Notes
Borrelia & Leptospira (Lyme Disease, Relapsing Fever)
Sections
Here we will learn about infections caused by the non-Treponemal Spirochetes Borrelia and Leptospira, with a focus on Borrelia.
Borrelia
Causes relapsing fever and Lyme disease
Large, coiled Spirochete bacteria
Microaerophilic
Difficult to culture due to their complex nutritional needs and long generation times of 18 hours or more.
Geimsa and Wright staining are used to visualize Borrelia, and light microscopy is used to identify the bacteria in blood.
Multiple flagella, which provide motility.
Proteins:
– Variable membrane proteins allow the bacteria to adapt to new environments as they move from reservoirs to hosts.
– Enable binding to host tissues, and even confer tissue tropism in some strains.
– Some proteins provoke host immune responses, which are largely responsible for the damages caused by infection.
For example, Borrelia lipoproteins trigger the release of inflammatory cytokines that damage host tissues. The bacteria, themselves, can often evade the host immune system.
Jarish-Herxheimer Reaction
Antibiotic treatment of Borrelia infections is associated with Jarish-Herxheimer reaction. This reaction tends to exacerbate symptoms, initially, but is not usually fatal (we discuss it in more detail in our tutorial on Treponemal infections).
Relapsing fever
Characterized by recurrent episodes of fever and septicemia, which are the result of bacterial proliferation.
Borrelia membrane proteins undergo antigenic variation, which promotes cycling between bacteremia and clearance.
Both types of relapsing fever are associated with extreme poverty and crowding.
Diagnosed using light microscopy of blood smears; in the image, we can see an example of a Borrelia cell among host blood cells.
Treatment includes: tetracycline or erythromycin; for patients with CNS involvement, penicillin is recommended.
Relapsing Cycles:
In response to bacteremia, host antibodies form and begin to clear the bacteria from the blood. Bacteremia recedes, and the host enters the afebrile stage. However, the bacteria are rapidly undergoing antigenic variation. These new variants evade host antibodies and proliferate in the host. Thus, the host enters a new febrile episode.
Louse-borne relapsing fever:
Caused by Borrelia recurrentis
Associated with more serious infections and higher mortality than tick-borne relapsing fever.
Associated with epidemics, particularly in parts of Africa.
Key vector = human body louse (Pediculus humanus)
Reservoir = humans
Transmission occurs when an infected body louse (or its feces) is crushed into openings in the skin; for example, when scratching or trauma creates abrasions.
Characterized by 5 febrile episodes; each episode lasts 3-7 days.
Febrile episodes are characterized by fever, chills, and headache, as well as joint and muscle pain, abdominal tenderness, jaundice, epistaxis, and thrombocytopenia. Some patients experience hepatic or cardiac failure, or cerebral hemorrhaging.
Tick-borne relapsing fever:
Endemic in many areas, and is not usually fatal.
Associated with several species of Borrelia.
Vector = Soft ticks
Key reservoirs = soft ticks and small vertebrates, especially rodents.
Transmission is the result of infected tick bites.
Characterized by 10 or more febrile episodes that last 3-7 days each.
Most episodes of tick-borne relapsing fever are mild, and are characterized by fever, chills, and headaches;
However, be aware that some species of Borrelia can cause more severe infections.
Lyme Disease
Aka, Lyme borreliosis.
Multi-system inflammatory disease
Borrelia burdorferi is responsible for Lyme disease in the United States.
Other Borrelia species, including Borellia garinii and Borellia afzelii, are responsible for Lyme disease in Europe and Central and Eastern Asia.
Diagnosed using serology tests that measure IgM and IgG antibodies.
Vectors = Various species of hard ticks, specifically black-legged Ixodes ticks.
Transmission occurs during prolonged episodes of tick feeding.
Key reservoirs = mice, deer, and pets.
Clinical features:
Early: Within 3-30 days of infection, localized erythema migrans. A centralized clearing in the lesion is common but not always present. They are characteristically large, red, and flat; the rash gradually expands to several centimeters in diameter.
Treatment: Early Lyme disease is treated with doxycycline, amoxicillin, tetracycline, or cefuroxime.
Late: Months or even years after untreated infection, late systemic manifestations may appear. These typically include re-appearance and spreading of erythema migrans, severe headache, neck stiffness, and arthritis, particularly of the knees and other large joints. Individuals can experience facial palsy, Lyme carditis, central nervous inflammation, nerve pain, numbness, and tingling.
