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Advanced Topics on Zoonoses
Chao-chin Chang, DVM, MS, PhD
Professor
Graduate Institute of Microbiology and Public Health National Chung Hsing University
Taichung, Taiwan
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Figure. The host-parasite
ecological continuum
(here parasites include
viruses and parasitic
prokaryotes).
Daszak P et al., Emerging
infectious diseases of
wildlife--threats to
biodiversity and human
health. Science
2000;287(5452):443-9
Published by AAAS
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BITE-ASSOCIATED
ZOONOSES
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Introduction
• Animal bites represent about 1% of all emergencydepartment visits. Between 70% and 90% of thesevisits are caused by dog bites (Tan, 1997) .
• It is estimated that only 3% to 5% of dog bites willbecome infected.
• Most infections associated with dog bites arepolymicrobial, with Staphylococcus spp.,Streptococcus spp., and Corynebacterium spp. as
the most frequently isolated aerobic organisms(Griege et al., 1995).
• However, bite-related zoonotic bacteria mainlyinclude Pasteurella species and Capnocytophagacanimorsus.
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Distribution of human rabies cases in mainland China, 2007.Red stars indicate ferret badger–associated human rabies cases.
Numbers in parentheses in key indicate number of affected provinces.
Zhang et al., Emerg Infect Dis 2009;15:946-949
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Dog and Cat Bites
Aerobes Anaerobes
Cat bites
Pasteurella spp,
Streptococcus spp,
Staphylococcus spp,
Moraxella spp
Fusobacterium spp,
Bacteroides spp,
Porphyromonas spp
Capnocytophaga spp
Dog bites
Pasteurella spp,
Streptococcus spp,
Staphylococcus spp,
Neisseria spp
Fusobacterium spp,
Bacteroides spp,Porphyromonas spp,
Prevotella spp,
Capnocytophaga spp
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Pasteurellosis
• Pasteurella are commensal bacteria isolated from the oral cavity ofdogs and cats.
• Carriage rates of Pasteurella in dogs: 22% to 81% (but Ganière et al.(1993) indicated that pathogenic strains were found in 28% of the dogstested (versus 77% of the cats).
• Pasteurella canis is the most common isolate from dog bites and
Pasteurella multocida subspecies multocida and P. septica were themost common isolates from cat bites (Talan et al., 1999).
• Penicillin is the antibiotic of choice for treatment, but most patients aremore frequently treated with a combination of a β-lactam antibiotic anda β-lactamase inhibitor (Talan et al., 1999). Usually, dog bite treatmentincludes the adminstration of Amoxicillin-clavulanate (250 mg orally 3
times a day).• Untreated affection can lead to severe complications, including abscess
formation, septic arthritis, osteomyelitis, endocarditis, pneumonia ormeningitis (Griego et al., 1995).
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Infectious agent:Most common species are Pasteurella canis
and Pasteurella multocidaCommensal organism within the oral cavity
of the dog
Gram negative, facultative anaerobe,
coccobacillus
Clinical signs
Swelling, inflammation and
intense pain at the bite site afew hours after the exposure
are the typical symptoms of
Pasteurella infection.
Dog: skin abscesses, arthritis, otitis
Dog & Cat Bites: Pasteurellosis
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Capnocytophaga canimorsus
• A gram-negative rod, is reported as part of the normal oral flora of
16% of dogs (Underman, 1987).
• Most (91%) of the known bite-related human cases resulted from a dog
bite (Lion et al., 1996).
• C. canimorsus systemic infections occur more often in
immunosuppressed or immuno-impaired individuals, such as
splenectomised individuals (33%), alcohol abuse (24%) or
immunosuppression (5%). Therefore, when fever occurs in
immunosuppressed patients after a dog bite, C. canimorsus infection
should be considered.
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Clinical signs
. No major sign in non-immunocompromised patients
. Septicemia, shock, disseminated intravascular coagulation
in immuno-compromised patients
Clinical features
Fever (90%), septicemia (94%),
septic shock (40%),
disseminated intravascular coagulation (32%),
meningitis (13%), renal failure (15%),
gangrene (14%),thrombocytopenic purpura (14%),
cardiopathy (11%), ARDS/Pneumonia (10-12%),
endocarditis (7%)….
Case-fatality rate: 30%
Dog Bites apnocytopha g a can im orsus
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Underlying Conditions and Fatality Rates (n=81)
Category Condition Cases (%) Fatalities (%)
Age > 50 yrs 42 (52) 17 (40)
Underlying Total 57 (70) 18 (32)
Condition Splenectomy 29 (36) 10 (34)
Neoplastic 20 (25) 6 (30)
Alcoholism 16 (20) 4 (25)
Pulmonary 13 (16) 6 (46)
Cardiovascul. 5 ( 6) 2 (40)
Steroid use 5 ( 6) 1 (20)
Dog Bites apnocytopha g a can im orsus
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Purpura fulminans associated with Capnocytophaga canimorsus infection.
Bryson et al. British Journal of Haematology 2003;121:1.
**C. canimorsus is susceptible to most antibiotics, and penicillin G is recommended as the drug of choice (Lion etal. (1999). The use of amoxicillin/clavulanic acid is a good alternative.
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MRSA-associated infection
of the left forearm of a 15-
year-oldpatient (A) whose cat had
developed recurrent MRSA
culture-positive skin
lesions of the perineal area(B)
Source: Oehler et al.
Lancet Infect Dis2009;9:439–447.
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Campylobacteriosis
• Campylobacter jejuni, a Gram-negative enteric organism, is a leadingcause of human enteritis.
• Campylobacteriosis has a higher incidence in AIDS patients than in thegeneral population, causing severe, often bloody, diarrhea andcramping, nausea and fever (Glaser et al., 1994).
• It is estimated that approximately 6% of enteric campylobacteriosis istransmitted from pet animals (Saeed et al., 1993).
• Most Campylobacter infections in dog and man are caused by C. jejuni,though C. coli infection does occur.
• Evidence indicates that contact with infected dogs, especially diarrheicdogs can increase risk of acquiring Campylobacter jejuni (Blaser et al.,
1978; Salfield and Pugh, 1987).
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Campylobacteriosis (cont.)
• Puppies are more likely to acquire the infection and show clinical signs(watery diarrhea lasting 3 to 7 days).
• In dogs, symptomatic puppies usually show a 3- to 7-day course of
diarrhea with or without anorexia, fever and vomiting (Willard et al.,
1987). The diarrhea may be watery, mucoid, or bloody. Infected dogs
may or may not show clinical signs of disease.
• Risk factors associated with non-clinical shedding include high density
housing, age less than six months, and autumn seasonality.
• Fecal shedding of C. jejuni in the dog is age-dependent and peaks in
the first year of life.
