Tag Archives: genetic disease

Lyme Disease In Canada And USA Has Epidemic Potential- New Microbes Discovered

Spring means fresh flowers and sunny days, but it also brings seasonal health issues as the weather gets warmer: from Rosacea to Lyme disease.

Most likely, you or someone you know has been affected by Lyme disease, the most common tick-borne illness in North America with more than 300,000 cases diagnosed each year. In a timely new book, Conquering Lyme Disease(Columbia University Press), Columbia University Medical Center physicians Brian A. Fallon and Jennifer Sotsky reveal that despite the challenges to find a cure for this complex, debilitating disease, precision medicine and biotechnology are accelerating the discovery of new tools with which doctors will be able to diagnose it and treat patients.

“Through rapid genetic sequencing, scientists can identify many different strains of Borrelia burgdorferi as well as new tick-borne microbial infections, such as Borrelia miyamotoi, Borrelia mayonii, and the Heartland virus.”  — Brian Fallon 

Could groundbreaking technologies that rapidly increase our understanding and open up new pathways mean a cure for Lyme disease one day soon? The Global Search for Education is pleased to welcome Dr. Brian Fallon to find out how tech is tackling the ticks.

“Modern technology using Next-Generation Sequencing (NGS) allows one to discover with great rapidity all microbes that may be present within a sample of fluid.” — Brian Fallon

Brian, how has technology improved the research process for tick borne diseases?

Consider the difference in price of genome sequencing between 20 years ago and today. In 2003, it had taken the Human Genome Project about 4 years and costs estimated between $500 million to 1 billion…by 2006 the cost for sequencing a single human genome had dropped to 14 million……today a whole human genome can be sequenced within days for less than $1,000.   This is a tremendous advance.

Why is genome sequencing so important?  Let’s look at human tick-borne diseases.  When two different people are infected with Borrelia burgdorferi (the microbe that causes Lyme disease), one will resolve the disease quickly after a course of antibiotics while the other may develop a chronic relapsing remitting illness.  Why?  Because one person might have gotten a more persistent strain, while the other received  a less invasive strain that stays localized to the skin.  Additionally, the genetic differences in the human determines how the immune system responds to the invading microbe. Understanding the genetics of the infection and of the human host allows scientists to unravel the mysteries of tick-borne illnesses.

Through rapid genetic sequencing, scientists can identify many different strains of Borrelia burgdorferi as well as new tick-borne microbial infections, such as Borrelia miyamotoi, Borrelia mayonii, and the Heartland virus.  When the genome of a microbe is sequenced, it provides a starting point for the study of pathogenesis, vaccine development, and treatment.  Discovery of these new microbes inside ticks has been enormously helpful.  A patient who has had typical symptoms of Lyme disease after a tick bite but has tested negative on the blood tests for Lyme disease might puzzle clinicians. They may criticize the insensitivity of the Lyme disease tests.  However, when this same patient is tested for the newly discovered tick-borne infection, Borrelia miyamotoi, the diagnosis is then clear. Yes, the patient had a Lyme-like illness, but it wasn’t Lyme disease: it was Borrelia Miyamotoi disease.

Modern technology using Next-Generation Sequencing (NGS) allows one to discover with great rapidity all microbes that may be present within a sample of fluid.   This  “discovery based” approach using “unbiased next generation sequencing” enabled a 14 year old boy to be rescued from a fatal infection within 48 hours (Wilson et al, NEJM, 2014). This boy had endured 3 hospitalizations over 4 months, had over 100 diagnostic tests, spent 44 days in an ICU for encephalitis of unknown etiology, had a brain biopsy, and had to be put into a medically induced coma to prevent damage from his ongoing seizures.

Eventually Dr. Charles Chiu at U.C.S.F. employed NGS analysis of more than 8 million sequences with a bioinformatics pipeline (SURPI) for the detection of all known pathogens. The cause of the boy’s meningoencephalitis was revealed as Leptospira santarosai. He had likely acquired it in Puerto Rico, as it is not present in the continental United States.  He received the appropriate antibiotics and was discharged 2 weeks later to rehab.  This same approach is especially useful for uncommon infections as they might not be suspected; for example, rare tick-borne viruses such as Powassan Virus or Heartland Virus can be rapidly  detected using this discovery approach.

DNA Double Helix
DNA Double Helix
How has big data impacted the way advocacy groups support research?

A patient-generated source of Big Data is LymeDisease.org.  This California based organization developed a survey called “My Lyme Data” that patients could fill out on the web about their clinical history and lab tests and treatments.  In a short period of time, they had data on 10,000 patients whom they track over time.  With this information, they provide a more comprehensive clinical view of the bulk of patients who are diagnosed with persistent symptoms despite treatment for Lyme Disease (aka Chronic Lyme Disease).

