Discussion

Clinical features and diagnosis Web sources for clinical information on disease recognition and laboratory diagnosis are listed in table 1. The Lyme disease home page of the CDC's Division of Vector-Borne Infectious Diseases (DVBID) provides concise and objective information (figure 1). As an agency that serves the public, the CDC targets information toward both the layperson and the scientific community. The site is aesthetically pleasing and is structured for efficient browsing. The authorship is expert, in that the DVBID scientists and CDC epidemiologists who contribute to the site work, in many cases, exclusively in the field of tickborne diseases. The bibliography of medical literature (accessible through the link “Scientific Literature”) is well chosen and comprehensive. A handy feature of the bibliography pages is the provision of links to hypertext and portable document format (PDF) versions of key Morbidity and Mortality Weekly Report (MMWR) documents. Specific sections of this Web site that are useful resources for epidemiology and tick biology are listed separately in relevant tables in the present article. The CDC's Lyme disease home page also contains a link to a description of a new disease, Southern tick-associated rash illness, and links to the Division of Viral and Rickettsial Diseases for information on other tickborne diseases.

The Web can be a tremendous resource for pictorial diagnostic aids, and these can be useful in treating patients with Lyme disease because of the many variations in the appearance of erythema migrans. The European Union Concerted Action on Lyme Borreliosis (EUCALB) Web site (figure 2) and an interactive on-line seminar from The Lancet [5] provide excellent digital images of erythema migrans rashes. The EUCALB site also has pictures of the skin manifestations acrodermatitis, chronica atrophicans, and borrelial lymphocytoma, which are seen exclusively in Europe.

Table 1 lists addresses for the Web sites of journals that have recently published review articles that contain clinical information on the disease. The Lancet seminar by Nadelman and Wormser is a hypertext-structured comprehensive reference that includes color graphics [5]. The extra steps involved in obtaining access to it are worth the effort. The American Lyme Disease Foundation's Web site (http://www.aldf.com) is primarily an education resource for patients, but the section “News from the Front” highlights many recent studies that the infectious diseases physician would want to peruse. A very concise patient's guide hosted by Pfizer Global Research is available at http://www.lymediseaseinformation.com, and a Lyme disease pamphlet can be ordered through the site.

Despite the accumulation of a wealth of experience with laboratory diagnosis of Lyme disease in areas of endemicity, many physicians continue to be skeptical about the reliability of laboratory diagnostic methods and are unfamiliar with the criteria for interpreting immunoblot results in Borrelia burgdorferi infection. The MMWR recommendations from a broad-ranging consensus conference in 1994 are easily accessible in the bibliography of the CDC's Web site. Information about the basis of and potential indications for use of 2 newer antibody tests (one of which is intended for office use) is available on the Immunetics and Wampole Laboratories Web sites, but a complete understanding of the role (if any) of these 2 tests in facilitating the diagnosis of Lyme disease requires a review of the original publications. Only those for the C6 peptide test are available, at http://www.specialtylabs.com/education/download_PDF/TN_1087.pdf. No objective review that would help further explain the role of these tests could be found on the Web. The “Questions and Answers” page from Specialty Laboratories for the C6 peptide test (http://www.specialtylabs.com/education/download_PDF/TN_1172.pdf) is instructive.

Epidemiology of Lyme disease Table 2 lists sources of information about the epidemiology of Lyme disease. There is marked variation in the incidence of Lyme disease within regions of endemicity, ranging from no cases to hyperendemicity. National and local maps of disease incidence or tick populations are useful guides that should be consulted when decisions about laboratory testing are made, because the predictive value of a test is enhanced by a higher prior probability. A calculator that can be used to calculate this is available on the American College of Physicians (ACP) Web site (http://www.acponline.org/lyme/calculator/). Detailed epidemiology information (for pretest probability estimates) is not available on-line for all regions, but some high-incidence states, notably Connecticut, have excellent pictorial or tabular guides on their health department Web pages. Among state health department sites, Connecticut's provides the best all-around information. Information on the biology of the deer tick life cycle and a National Lyme Disease Risk Map are excellent resources that are available from the CDC. The map represents a mathematical model constructed from information about tick prevalence, tick infection, and reported human cases. Emerging Infectious Diseases, a free journal from the CDC that is available on-line, is a noteworthy source of epidemiologic research on Lyme disease and other tickborne diseases.

Treatment recommendations Table 3 lists sites with information about treatment of Lyme disease. The Infectious Diseases Society of America (IDSA) treatment recommendations were published in 2000 as a consensus statement by infectious diseases and rheumatology experts on Lyme disease [8]. IDSA members may access them via on-line subscriptions to Clinical Infectious Diseases, and pediatricians can view them via the American Academy of Pediatrics Web site. The recommendations are detailed and evidence based.

Evidence-Based Medicine Reviews (EBMR) is a valuable on-line resource for information on treatment and prevention studies in Lyme disease (figure 3). Infectious diseases practitioners may already be familiar with the Cochrane Database of Systematic Reviews and Cochrane Controlled Trials Register from the Cochrane Collaboration project, which provides compilation and critique of the best evidence from medical research that can be translated into clinical practice. EBMR identifies studies from Cochrane and 2 other evidenced-based medicine sources, the ACP Journal Club and the Database of Abstracts of Reviews of Effectiveness; it is a full-text database of reviews of key studies that can be used in making treatment decisions. Ovid/EBMR is a collaborative arrangement between EBMR and Ovid Technologies (http://www.ovid.com [select “All EBM Reviews”]; available via institutional subscription, typically through the infectious diseases physician's hospital or medical school library). When the database was searched in January 2002 (the EBMR database is updated quarterly), 58 citations were obtained (figure 3). These consisted of 52 controlled studies, 4 reviews of effectiveness, and 2 reviews from the ACP Journal Club. Ovid MEDLINE is a subscription-based service that is generally available via hospital libraries; the service makes full-text links to articles from many journals available.

