Archive for the ‘research’ Category

Vector Competence Studies With Hard Ticks & Borrelia Sensu Lato Spirochetes: A Review

https://www.ncbi.nlm.nih.gov/pubmed/32067949

2019 Dec 14:101359. doi: 10.1016/j.ttbdis.2019.101359. [Epub ahead of print]

Vector competence studies with hard ticks and Borrelia burgdorferi sensu lato spirochetes: A review.

Eisen L1.

Abstract

Use of emerging technology allowing for identification of genetic material from pathogens and endosymbionts in ticks collected from humans, domestic animals, wildlife, or the environment has resulted in an avalanche of new data on tick-microorganism associations. This rapidly growing stream of new information is a tremendous resource but also presents challenges, including how detection of pathogen genetic material in ticks should best be interpreted. There is a tendency in the more recent published literature to incorrectly use the term “vector” based on detection of pathogen genetic material from tick species not experimentally confirmed to serve as vectors of the pathogen in question.

To serve as a vector of a horizontally maintained pathogen, such as a Borrelia burgdorferi sensu lato (s.l.) Lyme borreliosis spirochete, the tick species in question must be capable of acquiring the pathogen while feeding in the larval or nymphal stage on an infectious host, maintaining it transstadially through the molt, and then transmitting the pathogen to a naïve host while feeding in the subsequent nymphal or adult stage.

This review examines the experimental evidence for and against species of hard (ixodid) ticks from different genera to serve as vectors of B. burgdorferi s.l. spirochetes.

  • Of the 18 Ixodes species ticks evaluated to date, 13 were experimentally confirmed as vectors of B. burgdorferi s.l. spirochetes.
  • These studies focused primarily on the three major Lyme borreliosis agents: Borrelia burgdorferi sensu stricto, Borrelia afzelii, and Borrelia garinii.
  • In striking contrast, none of 8 tick species from other genera (1 Amblyomma species, 5 Dermacentor species, and 2 Haemaphysalis species) evaluated to date were unequivocally experimentally confirmed as vectors of B. burgdorferi s.l. spirochetes.

The strength of the evidence for or against each tick species to serve as a vector of B. burgdorferi s.l. spirochetes is discussed together with key knowledge gaps and research challenges.

_________________

**Comment**

This author, a CDC employee, is basing his findings on previous research.  There’s nothing new here.  

Also of import is the fact borrelia has been found in other ticks – just not enough for to be “statistically” important, OR in the instance of the Lone Star tick (Amblyomma americanum) there has been hot debate as to whether STARI is Lyme or not.  Patients and advocates alike claim the symptoms are one in the same.  The debate continues.

The trouble is, what if you are the poor sucker that gets bitten by that “statistically” insignificant tick?  Well, you lose because mainstream doctors are going to skim this review and conclude that ONLY certain ticks transmit Lyme/borrelia. They are going to write you off as psychosomatic:

Important excerpt:

Yes, vector competence was confirmed experimentally; No, vector competence was evaluated experimentally but could not be confirmed; Blank space, tick species not yet evaluated for this B. burgdorferi s.l. species.

There were numerous places where competence couldn’t be confirmed (which is a far cry different from it can’t happen) as well as the fact there were tons of blank spaces – which means the tick species hasn’t even been evaluated yet.

Here’s the dealeo, all ticks transfer fluid.  ALL TICKS should be suspect.  Period.  Remember all the research I’ve posted stating Lyme “didn’t exist” in various geographical places until someone pushed hard enough to get it recognized:  https://madisonarealymesupportgroup.com/2018/05/31/no-lyme-in-the-south-guess-again/

https://madisonarealymesupportgroup.com/2016/09/24/arkansas-kids-denied-lyme-treatment/

Excerpt:

According to Dr. Naveen Patil, Director of the Infectious Disease Program, ADH,

“We don’t have Lyme Disease in Arkansas, we have the ticks that transmit Lyme Disease but we don’t have any recorded cases of Lyme Disease.” 

