History

Fact Explanation
Asymptomatic Patients with subclinical disease can be asymptomatic.
Presence of risk factors These include recent visit to endemic areas. Consumption of unpasteurized dairy products, and raw or poorly cooked meat. Exposure to animal hosts (goats, sheep, cows, camels, pigs, reindeer, rabbits, or hares) is a risk factor. Certain occupations are at high risk of exposing to above animals. (eg: hunters, farmers, dairy workers, veterinarians) [1]
Fever [1,2,4] Most patients present with fever or prolonged fever.
Brest fed babies of infected mothers Brucellosis is transmitted via breast milk. [1]
Constitutional symptoms These include anorexia, fatigue, weight loss, arthralgia, low back pain and joint pain. [1]
Neuropsychiatric symptoms [1,3] Patients present with headache and depression. Some have unsteady gait.
Symptoms of gastrointestinal tract involvement Dyspepsia, constipation, diarrhea and abdominal pain are common complains. Abdominal pain is due to hepatic abscess.
Symptoms of urinary tract infection [5] Increased frequency of micturition, dysuria and nocturia are symptoms suggestive of a urinary tract infection.
Symptoms of orchitis [1,3,5] Patients complain of swelling and pain in the testicles.
Cough and dyspnea Bronchitis, bronchopneumonia and pleural effusions can cause dyspnea and cough. [6]
Pleuritic chest pain This is due to the irritation of the parietal pleura by the empyema. [6]
Muscular skeletal complications Arthiritis and joint swelling can present. [2]
References
  1. Brucellosis. Centers for Disease Control and Prevention. [online] [viewed 29 April 2014] Available from: http://www.cdc.gov/brucellosis/symptoms/index.html
  2. MARÍA PÍA FRANCO, MAXIMILIAN MULDER, ROBERT H GILMAN, HENK L SMITS. Human brucellosis: The Lancet Infections Diseases. [online] December 2007: 7(12): 775-786. [viewed 29 April 2014] Available from: doi:10.1016/S1473-3099(07)70286-4
  3. YETKIN MA, BULUT C, ERDINC FS, ORAL B, TULEK N. Evaluation of the clinical presentations in neurobrucellosis. Int J Infect Dis [online] 2006; 10: 446-452. [viewed 29 April 2014] Available from: doi:10.1016/j.ijid.2006.05.007
  4. PETER M. R., ZIMRA G.,ORDON, LYNDA O., Pet-Related Infections. Am Fam Physician. [online] 2007 Nov 1;76(9):1314-1322. [viewed 29 April 2014] Available from: http://www.aafp.org/afp/2007/1101/p1314.html
  5. STAMATIOU K. POLYZOIS K. DAHANIS S. LAMBOU T. SKOLARIKOS A. Brucella melitensis: a rarely suspected cause of infections of genitalia and the lower urinary tract. Braz J Infect Dis. [online] Apr. 2009: 13(2) [viewed 29 April 2014] Available from: http://dx.doi.org/10.1590/S1413-86702009000200003
  6. KEREM E., DIAV O., NAVON P., BRANSKI D. Pleural fluid characteristics in pulmonary brucellosis. Thorax. [online] Jan 1994; 49(1): 89–90. [viewed 29 April 2014] Available from: www.ncbi.nlm.nih.gov/uniquesig0/pmc/articles/PMC474117/
  7. SHAHID AZIZ, AWADH RAHAIL AL-ANAZI, ABDULKARIM IBRAHIM AL-ASKA. A review of gastrointestinal manifestations of Brucellosis. Saudi Journal of Gastroenterology. [online] 2005: 11(1) 20-27. [viewed 29 April 2014] Available from: http://www.saudijgastro.com/article.asp?issn=1319-3767;year=2005;volume=11;issue=1;spage=20;epage=27;aulast=Aziz

