Rickettsia parkeri Infection

Rickettsiae are strict intracellular bacteria requiring a host cell to replicate. Within the genus Rickettsia three groups are differentiated, one of which is the spotted fever group (SFG), whose members are associated mainly with ticks, but also with fleas and mites (Raoult and Roux, 1997). Within the SFG Rickettsia parkeri is an emerging human pathogen, for which the dog has an important sentinel function. It is an agent of tick-borne rickettsiosis in the Americas which has also been named American Boutonneuse fever (Goddard, 2004; Goddard and Varela-Stokes, 2009) or Tidewater spotted fever (Wright et al., 2011).

Pathogens

The genus Rickettsia is included in the bacterial tribe Rickettsiae, family Rickettsiaceae, order Rickettsiales. The genus Rickettsia includes many species of bacteria associated with important and severe human or animal disease, including those in the spotted fever group (SFG).

Rickettsia parkeri as one species of this group, has first been isolated in 1937 as a distinct rickettsial strain from Gulf Coast ticks (Amblyomma maculatum), by Ralph Robinson Parker, showing low-grade fever and periorchitis in the animal experiment (here: male guinea pigs). In 1965, the “maculatum agent” was named R. parkeri and described as a small, rod-shaped bacterium, with an average size of 1.6 x 0.5 µm, found in the nucleus and cytoplasm of infected cells (Lackman et al., 1965). Until 2002 the agent most often was relegated to the group of ‘non-pathogenic’ SFG rickettsiae, found in ticks in the United States, when the first confirmed infection with R. parkeri in a human was identified in Virginia (Paddock et al., 2004).

Epidemiology

Rickettsia parkeri is an emerging agent of tick-borne rickettsiosis in the Americas. More than 60 years after its initial isolation from tick vectors it was recognised as a human pathogen.

R. parkeri has been isolated from Gulf Coast ticks (Amblyomma maculatum) in Alabama, Georgia, Mississippi, and Texas (Parker et al., 1939; Parker, 1940; Philip and White, 1955; Philip et al., 1978). It could further be detected in Gulf Coast ticks collected again from Georgia, Florida, Kentucky, Mississippi, Oklahoma and South Carolina (Sumner et al., 2007). While the geographic range of A. maculatum has historically been the southeastern USA, particularly those states bordering the Gulf Coast, established populations of this tick have recently also been found in Virginia (Fornadel et al., 2011; Wright et al., 2011) and Delaware (Florin et al., 2014), suggesting the tick is expanding its range northward.

Apart from the United States, R. parkeri has also been described as an emerging human pathogen in Uruguay (Venzal et al., 2004) and was furthermore detected in ticks and dogs (seroconversion) in Brazil (Labruna et al., 2007; Silveira et al., 2007).

Summarizing the different vector tick species, A. maculatum, Amblyomma triste (Pacheco et al., 2006; Silveira et al., 2007) and Amblyomma tigrinum (Tomassone et al., 2010) have been reported. As these three vector ticks are established in at least 11 other Latin American countries (Guglielmone et al., 2003), the distribution of R. parkeri in the Americas is likely continental (Pacheco et al., 2006; Tomassone et al., 2010). Meanwhile the pathogen has also been detected in Amblyomma ovale (de Oliveira et al., 2019) as well as Amblyomma sculptum (Campos et al., 2020) (both in Brazil) and Amblyomma dubitatum (Lado et al., 2014) (in Uruguay).

Dogs have been characterised as sentinels for human rickettsiosis in rural areas in Brazil, Bolivia and Uruguay, by sharing the same tick species infesting humans and dogs (Labruna et al., 2007; Tomassone et al., 2010; Venzal et al., 2008). But seroconversion has also been reported in cats (Mendes et al., 2019).

Transmission

Rickettsia parkeri was first isolated from the Gulf Coast tick Amblyomma maculatum in 1937 (Parker et al., 1939). Meanwhile it has been isolated from several other Amblyomma species (see under Epidemiology). Experimental infection of Amblyomma cajennense ticks with R. parkeri (Sangioni et al., 2005) and transstadial and transovarial transmission of R. parkeri in Amblyomma americanum, the Lone Star tick, could also be proven in the lab (Goddard, 2003), so that the distribution of R. parkeri might even be larger than the documented distribution so far.

The agent is transmitted via the infected tick during feeding. Confirmed infections have resulted from bites of nymphal and adult-stage Gulf Coast ticks (Paddock et al., 2008; Whitman et al., 2007), but the preponderance of mid-to-late summer occurrences of this disease, when coupled with the phenology of A. maculatum in the southeastern United States (Cilek and Olson, 2000; Gleim et al., 2013; Hixson, 1940; Teel et al., 2010), suggest that most cases of R. parkeri rickettsiosis result from bites of adult rather than immature ticks (Paddock and Goddard, 2015).

