Brucella, a bacterium with multiple ways of causing infection

Abstract

Brucellosis is a zoonotic infection caused by the intracellular gram-negative bacterium Brucella. It is the most common zoonosis worldwide, and its transmission is classically associated with consumption of unpasteurized animal products. However, other mechanisms of transmission include contact of the skin or mucous membranes with infected animal tissue. We present a case of a patient who had more than one possible route of infection.

Brucellosis is a zoonotic infection transmitted to humans from infected animals (cattle, sheep, pigs) by ingestion of food products, such as unpasteurized dairy products.¹ The most common zoonosis worldwide, it is an important public health problem in many developing countries.¹ The prevalence of brucellosis has been increasing due to growing international tourism and migration.² Imported unpasteurized dairy products, such as fresh goat or sheep cheese from neighboring countries (particularly Mexico), are an important source of infection.³ Other mechanisms of infection include contact with mucous membranes of infected animal tissue (such as placenta or miscarriage products) or infected animal fluids (such as blood, urine, or milk) and inhalation of infected aerosolized particles.¹ In this report we present an interesting case of brucellosis with more than one mode of possible transmission.

CASE REPORT

A 68-year-old Hispanic woman with known diabetes mellitus type 2 and hypertension presented to Baylor University Medical Center at Dallas for evaluation of generalized weakness, intermittent dizziness, fever, decreased oral intake, nausea, back pain, and diarrhea for 1 week. She had unintentionally lost approximately 20 pounds over 3 months. She denied any chills, vomiting, abdominal pain, cough, or headaches. She had traveled to Mexico 3 months earlier. Her blood hemoglobin was 11.9 g/dL; serum sodium, 131 mEq/L; total bilirubin, 0.5 mg/dL; aspartate aminotransferase, 539 U/L; alanine aminotransferase, 308 U/L; alkaline phosphatase, 481 U/L; and white blood cell count, 6.2 K/μL. A chest radiograph showed no concerning findings, and computed tomography of her abdomen/pelvis with contrast showed normal enhancement of the liver and spleen parenchyma without hyperenhancing masses. She was treated with intravenous fluids and admitted to the hospital.

The following morning, her temperature was 102.9°F and blood cultures were obtained. Laboratory results showed a serum sodium of 136 mEq/L; aspartate aminotransferase, 367 U/L; alanine aminotransferase, 279 U/L; and alkaline phosphatase, 480 U/L (Table 1). Her nausea and diarrhea had resolved. The next day, blood cultures came back positive for gram-negative coccobacilli. She was started on meropenem, doxycycline, and gentamicin. Antibodies for Brucella were ordered and titer results were >1:1280, consistent with brucellosis. Her blood cultures eventually speciated Brucella melitensis. Both transthoracic and transesophageal echocardiograms were ordered, neither of which showed any vegetations around the heart valves.

Table 1.

The patient’s laboratory results^a

Test	Results						Reference value
	Presentation	Day 2	Day 9	Day 10	Day 11	Day 12
Glucose (mg/dL)	144	126	135	202	165	225	70–99
Blood urea nitrogen (mg/dL)	12	11	12	15	15	13	7–20
Creatinine (mg/dL)	0.72	0.56	0.38	0.55	0.45	0.63	0.55–1.02
Sodium (mEq/L)	131	136	142	139	140	135	136–145
Potassium (mEq/L)	3.8	3.6	4	4.5	4.4	3.8	3.5–5.1
Bilirubin, total (mg/dL)	0.5	0.6	0.4	0.9	0.5	0.5	0.2–1.0
Alkaline phosphatase (U/L)	481	480	378	859	715	646	45–117
Aspartate aminotransferase (U/L)	539	367	79	797	450	144	15–37
Alanine aminotransferase (U/L)	308	279	101	489	378	244	13–56
Albumin (g/dL)	2.6	2.8	2.3	2.6	2.2	2.5	3.4–5.0
International normalized ratio	1.1
White blood cells (K/μL)	6.2		3.7	4.3	3.8	4.9	4.5–11.0
Hemoglobin (g/dL)	11.9		10.5	10.3	10	11.3	12.0–16.0
Platelet count (K/μL)	251		312	334	341	415	140–440
Acetaminophen (μg/mL)	18.5	<2.0					10.0–20.0
C-reactive protein (mg/dL)		9.8	8.8				0.0–0.03
Syphilis screen	Negative
HIV serology	Negative
Blood cultures	Positive for Brucella melitensis
Brucella antibody	≥1:1280						<1:80

