Plaučių tuberkuliozė: paplitimas, diagnostikos metodai ir gydymo principai. Epidemiologija

Plaučių tuberkuliozė: paplitimas, diagnostikos metodai ir gydymo principai. Epidemiologija

Tuberkuliozė (TB) – tai lėtinė, infekcinė, granulominė liga, kurią sukelia tuberkuliozės mikobakterijos. TB sukelia penkios Mycobacterium tuberculosis (TM) komplekso bakterijos – Mycobacterium tuberculosis, Mycobacterium bovis, Mycobacterium africanum, Mycobacterium microti ir Mycobacterium canetti. Kitų rūšių mikobakterijos (pvz., Mycobacterium avium, Mycobacterium gordonae, Mycobacterium abscesus ir kt.) nustatomos rečiau, tuomet liga vadinama atipine mikobakterioze. Jos gydymo taktika nuo TB skiriasi.

Paprastai pažeidžiami plaučiai, tačiau gali būti ir ekstrapulmoninės TB forma (pleuros, limfmazgių, kaulų, urogenitalinio trakto, sąnarių, pilvo organų, smegenų dangalų ir kitų organų).

TB ir toliau išlieka viena labiausiai paplitusių infekcinių ligų pasaulyje, lemianti didelį sergamumą ir mirštamumą (1, 2). Maždaug trečdalis pasaulio gyventojų yra infekuoti TM) (3). Pasaulio sveikatos organizacija skelbia, kad 2015 metais nustatyta 10,4 mln. naujų TB atvejų, o beveik penktadalio jų išeitys buvo letalios (4). Nors Lietuvoje dėl tiesioginių TB komplikacijų miršta santykinai mažai pacientų, sergamumas šia liga yra vienas didžiausių Europos Sąjungoje – Lietuvoje nustatomi 56 nauji TB atvejai 100 tūkst. gyventojų per metus (4).

Pagrindinis infekcijos šaltinis yra žmogus, sergantis atvira plaučių TB forma. Įprasta manyti, kad kvėpavimo takų TB ir plaučių TB yra sinonimai, tačiau kvėpavimo takų TB apima plaučių, gerklų ir endobronchinę TB formas. Iš visų TB formų (įskaitant ir ekstrapulmoninę) užkrečiama tik plaučių ir kvėpavimo takų (tarp jų ir gerklų) TB. Liga plinta aerozoliniu būdu (per smulkius lašelius, patenkančius į aplinką kalbant, kosint, čiaudint ir pan. sergant plaučių ar kvėpavimo takų TB). Pavojingiausi asmenys, kurių skrepliuose atlikus mikroskopinį tyrimą nustatoma mikobakterijų.

TB suserga palyginti nedidelė dalis užsikrėtusių šia bakterija pacientų (apie 5–15 proc. iš 2–3 mlrd. infekuotų MT asmenų), likę serga latentine TB – šiuo atveju organizmas stabdo TM bakterijų augimą, nėra klinikinės TB išraiškos, ligoniai patys neperduoda infekcijos kitiems, nereikalingas ir gydymas (išskyrus tam tikrus atvejus, pavyzdžiui, prieš gydymą navikų nekrozės faktoriaus alfa blokatoriais). Būtina įvertinti, ar asmuo nėra užsikrėtęs žmogaus imunodeficito virusu (ŽIV), nes tikimybė susirgti TB yra daug didesnė, gali nebūti klinikinių simptomų net tada, kai TB yra aktyvi.

 

Klinika

 

TB simptomai yra nespecifiniai. Paprastai TB įtariama ilgiau užtrukus subfebriliam karščiavimui be aiškios priežasties, varginant kosuliui (naujai išsivysčiusiam ar pasikartojančiam, paprastai trunkančiam ilgiau kaip 3 savaites), skrepliavimui (su / be kraujo priemaišų), atsiradus silpnumui, prakaitavimui, suprastėjus apetitui, be aiškių priežasčių krintant kūno svoriui. Gali būti juntamas krūtinės, nugaros skausmas, pasireikšti pleuritas.

Kai yra kitų organų TB, pasireiškia jų pažeidimo simptomai ir bendrieji intoksikacijos simptomai (karščiavimas, silpnumas, svorio kritimas).

