{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T18:11:33Z","timestamp":1792174293693,"version":"4.4.0"},"reference-count":208,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2023,7,24]],"date-time":"2023-07-24T00:00:00Z","timestamp":1690156800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico (CNPq) fellowship","award":["307606\/221-0"],"award-info":[{"award-number":["307606\/221-0"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pathogens"],"abstract":"<jats:p>Kala-azar, also known as visceral leishmaniasis (VL), is a disease caused by Leishmania infantum and L. donovani. Patients experience symptoms such as fever, weight loss, paleness, and enlarged liver and spleen. The disease also affects immunosuppressed individuals and has an overall mortality rate of up to 10%. This overview explores the literature on the pathogenesis of preclinical and clinical stages, including studies in vitro and in animal models, as well as complications and death. Asymptomatic infection can result in long-lasting immunity. VL develops in a minority of infected individuals when parasites overcome host defenses and multiply in tissues such as the spleen, liver, and bone marrow. Hepatosplenomegaly occurs due to hyperplasia, resulting from parasite proliferation. A systemic inflammation mediated by cytokines develops, triggering acute phase reactants from the liver. These cytokines can reach the brain, causing fever, cachexia and vomiting. Similar to sepsis, disseminated intravascular coagulation (DIC) occurs due to tissue factor overexpression. Anemia, hypergammaglobulinemia, and edema result from the acute phase response. A regulatory response and lymphocyte depletion increase the risk of bacterial superinfections, which, combined with DIC, are thought to cause death. Our understanding of VL\u2019s pathogenesis is limited, and further research is needed to elucidate the preclinical events and clinical manifestations in humans.<\/jats:p>","DOI":"10.3390\/pathogens12070969","type":"journal-article","created":{"date-parts":[[2023,7,25]],"date-time":"2023-07-25T01:32:10Z","timestamp":1690248730000},"page":"969","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":103,"title":["From Infection to Death: An Overview of the Pathogenesis of Visceral Leishmaniasis"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7302-2006","authenticated-orcid":false,"given":"Carlos H. N.","family":"Costa","sequence":"first","affiliation":[{"name":"Centro de Investiga\u00e7\u00f5es em Agravos Tropicais Emergentes e Negligenciados, Instituto de Doen\u00e7as Tropicais Natan Portella, Universidade Federal do Piau\u00ed, Rua Artur de Vasconcelos 151-Sul, Teresina 64002-510, PI, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kwang-Poo","family":"Chang","sequence":"additional","affiliation":[{"name":"Department of Microbiology\/Immunology, Center for Cancer Cell Biology, Immunology & Infection, Chicago Medical School, Rosalind Franklin University, North Chicago, IL 60064, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dorcas L.","family":"Costa","sequence":"additional","affiliation":[{"name":"Centro de Investiga\u00e7\u00f5es em Agravos Tropicais Emergentes e Negligenciados, Instituto de Doen\u00e7as Tropicais Natan Portella, Universidade Federal do Piau\u00ed, Rua Artur de Vasconcelos 151-Sul, Teresina 64002-510, PI, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francisco Valmor M.","family":"Cunha","sequence":"additional","affiliation":[{"name":"Departament of Physiotherapy, Centro Universit\u00e1rio Uninovafapi, Rua Vitorino Orthiges Fernandes, 6123-Uruguai, Teresina 64073-505, PI, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,7,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1603","DOI":"10.1016\/S0140-6736(16)31460-X","article-title":"Global, regional, and national disability-adjusted life-years (DALYs) for 315 diseases and injuries and healthy life expectancy (HALE), 1990\u20132015: A systematic analysis for the Global Burden of Disease Study 2015","volume":"388","author":"Kassebaum","year":"2016","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"e3","DOI":"10.35500\/jghs.2020.2.e3","article-title":"Visceral leishmaniasis: A global overview","volume":"2","author":"Wamai","year":"2020","journal-title":"J. Glob. Health Sci."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Alvar, J., V\u00e9lez, I.D., Bern, C., Herrero, M., Desjeux, P., Cano, J., Jannin, J., den Boer, M., and WHO Leishmaniasis Control Team (2012). Leishmaniasis Worldwide and Global Estimates of Its Incidence. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0035671"},{"key":"ref_4","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_5","doi-asserted-by":"crossref","unstructured":"Kumar, V., Mandal, R., Das, S., Kesari, S., Dinesh, D.S., Pandey, K., Das, V.R., Topno, R.K., Sharma, M.P., and Dasgupta, R.K. (2020). Kala-azar elimination in a highly-endemic district of Bihar, India: A success story. PLoS Negl. Trop. Dis., 14.","DOI":"10.1371\/journal.pntd.0008254"},{"key":"ref_6","unstructured":"World Health Organization (WHO) (2021). Kala-azar in India\u2014progress and challenges towards its elimination as a public health problem. Wkly Epidemiol Rec., 96, 267\u2013279."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Cota, G., Erber, A.C., Schernhammer, E., and Sim\u00f5es, T.C. (2021). Inequalities of visceral leishmaniasis case-fatality in Brazil: A multilevel modeling considering space, time, individual and contextual factors. PLoS Negl. Trop. Dis., 15.","DOI":"10.1371\/journal.pntd.0009567"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1016\/0035-9203(75)90012-7","article-title":"Studies in Mediterranean leishmaniasis. 3. The leishmanin skin test in kala-azar","volume":"69","author":"Pampiglione","year":"1975","journal-title":"Trans. R. Soc. Trop. Med. Hyg."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"639","DOI":"10.1093\/infdis\/154.4.639","article-title":"A Prospective Study of Visceral Leishmaniasis in an Endemic Area of Brazil","volume":"154","author":"Badaro","year":"1986","journal-title":"J. Infect. Dis."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1124","DOI":"10.1093\/infdis\/166.5.1124","article-title":"Epidemiology of visceral leishmaniasis in northeast Brazil","volume":"166","author":"Evans","year":"1992","journal-title":"J. Infect. Dis."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Carstens-Kass, J., Paulini, K., Lypaczewski, P., and Matlashewski, G. (2021). A review of the leishmanin skin test: A neglected test for a neglected disease. PLoS Negl. Trop. Dis., 15.","DOI":"10.1371\/journal.pntd.0009531"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1016\/S0001-706X(02)00058-X","article-title":"The burden of Leishmania chagasi infection during an urban outbreak of visceral leishmaniasis in Brazil","volume":"83","author":"Werneck","year":"2002","journal-title":"Acta Trop."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"507","DOI":"10.1016\/S1286-4579(03)00071-6","article-title":"Early mechanisms of Leishmania infection in human blood","volume":"5","author":"Moreno","year":"2003","journal-title":"Microbes Infect."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"970","DOI":"10.1126\/science.1159194","article-title":"In vivo imaging reveals an essential role for neutrophils in leishmaniasis transmitted by sand flies","volume":"321","author":"Peters","year":"2008","journal-title":"Science"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1685","DOI":"10.1002\/iub.2129","article-title":"Leishmania species-dependent functional duality of toll-like receptor 2","volume":"71","author":"Jafarzadeh","year":"2019","journal-title":"IUBMB Life"},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Wu, T.