Lyme carditis: Early occurrence and prolonged recovery

Lyme carditis is an uncommon manifestation of early disseminated Lyme disease. This case illustrates a 66-year-old male with complaints of fatigue, myalgias, and fever after a tick bite 3 days earlier. A large erythema migrans was found on the chest wall. Initial electrocardiogram showed sinus rhythm with second degree 2:1 atrioventricular (AV) block, which progressed to intermittent complete AV block rapidly. He was treated with intravenous ceftriaxone. Over the course of 2-weeks of antibiotic therapy, the intermittent high-grade AV block improved slowly and progressively. This case highlights the importance of timely diagnosis and appropriate management to achieve a favorable prognosis.     

Lyme carditis: Sequential electrocardiographic changes in response to antibiotic therapy

Lyme disease is a tick-borne spirochetal infection that may involve heart. The cardiac manifestations of Lyme disease including varying degrees of atrioventricular heart block occur within weeks to months of the infecting tick bite. This report describes a 43 year-old man with Lyme carditis who presented with complete heart block. The heart block resolved with ceftriaxone therapy. Lyme carditis should be considered in the differential diagnosis in patients who present with new onset advanced heart block.     

Diagnosis not to be missed: Lyme carditis,rare but reversible cause of complete atrioventricular block

Lyme carditis is a known cause of atrioventricular block and in most cases, atrioventricular block is reversible with appropriate antibiotic treatment. The diagnosis can be challenging if the disease is either not suspected, or if the initial cutaneous manifestation of erythema migrans is missed. It is important to diagnose Lyme carditis as the cause of complete heart block if unnecessary pacemaker implantation is to be avoided. We present a 43-year-old male who presented with complete heart block and also illsustained ventricular tachycardia due to Lyme carditis that reversed completely with antibiotic therapy.     

Lyme Carditis Presenting With Complete Heart Block and Wide Complex Escape Rhythm

A 19-year-old woman with newly diagnosed Lyme disease presented with complete heart block and an accompanying escape rhythm with a right bundle branch block morphology. With antibiotics, her dysrhythmia resolved completely within 24 hours of presentation. This case highlights an unusual electrocardiographic manifestation of Lyme carditis.     

Cardiac Conduction Abnormalities in a Mouse Model of Lyme Borreliosis

Background: Borrelia Burgdorferi(BB) induces cardiac conduction abnormalities in infected humans. Mice models of Lyme disease have been developed, however their electrophysiologic (EP) properties of conduction are unknown. Methods: Seventy-six C3H/J mice (BB infected and age- and gender-matched controls) underwent blinded in vivo EP studies. In a first phase of the study, 40 male C3H/J mice were divided into 2 groups: Group (A) mice were infected at age 3 (weeks) and studied at 5, and Group (B) mice were infected at 9 and studied at 11. In a second phase, 36 female mice were divided into 2 groups: Group (C) mice were infected at 3 weeks and studied at 5, and Group (D) mice were infected at 3 and studied at 11. Results: Infected mice of group (A) and (C) had wider QRS complexes (21.0±1.6 versus 17.3±1.3[emsp4 ]ms, p0.0001 and 20.3±2.1 versus 18.5±1.7, p = 0.05, respectively) compared to the healthy controls (HC). Infected mice of group (B) and group (D) were similar to the HC. In all groups, the presence of conduction abnormalities correlated very closely with the amount of inflammation on pathology. Conclusion: This study describes the first EP mouse model of Lyme carditis. C3H/J mice exhibit conduction abnormalities that are reversible 8 weeks after inoculation, closely paralleling the resolution of inflammation on pathology. This model can be a valuable tool in the developing and testing of new modalities for the prevention and treatment of Lyme carditis.     

Pathogenesis of Lyme disease

Summary The etiology and pathogenesis of Lyme disease are reviewed and the value of the condition as a human model for an infectious etiology of rheumatic disease is discussed. Similarities between Lyme disease and rheumatoid arthritis are considered.     

Diagnosis and Treatment of Lyme Carditis: JACC Review Topic of the Week

The incidence of Lyme disease, a tick-borne bacterial infection, is dramatically increasing in North America. The diagnosis of Lyme carditis (LC), an early disseminated manifestation of Lyme disease, has important implications for patient management and preventing further extracutaneous complications. High-degree atrioventricular block is the most common presentation of LC, and usually resolves with antibiotic therapy. A systematic approach to the diagnosis of LC in patients with high-degree atrioventricular block will facilitate the identification of this usually transient condition, thus preventing unnecessary implantation of permanent pacemakers in otherwise healthy young individuals.     

