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Leishmaniasis, an emerging infection in travelers

Open ArchivePublished:October 21, 2010DOI:https://doi.org/10.1016/j.ijid.2010.06.019

      Summary

      Leishmaniasis is a vector-borne protozoan infection with a wide clinical spectrum, which ranges from asymptomatic infection to fatal visceral leishmaniasis. A review of the recent literature indicates a sharp increase in imported leishmaniasis cases in developed, non-endemic countries over the last decade, in association with increasing international tourism, military operations, and the influx of immigrants from endemic countries. South America is the main area for the acquisition of cutaneous leishmaniasis, and adventure travelers on long-term trips in highly-endemic forested areas are at particular risk. Popular Mediterranean destinations are emerging as the main areas of acquisition of visceral leishmaniasis for European travelers. Leishmaniasis should be considered in patients presenting with a compatible clinical syndrome and a history of travel to an endemic area, even if this occurred several months or years ago. Appropriate counseling should be provided to adventure travelers, military personnel, researchers, and other groups of travelers likely to be exposed to sandflies in endemic areas.

      Keywords

      1. Introduction

      Leishmaniasis is a vector-borne protozoan infection with a clinical spectrum that includes asymptomatic infection and three main clinical syndromes: visceral leishmaniasis (VL; also known as ‘kala-azar’), cutaneous leishmaniasis (CL), and mucosal leishmaniasis (ML). The disease remains a public health problem worldwide, affecting approximately 12 million people in 88 countries where 350 million people live, mainly in remote rural areas and underserved urban areas. Based on geographical distribution, leishmaniasis is divided into Old World and New World leishmaniasis. Infection is transmitted through hematophagus sandflies of the Phlebotomus genus in the Old World and the Lutzomyia genus in the New World. Infection can also be blood-borne, and can occur following organ transplantation or transmitted congenitally. There are more than 17 Leishmania species known to infect humans.
      • Maltezou H.C.
      Leishmaniasis.
      VL is endemic in more than 60 countries in tropical and subtropical areas, and in Mediterranean countries; however 90% of the 500 000 new cases that occur every year concern six countries only – India, Bangladesh, Nepal, Brazil, Ethiopia, and Sudan.
      • Maltezou H.C.
      Leishmaniasis.
      VL is caused by Leishmania donovani in the Indian subcontinent, Asia, and Africa, Leishmania infantum in the Mediterranean basin, and Leishmania chagasi in South America.
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      Leishmaniasis.
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      Imported leishmaniasis, a heterogeneous group of diseases.
      In Mediterranean countries and South America the disease is zoonotic and affects mainly infants and young children.
      • Kafetzis D.A.
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      Visceral leishmaniasis in paediatrics.
      In these countries stray and domestic dogs are the main reservoir for infection, and the VL cycle is sustained in well-defined foci by a high (up to 25%) prevalence of canine leishmaniasis and abundant sandflies.
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      Spread of vector-borne diseases and neglect of leishmaniasis, Europe.
      In the Indian subcontinent and Africa, VL is anthroponotic (human-to-human transmission through sandflies) and affects adults and children.
      • Maltezou H.C.
      Leishmaniasis.
      In the last decade leishmaniasis expanded or emerged in several foci worldwide due to climate and human factors (e.g., urbanization, deforestation).
      • Maltezou H.C.
      Leishmaniasis.
      Models predict that sandflies will further expand with global warming.
      • Sutherst R.W.
      Global change and human vulnerability to vector-borne diseases.
      The widespread emergence of resistance to pentavalent antimonials in India, where half of VL cases occur globally, and the emergence of HIV co-infection (in Northwest Ethiopia up to 30% of VL cases are HIV-co-infected) compromise its control.
      • Maltezou H.C.
      Drug resistance in visceral leishmaniasis.
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      • Dedet J.P.
      • et al.
      The relationship between leishmaniasis and AIDS: the second 10 years.
      CL is endemic in more than 70 countries, with an estimated of 1.5–2 million new cases every year.
      • Maltezou H.C.
      Leishmaniasis.
      Afghanistan, Syria, and Brazil are the main foci. CL is more common in rural areas in settings ranging from rainforests to arid regions; however it is becoming increasingly reported in urban and peri-urban areas of the Old and New World.
      • Maltezou H.C.
      Leishmaniasis.
      CL is caused by Leishmania tropica, Leishmania major, and L. infantum in the Old World and by Leishmania braziliensis, Leishmania guyanensis, Leishmania panamensis, Leishmania peruviana, Leishmania mexicana, Leishmania amazonensis, and Leishmania venezuelensis in the New World.
      • Maltezou H.C.
      Leishmaniasis.
      Although ML develops in only a small number of patients with New World CL, its course is chronic and may be life-threatening.
      • Maltezou H.C.
      Leishmaniasis.
      International travel is growing rapidly worldwide. It has been estimated that approximately 1 billion international travel movements will occur up to the end of 2010 and 1.6 billion up to 2020, most of which will take place in tropical and subtropical areas.

      World Tourism Organization. Tourism 2020 vision. Available at: http://www.world-tourism.org (accessed September 17, 2010).

      More than half of international travelers are traveling for leisure, however an increasing number of travelers are immigrants visiting friends and relatives in tropical and subtropical areas. International travelers are increasingly involved in adventure travel and outdoor activities,
      • Pérez-Ayala A.
      • Norman F.
      • Pérez-Molina J.A.
      • Herrero J.M.
      • Monge B.
      • López-Vélez R.
      Imported leishmaniasis, a heterogeneous group of diseases.

      Travel Industry Association. Travel market segments. Available at: http://www.ustravel.org/research/international-research (accessed September 17, 2010).

      which render them at increased risk of contracting leishmaniasis. Over the last decade there has been an increase in articles on imported cases in developed, non-endemic countries in association with increasing international tourism, military operations, the influx of immigrants from endemic countries, and HIV-infected persons.
      • Pérez-Ayala A.
      • Norman F.
      • Pérez-Molina J.A.
      • Herrero J.M.
      • Monge B.
      • López-Vélez R.
      Imported leishmaniasis, a heterogeneous group of diseases.
      • Antinori S.
      • Gianelli E.
      • Calattini S.
      • Longhi E.
      • Gramiccia M.
      • Corbellino M.
      Cutaneous leishmaniasis: an increasing threat for travelers.
      • 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.
      • Lawn S.D.
      • Whetham J.
      • Chiodini P.L.
      • Kanagalingham J.
      • Whatson J.
      • Behrens R.H.
      • et al.
      New world mucosal and cutaneous leishmaniasis: an emerging health problem among British travellers.
      • Morizot G.
      • Delgiudice P.
      • Caumes E.
      • Laffitte E.
      • Marty P.
      • Dupuy A.
      • et al.
      Healing of Old World cutaneous leishmaniasis in travelers treated with fluconazole: drug effect or spontaneous evolution?.
      • Stark D.
      • van Hal S.
      • Lee R.
      • Marriott D.
      • Harkness J.
      Leishmaniasis, an emerging imported infection: report of 20 cases from Australia.
      • Malik A.N.
      • John L.
      • Bryceson A.D.
      • Lockwood D.N.
      Changing pattern of visceral leishmaniasis, United Kingdom, 1985–2004.
      • Herwald B.L.
      • Stokes S.L.
      • Juranek D.D.
      American cutaneous leishmaniasis in U.S. travelers.

      Centers for Disease Control and Prevention. Update: cutaneous leishmaniasis in U.S. military personnel—Southwest/Central Asia, 2002–2004. MMWR Morb Mortal Wkly Rep 2004; 53:264–5.

      • Ahluwalia S.
      • Lawn S.D.
      • Kanagalingam J.
      • Grant H.
      • Lockwood D.N.
      Mucocutaneous leishmaniasis: an imported infection among travelers to Central and South America.
      CL is emerging among travelers involved in outdoor activities in endemic areas, and is one of the top 10 diseases among tourists returning from tropical countries with skin problems.
      • 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.
      A significant number of VL cases have also been reported among travelers in recent years.
      • Pérez-Ayala A.
      • Norman F.
      • Pérez-Molina J.A.
      • Herrero J.M.
      • Monge B.
      • López-Vélez R.
      Imported leishmaniasis, a heterogeneous group of diseases.
      • Stark D.
      • van Hal S.
      • Lee R.
      • Marriott D.
      • Harkness J.
      Leishmaniasis, an emerging imported infection: report of 20 cases from Australia.
      • Malik A.N.
      • John L.
      • Bryceson A.D.
      • Lockwood D.N.
      Changing pattern of visceral leishmaniasis, United Kingdom, 1985–2004.
      • Harms G.
      • Schönian G.
      • Feldmeier H.
      Leishmaniasis in Germany.
      In non-endemic countries the management of leishmaniasis remains a challenge for physicians, and delayed diagnosis and inappropriate treatment are frequently encountered.
      • Antinori S.
      • Gianelli E.
      • Calattini S.
      • Longhi E.
      • Gramiccia M.
      • Corbellino M.
      Cutaneous leishmaniasis: an increasing threat for travelers.
      • Lawn S.D.
      • Whetham J.
      • Chiodini P.L.
      • Kanagalingham J.
      • Whatson J.
      • Behrens R.H.
      • et al.
      New world mucosal and cutaneous leishmaniasis: an emerging health problem among British travellers.
      • Stark D.
      • van Hal S.
      • Lee R.
      • Marriott D.
      • Harkness J.
      Leishmaniasis, an emerging imported infection: report of 20 cases from Australia.
      • Malik A.N.
      • John L.
      • Bryceson A.D.
      • Lockwood D.N.
      Changing pattern of visceral leishmaniasis, United Kingdom, 1985–2004.
      This article reviews travel-acquired leishmaniasis with a focus on epidemiology and treatment. We searched the PubMed database for the period 1980 through January 31, 2010 using the words ‘leishmaniasis’, ‘imported’, ‘travelers’, and ‘travel-acquired’. Articles presenting original data on imported leishmaniasis cases were included in our review, and review articles were also studied.