-H., Hsieh, S.-C., Li, T.-H., Lu, C.-H., Liao, H.-T., Shen, C.-Y., Li, K.-J., Wu, C.-H., Kuo, Y.-M., and Tsai, C.-Y. (2022). Molecular Basis for Paradoxical Activities of Polymorphonuclear Neutrophils in Inflammation\/Anti-Inflammation, Bactericide\/Autoimmunity, Pro-Cancer\/Anticancer, and Antiviral Infection\/SARS-CoV-II-Induced Immunothrombotic Dysregulation. Biomedicines, 10.","DOI":"10.3390\/biomedicines10040773"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1991","DOI":"10.1182\/blood-2016-10-744441","article-title":"Neutrophils acquire the capacity for antigen presentation to memory CD4+ T cells in vitro and ex vivo","volume":"129","author":"Vono","year":"2017","journal-title":"Blood"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1080\/08916930701356960","article-title":"Apoptosis driven infection","volume":"40","author":"Solbach","year":"2007","journal-title":"Autoimmunity"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"685296","DOI":"10.3389\/fcimb.2021.685296","article-title":"Mechanisms of Immunopathogenesis in Cutaneous Leishmaniasis And Post Kala-azar Dermal Leishmaniasis (PKDL)","volume":"11","author":"Volpedo","year":"2021","journal-title":"Front. Cell. Infect. Microbiol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1093\/intimm\/dxx075","article-title":"How to master the host immune system? Leishmania parasites have the solutions!","volume":"30","author":"Rossi","year":"2018","journal-title":"Int. Immunol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"227","DOI":"10.3389\/fimmu.2019.00227","article-title":"Molecular Aspects of Dendritic Cell Activation in Leishmaniasis: An Immunobiological View","volume":"10","author":"Nunes","year":"2019","journal-title":"Front. Immunol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1038\/32588","article-title":"Dendritic cells and the control of immunity","volume":"392","author":"Banchereau","year":"1998","journal-title":"Nature"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"517","DOI":"10.1590\/0074-02760160185","article-title":"Comparison of optical microscopy and quantitative polymerase chain reaction for estimating parasitaemia in patients with kala-azar and modelling infectiousness to the vector Lutzomyia longipalpis","volume":"111","author":"Silva","year":"2016","journal-title":"Mem. Inst. Oswaldo Cruz"},{"key":"ref_24","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_25","doi-asserted-by":"crossref","first-page":"155322","DOI":"10.1016\/j.cyto.2020.155322","article-title":"Cytokine saga in visceral leishmaniasis","volume":"147","author":"Bhor","year":"2020","journal-title":"Cytokine"},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Volpedo, G., Bhattacharya, P., Gannavaram, S., Pacheco-Fernandez, T., Oljuskin, T., Dey, R., Satoskar, A.R., and Nakhasi, H.L. (2022). The History of Live Attenuated Centrin Gene-Deleted Leishmania Vaccine Candidates. Pathogens, 11.","DOI":"10.3390\/pathogens11040431"},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Kol\u00e1\u0159ov\u00e1, I., and Valigurov\u00e1, A. (2021). Hide-and-Seek: A Game Played between Parasitic Protists and Their Hosts. Microorganisms, 9.","DOI":"10.3390\/microorganisms9122434"},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Lypaczewski, P., Zhang, W.-W., and Matlashewski, G. (2021). Evidence that a naturally occurring single nucleotide polymorphism in the RagC gene of Leishmania donovani contributes to reduced virulence. PLoS Negl. Trop. Dis., 15.","DOI":"10.1371\/journal.pntd.0009079"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1017\/S003118201700169X","article-title":"Dermotropic Leishmania donovani in Sri Lanka: Visceralizing potential in clinical and preclinical studies","volume":"145","author":"Kariyawasam","year":"2018","journal-title":"Parasitology"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"e0206822","DOI":"10.1128\/mbio.02068-22","article-title":"Parasite Genotype Is a Major Predictor of Mortality from Visceral Leishmaniasis","volume":"13","author":"Grace","year":"2022","journal-title":"MBio"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1031","DOI":"10.1038\/s41591-022-01780-9","article-title":"Safety, tolerability and viral kinetics during SARS-CoV-2 human challenge in young adults","volume":"28","author":"Killingley","year":"2022","journal-title":"Nat. Med."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1186\/s13578-022-00775-w","article-title":"3D and organoid culture in research: Physiology, hereditary genetic diseases and cancer","volume":"12","author":"Carnero","year":"2022","journal-title":"Cell Biosci."},{"key":"ref_33","unstructured":"(2023, April 24). Chan Zuckerberg Initiative. Available online: https:\/\/chanzuckerberg.com\/newsroom\/biohub-chicago-engineer-technologies-measure-human-biology."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1038\/sj.gene.6364355","article-title":"Identification of a novel G245R polymorphism in the IL-2 receptor \u03b2 membrane proximal domain associated with human visceral leishmaniasis","volume":"8","author":"Bucheton","year":"2007","journal-title":"Genes Immun."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1212","DOI":"10.1086\/512683","article-title":"Genotypes of the Mannan-Binding Lectin Gene and Susceptibility to Visceral Leishmaniasis and Clinical Complications","volume":"195","author":"Alonso","year":"2007","journal-title":"J. Infect. Dis."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"912","DOI":"10.1016\/j.meegid.2011.02.014","article-title":"TGFB1 and IL8 gene polymorphisms and susceptibility to visceral leishmaniasis","volume":"11","author":"Frade","year":"2011","journal-title":"Infect. Genet. Evol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"813","DOI":"10.1007\/s00439-020-02130-w","article-title":"Human genetics of leishmania infections","volume":"139","author":"Blackwell","year":"2020","journal-title":"Hum. Genet."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1016\/S0035-9203(02)90227-0","article-title":"Risk factors associated with asymptomatic infection by Leishmania chagasi in north-east Brazil","volume":"96","author":"Caldas","year":"2002","journal-title":"Trans. R. Soc. Trop. Med. Hyg."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"679","DOI":"10.1111\/tmi.12877","article-title":"Causes and consequences of higher Leishmania infantum burden in patients with kala-azar: A study of 625 patients","volume":"22","author":"Zacarias","year":"2017","journal-title":"Trop. Med. Int. Health"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"531","DOI":"10.1016\/0035-9203(82)90157-2","article-title":"A review of kala-azar in China from 1949 to 1959","volume":"76","year":"1982","journal-title":"Trans. R. Soc. Trop. Med. Hyg."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1590\/S0034-89101990000500003","article-title":"Epidemia de leishmaniose visceral no Estado do Piau\u00ed, Brasil, 1980\u20131986","volume":"24","author":"Costa","year":"1990","journal-title":"Rev. Saude Publica"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1016\/S0001-706X(00)00068-1","article-title":"Leishmania donovani in blood smears of asymptomatic persons","volume":"76","author":"Sharma","year":"2000","journal-title":"Acta Trop."