Treatment: Late symptoms are treated with intravenous penicillin or ceftriaxone.
Some symptoms vary by the infecting species and geography.
– For example, European Lyme disease is associated with acrodermatitis chronica atrophicans, which presents as red-blue bruise-like areas, typically on the extensor surfaces of the extremities. Over time, the tissues become fibrotic.
More rarely, European Lyme disease is associated with lymphocytoma, which manifests as a reddish/bluish swelling, often on the earlobe.
Leptospira
Spirochetes that reside within the kidneys of small mammals, especially rodents. The animals then shed the bacteria into the environment. Thus, water-sport athletes and industrial workers in contact with contaminated water, soil, or animals are at higher risk of infection.
Mild leptospirosis produces flu-like symptoms and conjunctival suffusion.
The most severe infections are associated with Weil disease, which is characterized by jaundice, vasculitis, and organ failure, particularly involving the liver and kidneys, which can be fatal.
Full-Length Text
Here we will learn about infections caused by the non-Treponemal Spirochetes Borrelia and Leptospira, with a focus on Borrelia.
To begin, write that Borrelia causes relapsing fever and Lyme disease.
Borrelia are large, coiled bacteria;
They are microaerophilic, and are difficult to culture due to their complex nutritional needs and long generation times of 18 hours or more.
Geimsa and Wright staining are used to visualize Borrelia, and light microscopy is used to identify the bacteria in blood.
Write that Borrelia virulence derives from their multiple flagella, which provide motility, as well as proteins that serve multiple purposes.
For example, variable membrane proteins allow the bacteria to adapt to new environments as they move from reservoirs to hosts.
Bacterial bind to host tissues, and even confer tissue tropism in some strains.
Some proteins provoke host immune responses, which are largely responsible for the damages caused by infection.
For example, Borrelia lipoproteins trigger the release of inflammatory cytokines that damage host tissues.
The bacteria, themselves, can often evade the host immune system.
With this information as a background, let's learn about relapsing fever.
Write that it is characterized by recurrent episodes of fever and septicemia, which are the result of bacterial proliferation.
Borrelia membrane proteins undergo antigenic variation, which promotes cycling between bacteremia and clearance.
To illustrate this cycle, draw a circle;
Indicate Febrile status on one side, and, Afebrile status on the other.
We'll begin in the febrile stage.
Show that, in response to bacteremia, host antibodies form and begin to clear the bacteria from the blood.
Bacteremia recedes, and the host enters the afebrile stage.
However, the bacteria are rapidly undergoing antigenic variation;
These new variants evade host antibodies and proliferate in the host.
Thus, the host enters a new febrile episode.
There are two types of relapsing fever: Louse-borne relapsing fever and Tick-borne relapsing fever; louse-borne relapsing fever is associated with more serious infections and higher mortality.
Let's create a table to compare the causative Borrelia species, key vectors and reservoirs, routes of transmission, febrile episode number and duration, and common clinical features associated with Louse-borne and Tick-borne relapsing fever.
Be aware that, despite important clinical and epidemiological differences, both types of relapsing fever are associated with extreme poverty and crowding.
We'll begin with Louse-borne relapsing fever, which is associated with epidemics, particularly in parts of Africa.
It is caused by Borrelia recurrentis.
Write that the key vector is the human body louse (Pediculus humanus); humans are the sole reservoirs.
Transmission occurs when an infected body louse (or its feces) is crushed into openings in the skin; for example, when scratching or trauma creates abrasions.
Individuals with louse-borne relapsing fever experience approximately 5 febrile episodes; each episode lasts 3-7 days.
Febrile episodes are characterized by fever, chills, and headache, as well as joint and muscle pain, abdominal tenderness, jaundice, epistaxis, and thrombocytopenia.
Some patients experience hepatic or cardiac failure, or cerebral hemorrhaging.
In contrast, tick-borne relapsing fever is endemic in many areas, and is not usually fatal.
Write that it is associated with several species of Borrelia.
Soft ticks are the main vector;
Key reservoirs include soft ticks and small vertebrates, especially rodents.
Write that bacterial transmission is the result of infected tick bites.
Individuals experience 10 or more febrile episodes that last 3-7 days each. Notice that this is twice the number of expected febrile episodes associated with louse-borne relapsing fever.
Most episodes of tick-borne relapsing fever are mild, and are characterized by fever, chills, and headaches;
However, be aware that some species of Borrelia can cause more severe infections.
