Positive Lyme serology in subacute bacterial endocarditis. A study of four patients

Lyme borreliosis is a multisystem inflammatory disorder caused by the tick-borne spirochete Borrelia burgdorferi. Clinical manifestations are protean, involving the skin, joints, peripheral and central nervous systems, and the heart. However, the presentation of Lyme disease often overlaps with that of other conditions. We describe four patients from a region endemic for Lyme disease who had elevated levels of antibodies reactive to B burgdorferi and whose signs and symptoms were initially attributed to Lyme borreliosis but whose subsequent blood cultures established a diagnosis of nonspirochetal subacute bacterial endocarditis. Although immunoblots on serum samples from three of the four patients were consistent with prior infection from B burgdorferi, a positive immunoblot does not establish active infection. Similarly, seropositivity to B burgdorferi only indicates possible exposure to this organism. The occurrence of positive serologies to B burgdorferi in the presence of other diseases can lead to diagnostic confusion.     

Serologic evidences suggesting the presence of Borrelia burgdorferi infection in Mexico

BACKGROUND: Lyme disease is the most common vector-borne human disease in Europe and the United States. In Mexico, clinical cases suggestive of Lyme borreliosis have been reported; however, infection was not confirmed by serologic or microbiologic tests. METHODS: To study the prevalence of IgG antibodies against Borrelia burgdorferi among Mexican persons, a community-based sero-survey including all states of Mexico was done. A sample of 2,890 sera representing individuals of all ages and all socioeconomic levels was studied. Antibodies anti-B. burgdorferi were determined by enzyme-linked immunosorbent assay (ELISA) using a whole-cell sonicated extract of B. burgdorferi strain B31. Serum specimens positive for ELISA were further studied by Western blot (WB). A serum sample was considered positive by WB if at least three of the following protein bands were recognized: 18, 24, 28, 29, 31, 34, 39, 41, 45, 58, 62, 66, and 93 kDa. Some WB positive specimens were further confirmed with an immunodot-blot (IDB) test using recombinant and purified B. burgdorferi proteins. RESULTS: Of the 2,890 specimens, 34 were positive for ELISA; nine of these 34 were confirmed as positive by WB. Four of the nine WB positive sera were tested by IDB and all four were positive. The prevalence of WB confirmed cases in the sample studied was 0.3%. Positive specimens were from residents of the northeastern and central areas of Mexico. CONCLUSIONS: The serological evidences of this study suggest that Borrelia burgdorferi infection is present in the Mexican population. This finding should be confirmed by documenting the infection in clinical cases and in tick vectors.     

用免疫印迹法检查40例湖南病人血清莱姆病抗体

用免疫印迹法检查４０例具有某些莱姆病相关症状的病人血清，发现４例血清中同时存在高滴度抗－３１ＫＤａ和抗－４ＫＤａ莱姆病抗原的特异性抗体，占总检查例数的１０％。该４例病人分别被误诊为心肌炎和风湿性关节炎各１例，系统性红斑狼疮２例，无一例诊断为莱姆病。此结果证明湖南存在莱姆病     

Diagnosis of Lyme disease

The use of serologic testing and its value in the diagnosis of Lyme disease remain confusing and controversial for physicians, especially concerning persons who are at low risk for the disease. The approach to diagnosing Lyme disease varies depending on the probability of disease (based on endemicity and clinical findings) and the stage at which the disease may be. In patients from endemic areas, Lyme disease may be diagnosed on clinical grounds alone in the presence of erythema migrans. These patients do not require serologic testing, although it may be considered according to patient preference. When the pretest probability is moderate (e.g., in a patient from a highly or moderately endemic area who has advanced manifestations of Lyme disease), serologic testing should be performed with the complete two-step approach in which a positive or equivocal serology is followed by a more specific Western blot test. Samples drawn from patients within four weeks of disease onset are tested by Western blot technique for both immunoglobulin M and immunoglobulin G antibodies; samples drawn more than four weeks after disease onset are tested for immunoglobulin G only. Patients who show no objective signs of Lyme disease have a low probability of the disease, and serologic testing in this group should be kept to a minimum because of the high risk of false-positive results. When unexplained nonspecific systemic symptoms such as myalgia, fatigue, and paresthesias have persisted for a long time in a person from an endemic area, serologic testing should be performed with the complete two-step approach described above.     

