Treatment of cutaneous leishmaniasis with a sequential scheme of pentamidine and tamoxifen in an area with a predominance of Leishmania (Viannia) guyanensis: A randomised, non-inferiority clinical trial.

OBJECTIVE: To determine whether a combination of a single intramuscular (IM) dose of pentamidine (7 mg/kg) followed by oral tamoxifen 40 mg/day for 20 days is non-inferior to three IM doses of pentamidine 7 mg/kg in the treatment of cutaneous leishmaniasis with a margin of 15%. METHODS: Phase II, randomised, controlled, open-label, non-inferiority clinical trial. Primary outcome was the complete healing of the lesions 6 months after starting treatment. Secondary outcomes were healing 3 months after starting treatment and determining the presence and severity of adverse effects (AE). RESULTS: The research was concluded with 49 patients; Leishmania (Viannia) guyanensis was the most frequent species isolated. In the primary outcome, 18 (72%) (95% CI: 52.4%-85.7%) of the 25 patients allocated to the intervention group and 24 (100%) (95% CI: 86.2%-100%) of the control group (p = 0.015) met the established criteria of cure. There was no AE with tamoxifen. CONCLUSION: Although a 72% cure rate presented by the combination of tamoxifen and pentamidine was lower than in the control group that achieved a 100% cure, it is still a safe and is a clinically relevant result. It indicates that the therapeutic scheme evaluated may be a promising option for populations in remote areas, however it should be further studied, in order to include a larger number of patients.

Leishmanicidal and healing effects of 3ß,6ß,16ß-trihydroxy lup-20 (29)-ene isolated from Combretum leprosum on Leishmania braziliensis infection in vitro and in vivo.

Treatment of cutaneous leishmaniasis depends on drugs that potentially cause serious side effects and resistance. Thus, topical therapies are attractive alternatives to the drugs currently used. 3ß, 6ß, 16ß-trihydroxylup-20 (29)-ene is a lupane triterpene isolated from Combretum leprosum Mart. leaves (CLF-1), with reports of in vitro antileishmanial effect against L. amazonensis and to promote lesion healing in animal model. Herein, we evaluated the in vitro and in vivo antileishmanial and healing effects of CLF-1 against L. braziliensis. CLF-1 treatment showed low toxicity in macrophages and significantly reduced parasite load in vitro. CLF-1 induced higher IL-12 and TNF-α production and more discrete IL-4 and IL-10 production. For in vivo evaluation, a CLF-1 cream formulation was prepared to treat hamsters infected with L. braziliensis. CLF-1 treatment was able to reduce parasite load of the infected skin and lymph node more efficiently than the conventional treatment. Histopathological analysis indicated a strong inflammatory response accompanied by an important healing response. Data from this study indicate that topical CLF-1 treatment was effective and non-toxic in L. braziliensis infected hamsters suggesting its potential for further development as a future therapeutic intervention.

Case Report: Diffuse Cutaneous Leishmaniasis Successfully Treated with a Combination of Oral Rifampicin and Fluconazole.

Diffuse cutaneous leishmaniasis (DCL) is a rare parasitic infection caused by the Leishmania species. Diffuse cutaneous leishmaniasis commonly presents as non-ulcerating papules and nodules over the face, neck, and arms. A middle-aged female presented with multiple nodular lesions on her face, neck, and chest region. Histopathology of the lesions showed multiple amastigotes, confirming the diagnosis of DCL. She was successfully treated with a combination course of rifampicin and fluconazole. Here, we report the first case of DCL in north India, a non-endemic area for cutaneous leishmaniasis.

Description of the dermatoscopic features observed in sporotrichosis and American cutaneous leishmaniasis in a reference center in Rio de Janeiro, Brazil.

