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An Adolescent With Neurobrucellosis Caused by Brucella abortus Cattle Vaccine Strain RB51

Sarmiento Clemente, Adriana MD*; Amerson-Brown, Megan H. PhD; Foster, Catherine E. MD*

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The Pediatric Infectious Disease Journal: September 2021 - Volume 40 - Issue 9 - p e353-e355
doi: 10.1097/INF.0000000000003200


Brucellosis is a common zoonotic disease worldwide, most often transmitted to humans by the consumption of unpasteurized dairy or dairy products.1 Since 1996, the Brucella abortus strain RB51 (RB51) live-attenuated vaccine has been approved for use in cattle in the United States and other countries in an effort to eradicate both human and bovine disease.2 Since the introduction of this vaccine, there have been reports of vaccinated animals shedding the vaccine strain in milk and placing consumers of unpasteurized milk at risk for infection.2 Three confirmed uncomplicated infections under these circumstances have been reported within the United States.3 We present the first reported case of neurobrucellosis due to RB51.


An 18-year-old Hispanic female presented to our institution with a 1-month history of daily fevers (maximum temperature, 39.4°C), nausea, vomiting, fatigue, dizziness, double vision, and headaches. Her parents also noted new onset bilateral eye-crossing, more marked on the right, and an unintentional 15-pound weight loss. On admission, she reported mild anterior chest and lower back pain. She had no sick contacts and was fully vaccinated. She lived with her parents, siblings, and 2 dogs.

On physical examination, she was pale and febrile to 38.3°C with tachypnea and tachycardia. Ophthalmologic evaluation was notable for bilateral papilledema and bilateral cranial nerve VI palsy, worse on the right. The remainder of her examination was unremarkable. Laboratory studies showed a total white blood cell (WBC) count of 3000/µL, hemoglobin of 8.4 g/dL, and platelets of 184,000/µL. C-reactive protein was elevated at 3.9 mg/dL, and procalcitonin was normal. Empiric antimicrobial therapy with intravenous (IV) doxycycline was initiated for treatment of possible murine typhus. Magnetic resonance imaging of brain and orbits with contrast showed slight irregularity of the back of the globes, suggestive of papilledema, and minimal medial rotation of the right globe; the remainder of the study, including a venography of the brain, was otherwise normal. A lumbar puncture was performed. Analysis of the cerebrospinal fluid (CSF) showed: an elevated opening pressure at 52 cm of water, mild pleocytosis with 8 WBC/mm3, protein concentration of 39 mg/dL, and glucose concentration of 48 mg/dL. No organisms were seen on the direct Gram stain or acridine orange stain.

On the third hospital day, 3 of 3 peripheral blood cultures collected on admission grew Gram-negative rods, which were eventually identified as Brucella species (see Figure, Supplemental Digital Content 1,, which demonstrates growth on blood and chocolate agar plates). CSF culture remained negative. Intravenous ceftriaxone was added pending identification of the organism, and her fevers resolved. On further questioning, she reported consuming unpasteurized cheese brought from Mexico 1 month before the onset of her symptoms. Following identification of Brucella sp., an echocardiogram and full spine and pelvis radiographs were performed to screen for endocarditis and osteomyelitis. Both studies were normal.

For treatment, she was initiated on a triple-drug regimen of IV ceftriaxone and oral rifampin and doxycycline. She was also started on acetazolamide for management of increased intracranial pressure. After clinical improvement, she was discharged to continue therapy at home. Four weeks later, the Houston Health Department/Laboratory Response Network Laboratory identified the strain as B. abortus strain RB51. Given the specific resistance pattern of RB51, rifampin was switched to trimethoprim-sulfamethoxazole for the remainder of her treatment. She completed 6 weeks of IV ceftriaxone and 4.5 months total of oral therapy. At end of therapy follow up, she remained asymptomatic. Additionally, family members who had consumed the unpasteurized product received postexposure prophylaxis with doxycycline and trimethoprim-sulfamethoxazole for 21 days according to Centers for Disease Control and Prevention (CDC) guidelines for exposure to foods suspected to be contaminated with RB51.4


Brucellosis is a zoonotic disease transmissible to humans by contact with an infected animal or animal tissues or secretions or by consumption of animal products, including undercooked meat, unpasteurized dairy, or cheese.1 Although endemic to many regions of the world including the Middle East, Asia, Africa, and parts of Central and South America, only 100–200 cases of brucellosis are reported per year in the United States and only 19% of those cases occur in people younger than 24 years of age.5,6 Worldwide, most brucellosis cases are attributed to B. melitensis, which is usually isolated from goats and sheep.1 A smaller proportion of cases are caused by B. abortus, B. suis, and B. canis, isolated principally from cattle, swine, and dogs, respectively.1

Neurobrucellosis is a potential complication from systemic infection with Brucella spp. with a wide array of manifestations including as follows: encephalitis, meningitis, myelitis, cranial nerve involvement, radiculopathy, or neuropathy.7 The World Health Organization estimates neurologic complications affect around 5% of patients with brucellosis, and meningitis or meningoencephalitis are the most common presentations.1 In a retrospective study of 317 children less than 15 years of age diagnosed with brucellosis in Macedonia, only 3 (0.9%) had neurologic involvement in the form of meningitis, central or peripheral neuritis.8 In our patient, the presence of headache, vomiting, and double vision suggested neurologic involvement. Although she had mild CSF pleocytosis, we were not able to confirm the presence of Brucella in her CSF using traditional bacterial culture methods. Treatment with doxycycline before her lumbar puncture may have contributed to her negative CSF culture.

