Cutaneous Leishmaniasis Research Articles

Comparative assessment of macrophage responses and antileishmanial efficacy in dynamic vs. Static culture systems utilizing chitosan-based formulations.

The discovery of novel anti-leishmanial compounds is essential due to the limitations of current treatments and the lack of new drugs in development. In this study, we employed the Quasi Vivo 900 medium perfusion system (QV900, Kirkstall Ltd, UK) to simulate physiological fluid flow, allowing us to compare macrophage responses and therapeutic outcomes under dynamic versus static conditions. After 24 hours, phagocytosis and macropinocytosis decreased in all cell types under flow conditions compared to static cultures. Under slow (1.45 x 10-9 m/s) and faster (1.23 x 10-7 m/s) flow conditions ((simulating in vivo lymphatic flow), phagocytosis decreased by around 42.55% and 56.98% in peritoneal macrophages (PEMs), 42.21% and 56.11% in bone marrow-derived macrophages (BMMs), and 49.75% and 63.32% in THP-1 cells, respectively. Similarly, macropinocytosis decreased by approximately 40.7% and 62.2% in PEMs, 34.8% and 60.9% in BMMs, and 33.3% and 59.3% in THP-1 cell line under this same conditions. In this study, we further assessed the impact of medium perfusion on drug efficacy and macrophage functions using a Leishmania major amastigote-macrophage assay. We evaluated the performance of both standard and nanoparticle-based drug formulations within dynamic and static culture systems. After 72 hours of medium perfusion, chitosan solution, blank chitosan-sodium tripolyphosphate (TPP) nanoparticles, and amphotericin B (AmB)-loaded chitosan-TPP nanoparticles exhibited a statistically significant reduction in antileishmanial activity by approximately 30-50% under slow flow conditions and 60-80% under faster flow conditions. In comparison, pure AmB showed a 40% decrease in efficacy at slow flow and a 67% decrease at faster flow, both statistically significant. These results highlighted the importance of considering fluid flow dynamics in in vitro studies for a more accurate simulation of in vivo conditions, potentially leading to better therapeutic strategies for cutaneous leishmaniasis (CL).

Prevalence of and risk factors for cutaneous leishmaniasis in East Africa: a systematic review and meta-analysis

BackgroundCutaneous leishmaniasis (CL) is a neglected skin disease that affects millions of people worldwide. Its visible symptoms and impact on physical appearance can lead to social rejection, stigma, and discrimination for patients with cutaneous leishmaniasis. It is a public health and social problem in East Africa. However, there was no conclusive evidence on the pooled prevalence of cutaneous leishmaniasis in East Africa. Thus, we conducted a systematic review and meta-analysis to examine the current evidence on the burden of cutaneous leishmaniasis in East Africa.ObjectiveThe main purpose of this study was to estimate the pooled prevalence of cutaneous leishmaniasis and its risk factors in East Africa.MethodsThis systematic review and meta-analysis were conducted using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses and Stata software version 17. A forest plot and a random effects model were used to estimate the pooled prevalence of CL with a 95% confidence interval (CI) and heterogeneity of articles, respectively.ResultsA total of 221,365 study participants were included in the review. Based on the results, the forest plot was explained by I2 = 99.99% at p < 0.05. The prevalence of cutaneous leishmaniasis in primary studies ranged from 0.73% to 79.10%. The pooled prevalence of CL in East Africa was found to be 22.57% with a 95% CI (14.36, 30.78). The effect size showed statistically significant subgroup effects for study design, study setting, sample size, clinical forms of CL, year of publication, and study period at p < 0.05 according to the subgroup analyses.Conclusion and recommendationsThe pooled prevalence of cutaneous leishmaniasis in East Africa was high. This underscores the urgent need for targeted public health initiatives to mitigate the impact of this disease on affected populations. Collaborative efforts between governments, health organizations, and communities are crucial for the effective management and control of CL in the East Africa region.Systematic review registrationhttps://www.crd.york.ac.uk, identifier CRD42024576017.

