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Chapter 3Infectious Diseases Related To Travel
Rickettsial (Spotted & Typhus Fevers) & Related Infections (Anaplasmosis & Ehrlichiosis)
Marina E. Eremeeva, Gregory A. Dasch
INFECTIOUS AGENT
Rickettsial infections are caused by a variety of obligate intracellular, gram-negative bacteria from the genera Rickettsia, Orientia, Ehrlichia, Neorickettsia, and Anaplasma (Table 3-17). Rickettsia are further classified into the typhus group and spotted fever group (SFG), and Orientia makes up the classic scrub typhus group.
MODE OF TRANSMISSION
Most rickettsial pathogens are transmitted by ectoparasites such as fleas, lice, mites, and ticks during feeding or by scratching infectious feces into the skin. Inhaling dust contaminated with dried infected lice or flea feces may also cause infections. The specific vectors that transmit each form of rickettsiae are listed in Table 3-17. Transmission of infection after blood transfusion is rare but has been reported during the asymptomatic incubation period of some diseases.
EPIDEMIOLOGY
All age groups are at risk for rickettsial infections during travel to endemic areas. Transmission is increased during outdoor activities in the spring and summer months when ticks and fleas are most active. However, infection can occur throughout the year. Because of the 5- to 14-day incubation period for most rickettsial diseases, tourists may not necessarily experience symptoms during their trip, and onset may coincide with their return home or develop within a week after returning.
SFG rickettsial infections among travelers include Mediterranean (or Boutonneuse) spotted fever from southern Europe and Africa, Indian tick typhus from India, Astrakhan fever from southeastern Europe and central Africa, Israeli tick typhus from Mediterranean countries, Thai tick typhus from Asia and Australia, Queensland tick typhus and Australian spotted fever from eastern Australia, tickborne lymphadenopathy from European countries, north Asian tick typhus from China and Russia, Rocky Mountain spotted fever and Rickettsia parkeri from the Americas, and African tick-bite fever from Africa and the Caribbean islands. Game hunting and traveling to southern Africa from November through April are risk factors for African tick-bite fever in travelers. Contact with tick-infested dogs in areas endemic for certain SFG rickettsiae may increase the risk of disease. One study estimated that the risk of a traveler contracting a rickettsiosis in southern Africa is 4–5 times higher than that of acquiring malaria.
Rickettsialpox, transmitted by house-mouse mites, circulates in urban centers in Ukraine, South Africa, Korea, Balkan states, and the United States. Outbreaks of rickettsialpox most often occur after contact with infected rodents and their mites, especially during natural die-offs or extermination of infected rodents that causes the mites to seek out new hosts, including humans. The agent may spill over and occasionally be found in other wild rodent populations.
Scrub typhus is endemic in northern Japan, Southeast Asia, the western Pacific Islands, eastern Australia, China, maritime areas and several parts of south-central Russia, India, and Sri Lanka. More than 1 million cases occur annually. Unusual travel-associated cases of scrub typhus have been diagnosed in people returning from Ghana to Japan and from Dubai to Australia. Most travel-acquired cases of scrub typhus occur during visits to rural areas in endemic countries for activities such as camping, hiking, or rafting, but urban cases have also been described.
Fleaborne rickettsioses caused by R. typhi and R. felis are widely distributed, especially throughout the tropics and subtropics and in port cities and coastal regions with rodents. Humans exposed to flea-infested cats, dogs, and peridomestic animals while traveling in endemic regions or entering areas infested with rats are at most risk for fleaborne rickettsioses. Murine typhus has been reported among travelers returning from Asia, Africa, and southern Europe and has also been reported from Hawaii, California, and Texas in the United States.
Epidemic typhus occurs in communities and refugee populations where body lice are prevalent. Outbreaks often occur during the colder months when infested clothing is not laundered. Travelers at most risk for epidemic typhus include those who may work with or visit areas with large homeless populations, impoverished areas, refugee camps, and regions that have recently experienced war or natural disasters. Sylvatic epidemic typhus cases occur only from direct contact with flying squirrels or their nesting materials. Active foci of endemic typhus are known in the Andes regions of South America and in Burundi and Ethiopia. Sylvatic epidemic typhus is also endemic among flying squirrels in the eastern United States. Sylvatic typhus cases occur only from direct contact with flying squirrel ectoparasites or their nest materials. Tick-associated reservoirs of R. prowazekii have been described in Ethiopia, Mexico, and Brazil.