},{"key":"ref_43","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., 14.","DOI":"10.1371\/journal.pntd.0007995"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"e12874","DOI":"10.1111\/pim.12874","article-title":"Influence of sex hormones on the immune response to leishmaniasis","volume":"43","author":"Silva","year":"2021","journal-title":"Parasite Immunol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1046\/j.1365-3156.2002.00832.x","article-title":"Epidemiology and clinical manifestations of Leishmania donovani infection in two villages in an endemic area in eastern Sudan","volume":"7","author":"Khalil","year":"2002","journal-title":"Trop. Med. Int. Health"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"773983","DOI":"10.3389\/fimmu.2021.773983","article-title":"Multifunctional, TNF-\u03b1 and IFN-\u03b3-Secreting CD4 and CD8 T Cells and CD8High T Cells Are Associated With the Cure of Human Visceral Leishmaniasis","volume":"12","author":"Rodrigues","year":"2021","journal-title":"Front. Immunol."},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Akuffo, H., Costa, C., van Griensven, J., Burza, S., Moreno, J., and Herrero, M. (2018). New insights into leishmaniasis in the immunosuppressed. PLoS Negl. Trop. Dis., 12.","DOI":"10.1371\/journal.pntd.0006375"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"976","DOI":"10.1016\/j.pt.2021.07.003","article-title":"Leishmaniasis: The act of transmission","volume":"37","author":"Serafim","year":"2021","journal-title":"Trends Parasitol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"10125","DOI":"10.1073\/pnas.0802331105","article-title":"Quantification of the infectious dose of Leishmania major transmitted to the skin by single sand flies","volume":"105","author":"Kimblin","year":"2008","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1038\/s42003-019-0323-8","article-title":"Quantifying Leishmania Metacyclic Promastigotes from Individual Sandfly Bites Reveals the Efficiency of Vector Transmission","volume":"2","author":"Giraud","year":"2019","journal-title":"Commun. Biol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1111\/j.1365-2249.2006.03171.x","article-title":"Mixed inflammatory\/regulatory cytokine profile marked by simultaneous raise of interferon-gamma and interleukin-10 and low frequency of tumour necrosis factor-alpha(+) monocytes are hallmarks of active human visceral Leishmaniasis due to Leishmania chagas","volume":"146","author":"Prata","year":"2006","journal-title":"Clin. Exp. Immunol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"109098","DOI":"10.1016\/j.biopha.2019.109098","article-title":"Functional aspects of T cell diversity in visceral leishmaniasis","volume":"117","author":"Jawed","year":"2019","journal-title":"Biomed. Pharmacother."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"860","DOI":"10.1172\/JCI113969","article-title":"Antigen-specific immunosuppression in visceral leishmaniasis is cell mediated","volume":"83","author":"Carvalho","year":"1989","journal-title":"J. Clin. Investig."},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Caldas, A., Favali, C., Aquino, D., Vinhas, V., van Weyenbergh, J., Brodskyn, C., Costa, J., Barral-Netto, M., and Barral, A. (2005). Balance of IL-10 and interferon-gamma plasma levels in human visceral leishmaniasis: Implications in the pathogenesis. BMC Infect. Dis., 5.","DOI":"10.1186\/1471-2334-5-113"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"805","DOI":"10.1084\/jem.20061141","article-title":"Splenic accumulation of IL-10 mRNA in T cells distinct from CD4+CD25+ (Foxp3) regulatory T cells in human visceral leishmaniasis","volume":"204","author":"Maurya","year":"2007","journal-title":"J. Exp. Med."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"2066","DOI":"10.1172\/JCI112209","article-title":"Absence of gamma interferon and interleukin 2 production during active visceral leishmaniasis","volume":"76","author":"Carvalho","year":"1985","journal-title":"J. Clin. Investig."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"498","DOI":"10.1128\/iai.33.2.498-500.1981","article-title":"Cell-mediated immunity in American visceral leishmaniasis: Reversible immunosuppression during acute infection","volume":"33","author":"Carvalho","year":"1981","journal-title":"Infect. Immun."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"386","DOI":"10.1590\/S0037-86822010000400010","article-title":"Is severe visceral leishmaniasis a systemic inflammatory response syndrome? A case control study","volume":"43","author":"Costa","year":"2010","journal-title":"Rev. Soc. Bras. Med. Trop."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"621","DOI":"10.4269\/ajtmh.13-0376","article-title":"Bone Marrow Parasite Burden among Patients with New World Kala-Azar is Associated with Disease Severity","volume":"90","author":"Costa","year":"2014","journal-title":"Am. J. Trop. Med. Hyg."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1111\/cei.13014","article-title":"Redundant and regulatory roles for Toll-like receptors in Leishmania infection","volume":"190","author":"Chauhan","year":"2017","journal-title":"Clin. Exp. Immunol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"448","DOI":"10.1038\/ni.3153","article-title":"IL-6 as a keystone cytokine in health and disease","volume":"16","author":"Hunter","year":"2015","journal-title":"Nat. Immunol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"1403","DOI":"10.1016\/j.jhep.2016.02.004","article-title":"IL-6 pathway in the liver: From physiopathology to therapy","volume":"64","year":"2016","journal-title":"J. Hepatol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"3399","DOI":"10.1161\/01.ATV.17.12.3399","article-title":"Effect of human recombinant interleukin-6 and interleukin-8 on monocyte procoagulant activity","volume":"17","author":"Neumann","year":"1997","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1016\/j.tcm.2015.12.001","article-title":"Tissue factor as a link between inflammation and coagulation","volume":"26","author":"Witkowski","year":"2016","journal-title":"Trends Cardiovasc. Med."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"e12291","DOI":"10.1111\/xen.12291","article-title":"Human IL-6, IL-17, IL-1\u03b2, and TNF-\u03b1 differently regulate the expression of pro-inflammatory related genes, tissue factor, and swine leukocyte antigen class I in porcine aortic endothelial cells","volume":"24","author":"Gao","year":"2017","journal-title":"Xenotransplantation"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"1668","DOI":"10.1046\/j.1471-4159.1997.69041668.x","article-title":"Regulation of the Genes Encoding Interleukin-6, Its Receptor, and gp130 in the Rat Brain in Response to the Immune Activator Lipopolysaccharide and the Proinflammatory Cytokine Interleukin-1\u03b2","volume":"69","author":"Rivest","year":"1997","journal-title":"J. Neurochem."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1016\/j.semcdb.2015.10.038","article-title":"The central role of hypothalamic inflammation in the acute illness response and cachexia","volume":"54","author":"Burfeind","year":"2016","journal-title":"Semin. Cell Dev. Biol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"1805","DOI":"10.1172\/JCI200318921","article-title":"C-reactive protein: A critical update","volume":"111","author":"Pepys","year":"2003","journal-title":"J. Clin. Investig."},{"key":"ref_69","doi-asserted-by":"crossref","unstructured":"Veas, F. (2011). Acute Phase Proteins\u2014Regulation and Functions of Acute Phase Proteins, In Tech.","DOI":"10.5772\/756"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"ofv098","DOI":"10.1093\/ofid\/ofv098","article-title":"Acute Phase Reactants in Infections: Evidence-Based Review and a Guide for Clinicians","volume":"2","author":"Markanday","year":"2015","journal-title":"Open Forum Infect. Dis."