Leishmaniasis Relapse: Why Immunosuppression Matters

Leishmaniasis relapse occurs when the effectiveness of treatments like miltefosine is compromised, particularly in individuals with weakened immune systems. Immunosuppression can create an environment where the Leishmania parasite thrives, leading to a resurgence of the infection even after initial treatment. This is especially concerning in cases of HIV co-infection, where compromised immunity and high parasite burdens increase the risk of relapse. While miltefosine is still used for HIV co-infected patients, liposomal amphotericin B is a primary treatment in Europe. Therefore, understanding the interplay between immunosuppression and leishmaniasis is critical for developing effective strategies to prevent and manage relapses.

The study used Syrian golden hamsters infected with Leishmania infantum. To mimic immunosuppression, the hamsters were treated with cyclophosphamide (CPA). Following this, the hamsters were treated with miltefosine. Researchers then closely monitored the hamsters for clinical signs, changes in immune cell subsets in the blood, parasite loads in tissues, and the time it took for the infection to relapse. This thorough monitoring helped researchers understand how a suppressed immune system affects the parasite's response to miltefosine and the overall course of leishmaniasis.

The findings suggest that immunosuppression accelerates relapse of leishmaniasis but does not necessarily speed up the development of miltefosine resistance. This means that while weakened immunity makes individuals more susceptible to recurrent infections after treatment with miltefosine, the parasite itself does not become resistant to the drug at a faster rate. It underscores the importance of closely monitoring immunosuppressed individuals with leishmaniasis and tailoring treatment approaches to prevent and manage relapses effectively. It is vital to protect vulnerable populations affected by this parasitic disease.

Miltefosine faces challenges because of rising treatment failure rates, especially in regions such as the Indian subcontinent. Immunosuppression, often seen in conditions like HIV co-infection, further complicates treatment because it promotes high parasite burdens and increases the likelihood of relapse. Although liposomal amphotericin B is a primary treatment in Europe, miltefosine is still relevant for HIV co-infected patients. Understanding these factors is vital for developing more effective treatment strategies and addressing the growing problem of drug resistance.

The study tracked indicators such as body weight, immune cell composition, parasite burden in target organs (liver, spleen, and bone marrow), and the time it took for the infection to relapse after treatment with miltefosine. By monitoring these parameters, the research team gained insights into how immunosuppression impacts the progression of leishmaniasis and the effectiveness of miltefosine in controlling the infection. This comprehensive approach provided a detailed understanding of the complex dynamics between the parasite, the host's immune system, and treatment outcomes.