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Efficacy of Double-Dose Dapsone Combination Therapy

Abstract

Three patients with multi-year histories of relapsing and remitting Lyme disease and associated co-infections despite extended antibiotic therapy were each given double-dose dapsone combination therapy (DDD CT) for a total of 7–8 weeks. At the completion of therapy, all three patients’ major Lyme symptoms remained in remission for a period of 25–30 months. A retrospective chart review of 37 additional patients undergoing DDD CT therapy (40 patients in total) was also performed, which demonstrated tick-borne symptom improvements in 98% of patients, with 45% remaining in remission for 1 year or longer. In conclusion, double-dose dapsone therapy could represent a novel and effective anti-infective strategy in chronic Lyme disease/post-treatment Lyme disease syndrome (PTLDS), especially in those individuals who have failed regular dose dapsone combination therapy (DDS CT) or standard antibiotic protocols. A randomized, blinded, placebo-controlled trial is warranted to evaluate the efficacy of DDD CT in those individuals with chronic Lyme disease/PTLDS.
You can read the entire study here courtesy of MDPI Open Access.
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WKYT Investigates | COVID confusion

Initial coronavirus symptoms are common signs for other illnesses, too. That can cause problems for patients.

CARLISLE, Ky. (WKYT) – Lakyn Reid has always spent a lot of time in the woods, hiking, hunting and just enjoying nature. Now, though, she’s hesistant to go out.

“My life drastically changed,” she said. “Forever.”

Reid now spends hours each week, instead of outdoors, inside doctor offices dealing with chronic issues she believes could have been avoided.

One difficulty with the coronavirus is that symptoms are general and often mild, which can make it easy to confuse with other sicknesses. That is the confusion Reid ran into, when what eventually were diagnosed as tick-borne illnesses were initially confused for COVID.

“I was absolutely terrified,” Reid said. “And then it just got to the point I was so sick, being scared wasn’t even an option anymore.”

Reid says she has been diagnosed with Lyme Disease and Rocky Mountain Spotted Fever (RMSF), both of which are caused by ticks. But it took time for Reid to get the right treatment because of confusion over what her symptoms showed.

Advocates say she is not the only one.

“We’re having patients that are tested several times for COVID, and then later on finding that it was Lyme Disease,” Vicki Petsy, president of the Kentucky Lyme Disease Association told WKYT’s Garrett Wymer. “And this is happening too much.”

The problem is that initial symptoms can be similar. For Reid, that meant shortness of breath, headache, fever and chills.

“That sounds like a lot of things we’re dealing with right now, especially because of COVID,” said Dr. Ryan Stanton, an emergency physician speaking in general about the symptomatic similarities. “A lot of these are very difficult, very vague, to identify, especially when we’re in the middle of a pandemic where we’re so laser-focused on one particular virus.”

Reid says she was tested seven times for the coronavirus and tested negative each time.

The Centers for Disease Control and Prevention considers Kentucky part of the region where RMSF and Ehrlichiosis (another tick-borne illness) are most common. Lyme Disease used to be less common in Kentucky, but CDC data shows cases increasing in recent years. Still, cases are relatively rare.

Lyme Disease is known for a bullseye rash, which could have made it easier to figure out for Reid, but not everyone gets it. Reid says she did not, although she did eventually get a rash on her face.

“I was a completely healthy person before all of this,” Reid said. “I was normal before this. Then when the tick bite happened everything changed.”

Reid thinks she was exposed to a tick while out hiking earlier this year in eastern Kentucky. She knows she was bitten by another one in May.

Experts say prompt treatment is important with tick-borne illnesses like Lyme Disease to avoid chronic issues moving forward. Reid says, for her, it was two weeks from the time her symptoms first showed up before she was diagnosed and began getting treated with the proper antibiotics.

As she continues to deal with symptoms and other problems, Reid says she does not know what to expect now.

“It’s kind of scary to think about the outlook and the future,” she said, “but I’m trying to get through it day by day, make adjustments to my life, be as healthy as I can and take every day as it comes.”

Reid is trying to keep a positive outlook – from the inside looking out – and hoping someday to get back to the outdoors she loves so much.

Copyright 2020 WKYT. All rights reserved.

