Specific IgE response in patients with brucellosis.

In the search to find discriminative serological markers to differentiate between patients with acute brucellosis and those with chronic brucellosis, an enzyme-linked immunosorbent assay (ELISA) was used to determine and compare the brucella-specific IgE response in 80 sera from patients with acute brucellosis, 37 sera from patients with chronic brucellosis, 26 sera from patients with positive blood cultures for bacteria other than brucella and 51 sera from healthy controls. The IgE findings were compared to brucella-specific IgG, IgM, IgA and IgG1-4 demonstrated by ELISA, and to microagglutination test (MAT) results. Elevated (positive) antibrucella IgE titres were detected in 89 and 81% of sera from patients with acute and chronic brucellosis respectively. The predominant antibodies found in patients with acute brucellosis were of the IgG, IgM, IgA, IgE, IgG1 and IgG3 types while in chronic brucellosis IgG, IgA, IgE and IgG4 were found. Although IgE can be detected in patients with brucellosis, it does not discriminate between the acute and chronic stages of the disease.

Brucella arthritis: a study of 96 cases in Kuwait.

Of 400 patients with brucellosis, 104 (26%) had arthritis, of whom 96 could be followed up. The systemic disease in the 96 patients was acute in 54 (56%), subacute in 24 (25%), and chronic in 18 (19%). The main presenting symptoms were joint pain, fever, sweating, and easy fatigability. The joints most commonly affected were the sacroiliac joint (26%) and knee (25%) followed by hip (18%) and spine (8%). There was no particular pattern of joint affection in relation to age. Joint effusion occurred in 32/104 (30%) of cases, predominantly (94%) in the acute group. Culture of synovial fluid was negative in all, and analysis of synovial fluid for cellular profile, glucose, and protein content was not particularly helpful in diagnosis. Plain radiographs did not show major pathological changes. Among the laboratory tests, including haematological and liver function tests, the brucella enzyme linked immunosorbent assay (ELISA) was the most reliable in the diagnosis of disease, using serum and synovial fluid specimens. Treatment with a combination of streptomycin plus tetracyclines or rifampicin resulted in an excellent cure rate and resolution of arthritis without sequelae or mortality. Thus brucellosis should be considered in the differential diagnosis of arthritis, especially in areas in which the disease is endemic.

Pulmonary brucellosis.

Pulmonary abnormalities in brucellosis are rare. We report on nine cases (five adults and four children) with pulmonary brucellosis. All presented with fever, cough and mucopurulent sputum, and most had abnormal signs in the chest. Radiography of the chest showed pneumonic patches or consolidation in five patients, pleural effusion in three, granuloma of the lung in one and a picture of interstitial pneumonitis in one. All the patients had a brucella agglutination titre of 1:320 or more, and an elevated titre in the brucella-specific enzyme linked immunosorbent assay of IgM, IgG and IgA. Blood cultures grew Brucella melitensis in six patients while the pleural fluid aspirate grew the same organism in two of three patients. Treatment with oral oxytetracycline, doxycycline, rifampicin, trimethoprim-sulfamethoxazole alone, in combination with each other or together with intramuscular streptomycin was successful in all patients. All our patients recovered and none relapsed.

ELISA versus routine tests in the diagnosis of patients with systemic and neurobrucellosis.

Sera from patients in different stages of brucellosis as well as sera and cerebrospinal fluid (CSF) from patients with central nervous system (CNS) brucellosis and controls, were tested by ELISA for Brucella-specific IgG, IgM and IgA. The results were compared with culture findings, micro-agglutination (MA), slide agglutination with Rose Bengal (RB), and Brucella melitensis stained antigens (SA). In sera of patients with acute brucellosis (296), ELISA was positive for IgM (100%), IgG (97%) and IgA (98%), and comparable results were found in sera of patients with subacute brucellosis (44): IgG (100%), IgM (86%) and IgA (100%). However, in patients with chronic brucellosis (40), IgG and IgA were consistently positive (100%) while IgM was only positive in 33% of their sera. The MA and RB showed similar results, being more positive in patients with acute (98%) and subacute (84%) than in chronic (61%) brucellosis. The SA and culture showed significantly lower positive results. In the CSF of patients with CNS brucellosis (45), ELISA was positive in 100%, 20% and 85% for IgG, IgM and IgA, respectively, compared to 13% positive by culture, 25% by MA and 22% by RB. ELISA was negative in the CSF specimens from patients with brucellosis without CNS involvement (66), or meningitis other than Brucella (62), and no meningitis (144). Thus, ELISA with its IgG, IgM and IgA profiles is the test of choice in the diagnosis of patients with brucellosis, especially those with chronic or CNS infection.

