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History of Genus:

Amedee Borrel distinguished Borrelia from other spirochetes, and this discovery was later named after the microbiologist.

The Lyme disease rash was recognized by a dermatologist Arvid Afzelius--he also hypothesized the tick link

Discovery of Lyme Agent:

Lyme disease was first identified in 1970s after several arthritis cases followed by tick bites. Yale students discovered the link

In Shelter Island, NY 1981, Dr. Burgdorfer was examining ticks and identified spirochetes in the gut of the ticks. He later published his discovery and formally described the species as Borrelia Burgdorferi.

Sources:

https://www.ncbi.nlm.nih.gov/books/NBK532894/

https://pmc.ncbi.nlm.nih.gov/articles/PMC385417/

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Evolutionary Background:

Clades within genus:

Borrelia Burgdorferi Sensu Lato

Relapsing Fever Group

Echidna- Reptile Group

Classification:

Bergeys Manual:

Phylum: Spirochaetota (or spirochetes)

Class: Spirochaetia

Order: Spirochaetales

Family: Borreliaceae

Genus: Borreila

Hierarchy:

Domain: Bacteria

Phylum: Spirochaetota

Class: Spirochaetia

Order: Spirochaetales

Family: Borreliaceae

Genus: Borrelia

Species complex: B. burgdorferi sensu lato

Species example: B. burgdorferi sensu stricto (North America)

Key Traits:

Gram-negative spirochete

Linear chromosome

Low GC

Sources:

https://pmc.ncbi.nlm.nih.gov/articles/PMC8533607/

https://lpsn.dsmz.de/genus/borrelia

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Overview:

Borrelia are long spiral shaped bacteria which sets them apart from other bacteria due to their unique shape.

Key Cell Structures:

Cell Shape: Long, helical

Cell Wall: Gram negative

Membrane: Inner cytoplasmic membrane

Flagella: Between inner and outer membranes which cause corkscrew motion

Nucleoid: Linear chromosomes

Proteins: Surface exposed lipoprotein

Capsule: Lack capsule

Sources:

https://www.sciencedirect.com/topics/agricultural-and-biological-sciences/borrelia-burgdorferi

https://www.mdpi.com/2079-7737/10/7/567#:~:text=Borreliae%20are%20morphologically%20characterized%20as,humans%20happening%20inadvertently%20%5B8%5D.

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Week 4: Metabolism and Growth Requirements

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Week 4: Metabolism and Growth Requirements

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Metabolism Type:

Heterotroph and microaerophilic fermenter

Uses simple sugars

Slow growth

Growth Requirements:

Oxygen: Microaerophilic (too much oxygen is stressful)

Salt: Sensitive to salts and salinity

Nutrients: Requires rich medium like rabbit serum, amino acids etc

Temperature: Optimal growth at 32-35 degrees Celsius (similar to tick gut to human body)

pH: Around 7.6 in unfed tick but shifts to 6.8 when fed or in host

Other: Humidity is NEEDED

Is it a -phile?

Technically yes, based on environmental factors.

Sources:

https://pmc.ncbi.nlm.nih.gov/articles/PMC7942402/

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Genome Characteristics:

Type: Borrelia Burgdoferi--> spirochete bacterium with linear chromosomes and multiple linear and circular plasmids in infected isolates

Plasmids: It has a core set of plasmids

Genome Mapped/Size: ~800 core ORFs, the linear chromosome is about ~900 kb.

Antibiotic- Resistence Genes:

ARG presence: susceptible to most antibiotics. Most studies have have not identified significant plasmid antibiotic resistance.

Virulence Factors and Mechanisms:

Surface lipoproteins:

OspC

OspA

VlsE

Plasmid linked virulence:

Ip28-1

Ip56

Sources:

https://pmc.ncbi.nlm.nih.gov/articles/PMC10566445/

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Pathogenicity and virulence of Borrelia burgdorferi

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Infection with Borrelia burgdorferi often triggers pathophysiologic perturbations that are further augmented by the inflammatory responses of the host, resulting in the severe clinical conditions of Lyme disease. While our apprehension of the…

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Biochemistry and Biochemical Tests:

Metabolism: microaerophilic, slow growing spirochete. Obtains energy through glycolysis

Biochemical tests: Boriella does not typically grow on standard culture, so clinical microbiology does not work for this organism. Tests like that are not preformed

Diagnostic Tests:

Indirect:

Two tiered serology:

1: ELISA

2: Western Blot

Serology is not reliable in early infection because antibodies take time to develop

Direct:

PCR: Direct boriella in skin biopsy, blood samples etc BUT highly sensitive and can give false positives so not reliable.