We can thank a mother from Arkansas for getting Arkansas on the map for Lyme disease.

And so it goes:  https://madisonarealymesupportgroup.com/2017/10/24/no-lyme-in-oklahoma-yeah-right/

https://madisonarealymesupportgroup.com/2019/04/22/its-just-crazy-why-is-lyme-disease-treatment-so-difficult-to-find-in-mississippi/

https://madisonarealymesupportgroup.com/2019/11/25/hundreds-of-people-impacted-by-tick-borne-illnesses-in-north-carolina/

Tick research is similar in that until something gets documented (published), researchers and doctors alike treat it as if it’s never, ever happened, and therefore (circular reasoning) it won’t happen in the future.

Category:

research, Testing, Ticks, Transmission

Unusual Case of Suspected Lyme Disease in Patient With Ear Pain

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6906891/

. 2019 Oct-Dec; 11(4): 160–162.
Published online 2019 Nov 26. doi: 10.4103/jgid.jgid_75_19
PMCID: PMC6906891
PMID: 31849437

An Unusual Case of Suspected Lyme Neuroborreliosis in a Patient Presenting with Ear Pain

Michael Anthony Ramada, Saman Kannangara,1 and Hany Eskarous1

Abstract

We report a case of suspected Lyme neuroborreliosis (LNB) where the patient’s sole symptom was chronic, intermittent episodes of unilateral ear pain. This case was unusual because this patient did not show any other neurological or extraneurological symptoms of Lyme disease. LNB is a manifestation of infection by Borrelia burgdorferi spirochetes that can manifest in a number of different clinical presentations depending on the nervous system dissemination of the bacteria. Most commonly, these neurological findings present as peripheral nerve radiculopathies, but rarer involvement of the central nervous system (CNS) can occur if a patient goes untreated. Most often, CNS involvement presents as meningitis with increased lymphocytes but can, in rarer cases, involve the spinal cord or brain parenchyma.

The diagnosis of LNB was made after the patient was found to have suspicious lesions in the spinal cord and brain parenchyma on magnetic resonance imaging as well as cerebrospinal fluid Borrelia antibody index was consistent with CNS Lyme disease. We discuss this case as a unique clinical presentation of suspected LNB and the diagnostic findings associated with this infection.

_________________

**Comment**

Nothing surprises me about Lyme disease anymore.  “Not everything is Lyme, but Lyme CAN be anything.”  Truer words were never spoken.

 

 

Category:

Lyme, research, Testing

Dogs With Proteinuria Found to Have Exposure to Rickettsia, Ehrlichia, and Lyme Disease

https://www.ncbi.nlm.nih.gov/pubmed/31916316/

2020 Jan 8. doi: 10.1111/jvim.15610. [Epub ahead of print]

A retrospective study of vector-borne disease prevalence in dogs with proteinuria: Southeastern United States.

Purswell EK1, Lashnits EW1, Breitschwerdt EB1, Vaden SL1.

Abstract

BACKGROUND:

Proteinuria is a risk factor for progressive kidney injury in dogs. Enhanced understanding of potential associations between canine vector-borne diseases (CVBD) and proteinuria is needed.

OBJECTIVES:

To determine the proportion of evaluated proteinuric dogs exposed to ≥1 CVBD, including Babesia spp., Ehrlichia spp., spotted-fever group Rickettsia, Bartonella spp., Anaplasma spp., hemotropic Mycoplasma spp., Borrelia burgdorferi, and Dirofilaria immitis, and to determine if demographic or clinicopathologic differences exist between proteinuric dogs exposed to CVBD versus proteinuric dogs with no evidence of CVBD exposure.

ANIMALS:

Two-hundred nine proteinuric dogs, concurrently tested for CVBD, which were examined at a single academic veterinary hospital between January 2008 and December 2015.

METHODS:

Retrospective cross-sectional study. Demographic, clinicopathologic, and CVBD test results were extracted from medical records. A multivariable logistic regression model was used to assess associations between CVBD and selected variables.

