Curr Infect Dis Rep (2015) 17:10 DOI 10.1007/s11908-015-0467-8
SKIN, SOFT TISSUE, BONE AND JOINT INFECTIOUS DISEASES (N SAFDAR, SECTION EDITOR)
Skin Infections in Returned Travelers: an Update Robert F. Zimmerman & Elizabeth S. Belanger & Christopher D. Pfeiffer
# Springer Science+Business Media New York 2015
Abstract Dermatologic manifestations of travel-related illness are particularly vexing due to the broad differential diagnosis and clinicians’ unfamiliarity with uncommonly seen diseases. This paper aims to educate and update the reader on selected infectious diseases in the returned traveler whose disease manifestations are primarily dermatologic. First, the evolving epidemiology of these infections is examined; understanding the geographic distribution of infectious etiologies helps refine and narrow the differential diagnosis. This is followed by a discussion of six important clinical syndromes including cutaneous larva migrans (CLM), cutaneous leishmaniasis, tungiasis, myiasis, antibiotic-resistant skin and soft tissue infection, and selected infections associated with fever and rash (e.g., measles, chikungunya virus infection, dengue fever, rickettsial spotted fevers). Familiarity with these syndromes and a situational awareness of their epidemiology will facilitate a prompt, accurate diagnosis and lead to appropriate treatment and prevention of further disease spread.
Keywords Skin infection . Travel medicine . Cutaneous larva migrans . Cutaneous leishmaniasis . Tungiasis . Myiasis . Antibiotic resistance . Skin and soft tissue infection . Measles . Chikungunya
This article is part of the Topical Collection on Skin, Soft Tissue, Bone and Joint Infectious Diseases R. F. Zimmerman : E. S. Belanger : C. D. Pfeiffer Department of Medicine, Oregon Health & Science University, Portland, OR, USA C. D. Pfeiffer (*) Department of Hospital and Specialty Medicine, Portland Veterans Affairs Medical Center, P.O. Box 1034 P3-ID, Portland, OR 97239, USA e-mail: [email protected]
Introduction In an age of highly accessible international travel, returning travelers are commonly evaluated in both travel and primary care clinics. Often, these visits are the result of an acquired infectious disease abroad, which has unique clinical implications. Dermatologic manifestations of travel-related illness are particularly vexing due to the broad differential diagnosis and clinicians’ unfamiliarity with uncommonly seen diseases. This paper aims to educate and update the reader on selected infectious diseases in the returned traveler whose disease manifestations are primarily dermatologic. First, the evolving epidemiology of these infections is examined. This is followed by a discussion of six important clinical syndromes including cutaneous larva migrans (CLM), cutaneous leishmaniasis, tungiasis, myiasis, antibiotic-resistant bacterial skin and soft tissue infection, and selected infections associated with fever and rash. Notably, we have excluded diseases primarily related to immigration and/or long-term residency abroad (e.g., Hansen’s disease and filariasis).
Epidemiology A large, geographically diverse report on the burden of dermatologic complaints in returned travelers was published in 2013 by Leder et al. for the GeoSentinal Surveillance Network (GSN) [1••]. The GSN is a well-established network of 53 travel/tropical medicine clinics located in 24 countries; 21 (40 %) sites are located in North America. In these clinics, from 2007 to 2011, dermatologic diagnoses accounted for 20 % (8225/42,173) of all diagnoses in returning travelers, ranking third behind gastrointestinal diagnoses (34 %) and febrile illnesses (23 %). While epidemics and outbreaks do occur, endemic dermatologic tropical infectious diseases and the distribution of presentations have not changed
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substantially since prior reports. For example, data published on returning travelers to French travel clinics from 1991 to 1993 and prior GSN data from 1996 to 2006 were largely similar to the newer study [2, 3]. The major difference in the 2013 report was an increased number of patients presenting after an animal bite/scratch abroad including those presenting for rabies post-exposure prophylaxis. Of the specific dermatologic etiologic entities identified, CLM was the most common (10 %), followed by cutaneous leishmaniasis (3 %) and myiasis/tungiasis (3 %). Leprosy, gnathostomiasis, sporotrichosis, and cutaneous atypical mycobacterial infections were less commonly reported (4 weeks after exposure, with rare cases presenting months later [8]. The dermatosis is self-limited, but migration can persist for weeks to months with associated pruritus and discomfort. When left untreated, the lesions of CLM can become superinfected with bacterial pathogens, leading to cellulitis or abscesses. Unlike human hookworms, A. braziliense and A. caninum eventually die in the skin as they are unable to penetrate further. CLM is a clinical diagnosis. Although classically associated with hookworm larvae, this clinical syndrome of a creeping eruption can be difficult to differentiate from other infections, such as scabies or migratory myiasis. A similar localized skin eruption occurs with cutaneous invasion of Strongyloides stercoralis, known as larva currens. Unlike CLM, S. stercoralis infestations migrate much faster than hookworms at a rate of centimeters per hour as opposed to centimeters per day, the cutaneous lesions tend to persist for only hours to days, and the lesions may recur frequently. Although generally self-limiting, treatment of CLM is relatively simple and may help resolve persistent disease, disease complicated by secondary infection, and control symptoms. The two primary agents readily available and currently recommended by the Centers for Disease Control (CDC) are ivermectin and albendazole [9]. A single dose of ivermectin (200 μg/kg) is associated with a cure rate of 77 %; however, cure is achieved in 97 % with a second dose [10]. Albendazole (400 mg) is an alternative, but single doses are associated with higher rates of relapse so a 3–7-day course is recommended [9, 11]. Topical tiabendazole remains a third option but requires good compliance and application three times daily for a week. Cryotherapy is ineffective, injurious, and should be avoided.
