1. Dr.Jayaprada

2.  Bartonella are very small Gram negative bacilli
transmitted by arthropods which invade
mammalian endothelial cells and blood cells.
 Human pathogenic strains are B. bacilliformis, B.
quintana and B. henselae.
 Bartonella ( including some spp formerly known
as Rochalimaea) is a genus of short, Facultative
intracellular, pleomorphic, Gram negative
coccobacilli/bacillary rods.

3.  Bartonella belongs to:
 CLASS: Alphaproteobacteria.
 ORDER: Rhizobiales.
 FAMILY: Bartonellaceae.
 GENUS: Bartonella.
 Family Bartonellaceae contains two genera:
 Bartonella and Grahamella.
 Members of genus Grahamella do not infect humans.
 The genus Bartonella consists of 22 species.

4.  BARTONELLA SPP CONDITION
 B.bacilliformis-CARRION’S disease (Oroya fever/
Verruga peruana.
 B. quintana Trench fever, Bacillary
angiomatosis,Endocarditis, Chronic bacteremia.
 B.henselae Cat scratch disease, Endocarditis,
Myocarditis, Chronic bacteremia, Bacillary angiomatosis,
Neuroretinitis, Status epilepticus, Arthritis , Peliosis
hepatis, prolonged fever, weight loss, Glomeronephritis,
osteomyelitis……
 B.clarridgeiaeCSD ( serological only).
 B.elizibathae Endocarditis.
 B.vinsonii berkhoffi  Endocarditis.

5.  B.grahamii Uveitis, Bilateral retinal artery
occlusion.
 B.vinsonii arupensis fever, confusion, valvu
lopathy
 B. washoensis  Cardiopathy (myocarditis).
 Recently, Candidatus Bartonella washoensis
and Candidatus Bartonella melophagi were
respectively isolated from aortic valve of 1
patient with culture-negative endocarditis

6. RESERVOIR VECTOR
B. quintana Human Human Body Louse
B. bacilliformis Sand Flies
B. henselae Feline Cat flea (Ctenocephalides
felis)
B. elizabethae Rat
B. washoensis Gr. Squirrel
B. vinsonii arup Mice Deer tick (Ixodes
scapularis)
B. vinsonii berk. Canine Ticks
B. koehlare Cat Cat flea (Ctenocephalides
felis)
B. clarridgeae Cat flea (Ctenocephalides
felis)

7.  Organism Resevoir Transmission Disease(s)
 B. bacilliformis ?humans Sand flies Carrion's disease
 B. quintana ?humans Human body Trench fever, relapsing
?rodents louse fever, bacteremia,
endocarditis, bacillary
angiomatosis,
lymphadenopathy
 B. henselae Domestic Cat bites or Cat-scratch disease,
cats scratches bacteremia, endocarditis,
bacillary angiomatosis,
peliosis hepatitis
• Bartonella currently includes 22 species, only 5 cause human
disease

8. B. bacilliformis - sandfly, Lutzymia verrucarum
B. quintana - human body louse, Pediculus
humanus humanus
B. henselae - cat flea, Ctenocephalides felis

11.  B. bacilliformis is the causative agent of Oroya fever.
 An acute febrile illness consisting of severe anemia.
 This condition was first identified in the mountainous
parts of Peru in 1870 during the laying of railway lines
from Lima to Oroya in Peru.
 The outbreak of Oroya fever killed 1000 of workers
associated with this railway project.
 Some of the survivors developed nodular ulcerating
skin lesions, called verruga peruana.
 Daniel Carrion inoculated himself with material from
verruga and developed Oroya fever from which he
died.
 Oroya fever is therefore also known as Carrion's
disease.

12. Source: www.earlham.edu
PERUVIAN ANDES B. BACILLIFORMIS

13.  B. bacilliformis are short, Gram-negative
coccobacilli measuring 0.3-0.5 X 1.0-1.7µ.
 They are motile by the presence of as many as 10
flagella at one pole of the bacteria.
 They are aerobic and require an optimum pH of
7.8 and optimum temperature of 25-28°C for their
growth.
 It can grow in semisolid nutrient agar with 10%
rabbit serum and 0.5% hemoglobin.
 Growth is slow and takes about 10 days.
 No animal reservoir known. Humans remain
bacteremic for months ( 10%).

