Brucellosis Overview PDF

BRUCELLOSIS (Undulant fever or Malta Fever) A systemic bacterial disease of acute or insidious onset, with continued, intermittent or irregular or undulant fever of variable duration. OCCURRENCE Brucellosis is a worldwide disease. Cases are reported especially from Mediterranean countries (Europ...

BRUCELLOSIS (Undulant fever or Malta Fever) A systemic bacterial disease of acute or insidious onset, with continued, intermittent or irregular or undulant fever of variable duration. OCCURRENCE Brucellosis is a worldwide disease. Cases are reported especially from Mediterranean countries (Europe and Africa), Middle east. America, India and Mexico. It is predominantly an occupational disease of those working with infected animals like farm workers, veterinarians and abattoir workers. The disease is often unrecognized and unreported CYCLE OF INFECTION Causative agent The agent is intracellular gram-negative, non-motile, round or oval short bacilli. They are parasites of animals and man. There are four species: Brucella melitensis which affects mainly goats (Malta fever) and sheep. Brucella abortus which infects cows. Brucella suis which infects pigs. Brucella canis which infect dogs. Resistance of the organism The organisms are killed at a temperature of 60 °C in ten minutes and thus they are destroyed by pasteurization of milk. In fresh cheese undergoing lactic acid fermentation, the organisms are killed in a few days. They remain alive in infected butter for several days. The organisms are sensitive to sulpha, streptomycin, tetracycline, and chloramphenicol. Antigenic characteristics The species are very closely related antigenically. B. abortus antiserum will agglutinate B. melitensis suspension and B. melitensis antiserum will agglutinate B. abortus suspension. Reservoir of infection The reservoir of infection is cattle, swine, goats and sheep. In goats and cows, the organism causes bacteremia and sometimes abortion if the animal is pregnant (contagious abortion). The bacilli pass to the mammary glands where they remain and are excreted in the milk for long time. Mode of transmission 1\. Ingestion of unpasteurized milk and milk products from infected cows or sheep. 2\. Contact through breaks in the skin with infected animal's vaginal discharge, blood and urine or with infected carcasses. 3\. Airborne infection occurs in stables for animals and for humans in laboratories and abattoirs. No evidence that brucellosis is transmitted from person to person Susceptibility Severity and duration of clinical illness vary. The duration of post infection immunity is uncertain. PATHOLOGY & PATHOGENESIS Brucellae are facultative intracellular parasites; multiplication is mainly in monocyte-macrophage cells. This characteristic dominates the pathology, clinical manifestations and therapy of the disease. The organisms pass through the lymphatics, reach the blood and localize in the reticuloendothelial system where they are able to grow intracellularly and produce granulomatous nodules which may later form abscesses in the liver, spleen and bone marrow. The disease is characterized by an acute phase of bacteremia followed by a chronic phase that may last many years. CLINICAL PICTURE Incubation period The incubation period is variable and difficult to ascertain. It may range from 5 to 60 days. Occasionally, it may be several months. Clinical forms of brucellosis The clinical features of the disease are not specific. Subclinical disease Healthy individuals in endemic areas have positive serology, but no history of infection. Acute brucellosis The onset of the disease is either sudden or insidious. Manifestations include swinging temperature (39oC to 41oC) with chills and rigors, excessive sweating, headache, anorexia, lethargy and prostration, often musculoskeletal pain and arthralgia and constipation. On examination: the spleen is slightly enlarged and tender (20%); lymphadenopathy especially in children (10%); tender spines. Relapse occurs most often in the first 2 months after treatment. Chronic brucellosis Manifested by recurrent bouts of headache, malaise, musculoskeletal pain, extreme fatigue and depression. It may remain undiagnosed for many years. Complications Bones and joints Spondylitis (lumbosacral vertebrae) initially involves the intervertebral disc, followed by erosion of the anterior margin of the bodies of the adjacent vertebrae resulting in bony collapse. Excessive growth of osteophytes may lead to lamellar bone and bridging. Sometimes a paravertebral abscess develops, which may tunnel into psoas muscle (psoas abscess). Osteomyelitis affecting long bones (femur, tibia and humerus). Arthritis involving weight bearing joints (hip, knee, ankle, shoulder and elbow joints), and also small joints (sternoclavicular and metacarpophalangeal joints) may be involved. Arthritis is either due to infection of the affected joints or to reactive arthritis. The affected joint is hot, tender and swollen. Effusion of the knee may rupture posteriorly looking like Baker cyst. Some patients with skeletal involvement are afebrile despite positive blood culture. Cardiovascular complications Cardiovascular involvement is rare. It is in the form of infective endocarditis or myocarditis. Nervous system (neurobrucellosis) Meningitis, diplopia, meningeo-encephalitis, compression myelopathy, and cerebral vascular occlusion Complications of pregnancy (rare) Abortion; Intra-uterine fetal death; premature delivery; retention of placenta. Differential diagnosis 1\. Influenza. 