Brucellosis: Symptoms, Types, Causes and Treatment

Brucellosis is a complex and often misunderstood bacterial infection that affects both humans and animals. Known by other names such as Mediterranean fever, undulant fever, or Malta fever, brucellosis is a zoonosis—an infectious disease that naturally transmits from animals to people. Its symptoms can be vague, overlapping with many other illnesses, which makes diagnosis challenging. Understanding the symptoms, types, causes, and treatment options is crucial for both healthcare professionals and at-risk individuals. Let’s delve into the details of this important disease.

Symptoms of Brucellosis

Brucellosis presents a wide spectrum of symptoms, ranging from mild and nonspecific to severe and chronic. The early recognition of these symptoms can significantly influence the course of the disease, as timely diagnosis and treatment help prevent complications and relapses. However, these symptoms often mimic other diseases, contributing to frequent misdiagnosis and inadequate therapy.

Symptom	Frequency/Prevalence	Notes/Complications	Source(s)
Fever	80-90% (most common)	Can be undulant or intermittent	1,3,5
Fatigue	60-91%	Long-lasting, profound	1,3,4
Sweating	56-88%	Often night sweats	2,3,4
Arthralgia	62-81%	May lead to arthritis	1,3,8
Muscle pain	56%	Myalgia	1
Headache	Common, nonspecific		2,4
Hepatosplenomegaly	23-39%	Swollen liver/spleen	3,5
Insomnia	Frequently reported		2,4
Rash	More in children		1
Complications	Hepatitis, osteoarthritis, CNS, orchitis	Focal disease possible	1,3,5,8

Table 1: Key Symptoms of Brucellosis

Overview of Symptom Patterns

Brucellosis can manifest acutely, subacutely, or chronically.

• Acute brucellosis typically presents within 1-3 weeks after exposure, but symptoms can be delayed for several months. The hallmark sign is fever, which may be intermittent (“undulant”) and is often accompanied by excessive sweating—especially at night—profound fatigue, joint and muscle pain, headache, and general malaise. These nonspecific symptoms often resemble flu or malaria, complicating prompt recognition 2,3,6.
• Chronic brucellosis occurs when the infection persists for months or years, leading to recurring or continuous symptoms such as weakness, depression, irritability, and rheumatism. Chronic cases are more likely among those with repeated exposure, such as veterinarians and agricultural workers 4.

Age and Complication Differences

• Children: More likely to develop rash, respiratory, and cardiac complications, as well as orchitis/epididymitis in males 1,5.
• Adults: Hepatosplenomegaly and anemia are more common complications; joint involvement (arthritis, back pain) is frequent 3,5,8.
• Complications: In both age groups, complications such as hepatitis, osteoarthritis, and splenic or hepatic lesions can occur, potentially leading to more severe, debilitating sequelae if not treated early 1,3,5,8.

Diagnostic Challenges

Because brucellosis symptoms are nonspecific, misdiagnosis rates are high, particularly in non-endemic or nonpastoral areas. Routine biochemical and hematology tests, serological assays, and cultures help confirm the diagnosis, but clinical suspicion based on symptom profile and exposure history remains crucial 2,3,5.

Types of Brucellosis

Brucellosis is not a single entity but a group of infections caused by different Brucella species. Each type is associated with specific animal reservoirs and can vary in severity and clinical characteristics in humans.

Type/Species	Main Animal Reservoir(s)	Key Human Features/Complications	Source(s)
B. melitensis	Sheep, goats	Most severe, acute disease	6,7,9
B. abortus	Cattle	Milder, chronic cases possible	6,7,9
B. suis	Pigs	Focal complications, abscesses	6,7,9
B. canis	Dogs	Rare, mild to moderate symptoms	6
B. neotomae, B. ovis	Rodents (neotomae), sheep (ovis)	Rare in humans	6
Marine Brucella	Marine mammals	Emerging, complex transmission	6

Table 2: Main Types of Brucellosis

Brucella Species and Their Impact

• Brucella melitensis: The most virulent species for humans, commonly found in sheep and goats. Infection often results in more severe and acute disease, and is prevalent in the Mediterranean basin, Middle East, Latin America, and parts of Asia and Africa 6,7.
• Brucella abortus: Associated mainly with cattle, causing milder infection in humans but can lead to chronic brucellosis if not treated 6,7.
• Brucella suis: Found in pigs, this species is notable for causing focal abscesses and more localized complications, such as osteoarticular infections 6,7,9.
• Brucella canis: Originates from dogs and is a rare cause of human infection, typically resulting in less severe disease 6.
• Other species: B. neotomae and B. ovis rarely infect humans. Marine Brucella species (from marine mammals) are emerging as potential human pathogens, adding complexity to the epidemiology 6.

Acute vs. Chronic and Focal Disease

• Acute brucellosis: Most commonly associated with B. melitensis, with abrupt onset and pronounced symptoms 6,7.
• Chronic brucellosis: More likely with B. abortus or inadequately treated cases, marked by persistent symptoms and increased risk for focal complications such as spondylitis, arthritis, endocarditis, or epididymo-orchitis 4,8,13.
• Focal disease: Any Brucella species can cause focal infections, but B. suis is especially notorious for abscess formation. Osteoarticular complications—especially arthritis—are the most frequent focal issues, but pulmonary, hepatic, and cardiovascular involvement can also occur 3,8,15.

Causes of Brucellosis

Understanding the causes and transmission routes of brucellosis is key to prevention. It is a classic zoonotic disease—transmitted from animals to humans via several well-established pathways.

