Will New Vaccine Eliminate Lyme Disease?

By Joan Unger, RN, MS, ARNP-C

Summary-Lyme disease (LD) is an inflammatory, multisystem disease resulting from tick bites carrying the Borrelia burgdorferi spirochete. It is the most common vector-borne infection in the United States, and if untreated, it can result in chronic arthritic, nervous system, or cardiac abnormalities. The New England Journal of Medicine recently reported two studies involving more than 21,000 subjects who participated in randomized, double-blind, multicenter studies conducted in 45 sites in 10 states in which LD is endemic. Study one found the vaccine 68% effective in the first year and 92% effective after a booster vaccine in the second year. Study two found the vaccine 83% effective in year one and 100% effective in preventing asymptomatic infection after the year two booster. Both studies concluded the vaccine is safe and effective in preventing Lyme disease. Research must be done to determine how long protection lasts, the optimal regimen for administering the vaccine, and its effect on teens and children.

(Editor's note: In last month's issue of RN Advanced Practice Alert, we presented the first of this two-part series on Lyme disease discussing its prevalence, diagnosis, and treatment. This issue outlines results of two large multicenter trials of a promising Lyme disease vaccine.)

JUST 21% of patients reporting to Yale University Lyme Disease Clinic in New Haven, CT, had active Lyme disease (LD), yet 75% had received a total of 232 courses of antibiotic treatment. Sixty-nine patients with no evidence of LD had at least one minor adverse drug reaction.1 Much treatment appears inappropriate, yet the fear of LD is real for good reason. Untreated, LD can result in chronic arthritis; nervous system abnormalities including numbness, pain, Bell's palsy, and meningitis; or, less commonly, cardiac irregularities.

Immunization is second only to public health measures such as sanitation in preventing infectious disease. It was good news for health care providers when the July 23, 1998, issue of The New England Journal of Medicine published reports of promising new studies of vaccines to prevent Lyme disease.2-3

Study One

In study one,2 researchers set out to evaluate the efficacy of a recombinant vaccine of outer-surface protein A (OspA) without adjuvant in subjects at risk for LD who were recruited from 14 areas in the United States where LD was endemic. The randomized, double-blind study recruited 10,305 subjects ages 18 or older who each received two injections one month apart. Approximately half of the subjects (5149) received placebo, and the other half (5156) received vaccine. After 12 months, a booster dose was administered to 7515 of the subjects.

Researchers observed the subjects for two seasons at a time when risk of contracting LD was high. In the first year, there were 37 confirmed cases of LD in the placebo group and 12 in the vaccine group, giving an overall vaccine efficacy of 68%. In the second year, 28 cases were found in the placebo group, and only seven in the vaccine group. In subjects who received a booster dose, vaccine efficacy was 92%. Adverse effects were mild and self-limited. The incidence of adverse effects between groups was significant only during the first seven days after vaccination, when the most common complaints were pain or tenderness at the injection site. Adverse effects after seven days were insignificant between the groups.

During the study period, 2-3% of vaccine recipients and 4% of placebo recipients reported severe effects. Researchers expressed concern that if Borrelia burgdorferi vaccine prevented early signs of LD but did not prevent the infection, some infected patients might not seek timely medical attention until later in the course of the disease. Sixty percent of the study subjects were followed for four years, and no cases of late LD have been found.2

Study Two

In the same issue of The New England Journal of Medicine,3 researchers reported a multicenter, double-blind, randomized study using a recombinant Borrelia burgdorferi outer-surface lipoprotein A (OspA) with adjuvant. The study design was similar to study one in that 10,936 subjects (ages 15-70) living in Lyme disease endemic areas were recruited and received injections of the LD vaccine or placebo at enrollment, and the injections were repeated one and 12 months later.

Subjects were recruited from 31 sites in 10 states. Blood samples were obtained from all subjects at the time of the first injection, and two, 12, and 20 months later. Serum samples obtained at 12 and 20 months were tested for IgG antibody to B. burgdorferi to detect asymptomatic infection. When indicated, antibiotic treatment was recommended based on published guidelines.4

The number of subjects evaluated for LD was 1109 in the first year and 808 in the second. In the first year, 11% met criteria for asymptomatic or possible LD, and in the second year, 18% met criteria. Twenty-two subjects in the vaccine group and 43 in the placebo group contracted LD in the first year. In the second year (after three injections), 16 in the vaccine group and 66 in the placebo group contracted the disease. Vaccine efficacy was determined to be 49% in the first year, but it increased to 76% in the second year.

When serum samples at 12 and 20 months and positive samples were retested with baseline samples, two subjects in the vaccine group and 13 in the placebo group had asymptomatic IgG seroconversion in the first year. In the second year, 15 subjects, all in the placebo group, had asymptomatic seroconversion. Vaccine efficacy was 83% in year one and 100% in year two.

More vaccine than placebo group subjects reported adverse reactions during the first three days after injection. After 30 or more days, no significant differences in symptoms were found between vaccine and placebo recipients.3

Vaccine Deemed Safe and Effective

Researchers from both studies reached the same conclusion: Recombinant B. burgdorferi vaccine is indeed safe and effective in preventing LD and had an acceptable rate of systemic or local side effects. However, work remains to be done. Study one researchers state, "Further studies will be needed to evaluate the vaccine in children and adolescents. In addition, although the booster dose clearly increased the efficacy of the vaccine in the second year of the study, the optimal regimen remains to be determined."2 Study two researchers write, "Moreover, it will be critical to determine the duration of protection afforded by three injections of vaccine and whether or when additional booster injections will be necessary. . . . This vaccine provides an important new public health approach to the prevention of Lyme disease."3

Implications for Practice

Research showing that a vaccine for LD is practical, safe, and effective is welcome news for beleagured health care providers in endemic areas who must deal annually with the difficult diagnosis and treatment decisions it demands. In addition, studies show significant health care resources are expended each year treating LD that turns out not to be LD but rather the fear of the disease.1

However, considerable research and testing must be done before a B. burgdorferi vaccine will be available for general use. In the meantime, clinicians need to become skilled in recognition and management of LD, especially in highly endemic areas. (For more information on symptoms, laboratory testing, antibiotic treatment, and resources on Lyme disease, see RN Advanced Practice Alert, September 1998, p. 16.) Patients need to be educated about LD, and now you can assure them that thanks to health care research, a safe and effective preventative immunization lies in the not too distant future. (For copy of a patient handout on LD, see RN APA, September 1998, insert.)

References

    1. Reid MC, Schoen RT, Evans J, et al. The consequences of overdiagnosis and overtreatment of Lyme disease: An observational study. Ann Int Med 1998;128:354-362.

    2. Sigal LH, Zahradnik JM, Lavin P, et al. A vaccine consisting of recombinant Borrella burgdorferi outer-surface protein A to prevent Lyme disease. NEJM 1998;339:216-222.

    3. Steere AC, Sikand VK, Meurice F, et al. Vaccination against Lyme disease with recombinant Borrelia burgdorferi outer-surface lipoprotein A with adjuvant. NEJM 1998;339:209-215.

    4. Rahn DW, Malawista SE. Lyme disease: Recommen dations for diagnosis and treatment. Ann Intern Med 1991;114:472-481.

Recommended Reading

    · Verdon ME, Sigal LH. Recognition and management of Lyme disease. Am Fam Phys 1997;56:427-440.

    · Unger JA. Lyme disease: diagnostic challenge, treatment enigma. RN Advanced Practice Alert 1998; 1:17-20.