Borrelia burgdorferi Case File

Borrelia burgdorferi Case File

Eugene C.Toy, MD, Cynthia Debord, PHD, Audrey Wanger, PHD, Gilbert Castro, PHD, James D. Kettering, PHD, Donald Briscoe, MD

CASE 3

A 28-year-old woman presents to the office for the evaluation of a rash. She had just returned from a weeklong camping trip in the New England area, when she noted the presence of a circular, red rash on her lower abdomen. Also, she has had a low-grade fever, and some achiness and fatigue. Examination of her abdomen reveals a 10-cm flat, red, circular patch with some central clearing. No other skin rashes are noted, and the remainder of the examination is normal. The blood cultures are negative. You make the presumptive diagnosis of erythema migrans and send blood for confirmatory serologic studies.

◆ What organism is the etiologic agent of erythema migrans?

◆ What are the primary reservoir and vector of transmission of this agent?

ANSWERS TO CASE 3: Borrelia burgdorferi

Summary: A 28-year-old woman who has been recently camping in the New England area complains of fever and a skin rash consistent with erythema migrans. Confirmatory serologies are sent.

◆ Etiologic agent of erythema migrans: Borrelia burgdorferi

◆ Primary reservoir of infection: Small rodents, primarily the white footed mouse

◆ Primary vector of transmission: Ixodes tick

CLINICAL CORRELATION

Borrelia burgdorferi is the causative agent of Lyme disease and is transmitted to humans by Ixodes ticks. This disease was first recognized in Old Lyme, Connecticut, with the identification of cluster cases of arthritis in children. The infection is characterized by a “bull’s eye” skin lesion, which develops from the site of the tick bite, 1–4 weeks postinfection. Additional initial symptoms include fever, fatigue, headache, joint pain, or mild stiffness of the neck. Lyme disease is the most common vector-born disease in the United States, and if left undiagnosed and untreated, the infection usually progresses to involve the nervous or vascular systems and cause fluctuating or chronic arthritis.

APPROACH TO Borrelia SPECIES

Objectives

1. Know the characteristics and virulence factors of B. burgdorferi.
2. Know the reservoir, vector, and host involved in the transmission of B. burgdorferi.

Definitions

Erythema migrans: Skin lesion composed of redness (erythema) with central clearing (target lesion).

Spirochetes: Thin spiral bacteria of which three genera cause significant disease in humans: Leptospira, Borrelia, and Treponema, which lead to leptospirosis, Lyme disease, and syphilis, respectively (see Table 3-1 for an abbreviated listing).

Table 3-1

DISCUSSION

Characteristics of Borrelia Species

Borrelia burgdorferi belongs to the spirochete family of prokaryotes. It stains gram-negative, although spirochetes are considered neither gram-positive nor gram-negative. Spirochetes consist of a flexible, multilayer outer cell membrane and a more rigid, peptidoglycan-containing cytoplasmic membrane. Between these two layers are endoflagella that insert at the ends of the spirochete. Rotation of these flagella creates the characteristic cork-screw shape of these organisms. This provides for motility of the organism and hides the normally antigenic flagella from host defenses. These organisms are microaerophilic and have a doubling time of 8–24 hours. The disease is endemic in several regions of the United States including Northeastern, Midwest, and Pacific coast states. However, most reported cases occur in New York, Connecticut, Pennsylvania, and New Jersey.

The spirochetes that cause Lyme disease have been divided into genospecies. Three genospecies, B. burgdorferi sensu stricto, B. garinii, and B. afzelii, are known to cause Lyme disease and are known collectively as B. burgdorferi sensu lato. The outer membrane of B. burgdorferi contains unique outer surface proteins (Osps), which are thought to play a role in their virulence. Small rodents, particularly the white-footed mouse, are the primary reservoirs of B. burgdorferi, and the vector of transmission is the Ixodes tick. The larva of the tick is born uninfected. The ticks become infected with the spirochete on feeding on an infected animal. This usually occurs during the nymph stage of the tick’s life cycle. The spirochetes multiply in the gastrointestinal (GI) tract of the tick, and then are transmitted to the animal host by regurgitation or salivation during a subsequent feeding. Borrelia burgdorferi are next transmitted to humans via tick bite followed by dissemination through the bloodstream to the joints, heart, and central nervous system (CNS). The nymphal stage of the tick is more infective than the adult and larval stages. Most exposures to Borrelia occur between the months of May and July, when the nymphs are most active.

Clinically there are three stages of B. burgdorferi infection: stage 1, which occurs in the first 4 weeks postinfection, involves the initial characteristic skin lesion referred to as “erythema migrans”; stage 2 follows for months postinfection with neurologic and cardiac involvement; and stage 3 results in chronic arthritis of the joints.

