BARTONELLOSIS 2016

CIRO MAGUIÑA, M.D.

Vicerrector de Investigación UPCH

Alexander von Humboldt Tropical Medicine Institute
Ex -DECANO NACIONAL DEL CMP
Especialista en Infectologia- Medicina Tropical
Dermatologia
 HUMAN
BARTONELLOSIS
DR HUGO LUMBRERAS : LAST TRIP TO
HUAYOPAMPA: HUARAL, 1985
 CONTENT
• Introduction and new Bartonellas
• Bacilary Angiomatosis
• Cat Scratch Disease
• History of Carrión’s disease
• Carrión’s disease : epidemiology, clinical y
presentation and therapy
BARTONELLOSIS

• BARTONELLA SPP. ARE FASTIDIOUS HAEMOTROPIC

Gram- negative bacteria which are mainly transmitted by
vectors.
• Since the last 23 years , the number of Bartonella species or

wide range of
subspecies identified from a

mammals has increased

considerably.
BARTONELLOSIS

• Among the 13 species or subspecies known or

suspected to be pathogenic for human, FOUR have
been isolated from CATS
• DOMESTIC CATS ARE THE MAIN PRINCIPAL
RESERVOIR FOR BARTONELLA HENSELAE,, the
main agent of CSD, Bartonella clarridgeiae, which has
been suspected in a few cases of CSD an Bartonella
koehlerae, reported as the cause of human and dog
endocarditis
BARTONELLOSIS :CHOMEL BB, KASTEN RW.
JOURNAL OF APLLLIED MICROBIOLOGY, 109 (20)
743-750, 2010

• Recently, Bartonella quintana was isolated from a

pet cat and its owner.
• Domestic dogs have been shown to be infected
with a broad range of Bartonellla species, such as
B. vinsonii berkhoffii,
• B. Henselae, B. clarridgeiae, B.rochalimae,
B.quintana, B koehlerae, B. washoensis, and
Bartonella elizabethae.
B. ROCHALIMAE : EMERGING INFECTIOUS
DISEASES • WWW.CDC.GOV/EID • VOL. 15,
NO. 12, DECEMBER 2009

• Recently, B. rochalimae DNA was detected in a dog from Greece .

High (43%)prevalence of bacteremia observed in gray foxes in
California suggests that they might act as a wildlife reservoir for this
newly identified species.
• Furthermore, several B.clarridgeiae–like and
• B. rochalimae genes have been detected in fleas collected from
humans , rodents ,red foxes (Vulpes vulpes) , and the environment in
the Democratic Republic of Congo (12) during a plague out-break.
EMERGING INFECTIOUS DISEASES •
WWW.CDC.GOV/EID • VOL. 15, NO. 12, DECEMBER
2009

• Conclusions : We report the isolation or detection of

• B. rochalimae from red foxes, raccoons, and

coyotes from North America, Europe, and the Middle
East.
• Sequence analysis of 4 genes identified small variations in the
B. rochalimae isolates from these different geographic regions.
• A relatively high percentage (26%) of raccoons had B.
rochalimae bacteremia compared with only 9.5% (2/21)
coyotes.
B. TAMIAE ( TAILANDIA) J CLIN
MICROBIOL. 2008
FEBRUARY; 46(2): 772–775.

• Bartonella tamiae sp. nov ., a newly recognized

three human patients
pathogen isolated from

from Thailand. Kosov, et al J Clin

Microbiol. 2008 February; 46(2): 772–
775.centers for Disease Control and Prevention, Division of Vector
Borne Infectious Diseases, 3150 Rampart Road, Fort Collins, CO
80521, USA. mkosoy@cdc.gov
(10) HELLER R, KUBINA M, MARIET P, RIEGEL P,DELACOUR G, DEHIO C, ET AL.BARTONELLA
AL-SATICASP. NOV., A NEW BARTONELLA SPECIES ISOLATED FROM THE BLOOD OF WILD
RABBITS. INT J SYST BACTERIOL. 1999;49:283–8

• Bartonella spp. Are zoonotic agents that infect erythro-cytes of mammals in which they
cause chronic bacteremia .

