Listeriosis

1
Listeriosis

• Pornrith Pisuttimarn, M.D.

2
Outlines

• Case Study
• Reviews
• Updates

3
Case Study

• Patient Profiles ????????????? ???? 29 ??
  ???????? ????????????????? ????????? ?. ?????
  ?.???????

4
History

• Chief Complaint ??????????? 3
  ??????????????????

5
History

• Present Illness 3 ??? PTA ??????????????????????
  ?? ???????????????? 1 ???? 8 ????? ????????
  ?????????? ????? ?????????????
  ???????????????????? ????? ?????????

6
History

• Present Illness 2 ??? PTA ???????? ????????
  ????????????? ???????? ??????????
  ??????????????? ???????????
• 1 ??? PTA ???????????
  ????????????????? ?????? ?????????? ??.????? 1
  ???????????????????????????????????????

7
History

• Past History Hodgkins lymphoma s/p ABVD x 6
  cycles, ESHAPx6 cyclesXRT 30 ????? ??? ???????
  ?? 2552 Follow up ?????? 2553 ??? CT chest
  ??mediastinal node, Plan palliative treatment
  ?????? on prednisolone (5mg) 4x3pc , 7 days /
  month
• ?????????????????

8
History

• Personal History ??????????? ????????????

9
Physical Examinations

• GA A Thai adult male , good consciousness
• V/S BT 39 c, PR 80 /min, RR 20 /min,
• BP 115/80 mmHg

10
Physical Examinations

• HEENT pink conjunctivae, anicteric sclerae
• no oral thrush
• impalpable cervical lymph node
  

11
Physical Examinations

• Heart and Lungs unremarkable
• Abdomen impalpable liver and spleen

12
Physical Examinations

• Neurological Examinations E4V5M6, equal 3 mm in
  diameter pupils, slurred speech
• Cranial Nerves intact
• Muscle Power grade 5 all
• Sensation intact

13
Physical Examinations

• DTR 1 all
• Ophthalmoscopy no papilledema
• Nuchal rigidity

14
Investigations
15
complete blood count
Hb 10.9 E 0
Hct 32.2 B
Wbc 20700
Plt 344k
PMN 93 MCV 82
L 2.3
M 3.9
16
Blood chemistry
BS 125
BUN 6.7
Cr. 0.6
Na 129
K 3.7
HCO 25
Cl 90
Ca 8.6
Mg 1.8
PO4 2
Chol 120
TP 6.2
Alb 2.8
Glob 3.4
TB 1.1
DB 0.4
ALT 35
AST 25
ALP 141
17
Urinalysis
Appearance Clear
Spgr. 1.023
Albumin -ve
WBC -
RBC 0-1
Cast -
Bile -
18
(No Transcript)
19
CT SCAN OF BRAIN

• FINDINGS
• The study reveals normal attenuation of brain
  parenchyma without definite focal mass lesion.
  Asymmetrical dilatation of anterior and posterior
  horns of bilateral lateral ventricle causing
  pressure effect to the anterior horn of left
  lateral ventricle is observed, more dilatation on
  the left side. Dilatation of the third ventricle
  and mild dilatation of the fourth ventricle are
  demonstrated. Leptomeningeal enhancement after
  contrast administration at right frontotemporal
  region, left frontoparietal region and left
  cerebellum representing meningitis is noted.

20
CT SCAN OF BRAIN

• No effacement of cerebral cortical sulci and
  gyri of both cerebral hemispheres and good
  differentiation of gray-white matter are seen.
  Physiologic calcification at pineal gland is
  shown. All visible paranasal sinuses and both
  mastoid air cells are clear. No bony skull defect
  is present.
• IMPRESSION
• - Non-communicating hydrocephalus.
• - Evidence of meningitis.

