Discovering New Tickborne Diseases
CDC is partnering with the Minnesota Department of Health, Mayo Clinic, Tennessee Department of Health, and Vanderbilt University to obtain up to 30,000 clinical specimens from patients with suspected tickborne illness over a 3-year period. CDC will use advanced molecular detection methods to identify tickborne bacteria that may be the cause of these patients illnesses. Already, investigators have used AMD to sequence the full genome of a newly discovered bacteria, Borrelia mayonii, which is another cause of Lyme disease in upper Midwestern states.
Using advanced molecular detection techniques, CDC researchers analyzed over 13,000 leftover samples for the presence of bacteria from patients who were suspected of having tickborne illness. Twelve tickborne species of bacteria that cause illness in people were detected, including two not previously associated with human illness. This large-scale study involving researchers from the Minnesota Department of Health, Mayo Clinic, Tennessee Department of Health, and Vanderbilt University, showed that a single advanced molecular detection test can be used to:
- Detect tickborne bacterial pathogens in clinical samples
- Discover bacteria not previously associated with human infection, that are likely transmitted to humans by tick bite
- Identify tick-transmitted bacterial co-infections
- Understand which bacterial infections can cause symptoms that may be confused with tickborne diseases
Why Is The Study Of Lyme Disease A Priority For Niaid
State health departments reported 42,743 confirmed or probable cases to the Centers for Disease Control and Prevention in 2017. Reported cases are not believed to reflect the actual incidence of Lyme disease, and CDC estimates that 300,000 cases likely occur annually. The incidence of Lyme disease, as with many other tick-borne diseases, has increased dramatically over the past 10 years.
The Science Of Stopping Lyme
Creatures that spread diseases through bites such as mosquitos that transmit malaria and raccoons that transmit rabies usually deliver the virus, bacteria, or parasite instantly. But when a black-legged tick latches onto someone, it takes at least 36 hours to pass along the Lyme-causing bacterium, Borrelia burgdorferi, says Gary Wormser, MD, chief of the Division of Infectious Diseases at New York Medical College. That lag, he notes, provides time for antibodies to get into the ticks gut and prevent transmission of the bacterium before it sets off an infection in the human.
Whats more, the bacterium has virtually no machinery to survive mutation, Klempner says, so that researchers can identify and stick with antibodies that eradicate the bacterium rather than having to keep up with mutated versions.
LYMErix, manufactured by what was then SmithKline Beecham, induced patients to produce antibodies that a tick would absorb from its victims blood and that neutralized Borrelia burgdorferi. Studies showed the vaccine to be about 75% effective in blocking the disease. The FDA approved it in 1998.
It wasnt a perfect vaccine, but it was good, says Eugene Shapiro, MD, professor of epidemiology and investigative medicine at Yale School of Medicine in Connecticut.
That experience chilled research into prophylactic treatments against Lyme, Klempner says, even though biologically, its an easy target.
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Understanding Attitudes Towards Vaccination For Lyme Disease
CDC is currently conducting research to understand what concerns healthcare providers and the public may have about any potential Lyme disease vaccines.
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Azlocillin Comes Out On Top
The drug, which is not on the market, was tested in mouse models of Lyme disease at seven-day, 14-day and 21-day intervals and found to eliminate the infection. For the first time, azlocillin was also shown to be effective in killing drug-tolerant forms of B. burgdorferi in lab dishes, indicating that it may work as a therapy for lingering symptoms of Lyme disease.
Pothineni and Rajadas have patented the compound for the treatment of Lyme disease and are working with a company to develop an oral form of the drug. Researchers plan to conduct a clinical trial.
Rajadas is also a professor of bioengineering and therapeutic sciences at the University of California-San Francisco.
Other Stanford co-authors are Hari-Hara S. K. Potula, PhD, senior research scientist postdoctoral scholars Aditya Ambati, PhD, and Venkata Mallajosyula, PhD senior research scientist Mohammed Inayathullah, PhD and intern Mohamed Sohail Ahmed.
