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CDC Study: Significantly Higher Lyme Disease Rates Among Older Adults Than Previously Reported

The AHA! Team — Mon, 23 Sep 2024 08:24:32 +0000

Dr. Sanchari Sinha Dutta, Ph.D. via News-Medical – The U.S. Centers for Disease Control and Prevention (CDC), in association with the University of Iowa, USA, has conducted an epidemiological study to determine the incidence rate of Lyme disease among older adults in the United States. The study is published in the CDC’s Emerging Infectious Diseases journal. Background Lyme disease, also known as Lyme borreliosis, is a vector-borne bacterial infection caused by a species of Borrelia bacteria that spreads to humans by the bite of infected black-legged ticks (Ixodes scapularis). The main symptoms are fever, headache, fatigue, and a specific type of skin rash called erythema migrans. While Lyme disease can present with a characteristic erythema migrans rash, it can also lead to severe complications if left untreated, including facial nerve paralysis, arthritis, and even heart rhythm irregularities. In the United States, Lyme disease most commonly occurs in the Northeast, mid-Atlantic, and upper-Midwest regions. Previous studies estimating the prevalence of the disease have used employer-sponsored insurance claims data to quantify the disease diagnoses. However, this type of data does not include information on individuals aged 65 years and above who exhibit higher susceptibility to Lyme disease than their younger peers. In this study, scientists have determined the incidence of Lyme disease among older adults in the United States using Medicare fee-for-service data that includes information on individuals aged 65 years and above. Study design The study analyzed Medicare fee-for-service data together with drug treatment data to identify Lyme disease diagnoses among individuals aged 65 years and above. The data collected during 2016 – 2019 was included in the analysis. The Medicare fee-for-service study population was compared with the 2019 US Census estimation data for individuals aged 65 years and above to ensure that the two groups were age-, sex-, race-, ethnicity- and region-matched. Lyme disease diagnoses identified in the Medicare fee-for-service data were compared with the confirmed and probable cases among individuals aged 65 years and above obtained through national surveillance. However, the study also notes certain limitations, such as slight differences between the Medicare fee-for-service population and the U.S. Census population regarding race, ethnicity, and sex. These differences, though small, were stable throughout the study period. Important observations The Medicare fee-for-service population included in the study was estimated to have a median of 17,872,466 person-years during the study period, as compared to the US Census population of 51,561,372 individuals aged 65 years and above. Person-years refer to the number of years for which persons contribute data. The proportion of individuals from neighboring high-incidence states was higher in the Medicare population than in the US Census population. Incidence of Lyme disease A total of 88,485 Lyme disease cases were identified in the Medicare population during the 2016-2019 study period. This corresponded to an average incidence of 123.5 diagnoses per 100,000 person-years. The total number of Lyme disease cases reported through public health surveillance during the same period was 34,183. This corresponded to an average incidence of 16.6 cases per 100,000 persons. Symptoms include fever, headache, fatigue, and a bullseye rash. Approximately 82% of Lyme disease cases were identified among individuals residing in high-incidence states. The median incidence of Lyme disease diagnoses was 346.9 per 100,000 person-years among residents of high-incidence states, 35.3 per 100,000 person-years among residents of states or jurisdictions neighboring high-incidence states, and 29.4 per 100,000 person-years among residents of low-incidence states. Public health surveillance data revealed that about 93% of Lyme disease cases were among residents of high-incidence states. The median incidence of these cases was 57.1 per 100,000 persons among residents of high-incidence states, 3.6 per 100,000 persons among residents of states or jurisdictions neighboring high-incidence states, and 0.6 per 100,000 persons among residents of low-incidence states. The majority of Lyme disease diagnoses occurred in the summer months. Among residents of low-incidence states, a large proportion of disease diagnoses occurred in winter months. According to Medicare and surveillance data, the majority of Lyme disease cases were identified among men. In high-incidence states, men had the highest incidence of Lyme disease for all age groups. In low-incidence states, women had a slightly higher incidence than men only in the 65–69-year age group and 75–79-year age group. Study significance The study identified more than 88,000 adults aged 65 years and above diagnosed and treated with Lyme disease during 2016 – 2019 in the United States. Most Lyme disease cases have been identified among residents of high-incidence states. The study reports a 7-fold higher incidence of Lyme disease diagnoses compared to that reported through public health surveillance. These findings are similar to the findings reported in previous claims analyses. The study also acknowledges the issue of overdiagnosis, which may partly explain the differences observed between the Medicare data and public health surveillance data. Overdiagnosis has been reported in other analyses and may contribute to the higher incidence rates observed in this older population. A variation in Lyme disease seasonality has been observed when Medicare fee-for-service data is compared with surveillance data. Some differences in gender-specific disease susceptibility have also been observed when this study is compared with previous claims analyses. Antibiotics like doxycycline are effective treatments. In previous claims analyses, male children have shown higher susceptibility to Lyme disease in both high- and low-incidence states. In contrast, male older adults have shown higher susceptibility in high-incidence states. Overall, the study findings add insight into Lyme disease patterns unique to this older population in the United States. Journal reference: Schwartz AM. 2024. Epidemiology of Lyme Disease Diagnoses among Older Adults, United States, 2016–2019. Emerging Infectious Diseases. https://wwwnc.cdc.gov/eid/article/30/9/24-0454_article To read the original article click here.

