Review
Cutaneous leishmaniasis

https://doi.org/10.1016/S1473-3099(07)70209-8Get rights and content

Summary

Cutaneous leishmaniasis is endemic in the tropics and neotropics. It is often referred to as a group of diseases because of the varied spectrum of clinical manifestations, which range from small cutaneous nodules to gross mucosal tissue destruction. Cutaneous leishmaniasis can be caused by several Leishmania spp and is transmitted to human beings and animals by sandflies. Despite its increasing worldwide incidence, but because it is rarely fatal, cutaneous leishmaniasis has become one of the so-called neglected diseases, with little interest by financial donors, public-health authorities, and professionals to implement activities to research, prevent, or control the disease. In endemic countries, diagnosis is often made clinically and, if possible, by microscopic examination of lesion biopsy smears to visually confirm leishmania parasites as the cause. The use of more sophisticated diagnostic techniques that allow for species identification is usually restricted to research or clinical settings in non-endemic countries. The mainstays of cutaneous leishmaniasis treatment are pentavalent antimonials, with new oral and topical treatment alternatives only becoming available within the past few years; a vaccine currently does not exist. Disease prevention and control are difficult because of the complexity of cutaneous leishmaniasis epizoology, and the few options available for effective vector control.

Introduction

Leishmania parasites are the causal agents of leishmaniasis, a group of protozoan diseases transmitted to mammals, including human beings, by phlebotomine sandflies. Globally, there are an estimated 1·5–2 million new cases and 70 000 deaths each year, and 350 million people are at risk of infection and disease.1 Morbidity and mortality because of the leishmaniases cause an estimated 2·4 million disability-adjusted life-years.1

The leishmaniases are characterised by a spectrum of clinical manifestations: ulcerative skin lesions developing at the site of the sandfly bite (localised cutaneous leishmaniasis [LCL]); multiple non-ulcerative nodules (diffuse cutaneous leishmaniasis [DCL]); destructive mucosal inflammation (mucosal leishmaniasis); and disseminated visceral infection (visceral leishmaniasis). The clinical spectrum observed in patients indicates the complexity of leishmaniasis epizoology: several Leishmania spp can cause disease (table 1), and many sandfly and mammalian species have been implicated as vectors and reservoir hosts, respectively.

We critically review the most recent data on the burden of the cutaneous leishmaniases, namely LCL, DCL, and mucosal leishmaniasis, their epidemiology, clinical pathology, diagnosis, treatment, prevention, and control. Visceral leishmaniasis has been reviewed elsewhere;2, 3, 4 we did not review post kala-azar dermal leishmaniasis, because this is a manifestation seen in patients with visceral leishmaniasis after apparent clinical cure.

Section snippets

Disease burden and distribution

Cutaneous leishmaniasis is endemic in more than 70 countries worldwide, and 90% of cases occur in Afghanistan, Algeria, Brazil, Pakistan, Peru, Saudi Arabia, and Syria (figure 1).5 Surveillance data indicate that the global number of cases has increased during the past decade, as documented in Afghanistan,6 Bolivia,7 Brazil,8 Colombia,7, 9 Peru,7 and Syria.10 Such increases can be explained in part by improved diagnosis and case notification,11 but are also a result of inadequate vector or

Clinical symptoms

Several Leishmania spp can cause cutaneous leishmaniasis in human beings, although most infections probably remain symptomless.2 The first sign of an infection is typically a small erythema that develops after a variable prepatent period at the site where an infected sandfly has bitten the host. The erythema develops into a papule, then a nodule that progressively ulcerates over a period of 2 weeks to 6 months to become the lesion that is characteristic of LCL.35 LCL lesions vary in severity

Diagnosis

The broad clinical spectrum of cutaneous leishmaniasis makes diagnosis of present and past cases difficult. Differential diagnosis is important because diseases of other causes but with a similar clinical spectrum to leishmaniasis (eg, leprosy, skin cancers, tuberculosis, cutaneous mycoses) are common in leishmaniasis-endemic areas.14

Parasitological diagnosis remains the gold standard in cutaneous leishmaniasis diagnosis, because of its high specificity. It includes microscopic examination of

Vector and reservoir control

Because the strategies available are expensive and labour intensive, and because cutaneous leishmaniasis is a non-fatal disease, prevention and control strategies have mainly focused on treatment of the human disease, rather than on the elimination of reservoirs or reduction of human–vector contact.162 Hence, most approaches have been limited to pilot research studies and only a few have been brought up to operational scale.163

Sandflies are highly susceptible to insecticides. Although they

Conclusions

The leishmaniases are a complex group of diseases and although we know much more than we did a decade ago, we are no nearer to the prevention or control of this neglected disease, which mainly affects the world's poorest populations.183 To do so requires professional and financial commitment, focusing on key research and policy areas (panel). Over the past decade, several reviews and reports have identified priorities in research and public-health policy with regard to cutaneous leishmaniasis.

Search strategy and selection criteria

A comprehensive literature search of medical databases (Medline and Cochrane library) and non-medical search engines was done using several keywords: “leishmaniasis”, “leishmaniosis”, “leishmania”, “cutaneous”, “mucosal”, “mucocutaneous”, and “diffuse”. We paid particular attention to articles published in the non-English literature, as these have had little exposure in previous reviews. If appropriate, we contributed our personal knowledge on the subject. Our review focused on studies

References (183)

  • Y Dowlati

    Cutaneous leishmaniasis: clinical aspect

    Clin Dermatol

    (1996)
  • PD Marsden

    Mucosal leishmaniasis (“espundia” Escomel, 1911)

    Trans R Soc Trop Med Hyg

    (1986)
  • NG Saravia et al.