Pacientams, užsikrėtusiems ŽIV , sergantiems AIDS, TB gali pasireikšti klasikiniais ligos simptomais, tačiau dažniau simptomų būna mažiau, jie nespecifiški. Radiologiniai tyrimai neretai irgi klaidina – penktadaliui sergančių ŽIV ir TB pacientų krūtinės ląstos rentgenogramoje nestebima pokyčių (5).

Galimos plaučių TB komplikacijos: kraujo atkosėjimas, pneumotoraksas, bronchektazės, išplitęs plaučių pažeidimas su destrukcija, piktybiniai navikai, lėtinė plaučių aspergiliozė.

Kad ir kaip būtų gaila, persirgus TB imuniteto nesusidaro, todėl galima susirgti pakartotinai. TB recidyvu vadinama pakartotinė TB infekcija asmeniui, kuris buvo anksčiau gydytas nuo TB ir pasveiko, bet atlikus bakteriologinius tyrimus nustatoma TM. Tokiu atveju klinikinė simptomatika nesiskiria nuo naujai nustatytos TB. Kiek sudėtingiau, kai latentinė TB virsta aktyvia liga, nes simptomai pasireiškia tik esant pažengusiai liga, todėl aktyvi TB gali likti ilgai nenustatyta ir potencialiai užkrečiama 2–3 metus ar ilgiau.

 

Diagnostika

 

TB, kaip ir kitų ligų diagnostika, remiasi būdingais klinikiniais simptomais, ligos anamneze, galimų aplinkos rizikos veiksnių įvertinimu, objektyvaus tyrimo radiniais, laboratorine, mikrobiologine ir instrumentine diagnostika.

 

Rizikos veiksnių įvertinimas

 

TB rizikos veiksniai skirstomi į 2 pagrindines dalis (6):

  • imuniteto sutrikimai (vadinamieji šeimininko veiksniai);
  • padidėjusi užsikrėtimo rizika (nepalankūs aplinkos veiksniai).

Pirmai grupei priklauso alkoholio, narkotikų vartojimas, rūkymas, nevisavertė mityba (mažas svoris, vitamino D stoka, geležies stoka), lėtinės ligos (silikozė, onkologinės ligos, cukrinis diabetas, inkstų ligos, skrandžio operacijos, celiakija, kepenų cirozė), imunosupresinės būklės (ŽIV, AIDS, gydymas gliukokortikoidais, navikų nekrozės faktoriaus inhibitoriais, imunosupresija po transplantacijų), vyresnis amžius, vyriškoji lytis.

Antrai grupei priklauso artimas kontaktas su TB sergančiaisiais, gimimas TB endeminėje srityje, socioekonominis statusas, mažumų grupės, darbas sveikatos priežiūros ir kitose padidintos rizikos užsikrėsti TB įstaigose.

 

Objektyvus tyrimas

 

Sergant plaučių TB, objektyvaus ištyrimo požymiai nėra specifiniai. Paduslėjusi perkusija, susilpnėjęs vezikulinis alsavimas rodo pleuros sustorėjimą ar pleuritą. Karkalai gali būti girdimi viso įkvėpimo metu arba tik po trumpo kosulio arba iš viso neišklausomi. Esant pažeistam dideliam plaučių plotui, gali būti girdimas amforinis kvėpavimo garsas.

 

Laboratorinė diagnostika

 

Rutininiai bendrojo kraujo ir biocheminiai kraujo tyrimai ligos pradžioje paprastai yra nepakitę, šiek tiek gali padidėti C reaktyvusis baltymas (CRB). Vėliau gali išryškėti normocitinė anemija, trombocitozė, leukocitozė, retai – monocitozė, biocheminiu kraujo tyrimu nustatoma hipoalbuminemija ir hipergamaglobulinemija. Hiponatremija gali būti susijusi su nepakankamo antidiurezinio hormono sekrecijos sindromu, retai – su antinksčių nepakankamumu (6).

