Repurposing sodium stibogluconate as an uracil DNA glycosylase inhibitor against prostate cancer using a time-resolved oligonucleotide-based drug screening platform.

Repurposing drugs can significantly reduce the time and costs associated with drug discovery and development. However, many drug compounds possess intrinsic fluorescence, resulting in aberrations such as auto-fluorescence, scattering and quenching, in fluorescent high-throughput screening assays. To overcome these drawbacks, time-resolved technologies have received increasing attention. In this study, we have developed a rapid and efficient screening platform based on time-resolved emission spectroscopy in order to screen for inhibitors of the DNA repair enzyme, uracil-DNA glycosylase (UDG). From a database of 1456 FDA/EMA-approved drugs, sodium stibogluconate was discovered as a potent UDG inhibitor. This compound showed synergistic cytotoxicity against 5-fluorouracil-resistant cancer cells. This work provides a promising future for time-resolved technologies for high-throughput screening (HTS), allowing for the swift identification of bioactive compounds from previously overlooked scaffolds due to their inherent fluorescence properties.

Histological findings associated with treatment response in cutaneous leishmaniasis: a clinicopathological correlation study.

BACKGROUND: Treatment responses to cutaneous leishmaniasis (CL) observed in Sri Lanka show variability, ranging from quick healing to delayed or failed responses to routine medication. The determinants of these differences in treatment response are not well defined. This study aimed to identify predictive features of treatment response and outcome in localized CL caused by Leishmania donovani, focusing on both clinical and histopathological findings in the patients. METHODS: Tissue sections (n = 103) derived from 3 mm punch biopsies of parasitologically confirmed patients were assessed. Patients were followed up weekly until complete healing of skin lesions and were reviewed at the end of 6 months and 1 year. RESULTS: Healing required 7-21 weekly doses of intralesional sodium stibogluconate (IL-SSG) (mean = 12.2 ± 0.622). Twenty-nine (28.1%) patients were identified as delayed responders. None had recurred at the end of 1 year. The demographic or clinical features (age, gender, lesion type, size, location, and lesion duration) did not significantly influence the treatment response. A heavy parasite load and acanthosis were significant predictors of a delayed response to treatment (P < 0.001). Higher parasite loads were associated with inflammation of the entire dermis (P = 0.008), more intense infiltration of macrophages (p = 0.001), and epidermal atrophy (P = 0.033). Well-formed granulomas were inversely proportional to parasite loads. CONCLUSIONS: Histology findings proved to be better prognostic markers than clinical features for delayed responders to treatment and will aid in targeted patient management when tissue biopsies are performed in the initial diagnosis of CL.

A case report of an uncommon presentation of cutaneous leishmaniasis: A nose lesion.

Leishmaniasis is a widely spread zoonotic disease caused by the bite of infected sandflies, particularly in developing countries. Cutaneous leishmaniasis can have a diverse range of presentations, ranging from minor skin nodules to significant mucosal damage. However, nose involvement is infrequent. Our report highlights a 15-year-old female patient with a persistent skin lesion on her nose for three months, which is a rare manifestation of cutaneous leishmaniasis. The lesion started as a raised spot with a brownish-red color and a crust but eventually developed into an ulcer that spread over the entire lobe of the nose and even moved toward the eye. Microscopic examination revealed the presence of Leishmania amastigotes, and a biopsy confirmed a diagnosis of cutaneous leishmaniasis. The patient received daily intravenous sodium stibogluconate doses of 9 mg/kg for 20 days, and three weeks later, there was a significant clinical improvement, with the ulcer beginning to heal and no more amastigotes visible on microscopic examination. It is crucial to keep cutaneous leishmaniasis in mind as a possible diagnosis for patients with skin lesions, even in regions where the condition is not prevalent.