Role of serology in the diagnosis of Lyme disease.

Numerous concerns regarding the potential for misdiagnosis of Lyme disease using commercial assays have been voiced by the US Food and Drug Administration (FDA). We attempted to clarify the clinical value of serologic testing for Lyme disease using the results of commonly marketed assays for detecting antibody to Borrelia burgdorferi, the organism that causes Lyme disease. We reviewed published studies on B burgdorferi test performance published through 1998, package insert labeling from FDA-cleared test kits for B burgdorferi, and Lyme Disease Survey Set LY-A from the College of American Pathologists. We assessed the sensitivity and specificity of commercial serologic tests (enzyme-linked immunosorbent assay [ELISA], immunofluorescence antibody [IFA], and immunodot) for diagnosis of Lyme disease. To reduce this risk of misdiagnosis, it is important that clinicians understand the performance characteristics and limitations of these tests. These tests, in common use in clinical or commercial laboratories, should be used only to support a clinical diagnosis of Lyme disease, not as the primary basis for making diagnostic or treatment decisions. Serologic testing is not useful early in the course of Lyme disease because of the low sensitivity of tests in early disease. Serologic testing may be more useful in later disease, at which time sensitivity and specificity of the test are improved. Positive or equivocal results on an ELISA, IFA, or immunodot assay requires supplemental testing with a Western blot assay. A negative result on the Western blot or ELISA indicates that there is no serologic evidence of infection by B burgdorferi at the time the sample was drawn.     

Investigation of Lyme disease in Xinjiang.

From April through July 1988, an epidemiological investigation on Lyme disease was carried out in Nalati Xanyuan, Xinjiang Uygur Autonomous Region, China. Of 150 Ixodes persulcatus ticks examined by darkfield microscopy, 42 (28%) were found to have spirochetes. Two strains of spirochetes were isolated from I. persulcatus with BSK medium. Rabbits inoculated with the spirochetes showed erythema chronicum migrans at the sites of inoculation and the spirochetes were found in the cerebrospinal fluid by darkfield microscopy. Serum samples from 63 patients were examined for antibodies to B. burgdorferi by IFA test and 11 of them were positive with a titer of 1:64. Upon these results, it may be concluded that natural focus of Lyme disease exists in Xinjiang, China.

     

西北部分地区莱姆病与人、家养动物、啮齿动物关系的研究

1991—1999年,先后对甘肃铧尖、迭部和新疆阿勒泰铁热克提三地区莱姆病与人、家养动物、啮齿动物的关系作了调查研究。研究发现三地区森林草原为莱姆病自然疫源地,有传播莱姆病的媒介和保菌宿主,并从森林革蜱(D.silvarum)、草原革蜱(D.nuttalli)、日本血蜱(H.japoni-ca)和黑线姬鼠(A.agrarius)、黄毛鼠(R.losea)、棕背(鼠平)(C.rufocanus)、鼹形田鼠(E.talplinus)体内分离到了伯氏疏螺旋体(Borrelia burgdorferi),查到了特异性抗体,家养动物阳性率22.12％,啮齿动物阳性率18.48％,不仅发现当地人群中有一定程度的感染(受检2869人份,阳性241人份,阳性率8.40％),而且还先后发现病人126例。阐述了当地莱姆病流行上与人、家养动物和啮齿动物之间的相互关系,证实了两种传播方式,即1.莱姆病在啮齿动物之间流行,人进入该流行区被带伯氏螺旋体的蜱叮咬而患病;2.莱姆病在啮齿动物之间流行,家畜动物进入该流行区觅食时,将带有伯氏疏螺旋体的蜱又带到了人们的生活区,再叮咬生活区的人而发病。     

Borrelia burgdorferi infection may be the cause of sarcoidosis.

