I used this for my class presentation for diseases but the professors said that it isn't scientific. I guess I should have stuck with the boring black & white format.

1. By Lu Mei Ling
BSCD11806A
Cat Scratch
Disease

2. TABLE OF CONTENTS
2
01 04
0502
03
WHAT IS IT?
Introduction, History,
Epidemiology, Risk Factors
Diagnostic tests and Clinical
Manifestations (Symptoms)
ETIOLOGY
Main Etiologic Agent and Modes
of Transmission
TREATMENT
DIAGNOSIS
Therapeutic methods
PATHOGENESIS
Life Cycle, Invasion Mechanisms
and Pathogenic Factors
06PREVENTION
Ways to avoid getting CSD

3. WHAT IS IT?
Cat Scratch Disease (CSD), also known as Cat
Scratch Fever, is a zoonotic disease caused by
a bacterial infection, specifically Bartonella
henselae harbored by kittens and young cats,
and is characterised by chronic regional
lymphadenopathy following a cat scratch or
bite (Harms & Dehio, 2012).
3
INTRODUCTION

4. GENDER STATISTICS
Although females develop CSD more commonly than males,
inpatient admissions related to CSD were observed to be more
commonly males than females (Stockman, 2007).
CSD INCIDENCE IS HIGHEST IN:
OTHER STATISTICS
24,000 cases
PER YEAR
4
EPIDEMIOLOGY IN USA
● Those who live in southern USA
○ 6.4 cases/100,000 population
● Individuals below 18 years old
○ Especially 5 to 9 years old
○ accounts for 55% of CSD cases
○ 9.4 cases/100,000 population
● Fall and Winter periods
(Stockman, 2007)

5. 5
Bacillus or coccobacillus
Aerobic
Hemotropic
Non-motile
Non spore-forming
Class:
Alphaproteobacteria
Order: Rhizobiales
Family: Bartonellaceae
This bacteria can be
found in endothelial cells
and associated with
erythrocytes in
symptomatic CSD cases
ETIOLOGY
Bartonella henselae
a fastidious gram-negative bacterium
MAIN ETIOLOGIC AGENT OF CSD
(Harms & Dehio, 2012)

6. B. henselae is
carried in the
cat’s saliva,
The cat’s teeth and
claws can be
covered with B.
henselae-infected
saliva.
Cat fleas,
Ctenocephalides felis,
act as vectors for
transmission within cats.
6
MODES OF
TRANSMISSION
CAT FLEASCAT
SCRATCH
CAT BITE
Cats - Asymptomatic
RESERVOIR HOST:
INCIDENTAL HOST:
Humans
(Harms & Dehio, 2012)

7. Figure 1: An illustration of the concept of reservoir host
infections with Bartonella. Following transmission by an
arthropod vector, the Bartonella bacteria:
(a) colonise the primary niche, which involves entry
into migratory cells (CD34+ cells).
(b) transport to the vascular endothelium where the
bacteria persist intracellularly.
(c) From the primary niche, the bacteria are seeded
into the bloodstream.
(d) They invade erythrocytes and reinfect the
primary niche.
(e) After limited replication inside the erythrocyte,
they persist in the intraerythrocytic niche.
(f) They become competent for transmission by a
bloodsucking arthropod.
(g) This establishes a protected niche that is
competent for vector transmission in order to
proceed in the infection cycle.
7
LIFE CYCLE &
INFECTION STRATEGY
(Harms & Dehio, 2012)

8. 8
PATHOGENESIS
Figure 3: Interactions of
pathogenic factors of B. henselae
Trw-system (unknown
translocated effectors),
filamentous hemagglutinin
(FHA), Bartonella adhesin A
(BadA) and VirB/VirD4 type IV
secretion system (translocated
effectors: Beps).
BadA (and potentially FHA)
ensure a stable contact to the
host cell surface for further
bacteria-host cell interaction by
the type IV secretion system and
the Trw system (Franz & Kempf,
2011).
ABBREVIATIONS
IM: inner membrane
OM: outer membrane
Beps: Bartonella
effector proteins
Fn: fibronectin
BadA: Bartonella
adhesin A.

