Volume 14, Number 7—July 2008
Rickettsia felis as Emergent Global Threat for Humans
Rickettsia felis is an emergent pathogen belonging to transitional group rickettsiae. First described in 1990, R. felis infections have been reported to occur worldwide in fleas, mammals, and humans. Because clinical signs of the illness are similar to those of murine typhus and other febrile illnesses such as dengue, the infection in humans is likely underestimated. R. felis has been found throughout the world in several types of ectoparasites; cat fleas appear to be the most common vectors. R. felis infection should be considered an emergent threat to human health.
Rickettsia felis is a member of the genus Rickettsia, which comprises intracellular pathogens that produce infections commonly called rickettsioses. Although the genus has no recognized subspecies, rickettsiae have traditionally been subdivided into 2 groups: the spotted fever group (SFG) and the typhus group. Infections produced by these 2 groups are clinically indistinguishable; however, groups can be differentiated by outer membrane protein OmpA (absent in the typhus group) and by vector. SFG members are transmitted by ticks; typhus group members, by fleas and lice (1,2). More recently, Gillespie et al. (3) added to this classification by designating the transitional group of rickettsiae and describing an ancestral group of rickettsiae.
In 1990, Adams et al. described a rickettsia-like organism, which resembled R. typhi, in the cytoplasm of midgut cells of a colony of cat fleas (1). The new rickettsia received the initial name of ELB agent after the company from which the fleas were obtained (El Labs, Soquel, CA, USA) (4). The first observations, such as reactivity with antibodies to R. typhi (1), the type of vector in which it was first discovered (1), and the apparent absence of OmpA (5), suggested that the new organism belonged to the typhus group of rickettsiae (4).
The molecular characterization of the organism described by Adams and reported by Bouyer et al. in 2001 provided sufficient evidence to support the designation of R. felis as a member of the SFG (6), and in 2002, La Scola et al. provided further characterization (7). One noticeable characteristic is the temperature-dependent growth of the bacterium, which requires incubation temperatures of 28°–32°C for optimal growth. However, the most striking characteristic of the novel rickettsia was the plasmid DNA in its genome (8).
World Distribution in Potential Host Vectors
Soon after the initial description of the typhus-like rickettsia, Williams et al. (9) reported that cat fleas collected from opossums in an urban setting in California were infected with the novel rickettsia, but no organism was detected in the tissues of the opossums. Since this report, this organism has been described in infected vectors from 20 countries on 5 continents (9). Not until 2002 did interest in R. felis increase, when the United States (9), Brazil (10), Mexico (11), and Spain (12) were among the first countries to describe cat fleas (Ctenocephalides felis) infected with R. felis. During the following 5 years, 28 additional reports appeared from all over the world (Table 1). These reports describe new potential vectors being infected with the emergent rickettsia, including the following: fleas, such as C. canis (13–15), Anomiopsyllus nudata (16), Archaeopsylla erinacei (15,17), Ctenophthalmus sp (17), and Xenopsylla cheopis (18); ticks, Haemaphysalis flava (19), Rhipicephalus sanguineus (20), and Ixodes ovatus (19); and mites from South Korea (21) (Table 1). Despite the large number of potential vectors reported, the only vector currently recognized is C. felis because it has been demonstrated that this flea is able to maintain a stable infected progeny through transovarial transmission (4). In addition, production of antibody to R. felis has been noted in animals after they have been exposed to infected cat fleas (9). Other evidence to be considered is the fact that 68.8% of the reports state that the cat flea is the most recurrent vector in which R. felis has been detected. These data further support the wide distribution of rickettsiae because they correlate with the worldwide distribution of C. felis; this distribution represents a threat to the human population because of lack of host specificity of the cat flea.
R. felis infection is diagnosed by PCR amplification of targeted genes. The genes most commonly amplified by researchers are gltA and ompB; followed by the 17-kDa gene. Also, 25% of published articles report that R. felis was detected by amplifying >2 genes, and all report that amplicons were confirmed as R. felis by sequencing. The animal hosts from which the infected ectoparasites were recovered represent a diversity of mammals (Table 1), which included 9 different naturally infested animal species. However, in 16 of 33 articles, ectoparasites were recovered from dogs. Other hosts for ectoparasites were cats (in 13 of 33 reports); rodents (5 of 33 reports); opossums and hedgehogs (2 reports each); and horses, sheep, goats, gerbils, and monkeys (1 report for each animal species).
