Rocky Mountain Spotted Fever in Dogs, Brazil
Rocky Mountain
Spotted Fever in
Dogs, Brazil
Marcelo B. Labruna, Orson Kamakura,
Jonas Moraes-Filho, Mauricio C. Horta,
and Richard C. Pacheco
Clinical illness caused by Rickettsia rickettsii in dogs
has been reported solely in the United States. We report
2 natural clinical cases of Rocky Mountain spotted fever in
dogs in Brazil. Each case was confi rmed by seroconver-
sion and molecular analysis and resolved after doxycycline
therapy.
R
ickettsia rickettsii,
the etiologic agent of Rocky Moun-
tain spotted fever (RMSF), is the most pathogenic of
the rickettsiae for humans and some animals. RMSF has
been reported in North, Central, and South America, where
different tick species serve as vectors (
1). Although sero-
logic studies among healthy dogs in Brazil have indicated
past infection by
R. rickettsii (2,3), clinical illness caused
by
R. rickettsii in dogs has been reported solely in the Unit-
ed States (
4,5).
In Brazil, the most common vector-borne disease of
dogs is canine monocytic ehrlichiosis (CME), caused by
Ehrlichia canis (6). Clinical signs (fever, depression, pete-
chial hemorrhages, thrombocytopenia) in dogs with overt
RMSF infection or CME are often similar (
5). Doxycycline
is the treatment of choice for
R. rickettsii infection in dogs
(
7) and the most commonly prescribed treatment for CME
in Brazil. Thus, clinical cases of RMSF among dogs in Bra-
zil could be being misdiagnosed as CME. We describe 2
natural cases of RMSF in dogs in Brazil.
The Cases
On August 23, 2007, a 4-year-old, female, Dogue de
Bordeaux (dog 1) was brought to a veterinary clinic in São
Paulo because of a high load of ticks noticed 5 days after
she had been to a farm in the Itu Municipality (23°15′S,
47°17′W), state of São Paulo. The dog was treated with
fi pronil and sent home. Tick taxonomic identifi cation was
not performed. The next day, the dog had diarrhea and he-
matochezia and was taken back to the clinic, where labora-
tory test results were within reference ranges, except for
a slight leukocytosis (18,000 cells/mm
3) and elevated al-
kaline phosphatase level (278.6 U/L). Metronidazol was
prescribed, and the dog was again sent home. Three days
later, the dog was febrile (40.5°C), anorexic, and lethar-
gic. Blood was sent to a private laboratory, where a battery
of PCR tests failed to detect DNA of
Babesia spp., Borre-
lia
spp., Mycoplasma spp., or Ehrlichia spp. The dog was
treated with subcutaneous imidocarb and oral doxycycline.
The next day, the dog was still febrile (39.4°C) and anorex-
ic, and neurologic signs (ataxia and vestibular syndrome
with spontaneous nystagmus) had developed. The animal
was hospitalized; doxycycline was switched to the subcu-
taneous route; and the next day oral prednisone was added.
Blood values remained within reference range, except for
a slight leukocytosis (17,600 cells/mm
3). On August 30,
neurologic improvement was noted, and the dog had no fe-
ver (38.5°C) and started to eat. Despite slight nystagmus,
the dog was discharged the next day. On September 3, (8
days after doxycycline therapy began), the dog showed no
clinical abnormality, and a new blood sample was collected
for serologic testing. Another blood sample collected on
September 10 showed hematologic parameters within ref-
erence range except for leukopenia (6,900 cells/mm
3).
Serologic evaluation was performed by indirect immu-
nofl uorescence assay (IFA) by using antigens of 6
Rickett-
sia
isolates from Brazil (8). Plasma from the sample col-
lected on August 24 showed an IFA endpoint titer of 128
for
R. rickettsii and no reactivity for the remaining rick-
ettsial antigens at a 1:64 dilution. Plasma from the sample
collected on September 3 showed the following endpoint
titers for rickettsial antigens:
R. rickettsii 2,048, R. parkeri
512,
R. amblyommii 512, R. felis 512, R. rhipicephali, and
512;
R. bellii 256.
DNA was extracted from the blood samples collect-
ed on August 24 and September 3 (before and after anti-
microbial drug therapy) by using the DNeasy Tissue Kit
(QIAGEN, Chatsworth, CA, USA). Samples were tested
by 2 PCR protocols: one targeting a 147-bp fragment of the
rickettsial
gltA gene (9), and the other, a heminested PCR,
targeting a fragment of the rickettsial
ompA gene (10). Ex-
tracted DNA from the fi rst blood sample yielded expected
products by both PCR protocols. No product was obtained
from the second blood sample. Sequencing of the
ompA
product resulted in a 452-bp fragment 100% identical to
the corresponding sequence of the Bitterroot strain of
R.
rickettsii
from the United States (GenBank accession no.
U43804).
Ehrlichia spp. were not detected by PCR (6) in
either sample.
The second case was noted on August 28, 2007, when
a 10-month-old, female, miniature Schnauzer (dog 2) was
examined at the same veterinary clinic for anorexia, leth-
argy, fever (40.2°C), vomiting, and tick infestation. This
dog had visited the same farm at the same time as dog 1.
