Concurrent neurobrucellosis and central nervous system aspergillosis in an immunocompetent host: a case report

Abstract

Introduction

Neurological infections often present with diverse symptoms, making coinfections particularly challenging. This study highlights an unusual case of dual coinfections caused by brucellosis and aspergillosis, emphasizing the complexity and severity of such infections.

Case presentation

A 27-year-old Syrian male patient with a history of adequately treated systemic brucellosis 3 years prior, presented with a 6-month history of progressive bilateral hearing loss, lower limb weakness, and intermittent incontinence. Neurological examination revealed bilateral sensorineural hearing loss and lower limb proprioceptive loss. Diagnostic workup confirmed neurobrucellosis via elevated Brucella immunoglobulin G antibodies in the cerebrospinal fluid, and neuroaspergillosis by cerebrospinal fluid culture growing Aspergillus fumigatus. Initial treatment for neurobrucellosis with ceftriaxone, doxycycline, rifampicin, and levofloxacin was adjusted upon fungal diagnosis to include voriconazole and trimethoprim-sulfamethoxazole. The patient subsequently underwent surgical excision of a concomitant T5–T9 arachnoid cyst. After 4 months of antimicrobial and 2 months of antifungal therapy, follow-up revealed significant clinical improvement in limb strength and incontinence, along with normalization of cerebrospinal fluid parameters.

Conclusion

This case highlights the diagnostic challenges and rarity of coexisting neurobrucellosis and Aspergillus infection, a combination not previously reported in medical literature. Both conditions are uncommon in the central nervous system and typically affect immunocompromised patients, making diagnosis difficult due to nonspecific symptoms and broad differential diagnoses. The successful treatment of this unique case underscores the need for further research into managing such unusual co-infections.

Introduction

Neurological infections often present with a wide spectrum of symptoms, and therefore coinfection in particular poses a challenge. Herein, we report the first documented case of concurrent neurobrucellosis and central nervous system (CNS) aspergillosis in an immunocompetent host. Brucellosis is a common zoonotic infection caused by the bacterial genus Brucella, a Gram-negative bacterium, and remains a health problem in endemic areas.

Neurobrucellosis comprises a variety of complications, including meningitis coinfection, myelitis, myelopathies, peripheral and cranial neuropathies, and psychiatric manifestations. Direct invasion of the CNS is rare, occurring in less than 2% of cases [1], making it a rare clinical complication of brucellosis that can mimic tuberculosis [2]. Secondly, aspergillosis rarely affects the central nervous system (CNSAG) and is related to low immunity. The incidence rate of CNSAG is high in patients undergoing solid organ transplantation or hematological diseases, as well as in patients receiving long-term immunosuppressive treatment [3]. Despite advances in early diagnosis, initiation of treatment, and newer antifungal agents, CNS aspergillosis remains a devastating opportunistic infection with a discouraging prognosis in adults. It is described as a fatal disease with invariable death if detected late [4]. While both neurobrucellosis and CNS aspergillosis are typically associated with specific risk factors—zoonotic exposure for the former and profound immunosuppression for the latter—their simultaneous occurrence in an immunocompetent individual challenges conventional diagnostic paradigms. This case highlights the critical need to consider atypical and concurrent pathogens even in the absence of classic risk factors.

Ultimately, the paucity of data on CNS aspergillosis is attributable to the relatively low incidence of CNS infections. Furthermore, certain etiologies of these diseases result in high case fatality rates or severe sequelae, underscoring the significance of coinfection as a critical public health concern [5]. We present this unique case to highlight unprecedented diagnostic and therapeutic challenges and to expand the understanding of CNS coinfections beyond traditional immunosuppressive etiologies.

Case presentation

A 27-year-old Syrian male patient, with a history of direct contact with goats, presented to Damascus Hospital with a 6-month history of progressive neurological decline. Three years earlier, the patient experienced a systemic febrile illness characterized by profound fatigue, generalized arthralgia, abdominal discomfort, and malaise. He was diagnosed with systemic brucellosis and received a full 6-week course of doxycycline and rifampicin. According to the treating physician, the patient demonstrated complete clinical recovery, accompanied by a reported decline in serologic titers, although original laboratory documentation was not available. His current symptoms began with gradually progressive bilateral hearing loss, culminating in complete deafness, accompanied by lower limb weakness. This initially manifested as difficulty walking, then progressed to an inability to rise from a seated position, eventually requiring assisted walking. He also developed intermittent urinary and fecal incontinence, along with sexual dysfunction. Crucially, he reported no headache, fever, or vomiting throughout this period.

