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Treatment options are limited, and there are frequent cases of treatment failure and clinical relapse. To understand these phenomena better, a systematic review was conducted, considering studies published between 1990 and 2021 in Portuguese, English, and Spanish. The review included 64 articles divided into three categories. Case reports (26 articles) focused on treatment failure and clinical relapse in cutaneous leishmaniasis patients (47.6%), primarily affecting males (74%) and children (67%), regardless of the clinical manifestation. Experimental studies on the parasite (19 articles), particularly with L. major (25%), indicated that alterations in DNA and genic expression (44.82%) played a significant role in treatment failure and clinical relapse. Population data on the human host (19 articles) identified immunological characteristics as the most associated factor (36%) with treatment failure and clinical relapse. Each clinical manifestation of the disease presented specificities in these phenomena, suggesting a multifactorial nature. Additionally, the parasites were found to adapt to the drugs used in treatment. In summary, the systematic review revealed that treatment failure and clinical relapse in leishmaniasis are complex processes influenced by various factors, including host immunology and parasite adaptation.<\/jats:p>","DOI":"10.3390\/tropicalmed8090430","type":"journal-article","created":{"date-parts":[[2023,8,29]],"date-time":"2023-08-29T10:49:10Z","timestamp":1693306150000},"page":"430","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":34,"title":["Systematic Review of Treatment Failure and Clinical Relapses in Leishmaniasis from a Multifactorial Perspective: Clinical Aspects, Factors Associated with the Parasite and Host"],"prefix":"10.3390","volume":"8","author":[{"given":"Gustavo de Almeida","family":"Santos","sequence":"first","affiliation":[{"name":"Postgraduate Program in Health and Environment, Center for Biological and Health Sciences, Federal University of Maranh\u00e3o, S\u00e3o Lu\u00eds 65080-805, Brazil"},{"name":"Department of Biology, Center for Biological and Health Sciences, Federal University of Maranh\u00e3o, S\u00e3o Lu\u00eds 65080-805, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juliana Mendes","family":"Sousa","sequence":"additional","affiliation":[{"name":"Department of Biology, Center for Biological and Health Sciences, Federal University of Maranh\u00e3o, S\u00e3o Lu\u00eds 65080-805, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ant\u00f4nio Henrique Braga Martins de","family":"Aguiar","sequence":"additional","affiliation":[{"name":"Department of Biology, Center for Biological and Health Sciences, Federal University of Maranh\u00e3o, S\u00e3o Lu\u00eds 65080-805, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karina Cristina Silva","family":"Torres","sequence":"additional","affiliation":[{"name":"Department of Biology, Center for Biological and Health Sciences, Federal University of Maranh\u00e3o, S\u00e3o Lu\u00eds 65080-805, Brazil"},{"name":"Postgraduate Program in Health Sciences, Center for Biological and Health Sciences, Federal University of Maranh\u00e3o, S\u00e3o Lu\u00eds 65080-805, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana Jessica Sousa","family":"Coelho","sequence":"additional","affiliation":[{"name":"Department of Biology, Center for Biological and Health Sciences, Federal University of Maranh\u00e3o, S\u00e3o Lu\u00eds 65080-805, Brazil"},{"name":"Postgraduate Program in Health Sciences, Center for Biological and Health Sciences, Federal University of Maranh\u00e3o, S\u00e3o Lu\u00eds 65080-805, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andr\u00e9 Leite","family":"Ferreira","sequence":"additional","affiliation":[{"name":"Department of Biology, Center for Biological and Health Sciences, Federal University of Maranh\u00e3o, S\u00e3o Lu\u00eds 65080-805, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1033-1984","authenticated-orcid":false,"given":"Mayara Ingrid Sousa","family":"Lima","sequence":"additional","affiliation":[{"name":"Postgraduate Program in Health and Environment, Center for Biological and Health Sciences, Federal University of