Imported Leishmaniasis: A Heterogeneous Group of Diseases

Ana Pérez‐Ayala MD, Francesca Norman MD, José Antonio Pérez‐Molina, Juan María Herrero MD, Begoña Monge MD, Rogelio López‐Vélez MD, PhD
DOI: 395-401 First published online: 1 November 2009


Background. Leishmaniasis is endemic in many countries. The existence of different species combined with host factors may condition clinical presentation, treatment options, and disease outcome. In an endemic country, a predominance of certain species and presentations may be expected, whereas from the perspective of a tropical medicine referral unit a wider variety of cases from diverse geographical areas may be observed.

Methods. Retrospective study of imported leishmaniasis cases diagnosed at a Tropical Medicine referral unit in Spain, during the period of January 1995 to June 2008.

Results. In total, 18 cases were diagnosed: 12 cutaneous leishmaniasis (CL), 4 mucocutaneous leishmaniasis (ML), and 2 visceral leishmaniasis (VL) cases. Two patients were immunosuppressed. The majority of CL cases (9/12) occurring in travelers were acquired in New World countries and were treated with pentavalent antimonials. Three ML cases were acquired in the New World, two received initial treatment with pentavalent antimonials and two with liposomal amphotericin B (LAmB). For all four ML cases, a change in drug choice and multiple treatment courses were necessary, and one remained refractory to treatment. Both VL cases were acquired in Africa and responded well to LAmB treatment.

Conclusion. The management of leishmaniasis in non‐endemic countries is still a challenge for physicians. With the variety of cases presented, both in immigrants and travelers from different geographical areas, this series illustrates the great diversity of imported leishmaniasis in terms of presentation, treatment options, and outcome. We consider this entity is becoming increasingly more frequent and clinicians should be aware of strategies for its correct management.

The term leishmaniasis refers to a wide variety of clinical syndromes caused by the protozoan parasite Leishmania sp. The broad spectrum of the disease can be divided into two main clinical forms: tegumentary leishmaniasis (TL), which includes cutaneous leishmaniasis (CL) and mucocutaneous leishmaniasis (ML), and visceral leishmaniasis (VL).

Currently, there are 1–1.5 million symptomatic TL cases per year, 1 although the reported number of cases has been rising in the past decade. 2 It is endemic in 88 countries, 72 of which are developing countries. The parasite species causing TL are divided into Old World leishmaniasis (in Southern Europe, Middle East, Asia, and Africa), usually manifested as mild cutaneous disease, Leishmania (L.) tropica, Leishmania (L.) major, and Leishmania (L.) infantum being the main causative species, and New World leishmaniasis (in Latin America) characterized by different types of lesions. These may range from mild cutaneous disease to severe mucosal lesions caused by several species such as Leishmania (V.) braziliensis (the main species associated with ML), Leishmania (V.) guyanensis, Leishmania (V.) panamensis, Leishmania (V.) peruviana, Leishmania (L.) mexicana, Leishmania (L.) amazonensis, and Leishmania (L.) venezuelensis. 3

There are an estimated 0.5 million symptomatic VL cases per year worldwide. 1 It is mainly caused by Leishmania (L.) donovani in the Indian subcontinent and Africa and by L (L.) infantum/chagasi in the Mediterranean region, Southwest and Central Asia, and South America. Clinical presentation is similar in the different endemic areas, with symptoms suggestive of a persistent systemic infection (fever, weakness, weight loss) and parasitic invasion of bone marrow and the reticulo‐endothelial system (pancytopenia plus enlarged spleen, liver, or lymph nodes). 4 Atypical manifestations such as renal involvement, which has been described recently, may also occur. 5

Because of the variety in Leishmania species and the existing geographical differences, leishmaniasis could be considered to be a polymorphous group of complex diseases each with a variety of clinical features, treatment options, and different prognoses. While endemic countries can offer great experience based on cases reported from their specific geographical area and other conditions from foreign endemic areas, 6 travel medicine referral centers may observe a wider variety of cases of imported leishmaniasis acquired in different areas of the world.

In this article, we present our experience in the diagnosis, treatment, and follow‐up of a spectrum of imported leishmaniasis cases diagnosed at a Tropical Medicine Referral Center in a large European city.


A retrospective study of imported leishmaniasis cases diagnosed at the Tropical Medicine Unit, Infectious Disease Department of the Ramón y Cajal Hospital in Madrid, Spain between January 1995 and June 2008 was performed.

