Infectious Disease Compendium

Borrelia

Microbiology

The Lyme-y strains: B. burgdorferi (2014 NEJM Review), B. lonestari, Borrelia mayonii (named after its discoverers, the always modest Mayo Clinic. In Europe, there is B. burgdorferi, Borrelia garinii, Borrelia afzelii.

The relapsing fever strains: B. hermsii, B. recurrenti, Borrelia turicatae and others.

There is also a Borrelia from bats and spread to humans from bat ticks (PubMed). I remain amazed that Bruce Wayne does nothing about those bats.

US and European Lyme are NOT the same clinically or immunologically (Pubmed). Testing with US assays will likely miss the European st

Epidemiologic Risks

Tick bites, for US Lyme, the tick needs to be attached and slurping up blood greater than 4 hours to pass on the B. burgdorferi.

B. burgdorferi is predominantly in the US NE and midwest, including urban Chicago. West coast pockets in California including Los Angeles. But.

One of many illnesses whose range is changing as the ticks move, probably due to global warming. The ticks are on the move (PubMed)(PubMed)(PubMed)(PubMed).

Lyme may not be a rural disease; urban green spaces can be a source (Pubmed).

B. miyamotoi is where ever there is Lyme, but in a lower percentage of ticks, around 1 to 5%. Not uncommon in the NE & Midwest US (PubMed). It can be found in ticks in virtually all of Canada (PubMed). It is also in Europe and Japan (PubMed). There are also strains in California.

B. hermsii is endemic to the Western United States including the Bitterroot Valley of western Montana (PubMed) and southern British Columbia (map from PubMed). It is spreading into Eastern Arizona (PubMed).

B. lonestari is found in the American SE.

B. burgdorferi, B. lonestari (tick has a white spot on the back), and B. hermsii: tick.

Where you hike may determine your risk: cattle and goat fields have fewer ticks and the ticks are less likely to have Borrelia (PubMed), but who wants to hike in a cow pasture?

Borrelia mayonii: Lyme like illness (Pubmed). So far it is only been found in the upper Midwest.

Borrelia miyamotoi: worldwide with Japan, Russia, Europe, US (California, found in small animals (PubMed)) and China all with cases. Tick bite.

B. recurrentis: human body louse.

Borrelia turicatae is the cause of relapsing fever in Texas and dogs, coyotes, and raccoons may be part of the source (PubMed)(PubMed).

PCR can find unexpected Borrelia (PubMed) like Candidatus B. johnsonii a species previously detected in the bat tick.

There is also Candidatus Borrelia kalaharica from ticks in Southern Africa.

There is also a relapsing fever Candidatus B. fainii in Zambia, found in shrew mites and bats (Pubmed).

Syndromes

B. recurrentis and B. hermsii: relapsing fever. Also Candidatus Borrelia kalaharica (PubMed). There are a variety of Borrelia that cause relapsing fever. World wide in distribution. In Russia (but is found in the US and Europe) it can be due to B. miyamotoi. Diagnosis is made by looking at the CBC, in the era of automated CBC's I wonder if cases are being missed. Most of the cases I have seen have been made by the CBC tech looking at the differential, including a recent case from Mexico.

B. lonestari: causes a erythema chronic migrans like illness with no systemic, secondary or long term problems. Southern Tick Associated Rash Illness (STARI). However this organism has only been isolated in one case of STARI, so probably is not the cause after the Lone Star Tick Bite. STARI has been reported as far north as NY (PubMed).

There is ECM in the Caribbean of unknown etiology (PubMed).

Borrelia miyamotoi: Meningoencephalitis (chronic) (PubMed) and an acute/relapsing febrile illness with myalgias, headache, neutropenia, thrombocytopenia, and elevated LFT's (PubMed). Acute meningitis (PubMed). The duration of B. miyamotoi spirochetemia is relatively short so PCR not reliable (PubMed). And the C6 peptide assay for Lyme cross-reacts (PubMed).

