Where is rickettsia rickettsii found in the body

Types of ticks Open pop-up dialog box Close. Types of ticks Rocky Mountain spotted fever is caused by the organism Rickettsia rickettsii.

Share on: Facebook Twitter. Show references Bennett JE, et al. Rickettsia rickettsii and other spotted fever group Rickettsiae Rocky Mountain spotted fever and other spotted fevers. Philadelphia, Pa. Accessed June 8, Ferri FF. Rocky Mountain spotted fever.

In: Ferri's Clinical Advisor Sexton DJ. Clinical manifestations and diagnosis of Rocky Mountain spotted fever. Kliegman RM, et al. Spotted Fever Group Rickettsioses. In: Nelson Textbook of Pediatrics. Preventing ticks in the yard. Preventing tick bites. Centers for Disease Control and Prevention. How to remove a tick. Steckelberg, JM expert opinion.

Mayo Clinic, Rochester, Minn. June 12, Related Rash caused by Rocky Mountain spotted fever Types of ticks. Q fever Q Fever Q fever is related to rickettsial diseases and is caused by Coxiella burnetii, which live mainly in sheep, cattle, and goats.

Some people have mild symptoms, but most have flu-like symptoms These bacteria differ from most other bacteria in that they can live and multiply only inside the cells of another organism host and cannot survive on their own in the environment. Many species of these bacteria live in small animals such as rats and mice , which are called the host. Cattle, sheep, or goats are the hosts for Coxiella burnetii , which causes Q fever.

Humans are the usual host for Rickettsia prowazekii , which causes epidemic typhus. Host animals may or may not be ill from the infection. Rickettsiae and rickettsia-like bacteria are usually spread to people through the bites of ticks, mites, fleas, or lice that previously fed on an infected animal.

Ticks, mites, fleas, and lice are called vectors because they spread transmit organisms that cause disease from one host to another.

Q fever, caused by Coxiella burnetii , can be spread through the air or in contaminated food and water and do not require a vector. Some of these bacteria and the diseases they cause occur worldwide. Others occur only in certain geographic regions. Some of these bacteria infect the cells lining small blood vessels, causing the blood vessels to become inflamed or blocked or to bleed into the surrounding tissue.

Other bacteria Ehrlichia and Anaplasma enter white blood cells White blood cells The immune system is designed to defend the body against foreign or dangerous invaders. Such invaders include Microorganisms commonly called germs, such as bacteria, viruses, and fungi Parasites A sore covered by a black scab eschar may form at the site of the bite.

Because the rash often does not appear for several days, early rickettsial infection is often mistaken for a common viral infection, such as influenza. People may have swollen lymph nodes. As the infection progresses, people typically experience confusion and severe weakness—often with cough, difficulty breathing, and sometimes vomiting. When the infection is advanced, gangrene may develop, the liver or spleen may enlarge, the kidneys may malfunction, and blood pressure may fall dangerously low causing shock Shock Shock is a life-threatening condition in which blood flow to the organs is low, decreasing delivery of oxygen and thus causing organ damage and sometimes death.

Blood pressure is usually low Death can result. Because rickettsiae and rickettsia-like bacteria are transmitted by ticks, mites, fleas, and lice, doctors ask people. Being bitten is a helpful clue—particularly in geographic areas where rickettsial or a related infection is common. However, many people do not recall such a bite. If doctors suspect Q fever, they may also ask whether people were at or near a farm because cattle, sheep, and goats are the host for the bacteria that cause this infection.

A physical examination is done to determine which parts of the body are affected and what the rash looks like. Doctors also look for an eschar that people may not have noticed and for swollen lymph nodes. Testing is usually needed to confirm the diagnosis. During —, the average annual incidence of ehrlichiosis was 3. Cases have been reported from an increasing number of counties 5 Figure Incidence generally increases with age, with the highest age-specific incidences occurring among persons aged 60—69 years 5 , 13 , In areas where ehrlichiosis is endemic, the actual disease incidence is likely underrepresented in estimates that are based on passive surveillance 51 — The lone star tick is among the most commonly encountered ticks in the southeastern United States, with a range that extends into areas of the Midwest and New England states Figure Ehrlichiosis cases have been reported throughout the range of the lone star tick; states with the highest reported incidence rates include Arkansas, Delaware, Missouri, Oklahoma, Tennessee, and Virginia 5.

