Archive for the ‘research’ Category

10 Million for Lyme Research

http://www.hopkinsmedicine.org/news/media/releases/johns_hopkins_awarded_10_million_cohen_foundation_grant_to_expand_current_lyme_disease_research_initiatives

Johns Hopkins University received a $10 million grant from the Steven and Alexandra Cohen Foundation to explore Lyme disease and develop potential new therapies to address the illness. Johns Hopkins is the only institution in the nation to receive multiple Lyme disease grants from the foundation.

The grant will be divided among three Johns Hopkins research teams led by John Aucott, M.D.; Ying Zhang, M.D., Ph.D.; and Brian Schwartz, M.D.

John Aucott, M.D.
John Aucott, M.D., assistant professor of medicine, and colleague Mark Soloski, Ph.D., professor of medicine, both of the Johns Hopkins University School of Medicine, received a five-year grant for $6 million to support the continuation of the Johns Hopkins Lyme Disease Research Center’s Study of Lyme Disease Immunology and Clinical Events, a longitudinal effort that identifies patients at the onset of Lyme disease, initiates standard treatment and follows them over a one-year period. The aim is to characterize those patients that develop post-treatment Lyme disease syndrome and analyze the immunological pathways triggered as the disease progresses in those patients.

“This grant allows us to expand our research and gain a better understanding of the disease,” Aucott says. “It also allows for greater diversity among participants so we can get more substantive information that can inform future developments in the field of Lyme research and discovery.”

Aucott and Soloski’s work will involve detailed clinical, immunological and molecular profiling, and will be done in collaboration with Joel Dudley, Ph.D., assistant professor of genetics and genomic sciences and director of biomedical informatics at the Icahn School of Medicine at Mount Sinai, in New York City. Dudley will support Aucott and Soloski by developing high-level computer modeling that will aid in the analysis of the large data sets.

With support from the grant, Aucott, director of the Johns Hopkins Lyme Disease Research Center, plans to open a new research site each year of the grant. For year one, he has already begun expanding the Green Spring Station clinical research site in Lutherville, Maryland, nearly doubling the number of exam rooms. Aucott also plans to build a Lyme research clinic at Johns Hopkins Bayview Medical Center. For the second year, he is looking to set up a site in Howard County, Maryland. For year three, he hopes to expand into Pennsylvania. His plans for years four and five will explore sites throughout the East Coast.

“As Lyme cases continue to increase in the U.S., there is an increasing need to understand the disease and its outcomes,” says Aucott. “We have no way of predicting who will recover and who won’t. This grant will allow us to explore why post-treatment Lyme disease syndrome exists, the mechanisms behind the disease and the pathways through which it causes symptoms so that one day, we can use that information to develop ways to prevent the disease or develop more effective drugs. Currently, we don’t have a full understanding of the disease or the most effective ways to treat those it impacts.”

Ying Zhang, M.D., Ph.D.
Ying Zhang, M.D., Ph.D., professor of molecular microbiology and immunology at the Johns Hopkins Bloomberg School of Public Health, received $2.5 million from the foundation for a five-year grant that will allow him and his team to test potential new ways to treat Lyme disease. The grant will support Zhang’s efforts to develop optimal drug combinations to more effectively combat post-treatment Lyme disease syndrome, focusing on developing effective oral drug combination regimens. First, Zhang and his team will develop an oral version of a triple-drug combination that currently is only available through IV. The oral drug combinations will then be tested in vitro (test tube) for effectiveness against Borrelia persisters using novel methodologies recently developed by his group. Next, the drug combinations will be tested in a mouse model of persistent Lyme disease to confirm efficacy, followed by validation in a monkey model, to be performed by his collaborator Monica Embers, Ph.D., from Tulane University.

“This grant is very important for us because it provides stability to the Lyme research program here at Johns Hopkins,” Zhang says. “It will allow us to advance potential new and more effective therapies for this complex and intriguing disease. There is currently no therapy available that effectively treats post-treatment Lyme disease syndrome. “We may be able to fast-track the development of new and better ways to treat the disease.”

Brian Schwartz, M.D.
Brian Schwartz, M.D., professor in the Department of Environmental Health and Engineering at the Johns Hopkins Bloomberg School of Public Health, received more than $1 million from the foundation to conduct a three-year, two-phase investigation of Lyme disease in Pennsylvania, one of the hardest-hit regions for the disease.

In phase I, Schwartz and colleagues will conduct a large-scale, population-based study of the epidemiology of Lyme disease using data from electronic health records from the Geisinger Clinic. These data are available for over 500,000 patients from 2001 to present. Schwartz and colleagues will link that information to community data on land use and land cover — for example, agricultural land, forested land and low-density suburban development. In addition, Schwartz will evaluate populations vulnerable to Lyme disease, delayed diagnosis and treatment by looking at these features by age, sex, race/ethnicity, family socioeconomic status, community socioeconomic status, and a variety of other community and environmental variables.

