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Human Rickettsia felis infection, Canary Islands, Spain.


We report the first cases of human infection by Rickettsia rickettsia (rĭkĕt`sēə), any of a group of very small microorganisms, many disease-causing, that live in vertebrates and are transmitted by bloodsucking parasitic arthropods such as fleas, lice (see louse), and ticks.  felis in the Canary Islands Canary Islands, Span. Islas Canarias, group of seven islands (1990 pop. 1,589,403), 2,808 sq mi (7,273 sq km), autonomous region of Spain, in the Atlantic Ocean off Western Sahara. They constitute two provinces of Spain. Santa Cruz de Tenerife (1990 pop. . Antibodies against R. felis were found in 5 adsorbed serum samples from 44 patients with clinically suspected rickettsiosis rickettsiosis /rick·ett·si·o·sis/ (ri-ket?se-o´sis) infection with rickettsiae.

rick·ett·si·o·sis
n.
Infection with Rickettsia bacteria.
 by Western blot Western blot
A technique developed in 1979 that is used to confirm ELISA results. HIV antigen is purified by electrophoresis and attached by blotting to a nylon or nitrocellulose filter.
 serology Serology

The division of biological science concerned with antigen-antibody reactions in serum. It properly encompasses any of these reactions, but is often used in a limited sense to denote laboratory diagnostic tests, especially for syphilis.
. Fleas from 1 patient's dog were positive for R. felis by polymerase chain reaction polymerase chain reaction (pŏl`ĭmərās') (PCR), laboratory process in which a particular DNA segment from a mixture of DNA chains is rapidly replicated, producing a large, readily analyzed sample of a piece of DNA; the process is .

**********

Rickettsia felis is an intracellular bacterium (genus Rickettsia, spotted fever spot·ted fever
n.
A tick typhus caused by Rickettsia rickettsii, such as Rocky Mountain spotted fever.


spotted fever Rocky Mountain spotted fever, see there
 group [SFG SFG StanCorp Financial Group
SFG San Francisco Giants (baseball team)
SFG Special Forces Group
SFG Sum Frequency Generation
SFG Square Foot Gardening
SFG Symmetrical Field Geometry (JBL speaker technology) 
]) (1,2). Its biological cycle involves the cat flea cat flea

ctenocephalidesfelis.
 (Ctenocephalides felis) as the main vector (3). R. felis has been found in C. felis and C. canis in the Americas, Europe, Africa, Asia, and Oceania (1,3-6). Human disease caused by R. felis was unknown until 1994 (4). Since then, R. felis infection has been reported in Mexico (3 patients) (7), Germany (1 patient) (8), Brazil (2 patients) (1), and France (2 patients) (1). The clinical manifestations of the disease include high fever, rash, and elevation of liver enzymes (1,4,7). Exposure to fleas or to flea-prone animals is sometimes recorded (7,8).

On the Canary Islands (Atlantic islands of Spain This is a list of islands of Spain.
  • Balearic Islands
  • Majorca (Spanish and Catalan Mallorca)
  • Menorca
), autochthonous autochthonous /au·toch·tho·nous/ (aw-tok´thah-nus)
1. originating in the same area in which it is found.

2. denoting a tissue graft to a new site on the same individual.
 cases of murine typhus murine typhus
n.
A comparatively mild, acute, endemic form of typhus caused by the microorganism Rickettsia typhi, transmitted from rats to humans by fleas and characterized by fever, headache, and muscular pain. Also called endemic typhus.
 have been reported (9). Although we suspected that some patients with a clinical picture of murine typhus actually had R. felis infection, we were not able to confirm this hypothesis. Therefore, 44 serum samples from 44 patients from the Canary Islands with suspected murine typhus were sent to the Unite des Rickettsies in Marseille, France, for specific serologic tests. Here, we describe the first 5 human infections caused by R. felis on the Canary Islands.

The Study

Forty-four patients were recruited for a prospective study of fever of intermediate duration (i.e., fever without focal symptoms lasting 7-28 days). Demographic, clinical, and laboratory data were collected for all patients. Chest radiographs and blood and urine cultures were taken. Antibodies against R. typhi were tested by direct immunofluorescence Immunofluorescence

A technique that uses a fluorochrome to indicate the occurrence of a specific antigen-antibody reaction. The fluorochrome labels either an antigen or an antibody.
 test (bioMerieux, Marcy L'Etoile, France) in the Canary Islands. Among the 44 patients, 24 showed a positive serologic se·rol·o·gy  
n. pl. se·rol·o·gies
1. The science that deals with the properties and reactions of serums, especially blood serum.