A researcher at Loyola College in India also contributed to the work.
The study was funded by the Bay Area Lyme Foundation and Laurel STEM Fund.
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Lyme Disease Diagnostics Research
There is a great need to develop rapid, point-of-care tests to determine whether people are infected with Borrelia burgdorferi, the bacterium that causes Lyme disease. NIAID is committed to improving Lyme disease diagnostics by supporting innovative research projects.
Priorities include finding potential targetssubstances that new diagnostic tools might measure in patient samplesand improving the sensitivity and specificity of currently available diagnostic tests, thereby leading to more accurate results.
Scientists Find Promising New Treatment For Lyme Disease
A new study gives hope that an effective treatment for Lyme disease may be available in the future. The new treatment involves the drugs cefotaxime and azlocillin.
The new paper appears in the Nature journal Scientific Reports .
Lyme disease affects nearly 300,000 people a year in the United States and around 230,000 people a year in Europe, according to an article in the Journal of Public Health .
Bacteria belonging to the group Borrelia burgdorferi cause Lyme disease. Most people develop it after being bitten by a tick that carries the bacteria.
Approximately 6080% of people with Lyme disease develop a circular red skin rash called erythema migrans around the infected tick bite, and some also develop flu-like symptoms.
Most people develop the rash within 4 weeks of being bitten, but it can appear up to 3 months afterward.
of people with the disease later develop symptoms of fatigue, pain in their muscles, joints or nerves, and cognitive impairment.
These symptoms can continue for months or even years after their initial infection.
Researchers have suggested that this may because of drug-tolerant persisters, a group of bacterial cells that survive the initial dose of antibiotics.
Others believe its an immune disorder caused by bacteria during the first exposure, which causes a perpetual inflammation condition. Whatever the cause, the pain for patients is still very real.
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Monoarthritis Risk Stratification In Lyme Disease
In Lyme disease endemic areas, a noninvasive clinical prediction model to distinguish septic arthritis from Lyme arthritis would be useful, especially in children. A new study suggests that in highly selected patients, such prediction might be possible. But failure to recognize even a few cases of septic arthritis could have devastating consequences.
What Is Cdc Doing
CDC is currently conducting research to understand what concerns healthcare providers and the public may have about any potential Lyme disease vaccines. Once a Lyme disease vaccine is approved as safe and effective by the Food and Drug Administration , CDC will work with the Advisory Committee on Immunization Practices to develop recommendations about where in the U.S. the public might benefit from a Lyme disease vaccine. CDC will communicate these recommendations to increase awareness of a vaccine among the public and clinicians to prevent Lyme disease in the United States.
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Biorepositories And Research Cohorts
Well-characterized samples are an essential tool to help researchers develop and validate new diagnostic tests and to better understand the complexities of LD. Well-characterized sample sets can benefit medical providers, test developers, and the public at risk for LD . It is critical that sample users understand the criteria used to enroll participants, how samples were collected and stored, and what additional clinical and testing data may be available. Additional benefits can be realized when multiple sample users are using the same well-characterized sample sets. Current sample sets available for researchers include the CDC Lyme Serum Repository , the Lyme Disease Biobank , and samples from the Studies of Lyme Immunology and Clinical Events at Johns Hopkins University School of Medicine. Additionally, some investigators also have their own sample collections with, in some cases, blood samples, skin biopsy specimens and synovial fluid which form the basis for collaborative studies .
Lyme Disease Biobank
Lyme Disease Research Center
Long Island Outdoor Worker Cohort
All Tickborne Diseases Are On The Rise Nationally And Globally
The urgent public health problem of Lyme disease requires a swift, comprehensive solution. Doctors disagree on the best therapy and federal research funding has been limited.
Public health’s fresh approach to science-driven problem-solving is designed to answer crucial questions such as:
- How does the disease originate at the molecular level and then spread from ticks to human hosts?