BACKGROUND: The evaluation of American cutaneous leishmaniasis (CL) and sporotrichosis (SP) with dermoscopy may improve the diagnosis accuracy and clinical monitoring. OBJECTIVES: To describe the dermoscopic findings and patterns of skin lesions of patients with CL and SP followed up at the Laboratory of Clinical Research and Surveillance in Leishmaniasis (LaPClinVigiLeish), Evandro Chagas National Institute of Infectious Diseases (INI), Oswaldo Cruz Foundation, Rio de Janeiro, Brazil. METHODS: The authors included patients with a diagnosis of CL or SP, who attended at INI/ Fiocruz, between 2019‒2021. All patients had 3 dermoscopic examinations (DermLite DL4): before treatment (T0), during treatment (T1), and after healing (T2). Up to three lesions per patient were evaluated. RESULTS: The authors studied 47 patients with CL (74 lesions), and 19 patients with SP (24 lesions). The authors described dermoscopic structures such as rosettes, white lines, white dots, brown focal structureless areas, brown lines and dots, white perilesional circles, perilesional hyperchromic circles, microulcerations and the rainbow patterns. The authors created specific patterns; in CL: CL-T0 "central yellow scales with a white perilesional circle pattern", CL-T1 "diffuse structureless white area pattern" and CL-T2 "white and brown focal structureless areas pattern". In SP: SP-T0 the "pustule with erythema pattern"; SP-T1 the "focal structureless white areas with erythema pattern" and SP-T2 the "white linear pattern". STUDY LIMITATIONS: This study does not correlate dermoscopic findings with time of disease evolution at the first medical examination. CONCLUSIONS: The recognition of CL and SP dermoscopy patterns may be helpful tool for the differential diagnosis and monitoring of disease evolution.

Ionized alkaline water reduces injury in BALB/c mice infected with Leishmania amazonensis.

Ionized water has been reported to contribute to the tissue repair process and wound healing. Water purifiers can generate ionized water by means of activated charcoal with silver and minerals, the main purpose of which are to reduce microbiological and physicochemical contaminants. Moreover, when water is subjected to a magnetic field an organization of water molecules occurs due to the presence of mineral salts. The resulting water is thus more alkaline, which has been shown to be non-toxic to mice and can actually prolong survival. Cutaneous leishmaniasis is a neglected tropical disease, caused by obligate uni- and intracellular protozoa belonging to the genus Leishmania, that can manifest in the form of skin lesions. Thus, the objective of this study was to compare the evolution of disease in L. amazonensis-infected BALB/c mice that received tap water (TW) or ionized alkaline water (IAW). As a control, additional groups of mice receiving TW or IAW were also treated with the antileishmanial miltefosine. All mouse groups received either TW or IAW as drinking water 30 days prior to infection and the groups continued to receive the respective drinking water for 4 weeks, after which the blood and plasma were collected. Biochemical assays of aspartate aminotransferase, alanine aminotransferase, gamma-glutamyl transferase, creatinine, urea, glucose, triglycerides, and cholesterol were performed, in addition to hematology tests. There was a significant decrease in the volume of the lesion for groups that received IAW, in which the ingestion of ionized alkaline water favored the non-evolution of the lesion in the footpads of the animals. The results of the blood count and leukogram tests were within the normal values for BALB/c mice demonstrating that ionized water has no toxic effects on blood factors.

Use of liposomal amphotericin B in disseminated cutaneous leishmaniasis caused by Leishmania braziliensis in a pediatric patient with Down syndrome. / Uso de anfotericina B liposomal en leishmaniasis cutánea diseminada causada por Leishmania braziliensis en un paciente pediátrico con síndrome de Down.

We present a case of disseminated cutaneous leishmaniasis with extensive manifestation in a pediatric patient with Down syndrome. The case was confirmed by parasitological and immunological tests. The species was identified as Leishmania (Viannia) braziliensis by polymerase chain reaction-restriction fragment length polymorphisms (PCR-RFLP). The immune deficit that occurs as part of Down syndrome may have been the reason for the aggressive and prolonged clinical manifestations as well as the poor response to stibogluconate and deoxycholate amphotericin. The patient was treated with liposomal amphotericin B and at the end of therapy, showed clinical improvement of the lesions. This report highlights the challenges of the diagnosis and treatment of cutaneous leishmaniasis in immunosuppressed pediatric patients, especially under difficult social, economic and geographic conditions. Leishmaniasis should be considered as a differential diagnosis when treating atypical chronic dermatologic ulcers; the use of liposomal amphotericin in immunocompromised patients should also be considered in these cases.

