{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T00:27:04Z","timestamp":1777422424085,"version":"3.51.4"},"reference-count":41,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2024,5,25]],"date-time":"2024-05-25T00:00:00Z","timestamp":1716595200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Improvement of Higher Education Personnel (CAPES) for the Masters scholarship for RVSS, National Council for Scientific and Technological Development (CNPq)","award":["302571\/2015-9"],"award-info":[{"award-number":["302571\/2015-9"]}]},{"name":"Institute of Tropical Diseases \u201cNatan Portella\u201d","award":["302571\/2015-9"],"award-info":[{"award-number":["302571\/2015-9"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pathogens"],"abstract":"<jats:p>Visceral leishmaniasis (VL) results from protozoa Leishmania infantum and L. donovani infection. This study investigated whether host factors would explain the relapses. First, susceptibility to amphotericin B of L. infantum isolates was evaluated in vitro. Then, clinical data and the lipid profile of patients with relapsing and non-relapsing VL were assessed. Susceptibility to amphotericin B was similar between the isolates. CD4+ lymphocytes were reduced in both groups of patients in the first episode and with relapsing VL. Still, the strongest blood cell indicator associated with relapses was low total lymphocyte counts. Total plasma cholesterol, high-density lipoprotein, low-density lipoprotein, and, uniquely, triglycerides of the six individuals in the first episode and twenty-three with relapsing VL were lower in relapsing patients than those in the first episode. Deceased patients had extremely low low-density lipoprotein. After CD4+ decreases, lymphocyte CD8+ reduction is the final stage of immunological failure. The lower lipid concentrations appear to be secondary to the depletion of fat stores by inflammation-induced cachexia and fat exhaustion provoked by the co-occurrence of both diseases, which can finally lead to death.<\/jats:p>","DOI":"10.3390\/pathogens13060450","type":"journal-article","created":{"date-parts":[[2024,5,27]],"date-time":"2024-05-27T09:33:31Z","timestamp":1716802411000},"page":"450","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Low Plasma Lipids Are Associated with Relapsing and Lethal Visceral Leishmaniasis in HIV-Infected Patients"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9785-8246","authenticated-orcid":false,"given":"Renata V. S.","family":"Silva","sequence":"first","affiliation":[{"name":"Laborat\u00f3rio de Leishmanioses, Departamento de Medicina Comunit\u00e1ria, Universidade Federal do Piau\u00ed, Teresina 64002-510, PI, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8070-3704","authenticated-orcid":false,"given":"Silvia R. B.","family":"Uliana","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Leishmanioses, Instituto de Ci\u00eancias Biom\u00e9dicas, Universidade de S\u00e3o Paulo, S\u00e3o Paulo 05508-090, SP, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8472-7500","authenticated-orcid":false,"given":"Jenicer K. U. Y.","family":"Yasunaka","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Leishmanioses, Instituto de Ci\u00eancias Biom\u00e9dicas, Universidade de S\u00e3o Paulo, S\u00e3o Paulo 05508-090, SP, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cl\u00e1udio S.","family":"Veloso","sequence":"additional","affiliation":[{"name":"Instituto de Doen\u00e7as Tropicais \u201cNatan Portella\u201d, Teresina 64002-510, PI, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4311-1010","authenticated-orcid":false,"given":"Emille","family":"Sousa","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Leishmanioses, Centro de Intelig\u00eancia em Agravos Emergentes e Negligenciados, Teresina 64002-510, PI, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria M. L.","family":"Ferreira","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Leishmanioses, Centro de Intelig\u00eancia em Agravos Emergentes e Negligenciados, Teresina 64002-510, PI, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-1991-5766","authenticated-orcid":false,"given":"Vivianne S.","family":"Carvalho","sequence":"additional","affiliation":[{"name":"Centro de Diagn\u00f3stico, \u201cDr. Raul Bacellar\u201d, Funda\u00e7\u00e3o Municipal de Sa\u00fade, Teresina 64600-000, PI, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gabriel R.","family":"Ferreira","sequence":"additional","affiliation":[{"name":"Department of Microbiology-Infectious Disease and Immunology, Faculty of Medicine, University Laval, Quebec, QC G1V 0A6, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dorcas L.","family":"Costa","sequence":"additional","affiliation":[{"name":"Instituto de Doen\u00e7as Tropicais \u201cNatan Portella\u201d, Teresina 