In all patients in whom TL or VL was suspected, a skin biopsy or a bone marrow biopsy, respectively, was performed. Histological and Giemsa‐stained smear examination for the presence of amastigotes as well as culture on Novy‐McNeal‐Nicolle medium for promastigotes was performed on biopsy samples. Polymerase chain reaction (PCR) was also available for some biopsy specimens to detect parasite DNA both for the diagnosis and identification of Leishmania species. In cases with suspected mucosal/visceral involvement serology was also performed (Indirect Inmunofluorescent Assay IgG, Vircell, S.L. Granada, Spain, considered positive when titers ≥ 1/160).


In total, 18 cases were diagnosed (6 immigrants and 12 travelers): 16 with TL (12 CL and 4 ML) and 2 with VL. The main patient characteristics are summarized in Tables 1–3.

View this table:
Table 1

Cutaneous leishmaniasis

CasePatient type/sex * /ageOrigin Time Clinical presentation/siteDiagnosis §SpeciesTreatmentOutcome
1Immigrant F/27Brazil4 yOne cutaneous ulcer /lower limbGiemsa/cultureUnknownParenteral Sb+5 || Good response. No relapses
2Immigrant M/35Algeria3 yOne nodular lesion /right forearmPCRUnknownIntralesional Sb+5 Good response. No relapses
3Immigrant M/27Burkina Faso1 yTwo cutaneous ulcers / left thighGiemsa/ cultureUnknownLAmB # Good response. No relapses
HIV+Parenteral Sb+5 || (two courses)
4TravelerPanama2 moThree cutaneous ulcers /right ankleGiemsa/culture ** UnknownIntralesional Sb+5 Lost to follow‐up.
5TravelerEcuador (Amazonian area)/3 mo2 moOne nodular‐ulcerated lesion /left handCultureL braziliensisParenteral Sb+5 || Good response. No relapses
6TravelerColombia/ 2 y15 dOne cutaneous ulcer /left armUnknown ** UnknownParenteral Sb+5 || Good response. No relapses
7Traveler M/27Costa Rica/ 1 mo4 moThree cutaneous ulcers /right armGiemsa/ cultureL braziliensisIntralesional Sb+5+ ketoconazole †† Good response. No relapses
Parenteral Sb+5 ||
8Traveler M/30Peru/ 4 mo1 moOne cutaneous ulcer /lower limbUnknown ** UnknownParenteral Sb+5 || Good response. No relapses
9Traveler F/55Costa Rica/ 1 mo1 moOne cutaneous ulcer / lower limbCultureUnknownItraconazole ‡‡ No response.Lost to follow‐up
10Traveler M/38Morocco/ 1 mo15 dSix ulcers/lower limbs. Two ulcers/thoraxPCRL majorIntralesional Sb+5 Slow response.
11Traveler M/31Panama/ 3 mo1 moNumerous ulcers/lower limbsGiemsaUnknownParenteral Sb+5 || Bacterial super infection. Good response.
12Traveler M/39French Guyana/ 1 mo20 dOne cutaneous ulcer on lower limb. Thoracic lesion 1 mo afterPCRL braziliensisLAmB # Parenteral Sb+5 || Good response. No relapses
  • PCR = polymerase chain reaction; VFR = visiting friends and relatives.

  • *F, female/M, male.

  • Origin: country of origin in migrants and country and duration of travel in travelers.

  • Time: time elapsed between arrival from travel or immigration to Spain and diagnosis.

  • || Pentavalent antimonials (Glucantime®): 20 mg/kg/d 21–28 days either intravenous or intramuscular.

  • § Diagnosis: positive diagnostic procedures performed on skin biopsy.

  • Intralesional pentavalent antimonials (Glucantime®): 0.3–0.5 ml/lesion twice a week for 1 month.

  • # LAmB (Liposomal amphotericin B): 3 mg/kg/d i.v. on Days 1–5, 14, and 21.

  • ** Done out of the hospital: no. 4 in Panama, no. 6 in Colombia, and no. 8 in other Spanish hospital.

  • †† Ketoconazole: 600 mg/8 h 20 days.

  • ‡‡ Itraconazole: 200 mg/d 20 days.

