No thing to Disc lo se F un with F ung us C.g a ttii in the Ne - PowerPoint PPT Presentation

Crypto c o c c us g attii in Huma ns a nd Anima ls E milio De Be ss, DVM, MPVM Ore g o n He a lth Autho rity Po rtla nd, OR 97232 e milio .de b e ss@ sta te .o r.us

No thing to Disc lo se

F un with F ung us

C.g a ttii in the Ne ws

Histo ry  1970  F irst c linic a l c a se o f Crypto c o c c us g a ttii  1984  E pid e mio lo g y o f C.g attii ve rsus C.ne o fo rmans pub lishe d  C.g attii iso la te d to tro pic a l/ sub tro pic a l re g io ns  Austra lia , Bra zil, Ca mb o d ia , Ha wa ii, so uthe rn Ca lifo rnia , Me xic o , Pa ra g ua y, T ha ila nd , Vie tna m, Ne pa l, a nd c o untrie s in c e ntra l Afric a  1999  C.g attii d ia g no se d in a g ro up o f huma n a nd a nima l c a se s fro m Va nc o uve r Isla nd , British Co lumb ia  2004  C.g attii iso la te d in Ore g o n  Ste a d y rise in numb e r o f c a se s sinc e 2004  56 C.g attii c a se s re po rte d in Ore g o n to d a te

Crypto c o c c us T a xo no my C. gattii C. neoformans gattii grubii neoformans variet y Vs. B B or C A D AD AD serotypes VNI I VNB VNI VNIV VNIII VGI I VGI VGI I I VGI V molecular types (genotypes) VGI I c VGI I a VGI I b subtypes others Co urte sy o f Dr Julie Ha rris / CDC

Clinic a l Da ta fro m Austra lia  Spe e d a nd Dunt: a ll c a se s o f Crypto c o c c us fro m a po pula tio n-b a se d re g istry (1980-1990) a na lyze d fo r diffe re nc e s b e twe e n C.g attii a nd C. ne o fo rmans with re g a rds to c linic a l a nd ho st immune sta tus  71 c a se s we re type d  51 C.ne o fo rmans  46 ha d immuno suppre ssio n ( 23 HIV positive , 23 with a no the r unspe c ifie d immuno suppre ssing c o nd itio n) a nd o nly 5 d e sc rib e d a s he a lthy ho sts  20 C.g attii  a ll 20 we r one g a tive a nd no ne with immuno suppre ssing e HIV se r c o nd itio ns  Clinic a l pre se nta tio ns  C.g attii mo re like ly to ha ve pulmo na ry invo lve me nt  Bo th ha d hig h ra te s o f me ning e a l d ise a se (85% a nd 70%)  intra -c e re b ra l le sio ns a nd fo c a l sympto mo lo g y mo re c o mmo n with C.g attii  Outc o me s  No d e a ths in C.g attii g ro up ve rsus 30% mo rta lity in C.ne o fo rmans g ro up  C.g attii pa tie nts mo re like ly to suffe r ne uro lo g ic se q ue la e (39% ve rsus 3%) a nd to re q uire e ithe r CNS o r tho ra c ic surg e ry

Clinic a l Da ta fro m Austra lia (2)  Mitc he ll e t a l: A re tro spe c tive re vie w o f 118 c a se s o f c rypto c o c c a l CNS dise a se pre se nting to Austra lia n te a c hing ho spita ls b e twe e n 1985 a nd 1992 (a ll ro utine ly type d a s g a ttii o r ne o fo rma ns)  Immune de fic ie nc ie s  60 pa tie nts with AIDS  o nly 1 C.g attii c a se  23 pa tie nts with o the r immune d e fic ie nc ie s (13 he me ma lig na nc ie s, 10 o n immuno suppre ssing me d s)  Only 1 C.g atti i c a se  35 pa tie nts witho ut AIDS o r o the r immune d e fic ie nc ie s  26 (74%) C.g attii  9 (26%) C.ne o fo rmans  Outc o me s  C. g attii ha d mo rta lity ra te o f 15%

C.g attii in Austra lia Summa ry  Ho st risk fa c to rs a nd c linic a l fe a ture s o f c rypto c o c c o sis de pe nde nt o n the infe c ting spe c ie s  he althy hosts we re prima ry ta rg e t o f C.g attii infe c tio n  C.g attii (vs . C.ne o fo rmans ) wa s a sso c ia te d with  lo we r mo rta lity  a hig he r inc ide nc e o f c o mplic a tio ns  inc re a se d lo ng -te rm se q ue la e  fo c a l le sio ns  Wha t a b o ut C.g attii infe c tio n in BC a nd the Pa c ific NW US?

E nviro nme nta l Sa mpling - BC, Ca na da  C.g attii fo und in e nviro nme nta l sa mpling o n Va nc o uve r I sla nd  I nc re a sing dia g no se s b e twe e n 1999 a nd 2004 in pa tie nts o n the ma inla nd a nd in Pa c ific NW US (witho ut tra ve l e xpo sure )  Ma c Do ug a l e t a l: L a rg e sc a le e nviro nme nta l sa mpling fro m ma inla nd BC a nd Wa shing to n Sta te (2001-2005)  3% o f e nviro nme nta l sa mple s (so il, a ir, wa te r, swa b s fro m no n- E uc a lyptus tre e s a nd o the r struc ture s) po sitive fo r C.g attii

