Development of self-anchoring bone implants. II. Bone-implant interface characteristics in vitro

The number of reported cases of Lyme disease in the United States has increased steadily since 1982, and the increase coincides with a growth in deer populations in endemic regions. Application of careful epidemiologic principles has led to the identification of two new pathogens that produce syndromes closely related to Lyme disease. Coinfection with other pathogens such as Babesia has been shown to alter the clinical course of Lyme disease. Better understanding of the pathogenesis of Lyme disease has provided clues into the mechanisms responsible for persistent symptoms and will serve as a foundation for the design and implementation of appropriate therapic recommendations. A safe vaccine for the prevention of Lyme disease in humans has been developed, and clinical vaccine efficacy trials are close to completion.     

Lyme arthritis as the incorrect diagnosis in pediatric and adolescent fibromyalgia

In areas endemic for Lyme disease there is increasing concern and anxiety about possible chronic and untreatable manifestations of the disease. The authors have diagnosed fibromyalgia in many patients with chronic musculoskeletal complaints in whom chronic Lyme arthritis had previously been diagnosed as the cause of their joint pains. Fibromyalgia is a common disorder, causing arthralgia (not true arthritis), fatigue, and debility. The repeated and/or long-term antibiotic therapy prescribed for "chronic Lyme disease" is not successful in curing the symptoms of fibromyalgia. Especially in areas where anxiety about Lyme disease is great, it is important to be careful in diagnosing chronic Lyme disease. Fibromyalgia is a potentially treatable and curable cause of chronic complaints and should be considered in the differential diagnosis of "refractory Lyme arthritis."     

Direct effects of luteal regression on anterior pituitary response to GNRH

BACKGROUND: The risk of acquiring Lyme disease is high in areas in which the disease is endemic, and the development of a safe and effective vaccine is therefore important. METHODS: We conducted a multicenter, double-blind, randomized trial involving 10,936 subjects who lived in areas of the United States in which Lyme disease is endemic. Participants received an injection of either recombinant Borrelia burgdorferi outer-surface lipoprotein A (OspA) with adjuvant or placebo at enrollment and 1 and 12 months later. In cases of suspected Lyme disease, culture of skin lesions, polymerase-chain-reaction testing, or serologic testing was done. Serologic testing was performed 12 and 20 months after study entry to detect asymptomatic infections. RESULTS: In the first year, after two injections, 22 subjects in the vaccine group and 43 in the placebo group contracted definite Lyme disease (P=0.009); vaccine efficacy was 49 percent (95 percent confidence interval, 15 to 69 percent). In the second year, after the third injection, 16 vaccine recipients and 66 placebo recipients contracted definite Lyme disease (P<0.001); vaccine efficacy was 76 percent (95 percent confidence interval, 58 to 86 percent). The efficacy of the vaccine in preventing asymptomatic infection was 83 percent in the first year and 100 percent in the second year. Injection of the vaccine was associated with mild-to-moderate local or systemic reactions lasting a median of three days. CONCLUSIONS: Three injections of vaccine prevented most definite cases of Lyme disease or asymptomatic B. burgdorferi infection.     

Human granulocytic ehrlichiosis in a renal transplant patient: case report and review of the literature

BACKGROUND: Human ehrlichiosis, a newly described zoonotic infection, can be classified as human monocytic ehrlichiosis (HME) or human granulocytic ehrlichiosis (HGE). Although the clinical manifestations of HME and HGE are similar, the type of leukocyte infected, the etiologic agent, and the tick vector are distinct. METHODS: We report the first case of HGE in a solid organ transplant recipient and review the literature on HGE. RESULTS: Our patient displayed typical epidemiological, clinical, and laboratory features and responded promptly to therapy with doxycycline. CONCLUSIONS: Although opportunistic infections are relatively common in the posttransplant population, one must always consider other infections that occur in normal hosts as well. Human ehrlichiosis should be included in the differential diagnosis for transplant patients with fever, cytopenias, and hepatitis, especially if exposure to ticks in endemic areas has occurred.     