Pathogenesis

Rickettsia parkeri is an obligate intracellular bacterium in the order Rickettsiales, belonging to the spotted fever group (SFG) of Rickettsia. Generally, SFG rickettsiae can grow in the nucleus or in the cytoplasm of the host cell. Once inside the host, the rickettsiae multiply, resulting in damage and death of these cells.

Information on the pathogenesis regarding R. parkeri is scarce and manifestation in humans is often with non-specific clinical signs and symptoms.

Diagnosis

Serological assays as the indirect immunofluorescence assay (IFA) are used for the detection of antibodies in humans as well as in dogs. Generally for rickettsial diseases one limitation of serology is the cross-reactivity that might occur between the antigens of organisms within the same genus and in different genera (Parola and Raoult, 2001), so that serology is often only considered as the first step towards diagnosing a rickettsial disease (Parola et al., 2005). In order to differentiate infections within rickettsial antigens, difference in dilution as well as cross-absorption of sera and Western-blotting can be done when cross reaction is suspected (La Scola and Raoult, 1997; Parola et al., 2003; Raoult and Paddock, 2005).

Rickettsia isolation in cell culture can also be used as direct evidence of the pathogen, but is usually not used in routine diagnosis due to high laboratory standard and time needed.

Additionally polymerase chain reaction (PCR) and sequencing methods are also used to detect and identify rickettsiae in blood and skin biopsies (particularly the eschar), as well as in ticks. Various generic or species-specific PCRs are available to detect rickettsial DNA in those specimens (Wölfel et al., 2008).

Clinical Signs

Clinical signs of Rickettsia parkeri infection in humans have been described with a febrile illness associated with headache, myalgia, a maculopapular rash, and multiple eschars (Paddock et al., 2004). The agent produces a spotted fever-like illness similar to that of Boutonneuse fever in the Old World with areas of necrosis (eschars) at the sites of tick bites (Paddock et al., 2004; Paddock, 2005). For this reason, R. parkeri rickettsiosis in humans is sometimes referred to as American Boutonneuse fever or ABF (Goddard, 2004). It is assumed that the infection with R. parkeri has often been misdiagnosed as Rocky Mountain Spotted Fever (RMSF) in the United States. Several compelling lines of evidence suggest that infections with R. parkeri, and probably one or more other tick-borne spotted fever group (SFG) rickettsiae, are responsible for at least some of the yearly reported cases of RMSF in the US (Paddock, 2005).

In dogs seroreactivity to R. parkeri has been reported in serosurveys in several Southamerican countries (e.g., Brazil, Bolivia, Uruguay) with very different prevalences (Labruna et al., 2007; Lado et al., 2015; Saito et al., 2008; Tomassone et al., 2010). However, clinical signs in dogs correlating with a R. parkeri infection have not been described yet. Seropositivity has also been reported in surveys with cats (Mendes et al., 2019).

For special areas, where the transmitting tick species is found to infest dogs as well as humans (e.g., rural areas in Monte Negro region, Brazil), dogs have been described as sentinels (Labruna et al., 2007) and canine serology is suggested as risk indicator for spotted fever rickettsioses (Tomassone et al., 2010).

Treatment & Prevention

Treatment with antibiotics can control the disease, and generally doxycycline is the drug of choice for treatment of all tick-borne rickettsial diseases in humans. For more detailed information see Biggs et al. (2016).

As with other diseases transmitted by fleas or ticks, ectoparasite control is the basis of prevention. Products which repel and kill ticks and fleas are the appropriate means of choice in order to protect dogs and cats from becoming infected. The sentinel position which has been attributed to dogs in the context of Rickettsia parkeri infection makes an ectoparasite control even more important.

References

Introduction

Goddard J: American Boutonneuse fever – a new spotted fever rickettsiosis. Infect Med. 2004, 21, 207-10

Goddard J, Varela-Stokes AS: The discovery and pursuit of American Boutonneuse fever: a new spotted fever group rickettsiosis. Midsouth Entomol. 2009, 2, 47-52

Raoult D, Roux V: Rickettsioses as paradigms of new or emerging infectious diseases. Clin Microbiol Rev. 1997, 10, 694-719

Wright CL, Nadolny RM, Jiang J, et al.: Rickettsia parkeri in Gulf Coast ticks, southeastern Virginia, USA. Emerg Infect Dis. 2011, 17, 896-8

Pathogens

Lackman DB, Bell EJ, Stoenner HG, et al.: The Rocky Mountain spotted fever group of rickettsias. Health Lab Sci. 1965, 2, 135-41

Paddock CD, Sumner JW, Comer JA, et al.: Rickettsia parkeri: a newly recognized cause of spotted fever rickettsiosis in the United States. Clin Infect Dis. 2004, 38, 805-11
 

