Archive for the ‘research’ Category

Patients Can Die When Lyme Carditis Is Not Treated

https://danielcameronmd.com/patients-die-lyme-carditis-not-treated/

PATIENTS CAN DIE WHEN LYME CARDITIS IS NOT TREATED

Lyme carditis can cause a broad range of symptoms. Patients may initially appear to have only a flu-like illness, however the severity of symptoms can change rapidly. In the article “Fatal Lyme carditis in New England: Two case reports,” Marx and colleagues highlight the importance of early recognition and treatment, even empirically, as Lyme carditis can be deadly when left untreated.

By
“Death can occur when Lyme carditis is untreated,” writes Marx, from the Centers for Disease Control and Prevention (CDC), in the Annuals of Internal Medicine. “Before this report, only 9 fatal cases were reported in the literature.”

Case 1: Waiting for infectious disease appointment

“A 57-year-old man from Vermont presented to a primary care physician after 1 week of fever, fatigue, shortness of breath, and chest pain,” writes Marx.

The evidence for Lyme disease included a disseminated erythema migrans rash, heart block, and a positive Lyme ELISA and IgM Western blot test. Yet, the patient was not treated.

Eight days later, the man presented to an emergency room with worsening symptoms. Physicians suspected Lyme disease, but antibiotics were not prescribed. Instead, a consultation with an infectious disease doctor was scheduled. Unfortunately, it never happened.

Only 12 days after his “initial presentation and before his scheduled appointment, the patient was found unresponsive,” writes Marx.

Case 2: Before the first dose of antibiotics

“A 49-year-old woman from Massachusetts presented to an emergency department with severe headache, nausea, and vomiting,” writes Marx. She was diagnosed and treated for a headache.

“Two weeks later, she saw her primary care physician and reported 2 episodes of syncope with bowel and bladder incontinence, persistent fatigue and nausea, and shortness of breath.”

“An ECG during the office visit showed atrioventricular dissociation.” Lyme disease tests were ordered.

Two days later, Lyme disease tests revealed a positive ELISA and IgM Western blot.

Lyme carditis can cause sudden death. These 2 cases highlight the importance of early recognition. And treatment, even if it’s empirical, may save lives. CLICK TO TWEETShe was prescribed doxycycline. But the next day, before she took the first dose, “her cardiac monitoring recorded atrioventricular dissociation evolving to ventricular tachycardia after an R-on-T electrical impulse,” writes Marx.

In both patients, an evaluation of postmortem heart tissue found lymphohistiocytic pancarditis with immunohistochemical and molecular evidence of the spirochete Borrelia burgdorferi.

“Spirochetes were directly visualized in endocardial tissue [taken] from the Massachusetts patient,” writes Marx.

Lyme carditis was high on the list of possible diagnoses, according to Marx. Yet, neither patient was treated empirically with antibiotics when Lyme disease testing was performed.

The patients might have received treatment had the guidelines been followed.²

“Guidelines recommend simultaneous initiation of empirical antibiotic therapy and Lyme serologic testing when Lyme carditis is suspected,” states Yeung et al.

“Lyme carditis can progress rapidly,” explains Marx, “waiting for confirmatory diagnostic therapy to initiate antibiotic treatment may result in negative outcomes.”

Related Articles:

Study identifies 189 children with Lyme carditis

5 things to know about Lyme carditis

Lyme carditis causes complete heart block in 26-year-old man

References:
  1. Marx GE, Leikauskas J, Lindstrom K, Mann E, Reagan-Steiner S, Matkovic E, Read JS, Kelso P, Kwit NA, Hinckley AF, Levine MA, Brown C. Fatal Lyme Carditis in New England: Two Case Reports. Ann Intern Med. 2019 Oct 22.
  2. Yeung C, Baranchuk A. Diagnosis and treatment of Lyme carditis: JACC Review Topic of the Week. J Am Coll Cardiol. 2019;73:717-26

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**Comment**

This is just asinine.  Doctors are so afraid of Lyme/MSIDS they would rather have patients die before prescribing antibiotics.  Things must change.

The body count continues to mount in Lyme land.

Category:

Heart Issues, Lyme, research, Treatment

Immunoassay May Help Identify Pediatric Lyme Arthritis

https://www.medscape.com/viewarticle/922645?src=rss

Immunoassay May Help Identify Pediatric Lyme Arthritis

By Marilynn Larkin

December 18, 2019

NEW YORK (Reuters Health) – In Lyme disease-endemic areas, a C6 peptide enzyme immunoassay (EIA) test may help guide initial management of children with acute arthritis, an observational study suggests.

