The Journal of Emergency Medicine, Vol. 48, No. 5, pp. 562–565, 2015 Copyright Ó 2015 Elsevier Inc. Printed in the USA. All rights reserved 0736-4679/$ - see front matter
http://dx.doi.org/10.1016/j.jemermed.2014.12.044
Clinical Communications: Adults AFRICAN TICK-BITE FEVER IN A RETURNING TRAVELER William D. Binder, MD* and Rajat Gupta, MD† *Alpert School of Medicine, Brown University, Department of Emergency Medicine, 125 Whipple Street, Providence, RI 02902 and †Department of Cardiology, Brigham and Women’s Hospital, Boston, Massachusetts Reprint Address: William D. Binder, MD, Alpert School of Medicine, Brown University, Department of Emergency Medicine, 125 Whipple Street, Providence, RI 02902
, Abstract—Background: African tick bite fever (ATBF) is an emerging infection endemic to sub-Saharan Africa and increasingly noted in travelers to the region. Case Report: We present a case of ATBF in a 63-year-old man who presented with complaints of a rash and fever to the emergency department. Why Should an Emergency Physician be Aware of This?: Rickettsial diseases are increasingly common and are seen on every continent except Antarctica. Many factors are contributing to their prevalence, and they have become the second most common cause of fever behind malaria in the traveler returning from Africa. Due to the global distribution of rickettsial diseases, as well as increasing international travel, emergency physicians might encounter ill and febrile travelers. A careful travel history and examination will enable the emergency physician to consider spotted fever group rickettsial diseases in their differential diagnosis for single and multiple eschars. Ó 2015 Elsevier Inc.
CASE PRESENTATION A 63-year-old man presented to the emergency department with fever, myalgias, and a rash 2 weeks after returning from travel to India and South Africa. He stayed primarily in large cities in India for 3 weeks, followed by 1 week on a private game reserve safari in Kwa-zulu Natal. He was well during the trip, but did notice multiple mosquito bites on his legs. He did not notice any tick bites. Five days after his return, he was moving boxes and noticed generalized stiffness and soreness but without fever. Two days later, he developed fevers, chill, and nightsweats, as well as arthralgias. One week after the onset of symptoms, and 12 days after returning from South Africa, he noticed a quarter-sized erythematous lesion on his left hip. The following day he was febrile to 101 F, and he presented to our emergency department. The patient states that he spent about 4 h each morning on the game reserve, and then would retire to his hotel, and then would again go out on safari in the evening. He did not get out of his vehicle or have direct contact with animals. He denies drinking unpasteurized milk, he did not swim in local water, and he drank only bottled water. He was not using malaria prophylaxis. Medical history includes hypertension, left retinal artery occlusion, and his only medications are aspirin, hydrochlorothiazide, and lisinopril. He has no known drug allergies. The patient has an extensive travel
, Keywords—African tick bite fever; rickettsia
INTRODUCTION Fever and rash are common complaints of returning travelers. Epidemiology, geography, time course, physical diagnosis, and laboratory tests are important components of a successful emergency department diagnosis and are crucial in differentiating between the many emerging illnesses facing travelers throughout the world.
