Immunological factors, but not clinical features, predict visceral leishmaniasis relapse in patients co-infected with HIV

Takele, Yegnasew; Mulaw, Tadele; Adem, Emebet; Shaw, Caroline J.; Franssen, Susanne U.; Womersley, Rebecca; Kaforou, Myrsini; Taylor, Graham P.; Levin, Michael; Müller, Ingrid; Cotton, James A.; Kropf, Pascale

doi:10.1016/j.xcrm.2021.100487

Cited by 24 publications

(90 citation statements)

References 60 publications

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“…We have recently shown that throughout follow-up, as compared to VL patients, VL/HIV patients display (12): - higher parasite load; - impaired antigen-specific IFNγ production by whole blood cells; - lower CD4 + T cell counts; - higher PD1 expression on CD4 + and CD8 + T cells. Our data also show that 78.1% of VL/HIV patients experience at least one relapse (12). Reliable data on both clinical and immunological parameters from VL/HIV patients who experience VL relapse are still limited: the following markers have been shown to predict VL relapse in VL/HIV patients: - failure to clear parasite load after anti-leishmanial treatment (20), as well as presence of circulating Leishmania DNA (22); - low CD4 + T cell counts (5, 20); - previous VL episodes in VL/HIV patients (5, 20, 23), though a study showed no association between a previous history of relapse and increased risks of future relapse (24).…”

Section: Introductionsupporting

confidence: 64%

“…For this cross-sectional study, we followed the cohort of 49 VL/HIV patients (median age 33.5±1.0 years) that was described in (12). Twenty-one patients presented with their first episode of VL (primary VL/HIV, P VL/HIV) and 28 with at least one previous episode of VL (recurrent VL/HIV, R VL/HIV, Table 1).…”

Section: Methodsmentioning

confidence: 99%

“…Following the HIV-1 pandemic, VL has emerged as an opportunistic infection: HIV infection increases the risk of developing symptomatic VL and VL accelerates the progression of HIV infection to AIDS (7, 8). HIV co-infection presents a significant challenge in the prevention and control of VL (9, 10): VL/HIV co-infected patients experience increased rates of VL relapse, mortality and treatment failure compared to patients with VL alone (10–12). Our knowledge of the immunology of VL/HIV co-infections is still limited.…”

Section: Introductionmentioning

confidence: 99%

“…The work by Casado et al also showed that VL/HIV patients had an even worse immunological status as compared to ART treated HIV patients who failed to improve their CD4 + T cell counts (27). In our recent study, we showed that VL/HIV patients who did not relapse after initial clinical cure had lower parasite loads as measured by RNAseq in whole blood, produced higher levels of antigen-specific IFNγ, maintained higher CD4 + and CD8 + T cell counts and lower PD1 expression on CD4 + and CD8 + T cells, as compared to VL/HIV patients who did relapse (12). In this study (12), out of the 49 HIV patients who presented with VL at the treatment centre, 21 (43%) patients presented with their first episode of VL (Primary VL/HIV patients) and 28 (57%) had a previous history of VL (recurrent VL/HIV patients).…”

Section: Introductionmentioning

confidence: 99%

“…In our recent study, we showed that VL/HIV patients who did not relapse after initial clinical cure had lower parasite loads as measured by RNAseq in whole blood, produced higher levels of antigen-specific IFNγ, maintained higher CD4 + and CD8 + T cell counts and lower PD1 expression on CD4 + and CD8 + T cells, as compared to VL/HIV patients who did relapse (12). In this study (12), out of the 49 HIV patients who presented with VL at the treatment centre, 21 (43%) patients presented with their first episode of VL (Primary VL/HIV patients) and 28 (57%) had a previous history of VL (recurrent VL/HIV patients). In the current study, we assessed the impact of a previous history of VL relapse on relapse-free survival, clinical parameters and the immune response and compared those to HIV patients presenting with their first episode of VL.…”

Section: Introductionmentioning

confidence: 99%

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Previous visceral leishmaniasis relapses outperform immunological or clinical signs as predictors of further relapses in patients co-infected with HIV-1

Takele

Mulaw

Adem

et al. 2021

Preprint

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Patients co-infected with visceral leishmaniasis (VL) and HIV-1 (VL/HIV patients) suffer from recurrent VL relapses and increased mortality. The aim of our study was to test the hypothesis that HIV patients who present with their first episode of VL (primary VL/HIV patients) experience less relapses and lower mortality as compared to VL/HIV patients who have a previous history of VL relapses (recurrent VL/HIV patients). Our results show that primary VL/HIV patients have a lower parasite load and that their relapse-free survival is significantly longer. Relapses in both groups of patients occur independently of HIV viral load. Our clinical and immunological analyses of these patients at the time of diagnosis and during follow-up show that the poorer prognosis of recurrent VL/HIV patients is accompanied by lower weight gain and lower recovery of all blood cell lineages, as well as lower production of antigen-specific IFNγ, lower CD4+ T cell counts and higher expression levels of the inhibitory receptor PD1 on CD4+ and CD8+ T cells.We propose that in addition to the current treatments, novel interventions should be considered at the time of VL diagnosis in VL/HIV patients and suggest that improved anti-leishmanial and antiretroviral treatments, as well as immune therapy, through PD1/PDL-1 blockade and/or through IFNγ administration, could result in more efficient parasite killing and thereby reduce the relapse rate and improve survival.

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Section: Introductionsupporting

confidence: 64%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Previous visceral leishmaniasis relapses outperform immunological or clinical signs as predictors of further relapses in patients co-infected with HIV-1

Takele

Mulaw

Adem

et al. 2021

Preprint

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The Utility of a Controlled Human Infection Model for Developing Leishmaniasis Vaccines

Kaye

Parkash

Layton

et al. 2023

Vaccines for Neglected Pathogens: Strategies, Achievements and Challenges

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Controlled human infection models (CHIMs) are increasingly recognised as having an important role in the early development of vaccines for important human diseases, including those prevalent in low and middle-income countries. The leishmaniases are a group of clinically disparate parasitic diseases caused by multiple species of Leishmania. Widely heralded as potentially vaccine-preventable, progress in vaccine development for different forms of leishmaniasis has over past decades been slow, hampered by lack of funds, good experimental models and the challenges of progression through the normal clinical trial pathway. However, with a new generation of leishmaniasis vaccine candidates now progressing in clinical development, the value of a robust CHIM able to accelerate early-phase evaluation of new vaccine candidates has become increasingly apparent. Here, we briefly review the historic context of human infection studies in leishmaniasis and outline issues pertinent to the development of a new CHIM of sand fly-transmitted Leishmania major infection. Given the diversity and wide geographic distribution of the leishmaniases, we conclude with a discussion of future needs and challenges in the development of CHIMs for these important neglected diseases.

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Recurrent visceral leishmaniasis relapses in HIV co-infected patients are characterized by less efficient immune responses and higher parasite load

Takele¹,

Mulaw²,

Adem³

et al. 2023

iScience

Self Cite

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Immunological factors, but not clinical features, predict visceral leishmaniasis relapse in patients co-infected with HIV

Cited by 24 publications

References 60 publications

Previous visceral leishmaniasis relapses outperform immunological or clinical signs as predictors of further relapses in patients co-infected with HIV-1

Previous visceral leishmaniasis relapses outperform immunological or clinical signs as predictors of further relapses in patients co-infected with HIV-1

The Utility of a Controlled Human Infection Model for Developing Leishmaniasis Vaccines

Recurrent visceral leishmaniasis relapses in HIV co-infected patients are characterized by less efficient immune responses and higher parasite load

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