Differences in the Cellular Immune Response during and after Treatment of Sudanese Patients with Post-kala-azar Dermal Leishmaniasis, and Possible Implications for Outcome

Background: The host cellular immune response associated with two treatments for post-kala-azar dermal leishmaniasis (PKDL) - paromomycin plus miltefosine (Arm 1), and liposomal amphotericin B plus miltefosine (Arm 2) - was examined in Sudanese patients before treatment (D0), at the end of treatment...

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Autores: Torres Garcia, Ana Maria, Carrillo, Eugenia, Younis, Brima Musa, Alamin, Mohammed, Tesema, Samuel, Bernardo, Lorena, Solana, Jose Carlos, Moreno, Javier, Mustafa, Alaa-Aldeen, Alves, Fabiana, Musa, Ahmed Mudawi
Tipo de recurso: artículo
Fecha de publicación:2024
País:España
Institución:Instituto de Salud Carlos III (ISCIII)
Repositorio:Repisalud
Idioma:inglés
OAI Identifier:oai:repisalud.isciii.es:20.500.12105/26653
Acceso en línea:https://hdl.handle.net/20.500.12105/26653
Access Level:acceso abierto
Palabra clave:Cytokines
Leishmaniasis
Outcome
PKDL
Treatment
Whole blood assay
Adolescent
Adult
Amphotericin B
Antiprotozoal Agents
Female
Humans
Immunity, Cellular
Leishmaniasis, Cutaneous
Leishmaniasis, Visceral
Male
Middle Aged
Paromomycin
Phosphorylcholine
Sudan
Treatment Outcome
Young Adult
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spelling Differences in the Cellular Immune Response during and after Treatment of Sudanese Patients with Post-kala-azar Dermal Leishmaniasis, and Possible Implications for OutcomeTorres Garcia, Ana MariaCarrillo, EugeniaYounis, Brima MusaAlamin, MohammedTesema, SamuelBernardo, LorenaSolana, Jose CarlosMoreno, JavierMustafa, Alaa-AldeenAlves, FabianaMusa, Ahmed MudawiCarrillo, EugeniaCytokinesLeishmaniasisOutcomePKDLTreatmentWhole blood assayAdolescentAdultAmphotericin BAntiprotozoal AgentsCytokinesFemaleHumansImmunity, CellularLeishmaniasis, CutaneousLeishmaniasis, VisceralMaleMiddle AgedParomomycinPhosphorylcholineSudanTreatment OutcomeYoung AdultBackground: The host cellular immune response associated with two treatments for post-kala-azar dermal leishmaniasis (PKDL) - paromomycin plus miltefosine (Arm 1), and liposomal amphotericin B plus miltefosine (Arm 2) - was examined in Sudanese patients before treatment (D0), at the end of treatment (D42), and during the post-treatment period (D180). Methods: Whole blood samples were stimulated with soluble Leishmania antigen for 24 h (whole blood assay [WBA]) and the concentrations of Th1/Th2/Th17-associated cytokines, IP-10, PDL-1 and granzyme B were determined. Results: The Arm 1 treatment (98.2% cure rate) induced a Th1/Th2/Th17 response, while the Arm 2 treatment (80% cure rate) induced a Th1/Th2 response. Five Arm 2 patients relapsed and showed lower IFN-γ, TNF and IL-1β concentrations at D0 than non-relapsers in this Arm. In patients with low-IFN-γ-production at D0, Arm 1 treatment led to a better host immune response and clinical outcome than Arm 2 treatment. Conclusions: A Th1/Th2/Th17 response was associated with a higher cure rate. Patients with low IFN-γ, TNF and IL-1β before treatment are more likely to relapse if they undergo Arm 2-type treatment. Determining IFN-γ, TNF and IL-10 levels prior to treatment could help predict patients at higher risk of relapse/recovery from PKDL. Trial registration: ClinicalTrials.gov NCT03399955, Registered 17 January 2018, https://clinicaltrials.gov/study/ NCT03399955.SpringerInstituto de Salud Carlos IIIFrench Development AgencySwiss Agency for Development and CooperationWorld Health Organization (WHO/OMS)Médecins Sans FrontièresForeign, Commonwealth & Development Office20252025-05-1320242024-09-0120242024-09-01research articlehttp://purl.org/coar/resource_type/c_2df8fbb1VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttps://hdl.handle.net/20.500.12105/26653reponame:Repisaludinstname:Instituto de Salud Carlos III (ISCIII)InglésengES MVP322 19open accesshttp://purl.org/coar/access_right/c_abf2Attribution 4.0 Internationalhttp://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:repisalud.isciii.es:20.500.12105/266532026-06-12T12:43:37Z
dc.title.none.fl_str_mv Differences in the Cellular Immune Response during and after Treatment of Sudanese Patients with Post-kala-azar Dermal Leishmaniasis, and Possible Implications for Outcome
title Differences in the Cellular Immune Response during and after Treatment of Sudanese Patients with Post-kala-azar Dermal Leishmaniasis, and Possible Implications for Outcome
spellingShingle Differences in the Cellular Immune Response during and after Treatment of Sudanese Patients with Post-kala-azar Dermal Leishmaniasis, and Possible Implications for Outcome
Torres Garcia, Ana Maria
Cytokines
Leishmaniasis
Outcome
PKDL
Treatment
Whole blood assay
Adolescent
Adult
Amphotericin B
Antiprotozoal Agents
Cytokines
Female
Humans
Immunity, Cellular
Leishmaniasis, Cutaneous
Leishmaniasis, Visceral
Male
Middle Aged
Paromomycin
Phosphorylcholine
Sudan
Treatment Outcome
Young Adult
