Background

Campylobacter insulaenigrae was first isolated from the rectal swab of marine mammals (seals and a porpoise) of Scotland by Foster et al. in 2004 [1]. Later on, the bacterium was isolated from northern elephant seals in California [2] and the south American sea lion in Chile [3]. C. insulaenigrae is phylogenetically related to C. jejuni, C. coli, and C. lari [1]. The first case of infection caused by C. insulaenigrae in humans was reported by Chua K et al. in 2007 [4]. We report a case of C. insulaenigrae bacteremia with meningitis, as the second clinical case of C. insulaenigrae infection in humans.

Case presentation

An 89-year-old Japanese man without dementia presented with a fever of 38 °C and weakness in right leg since 5 days. His symptoms showed no improvement; and therefore, he was admitted to our hospital. The patient reported no interaction with marine mammals (e.g. going to the aquarium, a household pet), no history of previous infection caused by them, and no event of eating raw fish.

The patient had a medical history of hypertension, glaucoma, and organized chronic subdural hematoma (CSH), which was treated with craterization at the age of 80-years. He had been prescribed the following medication: valsartan, 80 mg/day; valproic acid, 800 mg/day; magnesium oxide, 750 mg/day; pantosin, 3.0 g/day; and triazolam, 0.25 mg/day.

At the time of admission, the patient was conscious and lucid, and his vital signs were as follows: heart rate, 79 beats/min and regular; body temperature, 38.0 °C blood pressure, 157/86 mmHg; respiratory rate, 16 breaths/min; peripheral oxygen saturation, 95% in room air. Physical test results showed paralysis of extraocular muscle at downward and left gaze, ataxia, and low manual muscle test (MMT) score of the right side. No meningeal irritation signs (jolt accentuation, neck stiffness, Kernig’s sign, and Brudzinski’s sign) were observed at the time of admission. Two sets of blood culture on day 2 were sterile, and cerebrospinal fluid (CSF) could not be obtained during admission despite all efforts. Head computed tomography (CT) scans and magnetic resonance imaging (MRI) scans were unremarkable, except for the presence of organized CSH. Based on these findings and consultation with the neurologist, we suspected that the patient had Miller Fisher syndrome. However, the anti-ganglioside antibody test result was negative.

After admission, the fever and neurological symptoms of the patient improved without treatment. He was discharged from the hospital and he stayed overnight at his home from day 21 to 22; he did not come into contact with saltwater or marine mammals and did not eat raw fish during his stay at home. He returned to the hospital on day 22 and presented with a fever of 38.8 °C and left hemiplegia with unconsciousness. Laboratory investigation results on day 24 were as follows (Table 1): white blood cell (WBC) count, 8610/μL (neutrophils, 84.8%; lymphocytes, 9.3%; and monocytes, 5.8%); and C-reactive protein (CRP), 19.42 mg/dL. Neurological findings on day 25 included positive meningeal irritation signs (Jolt accentuation and neck stiffness), ocular motility disorder in all directions, left cranial nerve disorder, low MMT score of left upper and lower limb, and extrapyramidal disorder. CSF examination results on the same day were as follows: initial pressure, 27 cmH2O; number of cells, 69/μL (number of monocytes, 13/μL; and number of apocytes 56/μL); protein, 168 mg/dL; and glucose level, 39 mg/dL (blood glucose level, 122 mg/dL). A phase-contrast MRI of the patient’s head indicated a contrast enhancement effect in his right meninges and cerebral edema in the frontal and parietal lobes, and blood culture reports showed the presence of spirillums. These results suggested bacteremia and meningitis. Taking into consideration the pharmacodynamics of antibiotics in CSF, we prescribed the patient with meropenem (2 g every 8 h) from day 24. The symptoms and laboratory findings improved after starting the treatment (Fig. 1).

