Streptococcus equi meningitis

Accepted Manuscript Letter to the editor: Streptococcus equi meningitis Anusha van Samkar, Matthijs C. Brouwer, Arie van der Ende, Diederik van de Beek PII:

S1198-743X(15)00818-6

DOI:

10.1016/j.cmi.2015.09.003

Reference:

CMI 374

To appear in:

Clinical Microbiology and Infection

Received Date: 2 September 2015 Accepted Date: 3 September 2015

Please cite this article as: van Samkar A, Brouwer MC, van der Ende A, van de Beek D, Letter to the editor: Streptococcus equi meningitis, Clinical Microbiology and Infection (2015), doi: 10.1016/ j.cmi.2015.09.003. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

ACCEPTED MANUSCRIPT Letter to the editor: Streptococcus equi meningitis Running title: Streptococcus equi meningitis Anusha van Samkara, Matthijs C. Brouwera, Arie van der Endeb,c, Diederik van de Beeka

a

Academic Medical Centre, Centre of Infection and Immunity Amsterdam (CINIMA),

b

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Department of Neurology, PO Box 22660, 1000DD, Amsterdam, the Netherlands.

Academic Medical Centre, Centre of Infection and Immunity Amsterdam (CINIMA),

Department of Medical Microbiology, PO Box 22660, 1000DD, Amsterdam, the Netherlands. Netherlands Reference Laboratory for Bacterial Meningitis, Academic Medical Centre,

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c

PO Box 22660, 1000DD, the Netherlands.

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Corresponding author: Diederik van de Beek Department of Neurology

Academic Medical Center, University of Amsterdam, the Netherlands

Fax +31205669374

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Telephone +31205663647

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E-mail [email protected]

Word count: 999 References: 5 Tables: 1

ACCEPTED MANUSCRIPT Sir,

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Streptococcus equi, part of the commensal flora of the upper respiratory tract in horses, is an uncommon cause of

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bacterial meningitis. Very little is known about its risk factors, presenting features and outcome. We report two

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cases of S. equi meningitis from a nationwide cohort study in the Netherlands performed from 2006 through

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2014, and performed a literature review.

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1

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The first case has been described previously [1] and concerned a 37-year old previously healthy horsewoman

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presenting with fever, headache and nausea 4 days after a horse bite. Neurological examination showed neck

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stiffness and an altered consciousness (Glasgow Coma Scale E3M5V3). CSF examination was consistent with

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bacterial meningitis (394 leukocytes/mm3, protein 1.21 g/L, glucose 0.60 mmol/L), and she was treated with

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ceftriaxone and dexamethasone. After one day, cultures became positive for S. equi ssp. zooepidemicus, and

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antibiotic treatment was switched to penicillin. During admission, she developed right-sided hemiparesis and

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aphasia. Cranial imaging showed multiple brain abscesses. Penicillin was continued for 8 weeks and she was

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discharged to a rehabilitation centre. During the months after admission, her aphasia improved, but severe

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memory deficits persisted and she was unable to live independently.

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The second case identified was a 41-year old previously healthy female who presented with headache and fever

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since one day. She had recreational contact with horses regularly. On physical examination she had a

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temperature of 39.0°C and neck stiffness. She opened her eyes and localized in response to painful stimuli and

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made sounds but no recognizable words (Glasgow Coma Scale E2M5V2). Her blood leukocyte count was 21.1

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per 109/L. Cranial CT showed brain oedema and CSF findings were consistent with bacterial meningitis (85

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leukocytes/mm3, protein 3.00 g/L, glucose 2.50 mmol/L). CSF Gram stain showed Gram-positive bacteria. She

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was admitted to the ICU, but died at day 2 due to respiratory and circulatory failure despite treatment with

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ceftriaxone and dexamethasone. After 2 days, CSF cultures showed S. equi ssp. zooepidemicus. Blood cultures

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remained negative.