RESULTS:

Based on serology and polymerase chain reaction testing,

  • 34% of proteinuric dogs (72/209) were exposed to ≥1 CVBD
  • Exposure to Rickettsia spp. (19%)
  • Ehrlichia spp. (12%)
  • B. burgdorferi (9%)

The CVBD exposure was lower in dogs tested in autumn or spring, higher in intact dogs, and higher in dogs with lower serum albumin and higher serum creatinine concentrations.

CONCLUSIONS AND CLINICAL IMPORTANCE:

Exposure to CVBD, particularly exposure to Rickettsia spp., Ehrlichia spp., and B. burgdorferi was found in proteinuric dogs from the southeast United States. Additional controlled prospective studies examining a potential causal relationship between CVBD and proteinuria are warranted.

__________________

**Comment**

The question of course is – does this also happen in humans and to what degree?

 

Category:

Activism, Ehrlichiosis, Lyme, research, Rickettsia

Potential Treatment For Lyme Disease Kills Bacteria That May Cause Lingering Symptoms, Study Finds (In a Petri Dish & Mice)

http://med.stanford.edu/news/all-news/2020/03/potential-treatment-for-lingering-lyme-disease.html

Potential treatment for Lyme disease kills bacteria that may cause lingering symptoms, study finds

Screening thousands of drugs, Stanford scientists determined that in mice, azlocillin, an antibiotic approved by the Food and Drug Administration, eliminated the bacteria that causes Lyme disease.

By TRACIE WHITE, a science writer in the Office of Communications. Email her at tracie.white@stanford.e

MAR 12, 2020

For decades, the routine treatment for Lyme disease has been standard antibiotics, which usually kill off the infection. But for up to 20% of people with the tick-borne illness, the antibiotics don’t work, and lingering symptoms of muscle pain, fatigue and cognitive impairment can continue for years — sometimes indefinitely.

A new Stanford Medicine study in lab dishes and mice provides evidence that the drug azlocillin completely kills off the disease-causing bacteria Borrelia burgdorferi at the onset of the illness. The study suggests it could also be effective for treating patients infected with drug-tolerant bacteria that may cause lingering symptoms.

“This compound is just amazing,” said Jayakumar Rajadas, PhD, assistant professor of medicine and director of the Biomaterials and Advanced Drug Delivery Laboratory at the Stanford School of Medicine. “It clears the infection without a lot of side effects. We are hoping to repurpose it as an oral treatment for Lyme disease.” Rajadas is the senior author of the study, which was published online March 2 in Scientific Reports. The lead author is research associate Venkata Raveendra Pothineni, PhD.

“We have been screening potential drugs for six years,” Pothineni said. “We’ve screened almost 8,000 chemical compounds. We have tested 50 molecules in the dish. The most effective and safest molecules were tested in animal models. Along the way, I’ve met many people suffering with this horrible, lingering disease. Our main goal is to find the best compound for treating patients and stop this disease.”

Hunting for alternative drug

Frustrated by the lack of treatment options for Lyme disease patients with lingering symptoms, Rajadas and his team began hunting for a better alternative in 2011. In 2016, they published a study in Drug Design, Development and Therapy that listed 20 chemical compounds, from about 4,000, that were most effective at killing the infection in mice. All 20 had been approved by the Food and Drug Administration for various uses. One, for instance, is used to treat alcohol abuse disorder.

 

In this most recent study, azlocillin, one of the top-20 contenders, was shown to eclipse a total of 7,450 compounds because it is more effective in killing B. burgdorferi and causes fewer side effects. Lyme disease affects more than 300,000 people annually, according to the Centers for Disease Control and Prevention. It can affect various organs, including the brain, skin, heart, joints and nervous system, and cause heart problems and arthritis if untreated. Symptoms include fever, headaches, chills, and muscle and joint pain.

