??????????? The Spirochaetes

1
??????????? The Spirochaetes
  families Spirochaetaceae and
Leptospiraceae   Leptospira, Brachyspira,
(Serpulina, Treponema) Borrelia
2
(No Transcript)
3
??????

• ?????????, ????????????
• ???? (mm 0.1-0.3), ???? ????? ???????
• ???? ???????, ????? ???????
• ?????? ?????? ???? ?????
• ????? ?????

4
???? ???????????
5
?????????Leptospira
 

• L. interrogans L.
  biflexa
• ????????? ???????
• ? 200 ??????? ???????? ??????.

6
?????
7
(No Transcript)
8
????? ???? ???? ?"?

• 8.12 ???? ??????? ???? ????? ????? ?????? ??
  ?????, ????? ????????? ???? ????? ???? ???? ?"?
  ????.
• ????? ???"? ?????? ?? ????? ???? ??? ????? ??????
  ????? ?????.
• ???? 11 ??? ???? ????? ??????.
• ??? ???? ??? ?? ??"? ???? ????????????? ???????
  ?? 51 ?????? ????? ?? ????? ?????? ??? ???
  ???????? ???????? ?????? ?????.

9
????? ???? ???? ?"?

• ?????? ?? ??? ????? ???? ???? ???? ??????, ??
  ???? ??????? ??????????.
• ????? ????? ?????? ???? ?. ??????? ??.
  ????????????? ??? ????? ?????? ??????? ?? ????.
• ????? ??? ??? ???? ??? ???? ????? ???? ???? ????
  ??????.
• ?????? ?? ????? ????? ???? ????? ?? ???.

10
????????????

• ???????????? ???? ????? ????? ??????? ????????
  ??????? ????? ?????????.
• ?????? ?? ??? ??????? ???????? ????? ?? ??
  ???????

11
????? 

•  ???? ?????? ???????? ????? ?? ??????????? ????
  200 ??????? ????? ????? ?????????? ??????????.
• ?? ????????????? ????????? ????? ???? ???
  L.interrogans
• ???????? ???????????, ????????? ????? ???? ????
  L. biflexa.

12
????? ?? ???? ???????

• ?????? ????????? ??????? ?? ????? ?? ?? MAT
  (microscopic agglutination test)
• ??????? ?????????? ??????? ???????? - serovars
• A serovar is a description of a leptospire whose
  homologous rabbit antiserum agglutinates it, but
  not other strains of leptospires.

13
?????

• ?????? ???? ?? ???? ????????? ????? ?? ??????
  ?????? ??? ????????.
• restriction endonuclease analysis of chromosomal
  DNA.
• Multiple Locus Sequence Typing
• ???? ???? 17 ????? ?????? (genomospecies)
  ???????? ?? ?????? ??????????.

14
Genetic relationships of the pathogenic
leptospires defined mainly by DNA-DNA
hybridization (adapted from Ramadass et. al.1992)
L. interrogans australis bataviae bratislava pomon
a canicola copenhageni hardjo
L. borgpetersenii hardjobovis
balcanica ballum javanica
L. noguchii fort brag
L.santarosai shermani
L weilii celledoni
L. kirschneri  cynopteri gripotyphosa
15
????? ????

• ???????? ???????????? ?? ?????? ?? ?????? ???????
• ?????? ??????

????? ????? ????? ?? ????? ?????

canicola ????,???, ???????, ??? ?????
icterohaemorrhagiae ???, ???, ????, ??? ??????
grippotyphosa ???, ????, ???, ???? ?? ??????
hardjo ???, ??? ???, ???
pomona ?????, ???? ?? , ???, ??? ??????
16
????? ??????

• ???? ?????? ?LPS ?? ?????? ????????? ??????
  ?????? ????? ????? ???????? ?????? ???????? ???
  ????? ?????? ????? ?????? ????? ??? ???? ?????
  ????? ??????.
• ????? ???????? ?? ??????????? ?????? ??????
  ?????? ?? ???? ?????? ??????? ??? ????? ??????
  ????? ?????? ?????? ??? ???????? ??????? ????
  ?????? ?????? ?? ???? ????.

David A. Haake James Matsunaga, Indian J Med
Res 121, March 2005, pp 143-145
17
????? ??????

