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  • 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, valvulopathy 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 VECTORB. quintana Human Human Body LouseB. bacilliformis Sand FliesB. henselae Feline Cat flea (Ctenocephalides felis)B. elizabethae RatB. washoensis Gr. SquirrelB. vinsonii arup Mice Deer tick (Ixodes scapularis)B. vinsonii berk. Canine TicksB. koehlare Cat Cat flea (Ctenocephalides felis)B. clarridgeae Cat flea (Ctenocephalides felis)
  • 7.  Organism Resevoir Transmission Disease(s) B. bacilliformis ?humans Sand flies Carrions 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 verrucarumB. quintana - human body louse, Pediculus humanus humanusB. henselae - cat flea, Ctenocephalides felis
  • 9.  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 Carrions disease.
  • 10. Source: www.earlham.eduPERUVIAN ANDES B. BACILLIFORMIS
  • 11.  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%).
  • 12.  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.
  • 13. 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.
  • 14.  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.
  • 15.  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 containing10% rabbit serum and 0.5% haemoglobin. (iii) Guinea pig inoculation leads to verruga peruana but not Oroya fever.
  • 16.  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.
  • 17.  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.
  • 18.  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.
  • 19. World War I
  • 20.  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.
  • 21.  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.
  • 22.  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.
  • 23.  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.
  • 24.  Bacillary angiomatosis also called epitheloid angiomatosis. It is a vasoproliferative disease characterized by violaceous/ colorless papular and nodular lesions. It clinically suggest Kaposis 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.
  • 25.  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.
  • 26.  Isolation of the bacteria from patients 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.
  • 27.  Thecondition can be treated with gentamicin alone or with erythromycin.
  • 28.  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 .
  • 29. Presence of B. henselaearrow) within naturallyinfected cat erythrocytes,as seen by confocalmicroscopy. Natural History ofBartonella Infections (anException to Koch’sPostulate) CVI, 2002
  • 30.  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
  • 31.  Vascular endothelial cells  Monocytes/macrophages Immunocompenent host  Self-limiting CSD  Swollen lymph nodes and fever Immunocompromised host  Bacilliaryangiomatosis-peliosis (BAP)  Tumour-like vasoproliferative lesions
  • 32.  Immunocompetent human host  Self-limiting CSD, swollen lymph nodes and fever Immunocompromised human host  Bacillary angiomatosis-peliosis (BAP)  Tumor-like vasoproliferative lesion
  • 34.  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
  • 35.  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
  • 36.  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
  • 37. Kyme, 2005
  • 38.  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
  • 39.  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).
  • 40.  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
  • 41.  The formation (A,B), engulfment (C,D) and internalization (E,F) of a bacterial aggregate represent the stages in invasome- mediated invasion.