Ehrlichiosis is most commonly reported in the southeastern and south-central United States where the lonestar tick, Amblyomma americanum, and white-tailed deer are commonplace. In Europe and Asia, transmission of monocytic ehrlichiosis may be due to Ehrlichia chaffeensis or related organisms such as E. muris that are associated with ticks of the Ixodes persulcatus complex, found on small rodents and passerine birds. Recent publications indicate that E. chaffeensis or similar agents also circulate in Brazil, Panama, and Africa, and E. muris circulates in the United States.
Anaplasmosis occurs worldwide, corresponding with the ranges of I. persulcatus–group ticks. Known endemic regions include the United States, Europe, China, Russia, and Korea.
Sennetsu fever occurs in Japan, Malaysia, and possibly other parts of Asia. Sennetsu fever can be contracted from eating raw infected fish.
Table 3-17. Classification, primary vector, and reservoir occurrence of rickettsiae known to cause disease in humans
ANTIGENIC GROUP | DISEASE | SPECIES | VECTOR | ANIMAL RESER- VOIR(S) |
GEOGRAPHIC DISTRIBUTION |
---|---|---|---|---|---|
Anaplasma | Human granulocytic anaplas- mosis |
Anaplasma phagocyto- philum |
Tick | Deer, elk, small mammals, and rodents | &Worldwide |
Ehrlichia | Human monocytic ehrlichosis | Ehrlichia chaffeensis | Tick | Deer, wild and domestic dogs, domestic ruminants, and rodents | Worldwide |
Ehrlichosis | E. muris | Tick | Deer and rodents | Western United States, Russia, Japan | |
Ehrlichosis | E. ewingii | Tick | Deer, wild and domestic dogs, and rodents | North America | |
Neorick- ettsia |
Sennetsu fever | Neorickett- sia sennetsu |
Trema- tode |
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 |
Spotted fever | Rickettsiosis | Rickettsia aeschliman- nii |
Tick | Unknown | South Africa, Morocco, Mediterranean littoral |
African tick-bite fever | R. africae | Tick | Ruminants | Sub-Saharan Africa, West Indies | |
Rickettsial- pox |
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 | |
Mediterran- ean spotted fever or Bouton- neuse 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- jiangensis |
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 | Tick | Unknown | Australia, Thailand | |
Japanese spotted fever | R. japonica | Tick | Rodents | Japan | |
Australian spotted fever | R. marmionii | Tick | Rodents, reptiles | Australia | |
Mediterran- ean spotted fever-like disease |
R. massiliae | Tick | Unknown | France, Greece, Spain, Portugal, Switzerland, Siciliy, central Africa, and Mali | |
Maculatum infection | R. parkeri | Tick | Rodents | North and South America | |
Rocky Mountain spotted fever, febre maculosa, São Paulo exanthem- atic typhus, Minas Gerais exanthem- atic typhus, Brazilian spotted fever |
R. rickettsii | Tick | Rodents | North, Central, and South America | |
North Asian tick typhus, Siberian tick typhus | R. sibirica | Tick | Rodents | Russia, China, Mongolia | |
Lymphan- gitis-associated rickettsiosis |
R. sibirica mongolotim- onae |
Tick | Rodents | Southern France, Portugal, China, sub-Saharan Africa | |
Tick-borne lymphaden- opathy (TIBOLA), Dermacent- or-borne necrosis and lymphaden- opathy (DEBONEL) |
R. slovaca | Tick | Lagomorphs, rodents | Southern and eastern Europe, Asia | |
Typhus fever |
Epidemic typhus, sylvatic typhus
Murine typhus |
R. prowazekii
R. typhi |
Human body louse, flying squirrel ecto- Flea |
Humans, flying squirrels
Rodents |
Central Africa, Asia, Central, North, and South America
Tropical and subtropical areas worldwide |
1Includes 4 different subspecies that can be distinguished serologically and by PCR assay and respectively 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).
CLINICAL PRESENTATION
Although the clinical presentations vary with the causative agent, some common symptoms that typically develop within 1–2 weeks of infection include fever, headache, malaise, and sometimes nausea and vomiting. Most symptoms associated with acute rickettsial infections are nonspecific and require further tests to make an accurate diagnosis. Most tick-transmitted rickettsioses are accompanied by a maculopapular, vesicular, or petechial rash or an eschar at the site of the tick bite. While many rickettsial diseases cause mild or moderate illness, epidemic typhus and Rocky Mountain spotted fever can be severe and may be fatal in 20%–60% of untreated cases.