• ?????? ?????? ??? ?? ???????? ???? ???? ?? ??????
  ????????? ?? ?LPS ??????? ?????? ?? ?DNA.
• ?????? ??????? ????? ?? ????? ?? ??? ????????
  ???????? ????? ????? ?? ???? ?????'?-?????
  ??????'?-???'???? ???? ??? ???? ?????? ????????
  ?? ????? ??????? ?????? ?????.

David A. Haake James Matsunaga, Indian J Med
Res 121, March 2005, pp 143-145
18
??????

• l ????? ??? ????? ?????? ?? ?????????????
• l???? ?????, ??? ???? ??????
• l???? mm 0.1 - ?????? ?????? 0.22 ? 0.45
• l 2 ??????? ???????
• l????? ????? ?????? ????????? ?? ???? ????
• l ??? ???, FA

19
?????

• l ??? ???? ??? ?????? ??????
• l ????? ???? ????? ?????
• l 30 ?????, ????
• l ????? ????? (7-30 ???)
• l????? ?"? ????? ??????? ?????????????

20
????????

• ???????? ???????? ????? ?? ? LPS ????????-???????
  (lipoproteins ) ??? ?????? ?????? ????????? (OMP
  outer membrane proteins )
• ???, ? - Type specific main (TM) antigen ???? ??
  ???????? ???????? ?? ????????.
• ???? ???????? ????? ???????? ???? ????????? ???
  ?????? ??????? ?????? ???????? ??????? ?????????.

21
????????

• ?????? ????? ?? ??????? ????????? ????? ?? ???'
  ???????????? - ???? ???? ??????
• ???????? ?? ?????? ??????? ??????? ????? ??????
  ??????? ?????? ????????? ????????.
• ?????? ??????? ??????? ??? ????? ?????.
•  

22
??????? ??????

• ?????????? ???????? ???? ?????? ??? ????
  ????????.
• ???????? ????? ?????? ????????.
• ?????? ?????.
• ????? ?pH ??? 8 ????? ? 6.
• ???????? ????? 8-gt ?? C 50lt
• ???????? ?????? ????? ?? 180 ??? ????? ?? ?? ???
  (?? ????).

23
Outbreaks from contaminated water sources

• Outbreak of leptospirosis among triathlon
  participants and community residents in
  Springfield, Illinois, 1998. Morgan J, Bornstein
  SL, Karpati AM, Bruce M, Bolin CA et. al. Clin
  Infect Dis. 2002 Jun 1534(12)1593-9.
• A total of 834 of 876 triathletes were contacted
  98 (12) reported being ill. Serum samples
  obtained from 474 athletes were tested 52 of
  these samples (11) tested positive for
  leptospirosis.
• An outbreak of leptospirosis among Israeli troops
  near the Jordan River. Hadad E, Pirogovsky A,
  Bartal C, Gilad J, Barnea A, Yitzhaki S, Grotto
  I, Balicer RD, Schwartz E. Am J Trop Med Hyg.
  2006 Jan74(1)127-31
• An outbreak of leptospirosis that involved 7 of a
  team of 27 Israeli troops occurred following a
  military exercise in northern Israel near the
  Jordan River.
• Outbreak of leptospirosis among triathlon
  participants in Germany, 2006 Stefan Brockmann,
  Isolde Piechotowski, Oswinde Bock-Hensley et.
  al. BMC Infectious Diseases 2010,
  1091doi10.1186/1471-2334-10-91
• A total of 142 of 507 triathletes were contacted
  among these, five confirmed leptospirosis cases
  were found.

24
????? ??????
An outbreak of leptospirosis among Israeli
troops near the Jordan River. Am J Trop Med Hyg.
2006 Jan74(1)127-31. Hadad E, Pirogovsky A,
Bartal C, Gilad J, Barnea A, Yitzhaki S, Grotto
I, Balicer RD, Schwartz E. .
25
????? ??????

• ??????? ??????????? ???? sphingomyelinase C
  phospholipase A ??????????? ???????? ??????????.
• ???????? ??????? ??????? ?????? ????????
• ????? ?????? ??????????
• ?????? ?????????? ?LOS- (lipooligosaccharide )
• ????? ?????????? ? DIC , ? ??????? ??, ???????.
• Il-1 , Il-6 , TNF? ? ??? ?????.

26
???????

