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a. Gram-negativeb. LPS outer membranec. Coccobacilliary rodsd. Pleomorphice. Flagellated
a. Physiology
i. Aerobicii. Facultative intracellular organism
b. Virulence factors
i. Multiple flagella – highly motileii. Deformin – water-soluble molecule which causes deformation and invagination of erythrocyte membranes and formation of intracellular vacuolesiii. Invasion-associated locus A and B genes – aid bacteria survival
c. Tropism
i. Capillary endothelial cells – active uptake, antigen-mediated, triggers activation of Rho GTPases
1. Leads to cytoskeletal rearrangements necessary for bacterial internalization2. May also stimulate angiogenic signaling that results in endothelial cell proliferation
ii. Erythrocytes – passive uptake, bacteria latches onto RBCs, causes pits and invaginations to form, cells lyse
d. Hosts: humans onlye. Lifecycle
i. Transmission through sandfly vectorii. Active uptake by capillary endothelial cells
1. antigen-mediated, triggers activation of Rho GTPases2. Leads to cytoskeletal rearrangements necessary for bacterial internalization3. May also stimulate angiogenic signaling that results in endothelial cell proliferation
iii. Period of residence in endothelial niche before bacteria seeded into bloodstreamiv. Passive uptake into erythrocytes
1. bacteria latches onto RBCs, causes pits and invaginations to form, cells lyse
v. Life cycle avoids detection by host immune response – "stealthy”
a. Reservoir
i. Humanii. Restricted to endemic area of Andes Mountains (Peru, Ecuador, & Colombia)
b. Vector
i. Sandfly - Lutzomyia verrucarum (formerly Phlebotomus verrucarum)ii. Females feed on mammal blood at dawn and dusk
a. Acute phase: Peripheral blood smear with Giemsastain, Columbia-blood agar cultures, immunoblot, IFI, and PCRb. Chronic phase: Warthin-Starry stain of wart biopsy, PCR, and immunoblot
a. Diagnostic methods
i. Acute phase (Carrión disease):
1. Oroya Fever - acute hemolytic bacteremia with fevers and severe anemia2. Transient immunosuppression, pallor, malaise, non-painful hepatomegaly, jaundice, lymphadenopathy, splenomegaly3. Myalgia, arthralgia, headache common4. Fatality at this stage in untreated patients is 40-80%, if there is also another opportunistic infection (such Salmonella) mortality increases to 90%
ii. Chronic phase (Verruga Peruana or “Peruvian Wart”):
1. Characterized by an eruptive phase, in which the patients develop chronic vasoproliferative nodules2. Cutaneous skin lesions, 1-2 cm
b. Differential diagnosis
i. Acute phase: Dengue fever, malaria, acute bacterial septicemiasii. Chronic phase- Kaposi’s sarcoma, fibrosarcoma, tuberculoid leprosy, yawsiii. Unique distinguishing feature is acute hemolytic anemia with feveriv. Prevalence limited to small endemic region, increases suspicion
c. Therapy
i. Preferred Antibiotics1. Chloramphenicol2. Ciprofloxacin3. Penicillin4. Doxycycline5. Rifampin6. Gentamicinii. Notes
1. Ciprofloxacin-, rifampicin-, and erythromycin-resistant strains of the bacterium have been discovered2. Have not been shown to be resistant to gentamicin or doxycycline, so these antibiotics are believed to be the current best methods for treatment
d. Prevention and controli. Use repellents and protective clothing to avoid sand fly bites in areas where Carrión's disease is endemicii. Limit outdoor