Acute brucellosis may present with symptoms such as [7]:

• Fever with chills and rigors 
• Anorexia 
• Headache
• Abdominal pain
• Muscular pain
• Fatigue and weakness
• Arthralgia
• Excessive sweating 
• Swollen lymph nodes 
• Hepatosplenomegaly with abdominal tenderness 
• Ocular findings such as uveitis, choroiditis, keratoconjunctivitis, etc.
• Cutaneous lesions such as erythema nodosum, maculopapular rashes, etc.

Fever is typically undulant, i.e it comes, reaches a high peak particularly in the afternoon or evening and then goes away for a while. When fever breaks, the patient may experience cold sweats and chills. After a few hours, fever spikes again. The associating symptoms may or may not persist.

• Splenomegaly

  She subsequently developed a fever and was diagnosed with pancytopenia and moderate splenomegaly. Laboratory and bone marrow results, including markedly increased serum ferritin levels, suggested haemophagocytic lymphohistiocytosis. [ncbi.nlm.nih.gov]

  However, hepatomegaly, splenomegaly, lymphadenopathy, and focal organ infection (e.g., osteomyelitis, endocarditis, spondylitis) may also occur. Recommended treatment is a combined regimen of doxycycline and rifampin. [amboss.com]

  Of 238 pts 194 (81.5 %) had fever > 37.5 C, 87 (36.5 %) had osteoarticular involvements, 55 (23 %) had hepatomegaly and 52 (21 %) splenomegaly. There were meningitis in three, orchitis in two and endocarditis in one. [trdizin.gov.tr]

  – May be associated with: non-specific gastrointestinal disorders, cough, hepato and/or splenomegaly, arthritis (knee), orchitis. Diagnosis is difficult because of the broad spectrum of fluctuating and non-specific clinical manifestations. [medicalguidelines.msf.org]

• Generalized Lymphadenopathy

  One patient presented with generalized lymphadenopathy, and 1 patient presented with meningitis. Eight (21.6%) of 28 patients exhibited >1 extrapulmonary complication of brucellosis. [academic.oup.com]

• Fever

  Brucellosis Other names undulant fever, undulating fever, Mediterranean fever, Malta fever, Cyprus fever, rock fever (Micrococcus Melitensis)[1] Specialty Infectious disease Symptoms coughing Brucellosis[2][3] is a highly contagious zoonosis caused by [en.wikipedia.org]

  It is also called Bang's disease; Bruce's septicaemia, Cyprus fever, Gibraltar fever, Malta fever, Mediterranean fever, Neapolitan fever. [whonamedit.com]

  […] noun mass noun A bacterial disease typically affecting cattle and causing undulant fever in humans. [en.oxforddictionaries.com]

  Cyprus fever; Undulant fever; Gibraltar fever; Malta fever; Mediterranean fever Beeching NJ, Madkour MM. Brucellosis. In: Farrar J, Hotez PJ, Junghanss T, Kang G, Lalloo D, White NJ, eds. Manson's Tropical Diseases. 23rd ed. [nlm.nih.gov]

• Pain

  Splanchnic vessels stenosis and an endothelial lesion may exacerbate the prevalent symptom of abdominal pain, as a form of colic pain, occurring after eating. The patient was diagnosed as brucellosis. [ncbi.nlm.nih.gov]

  Later symptoms include loss of appetite, weight loss, severe constipation, abdominal pain, joint pain, difficulty sleeping, weakness, irritability, and depression. [merckmanuals.com]

• Veterinarian

  A total of 1050 sera samples were collected from animal handlers, veterinarians, veterinary students, para-veterinarians and persons engaged in artificial insemination of animals. [ncbi.nlm.nih.gov]

  Contamination of skin wounds may be a problem for persons working in slaughterhouses or meat packing plants or for veterinarians. [web.archive.org]

  Contamination of skin wounds may be a problem for veterinarians, workers in slaughterhouses and meat packing plants, and people involved in the birthing process of infected animals. [epi.publichealth.nc.gov]

  Registered veterinarians inspect and advise on property biosecurity and undertake inspection and blood test rams on studs participating in the scheme. [agric.wa.gov.au]

• Fatigue

  Clinical symptoms include fever, fatigue, hyperhidrosis, and joint pain with common complication of osteoarticular involvement. [ncbi.nlm.nih.gov]