RECEIVED: 31 August 2014; FINAL SUBMISSION RECEIVED: 11 October 2014; ACCEPTED: 21 December 2014 562
African Tick-Bite Fever
history—he had served in the merchant marines in his 20s—and he has made > 30 trips to Africa and has visited this particular game reserve about 10 times. On physical examination, the patient had a temperature of 100.5 F, pulse 94 beats/min, and his blood pressure was 126/67 mm Hg. He was alert, well appearing, and conversant, and his HEENT (head, ears, eyes, nose, and throat) examination was unremarkable, with anicteric sclera, no conjunctival injection, and a clear oropharynx. His neck was supple and without adenopathy. His lungs were clear to auscultation, his heart examination demonstrated a normal s1s2 and he had a regular rate and rhythm, with no murmurs or rubs. His abdomen was soft, nontender, and there was no hepatosplenomegaly. His skin examination was remarkable for a 2-cm erythematous lesion with a black center on his left lateral hip. There was no fluctuance, it was minimally tender, and there was no associated lymphadenopathy in the inguinal area. He had several erythematous papules on his chest wall and neck. He had several scattered crusted papules on his lower extremities. Laboratory examination revealed a white blood cell count of 5600 with 48% polymorphonuclear leukocytes, 20% bands, 21 % lymphocytes, 10% monocytes, and no eosinophils. His chemistry examination was normal with a blood urea nitrogen of 21 mg/dL, and creatinine of 1.05 mg/dL. His liver enzymes were mildly elevated with an aspartate aminotransferase of 88 IU/L, and an alanine aminotransferase of 72 IU/L. A thick and thin smear was negative for malaria and babesia. A human immunodeficiency virus test was nonreactive. The patient had a rickettsial spotted fever group titer sent (Rickettsia rickettsii, Rickettsia akari, and Rickettsia conorii), which were initially negative, but at 4 weeks were IgM positive at 1:64 and IgG 1:256. R. Conorii cross reacts with Rickettsia africae and the final diagnosis of African tick bite fever (ATBF) due to R. africae was made in the patient. He was treated with doxycycline and his symptoms abated. DISCUSSION Rickettsia are classified primarily into the spotted fever group rickettsia and the typhus group rickettsia (1). While other rickettsiae groups exist as well, the tickborne rickettsioses, which belong to the spotted fever group of the rickettsia, have increased dramatically over the past several decades and numerous studies have postulated reasons for the increase in tickborne disease. Better detection methods, climate change, land use patterns, and widespread travel have led to an unprecedented resurgence in tickborne illness in every continent except Antarctica (2). In North America, the preceding factors, as well as an increased deer population, and the decreased
563
population of land-based mammals feeding on mice have all likely led to the increase in tick and human interaction, causing an increase in recognition of tickborne diseases (3). R africae, the causal agent of ATBF, is an obligate intracellular gram-negative bacteria. It is carried by the ticks of the genus, Amblyomma, and is distributed broadly across sub-Saharan Africa, where it has been detected in ticks as well as humans in > 20 sub-Saharan African countries (1). The disease was recognized in the early 20th century primarily as a rural illness and was associated with the ticks of cattle and game. It was isolated as an organism in 1990 and the first proven case of human infection was noted in 1992 (4). Before the organism’s isolation, it was believed that ATBF was caused by R. connori, the causal agent of Mediterranean spotted fever (5). The disease has had a global impact—it has been reported in numerous North African countries and has been noted in Australia, New Caledonia, and in Asia (6,7). Although the tick vector was imported into Guadalupe in the 1800s via Senegalese cattle, the first case was not reported in the Western hemisphere until 1998 (1,8). Since this initial description, the organism has been detected in Amblyomma variegatum ticks throughout the Caribbean (1). ATBF in North America and Europe is usually acquired by tourists, hunters, or deployed military members returning from areas where the disease is endemic. A study of travelers from sub-Saharan Africa reported by the GeoSentinel network found that it was the second most common cause of systemic fever in travelers returning from sub-Saharan Africa (9). Like many tickborne diseases, it begins about 5 7 days after a tick bite, with initial onset of myalgias, fatigue, headache, and fever. Inoculation eschars, the tache noire—an ulcerated black-crusted eschar with a red halo—are common, and are the sine qua non of the disease (Figure 1). After the bite of an infected tick, the rickettsia proliferate within the endothelial cells at the site of the original bite, leading to a localized vasculitis and the formation of an eschar (10). Multiple eschars are typical of the aggressive biting habits of the Amblyomma genus of ticks. An eschar is also commonly seen in Mediterranean (Bouttoneuse) spotted fever. Although not highly specific, the eschar is quite suggestive of ATBF, given the appropriate epidemiologic setting. Anywhere from 50% 100% of patients are affected. Other infectious and noninfectious causes of eschar are noted in Table 1 (1,11 14). Once again, time course of disease onset, severity of illness, and travel history are vital in helping to differentiate between these eschar-forming diseases. Other common features include a generalized maculopapular, or perhaps a papulovesicular, rash, as well as
564
W. D. Binder and R. Gupta
Diagnosis of ATBF is primarily a clinical diagnosis. Secondary laboratory findings can include a mildly elevated C-reactive protein, lymphopenia, and occasionally thrombocytopenia. Liver function tests may be slightly elevated. Biopsy and culture from an eschar, as well as polymerase chain reaction of cutaneous swabs, are two newer methods of diagnosis, but these are performed in specialized laboratories. Immunofluorescence assays are the most widely used microbiologic tests. While no commercially available test for ATBF exists, due to extensive cross reactivity between spotted fever groups, the detection of R. conorii antibodies are highly suggestive of R. africae in the appropriate clinical setting (16). Doxycycline remains the standard treatment for ATBF as well as other rickettsial diseases. Fluoroquinalones, while known to have an in vitro effect, have a potentially deleterious effect because it may upregulate a toxinantitoxin module (1). Clarithromycin, erythromycin, and telithromycin all have strong in vitro effect, and may be good options for children and pregnant woman (1). Pristinamycin has been noted to be quite effective, as well (17). Figure 1. Pustule and eschar associated with African tick bite fever.
