Outbreak of tick-borne relapsing fever at the north rim of the Grand Canyon: evidence for effectiveness of preventive measures.

An outbreak of tick-borne relapsing fever (TBRF) originating at the North Rim of Grand Canyon National Park was investigated in 1990. To determine risk factors for the disease, almost 7,000 parties of visitors were surveyed; over half responded, representing > 10,000 people. Fifteen cases of confirmed or probable TBRF were identified in visitors and 2 in employees. All patients except one experienced symptoms after overnight stays in a group of cabins that had not been rodent-proofed after a TBRF outbreak in 1973 (relative risk for visitors [RR] 8.2, 95% confidence interval [CI] 1.1-62). Seven cases of TBRF were associated with a single cabin (RR 98, 95% CI 30-219). Structural flaws and rodent nests were common in the implicated cabins and rare in unaffected cabins. This investigation suggests that measures to rodent-proof cabins at sites where TBRF is endemic prevent reinfestation of cabins by infected rodents and tick vectors, thereby preventing the spread of disease in humans.

Evaluation of a two-test serodiagnostic method for community assessment of Lyme disease in an endemic area.

Epidemiological methods are needed to evaluate community exposure to Borrelia burgdorferi, the causative agent of Lyme disease (LD). For LD serodiagnosis, the Centers for Disease Control and Prevention (CDC) recommends a 2-test approach that involves enzyme immunoassay (EIA) testing and Western immunoblotting (WB) of EIA-equivocal and EIA-positive specimens. The specificity of this approach was evaluated among residents of a LD-endemic community and was compared with WB alone and with a simplified 2-test approach (WB of equivocal EIA only). Participants reporting no previous diagnosis of LD were recruited during a community-wide serosurvey on Block Island, Rhode Island. Of 80 eligible participants, 20 had received LD vaccine. Seven (35%) of 20 vaccinees and 22 (37%) of 60 nonvaccinees reported nonspecific symptoms compatible with LD in the previous year. In this highly LD-endemic community, the overall specificity of the CDC-recommended approach was highest (100%), followed by WB alone (98.7%), then the simplified approach (95%).

Prophylaxis with single-dose doxycycline for the prevention of Lyme disease after an Ixodes scapularis tick bite.

BACKGROUND: It is unclear whether antimicrobial treatment after an Ixodes scapularis tick bite will prevent Lyme disease. METHODS: In an area of New York where Lyme disease is hyperendemic we conducted a randomized, double-blind, placebo-controlled trial of treatment with a single 200-mg dose of doxycycline in 482 subjects who had removed attached I. scapularis ticks from their bodies within the previous 72 hours. At base line, three weeks, and six weeks, subjects were interviewed and examined, and serum antibody tests were performed, along with blood cultures for Borrelia burgdorferi. Entomologists confirmed the species of the ticks and classified them according to sex, stage, and degree of engorgement. RESULTS: Erythema migrans developed at the site of the tick bite in a significantly smaller proportion of the subjects in the doxycycline group than of those in the placebo group (1 of 235 subjects [0.4 percent] vs. 8 of 247 subjects [3.2 percent], P<0.04). The efficacy of treatment was 87 percent (95 percent confidence interval, 25 to 98 percent). Objective extracutaneous signs of Lyme disease did not develop in any subject, and there were no asymptomatic seroconversions. Treatment with doxycycline was associated with more frequent adverse effects (in 30.1 percent of subjects, as compared with 11.1 percent of those assigned to placebo; P<0.001), primarily nausea (15.4 percent vs. 2.6 percent) and vomiting (5.8 percent vs. 1.3 percent). Erythema migrans developed more frequently after untreated bites from nymphal ticks than after bites from adult female ticks (8 of 142 bites [5.6 percent] vs. 0 of 97 bites [0 percent], P=0.02) and particularly after bites from nymphal ticks that were at least partially engorged with blood (8 of 81 bites [9.9 percent], as compared with 0 of 59 bites from unfed, or flat, nymphal ticks [0 percent]; P=0.02). CONCLUSIONS: A single 200-mg dose of doxycycline given within 72 hours after an I. scapularis tick bite can prevent the development of Lyme disease.

Tularemia as a biological weapon: medical and public health management.

