A review on potential therapeutic targets for the treatment of leishmaniasis.

Leishmania, a protozoan parasite, is responsible for the occurrence of leishmaniasis, a disease that is prevalent in tropical regions. Visceral Leishmaniasis (VL), also known as kala-azar in Asian countries, is one of the most significant forms of VL, along with Cutaneous Leishmaniasis (CL) and Mucocutaneous Leishmaniasis (ML). Management of this condition typically entails the use of chemotherapy as the sole therapeutic option. The current treatments for leishmaniasis present several drawbacks, including a multitude of side effects, prolonged treatment duration, disparate efficacy across different regions, and the emergence of resistance. To address this urgent need, it is imperative to identify alternative treatments that are both safer and more effective. The identification of appropriate pharmacological targets in conjunction with biological pathways constitutes the initial stage of drug discovery. In this review, we have addressed the key metabolic pathways that represent potential pharmacological targets as well as prominent treatment options for leishmaniasis.

Leishmanioses: Informe epidemiológico das Américas. Núm. 12 (Dezembro de 2023)

Este informe apresenta o perfil epidemiológico da Região em 2022, assim como descreve as análises das metas e principais indicadores do Plano de Ação para Fortalecer a Vigilância e o Controle das Leishmanioses nas américas 2017-2022, que em nível regional, não foram totalmente alcançados, mas quando analisados individualmente por país, observa-se que avanços importantes foram alcançados, demonstrando o compromisso e o esforço dos Ministérios da Saúde para com a vigilância, assistência e controle das leishmanioses. Com a aprovação da Iniciativa de Eliminação de Doenças da OPAS, o Roteiro da OMS para 2030, a publicação das resoluções transversais: a) Plano de Ação sobre Entomologia e Controle de Vetores 2018-2023 e, b) Saúde Única: Um enfoque integral para abordar as ameaças à saúde, o Plano de Ação para as Leishmanioses para o período 2023-2030 foi atualizado, discutido e acordado com países endêmicos, especialistas, colaboradores e parceiros. Com esse novo Plano, espera-se aprimorar e fortalecer s ações de vigilância e controle, a fim de obter melhores resultados, como ampliação do acesso e implementação de metodologias de diagnóstico, alternativas de tratamento para pessoas afetadas que vivem em áreas de risco, execução de ações de acordo com a estratificação de risco, redução de contato com o vetor, entre outros.

The changing epidemiology of human leishmaniasis in the non-endemic country of Austria between 2000 to 2021, including a congenital case.

BACKGROUND: Leishmaniasis is caused by infection with intracellular protozoans of the genus Leishmania. Transmission occurs predominantly by the bite of phlebotomine sandflies, other routes, including congenital transmission, are rare. The disease manifests as either cutaneous, visceral or mucosal/mucocutaneous leishmaniasis. In recent years, changes in the epidemiological pattern have been reported from Europe. PRINCIPAL FINDINGS: A total of 311 new and 29 published leishmaniasis cases occurring between 01/01/2000 and 12/31/2021 in Austria were collected and analyzed. These encompassed 146 cutaneous (CL), 14 visceral (VL), 4 mucosal, and 3 cases with concurrent VL and CL. In addition, asymptomatic infections, comprising 11 unspecified cases with Leishmania DNA detectable only in the blood and 162 cases with anti-Leishmania antibodies were reported. Particularly since 2016, the incidence of leishmaniasis has steadily risen, mainly attributable to increasing numbers of CL and cases with positive serology against Leishmania species, whereas the incidence of VL has slowly decreased. Analysis revealed that a shift in the causative species spectrum had occurred and that a substantial number of CL cases were caused by members of the Leishmania donovani/infantum complex. Simultaneous occurrence of VL and CL was identified in immunocompromised individuals, but also in a not yet reported case of an immunocompetent child after vertical transmission. CONCLUSIONS: The incidence of leishmaniasis has risen in the recent years. The numbers are anticipated to keep rising due to increasing human mobility, including travel and forced migration, growing reservoir host populations as well as expansion and dispersal of vector species caused by climate and habitat changes, urbanization and globalization. Hence, elevated awareness for the disease, including possible transmission in previously non-endemic regions and non-vector transmission modes, support of sandfly surveillance efforts and implementation and establishment of public health interventions in a One Health approach are pivotal in the global efforts to control and reduce leishmaniasis.

