Oral Leishmaniasis in HIV-Positive and HIV-Negative Patients: A Comparative Analysis with Two New Case Reports

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Methods We discuss the clinical manifestations, diagnostic methods, and therapeutic strategies, highlighting the clinical and histopathologic diagnostic features and distinct progression patterns based on HIV status. Our findings are compared with patterns observed in other countries, emphasizing the differences between the New World and Old World. Results In the New World, particularly in Brazil, mucocutaneous leishmaniasis often presents with localized oral lesions, even in the presence of systemic immunosuppression, whereas in the Old World, oral involvement is typically associated with visceral leishmaniasis in immunocompromised patients. These differences were due to variations in the parasite species involved. Conclusion This comparison underscores the importance of regional and immunological factors in the diagnosis and management of this neglected infectious disease. Oral Leishmaniasis HIV Co-infection Tegumentary Leishmaniasis Mucous Leihmaniasis Mucocutaneous Leishmaniasis Cutaneous Leishmaniasis Visceral Leishmaniasis Figures Figure 1 Introduction Leishmaniasis is a zoonosis caused by flagellated protozoans of the genus Leishmania , which comprises more than 20 known species that can cause disease in humans, including forms with significant oral involvement, particularly in endemic areas, such as Brazil [ 1 , 2 ]. First described in the early 20th century [ 1 ], these parasites have been progressively recognized and categorized. Leishmania species are transmitted to mammals by the bite of infected phlebotomine sand flies of the genera Phlebotomus and Lutzomyia , with approximately 98 species described as proven or suspected vectors of human disease [ 3 ]. Leishmania species exist in two basic forms: promastigotes (flagellated extracellular forms found in sandflies) and amastigotes (non-flagellated obligate intracellular forms found in vertebrate hosts) [ 4 ]. In mammalian hosts, protozoans live and multiply intracellularly within phagocytic cells [ 3 , 4 ]. The disease has a wide geographic distribution and is endemic in tropical and subtropical regions of the Americas, Mediterranean basin, parts of Asia, and Africa [ 1 ], where environmental conditions favor the survival of parasites and vectors. The World Health Organization (WHO) considers it a neglected infectious disease [ 5 ]. Clinical manifestations vary depending on the parasite species involved and the types of phagocytic cells invaded [ 1 ], including tegumentary (localized and diffuse cutaneous, mucocutaneous, and mucosal) and visceral (kala-azar) forms. In immunocompromised patients such as those with HIV, the disease may have a more severe clinical course [ 2 , 5 ]. In Latin America, mucocutaneous leishmaniasis occurs because of specific species of the protozoan Leishmania in well-defined areas [ 1 , 2 ]. The classical disease is characterized by primary skin lesions, followed by metastatic lesions in the mucosa of the nose, mouth, and/or throat after the initial skin lesions have healed [ 1 ]. Therefore, in the New World, oral leishmaniasis is considered a mucocutaneous manifestation of tegumentary leishmaniasis, and is not typically recognized as the primary site of infection. However, cases of mucosal leishmaniasis with primary oral involvement, including isolated lesions on the oral mucosa, have been reported [ 6 , 7 ]. Conversely, in the Old World, oral manifestations of leishmaniasis are generally related to visceral leishmaniasis and are often associated with immunocompromised conditions, such as HIV coinfection [ 8 , 9 , 10 , 11 , 12 ]. Considering the complexity of leishmaniasis and its epidemiological relevance worldwide, this study aimed to describe the clinical presentation, diagnosis, and outcomes of tegumentary leishmaniasis with primary oral manifestation in one HIV-negative and one HIV-positive patient diagnosed in an endemic area of Brazil. We discuss the clinical manifestations, diagnostic methods, and therapeutic strategies, reviewing how disease progression differs depending on the patient’s HIV status, and comparing findings between the New World and the Old World. Case 1: HIV-negative patient The first case involved a healthy 17-year-old male adolescent who presented with a single bleeding, ulcerative, erythematous, and asymptomatic lesion surrounded by a swollen area on the lower lip (Fig. 1 a). The lesion had been present for four months. No other symptoms or lymphadenopathy were observed. Given the diagnostic hypothesis of granulomatous infectious disease, an incisional biopsy was performed. Hematoxicilin and Eosin (H&E) staining of histological sections revealed the oral mucosal epithelium with intense inflammatory infiltrate (Fig. 1 b) and macrophages exhibiting structures similar to the ovoid amastigote forms of Leishmania with perinuclear kinetoplasts (Fig. 1 c, arrow). Histopathological diagnosis of tegumentary leishmaniasis was confirmed using the Montenegro skin test. The patient was treated with meglumine antimoniate, and four weeks later, the lesion healed completely without recurrence at the two-year follow-up. Case 2: HIV-positive patient The second case involved a 35-year-old male smoker who presented with multiple extensive erythematous, bleeding, and ulcerative oral lesions. These lesions extended from the anterior inferior gingival mucosa to the lower anterior and posterior alveolar ridges, resembling moriform stomatitis (Fig. 1 c), and were associated with intense burning symptoms. The lesions had been present for approximately six months. He had a history of weight loss and low-grade nocturnal fever, with no history of cutaneous lesions. Discrete lymphadenopathy, but no hepatosplenomegaly, was observed. The initial diagnosis was paracoccidioidomycosis. Incisional biopsy and histopathological analysis of the lesion were performed. The tissue fragments showed structures resembling the amastigote forms of Leishmania within macrophages in the lamina propria of the connective tissue underlying the epithelium (Figs. 1 c and 1 d). A Montenegro skin test confirmed the diagnosis of tegumentary leishmaniasis. The patient was referred for medical treatment, and additional examinations confirmed a positive HIV result. Bone marrow aspiration excluded visceral involvement, and the patient was treated with liposomal amphotericin B at a reference center as of our last contact. Discussion Leishmaniases are zoonoses characterized by a significant clinical spectrum and epidemiological diversity, contingent upon the subspecies of the parasite involved and the specific types of phagocytic cells that they invade [ 1 , 3 , 4 ]. The World Health Organization (WHO) classifies leishmaniasis as a "neglected infectious disease" and a major public health problem, estimating that there are two million new cases of the different clinical forms of the disease every year [ 2 , 5 ]. Tegumentary leishmaniasis encompasses cutaneous (both localized and disseminated), mucocutaneous, and mucosal forms of the disease and is widely distributed throughout the world, including the American continent [ 1 , 2 , 5 ]. In the Americas, cases have been reported from the extreme south of the United States to the north of Argentina, with the exception of Chile and Uruguay [ 1 ]. In the New World, skin lesions were first identified in Brazil by Juliano Moreira in 1895, who referred to them as "Bahia sore" or "Biskra sore" [ 13 ]. The confirmation of Leishmania forms in skin and nasobucopharyngeal ulcers (Bauru ulcers) occurred in 1909 when Adolpho Carlos Lindenberg and Antonio Carini, along with their colleague Ulysses de Freitas Paranhos, independently discovered the parasite in individuals working in deforested areas during highway construction in São Paulo [ 14 , 15 ]. Two years later, in 1911, Alfonso Splendore diagnosed the mucosal form of the disease [ 16 ], and Gaspar de Oliveira Vianna named the parasite Leishmania braziliensis [ 17 ]. Manifestations of leishmaniasis exclusively in the mucous membranes were first documented in 1913 by Castellani and Chalmers [ 18 ]. They observed ulcerations in the posterior wall of the pharynx and soft palate containing parasites, without a preceding cutaneous lesion, in a European patient, naming this condition "Indian oropharyngeal leishmaniasis" [ 18 ]. A similar situation was noted in Sudan, where none of the five patients with oral lesions in the study conducted by Milosev et al. [ 19 ] had a history of skin lesions, and no evidence of such lesions was found upon examination. The first known case of oral leishmaniasis in Brazil occurred in 1949 when De Castro observed a lesion on the lower lip of a man that resembled carcinoma [ 20 ]. Tegumentary leishmaniasis is characterized by a diversity of etiological agents, reservoirs, and vectors, with different transmission patterns and limited knowledge of various aspects, making it difficult to control [ 2 , 5 ]. Brazil is the primary country endemic for visceral leishmaniasis in the Americas, and in Tocantins, a northern state within the Legal Amazon, both visceral and tegumentary leishmaniasis are endemic and are frequently diagnosed [ 2 , 21 ]. This report presents two cases of oral leishmaniasis in Tocantins: one in an HIV-positive patient and one in an HIV-negative patient. To the best of our knowledge, these are the first reported cases of primary oral lesions of tegumentary leishmaniasis in this region of Brazil. In the HIV-negative patient, a single ulceration on the lower lip was diagnosed through histopathological analysis and Montenegro skin test. The lesion was successfully treated with pentavalent antimony. In contrast, the HIV-positive patient presented with multiple ulcerations on the gingiva and the anterior and posterior inferior alveolar ridges. Tegumentary leishmaniasis was confirmed using the same diagnostic test. Bone marrow aspiration excluded visceral involvement and the patient was treated with liposomal amphotericin B as of our last contact. The primary species of Leishmania