“In geographic areas where medical professionals are scarce, AI technologies will play an increasing role in improving patient care by allowing differential diagnoses to be generated and treatment options suggested through AI-based systems accessed through the internet.”  — Brian Fallon

Jobs in all professions are being automated. Do you believe AI technologies will only assist doctors or will they replace physicians in some tasks? What does this mean for doctors, nurses, and the future of medicine?
Borrelia transmission via Tick
Borrelia

While AI technologies will go a long way to assist health care providers to provide better care, its application to medical care is still just beginning.   One can anticipate, however,  that in geographic areas where medical professionals are scarce, AI technologies will play an increasing role in improving patient care by allowing differential diagnoses to be generated and treatment options suggested through AI-based systems accessed through the internet.

The general public has more access to information than ever before about Lyme disease from websites, medical organizations, articles and social media. Everyone can be their own “expert” or even their own “doctor.”  Can you speak about the pros and cons of online health data in the era of fake news?

This obviously is a huge area of concern. Individuals used to turn to their physician or to the medical information books, such as the Merck Manual. Now, they turn to the web.

In a recent survey of patients who used the web to obtain health information (Doherty-Torstrick 2016), we learned that more than half of the 730 patients reported they experienced increased distress as a result of checking the web.  We also learned from this survey that individuals who did not have a health education were more likely to spend more time on the web and were thus prone to develop more anxiety than those who were better educated from a health perspective.   While some of the information they find may be accurate, other information may be well-intentioned but ill-informed, misleading, and even harmful.

“Researchers can rapidly screen thousands of drugs to determine which agents have the strongest ability to kill Borrelia spirochetes.  This is possible because of the development of high throughput assays, which have proven more effective than the standard agents in eradicating both the stationary phase Borrelia and its more drug-tolerant persister-forms.” — Brian Fallon

Tick distribution Canada

Look into the future.  What are the technologies you are most excited about in terms of helping to find cures for Lyme disease and improve patients quality of life?

Researchers can rapidly screen thousands of drugs to determine which agents have the strongest ability to kill Borrelia spirochetes (Feng 2014).  This is possible because of the development of high throughput assays, which have identified new antibiotics that have proven more effective than the standard agents (doxycycline, amoxicillin) in eradicating both the stationary phase Borrelia and its more drug-tolerant persister-forms.  While it cannot be assumed that what is true in the lab setting will translate to efficacy in humans, biotechnology advances have enabled the identification of new therapeutic agents, offering  much hope for a wider array of treatment options for patients in the future.

Another major advance is “big data” conducted by biomedical information engineers trained in biostatistics and computer science.  Internet search engine queries are being monitored to predict outbreaks of infectious disease.  Unanticipated side effects of drugs and their interactions can be detected through analyzing millions of digital medical records from patients who have taken a particular drug.  One can examine whether patients given an antibiotic did better when treated for longer or shorter periods, or whether patients with a pre-existing autoimmune disease are more likely to develop complications from a new onset Tick-borne infection than those without a history of autoimmune problems.

Tick
2005 James Gathany; William Nicholson
The blacklegged ticks, I. pacificus, (depicted here), and I. scapularis, are known vectors for the zoonotic spirochetal bacteria Borrelia burgdorferi, which is the pathogenic bacteria responsible for causing Lyme disease. The ticks, inoculated with the bacterium when they bite infected mice, squirrels and other small animals, subsequently pass the pathogens to their human victims when they obtain a blood meal.B. burgdorferi bacteria can infect several parts of the body, producing different symptoms at different times. Not all patients with Lyme disease will have all symptoms, and many of the symptoms can occur with other diseases as well. If you believe you may have Lyme disease, it is important that you consult your health care provider for proper diagnosis.
The first sign of infection is usually a circular rash called “erythema migrans”, or EM. This rash occurs in approximately 70-80% of infected persons and begins at the site of a tick bite after a delay of 3-30 days. A distinctive feature of the rash is that it gradually expands over a period of several days, reaching up to 12 inches (30 cm) across. The center of the rash may clear as it enlarges, resulting in a bull’s-eye appearance. It may be warm but is not usually painful. Some patients develop additional EM lesions in other areas of the body after several days. Patients also experience symptoms of fatigue, chills, fever, headache, and muscle and joint aches, and swollen lymph nodes. In some cases, these may be the only symptoms of infection.