      2. Leishmaniasis in international travelers

      A sharp increase in imported leishmaniasis cases in industrialized, non-endemic countries, in association with increasing international travel, military activities, and immigration has been published in the last decade. We found 29 articles presenting original data on travel-acquired leishmaniasis.
      • Pérez-Ayala A.
      • Norman F.
      • Pérez-Molina J.A.
      • Herrero J.M.
      • Monge B.
      • López-Vélez R.
      Imported leishmaniasis, a heterogeneous group of diseases.
      • Antinori S.
      • Gianelli E.
      • Calattini S.
      • Longhi E.
      • Gramiccia M.
      • Corbellino M.
      Cutaneous leishmaniasis: an increasing threat for travelers.
      • Lawn S.D.
      • Whetham J.
      • Chiodini P.L.
      • Kanagalingham J.
      • Whatson J.
      • Behrens R.H.
      • et al.
      New world mucosal and cutaneous leishmaniasis: an emerging health problem among British travellers.
      • Morizot G.
      • Delgiudice P.
      • Caumes E.
      • Laffitte E.
      • Marty P.
      • Dupuy A.
      • et al.
      Healing of Old World cutaneous leishmaniasis in travelers treated with fluconazole: drug effect or spontaneous evolution?.
      • Stark D.
      • van Hal S.
      • Lee R.
      • Marriott D.
      • Harkness J.
      Leishmaniasis, an emerging imported infection: report of 20 cases from Australia.
      • Malik A.N.
      • John L.
      • Bryceson A.D.
      • Lockwood D.N.
      Changing pattern of visceral leishmaniasis, United Kingdom, 1985–2004.
      • Herwald B.L.
      • Stokes S.L.
      • Juranek D.D.
      American cutaneous leishmaniasis in U.S. travelers.

      Centers for Disease Control and Prevention. Update: cutaneous leishmaniasis in U.S. military personnel—Southwest/Central Asia, 2002–2004. MMWR Morb Mortal Wkly Rep 2004; 53:264–5.

      • Ahluwalia S.
      • Lawn S.D.
      • Kanagalingam J.
      • Grant H.
      • Lockwood D.N.
      Mucocutaneous leishmaniasis: an imported infection among travelers to Central and South America.
      • Harms G.
      • Schönian G.
      • Feldmeier H.
      Leishmaniasis in Germany.
      • El Hajj Thellier M.
      • Carriere J.
      • Bricaire F.
      • Danis M.
      • Caumes E.
      Localized cutaneous leishmaniasis imported into Paris: a review pf 39 cases.
      • Scarisbrick J.
      • Chiodini P.
      • Watson J.
      • Moody A.
      • Armstrong M.
      • Lockwood D.
      • et al.
      Clinical features and diagnosis of 42 travellers with cutaneous leishmaniasis.
      • Delgado O.
      • Silva S.
      • Coraspe V.
      • Rivas M.A.
      • Rodriguez-Morales A.J.
      • Navarro P.
      • et al.
      Cutaneous leishmaniasis imported from Colombia to Northcentral Venezuela: implications for travel advice.
      • Berens-Riha N.
      • Fleischmann E.
      • Pratlong E.
      • Bretzel G.
      • von Sonnenburg F.
      • Löscher T.
      Cutaneous leishmaniasis (Leishmania tropica) in a German tourist after travel to Greece.
      • Joseph M.
      • Soong V.
      • Soong L.
      Leishmania mexicana infection of the eyelid in a traveler to Belize.
      • Haider S.
      • Boutross-Tadross O.
      • Radhi J.
      • Momar N.
      Cutaneous ulcer in a man returning from central America.
      • Scope A.
      • Trau H.
      • Bakon M.
      • Yarom N.
      • Nasereddin A.
      • Schwartz E.
      Imported mucosal leishmaniasis in a traveler.
      • Weitzel T.
      • Mühlberger N.
      • Jelinek T.
      • Schunk M.
      • Ehrhardt
      • Bogdan C.
      • et al.
      Imported leishmaniasis in Germany 2001-2004: data of the SIMPID surveillance network.
      • Ju O.
      • Grove D.I.
      • Jaksic W.J.
      • Dart G.W.
      Visceral leishmaniasis: a trip to the Greek Islands is not always idyllic.

      Army Medical Surveillance Activity (AMSA). Leishmaniasis in relation to service in Iraq/Afghanistan, U.S. Armed Forces, 2001–2006. Medical Surveillance Monthly Report 2007; 14:2–5.

      • Woodrow J.P.
      • Hartzell J.D.
      • Czarnik J.
      • Brett-Major D.M.
      • Wortmann G.
      Cutaneous and presumed visceral leishmaniasis in a soldier deployed to Afghanistan.

      Centers for Disease Control and Prevention. Viscerotropic leishmaniasis in persons returning from Operation Desert Storm—1990–-1991. MMWR Morb Mortal Wkly Rep 1992; 41:131–4.

      Centers for Disease Control and Prevention. Cutaneous leishmaniasis in U.S. military personnel—Southwest/Central Asia, 2002–2003. MMWR Morb Mortal Wkly Rep 2003; 52;1009–12.

      Centers for Disease Control and Prevention. Two cases of visceral leishmaniasis in U.S. military personnel—Afghanistan, 2002–2004. MMWR Morb Mortal Wkly Rep 2004; 53:265–8.

