Leishmaniasis in otorhinolaryngology: an emerging disease and its relationship with anti-tumor necrosis factor-alpha drugs.

PURPOSE: To investigate the clinical manifestations, management and outcomes of Leishmania lesions in the ear-nose-throat (ENT) region, and its relationship with tumor necrosis factor (TNF)-α blocking drugs. METHODS: Single-center retrospective observational study. Patients diagnosed with cutaneous and mucosal leishmaniasis in the otorhinolaryngologic area at a tertiary referral center over a period of 8 years. RESULTS: Three cases of Leishmania lesions in the ear and two in the nose were encountered at our institution. All patients were under treatment with TNF-α blocking drugs. Diagnosis was challenging, and it was important to have a clinical suspicion in order to use accurate detection techniques. All patients received systemic treatment and achieved a complete resolution of the lesions. CONCLUSIONS: With the increasing use of biologic treatments like TNF-α blockers, this type of infection will be increasingly frequent in endemic areas and also worldwide. It is important to include leishmaniasis in the differential diagnosis of inflammatory/infectious lesions in the ENT region.

Adipose-Derived Stem Cells' Secretome Attenuates Lesion Size and Parasite Loading in Leishmaniasis Caused by Leishmania Major in Mice.

Background: Stem cell-derived secretome (SE) released into the extracellular space contributes to tissue repair. The present study aimed to investigate the impact of isolated secretome (SE) from adipose-derived mesenchymal stem cells (ASCs) on Leishmania major (L. major) lesions in BALB/c mice. Methods: This experimental study was conducted at Ahvaz University of Medical Sciences (Ahvaz, Iran) in 2021. Forty female BALB/c mice were infected with stationary phase promastigotes through intradermal injection in the bottom of their tail and randomly divided into four groups (n=10 per group). The mice were given SE (20 mg/mL), either alone or in combination with Glucantime (GC, 20 mg/mL/Kg), meglumine antimoniate (20 mg/mL/Kg) for the GC group, and phosphate-buffered saline (PBS) for the control group. After eight weeks, the lesion size, histopathology, the levels of Interleukin 10 (IL-10), and Interleukin 12 (IL-12) were assessed. For the comparison of values between groups, the parametric one-way ANOVA was used to assess statistical significance. Results: At the end of the experiment, the mice that received SE had smaller lesions (4.56±0.83 mm versus 3.62±0.59 mm, P=0.092), lower levels of IL-10 (66.5±9.7 pg/mL versus 285.4±25.2 pg/mL, P<0.001), and higher levels of IL-12 (152.2±14.2 pg/mL versus 24.2±4.4 pg/mL, P<0.001) than the control. Histopathology findings revealed that mice treated with SE had a lower parasite burden in lesions and spleen than the control group. Conclusion: The current study demonstrated that ADSC-derived SE could protect mice infected with L. major against leishmaniasis.

Randomized trial evaluating an mHealth intervention for the early community-based detection and follow-up of cutaneous leishmaniasis in rural Colombia.

BACKGROUND: In Latin America, cutaneous leishmaniasis primarily affects dispersed rural communities, that have limited access to the public health system and medical attention. Mobile health (mHealth) strategies have shown potential to improve clinical management and epidemiological surveillance of neglected tropical diseases, particularly those of the skin. METHODS: The Guaral +ST app for Android was designed to monitor cutaneous leishmaniasis treatment and assess therapeutic response. We carried out a randomized trial in the coastal municipality of Tumaco in southwestern Colombia, with parallel arms comparing a) follow-up aided by the app to b) standard institution-based follow-up. Treatment was prescribed according to national guidelines. Follow-up of therapeutic response was scheduled at the end of treatment and at 7, 13 and 26 weeks after the start of treatment. The primary endpoint was the proportion of participants who were monitored at or around week 26, allowing outcome and effectiveness of treatment to be determined. RESULTS: Follow-up of treatment and outcome assessment was achieved in significantly more patients in the intervention arm than the controls, Of the 75 participants in the two randomized arms, 74 had information on whether or not treatment was followed and outcome determined at or around week 26. Among these, 26/49 (53.1%) were evaluated in the intervention arm, and none (0/25, 0%) in the control arm (difference = 53.1%, 95% confidence interval 39.1-67.0%, p<0.001). Of the 26 participants evaluated at or around week 26 in the intervention arm, 22 (84.6%) had cured. There were no serious adverse events, nor events of severe intensity among patients monitored by CHW using the app. CONCLUSION: This study provides proof of concept for mHealth to monitor treatment of CL in remote and complex settings, deliver improved care and to provide information to the health system on the effectiveness of treatment as it is delivered to affected populations. CLINICAL TRIAL REGISTRATION: ISRCTN54865992.

