Chapter 4 Travel-Related Infectious Diseases
Rickettsial Diseases (Including Spotted Fever & Typhus Fever Rickettsioses, Scrub Typhus, Anaplasmosis, and Ehrlichioses)
William L. Nicholson, Christopher D. Paddock
Rickettsial infections are caused by multiple bacteria from the order Rickettsiales and genera Rickettsia, Anaplasma, Ehrlichia, Neorickettsia, Neoehrlichia, and Orientia (Table 4-19). 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. make up the scrub typhus group. The rickettsial pathogens most likely to be encountered during travel outside the United States include Rickettsia africae (African tick-bite fever), R. conorii (Mediterranean spotted fever), Anaplasma phagocytophilum (anaplasmosis), R. rickettsii (known as both Rocky Mountain spotted fever and Brazilian spotted fever), Orientia tsutsugamushi (scrub typhus), and R. typhi (murine typhus).
Most rickettsial organisms are transmitted by the bites or infectious fluids (such as feces) inoculated into the skins from ectoparasites such as fleas, lice, mites, and ticks. Inhaling bacteria or inoculating conjunctiva with infectious material may also result in infection. The specific vectors that transmit each form of rickettsiae are listed in Table 4-19. Transmission of a few rickettsial diseases from transfusion of infected blood products or by organ transplantation is rare but has been reported.
All travelers are at risk of acquiring rickettsial infections during travel to endemic areas. Transmission occurs throughout the year but is increased during outdoor activities. Because of the 5- to 14-day incubation period for most rickettsial diseases, tourists may not experience symptoms during their trip, and onset may coincide with their return home or within a week after returning. Although the most commonly diagnosed rickettsial diseases in travelers are usually in the spotted fever or typhus groups, travelers may acquire a wide range of rickettsioses, including emerging and newly recognized species not well known by many health care providers (see Table 4-19).
Spotted Fever Group Rickettsioses
Tickborne spotted fever rickettsioses are the most frequently reported travel-associated rickettsial infections. Those who go on safari—especially those walking in the bush, game hunters, and ecotourists to southern Africa—are at risk for African tick-bite fever. This disease remains the most commonly reported rickettsial infection acquired during travel. Cases commonly occur as clusters among travel groups, and the diagnosis of African tick-bite fever in a member of a family or tourist group can alert other similarly exposed people to seek care if they develop symptoms. R. africae is also endemic to several Caribbean islands, and imported cases have been described from this region.
Travel-associated cases of Mediterranean spotted fever are less commonly reported but occur over an even larger region, including (but not limited to) much of Europe, Africa, India, and the Middle East. Rocky Mountain spotted fever (also known as Brazilian spotted fever, as well as other local names) occurs throughout much of the Western Hemisphere, and cases are reported from Canada, the United States, Mexico, and many countries of Central and South America, including Argentina, Brazil, Colombia, Costa Rica, and Panama. Clusters of illness may be reported in families or in geographic areas. Contact with dogs in rural and urban settings, and outdoor activities such as hiking, hunting, fishing, and camping increase the risk of infection.
The causative agent of rickettsialpox, R. akari, is transmitted by house mouse mites and circulates in mainly urban centers in Ukraine, South Africa, Korea, the Balkan states, 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.
Typhus Group Rickettsioses
Flea-associated rickettsioses caused by R. typhi and R. felis are globally distributed, particularly in and around port cities and coastal regions with large rodent populations. Humans exposed to flea-infested cats, dogs, and peridomestic animals while traveling in endemic regions, or who enter or sleep in areas infested with rodents, are at most risk for fleaborne rickettsioses. Murine typhus has been reported among travelers returning from Asia, Africa, and the Mediterranean Basin. Most cases acquired in the United States are reported from Hawaii, California, and Texas.
Epidemic typhus caused by R. prowazekii infection is reported rarely among tourists but can occur in communities and in refugee or incarcerated populations where body lice are prevalent. Outbreaks often occur during the colder months. Travelers at most risk for epidemic typhus include those who work with large homeless populations or who visit, impoverished areas, refugee camps, and regions that have recently experienced war or natural disasters. Active foci of epidemic typhus are known in the Andes regions of South America and some parts of Africa (including, but not limited to, Burundi, Ethiopia, and Rwanda). Louseborne epidemic typhus does not occur regularly in the United States, but a zoonotic reservoir exists in the southern flying squirrel, and sporadic sylvatic epidemic typhus cases are reported when they invade houses.