Maranh\u00e3o, S\u00e3o Lu\u00eds 65080-805, Brazil"},{"name":"Department of Biology, Center for Biological and Health Sciences, Federal University of Maranh\u00e3o, S\u00e3o Lu\u00eds 65080-805, Brazil"},{"name":"Postgraduate Program in Health Sciences, Center for Biological and Health Sciences, Federal University of Maranh\u00e3o, S\u00e3o Lu\u00eds 65080-805, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,8,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1128\/CMR.00048-18","article-title":"Recent Development of Visceral Leishmaniasis Treatments: Successes, Pitfalls, and Perspectives","volume":"31","author":"Alves","year":"2018","journal-title":"Clin. Microbiol. Rev."},{"key":"ref_2","unstructured":"World Health Organization (WHO) (2022, May 06). Leishmaniasis. Available online: https:\/\/www.who.int\/news-room\/fact-sheets\/detail\/leishmaniasis."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Bansal, R., Sen, S.S., Muthuswami, R., and Madhubala, R. (2019). A Plant like Cytochrome P450 Subfamily CYP710C1 Gene in Leishmania donovani Encodes Sterol C-22 Desaturase and its Over-expression Leads to Resistance to Amphotericin B. PLoS Negl. Trop. Dis., 13.","DOI":"10.1371\/journal.pntd.0007260"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"913","DOI":"10.1128\/AAC.45.3.913-916.2001","article-title":"Glutatione induced conversion of 3-pentavalent antimony to trivalent antimony in meglumine antimoniate","volume":"45","author":"Demicheli","year":"2001","journal-title":"Antimicrob. Agents Chemoter."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1251","DOI":"10.1080\/14656566.2019.1609940","article-title":"Current and emerging medications for the treatment of leishmaniasis","volume":"20","author":"Chakravarty","year":"2019","journal-title":"Expert Opin. Pharmacother."},{"key":"ref_6","first-page":"131","article-title":"Magnitude of unresponsiveness to sodium stibogluconate in the treatment of visceral leishmaniasis in Bihar","volume":"18","author":"Das","year":"2005","journal-title":"Natl. Med. J. India"},{"key":"ref_7","unstructured":"World Health Organization (WHO) (2022, August 16). Manual on Case Management and Surveillance of the Leishmaniases in the Who European Region. Available online: https:\/\/www.euro.who.int\/__data\/assets\/pdf_file\/0006\/341970\/MANUAL-ON-CASE-MANAGEMENT_FINAL_with-cover-and-ISBN.pdf."},{"key":"ref_8","unstructured":"World Health Organization (WHO) (2022, August 16). Pan American Health Organization. Manual de Procedimientos Para Vigilancia y Control de las Leishmaniasis en las Am\u00e9ricas. Available online: https:\/\/iris.paho.org\/handle\/10665.2\/50524."},{"key":"ref_9","unstructured":"World Health Organization (WHO) (2022, August 16). Regional Office for the Eastern Mediterranean. Manual for Case Management of Cutaneous Leishmaniasis in the WHO Eastern Mediterranean Region. Available online: https:\/\/apps.who.int\/iris\/handle\/10665\/120002."},{"key":"ref_10","unstructured":"World Health Organization (WHO) (2022, August 16). Republic of the Sudan. Federal Ministry of Health Communicable and Non-Communicable. Diseases Control Directorate. Manual for the Diagnosis and Treatment of Leishmaniasis. Available online: https:\/\/www.humanitarianresponse.info\/sites\/www.humanitarianresponse.info\/files\/2019\/07\/Manual-for-the-diagnosis-%26-treatment-of-leishmaniasis-%282%29.pdf."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"937","DOI":"10.1586\/14787210.2014.916614","article-title":"Treatment failure in leishmaniasis: Drug-resistance or another (epi-) phenotype?","volume":"12","author":"Vanaerschot","year":"2014","journal-title":"Expert Rev. Anti-Infect. Ther."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1227","DOI":"10.2169\/internalmedicine.4096-19","article-title":"Failure of Liposomal-amphotericin B Treatment for New World Cutaneous Leishmaniasis due to Leishmania braziliensis","volume":"59","author":"Kosaka","year":"2020","journal-title":"Intern. Med."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"462","DOI":"10.1590\/abd1806-4841.20131885","article-title":"Recurrent cutaneous leishmaniasis","volume":"88","author":"Gomes","year":"2013","journal-title":"An. Bras. Dermatol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"101206","DOI":"10.1016\/j.bjid.2020.101206","article-title":"Tratamento de Recidiva de Leishmaniose Visceral em Crian\u00e7a com Terapia Tripla: Relato de caso","volume":"25","author":"Freitas","year":"2021","journal-title":"Braz. J. Infect. Dis."