Haigusjuht. Kesknärvisüsteemi infektsiooniga haige. BM etioloogia TK-tel. Bakteriaalne meningiit USAs 1995
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1 Haigusjuht Kesknärvisüsteemi infektsiooniga haige Kevad 27 Pühajärve Irja Lutsar 5 aastane laps elab Järvseljal hospitaliseeritakse palaviku (39 o C), peavalu, unisuse, iivelduse, oksendamisega haiguse 3 päeval. Kahtlustatakse meningiiti ja tehakse lumbaalpunktsioon Liikvor: pletsütoos 2; 8 PMNL; Valk 1 mg/dl Veri: üldleukotsütoos 14,7 rakku/ml; CRP 8 mg/dl Kas see on bakteriaalne või aseptiline meningiit? Liikvori kliiniline uuring Bakteriaalne meningiit USAs 1995 Võimalik Rakkude tekitaja arv/mls Bakter 15 (11) Rakkude Valk tüüp PMN 1 5 mg/dl Glükoos <4 mg/dl Tuberkuloos 51 Monotsüüdid 5 3 mg/dl <45 mg/dl Viirus 51 Monotsüüdid <2 mg/dl >45 mg/dl PMN Seened suurenenud lümfotsüüdid >45 mg/dl <4 mg/dl Norm: Rakkude arv 11/ml Valk 155 mg/dl Glükoos 48 mg/dl Lateks aglutinatsioon mikroobi kindlakstegemiseks Hib, S. pneumoniae, N. meningitidis, E. coli K1, S. agalactiae Mandell, 25 N Engl J Med 1997;337:97976 Bakteriaalse meningiidi etioloogia < 15 av lastel Eestis 1% BM etioloogia TKtel 8% 6% 4% 2% teadmata muud N. meningitidis S. pneumoniae H.influenzae 1% 75% 5% 25% tegemata teadmata muud Listeria Hib N.mening S.pneumoniae % % Tallinn tartu Lutsar et al. 2; Torm et al. 23; Uudelepp & Tamm, 25 1
2 Liikvori mikroskoopiline uuring (1) Gramivärvimine (69%) Sõltub mikroobide hulgast ja ravi algusest: 1 3 CFU/ml 25% + tulemus >1 5 CFU/ml 97% + tulemus Vale negatiivsed,1% Gramnegatiivsed Grampositiivsed H. influenzae 86% S. pneumoniae 8% N. meningitidis 75% S. agalactiae E. coli 5% L. monocytogenes < 5% Eelnev ab ravi tundlikkust Vanadel rakkudel sein deformeerub Lateks aglutinatsiooni test (2) Kombineeritud komplektid S.pneumoniae H.influenzae (PRP antigeen) N.meningitidis GBS E.coli K1 Hea tundlikkus Hible Pos või neg test ei eita ega jaata meningiiti Kui Hib kadunud kas on mõtet latex testi säilitada Diagnostiliste meetodite positiivsus N.meningitidis meningiidi korral (%) CSF Enne AB Pärast AB Veri Enne AB Pärast AB PCR LA Külv Tabel 5. Liikvori latekstesti ja Grami preparaadi ennustusväärtused Latekstest Vanemad lapsed Grami preparaat Vanemad lapsed Tundlikkus ,3 5 (%) Spetsiifilisus 93, (%) Positiivse testi ennustusjõud (%) Negatiivse testi 71,4 87,5 71,4 78,3 ennustusjõud (%) Efektiivsus (%) 73,1 91, ,1 Clin Micr Inf 26; 12: K.Tomberg, 21 Latekstesti Eesti laste bakteriaalsete meningiitide diagnoosimisel (236) S.pneumonia Hib N.meningitidis ML. Kumm, 27 Tundlikkus,81,84,25 Vastsündinud Vastsündinud Spetsiifilisus,94,84,98 Positiivse testi ennustusjõud,75,88,6 Negatiivse testi ennustusjõud,96,77,9 Korduslumbaalpunktisoon kas ja millal 2436 tundi pärast ravi algust Resistentne mikroob? Gneg; S.aureus Mitte S.pneumo; N.meningitidis Ravitaktika muutus Korduv meningiit on immuunsüsteemi häire mitte ebaefektiivne või ebaadekvaatne AB ravi Keskkonnatekkese meningiidi tekitajad ei ole aju abstsesside tekitajad Ravi lõpus mitte!!! 2
3 Trova vs CRO in childhood BM Antibiotic resistance levels (% of ir and R strains) 2125 Invasive S.pneumoniae Pen.7 AMP 3g. ceph Eryth 4.2 TMP/SMX 29 N.meningitidis 23* H.influenzae Carriage S.pneumoniae N.meningitidis H.influenzae 37 SaezLlorens, 22 Tamm et al. 27; Naaber et al. 21 * All βlactamase negative Aju abstsesside tekitajad Kestev palavik ja meningiit Palavik võib kesta kaua (23 päeva) Sekundaarne palavik 34% haigetest Lumbaalpunktsioon tavaliselt ei aita Otsida teist kollet Antibakteriaalse ravi vahetus ei ole näidustatud Sekundaarne palavik ja subduraalsed effusioonid Hib meningiidi hiliskomplikatsioonid Harva sisaldavad baktereid (S.pneumoniae, Hib) Paranevad tavaliselt ise Võivad vajada vedeliku eemaldamist Diagnostiline punktsioon koos mikrobioloogilise külviga Miks haiged meningiidi tagajärjel ikka surevad või invaliidiks jäävad? 3