• ????? ??????, ???? ???,??? ????, ??' ??????.
• ??????? 7-1 ????.
• ????????
• ???, ????? ????????, WBC ?, albuminuria .
• ??????? ??????? ???????? a ? ??????????????
• ??????? ??????? ??????? ?????? ???, ?????, ????,
  ????? ????, ???? ???? ????????.
• ????? ??????? ?? ??? ??? ?????.
• ??????? (ischaemia) ?????? ??????
• ??? ????????? ?????? ?????????? (???? ????????)
  ???????????????
• ??????? ??????????? ???????? ??????????

27
???????? ????? ??????

• ???? ?? ??????? ?? ?????????? ?????? ?? ??? ????
  ?? ?????? ??????.
• ?????? ????? ????? ????? ??? ?? ??-??????.
• ??? ?????? ?????? ?????? ??????.
• ?????? ?????? ??? ????? ??????? ??????
  ?????????????? ?? ?????.

28
????? ?????? ???

• ??? ?????, ???????? ??????? ?? ????'?, ??????
  ????????????.
• ???? ???? ????? ?? hardjobovis.
• ????'?
• ???? ??-????? ?? ????? ???? (????????)
• ???????, ???, ????????
• ?????, ????? ????????
• ???? ??????
• ???????,??????, ?????., ??????.
• ????, ??????????????, ??? - ????? ?????? ????
  ???? ????

29
Relationship Between L. Hardjo Titre and Time of
Abortion
L. hardjo titre

• Herd disease many infected animals may be
  sero-negative.

fever
Milk drop
Abortion
Excretion
Time weeks from infection
Modified from Pritchard, 1990
30
The number of herds in Israel with new outbreaks
of Leptospira hardjobovis
31
??? L.canicola

• ??? ?.?. ????? ?4 ?? 8 ??????
• ??? ????, ????, ??????????????, ????
• 40 ???? ?????
• ??? ??? 8 ?????? - ????
• ???? ?????? ?????????
• ????? ??????? ????? ???? ???????
• ?????? ????? ????? ???? ????? ?"? ????? ?????????

32
Clinical and epizootiological study of a
leptospirosis outbreak due to Leptospira canicola
in a feedlot. J S Afr Vet Assoc. 1997
Sep68(3)105-7Yeruham I, Bernstein M, Perl S,
Irlin S, Cohen A, Yacobson B, Machnai B. .
33

• ??? ?. ?. 2003
• ??? ?????, ????? ?????? ?????, CNS

????
34
L. pomona
??? ?. ?.

• ????? ???????? 35 ????? 3 ?????? ??????
• ??? ????? ??????? ???? ????? (?? ??? ?????)
• ????? ???? ?????? ??????
• ??????? ?????? ??????
• ????? ????/???? ????/?????
• ????? ????? ?????????

35
L. pomona
??? ?. ?.

• ????? ???????? 35 ????? 3 ?????? ??????
• ???? ?????? ??? ?????? ????? - ????????.
• ????? ???? ?????? ??????
• ??????? ?????? ??????
• ????? ????/???? ????/?????
• ????? ?????? ??????? ???? ????? (?? ??? ?????)
• ???? ????
• ????? ?????????
• ?????
• ???? ??? ???? ????, ????? ????? ?????? ?????.

36
???????? ?? ????? ??????? ????? ???? ????????
???? ??????? ???? ??????? ???? ????? ??? ??????.
37

• ???? ????? 2008 ?????? ??????? ?? ???? ??? ??????
  ?????, ??? ???? ???? ?????? ??? ???? ????. ?????
  ????? ??? ???? ?????? ???? ???? ?????? ?????.
• ???? ????? ???? ???? ?????? ????? ????????,
  ?????? ????? ????????? ????????? ????? ??????.
  ????? ??????? ?? ????? ??????? ??????, ?? ??????
  ?????? ????? ?????? ???? ?????? ?? 460 ?????
  ??????????.

38
Leptospira tarassovi
39

• ????? ??, ?????? ???????, ???? ????? ??????
  ???????, ?????? ?? ????, ????? ?????? ??????
  ????.
• ????? ???? ????? ???? ???????? ?? ????? ???
  ?????????? ?????? ???????? ??? ?? ?? ???? ???????
  ????.

40

• ????? ????? ?? ????? ?? ??? ????? ?????? ?????
  ???? ???.
• ??? ?? ???? ???"? ????? ????? ???????????? ????
  ?? ??????

