Rickettsial Infection 

Updated: Nov 22, 2021
Author: Mobeen H Rathore, MD, CPE, FAAP, FIDSA; Chief Editor: Russell W Steele, MD 



Rickettsiae comprise a group of microorganisms that phylogenetically occupy a position between bacteria and viruses. The genus Rickettsia is included in the bacterial tribe Rickettsiae, family Rickettsiaceae, and order Rickettsiales. They are obligate intracellular gram-negative coccobacillary forms that multiply within eukaryotic cells. Rickettsiae do not stain well with Gram stain, but they take on a characteristic red color when stained by the Giemsa or Gimenez stain. They have typical gram-negative cell walls and lack flagella. Their genome is very small, composed of 1-1.5 million bases.[1, 2]

Rickettsiae are a rather diverse collection of organisms with several differences; this prohibits their description as a single homogenous group. A general characteristic of rickettsiae is that mammals and arthropods are natural hosts. Rickettsioses are usually transmitted to humans by arthropods. Q fever, traditionally described among the rickettsial illnesses until recently, is primarily acquired by inhalation of contaminated airborne droplets.[3, 4, 5]

The epidemiology of human diseases caused by rickettsiae is intimately related to the biology of the vector that transmits it. Rickettsial diseases widely vary in severity from self-limited mild illnesses to fulminating life-threatening infections.[4]

Rickettsial illnesses, caused by organisms within the genus of rickettsiae, are recognized and can be divided into the following 3 biogroups:[2, 6]

Spotted fever biogroup (15 rickettsioses)

Included in this biogroup are the following:

  • Rocky Mountain spotted fever (RMSF), caused by Rickettsia rickettsii

  • Rickettsialpox, caused by Rickettsia akari

  • Boutonneuse fever (ie, Kenya tick-bite fever, African tick typhus, Mediterranean spotted fever, Israeli spotted fever, Indian tick typhus, Marseilles fever)

Typhus group

These are similar diseases that differ epidemiologically. The causative organisms (Rickettsia prowazekii and Rickettsia typhi) are similar to those of the spotted fever group but are antigenically distinct.

  • Louse-borne (epidemic) typhus

  • Brill-Zinsser disease (ie, relapsing louse-borne typhus)

  • Murine (endemic or flea-borne) typhus

Scrub typhus biogroup (Tsutsugamushi disease)

The rickettsial agents of scrub typhus have a single taxonomic name: Orientia tsutsugamushi. However, these organisms represent a heterogeneous group that strikingly differs from Rickettsial species of the spotted fever and typhus groups. The 3 major serotypes are Karp, Gilliam, and Kato.

Other rickettsioses and closely related illnesses

New or reemerging rickettsioses have been described in the last few decades, including tickborne lymphadenopathy (TIBOLA) and Dermacentor -borne-necrosis-eschar-lymphadenopathy (DEBONEL) related to Rickettsia slovaca infection, as well as lymphangitis-associated rickettsiosis attributed to Rickettsia sibricia infection.[1] Recently, a new Rickettsia species, 364D, that causes an eschar-associated illness was identified in California.[7, 8]

Ehrlichia organisms (the cause of human monocytic ehrlichiosis and Ehrlichia ewingii infection), Anaplasmaphagocytophilum (the cause of human granulocytic anaplasmosis), and Bartonella species (the cause of Catscratch disease, relapsing fever, and Trench fever) are organisms related to the rickettsiae. They are discussed in separate articles.

Q fever is a disease caused by Coxiella burnetii, which has recently been removed from the Rickettsiales.[5] The disease is described here for comparison with other rickettsioses.

Potential as biological weapons

The environmental stability, small size, aerosol transmission, persistence in infected hosts, low infectious dose, and high associated morbidity and mortality have made pathogenic rickettsiae desirable bioterrorism agents. In fact, R prowazekii and C burnetii have been weaponized. However, developing rickettsial pathogens as biological weapons has many drawbacks, such as the lack of direct host-to-host transmission and availability of therapeutic countermeasures against them.[9]


Rickettsiae microorganisms appear to exert their pathologic effects by adhering to and then invading the endothelial lining of the vasculature within the various organs affected. The adhesins appear to be outer membrane proteins that allow the rickettsia to be phagocytosed into the host cell. Once inside, the rickettsial organisms either multiply and accumulate in large numbers before lysing the host cell (typhus group) or they escape from the cell, damaging its membrane and causing the influx of water (spotted fever group).[4]

Rickettsiae rely on the cytosol of the host cells for growth. To avoid phagocytosis within the cells, they secrete phospholipase D and hemolysin C, which disrupt the phagosomal membrane, allowing for rapid escape.

The most important pathophysiologic effect is increased vascular permeability with consequent edema, loss of blood volume, hypoalbuminemia, decreased osmotic pressure, and hypotension. On the other hand, disseminated intravascular coagulation is rare and does not seem to contribute to the pathophysiology of rickettsiae.

Studies of murine models have demonstrated that rickettsiae are cleared by cytotoxic CD8 cells and by cytokine-activated rickettsicidal nitrogen and oxygen species. In fact, antibodies do not play an important role in immunity against pathogenic rickettsia upon fist exposure. Walker provided an excellent review of this topic.[1]

  • RMSF: In RMSF, rickettsiae multiply within the endothelial cells of small blood vessels and then gain access to the bloodstream after skin inoculation. Focal areas of endothelial proliferation and perivascular mononuclear cell infiltration cause leakage of intravascular fluid into tissue space. These vascular lesions can affect all organs; however, they most readily are found in the skin and adrenals. In the central nervous system and heart, a damaging host response (primarily cell-mediated) accompanies the vasculitis. The liver is usually affected with portal triaditis. Vascular wall destruction consumes platelets, causing thrombocytopenia. Multiple factors lead to hypoalbuminemia (eg, renal loss, decreased intake, hepatic involvement) and hyponatremia (eg, renal loss, extracellular fluid shifts, cellular exchange of sodium for potassium).

  • Rickettsialpox: The organism that causes this illness is known to cause angiitis similar to other rickettsiae. Biopsies, which are rarely needed to establish the diagnosis of rickettsialpox, show evidence of thrombosis and necrosis of capillaries, as well as perivascular mononuclear cell infiltration.

  • Boutonneuse fever: Features of this illness are related to involvement of the vascular structures of the dermis in a manner similar to that observed in RMSF. Endothelial cells of the capillaries, venules, and arterioles (ie, small-to-medium sized vessels) in various organs may also become involved as the organism disseminates.[10] Additionally, a few cases of leukocytoclastic vasculitis have been reported with this infection.

  • Louse-borne (epidemic) typhus: The pathology is similar to that described for the spotted fever group of rickettsial diseases. However, typhus group rickettsiae do not stimulate actin-based mobility and rather extensively multiply and accumulate intracellularly until they burst the endothelial cell and disseminate into the bloodstream.