• In humans, the clinical picture of Campylobacter infection is a brutalonset of fever, headache, abdominal pain and severe watery to bloody
diarrhea usually lasting less than a week. Rare cases of relapse, colitis,
arthritis and septicemia have been reported.
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Helicobacter infections
• The bacterial genus Helicobacter contains at least 18species.
• Some helicobacters, such as H. canis, H. pullorum, H.
heilmannii, and H. cinaedi may be zoonotic.
• H. pylori ??• Helicobacter species have been involved in human
peptic ulcer and neoplasia, enteritis and inflammatory
bowel disease.
• Chronic vomiting and subclinical gastritis are themain manifestations of dog infection with
Helicobacter (McDonough and Simpson, 1996).
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Salmonella Infections
• Typhoidal Salmonella infection
-- S. Typhi, S. Paratyphi
• Non-typhoidal Salmonella infection
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Non-typhoidal Salmonella serovars vs. Host
Cattle– S. Typhimurium, S. Dublin, S. Newport
Sheep– S. Typhimurium, S. Dublin, S. Anatum, S.
Montevideo Pigs— S. Typhimurium, S. Choleraesuis
Horse– S. Typhimurium, S. Anatum, S. Newport, S.
Enteritidis, S. Arizonae
Chicken—i) Pullorum disease: S. Pullorum; ii) Fowltyphoid: S. Gallinarum; ii)Avian paratyphoid: S.
Typhimurium, S. Enteritidis, S. Heidelberg
20
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Salmonellosis
• It has been estimated that 1% of the 40,000 annually-reportedsalmonellosis cases in the United States are associated with companionanimals (Stehr-Green and Schantz, 1987).
• From 1% to 30% of the fecal samples or rectal swabs taken fromhealthy domestic pet dogs, 16.7% of dogs boarded in kennels, and21.5% of dogs hospitalized were found to be positive on bacteriological culture for Salmonella (McDonough and Simpson,1996).
• Young dogs (
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Salmonellosis
• Salmonellosis causes clinical signs mainly in young puppies, pregnant
animals or aging dogs.
• Main clinical signs, after an incubation of 3 to 5 days, include diarrhea,
fever, vomiting, malaise, anorexia, dehydration, and possible vaginaldischarge or abortion in bitches.
• Mortality is usually low (< 10%).
• Recovering dogs may have intermittent diarrhea for up to 3 to 4 weeks
and can shed Salmonella in the stools for up to 6 weeks (McDonough
and Simpson, 1996; Willard et al., 1987).
• In humans, gastroenteritis with fever, vomiting, abdominal pain and
watery to mucoid diarrhea occurs within a few hours to 2 to 3 days
after exposure to infection.
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Table 1. Reports of Salmonella infection in reptiles in different countries.
Country Species Prevalence Serotypes Reference
German and Austrian Turtle 2.6 % (1/38) S. Newport
S. Othmarschen
S. Nottingham
SalmonellaⅢ b 47:k:z35
SalmonellaⅢ b 50:k:z
[Geue L and Löschner U, 2002]
Lizard 47.4 % (36/76)
Snake 71.6 % (48/67)
Total 54.1 % (86/159)
Japan Turtle 72.2 % (13/18) S. Bardo
S. Newport
S. Panama
S. Amsterdam
S. Minnesota
[Nakadai et al., 2005]
Lizard 66.1 % (47/71)
Snake 100.0 % (23/23)
Total 74.1 % (83/112)
Brazilian Turtle 25.8 % (15/58) SalmonellaⅢ b 60:r:z
S. Typhimurium
S. Enteritidis
S . Albany
[De Sá IVA and Solari-Braz CA,
2001]
Lizard 62.5 % (15/24)
Snake 53.3 % (8/15)
Total 39.1 % (38/97)
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Country Species Prevalence Serotypes Reference
Spain Turtle 32.4 % S. Anatum
S. Herzliya
S. Abony
SalmonellaⅢ b 18:l,v:z
SalmonellaⅡ9,12:z29:1,5
[Briones et al., 2004]
Lizard 40.9 %
Snake 54.3 %
Total 41.5 % (39/94)
Amphibian 0.0 % (0/72)
Italy Turtle 36.6 % S. Berta
SalmonellaⅣ44:z4,z23:-
S. Fluntern
S. Trimdon
S. Apapa
[Ebani et al., 2005]
Lizard 26.7 %
Snake 14.1 %
Total 23.9 % (73/305)
Table 1. Reports of Salmonella infection in reptiles in different countries. (cont.)
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Source Turtle Lizard Snake p value ¶ Total
Zoo 22.3 % (81/364) 57.1 % (16/28) 61.5 % (16/26) < 0.05 27.0 % (113/418)
Hospital 39.4 % (13/33) 40.0 % (2/5) 0 NS‡ 39.5 % (15/38)
Pet shop 100.0 % (3/3) 90.0 % (9/10) 100.0 % (7/7) NS‡ 95.0 % (19/20)
p value§ < 0.05 NS‡ NS‡ < 0.05
Total 24.3 % (97/400) 62.8 % (27/43) 69.7 % (23/33) < 0.05 30.9 % (147/476)
† by Chi-Square test ¶
The comparison of isolation prevalence among different reptile orders from the same collection source.§The comparison of isolation prevalence among different collection sources in a reptile order.‡ NS: not significant by Chi-square test
Table 2. Prevalence (%) of Salmonella infection in pet reptiles in Taiwan†.
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Identification of several Salmonella serotypes thatwere common in humans in the USA.
HD1
I
N O
51
B C1 C2
Figure 2. Percentages of Salmonella serotypes in pet reptiles in Taiwan.
1.1
7.3
1.1 1.1 0.82.5
5.0
0.6
3.9
0. 6 0. 6 0. 6 1.7 1.1 0.6
1.7 1.70.3 1.1
1.70.6
1.70.6
2.0
8.9
1.1 0.6
2.8 2.8
0.3
2.51.1
5.0
35.2
0.0
5.0
10.0
15.0
20.0
25.0
30.0
35.0
40.0
A b o n y
B r e d e n e y
J a v a
R e a d i n g
S a i n t
p a u l
S t a n l e y
T y p h i m
u r i u m
T y p h i m
u r i u m
v a r . C o
p e n h
a g e n
4 , [ 5 ] , 1 2
: i : -
B a r e i l l y
G a t o w
I n f a n
t i s F a
y e d
L i t c h
f i e l d
M u e n c h e
n
N e w p
o r t
P a n a m a
9 , 1 2 :
- : 1 , 5
A b a e t e t u b a
R u b i s
l a w
A g b e
n i P o
o n a
H a r b u r g
U z a r a m
o H e
r o n
H u l l
H v i t t i n g
f o s s
C e r r o
C o t h a
m
U r b a
n a
A d e l a i d e
5 0 : b
: z 6
T r e f o
r e s t
u n t y p
a b l e
Serotype
P e r c e n
t a g e
OHD1 I N 51B C1 C2 F G K M 50
Saintpaul
Typhimurium
4,[5],12:i:-Infantis
Muenchen
Newport
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Identification of several Salmonella serotypes that have been everreported in human cases in Taiwan. (CDC in Taiwan 2004,unpublished data)
HD1
I
N O
51
B C1 C2
Figure 2. Percentages of Salmonella serotypes in pet reptiles in Taiwan.
