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.

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.

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.

Clinical criteria for Mucosal Leishmaniasis diagnosis in rural South America: A systematic literature review.

BACKGROUND: Mucosal Leishmaniasis (ML), a neglected tropical disease caused by Leishmania parasites, impairs the quality of life of under-resourced populations in South America. If not treated promptly, this disease progresses to facial deformities and death. The low sensitivity of microscopy results and the unavailability of other accurate tests hamper the diagnosis. As clinical criteria are readily available in any setting, these may be combined in a syndromic algorithm, which in turn can be used as a diagnostic tool. We explore potential clinical criteria for a syndromic diagnostic algorithm for ML in rural healthcare settings in South America. METHODOLOGY/PRINCIPAL FINDINGS: The protocol for this systematic review was pre-registered in PROSPERO with the number: CRD42017074148. In patients with ML, described in case series identified through a systematic retrieval process, we explored the cumulative ML detection rates of clinical criteria. Participants: all patients with active mucosal disease from an endemic area in South America. Any original, non-treatment study was eligible, and case reports were excluded. PUBMED, EMBASE, Web of Science, SCIELO, and LILACS databases were searched without restrictions. The risk of bias was assessed with the JBI checklist for case series. We included 10 full texts describing 192 ML patients. Male gender had the highest detection rate (88%), followed by ulcer of the nasal mucosa (77%), age >15 (69%), and symptom duration >4 months (63%). SIGNIFICANCE: Within this selection of patients, we found that the male gender, ulcer of the nasal mucosa, age >15, and symptom duration >4 months lead to the highest detection rates. However, higher detection comes -naturally- with a higher rate of false positives as well. As we only included ML patients, this could not be verified. Therefore, the criteria that we found to be most promising should be validated in a well-designed prospective study.

A trespasser from a foreign land? A case report of primary mucosal leishmaniasis.

BACKGROUND: We report a clinically challenging and unusual case of L. donovani oral mucosal leishmaniasis. CASE PRESENTATION: Israeli resident with a former travel to central and North Africa, with no documented or prior cutaneous lesions presented with oral lesions of the maxillary gingiva and the upper lip. A delay in diagnosis and treatment have led to progression of the maxillary gingival lesions towards the hard palatal and the soft palate that could have potentially compromised the upper airway. CONCLUSIONS: This case highlights the importance of early diagnosis of leishmaniasis in patients with oral lesions and the laboratory workup necessary to appropriately characterize and treat the disease.

Leishmaniasis cutánea y mucocutánea / Cutaneous and Mucocutaneous Leishmaniasis

La leishmaniasis es una enfermedad crónica causada por un protozoo flagelado perteneciente al género Leishmania. Tiene distribución mundial, aunque la mayoría de los casos se agrupan en América del Sur, la cuenca mediterránea y algunas zonas de Asia y África. Existen 3 formas fundamentales de enfermedad: cutánea (la más frecuente), mucocutánea y visceral, también denominada kala-azar, la forma más grave. El diagnóstico se establece con la demostración de la presencia de los amastigotes en muestras clínicas, mediante visión directa al microscopio o mediante técnicas moleculares. Existen múltiples opciones terapéuticas, aunque la evidencia en la que se basa el tratamiento de la leishmaniasis cutánea es débil. Actualmente, las alteraciones de la inmunidad producidas por factores como el VIH o el uso de fármacos anti-TNF han cambiado tanto la forma de presentación de las formas clínicas clásicas como sus tratamientos (AU)

Leishmaniasis is a chronic disease caused by flagellate protozoa of the genus Leishmania. It is a global disease, but most cases are seen in South America, the Mediterranean, and some areas of Asia and Africa. The 3 main types of leishmaniasis are cutaneous (the most common), mucocutaneous, and visceral (the most severe). Visceral leishmaniasis is also known as kala-azar. Leishmaniasis is diagnosed by demonstrating the presence of Leishmania amastigotes in clinical specimens using direct microscopic examination or molecular analysis. Various treatments exist, although the evidence supporting the options available for cutaneous leishmaniasis is weak. Both the classical presentation of leishmaniasis and our management of the disease have changed in recent decades because of acquired immune deficiency caused by conditions such as HIV infection or the use of TNF inhibitors (AU)

Gestión de diagnóstico de leishmaniasis cutánea y mucocutánea en Ecuador 2019- 2020 / Diagnostic management of cutaneous and mucocutaneous leishmaniasis in Ecuador-2020

