American Tegumentary Leishmaniasis Research Articles

Evaluation of intralesional treatment in american tegumentary leishmaniasis in the amazon region: results and perspectives

Evaluation of intralesional treatment in american tegumentary leishmaniasis in the amazon region: results and perspectives

LEISHMANIOSE TEGUMENTAR AMERICANA EM UMA MICRORREGIÃO DA AMAZÔNIA BRASILEIRA ENTRE 2010-2019

Objective: The study sought to analyze the epidemiological profile of people with American Tegumentary Leishmaniasis (ATL) in the Lake Tucuruí Integration Region, between 2010 and 2019. Methods: Descriptive study, with data obtained from the Health System Notifiable Disease Information System. Results: There were 3,305 patients with ATL distributed in seven cities. Males, aged 15-39 and 40-59 years were the most affected. New cases are the main route of transmission and the most prevalent clinical form is cutaneous leishmaniasis. The cure was shown in four of the seven cities studied. The cities of Itupiranga and Novo Repartimento showed that the rural area is the main area of ​​infection. The urban area was the area of ​​greatest contagion for the cities of Jacundá and Tucuruí. Conclusion: The study for ATL showed that this zoonosis is endemic in this Amazon microregion and it mainly affects male individuals, with low education and aged between 15-39 and 40-59 years.

Self-reporting of hearing loss and tinnitus in the diagnosis of ototoxicity by meglumine antimoniate in patients treated for American tegumentary Leishmaniasis.

American Tegumentary Leishmaniasis (ATL) treatment is based on pentavalent antimonials (Sb5+), but these drugs have been associated to several adverse effects. Hearing loss and tinnitus during treatment with meglumine antimoniate (MA) have already been reported. This study aimed to describe the usefulness of self-reporting of hearing loss and tinnitus in diagnosing MA-induced ototoxicity. A prospective longitudinal study was conducted with 102 patients with parasitological diagnosis of ATL, treated with different MA schemes. The presence of clinical auditory toxicity was defined as the emergence or worsening of self-reporting hearing loss and/or tinnitus during monitoring. Measures of sensitivity, specificity, and the positive and negative predictive value of the patient's self-reporting of hearing loss and tinnitus in relation to the result of the audiometric test (considered the gold standard) were calculated. The age of the evaluated patients ranged from 15 to 81 years, with a median of 41 years, and most were male (73.5%). Seventy-five patients (73.5%) had cutaneous leishmaniasis and 27 (26.5%) mucosal leishmaniasis. Eighty-six patients (84.3%) received intramuscular (IM) treatment and 16 (15.7%) were treated with intralesional MA. During treatment, 18 (17,6%) had tinnitus and 7 (6,9%) had complaint of hearing loss. 53 (52%) patients had cochlear toxicity confirmed by tone threshold audiometry and high frequency audiometry, from which 60% received a dose of 20 mg Sb5+/kg/day (p = 0.015) and 96.2% were treated with IM MA (p = 0.001). Tinnitus has greater specificity and positive predictive value than hearing loss, with a low number of false positives, but with a high false negative value. Although the large number of false negatives suggests that self-report of hearing loss or tinnitus cannot be considered a good screening test for referring the patient to an audiometry, the low number of false positives suggests the need to value the patient's complaint for referral. Otherwise, this study reinforces the importance of audiological monitoring during treatment with MA, especially in those patients with self-reporting of hearing loss or tinnitus when treated with 20 mg Sb5+/kg/day via IM.

Design of Liquid Formulation Based on F127-Loaded Natural Dimeric Flavonoids as a New Perspective Treatment for Leishmaniasis.

Infectious and Parasitic Diseases (IPD) remain a challenge for medicine due to several interconnected reasons, such as antimicrobial resistance (AMR). American tegumentary leishmaniasis (ATL) is an overlooked IPD causing persistent skin ulcers that are challenging to heal, resulting in disfiguring scars. Moreover, it has the potential to extend from the skin to the mucous membranes of the nose, mouth, and throat in both humans and various animals. Given the limited effectiveness and AMR of current drugs, the exploration of new substances has emerged as a promising alternative for ATL treatment. Arrabidaea brachypoda (DC). Bureau is a native Brazilian plant rich in dimeric flavonoids, including Brachydin (BRA), which displays antimicrobial activity, but still little has been explored regarding the development of therapeutic formulations. In this work, we present the design of a low-cost liquid formulation based on the use of Pluronic F127 for encapsulation of high BRA concentration (LF-B500). The characterization techniques revealed that BRA-loaded F127 micelles are well-stabilized in an unusual worm-like form. The in vitro cytotoxicity assay demonstrated that LF-B500 was non-toxic to macrophages but efficient in the inactivation of forms of Leishmania amazonensis promastigotes with IC50 of 16.06 µg/mL. The results demonstrated that LF-B500 opened a new perspective on the use of liquid formulation-based natural products for ATL treatment.

