Lyme Disease

 

by Sue Hyun

 

 

Etiologic Agent, General Characteristics and Virulence Factors

 

Lyme disease or Lyme borreliosis is caused by spiral-shaped bacteria 20 to 30 micrometers long (13) from the genus Borrelia (11).  Borrelia burgdorferi sensu lato complex (5) are gram-negative microaerophiles which can be divided into eleven species, 3 of which are significant pathogens (11).  B. burgdorferi sensu stricto causes the disease in the United States, Europe and Asia.  However, in Europe and Asia the disease can also be caused by B. afzelii or B. garinii (5).  The spirochetes have outer surface proteins called endoflagella located in the periplasm that allows them to remain hidden from the host.          

 

Images of Borrelia burgdorferi                  (13)                                                                     (3)

 

 

 

History

 

The disease was named after Lyme, Connecticut in 1977 when arthritis was found in a group of children living in the area (3) and was originally called Lyme arthritis (10).  However, in the early 1900s, physicians in Europe noticed a characteristic red rash called erythema migrans (EM) among patients and deduced that bacteria carried by ticks were the source of illness.   In 1969, a doctor was able to treat a patient with EM using penicillin.  Borrelia burgdorferi was finally isolated in a deer tick gut in 1981 by Dr. Willy Burgdorfer (12) and the Centers for Disease Control began monitoring the disease (3).  It wasn’t until 1991 that Lyme disease was considered a notifiable disease by the Council of State and Territorial Epidemiologists (4). 

 

 

Transmission Vector and Reservoirs

 

Lyme disease is the most common vector-borne disease.  In the United States the disease is transmitted by the bite of infected deer ticks such as Ixodes scapularis (dammini) and the western black-legged tick, Ixodes pacificus.  It is found in northeastern, north-central and mid-Atlantic regions and along the Pacific Coast of the U.S. (3).  The disease occurs in temperate climates in Europe and Asia.  In Europe, it is transmitted by Ixodes ricinis while I. persulcatus is the main vector in Asia (11).     

 

From left to right: Deer tick adult female, adult male, nymph, and larva (3)

 

The ticks become infected during their larval state (1) when they feed on deer, rodents, birds and other small animals, which serve as reservoirs (3).  Infection is spread to humans or other mammals during the tick’s nymph stage (8).  The larva and nymph are the size of a pencil point.  The adult ticks are differentiated as the females are red and slightly larger than the black males (1).  Nymphal ticks are most predominant from May to August (3) whereas adult ticks are most prevalent from September to November (1).  The tick’s life cycle creates “Lyme season” from spring to autumn (2).

 

2 year life cycle of the deer tick (3)

 

 

Signs and symptoms

 

For the majority of people, once a tick has bitten its human host, a slow growing circular rash called erythema migrans appears around the site of the bite (2).  The incubation period is usually 7 days but the rash, resembling a “bull’s eye” due to a red ring left by the lightening of the center, can form anytime up to a month after exposure.  The first stage of Lyme disease occurs around this time and includes symptoms resembling the flu such as fever, chills, fatigue, swollen lymph nodes, headache, muscle and joint pain (9).

 

Erythema migrans (3)

 

The infection may begin to spread to other parts of the body in the second stage after some weeks or months after infection (2).  Neurological problems are involved at this stage including pain and numbness in legs or arms, facial paralysis, vision difficulties and symptoms associated with meningitis such as fever, neck stiffness, and strong headaches.  Also, moodiness, problems with memory, concentration and sleep, and damaged nerves in legs and arms may present themselves (9).

 

The third stage also called late or chronic Lyme disease may develop weeks or months later due to lack of treatment, insufficient treatment (2) or even recurring infection (1).  Chronic arthritis characterized by intermittent periods of swelling and pain in the joints (3), chronic muscle pain, disturbed sleep, and difficulties with memory and concentration may arise during this period (2).  It has been indicated that patients who have had sufficient treatment but still experience returning symptoms may have derived an autoimmune condition that damaged their tissues.  It is also possible that the symptoms are caused by yet other spirochete bacteria (1).

 

 

Diagnostic Testing

 

Diagnosis can be made with several serological tests, such as the indirect fluorescent antibody (IFA) test (3) and the ELISA (2) which detect increases of antibodies, immunoglobulins M (IgM) and G (IgG), against B. burgdorferi (6).   Since antibodies may remain in the body for a long time these tests do not reveal whether or not the disease is active.  It is also possible for the presence of antibodies to other spirochetes to return a false positive for the disease (1).  For these reasons, a positive or inconclusive result from the first test must then be confirmed by the Western blot used to detect specific antibodies against Lyme disease antigens (6).  Polymerase chain reaction (PCR) can detect B. burgdorferi but is limited to those found in body fluids (1).  Other less commonly used diagnostic measures include bacterial cultures obtained from erythema migrans lesions (3) and the Prevue B which also identifies antibodies (1).    