La leishmaniasis es un síndrome clínicamente heterogéneo causado por parásitos protozoarios intracelulares del género Leishmania. El espectro clínico de la leishmaniasis abarca la infección subclínica (no aparente), localizada (lesión cutánea) y diseminada (cutánea, mucocutánea y visceral). Un diagnóstico erróneo puede conducir a un resultado desfavorable. Utilizando los resultados del estudio microscópico, histológico y / o por métodos inmunológicos, se puede establecer un diagnóstico de leishmaniasis e iniciar el tratamiento. El manejo apropiado requiere un diagnóstico preciso, que a menudo incluye la identificación de la especie etiológica específica. Se realizó un estudio descriptivo de corte transversal para conocer la gestión de diagnóstico de leishmaniasis cutánea y mucocutánea en Ecuador. En el año 2019 se reportaron 1104 casos, 1084 tipo cutánea y 20 mucocutánea; hasta la semana epidemiológica 53 del año 2020, se notificaron 924 casos (894 cutáneo y 30 mucocutáneo). Este estudio abre el camino para una mayor investigación sobre la transmisión de la leishmaniasis en Ecuador, incluida la vigilancia de vectores y reservorios, así como para la intensificación de las actividades de investigación y control contra la leishmaniasis cutánea y la mucocutánea en la región(AU)

Leishmaniasis is a clinically heterogeneous syndrome caused by intracellular protozoan parasites of the genus Leishmania. The clinical spectrum of leishmaniasis encompasses subclinical (not apparent), localized (skin lesion), and disseminated (cutaneous, mucocutaneous, and visceral) infection. A misdiagnosis may lead to an unfavorable outcome. Using microscopic examination, histologic, and/or or by immunological methods study results, a diagnosis of leishmaniasis can be established and treatment initiated. Appropriate management requires an accurate diagnosis, which often includes identification of the specific etiologic species. A descriptive cross-sectional study was carried out to understand the diagnostic management of cutaneous and mucocutaneous leishmaniasis in Ecuador. In 2019, 1104 cases were reported, 1084 cutaneous and 20 mucocutaneous; Up to epidemiological week 53 of 2020, 924 cases were reported (894 cutaneous and 30 mucocutaneous). This study opens the path for further research on the transmission of leishmaniasis in Ecuador including vector and reservoir surveillance as well as for intensification of investigation and control activities against cutaneous and mucocutaneous leishmaniasis in the región(AU)

Potential antigenic targets used in immunological tests for diagnosis of tegumentary leishmaniasis: A systematic review.

Immunological tests may represent valuable tools for the diagnosis of human tegumentary leishmaniasis (TL) due to their simple execution, less invasive nature and potential use as a point-of-care test. Indeed, several antigenic targets have been used with the aim of improving the restricted scenario for TL-diagnosis. We performed a worldwide systematic review to identify antigenic targets that have been evaluated for the main clinical forms of TL, such as cutaneous (CL) and mucosal (ML) leishmaniasis. Included were original studies evaluating the sensitivity and specificity of immunological tests for human-TL, CL and/or ML diagnosis using purified or recombinant proteins, synthetic peptides or polyclonal or monoclonal antibodies to detect Leishmania-specific antibodies or antigens. The review methodology followed PRISMA guidelines and all selected studies were evaluated in accordance with QUADAS-2. Thirty-eight original studies from four databases fulfilled the selection criteria. A total of 79 antigens were evaluated for the detection of antibodies as a diagnostic for TL, CL and/or ML by ELISA. Furthermore, three antibodies were evaluated for the detection of antigen by immunochromatographic test (ICT) and immunohistochemistry (IHC) for CL-diagnosis. Several antigenic targets showed 100% of sensitivity and specificity, suggesting potential use for TL-diagnosis in its different clinical manifestations. However, a high number of proof-of-concept studies reinforce the need for further analysis aimed at verifying true diagnostic accuracy in clinical practice.

Challenges in diagnosis of genital ulcers: a genital leishmaniasis case series.

Leishmaniasis is a tropical infectious disease caused by Leishmania spp. protozoa and is transmitted by insects from the Phlebotominae subfamily. It can manifest as cutaneous leishmaniasis, a painless ulcer that can develop into a more serious systemic affliction as the protozoa spreads lymphatically or hematogenously, depending on the host's immunity. In this case series, the authors present a rare form of genital mucocutaneous leishmaniasis, with consideration of epidemiologic characteristics, clinical presentation, differential diagnosis, and treatments offered.

Implicación ORL en infecciones por Leishmania / ENT involvement in Leishmania infections