implicated in leishmaniasis, including oral lesions, vary between regions. In the Old World, these species include Leishmania major , Leishmania tropica , Leishmania aethiopica , Leishmania infantum , and Leishmania donovani [ 4 ]. In these regions, isolated oral lesions not associated with the visceral form have been reported in both HIV-positive and HIV-negative patients and are related to Leishmania infantum [ 10 , 22 , 23 , 24 ]. Conversely, oral lesions associated with visceral leishmaniasis in HIV-positive patients are caused by Leishmania donovani and Leishmania infantum [ 8 , 9 , 10 , 11 , 12 ]. In contrast, in the New World, the species associated with oral lesions are Leishmania (Viannia) braziliensis , Leishmania (Viannia) guyanensis , and Leishmania (Viannia) panamensis [ 1 , 4 , 23 ]. In these regions, cutaneous leishmaniasis can coincide with or develop into mucocutaneous leishmaniasis, and oral leishmaniasis may sometimes appear without preceding cutaneous lesions [ 4 ]. Therefore, the variability in Leishmania species between the Old World and New World may influence disease presentation and progression. HIV-positive patients often exhibit more severe systemic symptoms and may present with visceral leishmaniasis (kala-azar) in conjunction with mucosal lesions especially in Old World, whereas HIV-negative patients typically have cutaneous, mucocutaneous, or mucosal manifestations [ 2 , 5 ]. A study conducted by Motta et al. [ 6 ] evaluated the demographic data and clinical aspects of 11 patients diagnosed with mucocutaneous leishmaniasis in Brazil between 1985 and 2005. They found that eight patients presented with mucocutaneous leishmaniasis and three with mucosal leishmaniasis. Mucosal disease is most commonly found in the palate, followed by the oropharynx. Specifically, the hard or soft palate was affected in eight cases, the oropharynx in five cases, the upper lip in three cases, and the tongue, labial commissure, and larynx in one case each. Only one patient tested positive for HIV and only two were women [ 6 ]. Falcão et al. [ 7 ] reported seven new cases involving the oral cavity in Brazil. Of these cases, five were men, one was HIV-positive, and most had ulcerated lesions on the lips. Interestingly, one of the four cases of oral leishmaniasis reported by Nadler et al. [ 4 ] in Israel was caused by Leishmania braziliensis , a species that is typically associated with the New World. This highlights the potential for cross-continental transmission of Leishmania species. Individuals at risk of contracting different Leishmania species include those living in endemic areas and regional travelers, such as ecotourists, missionaries, and soldiers [ 4 ]. According to the literature [8–12; 20; 22–31] and case series (Table 1 ), the main demographic features of oral leishmaniasis indicate a predominance of male patients, which corroborates our cases and previous reviews [ 31 ]. Its geographic distribution spans several regions, with some differences between the Old World and the New World. In the Old World, cases have been reported in diverse countries, whereas in the New World, Brazil accounts for the majority of the cases [8–12; 20; 22–31]. Regarding HIV status, in the Old World, the majority of patients with oral leishmaniasis were HIV-positive [ 8 , 9 , 10 , 11 , 12 ], whereas in the New World, most of the patients were HIV-negative [ 6 , 7 , 25 , 26 , 27 , 28 , 29 , 30 ]. The age of the patients varied from 17 to 94 years, predominantly involving adults. Table 1 Oral Leishmaniasis: Comparison of Oral Lesions in New World and Old World Author Year Country Sex/Age HIV Status Clinical Presentation Diagnostic Method Treatment and Oucome De Castro [ 20 ] 1949 Brazil Not specified Not specified Lesion on the lower lip similar to carcinoma Histopathological examination, direct microscopic examination, Montenegro test Not specified Michel [ 22 ] 1954 Algeria M / 59y Not specified Asymptomatic. Thickened infiltrated oral mucosa with granulomatous texture affecting the palate, tongue, and cheek. Ulcerations with raised edges and opaline gray background on the lips. Histopathological examination, direct microscopic examination Glucantime; remission of lesions Abbas et al. [ 8 ] 1992 Sudan M / 45y Not specified Fever, hepatosplenomegaly, periodontitis, gingival swelling, loss of teeth, swollen and bleeding gingiva and oral mucosa, edematous and fissured mucosa, alveolar loss, lymphadenopathy. Histopathological examination, direct microscopic examination, bone marrow aspiration Stibogluconate sodium; remission of lesions Michiels et al. [ 9 ] 1994 France M / 28y HIV+ Fever, hepatosplenomegaly, ulcerated polypoid mass on the right palatine tonsil and soft palate, nodular oesophageal lesion. Histopathological examination, bone marrow aspiration Meglumine antimoniate; patient died of CMV infection Cortés et al. [ 10 ] 1997 Spain M / 30y HIV+ Lymphadenopathy, vegetative tumor-like ulcer in the left hard and soft palate Histopathological examination, culture, bone marrow aspiration Meglumine antimoniate and allopurinol before recurrence; itraconazole and allopurinol after recurrence; remission of lesions Cascio et al. [ 11 ] 2000 Italy M / 35y HIV+ Mild hepatomegaly, multiple erosive lesions with white exudate on gingival mucosa, swollen and erythematous lower lip, maxillary papule, erythematous tongue and perioral skin. Exfoliative cytology, leishmaniasis serology, bone marrow biopsy Liposomal amphotericin B; remission of lesions Milián et al. [ 12 ] 2002 London M / 28y HIV+ Hepatosplenomegaly, lymphadenopathy, hard palatal tumor with ulcerations Histopathological examination, bone marrow aspiration Meglumine antimoniate; no follow-up information Van Damme et al. [ 23 ] 2004 Netherlands M / 86y HIV- No fever, lymphadenopathy, hepatosplenomegaly, or rash. Reddish livid tumescent palate with fistulas, indurations, erosions, ulcerations, mucosal tags, and granulations. Histopathological examination, direct microscopic examination Patient refused treatment and went elsewhere Pellicioli et al. [ 25 ] 2011 Brazil M / 71y HIV- Multiple ulcerated nodules on the hard and soft palate extending to the oropharynx. Histopathological examination, Montenegro skin test Liposomal amphotericin B; remission of lesions Celentano et al. [ 24 ] 2015 Italy M / 50y HIV- Widespread exophytic mass of the left buccal mucosa extending to the upper and lower fornix and retromolar area. Hard lesion with erythematous erosions, keratosis, speckled and ulcerated. Histopathological examination Not specified Cruz et al. [ 26 ] 2016 Brazil M / 60y HIV- Weight loss, diffuse vegetative lesions with coarse granulations and multiple superficial fissures in palatal region. Histopathological examination, Montenegro skin test Meglumine antimoniate; remission of lesions Cruz et al. [ 26 ] 2016 Brazil M / 94y HIV- Enlarged nose, destruction of nasal septum, swelling of palatal mucosa with erythematous and granular surface causing multiple papillary lesions. Histopathological examination, Montenegro skin test, PCR Liposomal amphotericin B; died due to generalized infection Almeida et al. [ 27 ] 2016 Brazil M / 41y HIV- Painless irregular erythematous and edematous plates with granulomatous surface on the upper alveolar ridge/gingiva and hard palate. Histopathological examination, Montenegro skin test, immunohistochemistry N-methyl-glucamine; remission of lesions Dos Santos et al. [ 28 ] 2020 Brazil M / 80y HIV- Lymphadenopathy, no skin lesion, erythematous swelling of upper lip with granulomatous ulceration of labial mucosa extending to hard palate and nasal region. Histopathological examination, Montenegro skin test N-methylglucamine antimoniate; remission of lesions Dos Santos et al. [ 28 ] 2020 Brazil M / 62y HIV- Sudden weight loss, cutaneous lesion, ulcerated and irregular oral lesions on the upper alveolar ridge and palate. Histopathological examination, Montenegro skin test, immunohistochemistry N-methylglucamine antimoniate; remission of lesions Botelho et al. [ 29 ] 2021 Brazil M / 57y HIV- Painless indurated and ulcerated nodule on the right side of tongue dorsum with sessile base and reddish color. Histopathological examination, PCR assay Meglumine antimoniate; remission of lesions Silveira et al. [ 30 ] 2021 Brazil M / 65y HIV- Lesion on the buccal mucosa without skin lesions Histopathological examination, PCR assay Not specified Current case 2024 Brazil M / 17y HIV- Bleeding ulcerative erythematous lesion surrounded by a swollen area on the lower lip. Histopathological examination, Montenegro skin test Meglumine antimoniate; remission of lesions Current case 2024 Brazil M / 35y HIV+ Weight loss, low fever, and lymphadenopathy. Erythematous ulcerative lesion on the gingival mucosa and lower anterior and posterior alveolar ridges, similar to moriform stomatitis, with intense burning symptoms. Histopathological examination, Montenegro skin test, bone marrow aspiration Liposomal amphotericin B; not specified M : male; y : years; HIV+ : HIV-positive; HIV- : HIV-negative Clinically, in the Old World, oral leishmaniasis typically presents with visceral involvement, especially in immunocompromised individuals such as those with HIV [ 8 , 9 , 10 , 11 , 12 ]. These patients often exhibit systemic symptoms such as fever, hepatosplenomegaly, and lymphadenopathy. The most prevalent oral lesions of leishmaniasis are found on the hard or soft palate (Table 1 ), often with concurrent lesions on the mucosal gingiva, lips, and tonsils. These lesions are typically infiltrative, tumorlike (polypoid or exophytic), and ulcerated (Table 1 ). Regarding localization, our results differ from previous reviews who identified the tongue as the primary site for oral leishmaniasis lesions [ 31 ]. The co-occurrence of other opportunistic diseases, such as Kaposi’s sarcoma and cytomegalovirus, may occur. Ulcerative oral lesions can also be seen associated to deep fungal infections, cytomegalovirus, mycobacterial infections, and herpes simplex [ 11 ]. Conversely, mucocutaneous leishmaniasis is more prevalent in the New World, and oral lesions can occur independently of systemic