The white-tailed deer is a major host of all stages of lone star ticks and is thought to be an important natural reservoir for E. Consequently, the lone star tick is found most commonly in woodland habitats that have white-tailed deer populations.

The lone star tick feeds on a wide range of hosts, including humans, and has been implicated as the most common tick to bite humans in the southern United States 55 , Although all stages of this tick feed on humans, only adult and nymphal ticks are known to be responsible for transmission of E.

Most cases of E. During —, cases were primarily reported from Missouri; however, cases also were reported from 10 other states within the distribution of the principal vector, the lone star tick, A. Although E. No fatal cases of E. The ecologic features of E. In , a new species of Ehrlichia referred to as the EML agent was described as a human pathogen after detection in the blood from four patients three from Wisconsin and one from Minnesota by using molecular testing techniques Passive surveillance from — indicates that the average annual incidence of anaplasmosis was 6.

Incidence is highest in the northeastern and upper Midwestern states, and the geographic range of anaplasmosis appears to be expanding 3 , 66 Figure In Wisconsin, anaplasmosis has been identified as an important cause of nonspecific febrile illness during the tick season The reported case-fatality rate during — was 0. The bites of nymphal and adult ticks can transmit A. The relative roles of particular animal species as reservoirs of A.

Most anaplasmosis cases occur during June—November. The seasonality of anaplasmosis is bimodal, with the first peak during June—July and a smaller peak during October, which corresponds to the emergence of the adult stage of I.

The blacklegged tick also transmits nonrickettsial pathogens in certain geographic areas, including Borrelia burgdorferi the cause of Lyme disease , Babesia microti the primary cause of human babesiosis in the United States , Borrelia miyamotoi , a cause of tickborne relapsing fever , and deer tick virus Powassan virus, lineage II; a cause of tickborne encephalitis.

The preponderance of cases of human anaplasmosis occur in the same states that report high incidences of Lyme disease and human babesiosis. Simultaneous infections with A. Obtaining a thorough clinical history that includes questions about recent 1 tick exposure, 2 recreational or occupational exposure to tick-infested habitats, 3 travel to areas where tickborne rickettsial diseases are endemic, and 4 occurrence of similar illness in family members, coworkers, or pet dogs can provide critical information to make a presumptive diagnosis of tickborne rickettsial disease.

However, the absence of one or more of these factors does not exclude a diagnosis of tickborne rickettsial disease. Health care providers should be familiar with the epidemiologic clues that support the diagnosis of tickborne rickettsial disease but recognize that classic epidemiologic features are not reported in many instances Box 2.

A detailed history should be taken to elicit information about known tick bites or activities that might be associated with exposure to ticks. Although the recognition of a tick bite is helpful, unrecognized tick bites are common in patients who are later confirmed to have a tickborne rickettsial disease.

Therefore, absence of a recognized tick bite should never dissuade health care providers from considering tickborne rickettsial disease in the appropriate clinical context.

In fact, the absence of classic features, such as a reported tick bite, has been associated with delays in RMSF diagnosis and increased risk for death 9 , 18 , 74 , The location of the tick bite might be obscure, and the bite is typically painless. Bites from immature stages of ticks e. Some patients who do not report tick exposure might describe other pruritic, erythematous, or ulcerated cutaneous lesions that they refer to as mosquito, spider, chigger, or bug bites, all of which might be indistinguishable from a recent tick bite.

A thorough recreational and occupational history can help reveal potential exposures to tick habitats. In areas endemic for ticks, activities as commonplace as playing in a backyard, visiting a neighborhood park, gardening, or walking dogs are potential sources of tick exposure. Many types of environments serve as tick habitats, depending on the specific tick vector species.

Areas with high uncut grass, weeds, and low brush might pose a high risk for certain vector species; however, these tick species also seek hosts in well-maintained grass lawns around suburban homes Moreover, certain species can withstand drier conditions and might be found in vegetation-free areas or forest floors covered with only leaf litter or pine needles. Additional areas that might be inhabited by ticks include vegetation bordering roads, trails, yards, or fields; urban and suburban recreational parks; golf courses; and debris piles or refuse around homes 24 , 77 — Activities that commonly result in contact with potential tick habitats include recreational pursuits e.