14.  B. bacilliform is causes Oroya fever transmitted by
sandflies--Lutzymia verrucarum.
 The incubation period is 3 weeks to 3 months.
 Patient develops fever, severe headache and
chills, followed by severe anaemia due to
destruction of erythrocytes by the organism.
 Several weeks after recovery, patient may develop
nodular lesions on exposed part of the body. These
nodules may become secondarily infected producing
ulcers, this condition is known as Verruga peruana.

15. B bacilliformis, which uses a polar flagellum for
motility, adheres to and invades RBCs. After
entry, the organism replicates in vacuoles.
 B bacilliformis also makes an endothelial cell–
stimulating factor that causes proliferation of both
endothelial cells and blood vessels.
 Most
spp of Bartonella are biochemically inert
except for the production of peptidases.

16.  OROYA FEVER : It is characterized by progressive,
severe & febrile anemia with intravascular
hemolysis associated with the presence of
B.bacilliformis in the RBC’s. Mortality is 40-90% in
pre antibiotic era.
 Verruga peruana: It is characterized by nodular
angioproliferative cutaneous lesions called Verruga
peruana.

17.  Organisms can be demonstrated in blood smears
stained by Gimenez stain. They are seen in the
cytoplasm as well as adhering to cell surfaces.
 (ii) It can be grown on nutrient agar containing
10% rabbit serum and 0.5% haemoglobin.
 (iii) Guinea pig inoculation leads to verruga peruana
but not Oroya fever.

18.  Penicillin, streptomycin, tetracycline, and
chloramphenicol are effective for the treatment of
B. bacilliformis infection.
 Use of insecticides such as DDT to kill the sand fly
prevents transmission of the disease.

20.  B. quintana is a small Gram negative bacillus
measuring 0.3 - 0.5µ x 1.0 - 1.7µ.
 It does not possess flagella.
 It may show twitching movement on wet mounts
associated with the expression of TAAs-Trimeric
Autotransporter Adhesin.
 TAAs are responsible for cytoadherence & may
mediate specific interactions with extracellular
components and endothelial cells.

21.  Itgrows on rabbit or sheep blood agar.
Optimum temperature for growth is 35°C in
5% CO 2 .
 Colonies are smooth, flat, shiny & do not pit
the agar and appear after 14 days in primary
culture.
 It was formerly called Rochalimaea
quintana.
 It causes trench fever.

22. World War I

23.  B. quintana was earlier known as Rochalimaea
quintana as a causative agent of trench fever or 5-
day fever.
 This condition was first recognized in the soldiers
fighting in trenches in Europe during the First
World War.
 The causative agent was earlier identified as a
rickettsia and named Rickettsia quintana because
it caused a 5-day fever (from quintana, means
fifth), a synonym for trench fever.
 Currently, it has undergone further taxonomical
classification and has been reclassified as
Bartonella quintana.

24.  Rochalimaea differs from rickettsiae in the
following respects:
 (i) It occurs extracellularly in the arthropod host.
 (ii) It grows poorly in the yolk sac of chick embryo.
 (iii) It can be grown on blood agar.
 (iv) Convalescent sera from patients do not react
with rickettsial or Proteus antigens (Weil-Felix
reaction).
 (v) It does not cause experimental infection in any
of the common laboratory animals.
 Only monkeys can be infected besides man and the
louse.

25.  Trench fever is an exclusively human disease and no
animal reservoir is known. It is transmitted by the
body louse (Pediculus humanus humanus).
 The lice become infectious 5-9 days after feeding on a
trench fever patient, after which the lice remain
infectious throughout their life and excrete organisms
in their feces.
 The infected lice when bite a new host defecate on
surface of the skin. This feces when comes in contact
with minor scratches or abrasions on the surface of the
skin, the bacteria present in the feces enter the skin
and initiate the infection.

26.  Incubation period -- 14-30 days.
 The condition can vary from asymptomatic to
symptomatic infection.
 Severe headache, fever (giving the name of the
disease as 5-day fever), chills, weakness, and
severe pain in the back and legs, abdominal pain,
restlessness, insomnia.
 Several cases of endocarditis have been
associated with B.quitana infection.
 In HIV infected persons, bacteremia results in
recurrent fever, headache, hepatomegaly.
 B.quitana & B.henselae are the 2 Bartonella spp
involved in the aetiology of bacillary
angiomatosis.

27.  Bacillary angiomatosis also called epitheloid
angiomatosis.
 It is a vasoproliferative disease characterized by
violaceous/ colorless papular and nodular lesions.
 It clinically suggest Kaposi's sarcoma &
histologically resemble epitheloid haemangiomas.
 When visceral organs are involved,the condition is
called Bacillary peliosis hepatis, splenic peliosis,
systemic bacillary angiomatosis.
 Subcutaneous and lytic lesions in the bone are
associated with B .quintana infection.