Use of mobile tele-dermatology in managing cutaneous leishmaniasis from a remote district of Nepal during the COVID 19 pandemic: A case series.

With the invent of smart phones, tele-dermatology has become a cheap and cost-effective medium to provide medical services to rural population. Its usefulness is more prominently noted during the COVID 19 pandemic and much more in countries with difficult terrain with limited specialist health providers. Cutaneous leishmaniasis (CL) is a neglected tropical disease which may cause significant disability if treatment is delayed. Here, we discuss three cases of CL from a remote district by use of tele-dermatology during the pandemic lockdown.

Bases for a treatment of cutaneous leishmaniasis with moderate hyperthermia.

INTRODUCTION: Regional hyperthermia at between 38 and 39.5 °C has been used to treat inflammatory processes and, occasionally, skin infections. In areas where leishmaniasis is endemic, hot compresses are applied as anti-parasitic treatment. OBJECTIVE: To identify the bases of leishmaniasis thermal treatment in order to properly regulate it. METHODS: In vitro-cultured Leishmania mexicana parasites were incubated for variable periods at 37 and then at 25 °C. The parasites were then stained with Annexin V-FITC to detect apoptosis induction and with propidium iodide for viability. Post-treatment growth curves and cell cycle identification with anti-cyclin antibodies were performed. RESULTS: After 30 minutes of exposure to a temperature of 37 °C, a variable proportion of parasites lost their characteristic oval shape and became spherical, without refringence and with condensed nuclei, with these changes suggesting apoptosis, which was confirmed by Annexin V-FITC staining. The number of parasites that underwent apoptosis was proportional to exposure time. Parasites in which apoptosis was observed were stained with anti-cyclin antibodies. CONCLUSIONS: Constant, regulated and physiological elevation of temperature for more than 30 minutes induces apoptosis of in vitro-cultured L. mexicana parasites when they are in an active phase of the cell cycle.

INTRODUCCIÓN: La hipertermia regional entre 38 y 39.5 °C ha sido empleada para tratar procesos inflamatorios y, ocasionalmente, infecciones cutáneas. En zonas endémicas de leishmaniosis se aplican compresas calientes como tratamiento antiparasitario. OBJETIVO: Conocer las bases del tratamiento térmico de la leishmaniosis para regularlo adecuadamente. MÉTODOS: Parásitos Leishmania mexicana cultivados in vitro fueron incubados por periodos variables de 37 °C y después a 25 °C.. Los parásitos se tiñeron con anexina V-FITC y yoduro de propidio para detectar inducción de apoptosis y su viabilidad. Se realizaron curvas de crecimiento postratamiento e identificación del ciclo celular con anticuerpos anticiclinas. RESULTADOS: Después de 30 minutos de exposición a una temperatura de 37 °C, un porcentaje variable de parásitos perdieron su característica forma ovalada y se tornaron esféricos, sin refringencia y con núcleos condensados, cambios que sugirieron apoptosis, la cual fue confirmada mediante tinción con anexina V-FITC. La cantidad de parásitos en proceso de apoptosis fue proporcional al tiempo de exposición. Los parásitos en los que se observó apoptosis se tiñeron con anticuerpos anticiclinas. CONCLUSIONES: La elevación constante, regulada y fisiológica de la temperatura por más de 30 minutos induce apoptosis de parásitos Leishmania mexicana cultivados in vitro, cuando se encuentran en fase activa en el ciclo celular.

