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

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

doi:10.1016/j.isci.2022.105867

Cited by 8 publications

(5 citation statements)

References 48 publications

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“…The patients with VL-HIV presented low density splenic CD4 + cells in the WP, low expression of genes such as IL15 and of cytokines related to Th1 response in comparison to the patient with VL monoinfection, also, literature has associated upregulation of genes related to Th2 response and downregulation of IFNG gene before VL treatment in patients VL-HIV coinfected [ 40 ]. This observation concurs with previous findings, in which patients with VL-HIV presented more frequent disease relapse, associated to low CD4 counts and low IFNγ in circulating blood [ 41 ]. Conversely, IL15 a cytokine associated with induction of Th1 response through IFNγ signaling, contribute to cure in canine VL [ 42 ], is upregulated in the patient with VL only.…”

Section: Discussionsupporting

confidence: 93%

An integrated analysis of the structural changes and gene expression of spleen in human visceral leishmaniasis with and without HIV coinfection

Fontes,

Khouri,

Reinaldo

et al. 2024

PLoS Negl Trop Dis

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The spleen plays a pivotal role in the pathogenesis of visceral leishmaniasis. In severe forms of the disease, the spleen undergoes changes that can compromise its function in surveilling blood-circulating pathogens. In this study, we present an integrated analysis of the structural and gene expression alterations in the spleens of three patients with relapsing visceral leishmaniasis, two of whom were coinfected with HIV. Our findings reveal that the IL6 signaling pathway plays a significant role in the disorganization of the white pulp, while BCL10 and ICOSLG are associated with spleen organization. Patients coinfected with HIV and visceral leishmaniasis exhibited lower splenic CD4+ cell density and reduced expression of genes such as IL15. These effects may contribute to a compromised immune response against L. infantum in coinfected individuals, further impacting the structural organization of the spleen.

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Section: Discussionsupporting

confidence: 93%

An integrated analysis of the structural changes and gene expression of spleen in human visceral leishmaniasis with and without HIV coinfection

Fontes,

Khouri,

Reinaldo

et al. 2024

PLoS Negl Trop Dis

View full text Add to dashboard Cite

show abstract

“…The patient with VL-HIV presented lower density splenic CD4 + cells, low expression of genes such as IL15 and of cytokines related to Th1 response, upregulation of genes related to Th2 response and downregulation of IFNG gene before VL treatment (40) in comparison to the patients with VL monoinfection. This observation concurs with previous findings, in which patients with VL-HIV presented more frequent disease relapse, associated to low CD4 counts and low IFNγ in circulating blood (41). Conversely, IL15 a cytokine associated with induction of Th1 response through IFNγ signaling, contribute to cure in canine VL (42), is upregulated in the patient with VL only.…”

Section: Discussionsupporting

confidence: 93%

An integrated analysis of the structural changes and gene expression of spleen in human visceral leishmaniasis with and without HIV coinfection

Fontes,

Khouri,

Reinaldo

et al. 2023

Preprint

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The spleen plays a pivotal role in the pathogenesis of visceral leishmaniasis. In severe forms of the disease, the spleen undergoes changes that can compromise its function in surveilling blood-circulating pathogens. In this study, we present an integrated analysis of the structural and gene expression alterations in the spleens of three patients with relapsing visceral leishmaniasis, two of whom were coinfected with HIV. Our findings reveal that the IL6 signaling pathway plays a significant role in the disorganization of the white pulp, whileBCL10andICOSLGare associated with spleen organization. Patients coinfected with HIV and visceral leishmaniasis exhibited lower splenic CD4+ cell density and reduced expression of genes such asIL15. These effects may contribute to a compromised immune response againstL. infantumin coinfected individuals, further impacting the structural organization of the spleen.

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“…Moreover, opposing to the serological microscopy exhibits higher sensitivity in individuals who were HIV-positive in comparison to those who were HIV-negative. This phenomenon could be attributed to compromised immune systems in HIV-positive patients, resulting in elevated parasite loads in the tissue aspirate and subsequently a higher likelihood of a positive microscopic examination [60]. Furthermore, we observed a significant association between parasite density and DAT titer, which in agreement with a study done in Sudan [61] As the density of parasites in the microscopic examination increases, there was a corresponding increase in antibody titer and probability of testing positive for DAT [61].…”

Section: Discussionsupporting

confidence: 90%

Comparison of the Diagnostic Performance of Five Different Tests to Diagnose Visceral Leishmaniasis in an Endemic Region of Ethiopia

Hagos,

Kiros,

Mahmud

et al. 2023

Preprint

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The lack of accurate and feasible diagnostic tests poses a significant challenge to visceral leish-maniasis (VL) healthcare services in endemic areas. To date, various VL diagnostic tests have been or are being developed, and their diagnostic performance needs to be assessed.. In the present study, the diagnostic performance of rk39RDT, Direct Agglutination Test (DAT), Microscopy, Loop Mediated Isothermal Amplification (LAMP), and miniature direct-on-blood polymerase chain reaction - nucleic acid lateral flow immunoassay (mini-dbPCR-NALFIA) was assessed using quantitative polymerase chain reaction (qPCR) as reference test in an endemic region of Ethiopia. In this study, 235 patients VL suspected patients and 104 non-endemic healthy controls (NEHC) were recruited. Among the VL-suspected patients, 144(61.28%) tested positive with qPCR. Sensi-tivities for rk39 RDT, DAT, Microscopy, LAMP assay, and mini-dbPCR-NALFIA were 88.11%, 96.50%, 76.58%, 94.33%, and 95.80%, respectively. Specificities were 83.33%, 97.96%, 100%, 97.38%, and 98.92% for rk39 RDT, DAT, Microscopy, LAMP assay, and mini-dbPCR-NALFIA, respectively. In conclusion, Rk39 RDT and microscopy exhibited lower sensitivity, while DAT demonstrated excellent performance. LAMP and mini-dbPCR-NALFIA showed excellent perfor-mance with feasibility to implement in remote endemic areas, although the latter requires further evaluation in such regions.

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

Cited by 8 publications

References 48 publications

An integrated analysis of the structural changes and gene expression of spleen in human visceral leishmaniasis with and without HIV coinfection

An integrated analysis of the structural changes and gene expression of spleen in human visceral leishmaniasis with and without HIV coinfection

An integrated analysis of the structural changes and gene expression of spleen in human visceral leishmaniasis with and without HIV coinfection

Comparison of the Diagnostic Performance of Five Different Tests to Diagnose Visceral Leishmaniasis in an Endemic Region of Ethiopia

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