Search Results (972)

Background: The availability of laboratory tests to screen and diagnose migrants and travellers for neglected and tropical parasitic diseases significantly impacts individual and public health. Italian scientific societies for parasitology, tropical diseases, and global health developed a survey to assess number and geographical localisation of laboratories able to carry out adequate diagnostics. Methods: An open-ended and multiple-choice questionnaire was constructed and sent to 752 members working in Italian microbiology laboratories via scientific societies’ mailing lists. Data concerning malaria, cystic echinococcosis, leishmaniasis, schistosomiasis, strongyloidiasis, and Chagas disease were included. Results: Members from 96 laboratories replied. At least one laboratory responded from 18 out of 20 Italian regions. Serological tests for Schistosoma spp., Strongyloides stercoralis, Trypanosoma cruzi, Echinococcus spp., and Leishmania spp. are performed in <50% of responding laboratories. Only 56.6% of labs provide all three recommended tests for malaria diagnosis in the emergency room. Direct identification methods availability varies for Schistosoma eggs (75–95.8%), S. stercoralis larvae (53.1%), trypomastigotes (59.4%), and Leishmania amastigotes (53.1%). Geographical differences (mainly northern versus southern regions) were evident. Conclusions: The survey underlines the need to improve diagnosis for neglected and tropical diseases, to define a network of reference laboratories for testing less prevalent diseases, and to share information, education, and training for both clinicians and microbiologists/parasitologists. Full article

Background: Leishmaniasis is a vector-borne zoonotic disease caused by protozoa of the genus Leishmania. While it is endemic in the Mediterranean Basin and the Balkans, Romania remains a non-endemic country. However, climate change, increased international travel, and the documented presence of competent vectors (Phlebotomus spp.) have raised concerns about the potential emergence of autochthonous cases. Case Presentation: We report two cases of imported cutaneous leishmaniasis (CL) diagnosed in central Romania, a region without previously confirmed human or animal cases. The first case involved a 31-year-old male with a recent travel history to Spain, presenting with erythematous papules and plaques that evolved into ulcerated lesions. The diagnosis was confirmed histopathologically and by a PCR. Treatment with miltefosine was effective, with minimal hepatic toxicity and a sustained response at a six-month follow-up. The second case concerned an 11-year-old boy who had traveled to Elba, Italy. He developed ulcerative lesions that progressed rapidly and were complicated by Pseudomonas aeruginosa superinfection. Despite an initially negative smear, PCR testing of the skin lesion confirmed the presence of CL. Antifungal therapy with fluconazole led to clinical improvement; treatment was ongoing at the time of publication. Discussion: These cases highlight the diagnostic and therapeutic challenges associated with CL in non-endemic settings. The varied clinical evolution underscores the importance of considering leishmaniasis in the differential diagnosis of chronic, non-healing cutaneous lesions, particularly in patients with a travel history to endemic regions. Conclusions: Increased awareness among clinicians, supported by accurate diagnostic tools and public health surveillance, is essential to identify and manage imported leishmaniasis. Given the absence of a licensed vaccine and the growing risk of vector expansion in Eastern Europe, these cases support the WHO’s inclusion of leishmaniasis among the priority neglected tropical diseases targeted for intensified global control efforts by 2030. Full article

Leishmaniasis by Leishmania infantum has a zoonotic transmission cycle involving an increasing number of mammalian hosts, forming a cooperative network. The sand fly feeding on livestock is evidenced, but clinical confirmation regarding their infection is limited. We aimed to evaluate Leishmania seroprevalence in livestock to assess its impact on leishmaniasis epidemiology in an endemic area located in the Mediterranean region. A cross-sectional serological study screened livestock exposure to L. infantum and risk factors in Southern Spain. A total of 864 serum samples of clinically healthy sheep, goats, cattle, and pigs were examined by an indirect fluorescence antibody test, using a 1/80 cut-off titre to minimize cross-reactions. Global seroprevalence was 10.8%: 21.6% cattle, 15.4% sheep, 7.3% goats, and 0.6% pigs. Statistically significant differences in positive detection were observed among species (p < 0.001) and natural regions (p < 0.001). High positive reactions in cattle, goats, and sheep suggest livestock exposure to Leishmania spp. and potential asymptomatic infection. Livestock presence in biotopes could promote a dilution effect, reducing human leishmaniasis incidence. Further investigation is needed to confirm livestock roles in leishmaniasis maintenance and transmission. Full article

