Leishmaniasis Research Articles (Page 1)

A Presumptive Case of Mucocutaneous and Visceral Leishmaniasis in Nonendemic Country

Leishmaniasis is a significant vector-borne health problem affecting 88 countries, transmitted by the bite of female sandflies (phlebotomine). It manifests in various clinical forms, such as diffuse cutaneous leishmaniasis, mucocutaneous leishmaniasis, and visceral leishmaniasis (VL). The most chronic and possibly fatal form, VL, is caused by Leishmania donovani (L. donovani). The critical need for novel, effective therapeutic targets is highlighted by the escalating costs, toxicity, and side effects of existing treatments, as well as the increasing occurrence of drug-resistant parasites. The emergence of computational biology domains, including Bioinformatics and systems biology, has opened up a plethora of opportunities for researching and discovering therapeutic compounds for illnesses using in-silico techniques. Enzymes involved in key metabolic pathways of L. donovani were used to construct a PPI network, followed by topological analysis employing centrality measures such as degree, closeness, bottleneck, and betweenness centrality (BC). Gene Ontology (GO) enrichment indicated that the most connected proteins are involved in essential biological processes, including redox regulation, energy metabolism, and nucleic acid synthesis. MCODE clustering identified high-degree hub proteins within top modules. From this integrative network-based analysis, we propose four proteins that recur across multiple pathways and exhibit high centrality and modularity scores, underscoring their functional significance. These proteins likely serve as chokepoints or regulatory hubs, making them promising multi-pathway drug targets. Their inhibition may disrupt multiple vital cellular functions simultaneously, offering an effective strategy against multidrug-resistant L. donovani strains. This study provides a computational framework to prioritize and validate novel therapeutic targets in L. donovani, contributing to the development of more effective treatments for visceral leishmaniasis.

A novel colorimetric assay for early differentiation of mucocutaneous and cutaneous leishmaniasis via species-specific identification.

ABSTRACTAmerican tegumentary leishmaniasis (ATL) affects the skin and mucous membranes, with a spectrum shaped by Th1/Th2 responses. This study investigated inflammasome activation in correlation with macrophage subpopulations, tissue parasitism, and histological changes in cutaneous and mucocutaneous leishmaniasis. We assessed inflammasome activation, tissue parasitism, and macrophage populations by immunohistochemistry, correlating with histopathological alterations using 29 biopsies from cutaneous and mucocutaneous leishmaniasis. Cutaneous leishmaniasis showed higher parasite density and infected macrophages than mucocutaneous leishmaniasis skin and mucosal lesions (p < 0.05). CD68+ and CD163+ macrophages were more abundant in cutaneous leishmaniasis (p < 0.0001 and p < 0.05). Inflammasome markers IL‐1β+ and IL‐18+ were significantly higher in cutaneous leishmaniasis (p < 0.05). In cutaneous leishmaniasis, CD68+ macrophages correlated positively with inflammasome markers, whereas in mucocutaneous leishmaniasis, CD163+ cells showed strong negative correlations with IL‐1β and caspase‐1. Parasite density correlated positively with inflammasome activation in cutaneous leishmaniasis but negatively in mucocutaneous leishmaniasis. Findings suggest that inflammasome activation plays different roles in ATL. In cutaneous leishmaniasis, inflammasomes contribute to the inflammatory response and parasite clearance, while in mucocutaneous leishmaniasis, they are less relevant, possibly due to a more defined immune response with minimal parasitism.

Under pressure: Updated insights into the mechanisms of Leishmania's defense in response to oxidative stress.

Leishmaniasis is a globally significant vector-borne zoonotic disease caused by protozoan parasites of the genus Leishmania, affecting humans and various mammalian hosts, transmitted through the bite of infected sand flies. It manifests primarily in three clinical forms: visceral, cutaneous, and mucocutaneous leishmaniasis, each varying in severity and geographic prevalence. This disease is endemic in tropical and subtropical regions, with over one billion people at risk, especially among marginalised populations in developing countries. Transmission occurs via infected female phlebotomine sand flies, with both zoonotic and anthroponotic cycles contributing to disease persistence. Domestic dogs are primary reservoirs, though rodents and cats contribute, particularly in zoonotic transmission cycles. Despite ongoing control efforts, drug resistance, vector adaptability, and resource limitations continue to pose major challenges as the global burden remains substantial, with estimated annual cases ranging from 600,000 to 1 million for CL and 50,000 to 90,000 for VL, accompanied by significant morbidity and mortality. Environmental changes, urbanisation, and human mobility are expanding leishmaniasis into previously non-endemic areas. Comprehensive control strategies require integrated approaches encompassing vector control, reservoir management, early diagnosis, treatment, and surveillance to mitigate this neglected tropical disease’s impact worldwide.

