Author(s): William Nicholson, Christopher Paddock

Infectious Agent

Rickettsial infections are caused by various bacteria within 6 genera of the order Rickettsiales: Rickettsia, Orientia, Anaplasma, Ehrlichia, Neoehrlichia, and Neorickettsia (Table 5-04). Rickettsia spp. are classically divided into the spotted fever group (SFG) and the typhus group, although more recently these have been classified into as many as 4 groups. Orientia spp. comprise the scrub typhus group, which has only recently expanded from the single species O. tsutsugamushi.

Rickettsial species (and diseases) that travelers are more likely to encounter outside the United States include the SFG pathogens, Rickettsia africae (African tick-bite fever), R. conorii (Mediterranean spotted fever), R. rickettsii (Rocky Mountain spotted fever [RMSF], also known as Brazilian spotted fever); R. typhi (murine typhus); Orientia tsutsugamushi (scrub typhus); and Anaplasma phagocytophilum (anaplasmosis). Many other rickettsial agents cause human infections across the globe, but the true burden remains undetermined.

Transmission

Most rickettsial pathogens are transmitted directly to humans by infected arthropod vectors (i.e., fleas, lice, mites, or ticks) during feeding. Rickettsia also might be transmitted when a person inadvertently inoculates the arthropod bite wound (or other breaks in the skin) with rickettsial pathogens; this can happen by scratching skin contaminated with an arthropod’s infectious fluids or feces, or by crushing the arthropod vector at the bite site. Inhaling bacteria or inoculating conjunctiva with infectious material also can initiate infection for some rickettsial pathogens.

Vectors that transmit each rickettsial species are listed in Table 5-04; some details are discussed here. Transmission of a few pathogens, particularly Anaplasma and Ehrlichia spp., through transfusion of infected blood products or by organ transplantation, is less common.

Epidemiology

Regardless of the length of travel (short- or long-term), all age groups are at risk for rickettsial infections during visits to endemic areas. Transmission risk increases with time spent participating in outdoor activities, particularly during seasons of peak feeding and lifecycle activity for the vector. In many parts of the world, however, rickettsial infections occur year-round. The most diagnosed rickettsial diseases in travelers are in the spotted fever or typhus groups; notably, rickettsial infections can also be caused by emerging and newly recognized species.

Spotted Fever Group

Tickborne spotted fever rickettsioses are the most frequently reported travel-associated rickettsial infections.

African Tick-Bite Fever

Travelers who go on safari—especially those traveling to national parks, game hunters, and ecotourists to sub-Saharan Africa—are at risk for African tick-bite fever caused by R. africae. R. africae is also endemic to several islands of the Caribbean West Indies, and imported cases have been described from this region.

R. africae remains the most frequently reported rickettsial infection acquired during travel. Commonly, cases of African tick-bite fever cluster among people traveling together, and diagnosis of the disease in 1 member of a family or tourist group can alert other similarly exposed people to seek care if they develop compatible signs and symptoms.

Cat Flea Rickettsiosis

R. felis, the cause of cat flea rickettsiosis, has been identified in various invertebrate hosts worldwide and has been reported as a major cause of febrile illness in some countries of Africa.

Mediterranean Spotted Fever

Travel-associated cases of Mediterranean spotted fever (also known as Boutonneuse fever), caused by R. conorii, are less commonly reported but occur over a large geographic area, including but not limited to Africa, much of Europe, India, and the Middle East.

Rickettsialpox

The causative agent of rickettsialpox, R. akari, is transmitted by house mouse mites, and circulates mainly in urban centers in the Balkan states, Korea, South Africa, Ukraine, and the United States. Outbreaks of rickettsialpox most often occur after contact with infected peridomestic rodents and their mites, especially during natural die-offs or exterminations of infected rodents that cause the mites to seek out new hosts, including humans. Urban rodents seem more often associated with human cases, but the agent has been identified in a few wild rodent populations.

Rocky Mountain Spotted Fever or Brazilian Spotted Fever

RMSF (also known as Brazilian spotted fever and other local names) is caused by R. rickettsii. It occurs throughout much of the Western Hemisphere, and cases are reported from Canada, Mexico, the United States, and many countries of Central and South America, including Argentina, Brazil, Colombia, Costa Rica, and Panama. Clusters of illness might be reported in families or in geographic areas. Contact with dogs in rural and urban settings, and outdoor activities (e.g., camping, fishing, hiking, hunting) increase the risk for infection.