21
LUMBAR PUNCTURE

• Open pressure- 20 mmH2O
• Close pressure- 6 mmH2O
• CSFRBC-120 cell/cu.mm, WBC-740
• PMN- 99
• Indian Ink-negative
• CSF gram s stained no organism
• Protien- 159
• Sugar- 10 ( plasma-125 )

22
(No Transcript)
23
(No Transcript)
24
(No Transcript)
25
Diagnosis

• Hodgkins lymphoma
• Listeria monocytogenes bacteremia with
  meningoencephalitis

26
Listeria monocytogenes

• Introduction uncommon cause of illness in the
  general population

Lorber B Listeriosis.  Clin Infect
Dis  1997 241-11.
27
Introduction

• important cause of life-threatening bacteremia
  and meningoencephalitis in neonates, pregnant
  women, elderly persons, immunosuppressed
  transplant recipients, and others with impaired
  cell-mediated immunity

28
Microbiology

• facultatively anaerobic, nonsporulating,
  catalase-positive, oxidase-negative
• short, nonbranching, gram-positive rod that grows
  readily on blood agar
• producing incomplete ß-hemolysis

Bille J Listeria and Erysipelothrix.
  In Murray PR, Baron EJ, Jorgensen JH, et
al ed. Manual of Clinical Microbiology,  9th
ed. Washington, DC American Society for
Microbiology Press 2007474-484.
29
Microbiology

• one to five polar flagellae
• optimal growth occurs at 30 to 37?C
• exhibits a characteristic tumbling motility at
  25?C

Bille J Listeria and Erysipelothrix.
  In Murray PR, Baron EJ, Jorgensen JH, et
al ed. Manual of Clinical Microbiology,  9th
ed. Washington, DC American Society for
Microbiology Press 2007474-484
30
Microbiology

• cold enrichment
• colonies of L. monocytogenes appear blue-gray
• when grown on blood-free agar and viewed with
  light transmitted at a 45-degree angle
  (Henry's illumination)

31
Listeria monocytogenes
http//www.rosemerena.org/home/2009/04/06/greening
-the-foods-we-eat-or-current-applications-of-benja
min-franklins-green-economics-january-6-2009/
32
Listeria monocytogenes colonies
http//www.pmsmicro.co.uk/1263.htm
33
Microbiology

• routine media are effective for isolation
• grows best at neutral to slightly alkaline pH
• dies at pH below 5.5
• selective lithium chloride-phenylethanol-moxalac
  tam (LPM) agar

Bille J Listeria and Erysipelothrix.
  In Murray PR, Baron EJ, Jorgensen JH, et
al ed. Manual of Clinical Microbiology,  9th
ed. Washington, DC American Society for
Microbiology Press 2007474-484
34
Microbiology

• beta-hemolysis
• CAMP test reaction for S. aureus
• fermentation of mannitol -
• fermentation of alpha-methyl-D-mannoside
• fermentation of L-rhamnose
• fermentation of D-xylose -

Bille J Listeria and Erysipelothrix.
  In Murray PR, Baron EJ, Jorgensen JH, et
al ed. Manual of Clinical Microbiology,  9th
ed. Washington, DC American Society for
Microbiology Press 2007474-484
35
Microbiology

• fermentation of ribose -
• reduction of nitrate -
• hydrolysis of hippurate
• hydrolysis of esculin
• catalase test
• oxidase test -

Bille J Listeria and Erysipelothrix.
  In Murray PR, Baron EJ, Jorgensen JH, et
al ed. Manual of Clinical Microbiology,  9th
ed. Washington, DC American Society for
Microbiology Press 2007474-484
36
Listeria species
http//www.oxoid.com/UK/blue/prod_detail/prod_deta
il.asp?prSR0150cUKlangENminfoY
37
Listeria species

• only L. monocytogenes is pathogenic for humans
• at least 13 serovars of L. monocytogenes, based
  on cellular O and flagellar H antigens
• almost all disease is due to types 4b, 1/2a, and
  1/2b

.. Swaminathan B, Gerner-Smidt P The
epidemiology of human listeriosis.  Microbes
Infect.  2007 91236-1243.
38
Epidemiology

• zoonoses
• found in soil, decaying vegetation, and water
  and as part of the fecal flora of many mammals
• isolated from the stool of approximately 5 of
  healthy adults

Schlech III WF, Lavigne PM, Bortolussi RA, et
al Epidemic listeriosisevidence for
transmission by food.  N Engl J
Med  1983 308203-206 .
39
Epidemiology

• raw vegetables, raw milk, cheese, and meats,
  including fresh, frozen, chicken and beef
• 15 - 70
• CDC (1980 - 1986) annual 7.4 per million
  population,1850 cases per year in the US with 425
  deaths

Ciesielski CA, Hightower AW, Parsons SK, et
al Listeriosis in the United States
1980-1982.  Arch Intern Med  1988 1481416-1419.
40
Epidemiology