Culture: Does not work

Antigen detection: Not enough research and not used typically.

How is it diagnosed?

Mixture of clinical evaluation. indirect blood tests (ELISA).

Sources:

https://www.cdc.gov/lyme/diagnosis-testing/index.html

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CDC currently recommends a two-step testing process for Lyme disease using FDA-cleared tests.

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1. Research and Treatment:

1. Metronidazole

2. Tinidazole, nitazoxanide, and paromomycin

2. Chemotherapy Agents, Dose, Effectiveness and Duration

1. Metronidazole:

1. First line

2. 250mg PO- 5-7 days

3. 85-90% cure rate (increasing resistance!!)

2. Tinidazole:

1. Single dose

2. 2g PO - one dose

3. 90% success, fewer side effects

3. Nitazoxanide

1. (PEDS Friendly)

2. 500mg PO BID- 3 days

3. 85-90% cure rate

4. Paramomycin

1. (Pregnancy safe)

2. 10mg/kg TID- 5-10 days

3. 85%-90% cure rate

3. Side Effects:

1. Nausea, headaches, abdominal cramps, and other symptoms depend on each person

4. Is there a vaccine?

1. No vaccine

1. There is a vaccine for cats and dogs though! Save our furry friends

Sources:

https://www.ncbi.nlm.nih.gov/books/NBK532894/

https://www.mayoclinic.org/diseases-conditions/lyme-disease/symptoms-causes/syc-20374651

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Overview

Lyme disease is caused by four main species of bacteria. Borrelia burgdorferi and Borrelia mayonii cause Lyme disease in the United States, while Borrelia afzelii and Borrelia garinii are the leading causes in Europe and Asia. The most common tick-borne illness in these regions, Lyme disease is transmitted by the bite of an infected black-legged tick, commonly known as a deer tick.

You're more likely to get Lyme disease if you live or spend time in grassy and heavily wooded areas where ticks carrying Lyme disease thrive. It's important to take common-sense precautions in tick-infested areas.

Symptoms

The signs and symptoms of Lyme disease vary. They usually appear in stages, but the stages can overlap.

Early signs and symptoms

A small, red bump, similar to the bump of a mosquito bite, often appears at the site of a tick bite or tick removal and resolves over a few days. This normal occurrence doesn't indicate Lyme disease.

However, these signs and symptoms can occur within a month after you've been infected:

Rash. From three to 30 days after an infected tick bite, an expanding red area might appear that sometimes clears in the center, forming a bull's-eye pattern. The rash (erythema migrans) expands slowly over days and can spread to 12 inches (30 centimeters) across. It's typically not itchy or painful but might feel warm to the touch.

Erythema migrans is one of the hallmarks of Lyme disease, although not everyone with Lyme disease develops the rash. Some people develop this rash at more than one place on their bodies.

Other symptoms. Fever, chills, fatigue, body aches, headache, neck stiffness and swollen lymph nodes can accompany the rash.

Later signs and symptoms

If untreated, new signs and symptoms of Lyme infection might appear in the following weeks to months. These include:

Erythema migrans. The rash may appear on other areas of your body.

Joint pain. Bouts of severe joint pain and swelling are especially likely to affect your knees, but the pain can shift from one joint to another.

Neurological problems. Weeks, months or even years after infection, you might develop inflammation of the membranes surrounding your brain (meningitis), temporary paralysis of one side of your face (Bell's palsy), numbness or weakness in your limbs, and impaired muscle movement.

Less common signs and symptoms

Several weeks after infection, some people develop:

Heart problems, such as an irregular heartbeat

Eye inflammation

Liver inflammation (hepatitis)

Severe fatigue

When to see a doctor

If you've been bitten by a tick and have symptoms

Only a minority of tick bites leads to Lyme disease. The longer the tick remains attached to your skin, the greater your risk of getting the disease. Lyme infection is unlikely if the tick is attached for less than 36 to 48 hours.

