Neurobrucellosis associated with feral swine hunting in the southern United States
- Harry Ross Powers ,
- Jared R Nelson ,
- Salvador Alvarez and
- Julio C Mendez
- Division of Infectious Diseases, Mayo Clinic, Jacksonville, Florida, USA
- Correspondence to Dr Julio C Mendez; Mendez.Julio@mayo.edu
Abstract
Although uncommon, Brucella infection can occur outside the areas of high endemicity, such as the USA. In the southern USA, hunters of wild swine are at risk for brucellosis. We present a case of a patient with fever, headache and constitutional symptoms that were ongoing for 11 months. He was diagnosed with neurobrucellosis. The patient was treated successfully with intravenous ceftriaxone, oral doxycycline and oral rifampin therapy. He had persistent neurological sequelae after completing treatment. This case illustrates the high index of suspicion needed to diagnose neurobrucellosis in a non-endemic country because initial symptoms can be subtle. The disease can be treated successfully, but long-lasting neurological sequelae are common.
Background
Brucella is a genus of fastidious Gram-negative bacteria that reproduce intracellularly in the human body.1 Areas of high endemicity include the Mediterranean Basin and the Middle East.2 The usual route of acquisition is through the consumption of contaminated animal products (including unpasteurised milk and cheese). However, brucellosis also occurs in areas not considered endemic, such as the USA. In humans, 115 cases of Brucella infection were reported in the USA in 2010.3 An underappreciated source of Brucella infection in the USA is the hunting of feral swine.4 We report a case of neurobrucellosis in a patient who participated in feral swine hunting in the southern USA.
Case presentation
A 54-year-old man with an unremarkable medical history presented with concerns of chronic daily headache for 11 months. He described the headaches as a dull aching sensation that was most intense at the bilateral temples. Eleven months before his presentation, the patient reported an episode of numbness and speech difficulties, for which he underwent MRI at an outside hospital. This imaging was reportedly negative, and he was diagnosed with transient ischaemic attack. The patient also was having cognitive disturbances that consisted of short-term memory loss and difficulties with concentration. His wife reported that the patient was having changes in personality, including acting more aggressively and having mood swings. The patient reported systemic symptoms of fever, fatigue and weight loss.
The patient had smoked 0.5 packs per day of cigarettes for the past 40 years. He reported drinking three to four beers per day. He denied use of illicit drugs. The patient worked as a nurse in a prison. He was also an avid hunter, and the animals he hunted included deer and feral swine. He participated in field dressing of the carcasses without wearing gloves or other protective equipment.
The patient’s mental status gradually worsened, and he was admitted to the hospital for encephalopathy. He was initially started on empirical therapy for meningitis, with intravenous vancomycin, cefepime and acyclovir.
Investigations
On hospitalisation at Mayo Clinic in Florida, the patient had a complete blood cell count that was important for a white blood cell (WBC) count of 15.2×109/L (reference range, 3.6–9.4×109/L) with 66% neutrophils and 25% lymphocytes. His basic metabolic panel was clinically important for a serum creatinine value of 1.3 mg/dL (reference range, 0.74–1.35 mg/dL). The patient’s hepatic function panel was within normal limits. A lumbar puncture (LP) was performed. Cerebrospinal fluid (CSF) was important for a WBC count of 249 cells/μL (reference range, <5 WBCs/µL), with 50% lymphocytes and 47% neutrophils (table 1). CSF chemistry analysis showed protein of 238 mg/dL (reference range, 15–45 mg/dL) and glucose of 20 mg/dL (reference range, 40–60 mg/dL). Bacterial, fungal and mycobacterial cultures were negative. PCR testing for cytomegalovirus, herpes simplex virus 1 and 2, varicella zoster virus, meningitis (multiplex meningitis panel; BioFire Diagnostics), Borrelia burgdorferi (Lyme disease) and Mycobacterium tuberculosis (MTB) was negative for all factors. Cryptococcus CSF antigen test also was negative. Serum serology test for Coxiella burnetii and Francisella tularemia was negative. Urinary Histoplasma antigen test also had a negative test result.