Case Report: In Situ and Systemic Immune Response to Mucosal Leishmaniasis in an HIV-Infected Patient.

In situ and systemic evaluations of the immune responses of HIV-infected patients to mucosal leishmaniasis have been poorly described. We describe a recently diagnosed HIV-infected patient with mucosal leishmaniasis who was characterized by a CD4 count of 85 cells/mm3 and nasal septum destruction resulting from pruritic and ulcerated nasal mucosa with crust formation and progression over 2 years. In situ and systemic immune evaluations of T cell activation, memory, and exhaustion were conducted using cytofluorometric assays, and sequencing of the Leishmania species was performed. The immune profile of HIV-infected patient with mucosal leishmaniasis shows a mixed Th1/Th2 pattern and an activated and exhausted status.

Leishmaniasis: Informe epidemiológico de las Américas. Núm. 12 (Diciembre del 2023) 

Este informe presenta el perfil epidemiológico de la Región para el 2022, así como describe los análisis de las metas y de los principales indicadores del Plan de acción para fortalecer la vigilancia y control de las leishmaniasis en las Américas 2017-2022, que a nivel regional, no fueron plenamente alcanzadas en su totalidad, pero cuando se analizan de forma individual por países, se observan importantes avances que evidencian un compromiso y un esfuerzo de los ministerios de salud a respecto a la vigilancia, atención y control de las enfermedades. Con el marco de la aprobación de la iniciativa de la OPS para la eliminación de las enfermedades, la Hoja de Ruta para el 2030 de la OMS, y la publicación de las resoluciones transversales: a) Plan de acción sobre entomología y control de vectores 2018-2023 y, b) Una salud: un enfoque integral para abordar las amenazas para la salud, el Plan de acción de leishmaniasis 2023-2030 se actualizó, discutió y consensuó con los países endémicos, así como con especialistas, colaboradores y socios. Con este nuevo Plan se espera mejorar y fortalecer las acciones de vigilancia y control, como ampliación del acceso e implementación de metodologías para el diagnóstico, alternativas de tratamiento para las personas afectadas que viven en áreas de riesgo para leishmaniasis, ejecución de acciones de acuerdo con la estratificación de riesgo, reducción del contacto del vector, entre otras.

Leishmaniasis: Epidemiological Report for the Americas. No.12 (December 2023)

This report presents the 2022 epidemiological profile of the Region, as well as describes the analyses of the goals and main indicators of the Plan of Action to Strengthen the Surveillance and Control of Leishmaniasis in the Americas 2017-2022, which at the regional level, were not fully achieved, but when analyzed individually by country, significant progress has been made, demonstrating the commitment and effort of the Ministries of Health with regard to the disease surveillance, patient care and control. Within the framework of the approval of the PAHO's Disease Elimination Initiative, the WHO Roadmap for 2030, and the publication of the cross-cutting resolutions: a) Plan of Action on Entomology and Vector Control 2018-2023 and b) One Health: A Comprehensive Approach to Addressing Health Threats, the leishmaniasis Plan of Action for 2023-2030 was updated, discussed, and agreed upon with endemic countries, specialists, collaborators and partners. With this new Plan, it is expected to improve and strengthen surveillance and control actions to obtain better results, such as expand access and implementation of diagnostic methodologies, and treatment alternatives for affected people living in risk areas, also, execution of actions according to the risk stratification, reduction of vector contact, among others.

Stigma associated with cutaneous and mucocutaneous leishmaniasis: A systematic review.

