Transcript Infectious Diseases – 2014

Hot heads
3rd April 2014
Acute Medicine Study Day
Sarah Glover
Consultant in Medical Microbiology and Infectious Diseases
Case 1
• 19F student
• Admitted with 12 hour history of myalgia
headache neck stiffness photophobia
• 1 hr history of spreading rash
• O/E T 36. P 120. Neck stiffness. Rash –
mostly blanching but some non-blanching
• Impression in A&E: ?meningococcal
meningitis
• BCs sent, cefotaxime given, public health
notified, boyfriend given prophylaxis
• WCC 15 (neuts 14.5) CRP 67
• CT head (2 hrs after arrival): NAD
• CSF (6 hrs post CT):
WCC
13
Polymorphs
10
Mononuclear
3
RBC
62
No organisms seen
Protein
407 mg/l
(0-500)
Glucose
4.3 mmol/l
• No paired serum glucose
• Blood cultures positive Neisseria
meningitidis
• CSF no growth
• Positive meningococcal PCR on CSF
• Treated with 7 days of IV cefotaxime /
ceftriaxone
• Uneventful recovery
Commonest causes of community
acquired bacterial meningitis
Adult <50 years Neisseria meningitidis
Streptococcus pneumoniae
Adult >50 years Streptococcus pneumoniae
Listeria monocytogenes
Also cover Listeria if pregnant or immunosuppressed
Logan S Viral meningitis BMJ 2008;
336:36-40
%
Acute bacterial menignitis
in adults. A review of 493
episodes. Durand. NEJM
1993;328:21-8
Absence of one or more classic
findings is of little value.
13% had CSF WCC <100
50% had glucose > 2.2 mmol/l
• 696 episodes
• 12% had none of the characteristic CSF findings
(CSF glucose <1.9, CSF:blood glucose ratio of
<0.23, protein >2.2g, WCC >2000)
• Well recognised that meningococcal sepsis with
early meningitis may have low CSF WCC
Diagnosis
• Meningococcal septicaemia and
meningitis
Role of PCR in diagnosis of
invasive meningococcal disease
• NICE: all patients < 16 with suspected
meningococcal disease get:
– blood culture
– PCR on EDTA blood
– CSF culture with CSF PCR if culture is negative
• Data from MRU across all ages: 57% were
confirmed by PCR only, 22.5% by culture only,
20.4% by both tests
• Send blood cultures early
• Send an early EDTA blood for PCR
• Request PCR on CSF
• Early samples are more likely to be
positive
• PCR results may still be positive after
antibiotic administration
Case 2
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42F married secondary school teacher
Lives with husband and 2 adult children
Normally fit and well
BIBA to A&E
2-3 day history flu like symptoms
Back ache, severe headache, photophobia
Mild dysuria
• O/E: low grade fever, meningitic, in pain,
GCS 15, no focal neurology, no rash
• Bloods: CRP 8, WCC 13.9 (neuts 10)
• Cefotaxime started in A&E, referred to
medics (no blood culture sent)
• CT brain 2pm NAD
• CSF 5pm:
WBC
570
Polymorphs
10%
Mononuclear
90%
RBC
180
No organisms seen
Protein
2114 mg/l
Glucose
2.9 mmol/l
No paired serum glucose
• IV aciclovir added
(0-500)
Other history?
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No recent travel
No contacts unwell
No known TB contacts, never lived abroad
No immunosuppressive Rx
No previous episodes of meningitis
Thinks had all childhood vaccinations, unsure of
details
Married for 10 years
No new sexual partners
No recent antibiotics
Denies exposure to rodents or ticks
ROS: mild dysuria/perineal discomfort recently, no
response to canestan
Differential diagnosis?