Se presenta un caso de leishmaniasis selvática cutánea diseminada con manifestación extensa en una paciente pediátrica con síndrome de Down. El caso se confirmó a través de estudios parasitológicos e inmunológicos, mientras que la identificación se realizó mediante la técnica de reacción en cadena de la polimerasa-polimorfismos de longitud de fragmentos de restricción (PCR-RFLP, por sus siglas en inglés), determinándose la especie como Leishmania (Viannia) braziliensis. La manifestación clínica agresiva y prolongada con poca respuesta a estibogluconato y anfotericina desoxicolato pueden deberse al déficit inmunológico que se presenta como parte del síndrome de Down. La paciente eventualmente recibió tratamiento con anfotericina B liposomal y al término de la terapia, mostró mejoría clínica de las lesiones. El presente reporte ilustra los desafíos tanto de diagnóstico como tratamiento de leishmaniasis cutánea en pacientes pediátricos inmunosuprimidos, especialmente en un entorno de difícil acceso social, económico y geográfico, a los servicios de salud. Se recomienda considerar a la leishmaniasis en el diagnóstico diferencial cuando se atienda ulceras crónicas dermatológicas atípicas; así como tener en cuenta el uso de anfotericina liposomal en pacientes inmunocomprometidos.

'We do not rush to the hospital for ordinary wounds (sulu tuvala)': A qualitative study on the early clinical manifestations of cutaneous leishmaniasis and associated health behaviours in rural Sri Lanka.

BACKGROUND: Knowledge of early clinical manifestations, people's perceptions and behaviours is crucial in preventing and controlling neglected tropical diseases (NTDs). Cutaneous leishmaniasis is an NTD that causes skin lesions and affects millions worldwide. Delayed healthcare-seeking behaviour leading to prolonged treatment periods and complications is rife among people with cutaneous leishmaniasis. This study examined the patient-reported early clinical manifestations of cutaneous leishmaniasis, local interpretations and associated health behaviours within the socio-cultural context of rural Sri Lanka. METHODOLOGY/PRINCIPAL FINDINGS: We conducted a qualitative study among people with cutaneous leishmaniasis in three rural communities in the Anuradhapura district, Sri Lanka. Participants' experiences were explored through a study-bespoke participant experience reflection journal and in-depth interviews. We analysed the data using a narrative-thematic approach. The study included 30 people with cutaneous leishmaniasis (12 females and 18 males) aged between 18 and 75 years. We identified four major themes during the analysis: 1) patient-reported early clinical manifestations of cutaneous leishmaniasis, 2) local interpretations of the early skin lesion(s), 3) associated actions and behaviours, and 4) the time gap between the initial notice of symptoms and seeking healthcare for cutaneous leishmaniasis. Early clinical manifestations differed among the participants, while the majority misinterpreted them as a mosquito/ant bite, pimple, wart, eczema, macule, or worm infestation. Participants undertook different context-specific self-management actions to cure cutaneous leishmaniasis. We identified an average time gap between the notice of symptoms and the first visit to the healthcare facility ranging from three to twelve months. CONCLUSIONS/SIGNIFICANCE: Diverse early clinical manifestations, local interpretations, and associated behaviours of people with cutaneous leishmaniasis have led to a substantial delay in healthcare-seeking. The study sheds light on the importance of understanding the manifestations of NTDs within the social context. Our findings will inform designing context-specific health interventions to improve awareness and healthcare-seeking in cutaneous leishmaniasis in rural settings.

Photodynamic therapy mediated by a red LED and methylene blue inactivates resistant Leishmania amazonensis.

Cutaneous leishmaniasis is a neglected parasitic disease that leads to destructive lesions. The emergence of drug resistance has been a global concern over the past years. Photodynamic therapy (PDT) mediated by a red LED and methylene blue (MB) involves the overproduction of oxidative stress, which oxidizes several cellular biomolecules and prevents the selection of resistant strains. Herein, we investigated the potential of PDT mediated by MB against wild-type and miltefosine-resistant strains of Leishmania amazonensis. As a result, both strains were susceptible to PDT, thus encouraging us to seek the best conditions to overcome the drug resistance problem in cutaneous leishmaniasis.

