Archive for the ‘research’ Category

Case Report: ALS or Lyme Disease?

https://danielcameronmd.com/als-mimicked-by-lyme-disease/  Podcast here

CASE REPORT: ALS OR LYME DISEASE?

ALS-mimicked-lyme-disease

Hello, and welcome to another Inside Lyme Podcast. I am your host Dr. Daniel Cameron. In this episode, I will be discussing the case involving a 63-year-old man with ALS mimicked by Lyme disease.

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I first read about this case by Wirsching and colleagues in the journal Clinical Case Reports. [1]

Amyotrophic Lateral Sclerosis (ALS), also known as Lou Gehrig’s disease, is a progressive motor neuron disease.

The 63-year-old man developed bilateral atrophic arm paresis with preserved reflexes and met the criteria for probable ALS. However, he also tested positive for Lyme disease by spinal tap.

In the year prior to developing ALS symptoms, the patient reportedly had a tick bite without a rash.

“In July 2018, that is, within six months, he developed paraparesis of both arms and also suffered from cramps in the shoulder girdle and hand muscles,” wrote the authors. “By August 2018, the patient was severely impaired in everyday life activities.”

His spinal tap revealed pleocytosis (an elevated white count) and elevated protein. The spinal fluid was positive for IgM and IgG titers for Lyme disease. His blood test was positive by ELISA and IgG Western blot tests. The antibody index was higher in the spinal tap than the blood by IgM but not IgG.

He was prescribed a three-week course of intravenous ceftriaxone but his symptoms did not improve.

“Hence, it is unlikely that neuroborreliosis was the main cause of symptoms in our patient,” wrote the authors.

Instead, the authors concluded that the patient’s ALS mimicked by Lyme disease.

Considering Lyme disease in differential diagnosis

The authors of another study, suggested that Lyme disease should be considered in patients presenting with ALS. “There appears to be a statistically significant association between ALS and immunoreactivity to B burgdorferi.” [2] Subsequent larger studies did not show an association.

Although the association between these two diseases remains controversial, Wirsching et al. highlighted the importance of considering Lyme disease in an ALS workup.

“It is vital to exclude potentially treatable diseases in the differential diagnostic work-up of all patients not to miss seldom, but treatable differential diagnoses such as neuroborreliosis,” the authors concluded.

The following questions are addressed this podcast:

  1. What is ALS?
  2. What is the difference between motor and sensory nerve disease?
  3. Why was Lyme disease considered?
  4. What is the significance of the positive spinal tap for Lyme disease?
  5. Were there any other tick-borne infections discussed?
  6. Was a single 3-week course of IV antibiotics sufficient?
  7. Why is it important to consider reversible causes of ALS?
  8. Have you seen cases of motor nerve disease in your practice?

Editor’s note:

Harvey and Martz described the case of a patient with motor nerve disease (ALS) who improved with antibiotic therapy.[3]

I have had Lyme disease patients with motor neuron disease who have improved with antibiotic treatment and others who have failed. I continue to encourage research in this area.

    1. Thanks for listening to another Inside Lyme Podcast. You can read more about these cases in my show notes and on my website @DanielCameronMD.com. As always, it is your likes, comments, reviews, and shares that help spread the word about Lyme disease. Until next time on Inside Lyme.

Please remember that the advice given is general and not intended as specific advice as to any particular patient. If you require specific advice, then please seek that advice from an experienced professional.

Inside Lyme Podcast Series

This Inside Lyme case series will be discussed on my Facebook and made available on podcast and YouTube.  As always, it is your likes, comments, and shares that help spread the word about this series and our work. If you can, please leave a review on iTunes or wherever else you get your podcasts.