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A literature search identified 29 studies describing 33 episodes of S. equi meningitis, occurring between 1978

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and 2015 (Supplementary table 1). Combining these data with our cases (Table 1), we identified 34 patients with

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a median age of 61 years (range 0-83 years). Eighteen patients were male (53%) and five out of 25 patients

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(20%) were immunocompromised. A source of infection was identified in all 32 patients for whom it was

ACCEPTED MANUSCRIPT reported, mainly regular horse contact (66%) and consuming unpasteurized dairy products (28%). The classic

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meningitis triad of fever, neck stiffness and an altered consciousness was present in 22 patients (65%). CSF

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examination was abnormal in all. Blood cultures were positive in 25 out of 29 patients (86%) and CSF cultures

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in 31 out of 33 patients (94%). Subspecies zooepidemicus was identified in 32 cases and subspecies equi in 2

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cases. Cranial CT was performed in 18 patients and showed abnormalities in 9 (50%): brain edema and sinusitis

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each in 3 patients, mastoiditis and brain abscesses each in 2, and hydrocephalus and cerebral hypodensity each in

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one patient.

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Complications during admission were present in 15 out of 32 patients (47%) and consisted of sepsis in 4

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patients, endophthalmitis in 3, endocarditis, pneumonia, respiratory failure and brain abscesses each in 2, and

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intracranial hypertension, cardiac failure and multiple brain infarction each in one patient. Three patients had

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multiple complications. Infections outside the brain were present in 12 out of 32 patients (37%). Outcome was

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reported in all 34 patients: 7 patients died (21%). Of the surviving 27 patients, 14 patients had neurological

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sequelae (52%), consisting of hearing loss in 6, impaired vision in 2 (after endophthalmitis), amnesia in 2, and

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both deafness and blindness, vertigo, diplopia, and changed behaviour each in one patient.

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Meningitis caused by S. equi is a rare disease associated with high rates of unfavourable outcome (62%).

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Commonly identified risk factors were regular horse contact and consumption of unpasteurized dairy products.

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In 2005, a national study regarding horses in the USA showed that 4.6 million Americans were involved in the

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horse industry and 2 million people owned horses.[2] The small number of cases identified reflects the low

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chance of developing S. equi meningitis after horse contact. Unpasteurized dairy products may harbour several

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pathogens, such as Listeria monocytogenes and Campylobacter jejuni, and consumption is therefore discouraged

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by the Centers for Disease Control and Prevention.[3] An immunocompromised state was present only in 20% of

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the patients with S. equi meningitis, compared to 67% of the patients with L. monocytogenes meningitis being

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immunocompromised.[4]

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Most cases of S. equi meningitis were caused by subspecies zooepidemicus, and only two cases were caused by

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subspecies equi. Both pathogens were sensitive to penicillin, cefotaxime and ceftriaxone in all cases described.

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Penicillin is the recommended antimicrobial therapy in patients with streptococcal meningitis caused by an

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equine pathogen.

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ACCEPTED MANUSCRIPT Complications occurred in about half of patients with S. equi meningitis, most commonly distant infection foci,

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such as endophthalmitis and endocarditis. Endophthalmitis is a serious complication of S. equi infection that can

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lead to blindness. Endocarditis is an uncommon coexisting condition in bacterial meningitis identified in 2% of

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patients and is associated with high rates of unfavourable outcome (63%).[5] This condition needs to be treated

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with prolonged duration of antibiotics (6-8 weeks). Whether the primary focus of infection is the meningitis or

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endocarditis remains difficult to distinguish, because initial complaints of endocarditis can be nonspecific. Our

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findings indicate that endocarditis should be considered in all patients with S. equi meningitis.

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In conclusion, S. equi meningitis is associated with horse contact and consuming unpasteurized dairy products.

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Although rare, the associated mortality is high and many survivors suffer from neurological sequelae.

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Endocarditis should be considered in all patients with S. equi meningitis.

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The authors report no conflicts of interests. MCB is supported by a grant from the Netherlands Organization for

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Health Research and Development (ZonMw; NWO-Veni grant 2012 [916.13.078]). DvdB is supported by grants

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from the Netherlands Organization for Health Research and Development (ZonMw; NWO-Vidi grant 2010

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[016.116.358]), and the European Research Council (ERC Starting Grant 281156).

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References

1.

Brouwer MC, Kasanmoentalib ES, Opstelten FW, van der Ende A, van de Beek D. A horse bite to

2.

American Horse Council. The Economic Impact of the Horse Industry on the United States National

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Report2005. 3.

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remember. Lancet 2010; 376(9747):1194.

Centers For Disease Control And Prevention. Recurrent outbreak of Campylobacter jejuni infections associated with a raw milk dairy--Pennsylvania, April-May 2013. MMWR Morb Mortal Wkly Rep 2013; 62(34):702.