OBJECTIVE: The Working Group on Civilian Biodefense has developed consensus-based recommendations for measures to be taken by medical and public health professionals if tularemia is used as a biological weapon against a civilian population. PARTICIPANTS: The working group included 25 representatives from academic medical centers, civilian and military governmental agencies, and other public health and emergency management institutions and agencies. EVIDENCE: MEDLINE databases were searched from January 1966 to October 2000, using the Medical Subject Headings Francisella tularensis, Pasteurella tularensis, biological weapon, biological terrorism, bioterrorism, biological warfare, and biowarfare. Review of these references led to identification of relevant materials published prior to 1966. In addition, participants identified other references and sources. CONSENSUS PROCESS: Three formal drafts of the statement that synthesized information obtained in the formal evidence-gathering process were reviewed by members of the working group. Consensus was achieved on the final draft. CONCLUSIONS: A weapon using airborne tularemia would likely result 3 to 5 days later in an outbreak of acute, undifferentiated febrile illness with incipient pneumonia, pleuritis, and hilar lymphadenopathy. Specific epidemiological, clinical, and microbiological findings should lead to early suspicion of intentional tularemia in an alert health system; laboratory confirmation of agent could be delayed. Without treatment, the clinical course could progress to respiratory failure, shock, and death. Prompt treatment with streptomycin, gentamicin, doxycycline, or ciprofloxacin is recommended. Prophylactic use of doxycycline or ciprofloxacin may be useful in the early postexposure period.

An outbreak of primary pneumonic tularemia on Martha's Vineyard.

BACKGROUND: In the summer of 2000, an outbreak of primary pneumonic tularemia occurred on Martha's Vineyard, Massachusetts. The only previously reported outbreak of pneumonic tularemia in the United States also occurred on the island in 1978. METHODS: We conducted a case-control study of adults with pneumonic tularemia and investigated the environment to identify risk factors for primary pneumonic tularemia. Patients with confirmed cases were residents of or visitors to Martha's Vineyard who had symptoms suggestive of primary pneumonic tularemia, were ill between May 15 and October 31, 2000, and had a positive laboratory test for tularemia. Controls were adults who had spent at least 15 days on Martha's Vineyard between May 15 and September 28, 2000. RESULTS: We identified 15 patients with tularemia; 11 of these cases were primary pneumonic tularemia. Francisella tularensis type A was isolated from blood and lung tissue of the one man who died. Patients were more likely than controls to have used a lawn mower or brush cutter in the two weeks before the illness or before an interview, for controls (odds ratio, 9.2; 95 percent confidence interval, 1.6 to 68.0) and during the summer (odds ratio, undefined; 95 percent confidence interval, 1.8 to infinity). Lawn mowing and brush cutting remained significant risk factors after adjustment for other potentially confounding variables. Only one patient reported being exposed to a rabbit while cutting brush. Of 40 trapped animals, 1 striped skunk (Mephitis mephitis) and 1 Norway rat (Rattus norvegicus) were seropositive for antibodies against F. tularensis. CONCLUSIONS: Study of this outbreak of primary pneumonic tularemia implicates lawn mowing and brush cutting as risk factors for this infection.

Serodiagnosis of Louse-Borne relapsing fever with glycerophosphodiester phosphodiesterase (GlpQ) from Borrelia recurrentis.

Human louse-borne relapsing fever occurs in sporadic outbreaks in central and eastern Africa that are characterized by significant morbidity and mortality. Isolates of the causative agent, Borrelia recurrentis, were obtained from the blood of four patients during a recent epidemic of the disease in southern Sudan. The glpQ gene, encoding glycerophosphodiester phosphodiesterase, from these isolates was sequenced and compared with the glpQ sequences obtained from other relapsing-fever spirochetes. Previously we showed that GlpQ of Borrelia hermsii is an immunogenic protein with utility as a serological test antigen for discriminating tick-borne relapsing fever from Lyme disease. In the present work, we cloned and expressed the glpQ gene from B. recurrentis and used recombinant GlpQ in serological tests. Acute- and convalescent-phase serum samples obtained from 42 patients with louse-borne relapsing fever were tested with an indirect immunofluorescence assay (IFA) and an enzyme-linked immunosorbent assay (ELISA) that used whole cells of B. recurrentis and with immunoblotting to whole-cell lysates of the spirochete and Escherichia coli producing recombinant GlpQ. The geometric mean titers of the acute- and convalescent-phase serum samples measured by IFA were 1:83 and 1:575, respectively. The immunoblot analysis identified a high level of reactivity and seroconversion to GlpQ, and the assay was more sensitive than the whole-cell IFA and ELISA using purified, recombinant histidine-tagged GlpQ. Serum antibodies to GlpQ and other antigens persisted for 27 years in one patient. We conclude that assessment of anti-GlpQ antibodies will allow serological confirmation of louse-borne relapsing fever and determination of disease prevalence.