2.
 result. Antibodies against other agents (Coxiella burnetii Coxiella burnetii Infectious disease The single species of genus Coxiella, family Rickettsiaceae, a short, rod-shaped bacterium; it is global in distribution, causes Q fever, spreads by aerosol, primarily infects cattle, sheep, goats, multiplies well in the , R. conorii, Leptospira spp., Epstein-Barr virus Epstein-Barr virus (EBV), herpesvirus that is the major cause of infectious mononucleosis and is associated with a number of cancers, particularly lymphomas in immunosuppressed persons, including persons with AIDS. , cytomegalovirus cytomegalovirus (sī'təmĕg'əlōvī`rəs), member of the herpesvirus family that can cause serious complications in persons with weakened immune systems. , HIV HIV (Human Immunodeficiency Virus), either of two closely related retroviruses that invade T-helper lymphocytes and are responsible for AIDS. There are two types of HIV: HIV-1 and HIV-2. HIV-1 is responsible for the vast majority of AIDS in the United States. , and hepatitis B Hepatitis B Definition

Hepatitis B is a potentially serious form of liver inflammation due to infection by the hepatitis B virus (HBV). It occurs in both rapidly developing (acute) and long-lasting (chronic) forms, and is one of the most common chronic
 virus) were also tested; all were negative.

To search for evidence of infection with R. felis, all serologic results were confirmed by microimmunofluorescence (MIF (1) (Maker Interchange Format) An alternate file format for a FrameMaker document. A MIF file is ASCII text, which can be created in another program and imported into FrameMaker. ) in France, as previously described (10). Systematic testing of SFG rickettsia antigens present in Europe and Africa was performed in parallel. The MIF procedure was followed by the use of Western blot and cross-adsorption studies. An immunofluorescence assay was considered positive if immunoglobulin G immunoglobulin G
n. Abbr. IgG
The most abundant class of antibodies found in blood serum and lymph and active against bacteria, fungi, viruses, and foreign particles. Immunoglobulin G antibodies trigger action of the complement system.
 (IgG) titers were >1:64 or if IgM titers were >1:32. When cross-reactions were noted between the rickettsial rickettsial /rick·ett·si·al/ (ri-ket´se-al) pertaining to or caused by rickettsiae.

rick·ett·si·al
adj.
Relating to, or caused by a member of the genus Rickettsia.
 antigens, the analysis comprised 3 steps. First, a rickettsial antigen was considered to represent the agent of infection when IgG or IgM antibody titers against this antigen were [greater than or equal to] 2 serial dilutions higher than titers of IgG or IgM antibody against other rickettsial antigens (11). Second, when the difference in titers between R. felis and other antigens was <2 dilutions, Western blot assays were performed. A rickettsial antigen was considered the agent of infection when sera reacted only against the specific protein of this antigen. Expected molecular masses of the specific proteins were [approximately equal to] 125 kDa for R. typhi and 31 kDa for R. felis. Finally, when Western blot assays were not diagnostic, cross-adsorption studies were performed, as previously described (12). Specific diagnosis criteria after cross-adsorptions studies included a Western blot assay that showed exclusive reactivity with specific proteins of a sole agent. If reactivity with the 2 tested agents was still observed, diagnosis of an indeterminate rickettsial disease was made. With this strategy, patients were classified by 3 types: R. felis infection, R. typhi infection, and indeterminate rickettsial disease.

Five fleas from the dog of 1 R. felis-infected patient were tested by polymerase chain reaction (PCR PCR polymerase chain reaction.