• B. alsatica was first identified in 1999 in

Alsace,France, as an agent of bacteremia in
healthy wild rabbits (Heller 10).
• However, in 2006, interest in B. alsatica increased when it was considered to be a
human pathogen because it caused blood-culture–negative endocarditis in a patient
who had contacts with rabbits (5).
• The present case confirms that B. alsatica could be a human pathogen, especially in
persons who live in contact with rabbits and should be considered cause of
lymphadenopathy
BARTONELLA ALSATICA :
EMERGING INFECTIOUS
DISEASES • WWW.CDC.GOV/EID • VOL.
14, NO. 12, DECEMBER 2008

• Human Case of
• Bartonella alsatica
• Lymphadenitis
INT J. SYST EVOL MICROBIOLOGY 2009

• Bartonella rattaustraliani sp. nov.,

• Bartonella queenslandensis sp. nov.
• Bartonella coopersplainsensis sp. Nov.
• identified in Australian rats.
BARTONELLA 2010

• Bartonella japonica sp. nov.

• Bartonella silvatica sp. nov., isolated from
Apodemus mice.
• Int J. Syst Evol Microbiology 2010
http://www.ncbi.nlm.nih.gov/pubmed/19656930
#
MORE THAN 20 DIFFERENT BARTONELLA
SPECIES HAVE BEEN DESCRIBED

• In fact, after the implementation of more efficient

molecular tools for detection, the number of new
species is rapidly increasing. Moreover, four new
species pathogenic for humans have been described
in the last 3 years:

B. melophagi , B. tamiae and “Candidatus

Bartonella mayotimonensis”
Appl Environ Microbiol. 2010 December; 76(24):
8062–8070
 NEW BARTONELLAS
1993 -2016

• Bartonella weiss, Bartonella washoensis

• Bartonella schoenbuchii,Bartonella birtlessi
• Bartonella bovis, Bartonella capreoli

• : Bartonella rochalimae (Cuzco 2007)

BACTEREMIA, FEVER, AND SPLENOMEGALY CAUSED
BY A NEWLY RECOGNIZED BARTONELLA SPECIES

JUNE 2007

Marina E. Eremeeva, M.D., Ph.D., Helen L. Gerns, B.A., Shari L. Lydy, Ph.D.,
Jeanna S. Goo, B.S., Edward T. Ryan, M.D., Smitha S. Mathew, B.S.,
Mary Jane Ferraro, Ph.D., Judith M. Holden, M.P.H., William L. Nicholson, Ph.D.,
Gregory A. Dasch, Ph.D., and Jane E. Koehler, M.D.

N Engl J Med. 2007 Jun 7;356(23):2381-7.

N Engl J Med. 2007 Jun 7;356(23):2381-7.
NEW SPECIE : BARTONELLA ANCASHI JULY
2013. EMERG INFEC DISEASES
NEW SPECIE :
BARTONELLA ANCASHI
JULY 2013. EMERG INFEC
DISEASES

• In 2003, in Caraz, (Ancash) , new studies were made for the therapy of peruvian wart
, in one of them, it was compared the use of azytromycin vs rifampicin.

• 127 patients were enrolled and were cultivated

to isolate bartonellas. One of them , that had verruga peruana,
presented a genetic sequence different to Bartonella bacillofirmis
• This strain was an unknown species .
• This strain CO20 was undergone to genotypification (
using secuences of rrs, y gltA, y rpoB).
• It was compared with the genetic bank of species of
Bartonella.
• The sequence 1351-bp of the fragment rrs was very
similar to 99.0% of rrs of B. bacilliformis.
• The fragments 312 and bp 589 and the fragments of gltA,
y rpoB, respectivily, were similar of the parts of Bartonella
bovis to 89.4% (gltA), y 85.9% (rpoB),
 DISEASE CAUSED BY BARTONELLA
SPECIES IN HUMANS
• B. bacilliformis Carrion’ s disease (acute Oroya) and Peruvian WART
• B. quintana BA, endocarditis, trench fever, chronic bacteremia
• B. henselae CSD, BA, peliosis hepatis, endocarditis, bacteremia,
neuroretinitis
• B. clarridgeaie CSD ( serology)
• B. elizabethae Endocarditis
• B. grahammi Neuroretinis
• B. vinsonii
• B. rochalimae Bacteremia
 SECOND BARTONELLA