Comparación de la eficacia y toxicidad del estibogluconato de sodio y antimoniato de meglumina en el tratamiento de leishmaniasis cutánea en Perú / Efficacy and safety of sodium stibogluconate compared to meglumine antimoniate in the treatment of cutaneous leishmaniasis in Peru

Objetivos : Comparar la eficacia y toxicidad del antimoniato de meglumina (AM) y estibogluconato sódico (EGS) en el tratamiento de leishmaniasis cutánea (LC) en un hospital general. Material y métodos : Serie de casos comparativa de 193 pacientes con LC tratados en tres ensayos clínicos con AM (n=69) y EGS (n=124) durante 2001-2010. La administración de ambas drogas fue vía endovenosa lenta de 20 mg Sb5+/kg/día por 20 días consecutivos siguiendo las normativas de la OPS y OMS. La información clínica, toxicidad y eficacia fue obtenida de las historias clínicas almacenadas en el centro de investigación según la normativa local e internacional. Resultados : Las características demográficas fueron similares entre grupos, pero el tamaño y número de lesiones fueron mayores en el grupo AM. La eficacia del tratamiento con AM fue 76,0% versus 68,4% con EGS (p=0,340) y 55,1% versus 50,8% (p=0,570) en el análisis por protocolo y de intención de tratar, respectivamente. No se observaron efectos adversos inmediatos. Los síntomas más frecuentemente reportados fueron disgeusia (37,0%), mareos (32,0%), cefalea (36,0%), artralgias (31,0%) y linfangitis (21,0%). Los tres primeros síntomas, así como elevación de transaminasas, leucopenia, trombocitopenia y QTc prolongado fueron frecuentes en el grupo EGS, pero clínica y estadísticamente no significativos. El tratamiento fue suspendido definitivamente por toxicidad severa únicamente con EGS por emesis refractaria (2 participantes) y QTc prolongado con extrasístoles (1 participante). Conclusiones : La eficacia del tratamiento con AM y EGS fue comparable. La administración endovenosa de ambos no produjo efectos adversos inmediatos, aunque sí alteraciones clínicas y laboratoriales usuales.

SUMMARY Objectives : To compare the efficacy and safety of sodium stibogluconate (SS) and meglumine antimoniate (MA) in the treatment of cutaneous leishmaniasis (CL) in a general hospital. Methods: Case-series of 193 patients with CL treated in three clinical trials with MA (n=69) and SS (n=124) during 2001-2010. Both study drugs were administered intravenously at a slow speed at 20 mg Sb5+/kg/day for 20 consecutive days following WHO-PAHO recommendations. Clinical and safety data were gathered from clinical files. Results: Demographic characteristics were similar between the study groups, but the size and number of lesions were higher in the MA group. Efficacy was 76.0% in the MA vs. 68.4% in the SS group (p=0.340) and 55.1% vs. 50.8% (p=0.570) in the per protocol and intention to treat analysis. respectively. Side effects more frequently reported were dysgeusia (37.0%). dizziness (32.0%). headache (36.0%). arthralgia (31.0%) and lymphangitis (21.0%). These first three symptoms as well as elevation of transaminases, leukopenia, thrombocytopenia and prolonged QTc were numerically more frequent in the SS group but without reaching statistical significance. Treatment was stopped definitively for severe toxicity in the SS group due to refractory emesis (two patients) and prolonged QTc (one patient). Conclusions: The efficacy of MA and SS is comparable. The intravenous administration of these compounds did not produce immediate reactions, but it was associated with unusual clinical and laboratory abnormalities.

Effect of sodium stibogluconate in recruiting and awakening immune cells in the pleural fluid of pancreatic cancer: preparation for immunotherapy.