^aTests were also negative for hepatitis B surface antibody, hepatitis B core antibody immunoglobulin M, hepatitis C antibody, hepatitis A antibody immunoglobulin M, varicella zoster virus polymerase chain reaction, cytomegalovirus polymerase chain reaction, herpes simplex virus 1 and 2, Histoplasma antigen, syphilis screen, and human immunodeficiency virus serology.

The patient reported that while she was in Mexico during the summer, she would pet donkeys, goats, and horses. Her favorite horse was reportedly sick with what she thought was cancer, as it had multiple lumps on its joints. Eventually the horse died. The patient’s son confirmed that the patient had eaten local cheese, but other family members had consumed the same cheese and experienced no symptoms. Eventually, her symptoms improved and her fever broke. Her antibiotics were adjusted to gentamicin for 14 days and doxycycline for 12 weeks, with plans of adding rifampin once she completed her course of gentamicin.

DISCUSSION

Our patient with brucellosis presented with fever, generalized malaise, and diarrhea. The most common symptoms associated with brucellosis include fever (76%), malaise (68%), night sweats (72%), and arthralgias (80%).⁴ The incubation period is usually 2 to 4 weeks, but may be as long as several months, as in this case, where the patient was exposed around July and developed symptoms in September.⁴ Physical findings include hepatomegaly, splenomegaly, and/or lymphadenopathy.³ Laboratory findings of brucellosis may include elevated transaminases, anemia, leukopenia or leukocytosis, and thrombocytopenia.⁵ Our patient’s laboratory results showed elevated liver enzymes with a mixed hepatocellular and cholestatic pattern of liver injury. An abdominal ultrasound ruled out the possibility of biliary obstruction, but the spleen was noted to be mildly enlarged for the patient’s age and gender (Figure 1). Her liver function test results increased suddenly on day 10 of hospitalization (Figure 2). A careful review of her recently administered medications and possible interactions between them did not identify a drug known to cause hepatic injury. Acute liver failure has been noted in cases of brucellosis where patients appear to be asymptomatic at the time of presentation and improve with the continuation of antimicrobial treatment.⁶

Figure 1.

(a) Ultrasound Doppler of the right upper abdominal quadrant noting no biliary obstruction as well as a patent hepatic vasculature. (b) Abdominal ultrasound noting a spleen measurement of 10.5 cm in greatest length.

Figure 2.

Liver function tests from hospital day 1 to 13. Note the sudden rise in liver function tests on day 10 of the patient’s hospital stay. From that point on, values decreased with the continuation of antibiotics. AST indicates aspartate aminotransferase; ALT, ALT, alanine aminotransferase; ALP, alkaline phosphatase.

Brucellosis is typically associated with consumption of unpasteurized dairy products.¹ It is an occupational disease in shepherds, veterinarians, and dairy industry professionals.⁷ Rare cases of human-to-human transmission due to blood transfusion, breastfeeding, sexual contact, congenital transmission, and nosocomial infection have been described.^8–10 Our patient could have become infected from consuming local cheese or from petting her horse. It has been reported that horses infected with Brucella can develop carpal bursitis and a hygroma, a subcutaneous swelling over the cranial or dorsal aspect of the carpus.¹¹

Brucellosis can affect one or multiple organ systems. In humans, osteoarticular disease is the most common form of focal brucellosis; it occurs in up to 70% of patients with brucellosis.¹² Treatment for brucellosis is of prolonged duration and consists of rifampin and doxycycline combination therapy, given the high relapse rates with monotherapy.¹³