Short Communication
Q Fever as a Cause of Fever of Unknown Origin
and Thrombocytosis: First Molecular Evidence
of Coxiella burnetii in Brazil
Elba R.S. Lemos,1 Tatiana Rozental,1 Maria Ange´ lica M. Mares-Guia,1 Daniele N.P. Almeida,1
Namir Moreira,1 Raphael G. Silva,1 Jairo D. Barreira,1 Cristiane C. Lamas,1
Alexsandra R. Favacho,1 and Paulo V. Damasco2
Abstract
We report a case of Q fever in a man who presented with fever of 40 days duration associated with thrombocytosis.
Serological and molecular analysis (polymerase chain reaction) confirmed infection with Coxiella
burnetii. A field study was conducted by collecting blood samples from the patient’s family and from the animals
in the patient’s house. The patient’s wife and 2 of 13 dogs showed seroreactivity. Our data indicate that C. burnetii
may be an underrecognized cause of fever in Brazil and emphasize the need for clinicians to consider Q fever in
patients with a febrile illness, particularly those with a history of animal contact.
Key Words: Brazil—Fever of unknown origin—Q fever—Serologic and molecular diagnosis—Thrombocytosis.
Qfever is a worldwide zoonosis caused by Coxiella
burnetii, a small obligate intracellular Gram-negative
bacterium of the order Legionellales. The disease has a broad
spectrum of clinical manifestations, ranging from a limited
febrile illness, pneumonia, and hepatitis to life-threatening
forms such as endocarditis and meningoencephalitis (Tissot-
Dupont and Raoult 2008, Cunha et al. 2009). Ticks, farm animals,
pets, and many wild animals are possible reservoirs of
infection. Transmission to humans is usually via inhalation of
contaminated aerosols from urine, feces, milk, and birth
products or less commonly by ingestion of unpasteurized
milk from infected farm animals. Occupational groups such as
veterinarians, farmers, and slaughterhouse workers are at
highest risk. Although Q fever is distributed throughout the
world, its distribution in Brazil, where it is not a reportable
disease, is poorly defined.
Since the first seroepidemiologic study was published in
1953, little additional information has become available and
only four cases associated with endocarditis have been confirmed
by serology or Gimenez staining of valves (Branda˜o
et al. 1953, Travassos et al. 1954, Ribeiro do Valle et al. 1955,
Riemann et al. 1974, Costa et al. 2006, Siciliano et al. 2008,
Lamas et al. 2009).
On October 13, 2008, a 47-year-old man from Itaboraı´, state
of Rio de Janeiro, in southeastern Brazil, was admitted to the
Gaffre´e Guinle University Hospital/UNIRIO with a fever of
>40 days duration, associated with abdominal pain, headache,
nausea, fatigue, malaise, and depression. Physical examination
was unremarkable, except for abdominal pain on
palpation.
Laboratory exams revealed a high erythrocyte sedimentation
rate (82mm in the first hour), leukocytosis (13,100/mm3)
with neutrophilia (74%), and thrombocytosis (611,000/mm3).
Bone marrow aspiration showed slight hyperplasia of the
monocyte–macrophage system and granulocytic cells. Echocardiogram
and tomographic scans of the abdomen and
thorax were normal. Treatment with a fourth-generation
cephalosporin (cefepime 4 g/day) was begun, but without
improvement.
The patient reported that 3 months before falling ill he had
purchased 12 goats (Saneen breed), some of them for personal
milk supply and some to sell to the community. The goats
1Laboratory of Hantaviroses and Rickettsioses, Oswaldo Cruz Institute, FIOCRUZ, Rio de Janeiro, Brazil.
2Gaffre´e Guinle Hospital, Federal University of Rio de Janeiro—UNIRIO, Rio de Janeiro, Brazil.
Partial data of this study were presented as a poster at the XLV Brazilian Society of Tropical Medicine Meeting, Porto Alegre, Rio Grande
do Sul, Brazil, March 2009.
VECTOR-BORNE AND ZOONOTIC DISEASES
Volume 00, Number 00, 2010
ª Mary Ann Liebert, Inc.
DOI: 10.1089/vbz.2009.0261
1
were kept together with other animals, 14 dogs and 2 cats.
Additionally, the patient had a history of contact with the
birth products of three goats that had aborted, 3 weeks before
the onset of the symptoms.
Because of a high clinical suspicion of brucellosis, treatment
with doxycycline (200 mg/day) and rifampin (600 mg/day)
was begun and the fever disappeared in 4 days.
Serological testing for brucellosis, toxoplasmosis, leishmaniasis,
cytomegalovirus, hepatitis B and C, syphilis, bartonellosis,
ehrlichiosis, rickettsiosis, and histoplasmosis and
detection of circulating capsular polysaccharide antigen from
Cryptococcus neoformans performed on the first available serum
sample collected on 40th day after onset of illness were negative.
Mycobacteria, leishmania, and fungi cultures were also
negative. Two serum samples collected 40 and 70 days after
onset of the illness were tested for C. burnetii using a commercial
indirect immunofluorescence assay for IgG (Panbio).
Titers of specific antibodies to phase II antigen of 256 and 1024
were detected in the first and second serum samples, respectively.
After DNA extraction using a commercial kit (QIAamp
DNA; Qiagen), polymerase chain reaction (PCR) was performed
and heat shock proteins genes (htpAB) of C. burnetii
(687 bp) were amplified from the first serum sample DNA
(Hoover et al. 1992). The PCR was repeated without a positive
control and the result was confirmed, but DNA sequencing of
the amplicon detected was not possible because of insufficient
serum samples (Fig. 1). Rifampin was discontinued and the
patient was treated with doxycycline for 21 days.
