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Visceral leishmaniasis (VL) patients co-infected with HIV (VL/HIV patients) experience frequent treatment failures, VL relapses, opportunistic infections, and higher mortality. Their immune system remains profoundly suppressed after clinical cure and they maintain higher parasite load. This is in contrast with patients with VL alone (VL patients). Since neutrophils play a critical role in the control of Leishmania replication and the regulation of immune responses, we tested the hypothesis that neutrophil activation status and effector functions are fully restored in VL, but not in VL/HIV patients. Our results show the neutrophil counts and all activation markers and effector functions tested in our study were reduced at the time of diagnosis in VL and VL/HIV patients as compared to controls. CD62L, CD63, arginase 1 expression levels and reactive oxygen species production were restored at the end of treatment in both groups. However, neutrophil counts, CD10 expression and phagocytosis remained significantly lower throughout follow-up in VL/HIV patients; suggesting that dysregulated neutrophils contribute to the impaired host defence against pathogens in VL/HIV patients., Competing Interests: The authors have declared that no competing interests exist.

Visceral leishmaniasis (VL) has emerged as a clinically important opportunistic infection in HIV patients, as VL/HIV co-infected patients suffer from frequent VL relapse. Here, we follow cohorts of VL patients with or without HIV in Ethiopia. By the end of the study, 78.1% of VL/HIV-but none of the VL patients-experience VL relapse. Despite a clinically defined cure, VL/HIV patients maintain higher parasite loads, lower BMI, hepatosplenomegaly, and pancytopenia. We identify three immunological markers associated with VL relapse in VL/HIV patients: (1) failure to restore antigen-specific production of IFN-γ, (2) persistently lower CD4 + T cell counts, and (3) higher expression of PD1 on CD4 + and CD8 + T cells. We show that these three markers, which can be measured in primary hospital settings in Ethiopia, combine well in predicting VL relapse. The use of our prediction model has the potential to improve disease management and patient care., Competing Interests: The authors declare no competing interests., (© 2021 The Authors.)