In summary, the presence of R. felis in a diverse range of invertebrate and mammalian hosts represents a high potential risk for public health and the need for further studies to establish the role of ectoparasites other than C. felis as potential vectors. To date, whether any vertebrate may serve as the reservoir of this emergent pathogen has not been determined. However, preliminary data from our laboratory suggest that opossums are the most likely candidates.
World Distribution of Human Cases
In 1994, the first human case of infection with the new cat flea rickettsia was reported in the United States (2). This became the first evidence of R. felis’ potential as a human pathogen. R. felis infection had a similar clinical manifestation as murine typhus (including high fever [39°–40°C], myalgia, and rash). Although the initial idea was that the murine typhus–like rickettsia had a transmission cycle involving cat fleas and opossums (2,5,9), no viable R. felis has yet been isolated from a vertebrate host.
Three more cases of R. felis infection were reported from southeastern Mexico in 2000. The patients had had contact with fleas or animals known to carry fleas. The clinical manifestations were those of a typical rickettsiosis: all patients had fever and myalgia; but the skin lesions, instead of a rash, were similar to those described for rickettsialpox. In addition, for 3 patients, central nervous system involvement developed, manifested as photophobia, hearing loss, and signs of meningitis (33).
As occurred with the fast-growing reports of the worldwide detection of R. felis in arthropod hosts, the reports of human cases of R. felis infection increased rapidly in the following years (Table 2). But, in contrast, only 11 articles reported human infection by R. felis compared with 32 that reported ectoparasite infection with the new rickettsia. Nevertheless, these findings indicate that an effective surveillance system is urgently needed to distinguish R. felis rickettsiosis from other rickettsial infections such as murine typhus and Rocky Mountain spotted fever, and from other febrile illnesses such as dengue. Although PCR is still a method of choice for many laboratories, its high cost prevents many from using the technique, particularly in developing countries. Important advances have been achieved in diagnostics, such as the recent establishment of a stable culture of R. felis in cell lines that allows its use as antigen in serologic assays differentiating the cat flea rickettsia from others. Use of this culture in the immunofluorecent assay has enabled detection of additional human cases (38).
The first autochthonous human case in Europe was reported in 2002, which demonstrated that R. felis has a potential widespread distribution and is not confined to the Americas. It also confirmed the risk for human disease anywhere in the world (35). After the first report in Europe of a human infection of R. felis, other human cases have appeared in other countries around the world, including Thailand (36), Tunisia (38), Laos (39), and Spain (40); additional cases have been reported in Mexico and Brazil (34). All the data support the conclusion that the incidence of R. felis rickettsiosis and the simultaneous worldwide distribution of the flea vector plausibly explain its endemicity.
At present, the involvement of domestic animals (e.g., dogs and cats) or wild animals coexisting in urban areas (e.g., opossums) maintains R. felis infection in nature. C. felis fleas serve as the main reservoir and likely have a central role in transmission of human illness.
R. felis is an emergent rickettsial pathogen with a worldwide distribution in mammals, humans, and ectoparasites. The clinical manifestations of R. felis infections resemble those of murine typhus and dengue, which makes them difficult to diagnose without an appropriate laboratory test. For this reason, infections due to this emergent pathogen are likely underestimated and misdiagnosed. Although R. felis may require only fleas for its maintenance in nature, we still do not know the role of animals in the life cycle of flea-borne spotted fever rickettsia. In addition, flea-borne spotted fever should be considered in the differential diagnosis of infectious diseases. Further research should be conducted to determine the actual incidence of R. felis infection in humans, the spectrum of clinical signs and symptoms, and the severity of this infection and also to assess the impact on public health.
Mr. Pérez-Osorio is currently professor of microbiology at the Autonomous University of Yucatan. His research interests focus on rickettsial diseases.
We thank Patricia Croquet-Valdes for her comments and helpful advice.
This research was supported by grants from the CONACyT (44064-M) to J. E. Z.-V.
- Adams JR, Schmidtmann ET, Azad AF. Infection of colonized cat fleas, Ctenocephalides felis (Bouche), with a rickettsia-like microorganism. Am J Trop Med Hyg. 1990;43:400–9.
- 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.
- Gillespie JJ, Beier MS, Rahman MS, Ammerman NC, Shallom JM, Purkayastha A, Plasmids and rickettsial evolution: insight from Rickettsia felis. PLoS One. 2007;2:e266.
- Azad AF, Sacci JB Jr, Nelson WM, Dasch GA, Schmidtmann ET, Carl M. Genetic characterization and transovarial transmission of a typhus-like rickettsia found in cat fleas. Proc Natl Acad Sci U S A. 1992;89:43–6.
