Archive for the ‘research’ Category

Interrupted Blood Feeding in Ticks: Causes and Consequences

https://pubmed.ncbi.nlm.nih.gov/32560202/

Interrupted Blood Feeding in Ticks: Causes and Consequences

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Free article

Abstract

Ticks are obligate hematophagous arthropods and act as vectors for a great variety of pathogens, including viruses, bacteria, protozoa, and helminths. Some tick-borne viruses, such as Powassan virus and tick-borne encephalitis virus, are transmissible within 15-60 min after tick attachment. However, a minimum of 3-24 h of tick attachment is necessary to effectively transmit bacterial agents such as Ehrlichia spp., Anaplasma spp., and Rickettsia spp. to a new host. Longer transmission periods were reported for Borrelia spp. and protozoans such as Babesia spp., which require a minimum duration of 24-48 h of tick attachment for maturation and migration of the pathogen.

Laboratory observations indicate that the probability of transmission of tick-borne pathogens increases with the duration an infected tick is allowed to remain attached to the host. However, the transmission time may be shortened when partially fed infected ticks detach from their initial host and reattach to a new host, on which they complete their engorgement.

For example, early transmission of tick-borne pathogens (e.g., Rickettsia rickettsii, Borrelia burgdorferi, and Brucella canis) and a significantly shorter transmission time were demonstrated in laboratory experiments by interrupted blood feeding.

The relevance of such situations under field conditions remains poorly documented.

In this review, we explore parameters of, and causes leading to, spontaneous interrupted feeding in nature, as well as the effects of this behavior on the minimum time required for transmission of tick-borne pathogens.

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**Comment**

Partial feeding is not rare and needs to be taken into account. Unfortunately, authorities have followed a tightly controlled narrative when it comes to transmission times – which has only served to hurt patients for decades.

There are cases where Lyme (borrelia) has been transmitted within hours:  https://madisonarealymesupportgroup.com/2016/12/07/igenex-presentation/

Excerpt:

Bob Giguere of IGeneX states a case by Dr. Jones of a little girl who went outside to play about 8:30a.m. and came inside at 10:30 with an attached tick above her right eye.  By 2 o’clock, she had developed the facial palsy.  At the hospital she was told it couldn’t be Lyme as the tick hadn’t been attached long enough.  They offered a neuro-consult…..

By 4pm she couldn’t walk or talk.

Do not believe what the “experts” tell you about transmission times!

Authorities also talk about ticks having a “grace period” before they transmit which is hog-wash:  https://madisonarealymesupportgroup.com/2020/03/10/grace-period-for-ticks-nope/

For more:  https://madisonarealymesupportgroup.com/2017/04/14/transmission-time-for-lymemsids-infection/

https://madisonarealymesupportgroup.com/2019/04/26/three-strains-of-borrelia-other-pathogens-found-in-salivary-glands-of-ixodes-ticks-suggesting-quicker-transmission-time/

https://madisonarealymesupportgroup.com/2019/11/14/study-shows-ticks-can-transmit-rickettsia-immediately/

https://madisonarealymesupportgroup.com/2017/06/28/powassan-can-kill/

 

 

 

 

Case of Cerebral Vasculitis Due to Neurobartonellosis

https://nn.neurology.org/content/7/5/e791

A case of cerebral vasculitis due to neurobartonellosis

Meryim Poursheykhi, Farhan Mithani, Tanu Garg, Christian Cajavilca, Siraya Jaijakul, Steve Fung, Richard Klucznik, Rajan Gadhia

We report a case of a 60-year-old right-handed woman with hypertension, hyperlipidemia, and hypothyroidism who presented with a three-week history of:

  • recurrent thunderclap headaches 
  • photophobia (aversion to light)
  • phonophobi (aversion to sound)
  • nausea
  • vomiting

She reported one brief episode of:

  • slurred speech
  • expressive aphasia (inability to understand and formulate language)
  • right facial droop
  • right hemiparesis suggestive of a TIA