  Initial symptoms can include: fever sweats malaise anorexia headache pain in muscles, joint, and/or back fatigue Some signs and symptoms may persist for longer periods of time. Others may never go away or reoccur. [cdc.gov]

• Weight Loss

  The patient reported the loss of appetite, arthralgia and weight loss during previous five months. Finally, he was diagnosed with brucellosis by positive blood culture and high titer for Brucella agglutination test. [ncbi.nlm.nih.gov]

  The disease causes flu-like symptoms, including fever, weakness, malaise and weight loss. [who.int]

  Other symptoms may include fatigue, headache, weight loss, joint pain, and enlarged lymph nodes, spleen and liver. [tn.gov]

  It can cause a continuous or intermittent fever, headache, weakness, drenching sweats, chills, joint and muscle pain, weight loss and generalised aches. The severity and duration of symptoms can vary greatly between people. [conditions.health.qld.gov.au]

• Cough

  A 20-year-old man who had a living-donor kidney transplant 4 months earlier presented to our transplant clinic with fever, cough, and right flank pain. Clarithromycin and ceftriaxone were started for the diagnosis of pneumonia. [ncbi.nlm.nih.gov]

  – May be associated with: non-specific gastrointestinal disorders, cough, hepato and/or splenomegaly, arthritis (knee), orchitis. Diagnosis is difficult because of the broad spectrum of fluctuating and non-specific clinical manifestations. [medicalguidelines.msf.org]

  ‘Other causes of encephalitis include influenza, listeriosis, brucellosis, Rocky Mountain spotted fever, whooping cough, rabies and lead poisoning.’ [en.oxforddictionaries.com]

  Cough was reported by 25 patients (67.6%). Ten (27%) of these patients reported productive cough with expectoration, and 15 (40.5%) reported dry cough. One patient presented with paroxysmal, pertussis-like dry cough. [academic.oup.com]

• Dyspnea

  Dyspnea was reported by 8 (21.6%) of 37 patients. Arterial blood gas values were only randomly determined for these patients, and, thus, the level of dyspnea cannot be adequately evaluated. However, only 1 patient needed respiratory assistance. [academic.oup.com]

  Respiratory symptoms including a cough, dyspnea, and pleurisy may occur; however, in most cases, chest radiography is normal, although focal abscesses, effusions, granulomas, and abscesses have occurred. [ncbi.nlm.nih.gov]

  Although fever, cough and dyspnea are frequently reported among patients with brucellosis, true pulmonary disease is uncommon. [journals.lww.com]

• Hemoptysis

  One patient presented with hemoptysis. Dyspnea was reported by 8 (21.6%) of 37 patients. Arterial blood gas values were only randomly determined for these patients, and, thus, the level of dyspnea cannot be adequately evaluated. [academic.oup.com]

• Abdominal Pain

  Splanchnic vessels stenosis and an endothelial lesion may exacerbate the prevalent symptom of abdominal pain, as a form of colic pain, occurring after eating. The patient was diagnosed as brucellosis. [ncbi.nlm.nih.gov]

  Patients may present with fever, vomiting, abdominal pain and constipation [34]. Brucella melitensis is usually the causative organism [34],[35]. [saudijgastro.com]

• Loss of Appetite

  The patient reported the loss of appetite, arthralgia and weight loss during previous five months. Finally, he was diagnosed with brucellosis by positive blood culture and high titer for Brucella agglutination test. [ncbi.nlm.nih.gov]

  Acute brucellosis may begin with mild flu-like symptoms, or symptoms such as: Abdominal pain Back pain Chills Excessive sweating Fatigue Fever Headache Joint and muscle pain Loss of appetite Swollen glands Weakness Weight loss High fever spikes often [nlm.nih.gov]

  Symptoms of brucellosis are like the flu: a high temperature of 38C or above loss of appetite sweating headaches extreme tiredness back and joint pain Non-urgent advice: See a GP if you have symptoms of brucellosis and: you've had unpasteurised milk or [nhs.uk]

  The following are the first signs of brucellosis: Fatigue Fever Sweating Headache Muscle, joint, back discomfort Weakness, ill-feeling Loss of appetite The following are symptoms that may come back, last for a long while, or not go away: Fevers that come [my.clevelandclinic.org]