Borrelia mayonii was discovered by the Mayo Clinic in 2015 as a rare cause of Lyme in the US and they modestly named it after themselves (PubMed). Can't hold the Mayo.

B. miyamotoi, B. hermsii and B. burgdorferi all cross-react with current serologies (PubMed).

B. burgdorferi: Lyme disease. In Europe there is Borrelia garinii and Borrelia afzelii as well. Of the two, B. garinii causes typical early Lyme neuroborreliosis (PubMed) (Bannwarth syndrome (Pubmed)). B. afzelii is more indolent and may not present typically (PubMed).

Stage 1: Local spreading target lesions: erythema chronica migrans. They can be multiple and they may not be present.

The European versions, especially B. afzelii, are more likely to cause a Lymphocytoma (Pubmed).

Stage 2: Disseminated with oligoarticular arthritis, carditis (heart block most common) and/or meningitis (bells palsy is a common manifestation.

Stage 3: Chronic with arthritis and encephalitis. With a Bell's palsy, the patient has aseptic meningitis, painful neuropathy, more symptomatic systemically aka Bannwarths syndrome.

There is encephalitis, encephalopathy, chronic Lyme disease, post-treatment Lyme disease syndrome, and chronic Lyme disease (PubMed) and of the four, there is no post-treatment chronic Lyme disease (PubMed) (PubMed).

Depressive symptoms, at least in Europe, are not a manifestation of Lyme (PubMed). But when followed long term, patients treated for Lyme have no more medical complaints than non-Lyme patients (PubMed)(PubMed).

After culture-proven Lyme, fatigue is uncommon, perhaps in 3% of patients (PubMed).

You make the diagnosis of Lyme by (of course) history and physical and serology.

The standard is the two-step in the US: an Elisa and a Western blot. Will not accurately diagnose the European versions of the disease. For European, and perhaps the US as well, you need to order a C6 ELISA (PubMed), and perhaps for US cases as well (PubMed) (2016 Review of testing). Also the C6 cross-reacts with Borrelia miyamotoi (PubMed).

Two EIA tests are also an FDA approved way to make the diagnosis (PubMed) as long as "... new serologic assays include blind testing against a comprehensive challenge panel, and that new assays should only be recommended if their specificity, sensitivity, and precision equaled or surpassed the performance of tests used in the recommended two-test procedure."

CSF CXCL13 levels, a cytokine, may be helpful in diagnosing CNS disease (PubMed). "CSF CXCL13 is a sensitive and specific marker of neuroborreliosis in individuals with Borrelia-specific intrathecal antibody production. However, it does not distinguish individuals strongly suspected of having neuroborreliosis, but lacking confirmatory intrathecal antibodies, from those with other neuroinflammatory conditions (PubMed)."

There is more bad information out there about Lyme than any other infectious disease. The blood test is excellent, but there are labs that offer, let us say, unusual tests to diagnose Lyme. And a fair number of people seem to be committed to having this disease regardless of the supporting data. There are many labs that offer alternative Lyme testing, often in my experience beloved by ND's (it is short for Not a Doctor) that have not been validated.  And remember, if you live in an area with no Lyme (like PDX) a positive test is likely a false positive (PubMed). But try getting the patient to agree. So beware:

"CDC and the Food and Drug Administration (FDA) have become aware of commercial laboratories that conduct testing for Lyme disease by using assays whose accuracy and clinical usefulness have not been adequately established. These tests include urine antigen tests, immunofluorescent staining for cell wall--deficient forms of Borrelia burgdorferi, and lymphocyte transformation tests. In addition, some laboratories perform polymerase chain reaction tests for B. burgdorferi DNA on inappropriate specimens such as blood and urine or interpret Western blots using criteria that have not been validated and published in the peer-reviewed scientific literature (PubMed)."

