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PubMed2001

Cutaneous findings encountered in brucellosis and review of the literature.

BACKGROUND: Human brucellosis is an infectious disease produced by Brucella species: small, coccoid or rod-like, aerobic, Gram-negative bacteria. The infection is common in developing countries, and can also affect the skin. Its prevalence is high in our region of Turkey, where stockbreeding is one of the main economic sources, compared with the industrially developed areas of Turkey, and dermatologic complaints due to brucellosis are fairly common. MATERIALS AND METHODS: One hundred and three patients with serologically and clinically confirmed brucellosis were studied in order to investigate the prevalence of cutaneous findings and their variability in brucellosis. Fifty-two (50.49%) were males and 51 (49.51%) were females with an age range of 4-70 years (mean, 30.45 +/- 15.08 years). RESULTS: Of these patients, 14 (13.59%) had cutaneous findings probably related to brucellosis. These findings were more frequent in females (11 cases) than males, and most of the females (eight cases) were housewives; three were students. Urticaria-like papules and plaques were the most common findings; they were seen in six (35.3%) patients. One case had livedo reticularis and another palmar erythema, which have not been reported previously. No relationship was observed between the serologic values and the cutaneous findings. CONCLUSIONS: Cutaneous findings in our cases were more prevalent than in other reported studies. It is important to emphasize that cutaneous lesions are not specific to brucellosis and may be seen in a variety of other dermatologic diseases caused by many agents; therefore, these agents should be kept in mind in the differential diagnosis.

Adolescent↗
PubMed1993

Brucellosis among hospital employees in Saudi Arabia.

OBJECTIVE: To report experience with brucellosis among expatriate hospital employees in an area of the world where brucellosis is endemic. DESIGN: Review of cases from the viewpoints of direct supervisor and treating physician, including epidemiologic interviews and clinical follow-up. SETTING: Tertiary care hospital center in a developing country that increased from 125 beds to 450 beds during the period studied. PATIENTS: Employees with clinical findings suggesting brucellosis and in whom a positive blood culture or significantly elevated serologic test confirmed the diagnosis. RESULTS: Nine hospital employees from nonendemic areas developed brucellosis. Five were from England and four from North America. Seven were bacteriology technologists, one was a nurse, and one was an obstetrician. Each had an acute febrile illness with malaise, arthralgia, or headache. Brucella titers were > or = 1:1,280. Five were bacteremic with positive Brucella cultures. All responded to anti-Brucella therapy. Three patients had relapses, but there were no complications. CONCLUSIONS: Among Saudi patients, brucellosis is generally attributable to drinking infected milk or contacting infected animals. On the other hand, among expatriate hospital employees, the infection is likely due to processing Brucella cultures or dealing with infected body fluids. In 1988, the laboratory began stricter infection control measures. Since then, there has been only one case of brucellosis among the hospital employees.

Adult↗
PubMedDate not supplied

Localized brucellosis: popliteal artery aneurysm, mediastinitis, dementia, and pneumonia.

Four patients with unusual manifestations of brucellosis presented to two tertiary-care teaching hospitals over a 15-year period. These cases posed difficult diagnostic problems. Each patient presented with signs and symptoms suggestive of a localized disease process: ischemic limb, mediastinal mass, dementia, and pneumonia. Two were afebrile, and two were acutely ill with high fever. Three patients had normal agglutination titers on admission, although in one patient the titer rose to 1:5,120 during therapy. During this same 15-year period only 10 cases of acute uncomplicated brucellosis were diagnosed at the two hospitals. The rarity of focal manifestations of brucellosis and general inexperience with brucellosis led to delays in diagnosis of 5-14 days. In view of the protean clinical presentations of localized brucellosis, careful inquiries about possible exposure to livestock and repeated serologic tests for brucellosis are important in the management of any diagnostically difficult clinical problem.

Adult↗
PubMedDate not supplied

Serologic diagnosis of human brucellosis: analysis of 214 cases by agglutination tests and review of the literature.

