Transcript Report of an unusual case of persistent bacteriemia by Bartonella

Human
Bartonellosis
caused by
Bartonella
bacilliformis
1
Henríquez
César
Paul Pachas2
Phillip Lawyer3
Larry Laughlin3
Ciro Maguiña1
1. Instituto de Medicina Tropical Alexander von HumboldtUniversidad Peruana Cayetano Heredia
2. Oficina General de Epidemiologia
3. Uniformed Services University of the Health Sciences
2002
Introduction
• Human bartonellosis is the clinical
term to define the bacterial
infections by the genus Bartonella.
• There are five important species
that produce human diseases.
History and Archeology
Bartonellosis has been
known since Pre-Inca times.
Numerous artistic
representations in clay
“huacos” depict the chronic
phase of the disease.
The historian
Garcilazo De La Vega
described a disease
with warts in
Spanish troops when
they arrived for the
first time in CoaqueEcuador.
For a long time it was
thought that the
disease was endemic
only in Peru and that
it had only one
phase: “Peruvian
wart” or “Verruga
peruana”
Historical Figures
Daniel A. Carrión
(1858-1885)
In 1875 an outbreak,
characterized by fever and
anemia (Oroya fever)
occurred in the region of
construction of the railroad line
between Lima and Oroya. In
1885, Daniel A. Carrion, a
Peruvian medical student,
inoculated himself with material
taken from a patient with
Peruvian wart. He
subsequently acquired Oroya
fever and died a month later.
Later, Alberto Barton
discovered the etiologic agent
of “Carrion’s disease”
Dr. Alberto L.
Barton
(1871-1950)
Epidemiology
• Bartonellosis is endemic in
Perú, Ecuador and
Colombia.
• Geography and weather
conditions vary depending
of the region.
• Emergence or re-emergence
of several infectious
diseases, including
bartonellosis, seem to
coincide with “el Niño”
weather phenomena.
CASOS DE ENFERMEDAD
DE CARRION
EN EL PERU
Carrion’s
disease
cases
Y EL DEPARTAMENTO
DE ANCASH. 1945-2001
(1945-2001)
3500
3000
CASOS
2500
2000
1500
1000
500
AÑ0
YEAR
BO LETIN ESTADISDICA MINSA-O RE-PCMYO EM
DIRECCIO N REG IO NAL DE SALUD-CHAVIN
* HASTA LA S.E. 6
ANCASH
PERU
02
99
96
93
90
87
84
81
78
75
72
69
66
63
60
57
54
51
48
45
0
Ancash department
was the most
CASOS DE ENFERMEDAD DE CARRION
important endemicDEPARTAMENTOS.
area of
PERU 1945-94
bartonellosis since 1945 until 1994.
OTROS
16.9%
ANCASH
83.1%
PO
Reported cases of Carrion’s
disease
AMAZONAS
AMAZONAS
PIURA
CAJAMARCA
PIURA
PIURA
CAJAMARCA
CAJAMARCA
SAN MARTIN
SAN MARTIN
AMAZONAS
AMAZONAS
AR CA
CAJAM
(1995-2001)
LORETO
LIMA
ANCASH
HUANUCO
LIMA
HUANUCO
LIMA
HUANUCO
A
ANCASH
JUNIN
M
LI
ANCASH
SH
CA
AN
LA LIBERTAD
CUSCO
CUSCO
AYACUCHO
1995
1997
1999
2001
PIURA
2.4%
LIMA
3.4%
OTROS
2.9%
AMAZONAS
10.8%
CAJAMARCA
12.3%
CUSCO
15.5%
ANCASH
52.6%
Incidence of Carrion’s disease
by regions (1996-2002)
TASA DE INCIDENCIA ENFERMEDAD DE CARRION POR
REGIONES NATURALES. PERU 1996-02
50
TASA x 100,000 hab.
40
30
20
10
0
1996
1997
1998
1999
2000
AÑO
YEARS
DIRECCIO N EJECUTIVA DE INVESTIG ACIO N
O FICINA G ENERAL DE EPIDEMIO LO G IA
Coast
COSTA
Jungle
SELVA
Andes
SIERRA
2001
2002
New foci of Carrion’s disease
New epidemic
areas identified.
ALTO AMAZONAS
SAN IGNACIO
UTCUBAMBA
RIOJA
Mortality during the
outbreaks is high.
MOYOBAMBA
RODR IGUEZ DE MENDOZA
HUAMALIES
LEONCIO PRADO
CASMA YAROWIL CA
OYON
No cases of chronic phase
(Peruvian wart)in epidemic areas.
PACHITEA
CHANCHAMAYO
BARRANCA
HUAURA
LA CONV ENCION
CALCA
PAUCARTAMBO
URUBAMBA
QUISPIC ANC HI
ANTA
No animal reservoir identified.