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Molecular Microbiological and Immune Characterization of a Cohort of Patients Diagnosed with Early Lyme Disease

ABSTRACT

Lyme disease is a tick-borne infection caused by the bacteria Borrelia burgdorferi. Current diagnosis of early Lyme disease relies heavily on clinical criteria, including the presence of an erythema migrans rash. The sensitivity of current gold-standard diagnostic tests relies upon antibody formation, which is typically delayed and thus of limited utility in early infection. We conducted a study of blood and skin biopsy specimens from 57 patients with a clinical diagnosis of erythema migrans. Samples collected at the time of diagnosis were analyzed using an ultra-sensitive, PCR-based assay employing an isothermal amplification step and multiple primers. In 75.4% of patients, we directly detected one or more B. burgdorferi genotypes in the skin. Two-tier testing showed that 20 (46.5%) of those found to be PCR positive remained serologically negative at both acute and convalescent time points. Multiple genotypes were found in 3 (8%) of those where a specific genotype could be identified. The 13 participants who lacked PCR and serologic evidence for exposure to B. burgdorferi could be differentiated as a group from PCR positive participants by their levels of several immune markers as well as by clinical descriptors such as their number of acute symptoms and the pattern of their erythema migrans rash. These results suggest that within a Mid-Atlantic cohort, patient subgroups can be identified using PCR-based direct detection approaches. This may be particularly useful in future research such as vaccine trials and public health surveillance of tick-borne disease patterns.

Copyright © 2020 American Society for Microbiology.

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Lyme Carditis and Heart Block Can Strike Kids Too

A new case study from the Masonic Children’s Hospital in Minneapolis and University of Minnesota Medical School shows that a 16-year-old boy with Lyme carditis suffered from palpitations and a significant heart block. The patient recovered with antibiotic treatment. According to the study, the “take-away” lesson is that “carditis can be the presenting manifestation of B. burgdorferi infection in pediatric patients.”

Abstract

Background

The incidence of Lyme disease (LD) in North America has increased substantially in the past two decades. Concomitant with the increased incidence of infection has been an enhancement in the recognition of LD complications. Here, we report a case of Lyme carditis complicated by heart block in a pediatric patient admitted to our children’s hospital. What is unique about this case is that the complaint of chest palpitations is an infrequent presentation of LD, and what it adds to the scientific literature is an improved understanding of LD in the pediatric population.

Case presentation

The patient was a 16-year-old male who presented with the main concerns of acute onset of palpitations and chest pain. An important clinical finding was Erythema migrans (EM) on physical exam. The primary diagnoses were LD with associated Lyme carditis, based on the finding of 1st degree atrioventricular heart block (AVB) and positive IgM and IgG antibodies to Borrelia burgdorferi. Interventions included echocardiography, electrocardiography (EKG), and intravenous antibiotics. The hospital course was further remarkable for transition to 2nd degree heart block and transient episodes of complete heart block. A normal sinus rhythm and PR interval were restored after antibiotic therapy and the primary outcome was that of an uneventful recovery.

Conclusions

Lyme carditis occurs in < 5% of LD cases, but the “take-away” lesson of this case is that carditis can be the presenting manifestation of B. burgdorferi infection in pediatric patients. Any patient with suspected Lyme carditis manifesting cardiac symptoms such as syncope, chest pain, or EKG changes should be admitted for parenteral antibiotic therapy and cardiac monitoring. The most common manifestation of Lyme carditis is AVB. AVB may manifest as first-degree block, or may present as high-grade second or third-degree block. Other manifestations of Lyme carditis may include myopericarditis, left ventricular dysfunction, and cardiomegaly. Resolution of carditis is typically achieved through antibiotic administration, although pacemaker placement should be considered if the PR interval fails to normalize or if higher degrees of heart block, with accompanying symptoms, are encountered. With the rising incidence of LD, providers must maintain a high level of suspicion in order to promptly diagnose and treat Lyme carditis.

Read the entire study here.

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Can Google Identify Tick-borne Trends?

A new study from the Department of Dermatology and Allergy at the Technical University of Munich analyzed over 200 million Google searches in Germany. The data showed a high correlation between temperature, tick bite, and tick-borne illness, as well as between Google searches for Lyme and registered Lyme cases. More connections and trends might be waiting to be uncovered. 