immunosuppression. These lesions commonly present with ulcerative, nodular, or granulomatous textures in the oral cavity and are often localized [ 31 ]. Leishmaniasis can develop at any stage of HIV infection; however, clinical manifestations and diagnosis are more likely to coincide with periods of maximum immunosuppression [ 12 ]. Severe immunosuppression is associated with the appearance of atypical manifestations, progression from cutaneous to visceral disease, and coexistence of cutaneous lesions and visceral involvement [ 8 , 9 , 10 , 11 , 12 ]. The symptoms, extent, and localization of lesions depend on both the characteristics of the parasite and the host immune response [ 31 ]. HIV infection can reactivate latent leishmaniasis and increase transmission rates through sandflies or through intravenous drug use. HIV-infected patients often exhibit high parasite loads and atypical symptoms, particularly those with low CD4 counts. This group responds poorly to treatment and has high relapse rates [ 4 ]. In our HIV-positive patient, the lesions presented as moriform stomatitis with hemorrhagic points, closely resembling the clinical appearance of paracoccidioidomycosis, another fungal infection endemic in Brazil. Splendore was the first to observe the clinical similarity between mucosal leishmaniasis and fungal lesions [ 17 ]. This clinical feature has also been noted by other researchers in cases of oral leishmaniasis [ 27 ]. This similarity underscores the importance of using diverse diagnostic methods to identify and/or exclude coinfections, especially in patients who are unaware of their HIV-positive status or those manifesting AIDS. Diagnosing oral leishmaniasis poses significant challenges because of its atypical presentation and overlap with other conditions such as infectious diseases (including bacterial and deep fungal infections), granulomatous diseases (including sarcoidosis and Wegener's granulomatosis), foreign bodies, and squamous cell carcinoma [ 4 , 6 ]. The diagnosis involves clinical examination combined with other diagnostic methods [ 21 ]. Parasitological diagnosis includes direct microscopic examination of smears or cultures of skin lesions to confirm the presence of Leishmania parasites. Immunological tests include the Montenegro skin test, serological tests, and antigen detection tests. Molecular diagnosis using PCR detects Leishmania DNA in the tissue samples [ 21 ]. In the Old World, where visceral involvement is common, bone marrow aspiration and serological tests are often required for diagnosis. Conversely, in the New World, histopathological examination and Montenegro skin test are more frequently employed as region-specific diagnostic protocols [ 32 ]. In our HIV-positive patient, bone marrow aspiration was used to exclude visceral leishmaniasis, given that Tocantins is an endemic area. Histological sections of the oral lesions revealed fragments of hyperplastic mucosa with lamina propria containing a dense chronic inflammatory infiltrate, predominantly consisting of histiocytes and plasma cells, with occasional eosinophils. Numerous round-shaped intracellular inclusions are observed inside clear cytoplasm macrophages or even extracellularly, representing the typical appearance of Leishman bodies (amastigote, non-flagellated forms of the parasite) (Figs. 1 b, 1 c, 1 e and 1 f). These ovoid amastigote forms contain perinuclear kinetoplasts (Fig. 1 c, arrow), which are a distinct feature of these parasites [ 23 , 30 ]. Histopathological differential diagnoses for leishmaniasis include fungal infections such as histoplasmosis and other granulomatous diseases. The Periodic Acid-Schiff (PAS) reaction and Grocott methenamine silver stain (GMS) are negative for leishmaniasis, which can be used to rule out fungal infections [ 30 ]. Immunohistochemical diagnosis involves the use of specific antibodies to detect Leishmania species in the tissue samples. Immunohistochemistry has been used to detect Leishmania braziliensis , which is typically associated with oral lesions in Brazil [ 27 ]. Immunohistochemistry enhances sensitivity compared to conventional staining techniques, aiding the accurate identification of Leishmania amastigotes and improving diagnostic reliability, especially in endemic areas [ 27 ]. Treatment outcomes for oral leishmaniasis may vary based on geographic location due to differences in parasite types, disease manifestations, and HIV status. In Brazil, HIV-positive patients are typically treated with liposomal amphotericin B or amphotericin B deoxycholate at specialized reference centers [ 33 ]. These patients often experience higher relapse rates because of their compromised immune systems. Conversely, HIV-negative patients generally respond well to pentavalent antimonials such as meglumine antimoniate. The presence of HIV co-infection complicates treatment, necessitating a multidisciplinary approach to address diverse medical needs and optimize patient outcomes [ 33 ]. Early diagnosis and treatment are essential for preventing severe morbidity and improving patient outcomes. Public health initiatives should focus on increasing awareness among healthcare providers and at-risk populations, and developing effective prevention and control strategies. Our case studies from Brazil illustrate the diverse manifestations of oral leishmaniasis and highlight the critical importance of considering this diagnosis in patients with atypical oral lesions, particularly in endemic areas. The differences between HIV-positive and HIV-negative patients highlight the need for tailored diagnostic and therapeutic approaches. Conclusion Our findings highlight the importance of considering oral leishmaniasis in the differential diagnosis of oral lesions, especially in endemic areas, such as Brazil. Early diagnosis can significantly impact patient outcomes, particularly in immunocompromised populations such as those with HIV. Continued research and awareness are essential to improve diagnosis, treatment outcomes, and control strategies for leishmaniasis, especially in regions with a high prevalence. Declarations Funding: This study was not supported by any funding. Conflict of Interest: The authors declare that they have no conflict of interest. Ethical approval: All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. Consent to participate: Informed consent was obtained from all individual participants included in the study. Consent for publication: Consent for publication was obtained for every individual person’s data included in the study. Availability of data and materials: Research data supporting this publication are available from the Pubmed repository located at https://pubmed.ncbi.nlm.nih.gov/ and Internet Archive repository located at https://archive.org/ Code Availability: This article was prepared with the assistance of Paperpal software application for language editing Author contributions: All authors contributed to the study conception and design. Material preparation, data collection and analysis were performed by Ana Cláudia Garcia Rosa, André Machado de Senna, Fabrício Passador Santos and Andresa Borges Soares. The first draft of the manuscript was written by Ana Cláudia Garcia Rosa and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript. Acknowledgments: The authors wish to thank Nadir Severina de Freitas and Eliane Tomaz da Silva for their excellent technical expertise and assistance. The authors are also grateful to Maria Eliza de Barros Garcia for translating the French articles used in the construction of this manuscript. References Steverding D. History of leishmaniasis. Parasites Vectors. 2017;10:82. https://doi.org/10.1186/s13071-017-2028-5 . World Health Organization. (2023, January 12) Leishmaniasis. World Health Organization. https://www.who.int/news-room/fact-sheets/detail/leishmaniasis . Maroli M, Feliciangeli MD, Bichaud L, et.al. 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Br J Oral Maxillofac Surg. 2015;53:396–8. https://doi.org/10.1016/j.bjoms.2015.01.021 . Pellicioli AC, Martins MA, Sant'ana Filho M, et.al. Leishmaniasis with oral mucosal involvement. Gerodontology. 2012;29:e1168–71. https://doi.org/10.1111/j.1741-2358.2011.00512.x . Cruz AF, Resende RG, Albuquerque DR, et.al. Mucosal leishmaniasis in Brazilian patients: Two case reports with similar clinical presentations and different approaches. Oral Surg Oral Med Oral Pathol Oral Radiol. 2016;122:e199–203. https://doi.org/10.1016/j.oooo.2016.02.017 . Almeida TF, da Silveira EM, Dos Santos CR, et.al. Exclusive primary lesion of oral leishmaniasis with immunohistochemical diagnosis. Head Neck Pathol. 2016;10:533–7. https://doi.org/10.1007/s12105-016-0732-7 . Dos Santos RLO, Tenório JR, Fernandes LG, et.al. Oral leishmaniasis: A report of two cases. J Oral Maxillofac Pathol. 2020;24:402. https://doi.org/10.4103/jomfp.JOMFP_306_18 . Botelho MCB, Ferreira LL, Fikaris S, et.al. Tongue nodules as a primary manifestation of American cutaneous leishmaniasis in an immunocompetent patient. Head Neck Pathol. 2021;15:1069–73. https://doi.org/10.1007/s12105-020-01253-w . Silveira HA, Panucci BZM, Silva EV, et.al. Microscopic diagnosis of oral leishmaniasis: Kinetoplasts. Head Neck Pathol. 