INTRODUCCIÓN: La leishmaniasis comprende un grupo de enfermedades provocadas por parásitos protozoos del género Leishmania que se transmiten mediante la picadura de la hembra de mosquitos flebotomos infectados desde reservorios animales, generando 3 formas clínicas diferentes: cutánea, mucocutánea y visceral. Presentamos los hallazgos en cabeza y cuello de esta enfermedad observados en nuestra área de salud. PACIENTES Y MÉTODOS: Revisión de los últimos 26 años en nuestro hospital, anotando las características clínicas, diagnósticas y terapéuticas de los casos detectados. RESULTADOS: Fueron identificados 13 casos, 7 con síndrome cutáneo, 4 mucocutáneo y 2 visceral o kala azar. Su edad media fue de 53,7 ± 10,8 años. En un 61% de los casos se verificó inmunodeficiencia. La incidencia de la enfermedad fue de 1,5:100.000 habitantes-año, con una prevalencia del 2%. El 69% de los infectados mostraron afectación del área otorrinolaringológica. En 12 casos el diagnóstico se estableció mediante biopsia de las lesiones. El tiempo desde el inicio clínico al diagnóstico osciló entre 3 y 10 meses. Como tratamiento se emplearon compuestos antimoniales en 11 pacientes y anfotericina B en 3, sola o combinada con el anterior. Una forma cutánea se resolvió con escisión de la lesión. El 92% mostró curación clínica y parasitológica. CONCLUSIONES: La leishmaniasis en España genera frecuentes cuadros de afectación cutánea y mucocutánea, a menudo en la piel de cabeza, cara y cuello o mucosa de vías altas. Su presentación clínica es muy variable, debiéndose sospechar ante la ausencia de respuesta a terapias convencionales y en condiciones de inmunodeficiencia

INTRODUCTION: Leishmaniasis comprises a group of diseases caused by protozoan parasites of the genus Leishmania that are transmitted by the bite of infected phlebotomine mosquitoes from animal reservoirs. Three different clinical forms are generated: cutaneous, mucocutaneous and visceral. We present the findings in the head and neck of this disease observed in our health area. PATIENTS AND METHODS: A review of the last 26 years in our hospital, noting the clinical, diagnostic and therapeutic characteristics of the cases detected. RESULTS: Thirteen cases were identified, 7 cutaneous, 4 mucocutaneous and 2 visceral or kala-azar. The mean age was 53.7 ± 10.8 years. Immunodeficiency was identified in 61% of the cases. The incidence of the disease was 1.5:100,000 inhabitants/year, with a prevalence of 2%. Of those infected, 69% had involvement of the ear-nose-throat area. In 12 cases the diagnosis was established by biopsy of the lesions. The time from clinical debut to diagnosis ranged from 3 to 10 months. Antimony compounds were used as treatment in 11 patients and amphotericin B in 3, alone or combined with the former. One cutaneous form resolved with excision of the lesion. Ninety-two percent healed clinically and parasitologically. CONCLUSIONS: Leishmaniasis in Spain frequently entails cutaneous and mucocutaneous involvement, often of the skin of the head, face and neck or upper-airway mucosa. Its clinical presentation varies greatly, and it should be suspected if there is no response to conventional therapies and in conditions of immunodeficiency

Immunoproteomics characterization of Leishmania panamensis proteins for potential clinical diagnosis of mucosal Leishmaniasis.

Diagnosis of leishmaniasis based on antibodies detection represents a challenge due to cross-reaction of sera with other infectious agents, which co-exist in endemic areas of Leishmania sp, especially patients with Trypanosoma cruzi. This work is aimed at searching for immunogenic proteins in sera from patients with cutaneous and mucosal leishmaniasis that may be potential candidates for the development of diagnostic tests and/or vaccines that help control the infection. Total protein extracts of L. panamensis promastigotes were put in contact with sera from patients with cutaneous and mucosal leishmaniasis (immunoblots). Immunoreactive proteins were identified by mass spectrometry and bioinformatics tools. 81 proteins were identified. One of these was uniquely recognized by the sera from patients with ML but not from sera from either CL or Chagas disease patients. MS analysis of this band pointed to the putative leishmanial 3-oxoacyl-(Acylcarrierprotein) reductase.

Tongue Nodule as Primary Manifestation of American Cutaneous Leishmaniasis in an Immunocompetent Patient.

Leishmaniasis is a parasitic disease considered an endemic public health problem in developing countries, where it is a reportable disease. Isolated oral manifestation is rare, and its clinical manifestations are variable. In this paper we describe an unusual case of an immunocompetent patient, 57-year-old man with a painless reddish submucosal nodule located on the tongue dorsum. Microscopical analysis showed chronic inflammatory infiltrate with macrophages containing leishmania in cytoplasmic vacuoles. PCR assays confirmed the diagnosis and patient was treated with meglumine antimoniate for 30 days. Absence of the parasite was confirmed by PCR. Thirteen years after treatment, a scar fibrosis persisted on the tongue dorsum. The case reported reveals that leishmaniasis should be considered in the diagnosis of tongue nodules in immunocompetent patients.

Challenges in diagnosis of genital ulcers: a genital leishmaniasis case series

Abstract Leishmaniasis is a tropical infectious disease caused by Leishmania spp. protozoa and is transmitted by insects from the Phlebotominae subfamily. It can manifest as cutaneous leishmaniasis, a painless ulcer that can develop into a more serious systemic affliction as the protozoa spreads lymphatically or hematogenously, depending on the host's immunity. In this case series, the authors present a rare form of genital mucocutaneous leishmaniasis, with consideration of epidemiologic characteristics, clinical presentation, differential diagnosis, and treatments offered.