Although peak tick season is an important consideration, health care providers should remain aware that tickborne rickettsial illnesses have been reported in every month of the year, including winter 3 — 5 , 25 , Climate differences and seasonal weather patterns can influence the duration and peak of tick season in a given geographic region and a given year.

Queries about contact with pets, especially dogs, and a history of tick attachment or recent tick removal from pets might be useful in assessing potential human tick exposure. Pet dogs with attached ticks can serve as useful indicators of peridomestic tick infestation 17 , 82 , Tick-infested dogs can transfer ticks directly to humans during interactions and serve as transport hosts, carrying ticks in and around dwellings where the ticks can then transfer to the human occupants 84 see Similar Illness in Household Members, Coworkers, or Pets.

Health care providers practicing in areas where the incidence of tickborne rickettsial disease is historically low might be less likely to distinguish these diseases from other clinically similar and more commonly encountered infectious and noninfectious syndromes.

Tickborne rickettsial diseases typically are sporadic, and identifying these infections requires a high index of clinical suspicion, especially in environments in which the infections have not been recognized previously as occurring frequently. Knowledge of the epidemiology of tickborne rickettsial diseases, including the regions of the United States with a high incidence, is important. The distribution of tickborne rickettsial diseases is influenced by the geographic range of the tick vector, which can change over time.

Distribution maps of tick vectors and disease incidence can serve as guides; however, the distribution borders are not fixed in space or over time, and the ranges for many tick species might be expanding. Travel history within and outside of the United States can provide an important clue in considering the diagnosis of a tickborne rickettsial disease. Travel from an area where tickborne rickettsial diseases are endemic within 2 weeks of the onset of a clinically compatible illness could support a presumptive diagnosis of tickborne illness, especially if travel activities that might result in tick exposure are reported.

Tickborne rickettsial diseases occur worldwide, and the imported diseases might have epidemiologic, seasonal, and clinical features that differ from those in the United States. Selected additional tickborne rickettsial diseases that might be considered in returning international travelers are presented see Travel Outside of the United States and Appendix A.

Clustering of certain tickborne rickettsial diseases is a well-recognized epidemiologic occurrence, particularly after common exposures to natural foci of infected ticks. Temporally and geographically related clusters of illness have occurred among family members including their pet dogs , coworkers, or persons frequenting a particular common area.

Described clusters include ehrlichiosis among residents of a golfing community 80 , ehrlichiosis and RMSF among soldiers on field maneuvers 85 , 86 , and RMSF among family members 87 — Infections with R. Health care providers should ask ill patients about similar illnesses among family members, coworkers, community residents, and pet dogs. Dogs are frequently exposed to ticks and are susceptible to infections with many of the same tickborne rickettsial pathogens as humans, including R.

Evidence of current or past rickettsial infection in dogs might be useful in determining the presence of human risk for tickborne rickettsial diseases in a given geographic area Tickborne rickettsial infection in dogs can range from inapparent to severe. RMSF in dogs manifests with fever, lethargy, decreased appetite, tremors, scleral injection, maculopapular rash on ears and exposed skin, and petechial lesions on mucous membranes 91 — A veterinarian should be consulted when tickborne rickettsial disease is suspected in dogs or other animals see Protecting Pets from Tick Bites.

Documentation of a tickborne rickettsial disease in a dog should prompt veterinary professionals to warn pet owners about the risk for acquiring human tickborne disease. Cases of RMSF in dogs preceding illness in their owners 83 illustrate the value of communication between veterinarians and human health care providers when zoonotic diseases are suspected and emphasize the importance of a One Health approach to address zoonotic diseases.

Tickborne rickettsial diseases commonly have nonspecific clinical signs and symptoms early in the course of disease. Although the clinical presentations of tickborne rickettsial disease overlap, the frequency of certain associated signs and symptoms e. Familiarity with the clinical signs and symptoms and pathophysiology of tickborne rickettsial diseases, including RMSF and other SFG rickettsioses Box 3 , ehrlichioses Box 4 , and anaplasmosis Box 5 will assist health care providers in developing a differential diagnosis, prescribing appropriate antibacterial treatment, and ordering appropriate confirmatory diagnostic tests.

