Central nervous system infection

Dr. Koukeo Phommasone

CNS infection• Meningitis• Encephalitis• Myelitis• Focal Central Nervous System Syndrome

– Brain abscess– Subdural empyema– Epidural abscess

¦¾À¹©¢º¤ CNS infection• Virus: EV, HSV, VZV, CMV, Mumps, JE, Dengue• Bacteria: HIB, S. pneumoniae, N. meningitidis,

S. suis, M. tuberculosis…• Fungi: Cryptococcus• Protozoa• Parasites: Angiostrongylus cantonensis, …

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• Ä¢É (fever)• À¥ñ®¹ö¸ (headache)• ¦½ªò®Ò©ó (altered mental status)• Focal neurologicdeficits• Meningismus

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headache; photophobia; stiff neck; Kernig’s and

Brudzinski’s signs +; opisthotonus

Meningitis vs Encephalitis

Meningitis• Fever• Headache• Meningismus• Altered mental status

Encephalitis• Fever• Headache• Altered mental status

Mental status changes early in the disease course, prior to coma

• Focal or diffuse neurologicsigns (seizures and hemiparesis)

Both share many features

Meningoencephalitis

Definitions of WHO

Bacterial meningitis • Clinical description

– Acute onset of fever (usually >38.5 rectal, >38 axillary)

– Headache and – One of the following signs:

neck stiffness, altered consciousness or other meningeal signs

Acute encephalitis syndrome (AES)

• Clinical case definition– Acute onset of fever and at

least one of: • Change in mental status

(including symptoms such as confusion, disorientation, coma, inability to talk

• New onset of seizure ( including simple febrile seizure)

Meningitis and encephalitis• Life-threatening disease• Signs and symptoms are not specific • Physical examination may not be sufficient to accurately

identify patient with meningitis, especially in infants and young children

• Lumbar puncture result may be difficult to distinguish bacterial meningitis from viral meningitis

• Suspected bacterial meningitis is a medical emergency and need empirical antimicrobial treatment without delay

• Physicians who prescribe the initial dose of antibiotics should be aware of guidelines for antibiotics and adjunctive steroids

LP contraindication• Mass in the brain (eg. Brain tumor or abscess) causing raised intracranial pressure• Skin or soft tissue sepsis at the proposed LP site• Severe coagulopathy or severe thrombocytopenia

Risk for either mass or raised ICPrecent head injurya known immune system problemlocalizing neurological signsevidence on examination ofraised ICP

MRI or CT brain prior to

LP

Focal neurological signs,

papilloedema, falling level of

consciousness with falling pulse, rising BP and/or vomiting

Brainherniation

Typical CSF in meningitisPyogenic Tuberculosis Viral

Appearance Often turbid Often fibrin web

Usually clear

Predominant cells

polymorphs mononuclear mononuclear

Cell count/mm3 90-1000 10-1000 50-1000Protein (g/L) >1.5 1-5 <1glucose <1/2 plasma <1/2 plasma >1/2 plasma

Normal opening pressure: 50-190 mmH2O (depends on age)Appearance :clear; turbid; yellow or bloody

LP• Cell count: 0-5/mm3 in children and adult,

maybe up to 32/mm3 (mean of 8-9/mm3) in neonates– False positive eleviation of CSF white bloodcell

counts : traumatic LP, intracerebral or subarchnoidhemorrage

LP done at Mahosot

• Physicians decide to do Lumbar Puncture according to clinical symptoms/signs

• No contraindication for LP

• Informed written consent

LP doneatMahosot

• Lab staff assist the physician for LP• CSF drop on agar plate,• CSF collection in 3 tubes:

• adult: 8ml• children: 3ml

• Blood collection: (haemoculture, glucose and serology)

CSF

Hemoculture

Cell count, Glucose,

Protein, GS, ZN, Auramine, India

ink

Classical bacteriological &TB culture

Bacteria PCRBacteriological tests

Fungus & parasites

Viral tests

S. pneumoniae

H. influenzae

N. meningitidis

S. suis

RickettsiaScrub typhus

Murine typhus

Spotted fever

Malaria film

Cryptococcal Ag & culture

Serum RDT for murine and scrub typhus

Serology for Angiostrongyluscantonensis and Gnathostomaspinigerum

Panbio ELISA: Dengue (NS1, IgM, IgG), JE IgM

Viral PCR

Viral culture

EV, HSV, VZV, CMV, Dengue, JE, Nipha, Influenxa A

Mumps, measles, TBE, West Nile, Inluenza B, Panflavivirus

• Total included patients 2003-2009: 840 patients• Few bacteria isolated from CSF: 6% (67% AB before LP)• virus positive samples : 15.3%