1.1
7.3
1.1 1.1 0.82.5
5.0
0.6
3.9
0. 6 0. 6 0. 6 1.7 1.1 0.6
1.7 1.70.3 1.1
1.70.6
1.70.6
2.0
8.9
1.1 0.6
2.8 2.8
0.3
2.51.1
5.0
35.2
0.0
5.0
10.0
15.0
20.0
25.0
30.0
35.0
40.0
A b o n y
B r e d e n e y
J a v a
R e a d i n g
S a i n t
p a u l
S t a n l e y
T y p h i m
u r i u m
T y p h i m
u r i u m
v a r . C o
p e n h
a g e n
4 , [ 5 ] , 1 2
: i : -
B a r e i l l y
G a t o w
I n f a n
t i s F a
y e d
L i t c h
f i e l d
M u e n c h e
n
N e w p
o r t
P a n a m a
9 , 1 2 :
- : 1 , 5
A b a e t e t u b a
R u b i s
l a w
A g b e
n i P o
o n a
H a r b u r g
U z a r a m
o H e
r o n H u l l
H v i t t i n g
f o s s
C e r r o
C o t h a
m
U r b a
n a
A d e l a i d e
5 0 : b
: z 6
T r e f o
r e s t
u n t y p
a b l e
Serotype
P e r c e n
t a g e
OHD1 I N 51B C1 C2 F G K M 50
Stanely
Typhimurium
InfantisJavaBareilly
Newport
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Risk factor Prevalence p value
Feeding Habits
Carnivorous 66.0 % (31/47) < 0.05Omnivorous 42.9 % (42/98)
Herbivorous 21.7 % (68/313)
Unknown 33.3 % (6/18)
Raising condition
Group raising 25.0 % (93/360) < 0.05
Individual raising 50.0 % (39/78)
Living environment ¶
Aqua turtle 40.3 % (29/72) < 0.05
Tortoise 20.8 % (68/327)
Healthy status
Healthy 30.0 % (112/373) NS‡
Ill 34.0 % (35/103)
† by Chi-Square test‡ NS: not significant by Chi-Square test
¶Analysis for turtles only
Table 3. Association of Salmonella infection and risk factors†.
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Antimicrobial-resistant pattern Serogroups/Serotypes No. of isolates Percentage
None (susceptible to all antimicrobials) 279 80.4 %
S ¶ 28 8.1 %
AMP KF C CN NA S SXT TE S. Typhimurium 6 1.7 %AMP C S TE S. Typhimurium 6 1.7 %
AMP KF C CN NA F S SXT TE S. Typhimurium 5 1.4 %
NA S. Stanley 4 1.2 %
C NA F SXT TE S. Stanley 3 0.9 %
AMP S TE UT§
2 0.6 %
C NA F TE S. Stanley 2 0.6 %
F S TE serogroup C1
(UT§) 2 0.6 %
SXT TE S. Infantis 2 0.6 %
AMP KF ENR S serogroup W (UT§) 1 0.3 %
AMP KF F TE serogroup 53 (UT§) 1 0.3 %
AMP KF TE UT§
1 0.3 %
AMP KF UT§
1 0.3 %
AMP TE serogroup U (UT§) 1 0.3 %
KF S. Rubislaw 1 0.3 %
F UT§ 1 0.3 %
S TE S. Gatow 1 0.3 %
Total 347 100.0 %
¶Serogroups/Serotypes of resistance to streptomycin:S. Bredeney (2)、S. Muenchen (1)、S. Fayed (1)、S. Panama (1)、
S. Treforest (2)、S. Poona (1)、4,[5],12:i:- (2)、serogroup C2 (UT§) (1)、serogroup F (UT§) (3)、serogroup G (UT§) (2)、
serogroup I (UT§) (1)、serogroup N (UT§) (2)、serogroup X (UT§) (1)、serogroup V (UT§) (4)、serogroup 64 (UT§) (1)、UT§ (3)§UT:untypable
Table 11. Antimicrobial-resistant pattern of the 347 Salmonella isolates.
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Antimicrobial
agentS. Heron S. Bredeney S. Typhimurium S. Treforest 4,[5],12:i:-
Ampicillin 0.0 % (0/32) 0.0 % (0/26) 83.3 % (15/18) 0.0 % (0/18) 0.0 % (0/13)
Cephalothin 0.0 % (0/32) 0.0 % (0/26) 61.1 % (11/18) 0.0 % (0/18) 0.0 % (0/13)
Chloramphenicol 0.0 % (0/32) 0.0 % (0/26) 83.3 % (15/18) 0.0 % (0/18) 0.0 % (0/13)
Ciprofloxacin 0.0 % (0/32) 0.0 % (0/26) 0.0 % (0/18) 0.0 % (0/18) 0.0 % (0/13)
Enrofloxacin 0.0 % (0/32) 0.0 % (0/26) 0.0 % (0/18) 0.0 % (0/18) 0.0 % (0/13)
Gentamicin 0.0 % (0/32) 0.0 % (0/26) 61.1 % (11/18) 0.0 % (0/18) 0.0 % (0/13)
Nalidixic acid 0.0 % (0/32) 0.0 % (0/26) 61.1 % (11/18) 0.0 % (0/18) 0.0 % (0/13)
Nitrofurantoin 0.0 % (0/32) 0.0 % (0/26) 27.8 % (5/18) 0.0 % (0/18) 0.0 % (0/13)
Norfloxacin 0.0 % (0/32) 0.0 % (0/26) 0.0 % (0/18) 0.0 % (0/18) 0.0 % (0/13)
Streptomycin 3.1 % (1/32) 7.7 % (2/26) 83.3 % (15/18) 11.1 % (2/18) 15.4 % (2/13)
Trimethoprim-
sulfamethoxazole0.0 % (0/32) 0.0 % (0/26) 61.1 % (11/18) 0.0 % (0/18) 0.0 % (0/13)
Tetracycline 0.0 % (0/32) 0.0 % (0/26) 83.3 % (15/18) 0.0 % (0/18) 0.0 % (0/13)
Table 12. The comparison of percentages of Antimicrobial resistance of different
Salmonella serotypes isolated from pet reptiles.
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Salmonellosis
• Treatment is usually supportive rather than
antimicrobial, as antibiotics have been showncapable of extending the period of shedding and
triggering systemic disease (Willard et al., 1987).