2021;15:1085–6. https://doi.org/10.1007/s12105-021-01304-w . Mignogna MD, Celentano A, Leuci S, et.al. Mucosal leishmaniasis with primary oral involvement: A case series and a review of the literature. Oral Dis. 2015;21:e70–8. https://doi.org/10.1111/odi.12268 . Ministério da Saúde. (2024) Leishmaniose Tegumentar (LT) [Tegumentary Leishmaniasis (TL)] [Internet]. Brasília (DF): Ministério da Saúde. Retrieved May 15, 2024, from https://www.gov.br/saude/pt-br/assuntos/saude-de-a-a-z/l/lt . Ministério da Saúde (BR). (2022) Leishmaniose nas Américas: Recomendações para o Tratamento [Leishmaniasis in the Americas: Recommendations for Treatment] [Internet]. Brasília (DF): Ministério da Saúde. Retrieved May 21, 2024, from https://www.gov.br/saude/pt-br/centrais-de-conteudo/publicacoes/svsa/leishmaniose/3-leishmaniose-nas-americas-recomendacoes-para-o-tratamento . Additional Declarations No competing interests reported. Cite Share Download PDF Status: Under Review Version 1 posted Editorial decision: Revision requested 28 Jun, 2024 Reviews received at journal 28 Jun, 2024 Reviews received at journal 29 May, 2024 Reviewers agreed at journal 27 May, 2024 Reviewers agreed at journal 27 May, 2024 Reviewers invited by journal 27 May, 2024 Editor assigned by journal 27 May, 2024 Submission checks completed at journal 26 May, 2024 First submitted to journal 23 May, 2024 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-4468890","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Case Report","associatedPublications":[],"authors":[{"id":310252025,"identity":"1f85783c-60e8-48fb-a284-a7a084f4dd64","order_by":0,"name":"Ana Cláudia Garcia Rosa","email":"data:image/png;base64,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","orcid":"","institution":"Federal University of Tocantins","correspondingAuthor":true,"prefix":"","firstName":"Ana","middleName":"Cláudia Garcia","lastName":"Rosa","suffix":""},{"id":310252026,"identity":"48be2150-546e-4fb5-a434-678864a87237","order_by":1,"name":"André Machado de Senna","email":"","orcid":"","institution":"Afya Faculty of Medical Sciences","correspondingAuthor":false,"prefix":"","firstName":"André","middleName":"Machado","lastName":"de Senna","suffix":""},{"id":310252027,"identity":"d2ad5be8-75b9-4418-a0a5-a1d8f57f861d","order_by":2,"name":"Fabrício Passador-Santos","email":"","orcid":"","institution":"Faculdade São Leopoldo Mandic","correspondingAuthor":false,"prefix":"","firstName":"Fabrício","middleName":"","lastName":"Passador-Santos","suffix":""},{"id":310252028,"identity":"1b7bcfe6-5d35-404f-a21d-d41d5ada7fd6","order_by":3,"name":"Andresa Borges Soares","email":"","orcid":"","institution":"Faculdade São Leopoldo Mandic","correspondingAuthor":false,"prefix":"","firstName":"Andresa","middleName":"Borges","lastName":"Soares","suffix":""},{"id":310252029,"identity":"7bb1cc8e-5117-4dc2-a269-662cdae2615f","order_by":4,"name":"Vera Cavalcanti de Araújo","email":"","orcid":"","institution":"Faculdade São Leopoldo Mandic","correspondingAuthor":false,"prefix":"","firstName":"Vera","middleName":"Cavalcanti","lastName":"de Araújo","suffix":""}],"badges":[],"createdAt":"2024-05-23 20:24:14","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4468890/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4468890/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":58154307,"identity":"6696e4be-9ad5-48e6-9910-30bed411d454","added_by":"auto","created_at":"2024-06-11 20:38:51","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":1462416,"visible":true,"origin":"","legend":"\u003cp\u003eClinical and histopathological aspects of tegumentary leishmaniasis with oral involvement in HIV-negative\u003cstrong\u003e (Figs. 1a-1c) \u003c/strong\u003eand HIV-positive\u003cstrong\u003e(Figs. 1d-1f) \u003c/strong\u003epatients.\u003cstrong\u003e Fig. 1a: \u003c/strong\u003eAn ulcerated lesion extending from the vermilion of the lip to the lower labial vestibule with associated edema.\u003cstrong\u003e Fig. 1d: \u003c/strong\u003eUlcerations resembling moriform stomatitis extending from the lower gingiva to alveolar ridges.\u003cstrong\u003e Figs. 1b\u003c/strong\u003e,\u003cstrong\u003e 1c\u003c/strong\u003e,\u003cstrong\u003e 1e\u003c/strong\u003e,\u003cstrong\u003e \u003c/strong\u003eand\u003cstrong\u003e 1f: \u003c/strong\u003eHematoxylin and eosin (H\u0026amp;E) stained sections illustrating the histopathological features of leishmaniasis.\u003cstrong\u003e Fig. 1b: \u003c/strong\u003eIntense inflammatory infiltrate in connective tissue (200X). \u003cstrong\u003eFig. 1c: \u003c/strong\u003eAt higher magnification, ovoid amastigote forms of \u003cem\u003eLeishmania\u003c/em\u003e with perinuclear kinetoplasts are visible inside the macrofages (arrow) (1000X).\u003cstrong\u003e Fig. 1e: \u003c/strong\u003e\"Subepithelial macrophage flare\" (200X). \u003cstrong\u003eFig. 1f: \u003c/strong\u003eMacrophages containing various particles resembling amastigote forms of \u003cem\u003eLeishmania\u003c/em\u003e, which are often observed dispersed within connective tissue (1000X).\u003c/p\u003e","description":"","filename":"figure1.png","url":"https://assets-eu.researchsquare.com/files/rs-4468890/v1/9570cd0d7738cb0b9142ed89.png"},{"id":58154311,"identity":"f16743b3-e3b4-407c-8c7d-ae75539844bd","added_by":"auto","created_at":"2024-06-11 20:38:56","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":2735464,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4468890/v1/bb5bf60b-73df-4fea-925f-79c511b543c6.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Oral Leishmaniasis in HIV-Positive and HIV-Negative Patients: A Comparative Analysis with Two New Case Reports","fulltext":[{"header":"Introduction","content":"\u003cp\u003eLeishmaniasis is a zoonosis caused by flagellated protozoans of the genus \u003cem\u003eLeishmania\u003c/em\u003e, which comprises more than 20 known species that can cause disease in humans, including forms with significant oral involvement, particularly in endemic areas, such as Brazil [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. First described in the early 20th century [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e], these parasites have been progressively recognized and categorized. \u003cem\u003eLeishmania\u003c/em\u003e species are transmitted to mammals by the bite of infected phlebotomine sand flies of the genera \u003cem\u003ePhlebotomus\u003c/em\u003e and \u003cem\u003eLutzomyia\u003c/em\u003e, with approximately 98 species described as proven or suspected vectors of human disease [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. \u003cem\u003eLeishmania\u003c/em\u003e species exist in two basic forms: promastigotes (flagellated extracellular forms found in sandflies) and amastigotes (non-flagellated obligate intracellular forms found in vertebrate hosts) [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. In mammalian hosts, protozoans live and multiply intracellularly within phagocytic cells [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThe disease has a wide geographic distribution and is endemic in tropical and subtropical regions of the Americas, Mediterranean basin, parts of Asia, and Africa [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e], where environmental conditions favor the survival of parasites and vectors. The World Health Organization (WHO) considers it a neglected infectious disease [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. Clinical manifestations vary depending on the parasite species involved and the types of phagocytic cells invaded [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e], including tegumentary (localized and diffuse cutaneous, mucocutaneous, and mucosal) and visceral (kala-azar) forms. In immunocompromised patients such as those with HIV, the disease may have a more severe clinical course [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eIn Latin America, mucocutaneous leishmaniasis occurs because of specific species of the protozoan \u003cem\u003eLeishmania\u003c/em\u003e in well-defined areas [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. The classical disease is characterized by primary skin lesions, followed by metastatic lesions in the mucosa of the nose, mouth, and/or throat after the initial skin lesions have healed [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. Therefore, in the New World, oral leishmaniasis is considered a mucocutaneous manifestation of tegumentary leishmaniasis, and is not typically recognized as the primary site of infection. However, cases of mucosal leishmaniasis with primary oral involvement, including isolated lesions on the oral mucosa, have been reported [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. Conversely, in the Old World, oral manifestations of leishmaniasis are generally related to visceral leishmaniasis and are often associated with immunocompromised conditions, such as HIV coinfection [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e].\u003c/p\u003e \u003cp\u003e Considering the complexity of leishmaniasis and its epidemiological relevance worldwide, this study aimed to describe the clinical presentation, diagnosis, and outcomes of tegumentary leishmaniasis with primary oral manifestation in one HIV-negative and one HIV-positive patient diagnosed in an endemic area of Brazil. We discuss the clinical manifestations, diagnostic methods, and therapeutic strategies, reviewing how disease progression differs depending on the patient\u0026rsquo;s HIV status, and comparing findings between the New World and the Old World.\u003c/p\u003e"},{"header":"Case 1: HIV-negative patient","content":"\u003cp\u003eThe first case involved a healthy 17-year-old male adolescent who presented with a single bleeding, ulcerative, erythematous, and asymptomatic lesion surrounded by a swollen area on the lower lip (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003ea). The lesion had been present for four months. No other symptoms or lymphadenopathy were observed. Given the diagnostic hypothesis of granulomatous infectious disease, an incisional biopsy was performed. Hematoxicilin and Eosin (H\u0026amp;E) staining of histological sections revealed the oral mucosal epithelium with intense inflammatory infiltrate (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eb) and macrophages exhibiting structures similar to the ovoid amastigote forms of \u003cem\u003eLeishmania\u003c/em\u003e with perinuclear kinetoplasts (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003ec, arrow). Histopathological diagnosis of tegumentary leishmaniasis was confirmed using the Montenegro skin test. The patient was treated with meglumine antimoniate, and four weeks later, the lesion healed completely without recurrence at the two-year follow-up.