Simple and promising paper-based electrochemical platform for serological detection of American tegumentary leishmaniasis.

American tegumentary leishmaniasis (ATL) is an endemic neglected tropical disease (NTD), its conventional treatment is toxic, slow, and invasive. Rapid diagnosis is crucial for the clinical management of suspected patients, so the development and use of low-cost, miniaturised and portable devices could be the key. This work aimed to develop a simple paper-based electrochemical platform for the serological detection of ATL. Platform was fabricated in Whatman N°1 paper, contains a hydrophobic zone generated by wax printing, two pencil graphite electrodes, and uses specific crude extracts (CA) antigens for ATL immuno-determination. The platform performance was analysed by measuring the relative impedance change for different antigen-antibody combinations. Then, 10 serum human samples previously diagnosed by the gold standard (five positive ATL cases and five non-ATL cases) were evaluated. The platform presented a linear response for the charge transfer resistance (ΔRct) and the interface reactance (ΔXc). Also, optimal working conditions were established (1/60 serum dilution and 180 µg/mL CA concentration). Then, the platform permits to distinguish between ATL and non-ATL (p < 0.05) human serum samples. Our platform could allow the diagnosis, management, and monitoring of leishmaniasis while being an extremely simple and environmentally friendly technology.

Ecological aspects of sand fly fauna (Diptera: Psychodidae, Phlebotominae) of Sumidouro District, State of Rio de Janeiro, Brazil.

Aiming to compare and update the sand fly fauna of Portão de Pedra site, Sumidouro District, Rio de Janeiro State, Brazil, and considering the environmental changes occurred, the biology and ecology of the local sandfly species were examined five years later as a complementary study carried. Captures were made in the cave, surroundings of cave and forest of the region, from 6 p.m. to 6 a.m. Among the 2323 sandflies of eigth species of the Lutzomyia were captured: L. gasparviannai, L. edwardsi, L. tupynambai, L. hirsuta, L. whitmani, L. migonei, L. intermedia, Lutzomyia. sp and one species of the Brumptomyia Kind: B. brumpti. In 2009 and 2010 were collected 1756 samples from ten species of the former genus and two of the second. L. gasparviannai was predominant, in the three collection sites, in both periods. Five species implicated as vectors of Leishmania: L. intermedia, L. whitmani, L. migonei, L. hirsuta and L. davisi have been collected in the area. Poisson regression and ANOVA were used to perform statistical analysis of species most relevant. The record of L. intermedia and a case of American tegumentary leishmaniasis are relevant to the public health of municipality and of state of Rio de Janeiro.

Chlorella vulgaris extract and Imiquimod as new therapeutic targets for leishmaniasis: An immunological approach

The therapeutic regimen for the treatment of American Tegumentary Leishmaniasis (ATL) is targeted at the death of the parasite; therefore, it is essential to develop a treatment that can act on the parasite, combined with the modulation of the inflammatory profile. Thus, the aim of this study was to make an in vitro evaluation of the therapeutic potential of Chlorella vulgaris extract (CV) and Imiquimod for ATL. Selectivity indices (SI) were determined by inhibitory concentration assays (IC50) in L. braziliensis cells and cytotoxic concentrations (CC50) were measured in human cells using the MTT method, based on the CV microalgae extract (IC50 concentrations of 15.63 to 500 µg/mL; CC50 concentrations of 62.5–1000 µg/mL) in comparison with the reference drugs and Imiquimod. The immune response was evaluated in healthy human cells by gene expression (RT-qPCR) and cytokine production (Flow Cytometry). The CV extract (SI = 6.89) indicated promising results by showing higher SI than meglumine antimoniate (SI = 3.44) (reference drug). In all analyses, CV presented a protective profile by stimulating the production of Th1 profile cytokines to a larger extent than the reference drugs. Imiquimod showed a high expression for Tbx21, GATA3, RORc and Foxp3 genes, with increased production only of the TNF cytokine. Therefore, the data highlight the natural extract and Imiquimod as strong therapeutic or adjuvant candidates against ATL, owing to modulation of immune response profiles, low toxicity in human cells and toxic action on the parasite.