Typhus Group

Epidemic Typhus

Louseborne or epidemic typhus, caused by R. prowazekii, is rarely reported among tourists; more commonly, it occurs among people living in crowded conditions where body lice are prevalent (e.g., refugees housed in camps, incarcerated populations). Outbreaks often happen during the colder months. Travelers at greatest risk for epidemic typhus include people who provide medical or humanitarian aid to people living in refugee camps and those who visit impoverished areas affected by war, famine, or natural disasters. Active foci of epidemic typhus are in the Andes region of South America and some parts of Africa, including but not limited to Burundi, Ethiopia, and Rwanda.

Classical louseborne typhus has not occurred in the United States for approximately the past century; however, a zoonotic reservoir exists in the southern flying squirrel, and sporadic sylvatic epidemic typhus cases are reported when these animals invade people’s homes or cabins.

Murine Typhus

Murine typhus, caused by R. typhi, is distributed worldwide, particularly in and around port cities and coastal regions with large rodent populations. People are at risk for fleaborne rickettsioses when traveling in endemic regions and when they are exposed to flea-infested cats, dogs, and peridomestic animals, or enter or sleep in areas infested with rodents. Murine typhus has been reported among travelers returning from Africa, Asia, and the Mediterranean Basin. Most cases acquired in the United States are reported from California, Hawaii, and Texas.

Scrub Typhus Group

Scrub typhus can be transmitted by many species of trombiculid mites that live in high grass and brush. Scrub typhus is endemic to regions of east Asia (China, northern Japan), Southeast Asia (India, Indonesia, Sri Lanka), the Pacific (eastern Australia), and several parts of south-central Russia. Cases of disease also have been described from several unexpected regions, including the United Arab Emirates and southern Chile, and appear to be caused by newly recognized species of Orientia.

More people worldwide are at risk for scrub typhus than for any other rickettsial disease; >1 million cases occur annually, mostly in farmers or people with occupational exposure. Travel-acquired cases of scrub typhus occasionally are reported among people who visit rural regions of countries where O. tsutsugamushi is endemic, and exposure is often associated with participating in recreational activities (e.g., camping, hiking, rafting). Rare urban cases have been described.

Anaplasmosmis & Ehrlichiosis

Although anaplasmosis (caused predominately by A. phagocytophilum) and ehrlichiosis (caused predominately by E. chaffeensis, E. ewingii, and E. muris euclairensis) are tickborne infections commonly reported in the United States, pathogenic species can be found in many regions of the world. Infections with these and other Anaplasma and Ehrlichia spp. have been reported in Africa, South America, Asia, and Europe, and occasionally among travelers.

Neoehrlichia & Neorickettsia

Neoehrlichia mikurensis is a tickborne pathogen that occurs in many parts of Asia and Europe. It generally infects people who are older or who are immunocompromised. Sennetsu fever, caused by N. sennetsu, occurs in Japan, Malaysia, and parts of Southeast Asia. This disease can be contracted from eating raw fish infested with neorickettsiae-infected flukes.

Clinical Presentation

Rickettsial diseases are difficult to diagnose, even by health care providers experienced with these diseases. The incubation period for most rickettsial diseases ranges from 5–10 days. Travelers can experience signs and symptoms during their trip or not until 1–2 weeks after returning home.

Most symptomatic rickettsial diseases cause moderate illness, but others, including RMSF (also called Brazilian spotted fever), epidemic typhus, scrub typhus, and Mediterranean spotted fever, can be life-threatening in some cases, particularly when treatment is delayed. Clinical presentations vary with the causative agent and patient. Common symptoms that typically develop within 1 week of infection include fever, headache, malaise, nausea, or vomiting. Many rickettsioses also are accompanied by a maculopapular, petechial, or vesicular rash, or sometimes an eschar (a dark necrotic scab) at the site of the tick or mite bite (see Sec. 11, Ch. 8, Dermatologic Conditions).

Spotted Fever Group

African Tick-Bite Fever

African tick-bite fever is typically milder than most other rickettsioses, but recovery is facilitated with antimicrobial treatment. Suspect this disease in patients presenting with fever, headache, myalgia, and ≥1 eschars after recent travel to sub-Saharan Africa or the Caribbean.

Mediterranean Spotted Fever

Mediterranean spotted fever can be life-threatening, and clinicians should suspect it in patients with fever, rash, and an eschar after recent travel to northern Africa or the Mediterranean Basin.

Rocky Mountain Spotted Fever or Brazilian Spotted Fever

RMSF is characterized by fever, headache, abdominal pain, and nausea, and can progress rapidly into a serious systemic disease. A maculopapular or petechial rash is commonly reported, but eschars are not. RMSF is the most severe of the spotted fever rickettsioses, and case fatality ratios of 20%–40% are seen among patients for whom antimicrobial drug treatment was delayed.