- Higgins JA, Radulovic S, Schriefer ME, Azad AF. Rickettsia felis: a new species of pathogenic rickettsia isolated from cat fleas. J Clin Microbiol. 1996;34:671–4.
- Bouyer DH, Stenos J, Crocquet-Valdes P, Moron CG, Popov VL, Zavala-Velazquez JE, Rickettsia felis: molecular characterization of a new member of the spotted fever group. Int J Syst Evol Microbiol. 2001;51:339–47.
- La Scola B, Meconi S, Fenollar F, Rolain JM, Roux V, Raoult D. Emended description of Rickettsia felis (Bouyer et al. 2001), a temperature-dependent cultured bacterium. Int J Syst Evol Microbiol. 2002;52:2035–41.
- Ogata H, Renesto P, Audic S, Robert C, Blanc G, Fournier PE, The genome sequence of Rickettsia felis identifies the first putative conjugative plasmid in an obligate intracellular parasite. PLoS Biol. 2005;3:e248.
- Williams SG, Sacci JB Jr, Schriefer ME, Andersen EM, Fujioka KK, Sorvillo FJ, Typhus and typhuslike rickettsiae associated with opossums and their fleas in Los Angeles County, California. J Clin Microbiol. 1992;30:1758–62.
- Oliveira RP, Galvao MA, Mafra CL, Chamone CB, Calic SB, Silva SU, Rickettsia felis in Ctenocephalides spp. fleas, Brazil. Emerg Infect Dis. 2002;8:317–9.
- Zavala-Velazquez JE, Zavala-Castro JE, Vado-Solis I, Ruiz-Sosa JA, Moron CG, Bouyer DH, Identification of Ctenocephalides felis fleas as a host of Rickettsia felis, the agent of a spotted fever rickettsiosis in Yucatan, Mexico. Vector Borne Zoonotic Dis. 2002;2:69–75.
- Marquez FJ, Muniain MA, Perez JM, Pachon J. Presence of Rickettsia felis in the cat flea from southwestern Europe. Emerg Infect Dis. 2002;8:89–91.
- Horta MC, Chiebao DP, de Souza DB, Ferreira F, Pinheiro SR, Labruna MB, Prevalence of Rickettsia felis in the fleas Ctenocephalides felis and Ctenocephalides canis from two Indian villages in São Paulo Municipality, Brazil. Ann N Y Acad Sci. 2006;1078:361–3.
- Venzal JM, Perez-Martinez L, Felix ML, Portillo A, Blanco JR, Oteo JA. Prevalence of Rickettsia felis in Ctenocephalides felis and Ctenocephalides canis from Uruguay. Ann N Y Acad Sci. 2006;1078:305–8.
- Bitam I, Parola P, De La Cruz KD, Matsumoto K, Baziz B, Rolain JM, First molecular detection of Rickettsia felis in fleas from Algeria. Am J Trop Med Hyg. 2006;74:532–5.
- Stevenson HL, Labruna MB, Montenieri JA, Kosoy MY, Gage KL, Walker DH. Detection of Rickettsia felis in a New World flea species, Anomiopsyllus nudata (Siphonaptera: Ctenophthalmidae). J Med Entomol. 2005;42:163–7.
- De Sousa R, Edouard-Fournier P, Santos-Silva M, Amaro F, Bacellar F, Raoult D. Molecular detection of Rickettsia felis, Rickettsia typhi and two genotypes closely related to Bartonella elizabethae. Am J Trop Med Hyg. 2006;75:727–31.
- Jiang J, Soeatmadji DW, Henry KM, Ratiwayanto S, Bangs MJ, Richards AL. Rickettsia felis in Xenopsylla cheopis, Java, Indonesia. Emerg Infect Dis. 2006;12:1281–3.
- Ishikura M, Ando S, Shinagawa Y, Matsuura K, Hasegawa S, Nakayama T, Phylogenetic analysis of spotted fever group rickettsiae based on gltA, 17-kDa, and rOmpA genes amplified by nested PCR from ticks in Japan. Microbiol Immunol. 2003;47:823–32.
- Cardoso LD, Freitas RN, Mafra CL, Neves CV, Figueira FC, Labruna MB, Characterization of Rickettsia spp. circulating in a silent peri-urban focus for Brazilian spotted fever in Caratinga, Minas Gerais, Brazil [in Portuguese]. Cad Saude Publica. 2006;22:495–501.
- Choi YJ, Lee EM, Park JM, Lee KM, Han SH, Kim JK, Molecular detection of various rickettsiae in mites (Acari: Trombiculidae) in southern Jeolla Province, Korea. Microbiol Immunol. 2007;51:307–12.