Family history was remarkable for primary angiitis of the CNS (PACNS) in the mother. Neurologic examination was unremarkable. CT of the head was negative; CT angiography (CTA) of the head and neck suggested fibromuscular dysplasia in bilateral cervical internal carotid arteries and distal right vertebral artery. MRI of the brain showed no correlating abnormalities. A digital subtraction angiography (DSA) revealed multivessel intracranial medium and large vessel narrowing and fusiform dilatations, suggestive of reversible cerebral vasoconstriction syndrome (RCVS) vs vasculitis. Subsequent MR intracranial vessel wall imaging (IVWI) showed multifocal concentric vessel wall thickening and enhancement consistent with vasculitis (figure). Transcranial Doppler showed no evidence of elevated intracranial velocities. CSF studies were unremarkable with an opening pressure of 10 cm H2O, 2 white blood cells (normal 0–5/mm3), 2 red blood cells (normal 0–1/mm3), 58 mg/dL glucose (normal 40–70, serum glucose 87), 41 mg/dL protein (normal 15–45), normal Q-albumin ratio, normal IgG synthetic rate, and IgG index. Serum inflammatory and infectious studies had been negative thus far. Empiric high-dose IV steroids lead to complete symptom resolution.

Final infectious workup revealed strongly positive serum Bartonella IgM titer of 1:256 and negative IgG, consistent with her reported cat exposure.

She was started on an outpatient two-week course of doxycycline, rifampin, and oral steroids. Four weeks later, repeat vessel wall MRI and Bartonella serologies (IgM titer 1:80) showed improvement.

Figure
FigureVessel imaging

(A) Angiogram of the left internal carotid artery showing multifocal narrowing and fusiform dilatations (arrows) pretreatment. (B) Intracranial vessel wall MRI showing multifocal concentric vessel wall thickening and enhancement (arrows) pretreatment. (C) Intracranial vessel wall MRI showing reduction in vessel wall enhancement (arrows) posttreatment. (D) Magnetic resonance angiography (MRA) head showing multifocal stenoses (arrows) pretreatment. (E) MRA head showing improvement of stenoses (arrows) posttreatment.

Discussion

We present an individual with symptoms initially concerning for RCVS vs vasculitis who was subsequently found to have secondary CNS vasculitis due to cat-scratch disease (CSD). To our knowledge, this is the first adult case of Bartonella henselae-associated CNS vasculitis, particularly without encephalopathy as the presenting symptom.

CSD typically presents with self-limited regional lymphadenopathy and fever.1 Neurologic complications are rare, occurring in 2% of cases with encephalopathy as the most common manifestation.2 Neuroretinitis, seizures, coma, myelopathies, and cranial and peripheral nerve involvement have also been reported. CNS vasculitis associated with CSD, however, has only been reported in 2 pediatric cases which presented with strokes.3,4

Diagnostically, identifying primary and secondary CNS vasculitis can be challenging both clinically and radiographically. No specific studies in serum or CSF are available for the diagnosis of CNS vasculitis. As in neurobartonellosis, CSF may be unremarkable or reveal nonspecific mild lymphocytic pleocytosis. Cerebral vasculopathies can present with similar luminal patterns, and therefore, imaging modalities such as DSA, magnetic resonance angiography (MRA), and CTA provide nonspecific results leading to difficulties identifying and differentiating between common etiologies of intracranial disease including vasospasm, atherosclerosis, and inflammation. Although DSA remains the gold standard for vessel imaging, it is an invasive study that provides information limited to the vessel lumen. Conversely, IVWI allows direct visualization of the vessel wall by subtracting the signal of blood in the vessel lumen and has shown to improve diagnostic specificity.5 In CNS vasculitis, IVWI shows multifocal concentric vessel wall enhancement and thickening as seen in our patient. In RCVS, vessel wall thickening may be present but with minimal or no enhancement.5

At this time, there is no clear evidence-based treatment regimen or duration for neurologic manifestations of CSD including CNS vasculitis.1 We recommend concomitant treatment of the infection with antibiotics and secondary vasculitis with high-dose steroids. Our patient received a 2-week combination of doxycycline 100 mg and rifampin 300 mg twice daily per current expert opinion.6 In addition, we initiated 5 days of high-dose IV steroids, followed by a 1-week oral steroid taper. To avoid recurrent invasive testing, we repeated IVWI 4 weeks later for treatment monitoring and found significant reduction in vessel wall enhancement (figure).