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"2830503","DOI":"10.1155\/2018\/2830503","article-title":"The Association of Simultaneous Increase in Interleukin-6, C Reactive Protein, and Matrix Metalloproteinase-9 Serum Levels with Increasing Stages of Colorectal Cancer","volume":"2018","author":"Rasic","year":"2018","journal-title":"J. Oncol."},{"key":"ref_72","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_73","doi-asserted-by":"crossref","first-page":"226","DOI":"10.1093\/tropej\/45.4.226","article-title":"Prognostic value of serum C-reactive protein in kala-azar","volume":"45","author":"Singh","year":"1999","journal-title":"J. Trop. Pediatr."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1016\/j.clim.2006.11.008","article-title":"Circulating nitric oxide and C-reactive protein levels in Indian kala azar patients: Correlation with clinical outcome","volume":"122","author":"Ansari","year":"2007","journal-title":"Clin. Immunol."},{"key":"ref_75","first-page":"145","article-title":"C-reactive protein for the diagnosis and prognosis of visceral leishmaniasis caused by Leishmania infantum","volume":"51","author":"Costa","year":"2022","journal-title":"J. Trop. Pathol."},{"key":"ref_76","doi-asserted-by":"crossref","unstructured":"Endale, H.T., Mengstie, T.A., Dawit, D.D., Mohammed, R., Dessie, G., and Tesfa, K.H. (2021). Assessment of liver function test and associated factors among visceral leishmaniasis patients attending university of gondar leishmaniasis research and treatment center, Northwest Ethiopia. PLoS ONE, 16.","DOI":"10.1371\/journal.pone.0260022"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1007\/s12288-010-0027-1","article-title":"Hematologic changes in visceral leishmaniasis\/kala azar","volume":"26","author":"Varma","year":"2010","journal-title":"Indian J. Hematol. Blood Transfus."},{"key":"ref_78","first-page":"317","article-title":"Erythrocyte Sedimentation Rate and C-reactive Protein Measurements and Their Relevance in Clinical Medicine","volume":"115","author":"Bray","year":"2016","journal-title":"WMJ"},{"key":"ref_79","unstructured":"Tishkowski, K., and Gupta, V. (2022). Erythrocyte Sedimentation Rate, In Tech."},{"key":"ref_80","unstructured":"Davidson, S.J. (2013). Acute Phase Proteins, In Tech."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"812774","DOI":"10.3389\/fimmu.2022.812774","article-title":"Toll-Like Receptor Signaling and Its Role in Cell-Mediated Immunity","volume":"13","author":"Duan","year":"2022","journal-title":"Front. Immunol."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"1563","DOI":"10.1002\/cphy.c130033","article-title":"Mechanisms of fever production and lysis: Lessons from experimental LPS fever","volume":"4","author":"Roth","year":"2014","journal-title":"Compr. Physiol."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"2489","DOI":"10.1038\/s41423-021-00757-x","article-title":"The blood\u2013brain barrier in systemic infection and inflammation","volume":"18","author":"Galea","year":"2021","journal-title":"Cell. Mol. Immunol."},{"key":"ref_84","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":"Rijal","year":"2011","journal-title":"Am. J. Trop. Med. Hyg."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"e08002020","DOI":"10.1590\/0037-8682-0800-2020","article-title":"Nutritional status and vitamin A and zinc levels in patients with kala-azar in Piau\u00ed, Brazil","volume":"54","author":"Monteiro","year":"2021","journal-title":"Rev. Soc. Bras. Med. Trop."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"664","DOI":"10.7326\/0003-4819-124-7-199604010-00007","article-title":"Epidemic Visceral Leishmaniasis in Southern Sudan: Treatment of Severely Debilitated Patients under Wartime Conditions and with Limited Resources","volume":"124","author":"Seaman","year":"1996","journal-title":"Ann. Intern. Med."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"73","DOI":"10.2223\/1286","article-title":"American visceral leishmaniasis (kala-azar) in hospitalized children from an endemic area","volume":"81","author":"Rey","year":"2005","journal-title":"J. Pediatr."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"373","DOI":"10.4269\/ajtmh.2009.81.373","article-title":"Natural history of a visceral leishmaniasis outbreak in highland Ethiopia","volume":"81","author":"Herrero","year":"2009","journal-title":"Am. J. Trop. Med. Hyg."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"346","DOI":"10.1093\/trstmh\/traa010","article-title":"Prognostic factors associated with death from visceral leishmaniasis: A case-control study in Brazil","volume":"114","author":"Morais","year":"2020","journal-title":"Trans. R. Soc. Trop. Med. Hyg."},{"key":"ref_90","doi-asserted-by":"crossref","unstructured":"Abongomera, C., van Henten, S., Vogt, F., Buyze, J., Verdonck, K., and van Griensven, J. (2020). Prognostic factors for mortality among patients with visceral leishmaniasis in East Africa: Systematic review and meta-analysis. PLoS Negl. Trop. Dis., 14.","DOI":"10.1371\/journal.pntd.0008319"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1016\/j.yfrne.2009.10.002","article-title":"Hypothalamic inflammation and energy homeostasis: Resolving the paradox","volume":"31","author":"Thaler","year":"2010","journal-title":"Front. Neuroendocrinol."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"322","DOI":"10.1016\/j.bbi.2015.07.012","article-title":"Fever and sickness behavior: Friend or foe?","volume":"50","author":"Harden","year":"2015","journal-title":"Brain. Behav. Immun."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"664781","DOI":"10.3389\/fnins.2021.664781","article-title":"Role of the Preoptic Area in Sleep and Thermoregulation","volume":"15","author":"Rothhaas","year":"2021","journal-title":"Front. Neurosci."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1097\/SPC.0b013e3283186be2","article-title":"Cachexia, survival and the acute phase response","volume":"2","author":"Stephens","year":"2008","journal-title":"Curr. Opin. Support. Palliat. Care"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"168","DOI":"10.1097\/JES.0b013e3181f44f11","article-title":"Interleukin 6 as a key regulator of muscle mass during cachexia","volume":"38","author":"Carson","year":"2010","journal-title":"Exerc. Sport Sci. Rev."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1097\/SPC.0000000000000091","article-title":"Role of interleukin-6 in cachexia: Therapeutic implications","volume":"8","author":"Narsale","year":"2014","journal-title":"Curr. Opin. Support. Palliat. Care"},{"key":"ref_97","first-page":"76","article-title":"Evaluation of nausea and vomiting","volume":"76","author":"Scorza","year":"2007","journal-title":"Am. Fam. Physician"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1177\/1756283X15618131","article-title":"Nausea: A review of pathophysiology and therapeutics","volume":"9","author":"Singh","year":"2016","journal-title":"Therap. Adv. Gastroenterol."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"733","DOI":"10.1046\/j.1365-3156.2003.01088.x","article-title":"Visceral leishmaniasis and HIV in Tigray, Ethiopia","volume":"8","author":"Lyons","year":"2003","journal-title":"Trop. Med. Int. Health"},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"612","DOI":"10.1086\/381203","article-title":"Conflict and Kala-Azar: Determinants of Adverse Outcomes of Kala-Azar among Patients in Southern Sudan","volume":"38","author":"Collin","year":"2004","journal-title":"Clin. Infect. Dis."