Cases of cat-associated human plague in the Western US, 1977-1998.

Exposure to cats infected with Yersinia pestis is a recently recognized risk for human plague in the US. Twenty-three cases of cat-associated human plague (5 of which were fatal) occurred in 8 western states from 1977 through 1998, which represent 7.7% of the total 297 cases reported in that period. Bites, scratches, or other contact with infectious materials while handling infected cats resulted in 17 cases of bubonic plague, 1 case of primary septicemic plague, and 5 cases of primary pneumonic plague. The 5 fatal cases were associated with misdiagnosis or delays in seeking treatment, which resulted in overwhelming infection and various manifestations of the systemic inflammatory response syndrome. Unlike infections acquired by flea bites, the occurrence of cat-associated human plague did not increase significantly during summer months. Plague epizootics in rodents also were observed less frequently at exposure sites for cases of cat-associated human plague than at exposure sites for other cases. The risk of cat-associated human plague is likely to increase as residential development continues in areas where plague foci exist in the western US. Enhanced awareness is needed for prompt diagnosis and treatment.

Plague as a biological weapon: medical and public health management. Working Group on Civilian Biodefense.

OBJECTIVE: The Working Group on Civilian Biodefense has developed consensus-based recommendations for measures to be taken by medical and public health professionals following the use of plague as a biological weapon against a civilian population. PARTICIPANTS: The working group included 25 representatives from major academic medical centers and research, government, military, public health, and emergency management institutions and agencies. EVIDENCE: MEDLINE databases were searched from January 1966 to June 1998 for the Medical Subject Headings plague, Yersinia pestis, biological weapon, biological terrorism, biological warfare, and biowarfare. Review of the bibliographies of the references identified by this search led to subsequent identification of relevant references published prior to 1966. In addition, participants identified other unpublished references and sources. Additional MEDLINE searches were conducted through January 2000. CONSENSUS PROCESS: The first draft of the consensus statement was a synthesis of information obtained in the formal evidence-gathering process. The working group was convened to review drafts of the document in October 1998 and May 1999. The final statement incorporates all relevant evidence obtained by the literature search in conjunction with final consensus recommendations supported by all working group members. CONCLUSIONS: An aerosolized plague weapon could cause fever, cough, chest pain, and hemoptysis with signs consistent with severe pneumonia 1 to 6 days after exposure. Rapid evolution of disease would occur in the 2 to 4 days after symptom onset and would lead to septic shock with high mortality without early treatment. Early treatment and prophylaxis with streptomycin or gentamicin or the tetracycline or fluoroquinolone classes of antimicrobials would be advised.

Surveillance for Lyme disease--United States, 1992-1998.

PROBLEM/CONDITION: Lyme disease is caused by infection with the spirochete Borrelia burgdorferi and is the most commonly reported vector-borne disease in the United States. Borrelia burgdorferi is transmitted to humans by infected Ixodes scapularis and I. pacificus ticks. Lyme disease is typically evidenced in its early stage by a characteristic rash (erythema migrans), accompanied by nonspecific symptoms (e.g., fever, malaise, fatigue, headache, myalgia, and arthralgia). Lyme disease can usually be treated successfully with standard antibiotic regimens. REPORTING PERIOD: 1992-1998. DESCRIPTION OF SYSTEM: Lyme disease surveillance data are reported to CDC through the National Electronic Telecommunication System for Surveillance, a computerized public health database for nationally notifiable diseases. During 1992-1998, data regarding reported cases of Lyme disease included county and state of residence, age, sex, and date of onset. Descriptive analyses were performed, and cumulative incidence by state, county, age group, and sex were calculated. RESULTS: During 1992-1998, a total of 88,967 cases of Lyme disease was reported to CDC by 49 states and the District of Columbia, with the number of cases increasing from 9,896 in 1992 to 16,802 in 1998. A total of 92% of cases was reported from eight northeastern and mid-Atlantic states and two north-central states. Children aged 5-9 years and adults aged 45-54 years had the highest mean annual incidence. INTERPRETATION: Lyme disease is a highly focal disease, with the majority of reported cases occurring in the northeastern and north-central United States. The number of reported cases of Lyme disease increased during 1992-1998. Geographic and seasonal patterns of disease correlate with the distribution and feeding habits of the vector ticks, I. scapularis and I. pacificus. PUBLIC HEALTH ACTION: The results presented in this report will help clinicians evaluate the prior probability of Lyme disease and provide the framework for targeting human Lyme disease vaccine use and other prevention and treatment interventions.