Serum antibody to Borrelia burgdorferi was measured in 33 patients with sarcoidosis which was confirmed clinically and pathologically. The results showed that 81.8% of the patients were positive for anti-B. burgdorferi antibody. In addition, a strain of B. burgdorferi was isolated from a patient's blood. Fifteen patients received ceftriaxone 2g per day or penicillin 12 million U per day. The antibody titers of the patients decreased to nearly normal levels rapidly. Serum angiotensin converting enzyme (SACE) turned to normal range after the treatment. According to the findings mentioned above, we consider that B. burgdorferi infection may be the cause of sarcoidosis and sarcoidosis might be a specific type of Lyme disease.

     

Performance of 45 laboratories participating in a proficiency testing program for Lyme disease serology.

OBJECTIVE--We show that significant interlaboratory and intralaboratory variations exist in Lyme disease proficiency testing. DESIGN--Six case-defined Lyme serum samples and three serum samples from individuals with no history of Lyme disease were randomized in four shipments and distributed to 45 participating laboratories. RESULTS--Interlaboratory and intralaboratory performances were highly variable. Approximately 4% to 21% of laboratories failed to identify correctly positive serum samples with titers of 512 or more using polyvalent serum or immunoglobulin G conjugates. With lower levels of anti-Borrelia burgdorferi antibody in the serum sample, approximately 55% of participating laboratories did not identify a case-defined serum. There was also a striking inability of many laboratories to reproduce their results on split samples from the same individual. In addition, 2% to 7% of laboratories identified serum samples from individuals with no known exposure to B burgdorferi as positive using polyvalent serum. The false positivity rate increased to 27% with the use of immunoglobulin G conjugate. CONCLUSIONS--Our results indicate that there is an urgent need for standardization of current testing methodologies. Until a national commitment is made, serological testing for Lyme disease will be of questionable value for the diagnosis of the disease.     

Use of a novel technique of cutaneous lavage for diagnosis of Lyme disease associated with erythema migrans.

OBJECTIVE--Determining the microbial cause of cellulitis is often difficult. In this study, a novel two-needle lavage technique was used to culture Borrelia burgdorferi from the skin of suspected erythema migrans lesions. DESIGN--The yield of lavage cultures for B burgdorferi was compared with that of a 2-mm skin biopsy sample. SETTING--A Lyme disease diagnostic center located in an area in which Lyme disease is epidemic. PATIENTS--Forty-five patients with suspected erythema migrans who had not been treated with antimicrobial agents. INTERVENTION--Cutaneous lavage of the advancing edge of a suspected primary erythema migrans lesion was done for all 45 participants, 33 of whom also had a skin biopsy of the same lesion at an identical (14) or an adjacent (19) site. MAIN OUTCOME MEASURES--Growth of B burgdorferi in in vitro culture. RESULTS--Lavage fluid cultures grew B burgdorferi in 13 (29%) of the 45 cases (95% confidence interval [CI], 16% to 44%). Among the 33 cases in which both lavage and skin biopsy cultures were done, the yield of lavage culture was less than that of biopsy culture (P less than .09, 12/33 vs 20/33). If contaminated cultures are excluded, this difference is significant (P less than .05, 12/30 vs 20/27). CONCLUSION--Cutaneous lavage is a new diagnostic technique for recovery of B burgdorferi from erythema migrans lesions that has potential applicability to other types of cutaneous infections.     

黑龙江省苇河林区莱姆病自然疫源地媒介蜱的调查

1989年4～7月间,我们对黑龙江苇河林区莱姆病的媒介蜱作了调查。全沟硬蜱为当地优势蜱种,也是发现的唯一莱姆病媒介,4月初开始活动,5月中旬达活动高峰,7月底近乎绝迹。其伯氏疏螺旋体感染率为29.1％,但5月以后的感染率明显高于4月份的感染率。     

The pathologist's view of Lyme disease

Lyme disease is a multisystem disease caused by the spirochete Borrelia burgdorferi and is transmitted to humans primarily through Ixodid ticks. The clinical spectrum of the disease is continuing to expand while in its wake the pathology and histopathologic manifestations are being uncovered. We review the pathology of Lyme disease in man beginning with the tick bite. We present the pathologic changes of the rash, erythema migrans, as well as the neurologic, cardiac, and arthritic changes of the disease. We can expand our understanding of the immunobiology of Lyme disease by studying the interactions of B. burgdorferi in an experimental animal model.     