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Study Could Lead to New Antibiotics to Fight Bacterial Infections

AHA Publisher — Mon, 24 May 2021 07:00:46 +0000

UT Southwestern Medical Center via News-Medical – One member of a large protein family that is known to stop the spread of bacterial infections by prompting infected human cells to self-destruct appears to kill the infectious bacteria instead, a new study led by UT Southwestern scientists shows. However, some bacteria have their own mechanism to thwart this attack, nullifying the deadly protein by tagging it for destruction. The findings, published online today in Cell, could lead to new antibiotics to fight bacterial infections. And insight into this cellular conflict could shed light on a number of other conditions in which this protein is involved, including asthma, Type 1 diabetes, primary biliary cirrhosis, and Crohn’s disease. “This is a wonderful example of an arms race between infectious bacteria and human cells.” Neal M. Alto, Ph.D., Study Leader and Professor of Microbiology at UT Southwestern and Member of Harold C. Simmons Comprehensive Cancer Center Previous research has shown that the protein, called gasdermin B (GSDMB), was different from other members of the mammalian gasdermin family. Related gasdermin proteins form pores in the membranes of infected cells, killing them while allowing inflammatory molecules to leak out and incite an immune response. However, GSDMB – found in humans but not in some other mammalian species, including rodents – doesn’t form pores in the membranes of cultured mammalian cells, leaving its target a mystery. Using a novel screening technology, Alto and colleagues discovered that a protein toxin called IpaH7.8 from shigella flexneri, a bacterium that causes diarrheal disease, directly inhibits GSDMB. Biochemical experiments show that IpaH7.8 places a chemical tag on GSDMB that marks it for cellular destruction. To understand why shigella flexneri rids human cells of GSDMB, the researchers placed GSDMB within synthetic mammalian and bacterial cell membranes. While GSDMB left the synthetic mammalian membranes unharmed, it poked holes in the bacterial membranes. Further investigation showed that immune cells called natural killer cells stimulate this process. Alto notes that inhibiting the ability of shigella IpaH7.8 to counteract GSDMB could lead to new types of antibiotics. And because genetic variants of GSDMB have been linked to a variety of inflammatory diseases and cancer, better understanding this protein could lead to new treatments for these conditions too. To read the original article click here.