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.

Treatment of Cutaneous Leishmaniasis with Allopurinol Plus Itraconazole in Iran.

Cutaneous leishmaniasis (CL) is a serious tropical disease and a neglected health challenge in Iran. Although limited data are available regarding anthroponotic CL, cases resistant to meglumine antimoniate (Glucantime) are increasingly being reported. Via an open-label noncontrolled case series, allopurinol (10 mg/kg/day) plus itraconazole (3-4 mg/kg/day) were orally administered for 1 month to 27 patients (56 lesions) with anthroponotic CL, most of whom were resistant to Glucantime. A mean lesion size of 3.5 ± 1.9 cm at baseline was reduced to 0.6 ± 1.0 after 1 month of treatment. Excellent treatment response was observed in 85.7% of lesions after 1 month. Recurrence only occurred in one patient in the 3-month follow-up session. This study presents preliminary evidence that oral allopurinol plus itraconazole could be an effective treatment in patients with anthroponotic CL.

In Vivo Antileishmanial Effect of 3,5-Diaryl-isoxazole Analogues Based on Veraguensin, Grandisin, and Machilin G: A Glance at a Preclinical Study.

New treatment approaches targeting cutaneous leishmaniasis (CL) are required since conventional drugs exhibit limitations due to their several adverse effects and toxicity. In this study, we aimed to evaluate the in vivo intralesional treatment efficacy of five isoxazole derivatives previously synthesized and effective in vitro against intracellular amastigote forms of Leishmania (L.) amazonensis. Among the tested analogues, 7 exhibited relevant in vivo therapeutic effects. The in silico predictions provided interesting information about the toxicity, suggesting the safety of analogue 7. Experiments performed with Salmonella typhimurium strains (TA98, TA100, and TA102) showed a non-mutagenicity profile of 7. The treatment of Leishmania-infected BALB/c mice with isoxazole 7 showed remarkably smaller CL lesions and decreased the parasitism (by 98.4%) compared to the control group. Hence, analogue 7 is a promising drug candidate and alternative treatment for CL caused by L. amazonensis.

Efficacy of intralesional meglumine antimoniate in the treatment of canine tegumentary leishmaniasis: A Randomized controlled trial.

Dogs living in areas of Leishmania (Viannia) braziliensis transmission may present canine tegumentary leishmaniasis (CTL) characterized by cutaneous or muzzle ulcers as well as asymptomatic L. braziliensis infection. It is not clear if dogs participate in the transmission chain of L. braziliensis to humans. However, dogs may remain with chronic ulcers for a long time, and as there are no public policies about CTL, these animals die or are sacrificed. Here we compare the efficacy of intralesional meglumine antimoniate with intralesional 0.9% NaCl solution in CTL treatment. This randomized control study included 32 dogs with cutaneous or muzzle lesions who had L. braziliensis DNA detected by PCR in tissue biopsied. Group one received 5ml of intralesional Glucantime, and group two received 5ml 0.9% NaCl solution, both applied in the four cardinal points on days 0, 15, and 30. Cure was defined as complete healing of the ulcers in the absence of raised borders on day 90. There was no difference in animals' demographic and clinical features in the two groups (p >.05). While at the endpoint, the cure rate was 87.5% in the group test, and in those who received 0.9 NaCl the cure rate was only 12.5%. As important as the high cure rate, the healing time was faster in dogs treated with antimony than in those treated with saline (p < .001). Intralesional meglumine antimoniate is effective in the treatment of dogs with L. braziliensis infection and accelerates the healing time of CTL.

Dermoscopy of cutaneous granulomatous disorders: A study of 107 cases.

