European League Against Rheumatism recommendations for monitoring patients with systemic lupus erythematosus in clinical practice and in observational studies.

OBJECTIVES: To develop recommendations for monitoring patients with systemic lupus erythematosus (SLE) in clinical practice and observational studies and to develop a standardised core set of variables to monitor SLE. METHODS: We followed the European League Against Rheumatism (EULAR) standardised procedures for guideline development. The following techniques were applied: nominal groups, Delphi surveys for prioritisation, small group discussion, systematic literature review and two Delphi rounds to obtain agreement. The panel included rheumatologists, internists, dermatologists, a nephrologist and an expert related to national research agencies. The level of evidence and grading of recommendations were determined according to the Levels of Evidence and Grades of Recommendations of the Oxford Centre for Evidence-Based Medicine. RESULTS: A total of 10 recommendations have been developed, covering the following aspects: patient assessment, cardiovascular risk factors, other risk factors (osteoporosis, cancer), infection risk (screening, vaccination, monitoring), frequency of assessments, laboratory tests, mucocutaneous involvement, kidney monitoring, neuropsychological manifestations and ophthalmology assessment. A 'core set' of minimal variables for the assessment and monitoring of patients with SLE in clinical practice was developed that included some of the recommendations. In addition to the recommendations, indications for specific organ assessments that were viewed as part of good clinical practice were discussed and included in the flow chart. CONCLUSIONS: A set of recommendations for monitoring patients with SLE in routine clinical practice has been developed. The use of a standardised core set to monitor patients with SLE should facilitate clinical practice, as well as the quality control of care for patients with SLE, and the collection and comparison of data in observational studies.

Infectious antibodies in systemic lupus erythematosus patients.

Infections can act as environmental triggers that induce or promote systemic lupus erythematosus (SLE) in genetically predisposed individuals. New technologies, developed recently, enable simultaneous assessment of multiple antibodies. Antibodies to specific infectious agents may shed light into the mechanisms of induction of SLE. The aim of this study was to investigate the prevalence of seropositivity and the titers of antibodies to bacterial, viral, and parasitic agents in SLE patients compared with non-autoimmune controls. Sera from 260 individuals (120 SLE patients and 140 controls) were tested by the BioPlex 2200 Multiplexed Immunoassay method (BioRad) for the prevalence and titers of antibodies to eight infectious agents (Epstein-Barr virus: early antigen IgG, nuclear antigen IgG, viral capsid antigen IgG and IgM, heterophile IgM; cytomegalovirus IgG and IgM; Toxoplasma gondii IgG and IgM; rubella IgG and IgM; Treponema pallidum TPr15G, TPr17G, TPr47G; herpes simplex virus type 1 and 2 IgG; hepatitis C virus and hepatitis B core antibodies. Cytomegalovirus IgM and Epstein-Barr virus early antigen IgG (but not other Epstein-Barr virus antigens) were significantly more prevalent in SLE patients than in controls. Conversely, positive titers of hepatitis B core and rubella IgG antibodies were less prevalent in the SLE patients than in controls. Other differences in titer positivity prevalence were not detected between patients and controls. The titers of the cytomegalovirus IgM, Toxoplasma IgG, Epstein-Barr virus early antigen, and viral capsid antigen IgG antibodies were significantly higher in SLE compared with controls. Our data suggest the importance of previous exposure to infectious agents in the induction and the prevention of SLE.

Common infectious agents prevalence in antiphospholipid syndrome.

Antiphospholipid syndrome is characterized by thrombosis and pregnancy loss. Infections are generally associated with autoimmune diseases, but in the setting of antiphospholipid syndrome this link has been suggested as having a pathogenic role. In this study, 98 patients with antiphospholipid syndrome were screened for antibodies directed to several infectious agents. The main finding in this study is the significantly higher prevalence of IgM antibodies to toxoplasma and rubella. This novel finding suggests that these infections might be associated with antiphospholipid syndrome. As autoimmune diseases and, in particular, antiphospholipid syndrome are associated with infections, mainly the catastrophic type of the syndrome, this finding implies that a current infection with these agents, i.e. toxoplasma and rubella, might either be related to the pathogenesis of antiphospholipid syndrome or alternatively to its manifestations.