“Children with Lyme disease frequently present to the emergency department with an inflamed joint,” Dr. Lise Nigrovic of Boston Children’s Hospital told Reuters Health by email. “Although Lyme arthritis is initially treated with oral antibiotics, many children will undergo an invasive procedure such as a joint tap or even wash-out as part of the initial evaluation.”

“We demonstrated that the C6 EIA test, a previously approved first-tier test for Lyme disease, with results available within a few hours, could be used to safely guide initial management for children with inflamed joints to avoid unnecessary invasive procedures for children with Lyme arthritis,” she said.

The authors performed C6 EIA tests on 911 children presenting to a Pedi Lyme Net emergency department from 2015-2019. Lyme arthritis was defined as a positive or equivocal C6 EIA test followed by a positive supplemental immunoblot result; septic arthritis was defined as a positive synovial fluid culture result or a positive blood culture result with synovial fluid pleocytosis. Other cases were considered inflammatory arthritis.

As reported in Pediatrics, C6 EIA test results indicated that 211 children (23.2%) had Lyme arthritis, 11 (1.2%) had septic arthritis, and 689 (75.6%) had other inflammatory arthritis.

A positive or equivocal C6 EIA result had a sensitivity of 100% and specificity of 94.2% for Lyme arthritis. None of the 250 children with a positive or equivocal C6 EIA result had septic arthritis. However, of those with a positive first-tier Lyme disease test result, 75 underwent arthrocentesis (30%) and 27 had an operative joint washout performed (10.8%).

Dr. Eugene Shapiro of Yale School of Medicine in New Haven, Connecticut, coauthor of a related editorial, commented by email to Reuters Health, “In an area in which Lyme disease is endemic, although a positive C6 ELISA result in a child with arthritis of the knee is suggestive of Lyme disease, it does not rule out the possibility that it is due a different bacterium such as Staphylococcus aureus. Clinical judgement is still critical in deciding how to manage such patients.”

Lyme disease specialist Dr. Tania Dempsey, founder of Armonk Integrative Medicine in New York, commented, “The C6 EIA test has shown promise over the older ELISA test that is part of the two-tier Lyme testing recommended by the U.S. Centers for Disease Control and Prevention, dating back to 1995. There are serious limitations to the two-tier test, including a nearly 50% false-negative rate.”

“While this study shows promise . . . to accurately identify Lyme arthritis with the use of the C6 EIA test, it is not clear what the false negative rate was,” she told Reuters Health by email. “Their numbers show that they were able to diagnose 23.2% of children with Lyme arthritis and 1.2% with septic arthritis. But 75.6% were identified as having inflammatory arthritis, which means that the diagnosis is unclear. Based on the published false negative rate of this test, we can assume that a fair percentage of those with inflammatory arthritis probably had Lyme arthritis.”

“One key point is that the study design included a confirmatory immunoblot test for C6 EAI positive or equivocal results. This would be equivalent to a two-tier test,” she noted. However, “no immunoblot testing was done on any of the C6 EAI- negative results. Since we we know a large number of patients will be missed by this (test), it is discouraging to think of all those patients who might still be suffering with Lyme disease that was undetected with the screening C6 EAI test.”

“There is no question that we need better testing for Lyme disease,” she said. “The C6 EIA has some benefits but is clearly not sufficient.

SOURCE: http://bit.ly/34fODsR and http://bit.ly/2EgdP8g Pediatrics, online December 13, 2019.

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**Comment**

While this article desires to make you believe this test is accurate, Dr. Demsey clearly points out it has many problems including not knowing what the false negative rate was, as well as the fact 75.6% were identified as having inflammatory arthritis –  meaning that the diagnosis is unclear. And lastly, based on the published false negative’s, a fair percentage of those with inflammatory arthritis probably had Lyme arthritis.

Take away:  The test still sucks.

For more:  https://madisonarealymesupportgroup.com/2019/03/07/yet-another-worthless-study-showing-2-tiered-lyme-testing-can-not-rule-infection-out/

https://madisonarealymesupportgroup.com/2019/12/01/c6-peptide-test-for-lyme-disease-may-indicate-borrelia-miyamotoi-infection/

https://madisonarealymesupportgroup.com/2019/08/15/borrelia-miyamotoi-infection-leads-to-cross-reactive-antibodies-to-the-c6-peptide-in-mice-men/

https://madisonarealymesupportgroup.com/2018/09/12/lyme-testing-problems-solutions/

 

Category:

Lyme, research, Testing, Uncategorized

Bartonella & Blood: Infection of Erythrocytes

https://www.galaxydx.com/bartonella-and-blood/

written on

Bartonella and Blood: Infection of Erythrocytes

Bartonella species are notoriously difficult to detect when testing patient blood specimens.

