Infection with Brucella spp. continues to pose a human health risk globally despite strides in eradicating the disease from domestic animals. Brucellosis has been an emerging disease since the discovery of Brucella melitensis by Sir David Bruce in 1887. Although many countries have eradicated B. abortus from cattle, in some areas B. melitensis and B. suis have emerged as causes of this infection in cattle, leading to human infections. Currently B. melitensis remains the principal cause of human brucellosis worldwide including India. The recent isolation of distinct strains of Brucella from marine mammals as well as humans is an indicator of an emerging zoonotic disease. Brucellosis in endemic and non-endemic regions remains a diagnostic puzzle due to misleading non-speciÞ c manifestations and increasing unusual presentations. Fewer than 10% of human cases of brucellosis may be clinically recognized and treated or reported. Routine serological surveillance is not practiced even in Brucella -endemic countries and we suggest that this should be a part of laboratory testing coupled with a high index of clinical suspicion to improve the level of case detection. The screening of family members of index cases of acute brucellosis in an endemic area should be undertaken to pick up additional unrecognised cases. Rapid and reliable, sensitive and speciÞ c, easy to perform and automated detection systems for Brucella spp. are urgently needed to allow early diagnosis and adequate antibiotic therapy in time to decrease morbidity / mortality. The history of travel to endemic countries along with exposure to animals and exotic foods are usually critical to making the clinical diagnosis. Laboratory testing is indispensable for diagnosis. Therefore alertness of clinician and close collaboration with microbiologist are essential even in endemic areas to correctly diagnose and treat this protean human infection. Existing treatment options, largely based on experience gained > 30 years ago, are adequate but not optimal. In our experience, an initial combination therapy with a three drug-regimen followed by a two-drug regimen for at least six weeks and a combination of two drugs with a minimum of six weeks seems warranted to improve outcome in children and adult patients respectively with laboratory monitoring. A safe and effective vaccine in humans is not yet available. Prevention is dependent upon the control of the disease in animal hosts, effective heat treatment of dairy produce and hygienic precautions to prevent occupational exposure. This review compiles the experiences and diagnostic and treatment paradigms currently employed in Þ ghting this disease.

Brucellosis is an important re-emerging zoonosis with a worldwide distribution. It is still an uncontrolled serious public health problem in many developing countries including India. Brucellosis in India is yet a very common but often neglected disease. Currently, Brucella melitensis accounts for most recorded cases globally with cattle emerging as a important reservoir with the few cases of B. suis. Isolated cases of non-terrestrial brucellosis and continuing transmission from wild animals have raised important epidemiological issues. Routine serological surveillance along with high clinical suspicion and screening of family members of index cases would be essential in delineating the real magnitude of human brucellosis in endemic countries. Increased business and leisure travel to endemic countries have led to diagnostic challenge in non-endemic areas. Laboratory testing is indispensable for diagnosis. Advances in newer rapid, sensitive, and specific testing methodologies and alternate treatment strategies are urgently needed. A safe and effective vaccine in human is not yet available. Prevention is dependent upon increasing public awareness through health education programmes and safe livestock practices. Active co-operation between health and veterinary services should be promoted. This review collates world literature and its impact to the discovery, isolation and diagnosis and epidemiology along with the control measures adapted in the Indian scenario.

A prospective study was carried out to elucidate the clinical, epidemiological and laboratory features of human brucellosis. A total of 26 948 blood samples (from adults aged 15 years and above) were screened for serological evidence of brucellosis over a period of 16 years. The slide agglutination/Rose Bengal plate agglutination test gave positive results in 517 patients, of which 509 had detectable titres by the standard tube agglutination test (SAT). The diagnosis of brucellosis was documented in 495 (1?8 %) patients based on diagnostic titres (¢1 : 160, 490 cases) and rising titres from insignificant titres (four cases) by serology and for one case by blood-culture isolation alone. Blood cultures were carried out in 345 cases, of which 191 cases (55?3 %) yielded Brucella melitensis. In 77/79 cases undertaken for follow up, there was a steady fall in 2-mercaptoethanol (2ME) agglutination titres along with clinical improvement (P <0?01). SAT titres remained detectable in most cases for a longer period in spite of an effective antimicrobial therapy and clinical recovery. A substantial number of patients (84?2 %) presented with fever, this being the only complaint in 51?1 % of the cases. Complications were present in 8?8 % of the patients (arthritis excluded): this included the unusual complications of hydrocele (two cases), Stevens-Johnson syndrome (one case) and urinary tract infection (one case). Brucella agglutinins were demonstrated in synovial, testicular, hydrocele and cerebrospinal fluids. There was no clinical suspicion of brucellosis in 439 cases (88?7 %) and the diagnosis was made only by routine serology. A two-drug regimen for 42-84 days with a follow-up 2ME test resulted in lower levels of relapse. These results suggest that, in endemic areas of the world, it should be mandatory to screen routinely for brucellosis due to protean clinical manifestations. INTRODUCTIONBrucellosis is a worldwide zoonotic disease caused by Brucella spp. The genus Brucella comprises Gram-negative, facultative, intracellular pathogens (Alton et al., 1975). Currently, there are six recognized species of Brucella based on phenotypic characteristics, antigenic variation and prevalence of infection in different animal hosts: Brucella abortus (cattle), Brucella canis (dogs), Brucella melitensis (goats, sheep), Brucella neotomae (desert wood rats), Brucella ovis (sheep) and Brucella suis (pigs, reindeer and hares) (Corbel, 1997;Moreno et al., 2002). Recently, two Brucella strains from marine mammals have been reported (Bricker et al., 2000;Cloeckaert et al., 2000) and the names Brucella pinnipediae (seal/otter) and Brucella cetaceae (porpoise/ whale) have been proposed (Cloeckaert et al., 2003). There has also been a report of human infection with marine brucellae (Sohn et al., 2003). Although each species of Brucella has a preferred host, all can infect a wide range of animals, including humans. Brucellosis is a worldwide reemerging zoonosis causing high economic losses and severe human disease. It has areas of high endemicity...