The serum agglutination test (SAT) and 2-mercaptoethanol (2ME) agglutination were used in studies of the sera of 214 patients in whom brucellosis was suspected. On the basis of historical, epidemiologic, clinical, and serologic data, four groups were identified: group I (108 cases) had negative agglutination reactions, and brucellosis was considered unlikely; group II (57 cases) had positive agglutination reactions, and active brucellosis was diagnosed; group III (37 cases) had positive agglutination reactions, but other factors--notably, a history of prior infection--made inactive brucellosis likely; and group IV (12 cases) had positive agglutination reactions, but insufficient data were available for further classification. Most patients with active brucellosis had agglutinin titers of greater than or equal to 160; however, no single titer was always diagnostic. Although more sensitive tests are available, agglutination reactions provide data sufficient to differentiate active from inactive disease when other factors are considered and follow-up sera are tested. This article discusses individual cases and reviews the literature on the diagnosis of brucellosis.

Adolescent↗
PubMed2006

CD80/CD28 co-stimulation in human brucellosis.

Despite treatment, 10-30% of brucellosis patients develop chronic disease, characterized by atypical clinical picture and/or relapses. A defective T helper 1 (Th1) response and a low [corrected] percentage of CD4(+)/CD25(+) cells have been described in chronic brucellosis patients. CD80/CD28 co-stimulation is critical for an efficient Th1 response and has not been studied previously in human brucellosis. In order to investigate the role of CD80/CD28 co-stimulation, 13 acute brucellosis patients (AB), 22 chronic brucellosis patients (CB, 12/22 relapsing type-CB1 and 10/22 atypical type-CB2), 11 'cured' subjects and 15 healthy volunteers (controls) were studied. The percentage of CD4(+)/CD28(+) T lymphocytes and CD14(+)/CD80(+) monocytes were analysed by flow cytometry both ex vivo and after phytohaemagglutinin (PHA)-stimulation with or without heat-killed Brucella abortus (HkBA). Ex vivo analysis showed no differences between all groups studied. PHA stimulation up-regulated the percentage of CD80(+) monocytes in AB compared to 'cured' subjects and controls (P < 0.001), although the proportion of CD4(+)/CD28(+) cells did not alter. A higher percentage of CD80(+) monocytes was observed in the CB1 subgroup, compared to AB, 'cured' subjects and controls (P = 0.042, < 0.001 and < 0.001, respectively). CB2 was characterized by a lower percentage of CD80(+) monocytes in comparison to CB1 (P = 0.020). HkBA in PHA cultures down-regulated the percentage of CD80(+) monocytes compared to PHA alone in all groups, especially in AB and CB patients (P < 0.001 and P = 0.007, respectively). In conclusion, the diminished percentage of CD4(+)/CD25(+) T cells in CB is not associated with inadequate CD80/CD28 co-stimulation. We speculate that differential frequency of CD80(+) monocytes after PHA stimulation could serve as a qualitative parameter of disease status, related to the different clinical forms of chronic brucellosis.

Acute Disease↗
PubMed1992

A simple enzyme immunoassay for detecting brucellosis antibodies.

A simple enzyme immunoassay was developed and evaluated for serological diagnosis of brucellosis in 25 patients with various forms of brucellosis and 292 control patients with other conditions and disorders. All brucellosis patients gave a positive test with the initial sample. In 3 acute, febrile brucellosis patients with follow-up sera taken during therapy a sharp drop in specific antibody was noted. There was a less pronounced antibody reduction in 1 chronic and 2 relapse patients and an antibody increase in 1 chronic and 1 relapse case. All control samples gave negative results. In addition, the assay was evaluated as a screening test with 315 sera from 'healthy' individuals living in a brucellosis focus and representing 15% of that population. 11.5% (34/293) of subjects with no reported history of brucellosis and 45% (10/22) of cases treated in the past gave a positive test result. The agreement in those samples between the assay and the serum agglutination test was 95.5%.

Adolescent↗
PubMed2006

Th-1 cytokines gene polymorphism in human brucellosis.