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Salmonella in pigs and humans
in Taiwan
In Taiwan, the prevalence of 1.7% was determined, and thefour most frequently isolated Salmonella serotypes wereDerby (34%), Anatum (22%), Typhimurium (11%), and
Schwarzengrund (9%), according to a large-scalescreening program in pork carcasses in 2000-2003.
Chen TH et al., J Food Prot 69:674-678.
However, serotypes commonly seen in humans wereTyphimurium, Enteritidis, Stanley, Choleraesuis and
Derby (CDC, personal communication).
33
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Transmission
Usually by fecal-oral route
Animals can become infected through contaminated feed,
pasture, water or close contact with an infected host.
Humans and carnivores can be infected through meat, milk,
eggs and other animal products that are not thoroughly cooked.
Salmonella can be spread by fomites, rodents and wild birds, but
vectors are not required (??).
Salmonella can persist for months or years in the environment,
particularly in wet and warm environment.
S. Choleraesuis can survive in pig meat for up to 450 days and
for several months in feces.
Animals may become carriers for months to years.
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S. Choleraesuis in Pigs (Clinical Signs)
The disease is generally seen in pigs 3 weeks to 5 months
of age
Piglets are reluctant to move, anorexic, with high
temperature 40.5-41.6oC.
Piglets may have a shallow cough.
Yellow soft feces may be seen in diseased animals after a
couple of days of infection.
Septicemic salmonellosis is often associated with S.
Choleraesuis.
35
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S. Choleraesuis in Pigs
(Post-mortem Lesions)
Cyanosis of the ears, feet, tail and abdomen
Enlarged spleen
Congested lungs possibly with interlobular edema
Liver with white foci of necrosis
If the pigs survive the initial stages, it may present with
necrotic enterocolitis
36
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S. Choleraesuis in Humans
(J. Microbiol Immunol Infect 37(2):99-102)
Males : females = 2.2 : 1
56% of the patients are aged over 60 years old.
78% of the patients were with underlying diseases, such as
D.M., malignancy, peptic ulcer.
78% of the patients developed septicemia.
Gastro-intestinal manifestations (nausea/diarrhea) wereobserved only in 11%~13% of the patients.
Case-fatality rate: 18% Most feared complication in adult is mycotic aneurysm.
37
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II) The Use of Antibiotics in Food Animals
in Taiwan
38
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The Use of Antibiotics Critical to Human
Medicine in Food-Producing Animals in
Taiwan
McDonald LC, Chen MT, Lauderdale TL, Ho M.
J Microbiol Immunol Infect 2001;34:97-102
39
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Main Findings
Five animal drugs and the resistance of human drug/class they may select
for, included avoparcin, avilomycin, enrofloxacin, virginiamycin, and
kanamycin.
Tetracyclines were the class of antibiotic that was most widely used in the
greatest amount.
Farms(10) Chicken feed mills(8) Pig feed mills (6)
Avoparcin 10% 63% 0%
Avilomycin 0% 0% 50%
Enrofloxacin 40% 13% 50%
Virginiamycin 20% 63% 0%
Kanamycin 30% 13% 17%
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The Emergence in Taiwan of
Fluoroquinolone Resistance
in Salmonella enterica serotype Choleraesuis
Chiu CH, Wu TL, Su LH, Chu CS, Chia JH,
Kuo AJ, Chien MS, Lin TY
New Engl J Med 2002;346(6):413-419
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Main Findings
The proportion of total salmonella isolates made up by S.
enterica serotype Choleraesuis:
Before 1995: 8.4%
1996~1998: 2.7%1999-2000: 5%
Ciprofloxacin-resistant S. Choleraesuis has been observed
since 2000.
In the third quarter of 2001, 60% of the isolates wereresistant ciprofloxacin.
All the resistant isolates from humans and swine has
mutations that led to the substitution of Ser83Phe and
Asp87Asn. 43
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Introduction (cont
d)
Figure 1. Emergence of Fluoroquinolone Resistance among Salmonella enterica
Serotype Choleraesuis Isolates in Taiwan.Panel A shows the total annual numbers
of salmonella isolates from Chang Gung Memorial Hospital and Chang Gung
Children’s Hospital from 1987 through 2000 (bars) and the percentage of these
isolates that were S. enterica serotype choleraesuis (curve). (Chiu et al. 2002)44
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Introduction (cont
d)
Figure 1. Emergence of Fluoroquinolone Resistance among Salmonella entericaSerotype Choleraesuis Isolates in Taiwan. Panel B shows the total quarterlynumbers of S. enterica serotype choleraesuis isolates from these hospitals from thefourth quarter of 1996 through the third quarter of 2001 (bars) and the percentage
of these isolates that were resistant to ciprofloxacin (curve). (Chiu et al. 2002)45
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Judgment of Cause-effect Relationship
Correct temporality
Strength of association
Consistency of association
Specificity of association
Biological plausibility
Dose-response relationship
46
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Epidemiologic Relationship between
Fluoroquinolone-resistant Salmonella
enterica serovar Choleraesuis from Humans
and Pigs in Taiwan, 1997-2002
Chao-chin Chang, Yi-Hsuan Lin, Chao-Fu Chang, Kuang-ShengYeh, Cheng-Hsun Chiu, Chishih Chu, Maw-Sheng Chien, Yuan-
Man Hsu, Li-Shu Tsai, Chien-Shun Chiou*
Journal of Clinical Microbiology 2005;43(6):2798-2804.
47
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Results
48
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FIG 1. Dendrogram and PFGE patterns of Xba I-digested chromosomal DNA of Salmonella enterica serovar Choleraesuis and the num
of isolates from pig and human origins. The dendrogram was constructed by the UPGMA algorithm and the Dice similarity using
BioNumerics software with 3% optimization and 1% position tolerance.
A total of24 PFGE patterns
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FIG 2. Dendrogram and the
antibiograms of 12 antimicrobials
for the 106 gt-1a Salmonella
enterica serovar Choleraesuis
isolates and the number of isolates
from pig and human origins. Am:
ampicillin, C: chloramphenicol, S:
streptomycin, SxT: trimethoprim-sulfamethoxazole, Te: tetracycline,
Cip: ciprofloxacin, Na: nalidixic
acid, Nor: norfloxacin, Eno:
enrofloxacin, Cf: cephalothin, Gm:
gentamicin, F/m: nitrofurantoin
: resistant
: intermediate
: susceptible
A total of 44 patterns
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52% of the isolates were resistant to more than 7 antimicrobials:
Humans: 76% vs Pigs: 46%
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Discussion
Our findings suggested that the fluoroquinolone-resistant S.Choleraesuis was evolved from a gt-1a clone, emerged in2000, and then caused widely infections among humansand pigs since after.
It is still debatable that the source of the infection inhumans was from pigs, on the basis of the higherfluoroquinolone- and other antimicrobial-resistanceprevalences found in human isolates than in pig isolates.