MicroRNAs regulating macrophages infected with Leishmania L. (V.) Braziliensis isolated from different clinical forms of American tegumentary leishmaniasis.

Leishmaniasis is an infectious disease caused by protozoa of the genus Leishmania. There are still no vaccines, and therapeutic options are limited, indicating the constant need to understand the fine mechanisms of its pathophysiology. An approach that has been explored in leishmaniasis is the participation of microRNAs (miRNAs), a class of small non-coding RNAs that act, in most cases, to repress gene expression. miRNAs play a role in the complex and plastic interaction between the host and pathogens, either as part of the host's immune response to neutralize infection or as a molecular strategy employed by the pathogen to modulate host pathways to its own benefit. Monocyte-derived macrophages from healthy subjects were infected with isolates of three clinical forms of L. braziliensis: cutaneous (CL), mucosal (ML), and disseminated (DL) leishmaniasis. We compared the expression of miRNAs that take part in the TLR/NFkB pathways. Correlations with parasite load as well as immune parameters were analyzed. miRNAs -103a-3p, -21-3p, 125a-3p -155-5p, -146a-5p, -132- 5p, and -147a were differentially expressed in the metastatic ML and DL forms, and there was a direct correlation between miRNAs -103a-3p, -21-3p, -155-5p, -146a-5p, -132-5p, and -9-3p and parasite load with ML and DL isolates. We also found a correlation between the expression of miR-21-3p and miR-146a-5p with the antiapoptotic gene BCL2 and the increase of viable cells, whereas miR-147a was indirectly correlated with CXCL-9 levels. The expression of miRNAs is strongly correlated with the parasite load and the inflammatory response, suggesting the participation of these molecules in the pathogenesis of the different clinical forms of L. braziliensis.

The History of New World Leishmaniases From a Brazilian Perspective

Abstract This article addresses the leishmaniases in the Americas from a Brazilian perspective. The first cases of cutaneous and mucocutaneous leishmaniasis were described in 1909 in São Paulo. Latin American researchers gained international projection because of their work on this disease they considered autochthonous, which came to be known as American tegumentary leishmaniasis. But visceral leishmaniasis only emerged as a public health problem in the Americas in 1934 thanks to a new diagnostic technique for yellow fever. Zoonoses earned greater attention later, especially in the laboratory founded in 1965 at the Evandro Chagas Institute by Ralph Lainson and Jeffrey Shaw. Here we examine their connections with other teams and the resulting changes when they proved that parasite, vector, and host populations were much more heterogeneous than previously imagined. Technical innovations provided a better understanding of the distinct epidemiological characteristics of the illnesses caused by different Leishmania amid a backdrop of far-reaching transnational networks.

Mechanisms Involved in the Arthropod Transmission of Leishmania spp.

Mechanisms Involved in the Arthropod Transmission of Leishmania spp.

1395. The Path of Healing: Demographic Features and Therapeutic Trajectory of Patients with American Tegumentary Leishmaniasis in a City of Northern Brazil

Abstract Background American Tegumentary Leishmaniasis (ATL) is a neglected infectious disease caused by protozoa of the Leishmania genus. Its incidence in the state of Para, Northern Brazil, reached 38,95 cases per 100,000 individuals in 2017. During this illness, people will move through several layers of a healthcare structure on a path for solutions to their affliction. This is described as therapeutic trajectory or itinerary, and it is directly influenced by determinants of health. In this scenario, we question what the trajectory of patients with ATL within healthcare in the city of Ruropolis, Brazil, is. Methods This was a transversal retrospective study. Qualitative data was also obtained through patient interviews. The research was developed in the city of Ruropolis, in Northern Brazil, and included individuals who received care through the Brazilian Unified Health System (SUS). All patients or responsible adults involved in the research signed an informed consent form. Results A total of 49 patients were initially included, but only 27 were interviewed. In 2021, ATL was diagnosed and notified every month, although April had the highest incidence (12 new cases). Over half of the patients resided in rural areas, and most worked in agriculture. Clear differences in trajectory were noted between patients or urban versus rural areas, as the latter mostly visited the local Emergency Department (ED) for care. Histopathologic work-up of all patients as performed. Regarding treatment, individuals had to relocate up to 50 kilometers daily to receive injections. Home healthcare services were not available. Overall, 23 patients received intravenous treatment with meglumine antimoniate, and 10 had a myriad of effects, such as fatigue, peripheral edema, and vertigo. Only four patients had intralesional therapy. Of 27 patients, 22 did not know how to prevent ATL or refused to answer. Conclusion The struggles faced by patients with ATL are diverse. The local population is unaware of the different layers of service within healthcare, and a hospital-centric model seems to prevail. Patients seek care wherever it seems appropriate to solve their trouble. The narratives on knowledge of the disease reveal the need for further health education, preferably with the introduction of active teaching methods. Disclosures All Authors: No reported disclosures

Heterologous expression and biochemical characterization of the recombinant nucleoside triphosphate diphosphohydrolase 2 (LbNTPDase2) from Leishmania (Viannia) braziliensis.