Bacterial triggers and autoimmune rheumatic diseases.

Autoimmune rheumatic diseases are generally considered as a multifactorial aetiology, mainly genetic susceptibility combined with environmental triggers of which bacteria are considered one of the most prominent. Among the rheumatic diseases where bacterial agents are more clearly involved as triggers are: reactive arthritis (ReA), rheumatic fever (RF) and Lyme disease. The role of bacterial infections in inducing other seronegative spondyloarthritis and antiphospholipid antibody syndrome has been hypothesized but is still not proven. The classic form of ReA is associated with the presence of HLA-B27 and is triggered by the urethritis or enteritis causing pathogens Chlamydia trachomatis and the enterobacteria Salmonella, Shigella, and Yersinia, respectively. But several other pathogens such as Brucella, Leptospira, Mycobacteria, Neisseria, Staphylococcus and Streptococcus have also been reported to cause ReA. RF is due to an autoimmune reaction triggered by an untreated throat infection by Streptococcus pyogenes in susceptible individuals. Carditis is the most serious manifestation of RF and HLA-DR7 is predominantly observed in the development of valvular lesions. Lyme disease is a tick-transmitted disease caused by the spirochete Borrelia burgdorferi. Knowledge is limited about how this spirochete interacts with human tissues and cells. Some data report that Borrelia burgdorferi can manipulate resident cells towards a pro- but also anti-inflammatory reaction and persist over a long period of time inside the human body or even inside human cells.

Epstein-Barr virus and cytomegalovirus in autoimmune diseases: are they truly notorious? A preliminary report.

To date, it is believed that the origin of autoimmune diseases is one of a multifactorial background. A genetic predisposition, an immune system malfunction or even backfire, hormonal regulation, and environmental factors all play important roles in the pathogenesis of autoimmune diseases. Among these environmental factors, the role of infection is known to be a major one. Epstein-Barr virus (EBV) and cytomegalovirus (CMV) are considered to be notorious as they are consistently associated with multiple autoimmune diseases. A cohort of 1595 serum samples, of 23 different autoimmune disease groups, was screened for evidence of prior infection with EBV and CMV. All samples were screened for antibodies against EBV nuclear antigen-1 (IgG), EBV viral capsid antigen (IgG and IgM), EBV early antigen (IgG), EBV heterophile antibody, and CMV (IgG and IgM) antibodies using Bio-Rad's BioPlex 2200. A new association is proposed between EBV and polymyositis, as results show a significant increase in titers of various EBV target analytes when compared with healthy controls. Our results also support prior information suggesting the association between EBV and multiple autoimmune diseases, including SLE, antiphospholipid syndrome, rheumatoid arthritis, multiple sclerosis, pemphigus vulgaris, giant cell arthritis, Wegener's granulomatosis, and polyarteritis nodosa (PAN). Elevated CMV IgG titers were observed in sera of SLE patients. Our data support the theory that EBV is notoriously associated with many autoimmune diseases. CMV appears to be associated to autoimmune diseases as well, yet establishing this theory requires further investigation.

10th International Congress on Antiphospholipid Antibodies--summary.

The 10th International Congress on Antiphospholipid Antibodies (Sicily, Italy, September 29-October 3, 2002) (Fig. 1) provided enlightening aspects on the recent developments in antiphospholipid syndrome (APS) and antiphospholipid antibodies in more than 150 lectures and posters. Researchers from all aspects of medicine attended the meeting, implicating the systemic characteristics of APS. The important breakthroughs are summarized.

Coronary calcium and anti-cardiolipin antibody are elevated in patients with typical chest pain.