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1436","DOI":"10.3201\/eid1309.061446","article-title":"Recurrent American cutaneous leishmaniasis","volume":"13","author":"Gangneux","year":"2007","journal-title":"Emerg. Infect. Dis."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s12879-017-2571-x","article-title":"Recurrence of visceral and muco-cutaneous leishmaniasis in a patient under immunosuppressive therapy","volume":"17","author":"Darcis","year":"2017","journal-title":"BMC Infect. Dis."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"588","DOI":"10.1111\/j.1365-4632.2008.03240.x","article-title":"A rare case of leishmaniasis recidiva cutis evolving for 31 years caused by Leishmania tropica","volume":"47","author":"Stefanidou","year":"2008","journal-title":"Int. J. Dermatol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"e31","DOI":"10.1590\/s1678-9946202062031","article-title":"Recurrent kala-azar: Report of two cured cases after total splenectomy","volume":"62","author":"Reinaldo","year":"2020","journal-title":"Rev. Inst. Med. Trop. Sao Paulo"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"e20180211","DOI":"10.1590\/0037-8682-0211-2018","article-title":"Successful treatment of cutaneous leishmaniasis with intralesional meglumine antimoniate: A case series","volume":"52","author":"Arboleda","year":"2019","journal-title":"Rev. Soc. Bras. Med. Trop."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1016\/j.ijid.2014.12.036","article-title":"Mucosal relapse of visceral leishmaniasis in a child treated with anti-TNF\u03b1","volume":"33","author":"Jeziorski","year":"2015","journal-title":"Int. J. Infect. Dis."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"71","DOI":"10.4269\/ajtmh.2004.71.71","article-title":"Short report: Treatment failure due to mixed infection by different strains of the parasite Leishmania infantum","volume":"71","author":"Antoniou","year":"2004","journal-title":"Am. J. Trop. Med. Hyg."},{"key":"ref_22","first-page":"172","article-title":"Falla terap\u00e9utica del antimoniato de meglumina en el tratamiento de la leishmaniasis visceral Informe de un caso","volume":"73","author":"Rivera","year":"2005","journal-title":"Rev. Med. Hondur."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1076","DOI":"10.1086\/322643","article-title":"Leishmaniasis Recidivans Recurrence after 43 Years: A clinical and immunologic report after successful treatment","volume":"33","author":"Marovich","year":"2001","journal-title":"Clin. Infect. Dis."},{"key":"ref_24","first-page":"263","article-title":"Leishmaniasis cut\u00e1nea cr\u00f3nica: Respuesta a n-metil glucamina intralesional tras fracaso con paramomicina t\u00f3pica","volume":"4","author":"Melguizo","year":"2002","journal-title":"Actas Dermosifiliogr."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"e20180323","DOI":"10.1590\/0037-8682-0323-2018","article-title":"First report of treatment failure in a patient with cutaneous leishmaniasis infected by Leishmania (Viannia) naiffi carrying Leishmania RNA virus: A fortuitous combination?","volume":"52","author":"Heringer","year":"2019","journal-title":"Rev. Soc. Bras. Med. Trop."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"204","DOI":"10.1016\/j.ijid.2020.06.003","article-title":"Refractory mucocutaneous leishmaniasis resolved with combination treatment based on intravenous pentamidine, oral azole, aerosolized liposomal amphotericin B, and intralesional meglumine antimoniate","volume":"97","author":"Basile","year":"2020","journal-title":"Int. J. Infect. Dis."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1016\/S0163-4453(03)00002-1","article-title":"Visceral leishmaniasis. Persistence of parasites in lymph nodes after clinical cure","volume":"47","author":"Dereure","year":"2003","journal-title":"J. Infect."