ABSTRACT

Background: Borreliosis is the most frequently transmitted tick-borne disease in Europe. It is difficult to estimate the incidence of tick bites and associated diseases in the German population due to the lack of an obligation to register across all 16 federal states of Germany.

Objective: The aim of this study is to show that Google data can be used to generate general trends of infectious diseases on the basis of borreliosis and tick bites. In addition, the possibility of using Google AdWord data to estimate incidences of infectious diseases, where there is inconsistency in the obligation to notify authorities, is investigated with the perspective to facilitate public health studies.

Methods: Google AdWords Keyword Planner was used to identify search terms related to ticks and borreliosis in Germany from January 2015 to December 2018. The search volume data from the identified search terms was assessed using Excel version 15.23. In addition, SPSS version 24.0 was used to calculate the correlation between search volumes, registered cases, and temperature.

Results: A total of 1999 tick-related and 542 borreliosis-related search terms were identified, with a total of 209,679,640 Google searches in all 16 German federal states in the period under review. The analysis showed a high correlation between temperature and borreliosis (r=0.88), and temperature and tick bite (r=0.83), and a very high correlation between borreliosis and tick bite (r=0.94). Furthermore, a high to very high correlation between Google searches and registered cases in each federal state was observed (Brandenburg r=0.80, Mecklenburg-West Pomerania r= 0.77, Saxony r= 0.74, and Saxony-Anhalt r=0.90; all P<.001).

Conclusions: Our study provides insight into annual trends concerning interest in ticks and borreliosis that are relevant to the German population exemplary in the data of a large internet search engine. Public health studies collecting incidence data may benefit from the results indicating a significant correlation between internet search data and incidences of infectious diseases.

Read the full case study here.

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Lone Star Ticks Have Swarmed Aquinnah, Biologist Says

“Lone star ticks – and thousands of their larvae — have overrun the town of Aquinnah, biologist and tick expert Richard Johnson told Aquinnah selectmen at their meeting Wednesday, following reports that showed a high incidence of tick-borne disease in the town this year.

In a letter that went out last week, the town board of health reported 13 new cases of tick-borne illnesses since April of this year, including cases of Lyme disease, ehrlichiosis, babeosis and Rocky Mountain spotted fever. At the meeting, Mr. Johnson said he was in Aquinnah on Tuesday surveying yards for ticks and found lone star larvae in every location he visited.

“I was horrified,” Mr. Johnson said. “I’ve looked at a lot of ticks over the past 10 years and the number of lone star larvae I found was just astonishing,”

Mr. Johnson is director of the Martha’s Vineyard tick-borne illness reduction program. He said he receives at least one call or email a day alerting him to newly discovered clusters of lone star ticks on the Island.

“They’re everywhere,” Mr. Johnson said. “Every property that we have gone to in Aquinnah to do a survey we’ve found lone star ticks. They’re literally every place in the town except maybe the [Gay Head] Cliffs.”

Read the entire article here.

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HHS and the Steven & Alexandra Cohen Foundation Announce $25 Million “LymeX” Innovation Accelerator

Today, at the virtual LymeMIND exit disclaimer icon conference, the U.S. Department of Health and Human Services (HHS) and the Steven & Alexandra Cohen Foundation announced a new $25 million-dollar, public-private partnership — the LymeX Innovation Accelerator (LymeX). This is the largest Lyme disease public-private partnership in history. This partnership will be a force multiplier to expedite progress and catalyze change faster than government or other sectors can do on their own.

Our LymeX mission is to strategically advance Lyme and tickborne disease solutions in direct collaboration with Lyme patients, patient advocates, and diverse stakeholders across academia, nonprofits, industry, and government. LymeX will include up to $25 million for Lyme innovation and competition prize awards. The LymeX partnership will prioritize a series of diagnostics prize challenges for Lyme disease to move the next generation of diagnostic tools to market for better patient care.

“Lyme disease is exactly the kind of neglected public health issue that the Trump Administration has made a priority, including by strategic efforts to drive private sector innovation,” says HHS Secretary Alex Azar. “The new $25 million LymeX effort is the largest Lyme disease public-private partnership ever and will help support next-generation science and innovation to address the disease’s growing burden.”

LymeX does not in any way replace or supersede other government programs focused on ticks or tickborne diseases. Rather, it augments federally funded science, disease control and prevention, and regulatory approvals for next-generation diagnostics, treatments, vaccines, and technologies for Lyme and tickborne diseases.