Factors Associated with Early Referral for Pediatric Cutaneous Leishmaniasis.

Determinants of early referral to healthcare providers, which may be useful for health policy, have not been investigated in pediatric cutaneous leishmaniasis with multivariate analyses. We aimed to explore determinants of early healthcare seeking in children with cutaneous leishmaniasis. Records of 1115 children with cutaneous leishmaniasis admitted to our hospital in Adana, Turkey were reviewed. Effects of age, sex, residential distance, lesion number, and faciocervical onset on early referral were evaluated with multivariate logistic regression analyses. The mean duration of the disease was 12.7 months. Early referral was significantly more likely in patients aged 1-5 and 6-10 years (odds ratio 2.32 and 1.32, respectively) than patients aged 11-18 years. A borderline-significant association was present for faciocervical onset. Early referral in younger children might be due to the fact that the younger the child, the greater the parental concerns about their child's health problems. The rate of late referral in older children may be decreased by some school-based health interventions.

Exploring the cultural effects of gender on perceptions of cutaneous leishmaniasis: a systematic literature review.

BACKGROUND: More than one million people each year become infected by parasites that cause the disease cutaneous leishmaniasis (CL). This disease manifests as one or more skin lesions or ulcers that are slow to heal with variable response rates to drug treatments. Thus far, little attention has been paid to how the cultural effects of gender shape perceptions and experiences of CL. This review aims to bring together and analyse existing studies which use qualitative data to explore these differences. These studies offered insights into our specific research questions. METHODS: We conducted a systematic review of the literature pertaining to either CL or muco-cutaneous leishmaniasis (MCL) through EBSCO, EMBASE, Medline, Scopus and Web of Science databases. To meet inclusion criteria, articles had to be either qualitative or mixed-method with a qualitative component. They also had to include a reflection on how the gender of participants impacted the findings and addressed the lived experiences of CL. We did not exclude articles based on the language they were published in or in which country the study took place. RESULTS: From a total of 1589 potential articles, we found that thirteen met the inclusion criteria. These articles were published in English, Spanish or Portuguese and reported on studies carried out in various countries in Africa, Asia and South America. After using the principles of a meta-ethnography to analyse these studies, we generated several key themes. We found that health-seeking behaviours, treatment choices, stigma and the impact of scarring are shaped by gender in a variety of contexts. CONCLUSIONS: Gender impacts on an individual's experience of CL. In particular, women are more constricted in their health-seeking behaviours and experience more stigma both from the active lesions and from scarring than men. In many contexts, however, men are more at risk of becoming infected by the parasite that causes CL and may turn to more harmful or aggressive self-treatments. We recommend that future research on CL should consider the impact of gender as this can create very different experiences for individuals.

A Community Based Survey of Knowledge, Attitudes, and Practices Concerning Leishmaniasis in Central Morocco.

Leishmaniasis is a major health problem caused by a protozoan of the genus Leishmania, most commonly transmitted by infected female sand flies. Intersectoral collaboration is essential for the implementation of integrated vector management control with community participation. The present study aims to evaluate the knowledge, attitude and practices of the population toward leishmaniasis in central Morocco. A quantitative cross-sectional study was conducted using an administered questionnaire assisted by health professionals, on 750 people in the Marrakech Safi, endemic region of cutaneous leishmaniasis (CL). Of those, 702 agreed to be recruited for our study, of which 63,5% were women, 48,1% were aged between 18 and 40 years, and more than half of the participants (60%) were from rural areas. Overall, the knowledge, attitude and practices (KAPs) for leishmaniasis are too poor for more than 85% of the population in the study area. Basic knowledge and perceptions of leishmaniasis were good for 14,6% of respondents. While, 4,5% of the members had good knowledge of CL, only 0,7% had good level of knowledge about vesciral leishmaniasis (VL). Furthermore 3,7% of those polled have favorable attitudes and preventive practices. No association was found between knowledge and age, province or occupation. However, rural residents were four times more likely than urbain residents to have good basic knowledge (ORA = 4,74; CI95%: 1,04 -22,05). In addition, the female gender also has the chance to possess good basic knowledge and perceptions 3 times more than the men (ORA = 3,18; CI95%: 1,16 -8,69). The low level of KAPs regarding leishmaniasis proves the lack of community participation in the fight against leishmaniasis in central Morocco.