Host-pathogen interactions in the immunopathogenesis of Lyme disease

The immunopathogenesis of Lyme disease is complicated and requires a thorough understanding of the interaction among the causative organism, Borrelia burgdorferi, its tick vector, and its mammalian hosts. In vitro, animal and human studies have shown that the organism is capable of adapting to and utilizing elements from its environment to establish infection and persist despite a inducing a strong immune response. Indeed, the immune response may be responsible for many of the symptoms associated with Lyme disease. It appears that humoral immunity plays the greatest role in clearance of the organism. Cytokines released by Th 1 or Th 2 subsets of CD4+ cells have been shown to play an important role in determining outcome of the disease in animal models possibly through their effects on immunoglobulin class switching. In the small percentage of patients who have treatment resistant chronic Lyme disease, autoimmune mechanisms may play a role in persistent disease.     

Killing of Borrelia burgdorferi by antibody elicited by OspA vaccine is inefficient in the absence of complement

A Lyme disease vaccine, based on the Borrelia burgdorferi lipoprotein OspA, has recently undergone phase III trials in humans. The results of one of these trials indicate that vaccine efficacy positively correlates with anti-OspA antibody titer. Spirochete killing within the tick vector midgut, upon which vaccine efficacy appears to depend, may occur chiefly via a mechanism that involves antibody alone, as it has been reported that complement is degraded by tick saliva decomplementing factors. We compared the in vitro killing efficiencies of anti-OspA antibody elicited in rhesus monkeys by the OspA vaccine, in the presence and in the absence of monkey complement. Killing in the absence of complement was between 14 and 3,800 times less efficient than with complement present, depending on the spirochete strain. The relative inefficiency of the complement-independent killing mechanism by anti-OspA antibody may explain why OspA vaccine efficacy is critically dependent on antibody titer.     

Ticks and tick-borne diseases in Oklahoma

Tick-borne diseases are common in Oklahoma, especially the eastern part of the state where tick prevalence is highest. Three species of hard ticks are present in Oklahoma that are known vectors of human disease--the American dog tick (Rocky Mountain spotted fever; RMSF), the lone star tick (ehrlichiosis) and the black-legged tick (Lyme disease). Oklahoma consistently ranks among the top states in numbers of reported RMSF cases, and Ehrlichiosis may be as prevalent as RMSF. Although Lyme disease is frequently reported in Oklahoma, over-diagnosing of this disease due to false-positive test results is common; positive or equivocal screening tests should be confirmed by Western immunoblot. At present, it is unclear whether the disease seen here is Lyme disease or another Lyme-like disease. If true Lyme disease is present in the state, it is probably rare. Physicians should be aware of the most recent recommendations for diagnosis, therapy and prevention of tick-borne diseases.     

Geographic risk for lyme disease and human granulocytic ehrlichiosis in southern New York state

Ixodes scapularis, the tick vector of Lyme disease and human granulocytic ehrlichiosis (HGE), is prevalent in much of southern New York state. The distribution of this species has increased, as have reported cases of both Lyme disease and HGE. The unreliability of case reports, however, demonstrates the need for tick and pathogen surveillance in order to accurately define areas of high risk. In this study, a total of 89,550 m2 at 34 study sites was drag sampled in 1995 and a total of 51,540 m2 at 40 sites was sampled in 1996 to determine tick and pathogen distribution in southern New York state. I. scapularis was collected from 90% of the sites sampled, and regionally, a 2.5-fold increase in nymphal abundance occurred from 1995 to 1996. I. scapularis individuals from all sites were infected with Borrelia burgdorferi in 1995, while an examination of ticks for both B. burgdorferi and the agent of HGE in 1996 confirmed that these organisms were present in all counties; the average coinfection rate was 1.9%. No correlation was found between estimated risk and reported cases of Lyme disease. The geographic disparity of risk observed among sites in this study underscores the need for vector and pathogen surveillance on a regional level. An entomologic risk index can help identify sites for targeted tick control efforts.     

Lyme disease, Rocky Mountain spotted fever, ehrlichiosis: emerging and established challenges for the clinician

OBJECTIVE: The goal of this review is to facilitate the management of patients with tick-associated diseases. This article will discuss the epidemiology, clinical diagnosis, and antimicrobial therapy of Lyme disease, Rocky Mountain spotted fever, and ehrlichiosis. DATA SOURCES: References are limited to the English language and extend back to the beginning of the twentieth century. The human and veterinary literature were reviewed. Sources include computerized databases and bibliographies of recent articles and books. STUDY SELECTION: Papers were selected on the basis of their timeliness, explanation of important findings by major investigators, extrapolation of clinical data from large patient populations, and clarification of controversial issues. Approximately 50% of the articles initially reviewed are included in the bibliography. RESULTS: Standardization of laboratory testing for Lyme disease should facilitate more accurate diagnosis in the future. Clinical diagnosis of Rocky Mountain spotted fever and ehrlichiosis prior to laboratory confirmation is necessary in order to ensure timely institution of antimicrobial therapy. CONCLUSIONS: Knowledge of endemic regions and seasonal cycles of vectors, varying clinical presentations of disease and appropriate utilization of the laboratory are critical for the appropriate diagnosis and management of patients with tick-associated diseases.     