Epidemiology

Campos SDE, Cunha NCD, Machado CSC, et al.: Spotted fever group rickettsial infection in dogs and their ticks from domestic-wildlife interface areas in southeastern Brazil. Rev Bras Parasitol Vet. 2020, 29, e020219

de Oliveira PB, Harvey TV, Fehlberg HF, et al.: Serologic and molecular survey of Rickettsia spp. in dogs, horses and ticks from the Atlantic rainforest of the state of Bahia, Brazil. Exp Appl Acarol. 2019, 78, 431-42

Florin DA, Brinkerhoff RJ, Gaff H, et al.: Additional collections of the Gulf Coast tick, Amblyomma maculatum (Acari: Ixodidae), from the State of Delaware, the first reported field collections of adult specimens from the State of Maryland, and data regarding this tick species from surveillance of migratory songbirds in Maryland. Syst Appl Acarol. 2014, 19, 257-62

Fornadel CM, Zhang X, Smith JD, et al.: High rates of Rickettsia parkeri infection in Gulf Coast ticks (Amblyomma maculatum) and identification of “Candidatus Rickettsia andeanae” from Fairfax County, Virginia. Vector Borne Zoonotic Dis. 2011, 11, 1535-9

Guglielmone AA, Estrada-Peña A, Keirans JE, et al.: Ticks (Acari: Ixodida) of the Neotropical Zoogeographic Region. 2003, Int. Consort. Ticks and Tick-borne Diseases (ICTTD-2), Atlanta, Houten, The Netherlands

Labruna MB, Horta MC, Aguiar DM, et al.: Prevalence of Rickettsia infection in dogs from the urban and rural areas of Monte Negro municipality, western Amazon, Brazil. Vector Borne Zoonotic Dis. 2007, 7, 249-55

Lado P, Castro O, Labruna MB, et al.: First molecular detection of Rickettsia parkeri in Amblyomma tigrinum and Amblyomma dubitatum ticks from Uruguay. Ticks Tick Borne Dis. 2014, 5, 660-2

Mendes JCR, Kmetiuk LB, Martins CM, et al.: Serosurvey of Rickettsia spp. in cats from a Brazilian spotted fever-endemic area. Rev Bras Parasitol Vet. 2019, 28, 713-21

Pacheco RC, Venzal JM, Richtzenhain LJ, et al.: Rickettsia parkeri in Uruguay. Emerg Infect Dis. 2006, 12, 1804-5

Parker RR: A pathogenic Rickettsia from the Gulf Coast tick, Amblyomma maculatum. Proc. Third Int. Cong. Microbiol., New York, NY, USA, 1940, pp. 390-1

Parker RR, Kohls GM, Cox GW, et al.: Observations on an infectious agent from Amblyomma maculatum. Public Health Rep. 1939, 54, 1482-4

Philip C, White JS: Disease agents recovered incidental to a tick survey of the Mississippi Gulf Coast. J Econ Entomol. 1955, 48, 396-400

Philip RN, Casper EA, Burgdorfer W, et al.: Serologic typing of rickettsiae of the spotted fever group by microimmunofluorescence. J Immunol. 1978, 121, 1961-8

Silveira I, Pacheco RC, Szabó MP, et al.: Rickettsia parkeri in Brazil. Emerg Infect Dis. 2007, 13, 1111-3

Sumner JW, Durden LA, Goddard J, et al.: Gulf Coast ticks (Amblyomma maculatum) and Rickettsia parkeri, United States. Emerg Infect Dis. 2007, 13, 751-3

Tomassone L, Conte V, Parrilla G, et al.: Rickettsia infection in dogs and Rickettsia parkeri in Amblyomma tigrinum ticks, Cochabamba department, Bolivia. Vector Borne Zoonotic Dis. 2010, 10, 953-8

Venzal JM, Portillo A, Estrada-Peña A, et al.: Rickettsia parkeri in Amblyomma triste from Uruguay. Emerg Infect Dis. 2004, 10, 1493-5

Venzal JM, Estrada-Peña A, Castro O, et al.: Amblyomma triste Koch, 1844 (Acari: Ixodidae): Hosts and seasonality of the vector of Ricketsia parkeri in Uruguay. Vet Parasitol. 2008, 155, 104-9

Wright CL, Nadolny RM, Jiang J, et al.: Rickettsia parkeri in Gulf Coast ticks, southeastern Virginia, USA. Emerg Infect Dis. 2011, 17, 896-8

Transmission

Cilek JE, Olson MA: Seasonal distribution of ticks (Acari: Ixodidae) in northwestern Florida. J Med Entomol. 2000, 37, 439-44

Gleim ER, Conner LM, Yabsley MJ: The effects of Solenopsis invicta (Hymenoptera: Formicidae) and burned habitat on the survival of Amblyomma americanum and Amblyomma maculatum. J Med Entomol. 2013, 50, 270-6