regional lymphadenopathy. Aphthous stomatitis has been reported as well. While the disease is not usually fatal, severe manifestations, including myocarditis, neuropathy, and internuclear ophthalmoplegia have been reported. There is some evidence that in the elderly population the disease may have more virulent characteristics (15). Table 1. Infectious and Noninfectious Causes of Eschar Cutaneous anthrax Tularemia Disseminated fungal infection Spotted fever group Rickettsiae Tsutsugamushi or scrub typhus Spider bite Trauma Burn Phosgene oxime Ecthyma Diabetes Capnocytophaga Leukocytoplastic vasculitis Transdermal testosterone patch, bloodroot, other medications
Bacillus anthracis Francisella tularensis Blastomycosis, mucormycosis, aperigillosis R. parkeri, conorii, akari, felis, africae, phillipi (formerly 364D), and multiple others Orientia tsutsugamushi Brown recluse Pressure skin necrosis Thermal skin necrosis Chemical weapon Often caused by B-hemolytic streptococcus Multiple organisms Gram negative Multiple causes including immune complex deposition Chemical skin necrosis
WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS? ATBF is a well-established yet emerging cause of fever and illness in travelers to sub-Saharan Africa, as well as to countries around the globe. Clusters of outbreaks may occur in returning travelers. However, due to the rarity of this illness in nonendemic settings, serum testing for this tickborne disease is often delayed. In one report of French tourists returning from Africa, median time from illness onset to serum testing was 19 days, and none of the travelers reported a tick bite (18). Approximately 1 billion persons travel worldwide, and in the United States there are 60 million travelers annually, with almost 30 million traveling overseas. Of these, > 1% travel to Africa (19). It is likely that emergency physicians will encounter febrile travelers. Through a careful travel history and physical examination, emergency physicians can include spotted fever group rickettsial diseases in their differential diagnosis for single and multiple eschars in the traveler returning from Africa (20). REFERENCES 1. Parola P, Paddock CD, Socolovschi C, et al. Update on tick-borne rickettsioses around the world: a geographic approach. Clin Microbiol Rev 2013;26:657–702. 2. Dumler S. Fitness and freezing: vector biology and human health. J Clin Invest 2010;120:3087–90. 3. Pfaffie M, Littwin N, Muders SV, Petney TN. The ecology of tickborne diseases. Int J Parasitol 2013;43:1059–77.
African Tick-Bite Fever 4. Jackson Y, Chappuis F, Loutan L. African tick-bite fever: four cases among Swiss travelers returning from South Africa. J Travel Med 2004;11:225–30. 5. Parola P, Inokuma H, Camicas J-L, Brouqui P, Raoult D. Detection and identification of spotted fever group Rickettsiae and Ehrlichiae in African ticks. Emerg Infect Dis 2001;7: 1014–7. 6. Kernif T, Socolovschi C, Bitam I, Raoult D, Parola P. Vector-borne rickettsioses in North Africa. Infect Dis Clin N Am 2012;26: 455–78. 7. Eldin C, Mediannikov O, Bavoust B, et al. Emergence of Rickettsia africae, Oceania. Emerg Infect Dis 2011;17:100–2. 8. Mediannikov O, Trape JF, Diatta G, Parola P, Fournier PE, Raoult D. Rickettsia africae, Western Africa. Emerg Infect Dis 2010;16:571–3. 9. Jensenius M, Davis X, von Sonnenburg F, et al. Multicenter geosentinel analysis of rickettsial diseases in international travelers, 19962008. Emerg Infect Dis 2009;15:1791–8. 10. Shelley J. Rash and eschars in a returning traveller. Clin Exp Dermatol 2011;36:222–4. 11. Sundriyal D, Kumar N, Chandraskinaran A, Sharma B. Eschar: an important clue to diagnosis. BMJ Case Rep 2013; http:// dx.doi.org/10.1136/bcr-2013-010105.