Infection with R. If disease progresses untreated, it can result in end-organ damage associated with severe morbidity and death. Pathogen-mediated injury to the vascular endothelium results in increased capillary permeability, microhemorrhage, and platelet consumption Late-stage manifestations, such as noncardiogenic pulmonary edema acute respiratory distress syndrome [ARDS] and cerebral edema, are consequences of microvascular leakage.

Hyponatremia occurs as a result of appropriate secretion of antidiuretic hormone in response to hypovolemia Symptoms of RMSF typically appear 3—12 days after the bite of an infected tick or between the fourth and eighth day after discovery of an attached tick The incubation period is generally shorter 5 days or less in patients who develop severe disease Initial symptoms include sudden onset of fever, headache, chills, malaise, and myalgia.

Other early symptoms might include nausea or vomiting, abdominal pain, anorexia, and photophobia. A rash typically appears 2—4 days after the onset of fever; however, most patients initially seek health care before appearance of a rash 25 , 74 , The classic triad of fever, rash, and reported tick bite is present in only a minority of patients during initial presentation to health care 6 , 25 ; therefore, health care providers should not wait for development of this triad before considering a diagnosis of RMSF.

The RMSF rash classically begins as small 1—5 mm in diameter , blanching, pink macules on the ankles, wrists, or forearms that subsequently spread to the palms, soles, arms, legs, and trunk, usually sparing the face. Over the next several days of illness, the rash typically becomes maculopapular, sometimes with central petechiae Figures 21 and The classic spotted or generalized petechial rash, including involvement of the palms and soles, usually appears by day 5 or 6 and is indicative of advanced disease.

The rash might be atypical, localized, faint, or evanescent In some persons, skin pigmentation might make the rash difficult to recognize. The rash might resemble those of other infectious and noninfectious etiologies see Differential Diagnosis of Fever and Rash.

Lack of rash or late-onset rash in RMSF has been associated with delays in diagnosis and increased mortality 6 , 18 , Other clinical features that have been observed in association with RMSF include abdominal pain that mimics acute appendicitis , cholecystitis , or gastroenteritis; diarrhea; conjunctival suffusion; periorbital and peripheral edema more common in children ; calf pain; acute transient hearing loss; hepatomegaly; and splenomegaly 6 , Features of late illness might be confused with other diseases or syndromes.

For example, RMSF-associated cutaneous necrosis and gangrene might be difficult to distinguish clinically from purpura fulminans associated with meningococcemia RMSF-associated neurologic manifestations, renal failure, and thrombocytopenia have led to confusion with the diagnosis of thrombotic thrombocytopenic purpura TTP — RMSF-associated vasculitis has been confused with idiopathic, acute vasculitides, such as Kawasaki disease in pediatric patients.

RMSF might also mimic bacterial or viral meningoencephalitis Focal neurologic deficits, including cranial or peripheral motor nerve paralysis, or sudden transient hearing loss can occur — Clinical suspicion for RMSF should be maintained in cases of nonspecific febrile illness and sepsis of unclear etiology, particularly during spring and summer months.

Delay in diagnosis and treatment is the most important factor associated with increased likelihood of death, and early empiric therapy is the best way to prevent RMSF progression. Without treatment, RMSF progresses rapidly. Patients treated after the fifth day of illness are more likely to die than those treated earlier in the course of illness 9 , 18 , 74 , The frequency of hospital admission, intensive care unit admission, and death increases with time from symptom onset to initiation of appropriate antibacterial treatment 18 Table 2.

Delays in diagnosis and initiation of antirickettsial therapy have been associated with seeking health care early in the course of the illness 7 , 74 , late-onset or absence of rash 6 , 18 , and nonspecific or atypical early manifestations, such as gastrointestinal symptoms 18 , 98 or absence of headache Epidemiologic factors associated with increased risk for death include disease that occurs early or late in the typical tick season 74 and the lack of a report of a tick bite 9 , 75 , Although knowledge of the epidemiology might help guide diagnosis, the absence of epidemiologic clues can be misleading.

Experimental and accumulated anecdotal clinical data suggest that treatment of patients with RMSF using a sulfonamide antimicrobial can result in increased disease severity and death , Long-term neurologic sequelae of RMSF include cognitive impairment; paraparesis; hearing loss; blindness; peripheral neuropathy; bowel and bladder incontinence; cerebellar, vestibular, and motor dysfunction; and speech disorders 7 , , — These complications are observed most frequently in persons recovering from severe, life-threatening disease, often after lengthy hospitalizations, and are most likely the result of R.