Lyme disease affects more than 300,000 people in the United States each year. Tickborne diseases, including Lyme disease, are increasing in number; they are spreading to new areas; and new tickborne diseases are being discovered. According to the Centers for Disease Control and Prevention (CDC), domestic cases of tickborne diseases more than doubled from 2004 to 2018.

To reverse these current trends, the Steven & Alexandra Cohen Foundation partnered with HHS on LymeX for transformative impact. The Steven & Alexandra Cohen Foundation is the largest private funder of Lyme and tickborne disease research in the United States. Their philanthropy is inspired by Alex Cohen’s personal journey with Lyme disease.

U.S. government is prioritizing Lyme disease, as exemplified by the LymeX partnership and demonstrated by increasing government budget, leadership, and action for tickborne diseases. In December 2019, President Trump signed the Kay Hagan Tick Act. This authorized an additional $150 million for Lyme and vector-borne diseases over five years. In early 2020, the President’s 2021 Budget requested an increase of $58 million in one year — from $131 million to $189 million for tickborne diseases. Just last month, the HHS Deputy Secretary Eric Hargan and HHS Assistant Secretary for Health, Admiral Brett Giroir, committed $2 million to support LymeX stakeholder engagement, patient-centered innovation, and lab-to-market technologies for Lyme disease.

Challenges with Lyme disease are too big and complex for any one entity or one discipline to solve. Therefore, the LymeX partnership will bring together diverse stakeholders for a holistic approach with crosscutting collaborations for interdisciplinary solutions. Similar to the methods and success of the HHS KidneyX exit disclaimer icon Innovation Accelerator, LymeX will include patients in every step of its innovation process. Three focus areas of LymeX will advance tickborne disease innovation through:

(1) Stakeholder engagement to facilitate patient-centered innovations, using the Health+ model with HHS.

(2) Education and awareness through “open innovation” like crowdsourcing to raise awareness about risk and prevention.

(3) Next-generation diagnostics incentivized with a series of multi-million-dollar grand prize challenges, so prize winners who meet diagnostic performance benchmarks will receive cash prizes for delivering solutions. The first LymeX diagnostics prize will launch in 2021. These diagnostics prizes will be open to U.S. universities, non-profit organizations, private-sector companies, and domestic organizations, per the America COMPETES Reauthorization Act of 2010 – PDF, to improve diagnostics at all stages of Lyme disease.

The LymeX partnership fits within the broader, big-tent Lyme Innovation initiative that HHS launched in 2018. The LymeX partnership and program will reside within the HHS Office of the Assistant Secretary for Health (OASH), which manages the TickBorne Disease Working Group. OASH is also leading and coordinating interagency efforts to implement the U.S. national framework on vector-borne diseases including Lyme and tickborne diseases.

The entire original article can be found here.

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A Distinct Microbiome Signature in Posttreatment Lyme Disease Patients

ABSTRACT

Lyme disease is the most common vector-borne disease in the United States, with an estimated incidence of 300,000 infections annually. Antibiotic intervention cures Lyme disease in the majority of cases; however, 10 to 20% of patients develop posttreatment Lyme disease syndrome (PTLDS), a debilitating condition characterized by chronic fatigue, pain, and cognitive difficulties. The underlying mechanism responsible for PTLDS symptoms, as well as a reliable diagnostic tool, has remained elusive. We reasoned that the gut microbiome may play an important role in PTLDS given that the symptoms overlap considerably with conditions in which a dysbiotic microbiome has been observed, including mood, cognition, and autoimmune disorders. Analysis of sequencing data from a rigorously curated cohort of patients with PTLDS revealed a gut microbiome signature distinct from that of healthy control subjects, as well as from that of intensive care unit (ICU) patients. Notably, microbiome sequencing data alone were indicative of PTLDS, which presents a potential, novel diagnostic tool for PTLDS.