Brucellosis is a worldwide zoonosis. Infection with Brucella species results in the activation of cell-mediated immune response. The interaction between Th1and Th2 cytokines determines the outcome of disease. Production of each cytokine is in turn affected by genetic factors. In this study, we investigated the possible association between Th1 cytokines gene polymorphism and brucellosis. Different genotypes of TNF-alpha, IFN-gamma and IL-2 were determined by polymerase chain reaction-sequence-specific primer in 47 patients with brucellosis and in 166 healthy controls. Allele frequencies of these genotypes were compared using the chi2 test. The results showed a significant difference in the TNF-alpha genotype GG/GG in patients in comparison with controls (76.7% vs. 21%) (P = 0.001, OR = 12.42, 95%CI 5.7-27.7). There was no significant difference in the frequency distribution of the IFN-gamma genotypes between two groups. IL-2 GG genotype at position -330 was about two times more common in cases than in controls, but the difference was not significant (10.6 vs. 4.6 P value = 0.09). This study shows that genetically low producers of TNF-alpha are possibly susceptible to brucellosis and raise doubt about the role of gene polymorphism of INF-gamma in brucellosis which was demonstrated in previous studies. It seems that patients with brucellosis did not have a defect in producing IL-2 with even a trend towards producing higher amounts of this cytokine.

Adult↗
PubMed1996

Rapid laboratory confirmation of human brucellosis by PCR analysis of a target sequence on the 31-kilodalton Brucella antigen DNA.

We developed a PCR-based assay for the rapid and specific laboratory diagnosis of human brucellosis directly from whole blood. Specimens were collected in EDTA tubes from 17 patients with acute serologic brucellosis and 3 patients with chronic relapsing brucellosis as determined by serologic tests and the patient's clinical picture. DNA was extracted from peripheral mononuclear cells obtained from the blood of patients with brucellosis and control individuals. Specific primers for the PCR amplification of a 223-bp region on the sequence encoding the 31-kDa immunogenic Brucella abortus protein (BCSP 31) were used. All amplicons had the expected size of 223 bp. The specificity of amplification was determined by Southern hybridization and restriction endonuclease analysis. DNA extracted from blood taken from 30 healthy individuals as well as from 9 patients with typhoid fever did not show any amplification with the primers used. The test proved to be rapid and specific for the laboratory confirmation of acute human brucellosis. Further studies must be conducted to assess the utility of this test on additional patients with chronic relapsing brucellosis as well as patients under treatment.

Acute Disease↗
PubMed2000

Evaluation of an immunocapture-agglutination test (Brucellacapt) for serodiagnosis of human brucellosis.

We evaluated the validity and the usefulness of a new test for the diagnosis of human brucellosis based on an immunocapture-agglutination technique. A total of 315 sera from 82 patients with a diagnosis of brucellosis, 157 sera from patients in whom brucellosis was suspected but not confirmed, and 412 sera from people living in rural areas with endemic brucellosis were studied. The seroagglutination test (SAT), Coombs anti-Brucella test, and Brucellacapt test were evaluated. All the initial sera from the 82 patients proved to be positive in Brucellacapt and Coombs tests, while only 75 (91.4%) were positive in the SAT. If a >/=1/160 diagnostic threshold titer was defined for the Brucellacapt test, Coombs test, and SAT, the sensitivities were 95.1, 91.5, and 65.8%, respectively. Taking the same diagnostic threshold titer for the 157 sera from the unconfirmed but suspected patients, the specificities of the Brucellacapt, Coombs, and SAT were 81.5, 96.2, and 100%, respectively; for the 412 control sera, the specificities were 99.0, 99.8, and 100%. The diagnostic efficiency (area below the receiver operating characteristic curve) of Brucellacapt was 0.987852 (95% confidence interval [CI], 0.95109 to 0.99286), very similar to the diagnostic efficiency of the Coombs test (0.97611; 95% CI, 0.94781 to 0.99146) and higher than that of SAT (0.91013; 95% CI, 0.86649 to 0.94317). The results of the Brucellacapt test were compared with those of the Coombs test (correlation coefficient, 0.956; P = 0.000) and SAT (correlation coefficient, 0.866; P = 0.000). The study shows very good correlation between the Brucellacapt and Coombs tests, with a high concordance between titers obtained in the two tests. Nevertheless, lower correlation and concordance were found between the Brucellacapt and Coombs tests when the results for titers of >/=1/160 were compared (0.692; P = 0.000). In acute brucellosis, the Brucellacapt and Coombs tests render positive titers of >/=1/160. When the titers are lower, they increase significantly in the following 30 days, despite the evolution of SAT titers. In contrast, Brucellacapt and Coombs titers are always high (>/=1/640) in brucellosis with long evolution, whether SAT titers are higher or lower than 1/160.