},{"key":"ref_28","first-page":"216","article-title":"Leishmaniasis recidiva cutis of the lips mimicking granulomatous cheilitis","volume":"60","author":"Ekiz","year":"2015","journal-title":"Indian J. Dermatol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"250","DOI":"10.1111\/j.1540-9740.2007.06111.x","article-title":"Leishmaniasis Recidivans in a Palestinian Bedouin Child","volume":"6","author":"Nasereddin","year":"2007","journal-title":"Skinmed"},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Eichenberger, A., Buechi, A.E., Neumayr, A., Hatz, C., Rauch, A., Huguenot, M., Diamantis-Karamitopoulou, E., and Staehelin, C. (2017). A severe case of visceral leishmaniasis and liposomal amphotericin B treatment failure in an immunosuppressed patient 15 years after exposure. BMC Infect. Dis., 17.","DOI":"10.1186\/s12879-017-2192-4"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"204","DOI":"10.1016\/j.ijid.2014.02.015","article-title":"Multiple relapses of visceral leishmaniasis in a patient with HIV in India: A treatment challenge","volume":"25","author":"Patole","year":"2014","journal-title":"Int. J. Infect. Dis."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"298","DOI":"10.1016\/j.ijid.2014.03.1037","article-title":"Ambisome as first line treatment of a child with ALL associated with the relapse of leishmaniasis","volume":"21","author":"Alia","year":"2014","journal-title":"Int. J. Infect. Dis."},{"key":"ref_33","first-page":"145","article-title":"Leishmaniose Visceral em crian\u00e7a: Um relato de caso sobre a recidiva da doen\u00e7a","volume":"26","author":"Pereira","year":"2015","journal-title":"Comun. Ci\u00eanc. Sa\u00fade"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1590\/S0036-46652009000400011","article-title":"Two cases of visceral leishmaniasis in Colombia resistant to meglumine antimonial treatment","volume":"51","author":"Colmenares","year":"2009","journal-title":"Rev. Inst. Med. Trop. Sao Paulo"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"580","DOI":"10.4269\/ajtmh.2009.80.580","article-title":"Relapse of visceral leishmaniasis after miltefosine treatment in a Nepalese patient","volume":"80","author":"Pandey","year":"2009","journal-title":"Am. J. Trop. Med. Hyg."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1076","DOI":"10.4269\/ajtmh.20-0131","article-title":"Case Report: Coinfection by leishmania amazonensis and hiv in a brazilian diffuse cutaneous leishmaniasis patient","volume":"103","author":"Soares","year":"2020","journal-title":"Am. J. Trop. Med."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Morizot, G., Jouffroy, R., Faye, A., Chabert, P., Belhouari, K., Calin, R., Charlier, C., Miailhes, P., Siriez, J.Y., and Mouri, O. (2016). Antimony to Cure Visceral Leishmaniasis Unresponsive to Liposomal Amphotericin B. PLoS Negl. Trop. Dis., 10.","DOI":"10.1371\/journal.pntd.0004304"},{"key":"ref_38","unstructured":"World Health Organization (WHO) (2022, April 03). Status of Endemicity of Visceral Leishmaniasis, Worldwide, 2020. Available online: https:\/\/cdn.who.int\/media\/docs\/default-source\/2021-dha-docs\/leishmaniasis_vl_2020.pdf?sfvrsn=17eea7b2_7."},{"key":"ref_39","unstructured":"World Health Organization (WHO) (2022, April 03). Status of Endemicity of Cutaneous Leishmaniasis, Worldwide, 2020. Available online: https:\/\/cdn.who.int\/media\/docs\/default-source\/2021-dha-docs\/leishmaniasis_cl_2020.pdf?sfvrsn=716850a8_9."},{"key":"ref_40","first-page":"401","article-title":"Global leishmaniasis surveillance: 2019\u20132020, a baseline for the 2030 roadmap\/Surveillance mondiale de la leishmaniose: 2019\u20132020, une periode de reference pour la feuille de route a l\u2019horizon 2030","volume":"96","author":"Jain","year":"2021","journal-title":"Wkly. Epidemiol. Rec."},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Guerra-Silveira, F., and Abad-Franch, F. (2013). Sex Bias in Infectious Disease Epidemiology: Patterns and Processes. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0062390"},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Cloots, K., Burza, S., Malaviya, P., Hasker, E., Kansal, S., Mollett, G., Chakravarty, J., Roy, N., Lal, B.K., and Rijal, S. (2020). Male predominance in reported Visceral Leishmaniasis cases: Nature or nurture? A comparison of population-based with health facility-reported data. PLoS Negl. Trop. Dis., 4.","DOI":"10.1371\/journal.pntd.0007995"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"e0748","DOI":"10.1590\/0037-8682-0748-2020","article-title":"Is splenectomy an option for multiple relapses in a child with visceral leishmaniasis? A case report","volume":"54","author":"Campos","year":"2021","journal-title":"Rev. Soc. Bras. Med. Trop."