Ascites and pleural effusion are recognized complications of pancreatic cancer. These diseases are accompanied by ascites and pleural effusion, and drug treatment is limited by high costs, long hospital stays, and failure rates. Immunotherapy may offer new option, but in most patients with late stages of cancer, immune cells may lose the ability to recognize tumor cells, how to activate their immune cells is a major problem, sodium glucosidate (SSG) is injected into ascites as a protein tyrosine phosphatase inhibitor to wake up immune cells and prepare for immunotherapy. We used single-cell RNA sequencing (scRNA-seq) to investigate whether and how SSG injected into ascites of pancreatic cancer elicits an immune response. Our study showed that the process of SSG fusion treatment of ascites and pleural effusion, the interaction between TandNK cells, MPs cells, monocytes and neutrophils was induced, and large numbers of genes were expressed, resulting in upregulation of immune response, which also approved that SSG is not only used as a protein tyrosine phosphatase inhibitor, but also it works as a protein tyrosine phosphatase inhibitor. It can also be used to regulate immune cell function, recruiting immune cells to the right place with the help of PD-1 or PD-L1 to fight cancer cells in ascites and pleural effusions in cancer patients.

Case Report: Visceral Leishmaniasis-associated Hemophagocytic Lymphohistiocytosis in Adults: A Case Series and Literature Review.

Hemophagocytic lymphohistiocytosis (HLH) is a rare and fatal complication of visceral leishmaniasis (VL). To provide a basis for early and correct diagnosis and to improve prognosis in the future, we describe a case series of VL-associated HLH in adults in our center in the past decade after review of all reported cases of adult VL-associated HLH in English through May 2022. In our case series, a total of 111 patients were diagnosed with VL. Among these patients, only six cases were diagnosed with VL-associated HLH. All patients tested positive for serology. Leishmania was detected for the first time by bone marrow aspiration (BMA) in three of the six patients and in the other three patients after three or four BMAs. It took more than 1 month from onset to diagnosis of VL for all the six cases, and the longest time was 6 months. Five of the six patients recovered after receiving sodium stibogluconate. VL-associated HLH is rare but potentially life-threatening in adults and predisposes to early delays in diagnosis. However, diagnostic techniques are not complicated or difficult, so it is more important to consider that it is not recognized by physicians. Although guidelines recommend liposomal amphotericin B as the most effective therapy, our experience suggests that sodium stibogluconate can be an alternative option when liposomal amphotericin B is unavailable or unaffordable.

Sodium stibogluconate and CD47-SIRPα blockade overcome resistance of anti-CD20-opsonized B cells to neutrophil killing.

Anti-CD20 antibodies such as rituximab are broadly used to treat B-cell malignancies. These antibodies can induce various effector functions, including immune cell-mediated antibody-dependent cellular cytotoxicity (ADCC). Neutrophils can induce ADCC toward solid cancer cells by trogoptosis, a cytotoxic mechanism known to be dependent on trogocytosis. However, neutrophils seem to be incapable of killing rituximab-opsonized B-cell lymphoma cells. Nevertheless, neutrophils do trogocytose rituximab-opsonized B-cell lymphoma cells, but this only reduces CD20 surface expression and is thought to render tumor cells therapeutically resistant to further rituximab-dependent destruction. Here, we demonstrate that resistance of B-cell lymphoma cells toward neutrophil killing can be overcome by a combination of CD47-SIRPα checkpoint blockade and sodium stibogluconate (SSG), an anti-leishmaniasis drug and documented inhibitor of the tyrosine phosphatase SHP-1. SSG enhanced neutrophil-mediated ADCC of solid tumor cells but enabled trogoptotic killing of B-cell lymphoma cells by turning trogocytosis from a mechanism that contributes to resistance into a cytotoxic anti-cancer mechanism. Tumor cell killing in the presence of SSG required both antibody opsonization of the target cells and disruption of CD47-SIRPα interactions. These results provide a more detailed understanding of the role of neutrophil trogocytosis in antibody-mediated destruction of B cells and clues on how to further optimize antibody therapy of B-cell malignancies.

ASSESSMENT OF THE OXIDATIVE AND NITROSATIVE STRESS IN THE SERUM OF SAUDI PATIENTS WITH CUTANEOUS LEISHMANIASIS BEFORE AND AFTER TREATMENT.