41

• ??? ????? 2005, ?. ??????? ????? ?????? ????????
  ?? ????????? ??????? ????? ???? ????? ???????
• ???? ???? 2005 - 2007 ????? 19650 ??????? ?.
  ??????? ? - 642 ?????.
• 6173 ?????? ????? ?????? ?????? ?????? ???????
  ???? ?????, ????? ???? ??????? ????.
• 12479 ???? ????? ?????? ???? ???? ??????? ?????,
  ?????? ???, ??????.

42
  ???? ???? ?????? ???? ?? ???? gt 1100
1) ???? ????? ????? 204 8 (3.9)
????? ??? ?????? ????/ ????? 104 32 (30.8)
??????? ???? ?????? 204 14 (6.8)
 
??"?   512 54 (10.5)
       
2) ????? ????? 253 72 (28.4)
?????? ????? ???? 180 10 (18)
?????? ?????? ???? 150 28 (18.6)
??"?   583 110 ( 18.9)
       
??"? ????   1095 164 (16.6)
43
??????

• ??-????? ?? ????? ???? (????? ?? ??????, ????????
  ????????)
• ???? ????
• ???????,??????, ??????.
• ???? ??????, ?????, ?????? ????
• ??????., ?????., ????????
• ???, ????, ?????????????? ?????? ?????????
• ????? ??????? ????? ?? ?????? ? ?????.

44
?????? ???????

• ?10 ???? ?????
• 548 ?????? ?10 ?????
• ????? ???????? ?? ???????,???????????,
  ??????????????,???????, ??????, ????????, ?????
• ????????
• ?????
• ????? ??????
• ????? ?? ??????? ?????
• ???? ???????
• ????? ???????

45
?????

• ??????? ???????? ?????? ?
• ?????? ?????? ?????
  ???????? ?? ???
• ?????? ??????
• ???? ???????? ????????
• ???? ??????? ?? ??? ?????
• ??? ?????? ?????? ????
• ????? ???? ?????? ??? ???? ???????? ??? ??????
• ?????????????

46
????? 4 ???????

• ??-????? ?? ????????????? (????? ???????)
• ???? ??????? ?????? ???, ?????, ?????, ????? ??
  ?????? ????? (????? ??????.)
• ???? ?????? ??????, ????, ???, ????? ?? ?????
  ???? (??????? ???????.)
• ???? ?????? ?????? ???? ???? ?????, ?????????,
  ??? ?????, ????. (acute interstitial nephritis)
  ?? ????? ????? ?????? ( chronic interstitial
  nephritis )

47
Leptospira interogans serovar Canicola

• ?????? ????? ??????.
• ???? ???? ?? ??? ?? ?????.
• ???? ????? ??????? ???????? ?"? ?????? ??????
  ?????? ?? ??????.
• ??? ????? ?????? ?? ????? ??? ??? ??????

48
???? ??-????? (????? ?. ???????)Chronic /
Subclinical Infections

• ????? ????? ??????.
• ??? ???? ??????? ?????? ?????????? ?? ?? ???????.
• ???? ??? ?? ????? ?????????????? ????? ????
• ???? ????? ????????
• ????? ???????? ?? ??? ??? ???? ????? (PUO)
• ????? ?? ??????? ????? ?? ??? ??????
• ????? ?? anterior uveitis
• ????? ?????? ????? ????? ???????? ??
  ????????????.

49
???? ??-?????? Peracute Infection

• ???????????? ??-?????? ?????? ???????? ??????.
• ?????? ????? ????? ?????? ?? ??? ?????? ???????.
• ??? ????
• ?????
• ??????? (DIC)
• ??? - shock
• ????

50
(No Transcript)
51
(No Transcript)
52
???? ?????? ?????? Subacute Infections

• ???
• ???? ??????
• ?????
• ???????
• ????? ??????
• ?????? ?????? / ???? ?????
• ????? ?? ???????? ????????
• petechial and ecchymotic hemorrhages
• ????? ????? ??? ?? ????? ???? ??? oliguria or
  anuria
• ??? ????? stomatitis, halitosis
• ?????? ??????????? ?????? ??????, ???? ??? ??
  ???? ?? ?????? ???? ?????? ??/?? (blood brain
  barrier)

53
???? ??????

