Outbreak Reports: Integrated Approaches of Prevention and Medicine for Dealing with Central Nervous System Brucellosis: A Case from a Non-Epidemic Area — China, 2023

In March 2023, a 54-year-old woman presented at a local clinic with moderate headache, nausea, and vomiting, but no fever. Despite lacking a significant medical history, cerebrovascular disease was suspected based solely on her symptoms. She was treated with intravenous fluids as opposed to antibiotics, yet her condition did not improve. Two weeks later, she displayed irritability and incoherent speech. Subsequent evaluation at a county-level People’s Hospital, where a craniocerebral CT scan ruled out acute hemorrhage, revealed no definitive cause of her symptoms. That night, she experienced a seizure characterized by upward eye movements, clenched teeth, limb stiffness, and altered consciousness, lasting approximately one minute and resolving spontaneously. She regained full consciousness after about ten minutes. The following day, she developed convulsions, delirium, and a slight fever, which led to her transfer to another hospital’s Emergency Department on April 14, 2023. A craniocerebral magnetic resonance using a diffusion-weighted imaging (DWI) sequence did not show any acute cerebral infarction. Analysis of CSF indicated an elevated white blood cell count of 353×10⁶/L, with 82% mononuclear cells and 18% polymorphonuclear cells. Brucella spp. was suspected in the CSF sample, which was sent to Jinan CDC for confirmation. Initially treated with diazepam, mannitol, sodium valproate, acyclovir, and ceftriaxone, her condition continued to deteriorate, necessitating further management at the Department of Neurology of Qilu Hospital, Shandong University.

Brucella melitensis was isolated from a CSF sample sent to Jinan CDC, confirming brucellosis. The Infectious Disease Department at Qilu Hospital was promptly notified via the “Qilu Medicine-Prevention Innovative Integration” pathway (Figure 1). The patient was then transferred to the same department at Qilu Hospital. Treatment for CNS brucellosis was initiated with doxycycline (0.1 g po. b.i.d.), rifampicin (0.45 g po. b.i.d.), and ceftriaxone (IV every 12 h), supplemented with mannitol to reduce intracranial pressure. The blood test for brucellosis antibodies was positive. The patient’s peripheral blood leukocyte count was recorded at 6.15×10⁹/L, with neutrophils constituting 76.50% of the leukocytes. The C-reactive protein level was 3.67 mg/L. Tests for serum electrolytes, liver function, thyroid function, and autoimmune disease markers were all within normal limits. Additional diagnostics, including TB IFN-γ release assay, antineutrophil cytoplasmic antibodies, anticardiolipin antibody assay, lymphocyte subset assays, echocardiography, and lumbar magnetic resonance imaging (MRI), revealed no significant abnormalities. Given her history of consuming barbecued foods, she was diagnosed with a CNS infection caused by Brucella, which was associated with secondary epilepsy.

Figure 1. 

“Qilu Medicine-Prevention Innovative Integration” pathway.

Three days following treatment initiation, the patient regained normal consciousness and experienced no further convulsions. A subsequent lumbar puncture performed one month later revealed a reduced white blood cell count in the CSF, and cultures were negative for Brucella. The patient then underwent oral anti-infective therapy for approximately seven months, during which her symptoms resolved. CSF karyocyte counts eventually normalized (Table 1), leading to the discontinuation of antibiotics (Figure 2).

Figure 2. 

Timeline of the case report.

Abbreviation: CSF=cerebrospinal fluid.

Jinan CDC conducted screenings on all high-risk populations using culture and serological tests, with a total of 12 individuals tested and no infections detected. Medical institutions across Jinan were provided training to enhance their diagnostic and treatment capabilities for brucellosis. Additionally, health education on brucellosis was provided to all practitioners and the general public.

In this report, we describe a rare case of CNS brucellosis identified in a region not typically endemic for this infection. Brucellosis is a neglected zoonosis caused by the pathogenic bacterium Brucella (1) and may be transmitted to humans through direct or indirect contact with infected animals or by consuming their contaminated products (2–3). The infection in this patient likely originated from consuming barbecued meat. The detection of this case emphasizes the potential need for enhanced screening of suspect animal products.

Brucella is recognized for causing systemic diseases in humans, with CNS involvement being an uncommon manifestation. Consequently, the atypical clinical signs observed in patients frequently lead to misdiagnosis or inappropriate treatment (4–5). The current case was identified as CNS brucellosis due to a progression of symptoms beginning with headache, vomiting, and delirium; this contrasts with typically reported symptoms of CNS brucellosis, which include headache, fever, and confusion (4–5). Without precise diagnosis and prompt treatment of CNS involvement, the prognosis for brucellosis patients remains poor, highlighting the importance of early detection (2–4).

Although Brucella infection can be diagnosed through culture, serological testing, and polymerase chain reaction (PCR)-based methods, culture is still considered the gold standard for diagnosis (4–5). However, the sensitivity of cultures is low, and confirmation by the CDC is often required. Serodiagnosis of brucellosis does not offer direct evidence of the microorganism’s presence. Despite the high sensitivity of real-time PCR assays, a positive result does not always indicate an active infection. Brucella-specific serodiagnostic assays and nucleic acid amplification tests may not be conducted if the disease is not initially considered, potentially leading to missed diagnoses (5). In the case described, the initial diagnosis was based on symptoms. Following the patient’s presentation with disturbances in consciousness, CSF was examined, allowing for the isolation of Brucella in the CSF. Although lymphocytic pleocytosis was prevalent in 90% of CNS brucellosis cases, approximately 10% exhibited a predominance of CSF polymorphonuclear cells. It is important to note that CSF lymphocytosis is not specific to neurobrucellosis, as it is also observed in other types of meningitis, including tuberculosis and neurocryptococcosis.

CNS brucellosis is typically managed with a combination of doxycycline, rifampicin, and ceftriaxone. However, there is no established consensus regarding the choice of antibiotic, dosage, and treatment duration for neurobrucellosis. Some studies have reported continuing antimicrobial treatment for 4–9 months. Regimens based on ceftriaxone have shown greater success with shorter treatment durations compared to the standard oral treatment protocol (4).

Patients with diffuse CNS involvement exhibited worse prognoses, often resulting in frequent sequelae (4). The favorable outcome observed in this high-risk case of CNS brucellosis can be attributed to the timely diagnosis and treatment facilitated by an integrated system that involved coordinated collaboration between public health services and clinical institutions (Figure 1).

The establishment of an integrated medicine and prevention service system, which provides continuous services, enhances early disease diagnosis, prompt disease management, and reduces healthcare costs. Effective communication and information sharing among primary healthcare facilities, public hospitals, and public health institutions, coupled with the development of early warning systems, augment the system’s agility and response capability to health risks (6–7). Through this collaborative framework, medical institutions leverage shared technological and resource advantages to swiftly and accurately identify high-risk cases and report them to public health authorities. Consequently, these institutions can rapidly initiate epidemiological investigations and laboratory tests, assess risks meticulously, and inform hospital staff to implement appropriate treatment protocols (Figure 1).

In conclusion, the findings from this case emphasize the necessity for coordinated healthcare services across various levels and locations within and beyond the health sector, tailored to patient needs throughout their lifespan (8–10). Furthermore, integrating treatment and prevention services enhances patient-centered healthcare and integrated medical care, facilitating timely treatment through rapid diagnosis, particularly for rare infectious diseases.

No conflicts of interest.

Staff of the relevant hospital involved in clinical diagnosis and treatment.