  • Brill-Zinsser disease (ie, relapsing louse-borne typhus): The pathology is similar to that described for the spotted fever group of rickettsial diseases. However, the organisms appear to lie dormant, most likely in the cells of the reticuloendothelial system, until they are reactivated by an unknown stressor, multiply and cause another acute but milder infection.

  • Murine (endemic or flea-borne) typhus: Pathology is similar to that described for epidemic typhus.

  • Tsutsugamushi disease (ie, scrub typhus): After invading the host cell and replicating in its cytoplasm, the Orientia tsutsugamushi exits by budding enveloped by part of the host cell membrane as it invades adjacent cells. Perivasculitis of small blood vessels occurs similarly to other rickettsial diseases. Usually, a necrotic inflammatory skin lesion occurs at the mite bite site, and regional and generalized lymphadenopathy is associated with this infection.

  • Q fever: In Q fever, the Coxiella organism directly causes disease in various organs. It has been demonstrated in macrophages in the lungs and in vegetations of the heart valves. Host-mediated pathogenic mechanisms also appear to play an important role in disease pathogenesis; the disease causes granulomatous changes in reticuloendothelial organs (granulomatous hepatitis).



This disease is caused by R rickettsii.[1, 6]

Tick vectors of RMSF include the Rocky Mountain wood tick (Dermacentor andersoni) in the Western United States and Canada; the American dog tick (Dermacentor variabilis) in the Eastern United States, along the US Pacific coast, and in the central United States; and the Lone Star tick (Amblyomma americanum) in some southern areas.[3]  Examples of the ticks are shown in the images below.

This photo shows the relative sizes of the adult f This photo shows the relative sizes of the adult forms of Ixodes scapularis (right) and Dermacentor variabilis (left). These ticks are shown next to a common match for scale. I scapularis is also referred to as Ixodes dammini. Photo by Darlyne Murawski; reproduced with permission.
This photo is of an adult female, Amblyomma americ This photo is of an adult female, Amblyomma americanum, and a nymphal form of the same species (shown next to a common match for scale). Photo by Darlyne Murawski; reproduced with permission.

From 2002-2004, cases of RMSF reported from rural Arizona by Demma and colleagues were attributed to exposure to the common brown dog tick (Rhipicephalus sanguineus).[11]  This represents a change from the typical vectors for this disease.

Expansions in tick populations can introduce rickettsial agents to new geographic areas and previously unrecognized rickettsiae -vector-human host relationships continue to evolve and be described.[12]  Research from Germany identified a possible role for migratory birds in the distribution of emerging tick-borne pathogens including Rickettsiae.[13]

Rickettsiae multiply within ticks and pass to the next generation transovarially.

Rickettsiae are transmitted to a vertebrate host through saliva while a tick is feeding. It usually takes several hours of attachment and feeding before the rickettsiae are transmitted to the host. The risk of exposure to a tick carrying R rickettsii is low. Generally, about 1-3% of the tick population carries R rickettsii, even in areas where most human cases are reported.

Recognized or potential tick-borne spotted fever group rickettsial pathogens in the United States, other than R rickettsii include R akari, Rickettsia felis, Rickettsia parkeri, Rickettsia amblyomii, Rickettsia rhipicephali, and various unnamed serotypes (eg, Tillmook, 364-D).[14]


It is caused by R akari, a member of the spotted fever group of Rickettsiae.

The disease is distinguishable from other rickettsial infections by the presence of an eschar at the site of the mouse mite (Liponyssoides sanguineus) bite, a vesiculopustular eruption, and the absence of Weil-Felix agglutinins.

The house mouse (Mus musculus) is the natural host of the mite transmitting rickettsialpox in the United States. Other rodents have been associated with the disease in other parts of the world.[6]

Boutonneuse fever

This disease is a tick-borne infection caused by various subspecies of Rickettsia conorii complex (R conorii conorii is the cause of Mediterranean spotted fever; R conorii israelensis is the cause of Israeli spotted fever; R conorii caspica is the cause of Astrakhan spotted fever; and R conorii indica is the cause of Indian tick typhus) , Rickettsia africae (the cause of African tick–bite fever) , or R slovaca, which are obligate intracellular organisms transmitted to humans by various ticks, depending on the geographical location.[10]

Contact with dogs carrying infected ticks appears to be the important risk factor for human infection.

Louse-borne (epidemic) typhus

This disease is caused by R prowazekii.

It is transmitted to humans by lice (ie, Pediculus humanus). Humans are the primary reservoir for R prowazekii.

Brill-Zinsser disease (ie, relapsing louse-borne typhus)

The rickettsial cause is the same but is related to the reactivation of the organism from a poorly defined latent state.

Murine (endemic or flea-borne) typhus

This disease is primarily caused by R typhi (Rickettsia mooseri) and R felis, which share a large antigenic moiety with R prowazekii.

It is transmitted from rat-to-rat by a rat flea (X cheopis) and accidentally to humans by the feces of infected fleas.

The cat flea (C felis) can also transmit the disease.[15]

Tsutsugamushi disease (ie, scrub typhus)

This disease is caused by O tsutsugamushi, which has a remarkable antigenic heterogeneity.

It is transmitted to humans by the larval form of trombiculid mites (ie, chiggers) that live and breed in the soil and scrub vegetation. The mite is both the reservoir and the vector that passes the bacteria transovarially. Rodents are also reservoirs. Humans are accidentally infected.

Q fever

The name derives from "Query Fever," given in 1935 following an outbreak of febrile illness in an abattoir in Australia. The disease is caused by C burnetii, a short, Gram negative, strictly intracellular bacterium.

Originally classified in the order Rickettsiales, C burnetii has since been placed (with Legionella and Francisella) into the gamma subdivision of the Proteobacteria on the basis of sequences of the 16SrDNA encoding genes.[5]

Unlike human rickettsial infections, it is a zoonosis transmitted from diseased animals to humans by the aerosol route or ingestion of raw milk.

Animals commonly infected include domestic livestock, especially cattle, sheep, and goats, as well as rodents, marsupials (in Australia), and cats (in Canada).

Ticks play a very minor role, if any, in transmission of the disease to humans; however, they transmit the disease to rodents and domestic animals.