Adolescent↗
PubMed1999

Diagnosis of bovine brucellosis by skin test: conditions for the test and evaluation of its performance.

Brucellergene OCB (Rhône-Mérieux) was used as an allergen to define the intrinsic parameters of a skin test and to compare its properties with serology for the diagnosis of bovine brucellosis. The skin test was also evaluated for its capacity to solve problems associated with false positive reactions in serological tests. The optimal reading delay for the skin test was 72 hours. The brucellosis allergic reaction was two to three times less intense than the tuberculosis allergic reaction. An increase of 1.1 mm or more in the skin thickness was therefore considered to be an adequate cut-off. The specificity calculated for 1192 brucellosis-free animals (including animals from brucellosis-free herds in which false positive serological reactions had been reported) was 99-83 per cent (95 per cent confidence interval [CI] 99-40 to 99-98 per cent). The sensitivity determined from 27 experimentally infected heifers ranged from 93 per cent (95 per cent CI 76 to 100 per cent) to 78 per cent (95 per cent CI 58 to 91 per cent) when measured respectively one and six months after the infection. Allergic reactions could be detected in vaccinated animals up to four-and-a-half years after the vaccination. On the other hand, no sensitisation was recorded in naïve animals after up to eight monthly injections of the allergen. The skin test gave valuable information, in combination with the serological tests, in both acute and chronic brucellosis. The skin test discriminated brucellosis clearly from false positive serological reactions due to infections with Yersinia enterocolitica O9.

Allergens↗
PubMed2004

Cytokine profile and nitric oxide levels in sera from patients with brucellosis.

The aims of this study were to investigate the serum levels of some cytokines [tumor necrosis factor-alpha (TNF-alpha), interleukin 1beta (IL-1beta), IL-2R, IL-6, and IL-8] and nitric oxide (NO) levels in patients with untreated brucellosis and to test the correlation of these parameters with each other. The study was conducted on 67 subjects, 37 patients with brucellosis and 30 healthy individuals with no history of Brucella infection. Brucellosis was identified by a positive blood culture and/or increased Brucella antibodies in serological tests in addition to compatible clinical symptoms. Cytokine profile analysis was performed by the immulite chemiluminescent enzyme immunometric assay whose inter- and intra-assay coefficients of variance were 2.6-3.6 and 4.4-8.5%, respectively. The levels of nitrites/nitrates, which are representative of NO levels, were measured by the Griess method. Patients with brucellosis had significantly elevated serum levels of nitrites/nitrates, IL-2R, IL-6 and IL-8 (mean +/- SD, 102.8 +/- 23.8 micromol/l, 806.1 +/- 58.5 U/ml, 21.1 +/- 2.3 pg/ml, and 8.8 +/- 1.6 pg/ml, respectively) compared to healthy controls, whereas TNF-alpha and IL-1beta levels were unchanged. No statistically significant correlation was detected between any of the studied cytokine levels and nitrate/nitrite concentrations according to Pearson's linear correlation test. We conclude that only IL-6, IL-8 and IL-2R are elevated in brucellosis and the extent of elevation depends on the severity and clinical pattern of the disease. Moderate elevation in serum NO was comparable to that observed in previous studies. This explains the absence or very rare occurrence of septic shock in brucellosis.

Adult↗
PubMed2002

Brucellosis in wildlife.