Human brucellosis in Kuwait: a prospective study of 400 cases.

The clinical pattern of 400 cases of brucellosis in Kuwait is presented. The disease was acute in 77 per cent, sub-acute in 12.5 per cent and chronic in 10.5 per cent of cases. Raw milk was the major source of infection. The major features on presentation, irrespective of the course of the disease, were fever, sweating, headache, rigors, arthralgia, myalgia, and low back pain. Hepatosplenomegaly was present in 41 per cent of cases and in 32 per cent neither liver nor spleen were palpable. The haematologic findings were not specific and hepatic dysfunction (shown by liver enzyme abnormalities) was common. Skeletal (26 per cent) and genital (8.5 per cent) changes and neurobrucellosis (7 per cent) were the major complications. The ELISA was the most sensitive and reliable diagnostic test especially in relation to chronic brucellosis and neurobrucellosis. ELISA allowed the determination of brucella-specific immunoglobulins (Ig)G, IgM and IgA in the CSF, and provided profiles of Ig, in sera, which were different in patients with chronic (elevated IgG and IgA) from those with acute (elevated IgM alone or IgG, IgM and IgA) brucellosis. Treatment with tetracycline, doxycycline or rifampicin gave a cure rate of over 91 per cent in acute and subacute brucellosis. Co-trimoxazole was associated with a relapse rate of 50 per cent. Two drug combinations of streptomycin and tetracycline, streptomycin and rifampicin or streptomycin and doxycycline were effective, but one of five patients with chronic brucellosis relapsed. A combination of streptomycin, tetracycline and rifampicin with or without steroids was used successfully in neurobrucellosis, septicaemic shock and subacute bacterial endocarditis.

Evaluation of ELISA in the diagnosis of acute and chronic brucellosis in human beings.

An enzyme-linked immunosorbent assay (ELISA) was used to determine the levels of brucella-specific IgG, IgM and IgA in 173 patients with acute brucellosis, 22 patients with chronic brucellosis and in 281 controls consisting of 98 patients with other infectious etiologies, 20 patients with non-infectious diseases and 163 normal healthy adults. The ELISA results were compared with culture findings, the results of slide agglutination tests with Brucella melitensis (M), B. abortus (A) and Ross Bengal (RB) antigens, and of tube and microagglutination tests. Brucella cultures were positive in 53 and 5% of patients with acute and chronic brucellosis respectively. The slide agglutination tests with A, M, A plus M and RB antigens were positive in 42, 44, 51 and 98% of patients with acute brucellosis and in 23, 27, 27 and 64% of patients with chronic brucellosis. There was no significant difference in the results between the tube and microagglutination tests regardless of the type of antigen used. At a titre of greater than or equal to 80 or greater than or equal to 160 these tests were positive in 98% and 92% of patients with acute brucellosis and 60 and 40% of patients with chronic brucellosis. The brucella culture and agglutination tests were negative for all the controls. Brucella ELISA immunoglobulins (Ig) were detected in some individuals in the control groups but the majority of these had titres of less than or equal to 100 for IgG, IgM, and IgA. However, patients with brucellosis had significantly higher ELISA titres in all classes of Ig than controls but the sensitivity and specificity within each Ig class varied with the titre considered. At a titre of greater than or equal to 1600 the brucella IgG had a sensitivity and specificity of 98% for patients with acute or chronic brucellosis; this decreased with lower reciprocal titres. The brucella IgM titre of greater than or equal to 400 had a sensitivity of 98% and a specificity of 98% for patients with acute brucellosis. However, in patients with chronic brucellosis the brucella IgM was very low. The brucella IgA titre of greater than or equal to 200 showed a sensitivity of 98% and a specificity of 99% for patients with either acute or chronic brucellosis. This study indicates that brucella ELISA is a rapid, sensitive and specific assay, provides a profile of Ig classes in the diagnosis of acute and chronic brucellosis, is useful for mass screening and could be considered the method of choice for the serological diagnosis of brucellosis.