Leishmaniasis in deployed military populations: A systematic review and meta-analysis

Leishmaniasis affects military personnel deployed to endemic areas following exposure to sand flies infected with the protozoa Leishmania. This systematic review and meta-analysis of data specific to military populations aims to identify knowledge gaps to mitigate sand fly exposure and Leishmania transmission during deployments. The review was registered on PROSPERO (CRD42023463687). Random-effects meta-analyses and narrative synthesis were performed. Thirty-six studies were included, most of which reported on cutaneous leishmaniasis (CL), showing a mean cumulative incidence of 10% (95% CI: 5–16), suggesting higher rates in the Eastern Mediterranean region (14% [95% CI: 12–16]) compared to the African region (8%) and American region (9%). Asymptomatic Leishmania infection had a cumulative incidence of 11% (95% CI: 6–17), with higher rates in Eastern Mediterranean countries (20% [95% CI: 14–25]). Diagnosis involved parasitological, serological, and molecular methods, with L. (L) mexicana and L. (V.) braziliensis identified as the predominant CL pathogens in deployed troops in the Americas. Visceral leishmaniasis cases were less frequent, all reported from the Eastern Mediterranean and associated with the Leishmania donovani/infantum complex; whereas CL cases in the Old World were due predominantly to L. major and L. tropica. Regular use of long-lasting insecticidal nets to mitigate sand fly exposure demonstrated high potential effectiveness than other reported personal protective measures (PPMs) which yielded mixed or inconclusive results. In summary, the systematic review revealed the substantial variability between study designs and statistical integrity. There is need for more consistent and robustly designed studies including well-define controls and replication. Future studies would be advised to explore the long-term effectiveness and practicality of PPMs, both individually and in combination, across diverse deployment settings.

Advancing AI-driven thematic analysis in qualitative research: a comparative study of nine generative models on Cutaneous Leishmaniasis data

BackgroundAs part of qualitative research, the thematic analysis is time-consuming and technical. The rise of generative artificial intelligence (A.I.), especially large language models, has brought hope in enhancing and partly automating thematic analysis.MethodsThe study assessed the relative efficacy of conventional against AI-assisted thematic analysis when investigating the psychosocial impact of cutaneous leishmaniasis (CL) scars. Four hundred forty-eight participant responses from a core study were analysed comparing nine A.I. generative models: Llama 3.1 405B, Claude 3.5 Sonnet, NotebookLM, Gemini 1.5 Advanced Ultra, ChatGPT o1-Pro, ChatGPT o1, GrokV2, DeepSeekV3, Gemini 2.0 Advanced with manual expert analysis. Jamovi software maintained methodological rigour through Cohen’s Kappa coefficient calculations for concordance assessment and similarity measurement via Python using Jaccard index computations.ResultsAdvanced A.I. models showed impressive congruence with reference standards; some even had perfect concordance (Jaccard index = 1.00). Gender-specific analyses demonstrated consistent performance across subgroups, allowing a nuanced understanding of psychosocial consequences. The grounded theory process developed the framework for the fragile circle of vulnerabilities that incorporated new insights into CL-related psychosocial complexity while establishing novel dimensions.ConclusionsThis study shows how A.I. can be incorporated in qualitative research methodology, particularly in complex psychosocial analysis. Consequently, the A.I. deep learning models proved to be highly efficient and accurate. These findings imply that the future directions for qualitative research methodology should focus on maintaining analytical rigour through the utilisation of technology using a combination of A.I. capabilities and human expertise following standardised future checklist of reporting full process transparency.

High glucose heightens vulnerability to Leishmania braziliensis infection in human macrophages by hampering the production of reactive oxygen species through TLR2 and TLR4.

Diabetes increases susceptibility to infections, including Leishmania braziliensis (Lb). Our group previously demonstrated that diabetic patients with cutaneous leishmaniasis (CL) take longer to heal lesions compared to non-diabetics. Since macrophages play a critical role in CL pathogenesis, we investigated how high glucose levels impact their response during Lb infection. Macrophages cultured in high glucose conditions showed increased parasite load than those in normal glucose conditions. The production of inflammatory mediators was similar between glucose conditions, but basal reactive oxygen species (ROS) production was elevated under high glucose conditions and remained unchanged after Lb infection, indicating glucose-induced oxidative stress does not control the parasite. In contrast, macrophages in normal glucose conditions, exhibited increased ROS production only after infection. Additionally, high glucose reduced TLR2 and TLR4 expression, which was also observed after Lb infection. TLR2/4 inhibition increased Lb infection in normal glucose conditions, mediated by TLR-dependent ROS production. However, this mechanism was absent under high glucose conditions, where elevated basal ROS production appeared TLR-independent. Biopsies from diabetic CL patients corroborated these findings, showing decreased TLR2 and TLR4 expression compared to non-diabetics. These findings suggest that high glucose levels induce oxidative stress and reduces TLR expression, impairing macrophage functions and rendering them less effective at controlling Lb infection.