Write that relapsing fever is diagnosed using light microscopy of blood smears; in the image, we can see an example of a Borrelia cell among host blood cells.
Treatment includes tetracycline or erythromycin; for patients with CNS involvement, penicillin is recommended.
Next, let's learn about Lyme disease, aka, Lyme borreliosis.
Write that it is a multi-system inflammatory disease.
Borrelia burdorferi is responsible for Lyme disease in the United States;
Other Borrelia species, including Borellia garinii and Borellia afzelii, are responsible for Lyme disease in Europe and Central and Eastern Asia.
Create a table to organize the key vectors, reservoirs, and clinical features.
Various species of hard ticks, specifically black-legged Ixodes ticks, are the vectors;
The bacteria are transmitted to human hosts during prolonged episodes of tick feeding.
Key reservoirs include mice, deer, and pets.
Write that within 3-30 days of infection, the early stage of Lyme disease is characterized by localized erythema migrans.
In the image, we can see a centralized clearing, which is common but not always present. Notice that the cutaneous lesion is large, red, and flat; the rash gradually expands to several centimeters in diameter.
Months or even years after untreated infection, late systemic manifestations may appear.
These typically include re-appearance and spreading of erythema migrans, severe headache, neck stiffness, and arthritis, particularly of the knees and other large joints.
Individuals can experience facial palsy, Lyme carditis, central nervous inflammation, nerve pain, numbness, and tingling.
Write that some symptoms vary by the infecting species and geography.
For example, European Lyme disease is associated with acrodermatitis chronica atrophicans, which presents as red-blue bruise-like areas, typically on the extensor surfaces of the extremities. Over time, the tissues become fibrotic.
More rarely, European Lyme disease is associated with lymphocytoma, which manifests as a reddish/bluish swelling, often on the earlobe.
Write that Lyme disease is diagnosed using serology tests that measure IgM and IgG antibodies.
Early Lyme disease is treated with doxycycline, amoxicillin, tetracycline, or cefuroxime;
Later cases are treated with intravenous penicillin or ceftriaxone.
Write that antibiotic treatment of Borrelia infections is associated with Jarish-Herxheimer reaction. This reaction tends to exacerbate symptoms, initially, but is not usually fatal (we discuss it in more detail in our tutorial on Treponemal infections).
Finally, before we conclude, let's briefly consider Leptospirosis.
Leptospira are spirochetes that reside within the kidneys of small mammals, especially rodents. The animals then shed the bacteria into the environment. Thus, water-sport athletes and industrial workers in contact with contaminated water, soil, or animals are at higher risk of infection.
Write that mild leptospirosis produces flu-like symptoms and conjunctival suffusion;
The most severe infections are associated with Weil disease, which is characterized by jaundice, vasculitis, and organ failure, particularly involving the liver and kidneys, which can be fatal.
References:
Murray, P. R., Rosenthal, K. S., & Pfaller, M. A. Medical microbiology. Philadelphia: Elsevier/Saunders. (2013).
Levinson, W. E. Review of Medical Microbiology and Immunology. 14th Ed. Lange (2016).
Petzke, M., Schwartz, I. (2015). Borrelia burgdorferi Pathogenesis and the Immune Response. Clin Lab Med 35: 745–764.
Stanek, G., Fingerle, V., Hunfeld, K-P., Jaulhac, B., Kaisser, R., Krause, A., et al. 2010. Lyme borreliosis: Clinical case definitions for diagnosis and management in Europe. Clin Microbiol Infect 17:69-79.
Stanke, G., Wormser, G.P., Gray, J., Strle, F. (2011). Lyme borreliosis. The Lancet. DOI:10.1016/S0140-6736(11)60103-7.
Cutler, S.J. (2015). Relapsing fever Borreliae: a global review. Clin Lab Med. 35:847–865.
Maroun, E., Kushawaha, A., El-Charabaty, E., Mobarakai, N., El-Sayegh, S. (2011). Fulminant Leptospirosis (Weil's disease) in an
urban setting as an overlooked cause of multiorgan failure: a case report. Journal of Medical Case Reports. 5:7.
Bharti, A.R., Nally, J.E., Ricaldi, J.N., Matthias, M.A., Diaz, M.M., Lovett, M.A., et al. (2003). Leptospirosis: a zoonotic disease of global
importance. The Lancet Infectious Diseases. 3:757-771.
Images:
Borrelia (Centers for Disease Control; Public Health Image Library).
Erythema migrans (Centers for Disease Control; Public Health Image Library).