• CDC (2003) 3.1 cases per million, and deaths
  were 378
• highest infection rates in infants younger than
  1 month and adults older than 60 years

Voetsch AC, Angulo FJ, Jones TF, et al Reduction
in the incidence of invasive listeriosis in
foodborne diseases active surveillance network
sites, 1996-2003.  Clin Infect Dis  2007 44513-5
20.
41
Epidemiology

• 1983 outbreak of foodborne human listerial
  infection caused by contaminated coleslaw

Schuchat A, Deaver K, Hayes PS, et
al Gastrointestinal carriage of Listeria
monocytogenes in household contacts of patients
with listeriosis.  J Infect Dis  1993 1671261-12
62.
42
Epidemiology

• 2002 L. monocytogenes was found in sliced
  deli-style turkey meat and produced illness in 54
  patients in 9 states
• resulting in the largest recall of meat ever in
  the United States (gt30 million pounds of food
  products)

Gottlieb SL, Newbern EC, Griffin PM, et
al Multistate outbreak of listeriosis linked to
turkey deli meat and subsequent changes in US
regulatory policy.  Clin Infect
Dis  2006 4229-36.
43
Listeria Hysteria Who's To Blame?
http//www.cbsnews.com/stories/2002/10/16/national
/main525785.shtml
44
PulseNet

• http//www.cdc.gov/pulsenet/ network of public
  health and food regulatory laboratories
• L. monocytogenes was added to PulseNet in 1998

Sauders BD, Fortes ED, Morse DL, et al Molecular
subtyping to detect human listeriosis
clusters.  Emerg Infect Dis  2003 9672-680.
45
Pathogenesis

• human-to-human infection has not been documented
• transmitted via the ingestion of contaminated
  food
• oral inoculum dose 109 organisms
• incubation periods 11 - 70 days (mean of 31
  days)

Riedo FX, Pinner RW, Tosca ML, et al A
point-source foodborne listeriosis outbreak
documented incubation period and possible mild
illness.  J Infect Dis  1994 170693-696.
46
Pathogenesis

• intercurrent gastrointestinal infection with
  another pathogen may enhance invasion in
  individuals colonized with L. monocytogenes
  invasive listeriosis closely followed shigellosis

Lorber B Listeriosis following shigellosis.  Rev
Infect Dis  1991 13865-866.
47
Pathogenesis

• L. monocytogenes crosses the mucosal barrier
  aided by active endocytosis internalin which
  interacts with E-cadherin (receptor on epithelial
  cells and macrophages)
• hematogenous dissemination CNS and placenta

Lecuit M, Vandormael-Pournin S, Lefort J, et
al A transgenic model for listeriosis role of
internalin in crossing the intestinal
barrier.  Science  2001 2921722-1725.
48
mechanisms to invade the CNS

• direct invasion of endothelial cells of the
  blood-brain barrier
• transportation of bacteria to the CNS within
  circulating leukocytes in a phagocyte-facilitated
  (Trojan horse)
• via a neural route

Drevets DA, Bronze MS Listeria monocytogenes
epidemiology, human disease, and mechanisms of
brain invasion.  FEMS Immunol Med
Microbiol  2008 53151-165.
49
Steps in the invasion of cells and intracellular
spread by L. monocytogenes
http//microblog.me.uk/100
50
Novel Life Cycle

• doubling time about 1 hour
• listeriolysin O (major virulence factor)
  enables Listeria to escape from phagosomes and
  avoid intracellular killing
• host cell actin polymerization and propel
  themselves to the cell membrane

Schnupf P, Portnoy DA Listeriolysin O a
phagosome-specific lysin.  Microbes
Infect  2007 91176-1187.
51
Novel Life Cycle

• pushing against the host cell membrane filopods
• bacterial surface protein Act A major virulence
  factor (induction of actin filament assembly and
  cell-to-cell spread)

Schnupf P, Portnoy DA Listeriolysin O a
phagosome-specific lysin.  Microbes
Infect  2007 91176-1187.
52
Immunity

• innate and adaptive immune responses
• experiments of Mackaness immunity could be
  transferred by sensitized lymphocytes
• combined treatment with fludarabine and
  prednisone in patients with CLL increased
  incidence of listeriosis