2\. Infectious mononucleosis 3\. Typhoid fever 4. Rheumatic fever 5\. Pulmonary tuberculosis 6\. Subacute bacterial endocarditis DIAGNOSIS History Occupational history, history of exposure to animals, travelling to enzootic areas and ingestion of high-risk food (e.g. unpasteurized dairy products). Medical evaluation Suspected clinical features. Laboratory diagnosis Bacterial isolation The isolation and identification of Brucella confirm the diagnosis of brucellosis. Brucella is most commonly isolated from blood and bone marrow. Blood culture is done repeatedly in suspected cases. It is positive in 30-50% of cases. Blood culture bottles (containing sulphonated broth) are inoculated with the patient\'s blood or bone marrow and incubated in 5-10 % CO2 at 35º C -- 37º C. Subcultures are made every few days on solid media (serum agar and blood agar). Small, convex and smooth colonies appear after 2 -- 5 days. Blood culture bottles are retained for 3 weeks in the incubator before reporting negative results. Currently, whenever affordable, automated blood culture systems have replaced the conventional blood culture systems as they shorten the time needed to detect these organisms from blood and other body fluids. The organism can also be isolated from cerebrospinal fluid, lymph node, abscess, synovial fluid, tissue and biopsies from patients in whom complicated disease is suspected. Serological tests (suggestive of the diagnosis) Standard agglutination test (SAT) The SAT is usually included in Widal test. It detects agglutinogens of the IgG and IgM classes. The patient's serum may give a positive reaction after 7-10 days of the onset of the disease. In the acute stage, agglutinating antibodies may give high titers (1,000 or over). A titer of 80 or more is suggestive. Paired serum samples taken 2 weeks apart may show a rising titer. It is important to note that the sera of a certain proportion of the population may agglutinate Brucella suspension in low titer which may be due to past infection or a latent infection. A Prozone phenomenon may be observed; the inhibition of agglutination with low titers and the presence of agglutination with high titers, e.g. negative with 1/50 and 1/100 dilutions and positive with 1/400 and 1/800 dilution. It appears in the chronic stage and may persist for year. It can be defined as false negative SAT due to the relative excess of antibodies against antigens, therefore Ag-Ab ratio is not optimum whereby effectiveness of antibodies to form immune complexes is usually impaired when concentrations of antibodies are very high. Standard agglutination test with added 2-Mercaptoethanol test The addition of 2-Mercaptoethanol to the patient's serum destroys IgM leaving IgG for agglutination. It is useful in the diagnosis of chronic active disease. ELISA and radioimmunoassay They are for the detection of serum Brucella specific IgM, IgG and IgA Other laboratory results \- Hematological changes in acute brucellosis (normochromic normocytic anemia, normal or leukopenia with relative lymphocytosis and may be pancytopenia; rare) with modest increase in erythrocyte sedimentation rate. \- Liver function tests are abnormal in 50% of cases with mild elevation of aminotransferases and marked elevation of alkaline phosphatase indicating the presence of portal tract granuloma. \- Changes in cerebrospinal fluid include an elevation of protein content with lymphocytic pleocytosis and reduced sugar level. The organisms are difficult to find and prolonged culture is needed. TREATMENT 1\. Streptomycin 1gm daily as intramuscular injection for 14-21 days together with doxycycline 200mg daily for 6-8 weeks. Longer duration of treatment is needed when there is evidence of joint, neurologic lesions and endocarditis. 2\. Rifampin 600mg daily combined with doxycycline 200mg daily for 6 weeks. However, this combination can't be given to children under 8 years and during pregnant so, cotrimoxazole and rifampin are appropriate. 3\. Quinolones are thought to be effective. Refer to the pharmacology of aminoglycosides and tetracyclines and quinolones in infectious diseases I. PREVENTION 1\. Educate the public regarding the risk of consuming unpasteurized milk and milk products. 2\. Educate farmers and workers in slaughter houses, meat processing plants and butcher's shops about the nature of the disease and the risk of handling carcasses and products of potentially infected animals. 3\. Pasteurize milk and dairy products from cows, sheep and goats. Boiling of milk is also effective. 4\. Search for infection among livestock and segregate infected animals. 5\. Immunization of young goats and sheep in areas of high prevalence of the disease. CONTROL 1\. Reporting to local health authorities; case reporting is obligatory in most countries. 2\. Concurrent disinfection of purulent discharge 3\. Investigation of contacts and source of infection. Tracing infection to the common source usually infected domestic goats, swine or cattle or raw milk or dairy products from cows and goats. Test suspected animals and remove reactors. 4\. Specific treatment of cases