title_short Differences in the Cellular Immune Response during and after Treatment of Sudanese Patients with Post-kala-azar Dermal Leishmaniasis, and Possible Implications for Outcome
title_full Differences in the Cellular Immune Response during and after Treatment of Sudanese Patients with Post-kala-azar Dermal Leishmaniasis, and Possible Implications for Outcome
title_fullStr Differences in the Cellular Immune Response during and after Treatment of Sudanese Patients with Post-kala-azar Dermal Leishmaniasis, and Possible Implications for Outcome
title_full_unstemmed Differences in the Cellular Immune Response during and after Treatment of Sudanese Patients with Post-kala-azar Dermal Leishmaniasis, and Possible Implications for Outcome
title_sort Differences in the Cellular Immune Response during and after Treatment of Sudanese Patients with Post-kala-azar Dermal Leishmaniasis, and Possible Implications for Outcome
dc.creator.none.fl_str_mv Torres Garcia, Ana Maria
Carrillo, Eugenia
Younis, Brima Musa
Alamin, Mohammed
Tesema, Samuel
Bernardo, Lorena
Solana, Jose Carlos
Moreno, Javier
Mustafa, Alaa-Aldeen
Alves, Fabiana
Musa, Ahmed Mudawi
Carrillo, Eugenia
author Torres Garcia, Ana Maria
author_facet Torres Garcia, Ana Maria
Carrillo, Eugenia
Younis, Brima Musa
Alamin, Mohammed
Tesema, Samuel
Bernardo, Lorena
Solana, Jose Carlos
Moreno, Javier
Mustafa, Alaa-Aldeen
Alves, Fabiana
Musa, Ahmed Mudawi
author_role author
author2 Carrillo, Eugenia
Younis, Brima Musa
Alamin, Mohammed
Tesema, Samuel
Bernardo, Lorena
Solana, Jose Carlos
Moreno, Javier
Mustafa, Alaa-Aldeen
Alves, Fabiana
Musa, Ahmed Mudawi
author2_role author
author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Instituto de Salud Carlos III
French Development Agency
Swiss Agency for Development and Cooperation
World Health Organization (WHO/OMS)
Médecins Sans Frontières
Foreign, Commonwealth & Development Office
dc.subject.none.fl_str_mv Cytokines
Leishmaniasis
Outcome
PKDL
Treatment
Whole blood assay
Adolescent
Adult
Amphotericin B
Antiprotozoal Agents
Cytokines
Female
Humans
Immunity, Cellular
Leishmaniasis, Cutaneous
Leishmaniasis, Visceral
Male
Middle Aged
Paromomycin
Phosphorylcholine
Sudan
Treatment Outcome
Young Adult
topic Cytokines
Leishmaniasis
Outcome
PKDL
Treatment
Whole blood assay
Adolescent
Adult
Amphotericin B
Antiprotozoal Agents
Cytokines
Female
Humans
Immunity, Cellular
Leishmaniasis, Cutaneous
Leishmaniasis, Visceral
Male
Middle Aged
Paromomycin
Phosphorylcholine
Sudan
Treatment Outcome
Young Adult
description Background: The host cellular immune response associated with two treatments for post-kala-azar dermal leishmaniasis (PKDL) - paromomycin plus miltefosine (Arm 1), and liposomal amphotericin B plus miltefosine (Arm 2) - was examined in Sudanese patients before treatment (D0), at the end of treatment (D42), and during the post-treatment period (D180). Methods: Whole blood samples were stimulated with soluble Leishmania antigen for 24 h (whole blood assay [WBA]) and the concentrations of Th1/Th2/Th17-associated cytokines, IP-10, PDL-1 and granzyme B were determined. Results: The Arm 1 treatment (98.2% cure rate) induced a Th1/Th2/Th17 response, while the Arm 2 treatment (80% cure rate) induced a Th1/Th2 response. Five Arm 2 patients relapsed and showed lower IFN-γ, TNF and IL-1β concentrations at D0 than non-relapsers in this Arm. In patients with low-IFN-γ-production at D0, Arm 1 treatment led to a better host immune response and clinical outcome than Arm 2 treatment. Conclusions: A Th1/Th2/Th17 response was associated with a higher cure rate. Patients with low IFN-γ, TNF and IL-1β before treatment are more likely to relapse if they undergo Arm 2-type treatment. Determining IFN-γ, TNF and IL-10 levels prior to treatment could help predict patients at higher risk of relapse/recovery from PKDL. Trial registration: ClinicalTrials.gov NCT03399955, Registered 17 January 2018, https://clinicaltrials.gov/study/ NCT03399955.
publishDate 2024
dc.date.none.fl_str_mv 2024
2024-09-01
2024
2024-09-01
2025
2025-05-13
dc.type.none.fl_str_mv research article
http://purl.org/coar/resource_type/c_2df8fbb1
VoR
http://purl.org/coar/version/c_970fb48d4fbd8a85
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv https://hdl.handle.net/20.500.12105/26653
url https://hdl.handle.net/20.500.12105/26653
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.relation.none.fl_str_mv ES MVP322 19
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
Attribution 4.0 International
http://creativecommons.org/licenses/by/4.0/
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
Attribution 4.0 International
http://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv Springer
publisher.none.fl_str_mv Springer
dc.source.none.fl_str_mv reponame:Repisalud
instname:Instituto de Salud Carlos III (ISCIII)
instname_str Instituto de Salud Carlos III (ISCIII)
reponame_str Repisalud
collection Repisalud
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,81155

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