Traditional antibiotics, such as doxycycline, are effective as an early course of treatment for the infection in the majority of patients, but it remains unclear why these drugs fail to treat 10% to 20% of patients, Rajadas said.

“Some researchers think this may be due to drug-tolerant bacteria living in the body and continuing to cause disease,” said Rajadas, who is also a member of the Lyme Disease Working Group at Stanford. “Others believe it’s 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.”

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, azlocillinwas 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.

**Comment**
Those who go on to experience lingering symptoms are 40-60% of all patients:  https://madisonarealymesupportgroup.com/2019/02/25/medical-stalemate-what-causes-continuing-symptoms-after-lyme-treatment/ We keep being told it’s only 10-20% when that group only includes those diagnosed and treated early.  It doesn’t and shouldn’t included a larger group of 30-40% who are diagnosed and treated late.  Add the two groups and you have up to 60% going on with chronic symptoms.  That’s a big deal and should warrant much more attention than it’s currently getting.
The study mentions –
  • disulfiram:  Excerpt:  An interesting drug candidate identified in the study was the alcohol dehydrogenase inhibitor, disulfiram. Though the drug is used as a treatment of alcohol abuse, recently its anticancer potential has also been discovered. It has been known to make complexes with metal ions and cause the disruption of the proteasome, leading to death of the cancer cells. Similarly, the metabolites of the drug molecule have been known to significantly inhibit the growth of a number of bacterial species, including the biofilm-forming Pseudomonas aeruginosa.62 The drug molecule has a good bioavailability, and it passes the blood–brain barrier to show its effect in the central nervous system. Though most of the studies are concerned to the use of the drug molecule in alcoholism yet, being a safe, FDA-approved molecule, the drug can be repurposed for its antibacterial potential.  Study here:  https://flightpath.bio/wp-content/uploads/2020/02/liegner.pdf
  • azlocillin and cefataxime:   Excerpt:  As we observe that azlocillin sodium and cefotaxime acid show low MIC values, we studied time kill studies to determine the rate of antimicrobial activity. In our observation, both azlocillin sodium and cefotaxime acid reduced Borrelia no 3-log10-unit (99.9%) between 48 hours and 72 hours at concentrations 2.5 μM and 5 μM, respectively.  Study here:  https://flightpath.bio/wp-content/uploads/2020/03/s41598-020-59600-4.pdf
Azlocillin is currently only available overseas and in IV form but a company called Flightpath biosciences https://flightpath.bio/pipeline/ is working on an oral formulation and says it has demonstrated in vivo efficacy in mice. This could be a good alternative to Disulfiram as it doesn’t carry some of the risks associated with DSF and doesn’t require a whole lifestyle change.
From their website:

Azlocillin was approved as Azlin® by the FDA on September 3rd, 1982 as a semisynthetic broad spectrum penicillin antibiotic to treat Pseudomonas aeruginosa via intravenous administration. Commercially, the drug was safe and well tolerated and had a limited side effect profile, with warnings and contraindications related only to a patient history of penicillin sensitivities.

In laboratory plate experiments, our scientific team demonstrated that azlocillin significantly inhibited the growth of drug-tolerant Borrelia burgdorferi (Bb) bacteria in a manner far better than doxycycline (the standard of care).

Azlocillin also reduced Lyme disease related inflammation in mice infected with Bb for seven days, compared to the saline control, telismartin, and doxycycline. Upon completion of additional pharmacokinetic and efficacy studies in animals at Tulane University, we hope to advance FP-101 into clinical trials in acute and PTLDS indications in the near future.  https://flightpath.bio/pipeline/

Category:

Lyme, research, Treatment

Almost Half of Deer Ticks Carry Lyme Disease: New Study

https://www.pennlive.com/life/2020/03/almost-half-of-deer-ticks-carry-lyme-disease-new-study.html

Almost half of deer ticks carry Lyme disease: New study

Blacklegged/deer tick

The blacklegged ticks, Ixodes pacificus (depicted here), and I. scapularis, are known vectors for the zoonotic spirochetal bacteria, Borrelia burgdorferi, which is the pathogen 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. Here, you are looking at a dorsal view of a female I. pacificus hard tick. (Courtesy of CDC/ James Gathany; William L. Nicholson, Ph.D.)