View this table:
Table 2

Mucocutaneous leishmaniasis

CasePatient type/sex * /ageOrigin Time Clinical presentation/previous CLDiagnosis ||SpeciesTreatmentOutcome
13ImmigrantBolivia1 yCartilaginous nasal septum/laryngeal mucosa 9 y after CL treated with Sb+5 § 21 dPCRL braziliensisSb+5 (two courses)Poor response of nasal septum ulceration
M/50Intermittent LAmB 300 mg/mo 2 y
Miltefosine # + itraconazole ** + pentoxifylline †† + immunotherapy ‡‡ (three courses)
14ImmigrantEcuador1 yNasal mucosal ulcerationPCRL braziliensisSb+5Apparent relapse but lost to follow‐up
F/42No previous CLLAmB (3 g) + Allopurinol ‡‡
15Traveler M/49 Chronic steroidal treatmentIndia/5 mo2 yLaryngeal involvement: epiglottis and vocal chords No previous CLGiemsa/culture SerologyUnknownLAmB (9 g) Miltefosine # (two courses)Multiple relapses with LAmB, good response with Miltefosine.
16Traveler M/41Bolivia /Peru /Ecuador/ 1 1/2 mo1 yNasal congestion/gum lesions after CL (1 y ago) treated with LAmB (0.8 g)PCR SerologyL braziliensisLAmB (5 g) Miltefosine # No follow‐up
  • CL = Cutaneous leishmaniasis; PCR = polymerase chain reaction.

  • * F, female/M, male.

  • Origin: country of origin in migrants and country and duration of travel in travelers.

  • Time: time elapsed between arrival from the travel or immigration to Spain and diagnosis.

  • || Diagnosis: positive diagnostic procedures performed on skin biopsy.

  • § Pentavalent antimonials (Glucantime® ): 20 mg/kg/d 28 days.

  • LAmB (Liposomal amphotericin B): 5 mg/kg/d i.v. 10 days.

  • # Miltefosine: 100–150 mg/d 28 days.

  • ** Itraconazole: 200 mg/d 28 days.

  • †† Pentoxifylline: 400 mg/8 h 28 days.

  • ‡‡ Immunotherapy: 3 doses (0.12 ml) of heat‐killed L. braziliensis promastigotes + viable Bacillus Calmette‐Guerin.

  • |||| Alopurinol: 300 mg/12 h.

View this table:
Table 3

Visceral leishmaniasis

CasePatient type /sex * /ageOrigin Time Clinical presentationxsPositive diagnostic proceduresSpeciesTreatmentOutcome
17Traveler/Burkina Faso for 45 d/2 moFever/Bone marrow biopsy/ serologyUnknownLAmB § (1.5 g)Good response. No relapses
F/353 mo in Peru (2 y previously)hepatosplenomegaly/pancytopenia
18Immigrant/ M/17Cameroon/5 mo in Mediterranean littoral (7 mo previously)1 yFever/ hepatosplenomegaly/ pancytopeniaBone marrow biopsy/ serologyUnknownLAmB § (2 g)Good response. No relapses.
  • *F, female/ M, male.

  • Origin: country of origin in migrants and country and duration of travel in travelers.

  • Time: time elapsed between arrival from the travel or immigration to Spain and diagnosis.

  • §LAmB (Liposomal amphotericin B): 3 mg/kg/d 7–10 days.

Tegumentary lesions represented 1.4% of all patients coming to our unit because of cutaneous manifestations during the study period. In this series, 75% (12/16) were men, mean age 37 years and 75% were New World leishmaniasis. The majority of cases (68.7%) occurred in travelers and the median duration of travel was 30 days.

Of the 12 CL cases, 3 occurred in immigrants and 9 in travelers (8 Spanish travelers and 1 immigrant traveler visiting friends and relatives [VFR]). Of the 12 patients, 9 had New World CL (acquired in Brazil, Panama, Ecuador [Amazonian area], Colombia, Costa Rica, Peru, and French Guyana) and the other 3 had Old World CL (acquired in Algeria, Morocco, and Burkina Faso). In eight patients, the lesions were located on the lower limbs and in four on the upper limbs: all but one were ulcerated lesions. Species identification was obtained in four cases: three L (V.) braziliensis and one L (L.) major. Pentavalent antimonials (Sb+5) were used in 11 patients (11/12). For nine patients, this was the first line treatment: parenteral in five cases, intralesional in three, and sequential in one (intralesional followed by parenteral administration). For two patients, parenteral Sb+5 were used after liposomal amphotericin B (LAmB) was discontinued because of absence of response for one patient (no. 12) and because of the appearance of side effects in an HIV+ patient also undergoing treatment with HAART (no. 3). The latter had two big ulcers and needed two complete courses with Sb+5 until the lesions healed (Figure 1). One patient (no. 9) was treated with oral itraconazole with no response and was subsequently lost to follow‐up.

Figure 1

Extensive cutaneous leishmaniasis in an HIV+ immigrant from Burkina Faso (case no. 3).

