Severe visceral leishmaniasis in Ethiopia: Outcomes, co-infections and mortality in a prospective real-world cohort

Abstract

BACKGROUND: Visceral leishmaniasis (VL) remains a major public health challenge in East Africa, particularly in Ethiopia. Clinical trials on VL often exclude patients with severe comorbidities or laboratory abnormalities, limiting the generalizability of evidence used to guide real-world management. We comprehensively characterised the clinical profile, treatment outcomes, and mortality of VL patients treated in a referral centre. METHODOLOGY AND PRINCIPAL FINDINGS: This prospective cohort study enrolled patients at the Leishmaniasis Research and Treatment Center (LRTC), University of Gondar (02/2023-06/2024). All VL cases fulfilling eligibility criteria underwent detailed clinical, laboratory, and radiological assessments. VL treatment followed WHO guidelines. Outcomes, adverse events, and supportive care measures were recorded during treatment and over a 12-month follow-up period. Patients meeting at least one exclusion criterion (e.g., comorbidities, clinical signs of severe VL) of standard phase III VL treatment trials were defined as trial-ineligible patients and compared with trial-eligible patients. A total of 314 VL patients, mostly young adult males (median age 22 years), were enrolled. Of these, 21 (6.7%) had HIV co-infection; 204 (65%) met ≥ 1 key exclusion criterion typically used in VL clinical trials. Trial-ineligible patients had high parasitemia, more concurrent infections, more pronounced clinical and laboratory abnormalities and a higher need of supportive care measures including systemic antibiotics and blood transfusion. Overall cure rate was 90.1%. Mortality after the first VL treatment course was 6.4%, ranging from 1.8% in trial-eligible patients to 8.8% in trial-ineligible patients. Leading causes of death included severe bacterial infections, acute liver failure and haemorrhagic complications. CONCLUSIONS: These findings underscore the severity and complexity of VL in routine care in our study population, and highlight the limitations of current trial populations to inform broader clinical practice. Strengthening supportive care and expanding research inclusivity designed to respond to the needs of this patient population are critical to achieve VL elimination targets.