565 12. Orme C, Imaeda S. Eschar formation from testosterone patch. N Engl J Med 2012;366:e28. 13. Jellinek N, Maloney ME. Escharotic and other botanical agents for the treatment of skin cancer: a review. J Am Acad Dermatol 2005; 53:487–95. 14. Sunderkotter C, Bonsmann G, Sindrilaru A, Luger T. Management of leukocytoplastic vasculitis. J Dermatol Treat 2005;16:193–206. 15. Roch N, Epaulard O, Pelloux I, et al. African tick bite fever in elderly patients: 8 cases in French tourists returning from South Africa. Clin Infect Dis 2008;47:e28–35. 16. Fujisawa T, Kadosaka T, Fujito H, et al. Rickettsia africae infection in a Japanese traveller with many tick bites. Acta Dermatovenereol 2012;92:443–4. 17. Mechai F, Han Y, Gachot B, et al. Pristinamycin for Rickettsia africae infection. J Travel Med 2009;16:136–7. 18. Consigny PH, Rotain JM, Mizzi D, Raoult D. African tick bite fever in French travelers. Emerg Infect Dis 2005;11:1805–6. 19. US Travel and Tourism Advisory Board. Travel Statistics. Available at: travel.trade.gov/view/m-2013-O-001/index.html. Accessed July 19, 2014. 20. Raoult D, Fournier P, Fenollar F, et al. Rickettsia africae, a tickborne pathogen in travelers to sub-Saharan Africa. N Engl J Med 2001;344:1504–10.
http://dx.doi.org/10.1016/j.jemermed.2014.12.044
Clinical Communications: Adults AFRICAN TICK-BITE FEVER IN A RETURNING TRAVELER William D. Binder, MD* and Rajat Gupta, MD† *Alpert School of Medicine, Brown University, Department of Emergency Medicine, 125 Whipple Street, Providence, RI 02902 and †Department of Cardiology, Brigham and Women’s Hospital, Boston, Massachusetts Reprint Address: William D. Binder, MD, Alpert School of Medicine, Brown University, Department of Emergency Medicine, 125 Whipple Street, Providence, RI 02902
, Abstract—Background: African tick bite fever (ATBF) is an emerging infection endemic to sub-Saharan Africa and increasingly noted in travelers to the region. Case Report: We present a case of ATBF in a 63-year-old man who presented with complaints of a rash and fever to the emergency department. Why Should an Emergency Physician be Aware of This?: Rickettsial diseases are increasingly common and are seen on every continent except Antarctica. Many factors are contributing to their prevalence, and they have become the second most common cause of fever behind malaria in the traveler returning from Africa. Due to the global distribution of rickettsial diseases, as well as increasing international travel, emergency physicians might encounter ill and febrile travelers. A careful travel history and examination will enable the emergency physician to consider spotted fever group rickettsial diseases in their differential diagnosis for single and multiple eschars. Ó 2015 Elsevier Inc.