4.

Brouwer MC, van de Beek D, Heckenberg SG, Spanjaard L, de Gans J. Community-acquired Listeria monocytogenes meningitis in adults. Clin Infect Dis 2006; 43(10):1233-8.

5.

Lucas MJ, Brouwer MC, van der Ende A, van de Beek D. Endocarditis in adults with bacterial meningitis. Circulation 2013; 127(20):2056-62.

ACCEPTED MANUSCRIPT

n/N (%)

Median age (range)

61 (0-83)

Male sex

18/32 (53)

Immunocompromised

5/25 (20)

Diabetes mellitus

2/25 (8)

Immunosuppressive medication

2/25 (8)

Haematological malignancy

1/25 (4) 32/32 (100)

Regular horse contact

21/32 (66)

Consuming unpasteurized dairy products

9/32 (28)

Mother had regular contact with horses

1/32 (3)

Contact with sick dogs

1/32 (3)

Clinical presentation

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Identified source of infection

19/34 (56)

Fever

34/34 (100)

27/34 (79)

Altered mental status

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Classic meningitis triada CSF characteristics

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Headache

Neck stiffness

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Median CSF leukocytes/mm3 (range)

28/34 (82)

22/34 (65)

1919 (31-11000)

Median CSF protein (g/L) (range)

2.62 (0.71-62.29)

Median CSF glucose (mmol/L) (range)

2.02 (0.10-4.60)

Median blood leukocyte count (x 109/L)

16.8 (3.5-40.7)

Cultures Positive blood culture

25/29 (86)

Positive CSF culture

31/33(94)

Complications Sepsis

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Characteristics

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Table 1. Clinical characteristics, aetiology and clinical outcome for S. equi meningitis; combination of our patients and patients reported in the literature

15/32 (47) 4/32 (12)

ACCEPTED MANUSCRIPT Endophthalmitis

3/32 (9)

78

Other

11/32 (34)

79

Death

7/34 (21)

81

Hearing loss

7/27 (26)

82

Impaired vision

3/27 (11)

83

Other sequelae

5/27 (19)

84 85

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Defined as fever, neck stiffness, and altered mental status. Abbreviations: CSF: cerebrospinal fluid

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a

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80

Outcome

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Supplementary table 1. Cases of S. equi meningitis reported in the literature, combined with our patients

Age

Gender

Predisposing factor

Source of infection

Symptoms

CSF

RI PT

Study

Cranial CT

Complications

Outcome

Brain

Brain abscesses

Severe amnesia

Respiratory and

Death

leukocytes/mm3

41

Female

Female

None

Bitten by horse

None

Regular horse contact

1;2;3;4

73

Male

None

Sick horse

Pelkonen[2]

57

Male

N.R.

Regular horse

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Madzar[1]

394

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This study

37

1;2;4

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This study*

85

abscesses Brain edema

cardiac failure

1;2;3

3580

Normal

Endophthalmitis

Impaired vision

2;3;4

N.R.

N.R.

Septicaemia,

Full recovery

contact

59

Male

None

Unpasteurized dairy

1;2;3;4

1080

Mastoiditis

Pneumonia

Hearing loss

1;2;3;4

394

Brain

Brain abscesses

Severe amnesia

Multiple brain

Hearing loss

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Mori[3]

endocarditis

Brouwer[4]

Eyre[5]

37

79

Female

Male

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products

None

N.R.

Bitten by horse

abscesses Trampled by horse

1;2;4

360

Normal

ACCEPTED MANUSCRIPT

infarction 83

Male

None

Regular horse

2;4

31

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Rajasekhar[6]

contact 59

Female

Diabetes mellitus

Regular horse

2;4

contact 51

Female

Diabetes mellitus

Regular horse contact

Rivas[9]

30

Female

None

Regular horse

Jovanovic[10]

72

Female

None

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contact

2;3

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Minces[8]

2560

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Poulin[7]

Unpasteurized dairy

2;3;4

2140

1706

Normal

None

Amnesia

N.R.

Endocarditis,

Deafness, blindness

endopthalmitis Pansinusitis,

Respiratory

mastoiditis

failure

Edema,

Intracranial

hypodensity

hypertension

Full recovery

Full recovery

2;3;4

2500

N.R.