Our Lyme and Tick-borne Diseases Research Center, located at the Columbia University Irving Medical Center (CUIMC) in New York City, is right next door to an international data resource.  CUIMC is the coordinating center of a public health information initiative which includes medical records from approximately 400 million people drawn from eighty health-care organizations from around the world.  This represents a unique opportunity  to ask questions, generate hypotheses and get answers about Tick-borne diseases.  When discovery is optimized, medical care is enhanced.

For the Silo, David Wine/CM RubinWorld. 

Brian Fallon, MD, MPH is the Director of the Lyme and Tick-Borne Diseases Research Center at the Columbia University Irving Medical Center and the author with Jennifer Sotsky of Conquering Lyme Disease: Science Bridges the Great Divide, published in 2018 by Columbia University Press.

Disease Did Not Stop Marine Swimming Alcatraz To San Fran Blindfolded

Shackled but making waves- Jay Platt swimming from Alcatraz Island to San Francisco with his hands and feet tied.
Shackled but making waves- Jay Platt swimming from Alcatraz Island to San Francisco with his hands and feet tied.

For as long as he could remember, Jay Platt wanted to be a  U.S. Marine, and for nearly 15 years, he lived that dream. But in 1998, a rare condition called von Hippel Lindau syndrome (VHL), attacked his eyes, brain, spine and kidneys, forcing his retirement from the service.

“Before VHL I pretty much felt untouchable – until I started  having symptoms and the eventual diagnosis,” he says.

"I was scared, confused and angry" Jay Platt explains some of the emotions that he has learned to conquer.
“I was scared, confused and angry” Jay Platt explains some of the emotions that he has learned to conquer.

“I was scared, confused and angry for a number of years; I  couldn’t understand why God would do this to me. I went from feeling  invulnerable to officially being considered handicapped.”

After a personal journey of acceptance, Platt re-calibrated his sense of purpose by accepting challenges many world-class athletes wouldn’t  consider. Along with a record-breaking Mississippi swim while blindfolded,  handcuffed and shackled, he swam from Alcatraz Island to San Francisco with his  hands and feet tied, and he was one of fewer than 300 people to hike the more  than 2,100-mile southbound Appalachian Trail.

Platt, who is the subject of the new documentary, “Living  Unstoppable,” (www.LivingUnstoppable.com), explains his  transformation and how others might apply the lessons of his journey to their  own lives:

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The motivation of “can’t” … Something is triggered in people when they’re told they can’t do something. Those who want to do what they “can’t” eventually find a way if they’re motivated and determined. “I don’t care who you are – everybody goes through something in life; nobody gets through unscathed,” he says. “And everyone, at some point, faces something they believe they can’t do – but want very much. If you haven’t yet, you will, and coming to terms with it will be a process.” Use it as motivation for living life to the fullest, and let it show you how beautiful our time on Earth really is, he says.

The lesson of the severely handicapped little girl: Platt experienced a long period of despair, hopelessness and rage against the universe. One day while at the park, he heard the pure joy in the laughter of a severely handicapped girl who was being pushed in a wheelchair by her mother. “ ‘Listen to the birds, Momma,’ I heard her say – she was just so happy to experience that simple pleasure,” he says. “That has stayed with me ever since; if that little girl could get past her suffering and appreciate singing birds, then I could do much better.”

A promise to contribute to the greater good: The onset of his VHL symptoms, which included vision problems in his left eye and disorientation, was a very scary period for Platt. During this period he made a promise to himself and God to devote his life to others if he survived. He has kept that promise – his Appalachian Trail hike alone raised $109,000 for charity.

You are still you; don’t let tragedy totally define you: While Platt is officially retired from the USMC, he is still the same guy who fully lived a proud life as a Marine for a decade and a half. While how you respond to hardship says much about one’s character, you don’t have to remain psychically stuck in the worst part of your life by identifying most with a weakness. Use a handicap, for example, for what it’s worth – something that helps you strive for significance and fulfillment in life.  For the Silo, Ginny Grimsley. 

About Jay Platt
Jay Platt was medically retired from the Marine Corps in  1998 after suffering complications from von Hippel Lindau syndrome (VHL), a genetic disease that resulted in brain and spinal tumors, kidney cancer, and the loss of his left eye. When told his future would be considerably dimmer than his past, Platt set out to rebuild himself physically, mentally and spiritually, and to challenge himself by setting demanding physical goals. He was one of fewer than 300 people to have hiked the more than 2,100-mile southbound Appalachian Trail; one of three to swim from Alcatraz Island to San Francisco with hands and feet tied; and the only person to swim across the Mississippi River while blindfolded, handcuffed and shackled. The proceeds from his adventures and sales of his documentary benefit non-profits, including the VHL Family Alliance.