Leishmania braziliensis is a pathogenic protozoan parasite that causes American Tegumentary Leishmaniasis (ATL), an important tropical neglected disease. ENTPDases are nucleotidases that hydrolyze intracellular and/or extracellular nucleotides. ENTPDases are known as regulators of purinergic signalling induced by extracellular nucleotides. Leishmania species have two isoforms of ENTPDase, and, particularly, ENTPDase2 seems to be involved in infectivity and virulence. In this study, we conducted the heterologous expression and biochemical characterization of the recombinant ENTPDase2 of L. braziliensis (rLbNTPDase2). Our results show that this enzyme is a canonical ENTPDase with apyrase activity, capable of hydrolysing triphosphate and diphosphate nucleotides, and it is dependent on divalent cations (calcium or magnesium). Substrate specificity was characterized as UDP>GDP>ADP>GTP>ATP=UTP. The enzyme showed optimal activity at a neutral to basic pH and was partially inhibited by suramin and DIDS. Furthermore, the low apparent Km for ADP suggests that the enzyme may play a role in adenosine-mediated signalling. The biochemical characterization of this enzyme can open new avenues for using LbNTPDase2 as a drug target.

Clinical Presentation of American Tegumentary Leishmaniasis in a Leishmania (Viannia) braziliensis Endemic Hotspot: A 35-Year History.

American tegumentary leishmaniasis (ATL) is a neglected tropical disease affecting the skin and mucosa. American tegumentary leishmaniasis due to Leishmania (Viannia) braziliensis is endemic in Argentina, where the Department of Oran is a hyperendemic focus. All cases of ATL with laboratory confirmation evaluated at a referral center in Oran city between 1985 and 2019 were analyzed retrospectively. Information from cases included clinical form, lesion size and number, time of evolution, and anatomical location; sex, age, and geographic origin were also studied. The temporal distribution of cases was analyzed. A total of 3,573 cases were included in the analysis. The ratio of males to females was 3:1 and the median age was 33 years old. Eighty-seven percent of cases were from Oran city and its surroundings, highlighting the hyperendemic nature of the area. Regarding clinical forms, 92.5% of cases were cutaneous and 7.5% were mucosal, with a median evolution time until clinical evaluation of 30 days and 7 months, respectively. Single cutaneous lesions were more frequent, localized mainly on the exposed areas in the upper and lower limbs. Secondary events were observed and described in 140 (4%) cases, with a median interval of 3.8 years for the appearance of recurrent mucosal disease in previously cutaneous forms. This is the largest case series of ATL due to L. (V.) braziliensis. The most classic presentation is of adult males with single cutaneous ulcers in exposed body areas, with < 10% of cases with mucosal complications. This comprehensive clinical characterization serves as a basis for future studies of the care and control of this neglected tropical disease.

Increased Risk of American Tegumentary Leishmaniasis in an Urban and Rural Area of Caratinga, Brazil between 2016 and 2021.

We used spatial analysis tools to examine the epidemiological situation and spatial distribution of American tegumentary leishmaniasis in the municipality of Caratinga between 2016 and 2021. In addition, potential sandfly vectors were captured. All information used in this study was retrieved from public health archives and confirmed in the state health services databases. All cases were analyzed using Geographic Information Systems software. In addition, sandfly collections and molecular detection of Leishmania were carried out in areas with the highest number of cases. During the analyzed period, American tegumentary leishmaniasis (ATL) cases increased and remained high in the last years. The hotspots included urban areas of Caratinga city and the districts of Patrocínio of Caratinga and Sapucaia. The species Nyssomyia whitmani, Nyssomyia intermedia, and Migonemyia migonei were the most abundant species and the ITS1-polymerase chain reaction technique detected Leishmania DNA in these species. On the basis of our analyses, the urbanization of ATL in Caratinga has taken place in recent years. Because of the increase in the number of human cases and the presence of vectors, it is recommended that health authorities focus on control measures in hotspots.

