Emerg Infect DisEIDEmerging Infectious Diseases1080-60401080-6059Centers for Disease Control and Prevention12890332302344003-002310.3201/eid0907.030023DispatchLeishmaniasis in GermanyHarmsGundel*SchönianGabriele*FeldmeierHermannCharité, Humboldt University Berlin, Berlin, GermanyFree University of Berlin, Berlin, GermanyAddress for correspondence: Gundel Harms, Institute of Tropical Medicine Berlin, Spandauer Damm 130, 14050 Berlin, Germany; fax: +49-30-30116-888; email: gundel.harms@charite.de7200397872875

In 2000, a reference center was created to systematically record leishmaniases in Germany. We analyzed 58 cases of leishmaniases imported during a 2-year period. These findings will serve as a baseline for the sandfly vector’s anticipated northward move because of global warming and as an advisory for immunocompromised persons traveling to leishmaniasis-endemic areas.

Keywords: LeishmaniasisGermanyrisk factorsHIV infectiondispatch

Leishmaniases compose a spectrum of protozoal diseases currently endemic in 88 countries in Asia, Africa, the Americas, and southern Europe. The geographic distribution of leishmaniases has widened, and the disease is reported in areas in which leishmaniasis was previously nonendemic (1). Apart from cutaneous, mucocutaneous/mucosal, and visceral leishmaniases, HIV-1–associated leishmaniasis acquired in southern Europe and in other parts of the world have been observed in increasing numbers (1,2).

Leishmaniasis is not notifiable in Germany. In September 2000, a national advice and reference center was created at the Institute of Tropical Medicine in Berlin; the aim of the center was to monitor the frequency, origin, and type of leishmaniases seen in Germany; to advise physicians; and to improve information for travelers to disease-endemic areas. The healthcare professionals were informed about the reference center by the Robert-Koch-Institute, the center for surveillance of infectious diseases in Germany, as well as through the Journal of the German Medical Association, which is received by every registered physician (3). Leishmaniasis was diagnosed if parasites were detected in smears, culture, histologic sections, by polymerase chain reaction (PCR) of lesion biopsy specimens, bone marrow, or peripheral blood. For detection of Leishmania-specific antigen the small subunit (ssu rRNA), the internal transcribed spacer (ITS-1) region of the ribosomal RNA genes, or both, were amplified by PCR (4). Leishmania complexes and species were determined by digestion of the ribosomal ITS-1 PCR product with restriction enzymes (4).

Within 2 years, 70 cases of leishmaniases (43 cutaneous or mucocutaneous/mucosal; 27 visceral) were reported. For 58 case-patients (35 cutaneous or mucocutaneous/mucosal; 23 visceral), data were available on the age, sex, residence, travel destination, possible exposure location, reason for travel, duration of stay, duration and type of symptoms, concomitant diseases or therapies, type of diagnosis, and treatment received.

Cutaneous and Mucosal Leishmaniasis

Of the 35 patients with cutaneous or mucocutaneous/mucosal leishmaniasis, 30 were German tourists (Table 1). The male-to-female ratio was 1.5:1. Ten had contracted cutaneous or mucocutaneous/mucosal leishmaniasis in Europe, 11 in Central and South America, 6 in Asia, and 3 in Africa. Two persons had been infected during work stays of 1 to 4 months in French Guyana, one each in Peru and Libya, and one patient had immigrated from Afghanistan.

Characteristics of patients with cutaneous and mucosal leishmaniasis, Germany<sup>a</sup>
No.ExposureStatusSexAge (y)Leishmania speciesTreatmentOutcome
Europe

1
France
Tourist
F
64
L. donovani complex
No treatment
No cure
2
Italy
Tourist
F
24
L. donovani complex
Liposomal amphotericin B
Improved
3
Malta
Tourist
M
22
L. donovani complex
Perilesional pentavalent antimonials
Cured
4
Malta
Tourist
M
39
L. donovani complex
Perilesional pentavalent antimonials
Cured
5
Malta
Tourist
F
57
n.d.
Perilesional pentavalent antimonials
Cured
6
Malta
Tourist
M
62
n.d.
Perilesional pentavalent antimonials
Cured
7
Spain (Majorca)
Tourist
F
5
n.d.
Pentamidine isethionate
Cured
8
Spain (Majorca)
Tourist
M
13
L. donovani complex
Perilesional pentavalent antimonials
Cured
9
Spain
Tourist
F
31
L. donovani complex
No treatment
Unknown
10
Spain
Tourist
M
33
L. donovani complex
Antibiotic
Cured
Americas