Information about ongoing clinical trials that are recruiting patients for studies of Lyme disease can be viewed at a National Institutes of Health (NIH) Web site devoted to these trials and at the Web site for CenterWatch, which also lists industry-sponsored trials. For example, as of January 2002, ongoing studies of Lyme disease were “A Comprehensive Clinical, Microbiological and Immunological Assessment of Patients with Suspected Chronic Lyme Infection and Selected Control Populations” and a study designed to document the natural history of rigorously defined, treated Lyme disease. The New Jersey Department of Health has a handy table of choices for treatment of tickborne diseases on its site (table 2).

Tick morphology and biology Many infectious diseases physicians are interested in obtaining more information about ticks, and on-line sources are available to fill this need (table 4). A review of tickborne diseases, with images, was published in The New England Journal of Medicine in 1993 [9]. A very exhaustive recent review article on ticks and bacterial diseases transmitted by ticks worldwide can be accessed through the electronic edition of Clinical Infectious Diseases [10]. The University of California—Davis Entomology Department has a detailed collection of tick images and factual information that serves as an excellent introduction to the field. Ixodes scapularis at various stages can be viewed via the CDC's Lyme disease home page, and good images of common ticks of medical importance are available on the American Lyme Disease Foundation and EUCALB Web sites. An illustrated life cycle of the deer tick is also accessible on the EUCALB site, and the biology of deer tick distributions is described on the CDC's Lyme disease home page under “Vector Ecology.” There is an easy-to-access image collection that can be used for patient education purposes on Yahoo's health page.

Prevention Sources of information about prevention of Lyme disease are listed in table 5. Although the only vaccine in use ceased to be marketed in March 2002, sites dealing with outer-surface protein A (OspA) vaccine continue to be relevant for information on its safety and efficacy and on the duration of immunity after vaccination. Several thousand adults and children were immunized with the licensed or with investigational OspA vaccines. The recommendations of the Advisory Committee on Immunization Practices for use of Lyme disease vaccine and for tick bite prophylaxis and management are published in MMWR and are available on-line from the CDC [11]. The American Academy of Pediatrics based its document largely on these recommendations. Vaccine-prescribing information can still be accessed through the on-line Physician's Desk Reference (http://www.pdr.net) or the Web site of the OspA vaccine manufacturer (LYMErix OspA; GlaxoSmithKline). The American Lyme Disease Foundation has an insightful summary of OspA vaccine recommendations. The pivotal studies of OspA vaccine were published in The New England Journal of Medicine in 1998 [12, 13]. Data on pediatric use were published in Pediatrics in 2001 [14].

Research resources Table 6 lists on-line resources for research on Borrelia and Lyme disease. The complete genome of Borrelia burgdorferi, first published in Nature in 1997 [15], is available as an on-line database and as maps at the Institute for Genomic Research Web site. The site is interactive, well structured, and well maintained. The National Center for Biotechnology Information's taxonomy browser offers a definitive list of Borrelia strains, with links to genomic records and protein structures. The Institut Pasteur has a promising resource in its Borrelia burgdorferi sensu lato Molecular Genetics Server. A drawback is that the site has not been updated recently. Maintenance appears to have been ignored, and several links do not work. Nevertheless, the strain lists of Borrelia species, DNA sequence lists, and gene-protein indices are comprehensive; the site presents an electrotransformation protocol in detail; and the references are exhaustive. The EUCALB site maintains frequently updated, in-depth lists of published studies. EUCALB's consultants are clearly listed, links are judiciously chosen, and the site was updated in December 2001. Information for referral of patients to ongoing clinical research trials is available at the NIH and CenterWatch clinical trial Web sites.

Literature search services and other compendia Repeated searches performed on popular search engines sites such as AltaVista, Google, Excite, and Lycos confirmed that this search strategy is a far from optimal method of obtaining sites useful for medical and research purposes. Use of the search term “Lyme disease” is a little more likely to yield sites with scientifically sound information than use of “Lyme” alone (probably because the latter is a common lay term also used to describe symptom complexes in patients who have no serologic evidence of the infection); “Lyme” yielded ∼537,000 sites, compared with 215,000 for “Lyme disease.” After using the sites reviewed in this article, physicians should periodically augment their information on Lyme disease by registering (free of charge) with one of several Web sites that compile databases of scientific information. A recent visit to the clinical resources section of one site (Medscape) yielded a mixed bag, but the Lyme disease page in the Medscape Resource Center (http://www.medscape.com/pages/editorial/resourcecenters/public/lymedisease/rc-lymedisease.ov) was sound. Some services that provided links to Lyme disease information are listed in table 7 (along with the better-known National Library of Medicine's MEDLINE); on a recent visit to the National Guideline Clearinghouse Web site, for example, 9 documents on Lyme disease were found, including “Guidelines for laboratory evaluation in the diagnosis of Lyme disease” [16], an Annals of Internal Medicine position paper that is also accessible via the ACP Web site (http://www.acponline.org/journals/annals/15dec97/pplyme1.htm).