Our case reiterates the importance of ruling out rare causes of CNS vasculitis including assessing animal exposure before diagnosing PACNS. Detection of the etiology of vasculitis is essential to guide treatment and for prognostication. Noninvasive imaging such as an IVWI provides valuable diagnostic information and can be useful in assessing the treatment response over time by minimizing the need for repeat invasive DSA.

Study funding

No targeted funding reported.

Disclosure

M. Poursheykhi, F. Mithani, T. Garg, C. Cajavilca, S. Jaijakul, S. Fung, R. Klucznik, and R. Gadhia report no disclosures. Go to Neurology.org/NN for full disclosures.

Acknowledgment

The authors thank Dr. Gadhia for his mentorship.

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**Comment**

Since Bartonella is a vascular disease, it follows that it will cause vasculitis pretty much anywhere in the body.  https://madisonarealymesupportgroup.com/2020/01/05/bartonella-endocarditis-masquerading-as-systemic-vasculitis-with-rapidly-progressive-glomerulonephritis/

https://madisonarealymesupportgroup.com/2019/04/24/human-bartonellosis-an-underappreciated-public-health-problem/

It also creates tumors, many neurological manifestations including PANS and other mental health issues.

The concern with their treatment is it wasn’t long enough and she could relapse, which is common.  Bartonella, in my opinion, is as bad if not worse than Lyme disease and together it’s a one, two punch – you are out.

Marna Ericson’s work has demonstrated it to survive right along side a PICC line with antibiotics being pumped directly into the body:  https://madisonarealymesupportgroup.com/2019/02/27/advanced-imaging-found-bartonella-around-pic-line/  The subject is her son who has chronic bartonellosis.

 

 

 

RMSF Rare in NJ But Spreading Elsewhere

https://www.sciencedaily.com/releases/2020/06/200625124939.htm

Dangerous tick-borne bacterium extremely rare in New Jersey

The mystery behind the rise in spotted fever cases continues

Date:  June 25, 2020
Source:  Rutgers University
Summary:
There’s some good news in New Jersey about a potentially deadly tick-borne bacterium. Researchers examined more than 3,000 ticks in the Garden State and found only one carrying Rickettsia rickettsii, the bacterium that causes Rocky Mountain spotted fever. But cases of tick-borne spotted fevers have increased east of the Mississippi River, and more research is needed to understand why.  (See link for article)

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**Comment**

Important quote:  

“CDC researchers recently found that the invasive Asian longhorned tick, like the American dog tick and lone star tick, is an efficient vector of Rickettsia rickettsii in the lab,” said senior author Dina M. Fonseca.

I’m surprised they didn’t mention that the brown dog tick has outbreaks in Mexico.

This is worrisome because the brown dog tick is more likely to bite people and it adapts easily to living in a house.. Researchers worry it may be spreading to California and the Southern U.S.  It also appears to transmit a more virulent form of RMSF: https://madisonarealymesupportgroup.com/2018/08/16/new-tick-causes-epidemic-of-rmsf/

For more:  https://madisonarealymesupportgroup.com/2020/05/05/asian-longhorned-tick-able-to-transmit-rmsf-in-lab-setting-also-transmitted-within-ticks-through-ova/

https://madisonarealymesupportgroup.com/2019/07/25/kentucky-more-than-two-dozen-rocky-mountain-spotted-fever-cases-reported-in-grayson-county/

https://madisonarealymesupportgroup.com/2020/06/30/rocky-mountain-spotted-fever-can-be-deadly-how-to-prevent-diagnose-treat-it/

Disseminated Lyme Disease More Likely In Those With Weakened Immune System

https://danielcameronmd.com/impaired-immunity-increases-risk-of-disseminated-lyme-disease/

DISSEMINATED LYME DISEASE MORE LIKELY IN THOSE WITH WEAKENED IMMUNE SYSTEM

Sick woman sitting on couch with disseminated Lyme disease

Individuals with a weakened immune system are more susceptible to developing infections, such as COVID-19. A review study has also found that people with compromised immune systems are at a greater risk of developing disseminated Lyme disease. The authors of “Erythema Migrans: Course and Outcome in Patients Treated With Rituximab” investigated patients diagnosed with Lyme disease, who were also taking Rituximab, a medication known to impair immunity. [1]

The small study examined the risk of developing disseminated Lyme disease for people with weakened immune systems. Researchers enrolled 7 patients with an EM (erythema migrans) rash who were diagnosed with Lyme disease. All of the patients were receiving Rituximab for another underlying medical condition. Out of the 7 patients, 4 were also being treated with additional immunosuppressant drugs (e.g., corticosteroids, methotrexate, and bortezomid).