0704 An analysis of local therapeutic treatments for cutaneous and mucocutaneous leishmaniasis: A systematic review and meta-analysis

0329 An analysis of chemotherapeutic treatment avenues for cutaneous and mucocutaneous leishmaniasis: A systematic review and meta-analysis

Leishmaniasis remains a significant public health concern in Algeria, where both cutaneous and visceral forms are endemic. This systematic review aimed to assess the prevalence and spatial distribution of human leishmaniasis in Algeria, as well as the associated diagnostic methods and risk factors. Following PRISMA guidelines, a comprehensive literature search was conducted in Google Scholar, PubMed, ScienceDirect, and ResearchGate for studies published from January 2000 to March 2025. Eligible studies were required to focus on human leishmaniasis in Algeria and report prevalence data using cross-sectional or descriptive designs. Data were extracted on study location, sample size, diagnostic methods, and prevalence. Spatial analysis was performed using ArcGIS. Thirteen studies met the inclusion criteria. Most (76.9%) focused on cutaneous leishmaniasis (CL), with a concentration of studies in northeastern Algeria. Giemsa-stained smear microscopy was the most frequently used diagnostic method (84.6%), while PCR techniques were employed in a minority of studies. The estimated regional prevalence of CL was 46.65%, with regional rates ranging from 8.7% (Constantine) to 100% (M'sila). Visceral leishmaniasis (VL) showed a prevalence of 25.8%, peaking at 92.3% in Oran. One study reported mucocutaneous leishmaniasis (MCL) with a 100% prevalence in Tizi Ouzou. Leishmaniasis, particularly the cutaneous form, remains highly endemic in Algeria, with significant regional disparities. Continued epidemiological monitoring and the the large use of molecular diagnostic tools are essential to improve disease surveillance and control efforts.

Comprehensive insights into leishmaniasis: From etiopathogenesis to a novel therapeutic approach.

Abstract Leishmaniasis is a parasitic infection caused by a protozoan of the genus Leishmania, transmitted through infected female sandflies. Known risk factors for leishmaniasis include living in or travelling to endemic regions, particularly tropical areas such as the Mediterranean, and poor socioeconomic status and immunosuppression (Oryan A, Akbari M. Worldwide risk factors in leishmaniasis. Asian Pac J Trop Med 2016; 9: 925–32). We present the case of a 68-year-old White man on guselkumab for plaque psoriasis, who presented with persistent erythematous plaques that histologically were confirmed as cutaneous leishmaniasis. The patient was managing his psoriasis well with guselkumab, an anti-interleukin-23 monoclonal antibody. Five years into his treatment with guselkumab, in clinic, two erythematous plaques appeared on his left arm. They were pruritic but nontender. He reported frequent travel to Spain, Cape Verde and Brazil. These lesions were initially treated as psoriasis, but the plaques persisted despite the use of additional topical therapy. A biopsy was carried out, given the plaque’s persistence and patient’s past medical history of squamous cell carcinoma. Histopathology results showed no evidence of malignancy, but there were sheets of histiocytes in the dermis forming a florid non-necrotizing granulomatous infiltrate. The histiocytes contained abundant microorganisms within their cytoplasm. The appearances were highly suggestive of cutaneous leishmaniasis. The patient is currently cared for jointly with the infectious diseases team. The patient is progressing well and has commenced miltefosine, which has reduced the size of the lesions on his arms. The patient continues to do well on guselkumab for his psoriasis. There are cases of cutaneous leishmaniasis reported in patients on anti-tumour necrosis factor therapy (Valdés Delgado T, Rodríguez Delgado C, Pérez-Pérez M. Mucocutaneous leishmaniasis associated with anti-TNF therapy: a case report. Inflamm Bowel Dis 2022; 28: e3–4). However, to the best of our knowledge, we are the first to report a case of cutaneous leishmaniasis in a patient treated with guselkumab. Our case highlights the importance of early diagnosis and prompt management of cutaneous leishmaniasis to prevent disease progression, particularly in immunocompromised patients. Travel advice to endemic regions should also be considered in patients receiving biologics such as interleukin-23 inhibitors.