Cutaneous Leishmaniasis Leishmaniasis is a disease caused by an obligate intracellular protozoan of the genus Leishmania, of which there are many
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species. It is spread via the bite of a phlebotomine sand fly, an arthropod roughly one third the size of a mosquito [12]. Leishmania species are divided into Old World and New World, in relation to where they are most commonly found. New World species, which include Leishmania mexicana, Leishmania amazonensis, and Leishmania venezuelensis, are found in the Western Hemisphere in Mexico and Central and South America (with the exception of Uruguay and Chile). The geographic distribution may be expanding; recently, there are case reports of cutaneous leishmaniasis acquired in Texas and Oklahoma [13]. Old World species, such as Leishmania donovani, Leishmania major, Leishmania tropica, Leishmania aethipica, and Leishmania infantum, are mostly found in the Middle East, northern Africa, and southern Europe; endemic foci exist in southern France and Greece; and periodic outbreaks have occurred in Spain [14–16]. The disease can take a variety of forms but is generally characterized as cutaneous, mucosal (a.k.a. mucocutaneous or espundia), or visceral (a.k.a. kala-azar). Cutaneous leishmaniasis is the most common form and consists of parasitic infection of the macrophages found in the dermis. Mucosal leishmaniasis is infection of the mucous membranes of the nasopharynx and is due to metastasis of cutaneous leishmaniasis caused only by certain New World species, most commonly Leishmania braziliensis. It often develops years after resolution of cutaneous manifestations but can be found concurrent with cutaneous infection (i.e., mucocutaneous) [12]. Visceral leishmaniasis is infection primarily of the reticuloendothelial tissues, including the spleen and bone marrow, though the liver and other organs can be involved. The most common species associated with visceral leishmaniasis are L. donovani and L. infantum. Herein, we will focus on the form of leishmaniasis most likely to be encountered in the returned traveler—localized cutaneous leishmaniasis. Skin lesions due to localized cutaneous leishmaniasis are variable but often present as papules, plaques, or nodules that evolve into usually painless ulcers with raised borders and a central depression. The ulcers may or may not be covered by a scab. Because the lesions are located at the site of the sand fly bite, they are typically found on areas of exposed skin such as the extremities or face. The lesions can develop within weeks to months of exposure or even years later, often in the setting of trauma or immunosuppression. Lesions are more likely to be painful if located near a joint or when superinfected with bacteria. Lymphadenopathy is relatively common and may precede the skin lesions. It is possible to have multiple or satellite lesions, lymphangitic spread with a sporotrichoid pattern, or even bubonic lymph node involvement. Left untreated, lesions may last months to years [12, 17]. Diagnosis is usually made by biopsy of the active edge of the lesions with pathologic or cytologic evaluation to directly visualize the parasites, sometimes with immunohistochemical staining [17]. Culture is also available in specialty labs. PCR is
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used to identify the species, which can dictate treatment choice and duration. Serologic testing is available but is usually reserved for diagnosis of visceral disease and does not distinguish between active or prior infection. In the USA, the CDC provides reference diagnostic services for leishmaniasis. Information on appropriate specimen collection, handling, and shipping is available online [18•]. The decision to treat and which agent to use for cutaneous leishmaniasis are based on a variety of factors including geographic region, host, and the infecting species. For example, therapy is more important for certain of the New World species that are more likely to metastasize (i.e., become mucosal disease). Therapy also may be warranted for certain infection locations (e.g., periarticular or facial lesions) and lesion characteristics (e.g., large size and persistent or progressive lesions). In some endemic regions, humans serve as a reservoir for the disease and treatment is indicated to decrease transmission. Therapy must be individualized and can be systemic or local. Intravenous or intramuscular sodium stibogluconate is available through the CDC. An oral medication, miltefosine, was approved by the Food and Drug Administration (FDA) in March 2014 for treatment of cutaneous leishmaniasis due to three of the New World species after placebo-controlled trials demonstrated >90 % cure rates, a success similar to that of antimony therapy [12, 19, 20]. Other less commonly employed therapies include liposomal amphotericin B, pentamidine, or azoles including ketoconazole, itraconazole, or fluconazole. Local therapies include cryotherapy, thermotherapy, topical paromomycin, or intralesional injection of stibogluconate [12].
Tungiasis Tungiasis is a parasitic infection of the epidermis due to infestation with a female sand or jigger flea, Tunga penetrans. Other names for this flea include chigoe, nigua, chica, pico, pique, or suthi [21]. It is found in tropical and subtropical areas in South and Central America, sub-Saharan Africa, the Caribbean, and Madagascar and the Seychelles in the Indian Ocean. Rare cases have been reported in India and Pakistan. The infection is acquired by walking barefoot in regions where T. penetrans is found, usually beaches or sandy soil. Animal reservoirs include dogs, cats, pigs, and rats [22]. The tiny female flea, usually about 1 mm, burrows into the outer layer of the skin, leaving its posterior abdomen exposed through the skin surface, generating the characteristic white papule or nodule with a central black point [21, 23••]. The burrowing process is asymptomatic, but the gravid female increases in size to up to 1 cm in about 2 weeks, creating a pruritic or painful lesion from which eggs and feces are excreted. The flea usually dies and is sloughed with the host’s skin over several weeks [24]. The burrow containing the flea
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can become secondarily infected, leading to gangrene, tetanus, or even osteomyelitis, though this is normally found in indigenous residents from endemic areas with a high parasite load. Lesions are usually found on feet, often in the periungual folds, the sole, or the heel [25]. Treatment consists of cautiously removing the intact flea with a sterile needle or curette. Failure to remove the intact flea, either with retained flea material or exposure to internal contents of the flea, can result in a marked local inflammatory response. Consideration should be given to tetanus vaccination and, if the wound appears infected, antibiotic therapy [21].
Myiasis In contrast to the epidermal infestation of flea larvae in tungiasis, myiasis refers to a deeper, dermal infestation with fly larvae. Multiple genera are capable of producing larvae that will live in mammalian tissue, some as a necessary part of their life cycle, others incidentally. The human botfly, Dermatobia hominis, and the tumbu fly, Cordylobia anthropophaga, are examples of obligate myiasis as their life cycle requires a mammalian host, such as humans, pets, and livestock during their larval stage [26••]. Myiasis occurs worldwide, often in people with contact with livestock or animals, or in homeless populations. Travelers to the tropics and subtropics such as South America and Africa represent the bulk of cases of obligate myiasis seen in the USA. Risk factors for disease include open wounds, alcoholism, peripheral vascular disease, and immunosuppression [26••, 27]. Several mechanisms of infestation exist, and they vary by fly species. For example, fly larvae may be dropped on the skin by a bloodsucking vector such as a mosquito and then enter via the recently created blood meal wound. Alternatively, larvae can be deposited on the skin by an adult fly of the same species and subsequently burrow into the skin. Finally, other larvae take advantage of preexisting wounds, such as excoriations or ulcers, that come in contact with the larvae in the soil and surrounding environment [26••]. Myiasis can present in a variety of forms. If not associated with a preexisting wound, the typical lesion is nodular. Also, wounds may appear furuncular, and mistaking myiasis for a staphylococcal furuncle has been described [26••, 28]. The lesion usually has a small opening to allow for respiration, and patients sometimes report a sensation of movement within the lesion [26••]. Some species can migrate past the subdermis, which can lead to significant associated tissue damage. Treatment is surgical removal of the larva. Most sources advocate occlusion of the respiratory opening with a variety of agents, including Vaseline or a plastic dressing, to either
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prompt the larva to exit its burrow or suffocate it to aid in ease of removal. Recently, removal post-suffocation with a venom extractor has been described [29]. The ultimate goal is complete removal of the larva; antibiotics are indicated only for superinfected wounds [27].
Skin and Soft Tissue Infection The most common dermatologic diagnosis in travelers from the 2013 GSN report was skin and soft tissue infection [1]. With increasing travel including medical tourism, potential antibiotic resistance is a critical consideration when evaluating a returned traveler with bacterial cellulitis. Although the global emergence of methicillin-resistant Staphylococcus aureus (MRSA) is well documented, the clinician should be aware of S. aureus infection with other resistance phenotypes [30]. Vancomycin-resistant S. aureus (VRSA), while at this time exceedingly rare, has been reported in Japan, India, and Brazil [31, 32]. Additionally, linezolid resistance in S. aureus is becoming more common in areas such as Spain, and daptomycin-nonsusceptible S. aureus has been documented in Singapore [33•]. Another highly worrisome group of antibiotic-resistant organisms which merit particular consideration in patients who have received medical care during travel is carbapenem-resistant Enterobacteriaceae (CRE). For example, the first report of CRE due to New Delhi metallo-betalactamase (NDM) was described in a returned traveler from India [34]. Clinicians treating skin and soft tissue infections in the returning traveler should remain cognizant of the potential for antibiotic resistance.