      • Willard R.J.
      • Jeffcoat A.M.
      • Benson P.M.
      • Walsh D.S.
      Cutaneous leishmaniasis in soldiers from Fort Campell, Kentucky returning from Operation Iraqi Freedom highlights diagnostic and therapeutic options.
      • Bezold G.
      • Lange M.
      • Gethöffer K.
      • Pillekamp H.
      • Reindl H.
      • Richter C.
      • et al.
      Competitive polymerase chain reaction used to diagnose cutaneous leishmaniasis in German soldiers infected during military exercises in French Guiana.
      • Scope A.
      • Trau H.
      • Anders G.
      • Barzilai A.
      • Confino Y.
      • Schwartz E.
      Experience with New World cutaneous leishmaniasis in travelers.
      • Solomon M.
      • Baum S.
      • Barzilai A.
      • Scope A.
      • Trau H.
      • Schwartz E.
      Liposomal amphotericin B in comparison to sodium stibogluconate for cutaneous infection due to Leishmania braziliensis.
      • Zlotogorski A.
      • Gilead L.
      • Jonas F.
      • Horev L.
      • Klaus S.N.
      South American cutaneous leishmaniasis: report of ten cases in Israeli travelers.
      Of these, 21 referred to international travelers, including some cases of military personnel, while eight articles reported military personnel exclusively. The characteristics of these cases are shown in Table 1, Table 2. Out of 2577 published travel-acquired leishmaniasis cases, 80% concerned military personnel, of which almost all (99%) occurred from the year 2000 onwards. With regard to international travelers, more than 50% of cases for whom the year of acquisition of infection was reported occurred after 2000. Given the lack of familiarity of physicians in non-endemic countries with leishmaniasis and the fact that CL frequently self-heals, many cases may have remained unrecognized. It is expected that the risk and therefore the incidence of leishmaniasis among international travelers is likely to increase in the coming years, given the increasing popularity of travel and ecotourism in endemic destinations, as well as military operations and immigration. In the UK an increase in the annual number of imported CL cases has been noted – from 4 to 18 per year between 1995 and 2003.
      • Lawn S.D.
      • Whetham J.
      • Chiodini P.L.
      • Kanagalingham J.
      • Whatson J.
      • Behrens R.H.
      • et al.
      New world mucosal and cutaneous leishmaniasis: an emerging health problem among British travellers.
      The rise of L. braziliensis CL cases diagnosed in the UK is associated with the increasing number of travelers to South America (3.5-fold increase from 1995 to 2003), mainly to highly endemic foci in Bolivia and Belize.
      • Lawn S.D.
      • Whetham J.
      • Chiodini P.L.
      • Kanagalingham J.
      • Whatson J.
      • Behrens R.H.
      • et al.
      New world mucosal and cutaneous leishmaniasis: an emerging health problem among British travellers.
      Table 1Published cases of travel-acquired leishmaniasis
      Importation country [Ref.]Time periodNo. of casesArea of infectionTravel typeImmuno-compromisedAge (years)Male sexCases per clinical form CL/ML/VL/MCLTime to diagnosis (months)/outcome after treatment
      Australia
      • Stark D.
      • van Hal S.
      • Lee R.
      • Marriott D.
      • Harkness J.
      Leishmaniasis, an emerging imported infection: report of 20 cases from Australia.
      2005–200720Asia, Africa, southern Europe, South AmericaImmigrants (45%), travelers (55%)10%8–5985%18/-/2/-NA/NA
      Australia
      • Ju O.
      • Grove D.I.
      • Jaksic W.J.
      • Dart G.W.
      Visceral leishmaniasis: a trip to the Greek Islands is not always idyllic.
      20041Southern EuropeTourist18100%-/-/1/-12 months/cured
      Canada
      • Haider S.
      • Boutross-Tadross O.
      • Radhi J.
      • Momar N.
      Cutaneous ulcer in a man returning from central America.
      20031AfricaTourist54100%1/-/-/-3 months/cured
      France
      • Morizot G.
      • Delgiudice P.
      • Caumes E.
      • Laffitte E.
      • Marty P.
      • Dupuy A.
      • et al.
      Healing of Old World cutaneous leishmaniasis in travelers treated with fluconazole: drug effect or spontaneous evolution?.
      2003–200535AfricaNA1–7045.7%35/-/-/-1–12 months/15 complete clinical response,
      Twenty-seven patients with Leishmania major CL were treated with oral fluconazole.
      20 failed to respond
      France
      • El Hajj Thellier M.
      • Carriere J.
      • Bricaire F.
      • Danis M.
      • Caumes E.
      Localized cutaneous leishmaniasis imported into Paris: a review pf 39 cases.
      1992–200039Old World and New WorldTravelers, immigrants (NA)38
      Mean age.
      64%39/-/-/-Up to 10 months/35 cured, 2 self-healed, 2 not assessed
      Germany
      • Harms G.
      • Schönian G.
      • Feldmeier H.
      Leishmaniasis in Germany.
      2000–200258Southern Europe, South America, Asia, Middle East, AfricaTourists (50%), immigrants, workers (7%)20.6%
      Six cases of VL were HIV-seropositive.
      8 mo–7070.6%35 (CL+ML)/23/-1–16 months/42 cured, 2 improved, 3 no cure, 8 unknown, 1 relapse, 2 no relapse at 6–8 months
      Germany
      • Berens-Riha N.
      • Fleischmann E.
      • Pratlong E.
      • Bretzel G.
      • von Sonnenburg F.
      • Löscher T.
      Cutaneous leishmaniasis (Leishmania tropica) in a German tourist after travel to Greece.
      20091Southern EuropeTourist66100%1/-/-/-3 months/cured
      Germany
      • Weitzel T.
      • Mühlberger N.
      • Jelinek T.
      • Schunk M.
      • Ehrhardt
      • Bogdan C.
      • et al.
      Imported leishmaniasis in Germany 2001-2004: data of the SIMPID surveillance network.
      2001–200442Southern Europe, Africa, Asia, Middle East, South and Central AmericaTourist, expatriates, immigrants (NA)12%
      Six cases (five VL and one CL) were HIV-seropositive.
      1–7569%23/3/16/-0–30 months/5 treatment complications, 1 died (with HIV)
      Israel
      • Scope A.
      • Trau H.
      • Bakon M.
      • Yarom N.
      • Nasereddin A.
      • Schwartz E.
      Imported mucosal leishmaniasis in a traveler.
      20031South AmericaTraveler (NA)26100%-/1/-/-0.5 months/improved
      Israel
      • Scope A.
      • Trau H.
      • Anders G.
      • Barzilai A.
      • Confino Y.
      • Schwartz E.
      Experience with New World cutaneous leishmaniasis in travelers.
      1998–200112South AmericaTravelers23–2992%12/-/-/-1–3/cured
      Israel
      • Solomon M.
      • Baum S.
      • Barzilai A.
      • Scope A.
      • Trau H.
      • Schwartz E.
      Liposomal amphotericin B in comparison to sodium stibogluconate for cutaneous infection due to Leishmania braziliensis.
      2004–20057South AmericaTravelers21–2471%7/-/-/-NA/cured
      Israel
      • Zlotogorski A.
      • Gilead L.
      • Jonas F.
      • Horev L.
      • Klaus S.N.
      South American cutaneous leishmaniasis: report of ten cases in Israeli travelers.
      1994–199610South AmericaTravelers22–2980%100.6/NA
      Italy
      • Antinori S.
      • Gianelli E.
      • Calattini S.
      • Longhi E.
      • Gramiccia M.
      • Corbellino M.
      Cutaneous leishmaniasis: an increasing threat for travelers.
      2001–20024Asia, Africa, Central AmericaTourists (75%), soldier (25%)23–63100%3/1/-/-Up to 1 month/cured
      Spain
      • Pérez-Ayala A.
      • Norman F.
      • Pérez-Molina J.A.
      • Herrero J.M.
      • Monge B.
      • López-Vélez R.
      Imported leishmaniasis, a heterogeneous group of diseases.
      1995–200818Central and South America, Africa, AsiaMigrants (38%), travelers (62%)11%17–5566.6%12/4/2/-0.5–48 months/11 good response, 1 slow response, 2 relapse, 2 complications, 3 no follow-up
      UK
      • Malik A.N.
      • John L.
      • Bryceson A.D.
      • Lockwood D.N.
      Changing pattern of visceral leishmaniasis, United Kingdom, 1985–2004.
      1985–200439Southern Europe, Africa, Asia, South AmericaImmigrants–refugees (45.5%), tourists (55.5%)38.4%
      Thirteen cases were HIV-seropositive.
      2–6666.6%-/-/39/-1–11 months/34 cured, 3 died while on treatment, 2 refused treatment
      UK
      • Ahluwalia S.
      • Lawn S.D.
      • Kanagalingam J.
      • Grant H.
      • Lockwood D.N.
      Mucocutaneous leishmaniasis: an imported infection among travelers to Central and South America.
      20043South AmericaTourists (100%)17–3833.3%-/-/-/30–1 month/cured
      UK
      • Lawn S.D.
      • Whetham J.
      • Chiodini P.L.
      • Kanagalingham J.
      • Whatson J.
      • Behrens R.H.
      • et al.
      New world mucosal and cutaneous leishmaniasis: an emerging health problem among British travellers.
      1995 –200385South AmericaTourist (most), military (NA)17–8168%79/6/-/-0.5–2 months/cured (data available for ML only)
      UK
      • Scarisbrick J.
      • Chiodini P.
      • Watson J.
      • Moody A.
      • Armstrong M.
      • Lockwood D.
      • et al.
      Clinical features and diagnosis of 42 travellers with cutaneous leishmaniasis.
      1997–200042South America, southern Europe, Asia, AfricaTourists, military, scientific work, immigration (NA)NA64.2%42/-/-/-21 patients <3 months, 3 patients 3–6 months, 7 patients 6–12 months, 4 patients >12 months/cured
      USA
      • Herwald B.L.
      • Stokes S.L.
      • Juranek D.D.
      American cutaneous leishmaniasis in U.S. travelers.
      1985–199059Central America, South AmericaTravelers (39%), scientists (46%) (long-term) (NA)3–6467.7%59/-/-/-13–1022 days/NA
      USA
      • Joseph M.
      • Soong V.
      • Soong L.
      Leishmania mexicana infection of the eyelid in a traveler to Belize.
      20071South AmericaTourist50100%-/1/-/-1 month/cured
      Venezuela
      • Delgado O.
      • Silva S.
      • Coraspe V.
      • Rivas M.A.
      • Rodriguez-Morales A.J.
      • Navarro P.
      • et al.
      Cutaneous leishmaniasis imported from Colombia to Northcentral Venezuela: implications for travel advice.
      2001–200629South AmericaTravelers (100%)7–64NA (most males)29/-/-/-NA/NA
      CL, cutaneous leishmaniasis; ML, mucosal leishmaniasis; VL, visceral leishmaniasis; MCL, mucocutaneous leishmaniasis; NA, not available.
      a Twenty-seven patients with Leishmania major CL were treated with oral fluconazole.
      b Mean age.
      c Six cases of VL were HIV-seropositive.
      d Six cases (five VL and one CL) were HIV-seropositive.
      e Thirteen cases were HIV-seropositive.
      Table 2Published cases of travel-acquired leishmaniasis in military personnel
      Importation country [Ref.]Time periodNo. of casesArea of infectionTravel typeImmuno-compromisedAge (years)Male sexCases per clinical form CL/ML/VL/MCLTime to diagnosis/outcome after treatment
      USA

      Centers for Disease Control and Prevention. Update: cutaneous leishmaniasis in U.S. military personnel—Southwest/Central Asia, 2002–2004. MMWR Morb Mortal Wkly Rep 2004; 53:264–5.

      2002–2004522Southwest and Central AsiaMilitary18–5767.7%522/-/-/-NA
      USA

      Army Medical Surveillance Activity (AMSA). Leishmaniasis in relation to service in Iraq/Afghanistan, U.S. Armed Forces, 2001–2006. Medical Surveillance Monthly Report 2007; 14:2–5.

      2001–20061287Iraq/AfghanistanMilitary<3096%1283/-/4/-NA/NA
      USA
      • Woodrow J.P.
      • Hartzell J.D.
      • Czarnik J.
      • Brett-Major D.M.
      • Wortmann G.
      Cutaneous and presumed visceral leishmaniasis in a soldier deployed to Afghanistan.
      20061AfghanistanMilitary35100%1/-/1/-
      One patient had both CL and VL.
      3/0.25 months/cured
      USA

      Centers for Disease Control and Prevention. Viscerotropic leishmaniasis in persons returning from Operation Desert Storm—1990–-1991. MMWR Morb Mortal Wkly Rep 1992; 41:131–4.

      1990–19917Saudi ArabiaMilitary1
      One case of HIV infection.
      21–40100%-/-/7/-NA/cured
      USA

      Centers for Disease Control and Prevention. Cutaneous leishmaniasis in U.S. military personnel—Southwest/Central Asia, 2002–2003. MMWR Morb Mortal Wkly Rep 2003; 52;1009–12.