Scrub Typhus Group Rickettsioses
Scrub typhus can be transmitted by many species of trombiculid mites encountered in high grass and brush and is endemic to northern Japan, Southeast Asia, Indonesia, eastern Australia, China, several parts of south-central Russia, India, and Sri Lanka; rare cases have been reported from the United Arab Emirates and Chile. More than 1 million cases occur annually, often in farmers or other occupationally exposed people. Most travel-acquired cases of scrub typhus are reported after visits to rural areas in countries where O. tsutusgamushi is endemic, but urban cases have also been described.
Ehrlichiosis and anaplasmosis are tickborne infections most commonly reported in the United States, but pathogenic species can be found in many regions of the world. A variety of species are implicated in infection, but E. chaffeensis and A. phagocytophilum are most common. Infections with various Ehrlichia and Anaplasma spp. have also been reported in Europe, Africa, Asia, and South America.
Neoehrlichia mikurensis is a tickborne pathogen that occurs in many parts of Europe and Asia. It generally infects older or immunocompromised people. Sennetsu fever, caused by Neorickettsia sennetsu, occurs in Japan, Malaysia, and possibly other parts of Asia. This disease can be contracted from eating raw fish infected with neorickettsiae-infected flukes.
Table 4-19. Classification, primary arthropod vector, and host association of Rickettsiales known to cause disease in humans
|ANTIGENIC GROUP||DISEASE||SPECIES||VECTOR||ANIMAL RESER-
|Anaplasma||Human anaplasmosis||Anaplasma phagocytophilum||Tick||Small mammals, rodents, deer||Primarily United States, worldwide|
|Ehrlichia||Human ehrlichosis||E. chaffeensis
E. muris muris
Deer, wild and domestic dogs, domestic ruminants, rodents
|United States, possibly elsewhere in world|
|Human ehrlichosis||E. muris eauclairensis
|Worldwide; human cases in Venezuela, Costa Rica|
|Neoehrlichia||Neoehrlichiosis||Neoehrlichia mikurensis||Tick||Rodents||Europe, Asia|
|Neorickettsia||Sennetsu fever||Neorickettsia sennetsu||Trematode||Fish||Japan, Malaysia, possibly other parts of Asia|
|Scrub typhus||Scrub typhus||Orientia tsutsugamushi||Larval mite (chigger)||Rodents||Asia-Pacific region from maritime Russia and China to Indonesia and North Australia to Afghanistan; recently recognized in Chile as well as some countries of Africa|
|Orientia chuto||Unknown||Unknown||United Arab Emirates|
|Spotted fever||Rickettsiosis||Rickettsia aeschliman-
|Tick||Unknown||South Africa, Morocco, Mediterranean littoral|
|African tick-bite fever||R. africae||Tick||Ruminants||Sub-Saharan Africa, West Indies|
|Rickettsialpox||R. akari||Mite||House mice, wild rodents||Countries of the former Soviet Union, South Africa, Korea, Turkey, Balkan countries, North and South America|
|Queensland tick typhus||R. australis||Tick||Rodents||Australia, Tasmania|
|Mediterranean spotted fever or Boutonneuse fever||R. conorii1||Tick||Dogs, rodents||Southern Europe, southern and western Asia, Africa, India|
|Cat flea rickettsiosis||R. felis||Flea||Domestic cats, rodents, opossums||Europe, North and South America, Africa, Asia|
|Far Eastern spotted fever||R. heilong-
|Tick||Rodents||Far East of Russia, Northern China, eastern Asia|
|Aneruptive fever||R. helvetica||Tick||Rodents||Central and northern Europe, Asia|
|Flinders Island spotted fever, Thai tick typhus||R. honei, including strain "marmionii"||Tick||Rodents, reptiles||Australia, Thailand|
|Japanese spotted fever||R. japonica||Tick||Rodents||Japan|
|Mediterranean spotted fever-like disease||R. massiliae||Tick||Unknown, possibly dogs||France, Greece, Spain, Portugal, Switzerland, Siciliy, central Africa, Mali, United States|
|Mediterranean spotted fever-like illness||R. monacensis||Tick||Lizards, possibly birds||Europe, North Africa|
|Maculatum infection||R. parkeri||Tick||Rodents||North and South America|