BACKGROUND: Cutaneous (CL) and mucocutaneous leishmaniasis (MCL) are parasitic diseases caused by parasites of the genus leishmania leading to stigma caused by disfigurations. This study aimed to systematically review the dimensions, measurement methods, implications, and potential interventions done to reduce the CL- and MCL- associated stigma, synthesising the current evidence according to an accepted stigma framework. METHODS: This systematic review followed the PRISMA guidelines and was registered in PROSPERO (ID- CRD42021274925). The eligibility criteria included primary articles discussing stigma associated with CL and MCL published in English, Spanish, or Portuguese up to January 2023. An electronic search was conducted in Medline, Embase, Scopus, PubMed, EBSCO, Web of Science, Global Index Medicus, Trip, and Cochrane Library. The mixed methods appraisal tool (MMAT) was used for quality checking. A narrative synthesis was conducted to summarise the findings. RESULTS: A total of 16 studies were included. The studies report the cognitive, affective, and behavioural reactions associated with public stigma. Cognitive reactions included misbeliefs about the disease transmission and treatment, and death. Affective reactions encompass emotions like disgust and shame, often triggered by the presence of scars. Behavioural reactions included avoidance, discrimination, rejection, mockery, and disruptions of interpersonal relationships. The review also highlights self-stigma manifestations, including enacted, internalised, and felt stigma. Enacted stigma manifested as barriers to forming proper interpersonal relationships, avoidance, isolation, and perceiving CL lesions/scars as marks of shame. Felt stigma led to experiences of marginalisation, rejection, mockery, disruptions of interpersonal relationships, the anticipation of discrimination, fear of social stigmatisation, and facing disgust. Internalised stigma affected self-identity and caused psychological distress. CONCLUSIONS: There are various manifestations of stigma associated with CL and MCL. This review highlights the lack of knowledge on the structural stigma associated with CL, the lack of stigma interventions and the need for a unique stigma tool to measure stigma associated with CL and MCL.

The leishmaniases in Kenya: A scoping review.

BACKGROUND: The leishmaniases are a group of four vector-borne neglected tropical diseases caused by 20 species of protozoan parasites of the genus Leishmania and transmitted through a bite of infected female phlebotomine sandflies. Endemic in over 100 countries, the four types of leishmaniasis-visceral leishmaniasis (VL) (known as kala-azar), cutaneous leishmaniasis (CL), mucocutaneous leishmaniasis (MCL), and post-kala-azar dermal leishmaniasis (PKDL)-put 1.6 billion people at risk. In Kenya, the extent of leishmaniasis research has not yet been systematically described. This knowledge is instrumental in identifying existing research gaps and designing appropriate interventions for diagnosis, treatment, and elimination. METHODOLOGY/PRINCIPAL FINDINGS: This study used the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) methodology to determine the state of leishmaniases research in Kenya and identify research gaps. We searched seven online databases to identify articles published until January 2022 covering VL, CL, MCL, and/or PKDL in Kenya. A total of 7,486 articles were found, of which 479 underwent full-text screening, and 269 met our eligibility criteria. Most articles covered VL only (n = 141, 52%), were published between 1980 and 1994 (n = 108, 39%), and focused on the theme of "vectors" (n = 92, 34%). The most prevalent study types were "epidemiological research" (n = 88, 33%) tied with "clinical research" (n = 88, 33%), then "basic science research" (n = 49, 18%) and "secondary research" (n = 44, 16%). CONCLUSION/SIGNIFICANCE: While some studies still provide useful guidance today, most leishmaniasis research in Kenya needs to be updated and focused on prevention, co-infections, health systems/policy, and general topics, as these themes combined comprised less than 4% of published articles. Our findings also indicate minimal research on MCL (n = 1, <1%) and PKDL (n = 2, 1%). We urge researchers to renew and expand their focus on these neglected diseases in Kenya.

Co-expression analysis of lncRNA and mRNA suggests a role for ncRNA-mediated regulation of host-parasite interactions in primary skin lesions of patients with American tegumentary leishmaniasis.