DIAGNOSIS
If clinical symptoms and the epidemiologic history are compatible with rickettsial infections, the following diagnostic tests should be used during the acute stage of illness and at the time antibiotic treatment is initiated:
- PCR test on skin biopsy of rash or eschar or EDTA whole blood
- Specific immunohistologic detection of rickettsiae in skin biopsy of rash or eschar
The diagnosis can be confirmed at a later time by testing acute- and convalescent-phase serum from the patient or by isolation of a rickettsial agent by culture from samples collected at initial suspicion of disease. In patients suspected of having rickettsial disease, an acute-phase serum should be drawn and held in case serology is warranted at a later time. Most serum specimens collected during the acute stage of rickettsial diseases do not contain significant titers of antirickettsial antibodies, although immune responses to scrub typhus rickettsiae can be rapid. Detection of IgM class antibody alone should not be interpreted as recent exposure to the rickettsial agents and should be confirmed by detection of IgG or, preferably, IgG seroconversion by parallel evaluation with a convalescent-phase serum collected 4–6 weeks after onset of the illness. Contact the CDC Rickettsial Zoonoses Branch at 404-639-1075 for further information about testing and patient management.
TREATMENT
Diagnosing a rickettsial infection can be difficult, but early treatment with appropriate antibiotic therapy is critical for rapid recovery. Treatment must be based on clinical suspicion and not be delayed pending results of laboratory tests. The standard treatment regimen consists of 200 mg of doxycycline daily for 3–14 days or 2.2 mg/kg body weight per dose administered twice a day (orally or intravenously) for children weighing <45.4 kg (100 lb). However, the specific type and duration of antibiotic administered may vary, depending on the disease and kinetics of defervescence.
Antibiotics of the tetracycline class (doxycycline in particular) have a high degree of efficacy and low toxicity in treating rickettsial infections, even in children and pregnant women. Depending on the specific pathogen, chloramphenicol, azithromycin, fluoroquinolones, and rifampin may also be considered, but these are not universally effective for all rickettsial agents, nor have they been evaluated by controlled clinical trials.
PREVENTIVE MEASURES FOR TRAVELERS
No vaccines or drugs are available for preventing rickettsial infections. Antibiotics are not recommended for prophylaxis of rickettsial diseases and should not be prescribed to asymptomatic people exposed to ticks.
The best prevention is to minimize exposure to infectious arthropods (particularly lice, fleas, ticks, mites) and animal reservoirs, particularly dogs and cats, when traveling in endemic areas. The proper use of insect repellents, 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 2, Protection against Mosquitoes, Ticks, and Other Insects and Arthropods.
BIBLIOGRAPHY
- Dumler JS, Madigan JE, Pusterla N, Bakken JS. Ehrlichioses in humans: epidemiology, clinical presentation, diagnosis, and treatment. Clin Infect Dis. 2007 Jul 15;45 Suppl 1:S45–51.
- 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.
- Jensenius M, Fournier PE, Raoult D. Rickettsioses and the international traveler. Clin Infect Dis. 2004 Nov 15;39(10):1493–9.
- Jensenius M, Fournier PE, Raoult D. Tick-borne rickettsioses in international travellers. Int J Infect Dis. 2004 May;8(3):139–46.
- 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.
- Paddock CD, Eremeeva ME. Rickettsialpox. In: Raoult D, Parola P, editors. Rickettsial Diseases. New York: Informa Healthcare USA, Inc; 2007. p. 63–86.
- Parola P, Paddock CD, Raoult D. Tick-borne rickettsioses around the world: emerging diseases challenging old concepts. Clin Microbiol Rev. 2005 Oct;18(4):719–56.
- Raoult D, Parola P, editors. Rickettsial Diseases. New York: Informa Healthcare USA, Inc; 2007.
- Roch N, Epaulard O, Pelloux I, Pavese P, Brion JP, Raoult D, et al. African tick bite fever in elderly patients: 8 cases in French tourists returning from South Africa. Clin Infect Dis. 2008 Aug 1;47(3):e28–35.
- Walker DH. Rickettsial diseases in travelers. Travel Med Infect Dis. 2003 Feb;1(1):35–40.
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