The bacteria use immunosuppression as a tactic to avoid immune recognition, so serology tests that detect antibodies can be negative even during a long-standing infection. Furthermore, the bacteria move in and out of the blood in a relapsing pattern. Therefore, a PCR test designed to detect Bartonella species DNA in blood could be positive for a sample collected on one day and then negative on the next day even in blood collected from the same patient.

We’ve previously written about serology and PCR.

Bartonella bacteria adhere to and invade erythrocytes, that is, red blood cells. Diagnostically, how is it possible that a key niche for the bacteria is in the blood, and yet the bacteria often cannot be found there?

“Bartonella species and erythrocyte invasion remains incompletely understood,” said Dr. Ed Breitschwerdt, co-founder of Galaxy Diagnostics. “B. bacilliformis is an outlier in the context of a species that induces a severe, often acute hemolytic anemia. Also, laboratory studies with rodents don’t necessarily recapitulate what happens in larger animals, including humans.”

Nonetheless, Dr. Breitschwerdt and other researchers conclude that infection with Bartonella species should be considered in anemia of unknown origin.

Severe Cases and Anemia

As mentioned by Dr. Breitschwerdt, there is one species of Bartonella that is an outlier in this puzzle. Bartonella bacilliformis, a species endemic to South America and primarily transmitted by sand flies, is particularly adapted to entering erythrocytes for reasons that are unknown. This species causes Carrion’s disease, characterized by skin nodules and fever, with the acute stage of the infection being called Oroya fever. During the acute phase, there is a rapid rise in fever, sometimes accompanied by anemic shock and death. No one is certain why B. bacilliformis is so much more adept at infecting erythrocytes, but it may have something to do with its double flagella. This whip-like tail controls movement of the bacterium in liquid medium and also plays a role in interacting with the immune system.

Carrion’s disease, resulting from Bartonella bacilliformis infection, can cause damage to red blood cells leading to acute hemolytic anemia (Source: NIH).

In the Lab: Small Animals and Cell Cultures

Keeping in mind Dr. Breitschwerdt’s caution about how laboratory studies do not always apply to people, nonetheless we don’t have a lot of other places to turn for information. Research shows that this is what happens when rodents are experimentally infected with Bartonella species:

  • First, the infection is generally cleared from the bloodstream rapidly as the bacteria finds other niches.
  • At this point of initial infection, Bartonella species are generally not able to infect erythrocytes.
  • Bacteria multiply in other niches. Only after increasing in numbers and developing immune protection are they able to return to the blood stream and adhere to and enter erythrocytes.
  • They are more adept at infecting new erythrocytes than mature erythrocytes

In human cell cultures, Bartonella henselae have been recorded entering human erythrocytes within 72 hours of infection. At this point, their ability to avoid immune detection far exceeds comparator flagellates such as Salmonella species. Nonetheless, their replication is somewhat hampered. In laboratory studies, researchers have found that the bacterial count stabilizes at eight bacteria per erythrocyte.

The fact that most Bartonella species have trouble entering mature erythrocytes may be life-saving. It appears that most infection occurs in newly formed cells called reticulocytes, a developmental stage that only lasts about a day before they develop into mature erythrocytes. Overcoming this limitation may be part of what allows B. bacilliformis to infect mature erythrocytes, resulting in Oroya fever, hemolytic anemia and a more dramatic hematological disease than is associated with most other Bartonella infections.

Current Thinking on Erythrocyte Infections in Humans

The host response probably has a large influence on whether and to what degree an individual’s Bartonella species infection develops in erythrocytes. Immune factors influence whether the bacteria are detected in the blood when it is vulnerable as it adheres to an erythrocyte. Some level of bacterial destruction will happen during attempted erythrocyte invasion.

Another factor that is not well understood is infection of the progenitor cells that make erythrocytes. It may be that Bartonellas pecies are not good at invading erythrocytes at all, but rather originate in these progenitor cells. One study showed that CD34+progenitor cells isolated from humans could be colonized by Bartonella henselae and result in a persistent intraerythrocytic infection. Currently, B. henselae is the only species known to infect CD34+ progenitor cells.