The aim of this study was to examine whether detection of coronary calcium and the autoimmune response associated with atherosclerosis, either solely or in combination, are different in patients with typical and atypical chest pain. Coronary calcium as detected by spiral computerized tomography and levels of antibodies against cardiolipin (CL), oxidized low-density lipoprotein (ox-LDL), and beta2-glycoprotein-I (beta2-GPI) were studied in patients with typical chest pain (n = 52), atypical chest pain (n = 19), or without chest pain (n = 21). Patients with typical chest pain had higher mean levels of coronary calcium (expressed as natural transformation of total coronary calcium score) compared with patients with atypical chest pain and controls (5.04 vs 3.21 and 2.75, respectively; p < 0.001). The levels of anti-CL were (mean +/- SD of optical density multiplied by 1,000): 262 +/- 140, 170 +/- 82, and 230 +/- 115 for patients with typical chest pain, atypical chest pain, and controls, respectively (p = 0.016). No significant difference was found between groups regarding anti-ox-LDL and anti-beta2-GPI autoantibody levels. In the typical chest pain group, there was a higher prevalence of high total coronary calcium scores (p = 0.03) and high anti-CL levels (p = 0.01) than in the atypical chest pain group. Eighteen of 52 patients with typical chest pain (35%) had both high calcium scores and high antibody levels, whereas none of the 19 patients (0%) who had atypical chest pain had high levels of both (p = 0.003). A combination of both coronary calcium and anti-CL was associated with higher area under the receiver operator characteristic curves than for each separately. High coronary calcium scores or high anti-CL levels are found more often in typical than in atypical chest pain patients, but a combination of high levels of both can better differentiate typical from atypical chest pain patients.

Malignant thymoma associated with autoimmune diseases: a retrospective study and review of the literature.

OBJECTIVES: To determine whether malignant thymoma is associated with high rates of concomitantly occurring autoimmune diseases. METHODS: Sheba Medical Center computer records from 1966 to 1995 were reviewed to identify patients with malignant thymoma, either type I (invasive thymoma) or type II (thymic carcinoma). All patients who had malignant thymoma and autoimmune phenomena were analyzed. The diagnosis of thymic neoplasm was confirmed by two independent pathologists. The diagnosis of autoimmune diseases was based on both clinical and serological findings. RESULTS: Six of 22 (27%) cases of malignant thymoma had an autoimmune disease. Five patients had type I malignant thymoma and either myasthenia gravis (four patients) or Graves' disease (one patient). Only one patient had type II malignant thymoma with Sjögren's syndrome. The diagnosis of autoimmune disease preceded the diagnosis of thymic neoplasm in four cases, and was diagnosed simultaneously in two. CONCLUSIONS: Malignant thymomas are highly associated with autoimmune diseases, as are benign thymomas. To our knowledge, we report the first documented cases of a patient with thymic carcinoma and Sjögren's syndrome, and another with invasive thymoma and Graves' disease.

Intravenous immunoglobulin treatment of lupus nephritis.

OBJECTIVE: To evaluate the clinical response of treatment-resistant membranous and membranoproliferative lupus nephritis to intravenous immunoglobulin (IVIg). METHODS: Seven lupus nephritis patients who failed to respond to at least prednisone and cyclophosphamide were studied. A kidney biopsy showing either membranous or membranoproliferative glomerulonephritis was available in six patients. They were treated with six courses (patients 1 and 2) or 1 or 2 courses (patients 3 through 7) of high-dose IVIg. For patients 3 through 7, the plasma levels of albumin, total cholesterol, urea, creatinine, dsDNA antibody titers, and daily proteinuria were measured just before the IVIg therapy, immediately on completion, and 6 months later. RESULTS: All seven patients had a beneficial response to IVIg. In patient 1, decrease in proteinuria was evident 2 weeks after IVIg was started, nephrotic syndrome gradually disappeared, and she had no proteinuria in 3 years' follow-up. Decline in proteinuria was evident in patient 2 after the 4th IVIg course, but proteinuria reached the pretreatment level 4 months after the therapy ended. In patients 3 through 7, the mean daily proteinuria before IVIg (5.3 +/- 2.1 g) decreased after 1 or 2 IVIg courses (3.3 +/- 1.4 g), and further decreased when measured 6 months later (2.1 +/- 1.3 g). Similarly, the plasma cholesterol level decreased while the plasma albumin level increased after IVIg. CONCLUSIONS: IVIg might be effective in treatment-resistant membranous or membranoproliferative lupus nephritis. Future studies should concentrate on determining the preferred treatment protocol of IVIg for the various classes of lupus nephritis.

