MICOBATTERI - units.it · the latter accounting for the protective e!ect of antiretro-viral therapy...

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MICOBATTERI !Mycobacterium tuberculosis !Mycobacterium leprae

Transcript of MICOBATTERI - units.it · the latter accounting for the protective e!ect of antiretro-viral therapy...

Page 1: MICOBATTERI - units.it · the latter accounting for the protective e!ect of antiretro-viral therapy (ART). Until 2008, WHO estimates of TB mortality used VR data for only three countries.

MICOBATTERI

! Mycobacterium tuberculosis

! Mycobacterium leprae

Page 2: MICOBATTERI - units.it · the latter accounting for the protective e!ect of antiretro-viral therapy (ART). Until 2008, WHO estimates of TB mortality used VR data for only three countries.

! Bastoncini alcool-acido resistenti

Immobili

! Particolare composizione parietale

Asporigeni

Aerobi (anaerobi facoltativi?)

MICOBATTERI

Page 3: MICOBATTERI - units.it · the latter accounting for the protective e!ect of antiretro-viral therapy (ART). Until 2008, WHO estimates of TB mortality used VR data for only three countries.

Componente lipidica

cere

ACIDI MICOLICI ac. grassi a lunga catena, saturi, ramificati

MICOSIDI glicolipidi

FATTORE CORDALE: importante per la virulenza

CERE esteri di acidi grassi e alcoli a catena lunga

Parete dei micobatteri

Page 4: MICOBATTERI - units.it · the latter accounting for the protective e!ect of antiretro-viral therapy (ART). Until 2008, WHO estimates of TB mortality used VR data for only three countries.

La struttura della PARETE è responsabile di:

! Resistenza ambientale • Essicamento • Disinfettanti • Acidi • Alcali • Calore (pasteurizzazione a 62° x 30’) • SENSIBILI agli UV

! Crescita lenta • 3-4 settimane, su terreni di coltura particolari

Uccisi a: " 100° per 5’ "  80° per 20’

Page 5: MICOBATTERI - units.it · the latter accounting for the protective e!ect of antiretro-viral therapy (ART). Until 2008, WHO estimates of TB mortality used VR data for only three countries.

Mycobacterium tuberculosis: meccanismo di patogenicità

Page 6: MICOBATTERI - units.it · the latter accounting for the protective e!ect of antiretro-viral therapy (ART). Until 2008, WHO estimates of TB mortality used VR data for only three countries.

Patogenesi TBC

primaria

#tubercolo

Page 7: MICOBATTERI - units.it · the latter accounting for the protective e!ect of antiretro-viral therapy (ART). Until 2008, WHO estimates of TB mortality used VR data for only three countries.

Sezione del tubercolo

Page 8: MICOBATTERI - units.it · the latter accounting for the protective e!ect of antiretro-viral therapy (ART). Until 2008, WHO estimates of TB mortality used VR data for only three countries.

TUBERCOLOSI PRIMARIA

>90%

GUARIGIONE CALCIFICAZIONE

<10%

TUBERCOLOSI PRIMARIA PROGRESSIVA

• bronchi # TBC forma aperta • sangue # TBC miliare

Page 9: MICOBATTERI - units.it · the latter accounting for the protective e!ect of antiretro-viral therapy (ART). Until 2008, WHO estimates of TB mortality used VR data for only three countries.

TUBERCOLOSI MILIARE

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primaria

Patogenesi TBC

Page 11: MICOBATTERI - units.it · the latter accounting for the protective e!ect of antiretro-viral therapy (ART). Until 2008, WHO estimates of TB mortality used VR data for only three countries.