Rheumatic manifestations in Lyme borreliosis: personal experience in patients with oligoarthritis of "unknown" origin

Lyme borreliosis is an infectious illness caused by the spirochete Borrelia burgdorferi and is transmitted by tick vectors. A prospective study was performed from January 1990, to investigate whether Lyme arthritis might have been undetected among patients with (unclassified arthritis) oligoarthritis of "unknown" aetiology. 210 patients were tested for antibodies to Borrelia burgdorferi: 82 patients with oligoarthritis of "unknown" aetiology; 52 patients with Reiter's syndrome; 20 patients with seronegative, B-27 positive oligoarthritis and 56 controls. Serological testing for Borrelia burgdorferi was performed by indirect immunofluorescence assay. The occurrence of positive antibodies (1:80) in 11 (13.4%) patients with arthritis of "unknown" aetiology was significantly different from the combined control group (1.6%) (p < 0.05). Four out of 11 patients remembered a tick bite, two out of 11 patients developed erythema migrans after 3 to 10 days. Six weeks later 2 patients developed oligoarthritis and one patient after a month. In the remaining 8 patients arthritis was the first sign of the disease. Knees were most commonly affected (90%). Radiographic abnormalities (osteoporosis, soft tissue swelling) were noted in 3 patients. The synovial fluid findings were typical for inflammatory arthritides in 6 patients. The diagnosis of Lyme borreliosis was made according to following data: origin from an area endemic for Lyme borreliosis, tick bite, erythema migrans, significant levels of the antibodies to the Borrelia burgdorferi and oligoarthritis. It can be concluded that arthritis may be the main manifestation of Borrelia burgdorferi infection.     

Ear dominance and telephone sales

BACKGROUND: Lyme disease is caused by Borrelia burgdorferi which is transmitted in Europe by the tick ixodes ricinus. Erythema migrans is a skin lesion which is pathognomonic of Lyme disease. A retrospective study was carried out to determine the geographical distribution of the occurrence of tick bites and erythema migrans in the Netherlands and to identify ecological risk factors. METHODS: In April 1995, all general practitioners (GPs) in the Netherlands were asked to complete a postal questionnaire on the number of tick bites and erythema migrans case-patients seen in 1994 and the size of the practice. Reminders were sent to non-responders. Information on ecological risk factors by local government area was obtained from a geographical information system. RESULTS: The response rate was 79.9%. In 1994, GPs reported seeing approximately 33,000 patients with tick bites and 6500 with erythema migrans. The incidence rate of erythema migrans was estimated at 4.3 per 10,000 population. Ecological risk factors for both tick bites and erythema migrans were the proportion of the area covered by woods, sandy soil, dry uncultivated land, the number of tourist-nights per inhabitant and sheep population density. The cattle population density was a risk factor for erythema migrans. CONCLUSIONS: Using simple methods, a crude estimate of the incidence rate of erythema migrans was obtained rapidly, and high risk areas were identified. Lyme disease appears to be an important problem in the Netherlands.     

Tick-borne diseases in Texas: a 10-year retrospective examination of cases

The occurrence of Rocky Mountain spotted fever, human monocytotropic ehrlichiosis, tularemia, tick-borne relapsing fever, and a southern erythema migrans-like illness (Lyme/Lyme-like disease) is determined by the geographic distribution and seasonal activity of the particular vector tick(s). The flulike signs and symptoms early in the course of spotted fever rickettsiosis, ehrlichiosis, tularemia, and relapsing fever are nonspecific and do not readily suggest a particular diagnosis. Laboratory diagnosis, particularly during the acute stage of illness, often is elusive. Empiric treatment with doxycycline can be lifesaving for Rocky Mountain spotted fever and ehrlichiosis. This article provides insight into the significance of each of these tick-transmitted diseases in Texas.     