4 Keskkonnatekkelise bakteriaalse meningiidiga seotud suremus viimase 9 a jooksul Bakteriaalse meningiidi tekitajad ja virulentsusfaktorid S.pneumoniae N.meningitidis Kolonisatsioon Adhesiin, sekretoorne IgA, pneumolüsiin Pilid Põletiku faktorid Raku seina komponendid (lipoteihoiinhape, peptiidoglükaan) LOS H.influenzae Pilid, adhesiin LPS S.agalacteae E.coli Adhesiin Adhesiin Raku seina komponendid (lipoteihoiinhape, peptiidoglükaan) LPS K.pneumoniae Adhesiin LPS N Engl J Med 24;351: L.monocytogenes Internaliin Listeriolüsiin (hemolüsiin), transport rakust rakku Pathogenesis of pneumococcal meningitis Concentrations of WBC (cells/ml; left), TNF{alpha} (pg/ml; middle) and lactate (mmol/l; right) in the CSF control Lutsar, I. et al. J. Antimicrob. Chemother :651655; doi:1.193/jac/dkg417 Lancet Neurology, 26; 5: Järeldus: antibakteriaalse raviga ei ole aega oodata Concentrations of WBC (cells/ml), TNF{alpha} (pg/ml), lactate (mmol/l) and S. pneumoniae (log1 cfu/ml) in CSF in animals with pneumococcal meningitis control Sekundaarne põletikureaktsioon Deksametasoon Lutsar, I. et al. J. Antimicrob. Chemother :651655; doi:1.193/jac/dkg417 Amp closed triangels; DXM before open squares; DXM after closed squares 4
5 Aseptilise meningiidi tekitajad Viirused Enteroviirused (echo ja Coxackie), arboviirused, herpesviirused, HIV, adenoviirus, paragripi viirus, gripiviirus, leetriviirus Bakterid M.tuberculosis, Borrelia burgdorferi, T.pallidum, Leptospirae jt Seened C.albicans, Aspergillus spp Algloomad Mitteinfektsioossed põhjused Sagedasemad aseptilise meningiidi tekitajad Tekitaja Enteroviirused Arboviirused HSV CMV EBV Mumps Lümfotsütaarne koriomeningiit HIV Süüfilis Lyme tõbi Leptospiroos Sesoonsus Suvisügis Kevadsügis kevad Sügistalv Suvisügis Suvisügis Märkused Lapsed, noorukid Sõltub kohalikust epiidolukorrast Kõigis vanustes Immuunodefitsiitsed isikud IM tüsistus Lapsed ja noorukid Eelvev kokkupuude närilistega Mononukleoosi sündroom Riskigrupp Puugihammustus, ECM Kahefaasiline kulg, kokkupuude nakatunud veega Seasonal distribution of viral meningitis Enteroviirused Picornaviirused Klassifikatsioon Polioviirus 1, 2, 3 Coxsackie A 122, 24 Coxsackie B 16 Echoviirus (ECHO) 19, 1127, 2934 Enteroviirus 6871 ECHO enteric cytopathic human orphan Diagnostika Liikvori uuringud Kliiniline uuring Viiruse isoleerimine liikvorist Enamasti ebaefektiivne Viiruse isoleerimine teistest piirkondadest Enteroviirused ninaneel ja roe Koekultuurid (ahvi või inimembrüo neerurakud) Mumps ninaneel, uriin Koekultuuridel (ahvi neerukude) Diagnostika (2) PCR tehnika Enteroviiruste avastamine liikvoris HSV PCR liikvoris Seroloogilised testid + kliinik + tüüpiline aseptiline meningiit liikvori analüüsis + bakteriaalne meningiit eitatud HIV diagnostika IgM tüüpi akd mumpsi korral Paarisseerumid (4x IgG tüüpi akde tiitri tõus) Arboviirused (PE viirus), mumps, borrelioos, enteroviirused Süüfilis liikvori seroloogia Leptospiroos vere seroloogia, liikvori külv 5
