1 / 55

Tuberculosis

Tuberculosis. Tuberculosis. Definition An infectious disease caused by mycobacteria of tuberculosis complex ( Mycobacterium tuber - culosis , M.bovis , M.africanum ) and characteri - sed by the formation of granulomas in infected

atira
Download Presentation

Tuberculosis

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. Tuberculosis

  2. Tuberculosis Definition An infectiousdiseasecaused by mycobacteria of tuberculosiscomplex (Mycobacteriumtuber- culosis, M.bovis, M.africanum) and characteri- sed by theformation of granulomasininfected tissues and by cell - mediatedhypersensitivity. Most commonly a disease of thelungs but in- fectionsmayoccurat many tissuesidesor maydisseminate.

  3. Tb - epidemiology • 1/3 worldpopulationisinfected on Mycobacteriumtuberculosis • 50% issmear-positive • incidencerate of Tb isgrowingatapproximately 0,4%/ year, but much fasterinSub-SaharanAfrica and incountries of theformerSoviet Union

  4. TB - epidemiology • High riskgroupsinthe United Statesincludeimmigrantsfromareas of theworldwheretbis common

  5. High-Risk Groups for TB Infection Foreign-Born/Immigrants Foreign-born59% Foreign-born 27% U.S.-born 41% U.S.-born41% U.S.-born 73% Foreign-born 59% 1992 2008 Cases of TB in foreign-born and U.S.-born, 1992 and 2008

  6. Tb - epidemiology High - riskgroups for TB: • patientsinfectedwith HIV (HIVisthestrongestknownriskfactor for developing TB disease) • prolongedtherapywithcorticosteroids, immunosupressivetherapy, such as tumor necrosisfactor-alpha (TNF-α) • peopleinfectedwithM.tuberculosiswithin past 2 years (thehighestrisk of developing active TB in first 2 years)

  7. Tb - epidemiology High - riskgroups for TB: • infants and childrenyoungerthan 4 years old (due to underdevelopedimmune system) • peoplewithmedicalconditionsknown to increasetherisk for TB • diabetes • silicosis • severekidneydisease • certaintypes of cancer • certainintestinalconditions

  8. Tb - epidemiology High - riskgroups for TB: • immigrantsfrom high endemicareas • peoplewhoinjectdrugs (injectingdrugsmayweakenimmune system) • peopleaftertransplantations

  9. Tb - epidemiology Additionalfactors : • homelessness • poverty • poorlivingconditions(lack of hygiene, malnutrition) • substanceabuse

  10. Tb - ethiology GenusMYCOBACTERIUM • 30 well – characterised and many unclassifiedbaccili • most – not pathogenic for humans • most – freelivingsaprophytes • acid – fast • slow – growing (Lowenstein-Jansen medium) • non - sporulating

  11. Acid-fastness is a physical property of some bacteria referring to their resistance to decolorization by acids during staining procedures. acid-fast organisms are difficult to characterize using standard microbiological techniques high content of mycolic acid in cell walls Ziehl-Neelsen stain

  12. Tb - transmission • human to human via respiratory route • consumption of contaminatedcows’ milk • perinatal and woundtransmission (veryrare)

  13. Tb - transmission FACTORS AFFECTING THE POSSIBILITY OF INFECTION • infectiousness of person withactive TB • environment inwhichexposureoccurred • length of exposure • virulence (strength) of thetuberclebacilli • geneticpredisposition of an infected person

  14. Tb - transmission FACTORS THAT REDUCE THE RISK OF INFECTION • isolation of contagiouspersons • adequateventilation • effectivetreatment to infectiouspersons as soon as possible

  15. Tb - pathogenesis Entry of tuberclebacilliintolungs (alveoli) ↓ alveoli – subpleural, middle to upperzones ↓ bacilliingested by alveolarmacrophages (undergo slow multiplication) ↓ transport to theregionallymphnodes ↓ ↓ stoppingthedisseminationhematogenous atthelevel of regionallymphnodesdissemination (kidney, CNS, lungs)

  16. Tb - pathogenesis Hematogenous disseminations ↓ ↓ healing potencial foci of later reactivation

  17. Tb - pathogenesis 2-8 weeksafterprimeryinfection (whenbacillimultiplyinsidemacrofages) → development of cellmediatedhypersensivity (positivetuberculin skin test) → lymphocytes enter theareas of infection → chemotacticfactors (interleukins, lymphokines) → monocytes enter thearea → transformationintomacrophages and histiolyticcells → becomeorganisedintogranulomas

