Review
New world cutaneous leishmaniasis in travellers

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Summary

As travel to Latin America has become increasingly common, cutaneous leishmaniasis is increasingly seen among returning travellers—eg, the number of observed cases has doubled in the Netherlands and tripled in the UK in the past decade. A surprisingly high proportion of cases were acquired in rural or jungle areas of the Amazon basin in Bolivia. The clinical manifestations range from ulcerative skin lesions (cutaneous leishmaniasis) to a destructive mucosal inflammation (mucocutaneous leishmaniasis), the latter usually being a complication of infection with Leishmania (Viannia) braziliensis. PCR is now the diagnostic method of choice, since it has a high sensitivity and gives a species-specific diagnosis, allowing species-specific treatment. Treatment of cutaneous leishmaniasis aims to prevent mucosal invasion, to accelerate the healing of the skin lesion(s), and to avoid disfiguring scars. Pentavalent antimonials drugs are still the drug of choice for many patients. However, a high rate of adverse events, length of treatment, and relapses in up to 25% of cases highlight the limitations of these drugs. Although only used in a small number of patients thus far, liposomal amphotericin B shows promising results. Further studies are needed to find efficacious and better-tolerated drugs for new world leishmaniasis.

Introduction

Leishmaniasis is an infection caused by Leishmania spp, a group of intracellular protozoan parasites that are transmitted by various species of sandflies. Apart from disseminated visceral leishmaniasis (kala azar), ulcerative skin lesions and destructive mucosal inflammation comprise the wide range of clinical manifestations. With regard to cutaneous leishmaniasis and mucocutaneous leishmaniasis, the parasite species are divided into old world (southern Europe, the Middle East, Asia, and Africa) and new world leishmaniasis (Latin America). Whereas most of the old world species cause benign cutaneous disease, new world species cause a spectrum of disease ranging from mild cutaneous disease to severe mucosal lesions.

Here, we concentrate on new world cutaneous and mucocutaneous leishmaniasis, since cases of both conditions are increasingly seen among travellers returning from Latin American countries, and because the broad clinical spectrum and the limited knowledge of the disease among travellers and clinicians often leads to an incorrect initial diagnosis.1

Most cases of cutaneous leishmaniasis and mucocutaneous leishmaniasis in Latin America are caused by organisms in the Leishmania Mexicana and Leishmania Viannia subgenus complexes. There are three known organisms in the L Mexicana complex and four in the L Viannia complex that infect human beings (table 1). Symptoms generally present a few days to several months after infection as a gradually enlarging, erythematous and often pruritic papule that develops at the site of inoculation. The initial papule may become scaly. It further develops into an ulcer with a raised inflammatory outline. Verrucous and acneiform lesions are uncommon, but nodular lesions are seen in about 10% of cases. Ulcerative lesions are usually painless, unless secondarily infected.

The natural history varies depending on the species, the location of the lesion, and the immune status of the host. Leishmania (Mexicana) mexicana infections usually cause one or few lesions that heal spontaneously within 6 months.2 Lesions on the ear, called Chiclero ulcers, occur in 40% of patients in Mexico. Regional lymphadenopathy was observed in two-thirds of Brazilian patients infected with Leishmania (Viannia) braziliensis. Among these patients, 62% of lymph node aspirate cultures yielded leishmania parasites.3

Mucocutaneous lesions are typically not seen in L Mexicana complex infections except (rarely) in L amazonensis infections. However, they are a complication of the L Viannia complex infections and are seen more commonly in L braziliensis than in Leishmania (Viannia) panamensis or Leishmania (Viannia) guyanensis infections.4 The lesions usually appear weeks to years after the initial cutaneous lesion has healed. Erythema and oedema of the involved mucosa are followed by ulcerations covered with a mucopurulent exudate. Mutilating destruction of the nasal septum, palate, lips, pharynx, and larynx is often the result of such infections in endemic populations.