Aseptic meningitis
• Acute onset meningeal symptoms and
fever, with CSF pleocytosis and no growth
on routine bacterial culture
Aseptic meningitis
Kupila L Etiology of aseptic meningitis and encephalitis in an
adult population Neurology 2006 66 75-80
‘Aseptic’ meningitis
• Viral, UK
– Enterovirus
– HSV
– VZV
– HIV seroconversion
– Mumps
– EBV
– CMV (immunocompromised)
‘Aseptic’ meningitis
• Bacterial:
– Partially treated bacterial meningitis
(meningo, pneumo)
– Listeria
– TB meningitis
– Spirochetes: syphilis, Lyme, leptospira
– Mycoplasma, brucella
• Parameningeal infection (spinal abscess or
intracranial abscess)
• Endocarditis
Aseptic meningitis
• Fungal
– Cryptococcus
• Travel
– West Nile virus
– Other arboviruses
– Cerebral malaria
• Rodents
– Lymphocytic choriomeningitis (LCMV)
Aseptic meningitis
• Recent vaccination
• Non-infection:
– SAH
– Malignant meningitis
– Sarcoid
– SLE
– Behcet’s
– Drug induced (septrin, NSAIDs)
Other investigations in this
patient?
• Pregnancy test negative
• HIV negative
• PCRs on CSF (result within 24 hours):
Enterovirus
not detected
VZV
not detected
Meningococcus not detected
HSV 2 DNA
DETECTED
Other history
• Husband had prev hx of genital herpes –
no recent acute flares although mild
discomfort a month ago
• Pt herself had no prev hx genital herpes
• Treated with IV aciclovir then oral
valaciclovir and discharged
• Readmitted 1 week later with recurrent of
symptoms + active genital lesions
HSV
• HSV meningitis vs encephalitis
• HSV encephalitis:
– life threatening medical emergency
– reduced GCS, seizures, focal neurology,
confusion, disorientation, personality change,
speech disturbance
– prompt antiviral Rx life saving
– Usually HSV-1
– Reactivation from trigeminal ganglia (prev oral
mucosal acquisition)
• HSV meningitis is often a complication of genital
herpes especially HSV-2
• 36% of women and 13% of men with primary
genital HSV-2 infection had aseptic meningitis
• Frequently occurs in absence of genital lesions /
history of genital lesions
• May occur during reactivation
• May be complicated by radiculitis, myelitis, recurrent
meningitis (with or without genital symptoms)
• Role of antivirals in HSV-2 meningitis:
– Indicated for primary genital herpes infection
– Variability in practice for HSV-2 meningitis
– Prophylaxis: sometimes given. RCT of valaciclovir
500mg bd
• Asymptomatic intermittent shedding and transmission
years into a monogamous relationship
Differences in CSF findings
between enterovirus and HSV-2
Enterovirus
(n=22)
HSV-2
(n=8)
CSF WCC
(p<0.01)
51 (0-1298)
240 (180-2200)
CSF protein (mg/l)
(p<0.001)
640 (100-875)
1205 (611-3704)
• Clues in this case were dysuria high CSF
WCC and high protein
Ihekwana U. CID 2008; 47:783-9
Cases 3 & 4
• Husband and wife admitted with meningitic
illnesses
Mrs
• 36F, recently warfarinised for multiple
DVTs, under investigation ?factor V leiden
• Admitted with 24hr hx headache,
backache, then photophobia, neck pain
and nausea
• Subtherapeutic INR
• Initially investigated for ?venous sinus
thrombosis or intracranial bleed
• CT head + CT venogram NAD
• Febrile with GP and on day after
admission
• No encephalitic features
• Delayed attempts at LP due to
anticoagulation then unsuccessful
attempts
• CRP 9 WCC N Admission BCs neg
• 2 erythematous patches on lower leg,
clarithromycin prescribed
• Symptoms improved
Mr
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48 hours later, husband admitted
34M self employed in motor trade
Symptoms came on 48 hrs after wife’s
Headache, neck pain/stiffness, photophobia,
nausea, vomiting
• Febrile on admission 38.9, neck stiffness on
examination. GCS 15 no focal neurology
• Penicillin allergy so started chloramphenicol in
A&E
• CRP 9, WCC N
• CT brain NAD
• CSF:
WBC
52
mononuclear
73%
polymorphs
27%
RBC
22
No organisms seen
Protein
543 mg/l
Glucose
3.5 mmol/l
no paired serum
Risk factors for infection
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No recent travel
No TB contacts
No known immunosuppression
Live in New Forest
Neither noticed tick bites
Pet degu (desert rat)
2 children, 7 month old had diarrhoea and
vomiting illness one week ago
• BCs negative
• CSF PCRs:
– Meningococcus PCR
– HSV PCR
– VZV PCR
– Enterovirus PCR
• CSF culture negative
negative
negative
negative
negative
Diagnosis?