In December 2008, a field investigation was carried out in
the patient’s home and blood samples from his family (wife
and daughter) and 13 dogs were collected for analysis. His
wife, who handled and fed them goat milk, told the investigators
that one of their dogs (a 7-month-old female) had died,
and another had aborted puppies, while the patient was in
hospital. The wife was seroreactive for C. burnetti (titer of antiphase
II IgG of 128) and 2 of the 13 dogs showed indirect
immunofluorescence assay (IFA) reactivity (titers of antiphase
II IgG of 64 and 128) but displayed no clinical manifestations.
Unfortunately, the goats had been sold to another
farmer so biological samples from these animals were not
available for analysis.
All the symptoms were resolved and the patient was discharged
at 4 weeks after admission. A third sample of the
patient’s serum collected at 6 months after the onset of illness
was analyzed and showed an IgG titer of 128 against phase II
antigens of C. burnetii.
Although several classical clinical descriptions of Q fever
have been recognized in different regions of the world, some
atypical and severe forms can be difficult to identify. Fever of
unknown origin, clinical pictures mimicking systemic inflammatory
disease, or lymphoproliferative disorders have
also been described (Tissot-Dupont and Raoult 2008, Cunha
et al. 2009). This article reports a case of Q fever presenting as
fever of unknown origin and thrombocytosis that recovered
after 3 weeks of treatment with doxycycline. Although
thrombocytopenia occurs in about 25% of patients in the early
phase of the illness, the presence of reactive thrombocytosis
has also been described during its later phase (Tissot-Dupont
and Raoult 2008, Cunha et al. 2009).
Studies of C. burnetii in humans and animals are
frequently based on serologic tests, and the prevalence of
C. burnetii infection varies widely from one country to another
(Tissot-Dupont and Raoult 2008). Our findings provide
definitive confirmation of Q fever in Brazil, where there are
no molecular studies documenting C. burnetii infection in
humans or animals. Anti-C. burnetii antibodies were also
detected in the patient’s wife and in two dogs, providing
further evidence of the circulation of C. burnetii in Itaboraı´,
Rio de Janeiro, Brazil.
Although the PCR results were positive, DNA sequencing
of the detected amplicon was not possible because of lack of
sufficient biological material in the first serum sample.
Further studies including molecular characterization of
C. burnetii are necessary to establish the extent and the importance
of Q fever in Brazil.
Disclosure Statement
No competing financial interests exist.
References
Branda˜ o, H, Ribeiro do Valle, LA, Christova˜ o, DA. Investigac¸a˜o
sobre a febre Q em Sa˜o Paulo. 1. Estudo sorolo´ gico em opera
´rios de um frigorı´fico. Arq Fac Hig Su´de Publ Univ Sa˜o Paulo
1953; 7:127–134.
Costa, PS, Brigatte, ME, Greco, DB. Questing one Brazilian
query: reporting 16 cases of Q fever from Minas Gerais, Brazil.
Rev Inst Med Trop Sao Paulo 2006; 48:5–9.
Cunha, BA, Nausheen, S, Busch, L. Severe Q fever communityacquired
pneumonia (CAP) mimicking Legionnaires’ disease:
FIG. 1. Agarose gel electrophoresis of Coxiella burnetii
polymerase chain reaction product amplified from total
DNA of serum sample. S, sample from the patient with Q
fever; M, molecular size markers (100-bp ladder); N, negative
control. The arrow indicates the amplification of a 687-bp
htpAB fragment.
2 LEMOS ET AL.
clinical significance of cold agglutinins, anti-smooth muscle
antibodies and thrombocytosis. Heart Lung 2009; 38:
354–362.
Hoover, TA, Vodkin, MH, Williams, J. A Coxiella burnetii repeated
DNA element resembling a bacterial insertion sequence.
J Bacteriol 1992; 174:5540–5548.
Lamas, CC, Rozental, T, Boia, MN, Favacho, AR, et al. Seroprevalence
of Coxiella burnetii antibodies in human immunodeficiency
virus-positive patients in Jacarepagua´ , Rio de
Janeiro, Brazil. Clin Microbiol Infect 2009; 15:140–141.
Ribeiro do Valle, LA, Bassoi, ON, Castro, RM, Ferreira, JM.
Febre Q em Sa˜o Paulo. Primeiro caso confirmado por estudos
sorolo´ gicos. Rev Paul Med 1955; 46:81–90.
Riemann, HP, Brant, PC, Franti, CE, Reis, R, et al. Antibodies to
Toxoplasma gondii and Coxiella burneti among students and
other personnel in veterinary colleges in California and Brazil.
Am J Epidemiol 1974; 100:197–208.
Siciliano, RF, Ribeiro, HB, Furtado, RHM, Castelli, JB, et al.
Endocarditis due to Coxiella burnetii (Q fever): a rare or little
diagnosed disease? Case report. Rev Soc Bras Med Trop 2008;
41:409–412.
Tissot-Dupont, H, Raoult, D. Q fever. Infect Dis Clin North Am
2008; 22:505–514.
Travassos, J, Ubatuba, A, Silva, NP, Mello, MT. Febre Q no Rio
de Janeiro. Cienc e Cult 1954; 6:199–200.
Address correspondence to:
Elba R.S. Lemos
Laboratory of Hantaviroses and Rickettsioses
Oswaldo Cruz Institute
FIOCRUZ
Pavilha˜o He´lio Peggy Pereira
Sala B116, FIOCRUZ
Avenida Brasil, 4365
Rio de Janeiro 22040-900
Brazil
E-mail: elemos@ioc.fiocruz.br
Coxiella burnetii IN BRAZIL 3
Loja da Apple em Nova York teve cartazes
Repórter da BBC testa o iPad 2, lançado por Steve Jobs na quarta-feira (2) (Foto: Reprodução/BBC)
