Campylobacter fetus meningitis associated with eating habits of raw meat and raw liver in a healthy patient: A case report and literature review.

Meningitis caused by the zoonotic pathogen Campylobacter fetus in immunocompetent adults is rare. We report a 48-year-old Japanese woman with no underlying disease who was found to have meningitis caused by C. fetus. Both C. fetus subsp. fetus and C. fetus subsp. venerealis were isolated from the cerebrospinal fluid culture. The mode of infection in our patient was considered to be associated with the consumption of raw beef and raw cattle liver on a regular basis. Public awareness and education to avoid the consumption of raw or undercooked meat might help prevent C. fetus meningitis.

Introduction

Campylobacter fetus (formerly called as Spirillum serpens or Vibrio fetus) is a zoonotic pathogen with major reservoirs of cattle and sheep. C. fetus is a rare cause of bacterial meningitis. Thus far, C. fetus meningitis has been reported to occur in those who frequently chew khat (an alkaloid containing plant) in an animal sanctuary, come in contact with domestic animals, or consume the raw meat or raw liver of cattle and sheep [1].

C. fetus infections frequently occur among patients with impaired immunity including conditions such as chronic alcoholism, liver disease, old age, diabetes mellitus, and malignancies [2]. There are only a few case reports of C. fetus bacteremia and meningitis in healthy adults [[3], [4], [5], [6]]. However, immunosuppression may not be the sole risk factor [7]. In this study, we report a case of C. fetus meningitis in a healthy adult and conducted a literature review.

Case

While in the emergency department of our hospital, she was alert and oriented, and not in acute distress. Her blood pressure was 132/60 mmHg, her heart rate was 64/min, her respiratory rate was 30/min, and her body temperature was 38.4 °C. The physical examination revealed nuchal rigidity without focal neurological abnormalities. Her laboratory tests revealed a white blood cell count of 14,200/μL; she tested negative for human immunodeficiency virus (HIV) antigens and antibodies and her electrolyte and aminotransferase levels were within normal limits. Cerebrospinal fluid (CSF) testing revealed leukocytosis with high protein and low glucose levels (Table 1). Her CSF showed increased white blood cells with neutrophil dominance with no organisms seen on Gram stain. Dexamethasone, ceftriaxone, ampicillin, vancomycin, and acyclovir were administered to treat both bacterial and viral meningitis. In addition, minocycline was administered to treat rickettsiosis. The serum cryptococcal antigen and serum nontreponemal and treponemal tests were negative. The acid-fast bacilli smear test and tuberculosis polymerase chain reaction (PCR) of the CSF were both negative.

Table 1

Cerebrospinal fluid test.

Leukocytes	1219/μL
Polynuclear cells	799/μL (65%)
Mononuclear cells	418/μL (34%)
Protein	80 mg/dL
Glucose	51 mg/dL
(Blood glucose)	134 mg/dL

On day three of admission, the patient’s headaches began to recede. Vancomycin and dexamethasone were discontinued as meningitis due to Streptococcus pneumoniae was thought to be less likely as the CSF cultures were negative. On day five of admission, Gram-negative spiral bacilli were isolated from the CSF culture. Acyclovir, ampicillin, and minocycline were discontinued, and only ceftriaxone was continued. On day 12 of admission, matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF-MS) identified the organisms isolated from the CSF specimen as C. fetus subsp. venerealis (score 2.378) and C. fetus subsp. fetus (score 2.334). At this point, repeated history taking revealed that she had been consuming raw beef and raw cattle liver every weekend. Thus, the diagnosis of C. fetus as a cause of meningitis was made.

Ceftriaxone was changed to meropenem as she developed generalized skin rash most likely as a side-effect of ceftriaxone. She was discharged home after she received four weeks of intravenous antimicrobial treatment, and she did not show any signs of recurrence. 16S rRNA gene sequencing was performed to confirm the identification of the organisms. Gene sequencing revealed 100% coincidence with C. fetus subsp. venerealis and 99% coincidence with C. fetus subsp. fetus.