PCR
abbr.
polymerase chain reaction


Polymerase chain reaction (PCR) 
) (3). DNA DNA: see nucleic acid.
DNA
 or deoxyribonucleic acid

One of two types of nucleic acid (the other is RNA); a complex organic compound found in all living cells and many viruses. It is the chemical substance of genes.
 was extracted and amplified with primers that targeted the citrate synthase sequence, as previously described (3). For negative controls, we used sterile water and infection-free fleas previously tested in our laboratory; both negative controls were tested after every 7 samples. Amplicons were separated by electrophoresis on 1% agarose agarose

more highly purified form of agar with similar uses to agar and widely used in the separation of nucleic acid fragments.
 gels and then purified by using a QIAquick PCR purification kit (Qiagen, Hilden, Germany), as described by the manufacturer. PCR products were sequenced by using the d-rhodamine terminator-cycle sequencing kit (PE Applied BioSystems, Courtabeuf, France), as described by the manufacturer. The sequences obtained were compared with those available in the GenBank DNA database by using the program Basic Local Alignment Search Tool (BLAST, version 2.0, National Center for Biotechnology Information The National Center for Biotechnology Information (NCBI) is part of the United States National Library of Medicine (NLM), a branch of the National Institutes of Health. The NCBI is located in Bethesda, Maryland and was founded in 1988.  (http://www.ncbi.nlm.nih.gov/BLAST/).

A rickettsial infection rickettsial infection Rickettsial disease, rickettsiosis Any infection by Rickettsiae Groups 1. Typhus group–epidemic typhus, Brill-Zinsser disease, murine–endemic typhus, scrub typhus; 2.  was diagnosed by using MIF for 31 of the 44 patients: 5 patients with the final diagnosis of R. felis infection, 13 with the diagnosis of R. typhi infection, and 13 with the diagnosis of indeterminate rickettsioses Rickettsioses

Often severe infectious diseases caused by several diverse and specialized bacteria, the rickettsiae and rickettsia-like organisms. The best-known rickettsial diseases infect humans and are usually transmitted by parasitic arthropod vectors.
 (Table). The diagnosis of R. felis infection was based on Western blot results on adsorbed sera for all patients. All the antibodies of these patients were removed when the R. felis-adsorbed sera were analyzed with R. typhi and R. felis antigens, whereas antibodies to R. felis remained when the R. typhi-adsorbed sera were analyzed.

Western blots performed with unadsorbed and adsorbed sera are represented in the Figure. Features of patients are indicated in the online appendix (http://www.cdc.gov/ ncidod/EID/vol11no12/05-0711_app.htm). Some differences were found between groups. The interval between the beginning of clinical signs and symptoms and evaluation was significantly more prolonged in the R. felis group than others. In the R. typhi group, odynophagia, cough, and rash were more frequent. When we compared biologic data, no difference was observed between R. typhi and R. felis groups, except for milder hypertransaminasemia in the latter group. Finally, 2 PCR products were obtained and sequenced from 2 fleas. Both sequences were 100% similar to R. felis citrate synthase gene in GenBank accession no. AF210692. No fleas were positive for R. typhi. Amplification was unsuccessful in all negative controls.

[FIGURE OMITTED]

Conclusions

In the past 10 years, application of molecular tools has resulted in discovery of several new species of pathogenic rickettsiae, including R. felis. Since then, this bacterium was cultivated, and its genome was sequenced (1,13). Its pathogenic role was recently demonstrated in patients with serologic evidence of infection in Brazil, France, and Germany (1). R. felis DNA has also been detected in sera in Texas, Mexico, Brazil, and Germany (1,4,8,14). Autochthonous human rickettsioses that occur in the Canary Islands include murine typhus; SFG infections have never been reported (9). We diagnosed 5 cases of acute R. felis infection (15). The clinical picture is globally similar to murine typhus (4). However, the R. felis infection in our study seemed to be milder, and no skin rash was observed. The incidence of R. felis infection in the Canary Islands is probably underestimated; therefore, serologic tests for R. felis should be performed in patients with prolonged fever or suspected rickettsioses.