Leishmaniasis, caused by different Leishmania species, manifests as cutaneous or visceral forms. In the American continent, the cutaneous form is called American tegumentary leishmaniasis (ATL) and is primarily caused by Leishmania (Viannia) braziliensis. Mucosal leishmaniasis (ML), the most severe form of ATL, arises in approximately 20% of patients from a primary cutaneous lesion. Evidence indicates changes in overall expression patterns of mRNAs and lncRNAs of the host in response to Leishmania infection, with the parasite capable of modulating host immune response, which may contribute to disease progression. We evaluated whether the co-expression of lncRNAs and their putative target mRNAs in primary cutaneous lesions of patients with ATL could be associated with the development of ML. Previously available public RNA-Seq data from primary skin lesions of patients infected with L. braziliensis was employed. We identified 579 mRNAs and 46 lncRNAs differentially expressed in the primary lesion that subsequently progressed to mucosal disease. Co-expression analysis revealed 1324 significantly correlated lncRNA-mRNA pairs. Among these, we highlight the positive correlation and trans-action between lncRNA SNHG29 and mRNA S100A8, both upregulated in the ML group. S100A8 and its heterodimeric partner S100A9 form a pro-inflammatory complex expressed by immune cells and seems to participate in host innate immune response processes of infection. These findings expand the knowledge of the Leishmania-host interaction and indicate that the expression of lncRNAs in the primary cutaneous lesion could regulate mRNAs and play roles in disease progression.

The stigma associated with cutaneous leishmaniasis (CL) and mucocutaneous leishmaniasis (MCL): A protocol for a systematic review.

Leishmaniasis is a neglected tropical disease with three main clinical types; cutaneous leishmaniasis (CL), mucocutaneous leishmaniasis (MCL), and visceral leishmaniasis (VL). CL and MCL are considered to be highly stigmatizing due to potentially disfiguring skin pathology. CL and MCL-associated stigma are reported across the world in different contexts assimilating different definitions and interpretations. Stigma affects people with CL, particularly in terms of quality of life, accessibility to treatment, and psycho-social well-being. However, evidence on CL- and MCL-associated stigma is dispersed and yet to be synthesized. This systematic review describes the types, measurements, and implications of the stigma associated with CL and MCL and identifies any preventive strategies/interventions adopted to address the condition. This study was developed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis Protocols (PRISMA-P) statement which is registered in the International Platform of Registered Systematic Review and Meta-analysis Protocols PROSPERO (ID- CRD42021274925). We will perform an electronic search in MEDLINE, Embase, Scopus, PubMed, EBSCO, Web of Science, Global Index Medicus, Trip, and Cochrane Library databases, and in Google Scholar, using a customized search string. Any article that discusses any type of CL- and/or MCL-associated stigma in English, Spanish and Portuguese will be included. Articles targeting veterinary studies, sandfly vector studies, laboratory-based research and trials, articles focusing only on visceral leishmaniasis, and articles on diagnostic or treatment methods for CL and MCL will be excluded. Screening for titles and abstracts and full articles and data extraction will be conducted by two investigators. The risk of bias will be assessed through specific tools for different study types. A narrative synthesis of evidence will then follow. This review will identify the knowledge gap in CL-associated stigma and will help plan future interventions.

Detection of Leishmania RNA Virus 1 in Leishmania (Viannia) panamensis Isolates, Panama.

We detected Leishmania RNA virus 1 (LRV1) in 11 isolates of Leishmania (Viannia) panamensis collected during 2014-2019 from patients from different geographic areas in Panama. The distribution suggested a spread of LRV1 in L. (V.) panamensis parasites. We found no association between LRV1 and an increase in clinical pathology.

Clinicopathological characteristics of cutaneous and mucocutaneous leishmaniasis in patients treated with TNF-α inhibitors.

