Systemic inflammatory markers of visceral leishmaniasis treatment response in East Africa

BACKGROUND: Visceral leishmaniasis (VL) is the most severe form of leishmaniasis, with East Africa accounting for ~70% of global burden. It primarily affects malnourished children, young adults, and HIV co-infected individuals. Clinical outcomes range from asymptomatic to fatal, with relapse mostly linked to HIV co-infection, splenomegaly, high parasite load, poor immune responses, and elevated IgG1 concentration. In rodent VL models, systemic immune and metabolic abnormalities persist at the end of the drug treatment regime. However, the immune status of VL patients in East Africa at the end of treatment is not fully understood. METHODOLOGY/PRINCIPAL FINDINGS: We conducted ImmStat@cure, a multicentre clinical study to assess clinical and immune profiles of VL patients at admission and end of treatment (EoT) in East African countries. Clinical, haematological and inflammatory markers data were collected from patients from Ethiopia, Kenya, Sudan and Uganda on both time points and from convenience controls at a single time point. By integrating clinical data with haematological and inflammation markers, we have shown that patient clinical and inflammatory profiles varied at admission and partially reverted to healthy range at EoT. Partial least squares determination and logistic regression showed that concentrations of inflammatory markers, including soluble TNF receptors and sCD40L, consistently changed between admission and EoT in all four countries, and were associated with increased odds of hepatomegaly and splenomegaly. CONCLUSIONS/SIGNIFICANCE: The recovery of haematological parameters, alongside a reduction in systemic inflammatory markers may be indicative of successful treatment of VL in East Africa. The biomarker dynamics suggest a partial resolution of inflammation and restoration of immune homeostasis during treatment. To confirm their predictive value, these markers should be evaluated in cohorts with a larger number of patients who experience treatment failure.