Examination

Fact Explanation
Febrile This is a common examination finding. [1,4]
Palpable lymph nodes Lymphadenopathy is present in about 10% of patients. [2]
Examination of the joints Involved joints can be tender and swollen.
Signs of orchitis [7] Testicular swelling and tenderness are present. Testicle is erythematous due to inflammation.
Abdominal examination Tender hepatomegaly and or splenomegaly can be present. [1,2] Right upper quadrant pain and jaundice are indicative of hepatic abscess. If peritonitis develops diffuse abdominal tenderness, rebound tenderness, and sluggish or absent bowel sounds are present. [6]
Signs of infective endocarditis [1,4] Patients rarely can have Roth spots, splinter hemorrhages, Osler nodes, Janeway lesions, hepatosplenomegaly and changing murmurs. This is a rare complication of the disease. Infective endocarditis can be complicated with blindness due to embolic phenomenon.
Examination of the respiratory system Rales and wheezes are heard on auscultation. Pleural friction rubs results due to pleural involvement. Pleural effusion can present in some patients. [3]
Examination of the nervous system Meningismus, papilledema, altered mental status can be found in some patients. [5]
Skin involvement Erythema nodosum, skin abscesses, dermal cysts and papulonodular eruptions are the commonest. Some skin lesions are similar to impetigo, psoriasis, eczema, purpura, Stevens-Johnson syndrome and pityriasis rosea. Vasculitic lesions are seen in some. [2]
Ophthalmic manifestations [8] These include uveitis, conjunctivitis, nummular keratitis and cataracts.
References
  1. Brucellosis. Centers for Disease Control and Prevention. [online] [viewed 29 April 2014] Available from: http://www.cdc.gov/brucellosis/symptoms/index.html
  2. MARÍA PÍA FRANCO, MAXIMILIAN MULDER, ROBERT H GILMAN, HENK L SMITS. Human brucellosis. Human brucellosis. [online] December 2007: 7(12): 775-786. [viewed 29 April 2014] Available from: doi:10.1016/S1473-3099(07)70286-4
  3. KEREM E, DIAV O, NAVON P, BRANSKI D. Pleural fluid characteristics in pulmonary brucellosis. Thorax [online] 1994; 49: 89-90. [viewed 29 April 2014] Available from: www.ncbi.nlm.nih.gov/uniquesig0/pmc/articles/PMC474117/
  4. PETER M. R., ZIMRA G.,ORDON, LYNDA O., Pet-Related Infections. Am Fam Physician. [online] 2007 Nov 1;76(9):1314-1322. [viewed 29 April 2014] Available from: http://www.aafp.org/afp/2007/1101/p1314.html
  5. Brucellar Spinal Epidural Abscess. Am Fam Physician. [online] 2003 May 15;67(10):2071-2072. [viewed 29 April 2014] Available from: http://www.aafp.org/afp/2003/0515/p2071a.html
  6. SHAHID AZIZ, AWADH RAHAIL AL-ANAZI, ABDULKARIM IBRAHIM AL-ASKA. A review of gastrointestinal manifestations of Brucellosis. Saudi Journal of Gastroenterology. [online] 2005: 11(1) 20-27. [viewed 29 April 2014] Available from: http://www.saudijgastro.com/article.asp?issn=1319-3767;year=2005;volume=11;issue=1;spage=20;epage=27;aulast=Aziz
  7. STAMATIOU K. POLYZOIS K. DAHANIS S. LAMBOU T. SKOLARIKOS A. Brucella melitensis: a rarely suspected cause of infections of genitalia and the lower urinary tract. Braz J Infect Dis. [online] Apr. 2009: 13(2) [viewed 29 April 2014] Available from: http://dx.doi.org/10.1590/S1413-86702009000200003
  8. ISAIAS ROLANDO, LISET OLARTE, GUSTAVO VILCHEZ, MARINA LLUNCOR, LARISSA OTERO, MARK PARIS, CARLOS CARRILLO, EDUARDO GOTUZZO. Ocular Manifestations Associated with Brucellosis: A 26-Year Experience in Peru. Clin Infect Dis. [online] 2008: 46 (9):1338-1345. [viewed 29 April 2014] Available from: doi: 10.1086/529442