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A ‘Poison Arrow’ to Defeat Antibiotic Resistance

AHA Publisher — Wed, 08 Jul 2020 07:00:49 +0000

Emily Henderson, B.Sc. via News-Medical Net – News-Medical speaks to Dr. James Martin and Dr. Zemer Gitai from Princeton University about their research which led to the discovery of a new antibiotic. What led you to carry out this research? When I (James) started graduate school, I had never worked in bacteria before. I originally worked with Drosophila, but when I joined Zemer’s lab, we basically came to the table with the question, “How can we address the global need for new antibiotics in light of the escalating rates of antibiotic resistance?” This is a problem because as the rates of antibiotic resistance go up, we should be making new antibiotics that can treat those antibiotic-resistant infections. However, only six new classes of antibiotics have been approved in the past 20 years, and none of them can treat Gram-negative bacteria. There is this huge gap in the field that we wanted to address by, one, creating a new pipeline for discovering novel classes of antibiotics, and two, creating a way to quickly and efficiently characterize their mechanism of action. The aim was to find those mechanisms of action that are unique, such that bacteria would have never seen them before, and the hypothesis was that if a mechanism of action is new, bacteria will have a much harder time becoming resistant to it. Traditionally, antibiotic research and new leads have been done with a certain style that has sort of been dominated by these sorts of chemically-focused perspectives, and the big-picture idea was can we use some fresh approaches to get something new here. What is the difference between Gram-positive and Gram-negative antibiotics, and why is this important in your work? So first it is important to make it clear that the bacteria are the ones that come in two flavors, the Gram-positives and the Gram-negatives, and the antibiotics are the compounds that then kill those bacteria. When we say Gram-positive antibiotics we mean an antibiotic that kills a Gram-positive, or a Gram-negative antibiotic that kills a Gram-negative. The distinction is that Gram-positive bacteria only have one membrane layer and then a cell wall outside of that membrane, whereas Gram-negative bacteria have a second membrane outside of the cell wall; they have an inner membrane, then the cell wall, and then the outer membrane. Gram is simply the name of the person who invented this Gram stain to test for the second membrane layer. Because of that second membrane, the Gram-negative antibiotics are not stained and in the same way that they exclude that stain, that second membrane is also a mechanism to exclude or prevent entry for many different small molecules. The reason that Gram-negative pathogens are so insidious and hard to kill is that they have this second barrier, this outer membrane, and so they are harder to actually penetrate. Please explain your new antibiotic and how it works? This small molecule, SCH-79797 (SCH) was originally used in mammalian experiments to treat thrombosis, as it is a thrombin R inhibitor. We found that it has potent activity in bacteria, and in short, it works by two different mechanisms that complement one another. One mechanism is that it is able to penetrate and disrupt the membranes of Gram-positive and Gram-negative bacteria, but then it is also able to, once it is inside of the cell, disrupt intracellular processes. In particular, it disrupts the ability of the cell to make folate, which is a necessary nutrient that the bacterial cells need to make essential parts of life, DNA, amino acids, proteins. Without these things, the bacteria cell will never grow. Why has your technique been likened to a poisoned arrow? The idea is that for an antibiotic to work, it needs to get into the cell, and then it also has to kill. What we have found is that our antibiotic does two things simultaneously. First, it pokes holes in the bacterial membranes, and so that we liken that to an arrow. That alone is bad for the bacteria – obviously having a hole in your membrane is bad as stuff leaks out. However, it also then inhibits essential folate metabolism processes once it gets inside. We think of the membrane permeabilization, or the hole poking, as the arrow, and then the inhibition of the ability to then make the building blocks that are needed for the bacteria to grow and divide, the folate inhibition, as the poison. How did you develop your new antibiotic? Science is a collaborative effort, and we could not have done this work on our own. We had the help of our co-authors Joe Sheehan, Ben Bratton, and our other collaborators. Our compound is unique and has a mechanism of action that has not been characterized before. Something else that is interesting about this antibiotic is that we were not able to acquire resistance to it in our experiments. Resistance is one of the primary ways that scientists are able to ascertain the mechanism of action of an antibiotic. Without this, we had to employ various methods to come at the problem from different angles. We used metabolism; we used flow cytometry, where we looked at the membrane; we used quantitative high throughput imaging under the microscope; we used genetics; we used proteomics. Basically, to develop this new antibiotic, we employed all these different methods to get different pieces of the puzzle, and then we were able to piece them all together. At the end of the paper, we have this figure where we try to sum up the project. We did something known as bacterial cytological profiling, or BCP, where we can look at how bacteria are affected by a certain antibiotic. From this, we showed that no antibiotic that we tested looks similar to SCH. If you combine two antibiotics that have the two separate mechanisms of action of