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1016\/j.actatropica.2016.09.026","article-title":"Lymphoproliferative response after stimulation with soluble leishmania antigen (SLA) as a predictor of visceral leishmaniasis (VL) relapse in HIV+ patients","volume":"164","author":"Castro","year":"2016","journal-title":"Acta Trop."},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Ostyn, B., Hasker, E., Dorlo, T.P.C., Rijal, S., Sundar, S., Dujardin, J.C., and Boelaert, M. (2014). Failure of Miltefosine Treatment for Visceral Leishmaniasis in Children and Men in South-East Asia. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0100220"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"e0097121","DOI":"10.1128\/mBio.00971-21","article-title":"Diversity and Within-Host Evolution of Leishmania donovani from Visceral Leishmaniasis Patients with and without HIV Coinfection in Northern Ethiopia","volume":"12","author":"Franssen","year":"2021","journal-title":"mBio"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1018","DOI":"10.1086\/382135","article-title":"Persistence of Leishmania Parasites in Scars after Clinical Cure of American Cutaneous Leishmaniasis: Is there a sterile cure?","volume":"189","author":"Brito","year":"2004","journal-title":"J. Infect. Dis."},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Bamorovat, M., Sharifi, I., Dabiri, S., Meymandi, S.S., Karamoozian, A., Amiri, R., Heshmatkhah, A., Zarandi, M.B., Aflatoonian, M.R., and Sharifi, F. (2021). Major risk factors and histopathological profile of treatment failure, relapse and chronic patients with anthroponotic cutaneous leishmaniasis: A prospective case-control study on treatment outcome and their medical importance. PLoS Negl. Trop. Dis., 15.","DOI":"10.1371\/journal.pntd.0009089"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1846","DOI":"10.1086\/518041","article-title":"Influence of Leishmania (Viannia) species on the response to antimonial treatment in patients with American tegumentary leishmaniasis","volume":"195","author":"Arevalo","year":"2007","journal-title":"J. Infect. Dis."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"837","DOI":"10.26719\/2003.9.4.837","article-title":"Antimony-resistant Leishmania donovani in eastern Sudan: Incidence and in vitro correlation","volume":"9","author":"Abdo","year":"2003","journal-title":"East. Mediterr. Health J."},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Abtahi, M., Eslami, G., Cavallero, S., Vakili, M., Hosseini, S.S., Ahmadian, S., Boozhmehrani, M.J., and Khamesipour, A. (2020). Relationship of Leishmania RNA Virus (LRV) and treatment failure in clinical isolates of Leishmania major. BMC Res. Notes, 13.","DOI":"10.1186\/s13104-020-04973-y"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.exppara.2006.02.008","article-title":"Leishmania amazonensis: Metabolic adaptations induced by resistance to an abc transporter blocker","volume":"114","author":"Machuca","year":"2006","journal-title":"Exp. Parasitol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"849","DOI":"10.1021\/acsinfecdis.0c00857","article-title":"Ros3 (Lem3p\/CDC50) Gene Dosage Is Implicated in Miltefosine Susceptibility in Leishmania (Viannia) braziliensis Clinical Isolates and in Leishmania (Leishmania) major","volume":"7","author":"Espada","year":"2021","journal-title":"ACS Infect. Dis."},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Monte-Neto, R.L., Coelho, A.C., Raymond, F., L\u00e9gar\u00e9, D., Corbeil, J., Melo, M.N., Fr\u00e9zard, F., and Ouellette, M. (2011). Gene Expression Profiling and Molecular Characterization of Antimony Resistance in Leishmania amazonensis. PLoS Negl. Trop. Dis., 5.","DOI":"10.1371\/journal.pntd.0001167"},{"key":"ref_55","first-page":"601","article-title":"Sensitivity of Leishmania spp. to Glibenclamide and 4- Aminopiridine: A Tool for the Study of Drug Resistance Development","volume":"5","author":"Campos","year":"1997","journal-title":"Mem. Inst. Oswaldo Cruz"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"899","DOI":"10.1007\/s004360000257","article-title":"Changes in the infectivity, pyruvate kinase activity, acid phosphatase activity and P-glycoprotein expression in glibenclamide-resistant Leishmania mexicana","volume":"86","author":"Figarella","year":"2000","journal-title":"Parasitol. Res."