28.  Trench fever is an exclusively human disease. No
animal reservoir.
 The disease is transmitted from humans to
humans by the human body louse vector.
 Trench fever cases have been identified in
 some homeless persons living in unsanitary
 conditions in the USA.

29.  Isolation of the bacteria from patient's blood
on blood agar after 2 weeks of incubation.
 B. quintana can be isolated by allowing
healthy lice to feed upon the patient and the
organisms may be detected in the gut of
these lice (xenodiagnosis).
 Weil-Felix test used for diagnosis of
rickettsial infection is negative in trench
fever.
 PCR has also been used for detection of B.
quintana in the tissues.

30.  Thecondition can be treated with gentamicin alone
or with erythromycin.

32.  B. henselae is a small Gram negative bacillus
measuring 2.0-2.5 X 0.5-0.6µ.
 Like other Bartonella species, it can grow on
chocolate agar or Columbia agar supplemented with
5% sheep or rabbit blood.
 B. henselae produces 2 morphological types of
colonies:
 1. Irregular, raised,rough, dry white cauliflower-
like colonies.
 2.Small, circular, tan & moist, tending to pit the
agar and adhere to the agar after 5-15 days of
incubation at 35-37°C in the presence of 5% CO 2 .

33. Presence of B. henselae
arrow) within naturally
infected cat erythrocytes,
as seen by confocal
microscopy.
Natural History of
Bartonella Infections (an
Exception to Koch’s
Postulate) CVI, 2002

35.  Erythrocytes
 Firm bacterial adhesion
 Internalization
 Membrane-bound compartments
 Bacteria replicate within erythrocytes
 Circulate in the bloodstream (weeks to months)
 Long-lasting intraerythrocytic infection
 Specific adaption to the mode of
transmission

36.  Vascular endothelial cells
 Monocytes/macrophages
 Immunocompenent host
 Self-limiting CSD
 Swollen lymph nodes and fever
 Immunocompromised host
 Bacilliaryangiomatosis-peliosis (BAP)
 Tumour-like vasoproliferative lesions

37.  Immunocompetent human host
 Self-limiting CSD, swollen lymph nodes and fever
 Immunocompromised human host
 Bacillary angiomatosis-peliosis (BAP)
 Tumor-like vasoproliferative lesion

40. CATSCRATCH DISEASE

41.  Worldwide distribution
 Prevalence in warm/humid climates
~ 20,000 cases annually in US
 80% under the age of 20yrs
 30% of domestic cats are infected

42.  Endothelial Cell Invasion and Colonization:
 Human umbilical endothelial cells (HUVECs)
 Bacterial adhesion and invasion
 Actin-dependant mechanisms
 Intracellular membrane-bound compartments
 B. henselaeinfection leads to:
 Secretion of vascularproliferative compounds
 Inhibition of host cell apoptosis
 Host cell proliferation

43.  Conventional phagocytosis
 Bacteria reside in membrane-bound intracellular
compartments
 24hrs post infection
 BCVs do not mature into phagosomes
 Protects intracellular bacteria from degradation
 Site of bacterial replication

44. Kyme, 2005

45.  B.henselaedelays fusion of BCVs with
lysosomes
 Endocytic markers (LAMP1 and EEA1)
 Phagosome maturation controlled by active
modulation of host cell
 Bacterial surface adhesion protein, BadA prevents
phagocytosis
 B.
henselaehas an alternative cell entry
mechanism

46.  A) Stained with TR dextran
 B) LysoTracker Red
 C) LAMP1
 D) EEA1
 E) TfR
 Intracellular bacteria are green
(FITC) and extracellular bacteria
appear blue (FITC+Cy5).
 Intracellular B. henselae(green)
that co-localize with intracellular
markers (red) appear yellow.
 Normal phagosome maturation was
confirmed by strong accumulation
of LAMP1 (green).

47.  Dependent on the VirB/VirD4 type four
secretion system
 Cell surface bacterial aggregates
 Host cell membrane protrusions engulf
bacterial aggregates
 Internalization of bacterial aggregates
 Specific mechanism for endothelial cells
colonization in vivo
 Characteristic bacterial aggregates found in
bacillary angiomatosis lesions
 In association with proliferating endothelial cells

49.  The formation
(A,B), engulfment
(C,D) and
internalization
(E,F) of a bacterial
aggregate
represent the
stages in
invasome-
mediated invasion.