|Tickborne lymphadenopathy (TIBOLA), Dermcentor-borne necrosis and lymphadenopathy (DEBONEL)||R. raoultii||Tick||Unknown||Europe, Asia|
|Rocky Mountain spotted fever; Brazilian spotted fever, febre maculosa, São Paulo exanthematic typhus, Minas Gerais exanthematic typhus||R. rickettsia||Tick||Rodents||North, Central, and South America|
|North Asian tick typhus, Siberian tick typhus||R. sibirica||Tick||Rodents||Russia, China, Mongolia|
|Lymphangitis-associated rickettsiosis||R. sibirica mongolotimonae||Tick||Rodents||Southern France, Portugal, China, Africa|
|TIBOLA, DEBONEL||R. slovaca||Tick||Lagomorphs, rodents, European boar||Southern and eastern Europe, Asia; recently in US tick colony (unknown origin)|
Epidemic typhus, sylvatic typhus
Human body louse, flying squirrel ecto-
Humans, flying squirrels
Central Africa; Asia; North, Central and South America
Temperate, tropical and subtropical areas worldwide
1 Includes 4 proposed subspecies that can be distinguished serologically and by PCR assay and that are the etiologic agents of Boutonneuse fever and Mediterranean tick fever in southern Europe and Africa (R. conorii subsp. conorii), Indian tick typhus in South Asia (R. conorii subsp. indica), Israeli tick typhus in southern Europe and Middle East (R. conorii subsp. israelensis), and Astrakhan spotted fever in the North Caspian region of Russia (R. conorii subsp. caspiae), respectively.
Rickettsial diseases are difficult to diagnose, even by health care providers experienced with these diseases. Most symptomatic rickettsial diseases cause moderate illness, but some Rocky Mountain and Brazilian spotted fevers, Mediterranean spotted fever, scrub typhus, and epidemic typhus may be fatal in 20%–60% of untreated cases. Prompt treatment is essential and results in improved outcomes.
Clinical presentations vary with the causative agent and patient; however, common symptoms that typically develop within 1–2 weeks of infection include fever, headache, malaise, rash, nausea, or vomiting. Many rickettsioses are accompanied by a maculopapular, vesicular, or petechial rash or sometimes an eschar at the site of the tick or mite bite.
African tick-bite fever is typically milder than some other rickettsioses, and recovery is improved with treatment. It should be suspected in a patient who presents with fever, headache, myalgia, and an eschar (tache noir) after recent travel to southern Africa. Mediterranean spotted fever is a potentially life-threatening rickettsial infection and should be suspected in patients with fever, rash, and eschar after recent travel to northern Africa or the Mediterranean basin. Rocky Mountain spotted fever is characterized by fever, headache, nausea, and abdominal pain. A rash is commonly reported but eschars are not.
Patients with murine or epidemic typhus usually present with a severe but nonspecific febrile illness, and approximately half present with a rash. Scrub typhus should be suspected in patients with a fever, headache, and myalgia after recent travel to Asia. Eschar, lymphadenopathy, cough, and encephalitis may be present.
Ehrlichiosis and anaplasmosis should be suspected in febrile patients with leukopenia with an exposure history. The clinical signs are similar to those of the rickettsioses.
Diagnosis is usually based on clinical recognition, epidemiologic context, and serologic testing. Serologic testing provides much stronger evidence when acute- and convalescent-phase serum samples are compared; a >4-fold rise in titer is diagnostic in indirect immunofluorescence antibody assays. Because of cross-reactivity of antigens, some antibodies may react in group-targeted serologic tests and provide evidence of exposure to the group level. PCR assays and immunohistochemical analyses may also be helpful, but useful results are highly dependent upon the type and timing of specimen submitted.
