Lyme Disease Position Paper
Tick-Borne Disease
Background
Lyme disease is the most common tick-borne disease in the United States. It was named in 1977 when arthritis was observed in a cluster of children in and around Lyme, Connecticut. The disease is caused by a bacterial agent called Borrelia burgdorferi, which was first identified in North America in 1982. Although the majority of cases are reported from the mid-Atlantic, northeastern, mid-western, and far western regions of the country, several hundred cases annually are reported from the southeast and south-central United States. Humans and some animals contract this disease when they are bitten by ticks infected with this agent. Symptoms in humans usually begin about 7 to 10 days after the tick bite, although some people do not show any signs of illness until months to years later when complications occur. Early symptoms are intermittent and changing, which can make diagnosis difficult. These symptoms may include an annular or “bulls eye” skin rash called “erythema migrans” (EM), which occurs in 60 – 80% of Lyme disease patients. This rash is fairly specific to Lyme disease, although there are many other diseases that result in rash and not all Lyme disease patients develop EM. With or without EM, other early symptoms may include a general feeling of illness (“malaise”), fatigue, fever, headache, stiff neck, muscle and joint pain, and enlarged lymph nodes. These non-specific symptoms can be associated with many other ailments, which also makes the diagnosis of Lyme disease more difficult. Lyme disease, left untreated over months to years, can result in complications that include the heart, joints, and nervous system. These complications may subside (the patients thinks he/she is recovering), only to recur later and develop into a chronic condition.
Life Cycle of B. burgdorferi
The primary vector of Lyme disease in the eastern and midwestern United States is the deer tick, Ixodes scapularis. The primary vector in the western part of the country is I.pacificus. Ticks go through four stages in their development (egg, larva, nymph, adult), and B. burgdorferi is maintained (passed) in ticks as they pass from one stage to the next. When an infected tick bites a human or certain animals (after a period of attachment), the infectious agent can be transmitted, resulting in disease. Wild rodents and deer are part of the natural life cycle of B. burgdorferi. Infected larval and nymphal ticks feed on small mammals (usually rodents) while adult ticks feed on deer. The explosive repopulation of white-tailed deer in parts of the United States has been linked to the spread of Lyme disease. The majority of human Lyme disease cases result from bites by infected nymphs. At this stage the tick is small, less easily detected, and less likely to be promptly removed, which increases the possibility that it will transmit disease. Dogs, cattle, and horses develop disease that may include the joint and heart complications seen in humans. A vaccine is available for dogs, which in addition to protecting them, has a beneficial public health impact by decreasing the proximity of this disease to people. There is no evidence that Lyme disease has been transmitted directly from animal-to-animal, animal-to-human, or human-to-human. Although it is primarily transmitted through the bite of an infected tick, contamination of breaks in the skin or mucous membranes with crushed tissues or feces of ticks may occasionally lead to infection.
Diagnosis of Lyme Disease
Diagnosis is currently based on clinical findings supported by several types of laboratory tests. One type of test (called a “culture”) seeks to isolate the actual organism from the EM skin lesion, blood, joints, and cerebrospinal fluid. Other types of tests (called by the broad name “serology”) attempt to detect antibodies formed by the patient’s immune system against the organism. Currently, serology tests are poorly standardized and physicians must interpret them with caution. They are insensitive during the first several weeks of infection and may remain negative in people treated early with antibiotics. Test sensitivity increases when patients progress to later stages of the disease, but a small proportion of chronic Lyme disease patients never develop a positive blood test result. Another complicating factor is that there can be a cross-reaction in the blood test, giving a false positive result for Lyme disease in persons who really have conditions such as syphilis, Rocky Mountain spotted fever, human immunodeficiency virus (HIV) infection, infectious mononucleosis, lupus or rheumatoid arthritis. (Cross-reaction is a problem associated with tests for many diseases.) Although present diagnostics are not perfect, great strides have been made in the past twenty years. More sensitive and specific tests for Lyme disease are being developed.