Brucella abortus RB51 is a live-attenuated strain first approved for cattle vaccination in the United States in 1996, which replaced the previously used B. abortus strain 19 vaccine.2 It continues to be widely used in the United States and other Latin American countries including Mexico for vaccination of cattle.1 Multiple cases of accidental human exposure to the RB51 vaccine with the development of systemic symptoms have been described, mostly through needle stick.9 There have been reports of shedding RB51 in milk of vaccinated cattle2 and since August 2017, 3 confirmed cases of human infection by RB51 through consumption of raw milk have been described in the United States.3 We present, to our knowledge, the first case of neurobrucellosis by this strain.

As Brucella spp. isolation rates in cultures vary considerably (25–80%) and usually requires prolonged time for incubation and identification, serology is of significant value for diagnosis.10 RB51 differs from other strains as it does not produce an antibody response detectable by routine serologic tests, making diagnosis more challenging.11 RB51 grew in blood cultures from our patient after 62 hours of incubation allowing for a definitive diagnosis.

The RB51 strain is the only 1 described to be resistant to rifampin and penicillin in vitro, likely the result of being a product of selection in a rifampin and penicillin-enriched media.10,11 This unique resistance pattern makes expert management recommendations difficult to apply since rifampin is included in most oral regimens studied. Double or triple antimicrobial therapy has been recommended for decades for the treatment of brucellosis to avoid complications and relapse.1 Aminoglycosides have frequently been a part of these regimens, although now considered less often in the treatment of neurobrucellosis given questionable blood-brain-barrier penetrance and potential neurotoxicity with gentamicin use.12 Most recent studies have evaluated the use of ceftriaxone, given its excellent activity against Brucella in vitro and ability to achieve higher concentrations in CSF, although it is not recommended as monotherapy due to high relapse rates.12 Authors of a large multicenter retrospective study of neurobrucellosis, known as the Istanbul study, concluded that ceftriaxone therapy for at least 1 month combined and then followed by 1–2 months of oral therapy with doxycycline and rifampin eliminated negative outcomes like treatment failure and relapse in 96.5% of cases.13

When RB51 was identified as the strain causing disease in our patient, we adjusted her treatment according to resistance pattern specific for this strain and switched her from rifampin to trimethoprim-sulfamethoxazole. We considered substituting another agent for the ceftriaxone given concern of RB51 penicillin resistance; however, her clinical improvement at outpatient follow-up guided our decision to continue with ceftriaxone.

With prior cases of human infection in the United States with RB51 strain by consumption of raw milk or milk products, source identification and tracking of exposed individuals has been completed, and the CDC has recommended postexposure prophylaxis to those considered at risk.4 In our case, the unpasteurized cheese was brought into the United States from Mexico in an unregulated, noncommercial fashion, making contact tracing and source control extremely challenging. This highlights the importance of international efforts for veterinarian and dairy farm owner education on the risk that RB51 may pose to unpasteurized milk consumers.

In cases of suspected brucellosis, asking about consumption of unpasteurized food products is important and although human infection with RB51 is rare, infectious disease specialists should be aware of its unique antimicrobial resistance pattern. Finally, the lack of serologic tests that can detect immunologic response to the RB51 strain presents an additional challenge to diagnosis, thus a heightened index of suspicion for this infection is needed.


1. Corbel MJ; World Health Organization. Food and Agriculture Organization of the United Nations, World Health Organization & World Organisation for Animal Health. Brucellosis in humans and animals. (2006). Available at: Accessed April 2, 2021.
2. USDA, Animal Plant Health and Inspection Service (APHIS). Veterinary services. Bovine Brucellosis and RB51 fact sheet. May 2018. Available at: Accessed March 9, 2021.
3. Negron ME, Kharod GA, Bower WA, et al. Notes from the field: Human Brucella abortus RB51 infections caused by consumption of unpasteurized domestic dairy products—United States, 2017–2019. CDC Morbidity and Mortality Weekly Report (MMWR). 2019; 68:185.
4. CDC and Prevention National Center for Emerging and Zoonotic Infectious Diseases (NCEZID), Division of High-Consequence Pathogens and Pathology (DHCPP). Exposure to RB51 through Raw Milk or Milk Products: How to Reduce Risk of Infection. Available at: Accessed February 18, 2021.
5. Negrón ME, Tiller R, Kharod G. Brucellosis. In: CDC Yellow Book 2020: Health Information for International Travel. Oxford University Press; 2017.
6. Adams DA, Thomas KR, Jajosky RA, et al. Summary of notifiable infectious diseases and conditions—United States, 2015. CDC MMWR. 2017; 64:1–143.
7. Dreshaj S, Shala N, Dreshaj G, et al. Clinical manifestations in 82 neurobrucellosis patients from Kosovo. Mater Sociomed. 2016;28:408–411.
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10. Dorneles EM, Sriranganathan N, Lage AP. Recent advances in Brucella abortus vaccines. Vet Res. 2015;46:76.
11. Schurig GG, Roop RM II, Bagchi T, et al. Biological properties of RB51; a stable rough strain of Brucella abortus. Vet Microbiol. 1991;28:171–188.
12. Pappas G, Akritidis N, Christou L. Treatment of neurobrucellosis: what is known and what remains to be answered. Expert Rev Anti Infect Ther. 2007;5:983–990.
13. Erdem H, Ulu-Kilic A, Kilic S, et al. Efficacy and tolerability of antibiotic combinations in neurobrucellosis: results of the Istanbul study. Antimicrob Agents Chemother. 2012;56:1523–1528.

brucellosis; RB51; rifampin resistance

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