Cutaneous necrosis and gangrene Figure 23 might result in amputation of digits or limbs Long-term or persistent disease caused by R. The total white blood cell count is typically normal or slightly increased in patients with RMSF, and increased numbers of immature neutrophils often are observed.

Thrombocytopenia, slight elevations in hepatic transaminases aspartate transaminase and alanine transaminase , and hyponatremia might be present, particularly as the disease advances 25 , 77 ; however, laboratory values cannot be relied on to guide early treatment decisions because they are often within or slightly deviated from the reference range early in the course of illness Indicators of diffuse tissue injury, such as elevated levels of creatine kinase or serum lactate dehydrogenase, might be present later in the course of illness.

Disseminated intravascular coagulation DIC is rare. Symptoms develop a median of 5 days range: 2—10 days after the bite of an infected tick The first manifestation in nearly all patients is an inoculation eschar a dark, scabbed plaque overlying a shallow ulcer, typically 0. The presence of more than one eschar has been described Fever typically develops within a few days of the eschar. Shortly after the onset of fever approximately 0.

Gastrointestinal manifestations, such as nausea or vomiting, are rare 38 , Hospitalization from R. Because the clinical description of R. The first clinical description of a confirmed case of Rickettsia species D infection was published in Although the full spectrum of illness has yet to be described, D infection appears to be characterized by an eschar Figure 26 or ulcerative skin lesion with regional lymphadenopathy 43 , Fever, headache, myalgia, and fatigue have occurred among persons with confirmed infection.

Rash has not been a notable feature of this illness. Illnesses among the few described patients have been relatively mild and have readily responded to appropriate antimicrobial therapy. Ehrlichiae are obligate intracellular bacteria that infect peripheral blood leukocytes. The organisms multiply in cytoplasmic membrane-bound vacuoles, forming tightly packed clusters of bacteria called morulae. In patients with fatal E.

Unlike in RMSF, direct vasculitis and endothelial injury are rare in ehrlichiosis. The host systemic inflammatory response, rather than direct effects of the pathogen, is likely to be largely responsible for many of the clinical manifestations of ehrlichiosis Symptoms of E.

Abdominal pain, vomiting, and diarrhea might be more common among children Approximately one-third of patients develop a skin rash during the course of illness; rash occurs more frequently in children than in adults. Rash patterns vary in character from petechial or maculopapular , to diffuse erythema and typically occur a median of 5 days after illness onset The rash typically involves the extremities and trunk but can affect the palms, soles, or face Other severe manifestations include ARDS, toxic shock-like or septic shock-like syndromes, renal failure, hepatic failure, coagulopathies, and occasionally, hemorrhagic manifestations Severe cases have been mistaken for TTP , appendicitis , or fulminant viral hepatitis Heartland virus disease, a recently identified tickborne viral infection transmitted by the lone star tick, can closely resemble ehrlichiosis The severity of ehrlichiosis could be related, in part, to host factors such as age and the immune status of the patient.

Persons who have compromised immune systems as a result of immunosuppressive therapies, human immunodeficiency virus HIV infection , , organ transplantation , , or splenectomy more frequently have severe symptoms of ehrlichiosis and are hospitalized more often Case-fatality rates among persons who are immunosuppressed are higher than those among the general population, on the basis of U.

Receiving a sulfonamide antimicrobial agent might also predispose to severe ehrlichial illness — Confirmed reinfection with E. Characteristic laboratory findings in the first week of E. Mild-to-moderate hyponatremia might also be present During the recovery period, a relative and absolute lymphocytosis is seen in most patients In some cases, pancytopenia due to ehrlichiosis has prompted bone marrow aspirate and biopsy, which typically reveals normocellular or hypercellular marrow , In some patients, morulae might be observed in monocytes in peripheral blood Figure 28 and occasionally in CSF , or bone marrow.

In this context, a routine blood smear can provide a presumptive clue for early diagnosis; however, the visualization of morulae still requires confirmatory diagnostic testing see Confirmatory Diagnostic Tests. When CSF is evaluated, a lymphocytic pleocytosis is most commonly observed, although neutrophilic pleocytosis also can occur , Elevated CSF protein levels are common Clinical manifestations of E.