64002-510, PI, Brazil"},{"name":"Laborat\u00f3rio de Leishmanioses, Centro de Intelig\u00eancia em Agravos Emergentes e Negligenciados, Teresina 64002-510, PI, Brazil"},{"name":"Departamento de M\u00e3e e Filho, Universidade Federal do Piau\u00ed, Teresina 64002-510, PI, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7302-2006","authenticated-orcid":false,"given":"Carlos H. N.","family":"Costa","sequence":"additional","affiliation":[{"name":"Instituto de Doen\u00e7as Tropicais \u201cNatan Portella\u201d, Teresina 64002-510, PI, Brazil"},{"name":"Laborat\u00f3rio de Leishmanioses, Centro de Intelig\u00eancia em Agravos Emergentes e Negligenciados, Teresina 64002-510, PI, Brazil"},{"name":"Departamento de Medicina Comunit\u00e1ria, Universidade Federal do Piau\u00ed, Teresina 64002-510, PI, Brazil"},{"name":"Laborat\u00f3rio de Pesquisas em Leishmanioses, Centro de Investiga\u00e7\u00f5es em Agravos Tropicais Emergentes e Negligenciados, Instituto de Doen\u00e7as Tropicais \u201cNatan Portella\u201d, Universidade Federal do Piau\u00ed, Rua Artur de Vasconcelos 151, Teresina 64002-510, PI, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,5,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"951","DOI":"10.1016\/S0140-6736(18)31204-2","article-title":"Leishmaniasis","volume":"392","author":"Burza","year":"2018","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1179\/2047773213Y.0000000078","article-title":"Serum cytokines associated with severity and complications of kala-azar","volume":"107","author":"Costa","year":"2013","journal-title":"Pathog. Glob. Health"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"678","DOI":"10.1016\/0035-9203(95)90442-5","article-title":"Acute phase protein concentrations predict parasite clearance rate during therapy for visceral leishmaniasis","volume":"89","author":"Wasunna","year":"1995","journal-title":"Trans. R. Soc. Trop. Med. Hyg."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Alvar, J., V\u00e9lez, I.D., Bern, C., Herrero, M., Desjeux, P., Cano, J., Jannin, J., and den Boer, M. (2012). Who Leishmaniasis Control the WHO Leishmaniasis Control Team Leishmaniasis Worldwide and Global Estimates of Its Incidence. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0035671"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"342","DOI":"10.4269\/ajtmh.21-0376","article-title":"Splenectomy in Patients with Visceral Leishmaniasis Resistant to Conventional Therapy and Secondary Prophylaxis: A Retrospective Cohort","volume":"107","author":"Reinaldo","year":"2022","journal-title":"Am. J. Trop. Med. Hyg."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Cota, G.F., de Sousa, M.R., and Rabello, A. (2011). Predictors of Visceral Leishmaniasis Relapse in HIV-Infected Patients: A Systematic Review. PLoS Neglected Trop. Dis., 5.","DOI":"10.1371\/journal.pntd.0001153"},{"key":"ref_7","unstructured":"World Health Organization & Cochrane Response (2024, May 22). WHO Guideline for the Treatment of Visceral Leishmaniasis in HIV Coinfected Patients in East Africa and South-East Asia: Web Annex A: A Systematic Review on the Treatment of Visceral Leishmaniasis in HIV-Leishmania Coinfected Persons in East Africa and So. Available online: https:\/\/apps.who.int\/iris\/handle\/10665\/354546."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"280","DOI":"10.1016\/j.chom.2016.02.012","article-title":"Dissecting How CD4 T Cells Are Lost During HIV Infection","volume":"19","author":"Doitsh","year":"2016","journal-title":"Cell Host Microbe"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"3088","DOI":"10.1128\/JCM.00173-11","article-title":"Unusual Case of Resistance to Amphotericin B in Visceral Leishmaniasis in a Region in India Where Leishmaniasis Is Not Endemic","volume":"49","author":"Srivastava","year":"2011","journal-title":"J. Clin. Microbiol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1258","DOI":"10.1093\/jac\/dkab013","article-title":"Low antileishmanial drug exposure in HIV-positive visceral leishmaniasis patients on antiretrovirals: An Ethiopian cohort study","volume":"76","author":"Blesson","year":"2021","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"3146","DOI":"10.1128\/AAC.42.12.3146","article-title":"Pharmacokinetics, Distribution in Serum Lipoproteins and Tissues, and Renal Toxicities of Amphotericin B and Amphotericin B Lipid Complex in a Hypercholesterolemic Rabbit Model: Single-Dose Studies","volume":"42","author":"Wasan","year":"1998","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_12","first-page":"68","article-title":"In vitro sensitivity of Leishmania (Viannia) braziliensis and Leishmania (Leishmania) amazonensis Brazilian isolates to meglumine antimoniate and amphotericin B","volume":"15","author":"Miguel","year":"2010","journal-title":"Trop. Med. Int. Health"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"246","DOI":"10.1016\/j.ijpddr.2018.04.002","article-title":"Genomic and transcriptomic alterations in Leishmania donovani lines experimentally resistant to antileishmanial drugs","volume":"8","author":"Rastrojo","year":"2018","journal-title":"Int. J. Parasitol. Drugs Drug Resist."