Neurological examination revealed a conscious and oriented patient with normal speech. Cranial nerve assessment confirmed bilateral hearing loss, while fundoscopy showed no papilledema. Motor examination demonstrated normal upper limb strength, but lower limb strength was graded 3/5 proximally and 4/5 distally. Muscle tone and deep tendon reflexes were normal, with bilateral extensor plantar responses. Sensory testing indicated a profound bilateral proprioceptive loss in the lower limbs. Meningeal signs were negative, and vital signs were within normal limits.

Initial laboratory and imaging workup

Blood tests revealed a white blood cell count of 9000 cells/mm³ (61% neutrophils, 28% lymphocytes), hemoglobin of 12 g/dL, erythrocyte sedimentation rate (ESR) of 20 mm/hour, and C-reactive protein (CRP) of 4 mg/L. Wright’s test was positive at a titer of 1/320. Renal and liver function tests were normal. Serological tests for antinuclear antibodies (ANA), rheumatoid factor (RF), and human immunodeficiency virus (HIV) were negative. Brain magnetic resonance imaging (MRI) was unremarkable; however, spinal MRI identified an intradural extramedullary lesion extending from T5 to T9, consistent with an arachnoid cyst.

Diagnostic pivots and treatment evolution

Lumbar puncture and cerebrospinal fluid (CSF) analysis were critical. CSF showed 110 white cells/mm³ (85% lymphocytes, 15% neutrophils), a markedly elevated protein level of 388 mg/dL, low glucose at 25% of the simultaneous blood level, and high lactate at 48.5 mg/dL. Most importantly, Brucella immunoglobulin (Ig)G antibodies in the CSF were significantly elevated at 48.7, confirming the diagnosis of neurobrucellosis, while IgM was negative. CSF cultures for Mycobacterium tuberculosis (GeneXpert), and tests for abnormal cells and Angiotensin Converting Enzyme in cerebrospinal fluid (ACE) were negative, which is a finding commonly described due to the low sensitivity of CSF culture.

On the basis of the diagnosis of neurobrucellosis, a quadruple-drug regimen was initiated: intravenous ceftriaxone (2 g twice daily), oral doxycycline (100 mg twice daily), rifampicin (300 mg twice daily), and levofloxacin (750 mg once daily), the latter added due to concerns for potential resistance and to enhance CNS penetration.

CSF cultures were negative, which is a finding commonly described due to the low sensitivity of CSF culture. However, follow-up CSF culture showed that Aspergillus fumigatus subsequently grew, explaining the patient’s aggressive course. The treatment strategy was immediately adjusted: rifampicin was discontinued and replaced with oral trimethoprim-sulfamethoxazole (Bactrim 160/800 mg twice daily) to avoid drug interactions, and intravenous voriconazole (200 mg twice daily) was added as first-line therapy for CNS aspergillosis. The decision to switch to voriconazole was based on the confirmed culture and its superior CNS penetration and efficacy profile compared with the initial empirical amphotericin B trial, as per IDSA guidelines.

Further investigations included brainstem auditory evoked potentials, which indicated profound bilateral sensorineural hearing loss and tympanometry, which confirmed total hearing loss in both ears.

Clinical course, surgical intervention, and outcome

After 4 months of antimicrobial and 2 months of antifungal therapy, follow-up CSF analysis showed dramatic improvement: 15 white cells/mm³, protein at 41 mg/dL, and normalized glucose levels. Neurologically, the patient showed moderate improvement; lower limb strength improved to 4/5 proximally and 5/5 distally, enabling him to walk with a walker for short distances. He also regained partial urinary control.

The arachnoid cyst identified on spinal MRI was considered an incidental finding rather than a sequela or infectious nidus. The patient was referred to and underwent successful surgical excision of the T5–T9 cyst, but due to limitations in the local healthcare setting, the surgical specimen could not be cultured or examined histopathologically, preventing definitive assessment of its etiology. However, no intraoperative features suggested active infection.