Gastrointestinal symptoms have been described less commonly in E. Fewer severe manifestations have been reported with E. Similar to E. Symptomatic EML agent ehrlichiosis might be more common among persons who are immunosuppressed. No fatal cases have been reported to date. Morulae have not been observed yet in peripheral blood cells of patients infected with the EML agent. Similar to ehrlichiae, anaplasmae multiply in cytoplasmic membrane-bound vacuoles as microcolonies called morulae.

Infection with A. Altered host neutrophil function occurs with A. Patients with anaplasmosis typically seek medical care later in the course of illness 4—8 days after onset than patients with other tickborne rickettsial diseases 2—4 days after onset 8 , In most cases, anaplasmosis is a self-limiting illness.

Severe anaplasmosis can also resemble toxic shock syndrome, TTP , or hemophagocytic syndromes Serious and fatal opportunistic viral and fungal infections during the course of anaplasmosis infection have been described , Predictors of a more severe course of anaplasmosis include advanced patient age, immunosuppression, comorbid medical conditions such as diabetes, and delay in diagnosis and treatment 13 , Characteristic laboratory findings in anaplasmosis include thrombocytopenia, leukopenia, elevated hepatic transaminase levels, increased numbers of immature neutrophils, and mild anemia Similar to ehrlichiosis, lymphocytosis can be present during the recovery period CSF evaluation typically does not reveal any abnormalities Blood smear examination might reveal morulae within granulocytes Figure 28 see Confirmatory Diagnostic Tests.

Bone marrow is usually normocellular or hypercellular in acute anaplasmosis, and morulae might be observed , , The tick vector responsible for A. Response to treatment can provide clues to possible coinfection. For example, anaplasmosis should respond readily to treatment with doxycycline. If the clinical response is delayed, coinfection or an alternative infection might be considered in the appropriate epidemiologic setting — Conversely, if Lyme disease is treated with a beta-lactam antibacterial drug in a patient with unrecognized A.

Leukopenia or thrombocytopenia in a patient with Lyme disease should raise clinical suspicion for possible coinfection with A. The differential diagnosis of fever and rash is broad , Box 6 , and during the early stages of illness, tickborne rickettsial diseases can be clinically indistinguishable from many viral exanthemas and other illnesses, particularly in children. Tickborne rickettsial diseases can be mistaken for viral gastroenteritis, upper respiratory tract infection, pneumonia, urinary tract infection, nonrickettsial bacterial sepsis, TTP, idiopathic vasculitides, or viral or bacterial meningoencephalitides , Despite nonspecific initial symptoms of tickborne rickettsial diseases e.

The dermatologic classification of the rash, its distribution, pattern of progression, and timing relative to onset of fever, and other systemic signs provide clues to help guide the differential diagnosis. A complete blood count, peripheral blood smear, and routine chemistry and hepatic function panels also can be helpful in guiding the differential diagnosis. Epidemiologic clues e. Other life-threatening illnesses that can have signs and symptoms that are similar to those of tickborne rickettsial diseases, such as meningococcemia, are important to recognize, consider in the initial differential diagnosis, and treat empirically pending further diagnostic evaluation.

Diagnostic tests for rickettsial diseases, particularly for RMSF, are usually not helpful in making a timely diagnosis during the initial stages of illness. Treatment decisions for rickettsial pathogens should never be delayed while awaiting laboratory confirmation. Delay in treatment can lead to severe disease and long-term sequelae or death 74 , , A thorough clinical history, physical examination, and laboratory results e.

Because of the nonspecific signs and symptoms of tickborne rickettsial diseases, early empiric treatment for rickettsial diseases often needs to be administered concomitantly with empiric treatment for other conditions in the differential diagnosis. For example, for a patient in whom meningococcal disease and tickborne rickettsial disease are being considered, administering antibacterial therapy to treat potential Neisseria meningitidis infection in addition to administering doxycycline to treat rickettsial agents is appropriate while awaiting additional diagnostic information.

The recommended dose of doxycycline for the treatment of tickborne rickettsial diseases is mg twice daily orally or intravenously for adults and 2. Oral therapy is appropriate for patients with early stage disease who can be treated as outpatients. Intravenous therapy might be indicated for more severely ill patients who require hospitalization, particularly in patients who are vomiting or obtunded. The recommended duration of therapy for RMSF and ehrlichiosis is at least 3 days after subsidence of fever and until evidence of clinical improvement is noted 8 , , , ; typically the minimum total course of treatment is 5—7 days.