},{"key":"ref_101","doi-asserted-by":"crossref","unstructured":"de Ara\u00fajo, V.E.M., Morais, M.H.F., Reis, I.A., Rabello, A., and Carneiro, M. (2012). Early Clinical Manifestations Associated with Death from Visceral Leishmaniasis. PLoS Negl. Trop. Dis., 6.","DOI":"10.1371\/journal.pntd.0001511"},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"281572","DOI":"10.1155\/2012\/281572","article-title":"American Visceral Leishmaniasis: Factors Associated with Lethality in the State of S\u00e3o Paulo, Brazil","volume":"2012","author":"Madalosso","year":"2012","journal-title":"J. Trop. Med."},{"key":"ref_103","doi-asserted-by":"crossref","unstructured":"Belo, V.S., Struchiner, C.J., Barbosa, D.S., Nascimento, B.W.L., Horta, M.A.P., da Silva, E.S., and Werneck, G.L. (2014). Risk Factors for Adverse Prognosis and Death in American Visceral Leishmaniasis: A Meta-analysis. PLoS Negl. Trop. Dis., 8.","DOI":"10.1371\/journal.pntd.0002982"},{"key":"ref_104","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_105","doi-asserted-by":"crossref","first-page":"563","DOI":"10.1007\/s00281-017-0625-1","article-title":"Immune-mediated cytokine storm and its role in severe dengue","volume":"39","author":"Srikiatkhachorn","year":"2017","journal-title":"Semin. Immunopathol."},{"key":"ref_106","first-page":"535","article-title":"Visceral leishmaniasis in children: Prognostic factors","volume":"81","author":"Abdelmoula","year":"2003","journal-title":"Tunis. Med."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"174","DOI":"10.1007\/s15010-003-3139-9","article-title":"Prognostic Factors for Death from Visceral Leishmaniasis in Teresina, Brazil","volume":"31","author":"Werneck","year":"2003","journal-title":"Infection"},{"key":"ref_108","doi-asserted-by":"crossref","unstructured":"Sampaio, M.J.A.D.Q., Cavalcanti, N.V., Alves, J.G.B., Fernandes-Filho, M.J.C., and Correia, J.B. (2010). Risk factors for death in children with visceral leishmaniasis. PLoS Negl. Trop. Dis., 4.","DOI":"10.1371\/journal.pntd.0000877"},{"key":"ref_109","doi-asserted-by":"crossref","unstructured":"Coura-Vital, W., de Ara\u00fajo, V.E.M., Reis, I.A., Amancio, F.F., Reis, A.B., and Carneiro, M. (2014). Prognostic Factors and Scoring System for Death from Visceral Leishmaniasis: An Historical Cohort Study in Brazil. PLoS Negl. Trop. Dis., 8.","DOI":"10.1371\/journal.pntd.0003374"},{"key":"ref_110","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_111","doi-asserted-by":"crossref","unstructured":"Ben Helel, K., Ben Rejeb, M., Habboul, Z., Khattat, N., Mejaouel, H., Said-Latiri, H., Kaabi, B., Zhioua, E., Helel, K.B., and Rejeb, M.B. (2017). Risk factors for mortality of children with zoonotic visceral leishmaniasis in Central Tunisia. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0189725"},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"6688444","DOI":"10.1155\/2021\/6688444","article-title":"Temporal Validation of a Predictive Score for Death in Children with Visceral Leishmaniasis","volume":"2021","author":"Foinquinos","year":"2021","journal-title":"J. Trop. Med."},{"key":"ref_113","first-page":"371","article-title":"Haematological investigations in visceral leishmaniasis","volume":"38","author":"Kager","year":"1986","journal-title":"Trop. Geogr. Med."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"1492","DOI":"10.1111\/liv.12702","article-title":"Big spleens and hypersplenism: Fix it or forget it?","volume":"35","author":"Boyer","year":"2015","journal-title":"Liver Int."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"1271","DOI":"10.1172\/JCI200420945","article-title":"IL-6 mediates hypoferremia of inflammation by inducing the synthesis of the iron regulatory hormone hepcidin","volume":"113","author":"Nemeth","year":"2004","journal-title":"J. Clin. Investig."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"126","DOI":"10.3945\/an.116.013961","article-title":"Regulation of the Iron Homeostatic Hormone Hepcidin","volume":"8","author":"Sangkhae","year":"2017","journal-title":"Adv. Nutr."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"e12601","DOI":"10.1111\/pim.12601","article-title":"Hepcidin mediated iron homoeostasis as immune regulator in visceral leishmaniasis patients","volume":"41","author":"Singh","year":"2019","journal-title":"Parasite Immunol."},{"key":"ref_118","first-page":"605","article-title":"Morphology of the spleen and lymph nodes in fatal visceral leishmaniasis","volume":"33","author":"Veress","year":"1977","journal-title":"Immunology"},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1590\/S0036-46651987000300003","article-title":"Histopathological patterns of the liver involvement in visceral leishmaniasis","volume":"29","author":"Duarte","year":"1987","journal-title":"Rev. Inst. Med. Trop. Sao Paulo"},{"key":"ref_120","doi-asserted-by":"crossref","unstructured":"Dos-Santos, W.L., Pagliari, C., Santos, L.G., Almeida, V.A., e Silva, T.L., Coutinho, J.D., Souza, T., Duarte, M.I., de Freitas, L.A., and Costa, C.H. (2014). A case of conventional treatment failure in visceral leishmaniasis: Leukocyte distribution and cytokine expression in splenic compartments. BMC Infect. Dis., 14.","DOI":"10.1186\/1471-2334-14-491"},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"394","DOI":"10.3389\/fcimb.2018.00394","article-title":"Histological Disorganization of Spleen Compartments and Severe Visceral Leishmaniasis","volume":"8","author":"Hermida","year":"2018","journal-title":"Front. Cell. Infect. Microbiol."},{"key":"ref_122","doi-asserted-by":"crossref","unstructured":"Bhattacharya, P., Ghosh, S., Ejazi, S.A., Rahaman, M., Pandey, K., Ravi Das, V.N., Das, P., Goswami, R.P., Saha, B., and Ali, N. (2016). Induction of IL-10 and TGF\u03b2 from CD4+CD25+FoxP3+ T Cells Correlates with Parasite Load in Indian Kala-azar Patients Infected with Leishmania donovani. PLoS Negl. Trop. Dis., 10.","DOI":"10.1371\/journal.pntd.0004422"},{"key":"ref_123","doi-asserted-by":"crossref","unstructured":"Cavalcanti, A.S., Ribeiro-Alves, M., Pereira, L.D.O.R., Mestre, G.L., Ferreira, A.B.R., Morgado, F.N., Boit\u00e9, M.C., Cupolillo, E., Moraes, M.O., and Porrozzi, R. (2015). Parasite Load Induces Progressive Spleen Architecture Breakage and Impairs Cytokine mRNA Expression in Leishmania infantum-Naturally Infected Dogs. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0123009"},{"key":"ref_124","doi-asserted-by":"crossref","unstructured":"Reinaldo, L.G.C., Ara\u00fajo-J\u00fanior, R.J.C., Diniz, T.M., Moura, R.D., Meneses-Filho, A.J., Furtado, C.V.V.M., Santos, W.L.C., Costa, D.L., Eul\u00e1lio, K.D., and Ferreira, G.R. (2022). Splenectomy in Patients with Visceral Leishmaniasis Resistant to Conventional Therapy and Secondary Prophylaxis: A Retrospective Cohort. Am. J. Trop. Med. Hyg., in press.","DOI":"10.4269\/ajtmh.21-0376"},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"547","DOI":"10.1136\/jcp.47.6.547","article-title":"Liver morphology and function in visceral leishmaniasis (Kala-azar)","volume":"47","author":"Hashim","year":"1994","journal-title":"J. Clin. Pathol."},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1590\/S0037-86822010000400011","article-title":"Cytokine expression in the duodenal mucosa of patients with visceral leishmaniasis","volume":"43","author":"Luz","year":"2010","journal-title":"Rev. Soc. Bras. Med. Trop."