Deer, predators, and the emergence of Lyme disease

Lyme disease is the most prevalent vector-borne disease in North America, and both the annual incidence and geographic range are increasing. The emergence of Lyme disease has been attributed to a century-long recovery of deer, an important reproductive host for adult ticks. However, a growing body of evidence suggests that Lyme disease risk may now be more dynamically linked to fluctuations in the abundance of small-mammal hosts that are thought to infect the majority of ticks. The continuing and rapid increase in Lyme disease over the past two decades, long after the recolonization of deer, suggests that other factors, including changes in the ecology of small-mammal hosts may be responsible for the continuing emergence of Lyme disease. We present a theoretical model that illustrates how reductions in small-mammal predators can sharply increase Lyme disease risk. We then show that increases in Lyme disease in the northeastern and midwestern United States over the past three decades are frequently uncorrelated with deer abundance and instead coincide with a range-wide decline of a key small-mammal predator, the red fox, likely due to expansion of coyote populations. Further, across four states we find poor spatial correlation between deer abundance and Lyme disease incidence, but coyote abundance and fox rarity effectively predict the spatial distribution of Lyme disease in New York. These results suggest that changes in predator communities may have cascading impacts that facilitate the emergence of zoonotic diseases, the vast majority of which rely on hosts that occupy low trophic levels.     

An ecological approach to preventing human infection: vaccinating wild mouse reservoirs intervenes in the Lyme disease cycle

Many pathogens, such as the agents of West Nile encephalitis and plague, are maintained in nature by animal reservoirs and transmitted to humans by arthropod vectors. Efforts to reduce disease incidence usually rely on vector control or immunization of humans. Lyme disease, for which no human vaccine is currently available, is a commonly reported vector-borne disease in North America and Europe. In a recently developed, ecological approach to disease prevention, we intervened in the natural cycle of the Lyme disease agent (Borrelia burgdorferi) by immunizing wild white-footed mice (Peromyscus leucopus), a reservoir host species, with either a recombinant antigen of the pathogen, outer surface protein A, or a negative control antigen in a repeated field experiment with paired experimental and control grids stratified by site. Outer surface protein A vaccination significantly reduced the prevalence of B. burgdorferi in nymphal blacklegged ticks (Ixodes scapularis) collected at the sites the following year in both experiments. The magnitude of the vaccine's effect at a given site correlated with the tick infection prevalence found on the control grid, which in turn correlated with mouse density. These data, as well as differences in the population structures of B. burgdorferi in sympatric ticks and mice, indicated that nonmouse hosts contributed more to infecting ticks than previously expected. Thus, where nonmouse hosts play a large role in infection dynamics, vaccination should be directed at additional species.     

Perspectives on "chronic Lyme disease"

There is much controversy about the treatment of Lyme disease with respect to 2 poorly defined entities: “chronic Lyme disease” and “posttreatment Lyme disease syndrome.” In the absence of direct evidence that these conditions are the result of a persistent infection, some mistakenly advocate extended antibiotic therapy (≥6 months), which can do great harm and has resulted in at least 1 death. The purpose of this brief report is to review what is known from clinical research about these conditions to assist both practicing physicians and lawmakers in making sound and safe decisions with respect to treatment.     

莱姆病的诊断与治疗进展

莱姆病是一种主要发生在温带地区经蜱叮咬传播的人兽共患自然疫源性疾病。近年来,随着蜱媒宿主范围的不断扩大,莱姆病在我国的发病率呈不断上升态势。该病系全身性疾病,可影响皮肤、关节、神经系统和心脏等。患者如得不到早期诊断和及时治疗,致残率较高,对人类健康危害甚大。鉴于莱姆病的临床表现多样,诊断困难,为了提高临床一线医护人员对莱姆病的认知,现将其临床研究进展作一综述。     

Repeated detection ofBorrelia burgdorferi DNA in synovial fluid of a child with Lyme arthritis

Summary In the pathogenesis of late Lyme borreliosis the relative importance of the causative organism,Borrelia burgdorferi, and the immune response of the host, including autoimmune phenomena, is not yet known. We describe a 7-year-old boy with Lyme arthritis from whom two synovial fluid samples were obtained 5 months apart and up to 17 months after the first appearance of arthritis. Both synovial fluid specimens were shown to contain borrelial DNA by nested polymerase chain reaction for the amplification of portions of the genes for flagellin and OspA. Thus,Borrelia burgdorferi may persist within the joint even during late stages of the disease.     

