Background

Rickettsia is a genus of vector-borne, gram-negative, non-sporeforming, highly pleomorphic, non-motile bacteria. Bacteria in this genus are scientifically classified as Alphaproteobacteria, Rickettsiales by order, and Rickettsiaceae by family. Clinical presentation varies depending on specific disease; please refer to specific disease for information regarding symptoms and treatment. Rickettsia is named after Howard Taylor Ricketts (1871-1910) who studied Rocky Mountain spotted fever and typhus, and later died after contracting typhus in Mexico City. Rickettsia was originally classified into three groups based on serological testing (confirmed by DNA sequencing): spotted fever, typhus, and scrub typhus. However, the scrub typhus group has recently been reclassified as a new genus Orientia. Their genome is very small, composed of 1-1.5 million bases [1,2]. These obligate intracellular parasites can morphologically present as cocci (0.1 μm in diameter), rods (1-4 μm in length), or thread-like (10 μm in length). The survival of the Rickettsia infection is dependent on the organisms entry, growth, and replication within the cytoplasm of the eukaryotic host cells, usually endothelial cells. Rickettsia microorganisms appear to exert their pathologic effects by adhering to and invading the endothelial lining of the vasculature within the affected organ. Adhesions appear to be outer membrane proteins that allow the organism to be phagocytosed into the host cell. Once inside the host cell, the rickettsial organisms take one of two different paths depending on their group. Typhus group organisms multiply and accumulate in large numbers before lysing the host cell; while spotted fever group organisms escape from the host cell, damaging its membrane and cause the influx of water [3,11]. Rickettsia, like viruses, can only grow in living cells and therefore cannot live in artificial nutrient environments.

Vectors and Geography

The Rickettsia genus of bacteria is found worldwide and include such vectors: ticks, lice, mites, and fleas. Rickettsia causes a wide range of human diseases including: Rocky Mountain spotted fever, rickettsialpox, Boutonneuse fever (or Mediterranean fever), Australian tick typhus, Flinders Island spotted fever, African tick bite fever, Queensland tick typhus, Siberian tick typhus, Oriental spotted fever (also known as Japanese spotted fever), and multiple varieties of typhus. In the United States, species of concern for humans include: Rickettsia felis, Rickettsia parkeri, Rickettsia akari, Rickettsia rickettsii, Rickettsia prowazekii, and Rickettsia typhi. The spotted fever group includes: Rickettsia felis, Rickettsia parkeri, Rickettsia akari, and Rickettsia rickettsii; while Rickettsia prowazekii and Rickettsia typhi are in the typhus group. Rickettsia felis is transmitted by cat and dog fleas and causes a disease known as cat flea rickettsiosis. Rickettsia parkeri is transmitted by ticks and causes Maculatum infection in humans. Rickettsia akari, also known as rickettsialpox, is transmitted by mites from house mice (Mus musculus) and wild rodents. In the United States rickettsialpox most commonly occurs in the Northeast, especially in New York city. Rickettsia rickettsii is also a tickborne infection transmitted to humans by tick bite and is better known as Rocky Mountain spotted fever (RMSF). Tick vectors include the Rocky Mountain wood tick (Dermacentor andersoni) in the Western United States, the American dog tick (Dermacentor variabilis) in the eastern, central and Pacific Coast areas of the United States, the Lone Star Tick (Amblyomma americanum) and the brown dog tick (Rhipicephalus sanguineus) in some southern areas [4,10]. RMSF was first recognized in and thought to be limited to the Rocky Mountain area, however is now reported in all geographic areas of the United States. The average incidence of RMSF based on passive surveillance over the last 50 years is approximately 250-1200 cases annually [4]. Major endemic states today are: Delaware, Maryland, Washington D.C., Virginia, West Virginia, North Carolina, Oklahoma, South Carolina, Tennessee, Arkansas, Georgia and Florida; with over 35 percent of cases reported from North Carolina and Oklahoma alone [4]. RMSF is a seasonal disease which occurs in the United States between April and September and increased risk of infection occurs with frequent exposure to dogs or residence near wooded or high grass areas [4-6]. Rickettsia prowazekii causes Epidemic typhus and Sylvatic typhus and has several vectors including: Amblyomma genus ticks, flying squirrel ectoparasites and the human body louse (Pediculus humanus). Epidemic typhus is rare in the United States but has been diagnosed in 35 patients before the year 1991 [13]. Finally, Rickettsia typhi is transmitted by ticks and urban rodent fleas and causes the disease Murine typhus. Rickettsia typhi is associated mainly in areas where urban rat (Rattus rattus and Rattus norvegicus) populations are abundant [12]. In the United States, suburban areas of Texas and California are concentrated areas as the principal vector has been identified as the cat flea (Ctenocephalides felis) [12]. Several other rickettsial diseases have been reported by residents within the United States; however primary infection occurs while traveling elsewhere [2, 7-9].