- What are the best policies for containment and eradication?
Our vision is clearer and more urgent than ever. Smallpox was the first disease to be eradicated globally, using a multi-pronged attack by microbiologists, vaccine specialists, epidemiologists, clinicians, policy makers, advocates, and community workers. Similar collaborative efforts are targeting polio and parasitic worms. Lyme disease and all tickborne illnesses should be next.
Establish the Johns Hopkins Lyme and Tickborne Diseases Research and Education Institute
The Department of Molecular Microbiology and Immunology at the Johns Hopkins Bloomberg School of Public Health will host the Institute, where premier public health researchers can collaborate with medical school colleagues as well as national and international organizations such as the Global Lyme Alliance. Arturo Casadevall, chair of MMI, envisions the Institute as both a research hub and a critical training ground for the next generation of young scholars.
Estimated costs for the Institute:
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Has Niaid Looked At Whether Infection Persists After Antibiotic Therapy
Several recent studies suggest that B. burgdorferi may persist in animals after antibiotic therapy. In one study, NIAID-supported scientists found that remnants of B. burgdorferi remained in mice after antibiotic treatment. Another team of NIAID-supported investigators found that intact B. burgdorferi persist in nonhuman primates after antibiotic treatment. It was not possible to culture these bacteria and it is not clear whether they are infectious. More recent work by Hodzic et al. replicated the earlier finding of persisting DNA but non-cultivatable B. burgdorferi after antibiotic treatment using a mouse model. In 2017, scientists at the Tulane National Primate Research Centers, funded in part by an NIH research resources grant, reported evidence of persistent and metabolically active B. burgdorferi after antibiotic treatment in rhesus macaques.
In a first-of-its-kind study for Lyme disease, NIAID-supported researchers have used live, disease-free ticks to see if Lyme disease bacteria can be detected in people who continue to experience symptoms such as fatigue or arthritis after completing antibiotic therapy). This study remains underway.
Unraveling The Mystery Of Lyme Disease
Vol. 53 No. 4
Monitor on Psychology53
Long before the SARS-CoV-2 virus was linked to a syndrome we now call long COVID, researchers and clinicians were already debating over how to best assist patients experiencing lingering symptoms from Lyme disease. For reasons that are unclear, 10% to 20% of people who contract Lyme disease report ongoing or intermittent symptoms at least a year after completing antibiotic treatment, including fatigue, muscle aches, difficulties with memory, irritability, and other symptoms, according to a review of the research .
For patients, these ongoing and sometimes debilitating symptoms can erode their quality of life, potentially leading to depression, anxiety, and other mental health issues. But over the past few decades, researchers have also determined that the tick-borne infection itself, along with related inflammatory and other physiological effects, may directly cause mental health disorders.
One recent study, conducted by researchers from the Columbia University Irving Medical Center and the Copenhagen Research Centre for Mental Health, found that patients who received a hospital diagnosis of Lyme disease had a 28% higher rate of mental disorders and were twice as likely to have attempted suicide postinfection than individuals without a Lyme diagnosis .
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Do You Have Lyme Disease
Warm weather brings outdoor fun and also the risk of tick bites, which can cause Lyme disease. The Lyme disease rash is usually round or oval and gradually expands. It may be all red or have a bulls-eye appearance. If untreated, the infection may spread to other parts of the body and cause other problems, including paralysis of the face severe headaches and neck stiffness because of meningitis heart palpitations and dizziness because of changes in heartbeat and intermittent bouts of arthritis, with joint pain and swelling, particularly involving the knees.
If you suspect that you have Lyme disease, you may be eligible to participate in one of the research studies currently underway at the National Institutes of Health in Bethesda, Maryland. The studies offer evaluation, therapy, and follow up to patients with Lyme disease in hopes of learning more about the infection.