Cross-reactions in serologic testing for R. felis are unpredictable (3). In our study, patients with R. felis infection more frequently had high antibody titers (IgM >1:32 and IgG >1:64) to R. conorii and R. typhi (2 of 5 patients) than did patients with R. typhi infection (0 of 13). On the basis of R. felis data, we conclude that patients with R. felis infection may have no cross-reactivity with other rickettsiae, cross-reactivity with SFG rickettsiae, or cross-reactivity with both SFG rickettsiae and R. typhi. Genetic support for cross-reactivity with R. conorii is plausible because most membrane proteins of SFG and R. felis are extremely close (surface cell antigen [Sca] family). Genome analysis showed that several genes were present in R. felis and R. typhi and absent for other SFG, which could explain the cross-reactivity between R. felis and R. typhi (13). Finally, if <2-fold differences in IgG/IgM titers between R. felis and other SFG and typhus typhus, any of a group of infectious diseases caused by microorganisms classified between bacteria and viruses, known as rickettsias. Typhus diseases are characterized by high fever and an early onset of rash and headache.  group rickettsiae are observed, only Western blot and cross-adsorptions will allow a specific diagnosis once reactivity has disappeared after adsorption adsorption, adhesion of the molecules of liquids, gases, and dissolved substances to the surfaces of solids, as opposed to absorption, in which the molecules actually enter the absorbing medium (see adhesion and cohesion).  with R. felis antigen. By contrast, a band of [approximately equal to] 31 kDa for the R. felis antigen persists after adsorption with R. conorii and R. typhi.

Acknowledgments

We thank Kelly Johnston and Silpak Biswas for reviewing the manuscript.

This research was supported in part by a grant from the Canary Foundation of Investigation and Health.

References

(1.) Raoult D, La Scola B, Enea M, Fournier PE, Roux Roux , Pierre Paul Émile 1853-1933.

French bacteriologist. His work with the diphtheria bacillus led to the development of antitoxins to neutralize pathogenic toxins.
 V, Fenollar F, et al. A flea-associated Rickettsia pathogenic for humans. Emerg Infect Dis. 2001;7:73-81.

(2.) La Scola B, Meconi S, Fenollar F, Rolain JM, Roux V, Raoult D. Emended e·mend  
tr.v. e·mend·ed, e·mend·ing, e·mends
To improve by critical editing: emend a faulty text.
 description of Rickettsia felis (Bouyer et al. 2001), a temperature-dependent cultured bacterium. Int J Syst Evol Microbiol. 2002;52:2035-41.

(3.) Rolain JM, Franc M, Davoust B, Raoult D. Molecular detection of Bartonella quintana Bartonella quintana Rochalimaea quintana Infectious disease A slender, fastidious coccobacillary bacterium found in the normal flora of small rodents transmitted by body lice, which causes trench fever, bacillary splenitis, bacteremia, endocarditis, , B. koehlerae, B. henselae, B. clarridgeiae, Rickettsia felis, and Wolbachia pipientis in cat fleas, France. Emerg Infect Dis. 2003;9:338-42.

(4.) Schriefer ME, Sacci JB Jr, Dumler JS, Bullen MG, Azad AF. Identification of a novel rickettsial infection in a patient diagnosed with murine typhus. J Clin Microbiol. 1994;32:949-54.

(5.) Parola P, Sanogo OY, Lerdthusnee K, Zeaiter Z, Chauvancy G, Gonzalez JP, et al. Identification of Rickettsia spp. and Bartonella spp. in from the Thai-Myanmar border. Ann N Y Acad Sci. 2003;990:173-81.

(6.) Kelly PJ, Meads N, Theobald A, Fournier PE, Raoult D. Rickettsia felis, Bartonella henselae Bartonella henselae Rochalimaea henselae Infectious disease A slender, fastidious coccobacillary bacterium of the normal flora of cats associated with bacteremia, endocarditis, cat-scratch disease, bacillary angiomatosis, peliosis hepatis; it may affect , and B. clarridgeiae, New Zealand New Zealand (zē`lənd), island country (2005 est. pop. 4,035,000), 104,454 sq mi (270,534 sq km), in the S Pacific Ocean, over 1,000 mi (1,600 km) SE of Australia. The capital is Wellington; the largest city and leading port is Auckland. . Emerg Infect Dis. 2004; 10:967-8.

(7.) Zavala-Velazquez J, Ruiz-Sosa J, Sanchez-Elias R, Becerra-Carmona G, Walker D. Rickettsia felis in Yucatan. Lancet. 2000;9235:1079-80.

(8.) Richter J, Fournier P, Petridou J, Haussinger D, Raoult D. Rickettsia felis infection acquired in Europe and documented by polymerase chain reaction. Emerg Infect Dis. 2002;8:207-8.