Postoperatively, the patient’s condition improved further. MRI images pre- and post-surgery are shown in Figs. 1 and 2. The chronological sequence of clinical events, diagnostic pivots, and therapeutic interventions is summarized in Table 1.

Fig. 1.

Preoperative magnetic resonance imaging on T1W (A) and T2W (B)

Fig. 2.

Postoperative magnetic resonance imaging on T1W (A) and T2W (B)

Table 1.

Clinical timeline of diagnosis and management

Time point	Clinical presentation and events	Diagnostic findings	Interventions and management
T = −3 years	Diagnosis of systemic brucellosis	Positive Wright’s test	Full course of doxycycline + rifampicin (6 weeks). Confirmed resolution
T = 0 (admission)	Progressive bilateral hearing loss, lower limb weakness, incontinence, sexual dysfunction. No headache or fever	Neurological exam: bilateral hearing loss, lower limb strength 3/5. Spinal MRI: T5–T9 arachnoid cyst	Admission to neurology department
T =  +1 week	–	CSF: Lymphocytic pleocytosis, elevated protein (388 mg/dL), low glucose. Brucella IgG in CSF: 48.7	Initiated: ceftriaxone intravenous, doxycycline orally, rifampicin orally, levofloxacin orally
T =  +2 weeks	–	CSF culture: Aspergillus fumigatus. BAEP: Profound sensorineural hearing loss	Rifampicin discontinued. Voriconazole intravenous + trimethoprim-sulfamethoxazole orally added
T =  +2 months	Slight improvement in limb strength	–	Continued combination therapy
T =  +4 months	Moderate improvement in mobility. Partial recovery of urinary control	Follow-up CSF: marked improvement (15 cells/mm3, protein 41 mg/dL)	Completion of antimicrobial therapy. Antifungal therapy ongoing
T =  +6 months	Persistent neurological deficits	–	Referral to neurosurgery
T =  +7 months	Further improvement postoperatively	Postoperative MRI showing cyst excision	Surgical excision of T5–T9 arachnoid cyst

Discussion

To the best of our knowledge, this represents the first documented case of concurrent neurobrucellosis and central nervous system (CNS) aspergillosis in an immunocompetent host. This unique coinfection posed exceptional diagnostic and therapeutic challenges, broadening the spectrum of neurological infections beyond classical immunosuppressive etiologies. Neurobrucellosis is an uncommon complication, occurring in 3–10% of brucellosis cases, typically presenting with nonspecific symptoms such as headache and meningismus (6). Conversely, central nervous system (CNS) aspergillosis is a life-threatening infection that frequently affects immunocompromised patients. The mortality rate among patients with CNS aspergillosis is the highest among all forms of aspergillosis [7].

Unfortunately, the differential diagnosis for CNS aspergillosis can be extensive, as the clinical manifestations are not specific and culture sensitivities are lacking [8], [9]. Furthermore, it is common for CNS aspergillosis to occur in patients with severe immunosuppression, including those with prolonged neutropenia, recipients of hematopoietic stem cell transplants or solid organ transplants, and patients with advanced acquired immunodeficiency syndrome (AIDS) or chronic granulomatous disease [8].

Our case was particularly challenging; the patient was a 27-year-old young man with no history of chronic diseases who had previously contracted Brucella 3 years prior. He initially presented with symptoms of weakness and fever without headache. The symptoms initially improved with the diagnosis of systemic Brucella and the commencement of treatment. This initial symptom profile is consistent with systemic Brucella, which is characterized by milder, nonspecific symptoms [6]. Furthermore, chronic Brucellosis is often relapsing and can lead to complications such as neurobrucellosis, an unusual clinical complication of Brucellosis [2].

After 6 months, the disease recurred with symptoms of bilateral lower limb weakness and hearing loss, progressing to complete hearing loss without fever or headache. The progressive hearing loss and lower limb weakness are attributed to the central nervous system inflammation and damage caused by Brucella, as noted in the literature [6]. CSF analysis showed lymphocytic pleocytosis, decreased glucose concentration, and dramatically increased protein concentration, consistent with neurobrucellosis [10]. The absence of headache in the clinical presentation of neurobrucellosis is rare, as headache is often described in research, leading to a misleading presentation and extensive differential diagnosis. However, this is not surprising, as some studies describe CNS Brucellosis symptoms as atypical and nonspecific [11], [12]. In our patient, neurobrucellosis was confirmed by significantly elevated Brucella IgG antibodies in the CSF, which aligns with established diagnostic criteria [13].