Borderline Disseminated (Intermediate) Cutaneous Leishmaniasis: A Case-Based Approach to Diagnosis and Clinical Management in Pediatric Population

Background: Cutaneous leishmaniasis (CL) is a neglected tropical disease with diverse clinical manifestations, ranging from localized CL to severe forms such as diffuse CL and mucocutaneous leishmaniasis. Borderline disseminated CL (BDCL), an intermediate form, is characterized by multiple disseminated lesions and poses unique diagnostic and therapeutic challenges, especially in pediatric patients. This study explores pediatric BDCL to better understand its clinical presentation, diagnostic approaches and treatment outcomes. Methods: We report 4 pediatric cases of BDCL from Panama, identified through polymerase chain reaction and histopathological analysis. Species identification utilized polymerase chain reaction and heat shock protein 70 gene sequencing. Treatment included amphotericin B, meglumine antimoniate and miltefosine, with follow-up evaluations assessing lesion progression and treatment outcomes. Results: All patients exhibited multiple disseminated ulcerative and nodular lesions, with some involving mucosal sites. Species identification confirmed Leishmania guyanensis and Leishmania panamensis as causative agents. Two patients received meglumine antimoniate, achieving complete lesion resolution. Due to better tolerability, miltefosine was used in the remaining 2 patients, resulting in slower but complete lesion resolution over time. Amphotericin B demonstrated limited efficacy. Conclusions: Pediatric BDCL presents significant diagnostic and therapeutic challenges due to variable immune responses, clinical presentations and species-related treatment resistance. While meglumine antimoniate and miltefosine showed promising results, amphotericin B was less effective. Further research is needed to establish optimized treatment protocols for pediatric BDCL, considering species-specific responses and pharmacokinetic and pharmacodynamic differences in children.

Nanoemulgel mediated enhanced skin curcumin penetration/retention for local treatment of cutaneous leishmaniasis: in vitro and in vivo assessment

Background Skin delivery of a therapeutically effective drug is imperative for local cutaneous leishmaniasis (CL) treatment. Objective This study aimed to formulate, optimize, and characterize curcumin-loaded nanoemulgel for enhanced skin drug retention to treat CL locally. Methods Nanoemulsions were prepared by high-speed homogenization, characterized, and optimized for size, PDI, zeta potential, stability, morphology, drug contents, encapsulation efficiency, in vitro drug release, antileishmanial activity, and cell viability. The optimized nanoemulsion (C3) was then incorporated into a carbopol-based gel and evaluated for pH, viscosity, spreadability, and in vitro drug release. Both formulations were then assessed for ex-vivo and in vivo skin permeation/retention, and pharmacokinetic analysis. Results All nanoemulsion formulations had size in nano range with negative surface charge, homogeneously distributed, with spherical droplet geometries, where C3 being highly stable, had good encapsulation efficiency and drug contents (85 ± 5.4 and 68 ± 3.2%), released 90% of drug within 4 h, while C3 gel released the drug significantly sustained up to 46% in 24 h. The C3 formulation demonstrated significant in vitro antileishmanial activity across all tested concentrations, while the IC50 value against NIH3T3 fibroblasts was 0.6202 mM (Log IC50: 2.7, R 2: 0.98). The C3 gel showed significantly low skin permeation (341.7 ± 43.6 and 52.6 ± 8.9 µg) with significantly higher skin drug retention (129.5 ± 16.7 and 190.2 ± 33.4 µg) ex-vivo and in vivo, with significantly lower C max, AUC0- t , and AUC0-∞. Conclusion These results suggested that curcumin nanoemulgel could be an effective alternative strategy for treating CL locally.