• B. quintana ( Rochalimaea), the

causative agent of TRENCH FEVER
(1914)
• During World War I: severe trench
fever infected a million persons
 CUTANEOUS
BARTONELLOSIS
Bacillary angiomatosis (B. henselae and B.
quintana)
 Bacillary
Angiomatosis
1993
AIDS
 BACILLARY
ANGIOMATOSIS

• Organisms:
• B. henselae
• B. quintana

•Treatment : Doxycycline
 BARTONELLA HENSELAE
• Cat scracth disease +++
• Bacillary angiomatosis
• Bacillary peliosis hepatis
• Bacteremia/Fever
• Endocarditis
• Necroinflammatory parenchymal nodules HIV dementia(?)
• Neuroretinitis (CSD)
BARTONELLA HENSELAE
CAT SCRATCH DISEASE
CSD : LIMA PERU 1999
Serology IFI ( France)

• Bartonella henselae: 1/50- 1/800 (+ 14)

• Bartonella clarridgieae: 1/50 - 1/800 ( + 10)

Treatment: Azitromycyn

(Dr. Huarcaya, Dr Maguiña, 1999)

 BARTONELOSIS OCULAR

• Demostración de Bartonella
grahammi DNA en fluidos
oculares de un paciente con
neuroretinitis.
• Sindromes Oculares
• Retinochoroiditis Focal
• Conjuntivitis Granulomatosa
Nodular +

• Neuroretinitis
• Emmett T, Cunningham Jr.

J. of Clin Microb. 1999; 37: 4034-38

Am J. Ophtalm. 2002
 CSD IN PERÚ
Niña 5 años,
Febrile , Dx : UTI
Epilepsy
CRP:44
Sed rate:50
mm/hr
UA:Pathologic
IgM: Bartonella h.

Tx:
Rifampicine+Clari
tromycin:2
months

Polanco,Cornejo; MaguiñaPrimer reporte de enfermedad sistémica por arañazo

de gato (Bartonella henselae) en el Perú; Acta Med Per 25(4) 2008
CLINICAL CASE: ACUTE OSTEOMIELYTIS

Bone Scintigraphy
13/03/02
NEW SPECIES : BARTONELLA ANCASHI
JULY 2013
EMERG INFEC DISEASES
 STUDY
• 2003, Caraz, Ancash
• Azitromicin vs rifampicine trial for treatment of
Bartonellosis
• 127 pacientes enrolled and cultures obtained
• One isolate had a different sequence from B.
bacilliformis
• Strain CO20
• rrs, gltA, rpoB were sequenced
• rrs 1351-bp 99.0% similar to rrs of B.
Bacilliformis
• 312 bp and 589 fragmentos from gltA rpoB
similar to Bartonella bovis al 89.4% (gltA) y
85.9% (rpoB).
 HISTORY CARRIONS DISEASE
• Between 1870-1890, 7,000 railroad workers died
• They were building the highest railroad in the world
(Oroya’s railroad 3,800 meters above sea level)
• A Peruvian medical student, Daniel A. Carrión,
self-inoculated with fluid obtained from a verruga
lesion
• Days later he developed the acute phase of the
disease with severe anemia and eventually died (5
oct 1885)
 BARTONELLOSIS: HISTORY
• In 1905 Alberto Barton discovered the agent of
Oroya fever and named it ‘endoglobular body’.
• Mortality rates for the acute febrile phase varied
around 40-90% in the pre-antibiotic era.
• In 1913, Towsend discovered the vector of the
disease (“Titira”-Phlebotomus) (Today,
Lutzomyia)
NEW BOOK CARRION’S
DISEASE
 Henry MEIGGS
USA
Highest railroad in the world
(Oroya’s railroad 3,800 meters above sea level)
(1870-1885)
RAIL ROAD : LIMA - LA OROYA (3,800 MSNM)
VERRUGAS BRIDGE ( KM 61)
 Chilean soldier with “mulares” lesions. Paciente with“mular” lesions
Probably infected in Rimac valley during
invasion “La Breña”