Discussion

A literature search in Pubmed was performed, and all clinical cases of C. fetus meningitis in adults published in English and Japanese were reviewed. The following keywords were used: “meningitis AND Campylobacter fetus,” “meningitis AND Vibrio fetus,” and “Spirillum serpens AND meningitis.” The major findings are summarized in Table 2.

Table 2

Summary of previously reported Campylobacter fetus meningitis.

Case no.	Year	Author	Country	Age	Sex	Underlying conditions	Cause	Bacteriology	Method to identify the organism	Blood culture	CSF culture	Outcome
1	1960	Edwards CE	United States	50	F	Hypertention	Handling fecal discharges of rats	Spirillum serpens	Biochemical	+	+	Cured
2	1964	Collins S	United States	55	M	Chronic lymphatic leukemia	Unknown	Vibrio fetus	Biochemical	+	+	Relapsed → Cured
3	1966	Killam H	United States	48	F	Healthy	Frequent contact with domestic animals	Vibrio fetus	Biochemical	+	–	Hemiparesis
4	1969	Reyman TA	United States	69	F	Diabetes mellitus, Thrombocytopenia	Unkown	Vibrio fetus	Biochemical	+	+	Died
5	1971	Gunderson CH	United States	53	M	Drug abuse	Unknown	Vibrio fetus	Biochemical	+	+	Deeply comatose
6	1976	Gubina M	Yugoslavia	46	M	Healthy	Frequent contact with domestic animals	C. fetus subsp. intestinalisa	Biochemical	+	–	Cured
7	1976	Gubina M	Yugoslavia	40	M	Healthy	Frequent contact with domestic animals	C. fetus subsp. intestinalisa	Biochemical	–	+	Cured
8	1978	Zelinger KS	United States	50	M	Healthy	Handling raw meat	Vibrio fetus	Biochemical	+	–	Cured
9	1984	Hanai N	Japan	53	M	Liver dysfunction	Unknown	C. fetus subsp. fetus	Biochemical	+	+	Cured
10	1985	Fracioli P	Switzerland	68	M	Adenocarcinoma of rectum with hepatic metastasis	Unknown	C. fetus subsp. fetus	Biochemical	+	+	Died
11	1985	Fracioli P	Switzerland	65	M	Alcoholic cirrhosis	Unknown	C. fetus subsp. fetus	Biochemical	+	–	Relapsed → Cured
12	1986	Iida Y	Japan	30	M	Healthy (Appendectomy history, Herniated disc)	Ingesting raw cattle liver	C. fetus subsp. fetus	Biochemical	–	+	Cured
13	1986	Iida Y	Japan	42	M	Healthy	Unknown	C. fetus subsp. fetus	Biochemical	–	+	Cured
14	1986	Yamazaki E	Japan	53	M	Healthy	Unknown	C. fetus subsp. fetus	Biochemical	+	+	No data
15	1986	Yamazaki E	Japan	53	M	Healthy	Unknown	C. fetus subsp. fetus	Biochemical	+	+	No data
16	1987	Rao KV	United States	47	M	Cadaver kidney transplant recipient	Ingesting raw cattle liver	C. fetus subsp. intestinalisa	Biochemical	+	+	Cured
17	1990	Kato H	Japan	55	M	Chronic alcoholism, Diabetes mellitus, Lung tuberculosis	Unknown	C. fetus	Biochemical	–	+	Cured
18	1993	Inoue Y	Japan	40	M	Healthy (Appendectomy history)	Ingesting raw beef	C. fetus subsp. fetus	Biochemical	–	+	Cured
19	1996	Dronda F	United States	47	M	Chronic alcoholism, Previous infection with HBV	Unknown	C. fetus subp. fetus	Biochemical, PCR	+	+	Relapsed → Cured
20	1998	Ozeki T	Japan	49	M	Alcoholic liver disease	Unknown	C. fetus subsp. fetus	Biochemical	+	+	Hemiparesis
21	2002	Herve J	France	71	M	Diabetes mellitus	Unknown	C. fetus subsp. fetus	Biochemical, 16S rRNA gene sequencing	+	+	Cured
22	2004	Shioyama M	Japan	43	M	Healthy	Unkown	C. fetus	Biochemical	–	+	Cured
23	2006	Kanayama S	Japan	51	M	Healthy	Unkown	C. fetus subsp. fetus	Biochemical	+	+	Cured
24	2008	Umehara Y	Japan	40	M	Crohn's disease	Unkown	C. fetus	Biochemical	+	+	Cured
25	2010	Martínez-Balzano C	United States	28	M	Healthy	Khat chewing	C. fetus subsp. fetus	16S rRNA gene sequencing	+	–	Cured
26	2013	Suy F	France	75	M	Diabetes mellitus, Adenomatous sigmoid polyps	Ingesting raw sheep liver	C. fetus subsp. fetus	MALDI-TOF-MS, 16S rRNA gene sequencing	+	+	Cured
27	2016	van Samkar A	The Netherlands	23	F	Healthy	Frequent contact with domestic animals	C. fetus subsp. fetus	No data	–	+	Concentration problems
28	2016	van Samkar A	The Netherlands	52	M	Healthy	Frequent contact with domestic animals	C. fetus subsp. fetus	No data	+	+	Relapsed → Cured
29	2017	Present case	Japan	48	F	Healthy	Ingesting raw beef and cattle liver	C. fetus subsp. fetus/venrealis	No data	+	+	Relapsed → Cured