Of the four ML cases, two occurred in travelers and two in immigrants. Two lesions were located on the nasal mucosa and the other two in the larynx. Two patients (2/4) had a previous diagnosis of CL, with a mean period of 5 years between the appearance of the cutaneous lesion and the appearance of the mucosal lesion. Three cases were New World leishmaniasis (acquired in Bolivia, Ecuador, and Peru) because of L (V.) braziliensis. The other occurred in an immunosuppressed Spanish traveler who was dependent on steroids (intermittent parenteral, inhaled, and oral therapy for 35 years as a result of severe asthma since childhood) 2 years after return from India. Initially, all of them received parenteral treatment, two with Sb+5 and two with LAmB, but all needed repeated courses and a change in the drug of choice because of poor response. Two patients received LAmB followed by oral miltefosine: one responded well and the other was lost to follow‐up. One refractory case (no. 13) received two courses of parenteral Sb+5 without any clinical response, followed by repeated courses of LAmB during a 2‐year period, after which the lesions remained stable although complete cure was not achieved. Treatment was then followed by two 30‐day courses of oral treatment with miltefosine plus itraconazole plus pentoxifylline with immunotherapy [three doses (0.12 ml) of heat‐killed L (V.) braziliensis promastigotes + viable Bacillus Calmette‐Guerin] and despite significant initial clinical improvement after 11 months, the patient relapsed (PCR‐positive biopsy of the lesion). After this, the patient remained on continuous oral triple therapy achieving clinical stability. The last patient (no. 14) received one course of parenteral Sb+5 followed by three courses of LAmB, one of these associated with oral allopurinol (compassionate miltefosine use was denied) achieving initial clinical response but with an apparent relapse 3 years later (then lost to follow‐up).

During the study period, two patients (one immigrant and one traveler who was a humanitarian worker) were diagnosed with VL, both probably acquired in West Africa. The traveler (no. 17) spent 45 days in Burkina Faso but she had traveled to Peru for 3 months 2 years before. The immigrant (no. 18) was originally from Cameroon but had been living in the north of Africa (Melilla) for 5 months before arriving in Madrid. Both presented with classical kala‐azar (fever, hepatosplenomegaly, and pancytopenia). Both of them were considered to be cured after one course of LAmB.


This study describes 18 cases of imported leishmaniasis, displaying the varied spectrum of this heterogeneous disease. There are cases in travelers (66.7%) and immigrants (33.3%), acquired both in the “New” and “Old” World (66.7 and 33.3%, respectively), in immunocompetent and immunosuppressed patients (88.8 and 11.1%). All three main clinical forms are represented (66.7% CL, 22.2% ML, 11.1% VL) with the different responses to administered treatments.

There has been an increase in cases of imported leishmaniasis in different countries. The majority of imported cases in western countries is of CL, of the New World type and acquired by travelers 3 ; however, these only represented 44.4% of the total number of imported leishmaniasis cases in this series. In this article, we also report two cases of ML in travelers (2/4 cases of ML), which remains uncommon in travelers. 7–16 Another interesting finding was that only 3 of the 16 TL cases came from countries which, according to the literature, account for more than 90% of the cases worldwide (Brazil and Peru). 1 Imported VL in Europeans is uncommon and is mainly found in travelers to Mediterranean countries 17 : in this series, two cases of VL were acquired in Africa.

Identifying the country where leishmaniasis was acquired may pose a problem as occurred for cases 15, 17, and 18 in this series. The patient described in case no. 15 had traveled to India 2 years before diagnosis; so although L (L.) donovani could be responsible for the clinical picture, L (L.) infantum acquired in Spain could be a plausible explanation, as the patient had been living in an endemic zone for leishmaniasis in the South of Spain (Las Alpujarras) since his return from India. Although uncommon, this species can occasionally produce mucosal involvement. 18 For case no. 17, infection was most probably acquired during the trip to Burkina and, although the majority of described cases from West Africa are of CL because of L (L.) major, a few cases because of L (L.) donovani have also been described. 19 Another possibility would be that of reactivation of an infection acquired in Peru, although, once again, very few such cases have been reported and the patient had no associated risk factors for reactivation of latent infection. The last patient (no. 18) was an immigrant from Cameroon who could have become infected in his country of origin although there have been few cases of VL reported from that geographical area. 20 During his travels, he had lived for 5 months in Mediterranean areas of the north of Africa where L (L.) infantum is hyperendemic.