References:
  1. Wirsching I, Ort N, Uceyler N. ALS or ALS mimic by neuroborreliosis-A case report. Clin Case Rep. Jan 2020;8(1):86-91. doi:10.1002/ccr3.2569
  2. Halperin JJ, Kaplan GP, Brazinsky S, et al. Immunologic reactivity against Borrelia burgdorferi in patients with motor neuron disease. Arch Neurol. 1990;47(5):586-594.
  3. Harvey WT, Martz D. Motor neuron disease recovery associated with IV ceftriaxone and anti-Babesia therapy. Acta Neurol Scand. Feb 2007;115(2):129-31. doi:10.1111/j.1600-0404.2006.00727.x

For more:

Category:

Lyme, research, Testing, Treatment

Human Tacheng Tick Virus 2 Detected in China

https://wwwnc.cdc.gov/eid/article/27/2/19-1486_article

Volume 27, Number 2—February 2021
Dispatch

Human Tacheng Tick Virus 2 Infection, China, 2019

Zhihui Dong1, Meihua Yang1, Zedong Wang1, Shuo Zhao, Songsong Xie, Yicheng Yang, Gang Liu, Shanshan Zhao, Jing Xie, Quan LiuComments to Author , and Yuanzhi WangComments to Author 
Author affiliations: Shihezi University, Shihezi, China (Z. Dong, M. Yang, Shuo Zhao, Y. Yang, G. Liu, Shanshan Zhao, Y. Wang); Foshan University, Foshan, China (Z. Wang, Q. Liu); First Affiliated Hospital of Shihezi University, Shihezi (S. Xie, J. Xie); Shihezi People’s Hospital, Shihezi (Y. Yang)

Abstract

We used metagenomic analysis to identify Tacheng tick virus 2 infection in a patient with a history of tick bite in northwestern China. We confirmed the virus with reverse transcription-PCR, virus isolation, and genomic analysis. We detected viral RNA in 9.6% of ticks collected from the same region.

Important excerpt:

Emerging pathogenic tickborne viruses have attracted much attention because of the increasing incidence of tickborne viral diseases and their effects on human health (1–4). In 2015, high-throughput sequencing of samples from ticks in China revealed several novel phleboviruses, including

  • Tacheng tick virus 2 (TcTV-2)
  • Changping tick virus 1
  • Bole tick virus 1 (BlTV-1)
  • Lihan tick virus
  • Yongjia tick virus 1
  • Dabieshan tick virus (5)

However, the risk for human infection from these viruses is not yet known.

The 38-year old Chinese man who had frequent contact with horses and sheep removed a tick from his arm and had the following symptoms: chills, severe fatigue, headache, anorexia, nausea, vomiting, fever, erythema at the bite site and neck stiffness. 

The researchers further gathered nearly 350 ticks from the patient’s geographical area and found nearly 10% carried the virus.  The sequences from the ticks closely related the isolate in the patient.

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**Comment**

Despite the fact the authors stated this particular virus didn’t show growth in numerous media, a human contracted the virus.  This is important to remember.  All the statistics in the world don’t matter a tittle when you are the sorry sucker who becomes ill, despite everyone around you saying it’s ‘rare’! 

Phleboviruses can cause severe fever with thrombocytopenia syndrome, and multiple organ damage, including to the liver and kidneys.

For more:  https://madisonarealymesupportgroup.com/2018/08/20/first-identification-in-china-of-guertu-virus-from-ticks/  SFTS explained within – of which the Asian Longhorned tick is often the culprit, which is spreading through the U.S right now.

Category:

research, Testing, Ticks, Viruses

Lyme Found in Asian Long-horned Ticks Again

https://wwwnc.cdc.gov/eid/article/27/2/20-1552_article

Disclaimer: Early release articles are not considered as final versions. Any changes will be reflected in the online version in the month the article is officially released.