Lastly, a well-functioning lymph system, including the spleen, continually clears infected erythrocytes.

Read more about bartonellosis, lymph nodes and the spleen.

It may be that bacteria found in the blood don’t necessarily represent an unusual blood event but rather the disease process affecting the immune system. When the immune system is functioning normally, detectable Bartonella bacteria in the bloodstream may or may not be related to infection of erythrocytes. Rather, bloodstream infection may represent the periodic release of bacteria from other areas of the body.

Conclusion

Despite laboratory bench research and small animal experiments, bloodstream availability of Bartonella species bacteria in humans is incompletely understood. What is known is that despite the ability of bacteria to enter erythrocytes, they are rarely found in circulating erythrocytes in the bloodstream.

References

Deng, H. et al. (2018). Molecular mechanisms of Bartonella and mammalian erythrocyte interactions: A review. Frontiers in Cellular and Infection Microbiology, 8, 431. doi:10.3389/fcimb.2018.00431 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6299047/

Pitassi, L. H. et al. (2007). Bartonella henselae infects human erythrocytes. Utrastructural Pathology, 31(6), 369-372. doi:10.1080/01913120701696510 https://www.ncbi.nlm.nih.gov/pubmed/18098053

Vieira-Damiani, G. et al. (2016). Bartonella henselae initial infection of mature human erythrocytes observed in real time using bacterial endogenous fluorescence. Journal of Tropical Diseases and Public Health, 4(2), 207. doi:10.4172/2329-891X.1000207 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5639914/

McCullough, J. (2014). RBCs as targets of infection. Hematology, 2014(1), 404-409. doi:10.1182/asheducation-2014.1.404 https://www.ncbi.nlm.nih.gov/pubmed/25696886

Hong, J. et al. (2017). Lymphatic circulation disseminates Bartonella infection into bloodstream. Journal of Infectious Diseases, 215(2), 303-311. doi:10.1093/infdis/jiw526 https://www.ncbi.nlm.nih.gov/pubmed/27803173

Mändle, T. et al. (2005). Infection of human CD34+ progenitor cells with Bartonella henselae results in intraerythrocytic presence of B henselae. Blood, 106(4), 1215-1222. doi:10.1182/blood-2004-12-4670 https://ashpublications.org/blood/article/106/4/1215/21539/Infection-of-human-CD34-progenitor-cells-with

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For more:  https://madisonarealymesupportgroup.com/category/bartonella-treatment/

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

https://madisonarealymesupportgroup.com/2017/01/04/endocarditis-consider-bartonella/

https://madisonarealymesupportgroup.com/2017/05/11/bartonella-henselae-in-children-with-congenital-heart-disease/

https://madisonarealymesupportgroup.com/2019/09/07/keep-an-eye-out-for-bartonella/

https://madisonarealymesupportgroup.com/2019/12/05/cutaneous-manifestations-of-bartonellosis/

Dr. Ericson has incredible imaging showing Bartonella surviving around tissues where a PIC line pumped antibiotics directly into the body:  https://madisonarealymesupportgroup.com/2019/02/27/advanced-imaging-found-bartonella-around-pic-line/

Category:

Bartonella, research, Testing

General Symptom Questionnaire-30 (GSQ-30): A Brief Measure of Multi-System Symptom Burden in Lyme Disease

https://www.frontiersin.org/articles/10.3389/fmed.2019.00283/full

ORIGINAL RESEARCH ARTICLE
Front. Med., 06 December 2019 | https://doi.org/10.3389/fmed.2019.00283

The General Symptom Questionnaire-30 (GSQ-30): A Brief Measure of Multi-System Symptom Burden in Lyme Disease

Brian A. Fallon1,2*, Nevena Zubcevik3,4, Clair Bennett1,2, Shreya Doshi1,2, Alison W. Rebman5, Ronit Kishon1,2, James R. Moeller1,2, Nadlyne R. Octavien3 and John N. Aucott5

Introduction: The multi-system symptoms accompanying acute and post-treatment Lyme disease syndrome pose a challenge for time-limited assessment. The General Symptom Questionnaire (GSQ-30) was developed to fill the need for a brief patient-reported measure of multi-system symptom burden. In this study we assess the psychometric properties and sensitivity to change of the GSQ-30.