Macrophages, within which Leishmania species replicate, generate large amounts of reactive oxygen species (ROS) and reactive nitrogen species (RNS) to kill these parasites. The present study assessed the oxidative and nitrosative stress, and specific immune enzymes in the serum of patients with cutaneous leishmaniasis (Cl) before and after treatment and in the control individuals. Serum activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px), L-arginase, myeloperoxidase (MPO), and adenosine deaminase (ADA) and the levels of reduced glutathione, malondialdehyde (MDA), and nitric oxide (NO) were studied. The activities of L-arginase, MPO, and ADA and the levels of MDA and NO were significantly elevated (P < 0.001), while the activities of SOD, CAT, and GSH-Px, and the levels of reduced glutathione (GSH) were significantly (P < 0.001) reduced in untreated patients as compared with values of patients after treatment and of control individuals. The treatment, which included intramuscular injection of sodium stibogluconate and meglumine antimoniate, ameliorated these factors in comparison to the untreated group. These results suggest that oxidative and nitrosative stress may play an important role in the pathogenesis of untreated cutaneous leishmaniasis. Furthermore, the reduction in oxidative and nitrosative stress in the treated Cl patients may be due to the drug decreasing energy production by the parasite, which eventually leads to its death.

Comparison between cutaneous leishmaniasis patients with facial and non-facial lesions.

BACKGROUND: We compared demographic, clinical, treatment, and outcome characteristics of facial cutaneous leishmaniasis (CL) and non-facial CL. METHODS: In this retrospective cohort study, polymerase chain reaction confirmed Leishmania major CL patients with ≥2 documented hospital visits, 2014-2019, were included. RESULTS: Overall, 134 patients (34% and 66% with facial and non-facial CL, respectively) were included. Facial CL patients were younger (43% vs. 8% <18 years, P < 0.001), with a higher proportion of females (41% vs. 25%, P = 0.07) compared with non-facial CL. Clinical characteristics, including number and size of lesions and ulcer appearance, were similar in both the groups. Higher paromomycin/methylbenzethonium chloride ointment treatment rates were noted in facial CL (85% vs. 64%, P = 0.02). Intralesional sodium stibogluconate was given to 41% and 53% of facial CL and non-facial CL patients, respectively (P = 0.21). Cryotherapy and surgery were only used in non-facial CL patients (5% and 1% of all CL cases, respectively). Systemic treatment (oral miltefosine, intravenous [IV] sodium stibogluconate, IV liposomal amphotericin B) was used in <5% of the cases in both the groups. Overall, 84% of patients showed signs of improvement, including decreased lesion size or clinical improvement in 73% and 75% of patients, respectively. Only 5% of all cases healed without scarring. Outcome rates were similar in both groups. CONCLUSIONS: Facial CL patients were younger and received more frequently Leishmania-specific topical treatment than non-facial CL patients. In contrast, the two groups were similar regarding clinical characteristics and outcome. These findings suggest differences in disease severity perception by patients and physicians.

Antileishmanial efficacy and tolerability of combined treatment with non-ionic surfactant vesicle formulations of sodium stibogluconate and paromomycin in dogs.

Infection with Leishmania infantum causes the disease visceral leishmaniasis (VL), which is a serious clinical and veterinary problem. The drugs used to treat canine leishmaniasis (CanL) do not cause complete parasite clearance; they can be toxic, and emerging drug resistance in parasite populations limits their clinical utility. Therefore, in this study we have evaluated the toxicity and efficacy of joint treatment with a 1:1 mixture of sodium stibogluconate-NIV (SSG-NIV, 10 mg Sbv/day) and paromomycin-NIV (PMM-NIV, 10 mg PMM/kg/day), given intravenously daily for seven days from day 270 post-infection, to nine-month-old female beagle dogs (n = 6) experimentally infected with Leishmania infantum. Treatment significantly improved the clinical symptoms of VL infection in all the treated dogs, reduced parasite burdens in lymph nodes and bone marrow, and all symptomatic treated dogs, were asymptomatic at 90 days post-treatment. Treatment was associated with a progressive and significant decrease in specific IgG anti-Leishmania antibodies using parasite soluble antigen (p < 0.01) or rK39 (p < 0.01) as the target antigen. In addition, all dogs were classified as parasite negative based on Leishmania nested PCR and quantitative real time PCR tests and as well as an inability to culture of promastigote parasites from lymph nodes and bone marrow tissue samples taken at day 90 post-treatment. However, treatment did not cure the dogs as parasites were detected at 10 months post-treatment, indicating that a different dosing regimen is required to cause long term cure or prevent relapse.