Limitations of using molecular techniques to trace thesource of the infection
It is of urgent need to identify risk factors andtransmission routes of the infection in Taiwan.
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Main Conclusions
The low dosage used for growth promotion are anunquantified hazard.
Although some antibiotics are used both in animals and
humans, most of the resistance problem in humans arisenfrom human use.
Resistance can be selected in food animals, and resistant bacteria can contaminate animal-derived food, butadequate cooking destroys them.
In zoonotic salmonellosis, resistance may arise in animalsor humans, but human cross-infection is common.
56
Ri k A t f
S
Ch l i
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Risk Assessment of S. Choleraesuis
Pigs with low level of
bacteremia but notexcreting the bacteria
in feces
The bacteria are in
the meat but not on
the surface of the
meat
The bacteria
cannot be
detected by
traditional
methods
Pork products
available in
supermarkets
Pigs with bacteremia
but without clinicalsigns and
intermittently
shedding the bacteria
in feces
Contaminate
environmental
water and soil
Feces as
fertilizers
for organic
farms
Vegetables contaminated
with the bacteria
Humans get the infection
cooking
process
eating
drinking
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Modeling the Transmission Dynamics of
Fluoroquinolone-Resistant Salmonella
between Pigs and Humans in Taiwan.
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Materials & Methods
UV
W
X
Y
Z
a* π
κ
ε*(V+Z+Y)*(1-μ)
ε*(V+Z+Y)*(1-μ)δ
αγ
a*ρθ
σ
βη
l h d
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Materials & Methods
UV
W
X
Y
Z
a* π
κ
ε*(V+Z+Y)*(1-μ)
ε*(V+Z+Y)*(1-μ)δ
αγ
a*ρθ
σ
βη
i l & h d
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Materials & Methods
UV
W
X
Y
Z
a* π
κ
ε*(V+Z+Y)*(1-μ)
ε*(V+Z+Y)*(1-μ)δ
αγ
a*ρθ
σ
βη
i l & h d
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Materials & Methods
UV
W
X
Y
Z
a* π
κ
ε*(V+Z+Y)*(1-μ)
ε*(V+Z+Y)*(1-μ)δ
αγ
a*ρθ
σ
βη
M i l & M h d
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Materials & Methods
U
V
W
X
Y
Z
a* π
κ
ε*(V+Z+Y)*(1-μ)
ε*(V+Z+Y)*(1-μ)δ
αγ
a*ρθ
σ
βη
M i l & M h d
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Materials & Methods
U
V
W
X
Y
Z
a* π
κ
ε*(V+Z+Y)*(1-μ)
ε*(V+Z+Y)*(1-μ)δ
αγ
a*ρθ
σ
βη
M i l & M h d
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Materials & Methods
U
V
W
X
Y
Z
a* π
κ
ε*(V+Z+Y)*(1-μ)
ε*(V+Z+Y)*(1-μ)δ
αγ
a*ρθ
σ
βη
M t i l & M th d
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Materials & Methods
dV
dt=κV-[ a*π + ε(V+Z+Y)(1-μ)]*U
= [ a*π+ε(V+Z+Y)(1-μ)]*U – κ*Vdt
dU
Prevalence of FQR S. Choleraesuis in pigs (Pa) = 1-U = V
M t i l & M th d
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Materials & Methods
dWdt
=γZ+σY+αX-[δV+ε(V+Z+Y)(1-μ) +ηY+βZ]*W
= [δV+ε(V+Z+Y)(1-μ) +ηY+βZ]*W- (α+θ+a*ρ)*X
=θX- (σ+a*ρ)*Y
= a*ρ(X+Y)- γZ
dYdt
dt
dt
dX
dZ
Prevalence of FQR S. Choleraesuis in humans (Ph) = 1-W = X+Y+Z
M t i l & M th d
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Parameter Estimate
π Probability of fluoroquinolone use in pigs 0.05
a Rate at which bacteria becomes antibiotic-resistant after
antibiotic exposure
0.07/day
κ Natural loss rate, animals 0.007/day
δ Exposure rate from consumption/ handling of meat 10-3 /day
θ Colonization rate 0.01/dayρ Probability of fluoroquinolone use in humans 0.06
α Natural loss rate, exposed 0.09/day
σ Natural loss rate, colonized 0.03/day
γ Natural loss rate, amplified 0.014/day
ε Exposure rate from the environment, contributed by V, Y
and Z
10-6/day
μ Loss rate of contaminated excretion in the environment 0.005/day
β Transmission rate, amplified 0.5/day
η Transmission rate, colonized 10-5
/day
Materials & Methods
R lt
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Results - Baseline parameter estimates
34%
47%
R lt
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Results- 10-fold increase in FQ prescription
47%
90%
Results
-
Sensitivity analysis of FQR
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Results Sensitivity analysis of FQRS. Choleraesuis in humans
Varying FQ prescription
in humans
Varying FQ prescription inpigs
Results
-
Sensitivity analysis of FQR
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Results Sensitivity analysis of FQRS. Choleraesuis in pigs
Varying FQ prescription
in pigs
Varying FQ prescription in
humans
Results
-
Impact of increased human exposure
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Results Impact of increased human exposurevia consumption of contaminated pork
Discussion
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Substantial efforts have to be made to avoidunnecessary use of antibiotics in humans
• FQ prescription in pigs would only affect the time for
the emergence of FQR S. Choleraesuis in humans,while it had little impact on the equilibriumprevalence of antibiotic-resistant bacteria in humans.
• Human FQ prescription would not only hasten theemergence of FQR S. Choleraesuis in humans, butalso amplify their population density in the long term.
Discussion
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Discussion
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The situation of FQR S. Choleraesuis in humansand pigs in Taiwan
• In our study,FQR in animals was about 34%.
FQR in humans was about 47%.
• In other studies,In animals, it was about 15-34%.
In humans, it was about 60-73%.
Discussion
Discussion
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Better food hygiene to reduce and delay the emergence ofFQR S. Choleraesuis in humans.
• Improper handling or incomplete cooking of contaminated meatmay increase the burden of FQR S. Choleraesuis among humans.
• Comparing the effect of ρ and δ, it was found that δ would have astronger effect on the early occurrence of FQR S. Cholereasuis inhumans.
• Public health risk of Salmonella arising from the consumption ofcontaminated pork can be affected by a variety of factors, whileconsumers can control the risk from improper handling of pork.
Discussion
Conclusion
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• In the past, most studies favored the idea that antibioticuse in animals may be the most possible way to introducenew antibiotic-resistant bacteria into humans through foodproducts, especially when the pathogens are zoonotic.
• This study implies that antibiotic use in animal husbandryhas no substantial impact on the equilibrium prevalence ofantimicrobial-resistant bacteria in humans.
• Proper handling or cooking can also eliminate the risk offoodborne illness.