Exuberant, infiltrative, and disfiguring form of mucocutaneous leishmaniasis

Leishmaniasis, caused by protozoan parasites, is a widespread infectious disease and a prominent example of neglected tropical diseases. Brazil is among the countries most severely affected by this condition globally. Mucocutaneous leishmaniasis rarely involves oral sites, presenting diagnostic challenges. This study explores a case of mucocutaneous leishmaniasis discussing clinical presentation, diagnostic process and treatment. An 85-year-old woman presented with a progressively enlarging, painful palatal ulcer. The patient had a history of treated tuberculosis and reported additional symptoms including breathing difficulties, nosebleeds, osteoarthritis, hearing loss, and insomnia. Initial biopsy showed ulcerated squamous epithelium and nodular granulomatous inflammation. Despite negative diagnostic tests for tuberculosis, syphilis, HIV, and viral hepatitis, sarcoidosis was initially considered but treatment was ineffective. Worsening symptoms later revealed structures consistent with Leishmania sp. amastigote forms, confirmed by immunohistochemistry, leading to a diagnosis of oral leishmaniasis. Treatment with liposomal amphotericin B resulted in successful management. The rarity of oral manifestations further complicates diagnosis, highlighting the critical role of dentists in conducting a thorough assessment, administering the correct treatment, and ensuring proper follow-up to guarantee patient compliance.

A case report of concomitant infections of cutaneous, mucocutaneous, and visceral leishmaniasis.

Leishmaniasis, the third most common parasitic infection in persons living with HIV, typically presents in cutaneous, mucocutaneous, or visceral forms. This case report describes a 24-year-old male with advanced HIV/AIDS (CD4+ count 3 cells/mm3) who presented with neurological deterioration due to cerebral toxoplasmosis. During hospitalization, he developed atypical genital ulcers and persistent pancytopenia. Bone marrow examination revealed amastigotes consistent with Leishmania spp., indicating concurrent visceral and mucocutaneous leishmaniasis. Treatment with liposomal amphotericin B followed by miltefosine resulted in clinical improvement of the genital ulcers. This case highlights the atypical presentation of leishmaniasis in a patient living with HIV, deviating from classic descriptions and underscoring the diagnostic challenges. The presence of Leishmania amastigotes in the bone marrow, coupled with unusual cutaneous manifestations, emphasizes the need for a high index of suspicion for opportunistic infections in patients living with HIV/AIDS with unexplained findings, even without a history of travel to endemic areas. Timely diagnosis through bone marrow examination and appropriate multi-drug therapy are crucial for managing such complex co-infections.

Rationale: Australia is the only inhabited continent, which is not endemic to leishmaniasis. There are some published articles reporting cutaneous leishmaniasis in travellers, immigrants and refugees. However, mucocutaneous leishmaniasis has not been reported previously from the continent. Patient concerns: Lesions were present over the nasal septum and the oropharynx of a 34-year-old healthy non-indigenous male. Diagnosis was delayed as it took multiple biopsies as well as extensive discussions in a multidisciplinary team. Diagnosis: Mucocutaneous leishmaniasis. Interventions: Liposomal Amphotericin for 20 days. Outcomes: The patient was symptomatically improved after 3 weeks’ treatment. Lessons: With international travel resuming after the pandemic, it becomes imperative that physicians in Australia are aware of this imported disease and its various presentations.

BackgroundLeishmaniasis is a vector-borne parasitic disease caused by protozoa of the Leishmania genus; it is transmitted through the bites of infected phlebotomine sandflies. Clinically, it manifests in three primary forms: cutaneous, mucocutaneous, and visceral leishmaniasis (VL). Among these, VL represents the most severe form, characterized by high morbidity and mortality, and poses a considerable public health burden, particularly in endemic regions. This study utilizes data from the Global Burden of Disease (GBD) study 2021 to conduct a comprehensive analysis of the global epidemiological trends and burden of VL from 1990 to 2021, aiming to generate evidence-based insights to inform prevention and control strategies.MethodsUsing GBD 2021 data, this study examined trends in the incidence, prevalence, mortality, and disability-adjusted life years (DALYs) of VL across 204 countries and territories, stratified by age, sex, and sociodemographic index (SDI) levels. Average annual percent change (AAPC) was calculated to describe trends in age-standardized rates and indicator counts from 1990 to 2021.ResultsFrom 1990 to 2021, the global age-standardized incidence rate (ASIR; AAPC = −0.25, 95% confidence interval (CI) −0.25, −0.24), age-standardized prevalence rate (ASPR; AAPC = −0.06, 95% CI −0.06, −0.05), age-standardized mortality rate (ASMR; AAPC = −0.03, 95% CI −0.04, −0.02), and DALY rate (AAPC = −2.38, 95% CI −2.44, −2.33) for VL all showed a declining trend. The ASMR was highest among children under 5 years old and decreased progressively with age. VL remains a critical and under-recognized tropical disease in Latin America, the Middle East, Africa, and South Asia.ConclusionsVL disproportionately affects males and presents the highest risk in children under 5 years. Enhanced global collaboration in infectious disease control, with a focus on regions such as Latin America, Africa, the Middle East, and South Asia, is essential to further reduce the burden of VL.Graphical abstract