None

Full recovery

1;2;3;4

166

Brain

N.R.

Full recovery

N.R.

Death

BordesBenitez[12]

41

83

Male

Female

None

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Pati[11]

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products

None

Regular horse contact

edema, sinusitis

Unpasteurized dairy products

2;3

N.R.

N.R.

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66

Male

Immunosuppressive

Regular horse

medication

contact

1;2;3

Pansinusitis

None

Mild vertigo

583

N.R.

N.R.

Death

3011

N.R.

N.R.

Diplopia

6000

Normal

None

Hearing loss

2;3;4

1750

Normal

None

Full recovery

1;2;3;4

4650

N.R.

Endophthalmitis

Impaired vision

1;2;3;4

40

Normal

None

Full recovery

Sick horse

1;2;3;4

2000

N.R.

None

Full recovery

Regular horse

1;2;3;4

11000

N.R.

None

Full recovery

2

N.R.

N.R.

Septicaemia

Death

74

Male

None

Sick horse

2;3;4

Downar[15]

49

Female

N.R.

Kicked by horse

1;2;3;4

Shah[16]

13

Male

Immunosuppressive

Regular horse

1;2;3;4

medication

contact

None

Mother visited

0

Male

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Jenkins[17]

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Ural[14]

4336

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West[13]

horse regularly 66

Female

Leukaemia

Latorre[19]

62

Female

None

Sick horse

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Mattei[18]

Unpasteurized dairy

74

Male

None

Cheeseman[21]

24

Male

None

Edwards[22]

73

Male

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Ferrandière[20]

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products

N.R.

contact Unpasteurized dairy

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73

Male

None

Unpasteurized dairy

2;4

N.R.

N.R.

Septicaemia

Death

N.R.

N.R.

N.R.

Full recovery

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Edwards[22]

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products

products Edwards[22]

71

Male

N.R.

Unpasteurized dairy

2;4

products 80

Female

N.R.

Unpasteurized dairy products

Vergnes[23]

59

Female

None

Regular horse

Ghoneim[24]

66

Male

None

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contact

1;2;3;4

N.R.

N.R.

Septicaemia

Death

2;3

5618

Brain

Brain abscess

Full recovery

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Edwards[22]

Contact with sick

abscess

2;3;4

520

Normal

None

Full recovery

1;2;3;4

1818

N.R.

None

Changed behaviour

1;2;3;4

3229

Normal

Pneumonia

Hearing loss

Mohr[26]

24

59

Female

Male

None

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Low[25]

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dogs

None

Regular horse contact Unpasteurized dairy products

ACCEPTED MANUSCRIPT

77

Female

N.R.

N.R.

2;3;4

1200

N.R.

None

Death

Patey[27]

33

Male

N.R.

N.R.

1;2;3;4

5300

N.R.

None

Hearing loss

Elsayed[28]

13

Male

None

Regular horse

1;2;3;4

Hydro-

None

Hearing loss

None

Full recovery

75

Female

None

Regular horse contact

1;2;3;4

5200

cephalus Normal

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Popescu[29]

2175

SC

contact

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Patey[27]

*This patient from our cohort has been described previously.[4] Abbreviations: N.R: Not Reported; CSF: cerebrospinal fluid. Symptoms: 1 headache; 2 fever; 3 neck stiffness; 4 altered consciousness

1.

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Pelkonen S, Lindahl SB, Suomala P, et al. Transmission of Streptococcus equi subspecies zooepidemicus infection from horses to humans. Emerg Infect Dis 2013;

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19(7):1041-8. 3.

Mori N, Guevara JM, Tilley DH, et al. Streptococcus equi subsp. zooepidemicus meningitis in Peru. J Med Microbiol 2013; 62(Pt 2):335-7.

4.

Brouwer MC, Kasanmoentalib ES, Opstelten FW, van der Ende A, van de Beek D. A horse bite to remember. Lancet 2010; 376(9747):1194.

5.

Eyre DW, Kenkre JS, Bowler IC, McBride SJ. Streptococcus equi subspecies zooepidemicus meningitis--a case report and review of the literature. Eur J Clin Microbiol Infect Dis 2010; 29(12):1459-63.