C burnetii is a resilient organism that remains latent in infected hosts (eg, domestic livestock) until it is activated by a physiologic stressor, such as parturition. It then multiplies and contaminates the animals' surroundings, where it remains a potential source of infection for months. It is considered by the Center for Disease Control and Prevention (CDC) a potential agent of bioterrorism (class B).[6, 5]


United States statistics

An analysis of insurance claims data showed that 14,830 patients in the United States received a diagnosis of rickettsial disease during 2005 to 2017. Of those patients, 7517 (50.7%) had spotted fever rickettsiosis, 4571 (30.8%) had ehrlichiosis, 1362 (9.2%) had typhus group rickettsiosis, and 1193 (8.0%) had other rickettsial diseases.[16]


RMSF is caused by R rickettsii. Now reported in all geographic areas of the United States, RMSF was first recognized in and thought to be limited to the Rocky Mountain area. Its incidence sharply declined with the introduction of broad-spectrum antibiotics in the 1950s; the incidence soared again in the 1960s and peaked in 1981. Incidence has declined since that time. The average annual incidence from 1997-2002, based on passive surveillance, was 2.2 cases per million population. Incidence increased from 1.7 cases per million person-years in 2000 to 14.3 cases per million person-years in 2012.[17]  The major endemic areas in the United States today include North Carolina, Oklahoma, South Carolina, Tennessee and Arkansas. More than 90% of patients with RMSF are infected from April through September. Individuals with frequent exposure to dogs and who reside near wooded areas or areas with high grass are at an increased risk of infection.[3, 18, 19]


In the United States, rickettsialpox most commonly occurs in the Northeast, especially in New York City. Despite sporadic periodic outbreaks, incidence appears to be declining. The natural host is the common house mouse (Mus musculus).

Boutonneuse fever

This disease is very rare outside a limited geographical area in the Mediterranean, Africa, and India. With increased travel and ecotourism in endemic areas, more imported cases of the disease are described in travelers returning to the United States from Mediterranean regions.[10]

Louse-borne (epidemic) typhus

This is rare in the United States, but sporadic cases have been reported. The presumed source of infection is the southern flying squirrel.

Brill-Zinsser disease (ie, relapsing louse-borne typhus)

The distribution of this disease is analogous to louse-borne epidemic typhus. Recently, it has been rarely reported in the United States, and all cases had acquired the primary infection elsewhere.[20, 2, 21]

Endemic murine (flea-borne) typhus

This type of typhus is prevalent in urban cities and costal ports where rats are abundant. This is because it is transmitted rat-to-rat by a rat flea (Xenopsylla cheopis) and transmitted accidentally to humans by the feces of infected fleas. The cat flea (Ctenocephalides felis) may also serve as a vector for transmission of this disease to humans. These may be important vectors in Texas and southern California. Incidence has declined coincident with increased use of insecticides. Cases occur throughout the year, with peak prevalence from April through June in Texas and during the warm months of summer and early fall elsewhere.[20, 22]

Tsutsugamushi disease (ie, scrub typhus)

This is extremely rare outside the southwest Pacific and Southeast Asia.[23]

Q fever

Outbreaks are most common in slaughterhouses, research facilities, and plants, where handling of animals or their birth products is a source of exposure. Prevalence of Q fever in the United States is underestimated. Since Q fever became a nationally reportable disease in 1999 in the United States, a linear increase has been observed in the number of human cases identified (17 cases with onset in 2000 compared with 167 cases with onset in 2007). The incidence of Q fever increased similarly, from less than 0.1 case per million persons in 2000 to 0.6 case per million persons in 2007.

The surveillance case definition for Q fever was modified in 2008 to revise laboratory criteria for diagnosis and to allow for the separate reporting of acute and chronic Q fever. During 2008–2010, the number of reported cases decreased slightly, relative to 2007, and the incidence rate has decreased to 0.4 case per million persons. One hundred thirty-one cases of Q fever were reported with onset in 2010; of these, 106 were acute Q fever and 25 were chronic Q fever.[24]

International statistics

The spotted fever rickettsiae have been found in every continent except Antarctica.[2]


This primarily occurs in the continental United States but has been reported in southern Canada, Central America, Mexico, and parts of South America. It is rarely seen elsewhere.[18]


This may be more prevalent worldwide than is reported. It has been identified in large cities in Russia, South Africa, and Korea.

Boutonneuse fever

Boutonneuse fever has demonstrated an increased incidence in Mediterranean countries, such as Spain, Italy, and Israel. Along with African tick–bite fever, these infections have been identified in Algeria, Malta, Cyprus, Slovenia, Croatia, Kenya, Somalia, South Africa, Ethiopia, India, and Pakistan, as well as rural Sub-Saharan Africa, the eastern Caribbean, and around the Black Sea.[4, 10]

Louse-borne (epidemic) typhus

Epidemics have occurred in Europe, Asia, and Africa. African countries, especially Ethiopia and Nigeria, have reported most of the cases in the last 2 decades.

Brill-Zinsser disease (ie, relapsing louse-borne typhus)

This disease follows the epidemiology of louse-borne epidemic typhus and rarely, if ever, occurs in children because the reactivation usually occurs decades after primary infection.

Murine (endemic or flea-borne) typhus

This is prevalent in large cities around the world where rats abound. It has been reported in travelers returning from ports and beach resorts in Asia, Africa, and Europe.[2, 23] Human infections with rickettsia contracted after exposure to cat fleas was recently described in Australia. The fleas involved demonstrated the presense of Rfelis.[15]

Tsutsugamushi disease (ie, scrub typhus)

Cases are usually seen in rural south and southeast Asia, limited to the geographical area bound by Japan, the Solomon Islands, and Pakistan. It is estimated that 1 million cases occur each year.

Q fever

This zoonotic disease is observed in humans who come in contact with infected animals in Australia and Canada, as well as other areas of the world. Incidence figures widely vary.[5]

Race-, sex-, and age-related demographics

No specific racial predilection is observed.

Males appear to be at higher risk for infection with tick-borne rickettsioses.[17] This is likely because of greater recreational or occupational exposures to tick habitats. However, in some spotted fever illnesses (eg, Q fever), females seem to be less susceptible to the infection possibly due to a protective role of female hormones.[10]

Two thirds of patients with RMSF are aged 15 years or younger.[4]  Rickettsialpox, boutonneuse fever, epidemic and endemic typhus, and Tsutsugamushi disease affect all ages. Q fever occurs in all age group but is more prevalent between age 30-70 years.[5]


Overall prognosis


The overall mortality rate without specific therapy is approximately 25%; however, the mortality rates are higher for men, elderly persons, and black men with G-6-PD deficiency. In the United States, the overall mortality rate currently is 5-7%. Fatalities are mainly caused by delay in diagnosis and treatment. Solid immunity usually follows recovery from RMSF.


Rickettsialpox is usually self-limited. Deaths have not been reported.

Boutonneuse fever

Boutonneuse fever generally runs a benign course. Very rarely, it may follow a rapidly fatal course in otherwise healthy children.

Louse-borne (epidemic) typhus

The mortality rate in untreated cases correlates with the patient's age. Mortality may be uncommon in children younger than 12 years, but rates rise to as high as 60-70% in individuals older than 50 years. Most patients who recover develop immunity.

Brill-Zinsser disease (ie, relapsing louse-borne typhus)

This is analogous to primary louse-borne epidemic typhus, except that patients who recover do not develop immunity.

Murine (endemic or flea-borne) typhus

This is usually a mild illness without significant sequelae.

Tsutsugamushi disease (ie, scrub typhus)

Fatalities are rare with use of antibiotics. The heterogeneity of scrub typhus strains accounts for the frequent reinfections. Sporadic short courses of doxycycline or chloramphenicol may be required to prevent relapses.

