 infections in Georgia came from. We can draw Read more

Reddit as window into opioid withdrawal strategies

Drug abuse researchers are using the social media site Reddit as a window into the experiences of people living with opioid addiction. Abeed Sarker in Emory's Department of Biomedical Informatics has a paper in Clinical Toxicology focusing on the phenomenon of “precipitated withdrawal,” in collaboration with emergency medicine specialists from Penn, Rutgers and Mt Sinai. Precipitated withdrawal is a more intense form of withdrawal that can occur when someone who was using opioids starts medication-assisted treatment Read more

CROI: HIV cure report and ongoing research

The big news out of CROI (Conference on Retroviruses and Opportunistic Infections) was a report of a third person being cured of HIV infection, this time using umbilical cord blood for a hematopoetic stem cell transplant. Emory’s Carlos del Rio gave a nice overview of the achievement for NPR this morning. As del Rio explains, the field of HIV cure research took off over the last decade after Timothy Brown, known as “the Berlin patient,” Read more

infectious diseases

Tracing the start of COVID-19 in GA

At a time when COVID-19 appears to be receding in much of Georgia, it’s worth revisiting the start of the pandemic in early 2020. Emory virologist Anne Piantadosi and colleagues have a paper in Viral Evolution on the earliest SARS-CoV-2 genetic sequences detected in Georgia.

Analyzing relationships between those virus sequences and samples from other states and countries can give us an idea about where the first COVID-19 infections in Georgia came from. We can draw a few conclusions, such as: there was no “Patient Zero”, at least here.

According to sequence analysis in the paper, multiple early introductions of SARS-CoV-2 into Georgia occurred, probably coming from Asia, weeks before the first officially reported case in March 2020. The authors suggest that the early focus on returning international travelers was misplaced, as opposed to broader testing of patients with COVID-19 symptoms.

“SARS-CoV-2 was likely spreading within the state for approximately three weeks prior to detection in either diagnostic or sequencing data,” the authors write.

Tree showing relationships between SARS-CoV-2 genetic sequences from Georgia and other states/countries

In Georgia, the subclade, or swarm of related viruses, that was dominant early on (called 19B) disappeared by the end of April, eclipsed by variants carrying the D614G mutation. This was an early hint – even before the emergence of B117/Alpha and other variants such as Delta and Omicron — that SARS-CoV-2 would evolve through competition. 

Similarly, sequence analysis from Washington state – the site of the first COVID-19 case identified in the United States — has shown that the first official case did not lead directly to the initial wave of infections there. The first wave actually fizzled out as a result of public health interventions, but other undetected infections in Washington in February 2020 led to sustained downstream transmission. 

The co-first authors of the Viral Evolution paper are Emory infectious disease specialist Ahmed Babiker and graduate student Michael Martin, with co-authors from the Centers of Disease Control and Prevention. The paper analyzes sequences from Emory Healthcare patients along with previously available sequences.

In a few cases, scientists attempted to trace relationships between infected patients who had recently travelled to other countries (Italy, Switzerland) or other states (Louisiana, Colorado), but the available data did not confirm all of those connections. 

Keep in mind that SARS-CoV-2 testing was very limited at the start of the pandemic, because of short supplies as well as FDA policy. More extensive virus sequencing efforts at Emory did not begin until mid-March 2020. With respect to viruses, we only see what we look for, and scientists can’t analyze samples they don’t have. If more samples were available from January or February, what would we find? Also, this paper’s analysis does not include any (known) samples from a February 2020 funeral in Albany, GA that was considered a “super-spreader event.” 

Two years later, has SARS-CoV-2 genomic surveillance improved? Piantadosi says that her team’s paper should be viewed in combination with their recent paperon the detection of the first Omicron case in Georgia, a woman who became sick in November 2021 while visiting Cape Town, South Africa.

 “That’s an example of where we did better,” Piantadosi says. “It does speak to how much surveillance has improved. We were conducting routine surveillance – not focusing on returning travelers.”

In the Omicron case, the woman in question first went to a community testing site, and those samples were not available for sequence analysis.