 

Mikrobiologinė diagnostika

 

Skreplių tepinėlio mikroskopija: rekomenduojama atlikti bent 3 ėminius (ne daugiau kaip 2 tą pačią dieną), bent vienas jų turėtų būti paimtas ryte. Tiriant kitus bandinius – bronchų išplovas / pleuros punktatą ar kitus organizmo skysčius, pakanka vienos mikroskopijos. Remiantis šiuo metu galiojančiomis Pasaulio sveikatos organizacijos rekomendacijomis, laikyti, kad skreplių mikroskopija yra teigiama, užtenka vos vieno teigiamo mėginio.

Skreplių / bronchų išplovų / pleuros punktato / kitų organizmo skysčių kultūros. Pasėlio būdu užaugintos TM patvirtina TB ir leidžia ištirti jų jautrumą vaistams nuo TB. Tai ilgus metus išliekantis auksinis standartas diagnozuojant TB, tačiau reikalinga laboratorijos patirtis. Tyrimo atsakymas gali užtrukti iki 12 savaičių.

Būtina ištirti, ar visos laboratorijoje išskirtos mikobakterijų kultūros priklauso MT kompleksui.

 

Instrumentinė diagnostika

 

Radiologinis ištyrimas. Radiologiniai radiniai dažnai nėra specifiniai. Gali būti stebimi plaučių infiltratai, židiniai, periferinis (-iai) darinys (-iai) (dažnai su ertme viduje). Pagal radiologinius vaizdus klinikinėje praktikoje vis dar pasitaiko skirstymas į tarpuplaučio limfmazgių TB, infiltracinę plaučių TB, židininę plaučių TB, diseminuotą plaučių TB, kaverninę, fibrozinę ir cirozinę plaučių TB, tuberkulomą, pleuros tuberkuliozę ir pleuritą.

Dažniausiai TB pažeidžia viršutines plaučių skiltis. Tiesa, normali krūtinės ląstos rentgenograma TB diagnozės nepaneigia. Tam tikrais atvejais gali būti atliekami ir detalesni krūtinės ląstos radiologiniai tyrimai (pvz., krūtinės ląstos kompiuterinė tomografija).

Radiologiniai tyrimai kartu su bakteriologiniais tyrimais naudojami gydymo efektyvumui vertinti.

Įtarus TB, tam tikrais atvejais (ypač neatkosint skreplių) gali būti atliekama bronchoskopija – paimtos išplovos vertinamos mikroskopu dėl rūgščiai atsparių bakterijų, atliekamas pasėlis, retais, neaiškiais atvejais diferencinei diagnostikai gali būti paimama biopsija.

 

Histologinis tyrimas. TB būdinga imuninė granuloma su nekroze. Tačiau granuloma be nekrozės nepaneigia TB diagnozės. Visais atvejais, kai biopsijos medžiagoje randama granuloma, bet nenustatoma TM, būtina paneigti kitas granulomos priežastis, papildomai tirti ir ieškoti TM.

TB diagnozuojama aptikus TM arba tuberkuliozei būdingų morfologinių pokyčių, kai paneigtos kitos granulomų priežastys. Tik išskirtiniais atvejais TB gali būti diagnozuojama remiantis klinikiniais simptomais ir rentgeninio tyrimo duomenimis.

Molekulinės biologijos diagnostikos metodai. Tai galimybė greitai išskirti MT kompleksui priklausančias bakterijas, ištirti jautrumą izoniazidui ir rifampicinui. Šiais metodais galima nustatyti ir bakterijų genų mutacijas, nurodančias atsparumą vaistams.

Pasaulio sveikatos organizacijos rekomenduojamas greitos molekulinės diagnostikos tyrimas yra Gene Xpert® MTB / RIF tyrimas. Pirmą kartą plaučių TB diagnostikai tyrimas panaudotas 2010 metais. Nuo 2013-ųjų rekomenduojamas ir vaikams bei ekstrapulmoninės TB diagnostikai. Šis tyrimas yra daug tikslesnis, palyginti su mikroskopija, padeda nustatyti atsparumą rifampicinui.

LPA (angl. line-probe assays) tyrimu nustatomas TM atsparumas izoniazidui, LPA tyrimo jautrumas yra mažesnis (vidutiniškai 85 proc.) nei pasėlio. Vadovaujantis Pasaulio pasaulio sveikatos rekomendacijomis, LPA siūloma naudoti tik skreplių ėminiams, kuriuose mikroskopuojant aptikta RAB ar pasėlyje išaugo TM, tirti.