Prevalence of American Tegumentary Leishmaniasis in Brazil – a systematic review and meta-analysis

American tegumentary leishmaniasis (ATL) is a zoonotic disease that affects the skin and mucous membranes, and that is caused by different species of protozoa of the genus Leishmania. This disease has different clinical forms: cutaneous, disseminated cutaneous, diffuse and mucocutaneous leishmaniasis. The objective of this systematic review is to investigate the prevalence and distribution of ATL in Brazil. Studies that analised patients with ATL diagnosed by at least one of the parasitological gold standard methods, PCR, or by serological methods were included.  Thirteen studies from PubMed, Regional Portal of the Virtual Health Library (BVS), Brazilian Society of Dermatology, Virtual Health Library (IBECS), Literature in the Health Sciences in Latin America and the Caribbean (LILACS), Medical Literature Analysis and Retrieval System Online (Medline), Elsevier Embase, Cochrane Library, The National Institute for Health and Care Excellence (NICE), and Cumulative Index to Nursing and Allied Health Literature (CINAHL) were included. We found a combined prevalence in the general population of 40.0% (95% CI: 17.0–63.0%; weight 100%). When the prevalence was analyzed by state, we found a prevalence of 97.0% in Rio de Janeiro. The South and Southeast regions showed the highest percentage, with 48.0% followed by the Central-West region with 24.0%. The Montenegro’s intradermal reaction and cultures were the most used test to diagnose. This study revealed a high prevalence of ATL in several studies conducted in Brazil, a value that was influenced by the most studied regions such South and Southeast, where a prevalence of up to 48% was found.

A byproduct from the Valles Calchaquíes vineyards (Argentina) rich in phenolic compounds: a tool against endemic Leishmania dissemination.

Vineyard-derived pomace is a byproduct of the wine industry that can have a negative impact on the environment if it is only disposed of or used as a fertilizer. Owing to its polyphenol content, grape pomace is an alternative to biocontrol undesirable microorganisms. In the present study, we characterized the phenolic composition of red and white grape pomace from Valles Calchaquíes, Argentina, and explored its activity against Leishmania (Leishmania) amazonensis, an etiological agent of American tegumentary leishmaniasis, a neglected endemic disease in northern Argentina. Red and white pomace extracts similarly reduced Leishmania viability after a 48-h treatment, with the fractions containing a higher proportion of phenolic compounds being more active. Both extracts stimulated ATPase activity on the parasite plasma membranes, with white grape pomace having a stronger effect than red grape pomace. In addition, the extracts displayed fairly good anticholinesterase activity, which may have contributed to their anti-Leishmania activity. These results reinforce the potential applicability of grape pomace as an antimicrobial agent for the development of biopesticides.

Synthesis of 1,2,3-Triazole-Containing Methoxylated Cinnamides and Their Antileishmanial Activity against the Leishmania braziliensis Species.

Leishmaniasis is a group of infectious diseases caused by protozoan parasites that belong to the genus Leishmania. Currently, there is no human vaccine, and the available treatments are associated with toxicity, high cost, and the emergence of resistant strains. These factors highlight the need to identify new antileishmanial candidates. In this study, we synthesized twenty-four methoxylated cinnamides containing 1,2,3-triazole fragments and evaluated their antileishmanial activity against the Leishmania braziliensis species, which is the main etiological agent responsible for American Tegumentary Leishmaniasis (ATL). The cinnamides were synthetically prepared using nucleophilic acyl substitution and copper(I)-catalyzed azide-alkyne cycloaddition (CuAAC) reactions. The compounds were characterized using infrared, nuclear magnetic resonance, and high-resolution mass spectrometry techniques. We performed preliminary studies to evaluate the biological activity of these compounds against L. braziliensis promastigotes and axenic amastigotes. Compound 28, N-((1-(7-(diethylamino)-2-oxo-2H-chromen-3-yl)-1H-1,2,3-triazole-4-yl) methyl)-3,4-dimethoxy cinnamide, demonstrated relevant antileishmanial activity with low toxicity in murine cells. The selectivity index values for this compound were superior compared with data obtained using amphotericin B. Furthermore, this cinnamide derivative reduced the infection percentage and number of recovered amastigotes in L. braziliensis-infected macrophages. It also induced an increase in reactive oxygen species production, depolarization of the mitochondrial potential, and disruption of the parasite membrane. Taken together, these findings suggest that this synthetic compound holds potential as an antileishmanial candidate and should be considered for future studies in the treatment of ATL.