CASE PRESENTATION A 63-year-old man presented to the emergency department with fever, myalgias, and a rash 2 weeks after returning from travel to India and South Africa. He stayed primarily in large cities in India for 3 weeks, followed by 1 week on a private game reserve safari in Kwa-zulu Natal. He was well during the trip, but did notice multiple mosquito bites on his legs. He did not notice any tick bites. Five days after his return, he was moving boxes and noticed generalized stiffness and soreness but without fever. Two days later, he developed fevers, chill, and nightsweats, as well as arthralgias. One week after the onset of symptoms, and 12 days after returning from South Africa, he noticed a quarter-sized erythematous lesion on his left hip. The following day he was febrile to 101 F, and he presented to our emergency department. The patient states that he spent about 4 h each morning on the game reserve, and then would retire to his hotel, and then would again go out on safari in the evening. He did not get out of his vehicle or have direct contact with animals. He denies drinking unpasteurized milk, he did not swim in local water, and he drank only bottled water. He was not using malaria prophylaxis. Medical history includes hypertension, left retinal artery occlusion, and his only medications are aspirin, hydrochlorothiazide, and lisinopril. He has no known drug allergies. The patient has an extensive travel
, Keywords—African tick bite fever; rickettsia
INTRODUCTION Fever and rash are common complaints of returning travelers. Epidemiology, geography, time course, physical diagnosis, and laboratory tests are important components of a successful emergency department diagnosis and are crucial in differentiating between the many emerging illnesses facing travelers throughout the world.
RECEIVED: 31 August 2014; FINAL SUBMISSION RECEIVED: 11 October 2014; ACCEPTED: 21 December 2014 562
African Tick-Bite Fever
history—he had served in the merchant marines in his 20s—and he has made > 30 trips to Africa and has visited this particular game reserve about 10 times. On physical examination, the patient had a temperature of 100.5 F, pulse 94 beats/min, and his blood pressure was 126/67 mm Hg. He was alert, well appearing, and conversant, and his HEENT (head, ears, eyes, nose, and throat) examination was unremarkable, with anicteric sclera, no conjunctival injection, and a clear oropharynx. His neck was supple and without adenopathy. His lungs were clear to auscultation, his heart examination demonstrated a normal s1s2 and he had a regular rate and rhythm, with no murmurs or rubs. His abdomen was soft, nontender, and there was no hepatosplenomegaly. His skin examination was remarkable for a 2-cm erythematous lesion with a black center on his left lateral hip. There was no fluctuance, it was minimally tender, and there was no associated lymphadenopathy in the inguinal area. He had several erythematous papules on his chest wall and neck. He had several scattered crusted papules on his lower extremities. Laboratory examination revealed a white blood cell count of 5600 with 48% polymorphonuclear leukocytes, 20% bands, 21 % lymphocytes, 10% monocytes, and no eosinophils. His chemistry examination was normal with a blood urea nitrogen of 21 mg/dL, and creatinine of 1.05 mg/dL. His liver enzymes were mildly elevated with an aspartate aminotransferase of 88 IU/L, and an alanine aminotransferase of 72 IU/L. A thick and thin smear was negative for malaria and babesia. A human immunodeficiency virus test was nonreactive. The patient had a rickettsial spotted fever group titer sent (Rickettsia rickettsii, Rickettsia akari, and Rickettsia conorii), which were initially negative, but at 4 weeks were IgM positive at 1:64 and IgG 1:256. R. Conorii cross reacts with Rickettsia africae and the final diagnosis of African tick bite fever (ATBF) due to R. africae was made in the patient. He was treated with doxycycline and his symptoms abated. DISCUSSION Rickettsia are classified primarily into the spotted fever group rickettsia and the typhus group rickettsia (1). While other rickettsiae groups exist as well, the tickborne rickettsioses, which belong to the spotted fever group of the rickettsia, have increased dramatically over the past several decades and numerous studies have postulated reasons for the increase in tickborne disease. Better detection methods, climate change, land use patterns, and widespread travel have led to an unprecedented resurgence in tickborne illness in every continent except Antarctica (2). In North America, the preceding factors, as well as an increased deer population, and the decreased
563
population of land-based mammals feeding on mice have all likely led to the increase in tick and human interaction, causing an increase in recognition of tickborne diseases (3). R africae, the causal agent of ATBF, is an obligate intracellular gram-negative bacteria. It is carried by the ticks of the genus, Amblyomma, and is distributed broadly across sub-Saharan Africa, where it has been detected in ticks as well as humans in > 20 sub-Saharan African countries (1). The disease was recognized in the early 20th century primarily as a rural illness and was associated with the ticks of cattle and game. It was isolated as an organism in 1990 and the first proven case of human infection was noted in 1992 (4). Before the organism’s isolation, it was believed that ATBF was caused by R. connori, the causal agent of Mediterranean spotted fever (5). The disease has had a global impact—it has been reported in numerous North African countries and has been noted in