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Hot heads 3 rd April 2014 Acute Medicine Study Day Sarah Glover Consultant in Medical Microbiology and Infectious Diseases.

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Presentation on theme: "Hot heads 3 rd April 2014 Acute Medicine Study Day Sarah Glover Consultant in Medical Microbiology and Infectious Diseases."— Presentation transcript:

1 Hot heads 3 rd April 2014 Acute Medicine Study Day Sarah Glover Consultant in Medical Microbiology and Infectious Diseases

2 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

3 Impression in A&E: ?meningococcal meningitis BCs sent, cefotaxime given, public health notified, boyfriend given prophylaxis WCC 15 (neuts 14.5) CRP 67

4 CT head (2 hrs after arrival): NAD CSF (6 hrs post CT): WCC 13 Polymorphs10 Mononuclear 3 RBC 62 No organisms seen Protein 407 mg/l(0-500) Glucose 4.3 mmol/l No paired serum glucose

5 Blood cultures positive Neisseria meningitidis CSF no growth Positive meningococcal PCR on CSF Treated with 7 days of IV cefotaxime / ceftriaxone Uneventful recovery

6 Commonest causes of community acquired bacterial meningitis Adult <50 yearsNeisseria meningitidis Streptococcus pneumoniae Adult >50 yearsStreptococcus pneumoniae Listeria monocytogenes Also cover Listeria if pregnant or immunosuppressed


8 Logan S Viral meningitis BMJ 2008; 336:36-40

9 % 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

10 696 episodes 12% had none of the characteristic CSF findings (CSF glucose 2.2g, WCC >2000) Well recognised that meningococcal sepsis with early meningitis may have low CSF WCC

11 Diagnosis Meningococcal septicaemia and meningitis


13 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


15 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

16 Case 2 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

17 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)

18 CT brain 2pm NAD CSF 5pm: WBC 570 Polymorphs10% Mononuclear90% RBC 180 No organisms seen Protein 2114 mg/l (0-500) Glucose 2.9 mmol/l No paired serum glucose IV aciclovir added

19 Other history?

20 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

21 Differential diagnosis?

22 Aseptic meningitis Acute onset meningeal symptoms and fever, with CSF pleocytosis and no growth on routine bacterial culture

23 Kupila L Etiology of aseptic meningitis and encephalitis in an adult population Neurology 2006 66 75-80 Aseptic meningitis

24 ‘Aseptic’ meningitis Viral, UK –Enterovirus –HSV –VZV –HIV seroconversion –Mumps –EBV –CMV (immunocompromised)

25 ‘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

26 Aseptic meningitis Fungal –Cryptococcus Travel –West Nile virus –Other arboviruses –Cerebral malaria Rodents –Lymphocytic choriomeningitis (LCMV)

27 Aseptic meningitis Recent vaccination Non-infection: –SAH –Malignant meningitis –Sarcoid –SLE –Behcet’s –Drug induced (septrin, NSAIDs)

28 Other investigations in this patient?

29 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

30 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

31 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)

32 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

33 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

34 Differences in CSF findings between enterovirus and HSV-2 Clues in this case were dysuria high CSF WCC and high protein 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) Ihekwana U. CID 2008; 47:783-9

35 Cases 3 & 4 Husband and wife admitted with meningitic illnesses

36 Mrs 36F, recently warfarinised for multiple DVTs, under investigation ?factor V leiden Admitted with 24hr hx headache, backache, then photophobia, neck pain and nausea

37 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

38 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

39 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 Mr

40 CRP 9, WCC N CT brain NAD CSF: WBC 52 mononuclear73% polymorphs 27% RBC 22 No organisms seen Protein 543 mg/l Glucose 3.5 mmol/l no paired serum

41 Risk factors for infection 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

42 BCs negative CSF PCRs: –Meningococcus PCR negative –HSV PCR negative –VZV PCR negative –Enterovirus PCR negative CSF culture negative

43 Diagnosis?

44 Clues: household transmission, child with D+V Requested: –Throat swabs and stools/rectal swabs for enterovirus

45 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

46 Stool enterovirus PCR Kupila L, Diagnosis of enteroviral meningitis by use of PCR of CSF, stool and serum samples. CID 2005:40

47 Influence of sampling time on results of CSF PCR and stool PCR for detection of enterovirus in patients with enteroviral meningitis

48 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

49 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

50 CT head no contraindication to LP CSF: WBC35 mononuclear32 polymorphs3 RBC2 No organisms seen Protein2133 mg/l Glucose1.0 mmol/l No serum glucose

51 CXR no obvious consolidation/cavitation Differential diagnosis? Investigations?

52 Started on cefotaxime aciclovir amoxicillin quadruple TB therapy and steroids

53 BC and CSF culture negative CSF PCRs negative for HSV VZV enterovirus meningococcus HIV negative 0.5 mls CSF left AFB smear negative

54 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.

55 Continued TB Rx and steroids Other antimicrobials stopped

56 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

57 Safe recommended CSF volumes Mean CSF production rate (ml/h) CSF volume (mls) Safe CSF volume to take at LP (mls) Adult22150-17015-17

58 First CSF: smear and culture negative Second CSF: PCR positive, culture negative Patient progress not straightforward – useful to have confirmed diagnosis

59 Summary – Investigations in ?meningitis 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

60 Summary Early appropriate tests help make a diagnosis Early diagnosis helps target treatment, improve outcome and reduce LOS

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