It is customary to treat Brucellosis with a triple regimen of ceftriaxone, doxycycline, and rifampin for 4 weeks, followed by doxycycline and rifampin for at least 4 months. In our case, the triple therapy was supplemented with levofloxacin. Levofloxacin was added to the initial regimen due to its excellent CNS penetration and its documented role as an effective third agent in complicated or relapsing brucellosis. Several studies have shown that fluoroquinolone-based triple therapy may improve outcomes or provide an alternative in regions with rising antimicrobial resistance [14]. An infectious disease consultation revealed positive Aspergillus fumigatus in the CSF, a common pathogen in invasive aspergillosis [10]. The presence of Aspergillus in the CNS is often explained by hematogenous spread or local extension from sinuses or mastoid [15].

Therapeutically, there was no clear explanation for the presence of Aspergillus in the CNS, and the full extent of its association with Brucella remains unclear. This led doctors to initially administer empirical treatment with amphotericin, which provides broader antifungal coverage but did not improve the patient’s condition or CSF results despite a 1-month course. The empirical treatment was often attributed to the clinicians’ discomfort with using voriconazole due to a lack of data on appropriate therapeutic levels for managing CNS aspergillosis [7]. With the decision to adjust the drug coverage and use voriconazole, which is recommended as the first-line treatment for aspergillosis by the American Society of Infectious Diseases [16], the patient’s condition and CSF parameters showed marked improvement. The decision to switch from amphotericin B to voriconazole was supported by strong evidence demonstrating the superiority of voriconazole in invasive aspergillosis, including the pivotal NEJM randomized trial showing significantly higher survival and clinical response rates compared with amphotericin B. Moreover, rifampicin was discontinued because it is a potent CYP450 inducer known to markedly reduce voriconazole serum levels, rendering therapy ineffective—an interaction well documented in pharmacokinetic studies [17].

Generally, we found that neurobrucellosis and aspergillosis can occur concurrently, sometimes presenting without headache. Although many studies indicate the difficulty of surviving aspergillosis and consider it a fatal disease [7], despite its association with Brucella, which complicates the case, we achieved a medical success with the patient’s recovery, demonstrating the effectiveness of the treatments used.

Conclusion and recommendations

This case yields three critical lessons for clinical practice:

• Concurrent CNS infections should be considered in immunocompetent patients from brucellosis-endemic regions who present with atypical or severe neurological symptoms, even in the absence of classic features such as headache.

• Comprehensive CSF analysis is essential. Diagnosis relied on CSF serology for neurobrucellosis and culture for aspergillosis, highlighting the need for broad microbiological workup beyond standard tests.

• Combined medical-surgical management can be successful. A regimen containing levofloxacin for neurobrucellosis, alongside voriconazole for aspergillosis, followed by surgical excision of a structural lesion, resulted in a favorable outcome in this complex case.

We recommend maintaining a high index of suspicion for dual pathology in similar settings and adherence to established guidelines for targeted antimicrobial therapy.

Strengths and limitations

The principal strength of this report is documenting this unique coinfection in an immunocompetent host, providing insights into diagnostic challenges. However, as a single case report, generalizations are limited. The inability to perform detailed histopathological studies on the arachnoid cyst specimen restricts our understanding of its precise role. Despite these limitations, the successful outcome underscores the importance of comprehensive diagnostic workup and tailored therapy.

Author contributions

All authors contributed to the writing of the manuscript and reviewing the relevant literature. Rawan D and Ola A critically and linguistically revised the manuscript. Rawan D, Judy S, and Jamal A contributed to the revision and final preparation of the manuscript. All authors read and approved the final manuscript.

Funding

This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.

Data availability

All data generated or analyzed during this study are included in this published article. Any additional data are available from the corresponding author upon reasonable request.

Declarations

Ethics approval and consent to participate

Ethical approval for this case report was obtained from the Ethics Committee of Damascus Hospital (approval no. 883).

Consent for publication

Written informed consent was obtained from the patient’s legal guardian for publication of this case report and any accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal.

Competing interests

The authors declare that they have no competing interests.