},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Turner, K.G., Vacchina, P., Robles-Murguia, M., Wadsworth, M., McDowell, M.A., and Morales, M.A. (2015). Fitness and Phenotypic Characterization of Miltefosine-Resistant Leishmania major. PLoS Negl. Trop. Dis., 9.","DOI":"10.1371\/journal.pntd.0003948"},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Vanaerschot, M., Doncker, S.D., Rijal, S., Maes, L., Dujardin, J.C., and Decuypere, S. (2011). Antimonial Resistance in Leishmania donovani Is Associated with Increased In Vivo Parasite Burden. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0023120"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1392","DOI":"10.1017\/S0031182011001120","article-title":"Increased metacyclogenesis of antimony-resistant Leishmania donovani clinical lines","volume":"138","author":"Ouakad","year":"2011","journal-title":"Parasitology"},{"key":"ref_60","doi-asserted-by":"crossref","unstructured":"Deep, D.K., Singh, R., Bhandari, V., Verma, A., Sharma, V., Wajid, S., Sundar, S., Ramesh, V., Dujardin, J.C., and Salotra, P. (2017). Increased miltefosine tolerance in clinical isolates of Leishmania donovani is associated with reduced drug accumulation, increased infectivity and resistance to oxidative stress. PLoS Negl. Trop. Dis., 11.","DOI":"10.1371\/journal.pntd.0005641"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1128\/AAC.01023-13","article-title":"Treatment Failure and Miltefosine Susceptibility in Dermal Leishmaniasis Caused by Leishmania Subgenus Viannia Species","volume":"58","author":"Obonaga","year":"2014","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_62","doi-asserted-by":"crossref","unstructured":"Hadighi, R., Mohebali, M., Boucher, P., Hajjaran, H., Khamesipour, A., and Ouellette, M. (2006). Unresponsiveness to Glucantime treatment in Iranian cutaneous leishmaniasis due to drug-resistant Leishmania tropica parasites. PLoS Med., 3.","DOI":"10.1371\/journal.pmed.0030162"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"1031","DOI":"10.1128\/AAC.00030-11","article-title":"Mechanism of Amphotericin B Resistance in Clinical Isolates of Leishmania donovani","volume":"56","author":"Purkait","year":"2012","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"600","DOI":"10.1086\/377133","article-title":"Novel Mechanism of Drug Resistance in Kala Azar Field Isolates","volume":"88","author":"Singh","year":"2003","journal-title":"J. Infect. Dis."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"564","DOI":"10.1086\/314896","article-title":"Evidence that the high incidence of treatment failures in Indian kala-azar is due to the emergence of antimony-resistant strains of Leishmania donovani","volume":"180","author":"Lira","year":"1999","journal-title":"J. Infect. Dis."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"4866","DOI":"10.1128\/AAC.02521-13","article-title":"Heterogeneity of Molecular Resistance Patterns in Antimony-Resistant Field Isolates of Leishmania Species from the Western Mediterranean Area","volume":"58","author":"Jeddi","year":"2014","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1016\/j.ebiom.2018.09.029","article-title":"A Leishmania infantum genetic marker associated with miltefosine treatment failure for visceral leishmaniasis","volume":"36","author":"Carnielli","year":"2018","journal-title":"Ebiomedicine"},{"key":"ref_68","unstructured":"World Health Organization (WHO) (2022, August 16). Control of Neglected Tropical Diseases. Indicators for Monitoring and Evaluation of the Kala-Azar Elimination Programme (India, Nepal and Bangladesh). Available online: https:\/\/www.who.int\/publications\/i\/item\/9789241500371."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"601","DOI":"10.1016\/j.ad.2021.02.008","article-title":"Leishmaniasis cut\u00e1nea y mucocut\u00e1nea Cutaneous and Mucocutaneous Leishmaniasis","volume":"112","author":"Diago","year":"2021","journal-title":"Actas Dermosifiliogr."