“Rituximab is the anti-CD20 monoclonal antibody that influences B cells and consequently impairs secretion of antibodies, antigen presentation, and secretion of cytokines,” writes Maraspin and colleagues.

Rituximab is used for non-Hodgkin lymphoma, rheumatoid arthritis, chronic lymphocytic leukemia, and granulomatosis with polyangiitis (Wegener granulomatosis).

Signs of disseminated Lyme disease

According to the authors, 43% of the patients treated with Rituximab showed unusually high signs of disseminated Lyme disease, compared to 8% of immunocompetent individuals.

The isolation rates of Borrelia from the blood before antibiotic treatment were also unusually high (40%) when compared with immunocompetent patients (<2%).

“Impaired immunity might be an explanation for the complicated course of LB (signs of disseminated LB or unfavorable outcome after antibiotic treatment) present in 57% of our patients, but rarely seen in immunocompetent adult patients with EM, of whom only about 8% have disseminated disease and approximately 10% have treatment failure, most often the presence of LB-associated symptoms,” the authors write.

In their study, 3 of the patients with multiple EM rashes were treated with intravenous antibiotics. The remaining individuals received oral antibiotics.

READ MORE: Lyme disease manifests as autoimmune disorder

One patient, a 65-year-old woman, failed initial treatment. “Her skin lesion persisted for >2 months after the start of treatment with doxycycline,” explains Maraspin. “However, it disappeared after retreatment with amoxicillin and the subsequent clinical course was uneventful.”

At their 1-year follow-up, none of the patients had any objective (or physical) signs of Lyme disease. However, the authors did not mention the presence of other symptoms, such as fatigue, pain, and cognitive problems.

Retreatment for immunocompromised patients 

Meanwhile, a study by Maraspin and colleagues reports that 25% of Lyme disease patients who had received immunosuppressive drugs, such as adalimumab, infliximab, etanercept, golimumab, failed treatment for Lyme disease. Three of the four patients required retreatment.

Patients with weakened immune systems were also more likely (18.8%) to develop signs of disseminated Lyme disease when compared to Lyme disease patients who were immunocompetent.

Editors note: The increased chance of disseminated Lyme disease in patients with impaired immunity needs further study. I would also address the risk of treatment failures on other outcomes including fatigue, pain, and cognitive problems.

References:
  1. Maraspin, V., et al. (2019). “Erythema Migrans: Course and Outcome in Patients Treated With Rituximab.” Open Forum Infect Dis 6(7): ofz292.

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**Comment**

The one question that hasn’t been answered fully is what exactly is causing this impaired immunity?  While many would love to solely blame the patient’s immune system, many have yet to consider the interplay between how over time these pathogens directly impact the immune system negatively.  From experience I can state that most Lyme/MSIDS patients, prior to becoming infected, are some of the healthiest people I know.  They eat right, exercise, love the outdoors, and take their health seriously.

Until the answer to impaired immunity is determined (and it may vary from patient to patient), patients will not be treated appropriately.

For more:  https://madisonarealymesupportgroup.com/2020/03/09/the-long-term-persistence-of-borrelia-burgdorferi-antigens-dna-in-the-tissues-of-lyme-disease-patient/

New Treatments For Lyme Disease On The Horizon?

https://danielcameronmd.com/new-treatments-for-lyme-disease/

NEW TREATMENTS FOR LYME DISEASE ON THE HORIZON?

Patients with Lyme disease are typically treated with a standard antibiotic, which may include doxycycline, amoxicillin, or cefuroxime, for a 2 to 4 week period. However, studies have shown that between 36-63% of treated patients continue to suffer with persistent symptoms. [1]

Study findings suggest that current Lyme disease treatment may not eliminate the Borrelia burgdorferi infection or the immune system may fail to clear the infection or bacterial debris, resulting in ongoing symptoms. In the past few years, several new treatments for Lyme disease have been investigated in the laboratory or made available to patients in an effort to address chronic symptoms.