Select Infections of Travelers Associated with Fever and Rash While most travelers have been adequately vaccinated against measles, there is a growing population of unvaccinated travelers due to personal, religious, or cultural reasons. Unvaccinated individuals remain at risk for acquiring measles, especially if they travel to areas where the disease continues to have large outbreaks. While the incidence of measles declined 77 % globally from 2000 to 2012 (853,480 cases to 226,722 cases, respectively), the number of cases reported in the Region of the Americas actually increased from 63 to 143 [35••]. Most measles cases are reported from Africa and SE Asia, areas which continue to have inadequate vaccination coverage and regular outbreaks. Japan and France both had recent large outbreaks of measles, approaching the level of epidemic. From 2008 to 2011, there were over 20,000 new cases of measles in France [36]. In 2008, Japan had 11,000 new cases and China had 131,400 new cases [37]. The virus has an incubation period of about 10 days followed by systemic signs
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of fever, fatigue, conjunctivitis, and coryza prior to developing a maculopapular rash (hence, the term Bmorbilliform^ rash). Although classically described, not all cases have the small, white spots of the buccal mucosa and palate known as Koplik spots. The clinical diagnosis must be considered in a patient with a compatible clinical illness; confirmatory testing includes both RT-PCR of the throat and urine as well as serology (IgM and IgG) [38, 39]. While treatment remains supportive, early identification, isolation, and notification are paramount to prevent further cases. In December of 2013, an outbreak of chikungunya virus infection was initially described in the Caribbean island of St. Martin, ultimately encompassing a plurality of Caribbean nations within 6 months [40]. Chikungunya virus is an alphavirus classically found in tropical Africa and Asia, but outbreaks associated with returning travelers acting as intermediary hosts have been reported, demonstrated by an outbreak of 205 cases in northern Italy [41]. The clinical presentation is 3–5 days of fever following a short incubation period of 2–4 days, but post-viral polyarthralgia is typical and can persist for months. The clinical syndrome commonly includes a maculopapular exanthem or diffuse erythema [42]. Dengue fever presents with a similar maculopapular rash but is classically distinguished by severe myalgias; relatedly, the dengue virus shares a common geographic distribution and mosquito vector with chikungunya virus. Another important consideration is the rickettsial spotted fevers, many of which present with rashes. The type of rash is highly dependent on the causative species (e.g., petechial maculopapular exanthem, vesiculopapular exanthem, wound eschars) [43]. While the treatment of dengue fever and chikungunya fever is purely supportive, patients infected with suspected rickettsial spotted fevers should be treated with doxycycline for at least 3 days after fever abates and clinical improvement is evident (the typical treatment duration is 7–14 days) [44]. As noted in the recent GSN report, dengue fever remains a far more common diagnosis in the returning febrile traveler than the rickettsial spotted fevers or chikungunya virus infection (15 vs. 3 vs. 2 %) [1••].
Conclusions The returning traveler with a dermatologic presentation is a clinical challenge. Understanding the epidemiologic data and geographic distribution of infectious etiologies can help narrow the differential diagnosis and remains the key to interpreting the travel history. CLM, cutaneous leishmaniasis, tungiasis, myiasis, antibiotic-resistant bacterial skin and soft tissue infections, and systemic illnesses with dermatologic manifestations all represent important diagnoses to consider when evaluating the returned traveler. While some diagnoses, such as cutaneous leishmaniasis, require histopathology, most
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diagnoses are primarily clinical. Prompt evaluation and treatment depend on situational awareness and an inclusive differential diagnosis. Osler once said, BMedicine is a science of uncertainty and an art of probability^; this truism is exemplified by the combined art of clinical diagnosis and science of epidemiology in the infected skin of a returning traveler. Compliance with Ethics Guidelines Conflict of Interest Elizabeth Belanger has no conflicts of interest. Christopher Pfeiffer received funding for other work from Oregon Health Authority. Human and Animal Rights and Informed Consent This article does not contain any studies with human or animal subjects performed by any of the authors.
References Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance 1.•• Leder K, Torresi J, Libman MD, et al. GeoSentinel surveillance of illness in returned travelers, 2007-2011. Ann Intern Med. 2013;158(6):456–68. The most recent GeoSentinal review of the demographics, geography, and diseases associated with travel, an interesting read with great summary tables. 2. Caumes E, Carriere J, Guermonprez G, Bricaire F, Danis M, Gentilini M. Dermatoses associated with travel to tropical countries: a prospective study of the diagnosis and management of 269 patients presenting to a tropical disease unit. Clin Infect Dis. 1995;20(3):542–8. 3. Lederman ER, Weld LH, Elyazar IR, et al. Dermatologic conditions of the ill returned traveler: an analysis from the GeoSentinel Surveillance Network. Int J Infect Dis. 2008;12(6):593–602. 4. Bowman DD, Montgomery SP, Zajac AM, Eberhard ML, Kazacos KR. Hookworms of dogs and cats as agents of cutaneous larva migrans. Trends Parasitol. 2010;26(4):162–7. 5. Heukelbach J, Jackson A, Ariza L, Feldmeier H. Prevalence and risk factors of hookworm-related cutaneous larva migrans in a rural community in Brazil. Ann Trop Med Parasitol. 2008;102(1):53–61. 6. Galanti B, Fusco FM, Nardiello S. Outbreak of cutaneous larva migrans in Naples, southern Italy. Trans R Soc Trop Med Hyg. 2002;96(5):491–2. 7. Heukelbach J, Feldmeier H. Epidemiological and clinical characteristics of hookworm-related cutaneous larva migrans. Lancet Infect Dis. 2008;8(5):302–9. 8. Jelinek T, Maiwald H, Nothdurft HD, Loscher T. Cutaneous larva migrans in travelers: synopsis of histories, symptoms, and treatment of 98 patients. Clin Infect Dis. 1994;19(6):1062–6. 9. Centers for Disease Control and Prevention. Zoonotic Hookworm. http://www.cdc.gov/parasites/zoonotichookworm/. Accessed 1 June 2014. 10. Bouchaud O, Houze S, Schiemann R, et al. Cutaneous larva migrans in travelers: a prospective study, with assessment of therapy with ivermectin. Clin Infect Dis. 2000;31(2):493–8. 11. Caumes E, Carriere J, Datry A, Gaxotte P, Danis M, Gentilini M. A randomized trial of ivermectin versus
10
12. 13.
14.
15. 16.
17.
18.•
19.
20. 21. 22.
23.••
24.