• Vomiting

  He began to feel myalgia, arthralgia, malaise, shortness of breath, abdominal pain, vomiting, diarrhoea and lost weight eight months after initial symptoms occured. Because symptoms progressed he was admitted to our hospital in February 2009. [ncbi.nlm.nih.gov]

  Patients may present with fever, vomiting, abdominal pain and constipation [34]. Brucella melitensis is usually the causative organism [34],[35]. [saudijgastro.com]

  For the past month, he has had general malaise, daily fevers, and some nausea and vomiting. On physical exam, he has a low-grade fever but otherwise a normal physical exam. [medbullets.com]

  All 6 reported nausea, vomiting, and anorexia. One staff member developed fever and mild hepatitis and required admission to the hospital for monitoring. The symptoms resolved promptly with cessation of the course of antibiotics. [dx.doi.org]

• Nausea

  A 19-year-old man presented with a 2-week history of fever, sweating, low back and leg pain, lassitude, loss appetite, nausea and vomiting. He gave a history of raw milk ingestion and animal contact. [ncbi.nlm.nih.gov]

  For the past month, he has had general malaise, daily fevers, and some nausea and vomiting. On physical exam, he has a low-grade fever but otherwise a normal physical exam. [medbullets.com]

  All 6 reported nausea, vomiting, and anorexia. One staff member developed fever and mild hepatitis and required admission to the hospital for monitoring. The symptoms resolved promptly with cessation of the course of antibiotics. [dx.doi.org]

  Early symptoms may involve: General feeling of illness—malaise Fatigue Headache Muscle or joint pain Fever Chills Severe headache and backache Nausea, vomiting, or diarrhea Rash Brucellosis causes a high fever (104°F-105°F). [cancercarewny.com]

  Nausea and vomiting were registered in three patients in doxycycline plus rifampicin group and in one patient in ofloxacin plus rifampicin group. [bmcinfectdis.biomedcentral.com]

• Tachycardia

  Localized infection Arthralgias, low back pain → osteoarticular infection (e.g., osteomyelitis, spondylitis) Epididymal and testicular tenderness, flank pain → genitourinary infection (e.g., epididymo-orchitis, pyelonephritis) Murmurs, friction rubs, tachycardia [amboss.com]

• Hepatomegaly

  Physical examination of the patient revealed massive hepatomegaly. Abdominal ultrasonography and computerised tomography showed a single large cystic lesion of the liver. The echinococcus indirect haemagglutination was positive at a titre of 1/1280. [ncbi.nlm.nih.gov]

  However, hepatomegaly, splenomegaly, lymphadenopathy, and focal organ infection (e.g., osteomyelitis, endocarditis, spondylitis) may also occur. Recommended treatment is a combined regimen of doxycycline and rifampin. [amboss.com]

  Of 238 pts 194 (81.5 %) had fever > 37.5 C, 87 (36.5 %) had osteoarticular involvements, 55 (23 %) had hepatomegaly and 52 (21 %) splenomegaly. There were meningitis in three, orchitis in two and endocarditis in one. [trdizin.gov.tr]

• Hepatosplenomegaly

  Abstract Brucellosis is a systemic zoonotic infectious disease that may cause fever, fatigue, sweating, arthritis, hepatosplenomegaly, cytopenia, and lymphadenopathy. It continues to be an important health problem worldwide. [ncbi.nlm.nih.gov]

  Definition / general Due to Brucella abortus, melitensis or suis Either occupational or food related (milk and cheese) Fever, hepatosplenomegaly, rarely lymphadenopathy Case reports 22 year old woman with Kikuchi-Fujimoto necrotizing lymphadenitis associated [pathologyoutlines.com]

• Night Sweats

  A case is reported here of a 33-year-old woman with symptoms of night sweats, fever and low back pain. Rose-Bengal test for brucellosis was positive and Brucella standard tube agglutination test was positive at a titre of 1/160. [ncbi.nlm.nih.gov]

  Acute form (primary infection) – Remittent or intermittent fever (39-40 °C), associated with several signs or symptoms: chills, night sweats, joint and muscle pain, weight loss, fatigue, malaise, headache; adenopathies (particularly in children). – May [medicalguidelines.msf.org]