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Rajasekhar A, Clancy CJ. Meningitis due to group C Streptococcus: a case report and review of the literature. Scand J Infect Dis 2010; 42(8):571-8.

7.

Poulin MF, Boivin G. A case of disseminated infection caused by Streptococcus equi subspecies zooepidemicus. Can J Infect Dis Med Microbiol 2009; 20(2):59-61.

8.

Minces LR, Brown PJ, Veldkamp PJ. Human meningitis from Streptococcus equi subsp. zooepidemicus acquired as zoonoses. Epidemiol Infect 2011; 139(3):406-10.

9.

Rivas MT, Pascual J, Sesar A. [Group C streptococcus meningitis: a very uncommon condition]. Neurologia 2008; 23(9):604-6.

10.

Jovanovic M, Stevanovic G, Tosic T, Stosovic B, Zervos MJ. Streptococcus equi subsp. zooepidemicus meningitis. J Med Microbiol 2008; 57(Pt 3):373-5.

11.

Pati S, Al-Araji A, Orendi J. Atypical presentation of Streptococcus zooepidemicus bacteraemia and secondary meningitis. Clin Neurol Neurosurg 2007; 109(5):475-6.

12.

Bordes-Benitez A, Sanchez-Onoro M, Suarez-Bordon P, et al. Outbreak of Streptococcus equi subsp. zooepidemicus infections on the island of Gran Canaria

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6.

associated with the consumption of inadequately pasteurized cheese. Eur J Clin Microbiol Infect Dis 2006; 25(4):242-6. West CC, T.; Smilack, JD.; Hurley, BW. Streptococcus zooepidemicus Meningitis. Case report and review of literature. Infect Dis Clin Pract 2005; 13(1):27-30.

14.

Ural O, Tuncer I, Dikici N, Aridogan B. Streptococcus zooepidemicus meningitis and bacteraemia. Scand J Infect Dis 2003; 35(3):206-7.

15.

Downar J, Willey BM, Sutherland JW, Mathew K, Low DE. Streptococcal meningitis resulting from contact with an infected horse. J Clin Microbiol 2001; 39(6):2358-9.

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13.

Shah SS, Matthews RP, Cohen C. Group C streptococcal meningitis: case report and review of the literature. Pediatr Infect Dis J 2001; 20(4):445-8.

17.

Jenkins EL, McGuire W. Group C streptococcal meningitis in infancy. Acta Paediatr 2000; 89(9):1141-2.

18.

Mattei P, Beguinot I, Malet T, et al. [Meningitis, septicemia and endophthalmitis caused by Streptococcus equi subspecies zooepidemicus]. Presse Med 1995; 24(23):1089.

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19.

Latorre M, Alvarez M, Fernandez JM, et al. A case of meningitis due to "Streptococcus zooepidemicus". Clin Infect Dis 1993; 17(5):932-3.

20.

Ferrandiere M, Cattier B, Dequin PF, et al. Septicemia and meningitis due to Streptococcus zooepidemicus. Eur J Clin Microbiol Infect Dis 1998; 17(4):290-1.

21.

Cheeseman M, Genain C, Smith CD. Group C streptococcal meningitis with favorable recovery. A case report. J Ky Med Assoc 1990; 88(10):545-6.

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22.

Edwards AT, Roulson M, Ironside MJ. A milk-borne outbreak of serious infection due to Streptococcus zooepidemicus (Lancefield Group C). Epidemiol Infect 1988; 101(1):43-51. Vergnes DM, N.; Barrere, M.; Chabrol, H. Un cas de méningite à Streptococcus zooepidemicus (groupe C) chez un adulte. Médecine et Maladies Infectieuses 1982;

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13(3):202-3.

Ghoneim AT, Cooke EM. Serious infection caused by group C streptococci. J Clin Pathol 1980; 33(2):188-90.

25.

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26.

Mohr DN, Feist DJ, Washington JA, Hermans PE. Meningitis due to group C streptococci in an adult. Mayo Clin Proc 1978; 53(8):529-32.

27.

Patey O, Buisson CB, Soussy CJ. Group C streptococcal meningitis in adults. Rev Infect Dis 1990; 12(1):157-8.

28.

Elsayed S, Hammerberg O, Massey V, Hussain Z. Streptococcus equi subspecies equi (Lancefield group C) meningitis in a child. Clin Microbiol Infect 2003; 9(8):869-

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