25.
26.••
27.
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Page 6 of 6 albendazole for the treatment of cutaneous larva migrans. Am J Trop Med Hyg. 1993;49(5):641–4. Centers for Disease Control and Prevention. Leishmaniasis. http:// www.cdc.gov/parasites/leishmaniasis/. Accessed June 1, 2014. Clarke CF, Bradley KK, Wright JH, Glowicz J. Case report: emergence of autochthonous cutaneous leishmaniasis in northeastern Texas and southeastern Oklahoma. Am J Trop Med Hyg. 2013;88(1):157–61. Arce A, Estirado A, Ordobas M, et al. Re-emergence of leishmaniasis in Spain: community outbreak in Madrid, Spain, 2009 to 2012. Euro Surveill. 2013;18(30):20546. Lachaud L, Dedet JP, Marty P, et al. Surveillance of leishmaniases in France, 1999 to 2012. Euro Surveill. 2013;18(29):20534. Gkolfinopoulou K, Bitsolas N, Patrinos S, et al. Epidemiology of human leishmaniasis in Greece, 1981-2011. Euro Surveill. 2013;18(29):20532. Shirian S, Oryan A, Hatam GR, Panahi S, Daneshbod Y. Comparison of conventional, molecular, and immunohistochemical methods in diagnosis of typical and atypical cutaneous leishmaniasis. Arch Pathol Lab Med. 2014;138(2):235–40. Centers for Disease Control and Prevention. Practical guide for laboratory diagnosis of leishmaniasis (2012). http://www.cdc.gov/ parasites/leishmaniasis/resources/pdf/cdc_diagnosis_guide_ leishmaniasis.pdf. Accessed May 30, 2014. A very useful, straightforward step-by-step guide for the laboratory diagnosis of leishmaniasis available through the CDC, including specimen collection and shipping directions. Dorlo TP, Balasegaram M, Beijnen JH, de Vries PJ. Miltefosine: a review of its pharmacology and therapeutic efficacy in the treatment of leishmaniasis. J Antimicrob Chemother. 2012;67(11):2576–97. Soto J, Arana BA, Toledo J, et al. Miltefosine for new world cutaneous leishmaniasis. Clin Infect Dis. 2004;38(9):1266–72. Centers for Disease Control and Prevention. DPDx: tungiasis. http://www.cdc.gov/dpdx/tungiasis/. Accessed April 1, 2014. Karunamoorthi K. Tungiasis: a neglected epidermal parasitic skin disease of marginalized populations—a call for global science and policy. Parasitol Res. 2013;112(10):3635–43. Haddad Jr V, Cardoso JL, Lupi O, Tyring SK. Tropical dermatology: venomous arthropods and human skin: part I. Insect J Am Acad Dermatol. 2012;67(3):331 e331–314; quiz 345. A great summary for use in the evaluation of arthropod related skin lesions with pictures of rashes and the insects, applicable to both local patients and the returning traveler. Lefebvre M, Capito C, Durant C, Hervier B, Grossi O. Tungiasis: a poorly documented tropical dermatosis. Med Mal Infect. 2011;41(9):465–8. Feldmeier H, Sentongo E, Krantz I. Tungiasis (sand flea disease): a parasitic disease with particular challenges for public health. Eur J Clin Microbiol Infect Dis. 2013;32(1):19–26. Fydryszewski NA. Myiasis: diagnosis, treatment and medical use of maggots. Clin Lab Sci. 2013;26(2):76–81. A superb, succinct and practical discussion of myiasis from a clinical and laboratory standpoint. Centers for Disease Control and Prevention. Myiasis. http://www. cdc.gov/parasites/myiasis/. Accessed April 1, 2014. Accessed January 10.
28.
Adehossi E, Parola P. A woman with a skin lesion. Myiasis Clin Infect Dis. 2009;48(11):1584. 1628-1589. 29. West JK. Simple and effective field extraction of human botfly, Dermatobia hominis, using a venom extractor. Wilderness Environ Med. 2013;24(1):17–22. 30. Stefani S, Chung DR, Lindsay JA, et al. Meticillin-resistant Staphylococcus aureus (MRSA): global epidemiology and harmonisation of typing methods. Int J Antimicrob Agents. 2012;39(4):273–82. 31. Thati V, Shivannavar CT, Gaddad SM. Vancomycin resistance among methicillin resistant Staphylococcus aureus isolates from intensive care units of tertiary care hospitals in Hyderabad. Indian J Med Res. 2011;134(5):704–8. 32. Rossi F, Diaz L, Wollam A, et al. Transferable vancomycin resistance in a community-associated MRSA lineage. N Engl J Med. 2014;370(16):1524–31. 33.• Molton JS, Tambyah PA, Ang BSP, Lin LM, Fisher DA. The global spread of healthcare-associated multidrug-resistant bacteria: a perspective from Asia. Clin Infect Dis. 2013;56:1310–8. A topical, up to date review article of the new international resistant bacterial pathogens on the horizon. 34. Yong D, Toleman MA, Giske CG, et al. Characterization of a new metallo-beta-lactamase gene, bla(NDM-1), and a novel erythromycin esterase gene carried on a unique genetic structure in Klebsiella pneumoniae sequence type 14 from India. Antimicrob Agents Chemother. 2009;53(12):5046–54. 35.•• Perry RT, Gacic-Dobo M, Dabbagh A, et al. Global control and regional elimination of measles, 2000-2012. MMWR Morb Mortal Wkly Rep. 2014;63(5):103–7. The most recent report on measles epidemiology and progress towards elimination. 36. Antona D, Levy-Bruhl D, Baudon C, et al. Measles elimination efforts and 2008-2011 outbreak. Fr Emerg Infect Dis. 2013;19(3): 357–64. 37. Centers for Disease C, Prevention. Progress toward the 2012 measles elimination goal—Western Pacific Region, 1990-2008. MMWR Morb Mortal Wkly Rep. 2009;58(24):669–73. 38. Bellini WJ, Helfand RF. The challenges and strategies for laboratory diagnosis of measles in an international setting. J Infect Dis. 2003;187 Suppl 1:S283–290. 39. Centers for Disease Control and Prevention. Measles. http://www. cdc.gov/measles/hcp/index.html#features. Accessed June 10, 2014. 40. Centers for Disease Control and Prevention. Chikungunya. http:// www.cdc.gov/chikungunya/. Accessed June 1, 2014. 41. Rezza G, Nicoletti L, Angelini R, et al. Infection with chikungunya virus in Italy: an outbreak in a temperate region. Lancet. 2007;370(9602):1840–6. 42. Taubitz W, Cramer JP, Kapaun A, et al. Chikungunya fever in travelers: clinical presentation and course. Clin Infect Dis. 2007;45(1):e1–4. 43. Raoult D, Roux V. Rickettsioses as paradigms of new or emerging infectious diseases. Clin Microbiol Rev. 1997;10(4):694–719. 44. Centers for Disease Control and Prevention. Other tick-borne spotted fever rickettsial infections. http://www.cdc.gov/ otherspottedfever/. Accessed June 1, 2014.