Know your testing facility, they are not all equal. In areas of low prevalence, alternative labs, which will often find positive Lyme testing, are almost certainly false positive (PubMed). In the study, the alternative lab was Lab A.  I wish I knew which one, although I have my suspicions.

In areas of low Lyme disease, patients with 'chronic Lyme' have the same phenotype of chronic fatigue patients (PubMed) and false-positive Lyme serologies.

There is "cross-reactivity of Lyme screening among syphilis-positive sera but not false-positive syphilis screening tests from previous Borrelia burgdorferi infection (PubMed).

Treatment

B. lonestari

Doxycycline. Maybe

Lyme

see IDSA guidelines. New guidelines should be out in spring 2018.

Early infection (ECM): doxycycline 100 mg po bid for 14-21 d, most get 21 days although 10 and 15 days have equal efficacy (PubMed).

OR amoxicillin 500 mg po tid for 20-30 d. Although 14 days was enough in one small series (PubMed).

Doxycycline or amoxicillin allergy: Cefuroxime 500 mg po bid for 20-30 d OR erythromycin 250 mg po qid for 20-30 d.

However, since the guidelines were published, there was an article that suggests "patients treated for <=10 days with antibiotic therapy for early Lyme disease have long-term outcomes similar to those of patients treated with longer courses. Treatment failure after appropriately targeted short-course therapy, if it occurs, is exceedingly rare (PubMed)."

And longer iv antibiotics does not help with European Lyme either (Pubmed). Oral doxycycline or iv ceftriaxone for two weeks has the same results at 12 months for European ECM (PubMed).

Arthritis: Doxycycline 100 mg po bid for 30-60 d OR amoxicillin,500 mg po qid for 30-60 d. or Ceftriaxone 2 g IV qd for 14-30 d OR penicillin G 20 million U IV in 4 divided doses daily for 14-30 d.

Neurologic abnormalities: Ceftriaxone 2 g IV qd for 14-30 d OR penicillin G 20 million U IV in 4 divided doses daily for 14-30 d. Ceftriaxone or penicillin allergy: Doxycycline 100 mg po tid for 14-30 d.

For European CNS infection, oral doxycycline (100 bid) is equal to intravenous ceftriaxone (2 gm qd) for the treatment of European adults with Lyme neuroborreliosis (PubMed).

Facial palsy, isolated Doxycycline 100 mg po bid for 20-30 d OR amoxicillin 500 mg po tid for 20-30 d. Doxycycline or amoxicillin allergy: Cefuroxime 500 mg po bid for 20-30 d OR erythromycin 250 mg po qid for 20-30 d. Steroids? People do it but little data to say it helps or hurts (PubMed)(PubMed).

Cardiac involvement: Doxycycline 100 mg po bid for 20-30 d OR amoxicillin 500 mg po tid for 20-30 d. Doxycycline or amoxicillin allergy: Cefuroxime 500 mg po bid for 20-30 d OR erythromycin 250 mg po qid for 20-30 d.

High-degree AV block: Ceftriaxone 2 gm IV qd for 14-30 d OR penicillin G 20 million U IV in 4 divided doses daily for 30 d.

Relapsing Fever Louse borne

Tetracycline 500 mg po x 1 OR Erythromycin 0.5 g in a single po dose, is an equally effective alternative therapy.

Tick-borne relapsing fever: Post-exposure treatment to prevent TBRF due to Borrelia persica (in Israel) use doxycycline 200 mg the first day and then 100 mg per day for four days (PubMed). Tetracycline OR erythromycin, 0.5 g every 6 hours for 5 to 10 days, because of the higher rate of treatment failures and relapses in these patients. Meningitis or encephalitis should be treated with iv penicillin G, cefotaxime, or ceftriaxone, for 14 days or more.

Antibiotic treatment typically induces a Jarisch-Herxheimer reaction.