Piantadosi says that “we’ve achieved Phase I” – in that large hospitals or health systems such as Emory are collecting SARS-CoV-2 sequences, and the state Department of Public Health and large diagnostic services companies are also doing so. But as more SARS-CoV-2 testing is performed at home – generally a good thing for convenience and public health — surveillance for new variants needs to continue, she says.

Posted on by Quinn Eastman in Uncategorized Leave a comment

Combo approach vs drug-resistant fungus

Before 2020 and the COVID-19 pandemic, concern among infectious disease specialists was rising about Candida auris, an emerging fungal pathogen that is often drug-resistant and difficult to eradicate from hospitals.

CDC image of Candida auris

Many people know Candida can cause mouth or vaginal infections and diaper rashes. According to the CDC, Candida also can cause invasive infections in the bloodstream, particularly in hospital or nursing home patients with weakened immune systems. About 30 percent of patients with an invasive Candida infection die – and C. auris is just one particularly hardy variety.

Emory Antibiotic Resistance Center director David Weiss and colleagues have identified a combination of existing antifungal drugs (micafungin and amphotericin B) with enhanced activity against C. auris when used together. The results – in vitro only, so far — were published in a letter to The Lancet Microbe. Postdoctoral fellow Siddharth Jaggavarapu was the first author. Weiss reports his team continues to investigate combination approaches against C. auris.

Posted on by Quinn Eastman in Uncategorized Leave a comment

Improve old antibiotics rather than discover new ones, BME researchers propose

The resistance of bacteria to antibiotics is a global challenge that has been exacerbated by the financial burdens of bringing new antibiotics such as the Metronidazole 500mg tablets to market and an increase in serious bacterial infections as a result of the COVID-19 pandemic.

Biomedical engineering researchers at Georgia Tech and Emory are tackling the problem of antibiotic resistance not by creating new drugs, but by enhancing the safety and potency of ones that already exist.

Aminoglycosides are antibiotics used to treat serious infections caused by pathogenic bacteria like E. coli or Klebsiella.  Bacteria haven’t developed widespread resistance to aminoglycosides, as compared to other types of antibiotics.  These antibiotics are used sparingly by doctors, in part because of the toxic side effects they can sometimes cause.

In research published in the journal PLOS One, Christopher Rosenberg, Xin Fang and senior author Kyle Allison demonstrated that lower doses of aminoglycosides could be used to treat bacteria when combined with specific metabolic sugars.  Low concentrations of antibiotics alone often cannot eliminate dormant, non-dividing bacterial cells, but the researchers hypothesized based on a past study that combining aminoglycosides with metabolites such as glucose, a simple sugar, or mannitol, a sugar alcohol often used as sweetener, could stimulate antibiotic uptake.

The authors tested these treatment combinations against Gram-negative pathogens E. coli, Salmonella and Klebsiella. The results showed that aminoglycoside-metabolite treatment significantly reduced the concentration of antibiotic needed to kill those pathogens. The authors also demonstrated that this treatment combination did not increase bacterial resistance to aminoglycosides and was effective in treating antibiotic-tolerant biofilms, which are bacterial communities that act as reservoirs of infection.

Read more

Posted on by Quinn Eastman in Uncategorized 1 Comment

Fecal transplant replants microbial garden

When facing a life-threatening infection, the “yuck factor” is a minor concern. Fecal microbiota transplant (FMT for short) has become an accepted treatment for recurrent Clostridium difficile infection, which can cause severe diarrhea and intestinal inflammation.

In a new video, Emory physicians Colleen Kraft and Tanvi Dhere explain how FMT restores microbial balance when someone’s internal garden has been disrupted.

C. difficile or “C diff” is a hardy bacterium that can barge into the intestines after another infection has been treated with antibiotics, when competition for real estate is low. In the last few years, doctors around the world have shown that FMT can resolve recurrent C diff infection better than antibiotics alone.

At Emory, Kraft and Dhere have performed almost 300 FMTs and report a 95 percent success rate when treating recurrent C diff. They have established a standard slate of stool donors, whose health is carefully screened.