Australia, New Caledonia, and in Asia (6,7). Although the tick vector was imported into Guadalupe in the 1800s via Senegalese cattle, the first case was not reported in the Western hemisphere until 1998 (1,8). Since this initial description, the organism has been detected in Amblyomma variegatum ticks throughout the Caribbean (1). ATBF in North America and Europe is usually acquired by tourists, hunters, or deployed military members returning from areas where the disease is endemic. A study of travelers from sub-Saharan Africa reported by the GeoSentinel network found that it was the second most common cause of systemic fever in travelers returning from sub-Saharan Africa (9). Like many tickborne diseases, it begins about 5 7 days after a tick bite, with initial onset of myalgias, fatigue, headache, and fever. Inoculation eschars, the tache noire—an ulcerated black-crusted eschar with a red halo—are common, and are the sine qua non of the disease (Figure 1). After the bite of an infected tick, the rickettsia proliferate within the endothelial cells at the site of the original bite, leading to a localized vasculitis and the formation of an eschar (10). Multiple eschars are typical of the aggressive biting habits of the Amblyomma genus of ticks. An eschar is also commonly seen in Mediterranean (Bouttoneuse) spotted fever. Although not highly specific, the eschar is quite suggestive of ATBF, given the appropriate epidemiologic setting. Anywhere from 50% 100% of patients are affected. Other infectious and noninfectious causes of eschar are noted in Table 1 (1,11 14). Once again, time course of disease onset, severity of illness, and travel history are vital in helping to differentiate between these eschar-forming diseases. Other common features include a generalized maculopapular, or perhaps a papulovesicular, rash, as well as
564
W. D. Binder and R. Gupta
Diagnosis of ATBF is primarily a clinical diagnosis. Secondary laboratory findings can include a mildly elevated C-reactive protein, lymphopenia, and occasionally thrombocytopenia. Liver function tests may be slightly elevated. Biopsy and culture from an eschar, as well as polymerase chain reaction of cutaneous swabs, are two newer methods of diagnosis, but these are performed in specialized laboratories. Immunofluorescence assays are the most widely used microbiologic tests. While no commercially available test for ATBF exists, due to extensive cross reactivity between spotted fever groups, the detection of R. conorii antibodies are highly suggestive of R. africae in the appropriate clinical setting (16). Doxycycline remains the standard treatment for ATBF as well as other rickettsial diseases. Fluoroquinalones, while known to have an in vitro effect, have a potentially deleterious effect because it may upregulate a toxinantitoxin module (1). Clarithromycin, erythromycin, and telithromycin all have strong in vitro effect, and may be good options for children and pregnant woman (1). Pristinamycin has been noted to be quite effective, as well (17). Figure 1. Pustule and eschar associated with African tick bite fever.
regional lymphadenopathy. Aphthous stomatitis has been reported as well. While the disease is not usually fatal, severe manifestations, including myocarditis, neuropathy, and internuclear ophthalmoplegia have been reported. There is some evidence that in the elderly population the disease may have more virulent characteristics (15). Table 1. Infectious and Noninfectious Causes of Eschar Cutaneous anthrax Tularemia Disseminated fungal infection Spotted fever group Rickettsiae Tsutsugamushi or scrub typhus Spider bite Trauma Burn Phosgene oxime Ecthyma Diabetes Capnocytophaga Leukocytoplastic vasculitis Transdermal testosterone patch, bloodroot, other medications
Bacillus anthracis Francisella tularensis Blastomycosis, mucormycosis, aperigillosis R. parkeri, conorii, akari, felis, africae, phillipi (formerly 364D), and multiple others Orientia tsutsugamushi Brown recluse Pressure skin necrosis Thermal skin necrosis Chemical weapon Often caused by B-hemolytic streptococcus Multiple organisms Gram negative Multiple causes including immune complex deposition Chemical skin necrosis
WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS? ATBF is a well-established yet emerging cause of fever and illness in travelers to sub-Saharan Africa, as well as to countries around the globe. Clusters of outbreaks may occur in returning travelers. However, due to the rarity of this illness in nonendemic settings, serum testing for this tickborne disease is often delayed. In one report of French tourists returning from Africa, median time from illness onset to serum testing was 19 days, and none of the travelers reported a tick bite (18). Approximately 1 billion persons travel worldwide, and in the United States there are 60 million travelers annually, with almost 30 million traveling overseas. Of these, > 1% travel to Africa (19). It is likely that emergency physicians will encounter febrile travelers. Through a careful travel history and physical examination, emergency physicians can include spotted fever group rickettsial diseases in their differential diagnosis for single and multiple eschars in the traveler returning from Africa (20). REFERENCES 1. Parola P, Paddock CD, Socolovschi C, et al. Update on tick-borne rickettsioses around the world: a geographic approach. Clin Microbiol Rev 2013;26:657–702. 2. Dumler S. Fitness and freezing: vector biology and human health. J Clin Invest 2010;120:3087–90. 3. Pfaffie M, Littwin N, Muders SV, Petney TN. The ecology of tickborne diseases. Int J Parasitol 2013;43:1059–77.