C. fetus subsp. fetus is formerly described as C. fetus subsp. intesinalis [10].

Two subspecies of C. fetus were identified: C. fetus subsp. fetus and C. fetus subsp. venerealis. C. fetus subsp. fetus is associated with abortion in cattle and sheep and also causes infections in humans [2]. Conversely, C. fetus subsp. veneralis is associated with abortion in cattle [8], but its role in humans is uncertain. C. fetus subsp. veneralis has only been isolated from the stools of two homosexual men in Australia and from two women with bacterial vaginosis [2].

Our literature review revealed that all cases of meningitis were caused by C. fetus subsp. fetus. Our patient was unique as her CSF culture showed two subspecies: C. fetus subsp. fetus and C. fetus subsp. venerealis. MALDI-TOF-MS and 16S rRNA gene sequencing identified both subspecies. We considered two hypotheses. One was that our patient was infected by both the subspecies C. fetus subsp. fetus and venerealis. The other was that MALDI-TOF-MS and 16S rRNA gene sequencing failed to distinguish the two subspecies. Differentiation between the two subspecies has traditionally been determined by the 1% glycin tolerance test, and PCR assays have also been reported as a valuable adjunctive technique [9]. We did not perform these tests; however, C. fetus subsp. venerealis reported a higher score on performing MALDI-TOF-MS and a higher coincidence on performing 16S rRNA gene sequencing. C. fetus subsp. venerealis, an extremely rare organism to cause infections in humans, could be the pathogen that caused meningitis in our patient.

Another remarkable point in our literature review is that five patients were infected by consuming raw meat or raw liver and that three of them were Japanese with no past medical history, including our patient. It is not a rare occasion for people in Japan and other Asian countries to consume raw beef and raw cattle liver. Therefore, eating habits can be a major risk factor for these people even if they are immunocompetent.

In 2012, the Japanese Ministry of Health, Labour and Welfare prohibited serving raw cattle liver at restaurants. However, self-barbecue restaurants still provide raw meat and raw liver, and there are no legal restrictions regarding how restaurant customers cook raw meat and raw liver that was provided. Public awareness and education to prevent C. fetus meningitis should be warranted not only in Japan but also in other Asian countries where these eating habits exist.

Conflict of interest

All authors do not have any conflict of interest.