Pasaulyje dažniau naudojami greitos molekulininės diagnostikos testai, dažniau atsisakoma skreplių tepinėlio mikroskopijos, nors vertinant TB gydymo efektyvumą skreplių mikroskopija ir pasėlis yra būtini. Nepaisant pažangos diagnozuojant TB, vis dar pasitaiko atvejų, kai TB nustatoma be bakteriologinio patvirtinimo, pavyzdžiui, 2015 metais tik apie pusė (57 proc.) plaučių TB atvejų, apie kuriuos pranešė Pasaulio sveikatos organizacija, buvo patvirtinti bakteriologiniu tyrimu.

Kiti tyrimai. Mantu ir gama interferono testai nepadeda atskirti atvirosios TB nuo persirgtos ar buvusio skiepo, todėl paprastai atliekami diagnozuojant latentinę, o ne aktyvią TB.

Mantu testas – visiems žinomas ir dažnai taikomas diagnostinis TB metodas, kai po oda suleidžiama tuberkulino ir stebima organizmo reakcija odoje, t. y. sukietėjimas, eritema. Šiam testui trūksta specifiškumo, nes suleidžiamas mikobakterijų antigenų mišinys yra būdingas daugumai mikobakterijų – patogeniškų ir tų, kurių gausu aplinkoje, bet nepatogeniškų. Rezultatams įvertinti naudojamos ne itin tiksliai apibrėžtos ribos, jie nėra objektyvūs, nes susidaręs natūralus odos paraudimas aplink papulę gali sukelti klaidingą nuomonę apie pozityvų atsakymą. Kita problema – klaidingai teigiama reakcija asmenims, vakcinuotiems BCG (Bacillus Calmette Guerin) vakcina. Mantu testas gali sukelti klaidingai neigiamus rezultatus, kai žmogaus imunitetas yra nusilpęs (pvz., sergantiems ŽIV), dėl kitų neaiškių aplinkybių nevyksta reakcija į tuberkuliną.

Gama interferono testo jautrumas ir specifiškumas didesnis nei Mantu testo, nes mažiau kryžminių reakcijų su aplinkoje esančiomis mikobakterijomis ir vakcinos nuo TB antigenais. Mėginys laikomas teigiamu, kai išskirto gama interferono kiekis viršija tam tikrą lygį (atskirose laboratorijose gali šiek kiek skirtis).

 

Kuo skiriasi latentinė ir aktyvi TB?

 

Latentinė TB nustatoma tuomet, kai asmuo yra užsikrėtęs TM, tačiau bakterijos nėra aktyvios ir nesukelia jokių ligos simptomų: plaučių rentgenograma būna normali, mikroskopu bakterijų neaptinkama. Asmuo, sergantis latentine TB, neužkrečia kitų žmonių. Tokiu atveju mikobakterijų organizme nesidaugina, todėl jų nustatymas mikrobiologiniais tyrimais yra neefektyvus.

Tikimybė, kad latentinė TB gali virsti aktyvia TB, yra apie 10 proc. ir yra didžiausia pirmaisiais užsikrėtimo metais. Tai priklauso nuo asmens imuninės sistemos, amžiaus, įkvėpto bakterijų kiekio (ekspozicijos laikas), patogeniškumo. Latentinė TB gali tęstis nuo keleto savaičių iki kelerių metų ar net visą gyvenimą.

Aktyvia TB sergantys asmenys yra užkrato platintojai. Dažniausiai pasireiškia TB būdingi simptomai – kosulys, užsitęsęs 3 ir daugiau savaičių, dusulys, karščiavimas, naktinis prakaitavimas, nuolatinis skrepliavimas, apetito stoka, svorio netekimas, skausmas krūtinėje, atsikosėjimas krauju, bakteriologiniais, mikroskopiniais tyrimais nustatomos mikobakterijos, pakitusi plaučių rentgenograma…

Daugiau skaitykite žurnale „Internistas“ Nr.8, 2017.

Parengė gyd. Virginija Kalinauskaitė-Žukauskė


440 minčių apie “Plaučių tuberkuliozė: paplitimas, diagnostikos metodai ir gydymo principai. Epidemiologija

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