CSF analysis over time
| Test | At hospitalisation | At 10 days into hospitalisation | At 3 months into Brucella treatment | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Cerebrospinal fluid (CSF) analysis performed at hospital admission, 10 days into hospitalisation and 3 months into therapy. At admission, CSF analysis showed lymphocytic pleiocytosis, and elevated protein and low glucose levels. Ten days into therapy with intravenous cefepime, a CSF analysis showed improvement in lymphocytosis but persistent elevated protein and low glucose levels. Three months into treatment, lymphocytosis greatly improved and protein and glucose levels normalised. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| WBCs/μL | 249 | 103 | 15 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Neutrophils, % | 47 | 10 | 0 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Lymphocytes, % | 50 | 44 | 95 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Monocytes, % | 3 | 45 | 5 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| RBCs/μL | 3000 | 10 | 0 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Protein, mg/dL | 238 | 224 | 63 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Glucose, mg/dL | 20 | 19 | 55 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Differential diagnosis
Given the patient’s prolonged symptoms of 11 months and CSF findings, the initial diagnosis was chronic meningitis. The aetiological characteristics of chronic leptomeningitis include atypical bacterial infections (eg, Lyme disease and brucellosis), mycobacterial infection and fungal infection, as well as autoimmune conditions. Because this patient worked at a prison, the initial concern was for tuberculous meningitis.
The patient had a negative acid-fast bacilli (AFB) smear on CSF analysis and a negative MTB PCR. An AFB smear has a sensitivity of only 30%–60% for diagnosis of tuberculous meningitis.5 6 MTB PCR has a sensitivity of 80% for diagnosis of tuberculous meningitis.7 Mycobacterial CSF cultures were negative at 6 weeks. The sensitivity of culture for tuberculous meningitis is 71%.5 Given the low prevalence of tuberculosis in the USA and the patient’s negative test results, we did not believe that tuberculous meningitis was a likely diagnosis.
Chronic fungal meningitis was the next concern. The patient did not have an immunocompromising condition that would put him at risk for an invasive mold infection. In addition, he lived in southern Alabama, which is not known to have endemic fungi, such as Coccidioides or Histoplasma. Fungal cultures and Histoplasma urinary antigen were negative.
The patient reported substantial activities hunting with deer and feral swine and that he dressed and butchered the animals himself without gloves. For this reason, he was tested for Brucella, for which he had a positive serum serology test. Given the patient’s history of hunting, CSF findings and positive serum serology results, we were confident that the patient had Brucella meningitis.
Treatment
For this patient, Brucella meningitis treatment was started with intravenous ceftriaxone 2 g two times per day, and oral rifampin 600 mg per day and doxycycline 100 mg two times per day. He was discharged from the hospital with a peripherally inserted central catheter. The patient completed 4 weeks of intravenous ceftriaxone therapy. He then completed 6 months of oral doxycycline and rifampin treatment.
Outcome and follow-up
The patient was seen at 1, 3 and 6 months of therapy. By 1 month, his symptoms were vastly improved. He no longer had fevers or headaches. At 3 months, a repeat LP was performed. The CSF analysis showed a WBC count of 15 cells/μL with 95% lymphocytes, protein of 63 mg/dL and glucose of 55 mg/dL (table 1). At 6-month follow-up, the patient again reported no fevers, headaches or new paraesthesia. However, he did report continuing issues with short-term memory, attention and decision-making.
Discussion
The hunting of feral swine is an underrecognised source of brucellosis in the USA. Feral swine are found in 41 states in the USA, and 9 states (including Florida and Alabama) have confirmed Brucella infection in their feral swine population.8 Experts estimate that up to 52% of feral swine in some areas of the USA are seropositive for Brucella.9 The Centers for Disease Control and Prevention (CDC) presented three cases of Brucella infection that was acquired in Florida from hunting feral swine. The three patients were thought to have acquired the infection through field dressing the carcasses without proper protective equipment. This report had led the CDC to issue guidance to hunters to use gloves and eye protection when field dressing wild game and to thoroughly cook game meat.10
Brucellosis is diagnosed with cultures or serology testing of a patient who has symptoms that include fever, constitutional symptoms, headache and meningitis.11 Neurobrucellosis makes up 5%–12% of Brucella infection cases.12 The diagnosis of neurobrucellosis can be difficult to make because culture yield from CSF is low.13 In one study, only 15% of CSF cultures were positive for Brucella species .14 In our case, cultures for Brucella were taken after the patient was taking antibiotics for 2 weeks, limiting the yield even further.