Parasitic diseases represent a severe global burden, with current treatments often limited by toxicity, drug resistance, and suboptimal efficacy in chronic infections. This review examines the emerging role of triazole-based compounds, originally developed as antifungals, in advanced antiparasitic therapy. Their unique structural properties, particularly those of 1,2,3- and 1,2,4-triazole isomers, facilitate diverse binding interactions and favorable pharmacokinetics. By leveraging innovative synthetic approaches, such as click chemistry (copper-catalyzed azide–alkyne cycloaddition) and structure-based design, researchers have repurposed and optimized triazole scaffolds to target essential parasite pathways, including sterol biosynthesis via CYP51 and other novel enzymatic routes. Preclinical studies in models of Chagas disease, leishmaniasis, malaria, and helminth infections demonstrate that derivatives like posaconazole, ravuconazole, and DSM265 exhibit potent in vitro and in vivo activity, although their primarily static effects have limited their success as monotherapies in chronic cases. Combination strategies and hybrid molecules have demonstrated the potential to enhance efficacy and mitigate drug resistance. Despite challenges in achieving complete parasite clearance and managing potential toxicity, interdisciplinary efforts across medicinal chemistry, parasitology, and clinical research highlight the significant potential of triazoles as components of next-generation, patient-friendly antiparasitic regimens. These findings support the further optimization and clinical evaluation of triazole-based agents to improve treatments for neglected parasitic diseases. Full article

Visceral leishmaniasis (VL) is a severe parasitic disease caused by Leishmania spp., with a significant impact on pediatric populations, particularly in endemic regions. The diagnosis of VL in children requires a high index of suspicion, as clinical manifestations—such as prolonged fever, hepatosplenomegaly, and pancytopenia—overlap with other infectious and hematologic diseases. While serological and molecular tests aid in detection, bone marrow aspiration remains the gold standard for definitive diagnosis. In this case series, we describe five pediatric patients diagnosed with VL in Italy, emphasizing the importance of a timely and accurate diagnostic approach. Liposomal amphotericin B (LAmB) is the first-line treatment in Southern Europe due to its high efficacy and reduced toxicity. Our patients received a standard regimen of 3 mg/kg daily for five days, plus an additional dose on day 10, leading to rapid clinical improvement. However, some cases required supportive care, such as red blood cell transfusions, particularly in patients with co-infections. Despite being a neglected disease, VL is re-emerging in Europe, influenced by climate change, increased pet ownership, and migration from endemic regions. Prevention strategies focus on vector control, canine vaccination, and public health awareness. The global rise in pediatric VL highlights the need for improved surveillance, access to affordable treatments, and the development of effective vaccines to mitigate the disease burden in both endemic and non-endemic areas. Full article

Plants and plant-derived natural products have been used in traditional medicine for centuries. The lack of effective therapies in the modern world to address several diseases, the increasing development of drug resistance, and the growing interest in herbal medicine have led to the study and resurgence of natural ancient remedies. A. annua, commonly known as sweet wormwood or sweet annie, is a medicinal plant widely known for its antimalarial properties. In the past decade, increasing evidence has demonstrated the plant’s broad therapeutic potential, including antitumoral, antimicrobial, antiparasitic, metabolic, and immunomodulatory effects, among others. While most research has focused on human health, there is growing interest in exploring the veterinary applications of A. annua and its bioactive compounds, particularly artemisinin. This review aims to summarize the current knowledge on the beneficial effects of A. annua, artemisinin, and other compounds in animal health. It also highlights the need for standardizing A. annua metabolites to ensure the reliability and efficacy of treatments and explores how artemisinin works in synergy with other molecules present in A. annua. Full article