},{"key":"ref_14","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 Neglected Trop. Dis., 10.","DOI":"10.1371\/journal.pntd.0004304"},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Ponte-Sucre, A., Gamarro, F., Dujardin, J.-C., Barrett, M.P., L\u00f3pez-V\u00e9lez, R., Garc\u00eda-Hern\u00e1ndez, R., Pountain, A.W., Mwenechanya, R., and Papadopoulou, B. (2017). Drug resistance and treatment failure in leishmaniasis: A 21st century challenge. PLoS Neglected Trop. Dis., 11.","DOI":"10.1371\/journal.pntd.0006052"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"e16","DOI":"10.1086\/595710","article-title":"Parasite Susceptibility to Amphotericin B in Failures of Treatment for Visceral Leishmaniasis in Patients Coinfected with HIV Type 1 and Leishmania infantum","volume":"48","author":"Lachaud","year":"2009","journal-title":"Clin. Infect. Dis."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"2141","DOI":"10.1128\/AAC.42.8.2141","article-title":"Leishmania infantum: Lack of Parasite Resistance to Amphotericin B in a Clinically Resistant Visceral Leishmaniasis","volume":"42","author":"Durand","year":"1998","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1016\/j.actatropica.2017.05.011","article-title":"Exploring prognosis in chronic relapsing visceral leishmaniasis among HIV-infected patients: Circulating Leishmania DNA","volume":"172","author":"Cota","year":"2017","journal-title":"Acta Trop."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"728","DOI":"10.1590\/0037-8682-0258-2016","article-title":"Predicting death from kala-azar: Construction, development, and validation of a score set and accompanying software","volume":"49","author":"Costa","year":"2016","journal-title":"Rev. Soc. Bras. Med. Trop."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"100487","DOI":"10.1016\/j.xcrm.2021.100487","article-title":"Immunological factors, but not clinical features, predict visceral leishmaniasis relapse in patients co-infected with HIV","volume":"3","author":"Takele","year":"2022","journal-title":"Cell Rep. Med."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Silva-Freitas, M.L., Cota, G.F., Machado-De-Assis, T.S., Giacoia-Gripp, C., Rabello, A., Da-Cruz, A.M., and Santos-Oliveira, J.R. (2016). Immune Activation and Bacterial Translocation: A Link between Impaired Immune Recovery and Frequent Visceral Leishmaniasis Relapses in HIV-Infected Patients. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0167512"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"290","DOI":"10.1093\/infdis\/jit401","article-title":"CD8 T Cell Exhaustion in Human Visceral Leishmaniasis","volume":"209","author":"Gautam","year":"2014","journal-title":"J. Infect. Dis."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Silva-Freitas, M.L., Corr\u00eaa-Castro, G., Cota, G.F., Giacoia-Gripp, C., Rabello, A., Dutra, J.T., De Vasconcelos, Z.F.M., Savino, W., Da-Cruz, A.M., and Santos-Oliveira, J.R. (2020). Impaired Thymic Output Can Be Related to the Low Immune Reconstitution and T Cell Repertoire Disturbances in Relapsing Visceral Leishmaniasis Associated HIV\/AIDS Patients. Front. Immunol., Epub ahead of print.","DOI":"10.3389\/fimmu.2020.00953"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Francois, B., Jeannet, R., Daix, T., Walton, A.H., Shotwell, M.S., Unsinger, J., Monneret, G., Rimmele, T., Blood, T., and Morre, M. (2018). Interleukin-7 restores lymphocytes in septic shock: The IRIS-7 randomized clinical trial. JCI Insight., Epub ahead of print.","DOI":"10.1172\/jci.insight.98960"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"e15055","DOI":"10.1016\/j.heliyon.2023.e15055","article-title":"The cytokine\/chemokine response in Leishmania\/HIV infection and co-infection","volume":"9","author":"Maksoud","year":"2023","journal-title":"Heliyon"},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Szwarcwald, C.L., Malta, D.C., Pereira, C.A., Figueiredo, A.W., Almeida, W.d.S.d., Machado, I.E., Bacal, N.S., da Silva, A.G., J\u00fanior, J.B.d.S., and Rosenfeld, L.G. (2019). Valores de refer\u00eancia para exames laboratoriais de colesterol, hemoglobina glicosilada e creatinina da popula\u00e7\u00e3o adulta brasileira. Rev. Bras. Epidemiol., Epub ahead of print.","DOI":"10.1590\/1980-549720190002.supl.2"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1016\/j.cca.2007.04.007","article-title":"Hypocholesterolemia and increased triglyceride in pediatric visceral leishmaniasis","volume":"382","author":"Lal","year":"2007","journal-title":"Clin. Chim. Acta"},{"key":"ref_28","first-page":"1045","article-title":"Lipids, lipoproteins, triglyceride clearance, and cytokines in human immunodeficiency virus infection and the acquired immunodeficiency syndrome","volume":"74","author":"Grunfeld","year":"1992","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1016\/j.ramb.2012.11.003","article-title":"Lipid profile of HIV-infected patients in relation to antiretroviral therapy: A review","volume":"59","author":"Souza","year":"2013","journal-title":"Rev. Assoc. Med. Bras."