9. 9
PATHOGENESIS
● Adherence to the host is one of the most important steps during bacterial
infection processes.
● In B. henselae, this first and decisive adherence is provided by the trimeric
autotransporter Bartonella adhesin A (BadA).
● They are built in a characteristic trimeric, "lollipop"-like surface structure.
● The C-terminal membrane anchor is homologous throughout all trimeric
autotransporter adhesins, forms trimers and provides the auto-transport
activity.
● During assembly, these adhesins are secreted into the periplasm via the
secretory (Sec)-pathway and the membrane anchor forms a pore by
building a trimeric 12-stranded beta-barrel in the outer membrane. Head
and stalk domains are transported through the pore to the cell surface and
the C-terminal part of the stalk locks the pore (Franz & Kempf, 2011).
Pathogenic factor:
BadA
Taken from Figure 3:
Structure of BadA

10. 10
PATHOGENESIS
● BadA has an enormous length of 240 nm mainly due to the long and
highly repetitive stalk element, which plays a crucial role in fibronectin
(Fn) binding.
● Functions of BadA:
a. mediate bacterial auto-agglutination
b. bind to extracellular matrix components (e.g. collagens, laminin)
c. adhesion to host cells & induction of proangiogenic host cell
responses via the activation of hypoxia inducible factor (HIF)-1,
the key transcription factor involved in angiogenesis
d. Inhibition of phagocytosis
e. subsequent secretion of angiogenic cytokines [e.g. vascular
endothelial growth factor (VEGF)].
● These functional properties were assigned to the head domain of BadA
(Franz & Kempf, 2011).
BadA
Pathogenic factor:
BadA
Taken from Figure 3:
Structure of BadA

11. 11
● FHA are known to mediate adhesion to host cells in gram-
negative bacteria.
● In contrast to BadA, the presence of filamentous
hemagglutinin (FHA) necessarily depends on a second
partner (fhaC/HecB).
● After Sec-dependent secretion of both proteins to the
periplasm, fhaC/HecB forms a transmembrane beta-barrel
that allows FHA to cross the outer membrane. At the cell
surface, the protein is further modified and reaches final
maturity (Franz & Kempf, 2011).
Pathogenic factor:
Filamentous Hemagglutinin
Taken from Figure 3:
Structure of
Filamentous
Hemagglutinin
PATHOGENESIS

12. 12
● Type IV secretion systems (T4SS) are transporter complexes on
membranes that help transport substrate molecules to target cells.
● They span the inner and outer membrane of gram-negative bacteria and
transfer bacterial effector proteins or DNA to a bacterial or eukaryotic
recipient cell by a pilus.
● Functions of this system:
i. mediates rearrangements of the actin cytoskeleton resulting in
the formation of bacterial aggregates on the cell surface that are
subsequently internalised ("invasome" structure)
ii. triggers a proinflammatory response via activation of NF-kB that
in turn induces the secretion of interleukin-8 and the expression
of the cell adhesion molecules, intercellular adhesion molecule
(ICAM)-1 and E-selectin
iii. is crucial for the inhibition of endothelial apoptosis.
iv. elicits an angiogenic response whereby inflammatory cytokines
(e.g. TNF-α) are released & leads to angiogenesis (Franz & Kempf,
2011).
Pathogenic factor:
Type IV secretion system
Taken from Figure 3:
Structure of
VirB/VirD4
PATHOGENESIS

13. 13
● 7 Bartonella effector proteins (BepA-F) have been identified
that are translocated by the type IV secretion system
mechanism.
● BepA was found to protect endothelial cells from apoptosis
and promotes capillary sprouting in an 3-dimensional
endothelial spheroid infection model.
● BepG inhibits BepA-dependent sprouting. Therefore, both
proteins may control angiogenesis during B. henselae
infections.
● The combined action of BepC and BepF, but also of BepG
itself, induces "invasome"-mediated internalisation by
inhibiting bacterial endocytosis (Franz & Kempf, 2011).
Pathogenic factor:
Type IV secretion system
Taken from Figure 3:
Structure of
VirB/VirD4
PATHOGENESIS

14. 14
● Besides the VirB/VirD4 T4SS, the B. henselae genome
sequence revealed genes for a second Trw Type IV
secretion system.
● The Trw T4SS was suggested to be essential for
intracellular colonisation of erythrocytes..
● It mediates host-specificity of erythrocyte infections.
Therefore, the Trw type IV secretion system of B. henselae
might represent a further important pathogenic factor for
establishing chronic bacteremia in the primary feline
host and interacts with adhesins during the primary
infection process, comparable to the VirB/VirD4 Type IV
secretion system (Franz & Kempf, 2011).
Type IV secretion system:
Trw & VirB/VirD4 T4SS
Taken from Figure 3:
Structure of
Trw Type IV
PATHOGENESIS

15. Serology &
Immunofluorescence assay
(IFA) blood test for antibodies
against B. henselae
Polymerase Chain Reaction (PCR):
To detect different Bartonella
species with high specificity
Lymph node biopsy:
Histological examination of
the lymph node involved
Culture: Bartonella species
are difficult to culture, and
culture is not routinely
recommended
Physical examination:
Common CSD symptoms and
patient’s history with cats
15
DIAGNOSTIC TESTS
(Hansmann et al, 2005)