Q fever

Patients with uncomplicated Q fever recover within 1-3 months without sequelae. The mortality rate is less than 1%. On the other hand, complicated cases have a higher rate of permanent disabilities and fatalities.


Rickettsial diseases vary in clinical severity according to the virulence of the Rickettsia and host factors, such as age, male gender, and other underlying diseases. The most virulent rickettsiae are R rickettsii and R prowazekii, which kill a significant portion of infected persons unless the diseases are sufficiently treated early with an effective antimicrobial agent.[4, 9]

  • RMSF: The overall mortality rate is 4%, despite effective antibiotic therapy. This most likely is caused by delay in the diagnosis and initiation of proper treatment. Patients treated during the first week of illness have the highest chance of complete recovery; however, if the disease is allowed to progress to the second week untreated, even optimal therapy progressively becomes less effective.[25]  Deficiency of glucose-6-phosphate dehydrogenase (G-6-PD) enzyme is associated with a high proportion of severe cases of RMSF. This is a rare clinical course that is often fatal within 5 days of onset of illness.

  • Rickettsialpox: No mortality has occurred from this infection. Morbidity is minimal, as noted in Clinical.

  • Boutonneuse fever: This infection generally runs a benign course. Unusual presentations (eg, acute pancreatitis)[26] , rare complications (eg, hemophagocytic lymphohistiocytosis),[27]  and severe forms of the disease have been described and fatalities are rare.[10]

  • Louse-borne (epidemic) typhus: Mortality rates in untreated cases correlate with the patient's age. The mortality rate is approximately 10% in young adults but approaches 60-70% in patients older than 50 years.

  • Brill-Zinsser disease (ie, relapsing louse-borne typhus): These relapses tend to be milder, shorter, and less debilitating.

  • Murine (endemic or flea-borne) typhus: Complications and mortality (1% mortality rate in the United States) are uncommon.

  • Tsutsugamushi disease (ie, scrub typhus): The illness usually is mild and self-limited. However, if left without treatment complications may include pneumonitis, meningoencephalitis, disseminated intravascular coagulation and renal failure. Fatality rate ranges from 1-35%, depending on the virulence of the infecting strain, host factors, and institution of proper treatment.

  • Q fever: Uncomplicated disease is self-limited, lasting for 10-90 days. Complications requiring hospitalization are rare and may include endocarditis, encephalitis, pneumonia, hepatitis, and splenomegaly. Rates of hospitalization among Q fever cases reported to the US Centers for Disease Control and Prevention (CDC) averaged over 50% during 2002-2008. However, it is likely that mild Q fever infections, which do not require hospitalization, may be more likely to be under-recognized and therefore under-represented in current national surveillance systems.[24]  The overall mortality rate of Q fever is approximately 1%. However, the rate may increase to 30-60% with complications.[5]


The following are complications of rickettsial diseases:

  • RMSF: Complications are uncommon, especially if patients receive proper treatment. Acute complications may include a superimposed bronchopneumonia and congestive heart failure (caused by fluid overload). Long-term health problems following acute RMSF infection include partial paralysis of the lower extremities; gangrene requiring amputation of fingers, toes, arms, or legs; hearing loss; loss of bowel or bladder control; movement disorders; and language disorders. These rare complications are usually seen in severely affected individuals.[28]

  • Rickettsialpox: This is usually a self-limited disease with no complications.

  • Boutonneuse fever: Similarly to RMSF, the disease occasionally may follow a malignant and rapidly fatal course with multiorgan failure, encephalopathy, and coagulopathy.[10]

  • Louse-borne (epidemic) typhus: Complications are uncommon but include gangrene, parotitis, otitis, myopericarditis, pneumonia, and pleurisy.

  • Brill-Zinsser disease (ie, relapsing louse-borne typhus): Complications are similar to the primary illness; however, relapses usually are less severe.

  • Murine (endemic or flea-borne) typhus: Complications are similar to those observed in louse-borne typhus and are uncommon.

  • Tsutsugamushi disease (scrub typhus): Complications are generally uncommon. Deafness, atypical pneumonia, disease similar to adult respiratory distress syndrome, myocarditis, and disseminated intravascular coagulopathy have been reported.

  • Q fever: Complications include chronic Q fever, endocarditis, myocarditis, meningoencephalitis, glomerulonephritis, and syndrome of inappropriate antidiuretic hormone (SIADH).

Patient Education

Education of patient population regarding effective avoidance of ticks is highly important.

Physician education is also important to promote early diagnosis and proper treatment.

For excellent patient education resources, see WebMD's patient education article Tick Bites and the slideshow Guide to Tick-Borne Diseases.




Early signs and symptoms of these infections are notoriously nonspecific and may mimic benign viral illnesses, making the diagnosis more difficult. Certain features that aid in making the early diagnosis of rickettsial diseases include (1) a history of tick bite or exposure, (2) recent travel to endemic areas, and (3) similar illness in family members, coworkers, or family pets (especially dogs).

Rocky Mountain spotted fever (RMSF)[28]

  • Fever, headache, rash, confusion, and myalgia are cardinal features.

  • Onset may be gradual or abrupt, beginning approximately 1 week (range, 2-14 d) following a bite from an infected tick. As many as 40% of patients may be unaware of the tick bite, which is usually painless and may go unnoticed or be easily forgotten.

  • Headache is usually persistent, intense, and intractable.

  • Patients may appear toxic, and this usually progresses to mental confusion and delirium.

  • GI symptoms (eg, abdominal pain and diarrhea) commonly occur during early stages of illness.

  • Conjunctival injection may also be seen.


  • After an incubation period of 9-14 days, a red papule develops at the site of the mite bite. The papule subsequently develops an eschar. The appearance of the latter roughly coincides with the appearance of fever.

  • Irregular fluctuating fever (38-41°C) occurs and lasts for less than a week. Fever is accompanied by headache, chills, rigors, profuse sweating, myalgias, and occasionally by rhinorrhea, cough, sore throat, nausea, vomiting, and abdominal pain.

Boutonneuse fever

See the list below:

  • Incubation period is usually 6 days (ranges from 1-16 d).

  • An eschar or cutaneous necrosis caused by rickettsial vasculitis at the tick-bite site of inoculation, known as tache noire ("black spot"), is pathognomonic. However, it may not be seen in 14-40% of cases. This lesion heals slowly over 10-20 days without leaving a scar.

  • The disease has an acute onset with high fever (above 39°C), headache, malaise and arthromyalgias. Headaches are less frequent in children.[10] Unusual presentations, such as acute pancreatitis, have also been described.[26]

  • African tick bite fever is similar but has a more timid presentation. It differs from other similar rickettsioses in that it produces a painful lymphadenopathy, multiple eschars, nuchal myalgia, and, occasionally, a sparse vesicular rash.[1, 29]

Louse-borne (epidemic) typhus

See the list below:

  • The illness has an abrupt onset occurring 1-2 weeks following the bite of an infected louse.