Neurobrucellosis can be diagnosed with a standard antibody agglutination test of CSF or serum and CSF that shows evidence of meningitis (usually lymphocytic results, elevated protein level and low glucose level) or with brain imaging consistent with infection.13 The sensitivity and the specificity of positive serum Brucella IgM and positive serum Brucella IgG is 94% and 97%, respectively, and the sensitivity and the specificity of positive Brucella serum agglutination test is 95.6% and 100%, respectively, for active Brucella infection.15
In addition, neurobrucellosis can present with various radiological findings. The most common MRI findings include meningeal enhancement and white matter changes.16 Cerebral granulomas and infarctions have also been described.13 Interestingly, almost one-half of neurobrucellosis cases have normal MRI findings in the central nervous system.16
Symptoms of neurobrucellosis include headache, fever, paraesthesia and changes in consciousness.13 In one study, the most common neurological symptom was headache, which was present 85% of the time.14 Patients can present with cognitive and psychiatric changes, including depression and memory loss.17 In fact, according to one report, up to 30% of patients with brucellosis have depressive symptoms.18 Other common neuropsychiatric symptoms are behavioural changes, agitation and disorientation.13
The treatment of neurobrucellosis is controversial. The Ioannina guidelines released in 2007 did not address complicated Brucella infections.19 One Turkish study evaluated retrospectively three different treatment protocols: protocol 1 (P1), intravenous ceftriaxone, and oral rifampin and doxycycline; protocol 2 (P2), oral trimethoprim, sulfamethoxazole, rifampin and doxycycline; and protocol 3 (P3), P1 initially and then a switch to P2.20 The median duration of intravenous ceftriaxone therapy of the P1 arm was 30 days. When evaluating the combined clinical outcome of therapeutic failure or relapse, the study investigators concluded that the patient who received intravenous ceftriaxone performed better and that the P1 group had fewer adverse effects than the P3 group. This study formed the basis for the treatment regimen of our patient.
Even with treatment, neurological sequelae are common in neurobrucellosis. One study reported 19% of patients had persistent neurological symptoms after treatment, with the most common symptoms being walking difficulties and hearing loss.20 Another study observed that 22% of patients had persistent sequelae, including neurosensorial deafness, paresis and aphasia.13
Neurobrucellosis is an uncommon disease in the USA. However, it should be considered for patients with signs, symptoms and laboratory findings that are concerning for chronic meningitis. This is especially true for patients who have exposure to carcasses of wild swine either through field dressing or consuming undercooked meat.
Learning points
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Brucellosis needs to be considered in the differential diagnosis for fever of unknown origin in patients with a history of hunting wild game, even in areas not endemic for Brucella.
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Neurobrucellosis is an uncommon manifestation of Brucella infection that can present with subtle symptoms of fever, headache, and cognitive and psychiatric disturbances.
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Neurobrucellosis can be treated with combination therapy of intravenous ceftriaxone, and oral doxycycline and rifampin.
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Despite adequate treatment, neurological sequelae are common and can include persistent emotional and cognitive disturbances and sensory and motor deficits.
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Hunters of wild game should be advised to wear appropriate personal protective equipment when field dressing carcasses.
Footnotes
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Contributors HRP: wrote manuscript. JRN: wrote manuscript. SA: edited manuscript and provided mentorship. JCM: edited manuscript and provided mentorship.
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Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.
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Competing interests None declared.
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Patient consent for publication Obtained.
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Provenance and peer review Not commissioned; externally peer-reviewed.
- © BMJ Publishing Group Limited 2020. No commercial re-use. See rights and permissions. Published by BMJ.
References
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