SKIN, SOFT TISSUE, BONE AND JOINT INFECTIOUS DISEASES (N SAFDAR, SECTION EDITOR)
Skin Infections in Returned Travelers: an Update Robert F. Zimmerman & Elizabeth S. Belanger & Christopher D. Pfeiffer
# Springer Science+Business Media New York 2015
Abstract Dermatologic manifestations of travel-related illness are particularly vexing due to the broad differential diagnosis and clinicians’ unfamiliarity with uncommonly seen diseases. This paper aims to educate and update the reader on selected infectious diseases in the returned traveler whose disease manifestations are primarily dermatologic. First, the evolving epidemiology of these infections is examined; understanding the geographic distribution of infectious etiologies helps refine and narrow the differential diagnosis. This is followed by a discussion of six important clinical syndromes including cutaneous larva migrans (CLM), cutaneous leishmaniasis, tungiasis, myiasis, antibiotic-resistant skin and soft tissue infection, and selected infections associated with fever and rash (e.g., measles, chikungunya virus infection, dengue fever, rickettsial spotted fevers). Familiarity with these syndromes and a situational awareness of their epidemiology will facilitate a prompt, accurate diagnosis and lead to appropriate treatment and prevention of further disease spread.
Keywords Skin infection . Travel medicine . Cutaneous larva migrans . Cutaneous leishmaniasis . Tungiasis . Myiasis . Antibiotic resistance . Skin and soft tissue infection . Measles . Chikungunya
This article is part of the Topical Collection on Skin, Soft Tissue, Bone and Joint Infectious Diseases R. F. Zimmerman : E. S. Belanger : C. D. Pfeiffer Department of Medicine, Oregon Health & Science University, Portland, OR, USA C. D. Pfeiffer (*) Department of Hospital and Specialty Medicine, Portland Veterans Affairs Medical Center, P.O. Box 1034 P3-ID, Portland, OR 97239, USA e-mail: [email protected]
Introduction In an age of highly accessible international travel, returning travelers are commonly evaluated in both travel and primary care clinics. Often, these visits are the result of an acquired infectious disease abroad, which has unique clinical implications. Dermatologic manifestations of travel-related illness are particularly vexing due to the broad differential diagnosis and clinicians’ unfamiliarity with uncommonly seen diseases. This paper aims to educate and update the reader on selected infectious diseases in the returned traveler whose disease manifestations are primarily dermatologic. First, the evolving epidemiology of these infections is examined. This is followed by a discussion of six important clinical syndromes including cutaneous larva migrans (CLM), cutaneous leishmaniasis, tungiasis, myiasis, antibiotic-resistant bacterial skin and soft tissue infection, and selected infections associated with fever and rash. Notably, we have excluded diseases primarily related to immigration and/or long-term residency abroad (e.g., Hansen’s disease and filariasis).
Epidemiology A large, geographically diverse report on the burden of dermatologic complaints in returned travelers was published in 2013 by Leder et al. for the GeoSentinal Surveillance Network (GSN) [1••]. The GSN is a well-established network of 53 travel/tropical medicine clinics located in 24 countries; 21 (40 %) sites are located in North America. In these clinics, from 2007 to 2011, dermatologic diagnoses accounted for 20 % (8225/42,173) of all diagnoses in returning travelers, ranking third behind gastrointestinal diagnoses (34 %) and febrile illnesses (23 %). While epidemics and outbreaks do occur, endemic dermatologic tropical infectious diseases and the distribution of presentations have not changed
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substantially since prior reports. For example, data published on returning travelers to French travel clinics from 1991 to 1993 and prior GSN data from 1996 to 2006 were largely similar to the newer study [2, 3]. The major difference in the 2013 report was an increased number of patients presenting after an animal bite/scratch abroad including those presenting for rabies post-exposure prophylaxis. Of the specific dermatologic etiologic entities identified, CLM was the most common (10 %), followed by cutaneous leishmaniasis (3 %) and myiasis/tungiasis (3 %). Leprosy, gnathostomiasis, sporotrichosis, and cutaneous atypical mycobacterial infections were less commonly reported (4 weeks after exposure, with rare cases presenting months later [8]. The dermatosis is self-limited, but migration can persist for weeks to months with associated pruritus and discomfort. When left untreated, the lesions of CLM can become superinfected with bacterial pathogens, leading to cellulitis or abscesses. Unlike human hookworms, A. braziliense and A. caninum eventually die in the skin as they are unable to penetrate further. CLM is a clinical diagnosis. Although classically associated with hookworm larvae, this clinical syndrome of a creeping eruption can be difficult to differentiate from other infections, such as scabies or migratory myiasis. A similar localized skin eruption occurs with cutaneous invasion of Strongyloides stercoralis, known as larva currens. Unlike CLM, S. stercoralis infestations migrate much faster than hookworms at a rate of centimeters per hour as opposed to centimeters per day, the cutaneous lesions tend to persist for only hours to days, and the lesions may recur frequently. Although generally self-limiting, treatment of CLM is relatively simple and may help resolve persistent disease, disease complicated by secondary infection, and control symptoms. The two primary agents readily available and currently recommended by the Centers for Disease Control (CDC) are ivermectin and albendazole [9]. A single dose of ivermectin (200 μg/kg) is associated with a cure rate of 77 %; however, cure is achieved in 97 % with a second dose [10]. Albendazole (400 mg) is an alternative, but single doses are associated with higher rates of relapse so a 3–7-day course is recommended [9, 11]. Topical tiabendazole remains a third option but requires good compliance and application three times daily for a week. Cryotherapy is ineffective, injurious, and should be avoided.