BACKGROUND: Cutaneous granulomatous disorders (CGDs) can share some features, but an accurate assessment of various findings and their pattern can be useful in differentiating them. In addition to common dermoscopic findings for CGDs, some peculiar dermoscopic characteristics can be helpful in distinguishing them. OBJECTIVE: Herein, we aimed to evaluate dermoscopic findings in patients with CGDs and determine the dermoscopic criteria that could suggest the type of granulomatous disorder. MATERIAL AND METHODS: A total of 107 cases including 75 (70.09%) males and 32 (29.90%) females with an established diagnosis of cutaneous leishmaniasis (n = 49), cutaneous sarcoidosis (n = 23), granuloma annulare (GA) (n = 18), and tattoo granuloma (n = 17) confirmed by clinical and pathological studies were included. Based on the previous studies available in the literature, we wrote a checklist containing dermoscopic features of CGDs. Afterward, two dermatologists independently reviewed all dermoscopic images for the presence or absence of each item on the checklist. Descriptive analysis, fisher exact, chi-square, and t-test were used. The granulomatous disorders with larger sample sizes were selected for further analysis, including the univariate and conditional multivariate logistic regressions. RESULTS: The most prevalent nonvascular findings in all of our CGD patients were white scaling (N = 67%, 62.61%), diffuse or localized orange structureless areas (N = 53%, 49.53%), and diffuse erythema (N = 48%, 44.85%). Furthermore, the most frequent vascular findings in all of our CGD cases were branching and arborizing vessels (N = 30%, 28.03%), linear irregular (N = 30%, 28.03%), and dotted vessels (N = 27%, 25.23%). CONCLUSION: For differentiating leishmaniasis from sarcoidosis by dermoscopy, white scaling and white scarring areas are more suggestive of cutaneous leishmaniasis, whereas the presence of arborizing vessels would be more in favor of sarcoidosis. When comparing GA to cutaneous leishmaniasis, the latter significantly shows more linear irregular vessels, hairpin vessels, white scaling, and white scarring areas. In the case of differentiating sarcoidosis from GA, the presence of hairpin vessels would be suggestive of sarcoidosis.

Dermoscopic evaluation of cutaneous leishmaniasis.

Cutaneous leishmaniasis (CL) is an endemic disease in Iraq that is caused by protozoan infection. Dermoscopy has been applied to help in the diagnosis of multiple skin disease, including infestations. To evaluate the dermoscopic characteristics of CL lesions and their relationship with the disease duration, site, and pattern. Dermoscopic examination using (3 Gen Dermlite DL 100) at tenfold magnification of 91 lesions in 67 patients was elicited. This study was done from December 2019 to December 2020. The main dermoscopic features were generalized erythema (100%), hyperkeratosis with central erosion or ulceration (53.8%), white scar-like patch (41.8%), yellow tears (35.2%), white starburst sign (34.1%), and milia-like cyst (2.2%). We also observed vascular structures, including linear irregular (63.1%), dotted (57.1%), glomerular (38.1%), hairpin (22.6%), and comma-shaped vessels (16.7%). Linear irregular vessels were more commonly demonstrated on the face and upper limbs; while on the lower limbs, hyperkeratosis with erosion and ulceration were the most common finding. Hyperkeratosis with erosions/ulcerations (43.8%) was the most common finding in the papular pattern, linear irregular vessels (56.7%) in the nodular pattern, glomerular vessels (64.3%) was the most common finding in noduloulcerative pattern and linear irregular vessels (71%) was the most common finding in plaque pattern. The dermoscopic features would help in the diagnosis of CL lesions by dermoscopy, especially in endemic areas. There is a good relationship between the dermoscopic features and type of CL lesions.

Case Report: Simple Nodular Cutaneous Leishmaniasis Caused by Autochthonous Leishmania (Mundinia) orientalis in an 18-Month-Old Girl: The First Pediatric Case in Thailand and Literature Review.

