Systemic inflammatory markers of visceral leishmaniasis treatment response in East Africa

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Abstract 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 levels. 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 levels at EoT. Partial least squares determination and logistic regression showed that levels 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. Author summary Visceral leishmaniasis (VL) is a life-threatening disease caused by infection with Leishmania parasites. It mainly affects vulnerable groups such as malnourished children, young adults, and people with HIV. It is endemic to South America, Asia and Africa, and most cases now occur in East Africa. While some people recover , others relapse or die, especially if they have weakened immune systems. Although treatment exists, little is known about how inflammatory markers change during and shortly after therapy. ImmStat@cure studied patients from Ethiopia, Kenya, Sudan, and Uganda to understand how their health and immune responses change from hospital admission to the end of treatment. By analysing blood samples and clinical data, we found that while some signs of illness improved by the end of treatment, others did not fully return to normal levels. Variations in certain blood markers linked to inflammation, such as soluble TNF receptors and sCD40L, changed after treatment and were linked to symptoms like enlarged liver and spleen. These findings suggest that tracking these markers may help doctors understand how well a patient is recovering. Future research should test whether these indicators can predict which patients are at risk of not fully recovering or relapsing.

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