SCH, and co-treat bacteria with them at the same time, those bacteria now look similar to SCH when they die. We then made a derivative of this molecule which we call Irresistin-16. This was able to have even greater potency and have a greater therapeutic effect in our gonorrhea mouse model than SCH. How did you test the resistance of your antibiotic? In many ways, that was the hardest part, as scientifically it is impossible to prove a negative. We cannot prove that something cannot happen, and so we try to be careful and say that we were unable to detect resistance, or the resistance frequency was below the limit of our detection. This was a really important point that James worked on in a few different ways. The traditional way is to put bacteria on plates that have the antibiotic and the thought is that if one of the bacteria has a mutation that makes it resistant to the antibiotic, then it will grow even in its presence, and you will then be able to isolate the mutant. James tried that with no success, but then he tried a much more quantitative and careful approach, which convinced us that there was no detectable resistance. He took the drug in half the minimal concentration needed to kill the bacteria. In other words, he took a concentration of the drug where the bacteria can still grow, but not well. It was a multiple-month long experiment that he did, where every day or two he would come into the lab and he would grow up bacteria in this concentration that was right on the edge where the antibiotic is effective. The thought was that if there was even minimal mutation that conferred any advantage, those bacteria would grow faster, and because they would grow faster, they would then out-compete their neighbors and would become enriched in the population, and over time you would get this very gradual increase in the resistance. He tested this on many different antibiotics, including antibiotics that are notoriously hard to get resistance to, and he showed that this concept works. Gradually, he was able to evolve resistance to every other antibiotic that he tried, but to SCH there was zero increase in the resistance. It was a completely flat line. Why were you unable to use traditional methods to figure out the mechanisms of antibiotics in this research? The traditional way of figuring out how an antibiotic works is to find resistance mutants. Those usually map to the target of the drug, and then that tells you what the drug is. In this case, there is sort of a double-edged sword. Clinically, the fact that there is no resistance to these compounds is exactly what we want. That is the Holy Grail of antibiotics – an antibiotic that you cannot get resistance to, but at the same time, the reasons that we had to use all of these different approaches was the same reason that we could not eliminate resistance using the traditional way of figuring out the mechanism of action. What was the problem with the original SCH 79797 and how did you solve it? The problem with the original SCH is that it was great at killing bacteria, but when we tested it, it was almost as good at killing many mammalian cells. That is a problem in the sense that for an antibiotic we want something that will kill the bacteria but not kill us. Bleach, for example, is good at killing bacteria but is not a good antibiotic because it kills our cells just as well. In its original configuration, SCH was not quite like that, but it was in that direction, and so what we then did was make derivatives of SCH. We were very excited that we found this derivative of SCH, which we named Irresistin-16. The great thing about Irresistin-16 is that it maintains the same level of toxicity towards mammalian cells as SCH, but it kills bacteria at 100 to 1000 times lower levels, so there is more potency towards killing the bacteria. Since we did not change the level at which we kill the mammalian cells, but we dramatically changed the level at which we kill bacteria. This means we have this 100 to 1000-fold window of concentrations that can be below the concentration of killing the mammalian cells, but above the concentration of killing the bacterial cells. What examples of bacteria have you shown your antibiotic to be effective against? One is MRSA, methicillin-resistant Staphylococcus aureus which is a huge problem, especially in hospital settings. Another is Acinetobacter baumannii, which is a Gram-negative bacterium that is notorious for its antibiotic resistance. This bacteria was actually a big problem here in America during, I believe, the war in Iraq, because this bacteria is very heat tolerant, and so in those conditions, the bacteria would live and subsist on medical equipment or beds. Soldiers who needed amputations or something of that nature, would get this infection and bring it back home. Neisseria gonorrhoeae was a big one, and that was very important because it is Gram-negative and we are running out of antibiotics to treat drug-resistant gonorrhea. I believe we recently found resistance to the last-resort antibiotic, and so it is imperative. Even the World Health Organization says that this is a problem that needs to be addressed. One very exciting thing is that the World Health Organization has a strain of Neisseria gonorrhoeae that is resistant to almost all known antibiotics, and yet our drugs were able to kill those strains. That was very exciting for us, and it suggests that this concept that we started with, a genuinely new class of antibiotics, could really work in combatting antibiotic resistance. What stages are needed before your drug can hopefully be used to treat these infections in humans? First, we have to make it clear that there are a lot of steps between this and applying it to people. At the moment we have helped treat gonorrhea in mice. We are actively working on various things to improve the drug. There are three main things....