If an eschar is present, a swab or biopsy sample of the lesion can be evaluated by PCR and provides a species-specific diagnosis. If ehrlichiosis or anaplasmosis is suspected, PCR of a whole blood specimen provides the best diagnostic test. A buffy coat may provide presumptive evidence of infection if examined to identify characteristic intraleukocytic morulae. Ehrlichiosis, anaplasmosis, and spotted fever rickettsiosis are nationally notifiable diseases in the United States. Commercial laboratories offer rickettsial testing for rickettsioses, anaplasmosis, ehrlichiosis, and scrub typhus. However, some species-targeted serologic tests are not routinely available at commercial laboratories and are available only through the Rickettsial Branch at CDC (call 1-800-CDC-INFO).
Treatment of patients with possible rickettsioses should begin when the disease is suspected and while awaiting confirmatory testing, as certain infections can be rapidly progressive and fatal. Immediate empiric treatment with a tetracycline is recommended for all ages, most commonly doxycycline. Chloramphenicol may be an alternative in some cases, but its use is associated with increased risk of death, particularly from R. rickettsii infection, compared with use of a tetracycline. In some areas, tetracycline-resistant scrub typhus has been reported, and azithromycin may be an effective alternative. Limited clinical experience has shown that A. phagocytophilum and R. africae infections respond to treatment with rifampin, which may be an alternative drug for some pregnant or doxycycline-intolerant patients. Expert advice should be sought if alternative agents are being considered.
No vaccine is available for preventing rickettsial infections. Antibiotics are not recommended for prophylaxis of rickettsial diseases and should not be given to asymptomatic people.
Travelers should be instructed to minimize exposure to infectious arthropods during travel (including lice, fleas, ticks, mites) and to animal reservoirs (particularly dogs) when traveling in endemic areas. The proper use of insect or tick repellents on skin or clothing, self-examination after visits to vector-infested areas, and wearing protective clothing are ways to reduce risk. These precautions are especially important for people with underlying conditions that may compromise their immune systems, as these people may be more susceptible to severe disease. For more detailed information, see Chapter 3, Mosquitoes, Ticks & Other Arthropods.
CDC website: www.cdc.gov/ticks
- Biggs, HM, Barton Behravesh C, Bradley KK, Dahlgren FS, Drexler NA, Dumler JS, et al. Diagnosis and management of tickborne rickettsial diseases: Rocky Mountain spotted fever and other spotted fever group rickettsioses, ehrlichiosis, and anaplasmosis—United States: A practical guide for health care and public health professionals. MMWR Recommendations and Reports 2016;65:1–44.
- Cherry CC, Denison AM, Kato CY, Thornton K, CD Paddock. Diagnosis of spotted fever group rickettsioses in U.S. travelers returning from Africa, 2007–2016. Am J Trop Med Hyg. 2018 Jul;99(1):136–42.
- Hendershot EF, Sexton DJ. Scrub typhus and rickettsial diseases in international travelers: a review. Curr Infect Dis Rep. 2009 Jan;11(1):66–72.
- Jensenius M, Davis X, von Sonnenburg F, Schwartz E, Keystone JS, Leder K, et al. Multicenter GeoSentinel analysis of rickettsial diseases in international travelers, 1996–2008. Emerg Infect Dis. 2009 Nov;15(11):1791–8.
- Leshem E, Meltzer E, Schwartz E. Travel-associated zoonotic bacterial diseases. Curr Opin Infect Dis. 2011 Oct;24(5):457–63.
- Li H, Zheng YC, Ma L, Jia N, Jiang BG, Jiang RR, et al. Human infection with a novel tick-borne Anaplasma species in China: a surveillance study. Lancet Infect Dis. 2015 Jun; 15(6):663–70.
- Nachega JB, Bottieau E, Zech F, Van Gompel A. Travel-acquired scrub typhus: emphasis on the differential diagnosis, treatment, and prevention strategies. J Travel Med. 2007 Sep–Oct;14(5):352–5.
- Raoult D, Parola P, editors. Rickettsial Diseases. New York: Informa Healthcare USA; 2007.
- Silaghi C, Beck R, Oteo JA, Pfeffer M, Sprong H. Neoehrlichiosis: an emerging tick-borne zoonosis caused by Candidatus Neoehrlichia mikurensis. Exp Appl Acarol 2016;68: 279–97.
- Strand A, Paddock CD, Rinehart AR, Condit ME, Marus JR, Gillani S, et al. African tick bite fever treated successfully with rifampin in a patient with doxycycline intolerance. Clin Infect Dis 2017;65:1582–4.