We report an autochthonous case of simple, localized cutaneous leishmaniasis in a healthy 18-month-old girl from southern Thailand. The patient presented with a solitary chronic cutaneous nodular lesion on her left cheek for approximately 1 year. Histopathological dissection of the cheek skin biopsy demonstrated remarkably nodular and interstitial infiltrates of lymphocytes and histiocytes full of intracellular oval-shaped amastigotes, consistent with cutaneous leishmaniasis. The Leishmania promastigotes were also cultured successfully from the lesion biopsy and were designated with the WHO code MHOM/TH/2021/CULE5. Using internal transcribed spacer 1-specific polymerase chain reaction, the parasite DNA was demonstrated in both saliva and lesion biopsy. Based on the BLASTn and phylogenetic analysis, the parasite was identified as Leishmania orientalis, clustered in the Mundinia subgenus. The patient responded well to a 6-week course of oral itraconazole, without recurrence. To our knowledge, this is the fourth case of autochthonous leishmaniasis resulting from L. orientalis and the youngest patient of leishmaniasis ever reported in Thailand. More importantly, we also demonstrate the clinical course of the lesion according to the timeline before and after treatment, which can help physicians better understand and provide an accurate diagnosis with appropriate treatment of this emerging parasitic disease.

Brief communication: Vitamin D serum levels in American tegumentary leishmaniasis from an endemic area in Northeast Brazil.

INTRODUCTION: The pathogenesis of cutaneous and mucosal leishmaniasis is associated with different immune responses. Vitamin D may modulate the immune system. Here we evaluate the association of vitamin D levels with the severity of the clinical forms of cutaneous and mucosal leishmaniasis. METHODS: We conducted an observational study evaluating the association between vitamin D levels, disease severity and therapeutic response in patients with cutaneous and mucosal leishmaniasis. Additionally, we conducted a cross-sectional study to compare vitamin D levels in patients with leishmaniasis and healthy subjects. Hypovitaminosis D was defined as a serum level of 25 (OH) D < 30 ng/mL. RESULTS: In patients with leishmaniasis, vitamin D serum levels were 38.5 ± 11.54 ng/mL, and 37.5 ± 10.43 ng/mL in healthy subjects The prevalence of hypovitaminosis D was 23.3% and 20.0%, respectively (p = 0.72). There was no correlation between vitamin D serum levels, disease severity, and healing time in the mucosal leishmaniasis group. CONCLUSION: Vitamin D levels are not associated with neither susceptibility nor severity of tegumentary leishmaniasis.

Leishmania major Strain-Dependent Macrophage Activation Contributes to Pathogenicity in the Absence of Lymphocytes.

Infection of C57BL/6 wild-type mice with Leishmania major 5-ASKH or Friedlin strains results in relatively similar pathogenicity with self-healing lesions within weeks. Parasite clearance depends on nitric oxide production by activated macrophages in response to cytokines produced mainly by CD4+ Th1 cells. In contrast, C57BL/6 Rag2 knockout mice, which lack T and B lymphocytes, show distinct pathologies during infection with these strains. Despite of the similar parasite number, the 5-ASKH infection induced severe inflammation rather than the Friedlin. To determine the immunological factors behind this phenomenon, we infected C57BL/6 Rag2 knockout mice with these two strains and compared immune cell kinetics and macrophage activation status. Compared with the Friedlin strain, the 5-ASKH strain elicited increased pathology associated with the accumulation of CD11bhigh, Ly6Ghigh neutrophils by week four and increased the expression of macrophage activation markers. We then analyzed the differentially expressed transcripts in infected bone marrow-derived macrophages by RNA sequencing. It showed upregulation of multiple inflammatory transcripts, including Toll-like receptor 1/2 (TLR1/2), CD69, and CARD14, upon 5-ASKH infection. Our findings suggest that different L. major strains can trigger distinct macrophage activation, contributing to the disease outcome observed in the absence of lymphocytes but not in the presence of lymphocytes. IMPORTANCE Disease manifestations of cutaneous leishmaniasis (CL) range from self-healing cutaneous lesions to chronic forms of the disease, depending on the infecting Leishmania sp. and host immune protection. Previous works on mouse models of CL show the distinct pathogenicity of Leishmania major strains in the absence of lymphocytes. However, the mechanisms of this pathology remain uncovered. In the trial to understand the immunological process involved in lymphocyte-independent pathology, we have found a specific induction of macrophages by different L. major strains that affect their ability to mount innate responses leading to neutrophilic pathology when lymphocytes are ablated.