11
Belize
Tourist
M
36
L. braziliensis complex
Liposomal amphotericin B
Unknown
12
Belize
Tourist
F
32
n.d.
IFN-gamma
Cured
13
Bolivia
Tourist
M
35
L. braziliensis complex
Liposomal amphotericin B
Unknown
14
Brazil
Tourist
M
25
n.d.
Systemic pentavalent antimonials
Cured
15
Brazil
Tourist
M
39
L. braziliensis complex
Liposomal amphotericin B
Unknown
16
Brazil
Tourist
M
33
L. braziliensis complex
Liposomal amphotericin B
Cured
17
Ecuador
Tourist
F
29
L. braziliensis complex
Liposomal amphotericin B
Cured
18
Ecuador
Tourist
M
36
n.d.
Liposomal amphotericin B
Cured
19
French Guyana
Work stay
M
28
L. braziliensis complex
Liposomal amphotericin B
Cured
20
French Guyana
Work stay
M
22
L. braziliensis complex
Liposomal amphotericin B
Cured
21
Guatemala
Tourist
M
31
L. mexicana
Ketokonazole
Cured
22
Peru
Work stay
F
25
L. braziliensis complex
Liposomal amphotericin B
Cured
23
Peru
Tourist
F
33
L. braziliensis complex
Liposomal amphotericin B
Cured
24
Peru
Tourist
M
35
L. braziliensis complex
Liposomal amphotericin B
Cured
Asia

25
Afghanistan
Immigrant
M
21
L. tropica
Aminosidine ointment
No cure
26
Afghanistan
Tourist
F
12
n.d.
Aminosidine ointment
Cured
27
United Arab Emirates
Tourist
F
44
n.d.
Perilesional pentavalent antimonials
Cured
28
Syria
Tourist
M
5
n.d.
Perilesional pentavalent antimonials
Unknown
29
Syria
Tourist
F
3
n.d.
Perilesional pentavalent antimonials
Unknown
30
Turkey
Tourist
F
33
n.d.
Antibiotic
Cured
31
Turkey
Tourist
M
37
L. donovani complex
Liposomal amphotericin B
Improved
Africa

32
Egypt
Tourist
M
25
L. tropica
Aminosidine ointment
No cure
33
Egypt
Tourist
F
27
L. tropica
Aminosidine ointment
Cured
34
Kenya
Tourist
M
50
n.d.
Perilesional pentavalent antimonials
Cured
35LybiaWork stayM34n.d.Aminosidine ointmentCured

an.d., not done; IFN, interferon.

The median duration of lesions until the diagnosis of leishmaniasis was made was 4 months (range 3 weeks to 2 years). Sixteen patients had more than one lesion (median 2, range 1–6 lesions). Seventeen lesions were located in the face, including mouth and nose, 28 on the upper extremities and 21 on the lower extremities. Lesions were ulcerated in 39 cases, papular-nodular in 24, and plaque-like in 3. Parasites were detected in 13 of 20 smears, in 9 of 10 cultures, and in 14 of 16 histologic sections; by using PCR, Leishmania-specific DNA was detected in 16 of 16 biopsy specimens.

Patient 1 had lesions in the mouth caused by L. infantum. She was under continuous immunosuppressive treatment for severe bronchial asthma. Patient 2 had received methotrexate and steroids for treatment of systemic collagenosis for several weeks. Both patients were tested for leishmanial infection in the blood; in both patients, the Leishmania-specific PCR of the buffy coat of the blood was positive. Patient 22 had mucocutaneous leishmaniasis of the nasal septum. She had been treated for a skin lesion caused by L. braziliensis 3 years earlier.

Visceral Leishmaniasis

A total of 18 of the 23 visceral leishmaniasis patients were German tourists; 3 were immigrants from Angola, Iran, and Togo; and 2 were visitors from Italy and Portugal (Table 2). The male-to-female ratio was 6.7:1.