Lyme disease during pregnancy

Lyme disease is an increasingly recognized tick-borne illness caused by a spirochete, Borrelia burgdorferi. Because the etiologic agent of Lyme disease is a spirochete, there has been concern about the effect of maternal Lyme disease on pregnancy outcome. We reviewed cases of Lyme disease in pregnant women who were identified before knowledge of the pregnancy outcomes. Nineteen cases were identified with onset between 1976 and 1984. Eight of the women were affected during the first trimester, seven during the second trimester, and two during the third trimester; in two, the trimester of onset was unknown. Thirteen received appropriate antibiotic therapy for Lyme disease. Of the 19 pregnancies, five had adverse outcomes, including syndactyly, cortical blindness, intrauterine fetal death, prematurity, and rash in the newborn. Adverse outcomes occurred in cases with infection during each of the trimesters. Although B burgdorferi could not be implicated directly in any of the adverse outcomes, the frequency of such outcomes warrants further surveillance and studies of pregnant women with Lyme disease.     

Borrelia burgdorferi-specific immune complexes in acute Lyme disease

CONTEXT: Diagnosis of infection with Borrelia burgdorferi, the cause of Lyme disease (LD), has been impeded by the lack of effective assays to detect active infection. OBJECTIVE: To determine whether B. burgdorferi-specific immune complexes are detectable during active infection in LD. DESIGN, SETTING, AND PATIENTS: Cross-sectional analysis of serum samples from 168 patients fulfilling Centers for Disease Control and Prevention surveillance criteria for LD and 145 healthy and other disease controls conducted over 8 years. Tests were performed blinded. MAIN OUTCOME MEASURE: Detection of B. burgdorferi immune complexes by enzyme-linked immunosorbent assay and Western blot. RESULTS: The B. burgdorferi immune complexes were found in 25 of 26 patients with early seronegative erythema migrans (EM) LD; 105 of 107 patients with seropositive EM LD; 6 of 10 samples that were seronegative [corrected] with culture-positive EM; 0 of 12 patients who were treated and recovered from LD; and 13 of 13 patients with neurologic LD without EM. Among 147 controls, B. burgdorferi immune complex was found in 0 of 50 healthy individuals; 0 of 40 patients with persistent fatigue; 0 of 7 individuals with frequent tick exposure; and 2 of 50 patients with other diseases. CONCLUSION: These data suggest that B. burgdorferi immune complex formation is a common process in active LD. Analysis of the B. burgdorferi immune complexes by a simple technique has the potential to support or exclude a diagnosis of early as well as active LD infection.     

莱姆病在我国的首次报告

1986年作者在黑龙江省林区观察到莱姆病162例,此病又名伯格多费里疏螺旋体病,系由硬蜱传播,可引起人体多器官病变,早期皮肤病变是慢性游走性红斑,以后可有头痛、颈项强直、面瘫等神经系统症状和心脏、关节损害。免疫学检查发现恢复期病人血清中有高度特异性抗体。对部分现症病人青霉素治疗取得明显疗效。本病例报告系莱姆病在我国的首次报告。     

Toll样受体和趋化因子与莱姆关节炎发病的相关性

莱姆病是一种由伯氏疏螺旋体引起,经蜱传播的自然疫源性疾病,也是一种人兽共患病,莱姆关节炎是莱姆病的晚期临床表现,严重者可终生致残,严重影响了人们的健康和生活质量,目前,对莱姆关节炎的致病机制尚不清楚,国内外已经取得了一系列进展,但有待进一步研究.现就Toll样受体和趋化因子与莱姆关节炎发病关系的研究做一综述.     