Diagnosis?
• Clues: household transmission, child with
D+V
• Requested:
– Throat swabs and stools/rectal swabs for
enterovirus
Results
• Mr:
– Throat swab and stool both strongly positive
enterovirus PCR
• Mrs:
– Throat swab strongly positive enterovirus
PCR
• Lyme, mycoplasma, HIV and syphilis serology
negative
Stool enterovirus PCR
Kupila L, Diagnosis of enteroviral meningitis by use
of PCR of CSF, stool and serum samples. CID
2005:40
Influence of sampling time on
results of CSF PCR and
stool PCR for detection of
enterovirus in patients with
enteroviral meningitis
Kupila L, Diagnosis of
enteroviral meningitis by use
of PCR of CSF, stool and
serum samples. CID 2005:40
Diagnosis
• Enteroviral meningitis
• Enteroviruses include coxsackie, echoviruses,
poliovirus
• Causes hand foot and mouth disease,
myocarditis, maculopapular rash, meningitis
• Commonest in summer / autumn
• Commonly cause illness in children
• Commonest cause of viral meningitis
• May see some polymorphs early on
Case 5
• 58 Indian lady, lived in UK 10 years, last
visited 2 months ago, had renal stones
‘washed out’
• Saw GP pre admission, given
trimethoprim, urine grew MDR E coli
• 1 week of headache, unsteadiness, dizzy
• 24 hours confused
• GCS 10 on admission, T 38
• CRP 2 WCC 10 (neuts 8) malaria film neg
• CT head no contraindication to LP
• CSF:
WBC
35
mononuclear
32
polymorphs
3
RBC
2
No organisms seen
Protein
2133 mg/l
Glucose
1.0 mmol/l
No serum glucose
• CXR no obvious consolidation/cavitation
• Differential diagnosis?
• Investigations?
• Started on cefotaxime aciclovir amoxicillin
quadruple TB therapy and steroids
• BC and CSF culture negative
• CSF PCRs negative for HSV VZV
enterovirus meningococcus
• HIV negative
• 0.5 mls CSF left
• AFB smear negative
• Repeat LP for large volume CSF
• Day 2 of admission, 6mls CSF collected
and sent same day to TB ref lab for TB
PCR
• Result within 24 hours: PCR positive
indicating the presence of Mycobacterium
tuberculosis complex. Genotype is that
seen in rifampicin susceptible isolates.
• Continued TB Rx and steroids
• Other antimicrobials stopped
TBM
• All methods of TB detection in CSF are heavily
dependent on sample volume
• Sensitivity of smear and culture fall off rapidly
after Rx started
• PCR:
– ~30% sensitivity on 0.5 mls CSF
– Up to 70% sensitivity on large volume e.g. 6mls
– Negative doesn’t exclude but a positive result very
useful
Safe recommended CSF volumes
Adult
Mean CSF
production
rate (ml/h)
CSF
volume
(mls)
22
150-170
Safe CSF
volume to
take at LP
(mls)
15-17
• First CSF: smear and culture negative
• Second CSF: PCR positive, culture
negative
• Patient progress not straightforward –
useful to have confirmed diagnosis
Summary – Investigations in
?meningitis
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Clues in the history
Blood culture prior to antibiotics
EDTA blood for meningo/pneumo PCR
CSF: cell count, gram stain, culture, protein, glucose,
PCRs
Paired blood glucose
Bacterial throat swab
Viral throat swab + stool for enterovirus
HIV test
If TB suspected – large volume CSF, may need early
repeat
Summary
• Early appropriate tests help make a
diagnosis
• Early diagnosis helps target treatment,
improve outcome and reduce LOS