For phase II, a questionnaire-based study will be performed to assess vulnerabilities within the population. This will include aspects of individual, occupational and community risks, as well as an assessment of people’s knowledge, attitudes and practices regarding Lyme disease diagnosis, treatment and long-term prognosis. Investigators will also analyze who is getting Lyme disease and why, how long it takes until diagnosis, and appropriate treatment. This research will allow for the evaluation of Lyme disease risk, and assess diagnosis and treatment patterns, with a goal of identifying new management strategies to address Lyme disease.

Discovered more than four decades ago, Lyme disease has now spread rapidly throughout the East Coast and Midwest. It is estimated to afflict more than 300,000 people per year, becoming the sixth most common reportable infectious disease in the U.S. However, little is understood about the complex pathogenesis of the disease, which costs the U.S. economy up to $1.3 billion per year in treatment costs alone.

Related Stories:

First U.S. Center to Study Lyme Disease Launched at Johns Hopkins Medicine
On the Web:

Steven & Alexandra Cohen Foundation
Lyme Disease Research Center
FOR THE MEDIA

Contacts:

Helen Jones
410-502-9422
hjones49@jhmi.edu

Lauren Nelson
410-955-8725
laurennelson@jhmi.edu
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Probable Transfusion-Transmission of Babesiosis

The Brief case: Probable transfusion-transmitted babesiosis in a transplant recipient

Kitt E, Keaton AA, Graf EH.
Journal of Clinical Microbiology 54:2632–2634.

http://dx.doi.org/10.1128/JCM.00981-16

Case

A 3-year-old immunocompromised male who had been hospitalized for 7 months in the cardiac intensive care unit developed fever and tachycardia in December. He was prenatally diagnosed with hypoplastic left heart syndrome and received right ventricle to pulmonary artery conduit surgery days after delivery. Due to worsening right ventricular function, after a hemi-Fontan procedure, he received an orthotopic heart transplant at the beginning of his 3rd year of life.

His posttransplant course was complicated by multiple episodes of rejection, cytomegalovirus (CMV) pneumonitis, and several central-line-associated bloodstream infections. As a result of the rejection, necessitating plasmapheresis as well as frequent blood draws for management, which led to anemia, he received 36 packed red blood cell transfusions over the course of 7 months posttransplantation. These transfusions were evenly spaced, and he remained hospitalized during the 7 months.

At the time of the febrile episode, he was on caspofungin, trimethoprim-sulfamethoxazole, and ganciclovir. The subsequent diagnostic workup included multiple sets of blood cultures, a urine culture, and a CMV viral load analysis. He was started on vancomycin and cefepime while awaiting microbiologic results. Other pertinent test results included a complete blood count (CBC) with differential showing pancytopenia and an aspartate transaminase (AST) level of 200 U/liter (reference range, 20 to 60 U/liter), an alanine aminotransferase (ALT) level of 84 U/liter (reference range, 5 to 45 U/liter), and a C-reactive protein level of 3.1 mg/dl (reference range, 0 to 0.9 mg/dl), which increased to 7.1 mg/dl over 4 days.

On the 5th day of fever, another CBC with differential was ordered and was noted by the hematopathologist to contain intraerythrocytic parasites. Immediately, a blood smear with Giemsa stain (Harleco Giemsa stain; EMD Millipore, Billerica, MA, USA) was performed by the microbiology laboratory, yielding the definitive diagnosis. Babesia species with a parasitemia level of 18% was reported to the clinical team. Real-time PCR testing, performed by a reference laboratory, provided the species-level identity of Babesia microti. All other infectious workups were negative. The patient was started on azithromycin plus atovaquone due to the contraindications against treatment with quinidine (QT interval prolongation in a heart transplant recipient with declining heart function).

Three days later, clindamycin was added when his parasitemia level did not decline. He was also given an exchange transfusion on day 4 after diagnosis in an attempt to reduce his parasitemia. After 14 days of therapy, his parasitemia became undetectable and he completed 6 full weeks of therapy, at which time he remained aparasitemic. Since transfusion was the child’s only known risk factor for Babesia infection, a complete investigation into the blood products used was conducted, but the infectious unit/donor could not be definitively identified. Banked products from the organ donor were also tested, and it was determined that the heart transplant was not the source of the Babesia infection.

LD in Hemifacial Spasm

Hemifacial Spasm From Lyme Disease: Antibiotic Treatment Points to the Cause

LeWitt TM.

Clinical Neuropharmacology, online first, 2016 Oct 14.

http://doi.org/10.1097/WNF.0000000000000193

Abstract

A wide range of etiologies can cause hemifacial spasm (HFS), including infection. In this case report, a 44-year-old woman developed HFS and was explored surgically 7 years later. No abnormalities were found.