No neurologic signs were observed. Dog 2 was treated with
DISPATCHES
458 Emerging Infectious Diseases • www.cdc.gov/eid • Vol. 15, No. 3, March 2009
Author affi liations: University of São Paulo, São Paulo, Brazil (M.B.
Labruna, J. Moraes-Filho, M.C. Horta, R.C. Pacheco); and Instituto
Dog Bakery de Medicina Animal, São Paulo (O. Kamakura)
DOI: 10.3201/eid1503.081227
Rocky Mountain Spotted Fever in Dogs, Brazil
fi pronil and sent home with atropine, imizol, ranitidine,
dipirone, and doxycycline. Blood collected on August 28
had values within reference ranges, except for thrombocy-
topenia (thrombocytes 150,000/mm
3). IFA for rickettsial
antigens showed no reactivity at the 1:64 dilution for the
6 rickettsial antigens, but serum from a second sample col-
lected on September 3 (when the dog was showing no clini-
cal signs) showed the following endpoint titers:
R. rickettsii
4,096
R. parkeri 512, R. amblyommii 512, R. felis 256, R.
rhipicephali
256, and R. bellii 256.
DNA was extracted from the samples collected on Au-
gust 24 and September 3 (before and after antimicrobial
drug therapy) and processed by the PCR protocols cited
above. Extracted DNA from the fi rst sample yielded ex-
pected product for the
gltA-PCR, which was not sequenced.
No other PCR product was obtained.
Conclusions
Defi nitive diagnoses of naturally acquired R. rickettsii
infection in 2 dogs in Brazil are supported by 1) paired se-
rum samples with >8-fold rise in antibody titer to
R. rick-
ettsii
antigen; 2) titers to R. rickettsii >4-fold higher than
titers to other rickettsial antigens known to occur in Brazil;
3) detection of rickettsial DNA in canine blood, confi rmed
to be
R. rickettsii in at least 1 of the dogs; 4) compatible
clinical signs and laboratory abnormalities (i.e., thrombo-
cytopenia in at least 1 dog); 5) response to doxycycline;
and 6) compatible epidemiologic history (i.e., prior con-
tact with ticks in an RMSF-endemic area). This sixth state-
ment is supported by the fact that Itu municipality is an
area where RMSF laboratory-confi rmed cases in humans
have been reported since 2003 (www.cve.saude.sp.gov.br).
Owners of the 2 dogs reported here noted various capybaras
(
Hydrochoerus hydrochaeris) in the area where their dogs
had become infested with ticks (data not shown). Capyba-
ras are one of the main hosts of
Amblyomma cajennense
ticks, the most common important vector of
R. rickettsii in
Brazil (
9,11).
In a recent study of experimental infection, dogs ex-
posed to a Brazil isolate of
R. rickettsii had fever, lethargy,
anorexia, anemia, and thrombocytopenia; 1 also had ocular
lesions (
12). These clinical signs have been reported in the
United States for dogs with active
R. rickettsii infection
(
4,5) and were also noted in the present study under natural
conditions, except for anemia and ocular lesions. Studies in
the United States have shown that neurologic dysfunction
occurs in as many as 43% of dogs with RMSF; vestibular
dysfunction is possibly the most frequent neurologic ab-
normality (
13). These results suggest that clinical illness
caused by
R. rickettsii in dogs has similar patterns in Brazil
and the United States.
Veterinarians in Brazil should include
R. rickettsii in-
fection in their differential diagnoses of CME and other
acute nonspecifi c febrile illnesses of dogs, especially be-
cause
R. rickettsii is highly pathogenic for humans. In the
United States, several cases of human infection have been
preceded by RMSF in dogs (
14,15). Accurate diagnosis of
RMSF in dogs should lead to dog owners understanding
risk for infection from ticks in their location (
14) and pro-
vide valuable information for the surveillance of RMSF in
humans.
This work was supported by the Instituto Dog Bakery de
Medicina Animal, Fundação de Amparo a Pesquisa do Estado de
São Paulo, and CNPq-Conselho Nacional de Desenvolvimento
Científi co e Tecnológico.
Dr Labruna is associate professor of epidemiology of animal
parasitic diseases at the Faculty of Veterinary Medicine of the
University of São Paulo, Brazil. His research interests have fo-
cused on the ecology of ticks and tick-borne diseases.
References
1. Chapman AS, Bakken JS, Folk SM, Paddock CD, Bloch KC, Krusell
A, et al. Diagnosis and management of tickborne rickettsial diseases:
Rocky Mountain spotted fever, ehrlichioses, and anaplasmosis—
United States: a practical guide for physicians and other health-care
and public health professionals. MMWR Recomm Rep. 2006;55:1–
27.