Although still in the early stages, two new treatments for Lyme disease seem to show promising results. Published case reports describe the effectiveness of dapsone, an antibiotic typically used to treat skin conditions and disulfiram, frequently prescribed for alcohol abuse.

Dapsone

Horowitz et al. reviewed data from 200 patients to evaluate “the efficacy of dapsone combined with other antibiotics and agents that disrupt biofilms for the treatment of chronic Lyme disease/post-treatment Lyme disease syndrome (PTLDS).” [2]

They found that it “decreased eight major Lyme symptoms severity and improved treatment outcomes among patients with chronic Lyme disease/PTLDS and associated co-infections.”

This new treatment for Lyme disease was not without side effects, however. Horowitz reports, 46 of the 200 patients stopped treatment due to an ‘adverse reaction.’ The adverse effects were not specified.

When used for other conditions, dapsone’s side effects have included haemolysis, agranulocytosis, photosensitivity, skin eruptions, neuropathy, and toxic or cholestatic hepatitis. [3]

Disulfiram

Disulfiram, a medication used to treat alcohol abuse, may be one of the new treatments for Lyme disease in the near future. Two small studies have shown positive results.

Dr. Kenneth Liegner reports that 3 patients, who required extensive, ongoing antibiotic treatment due to neurological Lyme disease and Babesia, “were able to discontinue treatment and remain clinically well for periods of observation of 6–23 months following the completion of a finite course of treatment solely with disulfiram.” [4]

One patient did relapse at 6 months and was re-treated with disulfiram.

READ MORE: 6 reasons for delayed treatment of Lyme disease

The results from another group of 30 patients who received disulfiram were described by Liegner during the 2019 International Lyme and Associated Diseases Society (ILADS) annual conference. “Results have been impressive, and disulfiram use, with careful supervision, has been relatively safe.”

“It will remain to be seen whether disulfiram has a role in acute or early Lyme disease or babesiosis,” Liegner adds.

Furthermore, “Any role for disulfiram in children, with their incompletely matured nervous systems, remains to be determined and should be approached with caution, as there is little experience with its use in children.”

None of Liegner’s three patients stopped treatment with disulfiram. One patient had a temporary psychiatric hospitalization, and a second stopped after a syncope event that led to a concussion that required hospitalization. And according to Liegner, the risk of adverse events was even lower in the study involving 30 patients.

Disulfiram’s side effects, when prescribed for other conditions, have included “encephalopathy, convulsion, cranial and peripheral neuropathy, toxic optic neuropathy, irreversible injury to the basal ganglia with permanent neurological deficits, hypertension, and drug-induced psychosis, presumably due to the inhibition of dopamine beta-hydroxylase,” writes Liegner.

Another study investigating disulfiram as one of the new treatments for Lyme disease and co-infections was launched in 2019 by Dr. Brian Fallon, from the Lyme and Tick-Borne Diseases Research Center at Columbia University.

Azlocillin

A study by Stanford Medicine suggests that the antibiotic azlocillin “completely kills off the disease-causing bacteria Borrelia burgdorferi at the onset of the illness.” In addition, the authors say, azlocillin “could be effective for treating [Lyme disease] patients infected with drug-tolerant bacteria that may cause lingering symptoms.” [5]

Researchers tested azlocillin in mice infected with Lyme disease at 7-day, 14-day and 21-day intervals and found that it eliminated the infection. Additionally, in lab dishes, the azlocillin killed drug-tolerant forms of B. burgdorferi, “indicating that it may work as a therapy for lingering symptoms of Lyme disease,” according to the Stanford team.

Azlocillin has not yet been prescribed or studied in Lyme disease patients.

Azlocillin adverse events for other indications have included hypersensitivity reactions, hypocalaemia, hepatotoxicity, diarrhea, and leukopenia. [6] There are also costs and risks associated with the need to administer azlocillin intravenously.