CUSCO
February 2002
CANC HIS
Suspected vectors:
Phlebotomine sand flies
• Smaller than a
mosquito, larger than a
midge
• Coloration varies from
light brown (sandy or
fawn) to gray or black
• Require humid, not wet,
conditions
• Only female sand flies
take a blood meal
• Nocturnal feeding
behavior
Lutzomyia
verrucarum
Photo Courtesy Dr.Grieco
and Dr. Lawyer
Suspected Vectors:
Phlebotomine sand flies
• Sand fies are weak fliers
• Fly only at night unless
disturbed in their
daytime resting site
• Sand flies transmit
Bartonella bacilliformis
from infected to
uninfected hosts by bite
• At least two species
suspected in Peru: Lu.
verrucarum and Lu.
peruensis
Lutzomyia
peruensis
Courtesy Dr.Grieco and
Dr. Lawyer
Distribution of Carrion’s disease cases
and Lutzomyia verrucarum
Provinces with
Lutzomya verrucarum
Provinces with
Carrion’s disease cases
Etiologic agent:
Bartonella bacilliformis
Gram negative aerobic,
pleomorphic, flagellated,
motile, coccobacillary, 2-3
m large and 0,2 - 0,5 m
wide and facultative
intracellular bacterium.
For its isolation, special cultures
are required containing
complemental soy agar,
proteases, peptones, some
essential amino acids and blood.
The optimum growing
temperature is 19-29 ºC.
Pathogenesis
• Bartonella bacilliformis is
transmitted by the bite of the
suspected vector Lutzomyia spp
• Following transmission, the
bacterium infects red blood cells
and endothelial cells
• The physical damage and
introduction of antigens in the
membranes of the red cells
stimulate the Reticuloendothelial
System to produce an intense
erythrophagocytosis by
macrophages and histiocytic cells
resulting in severe extra vascular
hemolytic anemia
Endothelial cells: the last
target?
• The invasion of endothelial cells is
an active process dependent on
the activation of Rho, which is an
intracellular signal implicated in
the rearrangement of the host cell
actin cytoskeletal network
The disease
• The clinical symptoms of
bartonellosis are pleomorphic and
some patients may be
asymptomatic
• The two classical clinical
presentations are the acute phase
and the chronic phase,
corresponding to the two different
host cell types invaded by the
bacterium
Acute phase: Oroya fever
or Carrion’s disease
• The mean incubation time is 21 days
(range 10 to 270 days)
• The diagnostic tests in this phase are:
Diagnostic test
Blood smear
Immunoblot
PCR(16S-23S)
Sensitivity
Values in porcentaje
Specificity Reference
36-73
91-96
1
70
94
2
47
98
3
The diagnosis
The diagnosis in the
acute phase can be
done using the thin
blood film with
Giemsa stain.
It is possible to
observe the bacillus
inside the red blood
cells.
Molecular technics
M
Base
pairs
1500 bp
600 bp
1
2
3
4
M: DNA ladder (100 bp).
1: B. bacilliformis DNA from
culture extracted by thermal lysis
(100°C, 10 min.) using 16S 23S
primers (positive control).
2: Whole blood extraction from an
acute phase patient, using 16S
23S primers.
3: Whole blood extraction from an
acute phase patient, using primers
for Citrate Synthetase gene.
4: B. bacilliformis DNA from a
culture extraction using primers
for Citrate Synthetase gene.
Immunologic technics:
Sonicated immunoblot
20
18
17
14
kDa
kDa
kDa
kDa
A
B
C
D
Lane A: Positive control
pool
Lane Band C:
Bartonella bacilliformispositive serum taken
from a patient in acute
phase
Lane D: Negative
control pool
Chronic Phase: Peruvian
wart (Verruga Peruana)
Mularlesions
Chronic Phase: Peruvian
wart (Verruga Peruana)
Miliary lesions
Chronic Phase: Peruvian
wart (Verruga Peruana)
Miliary lesions with overwhelming infection
Chronic phase: some numbers
• The diagnostic tests in this phase
are blood culture (13% of patients
with verruga have bacteriemia),
culture of the verrugous warts and
Immunoblot with a sensitivity of
70% and specificity of 100%
• The IFA has a sensitivity of 82%
and specificity of 92%
Immunity and infection
• One factor that complicates the
clearance of the bacterium is that intraerythrocytic Bartonella are protected
from both humoral and cellular immune
responses due to a lack of major
histocompatibility complex (MHC)
molecules on the surface of the mature
erythrocytes
• They are unable to present antigens of
their invaders to the immune system
Conclusion
• Human bartonellosis is a bacterial infection
by the genus bartonella
• Bartonellosis caused by B. bacilliformis
(Oroya’s fever or Carrion’s disease) is
endemic in Peru, Ecuador and Colombia
• No animal reservoir identified
• Suspected vectors: Phlebotomine sand flies
• About the disease, there are two classical
clinical presentations: acute and chronic
phase
• New endemic areas identified: Emergent
infectious disease