  18. Tb - pathogenesis Granulomatouslesionsconsist of central area of necroticmaterial of a cheesynature, called caseation,surrounded by epithelioidcells and Langhans’ giantcellswithmultiplenuclei Subsequentlytheareamayhaelcompletly and becomecalcified Mycobacteriamaypersistin macrophages for years but theirfurther multiplication and spreadisusu. confined (theyare dormant but capable of beingactivated)

  19. Granulomatous leasion

  20. Tb manifestations • Primarytuberculosis • Latent (dormant) TB infection (LTBI) • Secondarytuberculosis (recrudescence, adulttypetb - caused by reactivationor less often by reinfection )

  21. Primarytuberculosis • first infectionwith M. tuberculosis • usu. asymptomatic (90-95% unrecognised) • mild flu-like symptoms • smalltransientpleuraleffusion • enlargment of hilarlymphnodes may sometimes occur • positivetuberculin skin test and Quantiferon

  22. Latent (dormant) infection • asymptomatic • positivetuberculine skin test • positiveQuantiferon People with latent TB infection are not infectious and cannot spread TB bacteria to others. However, if TB bacteria become active in the body and multiply, the person will get sick with TB disease.

  23. Reactivationpulmonary Tb • months to yearsafterprimaryinfection • oftenlocatedintheupperlobes of thelungs (areawherebacteriahavebeenable to persistin a dormant state afterspreading) • kidney, long bones, spinemay be sites of reactivation

  24. Reactivationpulmonary Tb • chestradiograph – infiltratesintheapical and posteriorbronchopulmonarysegments of theupperlobes, caesationnecrosis, pulmonarycavities withbaccili) • may be unilateralorbilateral

  25. Reactivation pulmonary Tb • gradualonset • tiredness, malaise, anorexia, loss of weight, fever, drenchingnightsweats, anxiety • cough: non productiveormucoid, purulentorbloodstained • dullacheinthechest • occasionallyhemoptysis

  26. Tb - symptoms EXTRAPULMONARY TUBERCULOSIS: • Lymphnodes – peripheralorhilar • Pleura – pleuraleffusion • Gastrointestinaltract – mainlytheileocaecalarea, occ. peritoneum • Genitourinary system – thekidney, mayalsocausepainless, craggyswellings of epididymis and salpingitis, tubalabscesses and infertilityinfemales • CNS • Skeletal system – arthritis and osteomyelitiswithcoldabscessformation

  27. Tb - symptoms EXTRAPULMONARY TUBERCULOSIS: F. Eye – chorioiditis, iridocyclitis, keratoconjunctivitis G. Pericardium – constrictivepericarditis H. Adenalglands – destruction and Addison’sdisease I. Skin – lupusvulgaris

  28. Tb – diagnostics • History and phisicalexamination • ChestX-ray • Bacteriology (thediagnosis of tuberculosisisestablishedwhentuberclebaciciareidentifiedinthesputum, urine, body fluid, ortissues of thepatient) - sputum/ inducedsputum/ bronchoalveolarlavageexamination: • stain • culture: 4-8 weeks on classical media, detectionusingradiometrictehniques • Identification of mycobacterialDNA-PCR

  29. Tb – diagnostics 4. Serologictests (ELISA – IgGantibody to selectedmycobacterialantigens) 5. Chromatographictechniques (identifycharacteristiclipids) 6. Tuberculin test – Mantoux test • isbased on cell-mediatedimmunity • mainlyused for: A. contacttracing B. BCG vaccinationprogrammes

  30. Tb – diagnostics Mantoux test: PPD/OT test PPD – purified protein derivative OT – old tuberculin • tuberculinis applied intradermally on theforearm • forearmshould be examinedwithin 48-72 hours • reactionistransversediameter of indurationaround injectionsiteassessed by gentlepalpation • erythema (redness) is not measured

  31. Tb – diagnostics Tuberculin test ispositivewhenindurationis ≥ 5 mm for personslikely to be infected : • peoplelivingwith HIV • immunosupressedpatients • peopleafter organ transplantations • recentclosecontacts of peoplewithinfectious TB • peoplewithchestX-rayfindingssuggestive of previous TB disease