 

 

Prevention

 

Measures can be taken to prevent Lyme disease.  The most obvious is avoiding areas where infected ticks are known to inhabit (3).  Deer ticks and western black-legged ticks are found in low-lying vegetation and prefer moist (1), wooded, and grassy areas such as lawns and gardens.  Lyme disease is most likely to be transmitted during spring and summer when people spend more time outdoors and more skin is exposed.  Wearing long-sleeved shirts and long pants that are tucked into socks or boots is recommended to minimize exposure to ticks (2).  Other precautions can be taken as well such as wearing light-colored clothing so that ticks are more visible, wearing tick repellant containing DEET (3), applying acaricides to clothing (5) and checking for ticks on pets and persons (2).  It is important to remove ticks promptly because ticks are not likely to transmit the bacteria in under 36 hours (5).  If a tick is attached, a fine-tipped tweezer should be used to grasp the tick as near to the skin as possible and must be pulled straight out (2).  The mouthparts may still remain behind but will not cause the disease since the bacteria is found mainly in the gut or saliva glands (5).  Finally, the area of the bite should be cleaned with antiseptic or alcohol.  Care should be taken to not use mineral oil, petroleum jelly (2), nail polish or a match to remove the tick (5).  More widespread preventive measures include landscape management, pesticides, (4) control of deer populations and killing ticks on animals (3).        

 

Currently there are no human vaccines available for Lyme disease since a manufacturer pulled its LYMErix™ Lyme disease vaccine off the market in February of 2002 due to lack of sales (5).  There is promising research in vaccinating wild mice populations against B. burgdorferi, which in turn would decrease disease transmission to humans by the vector tick.  However, other animals that may be reservoirs for B. burgdorferi and virulent strains of the bacteria must be identified for such vaccination programs to succeed.  Oral vaccines are under development (8).

 

 

Treatment

 

The standard treatment for Lyme disease is antibiotics such as doxycycline, amoxicillin or cefuroxime axetil (1).  For more serious cases involving the nervous system as with late stage Lyme disease, ceftriaxone or penicllin must be taken intravenously for a month or longer (3).  Azithromycin, clarithromycin or erythromycin is given to those patients who are allergic to penicillin (1).  Treatment is usually effective but some symptoms may persist in chronic Lyme disease (9).  On April 25, 2005, the press reported that the University of Texas Southwestern Medical Center identified a protein called BptA that was necessary for B. burgdorferi to be transmitted from ticks to humans.  Without the protein, the bacteria were not able to live in the tick’s gut (7).         

 

 

Incidence

 

United States distribution of Lyme disease vectors (3)

 

According to the Morbidity and Mortality Weekly Report by the Centers for Disease Control and Prevention, in 2002 the number of cases for Lyme disease in the United States reached 23,763, an increase of 40% from the previous year.  The majority of patients are children from ages 5 to 14 and adults from 50 to 59 years old (4).        

 

Lyme disease is one that can be frightening in that it can be relatively easily acquired, and can go unnoticed.  Despite this, there are preventative and precautionary measures to safeguard against the disease and is curable if treated early.  There is continuing research to find more efficient diagnostic tests and treatments, including an effective vaccine.  However, given that the highest prevalence of infection is in young children and persons nearing senior citizenship, it is essential that the prevention of Lyme disease continue to be a priority. 

 

 

REFERENCES

 

1.                  American Lyme Disease Foundation.  “Frequently Asked Questions”.  8/01/03.  URL: http://www.aldf.com/FAQ.asp accessed on 04/26/05.

 

2.                  American College of Physicians.  “Lyme Disease: A Patients Guide”.  2005.  URL: http://www.acponline.org/lyme/patient accessed on 04/26/05.

 

3.                  Centers for Disease Control and Prevention. “Lyme Disease”.  04/14/05.  URL: http://www.cdc.gov/ncidod/dvbid/lyme/index.htm accessed on 04/21/05.

 

4.                  Centers for Disease Control and Prevention.  “Lyme Disease --- United States, 2001-2002”.  05/06/04.  URL: http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5317a4.htm accessed on 04/21/05.

 

5.                  Centers for Disease Control and Prevention.  “Travelers’ Health: Lyme Disease”.  06/30/03.  URL: http://www.cdc.gov/travel/diseases/lyme.htm accessed on 04/26/05.

 

6.                  American Association for Clinical Chemistry: Lab Tests Online.  “Lyme Disease”.  01/25/05.  URL: http://www.labtestsonline.org/understanding/analytes/lyme/test.html accessed on 04/26/05.

 

7.                  Medline Plus.  “Lyme Disease bacteria need protein to live”.  04/25/05.  URL: http://www.nlm.nih.gov/medlineplus/news/fullstory_24285.html accessed on 04/26/05.

 

8.                  National Institutes of Health.  “Broad-based Vaccination of Wild Mice Could Help Reduce Lyme Disease Risk in Humans”.  12/13/04.  URL: http://www.nih.gov/news/pr/dec2004/niaid-13a.htm accessed on 04/21/05.

 

9.                  National Institute of Neurological Disorders and Stroke.  “NINDS Neurological Complications Of Lyme Disease Information Page”.  03/07/05.  URL: http://www.ninds.nih.gov/disorders/lyme/lyme.htm accessed on 04/26/05.

 

10.             World Health Organization.  “Lyme disease”.  2005.  URL: http://www.who.int/topics/lyme_disease/en/ accessed on 04/26/05.

 

11.             European Union Concerted Action on Lyme Borreliosis.  “Disease Overview: Part I”.  5/30/03.  URL: http://vie.dis.strath.ac.uk/vie/LymeEU/disease-overview_1.html accessed on 5/1/05.

 

12.              National Institute of Allergy and Infectious Diseases.  “Willy Burgdorfer, Ph.D., Scientist Emeritus”.  4/24/03.  URL: http://www.niaid.nih.gov/dir/labs/lhbp/burgdorfer.htm accessed on 5/01/05.

 

13.              Author Unknown  “Borrelia Burgdorferi”.  Date Updated Unknown.  http://www.users.fast.net/~esteckel/Borrelia%20burgdorferi.htm  accessed on 5/1/05.