Typhus Group

Murine Typhus

Patients with murine typhus usually present with a moderately severe but nonspecific febrile illness. Only about half of patients develop a maculopapular rash, typically on the trunk. Although generally less severe than diseases like RMSF or scrub typhus, patients with murine typhus can develop organ failure or other severe sequelae requiring hospital-based management. Death can occur.

Scrub Typhus

Clinicians should include scrub typhus in the differential diagnosis of patients with a fever, headache, myalgias, and eschar after recent travel to destinations where the disease is endemic. Cough, encephalitis, lymphadenopathy, and rash might be present, and multisystem organ failure can develop.

Anaplasmosis & Ehrlichiosis

Clinicians should consider anaplasmosis or ehrlichiosis in febrile patients with leukopenia and an appropriate exposure history. Rash might occur in some children with ehrlichiosis, but is not a feature of anaplasmosis. Other clinical signs are similar to those of other rickettsioses.

Diagnosis

As noted above, rickettsial diseases are difficult to diagnose, even by experienced clinicians. Timely presumptive diagnosis and initiation of antibiotic therapy is almost always based on clinical recognition and epidemiologic context. Serologic testing provides retrospective confirmation and is most accurate when acute and convalescent phase serum samples are compared; a ≥4-fold rise in antibody titer between paired specimens is diagnostic in indirect immunofluorescence antibody assays. Because of cross-reactivity of antigens, some antibodies might react in group-targeted serologic tests and provide evidence of exposure to the group level.

PCR assays and immunohistochemical analyses can be helpful, but results are highly dependent on the type and timing of submitted specimens. If an eschar is present, a swab or biopsy sample of the lesion can be evaluated by PCR to provide a species-specific diagnosis. Similarly, biopsy specimens of rash lesions or whole blood specimens can be evaluated by PCR but are generally less sensitive than samples derived from an eschar.

If anaplasmosis or ehrlichiosis is suspected, PCR of a whole blood specimen provides the best diagnostic test. A buffy coat might provide presumptive evidence of infection if examined to identify characteristic inclusion bodies within leukocytes (called intraleukocytic morulae).

Spotted fever rickettsiosis, anaplasmosis, and ehrlichiosis are nationally notifiable diseases in the United States. Commercial laboratories offer testing for rickettsioses, scrub typhus, anaplasmosis, and ehrlichiosis. Some species-targeted serologic tests are not routinely available at commercial laboratories, however, and are available only through CDC’s Rickettsial Zoonoses Branch (rzbepidiag@cdc.gov).

Treatment

Because some rickettsioses can progress rapidly to severe illness, clinicians should initiate therapy as soon as infection is suspected and not wait to receive confirmatory test results. Immediate empiric treatment with a tetracycline (most commonly, doxycycline) is recommended for patients of all ages. Almost no other broad-spectrum antibiotic provides effective treatment.

Rigorous reevaluation of earlier reports of doxycycline-resistant scrub typhus has revealed those reports to be incorrect. Orientia spp. are doxycycline sensitive. Limited clinical experience has shown that A. phagocytophilum and R. africae infections respond to treatment with rifampin, which can be an alternative for pregnant or doxycycline-intolerant patients. Chloramphenicol is the only recognized alternative treatment for diseases caused by Orientia and Rickettsia species, but oral formulations are not available in many areas; moreover, chloramphenicol use is associated with more deaths, particularly with R. rickettsii infection. Seek expert advice if considering treatment with an alternative antibiotic.

Prevention

No vaccine is available for preventing rickettsial infections. Antibiotic prophylaxis is not recommended for rickettsial diseases, and antimicrobial agents should not be given to asymptomatic people.

Instruct travelers going to rickettsia endemic areas to minimize their exposure to infectious arthropods (including fleas, lice, mites, ticks) and avoid animal reservoirs (particularly dogs and rats). Travelers can reduce risk for infection by properly using insect repellents on skin and clothing, conducting a self-examination after visits to vector-infested areas, and wearing protective clothing (see Sec. 4, Ch. 6, Mosquitoes, Ticks & Other Arthropods). These precautions are especially important for travelers with immune-compromising conditions, because they might be more susceptible to severe disease.

CDC websites:
Rocky Mountain Spotted Fever (RMSF)
Other spotted fever group rickettsioses
Flea-borne (murine) typhus
Anaplasmosis
Ehrlichiosis