Synergistic Effect Of Oral Allopurinol And Intralesional Sodium Stibogluconate In The Treatment Of Cutaneous Leishmaniasis.

BACKGROUND: Leishmaniasis is an endemic disease and a major public health problem throughout the world. Its geographic distribution has been extended over the past few years in Pakistan. The available treatment options of Leishmaniasis are limited and mostly parenteral, and hence a nontoxic oral alternative therapy is urgently needed to overcome the problem. The objective of this study was to evaluate the synergistic effect of Allopurinol as an adjunct therapy along with conventional intra-lesional sodium Stibogluconate in the treatment of cutaneous Leishmaniasis. METHODS: This single blinded randomized controlled trial was carried out at the tertiary care hospitals of district Peshawar, Pakistan. A total of one hundred and sixty-four (164) patients of age range from 19-56 years, consisting of both genders were included in this study. All subjects were randomly allocated to Group-1 and Group-2 where each group had 82 patients of comparable age and genders. Group-1 patients were given an intra-lesional injection of sodium Stibogluconate at a dose of 1-5 ml depending on the lesion size, where one ml injection contained 100 mg of the drug. Group-2 patients were given combination therapy of oral Allopurinol (20 mg/kg/day in divided doses) along with the same intra-lesional sodium Stibogluconate dose as group-1 until complete cure of the lesion. RESULTS: Combination therapy of sodium Stibogluconate along with Allopurinol was found superior to sodium Stibogluconate alone in terms of duration of treatment. Group-1, patients who received only sodium Stibogluconate required prolonged treatment duration of 6-9 weeks depending upon the lesion size, while group-2 patients who received combination therapy of sodium Stibogluconate and Allopurinol responded more quickly and their lesions cured in 3-6 weeks depending upon the lesion size. CONCLUSIONS: Oral Allopurinol has a synergistic effect when used with intra-lesional sodium Stibogluconate and effectively reduces the treatment duration required for complete cure of cutaneous Leishmaniasis. Treatment duration was reduced by 3 weeks in the present study when combination therapy was given to the patients of cutaneous Leishmaniasis.

Immunomodulator mediated changes in plasma membrane calcium ATPase in controlling visceral leishmaniasis.

Immunomodulation is an emerging concept to combat infection in recent years. Immunomodulators like arabinosylated-lipoarabinomannan (Ara-LAM) and glycyrrhizic-acid (GA) possess anti-leishmanial property, whereas sodium-antimony-gluconate (SAG) is still considered as the first choice for chemotherapy against leishmaniasis. During infection, invasion of Leishmania donovani needs the potential requirement of Ca2+, which is further responsible for apoptosis in intracellular amastigotes. However, suppression of elevated intracellular calcium by the activation of plasma-membrane-calcium-ATPase (PMCA4) facilitates survival of L. donovani in the host. In the present study, SAG, Ara-LAM, and GA were found to evoke significant increase in intracellular Ca2+ in L. donovani infected macrophages by inhibiting PMCA4. Moreover, PMCA4 inhibition by TFP or PMCA4 siRNA elevated the level of PKCß, whereas calcium-independent upregulation of PKCζ remained unchanged in infected macrophages. Furthermore, application of immunomodulators in infected macrophages resulted in down-regulation of PKCζ, conversion of anti-inflammatory to pro-inflammatory cytokines and inhibition of PMCA4. Plasma membrane-associated ceramide which is known to be elevated during leishmaniasis, triggered upregulation of PMCA4 via PKCζ activation. Interestingly, immunomodulators attenuated ceramide generation, which resulted into reduced PKCζ activation leading to the decreased PMCA expression in infected macrophages. Therefore, our study elucidated the efficacy of SAG, Ara-LAM, and GA in the reduction of parasite burden in macrophages by suppressing PMCA activation through inhibition of ceramide mediated upregulation of PKCζ.