Characteristics of patients with visceral leishmaniasis, Germany<sup>a</sup>
No.ExposureStatusSexAgeRisk factorLeishmania speciesTreatmentOutcome
1
Italy
Tourist
M
2 y
Child
n.d.
Liposomal amphotericin B
Cured
2
Italy
Tourist
F
5 y
Child
n.d.
Liposomal amphotericin B
Cured
3
Italy
Tourist
M
11 y
Child
n.d.
Liposomal amphotericin B
Cured
4
Spain
Tourist
F
8 mo
Child
n.d.
Liposomal amphotericin B
Cured
5
Spain
Tourist
M
9 mo
Child
L. donovani complex
Liposomal amphotericin B
Cured
6
Iran
Immigrant
M
7 y
Child
L. donovani complex
Liposomal amphotericin B
Cured
7
Spain
Tourist
M
43 y
HIV
L. donovani complex
Liposomal amphotericin B;
Maintenance therapy:
HAART plus liposomal amphotericin B once monthly
No relapse for 6 months
8
Spain (Ibiza)
Tourist
M
48 y
HIV
L. donovani complex
Liposomal amphotericin B;
Maintenance therapy:
HAART plus liposomal amphotericin B once monthly
No relapse for 8 months
9
Portugal
Visitor
M
29 y
HIV
n.d.
Liposomal amphotericin B;
Maintenance therapy:
HAART plus liposomal amphotericin B once monthly
unknown
10
France
Tourist
M
31y
HIV
L. donovani complex
Liposomal amphotericin B;
Maintenance therapy:
HAART plus liposomal amphotericin B once monthly
Relapse after 4 months; retreatment with Liposomal Amphotericin B; No relapse for 3 months
11
Angola
Immigrant
M
40 y
HIV
L. donovani complex
Systemic pentavalent antimonials
Maintenance therapy:
HAART plus pentavalent antimonials once monthly
unknown
12
Togo
Immigrant
M
37 y
HIV
L. donovani complex
Liposomal amphotericin B
Cured
13
Italy (Sicily)
Visitor
M
31 y
Thymoma
n.d.
Liposomal amphotericin B
Cured
14
Italy (Ischia)
Tourist
M
67 y
Methotrexate/steroids
L. donovani complex
Liposomal amphotericin B
Cured
15
Italy (Sicily)
Tourist
M
68 y
Methotrexate
n.d.
Liposomal amphotericin B
Cured
16
Italy (Ischia)
Tourist
M
70 y
Splenectomy
n.d.
Liposomal amphotericin B
Cured
17
Spain
Tourist
M
51 y
Splenectomy
L. donovani complex
Liposomal amphotericin B
Cured
18
Greece (Korfu)
Tourist
M
66 y
Diabetes mellitus Hypertonus
n.d.
Liposomal amphotericin B
Cured
19
Spain
Tourist
M
52 y
Hypertonus
Hypercholesterolemia
n.d.
Liposomal amphotericin B
Cured
20
Greece (Korfu)
Tourist
M
45 y
Diabetes mellitus
Emphysema
L. donovani complex
Systemic pentavalent antimonoials
Cured
21
Tunisia
Tourist
M
53 y
Hypertonus
L. donovani complex
Liposomal amphotericin B
Cured
22
Malta
Tourist
F
55 y
-
n.d.
Liposomal amphotericin B
Cured
23ChinaTouristM67 y-n.d.Liposomal amphotericin BCured

an.d., not done; IFN, interferon.

The median time between symptom onset and the correct diagnosis was 4 months (range 1–16 months). All case-patients had fever, 17 (74%) had splenomegaly, 11 (48%) hepatomegaly, 20 (87%) anemia, 17 (74%) leukopenia, and 8 (35%) thrombocytopenia.

Bone marrow smears indicated Leishmania in 18 of 20, bone marrow culture in 6 of 7, bone marrow histologic sections in 7 of 8, PCR of the bone marrow in 8 of 9, and PCR of the buffy coat of the blood in 7 of 7 cases. Additionally, antibodies were detected in medium to high concentration by an immunofluorescence test, enzyme-linked immunosorbent assay (ELISA), or both, in 14 of 15 cases. Species was identified in 7 of 18 visceral cases contracted in southern Europe and indicated Leishmania belonging to the L. donovani complex, which implicated infection with L. infantum.