African Tick-Bite Fever 4. Jackson Y, Chappuis F, Loutan L. African tick-bite fever: four cases among Swiss travelers returning from South Africa. J Travel Med 2004;11:225–30. 5. Parola P, Inokuma H, Camicas J-L, Brouqui P, Raoult D. Detection and identification of spotted fever group Rickettsiae and Ehrlichiae in African ticks. Emerg Infect Dis 2001;7: 1014–7. 6. Kernif T, Socolovschi C, Bitam I, Raoult D, Parola P. Vector-borne rickettsioses in North Africa. Infect Dis Clin N Am 2012;26: 455–78. 7. Eldin C, Mediannikov O, Bavoust B, et al. Emergence of Rickettsia africae, Oceania. Emerg Infect Dis 2011;17:100–2. 8. Mediannikov O, Trape JF, Diatta G, Parola P, Fournier PE, Raoult D. Rickettsia africae, Western Africa. Emerg Infect Dis 2010;16:571–3. 9. Jensenius M, Davis X, von Sonnenburg F, et al. Multicenter geosentinel analysis of rickettsial diseases in international travelers, 19962008. Emerg Infect Dis 2009;15:1791–8. 10. Shelley J. Rash and eschars in a returning traveller. Clin Exp Dermatol 2011;36:222–4. 11. Sundriyal D, Kumar N, Chandraskinaran A, Sharma B. Eschar: an important clue to diagnosis. BMJ Case Rep 2013; http:// dx.doi.org/10.1136/bcr-2013-010105.
565 12. Orme C, Imaeda S. Eschar formation from testosterone patch. N Engl J Med 2012;366:e28. 13. Jellinek N, Maloney ME. Escharotic and other botanical agents for the treatment of skin cancer: a review. J Am Acad Dermatol 2005; 53:487–95. 14. Sunderkotter C, Bonsmann G, Sindrilaru A, Luger T. Management of leukocytoplastic vasculitis. J Dermatol Treat 2005;16:193–206. 15. Roch N, Epaulard O, Pelloux I, et al. African tick bite fever in elderly patients: 8 cases in French tourists returning from South Africa. Clin Infect Dis 2008;47:e28–35. 16. Fujisawa T, Kadosaka T, Fujito H, et al. Rickettsia africae infection in a Japanese traveller with many tick bites. Acta Dermatovenereol 2012;92:443–4. 17. Mechai F, Han Y, Gachot B, et al. Pristinamycin for Rickettsia africae infection. J Travel Med 2009;16:136–7. 18. Consigny PH, Rotain JM, Mizzi D, Raoult D. African tick bite fever in French travelers. Emerg Infect Dis 2005;11:1805–6. 19. US Travel and Tourism Advisory Board. Travel Statistics. Available at: travel.trade.gov/view/m-2013-O-001/index.html. Accessed July 19, 2014. 20. Raoult D, Fournier P, Fenollar F, et al. Rickettsia africae, a tickborne pathogen in travelers to sub-Saharan Africa. N Engl J Med 2001;344:1504–10.