Anaissie E, Kontoyiannis DP, Kantarjian H, et
al Listeriosis in patients with chronic
lymphocytic leukemia who were treated with
fludarabine and prednisone.  Ann Intern
Med  1992 117466-469.
53
George Mackaness in 1957
http//www.nature.com/icb/journal/v77/n2/fig_tab/i
cb199921f8.htmlfigure-title
54
Immunity

• TNFa neutralizing agents (e.g., infliximab,
  etanercept) associated with invasive listeriosis
• Toll-like receptor 2 recognition and control of
  listerial infection
• production of nitric oxide by activated
  macrophages natural immunity to listeriosis
  independent of T-cell function

Carryn S, Van de Velde S, Van Bambeke F, et
al Impairment of growth of Listeria
monocytogenes in THP-1 macrophages by granulocyte
macrophage colony-stimulating factor release of
tumor necrosis factor-a and nitric oxide.  J
Infect Dis  2004 1892101-2109.
55
Clinical Syndrome

• extract of L. monocytogenes cell membrane
  potent monocytosis-producing activity in rabbits

Stanley NF Studies of Listeria monocytogenes. 1.
Isolation of a monocytosis-producing agent
(MPA).  Aust J Exp Biol Med Sci  1949 27123-131.

56
LOCALIZED INFECTION

• conjunctivitis, skin infection, and
  lymphadenitis
• hepatitis and hepatic abscess, cholecystitis,
  peritonitis, splenic abscess, pleuropulmonary
  infection
• joint infection, osteomyelitis, pericarditis,
  myocarditis, arteritis, and endophthalmitis

Painter J, Slutsker L Listeriosis in humans.
  In Ryser ET, Marth EH, ed. Listeria,
Listeriosis and Food Safety,  3rd ed. Boca Raton,
Florida CRC Press 200785-109.
57
ENDOCARDITIS

• 7.5 of adult listerial infections
• mortality of 48
• not bacteremia per se, may be an indicator of
  underlying gastrointestinal tract abnormality

Nieman RE, Lorber B Listeriosis in adults a
changing pattern report of eight cases and
review of the literature, 1968-1978.  Rev Infect
Dis  1980 2207-227.
58
CENTRAL NERVOUS SYSTEM INFECTION

• L. monocytogenes has tropism for the brain
  parenchyma, particularly the brain stem
• one of the three major causes of meningitis
• most common cause of bacterial meningitis in
  patients with impaired cell-mediated immunity

Clauss HE, Lorber B CNS infection with Listeria
monocytogenes.  Curr Infect Dis
Rep  2008 10300-306.
59
CENTRAL NERVOUS SYSTEM INFECTION

• most common predisposing factor for developing
  listerial meningitis was malignancy, occurring in
  24 of patients
• 36 of meningitis cases no risk factor was
  identified

Mylonakis E, Hohmann EL, Calderwood SB Central
nervous system infection with Listeria
monocytogenes 33 years' experience at a general
hospital and review of 776 episodes from the
literature.  Medicine  1998 77313-336.
60
Clinical features of Listerial meningitis

• headache in 88
• nausea in 83
• fever in 90
• only 75 of patients had a stiff neck

Brouwer MC, van de Beek D, Heckenberg SG, et
al Community-acquired Listeria monocytogenes
meningitis in adults.  Clin Infect
Dis  2006 431233-1238.
61
Clinical features of Listerial meningitis

• focal neurologic deficit was present in 37
• only 43 had the classic meningitis triad of
  fever, neck stiffness, and change in mental
  status
• CSF findings included a median white blood cell
  count of 620 (range 24-16,003) and protein of
  2.52 g/L

Brouwer MC, van de Beek D, Heckenberg SG, et
al Community-acquired Listeria monocytogenes
meningitis in adults.  Clin Infect
Dis  2006 431233-1238.
62
Encephalitis

• spinal fluid cultures are positive in about
  one-half of cases
• may mimic herpes encephalitis

Cunha BA, Fatehpuria R, Eisenstein LE Listeria
monocytogenes encephalitis mimicking Herpes
Simplex virus encephalitis the differential
diagnostic importance of cerebrospinal fluid
lactic acid levels.  Heart Lung  2007 36226-231.