Cause/Route	Description	Risk Factors/Notes	Source(s)
Unpasteurized Dairy	Ingestion of raw milk, cheese	Major global route, especially cheese	2,5,6
Undercooked Meat	Eating meat from infected animals	Less common than dairy	2,6
Animal Contact	Handling livestock, secretions	High risk for farmers, vets	2,3,5
Inhalation	Breathing contaminated aerosols	Lab workers, slaughterhouse employees	2,6
Skin Breaks	Contact with abraded skin	Handling placenta, aborted fetuses	2,6
Human-to-human	Extremely rare	Rarely via blood, tissue, or birth	2,7

Table 3: Causes and Transmission Routes of Brucellosis

Main Transmission Pathways

• Consumption of Unpasteurized Dairy: The most common route worldwide. Brucella bacteria survive in raw milk, cheeses (especially “fresh” cheeses), butter, and other dairy products 2,5,6.
• Direct Animal Contact: Handling infected animals, their tissues, or bodily fluids (especially birth products like placenta or aborted fetuses) places veterinarians, farmers, abattoir workers, and laboratory personnel at high risk 2,3,5.
• Inhalation: Inhalation of aerosolized Brucella can occur in laboratory or slaughterhouse settings, making occupational exposure a key concern 2,6.
• Ingestion of Undercooked Meat: Less common, but possible if meat from infected animals is not thoroughly cooked 2,6.
• Infection via Skin: Cuts or abrasions allow bacteria to enter the body during handling of animal products 2,6.
• Person-to-person Transmission: Exceptionally rare, but has been reported in cases involving blood transfusion, organ transplantation, and rarely from mother to child 2,7.

Risk Factors and Epidemiology

• Geographical Hotspots: Brucellosis is more common in the Mediterranean, Middle East, Africa, Asia, and Latin America—regions where unpasteurized dairy consumption and animal husbandry are prevalent 2.
• Occupational Risk: People working with livestock, veterinarians, and laboratory staff are at higher risk 3,4.
• Socioeconomic and Environmental Factors: Poor hygienic conditions, lack of animal vaccination, and traditional farming practices increase risk 2,6.

Treatment of Brucellosis

Effective treatment of brucellosis is vital to prevent relapses and complications. Brucella bacteria are intracellular pathogens, which makes them challenging to eradicate. Treatment regimens are tailored based on the patient’s age, disease severity, focal complications, and contraindications.

Regimen/Drug(s)	Typical Duration	Use Case/Notes	Source(s)
Doxycycline + Streptomycin	45 days + 14 days	First choice, adults	2,11,14
Doxycycline + Rifampicin	6 weeks or more	Second choice, adults	2,11,14
Doxycycline + Gentamicin	45 days + 7 days	Alternative for adults	2,13,14
Triple therapy (Doxycycline + Rifampicin + Levofloxacin)	12 weeks	For complications/focal disease	3,11
Rifampicin (pregnancy)	900 mg daily for 6 wks	Preferred in pregnancy	14
Rifampicin + Cotrimoxazole	45 days	Children <8 years	14
Monotherapy (Doxycycline)	45 days	Mild, uncomplicated, not preferred	13,14
Surgery + antibiotics	Variable	Endocarditis, abscesses	14

Table 4: Main Treatment Regimens for Brucellosis

Principles of Brucellosis Treatment

• Combination Therapy: Using two or more antibiotics is significantly more effective than monotherapy, reducing the risk of relapse 11,13,14. Doxycycline-streptomycin is considered the gold standard for most adults, but doxycycline-rifampicin is a widely used alternative.
• Duration: Treatment should be continued for at least 6 weeks, and up to 12 weeks for complicated or focal disease 2,3,11.
• Special Populations:
  • Pregnant women: Rifampicin is the drug of choice; tetracyclines are contraindicated 14.
  • Children under 8 years: Rifampicin plus cotrimoxazole is recommended, as tetracyclines can cause permanent tooth discoloration and bone effects 14.
• Focal Disease: Focal brucellosis such as spondylitis, endocarditis, or abscesses often requires triple therapy and may need surgical intervention 3,8,14.
• Relapse Prevention: Relapse rates are lower with combination regimens and longer duration; monotherapy is associated with higher failure and relapse 11,13.

New and Alternative Treatments

• Aminoglycosides: Gentamicin may substitute for streptomycin, with comparable efficacy 11,14.
• Quinolones: May be used in combination but are less effective than standard regimens 11,13.
• Pulmonary Involvement: Treated with the same antibiotic combinations as acute brucellosis; clinical outcomes are generally favorable 15.
• Vaccine Research: Although no human vaccine is available yet, promising research on multi-epitope peptide vaccines is underway, aiming to prevent brucellosis or support treatment in the near future 12.

Monitoring and Follow-up

• Laboratory Testing: Serial serological tests (e.g., SAT titers) help monitor treatment response. A decline in titers indicates effective therapy 2.
• Complication Management: Cases with endocarditis, central nervous system involvement, or antibiotic-resistant abscesses may require surgical intervention 14.
• Relapse Surveillance: Patients should be observed for several months after treatment due to the risk of relapse 11.

Conclusion

Brucellosis remains a significant public health challenge due to its varied symptoms, zoonotic nature, and the difficulties in diagnosis and treatment. To summarize:

• Symptoms: Brucellosis presents with fever, fatigue, sweating, joint pain, and can lead to chronic or severe complications if untreated.
• Types: Multiple Brucella species cause disease, with B. melitensis being most severe; types vary in their animal reservoirs and clinical impact.
• Causes: The main causes are consumption of unpasteurized dairy, direct animal contact, and occupational exposure.
• Treatment: Combination antibiotic therapy for at least six weeks is crucial; special regimens are needed for children and pregnant women, and longer or more intensive treatment is required for complicated cases.

By increasing awareness of brucellosis—its symptoms, causes, and treatment options—healthcare providers and at-risk individuals can better prevent, recognize, and manage this challenging disease.