The timing of color and location processing in the motor context

The contribution of migratory and resident birds to the introduction of Lyme disease will vary with the degree to which various species expose themselves to, and are infested by, juvenile vector ticks, and their ability to support and transmit the infectious agent. To examine the relative contribution of various passerine species during the emergence of this disease, we compared the abundance and infection rates of the blacklegged tick, Ixodes scapularis Say, removed from mist-netted birds with those from live-trapped mice at a coastal study site in southern Maine, collected during an 8-yr period in which the range of this tick and the incidence of Lyme disease increased in the state. Weekly bird-banding sessions using six 12-m Japanese mist nets were carried out from May through August 1989-1996. In 1989, 1991 and 1993, mice were live-trapped in a Sherman trap grid (7 by 7 m) during five 3-night sessions, June through August; in 1994-1996, 2 such grids were similarly trapped. Annual adult tick abundance was estimated by flagging vegetation. We removed 2,633 juvenile deer ticks from 1,713 of 1,972 birds examined. Twenty-five of 64 bird species were infested. The percentages of birds infested and the rate of infection among removed larvae and nymphs increased over the years, but species varied markedly in their ability to infect ticks. No infected larvae were removed from catbirds or towhees. The larval to nymphal ratio was higher in mice than in birds. Infection rates among bird-derived larvae were less than among mice-derived larvae, but increased with time. Because of the different ways in which individual species of passerine birds contribute to the availability of vector ticks and respond to the agent of Lyme disease in emerging areas, further research into host competency and borreliacidal mechanisms is needed.     

A simple technical modification for abdominal cardiac transplantation in rats

We report herein the first laboratory-diagnosed case of Lyme disease in a human in Taiwan. A 45-year-old Taiwanese man living in Taipei, in northern Taiwan, had an expanding skin lesion (measuring 23 by 15 cm) on his abdomen for 2 to 3 weeks and recurrent attacks of pain and swelling of the knee joint. Serologic tests indicated a significantly elevated titer of antibody to Borrelia burgdorferi. After appropriate antibiotic treatment for 3 weeks, the skin lesion was cured and the joint swelling was improved. Although several strains of Borrelia spirochetes had been isolated from rodents (Rattus losea) in Taiwan, the tick vector responsible for the transmission remains to be identified.     

Early Lyme disease: a flu-like illness without erythema migrans

The existence of a form of early Lyme disease characterized by a flu-like illness without erythema migrans is controversial. To confirm the existence and define the clinical characteristics of the flu-like illness without erythema migrans of localized Lyme disease, the authors studied patients from a Lyme disease endemic area of Connecticut who visited their primary care physicians with an undefined flu-like illness. Patients kept a diary of their symptoms. Acute and convalescent sera were obtained. The diagnosis of Lyme disease was based on the appearance of IgM or IgG antibodies to Borrelia burgdorferi as demonstrated by both enzyme-linked immunosorbent assay and immunoblot assay. Twenty-four untreated patients were studied. In five patients acute serologic evidence of Lyme disease developed. The flu-like illness in these five patients was characterized by fever and fatigue and resolved spontaneously in 5 to 21 days. Symptoms recurred in three of these five patients. The existence of a flu-like illness without erythema migrans of early Lyme disease has been clearly established. Prospective, controlled studies are needed to better define its incidence, characteristics, and prognosis so that appropriate diagnostic and therapeutic strategies can be developed.     

Differential expression of Borrelia burgdorferi genes during erythema migrans and Lyme arthritis

Borrelia burgdorferi, the agent of Lyme disease, selectively expresses genes in the arthropod vector and mammalian host. Specific B. burgdorferi gene expression during human infection was examined in tissue specimens, using RNA-polymerase chain reaction, from 3 patients with Lyme disease. ospA was investigated because OspA is down-regulated by B. burgdorferi in ticks during engorgement and is a vaccine candidate in phase III clinical trials. p35 and p37 were also assessed because these genes are induced by spirochetes during murine Lyme borreliosis and play roles in protective immunity. p35 and p37 mRNA were detected in erythema migrans biopsy specimens from 2 patients and in the synovium of 1 patient with Lyme arthritis. ospA mRNA was not identified in any of these tissues. These data show that ospA is repressed while p35 and p37 are induced in human infection; these results are the first direct demonstration of differential B. burgdorferi gene expression during Lyme disease.     