Section snippets

Epidemiology of cutaneous leishmaniasis in travellers

The geographic distribution of new world leishmaniasis strains is shown in figure 1. The disease is usually acquired in rural or jungle areas. Although urban transmission has been documented among local populations,5, 6 cases in travellers and military personnel are almost invariably acquired in jungle environments.

Scarce information exists on the incidence of cutaneous leishmaniasis in travellers for a number of reasons: (1) it is not a notifiable disease in most industrialised countries; (2)

Epidemiology of mucocutaneous leishmaniasis in travellers

Despite an increasing number of travellers to areas where mucocutaneous leishmaniasis is prevalent, only three cases were reported in the medical literature before 2003.15, 16, 17 11 cases of mucocutaneous leishmaniasis were reported between 2003 and 2005.11, 13, 14, 18 Half of the patients in whom the place of infection was known were infected in the Amazon region of Bolivia.13, 16, 19

There are no published data on the risk of travellers with L braziliensis cutaneous leishmaniasis progressing

Clinical presentation in travellers

Cutaneous lesions were diagnosed in a group of US military personnel at a median interval of 17 days (range 2–78 days) after infection with L panamensis.25 Our experience with L braziliensis in travellers shows that the average time that elapses between exposure and appearance of cutaneous lesions is 1·7 months (range 1–3 months).8 In French travellers, the mean interval between return and onset of lesion was 13 days (range 1–95 days) and between return and presentation 50 days (range 17–301

Diagnosis

Until recently, the diagnosis of cutaneous leishmaniasis and mucocutaneous leishmaniasis was based on direct visualisation of the parasite in the microscope in Giemsa-stained smears or histological sections.28 Direct visualisation of the amastigote parasite by using slit skin smear is very useful, simple, and gives rapid results (within 20 minutes), and should be the first step of diagnosis. Culturing aspirates or biopsy material in a special media is another potential diagnostic method;

Differential diagnosis in travellers

An analysis of the initial incorrect diagnosis of patients with cutaneous leishmaniasis seen at our institutions provides an overview of the differential diagnosis of the disease. Bacterial skin infections, unspecific skin reactions to insect bites, mycosis (including sporotrichosis in a patient with nodular lymphangitis), and tumours were the most frequent misdiagnoses. Other differential diagnoses include blastomycosis, yaws, syphilis, cutaneous tuberculosis, Mycobacterium marinum infections,

Treatment

The aim of treatment of cutaneous leishmaniasis is twofold: first, prevention of mucosal invasion by metastatic spread of the infection to the oropharyngeal site, and second, acceleration of the healing of the skin lesion(s) and avoidance of disfiguring scars. Systemic treatment is needed to achieve the first goal; local treatment might be sufficient for the second. The indications for systemic treatment are summarised in the panel.

Prevention

Personal protection against the vector sandflies (genus Lutzomyia) is crucial for travellers, whereby the variety of different sandfly species, their anthropophilic properties, and the time of feeding have to be respected. The most common vector of L braziliensis infections, Lutzomyia wellcomei, avidly bites human beings and rodents and, unlike most sandflies, feeds during daylight hours. By contrast, the vectors of the L Mexicana complex are much less anthropophilic and are usually nocturnal

Conclusions

Knowledge of leishmaniasis is limited among travellers and physicians. An increase in cases of imported cutaneous leishmaniasis and mucocutaneous leishmaniasis has been recorded in many countries because of increased travel to risk areas. Widely available PCR tests allow species-specific diagnosis of the causative organism. A multinational observational study using a standardised protocol is warranted to assess the pattern of disease and to optimise treatment in travellers.

Search strategy and selection criteria

Data for this review were identified by searches of Medline and references from relevant index articles. Numerous articles were identified through searches of the extensive files of the authors. Search terms included: “leishmaniasis”, “cutaneous leishmaniasis”, “mucocutaneous leishmaniasis”, “mucosal leishmaniasis”, “new world leishmaniasis”, “travellers”, and “tourists”. English, French, and German language papers were reviewed.

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