Disease Reporting and Case Definitions
The Centers for Disease Control and Prevention (CDC) maintains a list of nationally notifiable diseases [1]. RSMo 192.139, Communicable Disease Reporting, Guidelines for Department, stipulates that communicable disease reporting requirements established by the Missouri Department of Health and Senior Services (DHSS) shall be in accordance with guidelines, funding requirements, or recommendations established by CDC. DHSS has incorporated CDC-mandated diseases as well as selected other diseasesinto 19 CSR 20-20.020, Reporting Communicable, Environmental and Occupational Diseases [2]. These selected diseases have s tate-created case definitions that follow the same format as their federal counterparts. Each definition requires a clinical description that distinguishes the disease from other conditions as well as supporting laboratory diagnostics or other epidemiologic links discovered through investigation that establish exposure to a specific disease-causing organism. Local public health agencies and/or DHSS are notified by physicians, laboratories, and other reporters when diseases/conditions listed in 19 CSR 20-20.020 are confirmed or suspected. DHSS, in turn, reports cases to CDC.
Before a case is reported to CDC, it must meet a “case definition” specific for the disease in question. For the purpose of standardization of reporting, CDC has established national Case Definitions for Public Health Surveillance [3]. These definitions provide uniform criteria for reporting cases to increase the specificity of reporting and improve the comparability of diseases reported from different geographic areas. Generally, cases of disease are categorized as “suspect,” “probable,” or “confirmed,” depending upon the level of clinical, laboratory, and epidemiological data available to support disease identification. A case may be moved from one of these categories to another as investigation results become available. For most diseases, only “probable” and “confirmed” cases are reported by DHSS to CDC. However, for some conditions including Lyme disease, CDC has determined that only “confirmed” cases will be reported.
The usefulness of public health surveillance data depends on its uniformity, simplicity, and timeliness. CDC’s case definitions establish uniform criteria for disease reporting and should not be used as the sole criteria for establishing clinical diagnoses, determining the standard of care necessary for a particular patient, setting guidelines for quality assurance, or providing standards for reimbursement. Use of additional clinical, epidemiologic, and laboratory data may enable a physician to diagnose a disease even though the formal surveillance case definition may not be met.
Treatment
Lyme disease in humans and animals can be treated with common antibiotics. There is a sufficient range of antibiotics available, such that if an individual is allergic to one antibiotic an effective alternative can be substituted. However, as with the majority of diseases, treatment is most effective if it is begun early in the course of illness. Also, treatment failures may occasionally occur and retreatment may be necessary. The condition of persons who do not receive treatment until later stages of disease should improve, but sometimes symptoms do not go away completely. A vaccine for humans was available but was removed from the market in 2002, reportedly due to poor sales resulting from its relative ineffectiveness. There is currently no vaccine approved for humans on the market in the United States.
Prevention
Preventing infection involves avoidance of tick-infested areas, wearing protective clothing, and application of insect repellents. Also critical to disease prevention is the prompt removal of ticks from the body, since experimental evidence indicates that ticks must be attached for 24 hours or more before the infectious agent is transmitted to a host. (Hence, part of DHSS’ tick-borne disease prevention message on billboards and posters this season is “√√√ for Ticks!”). The manner in which embedded ticks are removed is as important as their prompt removal. Ticks should be grasped as close to the skin as possible with tweezers or a tick removal tool (an inexpensive device available in the outdoor section of many retail stores) and removed with gentle, steady traction. This will help ensure that the tick’s mouthparts do not remain in the skin. Ticks should never be squashed, burned, or suffocated in the removal process, as this might result in regurgitation of gut contents (including bacteria) into the host. The bite site should be cleansed and an antiseptic applied; hands should be washed following tick removal.
Lyme Disease in Missouri
The first question to ask is, “Does Lyme disease occur in Missouri?” There have been patients with symptoms (including EM rashes) indistinguishable from those in other areas of the United States, but B. burgdorferi has not yet been isolated from any patients in Missouri. Lyme disease is nationally notifiable and is therefore notifiable in Missouri. Missouri patients who fulfill the strict CDC case definition for Lyme disease are reported as such. Even though the Missouri EM rashes are identical to those in other parts of the country, they are referred to as EM-like by the Division of Vector-Borne Infectious Diseases, National Center for Infectious Diseases, CDC. The clinical syndrome associated with the EM-like rash appears similar to Lyme disease and is called Lyme-like disease (.pdf).
A limited number of studies have been conducted to determine if B. burgdorferi is found in ticks in Missouri. A survey by Feir et al. [4] of ticks collected in southeastern Missouri and around the city of St. Louis identified B. burgdorferi in 1.9% of Amblyomma americanum (Lone Star tick) and 2.0% of Dermacentor variabilis (American dog tick) specimens collected.