Multiple epiphyseal dysplasia: clinical and radiographic features, differential diagnosis and molecular basis

Multiple epiphyseal dysplasia is one of the more common skeletal dysplasias but it can still be difficult to diagnose. The presenting signs are often rheumatological ('joint pain') or neurological ('myopathy') in nature, and the cardinal feature of skeletal dysplasia (short stature) may not be present. A radiographic skeletal survey is necessary to delineate the pattern of generalized delayed epiphyseal ossification and changes in epiphyseal contour. Once the diagnosis of multiple epiphyseal dysplasia has been established, careful examination of the radiographs can help to determine which genes should be analysed. Mutations in at least six different genes can cause multiple epiphyseal dysplasia, and it can be either dominant or recessive. Molecular diagnosis is important for accurate prognosis and genetic counselling.     

Frequencies of Borrelia burgdorferi-reactive T lymphocytes in Lyme arthritis

Summary Using a limiting dilution system, frequencies of Borrelia burgdorferi-reactive T cells were determined in the blood and synovial fluid of four patients with chronic Lyme arthritis (LA), one patient with acrodermatitis chronica atrophicans (ACA), two patients with other inflammatory joint diseases, and two healthy individuals. B. burgdorferi-reactive precursor T cells ranged from 1/750 to 1/8 220 in case of LA and ACA patients and from 1/820 to 1/31 400 in case of controls. In vivo activated B. burgdorferi-reactive T cells were almost absent in control subjects. With one exception, they were detected in LA patients at frequencies ranging from 1/1 300 to 1/15 400. Interestingly, even after successful antibiotic therapy of LA patients, similar frequencies of in vivo activated B. burgdorferi-reactive T cells were observed in the peripheral blood, provided that low cell concentrations were used for culture. At higher cell numbers, the fraction of B. burgdorferi-reactive T cells apparently dropped, suggesting regulatory phenomena.     

Hypercholesterolemia and ApoE deficiency result in severe infection with Lyme disease and relapsing-fever Borrelia

The Lyme disease (Borrelia burgdorferi) and relapsing-fever (Borrelia hispanica) agents have distinct infection courses, but both require cholesterol for growth. They acquire cholesterol from the environment and process it to form cholesterol glycolipids that are incorporated onto their membranes. To determine whether higher levels of serum cholesterol could enhance the organ burdens of B. burgdorferi and the spirochetemia of B. hispanica in laboratory mice, apolipoprotein E (apoE)-deficient and low-density lipoprotein receptor (LDLR)-deficient mice that produce large amounts of serum cholesterol were infected with both spirochetes. Both apoE- and LDLR-deficient mice infected with B. burgdorferi had an increased number of spirochetes in the joints and inflamed ankles compared with the infected wild-type (WT) mice, suggesting that mutations in cholesterol transport that result in high serum cholesterol levels can affect the pathogenicity of B. burgdorferi. In contrast, elevated serum cholesterol did not lead to an increase in the spirochetemia of B. hispanica. In the LDLR-deficient mice, the course of infection was indistinguishable from the WT mice. However, infection of apoE-deficient mice with B. hispanica resulted in a longer spirochetemia and increased mortality. Together, these results argue for the apoE deficiency, and not hypercholesterolemia, as the cause for the increased severity with B. hispanica. Serum hyperlipidemias are common human diseases that could be a risk factor for increased severity in Lyme disease.Cholesterol is an essential structural component of the cell membrane of vertebrate animals, and it is required for membrane integrity and fluidity. In addition to being a component of the membrane, cholesterol is the precursor of steroid hormones and bile. In eukaryotic cells, cholesterol and sphingolipids are the main components of membrane microdomains known as lipid rafts. These microdomains are characterized as being more tightly packed than the surrounding bilayer and enriched with proteins involved in signaling (1–3).In the bloodstream of humans and other vertebrates, cholesterol is transported in lipoprotein complexes. Apolipoprotein E (apoE) binds cholesterol for transport through the circulatory system as apoE-containing chylomicrons and very-low-density lipoprotein (VLDL) particles. These apoE–cholesterol particles are internalized through the interaction with the low-density lipoprotein receptors (LDLRs). LDLR is one of the cell-surface receptors in cells that binds to apoE to clear the lipoprotein particles from the blood (4). Both apoE-deficient (apoE⁻) and LDLR-deficient (LDLR⁻) mice show elevated serum cholesterol levels and develop atherosclerotic plaques (5, 6). These mice are the most used mouse models for hyperlipidemia and atherosclerosis research.Lyme disease and relapsing-fever Borrelia have very distinct infection courses and niches in the host. In experimental mouse infections, relapsing-fever borreliae multiply in the blood, reaching high numbers (spirochetemia), until antibodies, mostly of the IgM class, clear the first peak, which is followed by several smaller peaks of antigenically variable organisms. Therefore, infection with Borrelia hispanica, an agent of relapsing fever, can be monitored by direct enumeration of the spirochetes from blood. Conversely, Borrelia burgdorferi, the agent of Lyme disease, does not have an overt spirochetemia, and it is difficult to detect in blood, but invades tissues including the skin, heart, and joints, where it can be quantified by molecular methods.The outer membrane of Borrelia is composed of phospholipids, including phosphatidylcholine and phosphatidylglycerol (7). The borreliae also have cholesterol glycolipids: cholesteryl 6-O-acyl-β-d-galactopyranoside and cholesteryl-β-d-galacto-pyranoside in B. burgdorferi; and 6-O-acylated cholesteryl β-d-glucopyranoside and cholesteryl β-d-glucopyranoside in relapsing-fever Borrelia. They also have noncholesterol glycolipids, monogalactosyl-diacylglycerol in B. burgdorferi and monoglucosyl-diacylglycerol in relapsing-fever Borrelia, as well as many lipoproteins (7–15). The presence of cholesterol is not common among prokaryotes, but it is increasingly being reported in bacterial pathogens other than Borrelia spp., including species of Helicobacter, Mycoplasma, Ehrlichia, Anaplasma, and Brachyspira (16–20).Recently, we demonstrated that B. burgdorferi acquires cholesterol from host cells (21). Cholesterol can remain free in the membrane or can be internalized and glycosylated by undetermined enzymes (22). Subsequently, cholesterol glycolipids are exported to the membrane, where they form lipid rafts (23, 24) that are cholesterol-rich domains with a selective presence of lipoproteins (25). The borreliae require cholesterol for growth and have to recruit it from the host because they cannot synthesize it. In this study, our goal was to determine whether serum hypercholesterolemia could lead to greater yields of bacteria in vivo by providing added cholesterol in a manner that would be accessible to the spirochetes. To this end, we infected apoE⁻ and LDLR⁻ mice that have increased levels of serum cholesterol with B. burgdorferi and B. hispanica. From these experiments, we concluded that infection of apoE⁻ and LDLR⁻ mice with B. burgdorferi resulted in greater severity of infection. In contrast, immune dysfunctions associated with deficiencies in the apoE⁻ mouse model, and not high cholesterol levels, led to increased severity in infection with relapsing-fever Borrelia.     