      2002–200322Afghanistan, Iraq, KuwaitMilitary21–4895%22/-/-/-NA/cured
      USA

      Centers for Disease Control and Prevention. Two cases of visceral leishmaniasis in U.S. military personnel—Afghanistan, 2002–2004. MMWR Morb Mortal Wkly Rep 2004; 53:265–8.

      2002–20042AfghanistanMilitary31,39100%2<1 month/cured
      USA
      • Willard R.J.
      • Jeffcoat A.M.
      • Benson P.M.
      • Walsh D.S.
      Cutaneous leishmaniasis in soldiers from Fort Campell, Kentucky returning from Operation Iraqi Freedom highlights diagnostic and therapeutic options.
      2003–2004237IraqMilitaryNA97%237NA/majority cured
      Germany
      • Bezold G.
      • Lange M.
      • Gethöffer K.
      • Pillekamp H.
      • Reindl H.
      • Richter C.
      • et al.
      Competitive polymerase chain reaction used to diagnose cutaneous leishmaniasis in German soldiers infected during military exercises in French Guiana.
      19992French GuianaMilitary21, 24100%2NA/cured
      CL, cutaneous leishmaniasis; ML, mucosal leishmaniasis; VL, visceral leishmaniasis; MCL, mucocutaneous leishmaniasis; NA, not available.
      a One case of HIV infection.
      b One patient had both CL and VL.
      The area of acquisition of infection reflects travel destinations of the population studied. In the USA most CL cases in civilians are acquired in Mexico and Central America, with an estimated incidence of one CL case treated with antimonials per 1000 travelers to Suriname and one per 1 million travelers to Mexico.
      • Herwald B.L.
      • Stokes S.L.
      • Juranek D.D.
      American cutaneous leishmaniasis in U.S. travelers.
      According to our review (Table 1), the New World accounts for 59% of imported cases in non-endemic countries. Data from the Geosentinel database for 1996–2004 show that CL is among the 10 most frequent dermatologic disorders encountered in returned travelers, and South America is the main area of acquisition of CL, followed by Central America.
      • Freedman D.O.
      • Weld L.H.
      • Kozarsky P.E.
      • Fisk T.
      • Robins R.
      • von Sonnenburg F.
      • et al.
      Spectrum of disease and relation to place of exposure among ill returned travelers.
      Data from the German Surveillance System for Imported Diseases collected during 2001–2004 indicate that the vast majority (81%) of VL cases were acquired in the countries of southern Europe, while almost half (48%) of CL cases were acquired in South America.
      • Weitzel T.
      • Mühlberger N.
      • Jelinek T.
      • Schunk M.
      • Ehrhardt
      • Bogdan C.
      • et al.
      Imported leishmaniasis in Germany 2001-2004: data of the SIMPID surveillance network.
      Germans on holiday accounted for most imported cases in Germany, however a non-negligible (19%) number were non-European immigrants.
      • Weitzel T.
      • Mühlberger N.
      • Jelinek T.
      • Schunk M.
      • Ehrhardt
      • Bogdan C.
      • et al.
      Imported leishmaniasis in Germany 2001-2004: data of the SIMPID surveillance network.
      In this study, the relative risk for acquisition of leishmaniasis per geographic area compared with southern Europe was estimated at 22.7 for South America, 5.4 for Asia, and 2.1 for Africa.
      • Weitzel T.
      • Mühlberger N.
      • Jelinek T.
      • Schunk M.
      • Ehrhardt
      • Bogdan C.
      • et al.
      Imported leishmaniasis in Germany 2001-2004: data of the SIMPID surveillance network.
      Similarly, imported VL cases to the UK during 1985–2004 were contracted in Italy, Spain, Greece, Cyprus, and Malta, and tourists accounted for 55.5% of them, while the remaining patients were immigrants; however after 2000 all patients were tourists.
      • Malik A.N.
      • John L.
      • Bryceson A.D.
      • Lockwood D.N.
      Changing pattern of visceral leishmaniasis, United Kingdom, 1985–2004.
      Of note, few imported cases are acquired in countries where the vast majority of the global burden of leishmaniasis occurs – Indian subcontinent, East Africa, and the Middle East. This highlights the different epidemiologic profile between indigenous and imported cases.
      Imported leishmaniasis is most frequently diagnosed among tourists and travelers traveling for professional reasons (researchers, construction workers, military personnel), as well as immigrants and expatriates (Table 1). Ecotourists, adventure travelers, soldiers, journalists, photographers, and researchers on long-term trips who work in forests during the nighttime (e.g., geologists, veterinarians) are at high risk for acquiring CL.
      • El Hajj Thellier M.
      • Carriere J.
      • Bricaire F.
      • Danis M.
      • Caumes E.
      Localized cutaneous leishmaniasis imported into Paris: a review pf 39 cases.
      In a 5.3-year study of American CL in US travelers, 39% occurred among tourists and 46% among scientists traveling in Central and South America. This represented one thousandth of the estimated annual cases of American CL in the USA (n = 59,300).
      • Herwald B.L.
      • Stokes S.L.
      • Juranek D.D.
      American cutaneous leishmaniasis in U.S. travelers.
      Long-term travel in endemic areas is a risk factor for the acquisition of leishmaniasis, however even short-term travelers may contract the disease. Men account for 64–71% of all travel-acquired leishmaniasis cases;
      • Herwald B.L.
      • Stokes S.L.
      • Juranek D.D.
      American cutaneous leishmaniasis in U.S. travelers.
      • Harms G.
      • Schönian G.
      • Feldmeier H.
      Leishmaniasis in Germany.
      • El Hajj Thellier M.
      • Carriere J.
      • Bricaire F.
      • Danis M.
      • Caumes E.
      Localized cutaneous leishmaniasis imported into Paris: a review pf 39 cases.
      • Weitzel T.
      • Mühlberger N.
      • Jelinek T.
      • Schunk M.
      • Ehrhardt
      • Bogdan C.
      • et al.
      Imported leishmaniasis in Germany 2001-2004: data of the SIMPID surveillance network.
      this is attributed to the overrepresentation of men in high-risk outdoor activities.
      More than 80% of imported leishmaniasis cases in returned travelers concern CL (Table 1). ML is rarely reported among travelers, however nowadays ML is increasingly identified among travelers to South America, with the vast majority of cases acquired in rural or forest areas of the Amazon basin in Bolivia, where highly endemic foci for L. braziliensis exist.
      • Lawn S.D.
      • Whetham J.
      • Chiodini P.L.
      • Kanagalingham J.
      • Whatson J.
      • Behrens R.H.
      • et al.
      New world mucosal and cutaneous leishmaniasis: an emerging health problem among British travellers.
      • Ahluwalia S.
      • Lawn S.D.
      • Kanagalingam J.
      • Grant H.
      • Lockwood D.N.
      Mucocutaneous leishmaniasis: an imported infection among travelers to Central and South America.
      VL is also rare in travelers.
      • Freedman D.O.
      • Weld L.H.
      • Kozarsky P.E.
      • Fisk T.
      • Robins R.
      • von Sonnenburg F.
      • et al.
      Spectrum of disease and relation to place of exposure among ill returned travelers.
      Imported VL cases usually concern adult male tourists, HIV-infected persons, or children.
      • Pérez-Ayala A.
      • Norman F.
      • Pérez-Molina J.A.
      • Herrero J.M.
      • Monge B.
      • López-Vélez R.
      Imported leishmaniasis, a heterogeneous group of diseases.
      • Stark D.
      • van Hal S.
      • Lee R.
      • Marriott D.
      • Harkness J.
      Leishmaniasis, an emerging imported infection: report of 20 cases from Australia.
      • Malik A.N.
      • John L.
      • Bryceson A.D.
      • Lockwood D.N.
      Changing pattern of visceral leishmaniasis, United Kingdom, 1985–2004.
      • Harms G.
      • Schönian G.
      • Feldmeier H.
      Leishmaniasis in Germany.
      • Weitzel T.
      • Mühlberger N.
      • Jelinek T.
      • Schunk M.
      • Ehrhardt
      • Bogdan C.
      • et al.
      Imported leishmaniasis in Germany 2001-2004: data of the SIMPID surveillance network.
      The diagnosis of CL or ML in returned travelers has been delayed several months or years after the onset of symptoms; similar delays have been reported for VL cases in non-endemic countries.
      • Lawn S.D.
      • Whetham J.
      • Chiodini P.L.
      • Kanagalingham J.
      • Whatson J.
      • Behrens R.H.
      • et al.
      New world mucosal and cutaneous leishmaniasis: an emerging health problem among British travellers.
      • Malik A.N.
      • John L.
      • Bryceson A.D.
      • Lockwood D.N.
      Changing pattern of visceral leishmaniasis, United Kingdom, 1985–2004.
      • Herwald B.L.
      • Stokes S.L.
      • Juranek D.D.
      American cutaneous leishmaniasis in U.S. travelers.
      • Harms G.
      • Schönian G.
      • Feldmeier H.
      Leishmaniasis in Germany.
      • El Hajj Thellier M.
      • Carriere J.
      • Bricaire F.
      • Danis M.
      • Caumes E.
      Localized cutaneous leishmaniasis imported into Paris: a review pf 39 cases.
      • Scarisbrick J.
      • Chiodini P.
      • Watson J.
      • Moody A.
      • Armstrong M.
      • Lockwood D.
      • et al.
      Clinical features and diagnosis of 42 travellers with cutaneous leishmaniasis.
      • Scope A.
      • Trau H.
      • Bakon M.
      • Yarom N.
      • Nasereddin A.
      • Schwartz E.
      Imported mucosal leishmaniasis in a traveler.
      • Weitzel T.
      • Mühlberger N.
      • Jelinek T.
      • Schunk M.
      • Ehrhardt
      • Bogdan C.
      • et al.
      Imported leishmaniasis in Germany 2001-2004: data of the SIMPID surveillance network.
      In contrast, in endemic countries VL is diagnosed as early as 2 weeks after the onset of symptoms.
      • Maltezou H.C.
      • Siafas C.
      • Mavrikou M.
      • Spyridis P.
      • Stavrinadis C.
      • Karpathios T.
      • et al.
      Visceral leishmaniasis during childhood in Southern Greece.
      Inappropriate management of leishmaniasis is also common.
      • Antinori S.
      • Gianelli E.
      • Calattini S.
      • Longhi E.
      • Gramiccia M.
      • Corbellino M.
      Cutaneous leishmaniasis: an increasing threat for travelers.
      • Lawn S.D.
      • Whetham J.
      • Chiodini P.L.
      • Kanagalingham J.
      • Whatson J.
      • Behrens R.H.
      • et al.
      New world mucosal and cutaneous leishmaniasis: an emerging health problem among British travellers.
      • Haider S.
      • Boutross-Tadross O.
      • Radhi J.
      • Momar N.
      Cutaneous ulcer in a man returning from central America.
      One patient with New World CL consulted six physicians, underwent two skin grafts, and paid a total of US$ 6600 before the correct diagnosis was considered.
      • Morizot G.
      • Delgiudice P.
      • Caumes E.
      • Laffitte E.
      • Marty P.
      • Dupuy A.
      • et al.
      Healing of Old World cutaneous leishmaniasis in travelers treated with fluconazole: drug effect or spontaneous evolution?.
      International travelers are frequently unaware about leishmaniasis and the appropriate protective measures. A survey conducted among 373 travelers in Manu National Park, Peru, revealed that only 6% of them had heard of leishmaniasis, although 96.5% had received pre-travel advice and 97.5% used protective measures.
      • Bauer I.L.
      Knowledge and behavior of tourists to Manu National Park, Peru, in relation to leishmaniasis.
      In another survey conducted among 58 American travelers with New World CL, 53% reported that they have heard about leishmaniasis, however only 29% were aware of protective measures; of note, 63% of the 47% travelers who had never heard about leishmaniasis had received pre-travel advice.
      • Herwald B.L.
      • Stokes S.L.
      • Juranek D.D.
      American cutaneous leishmaniasis in U.S. travelers.
      Travel and immigration may also contribute to the introduction of new Leishmania species in an already endemic area.
      • Kiiamov F.A.
      • Orlova L.S.
      • Topchin IuA
      • Shalabaev G.A.
      Cases of cutaneous leishmaniasis infection resulting from the importation of sandflies via transportation means.
      CL has been reported in patients with no history of travel to an endemic area, through importation of sandflies with various transportation means from endemic areas.
      • Kiiamov F.A.
      • Orlova L.S.
      • Topchin IuA
      • Shalabaev G.A.
      Cases of cutaneous leishmaniasis infection resulting from the importation of sandflies via transportation means.
      Importation of canine VL to a naïve area may have public health consequences. One case of canine VL was imported to French Guiana, most probably from France, with a recorded secondary case.
      • Rotureau B.
      • Ravel C.
      • Aznar C.
      • Carme B.
      • Detet J.P.
      First report of Leishmania infantum in French Guiana: canine visceral leishmaniasis imported from the Old World.

