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Jul 17, 2023 · Rocky Mountain spotted fever (RMSF) is an acute febrile tick-borne illness caused by Rickettsia rickettsii. In North America, it is both the most severe and the most common rickettsial infection. Without prompt antibiotic treatment, mortality rates are as high as 20 to 30 percent.
- Jessica Snowden, Kari A. Simonsen
- 2023/07/17
- Overview
- Summary
- Introduction
- Methods
- Epidemiology
- Clinical Signs and Symptoms and Pathophysiology of Disease
- Treatment and Management
- Special Considerations
- Confirmatory Diagnostic Tests
- Prevention of Tickborne Rickettsial Diseases
Tickborne rickettsial diseases continue to cause severe illness and death in otherwise healthy adults and children, despite the availability of low-cost, effective antibacterial therapy. Recognition early in the clinical course is critical because this is the period when antibacterial therapy is most effective. Early signs and symptoms of these ill...
Ticks (Acari: Ixodidae and Argasidae) transmit multiple and diverse pathogens (including bacteria, protozoa, and viruses), which cause a wide range of human and animal diseases, including rickettsial diseases, caused by bacteria in the order Rickettsiales. Vertebrate animals play an integral role in the life cycle of tick species, whereas humans are incidental hosts. Awareness, diagnosis, and control of tickborne rickettsial diseases are most effectively addressed by considering the intersecting components of human, animal, and environmental health that collectively form the foundation of One Health (1), an approach that integrates expertise from multiple disciplines and facilitates understanding of these complex zoonoses.
Tickborne rickettsial diseases in humans often share similar clinical features yet are epidemiologically and etiologically distinct. In the United States, these diseases include 1) Rocky Mountain spotted fever (RMSF) caused by Rickettsia rickettsii; 2) other spotted fever group (SFG) rickettsioses, caused by Rickettsia parkeri and Rickettsia species 364D; 3) Ehrlichia chaffeensis ehrlichiosis, also called human monocytic ehrlichiosis; 4) other ehrlichioses, caused by Ehrlichia ewingii and Ehrlichia muris-like (EML) agent; and 5) anaplasmosis, caused by Anaplasma phagocytophilum (2), also called human granulocytic anaplasmosis. Rickettsial pathogens transmitted by arthropods other than ticks, including fleas (Rickettsia typhi), lice (Rickettsia prowazekii), and mites (Rickettsia akari) are not included in this report. Imported tickborne rickettsial infections that might be diagnosed in returning international travelers are summarized; however, tickborne and nontickborne rickettsial illnesses typically encountered outside the United States are not addressed in detail in this report.
The reported incidence of tickborne rickettsial diseases in the United States has increased during the past decade (3–5). Tickborne rickettsial diseases continue to cause severe illness and death in otherwise healthy adults and children, despite the availability of effective antibacterial therapy. Early signs and symptoms of tickborne rickettsial illnesses are nonspecific, and most cases of RMSF are misdiagnosed at the patient’s first visit for medical care, even in areas where awareness of RMSF is high (6,7). To increase the likelihood of an early, accurate diagnosis, health care providers should be familiar with risk factors, signs, and symptoms consistent with tickborne rickettsial diseases.
This report provides practical information to help health care providers and public health professionals to
•recognize the epidemiology and clinical manifestations of tickborne rickettsial diseases;
•obtain an appropriate clinical history for suspected tickborne rickettsial diseases;
This report updates the 2006 CDC recommendations for the diagnosis and management of tickborne rickettsial diseases in the United States (8). Updated recommendations are needed to address the changing epidemiology of tickborne rickettsial diseases, provide current information about new and emerging tickborne rickettsial pathogens, and highlight advances in recommended diagnostic tests and updated treatment information.