(9.) Hernandez CM, Angel-Moreno A, Santana E, Bolanos M, Frances A, Martin-Sanchez MS, et al. Murine typhus with renal involvement in Canary Islands, Spain. Emerg Infect Dis. 2004;10:740-3.

(10.) Teysseire N, Raoult D. Comparison of Western blot immunoblotting immunoblotting,
n the immunologic methods for isolating and quantitatively measuring immunoreactive substances. When used with immune reagents such as monoclonal antibodies, the process is known generically as
Western blot analysis.
 and microimmunofluorescence for diagnosis of Mediterranean spotted fever. J Clin Microbiol. 1992;30:455-60.

(11.) Raoult D, Fournier P, Fenollar F, Jensenius M, Prioe T, De Pina J, et al. Rickettsia africae, a tick-borne pathogen in travelers to Sub-Saharan Africa. N Engl J Med. 2001;344:1504-10.

(12.) La Scola B, Rydkina L, Ndihokubwayo JB, Raoult D. Serological serological

pertaining to or emanating from serology.


serological test
one involving examination of blood serum usually for antibody.
 differentiation of murine typhus and epidemic typhus epidemic typhus
n.
A form of typhus characterized by high fever, mental and physical depression, and macular and papular eruptions; it is caused by Rickettsia prowazekii and transmitted by body lice.
 using cross-adsorption and western blotting. Clin Diag Lab Immunol. 2000;7:6124.

(13.) Ogata H, Renesto P, Audic S, Robert C, Blanc G, Fournier PE, et al. The genome sequence of Rickettsia felis identifies the first putative conjugative plasmid con·ju·ga·tive plasmid
n.
A plasmid that can move from one cell to another during the process of conjugation.
 in an obligate intracellular parasite Obligate intracellular parasites are parasitic microorganisms that cannot reproduce outside their host cell, forcing the host to assist in the parasite's reproduction.

Obligate intracellular parasites of humans include:
  • Viruses
. PLoS Biology. 2005;3:248.

(14.) Zavala-Velazquez JE, Zavala-Castro JE, Vado-Solis I, Ruiz-Sosa JA, Moron CG, Bouyer DH, et al. Identification of Ctenocephalides felis fleas as a host of Rickettsia felis, the agent of a spotted fever rickettsiosis in Yucatan, Mexico. Vector Borne Zoonotic Zoonotic
A disease which can be spread from animals to humans.

Mentioned in: Zoonosis
 Dis. 2002;2:69-75.

(15.) La Scola B, Raoult D. Laboratory diagnosis of rickettsioses: current approaches to diagnosis of old and new rickettsial diseases. J Clin Microbiol. 1997;35:2715-27.

Jose-Luis Perez-Arellano, * ([dagger]) (1) Florence Fenollar, ([double dagger]) (1) Alfonso Angel-Moreno,* ([dagger]) Margarita Bolanos, * ([dagger]) Michele Hernandez, * ([dagger]) Evora Santana, * ([dagger]) Marion Hemmersbach-Miller, * ([dagger]) Antonio-M Martin, * ([dagger]) and Didier Raoult ([double dagger])

* Hospital Universitario Insular de Las Palmas, Canary Islands, Spain; ([dagger]) Universidad de Las Palmas de Gran Canaria The University of Las Palmas de Gran Canaria, also known as the ULPGC (Spanish Universidad de Las Palmas de Gran Canaria) is a Spanish university located in Las Palmas de Gran Canaria, the capital of Gran Canaria island. , Canary Islands, Spain; and ([double dagger]) Universite de la Mediterranee, Marseille, France

(1) These authors contributed equally to this article.