天津地区莱姆病疫源地的发现与研究

目的通过对天津地区自然人群、动物宿主和媒介生物进行研究,以确定该地区是否为莱姆病疫源地。方法采用分层整群抽样方法选取3个代表性地区10个调查点的居民进行人群的莱姆病血清流行病学调查,同时用间接免疫荧光试验、病原分离培养和PCR方法对动物宿主和媒介生物进行血清学和病原学研究。并通过测序确定基因型。结果905份人群血清样本检测结果显示该地区人群的莱姆病感染率为5.97%;100份野鼠血清样本的感染率是32.00%,并从大林姬鼠、社鼠、小林姬鼠的脾脏和/或肾脏中检查到莱姆病螺旋体的特异片段。经聚类分析定为Borrelia garinii基因型,因此可以推断鼠类可能为此地区莱姆病螺旋体的重要储存宿主。共收集到1226只蜱,以长角血蜱为优势种。选取300只长角血蜱经PCR检测,其带菌率为4.67%(14/300)。结论首次发现天津蓟县山林地区可能为我国莱姆病的疫源地之一。     

Efficacy of a New Therapeutic Regimen Versus Two Routinely Prescribed Treatments for Eradication of Helicobacter Pylori: A Randomized, Double-Blind Study of Doxycycline, Co-Amoxiclav, and Omeprazole in Iranian Patients

This study compared a new regimen (group A: doxycycline, co-amoxiclav, omeprazole) and two routinely prescribed regimens (group B: amoxicillin, omeprazole, furazolidone, bismuth; group C: amoxicillin, clarithromycin, omeprazole) to find an acceptable first-line treatment option for Helicobacter pylori. The study population consisted of 189 patients who referred to our clinic to undergo endoscopy due to ulcer-like dyspepsia. The H. pylori eradication rate was 68% in group A, 56% in group B, and 70% in group C according to per-control analysis. There was no statistically significant difference in H. pylori eradication between groups A and B (P = 0.187), groups A and C (P = 0.857), and groups B and C (P = 0.15). In conclusion, although none of the three eradication regimens can be recommended as a first-line eradication treatment, the new regimen is at least as effective and probably better tolerated than the two routinely applied regimens.