},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"881","DOI":"10.2147\/IDR.S245991","article-title":"Incidence of mortality and its predictors among adult visceral leishmaniasis patients at the university of gondar hospital: A retrospective cohort study","volume":"13","author":"Yeshaw","year":"2020","journal-title":"Infect. Drug Resist."},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1002\/jpen.1451","article-title":"Hypoalbuminemia: Pathogenesis and Clinical Significance","volume":"43","author":"Soeters","year":"2019","journal-title":"JPEN. J. Parenter. Enteral Nutr."},{"key":"ref_129","doi-asserted-by":"crossref","unstructured":"Daher, E.F., Soares, D.S., Filho, S.L., Meneses, G.C., Freitas, T.V., Leite, T.T., and da Silva Junior, G.B. (2017). Hyponatremia and risk factors for death in human visceral leishmaniasis: New insights from a cross-sectional study in Brazil. BMC Infect. Dis., 17.","DOI":"10.1186\/s12879-017-2257-4"},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1016\/0035-9203(89)90712-8","article-title":"Interstitial pneumonitis in human visceral leishmaniasis","volume":"83","author":"Duarte","year":"1989","journal-title":"Trans. R. Soc. Trop. Med. Hyg."},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1111\/j.1365-3024.2008.01080.x","article-title":"In situ immune responses to interstitial pneumonitis in human visceral leishmaniasis","volume":"31","author":"Tuon","year":"2009","journal-title":"Parasite Immunol."},{"key":"ref_132","doi-asserted-by":"crossref","unstructured":"Bispo, A.J.B., Almeida, M.L.D., de Almeida, R.P., Bispo Neto, J., de Oliveira Brito, A.V., and Fran\u00e7a, C.M. (2020). Pulmonary involvement in human visceral leishmaniasis: Clinical and tomographic evaluation. PLoS ONE, 15.","DOI":"10.1371\/journal.pone.0228176"},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"842","DOI":"10.1016\/j.chest.2017.03.033","article-title":"The Role of Infection in Interstitial Lung Diseases","volume":"152","author":"Azadeh","year":"2017","journal-title":"Chest"},{"key":"ref_134","doi-asserted-by":"crossref","unstructured":"Montero, P., Milara, J., Roger, I., and Cortijo, J. (2021). Role of JAK\/STAT in Interstitial Lung Diseases; Molecular and Cellular Mechanisms. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22126211"},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"991","DOI":"10.2147\/DDDT.S353494","article-title":"Therapeutic Potential of Janus Kinase Inhibitors for the Management of Interstitial Lung Disease","volume":"16","author":"Huo","year":"2022","journal-title":"Drug Des. Devel. Ther."},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"451","DOI":"10.1097\/INF.0b013e318247f533","article-title":"Acute Kidney Injury in Children with Visceral Leishmaniasis","volume":"31","author":"Rocha","year":"2012","journal-title":"Pediatr. Infect. Dis. J."},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"449","DOI":"10.4269\/ajtmh.2010.09-0571","article-title":"Risk factors for acute kidney injury in visceral leishmaniasis (Kala-Azar)","volume":"82","author":"Oliveira","year":"2010","journal-title":"Am. J. Trop. Med. Hyg."},{"key":"ref_138","first-page":"434","article-title":"Kidney involvement in leishmaniasis\u2014A review","volume":"18","author":"Barros","year":"2013","journal-title":"Braz. J. Infect. Dis."},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"1046","DOI":"10.1111\/tmi.13127","article-title":"Visceral leishmaniasis-associated nephropathy in hospitalised Brazilian patients: New insights based on kidney injury biomarkers","volume":"23","author":"Meneses","year":"2018","journal-title":"Trop. Med. Int. Health"},{"key":"ref_140","first-page":"745","article-title":"Secondary amyloidosis with irreversible acute renal failure caused by visceral leishmaniasis in a patient with AIDS","volume":"26","author":"Navarro","year":"2006","journal-title":"Nefrologia"},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"1027","DOI":"10.1016\/S0399-8320(06)73378-4","article-title":"Liver involvement during visceral leishmaniasis","volume":"30","author":"Gangneux","year":"2006","journal-title":"Gastroenterol. Clin. Biol."},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"1170","DOI":"10.1016\/j.cgh.2008.04.033","article-title":"High Prevalence of Functional Liver Derangement in Visceral Leishmaniasis at an Indian Tertiary Care Center","volume":"6","author":"Mathur","year":"2008","journal-title":"Clin. Gastroenterol. Hepatol."},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"289","DOI":"10.2147\/JIR.S166564","article-title":"IL-1\u03b1 correlates with severity of hepatitis C virus-related liver diseases","volume":"11","author":"Tawfik","year":"2018","journal-title":"J. Inflamm. Res."},{"key":"ref_144","first-page":"30","article-title":"What is the real function of the liver \u201cfunction\u201d tests?","volume":"81","author":"Hall","year":"2012","journal-title":"Ulster Med. J."},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"1321","DOI":"10.1136\/jcp.2005.027029","article-title":"Unusual duodenal presentation of leishmaniasis","volume":"58","author":"Rada","year":"2005","journal-title":"J. Clin. Pathol."},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"e12","DOI":"10.1590\/s1678-9946201860012","article-title":"Visceral leishmaniasis in a Brazilian endemic area: An overview of occurrence, HIV coinfection and lethality","volume":"60","author":"Luz","year":"2018","journal-title":"Rev. Inst. Med. Trop. Sao Paulo"},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"17067","DOI":"10.1038\/nrdp.2017.67","article-title":"Severe childhood malnutrition","volume":"3","author":"Bhutta","year":"2017","journal-title":"Nat. Rev. Dis. Prim."},{"key":"ref_148","first-page":"309","article-title":"Chronic diarrhea and malabsorption caused by Leishmania donovani","volume":"25","author":"Baba","year":"2006","journal-title":"Indian J. Gastroenterol."},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1258\/095646206776790132","article-title":"Atypical disseminated leishmaniasis resembling post-kala-azar dermal leishmaniasis in an HIV-infected patient","volume":"17","author":"Boumis","year":"2006","journal-title":"Int. J. STD AIDS"},{"key":"ref_150","doi-asserted-by":"crossref","unstructured":"Zijlstra, E.E. (2014). PKDL and other dermal lesions in HIV co-infected patients with Leishmaniasis: Review of clinical presentation in relation to immune responses. PLoS Negl. Trop. Dis., 8.","DOI":"10.1371\/journal.pntd.0003258"},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"464","DOI":"10.1186\/s13071-016-1721-0","article-title":"The immunology of post-kala-azar dermal leishmaniasis (PKDL)","volume":"9","author":"Zijlstra","year":"2016","journal-title":"Parasit. Vectors"},{"key":"ref_152","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_153","doi-asserted-by":"crossref","first-page":"S204","DOI":"10.1046\/j.1440-1746.17.s3.2.x","article-title":"Non-cirrhotic portal hypertension versus idiopathic portal hypertension","volume":"17","author":"Okuda","year":"2002","journal-title":"J. Gastroenterol. Hepatol."},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1093\/tropej\/41.3.143","article-title":"The Haematological Manifestations of Visceral Leishmaniasis in Infancy and Childhood","volume":"41","year":"1995","journal-title":"J. Trop. Pediatr."},{"key":"ref_155","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1111\/j.1600-0609.1983.tb01451.x","article-title":"Influence of the Spleen on the Distribution of Blood Neutrophils","volume":"30","author":"Rohrer","year":"2009","journal-title":"Scand. J. Haematol."