Brucellae infections have been documented world-wide over the years in a great variety of terrestrial wildlife species. Recently, brucellae infections have also been reported in a wide variety of marine mammals. A very important consideration with regard to terrestrial brucellosis in wildlife is to distinguish between a spillover of infection from domestic animals and a sustainable infection in wild species. The probability of brucellosis becoming established and being sustainable in a species depends on a combination of factors including host susceptibility, infectious dose, contact with infected animals, management and environmental factors. In this context, the development of the game farming industry appears to have contributed to the re-emergence of brucellosis. The gold standard in brucellosis diagnosis remains the isolation of brucellae. If brucellosis is suspected in an animal or a wildlife population following positive serological results, attempts to isolate the organism should always be performed. The release of anti-brucellae vaccine strain in wildlife is of concern because this could lead to environmental contamination and infection of other wild species. Therefore, the appropriate dosage of the vaccine in target species as well as the safety of the vaccine in non-target species must be addressed in technical terms in order to assist decision-making regarding the management of wildlife brucellosis.

Animals↗
PubMed2004

Human and animal brucellosis in Jordan between 1996 and 1998: a study.

Between 1996 and 1998, a total of 2,494 samples of blood from humans and animals were collected and tested for brucellosis. This total included 1,594 samples of animal blood, collected from 1,050 sheep from 20 flocks, and 544 goats from eight herds. The serum samples were tested using the Rose Bengal test, the tube agglutination test, the complement fixation test and an enzyme-linked immunosorbent assay. Moreover, a complete history was compiled from each flock/herd. The rate of abortions in sheep due to brucellosis ranged from 0.5% to 56%, with a mean of 33.2%. The goats had a higher abortion rate. Thirty-four aborted sheep foetuses collected from these 20 flocks were bacteriologically and pathologically examined. A pure culture of Brucella melitensis biotype 3 was isolated from 21 of the aborted foetuses. The human blood samples were collected from two groups: first, from 800 apparently healthy people who were reporting to community hospitals for routine health checks and secondly, from 100 people from groups with a high-risk of contracting brucellosis, such as veterinarians, sheep-herders and laboratory technicians. The Brucella antibody titres for the 900 human serum samples were obtained using the microtitre agglutination test. The cumulative percentage of the serum samples showing a titre reading greater than 1:80 was higher in the at-risk group than among the normal population (7% compared to 4.1%). Although these results were not statistically significant, the higher percentage of positive reactors among the high-risk group may indicate an increased risk factor among professional agricultural and veterinary personnel in Jordan. It was concluded that brucellosis is common in sheep and goats in Jordan, subjecting the human population to high risks. Brucella melitensis Rev. 1 vaccination has been internationally recognised as the key to successfully controlling the disease. All animals in Jordan were repeatedly vaccinated between 1996 and 1998 on a trial basis, using a reduced dose of 1 x 10(5) colony-forming units (CFU). Cumulative data on the annual rate of human cases of brucellosis indicate that fewer people are affected each year. The same is true for the rate of abortions in animals. Such evidence strongly suggests that the vaccination programme has been successful. However, as wild strains of Brucella have also been isolated from vaccinated animals, the authors recommend increasing the amount of vaccine to a full dose of 1 to 2 x 10(9) CFU and vaccinating young female animals between the ages of three and eight months. To avoid brucellosis in humans, people should be educated about the dangers of contact with infected animals and the consumption of raw milk and milk products.

Abortion, Veterinary↗
PubMed2005

Etiological role of brucellosis in autoimmune hepatitis.

To show that brucellosis may trigger autoimmune hepatitis (AIH), in addition to nonspecific liver involvement and toxic hepatitis, due to a class effect of tetracycline family used for treatment. We present a female patient admitted to our hospital due to partially improved fatigue and elevated liver enzymes following doxycycline and streptomycin usage for brucellosis. Brucellosis is endemic in our country, Turkey. It may involve any organ in the body. Liver is frequently involved. Doxycycline used for treatment occasionally may lead to hepatotoxicity. AIH is a necroinflammatory disease of the liver. Certain drugs (e.g. minocycline), toxins, and viruses (hepatitis B, hepatitis C, EBV, etc.) can trigger AIH. Only one case of AIH probably caused by doxycycline and brucellosis was reported. We discuss the relationship between brucellosis, AIH, and hepatotoxicity of doxycycline. Brucellosis may trigger AIH.

Anti-Bacterial Agents↗
PubMed1998

[Brucellosis in pregnancy].