Garcia, U. Historiografia de la Enfermedad de Carrion. Ideas e Imágenes en la enfermedad de Carrión. Análisis Historiográfico
de la Iconografia de la Bartonellosis Humana. Parte II. Folia Dermatológica Peruana 1999; 10(1):57-63.
Ecuador has
reportaded
cases in the
coast at 150 m
above sea level

Alexander B. A review of bartonellosis in Ecuador and Colombia Am J Trop Med

Hyg 1995;52:354-359.
Colombia has reported
in the last 60 years
only two cases of
Carrion’s disease

It is not a public health

issue in Colombia
 BARTONELOSIS IN PERÚ 1945 – 2005*(SE08)
INCIDENCE RATE – HISTORIC CURVE

36.00

32.00

28.00

24.00 Año 2004:

Tasa x 100 000 hab.

Casos : 8,883 (A+V+P)

20.00
T.I. : 32 x 100,000hab.
16.00 T.M. : 0.18 x 100,000 hab.

12.00

8.00

4.00

0.00
1945
1947
1949
1951
1953
1955
1957
1959
1961
1963
1965
1967
1969
1971
1973
1975
1977
1979
1981
1983
1985
1987
1989
1991
1993
1995
1997
1999
2001
2003
2005
Fuente: Ministerio de Salud – ESN-Metaxenicas - DGSP Años
 TASA DE INCIDENCIA ENFERMEDAD DE CARRION POR
REGIONES NATURALES. PERU 1996-04

120

100
TASA x 100,000 hab.

80

60

40

20

0
1996 1997 1998 1999 2000 2001 2002 2003 2004
AÑO

SIERRA SELVA COSTA

GRUPO DE TAREA PATOGENOS ESPECIALES

OFICINA GENERAL DE EPIDEMIOLOGIA
Bartonellosis (Carrion`s disease): Epidemiology

• In Peru, the disease is endemic at an altitude

between 500-3,200 meters above sea level.
• Cases have been reported from the andean
valleys and high rain forest.
VERRUGA PERUANA
VERRUGA PERUANA (PERUVIAN WART)
San José de Lourdes
1993 : HIGH JUNGLE
(Jaén, Cajamarca)
NEW FOCI
CARRION’S DISEASE : LUTZOMYA

• L. verrucarum (+++): V.
Western Interandean
Valleys (Ancash, Lima,
Chachapoyas, etc.)
• L. peruensis : (Cuzco)
• L. robusta, L.
maronensis
(Cajamarca, etc.)
• L. serrana (Monzón,
Huánuco)
 HOURLY ACTIVITY OF LUTZOMYA
30

25

20

CHAUTE – LIMA
Lutz
15

10

5
2500 msnm
0

:0
0
:0
0
:0
0
:0
0
:0
0
:0
0
:0
0 00 00 00 00 00 00 00
17 18 19 20 21 22 23 0: 1: 2: 3: 4: 5: 6:

8
7

PILLCOPATA – CUSC
5 Lutz
4
3

2
700 msnm
1
0
00

00

00

00

00

00

00
0

0
:0

:0

:0

:0

:0

:0

:0

0:

1:

2:

3:

4:

5:

6:
17

18

19

20

21

22

23
 HUMAN RESERVOIR STUDY
CARAZ, 2000

• Asymptomatic 6/813 (0.7%)

• Seropositive 8/75 (11%)
• Convalescent 3/21 (14%)
• Verrucous phase 17/74 (23%)
BARTONELLOSIS - CARRION`S DISEASE :
MICROBIOLOGY
• The agent is Bartonella bacilliformis.
• A pleomorphic Gram negative bacilli. Direct
Giemsa, and Wright stains of blood are
useful for the diagnosis.
• Special culture media containing
hemoglobin, alanine and tryptophan are
required for its isolation.
• It grows at temperatures ranging from 25 to
28º C
• The bacterium has a single pollar flagelum
on electronic microscopic evaluation
 BARTONELLOSIS (CARRION'S DISEASE) IN THE
MODERN ERA 2001.
Maguiña C, García PJ, Gotuzzo E, Cordero L, Spach D
Alexander von Humboldt Tropical Medical Institute, Cayetano Heredia University of
Peru, Lima, Peru.