Building on their experience with the procedure, Kraft and Dhere are studying whether FMT can head off other antibiotic-resistant infections besides C diff in kidney transplant patients. They have teamed up with infectious disease specialists Aneesh Mehta and Rachel Friedman-Moraco to conduct this study. Read more

Posted on by Quinn Eastman in Uncategorized Leave a comment

Meningitis bacteria adapt to STI niche — again?

A new paper in PNAS from Emory scientists highlights a neat example of bacterial evolution and adaptation related to sexually transmitted infections. Neisseria meningitidis, a bacterium usually associated with meningitis and sepsis, sometimes appears in the news because of cases on college campuses or other outbreaks.

The N meningitidis bacteria causing a recent cluster of sexually transmitted infections in Columbus, Ohio and other US cities have adapted to the urogenital environment, an analysis of their DNA shows.

Update: May 2016 Clinical Infectious Diseases paper on the same urethritis cluster.

Genetic changes make this clade look more like relatives that are known to cause gonorrhea. Some good news is that these guys are less likely to cause meningitis because they have lost their outer capsule. They have also gained enzymes that help them live in low oxygen.

The DNA analysis helps doctors track the spread of this type of bacteria and anticipate which vaccines might be protective against it. Thankfully, no alarming antibiotic resistance markers are present (yet) and currently available vaccines may be helpful. Full press release here, and information about meningococcal disease from the CDC here.

This looks like a well-worn path in bacterial evolution, since N. gonorrhoeae is thought to have evolved from N. meningitidis and there are recent independent examples of N. meningitidis adapting to the urogenital environment. 

Posted on by Quinn Eastman in Immunology Leave a comment

Retaining the resistance: MCR-1, colistin + lysozyme

If you’ve been following the news about antibiotic resistant bacteria, you may have heard about a particularly alarming plasmid: MCR-1. A plasmid is a circle of DNA that is relatively small and mobile – an easy way for genetic information to spread between bacteria. MCR-1 raises concern because it provides bacteria resistance against the last-resort antibiotic colistin. The CDC reports MCR-1 was found in both patients and livestock in the United States this summer.
David Weiss, director of Emory’s Antibiotic Resistance Center, and colleagues have a short letter in The Lancet Infectious Diseases showing that MCR-1 also confers resistance to an antimicrobial enzyme produced by our bodies called lysozyme. MCR-1-containing strains were 5 to 20 times less susceptible to lysozyme, they report.
This suggests that the pressure of fighting the host immune system may select for MCR-1 to stick around, even in the absence of colistin use, the authors say.
While the findings are straightforward in bacterial culture, Weiss cautions that there is not yet evidence showing that this mechanism occurs in live hosts. For those that really want to get alarmed, he also calls attention to a recent Nature Microbiology paper describing a hybrid plasmid with both MCR-1 and resistance to carbapenem, another antibiotic.

Read more

Posted on by Quinn Eastman in Uncategorized Leave a comment

Fooling the test: antibiotic resistant bacteria that look susceptible

A diagnostic test used by hospitals says a recently isolated strain of bacteria is susceptible to the “last resort” antibiotic colistin. But the strain actually ignores treatment with colistin, causing lethal infections in animals.

Through heteroresistance, a genetically identical subpopulation of antibiotic-resistant bacteria can lurk within a crowd of antibiotic-susceptible bacteria. The phenomenon could be causing unexplained treatment failures in the clinic and highlights the need for more sensitive diagnostic tests, researchers say.

In Nature Microbiology (published online Monday, May 9), scientists led by David Weiss, PhD, describe colistin-heteroresistant strains of Enterobacter cloacae, a type of bacteria that has been causing an increasing number of infections in hospitals around the world.

“Heteroresistance has been observed previously and its clinical relevance debated,” Weiss says. “We were able to show that it makes a difference in an animal model of infection, and is likely to contribute to antibiotic treatment failures in humans.”

Weiss is director of the Emory Antibiotic Resistance Center and associate professor of medicine (infectious diseases) at Emory University School of Medicine and Emory Vaccine Center. His laboratory is based at Yerkes National Primate Research Center. The co-first authors of the paper are graduate students Victor Band and Emily Crispell.