Frontiers of SLE: review of the 5th International Congress of Systemic Lupus Erythematosus, Cancun, Mexico, April 20-25, 1998.

OBJECTIVE: To review the recent advances in clinical and experimental research in systemic lupus erythematosus (SLE). METHODS: Review of the 5th International Congress of SLE that took place in Cancun, Mexico, on April 20-25, 1998. RESULTS: The main topics presented at the conference are summarized. These include new findings about the genetics of SLE due to fine mapping of the patients' genes and lupus mouse models, the nucleosome as a major autoantigen in SLE, serving as an immunogen for pathogenic T helper and B cells and contributing to the development of lupus nephritis, abnormalities of apoptosis as a cause of SLE, and apoptotic mechanisms as a cause of autoimmunization. Other topics included the pathophysiologic role of anti-endothelial cell antibodies in lupus with central nervous system involvement, vasculitis, the thrombotic diathesis associated with the antiphospholipid syndrome, induction of endothelial cell apoptosis and its regulation by the idiotypic network, the penetration of antinuclear antibodies to the cytoplasm and nucleus and the subsequent interaction with cellular organelles, and new aspects in the antiphospholipid syndrome, including animal models of the disease and the importance of antibodies to beta-2-glycoprotein-I and prothrombin. Advances in the clinical aspects of SLE included clinical manifestations, diagnosis, pregnancy and neonatal SLE, infections, hormones, and treatment. Additionally, four "Lectures of A Lifetime," entitled (1) What causes lupus? (2) From natural autoimmunity to autoimmune disease; (3) The idiotypic network and SLE; and (4) Late-stage morbidity and mortality in SLE-the role of accelerated atherosclerosis were presented. CONCLUSIONS: Recent advances provide new insights into the pathogenesis of SLE, as well as hope for novel therapeutic modalities and diagnostic measures. These offer the possibility of improving life quality and decreasing mortality from the disease and its complications.

Thymoma, thymic hyperplasia, thymectomy and autoimmune diseases (Review).

There is a bidirectional relationship between autoimmunity and cancer: on the one hand, patients with autoimmune conditions develop neoplastic diseases, and on the other hand, malignant conditions are associated with paraneoplastic autoimmune syndromes. Thymoma is an epithelial tumor which is often accompanied by autoimmune diseases: about a third of the patients with thymoma have myasthenia gravis. Pure red cell aplasia, pemphigus and systemic lupus erythematosus, might also coexist with this tumor. Thymectomy is an optional treatment in some autoimmune diseases (i.e. myasthenia gravis, multiple sclerosis, autoimmune hemolytic anemia, ulcerative colitis, and systemic lupus erythematosus). In this communication we review and discuss the coexistence of autoimmune diseases, thymoma or thymic hyperplasia, and the dual effects of thymectomy on their course.

Anti-endothelial cell antibodies (AECA) in systemic sclerosis--increased sensitivity using different endothelial cell substrates and association with other autoantibodies.