Bartonellosis remains a major problem in Peru,

but many contemporary aspects of this disease
have not been adequately described. We
examined the cases of 145 symptomatic
patients in Lima, Peru, in whom bartonellosis
was diagnosed from 1969 through 1992,
including 68 patients in the acute (hematic)
phase and 77 patients in the eruptive (verruga)
phase. In modern Peru, symptomatic patients
who have acute-phase bartonellosis typically
present with a febrile illness and systemic
symptoms caused by profound anemia; most
patients respond successfully to treatment with
chloramphenicol. Patients who have eruptive-
phase bartonellosis most often present with
cutaneous verrugas but may have less specific
symptoms, such as fever and arthralgias;
diagnosis can be confirmed in such patients by
Western immunoblotting, and most patients
appear to respond to treatment with rifampin.

PMID: 11512081 [PubMed - indexed for

MEDLINE]
 CARRION’S DISEASE:
SIGNS AND SYMPTOMS
• Pallor 66(97%)
• Hepatomegaly 56(82%)
• T > 38 °C 53(78%)
• Cardiac murmur 53(78%)
• Jaundice 48(71%)
• Lymphadenopathy 47(69%)
• Tachycardia 38(56%)
• Splenomegaly 20(29%)
• Anasarca 6(9%)

Maguina et al. Bartonellosis( Carrion´s Disease in the Modern.: Clinical features of 68

patients with acute phase. CID 33:772-9 2001
 CARRION`S DISEASE NATURAL
HISTORY OF THE DISEASE
(MAGUIÑA, ET AL )
• Neurobartonellosis: Mental alteration, ranging from somnolence to
coma.

• Oportunistic infections
• Typhi and non-typhi
• Salmonella infections,
• toxoplasmic reactivation, TBC reactivation
• disseminated histoplasmosis,
• sepsis due to Shigella, Staphylococcus, Enterobacter,
Neumocystosis
• Typhus, Leptospirosis, Amebiasis
SUPERINFECTIONS ASSOCIATED WITH HUMAN
BARTONELLOSIS (ACUTE CARRION’S DISEASE)
AMONG INPATIENTS IN THE NORTHERN FOREST
OF PERU
PACHAS PE, ARANDA M, TROYES L, MATOS ARIAS J, PADILLA C, VENTURA
G, CANELO A, HUATUCO G, CHANCAFE JA, SUAREZ-OGNIO L.

• From 115 subjects enrolled, 75 were confirmed cases.

The median age was 9 years old (3months-62 years),
and 61% were male. The main superinfections
associated were: leptospirosis 54% (29/53),
toxoplasmosis 8.3% (4/48), Chagas disease 1,7%
(1/60), P. vivax 1.3% (1/75) and P. falciparum malaria
1.3%(1/75).
Abstracts ASTMH 56th Annual Meeting Philadelphia Marriott Downtown,
Philadelphia, Pennsylvania USA, November 4-8, 2007.
 CARDIOVASCULAR FINDINGS
COMPLICATIONS
• Heart failure 62.5%
• Effusive pericarditis 56.5%(#)
• Acute pulmonary edema 40%
• Cardiac Tamponade 17.5%
• Cardiovascular shock 15%
• Myocarditis 2.5%
• Endocarditis ( 2004, first case)

• (#) Ordaya, Maguiña , 2008 Acta Medica Peruana: constrictive subacute

Pericarditis
|
 CARRION’S DISEASE AND PREGNANCY

• Every pregnant woman that develops acute

bartonellosis must be considered and managed
as severe (or complicate)
• Complications associated:
• Abortion
• Fetal death
• Premature delivery
• Maternal death
• Placental and vertical transmission
• Newborn: develops the acute form with
high mortality
 CYTOKINES AND T-LYMPHOCYTE
COUNT IN PATIENTS IN THE
ACUTE AND CHRONIC PHASES OF
Bartonella bacilliformis INFECTION
IN AN ENDEMIC AREA IN PERU: A
PILOT STUDY

