Epidemiological and clinical features of 1,149 persons with Lyme disease identified by laboratory-based surveillance in Connecticut

Laboratory-based surveillance of Lyme disease in Connecticut during 1984 and 1985 identified 3,098 persons with suspected Lyme disease; 1,149 were defined as cases. Lyme disease incidence in Connecticut towns ranged from none to 1,407 cases per 100,000 population in 1985. A comparison of 1985 data with data from 1977 epidemiologic studies indicated that incidence increased by 129 percent to 453 percent in towns previously known to be endemic for Lyme disease and that Lyme disease had spread northward into towns thought to be free of Lyme disease in 1977. Children aged five to 14 years had the highest incidence. Of persons with Lyme disease, 83 percent had erythema migrans, 24 percent had arthritis, 8 percent had neurologic sequelae, and 2 percent had cardiac sequelae. The distribution of symptoms was age-dependent: case-persons less than 20 years old were almost twice as likely to have arthritis than older case-persons (35 percent versus 18 percent). Of persons with arthritis, 92 percent of those less than 20 years of age, compared to 68 percent of older persons, did not have antecedent erythema migrans. We conclude that Lyme disease is increasing in incidence and geographic distribution in Connecticut. Of those with Lyme disease, children may be more likely than adults to develop arthritis and have it as their first major disease manifestation.     

An indirect microhemagglutination test for Lyme disease.

We have developed an indirect microhemagglutination test (IMHA) for detecting antibodies to Borrelia burgdorferi using formalin-fixed chicken erythrocytes sensitized with a sonicated extract of the bacteria. The specificity of IMHA for Lyme disease was compared with that of a conventional indirect immunoperoxidase technique (IP) using sera from the patients with syphilis, randomly-chosen outpatients unrelated to Lyme disease, and from normal individuals. The IMHA was more specific than IP, giving little cross-reaction with syphilis. The IMHA also gave little background reactions with the sera of individuals unrelated to Lyme disease or syphilis. Therefore, the IMHA could be a useful test for the serodiagnosis of Lyme disease.     

Effects of Landscape Fragmentation and Climate on Lyme Disease Incidence in the Northeastern United States

Lyme disease is the most frequently reported vector borne illness in the United States, and incidences are increasing steadily year after year. This study explores the influence of landscape (e.g., land use pattern and landscape fragmentation) and climatic factors (e.g., temperature and precipitation) at a regional scale on Lyme disease incidence. The study area includes thirteen states in the Northeastern United States. Lyme disease incidence at county level for the period of 2002–2006 was linked with several key landscape and climatic variables in a negative binomial regression model. Results show that Lyme disease incidence has a relatively clear connection with regional landscape fragmentation and temperature. For example, more fragmentation between forests and residential areas results in higher local Lyme disease incidence. This study also indicates that, for the same landscape, some landscape variables derived at a particular scale show a clearer connection to Lyme disease than do others. In general, the study sheds more light on connections between Lyme disease incidence and climate and landscape patterns at the regional scale. Integrating findings of this regional study with studies at a local scale will further refine understanding of the pattern of Lyme disease as well as increase our ability to predict, prevent, and respond to disease.     

Comparative ecology and epidemiology of lyme disease and tick-borne encephalitis in the former Soviet Union

The recently defined range of human Lyme disease in Russia coincides with that of the intensively studied agent of tick-borne encephalitis (TBE). Although identical vectors transmit both infections during the same seasons and in the same locations, more than twice as many people suffer from Lyme disease as from TBE. Edward Korenberg here describes characteristic features of vectors with respect to their seasonal activity, abundance, rates of infection by TBE and Lyme disease agents, as well as incidence of human-tick contact, and how these factors determine the incidence of TBE and Lyme disease in different regions.     

Taxonomy of the Lyme disease spirochetes.