The CDC Rickettsial Zoonoses Branch reviewed the 2006 report and determined which subject-matter areas required updates or revisions. Internal and external subject-matter experts in tickborne rickettsial diseases, representing a range of professional experiences and viewpoints, were identified by the CDC Rickettsial Zoonoses Branch to contribute to the revision. Contributors represented various areas of expertise within the field of tickborne rickettsioses and included practicing physicians specializing in internal medicine, family medicine, infectious diseases, and pathology; veterinarians with expertise in state, national, and international public health; epidemiologists; tick ecologists; microbiologists; and experts in rickettsial laboratory diagnostics. The peer-reviewed literature, published guidelines, and public health data were reviewed, with particular attention to new material available since preparation of the previous report. The scientific literature was searched through February 2016 using the MEDLINE database of the National Library of Medicine. The terms searched were Rickettsia, Rickettsia infections, R. rickettsii, RMSF, Ehrlichia, ehrlichiosis, E. chaffeensis, anaplasmosis, Anaplasma, and A. phagocytophilum. Text word searches were performed on multiple additional terms tailored to specific questions, which included epidemiology, treatment, diagnosis, and prevention. Titles of articles and abstracts extracted by the search were reviewed, and if considered potentially relevant, the full text of the article was retrieved. Reference lists of included articles were reviewed, and additional relevant citations were provided by contributors. In certain instances, textbook references were used to support statements considered general knowledge in the field. Articles selected were in English or had available translations. Peer-reviewed publications and published guidelines were used to support recommendations when possible. Abstracts without a corresponding full-length publication, dissertations, or other non–peer-reviewed literature were not used to support recommendations. When possible, data were obtained from studies that determined the presence of tickborne rickettsial infection using confirmatory diagnostic methods. Additional criteria were applied on a per-question basis. For some questions, an insufficient number of studies was identified to support the development of a recommendation. In these instances, the report indicates that the evidence was insufficient for a recommendation, and when possible, general guidance is provided based on the available evidence and expert opinion of the CDC Rickettsial Zoonoses Branch. All contributors had the opportunity to review and provide input on multiple drafts of the report, including the final version. Future updates to this report will be dictated by new data in the field of tickborne rickettsial diseases.
Overview
Tickborne rickettsial pathogens are maintained in natural cycles involving domestic or wild vertebrates and primarily hard-bodied ticks (Acari: Ixodidae). The epidemiology of each tickborne rickettsial disease reflects the geographic distribution and seasonal activities of the tick vectors and vertebrate hosts involved in the transmission of these pathogens, as well as the human behaviors that place persons at risk for tick exposure, tick attachment, and subsequent infection ( Box 1). SFG rickettsiosis, ehrlichiosis, and anaplasmosis are nationally notifiable in the United States. Cases have been reported in each month of the year, although most cases are reported during April–September, coincident with peak levels of tick host-seeking activity (3–5,9–14). The distribution of tickborne rickettsial diseases varies geographically in the United States and approximates the primary tick vector distributions, making it important for health care providers to be familiar with the regions where tickborne rickettsial diseases are common. Travelers within the United States might be exposed to different tick vectors during travel, which can result in illness after they return home. Travelers outside of the United States might also be exposed to different tick vectors and rickettsial pathogens in other countries, which can result in illness after they return to the United States (see Travel Outside of the United States). Health care, public health, and veterinary professionals should be aware of changing vector distributions, emerging and newly identified human tickborne rickettsial pathogens, and increasing travel among persons and pets within and outside of the United States.
Spotted Fever Group Rickettsiae
SFG rickettsiae are related closely by various genetic and antigenic characteristics and include R. rickettsii (the cause of RMSF), R. parkeri, and Rickettsia species 364D, as well as many other Rickettsia species of unknown pathogenicity. RMSF is the rickettsiosis in the United States that is associated with the highest rates of severe and fatal outcomes. During 2008–2012, passive surveillance indicated that the estimated average annual incidence of SFG rickettsiosis was 8.9 cases per million persons in the United States (4). The passive surveillance category in the United States for SFG rickettsiosis might not differentiate between RMSF and other SFG rickettsioses because of the limitations of submitted diagnostic evidence. Reported annual incidence of SFG rickettsiosis has increased substantially during the past 2 decades. The highest incidence occurs in persons aged 60–69 years, and the highest case-fatality rate is among children aged <10 years, although illness occurs in all age groups (4). Incidence varies considerably by geographic area ( Figure 1). During 2008–2012, 63% of reported SFG rickettsiosis cases originated from five states: Arkansas, Missouri, North Carolina, Oklahoma, and Tennessee (4). However, SFG rickettsiosis cases have been reported from each of the contiguous 48 states and the District of Columbia (4,9,12,14). A notable regional increase in the reported incidence of SFG rickettsiosis occurred in Arizona during 2003–2013. Over this period, approximately 300 cases of RMSF and 20 deaths were reported from American Indian reservations in Arizona compared with three RMSF cases reported in the state during the previous decade (15). Since identification of the first case of locally transmitted RMSF in 2003 (16), RMSF has been found to be endemic in several American Indian communities in Arizona. On the three most affected reservations, the average annual incidence rate for 2009–2012 was approximately 1,360 cases per million persons (17). The 7%–10% case-fatality rate in these communities, which is the highest of any region in the United States, has been associated predominantly with delayed recognition and treatment (4,18).