REV. INST. MED. TROP. SAO PAULO 53(3):149-154, MAY-

JUNE, 2011
Erick HUARCAYA (1), Ivan BEST (1), Juan RODRIGUEZ-TAFUR (2), Ciro MAGUIÑA
(1), Nelson SOLÓRZANO (3), Julio MENACHO (4), Douglas LOPEZ DE
GUIMARAES (4), Jose CHAUCA (1) & Palmira VENTOSILLA .
 Results:
New immunological findings in both phases
Plasma levels of IL-10

Niveles de IL-10 (plasma)

150

120
*
IL-10 (pg/ml)

90

60

30

0
Control Fase verrucosa Fase aguda

(n = 9) (n = 8) (n = 11)
Control Eruptive Acute

Maguiña C, Huarcaya E.
Results:
New immunological findings in both phases
Plasma levels of Gamma Interferon

Niveles de IFN-gamma (plasma)

300
IFN-gamma (pg/ml) *

200

100

0
Control Fase verrucosa Fase aguda
(n = 9) (n = 8) (n = 11)
Control Eruptive Acute
LABORATORY DIAGNOSIS

Eruptive
Method Acute Phase Asintomáticos
phase
Smear + + +

Blood culture + + +

Biopsy culture - + -

Histology - + -

Serology + + +

PCR + + +
DIAGNOSIS ACUTE PHASE: CARRION`S
DISEASE : BACILLARY FORMS
COCCUS-LIKE FORMS
 Immunologic techniques:
Sonicated immunoblot

Lane A: Positive control

20 kDa
18 kDa pool
17 kDa
Lane B and C:
14 kDa
Bartonella bacilliformis-
positive serum taken
from a patient in acute
phase
Lane D: Negative
A B C D control pool
BARTONELLOSIS
ACUTE PHASE TREATMENT
• Ciprofloxacin(+++) > 14 years old
• Amoxi\clavulanic < 14 years.
• Cloramphenicol (+++)
• Penicillin
• Red blood cells
• Corticosteroids: Coma
• Follic acid
• Diuretics
• Pericardiocentesis
 VERRUGA PERUANA
TWO CENTURIES
1898 1984
Book by Odriozola Book by Maguiña
Clin Dermatol. 2009 May-
Jun;27(3):271-80.
Bartonellosis. Maguiña
C, Guerra H, Ventosilla P.
Bartonellosis. Maguiña C, Guerra H, Ventosilla P. Clin Dermatol. 2009 May-Jun;27(3):271-80. Review.
VERRUGA PERUANA

Miliary lesions
ESTUDIOS CARAZ: DR A.TARAZONA
Peruvian Wart
Pathology
 PERUVIAN WART
DIFFERENTIAL DIAGNOSIS
• Angioma,
• Granuloma pyogenicum (Botriomicoma)
• Bacillary angiomatosis
• Kaposi’s sarcoma
• Fibrosarcoma
• Leprosy.
• Malignant lymphoma
• Reticuloendotheliosis
• Molusco contagioso, varicela
 TREATMENT
PERUVIAN WART
First Secondary
Group
Drug Dosis Drug Dosis
600mg VO qd
Rifampin
21-28days
Adolescent 500mg VO qd 500mg VO qid
Azythromicin Erythromicin
And adult 7 days 14days
500mg c/12hs
Ciprofloxacin
14 días
600mg VO qd
1g VO qwk Rifampin
21-28days
Pregnancy Azythromicin for
500mg VO qid
3 weeks Erythromicin
14days
Bartonella bacilliformis: a systematic review of
the literature to guide the research agenda for
elimination.
PLoS Negl Trop Dis. 2012;6(10):e1819. doi:
10.1371/journal.pntd.0001819. Epub 2012 Oct 25.
Sanchez Clemente N, Ugarte-Gil CA, Solórzano N,
Maguiña C, Pachas P, Blazes D, Bailey R, Mabey D,
Moore D.