A total of 5726 blood specimens (from children aged 14 years and younger) were studied for the serological evidence of brucellosis. Ninety-three (1.6 per cent) showed diagnostic agglutinin titres with a geometric mean titre of 403 (SD +/- 547). Forty-three (59.7 per cent) blood specimens yielded the growth of Brucella melitensis. Thirty-nine patients (41.93 per cent) were shepherds, who constituted the major occupational group affected in the present series. More than 60 per cent of the patients had a history of both consumption of fresh goat's milk and close animal contact. The habit of consuming fresh goat's milk to obtain relief from chronic ailments was noted in nine patients. Seventy-three (78.49 per cent) were males and 20 (21.51 per cent) were females, with a male to female ratio of 3:1. The disease occurred mainly in the school age group (mean age 10.3 years). All the patients had an acute history of less than 2 months. Forty-nine (52.68 per cent) patients presented with persistent fever, 19 (20.43 per cent) with joint pain, and the rest with a combination of fever and joint pain with and without low backache, fever being the commonest complaint. One case presented with involuntary movements of limbs alone and the other with burning feet only. Pityriasis alba was the consistent physical finding, with fever in the majority of the patients. The major joint found to be involved was the knee (52.77 per cent). The synovial fluid obtained from the knee joint of five patients demonstrated Brucella agglutinins and also three grew B. melitensis. Eight patients presented with complications that included skin lesions (3), carditis (2), neurobrucellosis such as chorea (1), peripheral neuritis (1), and meningitis (1). Brucella melitensis biotype 1 was successfully isolated from the papular eruption of one out of three cases who presented with skin lesions. To our knowledge this is the fourth confirmed isolation of B. melitensis from skin lesions with brucellosis, reported in the literature. The cerebrospinal fluid obtained from the meningitis patient was positive for B. agglutinins. To our knowledge chorea of brucellar origin appears to be the first case reported in the literature. In 15 cases (16.13 per cent) brucellosis was suspected clinically whereas 78 (83.87 per cent) cases, only serological evidence of brucellosis confirmed the diagnosis. None of the cases relapsed. In our experience an initial combination therapy with a three-drug regimen followed by a two-drug regimen for a minimum of 6 weeks has been found to be effective in the prevention of a relapse.

We investigated the role of the lysis centrifugation blood culture technique over the conventional Castaneda technique for the diagnosis of human brucellosis. The lysis centrifugation technique has been found to be more sensitive in both acute (20% higher sensitivity; P < 0.00001) and chronic (40% higher sensitivity; P ‫؍‬ 0.087) forms of brucellosis. The major advantage of lysis centrifugation was in the mean detection time, which was only 2.4 days in acute and 2.7 days in chronic cases, with 103 out of 110 (93.6%) and 17 out of 20 (85%) cultures from acute and chronic brucellosis, respectively, detected before the conventional culture was positive. Our results confirmed the potential usefulness of the lysis technique in diagnosis and institution of appropriate antibiotic therapy.The spectrum of human brucellosis, a zoonosis, ranges from subclinical infection to acute (less than 2 months), subacute (2 to 12 months), and chronic illness, often manifested by recurrent symptoms over many years (1,10). A definitive diagnosis of this infection is based on culture from different samples, mainly blood. With acute forms produced by Brucella melitensis, the number of positive results from blood cultures by the conventional (Castaneda) technique is usually 70 to 80% (2). This figure is notably reduced for patients with long illness and focal complications; in these cases the percentage of positives rarely exceeds 30 to 50% (3, 6). Although a prior study (4) of the lysis centrifugation technique has demonstrated the possibility of detecting brucellae early along with an increased isolation rate, information concerning the use of this technique in the diagnosis of human brucellosis is scarce, especially for chronic illness. This study compares lysis centrifugation to the conventional blood culture technique for the diagnosis of acute and chronic brucellosis.The study group comprised 121 acute and 27 chronic brucellosis patients. A case of brucellosis was identified if the titers were Ն1:160 (9) by standard tube agglutination testing (Brucella abortus plain antigen; Indian Veterinary Research Institute, Izatnagar, India).Five milliliters of venous blood was inoculated aseptically into the broth phase of Castaneda's biphasic medium consisting of brain heart infusion agar and broth (High Media, Mumbai, India), in duplicate. The media were incubated at 37°C with and without a CO 2 atmosphere for 30 days, and the broth-blood mixtures were tilted over the solid phase every day.A modification of the method described by Etemadi et al. (4) was employed for lysis centrifugation. A 5-ml aliquot of blood drawn simultaneously along with that used for the Castaneda culture was added to a 50-ml screw-cap sterile centrifuge tube containing 20 ml of sterile distilled water and 1.5 ml of 4% sodium citrate. The contents were gently mixed, and the tube was centrifuged (model no. R8C; Remi, Mumbai, India) at 2,000 ϫ g for 30 min. The supernatant was discarded, and the sediment was inoculated onto brain heart infusion agar plates in duplicate. ...