If you think you've been bitten and have signs and symptoms of Lyme disease - particularly if you live in an area where Lyme disease is prevalent - contact your doctor. Treatment for Lyme disease is more effective if begun early.

See your doctor even if symptoms disappear

Consult your doctor even if signs and symptoms disappear - the absence of symptoms doesn't mean the disease is gone. Untreated, Lyme disease can spread to other parts of your body for several months to years after infection, causing arthritis and nervous system problems. Ticks can also transmit other illnesses, such as babesiosis and Colorado tick fever.

Causes

In the United States, Lyme disease is caused by the bacteria Borrelia burgdorferi and Borrelia mayonii, carried primarily by black-legged or deer ticks. Young brown ticks often are no bigger than a poppy seed, which can make them nearly impossible to spot.

To contract Lyme disease, an infected deer tick must bite you. The bacteria enter your skin through the bite and eventually make their way into your bloodstream.

In most cases, to transmit Lyme disease, a deer tick must be attached for 36 to 48 hours. If you find an attached tick that looks swollen, it may have fed long enough to transmit bacteria. Removing the tick as soon as possible might prevent infection.

Risk factors

Where you live or vacation can affect your chances of getting Lyme disease. So can your profession and the outdoor activities you enjoy. The most common risk factors for Lyme disease include:

Spending time in wooded or grassy areas. In the United States, deer ticks are found mostly in the heavily wooded areas of the Northeast and Midwest. Children who spend a lot of time outdoors in these regions are especially at risk. Adults with outdoor occupations also are at increased risk.

Having exposed skin. Ticks attach easily to bare flesh. If you're in an area where ticks are common, protect yourself and your children by wearing long sleeves and long pants. Don't allow your pets to wander in tall weeds and grasses.

Not removing ticks promptly or properly. Bacteria from a tick bite can enter your bloodstream if the tick stays attached to your skin for 36 to 48 hours or longer. If you remove a tick within two days, your risk of acquiring Lyme disease is low.

Complications

Untreated Lyme disease can cause:

Chronic joint inflammation (Lyme arthritis), particularly of the knee

Neurological symptoms, such as facial palsy and neuropathy

Cognitive defects, such as impaired memory

Heart rhythm irregularities

Prevention

The best way to prevent Lyme disease is to avoid areas where deer ticks live, especially wooded, bushy areas with long grass. You can decrease your risk of getting Lyme disease with some simple precautions:

Cover up. When in wooded or grassy areas, wear shoes, long pants tucked into your socks, a long-sleeved shirt, a hat and gloves. Try to stick to trails and avoid walking through low bushes and long grass. Keep your dog on a leash.

Use insect repellents. Apply insect repellent with a 20 percent or higher concentration of DEET to your skin. Parents should apply repellant to their children, avoiding their hands, eyes and mouth.

Keep in mind that chemical repellents can be toxic, so follow directions carefully. Apply products with permethrin to clothing or buy pretreated clothing.

Do your best to tick-proof your yard. Clear brush and leaves where ticks live. Mow your lawn regularly. Stack wood neatly in dry, sunny areas to discourage rodents that carry ticks.

Check your clothing, yourself, your children and your pets for ticks. Be especially vigilant after spending time in wooded or grassy areas. Deer ticks are often no bigger than the head of a pin, so you might not discover them unless you search carefully.

It's helpful to shower as soon as you come indoors. Ticks often remain on your skin for hours before attaching themselves. Showering and using a washcloth might remove unattached ticks.

Don't assume you're immune. You can get Lyme disease more than once.

Remove a tick as soon as possible with tweezers. Gently grasp the tick near its head or mouth. Don't squeeze or crush the tick, but pull carefully and steadily. Once you've removed the entire tick, dispose of it by putting it in alcohol or flushing it down the toilet, and apply antiseptic to the bite area.

Mayo Clinic Minute: Will there be a Lyme disease vaccine for humans?

Mayo Clinic Minute: Ways to avoid ticks

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Lyme disease is caused by four main species of bacteria. Borrelia burgdorferi and Borrelia mayonii cause Lyme disease in the United States, while Borrelia afzelii and Borrelia garinii are the leading causes in Europe and Asia. The most common tick-borne illness in these regions, Lyme disease is transmitted by the bite of an infected black-legged tick, commonly known as a deer tick.