Background/Objectives: Nifuroxazide (Nfz) is a drug that has been used as a scaffold for designing antimicrobial and antiparasitic agents. This study aimed to synthesize and evaluate in vitro of Nfz and twenty-five 4-hydroxybenzhydrazone derivatives as potential anti-Trypanosoma cruzi, anti-Leishmania mexicana, and anti-Mycobacterium tuberculosis agents. Methods: The compounds were synthesized by condensing 4-hydroxybenzhydrazide with appropriate aldehydes in acidic conditions and structurally confirmed by spectroscopic techniques. All compounds were evaluated in vitro against T. cruzi strains (NINOA and A1), L. mexicana (M379 and FCQEPS strains), and M. tuberculosis (H37Rv strain), followed by enzymatic assays against T. cruzi cysteine proteases. Results: Compound Nfz-24 (IC₅₀ = 6.8 μM) had better trypanocidal activity than the reference drugs benznidazole (IC₅₀ > 30 μM) and nifurtimox (IC₅₀ > 7 μM) against the NINOA strain, and Nfz-8 (IC₅₀ = 7.2 μM) was the compound most active against the A1 strain with a high inhibition of T. cruzi cysteine proteases (IC₅₀ = 4.6 μM) and low cytotoxic effects (CC₅₀ >100 μM). On the other hand, compound Nfz-5 (IC₅₀ = 5.2 μM) had a 25-fold better leishmanicidal effect than glucantime (IC₅₀ > 125 μM) against the L. mexicana M379 strain, and compound Nfz-13 had the best leishmanicidal effects (IC₅₀ = 10.2 μM) against the FCQEPS strain. Finally, Nfz, Nfz-1, and Nfz-2 had minimum inhibitory concentration (MIC) values of 12.3, 5.1, and 18.8 μg/mL against M. tuberculosis, respectively. Conclusions: In summary, these results suggest that the compounds Nfz-1, Nfz-2, Nfz-5, Nfz-8, Nfz-10, Nfz-15, Nfz-24, and Nfz-25 are candidates for further studies to develop new and more potent anti-T. cruzi, anti-leishmaniasis, and anti-M. tuberculosis agents. Full article

Leishmaniasis is a complex neglected tropical disease that impacts public health, particularly in resource-limited populations where access to accurate and timely diagnosis is often limited. Current diagnostic methods, primarily relying on microscopy, suffer from low sensitivity and specificity, hindering effective case management and disease control. The objective of this study was to validate a novel real-time PCR assay targeting the conserved Hsp20 gene for the detection of Leishmania spp. We evaluated the performance of the method using two distinct detection systems, such as SYBR Green and TaqMan probes, against a diverse panel of 225 clinical samples confirmed to have the disease. The real-time PCR targeting Hsp20 using SYBR Green demonstrated a sensitivity of 88% (95% CI: 83.53–92.47) and 100% specificity. Meanwhile, the TaqMan probe demonstrated a lower sensitivity of 47% (95% CI: 29.53–64.92). The high sensitivity and robust performance of the real-time PCR using SYBR Green establish its potential as a valuable diagnostic tool, particularly useful in endemic regions where rapid and accurate diagnosis is critical for timely treatment and effective disease control. Full article

Cutaneous leishmaniasis (CL) is a significant public health concern that affects many countries. This disease is caused by the protozoan parasite Leishmania spp. and is transmitted through the sandflies from the genus Phlebotomus and Lutzomyia. The clinical manifestations of CL can vary, often leading to challenges in accurate diagnosis and treatment. In 2022, a 51-year-old male patient presented to a tertiary care hospital in Puducherry, India, with progressively worsening facial lesions and granulomatous plaques. The patient had recently returned from Saudi Arabia, where he likely contracted the infection. Before he visited the tertiary care hospital in Puducherry, the patient had been misdiagnosed and treated for conditions such as Erysipelas and Acute Cutaneous Lupus Erythematosus (ACLE), highlighting the diagnostic challenges associated with CL. Skin scrapings from the patient were subjected to real-time PCR, confirming Leishmania spp.’s presence. Cytological examinations revealed the amastigote-like structures within macrophages, thereby establishing the identity of the parasite. For precise species-level identification, PCR-Restriction Fragment Length Polymorphism (PCR-RFLP) and Sanger sequencing of the Internal Transcribed Spacer-1 (ITS-1) region were performed. Molecular techniques confirmed the infection as being caused by Leishmania tropica. Following the accurate diagnosis, the patient was successfully treated with Liposomal Amphotericin B, a treatment known for its efficacy against Leishmania infections. This case underscores the critical importance of considering cutaneous leishmaniasis in the differential diagnosis of travelers returning from endemic areas who present with dermatological manifestations. The initial misdiagnosis and inappropriate treatment highlight the need for heightened clinical awareness and the utilization of advanced diagnostic tools for accurate identification. Effective and timely treatment, as demonstrated in this case, is essential for the management and control of the disease. This report emphasizes the necessity of vigilance among healthcare providers to recognize and appropriately address imported cases of cutaneous leishmaniasis. Full article