Has Niaid Looked At The Potential Benefits Of Long
Yes. NIAID has funded three placebo-controlled clinical trials on the efficacy of prolonged antibiotic therapy for treating PTLDS. The published results were subjected to rigorous statistical, editorial, and scientific peer review.
These trials were designed to ensure that several key parameters were addressed:
- The susceptibility of B.burgdorferi to the antibiotics used
- The ability of the antibiotics to both cross the blood-brain barrier and access the central nervous system and to persist at effective levels throughout the course of therapy
- The ability of the antibiotics to kill bacteria living both outside and inside mammalian cells
- The safety and welfare of patients enrolled in the trials
The first clinical trial, which included two multicenter studies, provided no evidence that extended antibiotic treatment is beneficial. In those studies, physicians examined long-term antibiotic therapy in patients with a well-documented history of previous Lyme disease but who reported persistent pain, fatigue, impaired cognitive function, or unexplained numbness. Those symptoms are common among people reporting PTLDS. Patients were treated with 30 days of an intravenous antibiotic followed by 60 days of an oral antibiotic.
In 2016, a clinical trial conducted in the Netherlands also concluded that in patients with persistent symptoms attributed to Lyme disease, longer term treatment with antibiotics did not provide additional benefits compared with shorter term regimens.
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Recent Progress In Lyme Disease And Remaining Challenges
Lyme disease is the most common vector-borne disease in the United States with an estimated 476,000 cases per year. While historically, the long-term impact of Lyme disease on patients has been controversial, mounting evidence supports the idea that a substantial number of patients experience persistent symptoms following treatment. The research community has largely lacked the necessary funding to properly advance the scientific and clinical understanding of the disease, or to develop and evaluate innovative approaches for prevention, diagnosis, and treatment. Given the many outstanding questions raised into the diagnosis, clinical presentation and treatment of Lyme disease, and the underlying molecular mechanisms that trigger persistent disease, there is an urgent need for more support. This review article summarizes progress over the past 5 years in our understanding of Lyme and tick-borne diseases in the United States and highlights remaining challenges.
What Is Lyme Disease
Lyme disease is an infection caused by Borrelia burgdorferi, a type of bacterium called a spirochete that is carried by deer ticks. An infected tick can transmit the spirochete to the humans and animals it bites. Untreated, the bacterium travels through the bloodstream, establishes itself in various body tissues, and can cause a number of symptoms, some of which are severe. Often, an erythema migrans rash appears within 7-14 days at the site of a tick bite .
LD manifests itself as a multisystem inflammatory disease that affects the skin in its early, localized stage, and spreads to the joints, nervous system and, to a lesser extent, other organ systems in its later, disseminated stages. If diagnosed and treated early with antibiotics, LD is almost always readily cured. Generally, LD in its later stages can also be treated effectively, but because the rate of disease progression and individual response to treatment varies from one patient to the next, some patients may have symptoms that linger for months or even years following treatment. In rare instances, LD causes permanent damage.
Although LD is now the most common arthropod-borne illness in the U.S. , its diagnosis and treatment can be challenging for clinicians due to its diverse manifestations and the limitations of currently available serological tests.
Borrelia burgdorferi
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Genomic Insights From Borreliaceae Lineages
Between 1982 and 2010, the B. burgdorferi species complex, known as B. burgdorferi sensu lato, steadily expanded from 1 to 18 species as isolates from tick vectors, their hosts, and patient samples were characterized . A subset of these species are associated with human disease. B. burgdorferi sensu stricto in the USA, as well as B. afzelii and B. garinii in Eurasia are the most common agents of LD in the Northern hemisphere. Cases of LD in Europe are also caused by Bb and B. bavariensis , but are less common. B. spielmanii , B. bisettiae , and B. lusitaniae have been identified in human specimens but their clinical importance is less clear. B. valaisiana has been identified in human specimens , but others have recently provided compelling reasons why existing evidence does not support it being considered a human pathogen . Additional species have been identified in tick vectors or their hosts, but not in patient samples.