Nearly half of more than 2,000 deer ticks collected last year for a new study in Connecticut were infected with Lyme disease.

Of 2,068 deer ticks tested at the Center for Vector Biology and Zoonotic Diseases at the Connecticut Agricultural Experiment Station in New Haven, Connecticut, 46 percent carry the Lyme disease pathogen Borrelia burgdorferi.

About 13 percent also carried the human disease-causing pathogen Babesia microti, which causes babesia, a life-threatening infection of the red blood cells in humans.

Researchers found that 9 percent of the adult ticks carried Anaplasma phagocytophilum, which causes anaplasmosis, which is marked by fever, headache, chills and muscle aches; 2 percent carried Borrelia miyamotoi, which cause hard tick relapsing fever, bacterial infection that can cause recurring bouts of fever, headache, muscle and joint aches and nausea; and 1 percent carried Powassan virus, which can cause Powassan encephalitis, which produces symptoms of fever, headache, vomiting and weakness, and can lead to encephalitis) meningitis.

The ticks were gathered in the first year of a new federally funded Connecticut-wide surveillance program for ticks and associated tick-borne diseases.

More than 2,500 ticks were collected throughout spring, summer and fall 2019 from 40 publicly accessible locations in all eight Connecticut counties and screened for five different human disease-causing pathogens.

Deer ticks, also known as black-legged ticks, were the most collected species, at 2,068 adult ticks, followed by American dog tick, at 437; lone star tick, at 3; and Asian longhorned tick, at 2.

All adult female and nymphal deer ticks were tested at CAES for the presence of the five different disease-causing pathogens.

About 15 percent of the nymphs carried Lyme disease, 6 percent carried babesiosis, 5 percent carried anaplasmosis and 2 percent carried hard tick relapsing fever.

The survey was funded by a one-year grant issued from the Centers for Disease Control and Prevention through the Connecticut Department of Public Health and has potential to continue into a multi-year effort to document tick and pathogen abundances statewide to inform the public so appropriate precautions are taken when spending time outdoors.

_________________

**Comment**

So, similarly to CDC 2-tiered testing, “heads you win, tails you lose.” 

A while back I posted the following information about nationwide tick testing results:

Our current research shows that 60% of tick tested are infected with at least one disease causing organism, 38% are co-infected with two or more, 15% carry three or more, and 5% of the ticks tested carry four or more.  https://www.tickcheck.com/statistics

The percentage of Wisconsin ticks being infected, as of 2017:

On average, about 22 percent of deer tick nymphs in Wisconsin have been found to be infected with Borrelia burgdorferi. The infection rate for adults is about twice as high, around 40-45 percent. In some locations, though, researchers have found infection rates as high as 75 percent of the tick population.

The number of deer ticks in specific areas of Wisconsin can vary widely by area, by landscape, and by forest type. Researchers have not found any relationship with the numbers of white-footed mice or white-tailed deer in any given areas.  https://www.wiscontext.org/deer-ticks-wisconsin-and-diseases-they-carry

Russell Labs states the following:

In 2019, we documented established populations of the deer tick in every Wisconsin County except for Dodge and Winnebago. In those two counties, we found a very low number. Any forested locations could be a source of deer ticks and Lyme Disease.  https://wisconsin-ticks.russell.wisc.edu

Waukesha, Dane, and Sauk counties have the highest reported rates of Lyme disease in Wisconsin: https://dhsgis.wi.gov/DHS/EPHTracker/#/map/Lyme%20Disease/lymeIndex/NOTRACT/Cases/lymeCtyIndex1

Please remember, this is only covers Lyme disease statistics. Wisconsin is home to many other diseases spread by ticks and we are a hot spot for Powassan Virus.

Category:

research, Ticks