Table 1 Laboratory investigation results of the patient on day 24
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Fig. 1
figure 1

Clinical course after starting treatment. MEPM, meropenem; ABPC, ampicillin

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Blood culture results on day 22 showed the presence of gram-negative spirillums belonging to the genus Campylobacter; however, the species of the bacteria was not confirmed. 16S rRNA gene sequencing of the bacteria obtained from the blood culture identified the bacterial strain as Campylobacter insulaenigrae. The number of cells (monocytes and apocytes) and glucose levels in CSF samples were a clear indicator of bacterial meningitis; however, the culture and genetic analyses showed that the CSF samples were sterile. We changed the treatment from meropenem to ampicillin (2 g every 4 h) from day 32, based on the result of the drug sensitivity test using the disk method (Table 2) and discontinued the treatment on day 53 (total duration 29 days); we observed that the day-to-day activity level of the patient reached levels similar to that before contracting bacteremia.

Table 2 Results of drug sensitivity test for Campylobacter insulaenigrae cultured on day 22
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Discussion and conclusion

This case report presents a case of C. insulaenigrae bacteremia with meningitis. To the best of our knowledge, this is the first report of meningitis caused by C. insulaenigrae in humans, and the second report of infection by C. insulaenigrae in humans.

C. insulaenigrae was first isolated from marine mammals [1]; however, the patient in this study reported no contact with any marine mammals. We enquired about eating raw fish; however, we could not verify the history of contact with marine mammals. Therefore, the portal of entry was uncertain in this case, similar to the report by Chua K et al. [4] (Table 3).

Table 3 Cases of Campylobacter insulaenigrae infection in humans
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The first case of infection due to C. insulaenigrae was reported by Chua K et al. in 2007 [4]; the patient, a 60-year-old woman under hemodialysis, for treating autosomal dominant adult polycystic kidney, presented with gastroenteritis diagnosed by fever, diarrhea, and stomachache.

In this study, the CSF culture did not show the presence of C. insulaenigrae; however, the low glucose levels in the CSF suggested bacterial meningitis. In addition, we could not identify any other sites in the patient that were affected by bacteremia. Therefore, we clinically diagnosed the patient with meningitis caused by C. insulaenigrae. The organized CSH had not changed after craterization (done 9 years ago); and therefore, the patient’s neurological findings could have been induced by transient cerebral edema and meningitis associated with organized CSH. The symptoms and findings at the time of admission improved without any treatment, blood culture results on day 2 were sterile, and CSF could not be obtained; therefore, the symptoms were suspected to have occurred because of chronic meningitis.

There are two possible routes of entry: 1) the patient had contracted the C. insulaenigrae infection before admission, which was not identified by the microbiological results at the time of admission. 2) He contracted the infection during his stay at home (day 21 to 22); he was readmitted to the hospital on day 22 when he presented with a fever and neurological symptoms. However, he confirmed that he was not in contact with salt water or marine mammals during that time.

We compared the characteristics of all the C. insulaenigrae strains reported until date (Table 4). The strains isolated from humans were able to grow at 42 °C, while the strains isolated from marine mammals were unable to grow at this temperature. In addition, the gene sequences for the 16S rRNA, obtained from GenBank were different between the strains isolated from humans and the strains isolated from marine mammals. This suggested that there are multiple genotypes of the bacterial strain, which could correspond to the different hosts or infection sites. Considering that the isolate from the current study caused infection in an immunocompetent patient, the difference in genotypes could be related to the differences in the pathogenicity of the bacterial strain.

Table 4 Characteristics of Campylobacter insulaenigrae isolated from marine mammals and humans
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TOnly two cases of C. insulaenigrae infection in humans have been reported so far, to the best of our knowledge; however, there is a possibility that C. insulaenigrae infection was reported as C. jejuni infection, because of the absence of sodium hippurate hydrolysis in both the strains. Whole genome sequencing of the two C. insulaenigrae strains might help uncover the reasons behind the differences in the infection sites and infection manifestation between these two strains. Further cases are needed to identify the differences in the characteristics of the bacterial strains arising from the different genotypes.