Differential Diagnoses

Fact Explanation
Syphilis Primary syphilis may be limited to skin rash but secondary syphilis can present with fever, lymphadenopathy, sore throat, patchy hair loss, headache, loss of weight, fatigue and myalgia. [1]
Tuberculosis Chronic cough, hemoptysis, chest pain, fatigue, loss of weight, loss of appetite, fever with or without chills and evening sweats are usual clinical features. Tuberculin skin test and chest X-ray will aid in diagnosis. [2]
Erythema nodosum Skin manifestations like acute, nodular, erythematous lesions are commonly seen in the extensor aspects of the lower legs. [3]
Fever of unknown origin Brucellosis can present as prolonged fever. The common causes include infective endocarditis, tuberculosis, infectious mononucleosis, vasculitis and connective tissue diseases (eg: Systemic lupus erythematosis) , malignancies (eg, lymphoma) and deep seated abscesses. [4]
Rickettsial diseases Non specific symptoms and skin manifestations are common to both. [5]
Spondyloarthropathies Symptoms of musculo-skeletal system involvement like arthralgia and joint swellings are common to both conditions.
Pneumonia Bacterial or viral pneumonia may mimic pulmonary manifestations of Brucellosis.
Urinary tract infection Brucellosis presenting with frequency and dysuria can mimic a urinary tract infection.
Meningitis Involvement of the central nervous system in Brucellosis produce symptoms and signs which are similar to meningitis.
References
  1. Syphilis. Centers for Disease Control and Prevention. [online] [viewed 29 April 2014] Available from: http://www.cdc.gov/std/syphilis/stdfact-syphilis.htm
  2. Learn the Signs and Symptoms of TB Disease. Centers for Disease Control and Prevention. [online] [viewed 29 April 2014] Available from: http://www.cdc.gov/features/tbsymptoms/
  3. JAGDEEP WHIG, VINEET MAHAJAN, ANIL KASHYAP, SUSHIL GUPTA. Erythema nodosum: Atypical presentation of common disease. Lung India. [online] 2010; 27(3): 181–182. [viewed 29 April 2014] Available from: doi: 10.4103/0970-2113.68319
  4. JAMES C. GIBSON. Pyrexia of Unknown Origin: An Approach to Diagnosis and Management. Can Fam Physician. [online] Dec 1982; 28: 2204–2207. [viewed 29 April 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2306656/
  5. Rickettsial (Spotted & Typhus Fevers) & Related Infections (Anaplasmosis & Ehrlichiosis). Centers for Disease Control and Prevention. [online] [viewed 29 April 2014] Available from: http://wwwnc.cdc.gov/travel/yellowbook/2014/chapter-3-infectious-diseases-related-to-travel/rickettsial-spotted-and-typhus-fevers-and-related-infections-anaplasmosis-and-ehrlichiosis