TUBERCOLOSI PRIMARIA

>90%

GUARIGIONE CALCIFICAZIONE

<10%

TUBERCOLOSI PRIMARIA PROGRESSIVA

RIATTIVAZIONE REINFEZIONE

TUBERCOLOSI SECONDARIA

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NEL MONDO, nel 2015: 1,4 milioni di morti

GLOBAL TUBERCULOSIS REPORT 2016 :: 27

Estimated new TB cases (all forms) per 100 000 population per year

0–24.925–99100–199200–299≥300No dataNot applicable

:: FIG. 3.3 Estimated TB incidence rates, 2015

HIV prevalencein new TB casesall ages (%)

0–4.95–9.910–1920–49≥50No dataNot applicable

:: FIG. 3.4 Estimated HIV prevalence in new and relapse TB cases, 2015

GLOBAL TUBERCULOSIS REPORT 2016 :: 29

of the country (e.g. as in China) provide an interim solu-tion. Mortality surveys can also be used to estimate deaths caused by TB. In 2015, most countries with a high burden of TB lacked national or sample VR systems, and few had conducted mortality surveys. In the absence of VR systems or mortality surveys, TB mortality can be estimated as the product of TB incidence and the case fatality ratio (CFR), or from ecological modelling based on mortality data from countries with VR systems.

TB mortality among HIV-positive people is hard to measure even when VR systems are in place, because deaths among HIV-positive people are coded as HIV deaths and contributory causes (e.g. TB) are often not reli-

ably recorded. TB deaths among HIV-positive people were estimated as the product of TB incidence and the CFR, with the latter accounting for the protective effect of antiretro-viral therapy (ART).

Until 2008, WHO estimates of TB mortality used VR data for only three countries. This was substantially im-proved to 89 countries in 2009, although most of the data were from countries in the European Region and the Region of the Americas, which accounted for less than 10% of the world’s TB cases. For the current report, VR data were used for 128 countries (Fig. 3.9), which collectively accounted for 52% of the estimated number of TB deaths (among HIV-negative people) globally in 2015. The WHO African

:: FIG. 3.5 Global trends in the estimated number of incident TB cases and the number of TB deaths (in millions), 2000–2015. Shaded areas represent uncertainty intervals.

All TB cases

Notifications of new and relapse cases

HIV-positive TB cases

TB deaths among HIV-negative people

TB deaths among HIV-positive people

TB incidence TB deaths

0

0.5

1

1.5

2

2000 2005 2010 2015

Mill

ions

0

5

10

2000 2005 2010 2015

Mill

ions

:: FIG. 3.6 Global trends in estimated TB incidence and mortality rates, 2000–2015. The black line show notifications of new and relapse cases, for comparison with estimates of the total incidence rate. Shaded areas represent uncertainty intervals.

All TB cases

Notifications of new and relapse cases

HIV-positive TB cases0

5

100

2000 2005 2010 20150

10

20

30

2000 2005 2010 2015

TB incidence TB mortality (HIV-negative)

Rate

per

100

000

popu

latio

n pe

r yea

r

Rate

per

100

000

popu

latio

n pe

r yea

r

150

200

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NELL’UNIONE EUROPEA

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In Italia

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FARMACI ANTITUBERCOLARI

$  Isoniazide (analogo vit B6) $  Pirazinamide $  Etambutolo $  Rifampicina $  Streptomicina

FARMACI DI 1a LINEA

Page 16: MICOBATTERI - units.it · the latter accounting for the protective e!ect of antiretro-viral therapy (ART). Until 2008, WHO estimates of TB mortality used VR data for only three countries.

Isoniazide

! Meccanismo d’azione "  inibisce allungamento acidi grassi (FAS2-fatty acid synthetase) "  blocca la sintesi degli acidi micolici (60-70 C)

!  profarmaco "  attivato dalla catalasi batterica katG

!  Meccanismi di resistenza "  modificazione bersaglio "  via metabolica alternativa

!  Effetti collaterali "  febbre, tossicità epatica

"  nevriti "  anemie

carenza vit B6 #assunzione B6

Page 17: MICOBATTERI - units.it · the latter accounting for the protective e!ect of antiretro-viral therapy (ART). Until 2008, WHO estimates of TB mortality used VR data for only three countries.

Pirazinamide

! Meccanismo d’azione "  inibisce FAS1 #blocco sintesi

acidi micolici

!  profarmaco "  attivato da pH acido

!  Effetti collaterali "  tossicità epatica "  % escrezione di acido urico

#gotta

Page 18: MICOBATTERI - units.it · the latter accounting for the protective e!ect of antiretro-viral therapy (ART). Until 2008, WHO estimates of TB mortality used VR data for only three countries.