Spatial and Temporal Modeling of Cutaneous Leishmaniasis in Yazd Province, Iran: Based on the Geographic Information System (GIS)

Background: Cutaneous Leishmaniasis (CL) remains a significant health concern in Iran, particularly in specific areas of Yazd province in central Iran. This investigation was conducted with the aim of presenting the spatial and temporal modeling of CL in Yazd province. Methods: This was an ecological study, using data from the health department of Yazd province. The data for the cases of CL during 2004-2013 were extracted and merged into Arc Geographic Information System (GIS) 9.3 software. Cochran-Armitage test, Choropleth Map, Hot-Spot Analysis, and High/Low Clustering analysis were used to determine time trend, distribution of disease, hot-spots, and possible abnormal clustering, respectively. Results: The results indicated a decreasing trend of incidence of CL from 199 to 29.2 cases (per 100,000 populations) during 2004-2013. The findings of the choropleth map showed that cities of Khatam and Abarkuh had a high incidence of CL. The results of the analysis of hot spots showed that during 2004-2008, cities of Yazd and Saduq were classified as cold spots of disease and the difference with neighboring cities was statistically significant (p = 0.031). No hot spots were obtained. In the cluster analysis, no results were obtained to separate high or low level. Conclusion: Maps of spatial distribution of CL were generated to facilitate the decision-making capacity at provincial health department. These results showed that in regions of Yazd province neighboring Fars, Isfahan and Kerman provinces, there was a high risk of disease. Hence, in these areas, preventive strategies can be focused and pursued more purposefully.

Residential environment, human behavior and socio-economic status in transmission of cutaneous leishmaniasis in central Iran

Cutaneous leishmaniasis (CL) is a vector-borne disease occurred through the bite of sandflies. Due to impact of environmental factors on the disease, this study aimed to assess the association between socio-economic status (SES), domestic, peri-domestic, and human behavior factors and the transmission of CL in Isfahan province in central Iran. This case-control study was conducted from March 2021 till March 2022 on 322 participants. Cases and controls were selected among CL patients and people with no history of leishmaniasis respectively by cluster random sampling method in a ratio of 1:1. A semi-structured questionnaire was completed for each patient and control. Multiple logistic regression models and odds ratio (OR) estimator were used to assess the relationships. In final model after adjusting for potential confounders the variables “moderate social and economic status”, “individuals who rest outside at night in summer”, “the presence of animals near the residence” and also the variables related to distance of homes to gathering places of insects remained significant. Adults and individuals who use preventive measures such as insecticides, insect repellent pen and sleeping the mosquito net significantly decrease the risk of disease. Our findings showed that human behavior and peri-domestic factors have most effects on transmission of leishmaniasis.

Occurrence of leprosy among patients with cutaneous leishmaniasis in a hyperendemic area for both diseases

Occurrence of leprosy among patients with cutaneous leishmaniasis in a hyperendemic area for both diseases

Community health of knowledge and attitude towards cutaneous leishmaniasis among rural residents in Esfarayen county, North Khorasan province of Iran

Community health of knowledge and attitude towards cutaneous leishmaniasis among rural residents in Esfarayen county, North Khorasan province of Iran

In vitro and in vivo leishmanicidal and trypanocidal activities of isoflavans from Tabebuia chrysantha (Jacq.) G. Nicholson timber by-products.

In vitro and in vivo leishmanicidal and trypanocidal activities of isoflavans from Tabebuia chrysantha (Jacq.) G. Nicholson timber by-products.

Pilot evaluation of thymol-loaded chitosan gel as a complementary topical therapy for cutaneous leishmaniasis

Pilot evaluation of thymol-loaded chitosan gel as a complementary topical therapy for cutaneous leishmaniasis

Analysis of the abandonment of cutaneous leishmaniasis treatment in the southern Amazon region of Brazil

Analysis of the abandonment of cutaneous leishmaniasis treatment in the southern Amazon region of Brazil

Local necrosis induced by intralesional treatment with amphotericin B- deoxycholate.

Local necrosis induced by intralesional treatment with amphotericin B- deoxycholate.

