Introduction Brucellosis is an infectious disease caused by bacteria. Brucellosis is a zoonotic infection , it is a disease that can be transmitted from animals to people Person-to-person spread of brucellosis is extremely rare.

Epidemiology A major, Zoonotic, worldwide disease appears mainly in south and center America, parts of Mexico, Indian subcontinent, Mediterranean basin and Arabian gulf. Prevalence: 1.7-70 cases per 100,000. (500,000 case/year)

Their incidence in USA is much less now (100 cases per year), but the imported uncooked meat from different countries, including Mexico, contribute to that number of cases inside of the USA. According to local doctors, their incidence in Hawler and Kurdistan are about five times more than typhoid fever cases. Researches done on Brucella melitensis ( most pathogenic one) in the northern of Saudi Arabia area suggests that the disease mostly effect people between 13-40 years old (60%) since this age is more likely to be exposed to infected animal through traveling and working. However, children showed a 21% incidence of having the disease, while older people (40 years and above) contribute to 18.5% of the total number of cases. same research showed that male to female ratio was 1.7:1

Risk factors Family history of having the disease while sharing the same life style. Stock breeding and being a farmer Ingestion of non- pasteurized milk and their product including chees. Uncooked meat can carry the pathogen as well. Being a laboratory Worker or veterinarians (direct contact with specious animal and dealing with them more frequently) Traveling and camping in endemic areas and countries. Being a hunter.

Clinical manifestations Because of transporting of the intracellular pathogens (Inside macrophages and other phagocytic cells) via blood and lymph stream to different organs and organ systems and their replication within cells, systemic symptoms (ex: fever) and localized focal lesions (ex: hepatic and splenomegaly) occur. Common symptoms include: Fever (High in acute phase, Low in chronic phase) between 38-40oC Anorexia, Sever fatigue, Malaise and weight loss (90%). Joint pain and swelling (arthritis) including Spondylitis and Low back pain (70%). GIT complications, including dyspepsia and abdominal pain (due to liver abscess), Constipation, diarrhea or vomiting (50%). Orchitis, Endocarditis and even nervous system diseases.

Laboratory tests Liver enzyme tests CBC (Complete Blood Count) is typically ordered for evaluating patients with potential infectious disease. Leukocytosis is rare, Neutropenia is common. Anemia is reported in 75% of patients (particularly in chronic infections). Thrombocytopenia in 40% of patients (when liver and spleen are involved) Pancytopenia in 6% of patients. Liver enzyme tests Slight elevation of the liver enzymes is very common, and it represents the degree of severity of hepatic involvement and it clinically correlates with hepatomegaly

Culture In cases of focal disease, Brucella isolation can be attempted in clinical samples, for example from bone marrow, spleen, synovial fluid and abscesses. Generally the most common biological material used in the isolation of Brucella is whole blood. Culture is the gold standard for proving the disease, but is not always achievable. The success of culture isolation is dependent on the disease phase ,the bacteremia level and the species of Brucella as well as on the isolation methodology. The biphasic Ruiz-Castaneda culture method requires a long culturing time (c. 6 weeks) . Using automated systems (Bactec and BacTAlert), a positive culture can be detected within the first week. - After a positive culture, subcultures are performed in various axenic media (trypticase-soy agar, Brucella agar, etc.) so as to determine the Brucella species causing the infection.

Serological tests Serologic testing is the most commonly used method of diagnosing brucellosis.  For a diagnosis to be made using serology, two serum samples are required. The first serum sample should be taken when a person is acutely ill (≤7 days after symptom onset); the second serum sample should be drawn 2-4 weeks later to check for a rise in antibodies (a fourfold or greater rise in antibodies would mean an individual is positive for brucellosis). Serum Agglutination Test (SAT) measures antibodies against smooth lipopolysaccharide (LPS) coats of the bacteria. Enzyme-linked immunosorbent assay (ELISA) typically uses the cytoplasmic proteins as antigens and measures IgM, IgG, and IgA, allowing better interpretation, especially in cases of brucellosis relapse. Rose Bengal Test (RBT) is now the most widely used serological test for screening and diagnosis of human brucellosis, it is a rapid slide agglutination test. SAT + IgM - acute phase IgG - chronic Serological concentration of antibodies in different phases of the disease

Polymerase chain reaction Polymerase chain reaction (PCR) tests have been developed for the detection and rapid diagnosis of Brucella species in human blood specimens. Urinalysis and urine culture Urinalysis, urine culture, sensitivity testing, or a combination thereof may be indicated in the presence of symptoms of urinary tract infection (UTI). The most likely finding is a sterile pyuria, similar to that seen with tuberculosis. Urine cultures may be helpful; the organism grows from the urine if the genitourinary tract is infected. Radiography A chest radiograph should be obtained if respiratory symptoms are present or if a source of infection is not apparent. Radiographic findings are typically absent in brucellosis, even in patients with prominent respiratory symptoms. Spinal radiographic findings in patients with osteoarticular disease occur later in the course of illness, usually 2-3 weeks after the onset of symptoms.

NON-PHARMACOLOGICAL TREATMENTS No special diet is required for the treatment of brucellosis. Discuss with patients the importance of consuming pasteurized milk and milk products and avoiding other possible sources of infection. Restriction of activity with bed rest appears to confer benefit in the acute phase of brucellosis, increasing the rate of recovery. Education may be provided to the family of the patient to avoid the transmission of the disease . Better handling of infected animals or animal products is essential .

PHARMACOLOGICAL TREAMENT ( ACUTE INFECTION ) Condition Antibiotic A Antibiotic B Adult and children > 8 years old (1) Doxycycline 100 mg PO twice daily For 6 weeks (more convenient , more risk for relapse) (2) Doxycycline (this regimen is believed to be more effective in preventing relapse ) Rifampin 600-900 mg/day PO For 6 weeks Streptomycin 1g/day (IM ) for 2-3 weeks or Gentamicin . Children ≤ 8 years TMP-SMZ Rifampin for 6 weeks Pregnant women (mono therapy or in combination )

PHARMACOLOGICAL TREAMENT ( ACUTE INFECTION ) patients with spondylitis or sacroiliitis, doxycycline and rifampin combined with an aminoglycoside (gentamicin) for the initial (2-3 weeks ), followed by 6 weeks of rifampin and doxycycline, is usually recommended. Patients with endocarditis require aggressive therapy. Aminoglycoside therapy with doxycycline, rifampin, and TMP-SMZ for at least 4 weeks, followed by at least 2-3 active agents (without aminoglycosides) for another 8-12 weeks, is preferred. patients with nervous system infections , Dcloxycyine is generally preferred to tetracyclines or aminoglycosides because the latter are less likely to cross the BBB.

PHARMACOLOGICAL TREAMENT(cont..) Chronic brucellosis ( > one year ) is treated with triple-antibiotic therapy. The combination of rifampin, doxycycline, and streptomycin often is used. The use of corticosteroids is reserved for symptomatic Brucella meningitis (3rd generation cephalosporin can be used also ). Any additional drugs needed for symptomatic treatment (antipyretics, analgesics) must be administered as well. Surgery , the main roles of surgery in patients with brucellosis lie in the treatment of endocarditis and paraspinal abscesses ( pus collection ) . prosthetic valvular structures have been involved in brucellosis , Valvular lesions are typically large and destructive, so valve replacement surgery is often recommended in addition to a prolonged course of antibiotics.