Bartonella bacilliformis - MegaMicro

a. Gram-negative

b. LPS outer membrane

c. Coccobacilliary rods

d. Pleomorphic

e. Flagellated

a. Physiology

i. Aerobic

ii. Facultative intracellular organism

b. Virulence factors

i. Multiple flagella – highly motile

ii. Deformin – water-soluble molecule which causes deformation and invagination of erythrocyte membranes and formation of intracellular vacuoles

iii. 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 internalization

2. 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 only

e. Lifecycle

i. Transmission through sandfly vector

ii. Active uptake by capillary endothelial cells

1. antigen-mediated, triggers activation of Rho GTPases

2. Leads to cytoskeletal rearrangements necessary for bacterial internalization

3. May also stimulate angiogenic signaling that results in endothelial cell proliferation

iii. Period of residence in endothelial niche before bacteria seeded into bloodstream

iv. 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. Human

ii. 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 PCR

b. 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 anemia

2. Transient immunosuppression, pallor, malaise, non-painful hepatomegaly, jaundice, lymphadenopathy, splenomegaly

3. Myalgia, arthralgia, headache common

4. 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 nodules

2. Cutaneous skin lesions, 1-2 cm

b. Differential diagnosis

i. Acute phase: Dengue fever, malaria, acute bacterial septicemias

ii. Chronic phase- Kaposi’s sarcoma, fibrosarcoma, tuberculoid leprosy, yaws

iii. Unique distinguishing feature is acute hemolytic anemia with fever

iv. Prevalence limited to small endemic region, increases suspicion

c. Therapy

i. Preferred Antibiotics

1. Chloramphenicol

2. Ciprofloxacin

3. Penicillin

4. Doxycycline

5. Rifampin

6. Gentamicin

ii. Notes

1. Ciprofloxacin-, rifampicin-, and erythromycin-resistant strains of the bacterium have been discovered

2. 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 control

i. Use repellents and protective clothing to avoid sand fly bites in areas where Carrión's disease is endemic

ii. Limit outdoor