American cutaneous leishmaniasis (ACL), caused by Leishmania (Leishmania) amazonensis and L. (Viannia) braziliensis, presents a wide spectrum of clinical and immunopathological manifestations, ranging from localized cutaneous leishmaniasis (LCL) to severe forms like anergic diffuse cutaneous (ADCL) and mucocutaneous leishmaniasis (MCL). Despite evidence of the immune response's complexity, the role of inflammasomes in disease severity and parasite persistence remains unclear. We investigated the transcriptomic and immunopathological profiles of inflammasome components in patient lesions across the clinical spectrum. Genes such as NLRP3, AIM2, NLRP12, NLRC4, CASP1, CASP5, GSDMD, and IL1B and all evaluated proteins, showed higher expression in ACL compared to healthy controls. Distinct inflammasome activation patterns were observed: MCL, the hyperreactive form, showed elevated NLRP3, AIM2, and IL-1β, indicating an intensified inflammatory environment. ADCL, the hyporeactive form, displayed increased NLRP12 and NLRC4 expression with reduced GSDMD. Localized forms showed transitional profiles, highlighting ACL's multifactorial pathogenesis. These findings advance our understanding of inflammasome mechanisms in ACL, identifying potential therapeutic targets to modulate inflammation and improve management.

Leishmaniasis is neglected infectious disease caused by a type of microscopic parasite called Leishmania spp. This disease can affect both humans and animals, as well as sandflies. There are more than 90 species of sandflies that can transmit Leishmania parasites, with Lutzomyia being the primary transmitter in the Americas and Phlebotomus being the primary transmitter elsewhere. The disease, prevalent in tropical and subtropical regions, including southern Europe, poses a significant global health concern due to increasing outbreaks spurred by climate change and heightened human and animal mobility. Leishmaniasis is categorized into three main forms: cutaneous, visceral (kala-azar), and mucocutaneous. These forms vary in clinical presentation, ranging from skin lesions to severe systemic involvement of internal organs and mucosal damage. The treatment of leishmaniasis is complex and depends on factors such as the disease type, parasite species, geographic region, and the host's health status. This review adopts a One Health approach, integrating human, animal, and environmental perspectives to provide a comprehensive update on leishmaniasis. It synthesizes recent advances in understanding the epidemiology, clinical manifestations, diagnostic techniques, and treatment strategies of cutaneous, mucocutaneous, and visceral leishmaniasis in humans and small animals. Understanding interconnection between animals and humans requires a holistic approach such as One Health perspective. This framework emphasizes the need for coordinated research, innovative treatments, and integrated prevention strategies to combat its growing global burden.

Cutaneous leishmaniasis (CL) is a neglected tropical disease with diverse clinical manifestations, ranging from localized CL to severe forms such as diffuse CL and mucocutaneous leishmaniasis. Borderline disseminated CL (BDCL), an intermediate form, is characterized by multiple disseminated lesions and poses unique diagnostic and therapeutic challenges, especially in pediatric patients. This study explores pediatric BDCL to better understand its clinical presentation, diagnostic approaches and treatment outcomes. We report 4 pediatric cases of BDCL from Panama, identified through polymerase chain reaction and histopathological analysis. Species identification utilized polymerase chain reaction and heat shock protein 70 gene sequencing. Treatment included amphotericin B, meglumine antimoniate and miltefosine, with follow-up evaluations assessing lesion progression and treatment outcomes. All patients exhibited multiple disseminated ulcerative and nodular lesions, with some involving mucosal sites. Species identification confirmed Leishmania guyanensis and Leishmania panamensis as causative agents. Two patients received meglumine antimoniate, achieving complete lesion resolution. Due to better tolerability, miltefosine was used in the remaining 2 patients, resulting in slower but complete lesion resolution over time. Amphotericin B demonstrated limited efficacy. Pediatric BDCL presents significant diagnostic and therapeutic challenges due to variable immune responses, clinical presentations and species-related treatment resistance. While meglumine antimoniate and miltefosine showed promising results, amphotericin B was less effective. Further research is needed to establish optimized treatment protocols for pediatric BDCL, considering species-specific responses and pharmacokinetic and pharmacodynamic differences in children.