Epidemiology, clinical features, and management of cutaneous leishmaniasis. A comprehensive review

Nº de DOI: 10.34896/RSI.2026.79.77.001

AUTHORS

1. María del Cisne Reyes Ramírez. General Practitioner. Attached to Private Clinics of Ecuador. Graduate of the National University of Loja. (Loja-Ecuador). https://orcid.org/0009-0007-8316-7189
2. Mary Carmen Barberán Moreira. General Practitioner. Attached to Private Clinics of Ecuador. Graduate of the University of Guayaquil. (Guayaquil-Ecuador). https://orcid.org/0009-0004-1967-7895
3. Kerty Lorena Benavides Moreira. General Practitioner. Attached to Private Clinics of Ecuador. Graduate of the University of Guayaquil. (Chone-Ecuador). https://orcid.org/0009-0002-5878-7152
4. Gisela Elizabeth Vinza Chuqui. General Practitioner. Attached to the Riobamba General Teaching Hospital. Graduate of the National University of Chimborazo. (Riobamba-Ecuador). https://orcid.org/0009-0000-4608-2062
5. Paula Jessenia Idrovo Campoverde. General Practitioner with a Master’s degree in Precision Nutrition Studies and Nutritional Epidemiology. Attached to the Homero Castanier Crespo General Hospital. Graduate of the Catholic University of Cuenca. (Biblián-Ecuador). https://orcid.org/0000-0003-3169-3244

SUMMARY

This review paper is intended to be an updated synthesis of available literature regarding the epidemiological patterns of CL, its clinical manifestations, recent advancements in diagnostic procedures, recent advancements in treatment of CL, and how this may serve as one of the valuable resources to improve patient care and control in both endemic and non-endemic areas.

KEY WORDS

Cutaneous leishmaniasis, Leishmania species, epidemiology, sandfly transmission, molecular diagnosis, PCR, LAMP, endemic regions, travel-related infections, treatment strategies.

RESUMEN

Este artículo de revisión pretende ofrecer una síntesis actualizada de la literatura disponible sobre los patrones epidemiológicos de la leishmaniasis cutánea (LC), sus manifestaciones clínicas y los avances recientes en los procedimientos diagnósticos y el tratamiento de la enfermedad; asimismo, busca servir como un recurso valioso para mejorar la atención al paciente y el control de la afección tanto en zonas endémicas como no endémicas.

PALABRAS CLAVE

Leishmaniasis cutánea, especies de *Leishmania*, epidemiología, transmisión por flebótomos, diagnóstico molecular, PCR, LAMP, regiones endémicas, infecciones asociadas a viajes, estrategias de tratamiento.

INTRODUCTION

Cutaneous leishmaniasis (CL) is a public health problem in many parts of the world including the Americas from Texas to Argentina and in the Old World (particularly in the Middle East and North Africa) where it creates a large amount of morbidity in affected populations. It is caused by a parasite that is transmitted by female sandflies and the majority of people affected are vulnerable populations, including travellers, immigrants, military personnel, and those who live in areas where there are endemic cases of this disease. In addition, incidence is affected by factors such as migration, travel, and military deployments. The clinical manifestation of CL is very diverse (ranging from localized ulcers to ulcerations that are disfiguring) and requires prompt and accurate diagnosis in order to provide effective management. Diagnostic capabilities have progressed from traditional methods primarily relying on skin scrapings and punch biopsies to newer methods using immunologic and molecular techniques (e.g. polymerase chain reaction assays) that have increased the ability to detect the disease and identify the species causing the disease. However, treatment options for patients with CL continue to be limited and depend on the response of the specific species of the leishmania parasite that is causing the disease, the severity of the disease, and the availability of resources, thus requiring more individualised approaches for optimal treatment. Understanding the epidemiology, clinical presentation, and management of cutaneous leishmaniasis is important for clinicians throughout the world, especially in light of the recent increase in global movement of people that puts patients at risk of developing this disease and potentially presenting with CL in a location where CL is not endemic. Therefore, there is an urgent need for increased awareness, and additional research on more effective diagnostic and therapeutic procedures for CL.

OBJECTIVE

To comprehensively analyze the epidemiology, risk factors, diagnostic advancements, and therapeutic strategies of cutaneous leishmaniasis (CL), with emphasis on species-specific management, challenges in endemic and non-endemic settings, and the integration of molecular diagnostics to optimize patient outcomes and public health control measures.