Ehrlichiae
In the United States, three Ehrlichia species are known to cause symptomatic human infection. E. chaffeensis, the cause of human monocytic ehrlichiosis, was described first in 1987 and is the most common agent of human ehrlichiosis (47). E. ewingii was reported as a human pathogen in 1999 after being detected in peripheral blood leukocytes of four patients with illness during 1996–1998 (48). EML agent ehrlichiosis, first described in 2011, is the most recently recognized form of human ehrlichiosis in the United States and was detected originally in the blood of four patients from Minnesota and Wisconsin in 2009 (49). During 2008–2012, the average annual incidence of ehrlichiosis was 3.2 cases per million persons, which is more than twice the estimated incidence during 2000–2007 (5). Cases have been reported from an increasing number of counties (5) ( Figure 11). Incidence generally increases with age, with the highest age-specific incidences occurring among persons aged 60–69 years (5,13,50). Case-fatality rates are highest among children aged <10 years and adults aged ≥70 years, and an increased risk for death has been documented among persons who are immunosuppressed (5,13). In areas where ehrlichiosis is endemic, the actual disease incidence is likely underrepresented in estimates that are based on passive surveillance (51–53).
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.g., rash and other cutaneous findings), typical laboratory findings, and case-fatality rates diff...
Doxycycline is the drug of choice for treatment of all tickborne rickettsial diseases in patients of all ages, including children aged <8 years, and should be initiated immediately in persons with signs and symptoms suggestive of rickettsial disease (8,178–180) (Box 7). 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 (74,116,181).
A thorough clinical history, physical examination, and laboratory results (e.g., complete blood count with differential leukocyte count, hepatic transaminase levels, and serum sodium level) collectively guide clinicians in developing a differential diagnosis and treatment plan. 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 100 mg twice daily (orally or intravenously) for adults and 2.2 mg/kg body weight twice daily (orally or intravenously) for children weighing <100 lbs (45 kg) (8) (Table 3). 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 (8,180,182,183); 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. burgdorferi (173). Children aged <8 years with anaplasmosis in whom concurrent Lyme disease is not suspected can be treated for a duration similar to that for other tickborne rickettsial diseases (173,183).
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. Severely ill patients might require >48 hours of treatment before clinical improvement is noted, especially if they have multiple organ dysfunction.
Patients with evidence of organ dysfunction, severe thrombocytopenia, mental status changes, or the need for supportive therapy should be hospitalized. Other important considerations for hospitalization include social factors, the likelihood that the patient can and will take oral medications, and existing comorbid conditions, including the patient’s immune status. 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 24-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 (184). Consultation with an intensive care or infectious disease specialist could be helpful in managing these complications.
Transfusion- and Transplant-Associated Transmission Travel Outside of the United States
International travel can pose a risk for infection with rickettsial pathogens not encountered in the United States (Appendix A). SFG rickettsioses are the most commonly diagnosed tickborne rickettsial diseases among returning travelers (239). The most frequently occurring among these are African tick bite fever, caused by Rickettsia africae, and Mediterranean spotted fever (also known as boutonneuse fever), caused by Rickettsia conorii (240,241). Approximately 90% of imported SFG rickettsioses occur among travelers returning from sub-Saharan Africa (239,242), and nearly all of these represent African tick bite fever (241,243). Patients with African tick bite fever typically have fever, headache, myalgia, one or more inoculation eschars, regional lymphadenopathy, and sometimes maculopapular or vesicular rash (241,244). The incubation period is typically 5–7 days but can be up to 10 days after the bite of an infected Amblyomma hebraeum or Amblyomma variegatum tick (241,244). The course of illness usually is mild. African tick bite fever can occur in clusters among game hunters, safari tourists, deployed troops, and humanitarian workers (243,245,246). Travel for tourism has been identified as a risk factor (239,241), and African tick bite fever is the second most common cause of febrile illness after malaria among travelers returning from sub-Saharan Africa (247,248). Mediterranean spotted fever is endemic in the Mediterranean basin, Middle East, parts of Africa, and the Indian subcontinent (240). This infection can be severe or fatal; in Portugal, a case-fatality rate of 21% among hospitalized adults has been described (249). Onset of Mediterranean spotted fever typically occurs abruptly with fever, myalgia, headache, eschar (usually singular), and maculopapular or petechial rash that can involve the palms and soles. Severe manifestations including neurologic, cardiac, and renal complications have been described. The mean incubation period is 6 days (range: 1–16 days) after being bitten by an infected tick (250). Rh. sanguineus is the principal tick vector in Europe, Israel, and North Africa. Dogs can serve as reservoir hosts for R. conorii (251), and infected Rh. sanguineus ticks can transfer from dogs to humans during interactions. Other tick vectors might play a role in transmission in sub-Saharan Africa (250,252). Like other tickborne rickettsial diseases, Mediterranean spotted fever and African tick bite fever respond readily to antibacterial treatment with doxycycline. Tickborne rickettsial pathogens found in the United States can also be encountered abroad. For example, R. rickettsii infection can be acquired in Canada and Mexico, as well as in Central America and South America, where cases are reported from Costa Rica, Panama, Brazil, Colombia, and Argentina (253–260). R. parkeri infections have been described in Uruguay, Brazil, and Argentina (38,253,261,262). Human anaplasmosis has been reported from several countries throughout Europe (263), as well as from several Asian countries, including China, Korea, Russia, and Japan (264–267).