      3. Clinical manifestations

      Clinical manifestations vary by Leishmania species, area of acquisition of infection, and host factors. CL is the most common form of leishmaniasis. VL is the most serious form of leishmaniasis. Infection with viscerotropic Leishmania species usually results in asymptomatic or mild illness followed by spontaneous resolution. Only one out of 30–100 infected cases develop typical VL. Factors predisposing to development of typical VL include young age, malnutrition, poverty, immune deficiency, and high leishmanial load.
      • Maltezou H.C.
      Leishmaniasis.
      Progression to typical VL usually takes 2–8 months or occasionally longer, however cases as short as 2 weeks after infection have been reported.
      • Maltezou H.C.
      Leishmaniasis.
      Typically the patient develops fever, weakness, anorexia, weight loss, pallor, hepatosplenomegaly (usually splenomegaly predominates), lymphadenopathy, and progressive deterioration.
      • Kafetzis D.A.
      • Maltezou H.C.
      Visceral leishmaniasis in paediatrics.
      As a rule, patients almost always present with fever, hepatosplenomegaly, and thrombocytopenia.
      • Maltezou H.C.
      • Siafas C.
      • Mavrikou M.
      • Spyridis P.
      • Stavrinadis C.
      • Karpathios T.
      • et al.
      Visceral leishmaniasis during childhood in Southern Greece.
      Children may also present with growth retardation.
      • Maltezou H.C.
      • Siafas C.
      • Mavrikou M.
      • Spyridis P.
      • Stavrinadis C.
      • Karpathios T.
      • et al.
      Visceral leishmaniasis during childhood in Southern Greece.
      Late findings include epistaxis, gingival hemorrhage, abdominal distension, edema, and ascites.
      • Maltezou H.C.
      Leishmaniasis.
      Laboratory findings include normocytic–normochromic anemia, neutropenia, thrombocytopenia, hypergammaglobulinemia, hypoalbuminemia, and increased hepatic transaminases.
      • Maltezou H.C.
      • Siafas C.
      • Mavrikou M.
      • Spyridis P.
      • Stavrinadis C.
      • Karpathios T.
      • et al.
      Visceral leishmaniasis during childhood in Southern Greece.
      Occasionally VL may manifest as acute hepatitis, cholecystitis, hemophagocytic syndrome, and Guillain–Barré syndrome.
      • Kafetzis D.A.
      • Maltezou H.C.
      Visceral leishmaniasis in paediatrics.
      If not treated, VL is almost always fatal. Death is caused by hemorrhage, severe anemia, or secondary infection.
      • Maltezou H.C.
      Leishmaniasis.
      American military personnel who served in the Middle East in the early 1990s developed a viscerotropic syndrome following infection with L. tropica characterized by prolonged fever, fatigue, cough, abdominal pain, and diarrhea.
      • Magill A.J.
      • Grogl M.
      • Gasser Jr., R.A.
      • Sun W.
      • Oster C.N.
      Visceral infection caused by Leishmania tropica in veterans of Operation Desert Storm.
      In the context of HIV co-infection, VL is usually the result of relapse after years of latency or represents a newly-acquired infection. Leishmaniasis may also be transmitted through needle sharing. HIV-infected patients usually have higher parasite loads and atypical symptoms (e.g., gastrointestinal), especially with low CD4 cell counts. This group of HIV-infected patients responds poorly to treatment and rates of relapse are high, regardless of treatment used.
      • Ritmeijer K.
      • Dejenie A.
      • Assefa Y.
      • Hundie T.B.
      • Mesure J.
      • Boots G.
      • et al.
      A comparison of miltefosine and sodium stibogluconate for treatment of visceral leishmaniasis in an Ethiopian population with high prevalence of HIV infection.
      • Molina I.
      • Falco V.
      • Crespo M.
      • Riera C.
      • Ribera E.
      • Curran A.
      • et al.
      Efficacy of liposomal amphotericin B for secondary prophylaxis of visceral leishmaniasis in HIV-infected patients.
      CL may manifest with one or more skin lesions on the exposed body within several weeks or months after the sandfly bite.
      • Morizot G.
      • Delgiudice P.
      • Caumes E.
      • Laffitte E.
      • Marty P.
      • Dupuy A.
      • et al.
      Healing of Old World cutaneous leishmaniasis in travelers treated with fluconazole: drug effect or spontaneous evolution?.
      • Herwald B.L.
      • Stokes S.L.
      • Juranek D.D.
      American cutaneous leishmaniasis in U.S. travelers.
      • Ahluwalia S.
      • Lawn S.D.
      • Kanagalingam J.
      • Grant H.
      • Lockwood D.N.
      Mucocutaneous leishmaniasis: an imported infection among travelers to Central and South America.
      Occasionally the lesions may appear months or years later. New World CL has variable clinical manifestations, ranging from ulcerative skin lesions to destructive mucosal inflammation, and is often accompanied with local lymphadenopathy,
      • Schwartz E.
      • Hatz C.
      • Blum J.
      New World cutaneous leishmaniasis in travellers.
      while Old World CL may present with multiple lesions.
      • Akilov O.E.
      • Khachemoune A.
      • Hasan T.
      Clinical manifestations and classification of Old World cutaneous leishmaniasis.
      The initial lesion is usually a papule, which subsequently progresses to nodule and then to ulcer during the next 1–3 months.
      • Maltezou H.C.
      Leishmaniasis.
      • Antinori S.
      • Gianelli E.
      • Calattini S.
      • Longhi E.
      • Gramiccia M.
      • Corbellino M.
      Cutaneous leishmaniasis: an increasing threat for travelers.
      • Herwald B.L.
      • Stokes S.L.
      • Juranek D.D.
      American cutaneous leishmaniasis in U.S. travelers.
      • Ahluwalia S.
      • Lawn S.D.
      • Kanagalingam J.
      • Grant H.
      • Lockwood D.N.
      Mucocutaneous leishmaniasis: an imported infection among travelers to Central and South America.
      • El Hajj Thellier M.
      • Carriere J.
      • Bricaire F.
      • Danis M.
      • Caumes E.
      Localized cutaneous leishmaniasis imported into Paris: a review pf 39 cases.
      • Scarisbrick J.
      • Chiodini P.
      • Watson J.
      • Moody A.
      • Armstrong M.
      • Lockwood D.
      • et al.
      Clinical features and diagnosis of 42 travellers with cutaneous leishmaniasis.
      • Berens-Riha N.
      • Fleischmann E.
      • Pratlong E.
      • Bretzel G.
      • von Sonnenburg F.
      • Löscher T.
      Cutaneous leishmaniasis (Leishmania tropica) in a German tourist after travel to Greece.
      • Haider S.
      • Boutross-Tadross O.
      • Radhi J.
      • Momar N.
      Cutaneous ulcer in a man returning from central America.
      • Scope A.
      • Trau H.
      • Bakon M.
      • Yarom N.
      • Nasereddin A.
      • Schwartz E.
      Imported mucosal leishmaniasis in a traveler.
      The face, upper limbs, and lower limbs are the most frequently involved.
      • Pérez-Ayala A.
      • Norman F.
      • Pérez-Molina J.A.
      • Herrero J.M.
      • Monge B.
      • López-Vélez R.
      Imported leishmaniasis, a heterogeneous group of diseases.
      • Herwald B.L.
      • Stokes S.L.
      • Juranek D.D.
      American cutaneous leishmaniasis in U.S. travelers.
      • Scarisbrick J.
      • Chiodini P.
      • Watson J.
      • Moody A.
      • Armstrong M.
      • Lockwood D.
      • et al.
      Clinical features and diagnosis of 42 travellers with cutaneous leishmaniasis.
      Leishmanial ulcers are typically painless and grow slowly with a granulomatous or crusted base and raised margins.
      • Ryan E.T.
      • Wilson M.E.
      • Kain K.C.
      Illness after international travel.
      Painful lesions may occur in the context of bacterial superinfection. Uncommon manifestations include lupoid, sporotrichoid, psoriasiform, mycetoma-like, and erysipeloid forms.
      • Maltezou H.C.
      Leishmaniasis.
      Occasionally CL may manifest as isolated lymphadenopathy
      • Ahluwalia S.
      • Lawn S.D.
      • Kanagalingam J.
      • Grant H.
      • Lockwood D.N.
      Mucocutaneous leishmaniasis: an imported infection among travelers to Central and South America.
      • Ryan E.T.
      • Wilson M.E.
      • Kain K.C.
      Illness after international travel.
      or progress into disseminated CL. Skin lesions may persist for months or years.
      • Nirwan P.S.
      • Rastogi V.
      Cutaneous leishmaniasis: an emerging infection in a non endemic area and a brief update.
      • Calvopina M.
      • Gomez E.A.
      • Sindermann H.
      • Cooper P.J.
      • Hashiguchi Y.
      Relapse of New World diffuse cutaneous leishmaniasis caused by Leishmania mexicana after miltefosine treatment.
      • Rhajaoui M.
      • Nasereddin A.
      • Fellah H.
      • Azmi K.
      • Amir F.
      • Jawabreh A.A.
      • et al.
      New clinicoepidemiologic profile of cutaneous leishmaniasis, Morocco.
      Despite the fact that CL is not a lethal disease and many lesions (especially due to Old World species) heal spontaneously over months to years, it is frequently associated with significant morbidity and may affect daily activities and social life when located on the hands and face.
      • Morizot G.
      • Delgiudice P.
      • Caumes E.
      • Laffitte E.
      • Marty P.
      • Dupuy A.
      • et al.
      Healing of Old World cutaneous leishmaniasis in travelers treated with fluconazole: drug effect or spontaneous evolution?.
      There is a potential concern of spreading of leishmanias to the mucosal surfaces of the nose or mouth causing ML, which might not be noticed until years after the initial skin lesions have healed. ML occurs in 1–10% of CL cases 1–5 years after healing.
      • Maltezou H.C.
      Leishmaniasis.
      • Pérez-Ayala A.
      • Norman F.
      • Pérez-Molina J.A.
      • Herrero J.M.
      • Monge B.
      • López-Vélez R.
      Imported leishmaniasis, a heterogeneous group of diseases.
      Risk factors for progression to ML include male sex, large or multiple lesions, and lesions above the waist. Clinical manifestations include chronic nasal congestion and bleeding, ulceration, and septal granulomas. ML is not self-cured and may progress and cause permanent or life-threatening complications such as ulcerative destruction of the nose, mouth, pharynx, and larynx, nasal septum perforation, and facial disfigurement, resulting in social stigma.
      • Lawn S.D.
      • Whetham J.
      • Chiodini P.L.
      • Kanagalingham J.
      • Whatson J.
      • Behrens R.H.
      • et al.
      New world mucosal and cutaneous leishmaniasis: an emerging health problem among British travellers.
      • Ahluwalia S.
      • Lawn S.D.
      • Kanagalingam J.
      • Grant H.
      • Lockwood D.N.
      Mucocutaneous leishmaniasis: an imported infection among travelers to Central and South America.
      • Scope A.
      • Trau H.
      • Bakon M.
      • Yarom N.
      • Nasereddin A.
      • Schwartz E.
      Imported mucosal leishmaniasis in a traveler.
      ML complicates almost exclusively New World CL, and L. braziliensis is the species most often involved.