METHODOLOGY

This review identified cutaneous leishmaniasis through a methodical review of peer-reviewed literature about epidemiology, diagnosis, treatment. Major electronic databases (PubMed, Scopus, Web of Science) were searched for relevant literature with specified search terms (e.g., cutaneous leishmaniasis epidemiology, identification of Leishmania species, diagnosis using PCR, diagnosis using LAMP, treatment of cutaneous leishmaniasis). Priority was given to studies from the last 20 years; however, some earlier foundational studies were included as necessary for putting historical and epidemiological developments into a historical context.

The retrieved literature was subsequently analysed and categorised according to thematic domains related to global distribution characteristics, demographic risk factors, methods of diagnosis (e.g., parasitological, immunologic, molecular; etc.) and different management strategies across different epidemiological contexts. Qualitative synthesis of the data was carried out with the intention of emphasising/summarising the clinical implications of this disease, the advancements in diagnostic techniques, and the variability of therapy according to species and severity, and the public health implications of controlling this disease. The methodology employed in this study produced a coherent, evidence-based synthesis of the current state of knowledge about cutaneous leishmaniasis while providing a clear indication of the areas in need of further study or research.

RESULTS

Epidemiology of Cutaneous Leishmaniasis:

What are the global distribution patterns of cutaneous leishmaniasis?

Cutaneous leishmaniasis (CL) has an extremely wide-ranging geographic distribution, with areas where it is endemic in the Americas, Eastern Mediterranean, North Africa, Central Asia, and ranges from the tropics to subtropics¹. A particularly noteworthy area of high endemic prevalence is North Africa, particularly in Morocco, Algeria, Tunisia, and Libya, where new endemic foci have developed since the 1980s and highlight the dynamic and growing trend in transmission of CL in this part of the world². CL occurs well beyond North Africa; Latin America and Mediterranean Basin are also major regions for CL, which illustrates the widespread geographic reach and some of the epidemiologic complexity of CL². An important feature of the global distribution of CL is the large number of Leishmania species responsible for causing CL, with three species (L. major, L. tropica and L. infantum) representing the major causes of CL and are found in distinct nosogeographical forms. Different nosogeographical forms of CL are attributed to varying clinical and epidemiological features of the cause and require distinct and tailored public health responses². Heterogeneity among species of Leishmania and their location in different bioclimatic zones leads to differences in the associated vectors and reservoir hosts, which further complicates CL control efforts and contributes to widespread patterns of endemicity within and among regions². Environmental change, including increased human encroachment into sand fly habitats and shifting ecological boundaries, has also impacted the transmission and distribution of CL on a global scale, resulting in the emergence of new endemic foci of CL and growing existing foci¹. The numbers associated with CL (600,000-1,000,000 newly reported cases each year) and the significant social and medical burden of CL in nearly 100 countries where it is endemic create an urgent need to establish a concerted effort to control the future spread of CL and reduce its global burden. This effort involves ongoing surveillance, ecological management and species-specific interventions to achieve an effective outcome^1,3.

How do travel, migration, and military deployment influence disease incidence?

A number of different things affect the extent to which people get ill from travel, moving to different places (migration), or going away for military service (deployment). For example, diarrheal disease is a good example, given that the rate of diarrheal disease due to deployment is 5-7% per 100 people per month higher than for many people, including deployed personnel and travellers alike hence the added vulnerability of those travelling/migrating to places they have never been or had a chance to prepare for (i.e., places with a different environment and different germs) ⁴. The increased risk of becoming infected with a gastrointestinal-related disease (e.g., E. Coli) will occur when they have inadequate handwashing facilities and must eat local food sources⁴. The same foods that people are predominantly forced to consume at a new location can also increase their risk of infection (e.g., E Coli, Campylobacter and Shigella) as well as complicate food security, local infrastructure, and infectious disease risk (e.g., how much access does the community have to clean water or sanitary conditions?) ⁴. These illnesses can really affect an individual’s health but also affect the mission of military personnel, as seen in past deployments where more than half of a deployed unit has been unable to perform their duties due primarily to illness; therefore, it is essential to implement proper sanitation, food safety procedures, and rapid medical response in order to be able to maintain both public health and the mission readiness of military personnel⁴. Therefore, addressing these issues needs to take a cooperative, multi-step approach that combines prevention of disease from a public health, strong logistic support systems, and ongoing surveillance in order to lessen the impact of travel, migration, and deployment on the incidence of disease.

What are the key risk factors and demographic groups affected in endemic regions?