Morphology, physiology, and DNA nucleotide composition of Lyme disease spirochetes, Borrelia, Treponema, and Leptospira were compared. Morphologically, Lyme disease spirochetes resemble Borrelia. They lack cytoplasmic tubules present in Treponema, and have more than one periplasmic flagellum per cell end and lack the tight coiling which are characteristic of Leptospira. Lyme disease spirochetes are also similar to Borrelia in being microaerophilic, catalase-negative bacteria. They utilize carbohydrates such as glucose as their major carbon and energy sources and produce lactic acid. Long-chain fatty acids are not degraded but are incorporated unaltered into cellular lipids. The diamino amino acid present in the peptidoglycan is ornithine. The mole % guanine plus cytosine values for Lyme disease spirochete DNA were 27.3-30.5 percent. These values are similar to the 28.0-30.5 percent for the Borrelia but differed from the values of 35.3-53 percent for Treponema and Leptospira. DNA reannealing studies demonstrated that Lyme disease spirochetes represent a new species of Borrelia, exhibiting a 31-59 percent DNA homology with the three species of North American borreliae. In addition, these studies showed that the three Lyme disease spirochetes comprise a single species with DNA homologies ranging from 76-100 percent. The three North American borreliae also constitute a single species, displaying DNA homologies of 75-95 percent. Lyme disease spirochetes and Borrelia exhibited little or no DNA homology (0-2 percent) with the Treponema or Leptospira. Plasmids were present in the three Lyme disease spirochetes and the three North American borreliae.     

Prevalence of <Emphasis Type="Italic">Borrelia burgdorferi</Emphasis> sensu lato in rodents from Gansu,northwestern China

Background  

Lyme disease is a multi-organ infection disease caused by Borrelia burgdorferi sensu lato. Lyme disease was first documented in north-east China in 1986. Since then more than 20 provinces in China were confirmed the existence of nature foci of Lyme disease. In the present study, a molecular epidemiological survey was conducted to investigate the presence of Borrelia burgdorferi sensu lato in rodents from Gansu Province for the first time.     

Of ticks, mice and men: understanding the dual-host lifestyle of Lyme disease spirochaetes

In little more than 30 years, Lyme disease, which is caused by the spirochaete Borrelia burgdorferi, has risen from relative obscurity to become a global public health problem and a prototype of an emerging infection. During this period, there has been an extraordinary accumulation of knowledge on the phylogenetic diversity, molecular biology, genetics and host interactions of B. burgdorferi. In this Review, we integrate this large body of information into a cohesive picture of the molecular and cellular events that transpire as Lyme disease spirochaetes transit between their arthropod and vertebrate hosts during the enzootic cycle.     

Health Care Costs,Utilization and Patterns of Care following Lyme Disease

BackgroundLyme disease is the most frequently reported vector borne infection in the United States. The Centers for Disease Control have estimated that approximately 10% to 20% of individuals may experience Post-Treatment Lyme Disease Syndrome – a set of symptoms including fatigue, musculoskeletal pain, and neurocognitive complaints that persist after initial antibiotic treatment of Lyme disease. Little is known about the impact of Lyme disease or post-treatment Lyme disease symptoms (PTLDS) on health care costs and utilization in the United States.Objectives1) to examine the impact of Lyme disease on health care costs and utilization, 2) to understand the relationship between Lyme disease and the probability of developing PTLDS, 3) to understand how PTLDS may impact health care costs and utilization.MethodsThis study utilizes retrospective data on medical claims and member enrollment for persons aged 0-64 years who were enrolled in commercial health insurance plans in the United States between 2006-2010. 52,795 individuals treated for Lyme disease were compared to 263,975 matched controls with no evidence of Lyme disease exposure.ResultsLyme disease is associated with $2,968 higher total health care costs (95% CI: 2,807-3,128, p<.001) and 87% more outpatient visits (95% CI: 86%-89%, p<.001) over a 12-month period, and is associated with 4.77 times greater odds of having any PTLDS-related diagnosis, as compared to controls (95% CI: 4.67-4.87, p<.001). Among those with Lyme disease, having one or more PTLDS-related diagnosis is associated with $3,798 higher total health care costs (95% CI: 3,542-4,055, p<.001) and 66% more outpatient visits (95% CI: 64%-69%, p<.001) over a 12-month period, relative to those with no PTLDS-related diagnoses.ConclusionsLyme disease is associated with increased costs above what would be expected for an easy to treat infection. The presence of PTLDS-related diagnoses after treatment is associated with significant health care costs and utilization.     

Paralytic strabismus as a manifestation of lyme borreliosis

Lyme disease is a multi-system organ disorder caused by Borrelia burgdorferi. Although ocular manifestations have been reported, these remain a rare feature of the disease. This report shows a 49-years old patient that has been bitten by a tick and as consequence of which developed symptoms of the Lyme disease. In 1998 the patient was hospitalized in our Eye Clinic due to operating treatment of the paralytic strabismus (abductal nerve paralysis), as a rare feature of the Lyme disease. Postoperative squint angle was significantly reduced, but without any temporal movement. Diplopia was still present, though slightly reduced with the use of prism eyeglasses. The improvement of the quality of life was achieved, as well as the patient's satisfaction.     