Diagnosis

The diagnosis of Lyme disease is made primarily by clinical presentation and patient history of exposure. Confirmation of a clinical diagnosis is made serologically via the detection of antibody by enzyme-linked immunoabsorbance or indirect immunofluorescence. However, serologic tests are most reliable 2–4 weeks postinfection, because of cross-reactivity with normal flora, and Western blot analysis should be used to confirm a positive serologic test. Alternately, new PCR-based tests are available to detect B. burgdorferi DNA. Borrelia burgdorferi is difficult to grow in culture, requiring complex culture media and a microaerophilic environment. It is also difficult to visualize under light microscopy, but can be seen under darkfield microscopy or when stained with Giemsa or silver stains.

Treatment and Prevention

Initial stages of infection with B. burgdorferi can be effectively treated with doxycycline or amoxicillin, while later stages of disease are better treated with penicillin G or ceftriaxone. Prevention of infection involves limiting exposure to ticks by wearing protective clothing in endemic areas, including long sleeves and long pants tucked into socks. Careful search for and removal of ticks is also an important preventative measure. Use of repellants is also helpful and administration of insecticides may reduce the number of active nymphal ticks for a given season. A vaccine containing recombinant OspA protein was developed for persons with the highest risk of exposure. The vaccine is approved for adults and shows approximately 75 percent efficacy.

COMPREHENSION QUESTIONS

[3.1] A 9-year-old boy presents with a migratory rash with central clearing on the back of his neck. The child had recently been on vacation with his family in Oregon and had gone hiking. The child’s pediatrician observes the rash and suspects an infection with B. burgdorferi. Which of the following is thought to be a virulence factor of this organism?

A. Intracellular growth in leukocytes

B. Endotoxin release

C. Localization in reticuloendothelial cells

D. Antiphagocytic capsular antigen

E. Expression of outer surface proteins

[3.2] If the child’s infection is left untreated, which of the following symptoms would most likely appear?

A. Urethritis

B. Centripetal spread of rash

C. Biphasic illness with fever and chills

D. Stiffness in the knees

E. Swelling of lymph nodes

[3.3] A small tick, of the genus Ixodes, most commonly transmits B. burgdorferi. Which of the following diseases is also transmitted by a tick?

A. Q fever

B. Leptospirosis

C. Ehrlichiosis

D. Yellow fever

E. Eastern equine encephalitis

Answers

[3.1] E. Differential expression of outer surface proteins is thought to be involved with virulence; answers A, B, C, and D are incorrect: (A) intracellular growth in leukocytes is a virulence factor of Ehrlichia; (B) endotoxins are characteristic of gram-negative organisms, not Borrelia; (C) localization in reticuloendothelial cells occurs in infections with Francisella tularensis; (D) an antiphagocytic capsular antigen is not a virulence factor of Borrelia.

[3.2] D. Later stages of infection with B. burgdorferi include arthritis, meningitis, nerve palsies, and cardiovascular abnormalities; answers A, B, C, E, are incorrect: (A) arthritis, not urethritis, is a later manifestation of infection with B. burgdorferi; (B) the skin rash or erythema migrans expands centrifugally, not centripetally; (C) biphasic illness with fever and chills occurs more commonly with Leptospira infections; (E) swelling of lymph nodes is more commonly associated with Yersinia infections.

[3.3] C. Similar to Lyme disease, ehrlichiosis is also transmitted via a tick vector; answers A, B, D, and E are incorrect: (A) Q fever is most commonly transmitted via inhalation of dried feces or urine contaminated with rickettsiae; (B) Leptospirosis is typically transmitted via ingestion of contaminated food or water; (D and E) both yellow fever and eastern equine encephalitis are transmitted by mosquitoes.

MICROBIOLOGY PEARLS ❖ Borrelia burgdorferi is a microaerophilic spirochete. ❖ Primary reservoirs of B. burgdorferi are small rodents (e.g., whitefooted mouse), and the vector of transmission is the Ixodes tick. ❖ States with highest incidence include: New York, Connecticut, Pennsylvania, and New Jersey. ❖ Primary treatment is doxycycline or amoxicillin. ❖ Prevention consists of wearing protective clothing, use of insect repellants or insecticides, and a recombinant OspA protein vaccine.

REFERENCES

Brooks GF, Butel JS, Morse SA. Jawetz, Melnick, & Adelberg’s Medical Microbiology, 23rd ed. New York: McGraw-Hill, 2004:336–338. 

Murray PR, Rosenthal KS, Pfaller MA. Medical Microbiology, 5th ed. St. Louis, MO: Mosby, 2005. 

Ryan JR, Ray CG. Sherris Medical Microbiology, 4th ed. New York: McGraw-Hill, 2004:431–434. 

Wilske B, Schriefer ME. Borrelia. In: Murray PR, Baron EJ, Jorgensen JH, et al., eds. Manual of Clinical Microbiology, 8th ed. ASM Press, 2003.

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