• ??? ??? 40 ?????
• ??????
• ???? ?????? ????
• ?????
• ????????
• ????? ????????? ???
• ????? ??????? ?????? ???????? ?????? ??? ???
  ??????? ? hematemesis, hematochezia, melena,
  epistaxis, petechiae
• ????
• ???? ???? ???? ???? - Intrahepatic cholestasis
  from hepatic inflammation
• ?????? ?? ???? ??? ?? ???????? ?????? , ?????? ??
  ??? ??? ???? ???? ?????? ??????, ????? ????,
  ????, ?????? ???? ???? (acites)
  hepatoencephalopathy.
• ?????? ??????????? ?????? ??????, ???? ??? ??
  ???? ?? ?????? ???? ?????? ??/?? (blood brain
  barrier)

54
Dogs tested in the KVI 2002-2012
Cause of death Disease Suspect
7 25 Positive
2 25 Suspect
104 539 Negative

702 113 589 total
55
??????

• ?????? ????? ????? ??? ????? (??? ???????
  ???????)
• ??? ??????? ?????? ?? ?????? ?????? ???????
• ???? ???????? ??????.

56
?????

• ????? - ??? 6 ????? ?????
• ?????? iridocyclitis, 'periodic opthalmia' ,
  moon blindness'(????????? ?? ?????)
• ???? ???, ????, ??????

57
???

• ????? ??-????? (????'?)
• ???? ?????? (?????? ) ???? ?????,
  ??????????????, ?????, ???? - ????? ?????.
• ????? ?????? ????? ?- hardjoprajitno

58
????? ??????

• ???
• ??? ??? ?????????? ?????????. ????? ?? ??
  ??????.

• ???????????????? (???? ??????)
• ????? ?????? - ?????? ??????, ?????, ????
  ??????.
• ????? ??????, ???? ????? ? ????? ?? ,
• ???????? ? ????? (????? ?? ??????? ??-????? ??
  restriction endonuclease
• PCR ??? ????? ?? ??????? ? ribosomal 16S rRNA
  gene

Infectieziekten Bulletin jaargang 13 nummer 8
(leptospirose) Blz. 315-316
59
Diagnosis

• Serology MAT
• F.A.
• PCR
• Culture

60
????????

• MAT (microscopic agglutination test)
• ?????? ????? ??? ??????? ????? ?????.
• ELISA
• Macroscopic agglutination ?? ??????
• ??? ???? ????? ??? ?????, ???? ????? ???????
• ???????? ?? ????? ??? ?? ????? ????

61
?????? ????????

• IgM ????? ???? ???? ???? ???????????? ?????
  ????? ?? ??????? ?????? ?-MAT .agglutinins
• IgG (neutralizing) ? 10 ???? ???? ??????. ???
  ???????? ?? ??????? ??????? 30-60 ???.
• ???? ?"? ??????? ??? ???? ???????.

62
?????? ????????

• ???
• ????? ??????? ???? - ???? ? 6-12 ??????
• ?????? ??????????? ???? ???? ????? ?? ?????, ???
  ?????? ????? ?????.
• Newer monovalent vaccines Leptavoid H (Sherring
  Plough) or Spirovac (Pfiser) better than
  pentavalent.
• Induce Th1 immunity comprising CD4 and gammadelta
  T- lymphocyte responses (cellular immune
  response)
• ?????? ?????? ?????? ?????? ?????
• ???? ????? ?? ???? ??? ? 30 ???
• ?? ???? ??? 6 ?10 ?????? ??? ???? ( ???).
• ?? ?????? ?? ???? ?????? - ???? ?????? ????.

63
?????? ????????
64
?????? ????????

• ?????
• ?. ??????? ???????????????? ?????? ?????? ??????
• ????"? ??????? ??????? ?????? ???? ??????,
  ?????????? ?????????. ??? ????? ????? ??????? ???
  ???? ??? ?????? ????? ?????.
• ???? ???? ? 6-12 ????
• ????? ?????? ???
• ??? ????