63
Rhombencephalitis

• usually occurs in healthy adults
• biphasic illness with a prodrome of fever,
  headache, nausea, and vomiting lasting about 4
  days

Armstrong RW, Fung PC Brainstem encephalitis
(rhombencephalitis) due to Listeria
monocytogenes case report and review.  Clin
Infect Dis  1993 16689-702.
64
Rhombencephalitis

• followed by the abrupt onset of asymmetrical
  cranial nerve deficits, cerebellar signs, and
  hemiparesis or hemisensory deficits, or both
• 40 of patients develop respiratory failure
• CSF findings are only mildly abnormal with a
  positive CSF culture in about one-third

Armstrong RW, Fung PC Brainstem encephalitis
(rhombencephalitis) due to Listeria
monocytogenes case report and review.  Clin
Infect Dis  1993 16689-702.
65
Rhomboencephalitis
66
Rhomboencephalitis
67
Brain Abscess

• 10 of CNS listerial infections
• bacteremia is almost always present
• isolation of L. monocytogenes from the CSF is
  found in 25 to 40

Cone LA, Leung MM, Byrd RG, et al Multiple
cerebral abscesses because of Listeria
monocytogenes three case reports and a
literature review of supratentorial listerial
brain abscess(es).  Surg Neurol  2003 59320-328.

68
FEBRILE GASTROENTERITIS

• gastrointestinal symptoms diarrhea, nausea, and
  vomiting, often accompanied by fever
• healthy, nonpregnant self-limited, febrile
  gastroenteritis
• Illness occurred 24 hours (range 6 hours to 10
  days) after ingestion

Schwartz B, Hexter D, Broome CV, et
al Investigation of an outbreak of listeriosis
new hypotheses for the etiology of epidemic
Listeria monocytogenes infections.  J Infect
Dis  1989 159680-685. 32.. Lorber B Listeriosi
s following shigellosis.  Rev Infect Dis  
69
BACTEREMIA

• primary bacteremia most common manifestation of
  listeriosis
• prodromal illness with diarrhea and nausea
• fever and myalgias
• transient bacteremias in healthy persons may go
  undetected

Swaminathan B, Gerner-Smidt P The epidemiology
of human listeriosis.  Microbes
Infect.  2007 91236-1243.
70
NEONATAL INFECTION

• in utero infection precipitate spontaneous
  abortion and the fetus may be stillborn or die
  within hours of a disseminated form of listerial
  infection known as granulomatosis infantiseptica
• neonatal infection manifests like group B
  streptococcal disease

Larsson S, Linell F Correlations between
clinical and postmortem findings in
listeriosis.  Scand J Infect Dis  1979 1155-58.
71
granulomatosis infantiseptica
http//www.technoinhome.com/vspcite/front/board/sh
ow.php?tbltblwb03gid22id828PHPSESSID880ef16
afce4cdc01f85b4176bc81af6
72
INFECTION IN PREGNANCY

• during gestation mild impairment of
  cell-mediated immunity
• 17-fold increase in risk
• CNS infection extremely rare during pregnancy
  in the absence of other risk factors

Mylonakis E, Paliou M, Hohmann EL, et
al Listeriosis during pregnancy a case series
and review of 222 cases.  Medicine  2002 81260-2
69.
73
INFECTION IN PREGNANCY

• occurs in the third trimester
• major decline in cell-mediated immunity seen at
  26 to 30 weeks of gestation
• stillbirth or neonatal death 22

Mylonakis E, Paliou M, Hohmann EL, et
al Listeriosis during pregnancy a case series
and review of 222 cases.  Medicine  2002 81260-2
69.
74
Diagnosis

• Clinical settings in which listeriosis should be
  considered
• Neonatal sepsis or meningitis
• Meningitis or parenchymal brain infection in
  susceptible hosts
• Subcortical brain abscess

Bille J Listeria and Erysipelothrix.
  In Murray PR, Baron EJ, Jorgensen JH, et
al ed. Manual of Clinical Microbiology,  9th
ed. Washington, DC American Society for
Microbiology Press 2007474-484.
75
Clinical Settings in Which Listeriosis Should be
Considered

• Spinal symptoms in the setting of acute
  bacterial meningitis
• Fever during pregnancy
• sterile specimen reported to have diphtheroids
  on Gram stain or culture
• Foodborne outbreak of febrile gastroenteritis

Bille J Listeria and Erysipelothrix.
  In Murray PR, Baron EJ, Jorgensen JH, et
al ed. Manual of Clinical Microbiology,  9th
ed. Washington, DC American Society for
Microbiology Press 2007474-484.
76
Diagnosis