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1186\/s12865-015-0106-z","article-title":"Increased inflammation but similar physical composition and function in older-aged, HIV-1 infected subjects","volume":"16","author":"Wallet","year":"2015","journal-title":"BMC Immunol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"543","DOI":"10.4269\/ajtmh.2011.10-0321","article-title":"Who Is a Typical Patient with Visceral Leishmaniasis? Characterizing the Demographic and Nutritional Profile of Patients in Brazil, East Africa, and South Asia","volume":"84","author":"Harhay","year":"2011","journal-title":"Am. J. Trop. Med. Hyg."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"S69","DOI":"10.1086\/367561","article-title":"Weight Loss and Wasting in Patients Infected with Human Immunodeficiency Virus","volume":"36","author":"Grinspoon","year":"2003","journal-title":"Clin. Infect. Dis."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1097\/00075197-200203000-00006","article-title":"Changes in the concentration and composition of plasma lipoproteins during the acute phase response","volume":"5","author":"Carpentier","year":"2002","journal-title":"Curr. Opin. Clin. Nutr. Metab. Care"},{"key":"ref_34","unstructured":"Feingold, K.R., Anawalt, B., Blackman, M.R., Boyce, A., Chrousos, G., Corpas, E., de Herder, W.W., Dhatariya, K., Dungan, K., and Hofland, J. (2024, May 22). The Effect of Inflammation and Infection on Lipids and Lipoproteins. [Updated 2022 Mar 7], Endotext [Internet], Available online: https:\/\/www.ncbi.nlm.nih.gov\/books\/NBK326741\/."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"4139","DOI":"10.3390\/ijerph7124139","article-title":"Dyslipidaemia and Undernutrition in Children from Impoverished Areas of Macei\u00f3, State of Alagoas, Brazil","volume":"7","author":"Veiga","year":"2010","journal-title":"Int. J. Environ. Res. Public Health"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"156","DOI":"10.17511\/ijpr.2018.i04.01","article-title":"Study of lipid profile levels in malnourished and healthy children: A case control study acquired pneumonia in children","volume":"5","author":"Verma","year":"2018","journal-title":"Pediatr. Rev. Int. J. Pediatr. Res."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Zhang, Z., Pereira, S.L., Luo, M., and Matheson, E.M. (2017). Evaluation of Blood Biomarkers Associated with Risk of Malnutrition in Older Adults: A Systematic Review and Meta-Analysis. Nutrients, 9.","DOI":"10.3390\/nu9080829"},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Stellaard, F. (2022). From Dietary Cholesterol to Blood Cholesterol, Physiological Lipid Fluxes, and Cholesterol Homeostasis. Nutrients, 14.","DOI":"10.3390\/nu14081643"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"534","DOI":"10.1111\/joim.12614","article-title":"Can cholesterol be too low? Possible risks of extremely low levels","volume":"281","author":"Olsson","year":"2017","journal-title":"J. Intern. Med."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Wu, Z., Huang, Z., Lichtenstein, A.H., Liu, Y., Chen, S., Jin, Y., Na, M., Bao, L., Wu, S., and Gao, X. (2021). The risk of ischemic stroke and hemorrhagic stroke in Chinese adults with low-density lipoprotein cholesterol concentrations < 70 mg\/dL. BMC Med., 19.","DOI":"10.1186\/s12916-021-02014-4"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"e0860","DOI":"10.1097\/CCE.0000000000000860","article-title":"Association Between Hypocholesterolemia and Mortality in Critically Ill Patients with Sepsis: A Systematic Review and Meta-Analysis","volume":"5","author":"Hofmaenner","year":"2023","journal-title":"Crit. Care Explor."}],"container-title":["Pathogens"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-0817\/13\/6\/450\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T14:48:35Z","timestamp":1760107715000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-0817\/13\/6\/450"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,5,25]]},"references-count":41,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2024,6]]}},"alternative-id":["pathogens13060450"],"URL":"https:\/\/doi.org\/10.3390\/pathogens13060450","relation":{},"ISSN":["2076-0817"],"issn-type":[{"value":"2076-0817","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,5,25]]}}}