Cutaneous leishmaniosis due to Leishmania mexicana in a cat treated with cryotherapy.

We report the novel use of cryosurgery to treat cutaneous feline leishmaniosis (FeL) in a domestic cat from mid-western Venezuela. Amastigotes, evident by microscopy in aspirates from the nodular, erythematous nose lesions, were identified as Leishmania mexicana by cytochrome b gene sequence analysis. Lesions resolved completely without relapse after 14 months.

Nous décrivons une nouvelle utilisation de la cryochirurgie pour traiter la leishmaniose féline cutanée (FeL) chez un chat domestique du centre-ouest du Venezuela. Les amastigotes, observés par microscopie dans les cytoponctions des lésions nodulaires et érythémateuses du nez, ont été identifiés comme Leishmania mexicana par analyse de la séquence du gène du cytochrome b. Les lésions ont complètement disparu sans rechute après 14 mois.

Describimos el uso novedoso de la criocirugía para tratar la leishmaniosis cutánea felina (FeL) en un gato doméstico del medio oeste de Venezuela. Los amastigotes, evidentes por microscopía en los aspirados de las lesiones nasales nodulares eritematosas, se identificaron como Leishmania mexicana mediante el análisis de la secuencia del gen del citocromo b. Las lesiones se resolvieron completamente sin recidiva tras 14 meses.

Neste estudo, relatamos a utilização inédita de criocirurgia para tratar leishmaniose felina cutânea (FeL) em um gato doméstico no centro-oeste da Venezuela. Amastigotas, evidentes à microscopia de aspirados da lesão nodular e eritematosa na região nasal, foram identificadas como Leishmania Mexicana por sequenciamento do gene do citocromo b. As lesões se resolveram completamente sem recidiva após 14 meses.

Barriers to cutaneous leishmaniasis care faced by indigenous communities of rural areas in Colombia: a qualitative study.

BACKGROUND: Neglected tropical diseases (NTDs) such as cutaneous leishmaniasis (CL) are often associated with rural territories and vulnerable communities with limited access to health care services. The objective of this study is to identify the potential determinants of CL care management in the indigenous communities in the rural area of the municipality of Pueblo Rico, through a people-centered approach. METHODS: To achieve this goal, qualitative ethnographic methods were used, and a coding framework was developed using procedures in accordance with grounded theory. RESULTS: Three dimensions that affect access to health care for CL in this population were identified: (1) contextual barriers related to geographic, economic and socio-cultural aspects; (2) health service barriers, with factors related to administration, insufficient health infrastructure and coverage, and (3) CL treatment, which covers perceptions of the treatment and issues related to the implementation of national CL treatment guidelines. This study identified barriers resulting from structural problems at the national level. Moreover, some requirements of the national guidelines for CL management in Colombia impose barriers to diagnosis and treatment. We furthermore identified cultural barriers that influence the perceptions and behavior of the community and health workers. CONCLUSIONS: While the determinants to CL management are multidimensional, the most important barrier is the inaccessibility to CL treatment to the most vulnerable populations and its inadequacy for the socio-territorial setting, as it is not designed around the people, their needs and their context.

Leishmaniose Tegumentar Americana: relato de caso de sucesso com tratamento exclusivamente homeopático / American Cutaneous Leishmaniasis: case report of successful exclusive homeopathic treatment