6 Puukidega levivad haigused TBE in Europe Puugiga peaks olema kokkupuude >48t KNS seotud infektsioonid Eestis Flaviviirus PE Lyme tõbi Viirusmeningiidid Tervisekaitseserver juhtude arv Puukentsefaliit (Venemaa ja Ida Euroopa) (kitsed, lambad, närilised puugid) Kollapalavik (ahvidsääsed) Jaapani entsefaliit LääneNiiluse entsefaliit (linnudsääsed) Dengue palavik (ahvidsääsed) RNA viirus Epidemic curve of the tickborne encephalitis outbreak linked to raw goat milk, Estonia, May June 25 Eurosurveillance Weekly 25; 1(25): 23 Jun Puukentsefaliidi diagnostilised kriteeriumid Võimalikud juhud Tüüpiline kliinilislaboratoorne pilt (2küüruline palavik ja meningiit[entsefaliit]) puukide aktiivsuse ajal Tõenäolised juhud Võimalik juht ja Viibimine ohtlikus piirkonnas ja IgM tüüpi ak tiiter vereseerumis Kinnitunud PE juhud Võimalik juht ja IgM tüüpi antikehade leid seljaajuvedelikus või 4 kordne IgG tüüpi antikehade tiitri tõus eelneva 3 kuu jooksul vaktsineerimata isikul või Viiruse isoleerimine seljaajuvedelikust Stefanov et al. 25 6
7 Euro Surveill. 25 Jan 1;1(1) Euro Surveill. 25 Jan 1;1(1) Puukentsefaliidi laboratoorne diagnoosimine Puukentsefaliit IgM ja IgG tüüpi akmääramine ELISA meetodil veres ja liikvoris Vaktsinatsioonistaatus on oluline IgG tüüpi antikehade tõus diagnostiline Viiruse määramine PCR meetodil Viiruse kasvatamine? raske Ei sobi KSR ja HPR Lyme tõve diagnostika Külvid spetsiaalsetele söötmetele (võtavad aega 34nädalat) Esmalt ELISA Positiivsete testi korral kontrollida WBga Testide interpreteerimine raske Pos IgM kliinilise pildita vale positiivne Esimestel nädalatel võib IgM olla negatiivne IgM test võib jääda kauaks jääda positiivseks isegi efektiivse ravi korral IgM akde leid 1 kuu pärast haigestumist on tõenäoliselt valepositiivne WB (edaspidi) WB IgM antikeha test 25 ECM haigel ägedas faasis positiivne kui olemas kaks kolmest 23, 39, 41 (CDC kriteerium) 7
8 WB IgG 25 haigel meningiidi või näonärvi halvatusega CDC kriteerium: viis kümnest peab olema positiivne Praktilisi näpunäiteid (1) Liikvori kliiniline uuring (pleotsütoos, valem, suhkur, valk, laktaat) Liikvori mikrobioloogia laborisse Grami järgi preparaat Külv S.pneumoniae, N.meningitidis, Hib Listeria riskigruppidel Lateks (tulemus küsitav kui Hib kadunud) Liikvori PCRl võib olla eeliseid Verekülv Külv S.pneumoniae, N.meningitidis, Hib, Listeria Liikvori külvi ja Grami järgi preparaadi peaks tegema igal juhul kui pleotsütoos > 3 raku/ml Praktilisi näpunäiteid (2) Viroloogilised uuringud (HSV, VZV, entero) Aseptiline meningiit (liikvor ei ole silmale hägune?) Antikehad Kahtlus puukentsefaliidile (puugihammustus ei ole obligatoorne) Liikvor ja veri (IgM) IgG tiitri 4X tiitri tõus Borrelioosi kliiniline pilt ELISA IgM kui haigestumisest möödas <1 kuu ELISA IgG hilisvormide korral Pos leid kinnitada WBga Neuroinfektsioonide tulevik Hib meningiit peaaegu kadunud Pneumokoki vaktsiin on langetanud invasiivseid infektsioone lastel aga ka vanadel inimestel; vaktsiini efektiivsus Eestis sõltub siin levivatest serotüüpidest) MenC vaktsiin efektiivne Supermeningiidi vaktsiin PE vaktsiini kiirendatud skeem (, 7, 21 päev) annab hea akde vastuse Herpes, Lyme tõve vaktsiin??? Kas neuroinfektsioonid kaovad? S. Pneumoniae serotype distribution in Estonia Percentage of subjects with antibody titres as determined by neutralization test 1, lines indicating 95% confidence intervals Proportion of all cases per age group (%) 1% 9% 8% 7% 6% 5% 4% 3% 2% 1% % Proportion of all IPD cases by S. pneumoniae serotypes and age >18 >18 *25 *25 Age other Crossreactive types 23F 19F 18C 14 9V 7F 6B Group R (vaccination on D, 7 and 21) Group C (vaccination on D, 28 and 3) Group M (vaccination on D, 21 and 3) Group A (vaccination on D, 14 and 3) *NF strains Vaccine 27; 25:
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