Severe or complicated disease could require longer treatment courses. Patients with anaplasmosis should be treated with doxycycline for 10 days to provide appropriate length of therapy for possible coinfection with B.

Fever typically subsides within 24—48 hours after treatment when the patient receives doxycycline in the first 4—5 days of illness. Lack of a clinical response within 48 hours of early treatment with doxycycline could be an indication that the condition is not a tickborne rickettsial disease, and alternative diagnoses or coinfection should be considered.

Patients with evidence of organ dysfunction, severe thrombocytopenia, mental status changes, or the need for supportive therapy should be hospitalized. Certain patients with tickborne rickettsial disease can be treated on an outpatient basis with oral medication, particularly if a reliable caregiver is available in the home and the patient adheres to follow-up medical care.

A critical step is for clinicians to keep in close contact with patients who are treated as outpatients to ensure that they are responding to therapy as expected. Similarly, if a hour watch-and-wait approach is taken with a febrile patient who otherwise appears well and has no obvious history of tick bite or exposure, a normal physical examination, and laboratory findings within reference ranges, ensuring close patient follow-up is essential.

Patients should be monitored closely because of the potential for rapid decline in untreated patients with tickborne rickettsial diseases, especially among those with RMSF. Management of severely ill patients with tickborne rickettsial disease should include assessment of fluid and electrolyte balance. Vasopressors and careful fluid management might be needed when the illness is complicated by hypotension or renal failure.

Patients with RMSF can develop ARDS or pulmonary infiltrates related to microvascular leakage that might be erroneously attributed to cardiac failure or pneumonia Consultation with an intensive care or infectious disease specialist could be helpful in managing these complications. The American Academy of Pediatrics and CDC recommend doxycycline as the treatment of choice for children of all ages with suspected tickborne rickettsial disease 8 , These results support the findings of a study published in reporting no evidence of tooth staining among 31 children with asthma exacerbation who were treated with doxycycline The use of doxycycline to treat children with suspected tickborne rickettsial disease should no longer be a subject of controversy — These data suggest that inappropriate or delayed RMSF treatment decisions might be contributing to disproportionately high RMSF case-fatality rates among young children.

Tetracyclines, including doxycycline, are the only antibacterial agents recommended for treatment of all tickborne rickettsial diseases. Chloramphenicol is the only alternative drug that has been used to treat RMSF; however, epidemiologic studies using CDC case report data suggest that patients with RMSF treated with chloramphenicol are at higher risk for death than persons who received a tetracycline 9 , Chloramphenicol is no longer available in the oral form in the United States, and the intravenous form is not readily available at all institutions.

Chloramphenicol is associated with adverse hematologic effects, which have resulted in its limited use in the United States, and monitoring of blood indices is required if this drug is used , In vitro evidence indicates that chloramphenicol is not effective in the treatment of ehrlichiosis or anaplasmosis , Therefore, if chloramphenicol is substituted for doxycycline in the empiric treatment of tickborne rickettsial diseases, ehrlichiosis and anaplasmosis will not be covered and RMSF treatment might be suboptimal.

Rifamycins demonstrate in vitro activity against E. Case reports document favorable maternal and pregnancy outcomes in small numbers of pregnant women treated with rifampin for anaplasmosis — Small numbers of children also have been treated successfully for anaplasmosis using rifampin ; however, no clinical trials demonstrating in vivo efficacy of rifampin in the treatment of anaplasmosis or ehrlichiosis have been conducted. Rifampin could be an alternative for the treatment of mild illness due to anaplasmosis in the case of pregnancy or documented allergy to tetracycline-class drugs Before considering treatment with rifampin, clinicians should use caution and ensure that RMSF can be ruled out because the early signs and symptoms of RMSF and anaplasmosis are similar, and rifampin is not considered an acceptable treatment for RMSF.

In addition, rifampin does not effectively treat potential coinfection of A. Many classes of broad-spectrum antibacterial agents that are used empirically to treat febrile patients, such as beta-lactams, macrolides, aminoglycosides, and sulfonamides, are not effective against tickborne rickettsial diseases 18 , Although some fluoroquinolones have in vitro activity against rickettsiae , their use for treatment of certain rickettsial infections has been associated with delayed subsidence of fever, increased disease severity, and longer hospital stay , Although A.