河北省承德林区莱姆病血清学调查研究

目的:调查承德地区林区动物莱姆病以及当地居民感染莱姆病螺旋体的情况.方法:血清流行病学检测承德林区牛、羊血清IgG抗体和当地居民血清IgG抗体,PCR法检测莱姆病螺旋体.结果:血清流行病学检测结果显示,在承德林区至少有牛、羊两种动物中有莱姆病的感染, 其感染率分别为 23.3%、30%;当地居民也存在莱姆病的感染,感染率为13.3%;PCR检测未查到阳性结果.结论:此次调查证实了牛、羊是承德林区莱姆病的重要贮存宿主;当地居民存在莱姆病的感染.     

莱姆病螺旋体重组质粒pBX1的DNA序列分析及其在大肠杆菌中的诱导表达

目的　为莱姆病血清学诊断和基因工程亚单位疫苗研制提供靶抗原。方法　采用 377型 DNA自动测序仪对莱姆病螺旋体重组质粒 p BX1的插入片段进行 DNA序列测定 ,并通过计算机软件对其进行限制性内切酶酶谱分析。然后将重组质粒 p BX1在大肠杆菌中进行诱导表达 ,并对其表达产物进行免疫印迹分析。结果　1重组质粒 p BX1插入片段大小为 477bp,其核苷酸序列与文献报道的 p83基因全序列相应区段相比较仅有一个碱基的变异 ,2成功绘制了该插入片段的限制性内切酶酶谱 ;3重组质粒在大肠杆菌中诱导表达后获得了 2 9kd的融合蛋白 ;4Western- blotting分析表明该融合蛋白能与莱姆病多价抗血清呈强阳性印迹反应。结论　该研究成功地对莱姆病螺旋体 83kd抗原蛋白特异性区段进行了基因重组和表达 ,为进一步研究其在莱姆病血清学诊断和基因工程亚单位疫苗研制中的应用奠定了基础。     

莱姆病螺旋体重组质粒pBX1的DNA序列分析及其在大肠杆菌中的诱导表达

目的 为莱姆病血清学诊断和基因工程亚单位疫苗研制提供靶抗原。方法 采用377型DNA自动测序仪对莱姆病螺旋体重组质粒pBX1的插入片段进行DNA序列测定,并通过计算机软件对其进行限制性内切酶酶谱分析。然后将重组质粒pBX1在大肠杆菌中进行诱导表达,并对其表达产物进行免疫印迹分析。结果 （1）重组质粒pBX1插入片段大小为477bp,其核酸序列与文献报道的p83基因全序列相应区段相比较仅有一个碱基的变异,（2）成功绘制了该插入片段的限制性内切酶酶谱;（3）重组质粒在大肠杆菌中诱导表达后获得了29kd的融合蛋白;（4）Western-blotting分析表明该融合蛋白能与莱姆病多价抗血清呈强阳性印迹反应。结论 该研究成功地对莱姆病螺旋体83kd抗原蛋白特异性区段进行了基因重组和表达,为进一步研究其在莱姆病血清学诊断和基因工程亚单位疫苗研制中的应用奠定了基础。     

The seroprevalence of hepatitis B, hepatitis C and human immunodeficiency virus infections in paediatric oncology patients in Turkey.

One hundred and two newly diagnosed children with malignancy followed up at the Pediatric Oncology Department of Ankara Oncology Hospital were investigated for hepatitis B, hepatitis C and human immunodeficiency virus markers. The ages ranged between seven months and 17 years with a median of 10 years; 62 were male. Twenty-four patients had Hodgkin''s disease, 11 had non-Hodgkin''s lymphoma and 67 patients had other solid tumours. Four patients had positive HBs-Ag, 15 developed immunity against hepatitis B and had anti-HBs antibodies. One patient had a previous infection with positive anti-HBc. Hepatitis C virus antibodies were positive in only one patient. HIV serology was negative in all patients. These results show the high prevalence of hepatitis B virus infection in paediatric oncology patients. In countries where hepatitis B is endemic, strict screening of blood donors, usage of disposable equipment and vaccination of patients is recommended. Although the incidence of hepatitis C and human immunodeficiency virus infections are rising, infection with hepatitis B is still by far the most common.