Address for correspondence: D. Raoult, Unite des Rickettsies, CNRS CNRS Centre National de la Recherche Scientifique (National Center for Scientific Research, France)
CNRS Centro Nacional de Referencia Para El Sida (Argentinean National Reference Center for Aids) 
 UMR UMR Unite Mixte de Recherche (French: Mixed Unit of Research )
UMR University of Missouri - Rolla
UMR Upper Mississippi River
UMR Uniform Methods and Rules (US Department of Agriculture)
UMR Unit Manning Report
 6020, Faculte de Medecine, Universite de la Mediterranee, 27 Bd Jean Moulin, 13385 Marseille CEDEX 05, France; fax: 33-4-91-38-77-72; email: Didier.Raoult@medecine.univ-mrs.fr

Dr Perez-Arellano is chief of the Infectious Diseases and Tropical Medicine tropical medicine, study, diagnosis, treatment, and prevention of certain diseases prevalent in the tropics. The warmth and humidity of the tropics and the often unsanitary conditions under which so many people in those areas live contribute to the development and  Service and professor in the Department of Medical and Surgical Sciences, Health Sciences Faculty, University of Las Palmas de Gran Canaria. His main research interests are imported and emerging infectious diseases.
Table. Clinical, epidemiologic, and biological data between Rickettsia
felis group, R. typhi group, and indeterminate rickettsiosis group

Characteristic                     R. felis            R. typhi

No.                                   5                   13
Mean age, y *                      45 (16)              29 (14)
Sex (M/F)                            5/0                 10/3
Contact with dogs or                 4/5                 11/13
  cats ([section])
Interval between clinical        12 (9.5-14)         9 (8.5-10.2)
  picture and evaluation,
  d ([paragraph])
Fever ([section])                    5/5                 13/13
Maximal temperature               39.3 (0.8)          39.6 (0.5)
  ([degrees]C) *
Headache ([section])                 4/5                 12/13
Conjunctivitis ([section])           1/5                 3/13
Arthralgia/myalgia ([section])       4/5                 6/13
Odynophagia ([section])              0/5                 6/13
Dry cough ([section])                3/5                 8/13
Nausea/vomiting ([section])          0/5                 2/13
Abdominal pain ([section])           1/5                 1/13
Rash ([section])                     0/5                 9/13
Past or actual tick                  1/5                 2/13
  bite ([section])
Hepatomegaly ([section])             1/5                 6/13
Splenomegaly ([section])             0/5                 3/13
Anemia (hemoglobin <13 mg/dL)        0/5                 3/13
Normal blood leukocyte counts        5/5               10/13 **
  (4,000-10,000/[micro]L)
Normal platelet counts               4/5        11/12 ([double dagger]
  (150,000-400,000/[micro]L)                           [double dagger])
Normal ratio prothrombin time        4/4                 10/13
  (0.8-1.2)
Normal ESR (<10 mm/h)                1/4                 11/12
Normal creatinine blood level        5/5                 11/13
  (62-106 [micro]mol/L)
Normal sodium blood level            2/4                 10/13
  (136-144 mmol/L)
Elevated AST (>35 IU/L)              4/5                 8/13
Mean AST (U/L)                       123                  254
Elevated ALT (>45 IU/L)              5/5                 8/13
Mean ALT (U/L) ([paragraphs])    185 (71-374)       354 (55-1,368)
Elevated GGT (>55 IU/L)              2/5                 3/13
Elevated total serum protein         0/5                 0/12
  concentration (>80 g/L)
Elevated gamma globulin              2/5                 5/12
  concentration (>13 g/L)

Characteristic                        Indeterminate

No.                                         13
Mean age, y *                            40 (17)
Sex (M/F)                                  12/1
Contact with dogs or                      11/13
  cats ([section])
Interval between clinical              9 (7.9-13.4)
  picture and evaluation,
  d ([paragraph])
Fever ([section])                         13/13
Maximal temperature                       39.40
  ([degrees]C) *
Headache ([section])                      13/13
Conjunctivitis ([section])                 2/13
Arthralgia/myalgia ([section])             5/13
Odynophagia ([section])                    0/13
Dry cough ([section])                      2/13
Nausea/vomiting ([section])                1/13
Abdominal pain ([section])                 0/13
Rash ([section])                           6/13
Past or actual tick                        1/13
  bite ([section])
Hepatomegaly ([section])                   5/13
Splenomegaly ([section])                   2/13
Anemia (hemoglobin <13 mg/dL)              1/13
Normal blood leukocyte counts    11/13 ([dagger][dagger])
  (4,000-10,000/[micro]L)
Normal platelet counts            11/13 ([double dagger]
  (150,000-400,000/[micro]L)            [double dagger])
Normal ratio prothrombin time             11/13
  (0.8-1.2)
Normal ESR (<10 mm/h)                      3/11
Normal creatinine blood level             10/13
  (62-106 [micro]mol/L)
Normal sodium blood level                 10/12
  (136-144 mmol/L)
Elevated AST (>35 IU/L)                    5/12
Mean AST (U/L)                              72
Elevated ALT (>45 IU/L)                    6/12
Mean ALT (U/L) ([paragraphs])          86 (34-292)
Elevated GGT (>55 IU/L)                    4/12
Elevated total serum protein               1/12
  concentration (>80 g/L)
Elevated gamma globulin                    8/10
  concentration (>13 g/L)

