Rickettsiae are small, obligate intracellular bacteria that can cause diseases in humans. They are transmitted through arthropod vectors like ticks and lice. Rickettsiae are divided into three groups based on the diseases they cause: spotted fever, typhus, and scrub typhus. Upon entering the body through a bite or broken skin, they infect endothelial cells. Some escape the phagosome and enter the cell cytoplasm, while others are released when the cell lyses. Doxycycline is the treatment of choice and preventing exposure to ticks can reduce risk of infection. Laboratory diagnosis involves serologic testing to detect antibodies in paired serum samples.

1. RICKETTSIAL DISEASES By, NorhadizahMudin KolejSainsKesihatanBersekutuKuching Program Diploma TeknologiMakmalPerubatan

2. Introduction to the Rickettsiae TheRickettsiae are small (0.3-0.5 x 0.8-2.0 um), Gram-negative, aerobic, coccobacilli that are obligate intracellular parasites of eucaryotic cells. They may reside in the cytoplasm or within the nucleus of the cell that they invade. They divide by binary. They have typical Gram-negative cell walls, and they lack flagella. The rickettsiae frequently have a close relationship with arthropod vectors that may transmit the organism to mammalian hosts.

3. The genus Rickettsiais included in the bacterial family Rickettsiaceae of the order Rickettsiales. This genus includes many species associated with human disease, including those in the spotted fever group and the typhus group (figure 1). The rickettsiae that are pathogens of humans are subdivided into three major groups based on clinical characteristics of disease: spotted fever group; typhus group; and scrub typhus group.

5. Virulence of Rickettsiae Adherence to the Host CellRickettsiae are inoculated into the dermis of the skin by a tick bite or through damaged skin from the feces of lice or fleas. The bacteria spread through the bloodstream and infect the endothelium. Adherence to the host cell is the first step of rickettsialpathogenesis. Invasion of Host CellsUpon attaching to the host cell membrane, rickettsiae are phagocytosed by the host cell. Once phagocytosed by the host cell, rickettsiae are observed to quickly escape from the phagosome membrane and enter the cytoplasm.

6. Movement within and Release from the Host Cell Observations in cell culture systems suggest that the mechanisms of intracellular movement and destruction of the host cells differ among the spotted fever group and typhus group rickettsiae. Typhus group rickettsiae are released from host cells by lysis of the cells. After infection with R. prowazekiior R. typhi, the rickettsiae continue to multiply until the cell is packed with organisms and then bursts. Spotted fever group rickettsiae seldom accumulate in large numbers and do not lyse the host cells. They escape from the cell by stimulating polymerization of host cell-derived actin tails, which propel them through the cytoplasm and into tips of membranous extrusions, from which they emerge.

7. Laboratory Diagnosis There is no widely available laboratory assay that provides rapid confirmation of early Rocky Mountain spotted fever. Treatment decisions must be based on epidemiologic and clinical clues, and should never be delayed while waiting for confirmation by laboratory results. Serologic assays are the most widely available and frequently used methods for confirming cases of Rocky Mountain spotted fever. The indirect immunofluorescence assay (IFA) is generally considered the reference standard in Rocky Mountain spotted fever serology and is the test currently used by CDC and most state public health laboratories.

8. IFA can be used to detect either IgG or IgM antibodies. Blood samples taken early (acute) and late (convalescent) in the disease are the preferred specimens for evaluation. Most patients demonstrate increased IgMtiters by the end of the first week of illness. Diagnostic levels of IgG antibody generally do not appear until 7-10 days after the onset of illness. It is important to consider the amount of time it takes for antibodies to appear when ordering laboratory tests, especially because most patients visit their physician relatively early in the course of the illness, before diagnostic antibody levels may be present. The value of testing two sequential serum or plasma samples together to show a rising antibody level is considerably more important in confirming acute infection with rickettsial agents because antibody titers may persist in some patients for years after the original exposure.

9. Treatment of Rickettsioses Doxycyclineis the drug of choice for the treatment of infections caused by Rickettsia except in cases of pregnancy and tetracycline hypersensitivity. Some studies have shown that doxycycline is superior to chloramphenicol for the treatment of Rocky Mountain spotted fever as it is associated with a lower case fatality rate and a lower hospitalization rate.

10. Prevention and Control Limiting exposure to ticks is the most effective way to reduce the likelihood of Rocky Mountain spotted fever infection. In persons exposed to tick-infested habitats, prompt careful inspection and removal of crawling or attached ticks is an important method of preventing disease. It may take several hours of attachment before organisms are transmitted from the tick to the host. CDC recommends the following prevention measures: Wear light-coloured clothing to allow you to see ticks that are crawling on your clothing. Tuck your pants legs into your socks so that ticks cannot crawl up the inside of your pants legs. Remove any tick you find on your body. Parents should check their children for ticks, especially in the hair, when returning from potentially tick-infested areas. Additionally, ticks may be carried into the household on clothing and pets. Both should be examined carefully.

11. (c) (b) (a) (d) (e) (f) Characteristic spotted rash of late-stage Rocky Mountain spotted fever on legs of a patient. Gimenezstain of tick hemolymph cells infected with R. rickettsii. American dog tick (Dermacentorvariabilis). Rocky Mountain wood tick (Dermacentorandersoni). Early (macular) rash on sole of foot. Late (petechial) rash on palm and forearm.

12. Composite diagram of the life cycle of Rocky Mountain spotted fever, rickettsialpox, and murine typhus. A. Life cycle of Rickettsiarickettsii in its tick and mammalian hosts B. Rickettsiaakari life cycle C. Rickettsiatyphi life cycle.

13. References http://www.cdc.gov/ncidod/eid/vol4no2/azadg.htm http://textbookofbacteriology.net/Rickettsia.html

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