Materials and Methods: 342 adult participants comprised 4 diagnostic groups: Lyme disease (post-treatment Lyme disease syndrome, n = 124; erythema migrans, n = 94); depression, n = 36; traumatic brain injury, n = 51; healthy, n = 37. Participants were recruited from clinical research facilities in Massachusetts, Maryland, and New York. Validation measures for the GSQ-30 included the Patient Health Questionnaire-4 for depression and anxiety, visual analog scales for fatigue and pain, the Sheehan Disability Scale for functional impairment, and one global health question. To assess sensitivity to change, 53 patients with erythema migrans completed the GSQ-30 before treatment and 6 months after 3 weeks of treatment with doxycycline.

Results: The GSQ-30 demonstrated excellent internal consistency (Cronbach α = 0.95). The factor structure reflects four core domains: pain/fatigue, neuropsychiatric, neurologic, and viral-like symptoms. Symptom burden was significantly associated with depression (rs = 0.60), anxiety (rs = 0.55), pain (rs = 0.75), fatigue (rs = 0.77), functional impairment (rs = 0.79), and general health (rs = −0.58). The GSQ-30 detected significant change in symptom burden before and after antibiotic therapy; this change correlated with change in functional impairment. The GSQ-30 total score significantly differed for erythema migrans vs. three other groups (post-treatment Lyme disease syndrome, depression, healthy controls).

The GSQ-30 total scores for traumatic brain injury and depression were not significantly different from post-treatment Lyme disease syndrome.

Conclusions and Relevance: The GSQ-30 is a valid and reliable instrument to assess symptom burden among patients with acute and post-treatment Lyme disease syndrome and is sensitive in the detection of change after treatment among patients with erythema migrans. The GSQ-30 should prove useful in clinical and research settings to assess multi-system symptom burden and to monitor change over time. The GSQ-30 may also prove useful in future precision medicine studies as a clinical measure to correlate with disease-relevant biomarkers.

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**Comment**

The good thing about this is it clearly shows that there is a significant change in symptom burden after antibiotic therapy.  In other words – the proof is in the pudding.  If you treat this properly, patients will improve.  This should shut the IDSA/CDC up, but it won’t.

Unfortunately they decided to keep the CDC/IDSA “Post Treatment Lyme Disease Syndrome” moniker rather than deal with persistent infection.  Until this issue is laid to rest, research will be skewed and authorities will not treat this appropriately.  There’s over 700-peer reviewed articles showing the persistence of Lyme disease: Peer-Reviewed Evidence of Persistence of Lyme:MSIDS copy

Another good thing this shows is the seriousness of symptoms that patients can be left with – the total scores aren’t significantly different from those with traumatic brain injury or depression. The symptoms are very, very real and very, very serious.

Please remember that those with the EM rash is highly variable:  https://madisonarealymesupportgroup.com/2019/02/22/why-mainstream-lyme-msids-research-remains-in-the-dark-ages/

Rashes-larger-blog-3

It is a bit of a head-scratcher as to why the authors felt compelled to do this study when a validated symptom questionnaire already exists:  https://madisonarealymesupportgroup.com/2017/09/05/empirical-validation-of-the-horowitz-questionnaire-for-suspected-lyme-disease/

https://madisonarealymesupportgroup.com/wp-content/uploads/2016/01/symptomlist.pdf

This symptom checklist is far more accurate than any serology testing at this point.  Doctors would be wise to utilize it.  There are also checklists for Babesia and Bartonella as well:

https://madisonarealymesupportgroup.com/2011/09/25/the-babesia-checklist-copyrighted-2011-james-schaller-md-mar-version-20/

https://madisonarealymesupportgroup.com/2011/09/25/the-bartonella-checklist-copyrighted-2011-james-schaller-md-version-11/

What we really need are checklists such as these for ALL tick-borne infections.  Then we desperately need doctor education.

Category:

Lyme, research, Testing

Dr. Neil Spector – Presentation on Therapeutic Strategies for Lyme Disease

 Approx. 50 Min.

State of the Art, Neil Spector, MD

Dr. Spector talks of collaborating with other groups to find new therapies for Lyme.  One of those is Argonne National Lab outside Chicago, which happens to have the largest genomic data base for prokaryotes.   borrelia (Lyme) and Bartonella.

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For more:  https://madisonarealymesupportgroup.com/category/lyme-disease-treatment/ Dapsone and Disulfiram are both discussed within this link.

Spector wrote, “Gone in a Heartbeat: A Physician’s Search for True Healing” – a memoir about his battle with Lyme disease in which he required a heart transplant.

More by Spector:  https://madisonarealymesupportgroup.com/2019/04/25/tick-talk-a-conversation-about-lyme-dr-neil-spector/

 

 

 

Category:

Lyme, research, Treatment