\u003c/p\u003e"},{"header":"Case 2: HIV-positive patient","content":"\u003cp\u003eThe second case involved a 35-year-old male smoker who presented with multiple extensive erythematous, bleeding, and ulcerative oral lesions. These lesions extended from the anterior inferior gingival mucosa to the lower anterior and posterior alveolar ridges, resembling moriform stomatitis (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003ec), and were associated with intense burning symptoms. The lesions had been present for approximately six months. He had a history of weight loss and low-grade nocturnal fever, with no history of cutaneous lesions. Discrete lymphadenopathy, but no hepatosplenomegaly, was observed. The initial diagnosis was paracoccidioidomycosis. Incisional biopsy and histopathological analysis of the lesion were performed. The tissue fragments showed structures resembling the amastigote forms of \u003cem\u003eLeishmania\u003c/em\u003e within macrophages in the lamina propria of the connective tissue underlying the epithelium (Figs.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003ec and \u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003ed). A Montenegro skin test confirmed the diagnosis of tegumentary leishmaniasis. The patient was referred for medical treatment, and additional examinations confirmed a positive HIV result. Bone marrow aspiration excluded visceral involvement, and the patient was treated with liposomal amphotericin B at a reference center as of our last contact.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eLeishmaniases are zoonoses characterized by a significant clinical spectrum and epidemiological diversity, contingent upon the subspecies of the parasite involved and the specific types of phagocytic cells that they invade [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. The World Health Organization (WHO) classifies leishmaniasis as a \"neglected infectious disease\" and a major public health problem, estimating that there are two million new cases of the different clinical forms of the disease every year [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. Tegumentary leishmaniasis encompasses cutaneous (both localized and disseminated), mucocutaneous, and mucosal forms of the disease and is widely distributed throughout the world, including the American continent [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. In the Americas, cases have been reported from the extreme south of the United States to the north of Argentina, with the exception of Chile and Uruguay [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eIn the New World, skin lesions were first identified in Brazil by Juliano Moreira in 1895, who referred to them as \"Bahia sore\" or \"Biskra sore\" [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. The confirmation of \u003cem\u003eLeishmania\u003c/em\u003e forms in skin and nasobucopharyngeal ulcers (Bauru ulcers) occurred in 1909 when Adolpho Carlos Lindenberg and Antonio Carini, along with their colleague Ulysses de Freitas Paranhos, independently discovered the parasite in individuals working in deforested areas during highway construction in S\u0026atilde;o Paulo [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e, \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. Two years later, in 1911, Alfonso Splendore diagnosed the mucosal form of the disease [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e], and Gaspar de Oliveira Vianna named the parasite \u003cem\u003eLeishmania braziliensis\u003c/em\u003e [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eManifestations of leishmaniasis exclusively in the mucous membranes were first documented in 1913 by Castellani and Chalmers [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]. They observed ulcerations in the posterior wall of the pharynx and soft palate containing parasites, without a preceding cutaneous lesion, in a European patient, naming this condition \"Indian oropharyngeal leishmaniasis\" [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]. A similar situation was noted in Sudan, where none of the five patients with oral lesions in the study conducted by Milosev et al. [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e] had a history of skin lesions, and no evidence of such lesions was found upon examination. The first known case of oral leishmaniasis in Brazil occurred in 1949 when De Castro observed a lesion on the lower lip of a man that resembled carcinoma [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eTegumentary leishmaniasis is characterized by a diversity of etiological agents, reservoirs, and vectors, with different transmission patterns and limited knowledge of various aspects, making it difficult to control [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. Brazil is the primary country endemic for visceral leishmaniasis in the Americas, and in Tocantins, a northern state within the Legal Amazon, both visceral and tegumentary leishmaniasis are endemic and are frequently diagnosed [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]. This report presents two cases of oral leishmaniasis in Tocantins: one in an HIV-positive patient and one in an HIV-negative patient. To the best of our knowledge, these are the first reported cases of primary oral lesions of tegumentary leishmaniasis in this region of Brazil.\u003c/p\u003e \u003cp\u003eIn the HIV-negative patient, a single ulceration on the lower lip was diagnosed through histopathological analysis and Montenegro skin test. The lesion was successfully treated with pentavalent antimony. In contrast, the HIV-positive patient presented with multiple ulcerations on the gingiva and the anterior and posterior inferior alveolar ridges. Tegumentary leishmaniasis was confirmed using the same diagnostic test. Bone marrow aspiration excluded visceral involvement and the patient was treated with liposomal amphotericin B as of our last contact.\u003c/p\u003e \u003cp\u003eThe primary species of \u003cem\u003eLeishmania\u003c/em\u003e implicated in leishmaniasis, including oral lesions, vary between regions. In the Old World, these species include \u003cem\u003eLeishmania major\u003c/em\u003e, \u003cem\u003eLeishmania tropica\u003c/em\u003e, \u003cem\u003eLeishmania aethiopica\u003c/em\u003e, \u003cem\u003eLeishmania infantum\u003c/em\u003e, and \u003cem\u003eLeishmania donovani\u003c/em\u003e [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. In these regions, isolated oral lesions not associated with the visceral form have been reported in both HIV-positive and HIV-negative patients and are related to \u003cem\u003eLeishmania infantum\u003c/em\u003e [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e, \u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e, \u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e]. Conversely, oral lesions associated with visceral leishmaniasis in HIV-positive patients are caused by \u003cem\u003eLeishmania donovani\u003c/em\u003e and \u003cem\u003eLeishmania infantum\u003c/em\u003e [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eIn contrast, in the New World, the species associated with oral lesions are \u003cem\u003eLeishmania (Viannia) braziliensis\u003c/em\u003e, \u003cem\u003eLeishmania (Viannia) guyanensis\u003c/em\u003e, and \u003cem\u003eLeishmania (Viannia) panamensis\u003c/em\u003e [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]. In these regions, cutaneous leishmaniasis can coincide with or develop into mucocutaneous leishmaniasis, and oral leishmaniasis may sometimes appear without preceding cutaneous lesions [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. Therefore, the variability in \u003cem\u003eLeishmania\u003c/em\u003e species between the Old World and New World may influence disease presentation and progression. HIV-positive patients often exhibit more severe systemic symptoms and may present with visceral leishmaniasis (kala-azar) in conjunction with mucosal lesions especially in Old World, whereas HIV-negative patients typically have cutaneous, mucocutaneous, or mucosal manifestations [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eA study conducted by Motta et al. [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e] evaluated the demographic data and clinical aspects of 11 patients diagnosed with mucocutaneous leishmaniasis in Brazil between 1985 and 2005. They found that eight patients presented with mucocutaneous leishmaniasis and three with mucosal leishmaniasis. Mucosal disease is most commonly found in the palate, followed by the oropharynx. Specifically, the hard or soft palate was affected in eight cases, the oropharynx in five cases, the upper lip in three cases, and the tongue, labial commissure, and larynx in one case each. Only one patient tested positive for HIV and only two were women [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. Falc\u0026atilde;o et al. [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e] reported seven new cases involving the oral cavity in Brazil. Of these cases, five were men, one was HIV-positive, and most had ulcerated lesions on the lips. Interestingly, one of the four cases of oral leishmaniasis reported by Nadler et al. [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e] in Israel was caused by \u003cem\u003eLeishmania braziliensis\u003c/em\u003e, a species that is typically associated with the New World. This highlights the potential for cross-continental transmission of \u003cem\u003eLeishmania\u003c/em\u003e species. Individuals at risk of contracting different \u003cem\u003eLeishmania\u003c/em\u003e species include those living in endemic areas and regional travelers, such as ecotourists, missionaries, and soldiers [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eAccording to the literature [8\u0026ndash;12; 20; 22\u0026ndash;31] and case series (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e), the main demographic features of oral leishmaniasis indicate a predominance of male patients, which corroborates our cases and previous reviews [\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e]. Its geographic distribution spans several regions, with some differences between the Old World and the New World. In the Old World, cases have been reported in diverse countries, whereas in the New World, Brazil accounts for the majority of the cases [8\u0026ndash;12; 20; 22\u0026ndash;31]. Regarding HIV status, in the Old World, the majority of patients with oral leishmaniasis were HIV-positive [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e], whereas in the New World, most of the patients were HIV-negative [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e, \u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e, \u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e, \u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e, \u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e, \u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e]. The age of the patients varied from 17 to 94 years, predominantly involving adults.