      4. Diagnosis

      Table 3 shows the differential diagnoses for all forms of leishmaniasis. The differential diagnosis of leishmaniasis varies by clinical form and area of acquisition of infection. Although very uncommon in travelers, VL should be suspected in persons with a relevant travel history to an endemic area and an unexplained febrile illness, especially when hepatosplenomegaly and thrombocytopenia are present, in particular in migrants. Given the long incubation period of leishmaniasis, it is critical for physicians to consider travel to endemic areas that occurred several months or years in the past. Risk factors for HIV infection should also be considered, including sexual encounters, intravenous drug use, and blood transfusions obtained abroad.
      • Markle M.H.
      • Markhoul K.
      Cutaneous leishmaniasis: recognition and treatment.
      Table 3Differential diagnosis of leishmaniasis
      Visceral leishmaniasisCutaneous and mucosal leishmaniasis
      Typhoid fever

      Brucellosis

      Subacute bacterial endocarditis

      Miliary tuberculosis

      Infectious mononucleosis

      Malaria

      Tropical splenomegaly syndrome

      Histoplasmosis

      Schistosomiasis

      Trypanosomiasis

      Leukemia

      Lymphoma

      Malnutrition
      Tuberculosis

      Non-tuberculous mycobacterial infection

      Buruli ulcer

      Leprosy

      Syphilis

      Yaws

      Actinomycosis

      Mycoses (histoplasmosis, coccidioidomycosis, blastomycosis, rhinosporidiosis)

      Bacterial infection

      Infected insect bites

      Sarcoidosis

      Skin cancer

      Wegener's granulomatosis

      Foreign body

      Nasal polyps

      Septal deviation
      Microscopic examination of bone marrow smears is the reference method for the diagnosis of VL, and is associated with >90% sensitivity rates in children and 70% in adults. Higher (>95%) sensitivity rates are noted with spleen aspirates; however in the context of profound thrombocytopenia, spleen sampling may trigger life-threatening hemorrhage.
      • Kafetzis D.A.
      • Maltezou H.C.
      Visceral leishmaniasis in paediatrics.
      • Boelaert M.
      • Bhattacharya S.
      • Chappuis F.
      • El Safi S.H.
      • Hailu A.
      • Mondal D.
      • et al.
      Evaluation of rapid diagnostic tests: visceral leishmaniasis.
      The diagnosis can also be confirmed with molecular methods using various clinical specimens (peripheral blood, bone marrow, spleen) with high sensitivity and specificity rates.
      • Boelaert M.
      • Bhattacharya S.
      • Chappuis F.
      • El Safi S.H.
      • Hailu A.
      • Mondal D.
      • et al.
      Evaluation of rapid diagnostic tests: visceral leishmaniasis.
      • Van der Meide W.
      • Guerra J.
      • Schoone G.
      • Farenhorst M.
      • Coelho L.
      • Faber W.
      • et al.
      Comparison between quantitative nucleic acid sequence-based amplification, real-time reverse transcriptase PCR, and real-time PCR for quantification of Leishmania parasites.
      Serologic testing (direct agglutination tests, enzyme-linked immunosorbent assay, and indirect immunofluorescence) are used in settings where other diagnostic methods are not available, with high sensitivity and specificity rates. Diagnostic cut-offs may depend on the area and prevalence rates of asymptomatic infection.
      • Maltezou H.C.
      Leishmaniasis.
      As a rule, IgG antibodies remain detectable for several years after successful treatment, and therefore serologic tests should not be used for relapse cases.
      Physicians should consider CL in persons with chronic, non-healing skin lesions who have a travel history in endemic areas. Laboratory confirmation of CL is achieved by detecting Leishmania parasites through microscopic examination of stained skin specimens because of its high specificity and ease. Punch biopsies with tissue-impression smears can also be useful. Needle aspiration from the margin of a lesion can yield fluid for culture in special medium to isolate the organism and identify the species.
      • Markle M.H.
      • Markhoul K.
      Cutaneous leishmaniasis: recognition and treatment.
      Serologic tests are not reliable for the diagnosis of CL.
      • Reithinger R.
      • Dujardin J.C.
      • Hechmi L.
      • Pirmez C.
      • Alexander B.
      • Brooker S.
      Cutaneous leishmaniasis.
      Polymerase chain reaction (PCR) is useful for the diagnosis of CL and ML because of low parasite numbers. PCR is the most common method available these days for the species-specific diagnosis of leishmaniasis, which is important in choosing the right treatment.
      • Maltezou H.C.
      Leishmaniasis.

