Rickettsiae are a diverse collection of bacteria that survive in the cells of mammals, including humans. Rickettsiae are zoonotic, meaning they can infect both animals and humans, and are often vector-borne, that is, they are transmitted from animal-to-animal or animal-to-human by ticks, lice, fleas and mites.

There are many different species of rickettsiae, with some of the most significant ones being Rickettsia typhi (murine typhus or endemic typhus fever), Rickettsia prowasekii (louse borne typhus or epidemic typhus), Rickettsia rickettsii (Rocky Mountain spotted fever), Rickettsia conorrii (Mediterranean spotted fever), and Orientia tsutsugamushi (scrub typhus). Rickettsiae are loosely grouped in to Typhus Group (such as R. typhi), Scrub Typhus Group (such as O. tsutsugamushi), spotted fever group (SFGR, such as R. rickettsii) and an intermediate group. Rickettsiae cause infections in humans that disseminate from the blood to many different organs. Symptoms of infection can vary from very mild and non-specific (such as a general feeling of being unwell, muscle aches and headaches, fever or chills) through to the appearance of rashes or a small sore called an eschar. More serious complications can occur if left untreated, and these may include problems with the heart, lungs, central nervous system and other organs, and may result in multi-organ failure and death.

Determining the global burden of rickettsial diseases can be problematic for a number of reasons. Often Rickettsial infections are miss-diagnosed as something else (the symptoms are very broad range and non-specific), or symptoms may be mild and go undocumented. Although rickettsial pathogens are found globally, there are many different species and these may be restricted to specific regions. With this distribution, and varying access to health facilities and rates of exposure, burden of infection will vary greatly from country to country and region to region. That said, for some of the most important rickettsial diseases we do have a good approximation of disease burden. In Southeast Asia, rickettsial infections are the second most frequently reported non-malarial disease, after dengue infections (that is of all the diseases other than malaria, rickettsia is the second most common infection). Scrub typhus (Orientia tsutsugamushi) has a seroprevalence ranging from 9.3% - 27.9% in Asia (that is 9.3 to 27.9% of the population has been exposed to scrub typhus in the past); whilst globally, it has been estimated that over a million scrub typhus cases occur each year and that a billion people are at risk of infection. In the USA, the most severe and most commonly reported rickettsial infection is Rocky Mountain spotted fever (RMSF) which is caused by Rickettsia rickettsii, with seven cases per million persons reported in 2007, and if left untreated may cause fatality rates as high as 20 - 25%.

The most typical signs and symptoms of rickettsial diseases include: fever, headache, nausea, vomiting, muscle aches, rashes, swollen lymph glands, abdominal pain, hypotension, and difficulty breathing. Commonly, a small hard black sore (clinically known as an eschar) tends to appear at the bite site where the infection started. In more severe cases, respiratory distress, acute renal failure, brain damage, or mortality may occur.

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The term rickettsial diseases refers to diseases caused by a diverse group of bacterial organisms which share the properties of obligate intracellular parasitism of their host and which are transmitted by an intermediate vector, often a biting tick (although lice and fleas are other notable vectors).

Examples of rickettsial diseases include scrub typhus (caused by Orientia tsutsugamushi), spotted fevers such as Rocky Mountain spotted fever (RMSF - caused by Rickettsia rickettsiae), and epidemic typhus-like infections such as murine typhus (caused by Rickettsia typhi).

In order to appropriately treat rickettsial diseases, one must usually have first considered their possibility. This is because the specific antibiotics which treat rickettsia are seldom routine empirical choices, this being especially true if the presentation is severe. Need for consideration of the diagnosis is not precluded by the commonly used non-specific diagnostic tests such as blood cultures, as these will not identify rickettsia. Thus, it is not possible to accidently make the diagnosis, which is important as the rickettsial diseases mentioned above have a considerable associated mortality.

Despite the diversity of rickettsial infections (both geographically and in terms of the phylogeny of the pathogens), certain epidemiological, historical, or clinical clues may suggest a rickettsial pathogen. A history of travel to an area where rickettsial diseases are recognised, a tick bite, an eschar (a black scab at the bite mark which appears later), and a particular constellation of symptoms may point to the clinical diagnosis. Additionally, non-response to a conventional first-line antibiotic, such as a beta-lactam, which are inactive against these infections, may suggest the diagnosis by exclusion.

Rickettsia of all types tend to be sensitive to the tetracycline class of antibiotic, of which doxycycline is the most widely used and has the best documented efficacy. Reports of resistance of rickettsia to these antibiotics have been very few, and newer evidence casts doubt on these. Doxycycline resistance should not pose a clinical concern for treating physicians. Concern about adverse effects of doxycycline in pregnancy, and in young children, have been found to be negligible in comparison to the significant morbidity and mortality associated with the disease. As such, doxycycline is the go-to treatment, unless truly contraindicated or an alternative with known equivalence is available in consultation with guidelines or expert advice.

Alternatives with proven efficacy include macrolide antibiotics (in particular azithromycin), which may prove to be equivalent in activity against certain rickettsia but inferior against others, such as Rickettsia typhi. Beta-lactam antibiotics (e.g. penicillins, cephalosporins, carbapenems) are inactive against the significant rickettsial pathogens mentioned above and should not be used for their treatment. The quinolones (e.g. ciprofloxacin) and chloramphenicol have variable activity and should only be considered when doxycycline or other alternatives cannot be used, and only in consultation with guidelines or expert advice.

Very little study has been done on measures to prevent rickettsial diseases. Accordingly recommendations are based on the common-sense application of measures which have been shown to be effective in the control of other insect-vector transmitted diseases. Additionally, there are currently no vaccines available for the prevention of rickettsial diseases.

The most important aspect of prevention of rickettsial diseases is likely to be vector avoidance. The chigger mite is the vector of scrub typhus and lives on low vegetation, in particular of scrubland. Avoidance of contact with vegetation in areas with high endemicity (which is often unrealistic for those who live off the land) is one possibility. Another is taking precautions to prevent being bitten, including the wearing of long trousers and sleeves and avoiding lying on the ground. Insect repellents (e.g. DEET) and insecticide-impregnated clothing (e.g. permethrin) are also likely to be effective deterrents. For murine typhus, where the vector is the flea, avoidance of animals with fleas (the reservoir), including domestic animals and rodents, rodent-control and flea-control (vector-control) measures of domestic animals are recommended. The role of reservoir-control, i.e. rodent-control, measures in scrub typhus is uncertain.

There is scant evidence on the effectiveness of chemoprophylaxis for the prevention of rickettsial disease, although breakthrough disease has occurred in those supposedly taking doxycycline malaria prophylaxis. Early identification and removal of the vector may limit the likelihood of transmission of the pathogen, although these may be hard to identify (e.g. chigger mites are very small). Evidence on the use of post-exposure prophylaxis is absent.