Cutaneous Leishmaniasis Leishmaniasis is a disease caused by an obligate intracellular protozoan of the genus Leishmania, of which there are many
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species. It is spread via the bite of a phlebotomine sand fly, an arthropod roughly one third the size of a mosquito [12]. Leishmania species are divided into Old World and New World, in relation to where they are most commonly found. New World species, which include Leishmania mexicana, Leishmania amazonensis, and Leishmania venezuelensis, are found in the Western Hemisphere in Mexico and Central and South America (with the exception of Uruguay and Chile). The geographic distribution may be expanding; recently, there are case reports of cutaneous leishmaniasis acquired in Texas and Oklahoma [13]. Old World species, such as Leishmania donovani, Leishmania major, Leishmania tropica, Leishmania aethipica, and Leishmania infantum, are mostly found in the Middle East, northern Africa, and southern Europe; endemic foci exist in southern France and Greece; and periodic outbreaks have occurred in Spain [14–16]. The disease can take a variety of forms but is generally characterized as cutaneous, mucosal (a.k.a. mucocutaneous or espundia), or visceral (a.k.a. kala-azar). Cutaneous leishmaniasis is the most common form and consists of parasitic infection of the macrophages found in the dermis. Mucosal leishmaniasis is infection of the mucous membranes of the nasopharynx and is due to metastasis of cutaneous leishmaniasis caused only by certain New World species, most commonly Leishmania braziliensis. It often develops years after resolution of cutaneous manifestations but can be found concurrent with cutaneous infection (i.e., mucocutaneous) [12]. Visceral leishmaniasis is infection primarily of the reticuloendothelial tissues, including the spleen and bone marrow, though the liver and other organs can be involved. The most common species associated with visceral leishmaniasis are L. donovani and L. infantum. Herein, we will focus on the form of leishmaniasis most likely to be encountered in the returned traveler—localized cutaneous leishmaniasis. Skin lesions due to localized cutaneous leishmaniasis are variable but often present as papules, plaques, or nodules that evolve into usually painless ulcers with raised borders and a central depression. The ulcers may or may not be covered by a scab. Because the lesions are located at the site of the sand fly bite, they are typically found on areas of exposed skin such as the extremities or face. The lesions can develop within weeks to months of exposure or even years later, often in the setting of trauma or immunosuppression. Lesions are more likely to be painful if located near a joint or when superinfected with bacteria. Lymphadenopathy is relatively common and may precede the skin lesions. It is possible to have multiple or satellite lesions, lymphangitic spread with a sporotrichoid pattern, or even bubonic lymph node involvement. Left untreated, lesions may last months to years [12, 17]. Diagnosis is usually made by biopsy of the active edge of the lesions with pathologic or cytologic evaluation to directly visualize the parasites, sometimes with immunohistochemical staining [17]. Culture is also available in specialty labs. PCR is
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used to identify the species, which can dictate treatment choice and duration. Serologic testing is available but is usually reserved for diagnosis of visceral disease and does not distinguish between active or prior infection. In the USA, the CDC provides reference diagnostic services for leishmaniasis. Information on appropriate specimen collection, handling, and shipping is available online [18•]. The decision to treat and which agent to use for cutaneous leishmaniasis are based on a variety of factors including geographic region, host, and the infecting species. For example, therapy is more important for certain of the New World species that are more likely to metastasize (i.e., become mucosal disease). Therapy also may be warranted for certain infection locations (e.g., periarticular or facial lesions) and lesion characteristics (e.g., large size and persistent or progressive lesions). In some endemic regions, humans serve as a reservoir for the disease and treatment is indicated to decrease transmission. Therapy must be individualized and can be systemic or local. Intravenous or intramuscular sodium stibogluconate is available through the CDC. An oral medication, miltefosine, was approved by the Food and Drug Administration (FDA) in March 2014 for treatment of cutaneous leishmaniasis due to three of the New World species after placebo-controlled trials demonstrated >90 % cure rates, a success similar to that of antimony therapy [12, 19, 20]. Other less commonly employed therapies include liposomal amphotericin B, pentamidine, or azoles including ketoconazole, itraconazole, or fluconazole. Local therapies include cryotherapy, thermotherapy, topical paromomycin, or intralesional injection of stibogluconate [12].
Tungiasis Tungiasis is a parasitic infection of the epidermis due to infestation with a female sand or jigger flea, Tunga penetrans. Other names for this flea include chigoe, nigua, chica, pico, pique, or suthi [21]. It is found in tropical and subtropical areas in South and Central America, sub-Saharan Africa, the Caribbean, and Madagascar and the Seychelles in the Indian Ocean. Rare cases have been reported in India and Pakistan. The infection is acquired by walking barefoot in regions where T. penetrans is found, usually beaches or sandy soil. Animal reservoirs include dogs, cats, pigs, and rats [22]. The tiny female flea, usually about 1 mm, burrows into the outer layer of the skin, leaving its posterior abdomen exposed through the skin surface, generating the characteristic white papule or nodule with a central black point [21, 23••]. The burrowing process is asymptomatic, but the gravid female increases in size to up to 1 cm in about 2 weeks, creating a pruritic or painful lesion from which eggs and feces are excreted. The flea usually dies and is sloughed with the host’s skin over several weeks [24]. The burrow containing the flea
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can become secondarily infected, leading to gangrene, tetanus, or even osteomyelitis, though this is normally found in indigenous residents from endemic areas with a high parasite load. Lesions are usually found on feet, often in the periungual folds, the sole, or the heel [25]. Treatment consists of cautiously removing the intact flea with a sterile needle or curette. Failure to remove the intact flea, either with retained flea material or exposure to internal contents of the flea, can result in a marked local inflammatory response. Consideration should be given to tetanus vaccination and, if the wound appears infected, antibiotic therapy [21].
Myiasis In contrast to the epidermal infestation of flea larvae in tungiasis, myiasis refers to a deeper, dermal infestation with fly larvae. Multiple genera are capable of producing larvae that will live in mammalian tissue, some as a necessary part of their life cycle, others incidentally. The human botfly, Dermatobia hominis, and the tumbu fly, Cordylobia anthropophaga, are examples of obligate myiasis as their life cycle requires a mammalian host, such as humans, pets, and livestock during their larval stage [26••]. Myiasis occurs worldwide, often in people with contact with livestock or animals, or in homeless populations. Travelers to the tropics and subtropics such as South America and Africa represent the bulk of cases of obligate myiasis seen in the USA. Risk factors for disease include open wounds, alcoholism, peripheral vascular disease, and immunosuppression [26••, 27]. Several mechanisms of infestation exist, and they vary by fly species. For example, fly larvae may be dropped on the skin by a bloodsucking vector such as a mosquito and then enter via the recently created blood meal wound. Alternatively, larvae can be deposited on the skin by an adult fly of the same species and subsequently burrow into the skin. Finally, other larvae take advantage of preexisting wounds, such as excoriations or ulcers, that come in contact with the larvae in the soil and surrounding environment [26••]. Myiasis can present in a variety of forms. If not associated with a preexisting wound, the typical lesion is nodular. Also, wounds may appear furuncular, and mistaking myiasis for a staphylococcal furuncle has been described [26••, 28]. The lesion usually has a small opening to allow for respiration, and patients sometimes report a sensation of movement within the lesion [26••]. Some species can migrate past the subdermis, which can lead to significant associated tissue damage. Treatment is surgical removal of the larva. Most sources advocate occlusion of the respiratory opening with a variety of agents, including Vaseline or a plastic dressing, to either
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prompt the larva to exit its burrow or suffocate it to aid in ease of removal. Recently, removal post-suffocation with a venom extractor has been described [29]. The ultimate goal is complete removal of the larva; antibiotics are indicated only for superinfected wounds [27].
Skin and Soft Tissue Infection The most common dermatologic diagnosis in travelers from the 2013 GSN report was skin and soft tissue infection [1]. With increasing travel including medical tourism, potential antibiotic resistance is a critical consideration when evaluating a returned traveler with bacterial cellulitis. Although the global emergence of methicillin-resistant Staphylococcus aureus (MRSA) is well documented, the clinician should be aware of S. aureus infection with other resistance phenotypes [30]. Vancomycin-resistant S. aureus (VRSA), while at this time exceedingly rare, has been reported in Japan, India, and Brazil [31, 32]. Additionally, linezolid resistance in S. aureus is becoming more common in areas such as Spain, and daptomycin-nonsusceptible S. aureus has been documented in Singapore [33•]. Another highly worrisome group of antibiotic-resistant organisms which merit particular consideration in patients who have received medical care during travel is carbapenem-resistant Enterobacteriaceae (CRE). For example, the first report of CRE due to New Delhi metallo-betalactamase (NDM) was described in a returned traveler from India [34]. Clinicians treating skin and soft tissue infections in the returning traveler should remain cognizant of the potential for antibiotic resistance.