IMPORTANCE Most patients with acute Lyme disease are cured with antibiotic intervention, but 10 to 20% endure debilitating symptoms such as fatigue, neurological complications, and myalgias after treatment, a condition known as posttreatment Lyme disease syndrome (PTLDS). The etiology of PTLDS is not understood, and objective diagnostic tools are lacking. PTLDS symptoms overlap several diseases in which patients exhibit alterations in their microbiome. We found that patients with PTLDS have a distinct microbiome signature, allowing for an accurate classification of over 80% of analyzed cases. The signature is characterized by an increase in Blautia, a decrease in Bacteroides, and other changes. Importantly, this signature supports the validity of PTLDS and is the first potential biological diagnostic tool for the disease.

You can read the entire study at American Society for Microbiology.

Word of caution: In its research definition, the published study uses the term “PTLDS,” or post-treatment Lyme disease syndrome, a term we object to because it suggests infection is completely gone and is often used to argue against further antimicrobial treatment. Project Lyme uses the term Persistent Lyme.

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Effects of Dapsone & Intracellular Antibiotics on B. Burgdorferi

Objective

Lyme disease is a tick-borne, multisystemic disease caused by Borrelia burgdorferi. Standard treatments for early Lyme disease include short courses of oral antibiotics but relapses often occur after discontinuation of treatment. Several studies have suggested that ongoing symptoms may be due to a highly antibiotic resistant form of B. burgdorferi called biofilms. Our recent clinical study reported the successful use of an intracellular mycobacterium persister drug used in treating leprosy, diaminodiphenyl sulfone (dapsone), in combination therapy for the treatment of Lyme disease. In this in vitro study, we evaluated the effectiveness of dapsone individually and in combination with cefuroxime and/or other antibiotics with intracellular activity including doxycycline, rifampin, and azithromycin against Borrelia biofilm forms utilizing crystal violet biofilm mass, and dimethyl methylene blue glycosaminoglycan assays combined with Live/Dead fluorescent microscopy analyses.

Results

Dapsone, alone or in various combinations with doxycycline, rifampin and azithromycin produced a significant reduction in the mass and protective glycosaminoglycan layer and overall viability of B. burgdorferi biofilm forms. This in vitro study strongly suggests that dapsone combination therapy could represent a novel and effective treatment option against the biofilm form of B. burgdorferi.

You can read the entire study on BMC Research Notes. 

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Lyme in the Arctic?

In the latest sign of climate change, Bartonella henselae, a coinfection of Lyme usually found in more temperate regions, has been detected in the blood of arctic foxes. Research suggests that migratory geese have given Bart-infected fleas a ride north, where the bacterium can now survive. Below we share the abstract of the study. You can read the entire @BioMedCentral post here. 

Abstract
Background
In a warmer and more globally connected Arctic, vector-borne pathogens of zoonotic importance may be increasing in prevalence in native wildlife. Recently, Bartonella henselae, the causative agent of cat scratch fever, was detected in blood collected from arctic foxes (Vulpes lagopus) that were captured and released in the large goose colony at Karrak Lake, Nunavut, Canada. This bacterium is generally associated with cats and cat fleas, which are absent from Arctic ecosystems. Arctic foxes in this region feed extensively on migratory geese, their eggs, and their goslings. Thus, we hypothesized that a nest flea, Ceratophyllus vagabundus vagabundus (Boheman, 1865), may serve as a vector for transmission of Bartonella spp.

Methods
We determined the prevalence of Bartonella spp. in (i) nest fleas collected from 5 arctic fox dens and (ii) 37 surrounding goose nests, (iii) fleas collected from 20 geese harvested during arrival at the nesting grounds and (iv) blood clots from 57 adult live-captured arctic foxes. A subsample of fleas were identified morphologically as C. v. vagabundus. Remaining fleas were pooled for each nest, den, or host. DNA was extracted from flea pools and blood clots and analyzed with conventional and real-time polymerase chain reactions targeting the 16S-23S rRNA intergenic transcribed spacer region.

Results
Bartonella henselae was identified in 43% of pooled flea samples from nests and 40% of pooled flea samples from fox dens. Bartonella vinsonii berkhoffii was identified in 30% of pooled flea samples collected from 20 geese. Both B. vinsonii berkhoffii (n = 2) and B. rochalimae (n = 1) were identified in the blood of foxes.

Conclusions
We confirm that B. henselae, B. vinsonii berkhoffii and B. rochalimae circulate in the Karrak Lake ecosystem and that nest fleas contain B. vinsonii and B. henselae DNA, suggesting that this flea may serve as a potential vector for transmission among Arctic wildlife.

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