The cost effectiveness of vaccinating against Lyme disease.

To determine the cost effectiveness of vaccinating against Lyme disease, we used a decision tree to examine the impact on society of six key components. The main measure of outcome was the cost per case averted. Assuming a 0.80 probability of diagnosing and treating early Lyme disease, a 0.005 probability of contracting Lyme disease, and a vaccination cost of $50 per year, the mean cost of vaccination per case averted was $4,466. When we increased the probability of contracting Lyme disease to 0.03 and the cost of vaccination to $100 per year, the mean net savings per case averted was $3,377. Since few communities have average annual incidences of Lyme disease >0. 005, economic benefits will be greatest when vaccination is used on the basis of individual risk, specifically, in persons whose probability of contracting Lyme disease is >0.01.

Evaluation of two-test serodiagnostic method for early Lyme disease in clinical practice.

The Centers for Disease Control and Prevention (CDC) recommend a two-test approach for the serodiagnosis of Lyme disease (LD), with EIA testing followed by Western immunoblotting (WB) of EIA-equivocal and -positive specimens. This approach was compared with a simplified two-test approach (WB of EIA equivocals only) and WB alone for early LD. Case-patients with erythema migrans (EM) rash >/=5 cm were recruited from three primary-care practices in LD-endemic areas to provide acute- (S1) and convalescent-phase serum specimens (S2). The simplified approach had the highest sensitivity when either S1 or S2 samples were tested, nearly doubling when S2 were tested, while decreasing slightly for the other two approaches. Accordingly, the simplified approach had the lowest negative likelihood ratio for either S1 or S2. For early LD with EM, the simplified approach performed well and was less costly than the other testing approaches since less WB is required.

Reported distribution of Ixodes scapularis and Ixodes pacificus (Acari: Ixodidae) in the United States.

Lyme disease, caused by infection with Borrelia burgdorferi, is the most frequently reported arthropod-borne disease in the United States. To develop a national map of the distribution of the vectors of B. burgdorferi to humans (Ixodes scapularis Say and Ixodes pacificus Cooley & Kohls ticks), we sent questionnaires to acarologists, health officials, and Lyme disease researchers; surveyed the 1966-1996 MEDLINE data base; and reviewed 1907-1995 National Tick Collection data. Tick collection methods cited included flagging and dragging, deer surveys, small- and medium-sized mammal surveys, CO2 baiting, and receipt of tick submissions. A total of 1,058 unique, county-specific I. scapularis and I. pacificus records was obtained. Tick populations were classified as "reported" (< 6 ticks and 1 life stage identified) or "established" (> or = 6 ticks or > 1 life stage identified). Established populations of I. scapularis were identified in 396 counties in 32 states in the eastern and central United States, whereas established populations of I. pacificus were found in 90 counties in 5 western states. Counties with established populations were most concentrated in the northeastern, upper northcentral, and west-coastal states but were also clustered in southeastern and Gulf-coastal states. A less concentrated distribution was found in the south-central states. Reports were notably missing from all but a few counties in Ohio, West Virginia, western Virginia and North Carolina, Kentucky, and Tennessee. They were absent in the Great Plains and Rocky Mountain regions and from large areas of western states east of the Cascade and Sierra Nevada cordilleras. These data are useful for identifying areas of Lyme disease risk, for targeting Lyme disease prevention strategies, and for monitoring trends in spatial distribution of Lyme disease vector ticks.

Emergence of Lyme disease in Hunterdon County, New Jersey, 1993: a case-control study of risk factors and evaluation of reporting patterns.

Reported cases of Lyme disease in Hunterdon County, New Jersey, increased almost 200% from 75 (67/100,000 population) in 1992 to 216 (193/100,000 population) in 1993. For evaluation of risk factors for Lyme disease and for determination of the cause of this increase, a case-control study was conducted, and the reporting practices of physicians' offices were evaluated. For cases reported in 1993, age and sex distribution, month of disease onset, and proportion of cases with erythema migrans rash were within expected limits. Analysis of age-matched case-control data showed that rural residence; clearing periresidential brush during spring and summer months; and the presence of rock walls, woods, deer, or a bird feeder on residential property were associated with incident Lyme disease. A review of physician reporting patterns suggested that the increase in reported cases in 1993 was due to improved reporting as well as to an increase in the numbers of patients diagnosed with Lyme disease. In addition, substantial underreporting of Lyme disease by physicians' offices was found.