A Leishmaniose Tegumentar Americana (LTA) é uma doença infecciosa, que evolui com destruição tecidual. O tratamento convencional é associado a efeitos adversos graves que podem resultar em abandono da terapia. Objetivo: Mostrar a homeopatia como uma opção terapêutica para o tratamento da LTA sem submeter o paciente aos efeitos deletérios do tratamento convencional. Métodos: Trata-se de um estudo de um caso de leishmaniose tegumentar americana atendido em um consultório particular. O paciente havia sido tratado com homeopatia clássica por um longo tempo. A intervenção foi feita por um medicamento individualizado a cada consulta. Vários medicamentos homeopáticos foram administrados, sendo um de cada vez. Resultados: Todas as manifestações da doença, incluindo a úlcera, foram curadas em 5 meses, sem efeitos colaterais e sem sinais de recaída após 12 anos de seguimento. Conclusão: O tratamento homeopático individualizado isoladamente foi eficaz para curar um caso de LTA em apenas alguns meses e seus efeitos permaneceram após 15 anos de seguimento. Ensaios clínicos controlados randomizados são necessários para demonstrar a eficácia do tratamento homeopático.

American cutaneous leishmaniasis (ACL) is a tissue destructing, potentially disfiguring vector-borne disease. Conventional treatment is associated with severe adverse effects which might result in dropout. Methods: Case report of an ACL patient presenting with a severe leg ulcer. The patient was followed up at a conventional specialized service but received individualized homeopathic treatment alone. Results: All manifestations of disease including the ulcer were healed in 5 months with no side effects and no signs of relapse after 13-year follow up. Conclusion: Individualized homeopathic treatment alone was effective to heal a case of ACL in just few months, the effects lasting after 15-year follow up. Randomized controlled trials are necessary to demonstrate the efficacy of the homeopathic treatment for ACL.

An investigation of a new cutaneous leishmaniasis endemic area in Western Sri Lanka.

BACKGROUND: The aim was to investigate an emerging focus of cutaneous leishmaniasis (CL) in Gampaha district, Western Sri Lanka. METHODS: Sociodemographics of CL patients in Mirigama, Gampaha district, were compared with controls using a structured questionnaire. Clinical data and geographic positioning system coordinates of patients were recorded. Sandflies collections were performed in four selected sites using indoor hand collection (162 units) and cattle-baited net traps (n=3). RESULTS: Of 73 patients (mean age 43.6 y; SD 20), 58.9% were males. Lesions consisted of nodules (52.1%) and ulcers (47.9%). Single lesions were seen in 69.9% of patients, while 30.1% had multiple lesions. Except for one mucosal lesion, all the others were cutaneous. Treatment consisted of sodium stibogluconate and cryotherapy (46.6%), sodium stibogluconate (45.2%) or cryotherapy (8.2%). Multiple lesions were more likely to receive combination therapy (p=0.013). The majority of those employed (81.1%; 27/33) were engaged in outdoor work. Male gender, low education attainment and poor disease awareness were significant risk factors for CL (p<0.05). Four households reported multiple cases. Phlebotomus argentipes was detected in all cattle-baited net traps and 35.3% of indoor hand collection units. CONCLUSIONS: CL is emerging in Gamapha district with Mirigama as the epicentre. Case distribution indicates local transmission, with P. argentipes as the probable vector.

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)

Interdependencies between Toll-like receptors in Leishmania infection.

Multiple pathogen-associated molecular patterns (PAMPs) on a pathogen's surface imply their simultaneous recognition by the host cell membrane-located multiple PAMP-specific Toll-like receptors (TLRs). The TLRs on endosomes recognize internalized pathogen-derived nucleic acids and trigger anti-pathogen immune responses aimed at eliminating the intracellular pathogen. Whether the TLRs influence each other's expression and effector responses-termed TLR interdependency-remains unknown. Herein, we first probed the existence of TLR interdependencies and next determined how targeting TLR interdependencies might determine the outcome of Leishmania infection. We observed that TLRs selectively altered expression of their own and of other TLRs revealing novel TLR interdependencies. Leishmania major-an intra-macrophage parasite inflicting the disease cutaneous leishmaniasis in 88 countries-altered this TLR interdependency unfolding a unique immune evasion mechanism. We targeted this TLR interdependency by selective silencing of rationally chosen TLRs and by stimulation with selective TLR ligands working out a novel phase-specific treatment regimen. Targeting the TLR interdependency elicited a host-protective anti-leishmanial immune response and reduced parasite burden. To test whether this observation could be used as a scientific rationale for treating a potentially fatal L. donovani infection, which causes visceral leishmaniasis, we targeted the inter-TLR dependency adopting the same treatment regimen. We observed reduced splenic Leishman-Donovan units accompanied by host-protective immune response in susceptible BALB/c mice. The TLR interdependency optimizes TLR-induced immune response by a novel immunoregulatory framework and scientifically rationalizes targeting TLRs in tandem and in sequence for redirecting immune responses against an intracellular pathogen.