},{"key":"ref_156","doi-asserted-by":"crossref","first-page":"584","DOI":"10.1016\/j.it.2019.04.013","article-title":"The Neutrophil Life Cycle","volume":"40","author":"Hidalgo","year":"2019","journal-title":"Trends Immunol."},{"key":"ref_157","doi-asserted-by":"crossref","first-page":"531","DOI":"10.1016\/j.it.2020.03.008","article-title":"How Neutrophils Meet Their End","volume":"41","author":"Lawrence","year":"2020","journal-title":"Trends Immunol."},{"key":"ref_158","doi-asserted-by":"crossref","first-page":"1840","DOI":"10.1128\/IAI.68.4.1840-1848.2000","article-title":"Enhanced Hematopoietic Activity Accompanies Parasite Expansion in the Spleen and Bone Marrow of Mice Infected with Leishmania donovani","volume":"68","author":"Cotterell","year":"2000","journal-title":"Infect. Immun."},{"key":"ref_159","doi-asserted-by":"crossref","first-page":"519","DOI":"10.1080\/00365540410020550","article-title":"Disseminated intravascular coagulation as an unusual presentation of kala-azar: Report of two cases","volume":"36","author":"Mishra","year":"2004","journal-title":"Scand. J. Infect. Dis."},{"key":"ref_160","first-page":"47","article-title":"Study of intravascular coagulation activation markers in patients with visceral leishmaniasis","volume":"124\u2013125","author":"Lomtadze","year":"2005","journal-title":"Georgian Med. News"},{"key":"ref_161","unstructured":"Thiagarajan, P., and Platelet Disorders Overview of Platelet Disorders (2022, October 23). Medscape. Published 2021. Available online: https:\/\/emedicine.medscape.com\/article\/201722-overview#a2."},{"key":"ref_162","doi-asserted-by":"crossref","first-page":"e12797","DOI":"10.1111\/pim.12797","article-title":"Biomarkers of the early response to treatment of visceral leishmaniasis: A prospective cohort study","volume":"43","author":"Zacarias","year":"2021","journal-title":"Parasite Immunol."},{"key":"ref_163","doi-asserted-by":"crossref","first-page":"224","DOI":"10.1177\/0049475515622862","article-title":"The clinical and biochemical characteristics of Yemeni adults and children with visceral leishmaniasis and the differences between them: A prospective cross-sectional study before and after treatment","volume":"46","year":"2016","journal-title":"Trop. Doct."},{"key":"ref_164","doi-asserted-by":"crossref","first-page":"e365","DOI":"10.1016\/S2352-3026(21)00056-9","article-title":"Polyclonal hypergammaglobulinaemia: Assessment, clinical interpretation, and management","volume":"8","author":"Zhao","year":"2021","journal-title":"Lancet Haematol."},{"key":"ref_165","doi-asserted-by":"crossref","first-page":"e121","DOI":"10.3324\/haematol.2019.219725","article-title":"Conditions associated with polyclonal hypergammaglobulinemia in the IgG4-related disease era: A retrospective study from a hematology tertiary care center","volume":"105","author":"Zhao","year":"2020","journal-title":"Haematologica"},{"key":"ref_166","doi-asserted-by":"crossref","first-page":"909","DOI":"10.4269\/ajtmh.19-0178","article-title":"LeishCare\u00ae: A software designed for the management of individuals with leishmaniases","volume":"103","author":"Ambrozio","year":"2020","journal-title":"Am. J. Trop. Med. Hyg."},{"key":"ref_167","doi-asserted-by":"crossref","unstructured":"Abongomera, C., Ritmeijer, K., Vogt, F., Buyze, J., Mekonnen, Z., Admassu, H., Colebunders, R., Mohammed, R., Lynen, L., and Diro, E. (2017). Development and external validation of a clinical prognostic score for death in visceral leishmaniasis patients in a high HIV co-infection burden area in Ethiopia. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0178996"},{"key":"ref_168","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1093\/tropej\/45.2.95","article-title":"Clinical and laboratory study of kala-azar in children in Nepal","volume":"45","author":"Singh","year":"1999","journal-title":"J. Trop. Pediatr."},{"key":"ref_169","doi-asserted-by":"crossref","first-page":"635","DOI":"10.1179\/136485908X311858","article-title":"Bacterial infections in children with visceral leishmaniasis: Observations made in Kerman province, southern Iran, between 1997 and 2007","volume":"102","author":"Barati","year":"2008","journal-title":"Ann. Trop. Med. Parasitol."},{"key":"ref_170","doi-asserted-by":"crossref","first-page":"e5261","DOI":"10.1097\/MD.0000000000005261","article-title":"Pediatric visceral leishmaniasis in northwest of Iran","volume":"95","author":"Abdinia","year":"2016","journal-title":"Medicine"},{"key":"ref_171","doi-asserted-by":"crossref","first-page":"101515","DOI":"10.1016\/j.berh.2020.101515","article-title":"Hemophagocytic lymphohistiocytosis: An update on pathogenesis, diagnosis, and therapy","volume":"34","author":"Griffin","year":"2020","journal-title":"Best Pract. Res. Clin. Rheumatol."},{"key":"ref_172","doi-asserted-by":"crossref","first-page":"504","DOI":"10.1016\/S0140-6736(82)90539-6","article-title":"Visceral leishmaniasis presenting with hypertrigliceridaemia","volume":"320","author":"Bertoli","year":"1982","journal-title":"Lancet"},{"key":"ref_173","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1007\/s15010-015-0811-9","article-title":"Hypertriglyceridemia: A possible diagnostic marker of disease severity in visceral leishmaniasis","volume":"44","author":"Lal","year":"2016","journal-title":"Infection"},{"key":"ref_174","first-page":"16","article-title":"Antiparasitic","volume":"18","author":"Brun","year":"2012","journal-title":"Clin. Microbiol. Infect."},{"key":"ref_175","doi-asserted-by":"crossref","unstructured":"Mottaghipisheh, H., Kalantar, K., Amanati, A., Shokripour, M., Shahriari, M., Zekavat, O.R., Zareifar, S., Karimi, M., Haghpanah, S., and Bordbar, M. (2021). Comparison of the clinical features and outcome of children with hemophagocytic lymphohistiocytosis (HLH) secondary to visceral leishmaniasis and primary HLH: A single-center study. BMC Infect. Dis., 21.","DOI":"10.1186\/s12879-021-06408-w"},{"key":"ref_176","first-page":"353","article-title":"Intestinal amyloidosis in hamsters with visceral leishmaniasis","volume":"67","author":"Insa","year":"1986","journal-title":"Br. J. Exp. Pathol."},{"key":"ref_177","doi-asserted-by":"crossref","first-page":"280","DOI":"10.1590\/0037-8682-0094-2016","article-title":"Spleen damage in a dog naturally infected by Leishmania infantum","volume":"50","author":"Lima","year":"2017","journal-title":"Rev. Soc. Bras. Med. Trop."},{"key":"ref_178","doi-asserted-by":"crossref","first-page":"1327","DOI":"10.1055\/s-0037-1616068","article-title":"Towards definition, clinical and laboratory criteria, and a scoring system for disseminated intravascular coagulation","volume":"86","author":"Taylor","year":"2001","journal-title":"Thromb. Haemost."},{"key":"ref_179","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1016\/j.cccn.2004.02.015","article-title":"Disseminated intravascular coagulation","volume":"344","author":"Wada","year":"2004","journal-title":"Clin. Chim. Acta"},{"key":"ref_180","doi-asserted-by":"crossref","first-page":"788","DOI":"10.1016\/j.arcmed.2021.07.003","article-title":"Roles of Coagulation Abnormalities and Microthrombosis in Sepsis: Pathophysiology, Diagnosis, and Treatment","volume":"52","author":"Iba","year":"2021","journal-title":"Arch. Med. Res."},{"key":"ref_181","doi-asserted-by":"crossref","first-page":"089","DOI":"10.1055\/s-0039-1694995","article-title":"Sepsis-Induced Coagulopathy and Disseminated Intravascular Coagulation","volume":"46","author":"Iba","year":"2020","journal-title":"Semin. Thromb. Hemost."},{"key":"ref_182","unstructured":"Levi, M. (2023, May 12). Disseminated Intravascular Coagulation (DIC). Medscape. Published. Available online: https:\/\/emedicine.medscape.com\/article\/199627-overview."