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eOral Leishmaniasis: Comparison of Oral Lesions in New World and Old World\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"8\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAuthor\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eYear\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eCountry\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eSex/Age\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eHIV Status\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eClinical Presentation\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003eDiagnostic Method\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c8\"\u003e \u003cp\u003eTreatment and Oucome\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDe Castro [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1949\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eBrazil\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eNot specified\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eNot specified\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eLesion on the lower lip similar to carcinoma\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eHistopathological examination, direct microscopic examination, Montenegro test\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eNot specified\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMichel [\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1954\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eAlgeria\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eM / 59y\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eNot specified\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eAsymptomatic. Thickened infiltrated oral mucosa with granulomatous texture affecting the palate, tongue, and cheek. Ulcerations with raised edges and opaline gray background on the lips.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eHistopathological examination, direct microscopic examination\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eGlucantime; remission of lesions\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAbbas et al. [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1992\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eSudan\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eM / 45y\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eNot specified\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eFever, hepatosplenomegaly, periodontitis, gingival swelling, loss of teeth, swollen and bleeding gingiva and oral mucosa, edematous and fissured mucosa, alveolar loss, lymphadenopathy.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eHistopathological examination, direct microscopic examination, bone marrow aspiration\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eStibogluconate sodium; remission of lesions\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMichiels et al. [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1994\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eFrance\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eM / 28y\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eHIV+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eFever, hepatosplenomegaly, ulcerated polypoid mass on the right palatine tonsil and soft palate, nodular oesophageal lesion.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eHistopathological examination, bone marrow aspiration\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eMeglumine antimoniate; patient died of CMV infection\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCort\u0026eacute;s et al. [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1997\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eSpain\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eM / 30y\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eHIV+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eLymphadenopathy, vegetative tumor-like ulcer in the left hard and soft palate\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eHistopathological examination, culture, bone marrow aspiration\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eMeglumine antimoniate and allopurinol before recurrence; itraconazole and allopurinol after recurrence; remission of lesions\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCascio et al. [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e2000\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eItaly\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eM / 35y\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eHIV+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eMild hepatomegaly, multiple erosive lesions with white exudate on gingival mucosa, swollen and erythematous lower lip, maxillary papule, erythematous tongue and perioral skin.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eExfoliative cytology, leishmaniasis serology, bone marrow biopsy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eLiposomal amphotericin B; remission of lesions\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMili\u0026aacute;n et al. [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e2002\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eLondon\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eM / 28y\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eHIV+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eHepatosplenomegaly, lymphadenopathy, hard palatal tumor with ulcerations\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eHistopathological examination, bone marrow aspiration\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eMeglumine antimoniate; no follow-up information\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVan Damme et al. [\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e2004\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eNetherlands\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eM / 86y\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eHIV-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eNo fever, lymphadenopathy, hepatosplenomegaly, or rash. Reddish livid tumescent palate with fistulas, indurations, erosions, ulcerations, mucosal tags, and granulations.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eHistopathological examination, direct microscopic examination\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003ePatient refused treatment and went elsewhere\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePellicioli et al. [\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e2011\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eBrazil\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eM / 71y\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eHIV-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eMultiple ulcerated nodules on the hard and soft palate extending to the oropharynx.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eHistopathological examination, Montenegro skin test\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eLiposomal amphotericin B; remission of lesions\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCelentano et al. [\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e2015\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eItaly\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eM / 50y\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eHIV-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eWidespread exophytic mass of the left buccal mucosa extending to the upper and lower fornix and retromolar area. Hard lesion with erythematous erosions, keratosis, speckled and ulcerated.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eHistopathological examination\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eNot specified\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCruz et al. [\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e2016\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eBrazil\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eM / 60y\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eHIV-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eWeight loss, diffuse vegetative lesions with coarse granulations and multiple superficial fissures in palatal region.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eHistopathological examination, Montenegro skin test\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eMeglumine antimoniate; remission of lesions\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCruz et al. [\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e2016\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eBrazil\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eM / 94y\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eHIV-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eEnlarged nose, destruction of nasal septum, swelling of palatal mucosa with erythematous and granular surface causing multiple papillary lesions.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eHistopathological examination, Montenegro skin test, PCR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eLiposomal amphotericin B; died due to generalized infection\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAlmeida et al. [\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e2016\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eBrazil\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eM / 41y\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eHIV-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003ePainless irregular erythematous and edematous plates with granulomatous surface on the upper alveolar ridge/gingiva and hard palate.