      5. Treatment

      An ideal anti-leishmanial agent should be effective, safe, easily administered, and affordable; in practice, however, no such agent is available. The choice of treatment is influenced by previous experience as well as availability of a particular drug within a country. Patients should be referred to specialized centers with past experience. Treatment for VL should be started as soon as the diagnosis is established.
      The pentavalent antimonials meglumine antimoniate and sodium stibogluconate remain the standard anti-leishmanial treatment for VL in developing endemic areas. However, India is an exception – their use has been abandoned here because of widespread antimonial resistance, and they have been replaced with conventional amphotericin B.
      • Maltezou H.C.
      Visceral leishmaniasis: advances in treatment.
      • Blum J.A.
      • Hatz C.F.
      Treatment of cutaneous leishmaniasis in travelers.
      Experience with antimonials for almost 70 years indicates efficacy rates of >90–95% and low fatality and relapse rates.
      • Maltezou H.C.
      • Siafas C.
      • Mavrikou M.
      • Spyridis P.
      • Stavrinadis C.
      • Karpathios T.
      • et al.
      Visceral leishmaniasis during childhood in Southern Greece.
      • Ritmeijer K.
      • Dejenie A.
      • Assefa Y.
      • Hundie T.B.
      • Mesure J.
      • Boots G.
      • et al.
      A comparison of miltefosine and sodium stibogluconate for treatment of visceral leishmaniasis in an Ethiopian population with high prevalence of HIV infection.
      • Raguenaud M.E.
      • Jansson A.
      • Vanlerberghe V.
      • Van der Auwera G.
      • Deborggraeve S.
      • Dujardin J.C.
      • et al.
      Epidemiology and clinical features of patients with visceral leishmaniasis treated by MSF clinic in Bakool region, Somalia, 2004–2006.
      • Minodier P.
      • Piarroux R.
      • Garnier J.M.
      • Unal D.
      • Perrimond H.
      • Dumon H.
      Pediatric visceral leishmaniasis in southern France.
      An advantage is their low cost; the main disadvantages include intramuscular route of administration, prolonged (20 mg/kg for 21–30 days) schedules, and transient but occasionally life-threatening side effects, such as cardiac arrhythmias, increased serum hepatic transaminases, pancreatitis, and pneumonitis.
      • Maltezou H.C.
      • Siafas C.
      • Mavrikou M.
      • Spyridis P.
      • Stavrinadis C.
      • Karpathios T.
      • et al.
      Visceral leishmaniasis during childhood in Southern Greece.
      • Maltezou H.C.
      Visceral leishmaniasis: advances in treatment.
      Conventional amphotericin B has an excellent anti-leishmanial activity, with >90% cure rates in Indian VL at a dose of 0.75 mg/kg in 15-day regimens.
      • Sundar S.
      • Chakravarty J.
      • Rai V.K.
      • Agrawal N.
      • Singh S.P.
      • Chauhan V.
      Amphotericin B treatment for Indian visceral leishmaniasis: response to 15 daily versus alternate-day infusions.
      Relapses are rare, except among HIV-infected patients. Because of disadvantages including prolonged hospitalization and administration, and frequent side effects (nephrotoxicity, hypokalemia, and infusion-related fever and chills), conventional amphotericin B does not offer any advantage over pentavalent antimonials for use outside India.
      • Maltezou H.C.
      Visceral leishmaniasis: advances in treatment.
      Lipid formulations of amphotericin B (liposomal amphotericin B, amphotericin B lipid complex, and amphotericin B cholesterol dispersion) are selectively taken by the reticulo-endothelial system of the host (where parasites replicate), offering the advantage of a highly localized increased efficacy with limited systemic toxicity.
      • Maltezou H.C.
      Leishmaniasis.
      Nowadays, liposomal amphotericin B is the first-line drug for VL in Europe, the USA, and other industrialized countries, because of its rapid and up to 100% cure rates with 3–5-day regimens, improved compliance of the patient, and reduced health care costs.
      • Olliaro P.L.
      • Guerin P.J.
      • Gerstl S.
      • Aga-Haaskjold A.
      • Rottingen J.A.
      • Shyan S.
      Treatment options for visceral leishmaniasis: a systemic review of clinical studies done in India, 1980–2004.
      In HIV-co-infected patients, liposomal amphotericin B is the first drug of choice for treatment as well as for secondary prophylaxis, because of its efficacy and safety profile,
      • Molina I.
      • Falco V.
      • Crespo M.
      • Riera C.
      • Ribera E.
      • Curran A.
      • et al.
      Efficacy of liposomal amphotericin B for secondary prophylaxis of visceral leishmaniasis in HIV-infected patients.
      while antimonials and conventional amphotericin B should be avoided due to serious toxicity and intolerance.
      • Maltezou H.C.
      Leishmaniasis.
      However, in poorly resourced endemic countries even short courses of liposomal amphotericin B are unaffordable.
      • Maltezou H.C.
      Drug resistance in visceral leishmaniasis.
      In a recent study in India, injectable paromomycin was shown to be non-inferior to amphotericin B for the treatment of VL.
      • Sundar S.
      • Jha T.K.
      • Thakur C.P.
      • Sinha P.K.
      • Bhattacharya S.K.
      Injectable paromomycin for visceral leishmaniasis in India.
      Miltefosine is the first oral anti-leishmanial drug. In a phase 4 trial of treatment with miltefosine in 1132 adults and children with VL in India, 95% cure rates were noted, while adverse effects, mainly gastrointestinal toxicity and increased hepatic transaminases and creatinine levels, were noted in 3% of patients.
      • Bhattacharya S.K.
      • Sinha P.K.
      • Sundar S.
      • Thakur C.P.
      • Jha T.K.
      • Pandey K.
      • et al.
      Phase 4 trial of miltefosine for the treatment of Indian visceral leishmaniasis.
      Currently, miltefosine is licensed in India, Germany, and Colombia. It is administered at a dose of 100 mg/kg/day for 28 days in adults ≥50 kg, 50 mg/kg/day in adults weighting <50 kg, and 2.5 mg/kg/day in children.
      • Maltezou H.C.
      Drug resistance in visceral leishmaniasis.
      Miltefosine should not be administered to women who may become pregnant within 2 months after drug discontinuation because of concerns of teratogenicity.
      The management of CL is not standardized, since comparison of therapeutic regimens is troublesome due to the fact that this form of leishmaniasis is usually self-cured. The management of travelers with imported CL is further complicated by the fact that there are no evidence-based data for this group of patients. Treatment is recommended to accelerate cure, reduce scars, and prevent mucosal dissemination in cases of New World CL.
      • Blum J.A.
      • Hatz C.F.
      Treatment of cutaneous leishmaniasis in travelers.
      Systemic treatment is indicated in cases of multiple or large (>4 cm) lesions, when the face or a joint are affected, when lesions are present on the hands or feet, for cosmetic reasons, and in immunosuppressed patients.
      • Reithinger R.
      • Dujardin J.C.
      • Hechmi L.
      • Pirmez C.
      • Alexander B.
      • Brooker S.
      Cutaneous leishmaniasis.
      Pentavalent antimonials have been used for several decades and are the gold standard of treatment. These agents are administered either systemically or intralesionally.
      • Maltezou H.C.
      Leishmaniasis.
      Intralesional treatment is not approved by the US Food and Drug Administration (FDA) and therefore is not in use in the USA.
      Pentamidine, an aromatic diamidine, can be used as an alternative to antimonials, and because of the long-lasting experience with regards to efficacy and safety is considered the first-line agent for L. guyanensis in French Guiana, Suriname, and Brazil. Pentamidine is administered at a dose of 300 mg once weekly for 3–5 weeks.
      • Blum J.A.
      • Hatz C.F.
      Treatment of cutaneous leishmaniasis in travelers.
      Elevation of creatinine kinase has been noticed with much higher doses, thus creatinine kinase and kidney function have to be controlled before each injection.
      • Blum J.A.
      • Hatz C.F.
      Treatment of cutaneous leishmaniasis in travelers.
      • Naafs B.
      Pentamidine induced diabetes mellitus.
      Glucose serum levels should be checked, since one case of hyperglycemia has been described after one dose of pentamidine at 200 mg.
      • Naafs B.
      Pentamidine induced diabetes mellitus.
      Preliminary studies show promising results with the use of miltefosine in New World CL and ML at a dosage of 2.5 mg/kg/day for 28 days. The most important side effects include nausea, vomiting, motion sickness, headache, and diarrhea. Elevated transaminases and creatinine kinase have also been reported.
      • Blum J.A.
      • Hatz C.F.
      Treatment of cutaneous leishmaniasis in travelers.
      • Sundar S.
      • Jha T.K.
      • Thakur C.P.
      • Bhattacharya S.K.
      • Rai M.
      Oral miltefosine for the treatment of Indian visceral leishmaniasis.
      • Soto J.
      • Berman J.
      Treatment of New World cutaneous leishmaniasis with miltefosine.
      The imidazoles and the structurally-related triazoles (fluconazole, itraconazole, and ketoconazole) also demonstrate anti-leishmanial activity. They can be administered orally and have a good safety profile,
      • Blum J.A.
      • Hatz C.F.
      Treatment of cutaneous leishmaniasis in travelers.
      however they are effective against a limited number of Leishmania species. A 6-week course of oral fluconazole was shown to be safe and a promising treatment for L. major CL in Iran, with cure rates of 36% and 88% at days 50 and 90, respectively.
      • Alrajhi A.A.
      • Ibrahim E.A.
      • De Vol E.B.
      • Khairat M.
      • Faris R.M.
      • Maguire J.H.
      Fluconazole for the treatment of cutaneous leishmaniasis caused by Leishmania major.
      However, in a study conducted among travelers with imported L. major CL, cure rates of 44.4% at day 50 were recorded with the same regimen, comparable to published rates of spontaneous healing.
      • Morizot G.
      • Delgiudice P.
      • Caumes E.
      • Laffitte E.
      • Marty P.
      • Dupuy A.
      • et al.
      Healing of Old World cutaneous leishmaniasis in travelers treated with fluconazole: drug effect or spontaneous evolution?.
      The effect of fluconazole has been questioned.
      • Morizot G.
      • Delgiudice P.
      • Caumes E.
      • Laffitte E.
      • Marty P.
      • Dupuy A.
      • et al.
      Healing of Old World cutaneous leishmaniasis in travelers treated with fluconazole: drug effect or spontaneous evolution?.
      Differences in efficacy depend to a great extent on Leishmania species and area of infection. Oral miltefosine is effective against L. major CL in Iran and L. braziliensis CL in Bolivia with 92.9% and 88% cure rates, respectively, however the same drug was found to be less effective in cases caused by the same species in Guatemala.
      • Maltezou H.C.
      Leishmaniasis.
      • Soto J.
      • Berman J.
      Treatment of New World cutaneous leishmaniasis with miltefosine.
      • Soto J.
      • Rea J.
      • Balderrama M.
      • Toledo J.
      • Soto P.
      • Valda L.
      • Berman J.D.
      Efficacy of miltefosine for Bolivian cutaneous leishmaniasis.
      Azithromycin demonstrates anti-leishmanial activity in vitro and has also been used for the treatment of CL and ML, however its use is limited to patients with treatment failure or contraindications for all other options, such as young children, pregnant women, or patients with a severe underlying disease.
      • Teixeira A.C.
      • Paes M.G.
      • Guerra Jde O.
      • Prata A.
      • Silva-Vergara M.L.
      Low efficacy of azithromycin to treat cutaneous leishmaniasis in Manaus, AM, Brazil.
      • Silva-Vergara M.L.
      • Silva Lde A.
      • Maneira F.R.
      • da Silva A.G.
      • Prata A.
      Azithromycin in the treatment of mucosal leishmaniasis.
      Pentavalent antimonials administered for 20–28 days either parenterally or intralesionally show high cure rates and remain the mainstay of treatment for CL or ML, providing cure with a low rate of recurrence.
      • Maltezou H.C.
      Leishmaniasis.
      • Blum J.A.
      • Hatz C.F.
      Treatment of cutaneous leishmaniasis in travelers.
      • Amato V.
      • Amato J.
      • Nicodemo A.
      • Uip D.
      • Amato-Neto V.
      • Duarte M.
      Treatment of mucocutaneous leishmaniasis with pentamidine isothionate.
      Satisfactory cure rates for CL are also achieved with pentamidine.
      • Krolewiecki A.J.
      • Romeo H.D.
      • Cajal S.P.
      • Abraham D.
      • Mimori T.
      • Mastumoto T.
      • et al.
      A randomized clinical trial comparing oral azithromycin and meglumine antimoniate for the treatment of American cutaneous leishmaniasis caused by Leishmania (Viannia) braziliensis.
      • Tuon F.F.
      • Amato V.S.
      • Graft M.E.
      • Siqueira A.M.
      • Nicodemo A.C.
      • Neto V.A.
      Treatment of New World cutaneous leishmaniasis—systemic review with a meta-analysis.
      A recent meta-analysis concluded that meglumine antimoniate is the drug of choice for ML with 88% cure rates compared with 51% cure rates for stibogluconate.
      • Amato V.S.
      • Tuon F.F.
      • Siqueira A.M.
      • Nicodemo A.C.
      • Neto V.A.
      Treatment of mucosal leishmaniasis in Latin America: systemic review.
      The use of liposomal amphotericin B for CL and ML has not been standardized yet; it is mainly used in patients with resistance or contraindications for pentavalent antimonials.
      • Blum J.A.
      • Hatz C.F.
      Treatment of cutaneous leishmaniasis in travelers.
      Topical application of immunomodulators (e.g., imiquimod cream) in CL caused by L. peruviana or L. braziliensis has been shown to improve the efficacy of pentavalent antimonials or induce a more rapid healing when given in combination. The combination of oral pentoxifylline with antimonials has also been shown to increase efficacy.
      • Blum J.A.
      • Hatz C.F.
      Treatment of cutaneous leishmaniasis in travelers.
      • Lessa H.A.
      • Machado P.
      • Lima F.
      • Cruz A.A.
      • Bacellar O.
      • Guerreiro J.
      • Carvalho E.M.
      Successful treatment of refractory mucosal leishmaniasis with pentoxifylline plus antimony.
      Physical treatment for CL such as heat, cryotherapy, laser, or a combination of cryotherapy with intralesional meglumine antimoniate has been successfully applied in endemic countries.
      • Sadeghian G.
      • Niforoushzadeh M.A.
      Effect of combination therapy with systemic Glucantime and pentoxifylline in the treatment of cutaneous leishmaniasis.
      • Junaid A.J.
      Treatment of cutaneous leishmaniasis with infrared heat.
      • Al Majali O.
      • Routh H.B.
      • Abuloham O.
      • Bhowmik K.R.
      • Muhsen M.
      • Hebeheba H.
      A 2-year study of liquid nitrogen therapy in cutaneous leishmaniasis.
      • Asilian A.
      • Sharif A.
      • Faghihi G.
      • Enshaeieh S.H.
      • Shariati F.
      • Siadat A.H.
      Evaluation of CO laser efficacy in the treatment of cutaneous leishmaniasis.
      Local infiltration of pentavalent antimony maximizes the concentration within lesions and has few systemic adverse effects, however it does not reach metastatic lesions.
      • Asilian A.
      • Sadeghinia A.
      • Faghihi G.
      • Momeni A.
      Comparative study of the efficacy of combined cryotherapy and meglumine antimoniate (Glucantime) vs cryotherapy and meglumine antimoniate (Glucantime) alone for the treatment of cutaneous leishmaniasis.
      Topical formulations containing 15% paromomycin, an aminoglycoside antibiotic, offer significant advantages over systemic therapy, including ease of administration, no systemic adverse effects, and reduced costs; however, penetration into intact skin is weak.
      • Blum J.A.
      • Hatz C.F.
      Treatment of cutaneous leishmaniasis in travelers.
      Elective surgery and tattooing should be avoided for at least 12 months after any treatment completion in order to avoid CL reactivation.
      • Wortmann G.W.
      • Aronson N.E.
      • Miller R.S.
      • Blazes D.
      • Oster C.N.
      Cutaneous leishmaniasis following local trauma: a clinical pearl.