Investigations - for Diagnosis

Fact Explanation
Full blood count Leucocytosis, leucopenia or thrombocytopenia are seen. [2]
Blood culture [1,2] This is the gold standard in diagnosis but becomes positive only about 40% to 50% of patients. [3]
Bone marrow cultures [1,2] This is fast and more sensitive when compared to blood culture. [2,3]
This is fast and more sensitive when compared to blood culture. [2,3] Culture of pus, tissue samples, and cerebrospinal, pleural, joint, or ascitic fluid will demonstrate the Brucella. [2,3]
Agglutination tests Rose Bengal test is used for screening and once positive serum agglutination test is done to confirm the disease. [2] Brucella microagglutination test (BMAT) detects detect antibodies to Brucella species. Fourfold or greater rise in antibody levels would bean an individual is positive for brucellosis. [1]
ELISA (Enzyme-Linked ImmunoSorbent Assay) Detects Ig G and IgM antibodies. [2] Fluorescent polarisation immunoassay (FPA) for brucellosis and immunochromatographic brucella lateral flow assay allows quick diagnosis of Brucella. [4]
Polymerase Chain Reaction (PCR) Detects diagnosis of genetic material hence it has higher sensitivity than culture. [2]
Computed tomography or magnetic resonance imaging Visualizes the cerebral lesions. [2]
Digital subtraction angiography Detect vascular lesions. [1]
References
  1. Brucellosis. Centers for Disease Control and Prevention. [online] [viewed 29 April 2014] Available from: http://www.cdc.gov/brucellosis/symptoms/index.html
  2. MARÍA PÍA FRANCO, MAXIMILIAN MULDER, ROBERT H GILMAN, HENK L SMITS. Human brucellosis. Human brucellosis. [online] December 2007: 7(12): 775-786. [viewed 29 April 2014] Available from: doi:10.1016/S1473-3099(07)70286-4
  3. SUPRIYA CHRISTOPHER, UMAPATHY B L, RAVIKUMAR K L. Brucellosis: Review on the Recent Trends in Pathogenicity and Laboratory Diagnosis. J Lab Physicians. [online] 2010 Jul-Dec; 2(2): 55–60. [viewed 29 April 2014] Available from: doi: 10.4103/0974-2727.72149
  4. MANTUR BG, BIRADAR MS, BIDRI C, MALLANA S, VERRAPPA K, et al. Protean clinical manifestation & diagnostic challenges of human brucellosis in adults: 16 yrs experiancein an endemic area. J Med Microbiol. [online] 2006;55:897–903. [viewed 29 April 2014] Available from: doi: 10.1099/jmm.0.46097-0

Investigations - Followup

Fact Explanation
Polymerase Chain Reaction (PCR) Reducing levels of Brucella DNA indicates successful treatment. Persistent high levels of DNA despite antibiotic therapy indicates treatment failure. [1]
Trans oesophageal echocardiography Aids in diagnosis of infective endocarditis. [1]
References
  1. MARÍA PÍA FRANCO, MAXIMILIAN MULDER, ROBERT H GILMAN, HENK L SMITS. Human brucellosis. Human brucellosis. [online] December 2007: 7(12): 775-786. [viewed 29 April 2014] Available from: doi:10.1016/S1473-3099(07)70286-4

Management - General Measures

Fact Explanation
Health education People should be advised not to consume raw meat or unpasteurized dairy products. Personal protective equipment (gloves, goggles, aprons) should be worn by people who are involved in high risk occupations. [1]
Orchiectomy If necrotizing orchitis, or abscesses develops patients may need orchiectomy. [2]
References
  1. Brucellosis. Centers for Disease Control and Prevention. [online] [viewed 29 April 2014] Available from: http://www.cdc.gov/brucellosis/symptoms/index.html
  2. STAMATIOU K. POLYZOIS K. DAHANIS S. LAMBOU T. SKOLARIKOS A. Brucella melitensis: a rarely suspected cause of infections of genitalia and the lower urinary tract. Braz J Infect Dis. [online] Apr. 2009: 13(2) [viewed 29 April 2014] Available from: http://dx.doi.org/10.1590/S1413-86702009000200003

Management - Specific Treatments

Fact Explanation
Oral antibiotics Doxycycline (200mg) and rifampicin (600—900 mg) daily for 6 weeks is the treatment of choice. [1,2]
Intravenous antibiotics Rifampicin (15 mg/kg) and streptomycin daily for 2—3 weeks. [1]
References
  1. MARÍA PÍA FRANCO, MAXIMILIAN MULDER, ROBERT H GILMAN, HENK L SMITS. Human brucellosis. Human brucellosis. [online] December 2007: 7(12): 775-786. [viewed 29 April 2014] Available from: doi:10.1016/S1473-3099(07)70286-4
  2. AKOVA M, GUR D, LIVERMORE DM, KOCAGOZ T, AKALIN HE. In vitro activities of antibiotics alone and in combination against Brucella melitensis at neutral and acidic pHs. Antimicrob Agents Chemother [online] 1999; 43: 1298-1300. [viewed 29 April 2014] Available from: www.ncbi.nlm.nih.gov/uniquesig0/pmc/articles/PMC89265/