Case Report: Autochthonous Case of Human Visceral Leishmaniasis in the West Bank, Palestine.

Human visceral leishmaniasis (HVL) is a parasitic disease infecting children in the Mediterranean region. Here, we portray a case of a 2-year-old child with an epidemiological description of the situation surrounding the case. The patient was suffering from recurrent fever, weakness, and abdominal discomfort associated with loss of appetite. Routine blood investigations showed pancytopenia, whereas examination revealed hepatomegaly. A diagnosis of HVL was made by demonstrating amastigotes in a Giemsa-stained smear from a bone marrow aspirate followed by genotyping by PCR and sequencing. In conclusion, early detection of VL infection followed by appropriate treatment protocols is essential to saving the patient.

Combined chemotherapy manifest less severe immunopathology effects in helminth-protozoa comorbidity.

BACKGROUND: Co-infection with Leishmania major and Schistosoma mansoni may have significant consequences for disease progression, severity and subsequent transmission dynamics. Pentavalent antimonials and Praziquantel (PZQ) are used as first line of treatment for Leishmania and Schistosoma infections respectively. However, there is limited insight on how combined therapy with the standard drugs impacts the host in comorbidity. The study aimed to determine the efficacy of combined chemotherapy using Pentostam (P) and PZQ in murine model co-infected with L. major and S. mansoni. METHODS: A 3 × 4 factorial design with three parasite infection groups (Lm, Sm, Lm + Sm to represent L. major, S. mansoni and L. major + S. mansoni respectively) and four treatment regimens [P, PZQ, P + PZQ, and PBS designating Pentostam (GlaxoSmithKline UK), Praziquantel (Biltricide®, Bayer Ag. Leverkusen, Germany), Pentostam + Praziquantel and Phosphate buffered saline] as factors was applied. RESULTS: Significant changes were observed in the serum Interferon gamma (IFN-γ), and Macrophage inflammatory protein-one alpha (MIP-1α) levels among various treatment groups between week 8 and week 10 (p < 0.05). There was increased IFN-γ in the L. major infected mice subjected to PZQ and PBS, and in L. major + S. mansoni infected BALB/c mice treated with P + PZQ. Subsequently, MIP-1α levels increased significantly in both the L. major infected mice under PZQ and PBS and in L. major + S. mansoni infected BALB/c mice undergoing concurrent chemotherapy with P + PZQ between 8 and 10 weeks (p < 0.05). In the comorbidity, simultaneous chemotherapy resulted in less severe histopathological effects in the liver. CONCLUSION: It was evident, combined first line of treatment is a more effective strategy in managing co-infection of L. major and S. mansoni. The findings denote simultaneous chemotherapy compliments immunomodulation in the helminth-protozoa comorbidity hence, less severe pathological effects following the parasites infection. Recent cases of increased incidences of polyparasitism in vertebrates call for better ways to manage co-infections. The findings presented necessitate intrinsic biological interest on examining optimal combined chemotherapeutic agents strategies in helminth-protozoa concomitance and the related infections abatement trends vis-a-vis host-parasite relationships.

Chemogenomic Profiling of Antileishmanial Efficacy and Resistance in the Related Kinetoplastid Parasite Trypanosoma brucei.