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New Killing Mechanism Discovered in ‘Game-Changing’ Antibiotic

AHA Publisher — Thu, 11 Jun 2020 07:00:15 +0000

University of Liverpool via EurekAlert – Scientists at the University of Liverpool and University of Utrecht have taken another step forward on their quest to develop a viable drug based on teixobactin – a new class of potent natural antibiotic capable of killing superbugs. *Teixobactin is a peptide-like secondary metabolite of some species of bacteria, that kills some gram-positive bacteria. It appears to belong to a new class of antibiotics, and harms bacteria by binding to lipid II and lipid III, important precursor molecules for forming the cell wall. Research published in Nature Communications provides fundamental new insights into how teixobactins kill bacteria, including the discovery of a new killing mechanism that could help inform the design of improved teixobactin-based drugs. Teixobactin was hailed as a ‘game changer’ when it was discovered in 2015 due to its ability kill multi-drug resistant bacterial pathogens such as MRSA without developing resistance. If made suitable for humans, it would mark the first new class of antibiotic drug for 30 years. Dr Ishwar Singh, an expert in Antimicrobial Drug Discovery and Development and Medicinal Chemistry at Liverpool’s Centre of Excellence in Infectious Diseases Research, has led pioneering research over the past six years to develop teixobactin-based viable drugs. His research team was the first in the world to successfully create simplified synthetic forms of teixobactins which are effective in treating bacterial infections in mice. Dr Singh explained: “We know that the therapeutic potential of simplified synthetic teixobactins is immense, and our ultimate goal is to have a number of viable drugs from our synthetic teixobactin platform which can be used as a last line of defence against superbugs to save lives.” In collaboration with NMR expert Professor Markus Weingarth at the University of Utrecht, the team used high resolution solid state NMR, and microscopy to show, for the first time, how synthetic teixobactins bind to lipid II (an essential component of the bacterial membrane) and kill the bacteria. Dr Singh said: “It had been assumed that teixobactins kill the bacteria by binding to bacterial cell wall bricks such as lipid II, but never shown until now. Our work also suggests that teixobactins kill the bacteria by capturing lipid II in massive clusters, a new killing mechanism, which we were excited to discover.” Antimicrobial resistance (AMR) is a grave threat to human health and prosperity. The O’Neill report, commissioned by the UK government and published in 2016, suggests that without action AMR will cause the deaths of 10 million people a year by 2050. The development of new antibiotics is therefore a crucial area of study for scientists around the world. Dr Singh added: “A significant amount of work remains in the development of teixobactins as a therapeutic antibiotic for human use. Our study is a real step in right direction and opens the door for improving teixobactins and moving these toward clinic. “So far, we have demonstrated that we can make teixobactins which are effective in treating infections from resistant bacterial pathogens and understand their binding modes in a bacterial membrane. Now we need to expand our understanding on mode of action on a library of teixobactins with different bacterial membranes to develop a catalogue of molecules which have potential to become a drug for human use.” This article has been modified. To read the original article click here. *information obtained here.

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