Conspicuous impacts of inconspicuous hosts on the Lyme disease epidemic

Emerging zoonotic pathogens are a constant threat to human health throughout the world. Control strategies to protect public health regularly fail, due in part to the tendency to focus on a single host species assumed to be the primary reservoir for a pathogen. Here, we present evidence that a diverse set of species can play an important role in determining disease risk to humans using Lyme disease as a model. Host-targeted public health strategies to control the Lyme disease epidemic in North America have focused on interrupting Borrelia burgdorferi sensu stricto (ss) transmission between blacklegged ticks and the putative dominant reservoir species, white-footed mice. However, B. burgdorferi ss infects more than a dozen vertebrate species, any of which could transmit the pathogen to feeding ticks and increase the density of infected ticks and Lyme disease risk. Using genetic and ecological data, we demonstrate that mice are neither the primary host for ticks nor the primary reservoir for B. burgdorferi ss, feeding 10% of all ticks and 25% of B. burgdorferi-infected ticks. Inconspicuous shrews feed 35% of all ticks and 55% of infected ticks. Because several important host species influence Lyme disease risk, interventions directed at a multiple host species will be required to control this epidemic.     

Estimation of the Transmission Probability of Lyme Borreliosis

Whether physicians should prophylactically treat tick bites in areas endemic for Lyme disease has been debated. The high rates of tick infection (10–50%) found in Lyme disease-endemic areas suggest that tick bites should be treated; conversely, the low rates of Lyme disease (1–4%) found in recent clinical trials of untreated tick-bite victims suggest caution in treatment. Medical advice given from Lyme-disease World Wide Web sites is equally contradictory, ranging from suggesting that all tick bites should be treated to suggesting that no tick bites be treated. To clarify this issue, we estimate the transmission probability of the causative agent of Lyme disease, Borrelia burgdorferi, for different durations of tick attachment. The data used to estimate this transmission probability is obtained from previously published animal studies. The accuracy of these estimates is assessed by comparing model predictions of the number of Lyme disease cases to that actually observed in clinical studies of Lyme disease. Our results suggest that tick bites should be treated only when it is known that the duration of tick attachment is longer than 48 hours.     

Whole-genome sequences of Borrelia bissettii, Borrelia valaisiana, and Borrelia spielmanii

It has been known for decades that human Lyme disease is caused by the three spirochete species Borrelia burgdorferi, Borrelia afzelii, and Borrelia garinii. Recently, Borrelia valaisiana, Borrelia spielmanii, and Borrelia bissettii have been associated with Lyme disease. We report the complete genome sequences of B. valaisiana VS116, B. spielmanii A14S, and B. bissettii DN127.     

Lyme borreliosis in central Italy (1995-1998)

From January 1995 to July 1998, 340 serum samples collected in Central Italy from patients clinically suspected of having Lyme borreliosis were investigated. All samples were tested for the presence of antibodies to B. burgdorferi by Elisa. The Elisa positive samples were subjected to further tests by Western Blot for confirmation. Out of 340 patients, 13 (3.8%) proved to be B. burgdorferi positive, while 9 (2.6%) were found to have Lyme disease with seroprevalence being higher in these latter than that of blood donors from Central Italy. Our results indicate that Lyme borreliosis is present in Central Italy. A comparison between Italian and European studies reveals that Lyme disease is still underestimated in Italy, the main reason being that a monitoring system for the study of Lyme borreliosis was only established in 1990.     

Epidemiologic features of Lyme disease in New York

During 1982, surveillance identified 207 cases of Lyme disease in New York State. Cases were clustered in two geographic areas, eastern Long Island and northern Westchester counties. Symptoms and signs of Lyme disease in cases were consistent with previous reports, with erythema chronicum migrans (ECM) being the most frequently (77 percent) reported sign of disease. Facial palsy was reported in a surprisingly high 18 percent of cases. Of 160 cases whose sera were submitted for Lyme spirochete specific IgG antibody testing, 112 (70 percent) had titers greater than or equal to 64, while 88 (55 percent) had titers greater than or equal to 128. Positive titers were not associated with any single sign or symptom of disease, but were significantly associated with symptom onset or tick bite occurring during the three-month period of June, July, and August. We conclude that the incidence of Lyme disease in New York is much higher than previously recognized. In addition, our data suggest that a serologic test for Lyme-spirochete IgG antibody lacks sensitivity, but can be useful in confirming the diagnosis of Lyme disease when antibody titers are high.     