OBJECTIVE: One of the main features of systemic sclerosis (SSc) is vascular damage, the mechanism of which is not understood. In the present study we examined whether screening of SSc patients for different anti-endothelial cells antibodies (AECA) of various origins increase the sensitivity of AECA detection in SSc patients. Secondary aim was an attempt to correlate AECA with other common autoantibodies. MATERIALS & METHODS: 478 SSc patients were studied for the presence AECA, anti-cardiolipin (aCL), anti-dsDNA, anti-heparin (AHA), anti-pyruvate dehydrogenase (PDH) and anti-PDC-E2 autoantibodies. AECA levels were detemined using human umbilical vein EC (HUVEC), bone marrow EC (BMEC), EC hybridoma (EA.hy 926) and Kaposi sarcoma EC (KS). RESULTS: Positive AECA were found in 49.5% of SSc patients (27.1% HUVEC; 34.3% BMEC; 26.3% EaHy 926 and 22.7% KS). The highest percent reactivity of AECA was obtained using microvascular BMEC. When combining BMEC and either other cell lines the reactivity ranged from 41.4% to 46%. A significant association between AECA on the one hand and AHA (p<0.001)) and anti-PDH (p<0.05) on the other was secn. Cross-reactivity with anti-PDC-E2 was excluded by inhibition tests, but AHA and anti-PDH may be part of the spectrum of AECA. CONCLUSIONS: Since false-negative AECA may result from lack of expression of various antigens on a specific EC, analysis of AECA in SSc patients requires using several EC types, including microvascular EC.

Autoimmune diseases and autoimmunity post-bone marrow transplantation.

BMT can both transmit and eliminate autoimmune diseases, and hence it has been suggested as an optional treatment for severe autoimmune conditions. In this communication we deal with the question of whether chronic GVHD is an autoimmune disease in itself, review the literature reports of autoimmune diseases following BMT in humans, and describe the autoimmune nature of the post-BMT state. Chronic GVHD, which is a frequent complication post-BMT, has clinical and pathogenic characteristics similar to autoimmune diseases, such as scleroderma and Sjogren's syndrome. Although the pathogenesis of chronic GVHD is not yet clear, thymic damage induced by acute GVHD may contribute to both the immunodeficiency and autoimmunity characterising chronic GVHD. A similar phenomenon is syngeneic GVHD, which results from an imbalance between autoreactive and autoregulatory lymphocytes. Additionally, other autoimmune diseases have been reported in post-BMT patients, and among these the most common are hypothyroidism, hyperthyroidism, myasthenia gravis and immune cytopenias. Although these diseases also occur also outside the post-BMT setting, they are unique with respect to pathogenesis (no association between myasthenia gravis and thymic pathology), diagnosis (symptoms of hyperthyroidism may be inadvertently related to other conditions), and prognosis (post-BMT autoimmune cytopenias may be fatal and treatment non-responsive). Nevertheless, many other autoimmune diseases have been reported after BMT, and these are mainly presented as case reports. Regarding the mechanism of post-BMT autoimmunity, the minority of cases stem from donor-related transfer of pathogenic lymphocytes or their progenitors, while most of the cases (either chronic GVHD or specific diseases) can be attributed to the immunologic imbalances characterising the post-BMT setting. The factors that may expose an individual to autoimmunity development post-BMT include genetic predisposition, an environmental factor such as CMV, and the nature of the donor who may aid in creating microchimerism and subsequently chronic GVHD and its related autoimmune manifestations.

Autoantibodies to oxidized low-density lipoprotein in coronary artery disease.

BACKGROUND: The significance of antioxidized low-density lipoprotein (oxLDL) antibodies in atherogenesis is not yet clear, and there are conflicting data regarding anti-oxLDL levels in early hypertension. METHODS: The levels of anti-oxLDL antibodies were studied in coronary artery disease patients with (n = 82) or without (n = 36) hypertension, in association to other risk factors for coronary artery disease. RESULTS: The levels of anti-oxLDL antibodies did not differ significantly between coronary artery disease patients with or without hypertension. (0.132 +/- 0.146 v 0.153 +/- 0.158 optical density at 405 nm, respectively; P = .48). No significant differences in anti-oxLDL antibodies were found between men and women with and without hypertension, between hypertensive patients with normal and abnormal blood pressure measurements, and between medicated and nonmedicated hypertensive patients. The presence of diabetes mellitus, smoking, and hypercholesterolemia, either solely or in combination, did not result in significant differences in antibody levels in the hypertensive or normotensive patients. CONCLUSIONS: Although the levels of oxLDL antibodies might be modified in early hypertension, once advanced coronary artery disease has developed the presence of hypertension does not affect anti-oxLDL levels.