Read more

Posted on by Quinn Eastman in Immunology Leave a comment

Why the RTS,S malaria vaccine is such a tease

Continuing from Monday’s post, IMP graduate student Taryn McLaughlin explains why the most advanced malaria vaccine is actually not that great.

Malaria has plagued humans for thousands of years. And while we have known the causative agents of the disease- for 150 years, malaria remains scientifically frustrating. In fact, one of the most common treatments for the disease is simply a derivative of a treatment used in ancient China.

One of the most frustrating features is that there is no sterilizing immunity. In other words, for many diseases once you are infected with the microbe responsible, you develop an immune response and then never get the disease again. Not so with malaria. Compounded with terrible treatment and the impracticality of ridding the world of mosquitos, a vaccine sounds like pretty much our only hope. And yet this has been scientifically challenging and unsuccessful for many many reasons.

In fact a number of vaccine candidates have come along in the last few decades that have seemed SO promising only to go on and break our hearts in clinical trials. The most recent of which is a vaccine that goes by the name RTS,S (named for the different components of the vaccine).

As a quick refresher, Plasmodium enters the body via mosquitos as a sporozoite. It then migrates through the skin going into the blood and eventually making it’s way to the liver. Here it goes inside liver cells where it replicates and turns into merozoites (such that one sporozoite becomes thousands of merozoites). This stage of the disease is asymptomatic. Some time later, all those merozoites burst out of your liver cells causing mayhem and invading your red blood cells. Here, they once again replicate and metamorphose. Fun times. Anyways, during the last stage, some of those plasmodium become gametes which get eaten by mosquitos thus completing the life cycle. Read more

Posted on by Quinn Eastman in Immunology Leave a comment

An effective alternative to fecal transplant for C. difficile?

Bacterial spores in capsules taken by mouth can prevent recurrent C. difficile infection, results from a preliminary study suggest.

Clostridium difficile is the most common hospital-acquired infection in the United States and can cause persistent, sometimes life-threatening diarrhea. Fecal microbiota transplant has shown promise in many clinical studies as a treatment for C. difficile, but uncertainty has surrounded how such transplants should be regulated and standardized. Also, the still-investigational procedure is often performed by colonoscopy, which may be difficult for some patients to tolerate.

The capsule study, published Monday in Journal of Infectious Diseases, represents an important step in moving away from fecal microbiota transplant as a treatment for C. difficile, says Colleen Kraft, MD, assistant professor of pathology and laboratory medicine and medicine (infectious diseases) at Emory University School of Medicine.

Kraft and Tanvi Dhere, MD, assistant professor of medicine (digestive diseases) have led development of the fecal microbiota transplant program at Emory. They are authors on the capsule study, along with investigators from Mayo Clinic, Massachusetts General Hospital, Miriam Hospital (Rhode Island), and Seres Therapeutics, the study sponsor.

While this study involving 30 patients did not include a control group, the reported effectiveness of 96.7 percent compares favorably to published results on antibiotic treatment of C. difficile infection or fecal microbial transplant. Read more

Posted on by Quinn Eastman in Uncategorized Leave a comment

Metagenomics explainer

A term we heard a bunch at the Emory Microbiome Symposium in November was “metagenomics”. Time for an explainer, with some help from Emory geneticist Tim Read.

Nature Reviews Microbiology defines metagenomics as “genomic analysis of microbial DNA that is extracted directly from communities in environmental samples.”

This technology — genomics on a huge scale — enables a survey of the different microorganisms present in a specific environment, such as water or soil, to be carried out. Metagenomics is also emerging as a tool for clinical diagnosis of infectious diseases.

Read notes that the term specifically refers to “shotgun” sequencing of environmental DNA.

“The shotgun approach is to randomly sample small pieces of the DNA in the tube, no matter which organism they came from,” he says. “The output is a mélange of different genes from bacteria, viruses, fungi, plants and humans.  The data is fascinating but the analysis is daunting.” Read more

Posted on by Quinn Eastman in Uncategorized 1 Comment