Can cutaneous leishmaniasis provoke a resurgence of kala-azar in the Indian subcontinent?

BackgroundThe ongoing kala-azar elimination program in Nepal is based on the assumption of anthroponotic transmission of the protozoan parasite Leishmania donovani. This parasite species was recently also found in lesions of cutaneous leishmaniasis (CL) cases, which are increasingly reported mainly from western Nepal. The question whether or not CL causing L. donovani can also contribute to VL is a crucial one to answer if the success of the VL elimination initiative in the Indian subcontinent is to be sustained, though evidence on sub-species level genomic differences between CL and VL causing L. donovani is currently lacking. This study aims to provide a genomic comparison of L. donovani parasites currently causing CL in Nepal with previously described L. donovani isolates.MethodsA case series study was carried out in sentinel dermatological sites in Western Nepal. Skin punch biopsies were collected from clinically suspected CL lesions. Molecular tests based on the ribosomal RNA gene array were used to detect and characterize the Leishmania parasites.ResultsLeishmania parasites detected in 26 cutaneous leishmaniasis patients were identified as L. donovani. Importantly, their analyzed DNA sequences were identical, and shared with previously documented sequences from both cutaneous and visceral disease-causing parasites in Nepal, India and Bhutan.ConclusionsOur study suggests that CL and VL are caused by similar if not identical L. donovani parasite strains, though additional sequencing is required to corroborate this finding. If confirmed, cutaneous lesions could act as a kala-azar parasite reservoir, which would have important implications for the kala-azar elimination program.

Ecological Dynamics of Sand Flies (Diptera: Psychodidae) in Two Leishmaniasis Endemic Foci in Sri Lanka

Background: Leishmaniasis has emerged as a significant global public health concern and has been notable in Sri Lanka since 1992, particularly in the Anuradhapura district, where Cutaneous Leishmaniasis is prevalent. The disease is caused by the Leishmania parasite, which is transmitted by sand flies of the genus Phlebotomus. Objective: This study compared the diversity, dominance, and density of sandfly species in selected locations within the Anuradhapura and Kegalle districts.Methods: Sand flies were collected monthly from January to March 2024 from locations identified through patient records from the Regional Epidemiologist’s unit. Collection was conducted using cattle-baited traps (CBT), and identification was performed morphologically and through DNA analysis. Ecological indices, includ-ing Simpson’s Dominance Index for species dominance and Shannon’s diversity index for species diversity, were calculated using the collected data.Results: A total of 154 sandflies were collected from ten locations in both areas. Among the collected samples, 87.6% (n=135) were P. argentipes and 5.19% (n=8) were P. stantoni, both of which belong to the genus Phle-botomus. Additionally, 7.4% (n=11) were Sergentomiya zelanica belonging to the genus Sergentomiya. P. ar-gentipes predominantly dominates locations in the Anuradhapura district, where Simpson’s dominance index is one (D=1), highlighting its high-risk status. In contrast, the Kegalle district showed higher species diversity with uneven distribution patterns. The Shannon Diversity Index reflected the highest diversity in Kegalle (H=0.6365), likely due to multiple species assemblages and ecological complexity.Conclusions and Recommendations: This comparative study underscores the importance of understanding sandfly population dynamics for targeting integrated vector control strategies. Tailored vector control is essential to prevent the annual emergence of new endemic foci of leishmaniasis in Sri Lanka. This study also emphasizes the integration of environmental, entomological, and epidemiological approaches for effective leishmaniasis control in Sri Lanka.

EPIDEMIOLOGY AND RISK FACTORS OF VECTOR BORNE DISEASE (CUTANEOUS LEISHMANIASIS)