A malignancy work-up in patients with cancer-associated (paraneoplastic) autoimmune diseases: pemphigus and myasthenic syndromes as cases in point (review).

Although some autoimmune diseases are known to be associated with a higher incidence of cancers, they are not usually considered as paraneoplastic diseases, but rather as autoimmune diseases that may be neoplasia-associated, since currently it is not known whether the tumor leads to their development, or alternatively another underlying condition turns the patients prone to both cancer and autoimmunity. We review the association of cancer with pemphigus, paraneoplastic pemphigus, myasthenia gravis and Eaton-Lambert syndrome, and discuss the importance of looking for an occult malignancy in a patient with a newly-diagnosed autoimmune disease that is known to be associated with cancer.

Autoantibodies, autoimmunity and cancer (review).

There is a strong association between neoplasms and autoimmune diseases. Numerous autoimmune phenomena have been reported in malignancies and conversely: malignant tumors are diagnosed in increasing frequency in autoimmune conditions. We review the most common autoimmune diseases and autoantibodies found in malignancies, discuss the therapeutic role of these autoantibodies in cancer, and summarize the current knowledge on malignant transformation in autoimmunity.

Anti-cardiolipin antibody from a patient with antiphospholipid syndrome (APS) recognizes only an epitope expressed by cardiolipin/beta 2-glycoprotein-I (beta 2GPI) complex and induces APS.

OBJECTIVE: As the antiphospholipid syndrome (APS) is characterized by antibodies which bind negatively charged phospholipids either directly or mainly through different target epitopes located on the beta-2-glycoprotein-I (beta 2GPI) molecule, the aim of this study is to describe an additional target epitope for anti-cardiolipin binding. METHODS: The binding characteristics of affinity purified anti-cardiolipin antibodies from a patient with monoclonal gammopathy associated with clinically overt APS were studied; inhibition studies were also carried out. These antibodies were used for the active induction of experimental APS. RESULTS: The affinity purified anti-cardiolipin antibodies were found to bind a target epitope created by the complex of cardiolipin/beta 2GPI, while not reacting with a complex composed by another phospholipid (phosphatidylserine/beta 2GPI), as confirmed by direct binding and competition assays. Immunization of naive mice with this unique affinity purified anti-cardiolipin antibody resulted in the induction of experimental APS (thrombocytopenia, prolonged coagulation timed and fetal resorptions). The anti-cardiolipin/beta 2GPI injected mice developed high titers of mouse anti-cardiolipin/beta 2GPI antibodies with the same binding characteristics as the human antibody which was used for disease induction. CONCLUSION: APS is a unique syndrome that is characterized by a diversity of pathogenic anti-phospholipid antibodies which may explain the diversity of clinical manifestations reported in patients.

Association of 16/6 and SA1 anti-DNA idiotypes with anticardiolipin antibodies and clinical manifestations in a large cohort of SLE patients. European Concerted Action on the Immunogenetics of SLE.