Altered growth of transgenic tobacco lacking leaf cytosolic pyruvate kinase.

Previously, we reported that transformation of tobacco (Nicotiana tabacum L.) with a vector containing a potato cytosolic pyruvate kinase (PKc) cDNA generated two plant lines specifically lacking leaf PKc (PKc-) as a result of co-suppression. PKc deficiency in these primary transformants did not appear to alter plant development, although root growth was not examined. Here we report a striking reduction in root growth of homozygous progeny of both PKc- lines throughout development under moderate (600 microE m-2 s-1) or low (100 microE m-2 s-1) light intensities. When both PKc- lines were cultivated under low light, shoot and flower development were also delayed and leaf indentations were apparent. Leaf PK activity in the transformants was significantly decreased at all time points examined, whereas root activities were unaffected. Polypeptides corresponding to PKc were undetectable on immunoblots of PKc- leaf extracts, except in 6-week-old low-light-grown PKc- plants, in which leaf PKc expression appeared to be greatly reduced. The metabolic implications of the kinetic characteristics of partially purified PKc from wild-type tobacco leaves are discussed. Overall, the results suggest that leaf PKc deficiency leads to a perturbation in source-sink relationships.

Test-treatment strategies for patients suspected of having Lyme disease: a cost-effectiveness analysis.

PURPOSE: To examine the cost-effectiveness of test-treatment strategies for patients suspected of having Lyme disease. DATA SOURCES: The medical literature was searched for information on outcomes and costs. Expert opinion was sought for information on utilities. STUDY SELECTION: Articles that described patient population, diagnostic criteria, dose and duration of therapy, and criteria for assessment of outcomes. DATA EXTRACTION: The decision analysis evaluated the following strategies: 1) no testing-no treatment; 2) testing with enzyme-linked immunosorbent assay (ELISA) followed by antibiotic treatment of patients with positive results; 3) two-step testing with ELISA followed by Western blot and antibiotic treatment for patients with positive results on either test; and 4) empirical antibiotic therapy. Three patient scenarios were considered: myalgic symptoms, rash resembling erythema migrans, and recurrent oligoarticular inflammatory arthritis. Results were calculated as costs per quality-adjusted life-year and were subjected to sensitivity analysis. Adjustment was made for the diagnostic value of common clinical features of Lyme disease. DATA SYNTHESIS: For myalgic symptoms without other features suggestive of Lyme disease, the no testing-no treatment strategy was most economically attractive (that is, had the most favorable cost-effectiveness ratio). For rash, empirical antibiotic therapy was less costly and more effective than other strategies. For oligoarticular arthritis with a history of rash and tick bite, two-step testing was associated with the lowest cost-effectiveness ratio. Testing with ELISA and empirical antibiotic therapy cost an additional $880,000 and $34,000 per quality-adjusted life-year, respectively. For oligoarticular arthritis with one or no other features suggestive of Lyme disease, two-step testing was most economically attractive. CONCLUSIONS: Neither testing nor antibiotic treatment is cost-effective if the pretest probability of Lyme disease is low. Empirical antibiotic therapy is recommended if the pretest probability is high, and two-step testing is recommended if the pretest probability is intermediate.

Laboratory evaluation in the diagnosis of Lyme disease.

PURPOSE: To provide a qualitative evaluation of the predictive value of the laboratory diagnosis of Lyme disease and to use the resultant data to formulate guidelines for clinical diagnosis. DATA SOURCES: A MEDLINE search of English-language articles or articles with English-language abstracts published from 1982 to 1996. DATA EXTRACTION: Sensitivity, specificity, and likelihood ratios were calculated, and a random-effects model was used to combine the proportions from the eligible studies. Prespecified criteria were used to determine which studies were eligible for analysis. DATA SYNTHESIS: Laboratory testing in general is not clinically useful if the pretest probability of Lyme disease is less than 0.20 or greater than 0.80. When the pretest probability is 0.20 to 0.80, sequential testing with enzyme-linked immunosorbent assay and Western blot is the most accurate method for ruling in or ruling out the possibility of Lyme disease. CONCLUSIONS: Laboratory testing is recommended only in patients whose pretest probability of Lyme disease is 0.20 to 0.80. If the pretest probability is less than 0.20, testing will result in more false-positive results than true-positive results; a negative test result in this situation effectively rules out the disease.