  • Patients develop fever, intractable headache, and rash. The rash appears on days 4-7 of illness and spreads from the trunk to the extremities, sparing the face, palms, and soles. The lesions progress from macules to maculopapules to petechiae.

  • Conjunctival injection, rales, and delirium commonly occur.

Brill-Zinsser disease (relapsing louse-borne typhus)

Presentation is analogous to primary louse-borne epidemic typhus but is milder.

Murine (endemic or flea-borne) typhus[20]

  • Murine typhus is similar to louse-borne typhus but tends to have a milder and shorter course.

  • Fever is less pronounced and remittent, headache is less severe, and rash is less extensive. The latter may be absent in approximately 50% of patients.

Tsutsugamushi disease (ie, scrub typhus)[20]

  • The incubation period is approximately 1-2 weeks.

  • In fewer than half of patients, the site of the mite bite develops a necrotic eschar with enlargement of regional lymph nodes similar to rickettsialpox.

  • Inquiring about history of travel to the Southwest Pacific or Southeast Asia, where patients almost exclusively contract this disease is also helpful.

Q fever[30, 5]

  • Primary infection is usually asymptomatic. Adults and men are more likely to have symptomatic infection compared with children and women, respectively.

  • Incubation period ranges from 2-6 weeks.

  • Acute Q fever infection usually has an abrupt onset, with fever, intractable headache, chills, myalgia, cough, and chest pain. The three clinical presentations more commonly observed are flulike illness, pneumonia, and hepatitis.

  • Rash is absent in over 90% of cases.

  • Chronic Q fever infection is less common (1-5%). It may be manifested as endocarditis, chronic or relapsing multifocal osteomyelitis, chronic hepatitis, chronic vascular infection, endocarditis, pericarditis, or myocarditis.[31] The infection may be insidious, developing months to years following the acute infection.

  • Humans contract the disease by inhaling contaminated aerosols when they come in contact with infected animals or materials contaminated by them. Workers who handle livestock (eg, cattle, sheep, goats), especially at the time of slaughter or parturition, are at an increased risk of infection. Human infection also occurs after ingestion of contaminated raw milk.[5]

Tickborne lymphadenopathy (TIBOLA) and Dermacentor -borne-necrosis-eschar-lymphadenopathy (DEBONEL)[1]

  • An eschar associated with painful cervical lymphadenopathy appears 1 week after a tick bite to the occipital scalp.

  • Fever and rash are seldom present.

  • Patients may develop persistent asthenia and alopecia at the site of the eschar.

Physical Examination


See the list below:

  • Fever reaches 40-41°C and, more commonly, has a persistent pattern rather than an oscillating one.[28, 4]

  • Rash starts on the second or third day of the illness. It usually appears peripherally on the wrists and ankles and spreads to involve the extremities and trunk. Rarely, the rash may be evanescent or localized to a particular region of the body.[32]

  • Typically, the lesions are small (1-5 mm), blanching, erythematous macules that may progress to maculopapules and petechiae.

  • Skin necrosis is rare. In as many as 20% of cases, patients may not develop a rash (spotless RMSF), but this should not delay institution of proper therapy based on historical and clinical data.

  • Signs of meningoencephalitis and coma may follow delirium.

  • Meningismus may accompany the disease but is not necessarily associated with abnormal cerebrospinal fluid (CSF) findings (eg, minor elevation of CSF lymphocyte count). Other neurologic findings may include cortical blindness, seizures, central deafness, ataxia, paralysis, and cranial palsies.

  • Cardiac involvement frequently occurs. Adequate monitoring and workup are necessary to exclude arrhythmias and congestive cardiac failure.

  • Pulmonary manifestations may range from atelectasis to infiltrates or pulmonary edema.

  • Myalgia is a common feature and usually manifests as thigh or calf tenderness.

  • Retinal disease (i.e., edema, papilledema, cotton wool exudates, hemorrhages, retinal artery occlusion) occurs more commonly than uveitis or iritis.

  • Enlargement of the liver or spleen is infrequent.


See the list below:

  • Regional lymph nodes at the area of the primary eschar typically become enlarged.

  • A macular rash develops within several days of the onset of fever. The lesions then develop into vesicular maculopapules over a few days. The rash is distributed on the face, neck, trunk, and extremities and easily may be confused with the rash of varicella, especially in adult patients (hence, the name). In addition to the exanthem, the disease also may involve the mucus membranes, causing an enanthem. The pox usually heals within 2-3 weeks without scarring.

  • In addition to the exanthem, the disease also may involve the mucus membranes, causing an enanthem.

Boutonneuse fever

See the list below:

  • Generalized myalgia occurs, and even myositis can be demonstrated.

  • Eschars can be often found in the trunk, arms and legs of cases. In young children they are frequently found on the scalp in a retroauricular area.

  • A rash appears on days 3-5 after the fever onset. It spreads from the extremities to the trunk, neck, palms, and soles within 36 hours. It usually spares the face.[10]

  • The lesions progress from macular to maculopapular and may persist for 2-3 weeks.

  • Atypical cutaneous findings may occur in a few patients and 1-4% of cases never develop a rash.

  • Cervical adenopathy may be found in 33-75% of affected children.

  • Patients with African tick–bite fever usually have a lower incidence of rash. It is usually vesicular and sparser than in Boutonneuse fever. Also, multiple eschars and prominent regional lymphadenopathy are present.[29]

  • Other manifestations and complications are similar to those seen in patients with RMSF.

Louse-borne (epidemic) typhus [20]

  • A rash appears on days 4-7 of illness and spreads from the trunk to the extremities, sparing the face, palms, and soles. Initially the rash may be concentrated in the axilla.

  • The lesions progress from macules to maculopapules to petechiae.

  • Uncommonly, complications such as gangrene, pericarditis, myocarditis, pleural effusion, and pneumonia may occur.

  • In severe cases, meningoencephalitis and delirium with fatal cardiac and renal failure may ensue.

Brill-Zinsser disease (ie, relapsing louse-borne typhus)

This is analogous to primary louse-borne epidemic typhus. The rash is usually milder and resolves faster.

Murine (endemic or flea-borne) typhus

See the list below:

  • It is similar to louse-borne typhus but tends to have a milder and shorter course.

  • The rash is less extensive. Unlike RMSF, the rash usually spreads from the trunk to the extremities.

Tsutsugamushi disease (ie, scrub typhus)

See the list below:

  • Unlike in other rickettsial diseases, generalized lymphadenopathy is a common feature (80%) of scrub typhus. It develops concomitantly with other manifestations, such as fever, headache, and rash.[20]

  • The rash, which occurs 1-3 weeks following exposure to the vector, is frequently truncal and has a short duration. In 50% of cases, patients have an inoculation eschar.

  • Hepatosplenomegaly, ocular pain, and conjunctival injection are relatively common.