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1590\/S0037-86822006000200001","article-title":"Fatores associados ao insucesso do tratamento da leishmaniose cut\u00e2nea com antimoniato de meglumina","volume":"39","author":"Rodrigues","year":"2006","journal-title":"Rev. Soc. Bras. Med. Trop."},{"key":"ref_71","doi-asserted-by":"crossref","unstructured":"Castro, M.D.M., Cossio, A., Velasco, C., and Osorio, L. (2017). Risk factors for therapeutic failure to meglumine antimoniate and miltefosine in adults and children with cutaneous leishmaniasis in Colombia: A cohort study. PLoS Negl. Trop. Dis., 11.","DOI":"10.1371\/journal.pntd.0005515"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1086\/524042","article-title":"Clinical and Parasite Species Risk Factors for Pentavalent Antimonial Treatment Failure in Cutaneous Leishmaniasis in Peru","volume":"46","author":"Tulliano","year":"2008","journal-title":"Clin. Infect. Dis."},{"key":"ref_73","first-page":"15","article-title":"Cuantificaci\u00f3n de niveles de INF-y-IL-13 y c\u00e9lulas T CD4+, CD8+ en pacientes con leishmaniasis tegumentaria con falla terap\u00e9utica","volume":"36","author":"Cabrera","year":"2013","journal-title":"Gac. M\u00e9d. Boliv."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"442","DOI":"10.1016\/j.clim.2008.05.007","article-title":"Local immunological factors associated with recurrence of mucosal leishmaniasis","volume":"128","author":"Tuon","year":"2008","journal-title":"J. Clin. Immunol."},{"key":"ref_75","first-page":"153","article-title":"Falla terap\u00e9utica y hepatotoxicidad de los esquemas de tratamiento endovenoso e intramuscular con estibogluconato de sodio en pacientes con leishmaniasis cut\u00e1nea\/Therapeutic failure and hepatotoxicity with schemes intravenous and intramuscular sodium stibogluconate treatment in patients with cutaneous leishmaniasis","volume":"24","year":"2014","journal-title":"Dermatol. Peru"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"6:443","DOI":"10.20344\/amp.8291","article-title":"Leishmaniose Visceral em Doentes com Infe\u00e7\u00e3o VIH: O desafio da reca\u00edda e fal\u00eancia terap\u00eautica","volume":"30","author":"Cipriano","year":"2017","journal-title":"Acta Med. Port."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1016\/j.ijid.2020.02.028","article-title":"Predictors of relapse of visceral leishmaniasis in inner S\u00e3o Paulo State, Brazil","volume":"95","author":"Fortaleza","year":"2020","journal-title":"Int. J. Infect. Dis."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"73","DOI":"10.5144\/0256-4947.2016.73","article-title":"Elevated TGF-beta levels in drug-resistant visceral leishmaniasis","volume":"36","author":"Elmekki","year":"2016","journal-title":"Ann. Saudi Med."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"1530","DOI":"10.1093\/cid\/cit102","article-title":"Increasing Failure of Miltefosine in the Treatment of Kala-azar in Nepal and the Potential Role of Parasite Drug Resistance, Reinfection, or Noncompliance","volume":"56","author":"Rijal","year":"2013","journal-title":"Clin. Infect. Dis."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"100583","DOI":"10.1016\/j.curtheres.2020.100583","article-title":"Multiple Relapses of Visceral Leishmaniasis in HIV Co-Infected Patients: A case series from ethiopia","volume":"92","author":"Mohammed","year":"2020","journal-title":"Curr. Ther. Res."},{"key":"ref_81","doi-asserted-by":"crossref","unstructured":"Goyal, V., Das, V.N.R., Singh, S.N., Singh, R.S., Pandey, K., Verma, N., Hightower, A., Rijal, S., Das, P., and Alvar, J. (2020). Long-term incidence of relapse and post-kala-azar dermal leishmaniasis after three different visceral leishmaniasis treatment regimens in Bihar, India. PLoS Negl. Trop. Dis., 14.","DOI":"10.1371\/journal.pntd.0008429"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1080\/00365540701466215","article-title":"Long term failure of miltefosine in the treatment of refractory visceral leishmaniasis in AIDS patients","volume":"40","author":"Troya","year":"2008","journal-title":"Scand. J. Infect. Dis."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1007\/s10096-005-1342-6","article-title":"Leishmaniasis as an opportunistic infection in HIV-infected patients: Determinants of relapse and mortality in a collaborative study of 228 episodes in a mediterreanean region","volume":"24","author":"Pasquau","year":"2005","journal-title":"Eur. J. Clin. Microbiol."