Lyme disease in northwestern coastal California.

To determine the incidence of physician-diagnosed Lyme disease in an endemic area of California, an active surveillance program was implemented in Lake, Mendocino, Sonoma, and southern Humboldt counties. More than 200 medical care providers were called monthly for their list of suspected cases of Lyme disease. Pertinent information was abstracted from the medical record of each patient. Of 153 cases of possible early Lyme disease ascertained from July 1991 to December 1992, 37% consisted of physician-diagnosed erythema migrans. Only 58% of erythema migrans rashes were at least 5 cm in diameter. An additional 43 patients had suspicious rashes not classified as erythema migrans. Of 166 patients with possible late-stage Lyme disease, 31% had specific clinical symptoms and 75% had a positive serologic test. With an incident case defined as physician-diagnosed erythema migrans of at least 5 cm in diameter, the annual incidence of Lyme disease in northwestern coastal California according to active surveillance only was 5.5 per 100,000. The rate of Lyme disease in California is substantially lower than that in the Atlantic northeastern United States. Many suspected cases of Lyme disease in this endemic area do not meet surveillance criteria, which are intentionally restrictive. Although some of the illnesses not meeting surveillance criteria may be due to infection with Borrelia burgdorferi, it appears that Lyme disease is being overdiagnosed in this area.     

Integrated Assessment of Behavioral and Environmental Risk Factors for Lyme Disease Infection on Block Island,Rhode Island

Peridomestic exposure to Borrelia burgdorferi-infected Ixodes scapularis nymphs is considered the dominant means of infection with black-legged tick-borne pathogens in the eastern United States. Population level studies have detected a positive association between the density of infected nymphs and Lyme disease incidence. At a finer spatial scale within endemic communities, studies have focused on individual level risk behaviors, without accounting for differences in peridomestic nymphal density. This study simultaneously assessed the influence of peridomestic tick exposure risk and human behavior risk factors for Lyme disease infection on Block Island, Rhode Island. Tick exposure risk on Block Island properties was estimated using remotely sensed landscape metrics that strongly correlated with tick density at the individual property level. Behavioral risk factors and Lyme disease serology were assessed using a longitudinal serosurvey study. Significant factors associated with Lyme disease positive serology included one or more self-reported previous Lyme disease episodes, wearing protective clothing during outdoor activities, the average number of hours spent daily in tick habitat, the subject’s age and the density of shrub edges on the subject’s property. The best fit multivariate model included previous Lyme diagnoses and age. The strength of this association with previous Lyme disease suggests that the same sector of the population tends to be repeatedly infected. The second best multivariate model included a combination of environmental and behavioral factors, namely hours spent in vegetation, subject’s age, shrub edge density (increase risk) and wearing protective clothing (decrease risk). Our findings highlight the importance of concurrent evaluation of both environmental and behavioral factors to design interventions to reduce the risk of tick-borne infections.     

Biodiversity of Borrelia burgdorferi strains in tissues of Lyme disease patients

Plant and animal biodiversity are essential to ecosystem health and can provide benefits to humans ranging from aesthetics to maintaining air quality. Although the importance of biodiversity to ecology and conservation biology is obvious, such measures have not been applied to strains of an invasive bacterium found in human tissues during infection. In this study, we compared the strain biodiversity of Borrelia burgdorferi found in tick populations with that found in skin, blood, synovial fluid or cerebrospinal fluid of Lyme disease patients. The biodiversity of B. burgdorferi strains is significantly greater in tick populations than in the skin of patients with erythema migrans. In turn, strains from skin are significantly more diverse than strains at any of the disseminated sites. The cerebrospinal fluid of patients with neurologic Lyme disease harbored the least pathogen biodiversity. These results suggest that human tissues act as niches that can allow entry to or maintain only a subset of the total pathogen population. These data help to explain prior clinical observations on the natural history of B. burgdorferi infection and raise several questions that may help to direct future research to better understand the pathogenesis of this infection.     

Protective immunity in lyme borreliosis

Lyme disease, caused by the spirochete Borrelia burgdorferi, is the most common vector-borne illness in the USA. Although early infection can be treated with antibiotics, the initial diagnosis is difficult and late disease may be recalcitrant to therapy. A vaccine against Lyme disease is therefore needed, and murine models of Lyme borreliosis have facilitated its development. In this review, Erol Fikrig, Fred Kantor, Stephen Barthold and Richard Flavell focus on the use of Borrelia surface antigens as vaccine candidates for Lyme disease.