},{"key":"ref_183","doi-asserted-by":"crossref","first-page":"1989","DOI":"10.1161\/ATVBAHA.108.177402","article-title":"Tissue factor in coagulation: Which? Where? When?","volume":"29","author":"Butenas","year":"2009","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_184","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1016\/j.cld.2012.03.006","article-title":"Evaluation of Elevated Liver Enzymes","volume":"16","author":"Lee","year":"2012","journal-title":"Clin. Liver Dis."},{"key":"ref_185","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/j.hbpd.2018.01.008","article-title":"Pathophysiological consequences of obstructive jaundice and perioperative management","volume":"17","author":"Pavlidis","year":"2018","journal-title":"Hepatobiliary Pancreat. Dis. Int."},{"key":"ref_186","doi-asserted-by":"crossref","first-page":"1354","DOI":"10.1093\/infdis\/162.6.1354","article-title":"Bacterial infections in patients with visceral leishmaniasis","volume":"162","author":"Andrade","year":"1990","journal-title":"J. Infect. Dis."},{"key":"ref_187","doi-asserted-by":"crossref","first-page":"879","DOI":"10.26719\/2000.6.5-6.879","article-title":"Childhood visceral leishmaniasis complicated by bacterial infections","volume":"6","author":"Kadivar","year":"2000","journal-title":"East. Mediterr. Health J."},{"key":"ref_188","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1097\/00003246-199601000-00026","article-title":"Toward a theory regarding the pathogenesis of the systemic inflammatory response syndrome","volume":"24","author":"Bone","year":"1996","journal-title":"Crit. Care Med."},{"key":"ref_189","doi-asserted-by":"crossref","first-page":"517","DOI":"10.1007\/s00281-017-0639-8","article-title":"Cytokine storm and sepsis disease pathogenesis","volume":"39","author":"Chousterman","year":"2017","journal-title":"Semin. Immunopathol."},{"key":"ref_190","doi-asserted-by":"crossref","first-page":"2255","DOI":"10.1056\/NEJMra2026131","article-title":"Cytokine Storm","volume":"383","author":"Fajgenbaum","year":"2020","journal-title":"N. Engl. J. Med."},{"key":"ref_191","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1159\/000324024","article-title":"Anti-inflammatory mechanisms of sepsis","volume":"17","author":"Shubin","year":"2011","journal-title":"Contrib. Microbiol."},{"key":"ref_192","doi-asserted-by":"crossref","first-page":"108","DOI":"10.3389\/fcell.2019.00108","article-title":"Sepsis: Inflammation Is a Necessary Evil","volume":"7","author":"Nedeva","year":"2019","journal-title":"Front. Cell Dev. Biol."},{"key":"ref_193","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1186\/s12944-021-01460-6","article-title":"Malnutrition affects cholesterol paradox in coronary artery disease: A 41,229 Chinese cohort study","volume":"20","author":"Wang","year":"2021","journal-title":"Lipids Health Dis."},{"key":"ref_194","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1038\/nrneph.2017.165","article-title":"Advances in the understanding and treatment of sepsis-induced immunosuppression","volume":"14","author":"Venet","year":"2018","journal-title":"Nat. Rev. Nephrol."},{"key":"ref_195","first-page":"56","article-title":"Sepsis-induced immunosuppression: Mechanisms, diagnosis and current treatment options","volume":"9","author":"Liu","year":"2022","journal-title":"Mil. Med. Res."},{"key":"ref_196","doi-asserted-by":"crossref","first-page":"R12","DOI":"10.1186\/cc11157","article-title":"Failure to normalize lymphopenia following trauma is associated with increased mortality, independent of the leukocytosis pattern","volume":"16","author":"Heffernan","year":"2012","journal-title":"Crit. Care"},{"key":"ref_197","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1097\/SHK.0000000000000234","article-title":"Persistent Lymphopenia After Diagnosis of Sepsis Predicts Mortality","volume":"42","author":"Drewry","year":"2014","journal-title":"Shock"},{"key":"ref_198","doi-asserted-by":"crossref","first-page":"7340266","DOI":"10.1155\/2022\/7340266","article-title":"ICU and Sepsis: Role of Myeloid and Lymphocyte Immune Cells","volume":"2022","author":"Wang","year":"2022","journal-title":"J. Oncol."},{"key":"ref_199","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1111\/imcb.12611","article-title":"Lymphopenia in sepsis\u2014An acquired immunodeficiency?","volume":"101","author":"Finfer","year":"2023","journal-title":"Immunol. Cell Biol."},{"key":"ref_200","doi-asserted-by":"crossref","first-page":"e98960","DOI":"10.1172\/jci.insight.98960","article-title":"Interleukin-7 restores lymphocytes in septic shock: The IRIS-7 randomized clinical trial","volume":"3","author":"Francois","year":"2018","journal-title":"JCI Insight"},{"key":"ref_201","doi-asserted-by":"crossref","first-page":"953","DOI":"10.3389\/fimmu.2020.00953","article-title":"Impaired Thymic Output Can Be Related to the Low Immune Reconstitution and T Cell Repertoire Disturbances in Relapsing Visceral Leishmaniasis Associated HIV\/AIDS Patients","volume":"11","author":"Cota","year":"2020","journal-title":"Front. Immunol."},{"key":"ref_202","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_203","doi-asserted-by":"crossref","first-page":"260","DOI":"10.1111\/j.1365-2567.2004.01948.x","article-title":"CD4+ CCR5+ and CD4+ CCR3+ lymphocyte subset and monocyte apoptosis in patients with acute visceral leishmaniasis","volume":"113","author":"Potestio","year":"2004","journal-title":"Immunology"},{"key":"ref_204","doi-asserted-by":"crossref","first-page":"12962","DOI":"10.1038\/s41598-019-49344-1","article-title":"Pro-Cellular Exhaustion Markers are Associated with Splenic Microarchitecture Disorganization and Parasite Load in Dogs with Visceral Leishmaniasis","volume":"9","author":"Pereira","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_205","doi-asserted-by":"crossref","unstructured":"Rytter, M.J.H., Kolte, L., Briend, A., Friis, H., and Christensen, V.B. (2014). The Immune System in Children with Malnutrition\u2014A Systematic Review. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0105017"},{"key":"ref_206","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1186\/s13054-020-02993-5","article-title":"Biomarkers of sepsis: Time for a reappraisal","volume":"24","author":"Pierrakos","year":"2020","journal-title":"Crit. Care"},{"key":"ref_207","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1038\/s41467-020-20569-3","article-title":"Characterization of a new Leishmania major strain for use in a controlled human infection model","volume":"12","author":"Ashwin","year":"2021","journal-title":"Nat. Commun."},{"key":"ref_208","doi-asserted-by":"crossref","first-page":"854112","DOI":"10.3389\/fmicb.2022.854112","article-title":"The Game for Three: Salmonella\u2013Host\u2013Microbiota Interaction Models","volume":"13","author":"Grzymajlo","year":"2022","journal-title":"Front. Microbiol."}],"container-title":["Pathogens"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-0817\/12\/7\/969\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T20:18:11Z","timestamp":1760127491000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-0817\/12\/7\/969"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,7,24]]},"references-count":208,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2023,7]]}},"alternative-id":["pathogens12070969"],"URL":"https:\/\/doi.org\/10.3390\/pathogens12070969","relation":{},"ISSN":["2076-0817"],"issn-type":[{"value":"2076-0817","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,7,24]]}}}