Volume 27, Number 2—February 2021

Borrelia burgdorferi Sensu Stricto DNA in Field-Collected Haemaphysalis longicornis Ticks, Pennsylvania, United States

Keith J. PriceComments to Author , Christine B. Graham, Bryn J. Witmier, Holly A. Chapman, Brooke L. Coder, Christian N. Boyer, Erik Foster, Sarah E. Maes, Ying Bai, Rebecca J. Eisen, and Andrew D. Kyle
Author affiliations: Pennsylvania Department of Environmental Protection, Harrisburg, Pennsylvania, USA (K.J. Price, B.J. Witmier, H.A. Chapman, B.L. Coder, C.N. Boyer, A.D. Kyle); Centers for Disease Control and Prevention, Fort Collins, Colorado, USA (C.B. Graham, E. Foster, S.E. Maes, Y. Bai, R.J. Eisen)

Abstract

We collected questing Haemaphysalis longicornis ticks from southeastern counties of Pennsylvania, USA. Of 263 ticks tested by PCR for pathogens, 1 adult female was positive for Borrelia burgdorferi sensu stricto, yielding a 0.4% infection rate. Continued monitoring of this invasive tick is essential to determine its public health role.

Borrelia burgdorferi sensu stricto is the causative agent of Lyme disease, the most commonly reported vectorborne disease in North America (1). In Pennsylvania, which is first in the United States in the number of reported Lyme disease cases, the spirochete has been identified in nearly 50% of adult Ixodes scapularis ticks, the primary vector (2). In 2018, Pennsylvania initiated a statewide active surveillance program to monitor tick distribution and density, by county, and tickborne pathogen prevalence. Although focused primarily on collecting and testing Ixodes scapularis ticks, initial surveillance efforts recovered, among other species, Haemaphysalis longicornis (Asian longhorned tick), an exotic species recently detected in North America (3), providing quantitative records of their presence in Pennsylvania public lands (4).

Since its US discovery in New Jersey during 2017, the number of states that have detected H. longicornis ticks has increased rapidly. In its native range, H. longicornis ticks have been found to carry a variety of pathogens endemic to Pennsylvania, including B. burgdorferi (5). However, because the ecologic characteristics and the pathogen diversity and prevalence of H. longicornis ticks in the United States are understudied, potential epidemiologic risks there remain unknown. We report surveillance program data on the presence of pathogen-infected H. longicornis in public areas in Pennsylvania.

The Study

We performed surveillance activities weekly in 38 Pennsylvania counties during May 1–September 6, 2019, capturing peak nymphal I. scapularis ticks, in addition to adult and nymphal H. longicornis tick densities (6). Sampling sites, primarily high-use public areas in deciduous forests, were selected for high risk of recreational and occupational tick encounters and suitable I. scapularis and reported H. longicornis tick habitat (6).

Collection processes were standardized to minimize spatial and temporal bias. We collected questing ticks by dragging a 1 m2 white felt cloth over vegetation and leaf litter for 100–600 m. We examined cloths every 10 m and transferred recovered ticks into vials containing 80% ethanol, which we shipped to a central laboratory where they were stored at −80°C until being identified using morphological keys.

We tested the majority (84%) of collected H. longicornis nymphs and adults for pathogens, then retained the rest as voucher specimens. We prepared DNA extracts from individual H. longicornis tick homogenates on the KingFisher Flex Purification System with the MagMAX CORE Nucleic Acid Purification Kit (ThermoFisher Scientific, External Link). We tested each extract for B. burgdorferi sensu stricto, B. mayonii, B. miyamotoi, and Babesia microti using probe-based real-time PCR assays comprising multiple targets for each pathogen (Table). We amplified a segment of the Borrelia dipeptidyl aminopeptidase (PepX) gene using seminested PCR and sequenced it to confirm B. burgdorferi sensu stricto–positive specimens. We followed real-time PCR and PepX amplification protocols published elsewhere (9). We amplified and sequenced a 667-nt fragment of the cytochrome oxidase subunit I (COI) gene using primers LCO1490 and HCO2198 (11) to confirm the tick species of positive specimens. The PCR mixture (25 µL) contained forward and reverse primers at a final concentration of 0.4 µmol and 5 µL of DNA template. Thermocycling conditions followed protocols published elsewhere (11). COI and PepX amplicons were sequenced as described elsewhere (9).