- Rolain JM, Franc M, Davoust B, Raoult D. Molecular detection of Bartonella quintana, B. koehlerae, B. henselae, B. clarridgeiae, Rickettsia felis, and Wolbachia pipientis in cat fleas, France. Emerg Infect Dis. 2003;9:338–42.
- Kenny MJ, Birtles RJ, Day MJ, Shaw SE. Rickettsia felis in the United Kingdom. Emerg Infect Dis. 2003;9:1023–4.
- Blair PJ, Jiang J, Schoeler GB, Moron C, Anaya E, Cespedes M, Characterization of spotted fever group rickettsiae in flea and tick specimens from northern Peru. J Clin Microbiol. 2004;42:4961–7.
- Kelly P, Rolain JM, Raoult D. Prevalence of human pathogens in cat and dog fleas in New Zealand. N Z Med J. 2005;118:U1754.
- Rolain JM, Bourry O, Davoust B, Raoult D. Bartonella quintana and Rickettsia felis in Gabon. Emerg Infect Dis. 2005;11:1742–4.
- Marie JL, Fournier PE, Rolain JM, Briolant S, Davoust B, Raoult D. Molecular detection of Bartonella quintana, B. Elizabethae, B. Koehlerae, B. Doshiae, B. Taylorii, and Rickettsia felis in rodent fleas collected in Kabul, Afghanistan. Am J Trop Med Hyg. 2006;74:436–9.
- Schloderer D, Owen H, Clark P, Stenos J, Fenwick SG. Rickettsia felis in fleas, Western Australia. Emerg Infect Dis. 2006;12:841–3.
- Bauer O, Baneth G, Eshkol T, Shaw SE, Harrus S. Polygenic detection of Rickettsia felis in cat fleas (Ctenocephalides felis) from Israel. Am J Trop Med Hyg. 2006;74:444–8.
- Psaroulaki A, Antoniou M, Papaeustathiou A, Toumazos P, Loukaides F, Tselentis Y. First detection of Rickettsia felis in Ctenocephalides felis fleas parasitizing rats in Cyprus. Am J Trop Med Hyg. 2006;74:120–2.
- Hawley JR, Shaw SE, Lappin MR. Prevalence of Rickettsia felis DNA in the blood of cats and their fleas in the United States. J Feline Med Surg. 2007;9:258–62.
- Labruna MB, Ogrzewalska M, Moraes-Filho J, Lep P, Gallegos JL, Lopez J. Rickettsia felis in Chile. Emerg Infect Dis. 2007;13:1794–5.
- Zavala-Velazquez JE, Ruiz-Sosa JA, Sanchez-Elias RA, Becerra-Carmona G, Walker DH. Rickettsia felis rickettsiosis in Yucatan. Lancet. 2000;356:1079–80.
- Galvao MA, Zavala-Velazquez JE, Zavala-Castro JE, Mafra CL, Calic SB, Walker DH. Rickettsia felis in the Americas. Ann N Y Acad Sci. 2006;1078:156–8.
- Richter J, Fournier PE, 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.
- Parola P, Miller RS, McDaniel P, Telford SR III, Rolain JM, Wongsrichanalai C, Emerging rickettsioses of the Thai-Myanmar border. Emerg Infect Dis. 2003;9:592–5.
- Znazen A, Rolain JM, Hammami A, Jemaa MB, Raoult D. Rickettsia felis infection, Tunisia. Emerg Infect Dis. 2006;12:138–40.
- Choi YJ, Jang WJ, Ryu JS, Lee SH, Park KH, Paik HS, Spotted fever group and typhus group rickettsioses in humans, South Korea. Emerg Infect Dis. 2005;11:237–44.
- Phongmany S, Rolain JM, Phetsouvanh R, Blacksell SD, Soukkhaseum V, Rasachack B, Rickettsial infections and fever, Vientiane, Laos. Emerg Infect Dis. 2006;12:256–62.
- Bernabeu-Wittel M, del Toro MD, Nogueras MM, Muniain MA, Cardenosa N, Marquez FJ, Seroepidemiological study of Rickettsia felis, Rickettsia typhi, and Rickettsia conorii infection among the population of southern Spain. Eur J Clin Microbiol Infect Dis. 2006;25:375–81.
Suggested citation for this article: Pérez-Osorio CE, Zavala-Velázquez JE, Zavala-Velázquez JE. Rickettsia felis as emergent global threat for humans. Emerg Infect Dis [serial on the Internet]. 2008 Jul [date cited]. Available from http://wwwnc.cdc.gov/eid/article/14/7/07-1656.htm