    Recurrent lesions in human Leishmania braziliensis infections—reactivation or reinfection?

    Lancet

    (1990)
  • V Yardley et al.

    Animal models of cutaneous leishmaniasis

  • A Gumy et al.

    The murine model of infection with Leishmania major and its importance for the deciphering of mechanisms underlying differences in Th cell differentiation in mice from different genetic backgrounds

    Int J Parasitol

    (2004)
  • J Alexander et al.

    T helper (h)1/Th2 and Leishmania: paradox rather than paradigm

    Immunol Lett

    (2005)
  • LR Antonelli et al.

    Activated inflammatory T cells correlate with lesion size in human cutaneous leishmaniasis

    Immunol Lett

    (2005)
  • G Bomfim et al.

    Variation of cytokine patterns related to therapeutic response in diffuse cutaneous leishmaniasis

    Exp Parasitol

    (1996)
  • VS Amato et al.

    Mucosal leishmaniasis: in situ characterization of the host inflammatory response, before and after treatment

    Acta Trop

    (2003)
  • S Guerbouj et al.

    Genomic polymorphism of Leishmania infantum: a relationship with clinical pleomorphism?

    Infect Genet Evol

    (2001)
  • G Schonian et al.

    Genetic variability within the species Leishmania aethiopica does not correlate with clinical variations of cutaneous leishmaniasis

    Mol Biochem Parasitol

    (2000)
  • KP Chang et al.

    Leishmania model for microbial virulence: the relevance of parasite multiplication and pathoantigenicity

    Acta Trop

    (2003)
  • L Rivas et al.

    Virulence and disease in leishmaniasis: what is relevant for the patient?

    Trends Parasitol

    (2004)
  • M Colmenares et al.

    Mechanisms of pathogenesis: differences amongst Leishmania species

    Trans R Soc Trop Med Hyg

    (2002)
  • SJ Turco et al.

    Is lipophosphoglycan a virulence factor? A surprising diversity between Leishmania species

    Trends Parasitol

    (2001)
  • The world health report 2004. Changing history

    (2004)
  • P Desjeux

    Leishmaniasis

    Nat Rev Mirobiol

    (2004)
  • R Reithinger et al.

    Anthroponotic cutaneous leishmaniasis, Kabul, Afghanistan

    Emerg Infect Dis

    (2003)
  • CR Davies et al.

    The epidemiology and control of leishmaniasis in Andean countries

    Cad Saúde Publica

    (2000)
  • RJ King et al.

    Predicting geographic variation in cutaneous leishmaniasis, Colombia

    Emerg Infect Dis

    (2004)
  • ZE Yadon et al.

    Assessment of leishmaniasis notification system in Santiago del Estero, Argentina, 1990–1993

    Am J Trop Med Hyg

    (2001)
  • R Molina et al.

    HIV and the transmission of Leishmania

    Ann Trop Med Parasitol

    (2003)
  • SL Croft et al.

    Drug resistance in leishmaniasis

    Clin Microbiol Rev

    (2006)
  • MA Escobar et al.

    American cutaneous and mucocutaneous leishmaniasis (tegumentary): a diagnostic challenge

    Trop Doct

    (1992)
  • R Reithinger et al.

    The transmission dynamics of canine American cutaneous leishmaniasis in Huánuco, Peru

    Am J Trop Med Hyg

    (2003)
  • JP Guthmann et al.

    Patients' associations and the control of leishmaniasis in Peru

    Bull World Health Organ

    (1997)
  • M Massoom et al.

    Current status of leishmaniasis in Pakistan

  • PJ Weina et al.

    Old world leishmaniasis: an emerging infection among deployed US military and civilian workers

    Clin Infect Dis

    (2004)
  • J Blum et al.

    Treatment of cutaneous leishmaniasis among travellers

    J Antimicrob Chemother

    (2004)
  • S Chiheb et al.

    Leishmania tropica cutaneous leishmaniasis in an emerging focus in North Morocco: new clinical forms

    Ann Dermatol Venereol

    (1999)
  • RL Jacobson et al.

    Outbreak of cutaneous leishmaniasis in northern Israel

    J Infect Dis

    (2003)
  • H Motazedian et al.

    Characterization of Leishmania parasites isolated from provinces of the Islamic Republic of Iran

    East Mediterr Health J

    (2002)
  • S Brooker et al.

    Leishmaniasis in refugee and local Pakistani populations

    Emerg Infect Dis

    (2004)
  • L Castellucci et al.

    Familial aggregation of mucosal leishmaniasis in northeast Brazil

    Am J Trop Med Hyg

    (2005)
  • ZE Yadon et al.

    Indoor and peridomestic transmission of American cutaneous leishmaniasis in northwestern Argentina: a retrospective case-control study

    Am J Trop Med Hyg

    (2003)
  • C Miranda et al.

    Satellite remote sensing as a tool for the analysis of the occurrence of American cutaneous leishmaniasis in Brazil

    Rev Saúde Publica

    (1998)
  • LF Chaves et al.

    Climate cycles and forecasts of cutaneous leishmaniasis, a nonstationary vector-borne disease

    PLoS Med

    (2006)
  • BL Herwaldt

    Laboratory-acquired parasitic infections from accidental exposures

    Clin Microbiol Rev

    (2001)
  • Alexander B, Agudelo LA, Navarro JF, et al. Relationship between coffee cultivation in Colombia and exposure to...
  • DH Campbell-Lendrum et al.

    Domesticity of Lutzomyia whitmani (Diptera: Psychodidae) populations: field experiments indicate behavioural differences

    Bull Entomol Res

    (2000)
  • Cited by (1126)

    View all citing articles on Scopus
    View full text