Six cases of visceral leishmaniasis occurred in children 2 months of age to 11 years of age. Four German tourists and two immigrants had long-known HIV infection (median duration 3 years, range 8 months–6 years). All HIV–co-infected patients had CD4-cell counts below 200/μL (median 108, range 23–185 CD4 cells/μL) when the diagnosis of visceral leishmaniasis was made. Of the remaining 11 patients, 1 had a thymoma with impaired T-helper-1 cell function, 2 had received intermittent immunosuppressive therapy (methotrexate and steroids) for rheumatologic disease, and 2 patients had their spleens removed. Three patients were in an impaired general condition because of combinations of diabetes, hypertonus, hypercholesterolemia, and emphysema. In the remaining three patients (53–68 years of age), apart from hypertonus in one, no impairing condition was detected.

Discussion

Information on single cases and a small case series of imported leishmaniases in Germany is available, but systematic reporting on frequency, type, and origin of leishmanial infections in Germany did not exist until 2000 (57). Our recent surveillance is dependent on passive consultation and reporting and therefore may have selection bias because if visceral leishmaniasis, a potentially fatal disease that requires hospitalization, is suspected, advice on diagnosis and treatment is sought more often than for the skin infection. We assume that our system captures approximately half of the visceral leishmaniasis cases and approximately one third of the classical cutaneous cases imported to Germany.

A total of 47% of all cases, but 78% of the visceral cases were contracted in the European Mediterranean area and Portugal, and most of the infections indicated a species of the L. donovani complex, most probably L. infantum, as the probable causative agent. Thirteen infections (22%) were acquired on the Mediterranean islands of Ibiza, Ischia, Majorca, Malta, Korfu, or Sicily.

This distribution reflects the fact, that the Mediterranean countries, Spain, Italy, and the Mediterranean islands, in particular, are the favorite vacation areas for Germans. Annually, Germans take 18 million vacations to the European Mediterranean area (including 8 million to Spain and 6 million to Italy) with a median duration of 2 weeks. Sixty percent of travel to Italy and 90% of travel to Spain are to Leishmania-endemic areas.

While leishmaniasis has always been endemic in the Mediterranean countries, the maximum northern latitude for sandfly survival is speculated to move further to the North, beyond Germany (1) because of global warming. If this scenario is correct, the imported cases may serve as a potential substrate for the sandfly vector. Dogs that are imported as pets from the disease-endemic areas of southwestern Europe or that contract the infection when accompanying their owners for vacation are another potential substrate (8).

Infections with L. infantum in a child, as well as in a horse who had never left Germany, have recently been described and have led to speculations about an autochthonous focus (9,10). Also recently, the first sandfly species, Phlebotomus mascittii Grassi, 1908, was detected in southern Germany, although its potential as a vector of Leishmania remains to be demonstrated (11).

As expected, visceral leishmaniasis is often manifested in persons with impaired immunocompetence because of young age, HIV infection, immunosuppressive therapy and, in our analysis, in older persons with concomitant diseases.

Notably, 12 (67%) of 18 of the visceral cases contracted in the European Mediterranean area were in adults, thus confirming a change in age groups affected. Formerly, visceral leishmaniasis was known mainly as a disease of children (1,2). This change may partly be explained by the increased proportion of Leishmania and HIV–co-infected persons and partly by increased travel activities of otherwise immunocompromised persons, including elderly persons.

Furthermore, even in patients with cutaneous leishmaniasis, dissemination of parasites has to be excluded in case of impaired immunocompetence (e.g., immunosuppressive treatment). In these cases, Leishmania-specific PCR of the buffy coat of the peripheral blood is a sensitive method for detecting parasite spread beyond the skin.

Parents of small children and persons with reduced immunocompetence should be informed about their increased susceptibility to infection with Leishmania when traveling to disease-endemic areas. Measures to reduce the exposure to sandflies, such as clothes, repellents, and mosquito nets as well as collars impregnated with repellents for accompanying dogs, should be recommended.

Suggested citation for this article: Harms G, Schönian G, Feldmeier H. Leishmaniasis in Germany. Emerg Infect Dis [serial online] 2003 Jul [date cited]. Available from: URL: http://www.cdc.gov/ncidod/EID/vol9no7/03-0023.htm

Acknowledgments

We thank colleagues at German hospitals and health institutions who discussed their patients with us or kindly contributed to the data collected on leishmaniases.

Dr. Harms is a senior lecturer and researcher in tropical medicine and international health at the Institute of Tropical Medicine and at the Medical Faculty Charité, Humboldt University Berlin, Germany. Her primary research interests are the interaction of HIV/AIDS and parasitic infections, leishmaniasis in particular.

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