Brucellosis is rare in pregnancy. Recently, an increase in the incidence of this disease has been observed in our area. We present 7 cases of brucellosis in pregnancy and review the literature on the effects of brucellosis on the outcome of pregnancy. Brucellosis is rare in the Middle East and Africa and the most common source of infection is unpasteurized milk products. Brucella is a coccobacillus, gram-negative bacterium, whose hosts are mostly animals. There is controversy about the relationship between brucellosis and the outcome of pregnancy. There is some evidence that there is a higher rate of complications such as abortion, premature rupture of membranes and preterm delivery in infected animals. Reasons for this difference in the impact of brucella in animals and man include the absence of the carbohydrate erythritol in the human placenta, which appears to be a preferential medium and growth factor for brucella in the placentas of animals. There is uncertainty regarding effects of brucella in early pregnancy and no evidence of its transplacental passage in later pregnancy, causing adverse obstetrical outcome, although recently there has been a single report of Brucella abortus (biotype 2). We present 7 cases of brucellosis in pregnant women found between 1977-1988. Its incidence among the women who delivered here is 0.007% (7/92, 768 deliveries). Our first case was complicated by preterm premature rupture of membranes and preterm delivery in the 20th week of gestation. In 2 other cases there was preterm delivery with 1 developing clinical chorioamnionitis. The 4 remaining women delivered at term, although 1 had preterm premature rupture of membranes and intra-uterine growth retardation, and 2 had postpartum endometritis.

Adult↗
PubMed1999

[Control of brucellosis in Taibe: multi-central collaboration].

Brucellosis is contracted from domestic animals. Poor hygiene, primitive animal breeding methods and traditional food preparation are the main contributory factors. We describe an intersectoral program for controlling brucellosis in Taibe, an Arab town in Israel, which had a particularly high incidence of the disease in 1992 and 1993. At the beginning of 1994 the Israel Ministry of Health and the Community Pediatric Center of Taibe established a community-based program for controlling brucellosis in Taibe. It included an intensive public health education campaign and periodic examination and vaccination of animals. Physicians, veterinarians, nurses, school officials and health inspectors were recruited for this purpose. Residents' awareness of brucellosis was determined before and after the study. After intervention, the incidence of the disease sharply declined from 176.6 and 175.0/100,000 in 1992 and 1993 respectively, to 5.7, 10.4 and 2.5/100,000 in 1994, 1995 and 1996, respectively, (odds-ratio 24.44; p < 00000). Residents' awareness of brucellosis and preventive measures were significantly increased by the end of the study. We conclude that intersectoral collaboration is an important tool for controlling brucellosis.

Animals↗
PubMed2001

Ascites caused by brucellosis: a report of two cases.

Brucellosis is a zoonosis still endemic in developing areas of the world. Focal complications of Brucellosis are well known and often troubling in the differential diagnosis. Gastrointestinal complications of Brucellosis are randomly reported, ascites being particularly rare, and usually in the context of a predisposing condition such as cirrhosis. We describe two cases of ascites attributed to Brucellosis, one in a previously healthy patient with an accompanying clinical picture of acute Brucellosis, in whom ascites reflected the response of the peritoneal mononuclear phagocytic system, and one in a HBsAg-positive, but not cirrhotic, patient, in whom Brucellosis seemed to act as a trigger effect for the development of ascites. Both cases of ascites were of an effusion type, with a predominantly lymphocytic cell count, and exhibited an excellent response to treatment with tetracycline and rifampicin.

Adult↗
PubMed1975

Use of the brucellosis card test for screening cattle in Saskatchewan.

One group of 28,714 bovine sera were tested by both the brucellosis tube serum agglutination test and the brucellosis card test. The tube serum agglutination test confirmed 99.8% of the negative brucellosis card test results. The brucellosis card test identified 63% of the tube serum agglutination test reactors. In a second group of 496 sera reacting to either the tube serum agglutination test, complement fixation test, plate serum agglutination test or acid antigen serum agglutination test the brucellosis card test identified 99.1% of the complement fixation test positive sera and 91.3% of the sera reacting to any of the other serological tests. The brucellosis card test showed satisfactory agreement with both the complement fixation test and tube serum agglutination test. It appears to be a useful screening test in operations involving large numbers of animals since under these conditions the reactors can be quickly identified and isolated.

Agglutination Tests↗