Afterward, treatment of a surgical wound infection with an oral cephalosporin resulted in a temporary HFS remission that had never occurred previously. This antibiotic experience prompted further workup for an underlying infection, which ultimately led to diagnosis of Lyme disease.

Presentation of HFS due to Lyme disease has not been reported. Because its diagnosis can be occult and antibiotic therapy can be both diagnostic and therapeutic, Lyme disease should be a consideration for cases of HFS.

http://www.merckmanuals.com/home/brain,-spinal-cord,-and-nerve-disorders/cranial-nerve-disorders/hemifacial-spasm  Hemifacial spasm is painless involuntary twitching of one side of the face due to malfunction of the 7th cranial nerve (facial nerve). This nerve moves the facial muscles, stimulates the salivary and tear glands, enables the front two thirds of the tongue to detect tastes, and controls a muscle involved in hearing.  The diagnosis is made when doctors see the spasms.

Treatment:  Botulinum toxin, sometimes surgery

Botulinum toxin is the drug of choice. It is injected into the affected muscles. The same drugs used to treat trigeminal neuralgia—carbamazepine, gabapentin, phenytoin, baclofen, and tricyclic antidepressants (see Table: Drugs Used to Treat Depression)—may be tried but are usually not helpful.  If drug treatment is unsuccessful, surgery may be done to separate the abnormal artery from the nerve by placing a small sponge between them.

This case is another great example of doctors stumbling upon a diagnosis of LD due to positive results after antibiotic therapy.  Also, due to an “official” reporting, hopefully doctors will consider LD in their differential diagnosis with other patients presenting with hemifacial spasming.  I can’t help but wonder how many doctors would not even consider LD because there had been no “official” reporting in the past.

Survival of B. Miyamotoi

https://experiment-uploads.s3.amazonaws.com/file-attachments/7615/nDAfJhZdSeu93R5i5nrC_Thorp_et_al-2016-Transfusion%20B%20miyamotoi.pdf

Transfusion Complications: Volume 56, March 2016

Aaron M. Thorp and Laura Tonnetti

BACKGROUND: Borrelia miyamotoi, the agent of relapsing fever, is a tick-borne spirochete first isolated in Japan in 1994. Since then, the spirochete has been detected in ticks globally, generally in the same vectors as the Lyme disease agent. Human infection has been reported in Russia, Europe, Japan, and the United States, as influenza-like febrile illness. In addition, two cases of meningoencephalitis caused by B. miyamotoi have also been reported in immunocompromised patients. Here we evaluate the ability of the spirochete to survive in human blood components stored under standard blood bank conditions.

STUDY DESIGN AND METHODS: Freshly collected human whole blood was spiked with in vitro cultured B. miyamotoi or B. miyamotoi–infected mouse plasma and separated into red blood cells (RBCs), plasma, and platelets. Components were either injected into immunocompromised (SCID) or wild-type immunocompetent mice or cultured in vitro, right after separation and after storage at the appropriate conditions. Infection was monitored by microscopic observation, blood smears, and polymerase chain reaction.

RESULTS: In vivo, all the SCID mice challenged with the components before storage and the RBCs stored for up to 42 days developed the infection. Wild-type mice also developed the infection when injected with prestorage samples from all components, while a lower number of mice were infected by RBCs stored for 42 days. In vitro, spirochetes grew in all samples but frozen plasma.

CONCLUSIONS: This study demonstrated that B. miyamotoi can survive standard storage conditions of most human blood components, suggesting the possibility of transmission by blood transfusion.

Unlike Mosquitoes, Ticks Year Long Threat

http://www.omaha.com/living/move-over-mosquitoes-tick-fight-takes-attention/article_996c6495-f986-59cf-8649-6bfd46fc4209.html

According to the Companion Animal Parasite Council (CAPC) 2016 is going to be a banner year for ticks, with the CDC listing 15 different tick borne diseases (TBI’s) which range from debilitating to fatal.

The council sates that they thrive everywhere from wooded areas to gardens, landscape plants and even backyard grasses with most people coming into contact with them in their own backyards.

The article states a big help in lowering the tick population is by deterring deer from your living area by planting vegetation deer don’t like to building a tall fence, although they can jump over fences as high as 10 feet. They state a foliar spray such as Bobbex Deer Repellent is effective year-round and supposedly safe for use around children and pets and won’t wash off from rain or snow. It was found to be 93% effective in deterring deer when compared to other like repellents.

According to Sam Telford, a professor of infectious diseases at Tufts, “One or two years of severe weather may depress their numbers, but remember….the successful feeding of one female tick on a deer translates to 2,000 eggs.”

Many believe that ticks are not active in the winter. Unfortunately, this is a myth.

https://madisonarealymesupportgroup.com/2016/01/20/polar-vorticks/