While deployed military personnel face a higher level of risk than non-deployed personnel, endemic areas also have several key risk factors and demographic groups (e.g., ethnicity) that have been affected disproportionately by two major forces: biophysical (biological) and sociopolitical (socio-economic). As population growth occurs and populations are distributed unevenly, the number of persons located within high-risk areas with insufficient public health infrastructure increases, contributing to the challenges associated with disease prevention and control⁵. Furthermore, certain characteristics of specific groups may inhibit their ability to prepare for, respond to, and recover from disease outbreaks; individuals with lower incomes (e.g., Latinos living in the United States) represent one such example of a population with increased vulnerability to the negative impacts of endemic illness due to low-to-no socioeconomic power⁵. Language barriers and culturally based beliefs (e.g., misunderstandings of official warnings and fears of deportation) further increase the vulnerability of migrant and minority populations by resulting in poor disaster response and delayed access to health care services⁵. In addition, foreign military personnel, aid workers, international travelers, and refugees (especially in camps) are frequently at elevated risk for infectious disease because of their transient status, living in crowded conditions, and limited access to resources. This highlights the relationship and interaction among three key factors: mobility, demography, and disease transmission⁶. To effectively address multi-factorial risk factors related to public health in endemic populations, targeted interventions should be based on socio-economic disadvantages, culturally specific characteristics, and mobile (migrant) populations.

Which diagnostic methods are most effective for confirming cutaneous leishmaniasis?

The effective confirmation of cutaneous leishmaniasis (CL) in North Africa and other endemic regions depends on the selection and application of appropriate diagnostic techniques; there are several different techniques available that have their own advantages and disadvantages. Historically, the gold standard for diagnosis of CL has been the use of microscopy (i.e. by identification of Leishmania amastigotes in lesion smears) because of its high specificity and by allowing the direct visualisation of the parasite^7,8. However, this technique has limited (and variable) sensitivity, particularly when examining chronic lesions with low parasite burdens; in addition, microscopy requires an experienced operator^8,9. Microscopy is further complicated by the need to obtain samples using invasive methods (e.g. punch biopsy, scraping tissue) which introduce both technical challenges as well as risk to the patient⁸. PCR and LAMP are both molecular techniques that provide improved sensitivity and specificity as compared to microscopic evaluation, with PCR being the preferred method when diagnosing lesions that have been present for prolonged periods, as microscopic evaluation cannot be performed in many of these cases^7,9. Molecular techniques also provide the ability to determine the species of Leishmania, which is important in North Africa due to the presence of multiple species of Leishmania that are involved in CL and the need for clinical management to be based on the species present^9,10. Unfortunately, there are several drawbacks associated with molecular diagnostics, including the need for capital equipment and supply resources, trained personnel, and financial investment; these limitations can be particularly problematic in resource-poor settings^8,9. Rapid diagnostic tests (RDTs) are also an important alternative for CL diagnosis since they can potentially enable point-of-care testing; however, RDTs do not provide as accurate results or confirm a species-level diagnosis as do molecular techniques^7,9. The interrelatedness of the dominant modalities demonstrates the need for the integration of various methods of CL diagnosis (i.e. combining traditional parasitological confirmation with modern molecular typing techniques) to achieve the maximal level of both accuracy and applicability when diagnosing CL in all epidemiological settings. To address major gaps in diagnostic testing for CL and to provide optimal disease management and control of CL in North Africa, significant investment in capacity building for laboratory infrastructure and training as well as expanded access to molecular testing must take place as soon as possible.

How do new immunologic and molecular diagnostic tools improve detection accuracy?

The use of newly developed immunologic and molecular diagnostic techniques has improved the accuracy of detecting infectious diseases in complex (e.g., military deployment) and high-risk environments. The use of immunoassays to identify serum and tissue biomarkers, such as gastrointestinal and respiratory infections common in deployed personnel, using ELISA, electrochemiluminescence or chemiluminescent immunoassays provide a highly sensitive detection method that allows rapid identification and monitoring of these infections from the time of initial patient diagnosis through to completion of treatment. Similarly, both nucleic acid amplification tests (NAAT) and next-generation sequencing provide accurate and timely diagnostics; however, they provide additional information about the presence of antimicrobial resistance in addition to simply confirming the presence of the pathogenic organism, thereby facilitating optimal selection of treatment and reducing the risk for dehydration and heat injury¹¹. The combination of immunoassay and molecular diagnostics along with advancements in artificial intelligence tools capable of processing large datasets and predicting result outcomes will develop a reliable diagnostic resource that decreases the amount of time required to reach a diagnosis, which will enhance the patient’s chance of being treated effectively and improve clinical outcomes^11,12. Continued interdisciplinary research and collaboration will ensure that the use of these technologies will provide maximum possible benefit by enabling adaptation and implementation of diagnostic tools within diverse operational environments to protect the health and readiness of service members that are deployed¹².