Conclusion
Conclusion
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To combat FQR S. Choleraesuis infection in humans
• our model suggested that while prudent use of
agricultural antibiotics has to be applied in hope oflowering the emergence of resistance among animals
and delaying the onset of resistant bacteria in
humans, substantial efforts has to be made to avoid
unnecessary use of antibiotics in humans.
Conclusion
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Teacher:Chao-Chin Chang
Presenting Student:Ping-Yen Yang
Using Caenorhabditis elegans Model to
Study Virulence of Salmonella IsolatesCarrying Variants of Salmonella
Genomic Island and Salmonella
Pathogenicity Island
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Salmonella Pathogenicity Island
The complex infection cycle of Salmonella relies on
several sets of virulence genes, many of which are
contained on Salmonella pathogenicity islands (SPIs).
Various SPIs, SPI1-21, have been identified according tothe differences of their functional genes.
81
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SPIs and Virulence Association The mutants of SPI-1 and SPI-2 significantly decreased the
virulence of Salmonella in the chicken model, while the
strains absence of SPI1-SPI5 were barely invading to thechickens’ spleen.
The mutations in sopB, sopD and pipD genes decreased
the Salmonella enteropathogenicity in the bovine model.
-Ivan , et al., (2009)
-Zhang , et al., (2002)
83
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Multidrug Resistance Salmonella enterica serovar Typhimurium phage type
DT104 , emerged in the 1990s, was found to own the
ability of multidrug resistance, specifically to ampicillin,chloramphenicol, streptomycin, sulfonamides and
tetracycline (ACSSuT).
84
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Salmonella Genomic Island 1 Salmonella genomic island 1 (SGI1) is a 43 kb genomic
island containing 44 open reading frames with MDR gene
cassettes.
Several studies indicated that DT104 carrying the MDR
region is a hyper-virulent strain, as compared to DT104
strains without MDR or other Salmonella enterica
serotypes.
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Antibiotic Resistance and
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Antibiotic Resistance and
Virulence Association The positive relationship between fluoroquinolone
resistance and carriage of exoU suggests that
fluoroquinolone resistant Pseudomonas aeruginosa
infections may be attributable to enhance virulence.-Wong , et al., (2008)
-Rudkin , et al., (2012)
The methicillin resistance reduces the virulence of
Staphylococcus aureus by interfering with the agrquorum-sensing (QS) system that the ability of the
bacteria to secrete cytolytic toxins is reduced.
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Salmonella Virulence Properties
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Salmonella Virulence Properties
in C. elegans (I) The MDR Salmonella enterica Typhimurium DT104 has
been shown to be more virulent in C. elegans.
-Surasri , et al., (2013)
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Salmonella Virulence Properties
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Salmonella Virulence Properties
in C. elegans (II) The mutations in sopB, sopD and pipD genes of both
Salmonella serovars did not exhibit significant decrease in
virulence towards the nematode.-Chai-Hoon , et al., (2015)
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Caenorhabditis elegans
The soil nematode, C. elegans, has beenused as an invertebrate host model to
identify and assess virulence factors of
several human pathogens, including
Salmonella enterica Typhimurium.
90
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C. elegans Life Cycle
C. elegans embryos
develop rapidly andhatch after 14 hours.
C. elegans proceed
through four moltcycles (L1-L4) before
becoming adults.
91
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Aim
The objective of this study is to compare virulence among
Salmonella isolates carrying different SGI1 variants and
SPIs by C. elegans nematode model.
92
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Selection of SGI1 Isolates
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Salmonella pathogenicity island Virulence genes
SPI1 invA, hilA
SPI2 spiC, ttrC
SPI3 misL, mgtC
SPI4 orfL, SPI4R
SPI5 pipD, sopB
Selection of SPI Isolates
*These isolates were without carrying SGI1 or its variants.
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Comparison between SGI and
non SGI isolates
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non-SGI isolates
Comparison among SGI
variants
Further comparison
among SGI variants
stratified by serovars,hosts and phenotypes of
antibiotic resistance.
Comparison among
isolates carrying different
numbers of SPIs
Further comparison
among isolates carrying
different sets of SPIs by
phenotypes of antibiotic
resistance.
With SGIs Without SGIs
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Zoonoses through the Respiratory Tract
B d t ll b hi ti
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Bordetella bronchiseptica
• B. bronchiseptica is a Gram-negative coccobacilluscommonly isolated from the respiratory tract of variousmammals.
• It is one of the infectious agents involved in the higlycontagious Kennel Cough syndrome.
• In the few human cases, pneumonia with interstitialinfiltrate the main clinical feature (Ford, 1995).
• Causing pneumonia in a few immunocompromisedindividuals
• Vaccination of the dogs may help reduce such a risk, butwill not eliminate it, as these dogs can still be potentialcarriers of the bacterium.
M b t i l i f ti
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Mycobacterial infections
• Tuberculosis (TB) caused by M. tuberculosis is certainly arare disease in dogs, most often resulting from a humansource (Acha and Szifres, 1989, Anonymous, 1999).
• However, the infected dog can become the source of otherhuman infections.
• There is potential for infection of pet dogs, especially thoseowned by homeless or economically impaired persons.
• Because canine tuberculosis often is the marker of thedisease in humans, its early recognition in dogs is essential(Clercx et al., 1992).
• In developing countries, where bovine tuberculosis is stillenzootic, dogs can be infected by M. bovis by consumptionof raw milk or possibly raw meat or offal from affectedcattle.
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Q F
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Q Fever
• Caused by Coxiella burnetii
• mainly transmitted to humans and other mammals throughinhalation of infectious particles
• In nature, C. burnetii is maintained by a wildlife-tick cycle.
• Infection through tick bites has been reported for various
species, including humans.• Dermacentor, Rhipicephalus and Amblyomma ticks are
probably responsible for the transmission of C. burnetiiamong dogs and wildlife (Hibler et al., 1985).
• The primary reservoir hosts for C. burnetii are ticks, andvertical transmission (trans-ovarial and trans-stadial) iscommon.
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Q Fever (cont.)
• Laughlin et al. (1991) reported an outbreak in a familyafter exposure to a deer and infected pregnant dog.
• Farmers having Q fever outbreaks in their flocks or herds
should be aware of the risk associated with their pets.
• Tick prevention and control is also important, especially indogs.
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Table 1. Univariate analysis of factors associated with Q fever in southern Taiwan.
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Table 2. Seroprevalence of Q fever in different animal species in sounthern Taiwan.
Table 3. Multiple logistic regression for risk factors associated with Q fever in southern Taiwan.
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ZOONOSES THROUGH
EXCRETIONS OF GENITO-URINARY
TRACT
Brucellosis
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Brucellosis
• Dogs can be infected by several species of Brucella,including B. abortus, B. melitensis and B. canis.
• Evidence exists for transmission from cattle to dog by
ingestion of infected reproductive tissues.