Notes

There are two schools of thought for the treatment of Lyme: the IDSA and the ILADS. I am strongly in the IDSA camp, but have some ever so slight doubts with testing. I just wonder if serology based on NE strains will find strains far removed from the NE. But all good data suggests no such thing as chronic Lyme after therapy (PubMed).

BTW: long term po amoxicillin po adds NOTHING for Lyme (PubMed). Nor does prolonged antibiotic treatment help cognition in patients with Lyme borreliosis (PubMed).

And long term iv antibiotics for a disease that does not exist is not benign: "Of IV-treated patients, 7.3% experienced an incident all-cause inpatient stay and 11.3% an incident all-cause emergency department visit, compared with, respectively, 2.2% and 3.4% of those treated with oral antibiotics and 0.9% and 1.9% of nontreated patients (PubMed)."

If carefully evaluated, up to 80% of patients with chronic Lyme will have an alternative, non-infectious, diagnosis and they do NOT get better with antibiotics (Pubmed).

That is not to say those with 'chronic' Lyme are not ill. They are. It is just usually not due to Lyme or other infectious diseases.

While many infections can cause post-infectious fatigue, many of the prolonged symptoms after Lyme treatment are likely due to other medical issues that might not be considered due to premature closure (Pubmed).

And Lyme kills almost no one (PubMed).

If you are interested in an analysis of 'chronic Lyme' might I suggest Lyme: Two Worlds Compared and Contrasted by me and other articles at SBM.

"Among patients referred to an academic Infectious Diseases practice for Lyme disease, incorrect diagnoses, and unnecessary antibiotic treatment were common, both for Lyme disease and for coinfections (PubMed)." To paraphrase Louie, I'm shocked, shocked to find Lyme misdiagnosis going on here."

To get a hint of the wackaloon therapies offered to patients with chronic Lyme, see Unorthodox Alternative Therapies Marketed to Treat Lyme Disease. And these therapies are not without harm. Long term iv antibiotics leads to serious line infections (PubMed).

Recurrent Lyme is always reinfection, not a relapsing infection (PubMed).

With the rare exception of B. microti, co-infections with Lyme are not seen (PubMed).

Relapsing fever Borrelia produces new outer membrane proteins to avoid immunity directed against the original infecting strain. The patient improves until the Borrelia, with all new surface proteins, multiplies to cause another relapse. It can only accomplish this change 5 to 7 times before it finally dies. Elie Metchnikoff, one of the pioneers of immune system research and a Nobel Prize winner, proved the blood-borne nature of relapsing fever in 1881 by injecting himself with the organism in an unsuccessful suicide attempt.

They sequenced the genome of a B. recurrentis in a 15th-century skeleton from Oslo (PubMed).

One of the usually careful and thoughtful evaluations of the medical literature I have received: "Yawn. “Doctors” like you are really a scourge on the medical profession. Too obtuse to think outside the box and convinced they are smarter than their “delusional” patients. The only good news: The Universe has a way of teaching those who lack knowledge and empathy—rather definitively—and before you have the chance to hurt too many others. In other words “Doctor,” that haughty attitude of yours will eventually end up in the trash heap where it belongs. See there is this little thing called contemporary research. Dr. Eva Sapi. Or Dr. Richard Horowitz. And if you’re really feeling inspired, the Charles E. Holman Foundation might help you through your fog of idiocy. Good luck. I have a feeling the chronic Lyme and those co-infections you so merrily dismiss will be gracing you or your family in the near future. Dense and completely lacking in common sense. Ripe for the teaching. And you are to be taken seriously or held in high esteem again...why? “Edgy” ? uh hmmm. Sure. Lol."

Curious Cases

Relevant links to my Medscape blog

The Same but Different

Lying liars and their lying lies.

Why I Am Not Upset When Bambi's Mother Is Shot

Bayes-en at the moon.

Serendipitous Diagnosis

A Swell Joint

Go West Young Vector

Relapsing Price Gouging

Nail Freak

Last update: 10/02/19