Viral causes Tested POS %

EV PCR 345 CSF 7 2%

HSV PCR 344 CSF 3 0.9%

VZV PCR 385 CSF 2 0.5%

CMV PCR 243 CSF 4 1.6%

Mumps PCR 344 CSF 2 0.9%

JEV PCR 344 CSF 2 0.9%

JE culture 200 CSF 1 0.5%

JEV IgM 700 CSF 48 6.8%

Dengue 344 sera 4 (3D1,1D4) 1.2%

Treatment of meningitisMahosot Microbiology Review

• Antibiotic recommendation– Ceftriaxone 80-100 mg/kg/day divided into 2 daily

doses (50kg adult 2g IV every 12 h)– Or in neonates:

• Aged 0-7 days cefotaxime100-150 mg/kg/day (dose interval every 8-12h) or aged 8-28 days 150-200 mg/kg/day IV (dose interval 6-8h)

• And if Listeria is suspected (usually in infant < 1 month old) give ampicillin

Treatment of meningitisMahosot Microbiology Review

Age 0-7 days 8-28 days <15 y >15 y

Daily dose IV 150 mg/kg/day 200 mg/kg/day 300 mg/kg/day 12 g/day

Dose interval Every 8h Every 6-8h Every 6h Every 4 h

• If ceftriaxone is not available give chloramphenicol

Treatment of meningitisMahosot Microbiology Review

Age 0-7 days 8-28 days <15 y >15 y

Daily dose IV 25 mg/kg/day 50 kg/day 75-100mg/kg/day 4-6g/day

Dose interval 24h 12-24h 6h 6h

If suspected rickettsial disease add in: oral doxycycline 4 mg/kg stat followed by 2mg/kg every 12h for 1 week. In adult doxycycline 200 mg loading dose followed by 100 mg every 12h

Adjunctive treatment with dexamethasone

• Neurological sequelae are common in survivors of meningitis (hearing loss, cognitive impairement, developmental delay)

• Adjuvant therapy with dexamethasone reduces the mortality and neurological sequelae among adults with bacterial meningitis in the developed world

• There have been few clinical trials in Asian patients – unclear whether should be given ?

Systemic steroids (dexamethasone, 10 mg IV) are important adjunctive treatment for patients with suspected bacterial meningitis and should be given with the first dose of antibiotics and

continued every 6 h for 4 days (but unclear whether beneficial in developing countries)

Prevention• Viral meningitis: Immunoprophylaxis - JEV• Bacterialmeningitis:Vaccine available for Hib, 7 serotype of S.

pneumoniae and N. meningitidis group A, C, Y and W135• Chemoprophylaxis for bacterial meningitis patients/contacts– Haemophulus influenzae

• Eradication of nasopharyngeal colonization of Hib– Rifampicin 20 mg/kg daily for 4 days (2 days of rifampicin is efficacious as 4

days’ treatment– Ampicillin and chloramphenicol, unlike ceftriaxone and cefotaxime, do not

effectively eliminate nasopharyngeal colonization– Rifampicin is Not recommended in pregnant women

• Chemoprophylaxis is not currently recommended for daycare contacts 2 y old or older unless two or more cases occur in the daycare center within 60 days-period

• For children <2 y, the CDC recommends prophylaxis for daycare contacts

– Neisseria meningitidis• Chemoprophylaxis:

– Ceftriaxone IM 250 mg in adult and 125 mg in children– Ciprofloxacin 500 mg oral in adult single dose– in adults, rifampin 600 mg bid for 2 days. In children 1 month or older 10

mg/Kg and infant youngerthan 1 month 5m/kg • Chymoprophylaxis is recommended for household contacts,

daycare center members, any person exposed to the patient’s oral secretion

• Chemoprophylaxis is not recommended for school, work or transport contacts

• High dose penicillin or chloramphenicol do not reliably eradicate meningococci from the nasopharynx of colonized patients

– S. pneumoniae: the risk of secondary pneumococcal disease in contacts of infected patient has not been defined

– Streptococcus agalactiae• All pregnant should be screenat 35-37 weeks gestation for

anogenital colonization with group B streptococci

Microbiology LaboratoryMahosot Hospital

Thank you for your attention