Goddard J: Experimental infection of lone star ticks, Amblyomma americanum (L.), with Rickettsia parkeri and exposure of guinea pigs to the agent. J Med Entomol. 2003, 40, 686-9

Hixson H: Field biology and environmental relationships of the Gulf Coast tick in southern Georgia. J Econ Entomol. 1940, 33, 179-89

Paddock CD, Finley RW, Wright CS, et al.: Rickettsia parkeri rickettsiosis and its clinical distinction from Rocky Mountain spotted fever. Clin Infect Dis. 2008, 47, 1188-96

Paddock CD, Goddard J: The evolving medical and veterinary importance of the Gulf Coast tick (Acari: Ixodidae). J Med Entomol. 2015, 52, 230‐52

Parker RR, Kohls GM, Cox GW, et al.: Observations on an infectious agent from Amblyomma maculatum. Public Health Rep. 1939, 54, 1482-4

Sangioni LA, Horta MC, Vianna MC, et al.: Rickettsial infection in animals and Brazilian spotted fever endemicity. Emerg Infect Dis. 2005, 11, 265-70

Silveira I, Pacheco RC, Szabó MP, et al.: Rickettsia parkeri in Brazil. Emerg Infect Dis. 2007, 13, 1111-3

Teel PD, Ketchum HR, Mock DE, et al.: The Gulf Coast tick: a review of the life history, ecology, distribution, and emergence as an arthropod of medical and veterinary importance. J Med Entomol. 2010, 47, 707-22

Whitman TJ, Richards AL, Paddock CD, et al.: Rickettsia parkeri infection after tick bite, Virginia. Emerg Infect Dis. 2007, 13, 334-6

Diagnosis

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

Parola P, Davoust B, Raoult D: Tick- and flea-borne rickettsial emerging zoonoses. Vet Res. 2005, 36, 469-92

Parola P, Miller RS, McDaniel P, et al.: Emerging rickettsioses of the Thai-Myanmar border. Emerg Infect Dis. 2003, 9, 592–5

Parola P, Raoult D: Ticks and tickborne bacterial diseases in humans: an emerging infectious threat. Clin Infect Dis. 2001, 32, 897–928. Erratum: Clin Infect Dis. 2001, 33, 749

Raoult D, Paddock CD: Rickettsia parkeri infection and other spotted fevers in the United States. New Engl J Med. 2005, 353, 626-7

Wölfel R, Essbauer S, Dobler G: Diagnostics of tick-borne rickettsioses in Germany: A modern concept for a neglected disease. Intern J Med Microbiol. 2008, 298 (Suppl. 1), 368-74

Clinical Signs

Goddard J: American Boutonneuse fever – a new spotted fever rickettsiosis. Infect Med. 2004, 21, 207-10

Labruna MB, Horta MC, Aguiar DM, et al.: Prevalence of Rickettsia infection in dogs from the urban and rural areas of Monte Negro municipality, western Amazon, Brazil. Vector Borne Zoonotic Dis. 2007, 7, 249-55

Lado P, Costa FB, Verdes JM, et al.: Seroepidemiological survey of Rickettsia spp. in dogs from the endemic area of Rickettsia parkeri rickettsiosis in Uruguay. Acta Trop. 2015, 146, 7‐10

Mendes JCR, Kmetiuk LB, Martins CM, et al.: Serosurvey of Rickettsia spp. in cats from a Brazilian spotted fever-endemic area. Rev Bras Parasitol Vet. 2019, 28, 713-21

Paddock CD, Sumner JW, Comer JA, et al.: Rickettsia parkeri: a newly recognized cause of spotted fever rickettsiosis in the United States. Clin Infect Dis. 2004, 38, 805-11

Paddock CD: Rickettsia parkeri as a paradigm for multiple causes of tick-borne spotted fever in the western hemisphere. Ann N Y Acad Sci. 2005, 1063, 315-26

Saito TB, Cunha-Filho NA, Pacheco RC, et al.: Canine infection by rickettsiae and ehrlichiae in southern Brazil. Am J Trop Med Hyg. 2008, 79, 102-8

Tomassone L, Conte V, Parrilla G, et al.: Rickettsia infection in dogs and Rickettsia parkeri in Amblyomma tigrinum ticks, Cochabamba Department, Bolivia. Vector Borne Zoonotic Dis. 2010, 10, 953‐8

Treatment & Prevention

Biggs HM, Behravesh CB, Bradley KK, et al.: Diagnosis and management of tickborne rickettsial diseases: Rocky Mountain spotted fever and other spotted fever group rickettsioses, ehrlichioses, and anaplasmosis - United States. MMWR Recomm Rep. 2016, 65, 1-44