The arsenal of drugs used to treat leishmaniasis, caused by Leishmania spp., is limited and beset by toxicity and emergent resistance. Furthermore, our understanding of drug mode of action and potential routes to resistance is limited. Forward genetic approaches have revolutionized our understanding of drug mode of action in the related kinetoplastid parasite Trypanosoma brucei Therefore, we screened our genome-scale T. brucei RNA interference (RNAi) library against the current antileishmanial drugs sodium stibogluconate (antimonial), paromomycin, miltefosine, and amphotericin B. Identification of T. brucei orthologues of the known Leishmania antimonial and miltefosine plasma membrane transporters effectively validated our approach, while a cohort of 42 novel drug efficacy determinants provides new insights and serves as a resource. Follow-up analyses revealed the antimonial selectivity of the aquaglyceroporin TbAQP3. A lysosomal major facilitator superfamily transporter contributes to paromomycin-aminoglycoside efficacy. The vesicle-associated membrane protein TbVAMP7B and a flippase contribute to amphotericin B and miltefosine action and are potential cross-resistance determinants. Finally, multiple phospholipid-transporting flippases, including the T. brucei orthologue of the Leishmania miltefosine transporter, a putative ß-subunit/CDC50 cofactor, and additional membrane-associated hits, affect amphotericin B efficacy, providing new insights into mechanisms of drug uptake and action. The findings from this orthology-based chemogenomic profiling approach substantially advance our understanding of antileishmanial drug action and potential resistance mechanisms and should facilitate the development of improved therapies as well as surveillance for drug-resistant parasites.

Leishmaniasis cutánea, a propósito de un caso / Cutaneous leishmaniasis, a purpose of a case

La Leishmaniasis es una enfermedad parasitaria catalogada como emer-gente y sin control debido al cambio en el perfil epidemiológico por el sur-gimiento de nuevos focos y urbanización del ciclo de transmisión. Se des-cribe el caso de un adolescente de la Comunidad Dos Ríos, del Cantón Taisha, quien presentó varias lesiones ulceradas, confirmándose diagnós-tico de Leishmaniasis Cutáneamediante estudio histológico, iniciándose tratamiento con sales de antimonio pentavalentes, logrando una resolución progresiva y paulatina de las lesiones. Destacándose la importancia del diagnóstico temprano, tratamiento supervisado, y seguimiento para preve-nir complicaciones.

Leishmaniasis is a parasitic, emergent and uncontrolled disease due to the change in the epidemiological profile for the appearance of new outbreaks and urbanization of the transmission cycle. A case of a 15-years-old ado-lescent, who is resident of the Community Dos Ríos located on the Taisha Canton, was described. The patient presented ulcerated lesions, confir-ming the diagnosis of Cutaneous Leishmaniasis through the histological study of the lesions, and starting intramuscular treatment with pentavalent antimony salts observing healing with a progressive and gradual resolution of the lesions and emphasizing the importance of early diagnosis, supervi-sed treatment, and monitoring to prevent complications.

Fractional Ablative CO2 Laser Followed by Topical Application of Sodium Stibogluconate for Treatment of Active Cutaneous Leishmaniasis: A Randomized Controlled Trial.

Conventional treatment of cutaneous leishmaniasis often leaves permanent scars with frequent psychosocial sequelae. The aim of this study was to compare the efficacy, safety, associated pain and final cosmetic outcome of fractional carbon dioxide (CO2) laser followed by topical application of sodium stibogluconate vs. sodium stibogluconate injections for the treatment of cutaneous leishmaniasis. A total of 181 lesions (20 patients) were randomly assigned to receive intralesional injections of sodium stibogluconate (control group) or fractional CO2 laser treatment followed by topical application of sodium stibogluconate (study group). The visual analogue scale (VAS) score of the control group was much higher than that of the study group (6.85 vs. 3.5, respectively, p<0.001). Both the patients and 2 blinded dermatologists found the final cosmetic outcome to be superior for laser-treated lesions (p = 0.001 vs. p =0.008 for controls). Fractional CO2 laser treatment followed by topical application of sodium stibogluconate is less painful and leads to a better final cosmetic outcome compared with intralesional injections of sodium stibogluconate.

Sodium stibogluconate loaded nano-deformable liposomes for topical treatment of leishmaniasis: macrophage as a target cell.