16. FLU-LIKE
BODY RASH
Bump (papule) or blister (pustule) at site of
injury, whereby a cat bite or scratch
becomes reddened or swollen within a few
days.
LYMPHADENOPATHY
Subacute or chronic swelling
of lymph nodes closest to
original site of scratch or bite
16
Headache, loss of appetite, fatigue,
joint pain, malaise or fever
COMMON SYMPTOMS
(Eagle, 2009)

17. 17
SYMPTOMS
Figure 6: Bumps or
blisters at the bite or
scratch site
Figure 7:
Lymphadenopathy near the
bite or scratch site
(Eagle, 2009)

18. 18
A skin disorder
characterised by red,
elevated lesions surrounded
by a scaly ring. This disorder
is more widespread as it
involves internal organs.
A condition that involves a red,
irritated and painful eye (similar to
conjunctivitis), fever, and swollen
lymph nodes in front of the ear on
the same side.
BACILLARY ANGIOMATOSIS
Most healthy people do not have
complications from CSD. However,
it can occur in
immunocompromised individuals.
PARINAUD’S OCULOGLANDULAR
SYNDROME
COMPLICATIONS
(Eagle, 2009)

19. Treatment with
trimethoprim-
sulfamethoxazole,
ciprofloxacin,
doxycycline,
erythromycin,
clarithromycin or
azithromycin.
ANTIBIOTICS
SELF-CARE
Supportive care
including antipyretics
and anti-
inflammatory
medications in
addition to warm
compresses to the
inoculation site.
19
TREATMENT
(Hansmann et al, 2005)

20. 2. If you get scratched or bitten by a
cat, wash the area with soap and
water.
3. Use flea control measures to lower
the risk of your cat developing the
disease.
1. Wash hands thoroughly with soap
and water after playing with cats.
2. Minimise contact with cats or avoid
rough play with cats to reduce risk of
scratches and bites.
3. Avoid interacting with feral cats.
1. Do not let a cat to lick your skin,
eyes, mouth, or open wounds.
20
PREVENTION
(Hansmann et al, 2005)

21. CONCLUSION
B. henselae infections are of increasing interest in
veterinary and human medicine. The pathogen
causes a long-lasting bacteremia in its feline
primary host and CSD, bacillary angiomatosis,
peliosis hepatis and other diseases in humans.
21
CONCLUSIONS

22. 22
THANK YOU
Any questions?

23. Arvand, M. & Schad, S.G., 2006. Isolation of Bartonella henselae DNA from the Peripheral Blood of a Patient with Cat
Scratch Disease up to 4 Months after the Cat Scratch Injury. Journal of Clinical Microbiology, 44(6), pp.2288–2290.
Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1489392/ [Accessed December 26, 2019].
Eagle, R., 2009. A Case of Fatal Disseminated Bartonella henselae Infection (Cat-Scratch Disease) With Encephalitis.
Yearbook of Ophthalmology, 2009, pp.239–240. Available at:
https://www.archivesofpathology.org/doi/pdf/10.1043/1543-2165(2007)131[1591:ACOFDB]2.0.CO;2 [Accessed
December 26, 2019].
Franz, B. & Kempf, V.A., 2011. Adhesion and host cell modulation: critical pathogenicity determinants of Bartonella
henselae. Parasites & Vectors, 4(1). Available at: https://parasitesandvectors.biomedcentral.com/articles/10.1186/1756-
3305-4-54#citeas [Accessed December 26, 2019].
Hansmann, Y. et al., 2005. Diagnosis of Cat Scratch Disease with Detection of Bartonella henselae by PCR: a Study of
Patients with Lymph Node Enlargement. Journal of Clinical Microbiology, 43(8), pp.3800–3806. Available at:
https://jcm.asm.org/content/43/8/3800 [Accessed December 26, 2019].
Harms, A. & Dehio, C., 2012. Intruders below the Radar: Molecular Pathogenesis of Bartonella spp. Clinical
Microbiology Reviews, 25(1), pp.42–78. Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3255967/
[Accessed December 26, 2019].
Stockman, J., 2007. Epidemiology of Cat-Scratch Disease Hospitalizations Among Children in the United States.
Yearbook of Pediatrics, 2007, pp.238–239. Available at: https://www.ncbi.nlm.nih.gov/pubmed/16094224 [Accessed
December 26, 2019]. 23
REFERENCES