Etambutolo

! Meccanismo d’azione "  arabinosiltransferasi

#blocco sintesi arabinogalattani (parete)

!  Rifampicina !  Streptomicina

Page 19: MICOBATTERI - units.it · the latter accounting for the protective e!ect of antiretro-viral therapy (ART). Until 2008, WHO estimates of TB mortality used VR data for only three countries.

1a FASE !  4 farmaci per 2 mesi

&  isoniazide &  rifampicina &  etambutolo &  pirazinamide

TERAPIA ANTITUBERCOLARE

2a FASE !  2 farmaci per 4 mesi

&  isoniazide &  rifampicina

Page 20: MICOBATTERI - units.it · the latter accounting for the protective e!ect of antiretro-viral therapy (ART). Until 2008, WHO estimates of TB mortality used VR data for only three countries.

Considerazioni Epidemiologiche Anni ‘70: convinzione che TBC fosse sotto controllo e quasi eliminata. Però:

! Emergenza AIDS nelle nazioni più povere ! Viaggi internazionali ! Immigrazione ! Mancato completamento protocollo terapeutico

NUOVA EMERGENZA $ ceppi MDR (resistenti a isoniazide e rifampicina)

OMS #DOTS directly observed treatment

Page 21: MICOBATTERI - units.it · the latter accounting for the protective e!ect of antiretro-viral therapy (ART). Until 2008, WHO estimates of TB mortality used VR data for only three countries.

FARMACI ANTITUBERCOLARI

$  fluorochinoloni $  etionamide $  cicloserina $  acido aminosalicilico (PAS) $  amikacina, kanamicina (aminoglicosidi) $  capreomicina

FARMACI DI 2a LINEA

OMS: TB & resistenze ! MDR # isoniazide e rifampicina ! XDR # MDR + fluorochinoloni + uno di 2a linea

Page 22: MICOBATTERI - units.it · the latter accounting for the protective e!ect of antiretro-viral therapy (ART). Until 2008, WHO estimates of TB mortality used VR data for only three countries.

! Diversi farmaci in fase sperimentale

Necessità urgente di NUOVI FARMACI antitubercolari !

40 :: GLOBAL TUBERCULOSIS REPORT 2016

:: FIG. 3.18 Percentage of new TB cases with MDR/RR-TBa

Percentage of cases0–2.93–5.96–11.912–17.9>18No dataNot applicable

a Figures are based on the most recent year for which data have been reported, which varies among countries. Data reported before the year 2001 are not shown.

:: FIG. 3.19 Percentage of previously treated TB cases with MDR/RR-TBa

Percentage of cases0–5.96–11.912–29.930–49.9>50No dataNot applicable

a Figures are based on the most recent year for which data have been reported, which varies among countries. Data reported before the year 2001 are not shown. The high percentages of previously treated TB cases with MDR-TB in Bahamas, Bahrain, Belize, Bonaire – Saint Eustatius and Saba, French Polynesia and Sao Tomé and Principe refer to only a small number of notified cases (range: 1-8 notified previously treated TB cases).

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Prevenzione •  Misure di carattere generale

" trattamento contatti, disinfezione

•  Vaccinazione - protezione 70% " BCG (Bacillo di Calmette e Guérin)

ceppo attenuato (variante apatogena di Mycobacterium bovis)

•  Individuare precocemente l’infezione " test di Mantoux

Page 24: MICOBATTERI - units.it · the latter accounting for the protective e!ect of antiretro-viral therapy (ART). Until 2008, WHO estimates of TB mortality used VR data for only three countries.

Test cutaneo: reazione di Mantoux Inoculazione intradermo di 0.1 ml di PPD* * PPD: Protein Purified Derivative

Dopo 48-72 ore: eritema con indurimento > a 10 mm

! Reattività crociata BCG - M. tuberculosis

Quantiferon ☛  approvato dalla FDA ☛  costoso!!