Topical drug delivery against cutaneous leishmaniasis (CL) signifies an effective alternate for improving the availability and reducing the toxicity associated with the parenteral administration of conventional sodium stibogluconate (SSG) injection. The basic aim of the study was to develop nano-deformable liposomes (NDLs) for the dermal delivery of SSG against CL. NDLs were formulated by a modified thin film hydration method and optimized via Box-Behnken statistical design. The physicochemical properties of SSG-NDLs were established in terms of vesicle size (195.1 nm), polydispersity index (0.158), zeta potential (-32.8 mV), and entrapment efficiency (35.26%). Moreover, deformability index, in vitro release, and macrophage uptake studies were also accomplished. SSG-NDLs were entrapped within Carbopol gel network for the ease of skin application. The ex vivo skin permeation study revealed that SSG-NDLs gel provided 10-fold higher skin retention towards the deeper skin layers, attained without use of classical permeation enhancers. Moreover, in vivo skin irritation and histopathological studies verified safety of the topically applied formulation. Interestingly, the cytotoxic potential of SSG-NDLs (1.3 mg/ml) was higher than plain SSG (1.65 mg/ml). The anti-leishmanial activity on intramacrophage amastigote model of Leishmania tropica showed that IC50 value of the SSG-NDLs was ∼ fourfold lower than the plain drug solution with marked increase in the selectivity index. The in vivo results displayed higher anti-leishmanial activity by efficiently healing lesion and successfully reducing parasite burden. Concisely, the outcomes indicated that the targeted delivery of SSG could be accomplished by using topically applied NDLs for the effective treatment of CL.

Case Report: Mucosal Leishmaniasis Presenting with Nasal Septum Perforation after Almost Thirty Years.

Mucosal leishmaniasis (ML) is associated with progressive tissue destruction and granuloma formation, often after a considerable period of latency from an initial cutaneous infection. We report a case of recurrent epistaxis of 3 years duration and nasopharyngeal obstruction in a woman with treated cutaneous leishmaniasis nearly 30 years before and with no further exposure to Leishmania. Computed tomography revealed nasal septal perforation and histopathology demonstrated chronic inflammation. Microscopy was negative for amastigotes, but molecular testing of nasal mucosa biopsy detected Leishmania (Viannia) braziliensis. The patient underwent 28 days of treatment with IV sodium stibogluconate and her symptoms improved significantly. Sixteen months after treatment, she continues to have episodic epistaxis and detectable parasite load in her nasal lesion. Although ML is known to take years to decades to develop, there are few reported cases in the literature of such a long latency period. This report highlights the importance of considering ML in the differential diagnosis of chronic epistaxis in countries where leishmaniasis is endemic or in immigrants from these countries, even when presentation occurs decades after leaving an endemic region.

Decanethiol functionalized silver nanoparticles are new powerful leishmanicidals in vitro.

We evaluated, for the first time, the leishmanicidal potential of decanethiol functionalized silver nanoparticles (AgNps-SCH) on promastigotes and amastigotes of different strains and species of Leishmania: L. mexicana and L. major isolated from different patients suffering from localized cutaneous leishmaniasis (CL) and L. mexicana isolated from a patient suffering from diffuse cutaneous leishmaniasis (DCL). We recorded the kinetics of promastigote growth by daily parasite counting for 5 days, promastigote mobility, parasite reproduction by CFSE staining's protocol and promastigote killing using the propidium iodide assay. We also recorded IC50's of promastigotes and amastigotes, therapeutic index, and cytotoxicity by co-culturing macrophages with AgNps-SCH or sodium stibogluconate (Sb) used as reference drug. We used Sb as a reference drug since it is used as the first line treatment for all different types of leishmaniasis. At concentrations 10,000 times lower than those used with Sb, AgNps-SCH had a remarkable leishmanicidal effect in all tested strains of parasites and there was no toxicity to J774A.1 macrophages since > 85% were viable at the concentrations used. Therapeutic index was about 20,000 fold greater than the corresponding one for Sb treated cells. AgNps-SCH inhibited > 80% promastigote proliferation in all tested parasites. These results demonstrate there is a high leishmanicidal potential of AgNps-SCH at concentrations of 0.04 µM. Although more studies are needed, including in vivo testing of AgNps-SCH against different types of leishmaniasis, they can be considered a potential new treatment alternative.