65
3
66
(No Transcript)
67
(No Transcript)
68
Veterinary Record Published
Online 23 November 2012 A novel tetravalent
Leptospira bacterin protects against infection
and shedding following challenge in dogs H. L.
B. M. Klaasen, PhD DVM, M. van der Veen, BSc, M.
J. C. H. Molkenboer, BSc, D. Sutton, BVetMed,
MRCVS Author Affiliations Abstract Recent
evidence based on the current epidemiological
situation suggests that vaccines against canine
leptospirosis in Europe should be directed
against infection with Leptospira interrogans
(sensu lato) serogroups Canicola,
Icterohaemorrhagiae, Grippotyphosa and Australis.
In the eight studies presented here, dogs were
vaccinated with Nobivac L4 (MSD Animal Health), a
new tetravalent inactivated vaccine containing
antigen from four strains representing these four
serogroups. The dogs were then challenged,
together with unvaccinated control dogs, using
heterologous strains from the same four
serogroups. In four of the studies, pups without
agglutinating antibodies against the four
serogroups were vaccinated with Nobivac L4
vaccine. In a further four studies, Nobivac L4
vaccine was given 48 hours after administration
of antiserum from vaccinated dogs designed to
mimic the serological status of pups with
maternally derived antibodies against these
serogroups. In all eight studies, vaccine
efficacy was assessed in terms of antibody
response, clinical signs, fever, thrombocyte
count, frequency of positive isolation of
challenge organisms from blood, urine and kidney
and frequency of interstitial nephritis. The
results demonstrate that Nobivac L4 vaccine
induces sterile immunity against leptospiraemia
and renal infection with strains of serogroups
Canicola, Icterohaemorrhagiae and Grippotyphosa,
and induces sterile immunity against
leptospiraemia with a strain of serogroup
Australis. Since sterile immunity was achieved in
pups pretreated with antiserum as well, it can be
concluded that this vaccine is also likely to be
efficacious in the face of maternally derived
antibodies in pups from the age of six weeks.
69
Veterinary Record A novel tetravalent
Leptospira bacterin protects against infection
and shedding following challenge in dogs H. L.
B. M. Klaasen, PhD DVM Department of
Microbiological RD, MSD Animal Health, Wim de
Körverstraat 35, Boxmeer 5831 AN, The
Netherlands M. van der Veen, BSc Department of
Microbiological RD, MSD Animal Health, Wim de
Körverstraat 35, Boxmeer 5831 AN, The
Netherlands M. J. C. H. Molkenboer,
BSc Department of Global Regulatory Affairs
Immunologicals, MSD Animal Health, Boxmeer 5831
AN, The Netherlands D. Sutton, BVetMed,
MRCVS Global Marketing Department, Merck Animal
Health, Milton Keynes, Buckinghamshire,
UK E-mail for correspondence eric.klaasen_at_merck.
com Author Affiliations
70
(No Transcript)
71
?????? ???????? ??? ????? ????? ?? ??????? ??
????? ????? ??. ??????? ??. ??????????????, ?????
???????? ?? ????? ?? ?. ???????????, ?. ????????
?? ?. ??????.
???? ?????? ?? ????? ?????? ?????? ?? ???? ????
?????? ????? ?? ???????.
72
?????

• ???
• Dihydrostreptomycin 25 mg / kg 2x ????? ?????
  ?? ???? ???? ?????.
• ?????
• ????? ???? ?? ?? ??????? ????????
• ????????, ????????? ????? ?????? ?? ???? ?????
  ?????
• ???????????, ???????????? ??? ?????? ?????
  ??????.

73
????????

• ??????? ????? (Weil's disease, canicola fever,
  etc)
• ???? ????. ???, ???? ???,???? ?????? ??????, ????
  ??????, ?????? ????????. ????? ?????? - ????,
  ????? ??, ??? ??????, ?????? ????.
• ???? ?????? ???? ????? ?????.
• ??????? ????? ???? ??????? ??? .

74
Mild type

• Characteristically with serovars hardjo,
  grippotyphosa, pomona or others.
• Initial symptoms followed by a transient
  remission (3-5 days)
• May proceed to exacerbation including meningitis,
  renal failure and abdominal or chest pains.
• Recovery is generally complete, but weakness,
  tiredness, depression or psychosis may extend for
  weeks or months.

75
Severe type

• Characteristically with serovars
  icterohaemorrhagiae, copenhageni, bataviae,
  javanica and others.
• Illness worsens rapidly (7-10 days)
• Renal failure, skin and mucosal haemorrhages,
  haemoptysis, myocarditis or liver failure
• ?death if untreated.

76
Total 26
77
Management

• ????? ???????
• ????? ??? ?? ?????
• ????? ????? ??????? ??????? (??????? ??????? ???
  ???????? ??? ???"? ??????.
• ????? ?? ????? ??? ???? ????.
• ???????.

78
???????? ?????? ??? ???

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79
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• ???? ??????
• ?????

80
?????

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81
?????? ????? ???? ?????? ????

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• P
• L ?????? ???????????
• A ????? ??????
• B ?????? ???????
• C ????? ??????
• P ????? ???? ?????? ( ??????, ?????, ???????,
  ???????)