Characteristic                          p value

No.                                        --
Mean age, y *                        NS ([dagger])
Sex (M/F)                         NS ([double dagger])
Contact with dogs or              NS ([double dagger])
  cats ([section])
Interval between clinical              <0.05 (#)
  picture and evaluation,
  d ([paragraph])
Fever ([section])                 NS ([double dagger])
Maximal temperature                  NS ([dagger])
  ([degrees]C) *
Headache ([section])              NS ([double dagger])
Conjunctivitis ([section])        NS ([double dagger])
Arthralgia/myalgia ([section])    NS ([double dagger])
Odynophagia ([section])          0.01 ([double dagger])
Dry cough ([section])            0.04 ([double dagger])
Nausea/vomiting ([section])       NS ([double dagger])
Abdominal pain ([section])        NS ([double dagger])
Rash ([section])                 0.03 ([double dagger])
Past or actual tick               NS ([double dagger])
  bite ([section])
Hepatomegaly ([section])          NS ([double dagger])
Splenomegaly ([section])          NS ([double dagger])
Anemia (hemoglobin <13 mg/dL)              NS
Normal blood leukocyte counts     NS ([double dagger])
  (4,000-10,000/[micro]L)
Normal platelet counts            NS ([double dagger])
  (150,000-400,000/[micro]L)
Normal ratio prothrombin time     NS ([double dagger])
  (0.8-1.2)
Normal ESR (<10 mm/h)             NS ([double dagger])
Normal creatinine blood level     NS ([double dagger])
  (62-106 [micro]mol/L)
Normal sodium blood level         NS ([double dagger])
  (136-144 mmol/L)
Elevated AST (>35 IU/L)           NS ([double dagger])
Mean AST (U/L)                    0.01 ([subsection])
Elevated ALT (>45 IU/L)              NS ([dagger])
Mean ALT (U/L) ([paragraphs])     <0.01 ([subsection])
Elevated GGT (>55 IU/L)           NS ([double dagger])
Elevated total serum protein      NS ([double dagger])
  concentration (>80 g/L)
Elevated gamma globulin           NS ([double dagger])
  concentration (>13 g/L)

* Data are expressed as mean (SD). Samples are distributed normally and
have similar SD. NS, nonsignificant; ANOVA, analysis of variance test;
ESR, erythrocyte sedimentation rate, AST, aspartate aminotransferase,
ALT, alanine aminotransferase; GGT, gamma-glutamyl transpeptidase.

([dagger]) ANOVA.

([double dagger]) [chi square] test.

([section]) No. patients with these epidemiologic or clinical data/
no. patients evaluated.

([paragraph]) Data are expressed as median and 95% confidence
intervals; [greater than or equal to] 1 samples have a non-gaussian
distribution.

(#) Significant differences between R. felis and R. typhi
groups (p<0.05) with Dunn test.

** Leukopenia in 1 patient (3,700/[micro]L), leukocytosis in 2 patients
(11,500/[micro]L and 16,000/[micro]L).

([dagger][dagger]) Leukopenia in 2 patients.

([double dagger][double dagger]) All patients with an abnormal platelet
count presented with thrombocytopenia in all cases.

([subsection]) ANOVA; all cases.

([paragraphs]) Data are expressed as mean (range values). Samples are
distributed normally and have similar SD.
COPYRIGHT 2005 U.S. National Center for Infectious Diseases
No portion of this article can be reproduced without the express written permission from the copyright holder.
Copyright 2005, Gale Group. All rights reserved. Gale Group is a Thomson Corporation Company.

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Title Annotation:DISPATCHES
Author:Raoult, Didier
Publication:Emerging Infectious Diseases
Geographic Code:6CANA
Date:Dec 1, 2005
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