Detection Strategies

There are three main detection strategies for the presence of Rickettsia: serologic, microscopic and molecular. Blood-borne microscopic visualization of the bacteria is possible if the host has a current infection in the blood stream and if the parasitemia concentration sufficiently high. Rickettsia can be picked up by microscopic analysis by the trained eye as they take on a characteristic red color when stained by Giemsa stain. Serological testing relies on the presence of specific antibodies produced by the host in response to the infection (IgG or IgM). Serological testing for Rickettsia rickettsii and Rickettsia typhi are available through Fry Laboratories. Molecular techniques such as Polymerase Chain Reaction (PCR) may also be used to detect the DNA signature of the organism in the blood stream if the concentration is within the detectible levels of the assay. Fry Laboratories confirms the signature of any suspicious band through DNA sequencing so that results are unambiguous. PCR testing for Rickettsia is currently in development at Fry Laboratories. By utilizing all three testing methods, individual assay weaknesses may be addressed.

1. Walker DH. Rickettsiae and rickettsial infections: the current state of knowledge. Clin Infect Dis July 15 2007;45 suppl 1:539-44. 2. Jensenius M, Fournier P, Raoult D. Rickettsioses and the international traveler. Clin Infect Dis 2004;34(10):1493-9. 3. Edwards MS, Feigin RD. Rickettsial diseases. In: Feigin RD, Cherry JD, Demmler GJ, et al. Textbook of Pediatric Infectious Diseases. 5th ed. WB Saunders Co;2004:2497-2515/Chapter 195. 4. Center of Disease Control and Prevention (CDC). Rickettsial Diseases. Infectious Disease information. Available at http://www.cdc.gov. 5. Dumler JS, Walker DH. Rocky Mountain spotted fever changing ecology and persisting virulence. N Engl J Med Aug 11 2005;353(6):551-3. 6. Graf PC, Chertien JP, Ung L, et al. Prevalence of seropositivity to spotted fever group rickettsiae and Anaplasma phagocytophilum in a large, demographically diverse US sample. Clin Infect Dis Jan 2008;46(1):70-77. 7. Rovery C, Raoult D. Meditteranean Spotted Fever. Infect Dis Clin N Am Sep 2008;22:515-530. 8. Cowan G. Rickettsial diseases: The typhus group of fevers a review. Postgrad Med J May 2000;76(895):269-72. 9. Marshall GS. Rickettsia typhi seroprevalence among children in the southeast United States. Tick-Borne Infections in Children Study (TICKS) Group. Pediatr Infect Dis J Nov 2000;19(11):1103-4. 10. Demma LJ, Traeger MS, Nicholson et al. Rocky Mountain spotted fever from an unexpected tick vector in Arizona. N Engl J Med Aug 11 2005;353(6):587-94. 11. Hackstadt T. The biology of rickettsiae. Infect Agents Dis Jun 1996;5(3):127-43. 12. Civen R, Ngo V. Murine Typhus: An unrecognized suburban vectorborne disease. Clin Pract Mar 15 2008;46:913-8. 13. Walker DH, Fishbein DB. Epidemiology of Rickettsial Diseases. Eur J Epidemiol May 1991;7(3):237-45.