American cutaneous leishmaniasis (ACL), caused by Leishmania (Leishmania) amazonensis and L. (Viannia) braziliensis, presents a wide spectrum of clinical and immunopathological manifestations, ranging from localized cutaneous leishmaniasis (LCL) to severe forms like anergic diffuse cutaneous (ADCL) and mucocutaneous leishmaniasis (MCL). Despite evidence of the immune response’s complexity, the role of inflammasomes in disease severity and parasite persistence remains unclear. We investigated the transcriptomic and immunopathological profiles of inflammasome components in patient lesions across the clinical spectrum. Genes such as NLRP3, AIM2, NLRP12, NLRC4, CASP1, CASP5, GSDMD, and IL1B and all evaluated proteins, showed higher expression in ACL compared to healthy controls. Distinct inflammasome activation patterns were observed: MCL, the hyperreactive form, showed elevated NLRP3, AIM2, and IL-1β, indicating an intensified inflammatory environment. ADCL, the hyporeactive form, displayed increased NLRP12 and NLRC4 expression with reduced GSDMD. Localized forms showed transitional profiles, highlighting ACL’s multifactorial pathogenesis. These findings advance our understanding of inflammasome mechanisms in ACL, identifying potential therapeutic targets to modulate inflammation and improve management. Full article

Background/Objectives: In Brazil, Leishmania braziliensis is the main etiological agent of cutaneous leishmaniasis and represents an important public health problem. The actual pharmacotherapy of leishmaniasis has several disadvantages, making the development of new therapeutic options essential. The present study aimed to carry out the bioprospecting and selection of products of Amburana cearensis, including extracts and active principles with a leishmanicidal effect and to evaluate its possible mechanism of action. Methods: A dry extract of A. cearensis (DEAC) was characterized by HPLC, with the following active markers: coumarin (CM), amburoside A (AMR), and vanillic acid (VA). The leishmanicidal effect of DEAC was assessed, and the in vitro inhibitory action of the phenolic fraction, including CM, AMR, and VA, on promastigote and amastigote forms were determined. Results: CM showed the best reductions (maximal inhibition: 57%) of the promastigote form of L. braziliensis, followed by the plant extract (40% inhibition) and other test drugs (maximal reduction: 29%). The treatment of macrophages infected by L. brasiliensis with CM (10 μg/mL) reduced the intracellular parasite load (amastigote form, maximal reduction: 50%), increased the production of nitric oxide, TNF-α, IL-12, and IL-10, and decreased the production of IL-4. These effects were not related to cytotoxicity (MTT test). Glucantime (4 mg/mL, standard drug) reduced the amastigote form by 65%. Conclusions: CM showed promising leishmanicidal activity against both forms of L. brasiliensis, and this effect seems to be associated, at least in part, to its immunomodulatory action by tilting the Th1/Th2 imbalance in favor of Th1. Full article