• isolation of L. monocytogenes standard
  microbiologic techniques
• antibodies to listeriolysin O useful during
  foodborne outbreaks
• MRI is superior to CT
• PCR

Bille J Listeria and Erysipelothrix.
  In Murray PR, Baron EJ, Jorgensen JH, et
al ed. Manual of Clinical Microbiology,  9th
ed. Washington, DC American Society for
Microbiology Press 2007474-484.
77
TREATMENT

• almost susceptible to penicillins,
  aminoglycosides and trimethoprimsulfamethoxazole
• current recommendations for a severe infection
  combination of IV ampicillin (2g q4h) plus IV
  gentamicin (1.52mg/kg q8h) for 24 weeks

Lorber B Listeria monocytogenes.
  In Yu VL, Weber R, Raoult D, ed. Antimicrobial
Therapy and Vaccines,  2nd ed. New York Apple
Trees Productions 2002429-436.
78
Alternative Treatments

• IV trimethoprimsulfamethoxazole (20mg/kg q24h
  trimethoprim part divided into two to four doses)
  for 23 weeks
• Carbapenems
• Vancomycin

Lorber B Listeria monocytogenes.
  In Yu VL, Weber R, Raoult D, ed. Antimicrobial
Therapy and Vaccines,  2nd ed. New York Apple
Trees Productions 2002429-436.
79
PREVENTION

• food-borne
• sporadically (gt90) than as an outbreak
• pathogen elimination at production level of
  ready-to-eat at-risk food

Goulet V What can we do to prevent listeriosis
in 2006?.  Clin Infect Dis  2007 44529-530.
80
in the Consumer Kitchen

• wash raw vegetables keep refrigerator
  temperature below 5 C
• keep raw food products separate, wash hands and
  kitchen instruments after use, and cook raw meat
  properly

Goulet V What can we do to prevent listeriosis
in 2006?.  Clin Infect Dis  2007 44529-530.
81
Updates
82
Aetiologies in 278 episodes of acute
communityacquiredbacterial meningitis
83
Comparison of episodes of acute
community-acquired Lm meningitis versus other
aetiologies

• Age (median IQR) 69 30 vs 56 33
• Immunocompromised 67 vs 37
• Previous otitis 2.1 vs 19.5
• Focal neurological deficit 32 vs 12
• Cerebellum dysfunction 12 vs 2

84
Comparison of episodes of acute
community-acquired Lm meningitis versus other
aetiologies

• WBC count CSF (median IQR) 550 2480 vs
  2860 9380
• CSF neutrophils ( medianIQR) 70 59 vs 90
  13
• CSF/blood glucose (median IQR) 0.26 0.24 vs
  0.09 0.26
• Protein level g/L ( median IQR) 2.0 1.96 vs
  3.68 5.53

85
Characteristics of patients with acute
community-acquired Lm meningitis

• Classic Triad 45 vs 71
• CSF WBC count (median IQR)
• gt 999 cells/Ml 49 vs 15
• 
  

86
Description of patients with acute
community-acquired Lm meningitis who survivied or
died

• Definitive Ampicillin gentamicin therapy 32
  vs 67
• addition of an aminoglycoside may be harmful
  drugs associated nephrotoxicity and inability to
  cross the BBB

87
Updates
88
Demographic data and clinical presentation of 102
patients with infection by L. monocytogenes

• Diagnosis before year 2000 84.8 vs 52.2
• corticosteroids 57.6 vs 20.3
• DM 33.3 VS 11.6
• coma 21.2 VS 5.7
• overall mortality 33.3 VS 14.5
• early mortality 27.3 VS 4.3

89
Empirical antibiotic treatment in 102 evaluable
patients with L. monocytogenes infection

• Active antibiotic (51.9) 42.4 VS 56.5
• Non-adequate treatment (48.1) 57.6 VS 43.4

90
Association between characteristics of patients
and L. monocytogenes early mortality

• Multivariate analysis
• over 65 years old OR 12.2
• corticosteroids OR 5.89
• renal failure OR 4.88

91
Association between characteristics of patients
and L. monocytogenes late mortality

• Multivariate analysis
• neoplastic disease OR 10.57
• coma OR 15.07

92
Thank You !

• www.themegallery.com