The uncertainty regarding the occurrence of Lyme disease is not unique to Missouri (nor is it unique to Lyme disease). Determining the geographic distribution and prevalence of a disease-causing agent is always challenging, particularly when the agent is a relatively recently identified one. This problem is compounded many fold, when one realizes that it is not only the distribution and prevalence of the agent that must be considered, but also that of possible reservoirs and vectors that maintain and transmit the agent. All of these factors (agent, reservoir, vector) must come together at the same place and time before disease can be caused in a host.
It is entirely possible that there are a number of bacterial agents similar or related to B. burgdorferi that cause similar (Lyme-like) diseases, complicating the clinical and diagnostic pictures. Such an agent could be a subtype of B. burgdorferi, a different species within the genus Borrelia, or a different genus altogether. The CDC case definition “looks” only for infection by B. burgdorferi. Broadening the definition to possibly capture other, related agents without a scientific basis for doing so would result in less meaningful surveillance data from which significant conclusions could not be drawn.
One possible related agent is B. lonestari, which has been hypothesized to cause a condition recently termed “Southern tick associated rash illness” (STARI). A study conducted by Wormser et al. [5] of 30 patients from the Cape Girardeau, Missouri area with EM-like skin lesions concluded that neither B. burgdorferi nor B. lonestari is likely to be the cause of these lesions in patients from this part of the state. The cause of this condition remains unknown. It was unclear what role either of these agents might play in other regions of Missouri. The authors further stated that, although it is unknown whether an infectious agent causes this rash illness, the study did not rule out the possible use of antibiotics in treating this condition. These findings were consistent with results from Bacon et al. [6], who were unable to find B. lonestari in four skin biopsy samples obtained from patients with EM-like lesions in Butler County, Missouri.
Other studies in Missouri and several southern states also found that B. burgdorferi was not the cause of EM-like rashes on patients included in those studies. Furthermore, Wormser et al. [5] concluded that the lack of cross-reactivity demonstrated in their study diminishes the likelihood that any borrelial agent is the cause of EM in Missouri.
Wormser et al. [5] could not detect B. lonestari in any of 312 field-collected Amblyomma americanum ticks or two A. americanum ticks removed from patients who later developed EM-like rashes. Bacon et al. [6] tested 206 A. americanum ticks collected in Butler County, Missouri and estimated the prevalence of B. lonestari infection to be 5.6%.
Summary
Currently, the most scientific and effective way to address the issue of Lyme or Lyme-like illness being caused by agents that have yet to be identified is to focus on the prevention of all tick-borne diseases. Rocky Mountain spotted fever, ehrlichiosis, and tularemia are found in Missouri. DHSS believes that increased awareness of all tick-borne diseases in the state is critical to our citizens who depend on the outdoors for their livelihood and recreation. DHSS has begun to address this need by promoting personal protection and prevention – the use of insect repellants containing an active ingredient that repels or kills ticks and the practice of frequent tick-checks when working or recreating in tick habitat. Educational tools include paid radio announcements, billboards, posters, as well as tick-borne disease training for local public health agencies.
References
- Centers for Disease Control and Prevention. Nationally Notifiable Infectious Diseases. http://www.cdc.gov/epo/dphsi/phs/infdis2005.htm
- 19 CSR 20-20.020, Reporting Communicable, Environmental and Occupational Diseases. http://www.sos.mo.gov/adrules/csr/current/19csr/19c20-20.pdf
- Centers for Disease Control and Prevention. Case Definitions for Infectious Conditions Under Public Health Surveillance. MMWR 1997;46(No. RR-10). http://www.cdc.gov/epo/dphsi/casedef/index.htm
- Feir D, Santanello C, Li B, et al. Evidence Supporting the Presence of Borrelia Burgdorferi in Missouri. American Journal of Tropical Medicine, 1994; 51(4):475-482.
- Wormser G, Masters E, Liveris D, et al. Microbiologic Evaluation of Patients from Missouri with Erythema Migrans. Clinical Infectious Diseases, 2005; 40:423-428.
- Bacon R, Gilmore R, Quintana M, et al. DNA Evidence of Borrelia lonestari in Amblyomma americanum (Acari:Ixodidae) in Southeast Missouri. Journal of Medical Entomology, 2003; 40:590-592.
- Protocol – A Study to Determine the Etiology of Southern Tick-Associated Rash Illness (STARI) in the United States; Principal Investigator, Barbara J. B. Johnson, PhD, Chief, Microbiology and Pathogenesis Laboratory, Bacterial Zoonoses Branch, Division of Vector-Borne Infectious Diseases, NCID, CDC, 2005.
Additional Resources
Web sites that Lyme disease patients may find helpful include:
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