Tegumentary leishmaniasis (TL) presents two main clinical forms: cutaneous (CL) and mucosal (ML) leishmaniasis affecting skin and nasopharyngeal mucosa. Due to parasite localization through disease stages, recruitment of T cells expressing chemokine receptors and their ligands will influence the generated host responses. The aim of this work was to characterize differential profiles of T cells expressing chemokine receptors and their plasma ligands by flow cytometry and ELISA. CL patients showed increased numbers of effector memory CD4⁺ T cells expressing skin homing receptors (CLA, CCR4), with the reversion of this effector phenotype observed after achieving clinical recovery. Meanwhile, ML patients showed higher frequencies of effector memory/terminal effector CD4⁺ and CD8⁺ T cells expressing chemokine receptors directed to skin (CLA, CCR4, CCR10) and mucosal (CCR6) tissues. Additionally, we reported that plasma amounts of ligands (CCL17, CCL20) vary according to the clinical form of TL. Finally, we demonstrated the ability of Leishmania spp. to modulate chemokine production (CCL17) in vitro. This work highlights the effector T cell response directed to skin and mucosal tissues in TL, emphasizing the role of cytotoxic functions in ML. The studied chemokine receptors could contribute to predicting disease progression and guiding future studies targeting relevant receptors to diminish pathogenic effector functions. Full article

Neglected tropical diseases (NTDs), including Chagas disease, human African trypanosomiasis (HAT), leishmaniasis, and malaria, remain a major global health challenge, disproportionately affecting low-income populations. Current therapies for these diseases suffer from significant limitations, such as reduced efficacy, high toxicity, and emerging parasite resistance, highlighting the urgent need for new therapeutic strategies. In response, substantial efforts have been directed toward the synthesis of new molecules with improved potency, selectivity, and pharmacokinetic profiles. However, despite many of these compounds exhibiting favorable ADMET (absorption, distribution, metabolism, excretion, and toxicity) profiles and strong in vitro activity, their translation into in vivo models remains limited. Key challenges include the lack of investment, the absence of fully representative experimental models, and difficulties in extrapolating cell-based assay results to more complex biological systems. In this review, we analyzed the latest advancements (2019–2024) in the development of these compound classes, correlating predictive parameters with their observed biological activity. Among these parameters, we highlighted the partition coefficient (LogP), which measures a compound’s lipophilicity and influences its ability to cross biological membranes, and Caco-2 cell permeability, an in vitro model widely used to predict intestinal drug absorption. Additionally, we prioritized the most promising molecules and structural classes for pharmaceutical development, discussing structure–activity relationships (SARs) and the remaining challenges that must be overcome to enable the clinical application of these compounds in the treatment of NTDs. Full article

Caffeic acid phenethyl ester (CAPE) is a polyphenol produced by many plants and is found in red and green propolis. Here, we evaluated the antileishmanial activity of this natural product against Leishmania amazonensis. CAPE exhibited IC₅₀ values of 8.07 µM (95% CI, 6.79–9.62 µM) and 13.51 µM (95% CI, 10.71–17.16 µM) against L. amazonensis promastigotes and intracellular amastigotes, respectively. Additionally, CAPE inhibited L. amazonensis arginase in a non-competitive manner with a K_i value of 1.51 ± 0.04 µM. These results highlight the potential of CAPE as a promising lead compound for developing new therapies against leishmaniasis. Full article

Cutaneous leishmaniasis (CL) is a vector-borne infection caused by protozoan parasites belonging to the genus Leishmania. CL is an emerging global health concern due to increasing migration, travel, and climate change. Traditionally, it was confined to endemic regions such as the Americas, the Middle East, and Central Asia; however, it is now spreading to non-endemic areas. Climate change has further contributed to the expansion of sandfly habitats, increasing CL transmission risk in previously unaffected areas. Healthcare providers in non-endemic regions often misdiagnose CL, delaying treatment and morbidity. Diagnosis remains challenging due to the need for species-specific identification, while treatment is limited by cost, availability, and personnel expertise. This review explores the epidemiology, clinical presentation, diagnostic challenges, and management of CL in the context of global mobility. It highlights rising CL cases in refugee settlements, particularly in Lebanon and Jordan, due to poor living conditions, inadequate vector control, and healthcare barriers. While there have been advances in systemic and topical therapies, access in refugee and resource-poor settings remains a barrier. Addressing the global burden of CL requires improved surveillance, healthcare provider training, and increased awareness. By enhancing global collaboration and policy changes, public health efforts can mitigate the expanding impact of CL. Full article