OBJECTIVE: The SA1 and 16/6 idiotypes can be found in some patients with systemic lupus erythematosus (SLE) or anti-phospholipid syndrome (APS). The aim of this study was to ascertain the prevalence of these idiotypes in a large cohort of SLE patients, and to determine whether their presence is correlated with the anticardiolipin (aCL) and anti-dsDNA antibodies or with the clinical manifestations of SLE. METHODS: 492 SLE patients were evaluated for clinical manifestations of SLE and were assigned a disease severity score. ds-DNA autoantibodies, aCL autoantibodies of the IgM, IgG and IgA isotypes, and SA1 and 16/6 idiotypes were also determined in these patients. RESULTS: The prevalence of the SA1 and 16/6 idiotypes in the 492 SLE patients was found to be 11% and 5.1%, respectively, and these idiotypes were significantly more prevalent in the patients who had aCL antibodies of either the IgG, IgM or IgA isotypes. Moreover, while the 16/6 idiotype was not associated with the clinical manifestation of either SLE or APS, the SA1 idiotype was found significantly more frequently in patients who had vascular events Raynaud's phenomenon or hemolytic anemia (p = 0.016, 0.01, 0.01, respectively). CONCLUSION: SLE patients with the SA1 idiotype may run a higher risk of developing vascular events, Raynaud's phenomenon or hemolytic anemia. These clinical manifestations can be attributed to both SLE and secondary APS when aCL autoantibodies are also found. These results indicate that the possible pathogenicity of certain idiotypes in SLE cannot be excluded.

Comparative clinical study of cefonicid, chloramphenicol, and penicillin in community-acquired pneumonia.

Community-acquired pneumonia is one of the most common infectious conditions that require hospitalization. When intravenous treatment is indicated, cefonicid is usually the drug of choice. The aim of this study was to find out if chloramphenicol, which is superior to the standard drugs from a financial point of view, could serve as an equally efficient treatment, especially in the elderly. The outcomes of 3 pneumonia patient groups who were either treated with cefonicid, chloramphenicol or penicillin-G (n = 59, 17, 24, respectively) were retrospectively compared. Data about demographic characteristics of the patients, clinical outcomes, rehospitalization rates, duration of improvement/treatment/ hospitalization and clinical laboratory tests were obtained from each patient's medical records. Only minor differences (even though occasionally significant) were found with respect to rehospitalization and improvement rates, duration of hospitalization, treatment and improvement, death rates and clinical laboratory tests. However, chloramphenicol patients were found to be significantly older than cefonicid patients. Moreover, no bone-marrow suppression was associated with chloramphenicol treatment. All 3 drugs tested seem to have the same efficacy. We conclude that since chloramphenicol is as safe as, and much cheaper than cefonicid, this antibiotic agent is not inferior to the others, its usage in older patients with pneumonia should be considered.

Brucellosis outbreak: analysis of risk factors and serologic screening.

Israel is one of the Mediterranean countries in which Brucellosis is endemic. As recently there has been a Brucellosis outbreak in a kibbutz, the aim of this study is to identify asymptomatic infected Kibbutz members, and to delineate the manner of infection in this setting. Therefore, all the asymptomatic Kibbutz members were screened by the Rose Bengal test for Brucellosis, while both patients and healthy members were asked to fill in a questionnaire in order to pinpoint the manner of infection, and signs and symptoms of the disease. In addition to the 14 patients with Brucellosis, 2 other Kibbutz members were also found to be infected by the screening tests. Analysis of the data of the questionnaires from 142 healthy and 16 patients disclosed that almost all of the infected patients (15/16) worked in the cowshed, as opposed to only 24 out of 142 (16.9%) of the healthy members. The infected tended to participate more in calf deliveries, and had contact with cow's blood and placenta, compared with the healthy subjects (P<0.001), while there were no significant differences with respect to having cuts on hands, or working in the cowshed without gloves. In addition, 15 out of 16 (93.8%) infected persons also drank unpasteurized milk, as compared with only 17 of the 142 (12%) healthy members (P<0.001), and thus were exposed to 2 major risk factors (working in the cowshed and consumption of unpasteurized milk). As the cows of the Kibbutz's cowshed were affected by Brucella melitensis (which usually affects flocks of goats and sheep rather than cows), the microbe was probably transmitted to the cowshed from neighboring flocks by wandering dogs, and then to the infected humans.