  32. Tb – diagnostics Tuberculin test ispositivewhenindurationis ≥ 10 mm for personsfrompopulationgroupsatelevatedrisk of TB: • peoplewhohaverecentlycome to US fromareaswhere TB iscommon • peoplewhoinjectdrugs • peoplewithcertainmedicalconditionsthatincreaserisk for TB • childrenyoungerthan 4 years old

  33. Tb – diagnostics Tuberculin test ispositivewhenindurationis ≥ 15 mm for persons: • fromlowriskpopulationsesp. ingeographicareasknown to have a high prevalance of nonspecifictuberculinreactivity

  34. Tb - prevention 1. Nonspecific 2. Specific • Chemoprophylaxis • BCG vaccination BacillusCameletteGuerinis an attenuatedstrain of M. bovis. Itinducestuberculinhypersensivity. Dermalreactionisusu. not as large as thatwhich follows natural infection, does not persist as long, and variesstrain to strain of vaccine.

  35. Treatment of LTBI -chemoprophylaxis Prophylacticantituberculouschemotherapyshould receivepatientswithpositive QuantiFERON and TBT with: • high risk for developing active TB disease onceinectedwithM.tuberculosis

  36. Chemoprophylaxis • INH 300 mg/d (for children 5 mg/kg/d) • For 6 month • One single morning dose

  37. Tb treatment • combinations of drugsarerequired, to preventtheresistanceduringthecourse of therapy (mycobacteriacandevelopetheresistance to ant single drug) • treatmentmust be administered for months to years (depending on kinds of drugs), becoursetheresponse of mycobacterialinfections to chemotherapyis slow

  38. Tb - treatment „First-line” drugs: Isoniazid (INH), Rifampin (RIF), Pyrazinamide (PZA), Ethambutol (EMB), Streptomycin (SM) „Second-line” drugs: • In thecase of resistance to thedrugs of first choice • In case of failure of clinicalresponse to conventionaltherapy Ethionamid, Capreomycin, Cycloserine, AminosalicylicAcid (PAS), Ciprofloxacin, Ofloxacin, Rifabutin, Clofazimine

  39. Tb treatment • Antituberculousdrugscan be dividedinto: bacteriostatics: • EM bactericidal: • SM • INH (againstrapidlygrowingmycobacteria) • RMP (againstslowlygrowingorganisms)

  40. Tb - treatment Tuberclebaccilliexistintuberculouspatiens inthreepools: • extracellularpool (RMP, INH+SM) • intracellularpool (RMP, INH+ PZA) • necroticcaseumpool (RMP)

  41. Tb treatment INH (5 mg/kg/d - us. 300mg/d) + RMP (10 mg/kg/d – us.600mg/d) + PZA (25mg/kg/d) + EMB (15 mg/kg/d) or SM (15mg/kg/d) for 2 month followed by: INH (5 mg/kg/d - us. 300mg/d) + RMP (10 mg/kg/d – us.600mg) for 4 month

  42. Adversereactions of antituberculousdrugs: INH • Allergyreactions – fever and skin rashes, lupuserythematosus • Toxiceffect – injury to theliver • In 10 to 20% of treatedpatients, seriousin 1-2% (transaminasevalueincreasesup to 3 to 4 timesnormal • Oftenasymptomatic, rarewithloss of appetite, nausea, vomiting, jaudince • Toxicitydepends on age, isgreaterinalcoholic, duringpregnency and post-partum period,

  43. Adverse reactions of antituberculous drugs: C. Peripheralneuropathy • Due to INH-inducedpyridoxinedeficiency • More frequentinalcoholic, poornourishedpersons, elderly • Dailydose of 25 to 50 mg of pyridoxinecanpreventthiscomplications D. Anemia E. Agranulocytosis

  44. Adverse reactions of antituberculous drugs: RIF • Hepatitis ( transientincrease of transaminase and bilirubin) and cholestaticjaudince (rare) • Thrombocytopenia • Renalfailure • Fever • Allergicreactions

  45. Adverse reactions of antituberculous drugs: PZA • Hepatotoxicity (1-5% patients) especially, when high dosesareused • Hiperurykemia • Gastrointestinalsymptoms

  46. Adverse reactions of antituberculous drugs: EMB • Canaffectocularnerve (first symptom is inability to distinquishbluefromgreen) B. Hiperurykemia

  47. Adverse reactions of antituberculous drugs: SM • Nephrotoxicity – renaltubulardamage • Ototoxicity • Vestibulardamage

  48. Drug-Resistant TB

More Related