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eHistopathological examination, Montenegro skin test, immunohistochemistry\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eN-methyl-glucamine; remission of lesions\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDos Santos et al. [\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e2020\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eBrazil\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eM / 80y\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eHIV-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eLymphadenopathy, no skin lesion, erythematous swelling of upper lip with granulomatous ulceration of labial mucosa extending to hard palate and nasal region.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eHistopathological examination, Montenegro skin test\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eN-methylglucamine antimoniate; remission of lesions\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDos Santos et al. [\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e2020\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eBrazil\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eM / 62y\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eHIV-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eSudden weight loss, cutaneous lesion, ulcerated and irregular oral lesions on the upper alveolar ridge and palate.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eHistopathological examination, Montenegro skin test, immunohistochemistry\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eN-methylglucamine antimoniate; remission of lesions\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBotelho et al. [\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e2021\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eBrazil\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eM / 57y\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eHIV-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003ePainless indurated and ulcerated nodule on the right side of tongue dorsum with sessile base and reddish color.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eHistopathological examination, PCR assay\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eMeglumine antimoniate; remission of lesions\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSilveira et al. [\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e2021\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eBrazil\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eM / 65y\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eHIV-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eLesion on the buccal mucosa without skin lesions\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eHistopathological examination, PCR assay\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eNot specified\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCurrent case\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e2024\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eBrazil\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eM / 17y\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eHIV-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eBleeding ulcerative erythematous lesion surrounded by a swollen area on the lower lip.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eHistopathological examination, Montenegro skin test\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eMeglumine antimoniate; remission of lesions\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCurrent case\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e2024\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eBrazil\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eM / 35y\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eHIV+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eWeight loss, low fever, and lymphadenopathy. Erythematous ulcerative lesion on the gingival mucosa and lower anterior and posterior alveolar ridges, similar to moriform stomatitis, with intense burning symptoms.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eHistopathological examination, Montenegro skin test, bone marrow aspiration\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eLiposomal amphotericin B; not specified\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"8\"\u003e\u003cb\u003eM\u003c/b\u003e: male; \u003cb\u003ey\u003c/b\u003e: years; \u003cb\u003eHIV+\u003c/b\u003e: HIV-positive; \u003cb\u003eHIV-\u003c/b\u003e: HIV-negative\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eClinically, in the Old World, oral leishmaniasis typically presents with visceral involvement, especially in immunocompromised individuals such as those with HIV [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. These patients often exhibit systemic symptoms such as fever, hepatosplenomegaly, and lymphadenopathy. The most prevalent oral lesions of leishmaniasis are found on the hard or soft palate (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e), often with concurrent lesions on the mucosal gingiva, lips, and tonsils. These lesions are typically infiltrative, tumorlike (polypoid or exophytic), and ulcerated (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). Regarding localization, our results differ from previous reviews who identified the tongue as the primary site for oral leishmaniasis lesions [\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e]. The co-occurrence of other opportunistic diseases, such as Kaposi\u0026rsquo;s sarcoma and cytomegalovirus, may occur. Ulcerative oral lesions can also be seen associated to deep fungal infections, cytomegalovirus, mycobacterial infections, and herpes simplex [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eConversely, mucocutaneous leishmaniasis is more prevalent in the New World, and oral lesions can occur independently of systemic immunosuppression. These lesions commonly present with ulcerative, nodular, or granulomatous textures in the oral cavity and are often localized [\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eLeishmaniasis can develop at any stage of HIV infection; however, clinical manifestations and diagnosis are more likely to coincide with periods of maximum immunosuppression [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. Severe immunosuppression is associated with the appearance of atypical manifestations, progression from cutaneous to visceral disease, and coexistence of cutaneous lesions and visceral involvement [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. The symptoms, extent, and localization of lesions depend on both the characteristics of the parasite and the host immune response [\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e]. HIV infection can reactivate latent leishmaniasis and increase transmission rates through sandflies or through intravenous drug use. HIV-infected patients often exhibit high parasite loads and atypical symptoms, particularly those with low CD4 counts. This group responds poorly to treatment and has high relapse rates [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eIn our HIV-positive patient, the lesions presented as moriform stomatitis with hemorrhagic points, closely resembling the clinical appearance of paracoccidioidomycosis, another fungal infection endemic in Brazil. Splendore was the first to observe the clinical similarity between mucosal leishmaniasis and fungal lesions [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. This clinical feature has also been noted by other researchers in cases of oral leishmaniasis [\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e]. This similarity underscores the importance of using diverse diagnostic methods to identify and/or exclude coinfections, especially in patients who are unaware of their HIV-positive status or those manifesting AIDS.\u003c/p\u003e \u003cp\u003eDiagnosing oral leishmaniasis poses significant challenges because of its atypical presentation and overlap with other conditions such as infectious diseases (including bacterial and deep fungal infections), granulomatous diseases (including sarcoidosis and Wegener's granulomatosis), foreign bodies, and squamous cell carcinoma [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. The diagnosis involves clinical examination combined with other diagnostic methods [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]. Parasitological diagnosis includes direct microscopic examination of smears or cultures of skin lesions to confirm the presence of \u003cem\u003eLeishmania\u003c/em\u003e parasites. Immunological tests include the Montenegro skin test, serological tests, and antigen detection tests. Molecular diagnosis using PCR detects \u003cem\u003eLeishmania\u003c/em\u003e DNA in the tissue samples [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eIn the Old World, where visceral involvement is common, bone marrow aspiration and serological tests are often required for diagnosis. Conversely, in the New World, histopathological examination and Montenegro skin test are more frequently employed as region-specific diagnostic protocols [\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e]. In our HIV-positive patient, bone marrow aspiration was used to exclude visceral leishmaniasis, given that Tocantins is an endemic area.\u003c/p\u003e \u003cp\u003eHistological sections of the oral lesions revealed fragments of hyperplastic mucosa with lamina propria containing a dense chronic inflammatory infiltrate, predominantly consisting of histiocytes and plasma cells, with occasional eosinophils. Numerous round-shaped intracellular inclusions are observed inside clear cytoplasm macrophages or even extracellularly, representing the typical appearance of Leishman bodies (amastigote, non-flagellated forms of the parasite) (Figs.