• Arthritis

  When the patients were divided into groups as arthritis positive and arthritis negative and compared to the control group; we found that the NLR is more significant in between the arthritis positive and control group (p = 0.013). [ncbi.nlm.nih.gov]

• Back Pain

  A case is reported here of a 33-year-old woman with symptoms of night sweats, fever and low back pain. Rose-Bengal test for brucellosis was positive and Brucella standard tube agglutination test was positive at a titre of 1/160. [ncbi.nlm.nih.gov]

  Figure 1: (A) Sagittal computed tomographic reconstruction of the spine of a 68-year-old woman with lower back pain showing erosive changes at the superior end plate of L3 (black arrow). [doi.org]

  In humans, brucellosis can cause symptoms that are similar to the flu, including fever, sweats, headaches, back pains and physical weakness. Severe infections of the central nervous system or of the lining of the heart (endocarditis) may occur. [epi.publichealth.nc.gov]

• Arthralgia

  A 15-year-old girl, who was evaluated for arthralgia of knees, was diagnosed as having brucellosis by serum agglutination and enzyme linked immunosorbent assay tests. Physical examination of the patient revealed massive hepatomegaly. [ncbi.nlm.nih.gov]

• Myalgia

  Common clinical findings are usually nonspecific involving fever, arthralgia, myalgia, weakness and malaise. Since none of the symptoms of brucellosis is pathognomonic, it may have a similar course with various multisystemic diseases. [ncbi.nlm.nih.gov]

• Low Back Pain

  A case is reported here of a 33-year-old woman with symptoms of night sweats, fever and low back pain. Rose-Bengal test for brucellosis was positive and Brucella standard tube agglutination test was positive at a titre of 1/160. [ncbi.nlm.nih.gov]

  People typically have a fever, chills, a severe headache, low back pain, bone and joint pain, and other bodywide symptoms. Most people recover in 2 to 3 weeks, even without treatment. [merckmanuals.com]

  […] lymphadenopathy Localized infection Arthralgias, low back pain → osteoarticular infection (e.g., osteomyelitis, spondylitis) Epididymal and testicular tenderness, flank pain → genitourinary infection (e.g., epididymo-orchitis, pyelonephritis) Murmurs [amboss.com]

• Dysuria

  Endocarditis [26], pulmonary involvement [27], hepatobiliary and hematologic [28], pyelonephritis and dysuria [29], and arthritis [30] were other presentations of the disease. [intechopen.com]

  Goats:Mature female Sign Reproductive Signs / Retained placenta, fetal membranes Sheep & Goats:Mature female Sign Respiratory Signs / Coughing, coughs Sheep & Goats:Gimmer,Sheep & Goats:Mature female,Sheep & Goats:Breeding male Sign Urinary Signs / Dysuria [cabi.org]

• Testicular Swelling

  Following 3 days of this treatment, the testicular swelling reduced considerably and orchidectomy was not required. Indeed, after a week, swelling was completely resolved and the patient was discharged. [ncbi.nlm.nih.gov]

  Brucellosis can also cause long-lasting or chronic symptoms such as recurrent fevers, joint pain, testicular swelling, heart infections, nervous system impairment, depression, and fatigue. Death from brucellosis is rare. [health.ny.gov]

• Headache

  The patient also suffered from headache, partial seizures, changes of personality and static tremor of both upper limbs. [ncbi.nlm.nih.gov]

  Or symptoms may begin gradually, with a feeling of being slightly ill, muscle pain, headache, and pain in the back of the neck. The fever may come and go for several weeks. [merckmanuals.com]

  […] and RSS » bru·cel·lo·sis (br s -l s s) KEY NOUN: An infectious bacterial disease of humans that is caused by brucellae, transmitted by contact with infected animals, and characterized by fever, malaise, and headache. [web.archive.org]

• Confusion

  Background & objectives: Brucellosis can lead to haematological abnormalities including cytopenia confusing with haematological malignancies. [ncbi.nlm.nih.gov]

  A small percentage of vaccinated calves develop antibodies to Strain 19 that may persist for years and can confuse diagnostic test results. To minimize this problem, calves in the USA are mostly vaccinated with a vaccine of Strain RB51. [merckvetmanual.com]

  This recurring febrile disease can be confused with other recurring febrile illnesses (e.g., malaria and relapsing fever). Table P-3 lists the differences in the length of the fever and fever periodicity. Table P-3. [atsu.edu]

  Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances Although Brucella species are relatively resistant to adverse environmental [mayomedicallaboratories.com]

• Irritability

  Later symptoms include loss of appetite, weight loss, severe constipation, abdominal pain, joint pain, difficulty sleeping, weakness, irritability, and depression. [merckmanuals.com]

  The infection may spread to the central nervous system causing depression, headache, and irritability or, in advanced cases, meningoencephalitis. [dermnetnz.org]

  In addition to the list above, late symptoms may involve: Loss of appetite Weight loss Belly pain Weakness Irritability Insomnia Serious problems may involve: Abscesses within the liver or spleen Enlargement of the liver, spleen, or lymph nodes Inflammation [cancercarewny.com]

  […] múltiple A02 Escalofríos A03 Fiebre A04 Astenia/cansancio/debilidad A05 Sensación de enfermedad A06 Desmayo/síncope A07 Coma A08 Inflamación A09 Problemas de sudoración A10 Sangrado/hemorragia NE A11 Dolor torácico NE A13 Miedo al tratamiento A16 Lactante irritable [iqb.es]

• Guillain-Barré Syndrome

  Acinetobacter baumannii Xanthomonadaceae Stenotrophomonas maltophilia Cardiobacteriaceae Cardiobacterium hominis HACEK Aeromonadales Aeromonas hydrophila/Aeromonas veronii Aeromonas infection ε Campylobacterales Campylobacter jejuni Campylobacteriosis, Guillain–Barré [en.wikipedia.org]

Workup consists of a detailed history and physical examination.

Laboratory tests

• Complete blood count
• Liver function tests
• Culture
• Serology is unreliable. A four-fold rise in titre of agglutinating antibody, which detects IgM antibody, may be diagnostic but cross reactions are common [8]. 
• Arthrocentesis: In patients with joint involvement to rule out septic arthritis. 
• CSF culture: In patients with CNS involvement.
• PCR 
• Bone marrow biopsy
• Urinalysis

Imaging

Imaging studies are conducted if systemic manifestations are present. They may include:

• Chest X-ray if respiratory system seems to be involved. 
• Spinal X-ray to examine vertebral involvement.
• Radionuclide scintography [9]
• CT scan
• Echocardiography to rule out endocarditis

Test Results

Test results are enough to form a definitive diagnosis and treatment needs to be started immediately. An empiric antibody trial may be started if test results are awaited.

• Blood Culture Positive

  A diagnosis of acute brucellosis was considered due to positive serological tests and a blood culture positive for Brucella spp. [ncbi.nlm.nih.gov]

• Granulomatous Tissue

  For instance, in minke and Bryde’s whales the conspicuous testicular lesions were mainly characterized by granulomatous tissue with caseation and mineralization, and in some instances abscesses displaying caseous necrosis. [doi.org]

Antibiotics are the primary treatment. The most common and most efficacious of used agents include:

• Streptomycin
• Doxycycline 
• Gentamycin
• Rifampin
• Cotrimoxazole
• Ciprofloxacin

Of the currently existing alternative regimens, only the combination of doxycycline with gentamycin can be considered therapeutically adequate and cost-effective, the latter factor being a major obstacle in using quinolones for brucellosis [10].

Even though initial symptoms may appear to be debilitating, brucellosis has an excellent prognosis. With appropriate treatment for a few weeks to months, this disease can be cured with no lasting effects. Relapse may sometimes occur. It should be noted, however, that in patients with comorbidities such as congestive heart failure, prognosis can be negatively affected. Overall, mortality rate in uncomplicated cases is less than 2 to 5%.

Complications

Infection in pregnancy may result in abortion, congenital and neonatal infections, and infections of the delivery team [6]. Other complications include endocarditis, CNS disorders (neurobrucellosis), meningitis, skin lesions, ulcers and eye infections.

The causative agent of brucellosis is an unencapsulated gram negative rod called Brucella. There are three main human pathogens of Brucella, each with their specific animal reservoirs:

• Brucella melitensis (goats and sheep)
• Brucella suis (pigs)
• Brucella abortus (cattle)

Brucella canis (dogs) may also infect humans but it is rare and clinically indistinguishable from B. abortus infection.