Dogs Harbor Leishmania braziliensis and Participate in the Transmission Cycle of Human Tegumentary Leishmaniasis.

Dogs play an important role in transmission of Leishmania infantum, but epidemiologic and clinical studies of canine tegumentary leishmaniasis (CTL) are scarce. In an endemic area of human American tegumentary leishmaniasis (ATL) caused by Leishmania braziliensis, we determine the prevalence and incidence of both CTL and subclinical (SC) L. braziliensis infection in dogs and evaluated if the presence of dogs with CTL or SC L. braziliensis infection is associated with the occurrence of human ATL. SC infection in healthy animals and CTL in animals with ulcers were determined by PCR on biopsied healthy skin or on ulcers or by detecting antibodies against soluble leishmania antigen. We compared the occurrence of human ATL in homes with dogs with CTL or SC infection with control homes without dogs or with dogs without CTL or SC infection. The prevalence of SC infection was 35% and of CTL 31%. The incidence of SC infection in dogs was 4.6% and of CTL 9.3%. The frequency of ATL in humans was 50% in homes with infected dogs and 13% in homes without L. braziliensis infection in dogs. CTL and SC infection is highly prevalent, and dogs may participate in the transmission chain of L. braziliensis.

Co-expression analysis of lncRNA and mRNA suggests a role for ncRNA-mediated regulation of host-parasite interactions in primary skin lesions of patients with American tegumentary leishmaniasis

Leishmaniasis, caused by different Leishmania species, manifests as cutaneous or visceral forms. In the American continent, the cutaneous form is called American tegumentary leishmaniasis (ATL) and is primarily caused by Leishmania (Viannia) braziliensis. Mucosal leishmaniasis (ML), the most severe form of ATL, arises in approximately 20% of patients from a primary cutaneous lesion. Evidence indicates changes in overall expression patterns of mRNAs and lncRNAs of the host in response to Leishmania infection, with the parasite capable of modulating host immune response, which may contribute to disease progression. We evaluated whether the co-expression of lncRNAs and their putative target mRNAs in primary cutaneous lesions of patients with ATL could be associated with the development of ML. Previously available public RNA-Seq data from primary skin lesions of patients infected with L. braziliensis was employed. We identified 579 mRNAs and 46 lncRNAs differentially expressed in the primary lesion that subsequently progressed to mucosal disease. Co-expression analysis revealed 1324 significantly correlated lncRNA-mRNA pairs. Among these, we highlight the positive correlation and trans-action between lncRNA SNHG29 and mRNA S100A8, both upregulated in the ML group. S100A8 and its heterodimeric partner S100A9 form a pro-inflammatory complex expressed by immune cells and seems to participate in host innate immune response processes of infection. These findings expand the knowledge of the Leishmania-host interaction and indicate that the expression of lncRNAs in the primary cutaneous lesion could regulate mRNAs and play roles in disease progression.

Synergistic Antileishmanial Effect of Oregano Essential Oil and Silver Nanoparticles: Mechanisms of Action on Leishmania amazonensis.

American tegumentary leishmaniasis, a zoonotic disease caused by the Leishmania genus, poses significant challenges in treatment, including administration difficulty, low efficacy, and parasite resistance. Novel compounds or associations offer alternative therapies, and natural products such as oregano essential oil (OEO), extracted from Origanum vulgare, have been extensively researched due to biological effects, including antibacterial, antifungal, and antiparasitic properties. Silver nanoparticles (AgNp), a nanomaterial with compelling antimicrobial and antiparasitic activity, have been shown to exhibit potent leishmanicidal properties. We evaluated the in vitro effect of OEO and AgNp-Bio association on L. amazonensis and the death mechanisms of the parasite involved. Our results demonstrated a synergistic antileishmanial effect of OEO + AgNp on promastigote forms and L. amazonensis-infected macrophages, which induced morphological and ultrastructural changes in promastigotes. Subsequently, we investigated the mechanisms underlying parasite death and showed an increase in NO, ROS, mitochondrial depolarization, accumulation of lipid-storage bodies, autophagic vacuoles, phosphatidylserine exposure, and damage to the plasma membrane. Moreover, the association resulted in a reduction in the percentage of infected cells and the number of amastigotes per macrophage. In conclusion, our findings establish that OEO + AgNp elicits a late apoptosis-like mechanism to combat promastigote forms and promotes ROS and NO production in infected macrophages to target intracellular amastigote forms.