Sulfonamide antimicrobials are associated with increased severity of tickborne rickettsial diseases. Experimental and accumulated anecdotal clinical data suggest that treatment of patients with RMSF with a sulfonamide drug can result in increased disease severity and death , Cases of severe ehrlichiosis also have been associated with the use of trimethoprim-sulfamethoxazole — In some patients treated with sulfonamide or beta-lactam drugs, diagnosis and appropriate treatment of tickborne rickettsial illness was delayed because the development of a rash was mistaken for a drug eruption rather than recognized as a manifestation of rickettsial illness Severe doxycycline or tetracycline allergy in a patient with a suspected tickborne rickettsial disease poses a challenge because of the lack of equally effective alternative antimicrobial agents.

In a patient reporting an allergy to a tetracycline-class drug, determining the type of adverse drug reaction and whether it is potentially life threatening e. Consultation with an allergy and immunology specialist could be helpful in making this determination. In patients with non—life-threatening tetracycline-class drug reactions, administering doxycycline in an observed setting is an option; however, the risks and benefits should be evaluated on a case-by-case basis.

In patients with a life-threatening tetracycline allergy, options include use of alternative antibacterial agents discussed in the preceding section or, possibly for immediate hypersensitivity reactions, rapid doxycycline desensitization in consultation with an allergy and immunology specialist. Anaphylactic reactions to tetracycline-class drugs, although rare, have been reported , Rapid doxycycline desensitization accomplished within several hours in an inpatient intensive care setting in patients with a history of immediate hypersensitivity reactions including anaphylaxis has been described , ; however, data are limited to individual case reports.

Use of tetracycline-class drugs has generally been contraindicated during pregnancy because of concerns about potential risk to the musculoskeletal development of the fetus, cosmetic staining of primary dentition in fetuses exposed during the second or third trimester, and development of acute fatty liver of pregnancy in the mother — Although these adverse effects were observed in association with the use of tetracycline and older tetracycline derivatives, the contraindication for use during pregnancy has been applied across the class of tetracyclines, which includes newer derivatives, such as doxycycline.

Controlled studies to assess the safety of doxycycline use in pregnant women have not been conducted, and available data are primarily observational. An expert review on doxycycline use during pregnancy concluded that therapeutic doses were unlikely to pose a substantial teratogenic risk; however, the data were insufficient to conclude that no risk exists , The risk for cosmetic staining of the primary teeth by doxycycline could not be determined because of limited data A recent systematic review reported no evidence of teratogenicity associated with doxycycline use during pregnancy; however, limited data and a lack of controlled studies were limitations No reports of maternal hepatic toxicity associated with doxycycline use have been published — Rarely, fatty liver of pregnancy has occurred in patients who received high-dose intravenous tetracycline , ; however, the dosages administered in these cases exceeded what is recommended for the treatment of tickborne rickettsial disease.

Only limited clinical data exist that support the use of antibacterial agents other than doxycycline in the treatment of tickborne rickettsial disease during pregnancy. Doxycycline has been used successfully to treat tickborne rickettsial diseases in several pregnant women without adverse effects to the mother; however, follow-up to address adverse effects to the fetus was limited , Chloramphenicol is a potential alternative treatment for RMSF during pregnancy; however, care must be used when administering the drug late during the third trimester of pregnancy because of the theoretical risk for gray baby syndrome , Chloramphenicol is not an alternative for the treatment of ehrlichiosis or anaplasmosis , Limited case report data suggest that rifampin could be considered an alternative to doxycycline for the treatment of mild anaplasmosis during pregnancy , , Patient counseling and discussion of potential risks versus benefits with the pregnant woman by the health care provider are important components in treatment decision-making during pregnancy; nonetheless, for potentially life-threatening illnesses, such as RMSF and E.

Doxycycline is excreted into breast milk at low levels; however, the extent of absorption by nursing infants is unknown. Short-term use of doxycycline as recommended for the treatment of tickborne rickettsial disease is considered probably safe during lactation on the basis of available literature and expert opinion Studies of preventive antibacterial therapy for rickettsial infection in humans are limited.

Available data do not support prophylactic treatment for rickettsial diseases in persons who have had recent tick bites and are not ill.