Management and Treatment Approaches for Cutaneous Leishmaniasis:

What are the current best practices for treating cutaneous leishmaniasis?

In recent research, particular focus has been put on exploring topical applications as options to reduce systemic toxic effects from Amphotericin B because it theoretically should deliver medication to the site with less risk of side effects associated with currently used methods of deliver. However, topical therapy has produced limited success in treating uncomplicated New World Cutaneous Leishmaniasis due to the lack of evidence in clinical trials, as well as more extensive testing of efficacy in treating New World and Old World manifestations of this disease have shown that topical Amphotericin B consistently produces no reliable therapeutic result. Furthermore, no conclusive research comparing intralesional treatment with meglumine antimoniate to treated with topical liposomal Amphotericin B for cases of L. major has shown that either method produced better outcomes. Therefore, there is a need for vigorous research that will assist with establishing standard protocols for treatment of Cutaneous Leishmaniasis regardless of the Leishmania species involved and the variety of responses to currently utilized therapies.

How does treatment vary based on species identification and disease severity?

Although there is considerable variety in the treatments for leishmaniasis, the specific treatment approach will depend primarily on the Leishmania species responsible for the infection and the severity of the disease. Pathogen biology and clinical presentation are complexly related to one another, and there is no simple, straightforward explanation for how specific species affect the outcomes of their treatments¹⁴. Rapidly identifying the specific species of Leishmania is critical for guiding the therapy because it allows physicians to anticipate how well a patient will respond to a given treatment, as well as which treatment regimen will be the most effective and what complications may arise from that treatment. For example, Leishmania tropica and all of the species within the Viannia group exhibit prolonged healing times and typically require more extensive or aggressive treatment than leishmaniasis caused by other Leishmania species (e.g., L. mexicana and L. major), which will often cure spontaneously and can therefore be managed relatively conservatively¹⁴. The severity and location of the lesions (e.g., whether the lesions are located in the mucosa or involve the palate or larynx) will also affect the types of medications used in a leishmaniasis treatment regimen, since more extensive lesions or lesions located in the mucosa are usually not as responsive to standard therapies, are more likely to relapse, and may require adjunctive therapies such as corticosteroids to reduce airway complications or require closer monitoring and management¹⁴. Similarly, treatment for leishmaniasis in an immunocompromised patient or in patients with comorbidities is even more complex than other patients; therefore, species identification is key to making the best treatment choice for these patients to maximize their benefit and minimize any negative side effects associated with the treatment¹⁴. The interrelationships between these factors highlight the need for rapid and accurate diagnostics, matched with individualized treatment options that take into consideration the species of organism causing the infection and the clinical presentation of the patient to better direct research and surveillance efforts as well as guidelines for the treatment of leishmaniasis in different epidemiologic settings to improve the prognosis of leishmaniasis patients.

What are the challenges and advancements in managing cases in both endemic and non-endemic settings?

Dealing with cases of infectious diseases such as Chagas disease is a multi-dimensional issue due to factors including: epidemiology, availability of healthcare resources, and characteristics of the infected person.

When attempting to assess risk for infecting others or transmitting Chagas disease from person to person in endemic areas of the world, local issues such as sanitation systems and vector populations greatly influence local epidemiology and the strategic planning for effective and appropriate ways to prevent transmission through interventions. Thus, prevention and control of Chagas disease must utilize a localized approach tailored to ensure both research participant safety as well as that of the surrounding communities¹⁵.

On the other hand, clinical management of Chagas disease in non-endemic areas is complicated by lower rates of disease awareness among healthcare providers, as well as specific and defined needs associated with certain migrant populations; therefore targeted screening and public health strategies must be developed based on sound epidemiological data (depending on migrant group’s history)¹⁶.