In our series, clinical manifestations in immunocompetent patients with CL, ML, and VL were similar to those described by other authors. ML usually develops as a complication of CL, occurring 1–5 years after CL has healed and without any signs that may indicate disease progression, although cases have been described of ML occurring decades after exposure in endemic countries. 21 It can also occasionally appear in patients with no previous skin lesions, 12 as happened with two of our patients (nos 14 and 15). Clinical manifestations of CL in immunocompromised patients can present in a variety of ways, making the differential diagnosis more difficult, and immunosuppression increases the risk of developing visceral illness and of poor response to treatment. 22 Two cases in immunocompromised hosts are presented: an HIV+ patient (no. 3) with two extensive skin ulcers with slow response to parenteral treatment and a steroid‐dependent patient (no. 15) with laryngeal mucosal involvement, with no known previous CL, multiple relapses, and slow response to treatment.

Initial therapeutic approach may be difficult and should be individually tailored according to clinical form, place of acquisition, and the most probable species involved. A few general recommendations could be concluded.

Most cases of Old World CL may cure spontaneously and otherwise have good response to intralesional Sb+5. Because of this, we treated cases 2 and 10 with this approach. The third patient (no. 3) with Old World leishmaniasis was treated parenterally because of his immunosuppression. One case (no. 4) of New World CL was also treated with intralesional Sb+5 because she was a pregnant woman. Case no. 7 was initially managed with intralesional treatment plus ketoconazole, but as a result of poor response and later identification of L (V.) braziliensis this was then changed to parenteral Sb+5 treatment.

The cases of New World CL are more complex, they can be produced by different species like L (L.) mexicana that may cure spontaneously in a period of a few months or by L (V.) braziliensis that has a high risk of mucosal progression (2&–10% of L (V.) braziliensis CL which are not treated result in ML 23 ). In the latter cases, parenteral therapy should be used as some studies have supported the hypothesis that early systemic treatment may prevent mucosal invasion. 3 As initially both lesions may be totally identical, it is important to attempt species identification early even though some of these techniques, like PCR, are not available in all laboratories. All our CL cases with known or suspected (because of the place of acquisition) L (V.) braziliensis infection were treated with parenteral Sb+5. Case no. 12 had a metastatic lesion in the thorax that alerted us to the possibility of L (V.) braziliensis that was later confirmed, but he was first treated with LAmB because more than 95% of cases of CL in French Guyana are due to L (V.) guyanensis against which systemic Sb+5 is not effective. 24,25 In cases in which the probability of L (V.) braziliensis is low, treatment with oral therapy (because of easier administration and less toxicity) could be a first option 26 as in case no. 9 who was treated with oral itraconazole.

Parenteral Sb+5 and LAmB are first line choices for cases of confirmed ML and VL, although there are some other appropriate alternatives like oral miltefosine. 27,28

Although cases of CL usually respond well, occasionally, as for no. 10 in our series, response is unusually slow and numerous injections are required. In some cases of ML, response is poor to standard treatment and multiple courses, change of drug, and even combined treatment 29 may be needed, as happened in cases 13 and 14. Case no. 13 illustrates this well, as this patient received various intravenous and oral treatments for several years, some in combination with pentoxifylline and immunotherapy shown to be effective for some refractory cases of ML. 30,31 Oral treatment with miltefosine (nos 15 and 16) has shown promising cure rates, but response to treatment changes depending not only on the infecting species but also according to each endemic region: 91% cure rates in L (V.) panamensis, 88% in L (V.) braziliensis in Bolivia but 53% in Guatemala. 32,33

The diagnosis of TL in non‐endemic countries is still a challenge for physicians. There is a broad spectrum of diseases that can resemble it and clinical manifestations, independent of the species, may be indistinguishable. We consider that the term imported leishmaniasis covers different illnesses, characterized by both complexity and diversity, showing a very wide clinical spectrum depending on the area of acquisition, the species, and the degree of host immunity. Without the identification of the causative species, it is difficult to predict the outcome. All these are determinants that may not only aid in the choice of adequate treatment but also reflect the difficulty in managing this complex illness.


The clinical research team acknowledges the support provided by the Red de Investigación de Centros de Enfermedades Tropicales (RICET).RED: RD06/0021/0020. We would like to acknowledge the assistance of Israel Cruz (Instituto de Salud Carlos III, Madrid, Spain) with the PCR and we would also like to thank Dr Jacinto Convit (Universidad Central de Venezuela, Caracas, Venezuela) for providing the doses for immunotherapy.

Declaration of interests

The authors state they have no conflicts of interest to declare.


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