MICOBATTERI - units.it · the latter accounting for the protective e!ect of antiretro-viral therapy...
Transcript of MICOBATTERI - units.it · the latter accounting for the protective e!ect of antiretro-viral therapy...
MICOBATTERI
! Mycobacterium tuberculosis
! Mycobacterium leprae
! Bastoncini alcool-acido resistenti
Immobili
! Particolare composizione parietale
Asporigeni
Aerobi (anaerobi facoltativi?)
MICOBATTERI
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
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’
Mycobacterium tuberculosis: meccanismo di patogenicità
Patogenesi TBC
primaria
#tubercolo
Sezione del tubercolo
TUBERCOLOSI PRIMARIA
>90%
GUARIGIONE CALCIFICAZIONE
<10%
TUBERCOLOSI PRIMARIA PROGRESSIVA
• bronchi # TBC forma aperta • sangue # TBC miliare
TUBERCOLOSI MILIARE
primaria
Patogenesi TBC
TUBERCOLOSI PRIMARIA
>90%
GUARIGIONE CALCIFICAZIONE
<10%
TUBERCOLOSI PRIMARIA PROGRESSIVA
RIATTIVAZIONE REINFEZIONE
TUBERCOLOSI SECONDARIA
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
NELL’UNIONE EUROPEA
In Italia
FARMACI ANTITUBERCOLARI
$ Isoniazide (analogo vit B6) $ Pirazinamide $ Etambutolo $ Rifampicina $ Streptomicina
FARMACI DI 1a LINEA
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
Pirazinamide
! Meccanismo d’azione " inibisce FAS1 #blocco sintesi
acidi micolici
! profarmaco " attivato da pH acido
! Effetti collaterali " tossicità epatica " % escrezione di acido urico
#gotta
Etambutolo
! Meccanismo d’azione " arabinosiltransferasi
#blocco sintesi arabinogalattani (parete)
! Rifampicina ! Streptomicina
1a FASE ! 4 farmaci per 2 mesi
& isoniazide & rifampicina & etambutolo & pirazinamide
TERAPIA ANTITUBERCOLARE
2a FASE ! 2 farmaci per 4 mesi
& isoniazide & rifampicina
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
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
! 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).
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
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!!