• At present, the zoonotic potential of B. abortustransmission between dog and man appears limited.
Conversely, dogs are the main reservoir of B. canis, which
is pathogenic to humans.
• B. canis is transmitted primarily by ingestion or inhalation
of aerosolized post-abortion material, but venereal
transmission is also reported (Johnson and Walker, 1992).
Brucellosis (cont.)
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Brucellosis (cont.)
• In the dog, B. canis infection is characterized by prolonged
bacteremia and reproductive failure in both males andfemales.
• In the pregnant bitch, B. canis causes embryonic or fetaldeath or abortion.
• In the male dog B. canis causes epididymitis and infertility.
• In both genders infection is largely asymptomatic andoften remains undetected unless the animal is bred.
• Treatment is based on the use of doxycycline and anaminoglycoside (streptomycin, gentamycin, or netilmicin)
for 4 weeks followed by doxycyline (200 mg/d) andrifampin (600-900 mg/d) orally for 4 to 8 weeks (Tan,1997).
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Brucellosis (cont.)
• Symptoms of B. canis infection in humans are largely non-
specific including fever, splenomegaly, malaise, myalgia,
headache, and anorexia (Lum et al., 1985).
• Septicemia has been reported in 50% of patients (Rousseau,1985).
• Though most cases respond well to antibiotic therapy, as
many as 3% of treated patients may die from endocarditis
or other complications(Rousseau, 1985).
L t i i
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Leptospirosis
• The etiological agents of leptospirosis belong to the more
than 200 pathogenic serovars within the 23 serogroups of Leptospira interrogans (André-Fontaine et al., 1994).
• the main serovars involved in zoonotic transmission between canid and humans were L. canicola and L.
icterohaemorrhagiae (Farr, 1995).• More recently, canine outbreaks caused by L. pomona and
L. grippothyphosa have been reported in Europe and in theU.S.A. (André-Fontaine et al., 1994; Brown et al., 1996),and at a lesser extent by L. australis, L. automnalis, or
some other serovars.• The range of serovars common in temperate regions is
much smaller than that found in tropical countries (Levett,1999).
Leptospirosis (cont.)
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• The course of infection caused by exposure to a leptospiralagent is largely dependent on host adaptation of the serovar.
• In humans, the mortality rate may reach 10 to 20%.
• Leptospira may be isolated from the patient’s blood orcerebrospinal fluid during the 10 days of infection or theurine after 21 days, and identified by dark-phase
microscopy or culture.• Laboratory diagnosis is still mainly based on serology,
especially micro-agglutination test (MAT).
• Leptospires are very sensitive to penicillin G anddoxycycline,which are the most effective antibiotics indogs and humans, especially when administered in theearly phase of the disease.
• Prevention is based on rodent control and exposurereduction as well as dog vaccination.
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Leptospirosis
• Leptospirosis is solely a zoonotic disease. Human-to-
human transmission is extremely rare.
• Leptospira is well adapted to a variety of mammals,
particularly wild animals and rodents.• Rodents are the only major animal species that can shed
leptospires throughout their life span without clinical
manifestations.
• Humans are infected by exposure to water or foodcontaminated by urine.
Leptospirosis (cont )
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Leptospirosis (cont.)
Serovars Principal hosts (clinical hosts)
L. icterohaemorrhagiae Rodents (dogs, horses, cattle,
swine)
L. grippotyphosa Rodents (dogs, cattle, swine)
L. canicola Dogs (swine, cattle)
L. pomona Cattle, swine (horses, sheep, sea
lions)
L. hardjo cattle
L. bratislava Swine (horses, sea lions)
Leptospirosis (cont )
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Leptospirosis (cont.)
• Infection with leptospires most frequently results fromhandling infected animals or from aerosol exposure duringcage cleaning (a story of toothbrush).
• Skin abrasions or exposure to mucous membranes may serveas the portal of entry (a story of a polluted river).
• All secretions and excretions from infected animals should beconsidered infective.
• The disease may vary from inapparent infection to severeinfection and death.
• Infected individuals may experience a biphasic disease.• Ampicillin and doxycycline are effective in the treatment of
human patients. Tetracycline can be used to eradicate L.ballum in a mouse colony.
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VECTOR-BORNE ZOONOSES
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Plague Pneumonia – California
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Plague Pneumonia California.
MMWR 1984;33(34);481-3
• The patient, who is a veterinarian and has a small-animal
practice, denied contact with wild animals or travel outside his
local area. He had no history of a needlestick injury or cut
during surgery or other procedures. His office and home
environment were investigated as potential sources of infection.Office records and charts of all animals seen by the veterinarian
during the week before onset of symptoms were evaluated. Only
one animal, cat A, had an illness with symptoms compatible
with those usually seen with pneumonic plague (difficulty
breathing and hemoptysis) but had no fever. The cat died, andits body was not available for autopsy. No suspicious illnesses
among neighborhood animals or owners were noted, but 51 pet
owners were contacted and advised to disinfest their pets and to
avoid contact with ground squirrels and other rodents.
Cat-Transmitted Fatal Pneumonic Plague in a
Person who Traveled from Colorado to Arizona
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Person who Traveled from Colorado to Arizona
Doll JM et al., Am J Trop Med Hyg
1994;51:109-114• The study reported the case investigation of a patient,
presumably exposed to a plague-infected cat in Colorado,
who presented with gastrointestinal symptoms, and
subsequently died of primary pneumonic plague.
• Public health officials should be vigilant for plague activity
in rodent populations
• Veterinarians should suspect feline plague in ill or
deceased cats.
• Physicians should have a high index of suspicion for
plague in any person who has traveled to plague enzootic
areas.
Cat Scratch Disease (Bartonella
henselae)
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henselae)Epidemiology:
• Cats are the main reservoir (28% of USpet cats sero +). Cats can be
bacteremic for months. Stray cats,
young cats more likely to be bacteremic.
No vertical/horizontal transmission.
• Fleas are main vector from cat to cat.
• Cat to humans: mainly scratch, likely
inoculation of infective flea feces at time
of scratch.• Flea transmission to humans possible,
not clearly demonstrated.
• Recent suggestion of possible tick
transmission.
Cat Scratch Disease: Mode of
transmission
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transmission
Bartonella henselae
– Cat Scratch: + + + (76%, Margileth, Adv. Pediatr. Infect.
Dis., 1993
– Cat Bite: ? ? ?
– Flea Bite: +/- ?
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Bacillary Angiomatosis
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Bartonella henselae
infection in HIV
-
patients and theircats. Chang et al., J. Infect. Dis. , 2002, 186:1733-1739.
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Unknown Fever and Back Pain Caused
by Bartonella henselae in a Veterinarian
after a Needle Puncture
Lin J.W., Chen C.M., Chang C.C.*
Vector Borne Zoonotic Dis 2011; 11(5):589-591.
