Revisiting visceral leishmaniasis in immunocompromised patients: Ongoing gaps and advances in diagnostics, therapies,...

The visceral leishmaniasis (VL) caused by Leishmania infantum and Leishmania donovani is regarded as one of the deadliest forms of parasitic diseases, claiming thousands of victims a year, and is particularly prevalent in tropical and subtropical climates. Even though a healthy immune system can often combat or control the infection, in immunocompromised individuals, the disease emerges chronically, aggressively, and often fatally. In recent years, VL has become a significant public health threat in vulnerable populations due to the increased prevalence of conditions such as HIV/AIDS, hematological malignancies such as lymphoma and leukemia, and the increased use of immunosuppressive drugs among organ transplant recipients. This review aimed to provide an overview of the challenges and limitations related to diagnosing, preventing, and treating VL in immunocompromised patients, as well as their clinical and epidemiological consequences. An analysis of recent clinical and epidemiological data has indicated that common diagnostic tests, especially serological tests such as rK39 and DAT, are insufficiently sensitive and specific for immunocompromised patients, and that molecular methods such as PCR and qPCR are necessary to accurately diagnose and treat early. In the context of treatment, liposomal amphotericin B is still regarded as a first-line drug in many regions of the world, but its effectiveness has been significantly limited due to toxicity, drug resistance, and frequent relapses in immunocompromised individuals. Moreover, prevention programmes for this group of patients remain ineffective due to the lack of definitive preventive drugs and effective vaccines, as well as weak population screening. According to recent immunological studies, deficiencies in cellular immune responses, particularly impaired T helper cell (CD4+) function, defective IFN-γ production, and compromised macrophage function in parasite clearance, play a significant role in the complex pathogenesis of VL in immunosuppressed patients. In patients infected with HIV, Leishmania infection synergistically increases viral loads, reduces antiretroviral therapy response, and increases mortality. In conclusion, the results of this study indicate that VL among immunocompromised patients is not only clinically and therapeutically more challenging but may also, epidemiologically, play a hidden role in the survival of the human reservoir and the spread of the disease.