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Week 9: Disease Transmission and Epidemiology 

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Week 9: Disease Transmission and Epidemiology 

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Disease Transmission:

Vectors

Direct or Indirect Transmission:

No direct nor indirect transmission

Fomites:

No role- no survival outside tick vector

Vectors:

Ticks: Some ticks ingest Borrelia when feeding host. This goes to the ticks gut and is transferred during next feeding.

Mechanical vectors: Not applicable for Lyme disease.

Epidemiology. Prevalence and Morbidity

Notifiable disease:

Nationally notified condition since 1991

Prevalence:

Estimated over 476,000 cases in US are treated and diagnosed per year

Annual incidence in 2022, was about 18.8 cases per 100,000 population compared to the 11.2 per 100,00 in 2017-2019.

Morbidity

Death is rare, but untreated cases can lead to serious morbidity.

Outbreaks and Epidemics:

Lyme disease is not associated with human-human contact so it doesn't spread as other diseases or sicknesses would. But it is tied to specific regions and tick populations.

Sources:

https://www.cdc.gov/lyme/data-research/facts-stats/index.html

https://www.cdc.gov/mmwr/volumes/73/wr/pdfs/mm7306a1-H.pdf

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Over 63,000 cases of Lyme disease were reported to CDC by state health departments and the District of Columbia in 2022. This number reflects cases reported through routine national surveillance, which is only one way public health officials track diseases. Recent estimates using other methods suggest that approximately 476,000 people may be diagnosed and treated for Lyme disease each year in the United States. This number likely includes patients who are treated based on clinical suspicion but do not actually have Lyme disease.

Surveillance data explained

Lyme disease has been a nationally notifiable condition in the United States since 1991. Reports of Lyme disease are routinely collected and verified by state and local health departments in accordance with their legal mandate and surveillance practices. After removal of personal identifiers, selected information on cases is shared with CDC through the National Notifiable Diseases Surveillance System (NNDSS). Policies regarding case definitions, reporting, confidentiality, and data release are determined by states and territories under the auspices of the Council of State and Territorial Epidemiologists (CSTE). Surveillance data have a number of limitations that need to be considered in the analysis, interpretation, and reporting of results.

1. Under-reporting and misclassification are features common to all surveillance systems. Not every case of Lyme disease is reported to CDC, and some cases that are reported may be due to another cause.

2. Surveillance data are captured by county of residence, not county of exposure.

3. States may close their annual surveillance dataset at a different time than CDC. Thus, the final case counts published by CDC may not exactly match numbers published by each state agency for a given year.

4. Following its implementation in 1991, the national surveillance case definition for Lyme disease was modified in 1996, 2008, 2011, 2017, and again in 2022. Some of these changes impacted surveillance data and must be considered when attempting to interpret trends. Case definitions for each period are available.

Alternative data sources

CDC is currently working to establish enhanced surveillance and research platforms for Lyme disease using electronic health records (EHRs) from large healthcare systems in areas of the U.S. with a high incidence of Lyme disease. The Surveillance Based Lyme Disease Network is comprised of partners in healthcare systems from Maine, Massachusetts, Pennsylvania, and Wisconsin. CDC will use these EHR data in concert with traditional public health surveillance data to better understand how Lyme disease affects the American public.

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Available Lyme disease data including how many people get Lyme disease, and where.

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Signs and Symptoms:

Early localized:

Rash

Fever

Headache

Myalgia

Early Disseminated

EM lesions

Myocarditis

AV block

Facial palsy

meningitis

Late Disseminated:

Lyme arthritis

Large tissue damage

Immune Response:

Innate Immunity and Cell Recruitment:

Sensors: TLR2/MyD88

This activates--> Monocytes and macrophages

Adaptive Immunity:

igG antibodies: crucial for limiting tissue burdens but can't clear infection

CD4T cells help regulate B cell responses

Autoimmunity:

Some individuals with certain HLA alleles may be more prone to becoming autoimmune

PTLDS: Persistent symptoms after treatment due to tissue damage.

Sources:

https://www.pathologyoutlines.com/topic/microbiologybburgdorferi.html

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Microbiology & infectious diseases - Borrelia burgdorferi / Lyme disease