Results
County map of Pennsylvania, USA, and the southeastern region (inset) showing locations of active tick surveillance, where Haemaphysalis longicornis ticks were recovered, and where Borrelia burgdorferi sensu stricto–positive H. longicornis ticks were found, May 1–September 6, 2019. Pennsylvania county map shows 38 counties sampled weekly and an additional 14 counties sampled opportunistically that yielded low tick recovery (Ixodes scapularis ticks only).

 

Figure. County map of Pennsylvania, USA, and the southeastern region (inset) showing locations of active tick surveillance, where Haemaphysalis longicornis ticks were recovered, and where Borrelia burgdorferisensu…

A total of 668 H. longicornis ticks (356 larvae, 166 nymphs, 146 adults) were collected from 4 counties in southeastern Pennsylvania (Figure). During the same period, 265 I. scapularis ticks (174 larvae, 78 nymphs, 13 adults) were collected from the same 4 counties. Of the subset of H. longicornis ticks tested by using real-time PCR (n = 263), 1 (0.4%) adult female collected from a county park in Bucks County on June 14, 2019 was positive for B. burgdorferi sensu stricto. A 570-nt segment of the PepX gene from this specimen was identical to B. burgdorferi sensu stricto reference sequences (GenBank accession nos. CP002312.1:657467–658036). The COI gene fragment from this tick showed 99.8% identity to an H. longicornis tick sequence in the GenBank database (accession no. JQ737090). No H. longicornis ticks were positive for B. miyamotoi, B. mayonii, or B. microti.

Conclusions

We document detection of the Lyme disease spirochete, B. burgdorferi sensu stricto, in invasive H. longicornis ticks. The overall infection rate of 0.4% was low. In comparison, B. burgdorferi sensu lato infection rates in I. scapularis ticks collected during the same surveillance period and in the same counties ranged from 16.7% to 57.1% (M.P. Price et al., unpub. data). This finding is consistent with recent findings that H. longicornis ticks are relatively averse to feeding on white-footed mice (Peromyscus leucopus), the primary reservoir of B. burgdorferi sensu stricto (12). Our findings support laboratory studies demonstrating that H. longicornis ticks can acquire B. burgdorferi sensu stricto while feeding on experimentally infected mice; however, those studies suggested that H. longicornis ticks are unlikely to contribute to transmission of B. burgdorferi sensu stricto because infection is lost during molting (13). However, refeeding and transmission of Lyme spirochetes by partially-fed ixodid ticks has been documented (14).

Based on microscopy, we estimated that ≈10% of the host-seeking H. longicornis ticks that we recovered were partially fed, suggesting the possibility that transmission could occur before the ticks molt. Of note, however, although we detected B. burgdorferi sensu stricto DNA in the tick, we have no evidence to suggest the spirochetes were viable. Unique ecologic traits of H. longicornis ticks (e.g., cold hardiness, parthenogenetic reproduction, host generality), which may enable the species’ rapid establishment and high density (4), could confound efforts to determine the extent to which the tick may be involved in maintenance of B. burgdorferi sensu stricto in nature.

Continued monitoring to identify infested areas is essential, especially in densely populated regions (e.g., southeastern Pennsylvania). Despite limited documentation of H. longicornis ticks biting humans in the United States (15), findings presented here support continued use of personal protective measures. H. longicornis ticks are a vector of human pathogens in its native range; further investigation is needed to determine its potential public health significance in the United States.

Dr. Price is a microbiologist at the Pennsylvania Department of Environmental Protection, Division of Vector Management, Harrisburg, PA. His research interests include vector ecology and vector-borne disease epidemiology.

Acknowledgments

We thank field personnel for collection efforts, Rebecca Eckert for helpful comments, and Pennsylvania Department of Health, especially Leah Lind, for cooperation and support.

Funding for this study was provided, in part, by an epidemiology subgrant (#4100082142) from the Pennsylvania Department of Health.