  • Other less common manifestations include deafness, tinnitus, myocarditis, atypical pneumonia, and adult respiratory distress syndrome.

Q fever [30]

  • Pneumonitis occurs in more than half of patients. Cough is usually nonproductive and physical findings may not be pronounced.

  • Radiography may reveal a wide variety of pathologic findings, ranging from multiple segmental opacities to pleural effusion, lobar consolidation, or linear atelectasis.

  • Hepatitis presents with a fever and silent elevation of liver enzymes (transaminases). Hepatosplenomegaly may be present.[5]

  • Chronic Q fever infection must be excluded in patients with multifocal osteomyelitis, especially if a history of exposure to farm animals is noted.[31]





Laboratory Studies

Rickettsiae are not evident on blood smear findings and do not stain with most conventional stains.[3, 4]

No rapid laboratory tests are available to diagnose rickettsial diseases early in the course of illness.

Serologic assays that demonstrate antibodies to rickettsial antigens (eg, indirect immunofluorescence, complement fixation, indirect hemagglutination, latex fixation, enzyme immunoassay, microagglutination) are preferable to the nonspecific and insensitive Weil-Felix test based on the cross-reactive antigens of Proteus vulgaris strains. Serologic findings usually take 10-12 days to become positive. The value of testing 2 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.

Immunofluorescence assay (IFA) is currently considered to be the reference serological method. However, it cannot determine the causative agent to the species level.

Polymerase chain reaction (PCR) to detect rickettsiae in blood or tissue provides promise for early diagnosis. PCR testing and immunohistochemical staining of skin specimen obtained by performing a biopsy may help confirm the clinical diagnosis in patients with rash (high expertise is usually needed to interpret the biopsy result).

Preliminary findings of new research is indicating that swabs of eschars may be used for molecular detection of rickettsial infections when biopsies are difficult to perform.[33, 34, 35] However, serology remains the mainstay of diagnosis because these other tests are expensive and less available to clinicians.

Rickettsial isolation in culture is unnecessary, laborious, and hazardous to laboratory personnel.

Rocky Mountain spotted fever (RMSF)

Serology is the mainstay to confirm diagnosis.

Another approach to RMSF diagnostics is immunostaining whereby a skin biopsy of the rash from an infected patient is tested prior to therapy or within the first 48 hours after antibiotic therapy has been started. This test's use remains highly operator-dependent.

Other tests, such as PCR, are rather expensive and not readily available.

Nonspecific laboratory findings, such as thrombocytopenia, leukopenia, and mild hyponatremia, may give helpful clues to the treating physician.

If cerebrospinal fluid is examined, pleocytosis (generally < 100 cells/μ L) is typically observed with polymorphonuclear or lymphocyte predominance, moderately elevated protein levels (100-200 mg/dL), and normal glucose levels.


As with other rickettsial infections, diagnosis is clinical and may be confirmed by serology.

The Weil-Felix test is not useful because R akari does not produce Weil-Felix agglutinins.

R akari has a soluble antigen that cross-reacts with R rickettsii (the cause of RMSF) and other spotted fever groups of rickettsiae.

Boutonneuse fever

Serologic laboratory confirmation (complement fixation, microagglutination, western blot, indirect immunofluorescent tests) usually provides support for the diagnosis made on clinical and epidemiologic grounds. Additionally, a latex agglutination test for detection of antibodies to R conorii that is both specific and sensitive now can be performed in specialized laboratories.

R conorii has been detected from the tache noire by restriction fragment length polymorphism (RFLP) and by PCR.[10]

Louse-borne (epidemic) typhus

Serologic laboratory confirmatory tests are available as in RMSF. Patients initially have an IgM response followed by production of immunoglobulin G (IgG) antibodies.

However, a significant antigenic crossing is noted between this rickettsial organism and those of the spotted fever group.

PCR promises to be a rapid diagnostic test but is expensive and not yet widely available.

Brill-Zinsser disease (ie, relapsing louse-borne typhus)

Laboratory studies are similar to those for primary louse-borne epidemic typhus. However, patients develop an anamnestic immune response whereby only IgG is produced.

Murine (endemic or flea-borne) typhus

Laboratory studies are analogous to those mentioned for epidemic louse-borne typhus.

Additionally, a mild-to-moderate elevation of serum aspartate aminotransferase (AST) level is present in approximately 90% of patients. Other indices of hepatocellular injury (alanine aminotransferase, alkaline phosphatase, lactate dehydrogenase) are often also elevated.

Tsutsugamushi disease (ie, scrub typhus)

Serologic testing using specific methods (eg, immunofluorescence antibody test, indirect immunoperoxidase test, enzyme immunoassay) is superior to the Weil-Felix reaction.

However, these tests are cumbersome and only available in a few special laboratories.

Q fever

Laboratory findings in acute Q fever infection may include thrombocytopenia in approximately 25% of cases and elevated hepatic transaminases. In prolonged infections, autoantibodies (eg, anti-smooth muscle antibodies) may be found.[5]

In addition to clinical and epidemiologic features, serology (eg, microimmunofluorescence, complement fixation, enzyme immunoassay) remains the mainstay of diagnosis in acute and chronic illnesses.

As with other rickettsiae, attempts to isolate the organism are biohazardous and unnecessary.

PCR may be used; however, it remains less available and more expensive than serology.

Chronic Q fever endocarditis is diagnosed by demonstration of high antibody (IgG and IgA) titers against C burnetii in patients with signs of endocarditis whose blood cultures contain no organisms (ie, culture-negative endocarditis). These patients may have elevated erythrocyte sedimentation rate, anemia, thrombocytopenia, and hematuria.[30, 5]

Imaging Studies

Chest radiography may be required in patients with severe illness or pulmonary manifestations, especially in patients with RMSF and Q fever.

Other imaging studies may be necessary, depending on the severity of organ involvement and development of complications.


A Lumbar Puncture and other procedures may be needed to exclude other possible etiologies.

Histologic Findings

Evidence of vasculitis, angiitis, and perivascular mononuclear cell infiltration may be evident in involved organs.

Chronic Q fever infection of the skeletal system causes the formation of granulomatous lesions.



Medical Care

Specific therapy

Adequate antibiotic therapy initiated early in the first week of illness is highly effective and is associated with the best outcome. Fever usually subsides within 24-72 hours after starting antibiotic therapy. If fever fails to subside with the use of a suitable antibiotic, the diagnosis of rickettsial disease should be reconsidered. Treatment may be terminated 2-3 days after the patient is afebrile and at least 10 days of therapy has been given.[36]

Doxycycline is the drug of choice; it is preferred over other tetracyclines for treatment of rickettsial infections and, at such low dose and short duration, is rarely associated with staining of teeth in children younger than 8 years.[37, 10, 16]

Chloramphenicol may be used as an alternative. However, it is rarely used in the United States because of its potential bone marrow toxicity.