Clinic a l E pide mio lo g y fro m BC  Ga la nis a nd Ma c Do ug a l: 218 c a se s (124 c o nfirme d b y c ulture a nd 94 pro b a b le with po sitive CrAg , histo pa tho lo g y, o r mic ro sc o py a nd HI V se ro ne g a tive ) fro m la b re po rting to BC pub lic he a lth a utho ritie s (1999-2006)  Rise in inc ide nc e o f infe c tio n in British Co lumb ia o ve r study pe rio d  6 c a se s in 1999 to 38 c a se s in 2006  Ave ra g e a g e wa s 58 ye a rs, 55% we re ma le  38% immuno c o mpro mise d (HI V, tra nspla nt, c a nc e r, ste ro ids)  Pre se nting c linic a l fe a ture s  re spira to ry syndro me in 76.6%  CNS syndro me in 7.8%  b o th in 10%

Clinic a l E pide mio lo g y fro m BC # 2  L ung no dule s (sing le o r multiple ) we re mo st c o mmo n ra dio g ra phic finding s  19 to ta l de a ths  CF R 8.7% (c o nfirme d a nd pro b a b le ) a nd CF R 12.1% (c o nfirme d)  Mo rta lity a sso c ia te d with o lde r a g e (p=0.019) a nd CNS syndro me (p=0.014)  74% o f tho se who die d ha d unde rlying me dic a l c o nditio ns  c a nc e r, COPD, a sthma , live r dise a se , dia b e te s, HIV infe c tio n, lung tra nspla nt, CHF a nd c o ng e nita l c a rdia c dise a se .  47% o f tho se who die d we re immuno c o mpro mise d (p=0.267)

Clinic a l E pide mio lo g y in Ore g o n  De Be ss e t a l: 60 c a se s o f C.g attii re po rte d in Pa c ific NW US (WA, OR, CA, I D) thro ug h July 2010  54% ma le , a nd 45% o f c a se s we re a g e d 50-69 ye a rs  81% (o f 47 pa tie nts fo r who m da ta wa s a va ila b le ) ha d a c linic a lly re c o g nize d pre dispo sing c o nditio n  29% e ithe r HI V o r tra nspla nt  Mo rta lity o f 33% (o f 45 pa tie nts with kno wn o utc o me s)  20% o f pa tie nts die d due to C.g attii  13% o f pa tie nts die d with C.g attii  (hig he r tha n the re po rte d c a se fa ta lity ra te s in b o th BC a nd in Austra lia )

Ba c kg ro und Summa ry  Uniq ue stra in in a no ve l e nviro nme nt  E pide mio lo g y sug g e sts uniq ue c linic a l fe a ture s c o mpa re d to the pre vio usly pub lishe d da ta  Sc a rc ity o f la rg e c linic a l se rie s o f C.g attii i nfe c tio n, the re fo re la c k o f de ta ile d c linic a l a nd o utc o me info rma tio n  T he la rg e numb e r o f c a se s re po rte d re c e ntly in Ore g o n pro vide s o ppo rtunity to impro ve o ur unde rsta nding o f this infe c tio n a nd the c linic a l c a re o f the se pa tie nts

Crypto c o c c us g attii Huma n I nfe c tio n in Ore g o n

Culture -c o nfirme d C.g attii in Ore g o n, b e twe e n No ve mb e r 2004 a nd No ve mb e r 2010 Ge nde r a nd Ag e Numbe r of Ca se s by  27 fe ma le , 19 ma le Ye a r 20  Me dia n a g e 58 ye a rs 18  Ra ng e 15-96 16  No diffe re nc e b y g e nde r 14 12 10 Numb e r (%) o f Ca se s b y Site o f 8 I nfe c tio n 6 21 (46 ) Pulmo na ry 4 12 (26) CNS 2 9 (20) CNS & Pulmo na ry 0 1 (2) Blo o dstre a m a lo ne 2004 2005 2006 2007 2008 2009 2010 3 (6) Othe r n=46 c a se s

Clinic a l Pre se nta tio ns Ma jor Site s of Symptom onse t to dia g nosis Pr e se nting Compla int(s) & Infe c tion Me dia n # da ys (r a ng e ) # of pa tie nts He a da c he 7 Co nfusio n 4 CNS 22 (7-180) Se izure 1 Visua l fie ld de fic it 1 Dyspne a 8 Co ug h 5 Asympto ma tic 4 Pulmo na ry 37 (12-180) F e ve r 2 We a kne ss 1 Co nfusio n 1 He a da c he 3 Co ug h 3 CNS & He mo ptysis 2 33 (6-51) Pulmo na ry Dyspne a 1 Co nfusio n 1 Sync o pe 1

Pre dispo sing Co nditio ns: T o ta ls** Pr e disposing Conditions Numbe r of patie nts (% ) At le a st o ne immune - suppr e ssing c ondition (So lid o rg a n tra nspla nt, 24 (52%) a uto immune dise a se , a c tive ma lig na nc y, HI V) No immune -suppre ssing c o nditio ns b ut a t le a st o ne c hr onic me dic al 10 (22%) c ondition (Chro nic re na l, live r o r lung dise a se , o r dia b e te s) No immune -suppre ssing o r c hro nic 12 (26%) me dic a l c o nditio ns **e a c h pa tie nt re pre se nte d o nly o nc e

CNS Ca se s  21 pa tie nts ha d CNS infe c tio n  9 o f 21 a lso ha d pulmo na ry infe c tio n  4 o f 21 ha d fo c a l c rypto c o c c o ma s  Initia l CSF re sults fo r 17 pa tie nts with me ning itis: (no n-fo c a l CNS infe c tio n) CSF F e a ture (n) Me dia n Ra ng e Ope ning Pre ssure in c m H2O 41 17-55 (n=8) WBC / mm3 (n=17) 172 1-1090 Pe rc e nt mo no nuc le a r c e lls 73 26-100 (n=17) Pro te in mg / dL (n=17) 115 30-571 Gluc o se mg / dL (n=16) 38 2-100