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**Comment**

While the article is quick to point out the low borrelia infection rate, this is the tick that clones itself multiplying like wild-fire and spreading geographically.  I think we should be concerned.  A study last year found the following:

At least 30 human pathogens were associated with H longicornis, including seven species of spotted fever group rickettsiae, seven species in the family of Anaplasmataceae, four genospecies in the complex Borrelia burgdorferi sensu lato, two Babesia species, six species of virus, and Francisella, Bartonella, Coxiella, and Toxoplasma, which were mainly reported in eastern Asia. The predictive modelling revealed that H longicornis might affect more extensive regions, including Europe, South America, and Africa, where the tick has never been recorded before.  https://www.thelancet.com/journals/lanplh/article/PIIS2542-5196(20)30145-5/fulltext

For more:  

The very important issue of interrupted/partial feeding in ticks is not very well understood but would explain quicker transmission times:

https://madisonarealymesupportgroup.com/2020/07/05/interrupted-blood-feeding-in-ticks-causes-and-consequences/

Category:

Lyme, research, Ticks

Lyme Disease Mimics Cellulitis Skin Infection

https://danielcameronmd.com/lyme-disease-mimics-cellulitis-skin-infection/

LYME DISEASE MIMICS CELLULITIS SKIN INFECTION

patient with lyme disease being examined for cellulitis

Lyme disease can mimic acute and chronic illness. In their article “Lyme Disease Mimics Postoperative Cellulitis,” the authors describe a patient who developed an abdominal rash, which was initially diagnosed as cellulitis, six days after a laparoscopic left salpingo-oophorectomy surgery. [1]

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The 40-year-old woman, who developed redness, swelling, pain, and a rash at the excision site, was treated with cephalexin and later switched to trimethoprim/sulfamethoxazole (TMP/SMX).

“Over the next 24 hours, there was a rapid expansion of abdominal redness and patchy areas of redness on her left groin and her right forearm,” the authors write. The patient had complained of muscle and joint stiffness but attributed it to recent outdoor camping and exercise.

The woman was “admitted for postoperative cellulitis remote from surgery.” She was treated with doxycycline for possible Lyme disease, due to her recent camping trip and exposure to ticks.

Within hours of starting doxycycline, the patient’s “abdominal erythema [rash] significantly receded, the forearm and leg rashes resolved, and the joint pain and stiffness improved markedly.”

The Lyme disease diagnosis was confirmed with an IgM Western blot test.

“Initial suppression of the worsening rash could have been due to a low level of TMP/SMX activity on Borrelia burgdorferi stationary phase cells,” the authors explain.

The woman’s IgG Western blot test was negative.

Although Lyme disease can present with erythema migran rashes, early rashes can be confused with cellulitis. The authors suggest, “Lyme disease should be considered in patients with cellulitis in areas of endemic Lyme.”

Lyme disease rashes have been misidentified

Lyme disease rashes were misidentified in a case series involving 88 patients who presented with an erythema migrans (EM).  In 13 of these patients, the rash had been incorrectly identified or treated.

“Rashes were often misidentified by clinicians and patients as a spider bite, cellulitis, or shingles,” wrote Aucott and colleagues. [2]

The authors concluded, “Until more accurate tests are developed for early Lyme disease, cases without a diagnostic EM rash will need to be managed carefully.

In patients with cutaneous lesions where the differential diagnosis of cellulitis is not certain, empiric antibiotics should be chosen that will have activity against both Lyme disease and common agents of cellulitis.”

Editor’s note: I have prescribed cefuroxime or amoxicillin/clavulanic acid if Lyme disease is a consideration. Neither cephalexin nor TMP/SMX are effective against Lyme disease. If I believe Lyme disease is involved, I will treat patients longer than 7 to 10 days.  You can look at the rash yourself as the journal is open access.

Related Articles:

What does a Lyme disease rash look like?