Incidence

The reported frequency in USA is 0.04 per 100,000 people [2]. It has been known to cause more than 500,000 infections annually worldwide.

Age

Brucellosis can occur at any age but it is more common in young adults. Infection among children is generally more benign than in adults with respect to likelihood and severity of complications and response to treatment [3].

Sex

Brucellosis is much more common in males than in females. This predisposition to the male gender is attributed to males being more involved in activities, such a cattle farming, that increase chances of exposure.

The organisms enter the body either by ingestion of contaminated milk products or through skin due to contact in occupational setting such as an abattoir [4]. Once inside, these organisms localise in the reticuloendothelial system, where some of them are phagocytosed by macrophages. Some, however, survive within the cells and remain protected from antibodies.

The host response is granulomatous, with lymphocytes and epitheloid giant cells, which can progress to form focal abscesses [4].  The incubation period is usually one to four weeks; occasionally, it may be as long as several months [5].

Prevention can be possible with pasteurisation of milk, immunisation of animals, and slaughtering of infected animals. There is no human vaccine [4].

Brucellosis is a systemic infection with a broad clinical spectrum, ranging from asymptomatic disease to severe and/or fatal illness [1]. It has many other names such as Crimean Fever, Malta Fever, Undulant Fever, Mediterranean Fever, etc. It comes under the category of zoonotic diseases which refers to the group of diseases caused by organisms associated with animal reservoirs. Brucellosis is the most common zoonotic disease.

Definition

Brucellosis is a systemic infection which has a broad clinical spectrum. It may be asymptomatic to, in some extremely rare cases, fatal. It is also known as undulant fever, Malta fever, Mediterranean fever, etc.

Cause

It is caused by a bacteria called Brucella, which lives in animals like sheep, goats, dogs and pigs. Drinking unpasteurised milk or eating the meat of infected animals may result in this infection.

Symptoms

Symptoms include fever with chills and rigors, fatigue, headache, abdominal pain, muscular pain, sweating and sometimes it may be accompanied with skin rashes, eye infections and CNS disorders.

Treatment

Antibiotics are the treatment of choice and this disease can be completely cured in a few weeks of therapy.

Prevention

Brucellosis is easily preventable. By avoiding the use of unpasteurised milk and other dairy products, and eating the meat only from high quality stores, brucellosis can be prevented.

1. Colmenero JD, Reguera JM, Martos F, et al. Complications associated with Brucella melitensis infection: a study of 530 cases. Medicine (Baltimore) 1996; 75:195.
2. Maloney GE. Brucellosis. eMedicine. Apr 2009. Retrieved Sept 26 2014.
3. Mantur BG, Amarnath SK, Shinde RS. Review of clinical and laboratory features of human brucellosis. Indian J Med Microbiol 2007; 25:188.
4. Warren Levinson. Review of Medical Microbiology and Immunology. 11th ed. Pa: McGraw Hill. Lange. Chap 20 p146-7. ISBN 978-0-07-170028-3.
5. Fiori PL, Mastrandea S, Rappelli P, Cappuccinelli P. Brucella abortus infections quoted in microbiology laboratories. J Clin Microbiol 2000; 38:2005.
6. Karcaaltincaba D, Sencan I, Kandemir O, et al. Does brucellosis in human pregnancy increase abortion risk? Presentation of two J Obstet Gynecol Res. 2010 Apr;36(2):418-23.
7. Young EJ. Brucella species. In: Mandell GL, Bennett JE, Dolin R, eds. principles and Practice of Infectious Disease. 7th ed. Philadelphia. PA: Elsevier Churchill Livingstone. 2009:chap 226.
8. Davidson's Principles and Practice of Medicne: A textbook for students and doctors. Christopher RWE, Ian ADB, eds. 16th ed. PA: Elsevier Churchill Livingstone. Chap 5, p130-1.
9. el-Desouki M. Skeletal Brucellosis: assessment with bone scintigraphy. Radiology. Nov 1991;181(2):415-8 [Medline].
10. Hasanjani Roushan MR, Mohraz M, Hajiahmadi M, et al. Efficacy of gentamycin plus doxycycline versus streptomycin plus doxycycline in the treatemt of brucellosis in humans. Clin Infect Dis. 2006 Apr 15;42(8):1075-80. epub 2006 Mar 13.