BACKGROUND AND OBJECTIVES: The increasing use of biologics in the treatment of inflammatory diseases has led to more cases of leishmaniasis in patients subjected to iatrogenic immunosuppression. The main objective was to describe the characteristics of the patients with cutaneous (CL) or mucocutaneous (MCL) leishmaniasis who were receiving a biological therapy at the time of diagnosis. PATIENTS AND METHODS: A multicenter retrospective study was design based on a cohort of patients diagnosed with CL or MCL. All patients who were being treated with biologicals were included. For each case, two matched non-exposed patients were included for comparison. RESULTS: 38 patients were diagnosed with CL or MCL while being treated with tumor necrosis factor alpha (TNF-α) inhibitors. Leishmaniasis presented more frequently as a plaque (58.3%) with a larger median lesion size (2.5 cm), ulceration (92.1%), and required a greater median number of intralesional meglumine antimoniate infiltrations (3 doses) (P < 0.05) than in non-exposed patients. We found no systemic involvement in patients being treated with anti-TNF-α. We did not find differences regarding the treatment characteristics whether biologic therapy was modified or not. CONCLUSIONS: Although management should be individualized, maintenance of biologic therapy does not seem to interfere with treatment of CL or MCL.

Fever with perinasal and tongue lesions: A diagnostic challenge.

The diagnosis may be challenging, and high suspicion index should be maintained in immunosuppressed patients with unusual mucocutaneous lesions, even in non-endemic areas for mucocutaneous leishmaniasis.

Leishmania RNA Virus Is Not Detected in All Species of the Leishmania Viannia Subgenus: The Case of L. (V.) panamensis in Colombia.

The endosymbiotic Leishmania RNA virus 1 (LRV1) has been associated with severity and clinical manifestations of American tegumentary leishmaniasis caused by species of the Leishmania (Viannia) subgenus. Between and within Leishmania species, and among endemic countries, the prevalence of LRV is highly variable. The LRV virus has not been detected in L. (V.) panamensis, the second-most prevalent species in Central America and Colombia. However, no systematic screening of LRV has been conducted in L. (V.) panamensis, and thus it is still controversial whether this virus is truly absent from the species. We sought to determine the prevalence of LRV1 in L. (V.) panamensis clinical strains isolated from patients with cutaneous leishmaniasis (CL), from different geographic areas of Colombia. We analyzed 219 clinical strains; 78% were L. (V.) panamensis, 18% were L. (V.) braziliensis, and 4% were L. (V.) guyanensis. Screening for LRV1 was performed by quantitative reverse transcription-polymerase chain reaction. The LRV1 was detected in 18% (7 of 40) of L. (V) braziliensis strains, and was not detected in any of the L. (V.) guyanensis or L. (V.) panamensis strains. The LRV1-positive L. (V). braziliensis strains came from the Amazon Basin. Of the seven LRV1-positive strains, two were isolated from patients with mucocutaneous leishmaniasis, and the remaining from patients with CL. Our results confirm the absence of LRV1 in L. (V.) panamensis in Colombia.

Mucosal Leishmaniasis of the lip: Report of an Exuberant case in a Young man.

BACKGROUND: Leishmaniasis is a tropical disease caused by protozoan parasites of the genus Leishmania. Mucosal leishmaniasis has been described as secondary to the cutaneous form; however, isolated mucosal involvement can also occur. Specifically, mucosal leishmaniasis of the lip is poorly described and its diagnosis challenges clinicians. METHODS: We herein report a case of mucosal leishmaniasis affecting the lower lip without cutaneous involvement in a 20-year-old Venezuelan man. The patient had no relevant past medical history. Clinically, a mass-like lesion with ulcerations and crusts was observed. RESULTS: Microscopically, the lesion was composed of granulomatous inflammation along with macrophages containing intracytoplasmic inclusions similar to round-shaped Leishmania. The species Leishmania (Viannia) braziliensis was confirmed. Treatment with meglumine antimonate was effective. The lesion healed satisfactorily, and no side effects or recurrences were observed. CONCLUSION: Clinicians should be aware of isolated forms of mucosal leishmaniasis of the lip, even in cases where the cutaneous lesion is undetected or clinically manifests as self-limiting. Knowing the endemic areas in the scenario of the dynamics of the ecoepidemiology of leishmaniasis is also essential for surveillance and counselling of the population.