Furthermore, there is currently limited information available comparing migrant populations living in high (endemic) vs. low prevalence (non-endemic) areas of the world. This lack of subgroup analysis restricts the ability to establish screening priorities for a given population and how best to allocate available resources, emphasizing the need for a greater number of epidemiological studies that report on smaller subgroup populations¹⁶. Although these complexities exist, advances such as using internationally accepted evidence prevalence estimates and utility values derived from Latin American studies to develop better and more equitable assumptions about how to design and conduct studies in non-endemic areas of the world exist¹⁶. In order for optimal disease management and allocation of resources to occur equally in both endemic and non-endemic countries, data collection must be strengthened; risk assessments further refined; and contextually relevant research must be performed to include both clinical and public health components of Chagas disease. The result will be improved interventions and policy decisions that are developed based upon the complex realities of both endemic and non-endemic countries.

DISCUSSION

In this study it presents an extensive examination of cutaneous leishmaniasis (CL) which reflects highly miscellaneous nature of this disease and its very large geographical range. The epidemiological circumstances, environmental factors and socioeconomic conditions all play important roles in determining the transmission and management of CL. The presence of several Leishmania species (e.g., L. major, L. tropica, L. infantum) having distinct clinical and epidemiological characteristics indicates that disease-specific diagnostic and therapy approaches must be developed for each species. The use of advanced molecular diagnostics (e.g., PCR, LAMP) is a great advancement towards improving sensitivity for detecting CL and allowing for accurate species identification, both critical for effective individualized therapy. However, despite the advancements in technology, there remain significant barriers to widespread utilization of these diagnostic methods in endemic areas with limited resources/infrastructure. The review highlights the contribution of environmental factors (e.g., environment, ecological changes) to the occurrence of CL and indicates that control efforts must go beyond the use of clinical approaches and include environmental management and surveillance. In addition to ecological factors, many of the issues affecting susceptibility to disease and the access to public health services are also related to socio-economic factors, migration, and cultural differences. The variability of treatment efficacy based on the species and severity of disease confirms the need for new and more effective treatments, especially topical treatments with minimal systemic effects. Limitations of this review include dependence upon available literature which is subject to publication bias and variable quality/heterogeneity across studies therefore limiting the generalizability of the literature. Future studies should be aimed at developing low-cost point-of-care diagnostic tests appropriate for endemic regions, investigating new therapeutic alternatives, and evaluating the impact of integrated strategies which consider the ecological, social and clinical determinants of CL. There is also a need for longitudinal studies to improve our understanding of the long-term outcomes and possible relapse or mucosal recurrence from CL particularly in areas undergoing rapid environmental and demographic changes. In conclusion, a multidisciplinary approach (epidemiological surveillance, ecological management, socio-economic approach, clinical advancement) is necessary to reduce the global burden of CL and its worldwide impact.

CONCLUSIONS

1. Though cutaneous leishmaniasis was previously considered an increasingly important global public health issue due to the effects of environmental, migration, economic and ecological change, it remains a major global public health issue that is largely neglected by many developing countries. The existence of many species of Leishmania with unique clinical and geographical manifestations demonstrates the need for the accurate identification of the Leishmania species involved so as to accurately administer treatment and project disease progression. The use of molecular diagnostic methods such as PCR and LAMP offer a far more accurate and faster method of diagnosing these parasites than traditional microscopy techniques; however, access to these methods in developing countries is still a barrier to the optimal management of this disease.
2. Treatment regimens for cutaneous leishmaniasis must be specific to the individual patient, taking into consideration the species of Leishmania (when known), the location and size of the lesions, the immune status of the patient and any other concurrent illness. While there are still many effective treatments available for cutaneous leishmaniasis, including systemic and intralesional anti-leishmanial agents, amphotericin B preparations and other medications, variable clinical results from treatment and the occurrence of potential side effects demonstrate a need for further investigation into the development of new, more effective and safer treatment options. The challenges of endemic areas (limited laboratory infrastructure and inadequate public health resources) differ from those experienced by patients who receive treatment in non-endemic areas and may result in decreased awareness of the clinical features of cutaneous leishmaniasis and therefore delayed diagnosis among travelers and migrants.
3. For the effective control and appropriate management of patients suffering from cutaneous leishmaniasis, a multidisciplinary strategy must incorporate epidemiological surveillance, ecological control of sandfly vectors, socio-economic factors and technological advances in clinical diagnosis/therapy. The implementation of point-of-care molecular diagnostic tests in addition to improving laboratory capacity and establishing species-specific treatment guidelines will contribute to lowering the overall disease burden burden and improving patient care. Creation of longitudinal studies and fostering international collaboration will be necessary to unravel the complex evolving epidemiology of the cutaneous leishmaniasis disease process.

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