Recent data from Europe suggest that fluoroquinolones, such as ciprofloxacin and ofloxacin, may be effective in the treatment of certain rickettsioses.[25, 5] However quinolones, which are not FDA approved for use in children younger than 18 years, have been associated with clinical failures despite good in vitro activity.

Sulfonamides were found to have a harmful effect either by delaying the institution of proper antimicrobial therapy or by directly stimulating growth of the organisms. They are contraindicated in rickettsial infections.[4, 36]

Supportive therapy

Thrombocytopenia, hypoalbuminemia, hypotension, and coagulation defects require supportive management. Hyponatremia is best managed with maintenance fluids or even modest fluid restriction. Whether or not steroids are helpful in shortening the febrile period in Rocky Mountain spotted fever (RMSF) is controversial.[1, 38]

  • RMSF: Antibiotic treatment may be terminated 2-3 days after the patient is afebrile and at least 10 days of therapy has been given. Longer courses may be required in complicated illness.[36]

  • Rickettsialpox: Antibiotics are the mainstay of treatment. However, in infants and young children with mild illness, antibiotics may be withheld because the infection is self-limited.

  • Boutonneuse fever: Doxycycline remains the drug of first choice; however, the newer macrolide may be of interest.[10] Improvement usually occurs within 48 hours of therapy. Duration of therapy has not been definitively established; however, recommendations state that antibiotic treatment should continue for 24 hours after fever has abated.

  • Louse-borne (epidemic) typhus: Treatment is analogous to that of RMSF. The use of insecticides and pediculicides (eg, lindane, crotamiton, malathion) can be highly effective in reducing louse infestation and may serve as important adjuncts to specific therapy in curtailing louse-borne typhus epidemics.

  • Brill-Zinsser disease (ie, relapsing louse-borne typhus): Treatment is analogous to that of RMSF.

  • Murine (endemic or flea-borne) typhus: A single dose of doxycycline is the treatment of choice for this disease. Other tetracyclines and chloramphenicol are also effective agents. The control of rat fleas with insecticides followed by control of rat populations with rodenticides is an important adjunct measure to combat the spread of this disease.

  • Tsutsugamushi disease (ie, scrub typhus): Antibiotic treatment with tetracyclines or chloramphenicol, similar to that of the spotted fever group, is recommended. However, sporadic short antibiotic courses of doxycycline or chloramphenicol may be required to prevent relapses.[37]

  • Q fever

    • Acute disease responds to tetracyclines or chloramphenicol. Fluoroquinolones and the newer macrolides (eg, azithromycin) have also been used successfully for treatment of acute infection. Generally, relapses are rare.[5]

    • Chronic Q fever infections, on the other hand, require prolonged courses of antimicrobial therapy. In cases of endocarditis caused by chronic Q fever, combination therapy with hydroxychloroquine and doxycycline is the preferred treatment. Duration of therapy is 18-36 months depending on the serologic response. Several alternative combination regimens (eg, a fluoroquinolone with doxycycline or rifampin with doxycycline) have been proposed but not adequately studied yet.[31, 5]


Infectious disease subspecialists play a vital role in diagnosis confirmation, management, and exclusion of other illnesses on the differential.

Other subspecialists may be consulted, depending on the course of the illness (eg, cardiologist, pulmonologist, nephrologist, intensivist).


No dietary restriction is required in uncomplicated rickettsial infections.



Guidelines Summary

In 2016, the Centers for Disease Control and Prevention updated their recommendations on the diagnosis and management of tickborne rickettsial diseases in the United States.

Recommendations include the following[39] :

Summary of epidemiologic clues from the clinical history

  • The absence of known tick attachment should never dissuade a health care provider from considering the diagnosis of tickborne rickettsial disease.
  • Clustering of certain tickborne rickettsial diseases is well recognized and has been reported among family members, pet dogs, coworkers, military personnel, and other groups.
  • Dogs and humans are susceptible to infection with many of the same tickborne rickettsial pathogens, including Rickettsia rickettsii, Ehrlichia chaffeensis, Ehrlichia ewingii, and Anaplasma phagocytophilum; in some instances, pet dogs might serve as sentinels for tickborne rickettsial disease in humans.

Summary of clinical features of Rocky Mountain spotted fever and other spotted fever group rickettsioses

  • Rocky Mountain Spotted Fever (RMSF) is the most severe rickettsial illness in the United States. Delay in recognition and treatment is the most important factor associated with risk of death from RMSF.
  • The classic triad of fever, rash, and reported tick bite is rarely present when patients with RMSF first seek care.
  • Rash is present in most patients during the course of RMSF, although it can appear late or be atypical, localized, faint, evanescent, and difficult to recognize in persons with darker pigmented skin.
  • Rickettsia parkeri rickettsiosis is typically milder than RMSF, and the first manifestation in nearly all patients is an inoculation eschar.

Summary of clinical features of ehrlichioses

  • Symptoms of Ehrlichia chaffeensis ehrlichiosis typically include fever, headache, malaise, myalgia, and gastrointestinal symptoms. With E chaffeensis ehrlichiosis, rash is present in approximately one third of patients but is more common among children than among adults.
  • Neurologic manifestations are reported for approximately 20% of patients with E chaffeensis ehrlichiosis.
  • Increased severity of E chaffeensis ehrlichiosis has been associated with increased age (≥60 yr) and immunosuppression.
  • Leukopenia, thrombocytopenia, and elevated hepatic transaminase levels are characteristic laboratory findings in the first week of E chaffeensis ehrlichiosis.
  • E chaffeensis has a predilection for mononuclear phagocytic cells, and morulae might be observed in monocytes of the blood, CSF, or bone marrow phagocytes.
  • Ehrlichia ewingii ehrlichiosis has similar clinical features as E chaffeensis ehrlichiosis; however, rash and gastrointestinal symptoms are less common. E ewingii has a predilection for granulocytes, and morulae might be observed in granulocytes of the blood, CSF, or bone marrow.
  • The case-fatality rate for E chaffeensis ehrlichiosis is approximately 3%; no deaths from E ewingii or E muris-like (EML) agent ehrlichiosis have been reported.

Summary of clinical features of anaplasmosis

  • Anaplasma phagocytophilum has a predilection for granulocytes, and blood smear or bone marrow examination might reveal morulae within these cells.
  • The tick vector that transmits A phagocytophilum also transmits other pathogens, and coinfections with Borrelia burgdorferi or Babesia microti have been described.