Select Infections of Travelers Associated with Fever and Rash While most travelers have been adequately vaccinated against measles, there is a growing population of unvaccinated travelers due to personal, religious, or cultural reasons. Unvaccinated individuals remain at risk for acquiring measles, especially if they travel to areas where the disease continues to have large outbreaks. While the incidence of measles declined 77 % globally from 2000 to 2012 (853,480 cases to 226,722 cases, respectively), the number of cases reported in the Region of the Americas actually increased from 63 to 143 [35••]. Most measles cases are reported from Africa and SE Asia, areas which continue to have inadequate vaccination coverage and regular outbreaks. Japan and France both had recent large outbreaks of measles, approaching the level of epidemic. From 2008 to 2011, there were over 20,000 new cases of measles in France [36]. In 2008, Japan had 11,000 new cases and China had 131,400 new cases [37]. The virus has an incubation period of about 10 days followed by systemic signs
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of fever, fatigue, conjunctivitis, and coryza prior to developing a maculopapular rash (hence, the term Bmorbilliform^ rash). Although classically described, not all cases have the small, white spots of the buccal mucosa and palate known as Koplik spots. The clinical diagnosis must be considered in a patient with a compatible clinical illness; confirmatory testing includes both RT-PCR of the throat and urine as well as serology (IgM and IgG) [38, 39]. While treatment remains supportive, early identification, isolation, and notification are paramount to prevent further cases. In December of 2013, an outbreak of chikungunya virus infection was initially described in the Caribbean island of St. Martin, ultimately encompassing a plurality of Caribbean nations within 6 months [40]. Chikungunya virus is an alphavirus classically found in tropical Africa and Asia, but outbreaks associated with returning travelers acting as intermediary hosts have been reported, demonstrated by an outbreak of 205 cases in northern Italy [41]. The clinical presentation is 3–5 days of fever following a short incubation period of 2–4 days, but post-viral polyarthralgia is typical and can persist for months. The clinical syndrome commonly includes a maculopapular exanthem or diffuse erythema [42]. Dengue fever presents with a similar maculopapular rash but is classically distinguished by severe myalgias; relatedly, the dengue virus shares a common geographic distribution and mosquito vector with chikungunya virus. Another important consideration is the rickettsial spotted fevers, many of which present with rashes. The type of rash is highly dependent on the causative species (e.g., petechial maculopapular exanthem, vesiculopapular exanthem, wound eschars) [43]. While the treatment of dengue fever and chikungunya fever is purely supportive, patients infected with suspected rickettsial spotted fevers should be treated with doxycycline for at least 3 days after fever abates and clinical improvement is evident (the typical treatment duration is 7–14 days) [44]. As noted in the recent GSN report, dengue fever remains a far more common diagnosis in the returning febrile traveler than the rickettsial spotted fevers or chikungunya virus infection (15 vs. 3 vs. 2 %) [1••].
Conclusions The returning traveler with a dermatologic presentation is a clinical challenge. Understanding the epidemiologic data and geographic distribution of infectious etiologies can help narrow the differential diagnosis and remains the key to interpreting the travel history. CLM, cutaneous leishmaniasis, tungiasis, myiasis, antibiotic-resistant bacterial skin and soft tissue infections, and systemic illnesses with dermatologic manifestations all represent important diagnoses to consider when evaluating the returned traveler. While some diagnoses, such as cutaneous leishmaniasis, require histopathology, most
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diagnoses are primarily clinical. Prompt evaluation and treatment depend on situational awareness and an inclusive differential diagnosis. Osler once said, BMedicine is a science of uncertainty and an art of probability^; this truism is exemplified by the combined art of clinical diagnosis and science of epidemiology in the infected skin of a returning traveler. Compliance with Ethics Guidelines Conflict of Interest Elizabeth Belanger has no conflicts of interest. Christopher Pfeiffer received funding for other work from Oregon Health Authority. Human and Animal Rights and Informed Consent This article does not contain any studies with human or animal subjects performed by any of the authors.
References Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance 1.•• Leder K, Torresi J, Libman MD, et al. GeoSentinel surveillance of illness in returned travelers, 2007-2011. Ann Intern Med. 2013;158(6):456–68. The most recent GeoSentinal review of the demographics, geography, and diseases associated with travel, an interesting read with great summary tables. 2. Caumes E, Carriere J, Guermonprez G, Bricaire F, Danis M, Gentilini M. Dermatoses associated with travel to tropical countries: a prospective study of the diagnosis and management of 269 patients presenting to a tropical disease unit. Clin Infect Dis. 1995;20(3):542–8. 3. Lederman ER, Weld LH, Elyazar IR, et al. Dermatologic conditions of the ill returned traveler: an analysis from the GeoSentinel Surveillance Network. Int J Infect Dis. 2008;12(6):593–602. 4. Bowman DD, Montgomery SP, Zajac AM, Eberhard ML, Kazacos KR. Hookworms of dogs and cats as agents of cutaneous larva migrans. Trends Parasitol. 2010;26(4):162–7. 5. Heukelbach J, Jackson A, Ariza L, Feldmeier H. Prevalence and risk factors of hookworm-related cutaneous larva migrans in a rural community in Brazil. Ann Trop Med Parasitol. 2008;102(1):53–61. 6. Galanti B, Fusco FM, Nardiello S. Outbreak of cutaneous larva migrans in Naples, southern Italy. Trans R Soc Trop Med Hyg. 2002;96(5):491–2. 7. Heukelbach J, Feldmeier H. Epidemiological and clinical characteristics of hookworm-related cutaneous larva migrans. Lancet Infect Dis. 2008;8(5):302–9. 8. Jelinek T, Maiwald H, Nothdurft HD, Loscher T. Cutaneous larva migrans in travelers: synopsis of histories, symptoms, and treatment of 98 patients. Clin Infect Dis. 1994;19(6):1062–6. 9. Centers for Disease Control and Prevention. Zoonotic Hookworm. http://www.cdc.gov/parasites/zoonotichookworm/. Accessed 1 June 2014. 10. Bouchaud O, Houze S, Schiemann R, et al. Cutaneous larva migrans in travelers: a prospective study, with assessment of therapy with ivermectin. Clin Infect Dis. 2000;31(2):493–8. 11. Caumes E, Carriere J, Datry A, Gaxotte P, Danis M, Gentilini M. A randomized trial of ivermectin versus
10
12. 13.
14.
15. 16.
17.
18.•
19.
20. 21. 22.
23.••
24.
25.
26.••
27.