Physician-diagnosed erythema migrans and erythema migrans-like rashes following Lone Star tick bites

OBJECTIVE: To differentiate cases of physician-diagnosed erythema migrans and erythema migrans-like rashes associated with Lone Star tick (Amblyomma americanum) bites. DESIGN: Retrospective case series. SETTING: Private primary care clinic in rural Missouri. PATIENTS: Seventeen patients with physician-diagnosed erythema migrans following a definite Lone Star tick bite at the rash site. INTERVENTIONS: A biopsy was performed on all rash sites. All patients were treated with oral antibiotics. MAIN OUTCOME MEASURES: Rash appearance, size, body location, multiple lesions, incubation times, associated symptoms, seasonal occurrence, histopathological features, tick stage and sex, patient age and sex, treatment response, growth in BSK II culture media, and serologic evaluation. RESULTS: Rashes associated with Lone Star ticks were similar to erythema migrans vectored by other Ixodes ticks. Differences were noted in Lyme disease serology results, especially flagellin-based enzyme immunoassays, and failure to yield spirochetes in BSK II cultures. Lyme serology results were often negative, but were also frequently inconsistent with results of controls without Lyme disease. CONCLUSIONS: Lone Star ticks are associated with rashes that are similar, if not identical, to erythema migrans associated with borrelial infection. The recent isolation and cultivation of Borrelia burgdorferi from ticks (including 1 Lone Star tick) from the farm of a patient included in this report has raised the possibility that Lone Star ticks are "bridge vectors" for human borrelial infection. Although further investigation is needed, these rashes may be secondary to spirochetal infection.     

Lyme disease in children and adolescents

148 children and adolescents with Lyme borreliosis and tick bite or suspection on tick bite were examined. The examined patients were aged from 14 months to 24 years and divided into four age groups. Skin lesions were discovered in 25 percent of patients with tick bite. Erythema migrans occurred in 91 percent, Lymphocytoma in 3 percent and sclerodermatous lesions (Lichen sclerosus et atrophicus and Morphea) in 6 percent of patients with Lyme disease. Serologic tests on the presence of antibodies to Borreliae burgdorferi were performed in 96 percent of cases with tick bite. Antibody titer 1:80 or higher in 8 percent of patients with tick bite, was discovered. We found positive serologic test results in 5 (29 percent) of 29 persons with Erythema migrans, in 4 (4 percent) of 110 patients with tick bite (without skin lesions), as well as, in 1 patient with Lymphocytoma. Antibiotic therapy was applied in all cases with Erythema migrans, in person with Lymphocytoma, as well as, in patients with asymptomatic infections (patients without skin lesion recalling a tick bite and with antibodies against Borrelia burgdorferi). A general sensitivity, to infection with Borrelia burgdorferi, is stressed, a fact based on appearance by Lyme borreliosis in all age groups even in the newborn children.     

Temporal correlations between tick abundance and prevalence of ticks infected with Borrelia burgdorferi and increasing incidence of Lyme disease

The abundance of host-seeking Ixodes scapularis nymphs, the principal vector for the Lyme disease agent, Borrelia burgdorferi, in Old Lyme, Lyme, and East Haddam, Connecticut, was compared with the incidence of reported human Lyme disease in the 12-town area around the Connecticut River and the State of Connecticut for the period 1989 to 1996. Ticks were sampled from lawns and woodlands by dragging flannel over the vegetation and examined for the presence of B. burgdorferi by indirect fluorescent antibody staining. The infection rate of the nymphal ticks by B. burgdorferi during the 9-year period was 14.3% (of 3,866), ranging from 8.6% (1993) to 24.4% (1996). The incidence of Lyme disease was positively correlated with tick abundance in the 12 town area (r = 0.828) and the State of Connecticut (r = 0.741). An entomological risk index based upon the number of I. scapularis ticks infected by B. burgdorferi was highest in 1992, 1994, and 1996 and was highly correlated with the incidence of Lyme disease in Connecticut (r = 0.944). The number of Lyme disease cases has been influenced, in part, by annual changes in population densities of I. scapularis and, presumably, a corresponding change in the risk of contact with infected ticks. Based upon tick activity and spirochetal infection rates, epidemiologically based Lyme disease case reports on a regional scale appear to reflect real trends in disease.