Comparative assessment of interventions for treating cutaneous leishmaniasis: A network meta-analysis of randomized clinical trials.

INTRODUCTION: Various interventions including laser therapy, heat therapy, and several drugs have been trialed in patients with cutaneous leishmaniasis. Due to the lack of an evidence-based comparison of all these interventions, we carried out the present network meta-analysis. METHODS: Electronic databases were searched for randomized clinical trials evaluating the efficacy and safety of any interventions in patients with cutaneous leishmaniasis. The proportion of patients with complete cure was the primary outcome. The proportion of lesions cured at the end of treatment, the proportion of lesions with minimal/no response to treatment, and proportion of wounds with minimal/no change were the secondary outcomes. Random-effects modeling was used for generating pooled estimates. Rankogram plot was used for identifying the 'best intervention'. For interventions containing a combination of treatments, backslash (/) has been used for depicting the same. RESULTS: One-hundred and thirty-one studies were included. Intralesional meglumine, topical paromomycin/gentamicin, topical paromomycin, parenteral sodium stibogluconate, topical honey/intralesional meglumine, topical liposomal amphotericin B, oral zinc sulphate, oral miltefosine, parenteral meglumine, heat therapy, topical liposomal azithromycin, intralesional meglumine/silver dressing, intralesional sodium stibogluconate, parenteral meglumine/intralesional meglumine, oral allopurinol/parenteral meglumine, topical trichloroacetic acid/heat therapy, oral zinc sulphate/oral ketoconazole, topical imiquimod/cryotherapy, intralesional meglumine/cryotherapy, topical herbal extract of Z-HE, parenteral pentamidine, topical trichloroacetic acid/intralesional meglumine, carbon-dioxide laser, topical recombinant granulocyte-macrophage colony-stimulating factor/parenteral meglumine, intralesional dapsone, carbon-dioxide laser/intralesional meglumine, moist wet dressing with sodium hypochlorite, parenteral sodium stibogluconate/intralesional recombinant granulocyte-macrophage colony-stimulating factor, oral dapsone, intralesional sodium stibogluconate/oral ketoconazole, intralesional sodium stibogluconate/parenteral sodium stibogluconate and electrocautery/moist wet dressing with sodium hypochlorite were observed with significantly greater proportion of patients with complete cure compared to placebo/untreated controls. Rankogram analysis revealed that parenteral pentamidine has the highest statistical probability of being the best in the pool. CONCLUSION: We observed several interventions to be effective for treating cutaneous leishmaniasis. However, greater caution is required in interpreting the results as the estimates are likely to change with the advent of results from future studies.

Cutaneous Leishmaniasis.

Leishmaniasis is a parasitic infection that can involve the skin, mucosal membranes, and internal organs. Soldiers are at highrisk of leishmaniasis when conducting operations in endemic regions. Medical providers should have a low threshold to consider Leishmaniasis as the cause of persisting skin lesions.

Therapeutic Response to Thermotherapy in Cutaneous Leishmaniasis Treatment Failures for Sodium Stibogluconate: A Randomized Controlled Proof of Principle Clinical Trial.