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Page 6 of 6 albendazole for the treatment of cutaneous larva migrans. Am J Trop Med Hyg. 1993;49(5):641–4. Centers for Disease Control and Prevention. Leishmaniasis. http:// www.cdc.gov/parasites/leishmaniasis/. Accessed June 1, 2014. Clarke CF, Bradley KK, Wright JH, Glowicz J. Case report: emergence of autochthonous cutaneous leishmaniasis in northeastern Texas and southeastern Oklahoma. Am J Trop Med Hyg. 2013;88(1):157–61. Arce A, Estirado A, Ordobas M, et al. Re-emergence of leishmaniasis in Spain: community outbreak in Madrid, Spain, 2009 to 2012. Euro Surveill. 2013;18(30):20546. Lachaud L, Dedet JP, Marty P, et al. Surveillance of leishmaniases in France, 1999 to 2012. Euro Surveill. 2013;18(29):20534. Gkolfinopoulou K, Bitsolas N, Patrinos S, et al. Epidemiology of human leishmaniasis in Greece, 1981-2011. Euro Surveill. 2013;18(29):20532. Shirian S, Oryan A, Hatam GR, Panahi S, Daneshbod Y. Comparison of conventional, molecular, and immunohistochemical methods in diagnosis of typical and atypical cutaneous leishmaniasis. Arch Pathol Lab Med. 2014;138(2):235–40. Centers for Disease Control and Prevention. Practical guide for laboratory diagnosis of leishmaniasis (2012). http://www.cdc.gov/ parasites/leishmaniasis/resources/pdf/cdc_diagnosis_guide_ leishmaniasis.pdf. Accessed May 30, 2014. A very useful, straightforward step-by-step guide for the laboratory diagnosis of leishmaniasis available through the CDC, including specimen collection and shipping directions. Dorlo TP, Balasegaram M, Beijnen JH, de Vries PJ. Miltefosine: a review of its pharmacology and therapeutic efficacy in the treatment of leishmaniasis. J Antimicrob Chemother. 2012;67(11):2576–97. Soto J, Arana BA, Toledo J, et al. Miltefosine for new world cutaneous leishmaniasis. Clin Infect Dis. 2004;38(9):1266–72. Centers for Disease Control and Prevention. DPDx: tungiasis. http://www.cdc.gov/dpdx/tungiasis/. Accessed April 1, 2014. Karunamoorthi K. Tungiasis: a neglected epidermal parasitic skin disease of marginalized populations—a call for global science and policy. Parasitol Res. 2013;112(10):3635–43. Haddad Jr V, Cardoso JL, Lupi O, Tyring SK. Tropical dermatology: venomous arthropods and human skin: part I. Insect J Am Acad Dermatol. 2012;67(3):331 e331–314; quiz 345. A great summary for use in the evaluation of arthropod related skin lesions with pictures of rashes and the insects, applicable to both local patients and the returning traveler. Lefebvre M, Capito C, Durant C, Hervier B, Grossi O. Tungiasis: a poorly documented tropical dermatosis. Med Mal Infect. 2011;41(9):465–8. Feldmeier H, Sentongo E, Krantz I. Tungiasis (sand flea disease): a parasitic disease with particular challenges for public health. Eur J Clin Microbiol Infect Dis. 2013;32(1):19–26. Fydryszewski NA. Myiasis: diagnosis, treatment and medical use of maggots. Clin Lab Sci. 2013;26(2):76–81. A superb, succinct and practical discussion of myiasis from a clinical and laboratory standpoint. Centers for Disease Control and Prevention. Myiasis. http://www. cdc.gov/parasites/myiasis/. Accessed April 1, 2014. Accessed January 10.
28.
Adehossi E, Parola P. A woman with a skin lesion. Myiasis Clin Infect Dis. 2009;48(11):1584. 1628-1589. 29. West JK. Simple and effective field extraction of human botfly, Dermatobia hominis, using a venom extractor. Wilderness Environ Med. 2013;24(1):17–22. 30. Stefani S, Chung DR, Lindsay JA, et al. Meticillin-resistant Staphylococcus aureus (MRSA): global epidemiology and harmonisation of typing methods. Int J Antimicrob Agents. 2012;39(4):273–82. 31. Thati V, Shivannavar CT, Gaddad SM. Vancomycin resistance among methicillin resistant Staphylococcus aureus isolates from intensive care units of tertiary care hospitals in Hyderabad. Indian J Med Res. 2011;134(5):704–8. 32. Rossi F, Diaz L, Wollam A, et al. Transferable vancomycin resistance in a community-associated MRSA lineage. N Engl J Med. 2014;370(16):1524–31. 33.• Molton JS, Tambyah PA, Ang BSP, Lin LM, Fisher DA. The global spread of healthcare-associated multidrug-resistant bacteria: a perspective from Asia. Clin Infect Dis. 2013;56:1310–8. A topical, up to date review article of the new international resistant bacterial pathogens on the horizon. 34. Yong D, Toleman MA, Giske CG, et al. Characterization of a new metallo-beta-lactamase gene, bla(NDM-1), and a novel erythromycin esterase gene carried on a unique genetic structure in Klebsiella pneumoniae sequence type 14 from India. Antimicrob Agents Chemother. 2009;53(12):5046–54. 35.•• Perry RT, Gacic-Dobo M, Dabbagh A, et al. Global control and regional elimination of measles, 2000-2012. MMWR Morb Mortal Wkly Rep. 2014;63(5):103–7. The most recent report on measles epidemiology and progress towards elimination. 36. Antona D, Levy-Bruhl D, Baudon C, et al. Measles elimination efforts and 2008-2011 outbreak. Fr Emerg Infect Dis. 2013;19(3): 357–64. 37. Centers for Disease C, Prevention. Progress toward the 2012 measles elimination goal—Western Pacific Region, 1990-2008. MMWR Morb Mortal Wkly Rep. 2009;58(24):669–73. 38. Bellini WJ, Helfand RF. The challenges and strategies for laboratory diagnosis of measles in an international setting. J Infect Dis. 2003;187 Suppl 1:S283–290. 39. Centers for Disease Control and Prevention. Measles. http://www. cdc.gov/measles/hcp/index.html#features. Accessed June 10, 2014. 40. Centers for Disease Control and Prevention. Chikungunya. http:// www.cdc.gov/chikungunya/. Accessed June 1, 2014. 41. Rezza G, Nicoletti L, Angelini R, et al. Infection with chikungunya virus in Italy: an outbreak in a temperate region. Lancet. 2007;370(9602):1840–6. 42. Taubitz W, Cramer JP, Kapaun A, et al. Chikungunya fever in travelers: clinical presentation and course. Clin Infect Dis. 2007;45(1):e1–4. 43. Raoult D, Roux V. Rickettsioses as paradigms of new or emerging infectious diseases. Clin Microbiol Rev. 1997;10(4):694–719. 44. Centers for Disease Control and Prevention. Other tick-borne spotted fever rickettsial infections. http://www.cdc.gov/ otherspottedfever/. Accessed June 1, 2014.