Combination: daptomycin, doxycycline, and ceftriaxone

Researchers from Johns Hopkins School of Public Health found that a combination of antibiotics – daptomycin, doxycycline, and ceftriaxone − eradicated the slow-growing variant form (persisters) of the Lyme bacteria in a mouse model. Scientists believe persisters may be responsible for the chronic symptoms that some Lyme disease patients experience.

“There is a lot of excitement in the field because we now have not only a plausible explanation but also a potential solution for patients who suffer from persistent Lyme disease symptoms despite standard single-antibiotic treatment,” says Ying Zhang, MD, Ph.D., senior author on the study.

Zhang and his team hope to test the drug combination in people with persistent Lyme disease

Daptomycin has not yet been prescribed to Lyme disease patients, and adverse effects, for other conditions, have included myopathy/rhabdomyolysis, eosinophilic pneumonia, and anaphylactic hypersensitivity reactions. [8]

There are also costs and risks associated with the need to administer daptomycin intravenously.

Editor’s note: I am encouraged by all the research seeking to identify new treatments for Lyme disease and remain hopeful that we will develop research designs to evaluate the value of these and other treatments for tick-borne diseases.

References:
  1. Adrion ER, Aucott J, Lemke KW, Weiner JP (2015) Health Care Costs, Utilization and Patterns of Care following Lyme Disease. PLOS ONE 10(2): e0116767. https://doi.org/10.1371/journal.pone.0116767
  2. Horowitz RI, Freeman PR. Precision medicine: retrospective chart review and data analysis of 200 patients on dapsone combination therapy for chronic Lyme disease/post-treatment Lyme disease syndrome: part 1. Int J Gen Med. 2019;12:101-119.
  3. Wozel G, Blasum C. Dapsone in dermatology and beyond. Arch Dermatol Res. 2014;306(2):103-124.
  4. Liegner KB. Disulfiram (Tetraethylthiuram Disulfide) in the Treatment of Lyme Disease and Babesiosis: Report of Experience in Three Cases. Antibiotics (Basel). 2019;8(2).
  5. Pothineni VR, Potula HSK, Ambati A, et al. Azlocillin can be the potential drug candidate against drug-tolerant Borrelia burgdorferi sensu stricto JLB31. Sci Rep. 2020;10(1):3798.
  6. Parry MF. The tolerance and safety of azlocillin. J Antimicrob Chemother. 1983;11 Suppl B:223-228.
  7. Feng J, Li T, Yee R, et al. Stationary phase persister/biofilm microcolony of Borrelia burgdorferi causes more severe disease in a mouse model of Lyme arthritis: implications for understanding persistence, Post-treatment Lyme Disease Syndrome (PTLDS), and treatment failure. Discov Med. 2019;27(148):125-138.
  8. Patel S, Saw S. Daptomycin. In: StatPearls. Treasure Island (FL)2020.

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**Comment**

This type of work has been a long time coming but is desperately needed.  I’ve posted on all of these treatments before here:

Dapsone and PZA (mycobacterium drugs):

Azlocillin (antibiotic):

Ceftriaxone (antibiotic):

Disulfiram (old drug used for alcoholism – also called Antabuse):  

My husband and I both tried Disulfiram.  He did fine on it while I suffered with psychosis:  https://madisonarealymesupportgroup.com/2019/10/15/disulfiram-psychosis-update/.  Others have suffered the same side-effect; however, work with your doctor to mitigate risks as much as possible by titrating up slowly and only using the dose required for you to achieve benefit.  For some, this dosage is quite small.

I’m still glad I tried it and would recommend it; however, if you are a single patient, make sure you have a support system in place and people checking in on you regularly.  I had no idea I was going mad.  Thankfully my family picked up on it.  I spent a week in the hospital with the most severe toxic reaction to disulfiram the UW hospital has ever seen.  Buyer beware.

Lyme Disease Treatment:

Effective Lyme treatment is typically overlapping in nature to address all forms of borrelia as well whatever coinfections are present. Each case is extremely individual based upon what pathogens are at play as well as nutritional, hormonal, mineral, environmental, and immune status challenges.

Lyme/MSIDS weakens the body in many areas.  Supporting those areas is key and takes savvy in hunting down and addressing.  Partner with your practitioner by learning as much as you can so you can bring ideas to the table.

Addressing this is a partnership and will require your participation.