2. Horta MC, Labruna MB, Pinter A, Linardi PM, Schumaker TTS.
Rickettsia infection in fi ve areas of the state of São Paulo. Mem
Inst Oswaldo Cruz. 2007;102:793–801. DOI: 10.1590/S0074-
02762007000700003
3. Pinter A, Horta MC, Pacheco RC, Moraes-Filho J, Labruna MB.
Serosurvey for
Rickettsia spp in dogs and humans from a Brazilian
spotted fever endemic area in the state of São Paulo. Cad Saude Pub-
lica. 2008;24:247–52. DOI: 10.1590/S0102-311X2008000200003
4. Gasser AM, Birkenheuer AJ, Breitschwerdt EB. Canine Rocky
Mountain spotted fever: a retrospective study of 30 cases. J Am
Anim Hosp Assoc. 2001;37:41–8.
5. Grindem CB, Breitschwerdt EB, Perkins PC, Cullins LD, Thomas
TJ, Hegarty BC. Platelet-associated immunoglobulin (antiplatelet
antibody) in canine Rocky Mountain spotted fever and ehrlichiosis.
J Am Anim Hosp Assoc. 1999;35:56–61.
6. Aguiar DM, Cavalcante GT, Pinter A, Gennari SM, Camargo
LMA, Labruna MB. Prevalence of
Ehrlichia canis (Rickettsiales:
Anaplasmataceae) in dogs and
Rhipicephalus sanguineus (Acari:
Ixodidae) ticks from Brazil. J Med Entomol. 2007;44:126–32. DOI:
10.1603/0022-2585(2007)44[126:POECRA]2.0.CO;2
7. Breitschwerdt EB, Papich MG, Hegarty BC, Gilber B, Hancock SI,
Davidson MG. Ef fi cacy of doxycycline, azithromycin, or trova fl oxa-
cin for treatment of experimental Rocky Mountain spotted fever in
dogs. Antimicrob Agents Chemother. 1999;43:813–21.
8. Labruna MB, Horta MC, Aguiar DM, Cavalcante GT, Pinter A, Gen-
nari SM, et al. Prevalence of
Rickettsia infection in dogs from the ur-
ban and rural areas of Monte Negro municipality, western Amazon,
Brazil. Vector Borne Zoonotic Dis. 2007;7:249–55. DOI: 10.1089/
vbz.2006.0621
9. Guedes E, Leite RC, Prata MCA, Pacheco RC, Walker DH, Labruna
MB. Detection of
Rickettsia rickettsii in the tick Amblyomma ca-
jennense
in a new Brazilian spotted fever-endemic area in the state
of Minas Gerais. Mem Inst Oswaldo Cruz. 2005;100:841–5. DOI:
10.1590/S0074-02762005000800004
Emerging Infectious Diseases • www.cdc.gov/eid • Vol. 15, No. 3, March 2009 459
10. Eremeeva ME, Bosserman EA, Demma LJ, Zambrano ML, Blau
DM, Dasch GA. Isolation and identifi cation of Rickettsia massiliae
from
Rhipicephalus sanguineus ticks collected in Arizona. Appl En-
viron Microbiol. 2006;72:5569–77. DOI: 10.1128/AEM.00122-06
11. Labruna MB, Whitworth T, Horta MC, Bouyer DH, McBride JW,
Pinter A, et al.
Rickettsia species infecting Amblyomma cooperi ticks
from an area in the state of São Paulo, Brazil, where Brazilian spot-
ted fever is endemic. J Clin Microbiol. 2004;42:90–8. DOI: 10.1128/
JCM.42.1.90-98.2004
12. Piranda EM, Faccini JLH, Pinter A, Saito TB, Pacheco RC,
Hagiwara MK, et al. Experimental infection of dogs with Brazil-
ian strain of
Rickettsia rickettsii: clinical and laboratory fi ndings.
Mem Inst Oswaldo Cruz. 2008;103:696–701 10.1590/S0074-
02762008000700012. DOI: 10.1590/S0074-02762008000700012
13. Mikszewski JS, Vite CH. Central nervous system dysfunction as-
sociated with Rocky Mountain spotted fever infection in fi ve dogs. J
Am Anim Hosp Assoc. 2005;41:259–66.
14. Paddock CD, Brenner O, Vaid C, Boyd DB, Berg JM, Joseph RJ, et
al. Short report: concurrent Rocky Mountain spotted fever in a dog
and its owner. Am J Trop Med Hyg. 2002;66:197–9.
15. Elchos BN, Goddard J. Implications of presumptive fatal Rocky
Mountain spotted fever in two dogs and their owner. J Am Vet Med
Assoc. 2003;223:1450–2. DOI: 10.2460/javma.2003.223.1450
Address for correspondence: Marcelo B. Labruna, Departamento de
Medicina Veterinária Preventiva e Saúde Animal, Faculdade de Medicina
Veterinária e Zootecnia, Universidade de São Paulo, São Paulo, SP, Brazil
05508-270; email: labruna@usp.br
DISPATCHES
460 Emerging Infectious Diseases • www.cdc.gov/eid • Vol. 15, No. 3, March 2009
All material published in Emerging Infectious Diseases is in the
public domain and may be used and reprinted without special
permission; proper citation, however, is required.
TitleDispatches.indd
Authorrpt4
Created Date2/18/2009 10:40:35 AM