Effectiveness of intralesional sodium stibogluconate for the treatment of localized cutaneous leishmaniasis at Boru Meda general hospital, Amhara, Ethiopia: Pragmatic trial.

BACKGROUND: Cutaneous leishmaniasis (CL) is generally caused by Leishmania aethiopica in Ethiopia, and is relatively hard to treat. Sodium stibogluconate (SSG) is the only routinely and widely available antileishmanial treatment, and can be used systemically for severe lesions and locally for smaller lesions. There is limited data on the effectiveness of intralesional (IL) SSG for localized CL in Ethiopia and therefore good data is necessary to improve our understanding of the effectiveness of the treatment. METHODOLOGY/PRINCIPAL FINDINGS: A pragmatic (before and after Quazi experimental) study was done to assess the effectiveness of intralesional SSG among localized CL patients at Boru Meda general hospital, Northeast Ethiopia. Patients who were assigned to intralesional SSG by the treating physician were eligible for this study. Study subjects were recruited between January and August 2021. Infiltration of intralesional SSG was given weekly to a maximum of six doses. However, when a patient's lesions were already cured before getting 6 doses, treatment was not conintued, and patient were only asked to come for lesion assessment. Skin slit smears (SSS) were taken each week until they became negative. Outcomes were assessed at day 90, with patients who had 100% reepithelization (for ulcerative lesions) and/or flattening (for indurated lesions) defined as cured. Multi-level logistic regression was done to assess factors associated with cure. A total of 83 patients were enrolled, and final outcomes were available for 72 (86.75%). From these 72, 43 (59.7%, 95% confidence interval 0.44-0.69) were cured at day 90. Adverse effects were common with 69/72 patients (95.8%) reporting injection site pain. Factors associated with cure were age (OR 1.07 95% CI: 1.07-1.27), being male (OR 1.79, 95% CI: 1.10-2.25), size of the lesion (OR 0.79, 95% CI: 0.078-0.94) and skin slit smear (SSS) result +1 grading (OR 1.53, 95% CI: 1.24-1.73) and +2 grading (OR 1.51, 95% CI: 1.41-3.89) compared to the SSS grade +6. CONCLUSION: Our findings revealed that intralesional sodium stibogluconate resulted in a cure rate of around 60%, with almost all patients experiencing injection site pain. This emphasizes the need for local treatment options which are more patient-friendly and have better cure rates.

Multiparametric analysis of host and parasite elements in new world tegumentary leishmaniasis.

Tegumentary leishmaniasis is a tropical disease caused by protozoa of the genus Leishmania. Clinically, the disease presents a broad spectrum of symptoms, the mechanisms underlying the development of lesions remaining to be fully elucidated. In the present work, we performed a correlation and multiparametric analysis to evaluate how parasite- and host-related aspects associate with each other, and with the different clinical manifestations of tegumentary leishmaniasis. This cross-sectional study involved 75 individuals from endemic areas of Brazil, grouped according to their symptoms. Leishmania species were determined by DNA sequencing, and parasite load, antibody production, and cytokine profile were evaluated by kDNA qPCR, ELISA, and flow cytometry. Data were analyzed using the Chi-square test, principal component analysis, canonical discriminant analysis, and correlation analysis. Among the recruited patients, 23 (31%) were asymptomatic, 34 (45%) had primary cutaneous leishmaniasis, 10 (13%) presented recurrent cutaneous leishmaniasis, and eight (11%) had mucocutaneous leishmaniasis. Leishmania species identified included L. amazonensis, L. braziliensis, and L. guyanensis. Surprisingly, no Leishmania RNA virus infection was detected in any sample. In summary, our work showed that parasite load, antibody production, and cytokine levels alone are not determinants for tegumentary leishmaniasis symptoms. However, the correlation analysis allowed us to observe how these factors are correlated to each other within the groups, which revealed a unique network for each clinical manifestation. Our work reinforces the complexity of tegumentary leishmaniasis outcomes - which are associated with multiple host and parasite-related elements and provides a holistic model of the disease.