Treatment failure to intralesional sodium stibogluconate (IL-SSG) is a health challenge for cutaneous leishmaniasis (CL) in Sri Lanka. A randomized controlled proof of principle clinical trial, with two arms (viz., radio frequency-induced heat therapy [RFHT] by a ThermoMed™ device (Model 1.8, Thermosurgery Technologies, Inc., Phoenix, AZ) and thermotherapy by a handheld exothermic crystallization thermotherapy for CL [HECT-CL] device) was conducted on 40 CL treatment failures to IL-SSG, from three hospitals in Tangalle, Hambantota, and Anuradhapura, from January 2017 to January 2018, followed up for 180 days post-thermotherapy with a final follow-up in February 2020. Intention-to-treat cure rates were calculated at day 90 (initial cure rate) and at day 180 (final cure rate) posttreatment. Radio frequency-induced heat therapy group: the initial cure rate was 100% (20/20) and the final cure rate was 95% (19/20), with one patient relapsing. The HECT-CL group: both the initial and final cure rates were 80% (16/20), with no relapses and one excluded from the trial. In February 2020 (1.6-3 years posttreatment), 27 traceable patients (RFHT = 16, HECT-CL = 11) remained healed. Second-degree burns were observed with RFHT in 65% (13/20), with HECT-CL in 15% (3/20), which completely resolved subsequently. The cure rates between the two treatment groups were comparable (P = 0.15). Radio frequency-induced heat therapy consumed less time and required only a single hospital visit. Handheld exothermic crystallization thermotherapy for CL is potentially usable at community settings with both being less costly than IL-SSG. This study is the first proof that thermotherapy is an efficacious and safe treatment for CL patients in Sri Lanka, complicated by treatment failure to IL-SSG.

Major risk factors and histopathological profile of treatment failure, relapse and chronic patients with anthroponotic cutaneous leishmaniasis: A prospective case-control study on treatment outcome and their medical importance.

Over the last years, there has been a remarkable increase in the number of unresponsive patients with anthroponotic cutaneous leishmaniasis (ACL) reported worldwide. The primary objective of this study was to explore the role of demographic, clinical and environmental risk related-factors in the development of treatment failure, relapse and chronic cases compared to responsive patients with ACL. Moreover, molecular, histopathological and immunohistochemical (IHC) findings between these forms were explored. This work was undertaken as a prospective and case-control study in southeastern Iran. Culture media and nested PCR were used to identify the causative agent. Univariate multinomial and multiple multinomial logistic regression models and the backward elimination stepwise method were applied to analyze the data. A P<0.05 was defined as significant. Also, for different groups, skin punch biopsies were used to study the histopathological and immunohistochemical (IHC) profile. All samples showed that L. tropica was the only etiological agent in all unresponsive and responsive patients with ACL. Data analysis represented that 8 major risk factors including nationality, age groups, occupation, marital status, history of chronic diseases, duration of the lesion, the lesion on face and presence of domestic animals in the house were significantly associated with the induction of unresponsive forms. The histopathological and immunohistochemical findings were different from one form to another. The present findings clearly demonstrated a positive relation between ACL and distinct demographic, clinical and environmental risk determinants. Knowledge of the main risk factors for ACL infection is crucial in improving clinical and public health strategies and monitor such perplexing factors.

The potential therapeutic effect of adipose-derived mesenchymal stem cells in the treatment of cutaneous leishmaniasis caused by L. major in BALB/c mice.

Leishmaniasis is one of the most neglected tropical infectious diseases in the world. The emergence of drug resistance and toxicity and the high cost of the available drugs with a lack of new anti-leishmanial drugs highlight the need to search for newer therapies with anti-leishmanial activities. Due to the mesenchymal stem cell (MSC) immunomodulatory capacity, they have been applied in a wide variety of disorders. In this study, the potential effects of adipose-derived MSC (AD-MSCs) therapy and its combination with glucantime were evaluated in a murine model of cutaneous leishmaniasis induced by L. major. The results showed that AD-MSCs improved wound healing and decreased parasite burden. The real-time PCR results obtained from mice treated with AD-MSCs showed that IL-12 and TNF-α genes were upregulated. IL-10, arginase, and FOXP3 genes were downregulated whereas no differences in expression of the IL-4 gene were found. Overall, it seems that AD-MSCs therapy enhances Th1 immune response in L. major infected BALB/c mice. Unexpectedly, our results showed that the association of glucantime to AD-MSCs treatments did not lead to an increment in the anti-leishmanial activity.