How the incidence of an EM rash can be inflated

Single dose prophylactic treatment of a tick bite only prevents a Lyme rash

References:
  1. Miles S, Mansuria S. Lyme Disease Mimics Postoperative Cellulitis. J Minim Invasive Gynecol. Nov 15 2020;doi:10.1016/j.jmig.2020.11.002
  2. Aucott J, Morrison C, Munoz B, Rowe PC, Schwarzwalder A, West SK. Diagnostic challenges of early Lyme disease: lessons from a community case series. BMC Infect Dis. Jun 1 2009;9:79. doi:10.1186/1471-2334-9-79

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For more:  

Category:

Lyme, research, vaccines

1st Cases of Natural Infections With Borrelia Hispanica in European Dogs and Cat

https://pubmed.ncbi.nlm.nih.gov/32824647/

First Cases of Natural Infections with Borrelia hispanica in Two Dogs and a Cat from Europe

Gabriele Margos 1, Nikola Pantchev 2, Majda Globokar 2, Javier Lopez 3, Jaume Rodon 3, Leticia Hernandez 3, Heike Herold 4, Noelia Salas 3, Anna Civit 3, Volker Fingerle 1

Free PMC article

Abstract

Canine cases of relapsing fever (RF) borreliosis have been described in Israel and the USA, where two RF species, Borrelia turicatae and Borrelia hermsii, can cause similar clinical signs to the Borrelia persica in dogs and cats reported from Israel, including fever, lethargy, anorexia, thrombocytopenia, and spirochetemia. In this report, we describe the first clinical cases of two dogs and a cat from Spain (Cordoba, Valencia, and Seville) caused by the RF species Borrelia hispanica. Spirochetes were present in the blood smears of all three animals, and clinical signs included lethargy, pale mucosa, anorexia, cachexia, or mild abdominal respiration. Laboratory findings, like thrombocytopenia in both dogs, may have been caused by co-infecting pathogens (i.e., Babesia vogeli, confirmed in one dog). Anemia was noticed in one of the dogs and in the cat. Borrelia hispanica was confirmed as an infecting agent by molecular analysis of the 16S rRNA locus. Molecular analysis of housekeeping genes and phylogenetic analyses, as well as successful in vitro culture of the feline isolate confirmed the causative agent as B. hispanica.

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**Comment**

Our feline and canine friends are sentinels for human diseases and these cases are no different.

To date, 23 TBRF-related Borrelia species have been confirmed, but additional species are proposed (2). B. hispanica is the primary TBRF-related Borrelia species identified in Spain (3,4), where it is endemic.  It is transmitted mainly through the bite of O. erraticus ticks (5) but also can be transmitted by O. occidentalis ticks (4). B. hispanica also has been found in Portugal (6), Morocco (4,7,8), and Tunisia (4).  https://wwwnc.cdc.gov/eid/article/26/5/19-0745_article?deliveryName=USCDC_331-DM26146

As of 2015, B. hispanica is considered an emerging infectious agent causing Neuroborreliosis:  https://n.neurology.org/content/84/14_Supplement/P6.310

Please keep in mind that migrating birds and animals are transporting ticks everywhere and spreading the pathogens they carry.

O. erraticus ticks feed nocturnally on multiple warm- blooded vertebrate hosts, including humans, and are found living buried in soil of traditional pigpens: https://repository.uel.ac.uk/download/ef62f8a0e6b1b15a27c35d240d126464385ad171f0be9af9d7768571b17460b0/128662/Portuguese%2520hosts%2520for%2520Ornithodoros%2520erraticus%2520ticks.pdf

Regarding O. occidentals ticks, according to this 2020 article,

“we have not sampled Ornithodoros ticks to evaluate densities and infection rates, nor have we collected samples from small mammals to investigate the reservoir of Borrelia spp.” 19-0745

Important excerpt:

Because the spirochetemia phase is short and laboratory diagnosis is exclusively dependent on the observer, we believe TBRF is underdiagnosed, even in areas where suspicion should be relatively high. 19-0745

Category:

research, Tickborne Relapsing Fever, Ticks