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eb, \u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003ec, \u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003ee and \u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003ef). These ovoid amastigote forms contain perinuclear kinetoplasts (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003ec, arrow), which are a distinct feature of these parasites [\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e, \u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e]. Histopathological differential diagnoses for leishmaniasis include fungal infections such as histoplasmosis and other granulomatous diseases. The Periodic Acid-Schiff (PAS) reaction and Grocott methenamine silver stain (GMS) are negative for leishmaniasis, which can be used to rule out fungal infections [\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e]. Immunohistochemical diagnosis involves the use of specific antibodies to detect \u003cem\u003eLeishmania\u003c/em\u003e species in the tissue samples. Immunohistochemistry has been used to detect \u003cem\u003eLeishmania braziliensis\u003c/em\u003e, which is typically associated with oral lesions in Brazil [\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e]. Immunohistochemistry enhances sensitivity compared to conventional staining techniques, aiding the accurate identification of \u003cem\u003eLeishmania\u003c/em\u003e amastigotes and improving diagnostic reliability, especially in endemic areas [\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e].\u003c/p\u003e \u003cp\u003e Treatment outcomes for oral leishmaniasis may vary based on geographic location due to differences in parasite types, disease manifestations, and HIV status. In Brazil, HIV-positive patients are typically treated with liposomal amphotericin B or amphotericin B deoxycholate at specialized reference centers [\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e]. These patients often experience higher relapse rates because of their compromised immune systems. Conversely, HIV-negative patients generally respond well to pentavalent antimonials such as meglumine antimoniate. The presence of HIV co-infection complicates treatment, necessitating a multidisciplinary approach to address diverse medical needs and optimize patient outcomes [\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e]. Early diagnosis and treatment are essential for preventing severe morbidity and improving patient outcomes. Public health initiatives should focus on increasing awareness among healthcare providers and at-risk populations, and developing effective prevention and control strategies.\u003c/p\u003e \u003cp\u003e Our case studies from Brazil illustrate the diverse manifestations of oral leishmaniasis and highlight the critical importance of considering this diagnosis in patients with atypical oral lesions, particularly in endemic areas. The differences between HIV-positive and HIV-negative patients highlight the need for tailored diagnostic and therapeutic approaches.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003e Our findings highlight the importance of considering oral leishmaniasis in the differential diagnosis of oral lesions, especially in endemic areas, such as Brazil. Early diagnosis can significantly impact patient outcomes, particularly in immunocompromised populations such as those with HIV. Continued research and awareness are essential to improve diagnosis, treatment outcomes, and control strategies for leishmaniasis, especially in regions with a high prevalence.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eFunding:\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was not supported by any funding.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConflict of Interest:\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no conflict of interest.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthical approval:\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent to participate:\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eInformed consent was obtained from all individual participants included in the study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication:\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eConsent for publication was obtained for every individual person\u0026rsquo;s data included in the study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials:\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eResearch data supporting this publication are available from the Pubmed repository located at https://pubmed.ncbi.nlm.nih.gov/ and Internet Archive repository located at https://archive.org/\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCode Availability:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis article was prepared with the assistance of Paperpal software application for language editing\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor contributions:\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll authors contributed to the study conception and design. Material preparation, data collection and analysis were performed by Ana Cl\u0026aacute;udia Garcia Rosa, Andr\u0026eacute; Machado de Senna, Fabr\u0026iacute;cio Passador Santos and Andresa Borges Soares. The first draft of the manuscript was written by Ana Cl\u0026aacute;udia Garcia Rosa and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgments:\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors wish to thank Nadir Severina de Freitas and Eliane Tomaz da Silva for their excellent technical expertise and assistance. The authors are also grateful to Maria Eliza de Barros Garcia for translating the French articles used in the construction of this manuscript.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eSteverding D. History of leishmaniasis. 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Retrieved May 21, 2024, from \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://www.gov.br/saude/pt-br/centrais-de-conteudo/publicacoes/svsa/leishmaniose/3-leishmaniose-nas-americas-recomendacoes-para-o-tratamento\u003c/span\u003e\u003cspan address=\"https://www.gov.br/saude/pt-br/centrais-de-conteudo/publicacoes/svsa/leishmaniose/3-leishmaniose-nas-americas-recomendacoes-para-o-tratamento\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"head-and-neck-pathology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"","sideBox":"Learn more about [Head and Neck Pathology](https://www.springer.com/journal/12105)","snPcode":"12105","submissionUrl":"https://submission.springernature.com/new-submission/12105/3","title":"Head and Neck Pathology","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"Oral Leishmaniasis, HIV Co-infection, Tegumentary Leishmaniasis, Mucous Leihmaniasis, Mucocutaneous Leishmaniasis, Cutaneous Leishmaniasis, Visceral Leishmaniasis","lastPublishedDoi":"10.21203/rs.3.rs-4468890/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4468890/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003ePurpose\u003c/h2\u003e \u003cp\u003eThis case report examines the clinical presentation, diagnosis, treatment, and outcomes of mucocutaneous leishmaniasis with primary oral involvement in HIV-positive and HIV-negative patients diagnosed in Brazil.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eWe discuss the clinical manifestations, diagnostic methods, and therapeutic strategies, highlighting the clinical and histopathologic diagnostic features and distinct progression patterns based on HIV status. Our findings are compared with patterns observed in other countries, emphasizing the differences between the New World and Old World.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eIn the New World, particularly in Brazil, mucocutaneous leishmaniasis often presents with localized oral lesions, even in the presence of systemic immunosuppression, whereas in the Old World, oral involvement is typically associated with visceral leishmaniasis in immunocompromised patients. These differences were due to variations in the parasite species involved.\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e \u003cp\u003eThis comparison underscores the importance of regional and immunological factors in the diagnosis and management of this neglected infectious disease.\u003c/p\u003e","manuscriptTitle":"Oral Leishmaniasis in HIV-Positive and HIV-Negative Patients: A Comparative Analysis with Two New Case Reports","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-06-11 20:38:46","doi":"10.21203/rs.3.rs-4468890/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2024-06-28T19:46:38+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-06-28T15:04:37+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-05-29T18:35:49+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"255257864695200859331054052629006044325","date":"2024-05-28T03:58:55+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"106265190032084029682195744926068669042","date":"2024-05-27T21:33:57+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2024-05-27T11:10:13+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2024-05-27T11:05:34+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2024-05-27T03:13:04+00:00","index":"","fulltext":""},{"type":"submitted","content":"Head and Neck Pathology","date":"2024-05-23T20:22:57+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"head-and-neck-pathology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"","sideBox":"Learn more about [Head and Neck Pathology](https://www.springer.com/journal/12105)","snPcode":"12105","submissionUrl":"https://submission.springernature.com/new-submission/12105/3","title":"Head and Neck Pathology","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"8e6a4432-7ab8-4c32-aac4-17b85005964b","owner":[],"postedDate":"June 11th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2024-07-06T16:16:20+00:00","versionOfRecord":[],"versionCreatedAt":"2024-06-11 20:38:46","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-4468890","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4468890","identity":"rs-4468890","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}