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"202","DOI":"10.1007\/s100960100457","article-title":"Relapsing Visceral Leishmaniasis in HIV-Infected Patients Undergoing Successful Protease Inhibitor Therapy","volume":"20","author":"Casado","year":"2001","journal-title":"Eur. J. Clin. Microbiol."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1093\/infdis\/jiv355","article-title":"Presence of Leishmania RNA Virus 1 in Leishmania guyanensis Increases the Risk of First-Line Treatment Failure and Symptomatic Relapse","volume":"213","author":"Bourreau","year":"2015","journal-title":"J. Infect. Dis."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1016\/j.ijid.2018.07.008","article-title":"Leishmaniasis recidivans by Leishmania tropica in Central Rift Valley Region in Kenya","volume":"74","author":"Gitari","year":"2018","journal-title":"Int. J. Infect. Dis."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1016\/j.tmaid.2018.02.010","article-title":"Use of the intramuscular route to administer pentamidine isethionate in Leishmania guyanensis Cutaneous Leishmaniasis increases the risk of treatment failure","volume":"24","author":"Christen","year":"2018","journal-title":"Travel Med. Infect. Dis."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"4103819","DOI":"10.1155\/2019\/4103819","article-title":"Sex-Related Differences in Immune Response and Symptomatic Manifestations to Infection with Leishmania Species","volume":"2019","author":"Lockard","year":"2019","journal-title":"J. Immunol. Res."},{"key":"ref_89","unstructured":"World Health Organization (WHO) (2010). Control of the Leishmaniases: Report of a Meeting of the WHO Expert Committee on the Control of Leishmaniases, WHO. Available online: https:\/\/apps.who.int\/iris\/bitstream\/handle\/10665\/44412\/WHO_TRS_949_eng.pdF.;jsessionid=528A345D021696FAE84536A9CFE1FDF6?sequence=1."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"456","DOI":"10.4269\/ajtmh.2001.65.456","article-title":"Comparison of Cutaneous Leishmaniasis due to Leishmania (Viannia) braziliensis and L. (V.) guyanensis in brazil: Therapeutic response to Meglumine Antimoniate","volume":"65","author":"Romero","year":"2001","journal-title":"Am. J. Trop. Med. Hyg."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"775","DOI":"10.1126\/science.1199326","article-title":"Leishmania RNA Virus Controls the Severity of Mucocutaneous Leishmaniasis","volume":"331","author":"Ives","year":"2011","journal-title":"Science"},{"key":"ref_92","doi-asserted-by":"crossref","unstructured":"Cantanh\u00eade, L.M., J\u00fanior, C.F.S., Ito, M.M., Felipin, K.P., Nicolete, R., Salcedo, J.M.V., Porrozzi, R., Cupolillo, E., and Ferreira, R.G.M. (2015). Further Evidence of an Association between the Presence of Leishmania RNA Virus 1 and the Mucosal Manifestations in Tegumentary Leishmaniasis Patients. PLoS Negl. Trop. Dis., 9.","DOI":"10.1371\/journal.pntd.0004079"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"99","DOI":"10.3389\/fcimb.2012.00099","article-title":"Leishmania RNA virus: When the host pays the toll","volume":"2","author":"Hartley","year":"2012","journal-title":"Front. Cell. Infect. Microbiol."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1006\/viro.1995.1456","article-title":"The complete sequence of Leishmania RNA virus LRV2-1, a virus of an Old World parasite strain","volume":"212","author":"Scheffter","year":"1995","journal-title":"Virology"}],"container-title":["Tropical Medicine and Infectious Disease"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2414-6366\/8\/9\/430\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T20:41:57Z","timestamp":1760128917000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2414-6366\/8\/9\/430"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,8,29]]},"references-count":94,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2023,9]]}},"alternative-id":["tropicalmed8090430"],"URL":"https:\/\/doi.org\/10.3390\/tropicalmed8090430","relation":{},"ISSN":["2414-6366"],"issn-type":[{"value":"2414-6366","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,8,29]]}}}