Recommended treatment for tickborne rickettsial diseases

  • Doxycycline is the drug of choice for treatment of all tickborne rickettsial diseases in children and adults; empiric therapy should be initiated promptly in patients with a clinical presentation suggestive of a rickettsial disease.
  • Tickborne rickettsial diseases respond rapidly to doxycycline, and fever persisting for >48 hr after initiation of therapy should prompt consideration of an alternative or additional diagnosis, including the possibility of coinfection.
  • Doxycycline is recommended by the American Academy of Pediatrics and CDC as the treatment of choice for patients of all ages, including children aged < 8 yr, with a suspected tickborne rickettsial disease.
  • Delay in treatment of tickborne rickettsial diseases can lead to severe disease and death.
  • In persons with severe doxycycline allergy or who are pregnant, chloramphenicol may be an alternative treatment for RMSF; however, persons treated with chloramphenicol have a greater risk of death compared with those treated with doxycycline.
  • Chloramphenicol is not an acceptable alternative for the treatment of ehrlichiosis or anaplasmosis.
  • For mild cases of anaplasmosis, rifampin might be an alternative to doxycycline for patients with a severe drug allergy or who are pregnant.
  • Data on the risks of doxycycline use during pregnancy suggest that treatment at the recommended dose and duration for tickborne rickettsial diseases is unlikely to pose a substantial teratogenic risk; however, data are insufficient to state that no risk exists.
  • Prophylactic use of doxycycline after a tick bite is not recommended for the prevention of tickborne rickettsial diseases.
  • Treatment of asymptomatic persons seropositive for tickborne rickettsial disease is not recommended, regardless of past treatment status, because antibodies can persist for months to years after infection.

Summary of confirmatory diagnostic tests

  • Antibacterial treatment should never be delayed while awaiting laboratory confirmation of rickettsial illness, nor should treatment be discontinued solely on the basis of a negative test result with an acute phase specimen.
  • The reference standard for diagnosis of tickborne rickettsial diseases is the indirect immunofluorescence antibody (IFA) assay using paired serum samples obtained soon after illness onset and 2-4 wk later. Demonstration of at least a 4-fold rise in antibody titer is considered confirmatory evidence of acute infection.
  • Patients usually do not have diagnostic serum antibody titers during the first week of illness, and a negative result by IFA assay or enzyme-linked immunosorbent assay (ELISA) during this period does not exclude the diagnosis of tickborne rickettsial diseases.
  • For ehrlichioses and anaplasmosis, diagnosis during the acute stage can be made using polymerase chain reaction (PCR) amplification of DNA extracted from whole blood.
  • PCR assay of whole blood is less sensitive for diagnosis of RMSF than it is for ehrlichiosis or anaplasmosis; however, sensitivity increases in patients with severe disease.
  • For spotted fever group (SFG) rickettsioses, immunostaining of skin rash or eschar biopsy specimens or a PCR assay using DNA extracted from these specimens can help provide a pathogen-specific diagnosis.
  • Immunostaining of autopsy specimens can be particularly useful for diagnosing fatal tickborne rickettsial infections.
  • Blood-smear or buffy-coat preparation microscopy might reveal the presence of morulae in infected leukocytes, which is highly suggestive of anaplasmosis or ehrlichiosis. Blood-smear microscopy is not useful for RMSF, other SFG rickettsioses, or EML agent ehrlichiosis.
  • Rickettsiae cannot be isolated with standard blood culture techniques because they are obligate intracellular pathogens; specialized cell culture methods are required. Because of limitations in availability and facilities, culture is not often used as a routine confirmatory diagnostic method for tickborne rickettsial diseases.

Summary of prevention of tickborne rickettsial diseases

  • Use tick repellents containing DEET, IR3535, picaridin (1-piperidinecaboxylic acid, 2-[2-hydroxyethyl], 1-methlypropyl ester), or other EPA-registered products when outdoors. Follow package label instructions for application.
  • Wear protective clothing, including long-sleeved shirts, pants, socks, and closed-toe shoes.
  • Permethrin-treated or impregnated clothing can significantly reduce the number of tick bites when working outdoors.
  • Protect pets from tick bites by regularly applying veterinarian-approved ectoparasite control products, such as monthly topical acaricide products, acaricidal tick collars, oral acaricidal products, and acaricidal shampoos.


Medication Summary

Adequate antibiotic therapy initiated early is highly effective and associated with the best outcomes.


Class Summary

Empiric antimicrobial therapy must be comprehensive and should cover all likely pathogens in the context of the clinical setting.

Doxycycline (Bio-Tab, Doryx, Vibramycin)

DOC. Inhibits protein synthesis and, thus, bacterial growth by binding to 30S and, possibly, 50S ribosomal subunits of susceptible bacteria.

Chloramphenicol (Chloromycetin)

Binds to 50S bacterial-ribosomal subunits and inhibits bacterial growth by inhibiting protein synthesis. Effective against gram-negative and gram-positive bacteria. It may not be as effective against rickettsia as doxycycline.

If administered on an outpatient basis, 30% of patients subsequently require hospitalization, compared with 11% of patients treated with tetracyclines.



Further Inpatient Care

Patients with rickettsial infection may require hospitalization only if they are clinically unstable or have developed complications.


Rickettsial infections with severe complications may require transfer to tertiary care facilities.


Personal avoidance of ticks (wearing proper clothing and use of repellants) remains an integral part of protection against rickettsial infections. In case of bites, prompt removal of ticks might prove extremely beneficial in prevention of infection. Attempting to control the tick reservoir is not usually feasible. Use of antibiotics following tick exposure is not currently indicated to prevent rickettsial infection.

  • Rocky Mountain spotted fever (RMSF): Various vaccines have been developed; however, they have not yet been proven efficacious or safe to recommend for routine use in patients. An improved killed chicken embryo vaccine has shown that it may provide partial protection against RMSF and ameliorate the illness when it occurs.[40]

  • Rickettsialpox: Avoidance of contact with and control of house mouse infestations is important to prevent acquisition of infection.

  • Boutonneuse fever: Natural immunity occurs following infection. Effective vaccines are not yet available.

  • Typhus group (epidemic and endemic typhus): Delousing of individuals and use of insecticides to treat clothing are effective preventive measures against the spread of louse-borne typhus. Killed vaccines that are no longer available in the United States were shown to reduce mortality rates but were not effective in prevention of disease.

  • Brill-Zinsser disease (ie, relapsing louse-borne typhus): This is analogous to primary louse-borne epidemic typhus.

  • Murine (endemic or flea-borne) typhus: Prevention is primarily by controlling the flea and rat populations. Insecticides should be used before rodenticides to prevent rat fleas from seeking alternate hosts if rats are no longer available. As with louse-borne typhus, a vaccine is no longer available in the United States.

  • Tsutsugamushi disease (ie, scrub typhus): Prevention can be achieved by vector control or chemoprophylaxis. The agent of choice for chemoprophylaxis is doxycycline, given as a weekly dose started before exposure to infection and continued for 6 weeks postexposure.

  • Q fever: A whole-cell vaccine for Q fever has been developed in Australia for clinical use in the occupational setting.[5] Control of disease in domestic animal population has been difficult because animals that have no detectable antibodies to C burnetii still shed the organism at parturition. Q fever outbreaks in research laboratories using animals (especially sheep) can be prevented by instituting proper control measures designed to protect the environment from fomite and aerosol transmission.