      6. Prevention

      No vaccine against leishmaniasis is available. Travelers to endemic areas should be advised that the only preventive measures are those of protection against sandfly bite. These include avoidance of outdoor activities, in particular from dusk to dawn when sandflies are mostly active; protective clothes should be worn and DEET (N,N-diethyl-meta-toluamide)-containing repellents applied to exposed skin. Sandflies are weak fliers and therefore their movement may be inhibited by fans or ventilators. Sleeping in air-conditioned or well-screened areas is also advisable, as well as indoor spraying. Sandflies are smaller than mosquitoes and they can pass through the holes of ordinary bed-nets. The treatment of bed-nets with a pyrethroid-containing insecticide (permethrin or deltamethrin) may protect against indoor transmission.
      • Kroeger A.
      • Avila E.V.
      • Morison L.
      Insecticide impregnated curtains to control domestic transmission of cutaneous leishmaniasis in Venezuela: cluster randomised trial.
      A randomized study in Venezuela evaluated the implementation of pyrethroid-impregnated curtains in an urban area with a 4% incidence of CL.
      • Kroeger A.
      • Avila E.V.
      • Morison L.
      Insecticide impregnated curtains to control domestic transmission of cutaneous leishmaniasis in Venezuela: cluster randomised trial.
      A total of 2913 inhabitants from 569 homes were enrolled. The use of pyrethroid-impregnated curtains reduced the sandfly population and 12 months later the incidence of CL was eliminated to 0%.
      • Kroeger A.
      • Avila E.V.
      • Morison L.
      Insecticide impregnated curtains to control domestic transmission of cutaneous leishmaniasis in Venezuela: cluster randomised trial.

      7. Conclusions

      Imported leishmaniasis is an uncommon but emerging infectious disease among international travelers. The management of leishmaniasis in developed, non-endemic countries is a challenge because of the unfamiliarity of physicians with its wide clinical spectrum, the diagnostic modalities, and available treatment options. Leishmaniasis should be considered in travelers with compatible clinical findings and a history of travel to an endemic area, even months or years ago. Information regarding leishmaniasis and appropriate protective measures should be offered to adventure travelers, military personnel, and immigrants likely to be exposed to sandflies in endemic areas.

      Conflict of interest

      No conflict of interest to declare.

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