Several categories of laboratory methods are used to diagnose tickborne rickettsial diseases; these vary in availability, time to obtain results, performance characteristics, and the type of information each provides. Rapid confirmatory assays are rarely available to guide treatment decisions for acutely ill patients; therefore, it is imperative that therapeutic interventions are based on clinical suspicion. Because of the rapidly progressive nature of certain rickettsial diseases, antibacterial treatment should never be delayed while awaiting laboratory confirmation of a rickettsial illness (268), nor should treatment be discontinued solely on the basis of a negative test result on an acute phase specimen. Nonetheless, these laboratory assays provide vital information that validates the accuracy of the clinical diagnosis (268–270) and are crucial for defining the changing epidemiology and public health impact of tickborne rickettsial diseases (3–5).
Determining the most appropriate diagnostic assays to request for suspected tickborne rickettsial illness requires consideration of several factors (Box 8). These include the suspected pathogen, the timing relative to symptom onset, and the type of specimens available for testing (Appendix B) (Table 4). Diagnostic assays should always be ordered and interpreted in the context of a compatible illness and appropriate epidemiologic setting to obtain optimal positive and negative predictive values (271). Misuse of specialized assays for patients with a low pretest probability of a rickettsial disease can result in confusion. For example, antirickettsial antibodies can remain detectable for months to years after infection (222,223,272,273); however, in the absence of a clinically compatible acute illness, detectable antibodies are not an indication for treatment for tickborne rickettsial disease.
No vaccine is licensed for the prevention of tickborne rickettsial diseases in the United States. Avoiding tick bites and promptly removing attached ticks remain the best disease prevention strategies. General tick bite prevention strategies include various personal protective measures and behavior change components (Box 9).
- Holly M. Biggs, Casey Barton Behravesh, Kristy K. Bradley, F. Scott Dahlgren, Naomi A. Drexler, J. S...
- 2016
Aug 25, 2022 · Rocky Mountain spotted fever (RMSF) is an illness you get from the bacteria Rickettsia rickettsii ( R. rickettsii). It spreads through tick bites. Symptoms start out similar to many other illnesses, including headache, fever and rash. But if not treated right away, RMSF can be life-threatening.
Hard-shelled ticks (family Ixodidae) harbor R. rickettsii, and infected females transmit the agent to their progeny. These ticks are the natural reservoirs. Dermacentor andersoni (wood tick) is the principal vector in the western United States.
Sep 1, 2020 · A Spanish study, indeed, shows that 4–8% of the population carry antibodies against Rickettsia but without a previous clinical history of MSF. 53. The most common symptoms are fever (93–98%), myalgia (64–75%), headache (48–65%), and asthenia (27%).
- Andrea De Vito, Nicholas Geremia, Sabrina Maria Mameli, Vito Fiore, Pier Andrea Serra, Gaia Rocchitt...
- 10.4084/MJHID.2020.056
- 2020
- 2020
Mar 16, 2006 · R. rickettsii infects endothelial cells, causing vasculitis, which leads to rash and life-threatening damage to the brain, lungs, and other viscera. R. rickettsii is not evident in blood smears, and these bacteria and do not stain with the majority of conventional stains.
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Jul 21, 2022 · In the US, Rocky Mountain spotted fever (RMSF), caused by R rickettsii, is the most dangerous of the rickettsial infections. There were more than 5000 cases of RMSF in the US in 2019, slightly lower than the peak in 2017 of more than 6000 cases.