Background: Cutaneous leishmaniasis (CL) is a vector-borne disease caused by Leishmania parasites, transmitted by infected sandflies. It is endemic in various regions of Pakistan, including Punjab, where environmental and socioeconomic conditions contribute to its persistence. Despite its widespread prevalence, epidemiological data remain limited. Identifying key demographic, occupational, and socioeconomic factors associated with CL is essential for developing targeted public health interventions and improving disease control strategies. Objective: This study aimed to assess the prevalence of CL in Punjab, Pakistan, and evaluate its association with gender, occupation, and socioeconomic status to identify high-risk groups and inform preventive measures. Methods: A cross-sectional study was conducted from January 2024 to December 2024, analyzing 485 confirmed cases from multiple healthcare centers in Punjab. Data were collected through structured interviews and clinical examinations. Diagnosis was confirmed using microscopic evaluation of stained blood smears and polymerase chain reaction (PCR). Statistical analyses were performed using SPSS 26 to assess associations between CL prevalence and demographic, occupational, and socioeconomic factors. Results: The prevalence of CL varied between 8.0% and 22.0%, with males (57.3%) more affected than females (42.7%). The highest infection rates were observed in rural areas (62.9%) compared to urban regions (37.1%). Occupational distribution showed farmers (22.0%), students (21.0%), and laborers (18.5%) as the most affected groups. Lower socioeconomic areas exhibited higher infection rates, particularly in regions with poor housing conditions, limited healthcare access, and greater vector exposure. Conclusion: The study highlights a strong correlation between CL prevalence and demographic, occupational, and socioeconomic factors. The findings emphasize the need for region-specific interventions, including enhanced vector control, improved housing infrastructure, and targeted health education programs. Implementing preventive strategies, particularly in farming communities and low-income areas, is crucial for reducing disease burden and limiting transmission.

Bioactive Compounds with Leishmanicidal Potential from Helianthus tuberosus and Vernonanthura squamulosa

Leishmaniasis is a neglected tropical disease caused by protozoan parasites of the genus Leishmania. An estimated 700,000 to 1 million new cases occur annually. Current therapies are limited by high toxicity, cost, prolonged treatment period, and rising resistance in endemic regions. The Asteraceae family has emerged as a promising source of bioactive compounds with proven leishmanicidal activity. In this study, the assessment of the antileishmanial activity of Helianthus tuberosus and Vernonanthura squamulosa extracts, the isolation of the sesquiterpene lactones heliangin and glaucolide A, respectively, and the evaluation of the activity of the compounds were conducted. Dichloromethane extracts of H. tuberosus and V. squamulosa were active on Leishmania amazonensis promastigotes, inhibiting the replication of the parasites in 97.2 ± 3.1% and 89.1 ± 1.1%, respectively, at 100 μg/mL. Heliangin was active against promastigotes of L. amazonensis (IC50 = 9.3 μM) and intracellular amastigotes (IC50 = 0.8 μM), while glaucolide A exhibited moderate activity against promastigotes (IC50 = 46.7 μM) and did not show activity against intracellular amastigotes. Based on these results, heliangin was further evaluated in an animal model of cutaneous leishmaniasis using BALB/c mice infected with L. amazonensis. Heliangin (8 mg/Kg), when administered in combination with Glucantime, significantly reduced lesion progression and parasite load compared to the vehicle-treated group (p < 0.001). These findings show that heliangin is a potential candidate for leishmaniasis treatment, especially in combination with therapeutic drugs.

An assessment of interobserver agreement on lesion size, morphology and clinical phenotype in cutaneous leishmaniasis caused by Leishmania aethiopica in Ethiopia

Introduction Cutaneous leishmaniasis (CL) remains a major public health challenge, especially in endemic regions like Ethiopia, where an estimated 40,000 new cases occur annually. Effective treatment evaluation for CL relies on consistent clinical assessments, yet variability in lesion descriptions can complicate reliable outcome measures. Methods We conducted an inter-reliability study of clinicians’ evaluations of CL lesion morphology and size at ALERT Hospital, Addis Ababa. Twelve clinicians independently examined 12 patients with parasitologically confirmed CL, each clinician assessing lesion morphology, size, and severity. Results We found high consistency in reporting major morphological categories (e.g., plaques) but significant variability in secondary features like dyspigmentation and scale, as well as mucosal involvement. Lesion size measurements showed limited variability, suggesting its reliability as a potential measure for future clinical trials. Disparities in severity assessments highlight the need for a standardized scoring system in CL. Discussion Our findings underscore the importance of training for consistent, high-quality clinical evaluations of CL and suggests that lesion size could be a reproducible outcome measure in treatment efficacy trials.