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• A male patient who was a 32 year-old veterinarianworking in a private veterinary clinic, sought for clinical
help due to unknown fever and persistent back pain for
at least a month.
• According to the patient’s description, the fever was
undulant and right back pain was noted during fever
bouts. Fever was only improved after use of analgesic,
but soon exacerbated with chills for several hours.
• He was not noted any obvious blisters, rashes or bites
from insects or animals. However, before the illness,
he recalled a needle puncture several days ago.
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Figure. Dot-blot analysis with a specific probe
for B. henselae. N: negative control, sterile water
substituted for DNA templates; NP: blood
sample from a normal individual without CSD; P:positive control, B. henselae ATCC49882; B1:
the patient’s blood sample before treatment for
CSD; B2: the patient’s blood sample after
treatment for CSD; LN: lymph node aspiratesfrom the patient before treatment for CSD.
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• For the clinical treatment, the patient was givenintravenous rocephine on the initial 6 days, and then
oral doxycycline and azithromycin were given in turn
for 4 days and 5 days, respectively. The patient was
also given intravenous decadron on the seventh day,
which was replaced by oral prednisolone for the
remaining 9 days. The pain and fever disappeared
within one week.
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Discussion
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• The main route for humans acquiring CSD infection isthrough the wound contaminated with infectious flea
feces after animal’s scratches or bites.
• This event highlights the importance of wound
management for CSD prevention, especially in high
risk population, such as veterinarians.
• Unknown fever combined with back pain in patients
with cat exposure and/or who are participating
veterinary-associated professionals should consider B.
henselae infection, after ruling out other suspected
infections.
Transmission of Bartonella spp.
among animals and humans
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B. weissii , B. chomelii , B. schoenB. alsatica
B. henselae
B. henselae, B. clarridgeiae, B.B. vinsonii subsp. berkhoffii
B. elizabethae, B. grahamii,
B. vinsonii subsp. arupensis,
B. washoensis
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Isolation of Bartonella species from rodents in
Taiwan, including a strain closely related to
Bartonella rochalimae from Rattus
norvegicus.
Jen-Wei Lin, Chun-Yu Chen, Wan-ching Chen, Bruno B. Chomel, Chao-chin Chang*
Journal of Medical Microbiology 2008; 57:1496-1501
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Lyme Disease
Medical and Veterinary Importance
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of ticks
• Dermatoses
• Otoacarisis
• Tick paralysis: esp. female ticks; 10% case-
fatality rate• Transmission of animal and/or zoonotic disease
agents
• Envenomization: toxic salivary components
• Exsanguination: anemia
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Soft t ick versus hard t ick
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Epidemiologic Characterics
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• LD accounts for more than 95% of all reportedcases of vector-borne illness in the U.S.
• According to CDC, the mean national annual rate
was 5.5 cases/100,000 population (1993-1997).
• The highest reported rates are in children aged
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Lyme Disease in Taiwan
• Isolation of Lyme disease agents has been reported
• Climatic conditions in Taiwan
• Ecological factors supporting tick survival in Taiwan
• Role of dogs in transmission of Lyme disease
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Figure. The host-parasiteecological continuum
(here parasites include
viruses and parasitic
prokaryotes).
Daszak P et al., Emerging
infectious diseases ofwildlife--threats to
biodiversity and human
health. Science
2000;287(5452):443-9
Published by AAAS
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Thanks for Your Attention
Materials & Methods
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π Probability of fluoroquinolone use in pigs 0.05
ρ Probability of fluoroquinolone use in humans 0.06a Rate at which bacteria becomes antibiotic-resistant after
antibiotic exposure
0.07/day
• In Taiwan, fluoroquinolones are allowed to be used in animal husbandry only for
therapeutic purposes. Its use for growth promotion has been currently prohibited.• We assume a 5% of fluoroquinolone usage in pigs, including those for therapy and
possible violation.
• In humans, about 60% of Taiwanese patients received an antibiotic prescription. Among
which, fluoroquinolones usage was about 10%.
• The probability of fluoroquinolone use in humans = 60% * 10%
• The average time for bacteria to become antibiotic-resistant after fluoroquinolone
exposure was studied to happen at around 2 weeks.
N t l l t i l 0 007/d
Materials & Methods
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κ Natural loss rate, animals 0.007/day
α Natural loss rate, exposed 0.09/day
σ Natural loss rate, colonized 0.03/day
γ Natural loss rate, amplified 0.014/day
μ Loss rate of contaminated excretion in the environment 0.005/day
• In pigs, there would be a long-term excretion of S. Choleraesuis for about 150 days.
• In humans, the duration of excretion for short term Salmonella carriers is about 11 days,
while the duration of Salmonella excretion in colonized population is about 5 weeks.
• Antibiotic therapy in acute salmonellosis in humans can prolong the duration of fecal
excretion of Salmonella to approximately two-fold of that without antibiotic use.
• The natural turnover rates per day is calculated by the inverse of the duration of
Salmonella excretion in each status.
• In the environment, the spontaneous loss of resistant in antibiotic-resistant culture is
studied to be around 0.5%.
Materials & Methods
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θ Colonization rate 0.01/day
• Studies have shown that after exposure to antibiotic-resistant bacteria, about 1% of
antibiotic-resistant bacteria in the exposed population would colonize.
Materials & Methods
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ε Exposure rate from the environment, contributed by V, Y
and Z
10-6/day
δ Exposure rate from consumption/ handling of meat 10-3 /day
• In developed countries, such as Taiwan, environmental exposure of antibiotic-resistant
bacteria was considered to be rare.
• Thorough cooking of meat could kill both the susceptible and resistant bacteria.
• It is assumed that FQR S. Choleraesuis in pork can infect humans via improper cooking
or poor kitchen hygiene during food preparation.
Materials & Methods
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β Transmission rate, amplified 0.5/dayη Transmission rate, colonized 10-5/day
• The amplified population is assumed to carry a relatively high load of FQR S. Choleraesuis
and is highly contagious.
• Thus, the transmission rate β is assumed to be much higher than η.
Discussion
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Uncertainties in parameter estimation
• Probability of FQ prescription in pigs
• The exposure rate of FQR S. Choleraesuis viaconsumption/handling of contaminated pork
• The environmental exposure rate of FQR S.Choleraesuis
Discussion
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Rate of the development of FQR in S. Choleraesuis
• Continuous low-level use of antibiotics for growth promotion in animals mayresult in a faster rate for the development of antibiotic resistance in bacteria.
• Double the rate of a in pigs (a*=0.14/day)
• The equilibrium prevalence of FQR S. Choleraesuis in pigs would rise to 50%,while that in humans remained at 47%.
• Double the rate of a in humans (a*=0.14/day)
• The equilibrium prevalence of FQR S. Choleraesuis in humans would rise to