# Assessment of Long-Term Sequelae After Severe Malaria: A Retrospective Study

## TL;DR

This study finds that many adults who survive severe malaria experience lasting kidney and neurological issues, with certain factors predicting who is at higher risk.

## Contribution

The study provides novel insights into long-term sequelae of severe malaria in non-endemic regions and identifies prognostic factors for persistent complications.

## Key findings

- 14.6% of patients had sequelae at day 28, primarily kidney or neurological issues.
- 18.2% of patients still had sequelae during remote follow-up, with neurological symptoms being most common.
- Older age, neurological failure, and renal impairment at admission were key risk factors for long-term complications.

## Abstract

Background: Data on long-term sequelae after severe imported Plasmodium falciparum malaria in adults are scarce in non-endemic settings. We aimed to quantify early and medium term renal and neurological outcomes and identify prognostic factors. Therapeutic strategies have evolved with widespread intravenous artesunate, yet survivorship data remain limited. Methods: We performed a retrospective study of cases of severe malaria at the University Hospital of Marseille (France) between January 2018 and December 2024. This study is a single-centre retrospective cohort with prospective follow-up using standardised questionnaires. Adults meeting the criteria for severe falciparum malaria were included. The primary endpoint was a composite of renal impairment and/or neurological sequelae assessed at day 28 (D28) and at remote post-discharge follow-up. Patient-reported outcomes were collected at one year. Associations with baseline features were tested using the Fisher’s exact and Wilcoxon–Mann–Whitney tests. Results: Among 474 malaria cases, 66 (13.9%) were severe; of these, 57 met inclusion criteria. Fifty-seven of them were included. All received intravenous artesunate with oral step-down; 35% required ICU care. At D28, 6/41 patients (14.6%) had sequelae (four renal, one neurological, one both). Sequelae at D28 were associated with neurological failure (66.7% vs. 14.3%; p = 0.015), severe metabolic acidosis (50.0% vs. 2.9%; p = 0.007) and renal impairment at admission (83.3% vs. 2.9%; p < 0.001). At remote follow-up, 6/33 patients (18.2%) had sequelae (two renal, three neurological, one both), associated with older age (61.0 ± 5.3 vs. 39.8 ± 15.8 years; p = 0.008), D3 blood smear positivity (66.7% vs. 11.5%; p = 0.012), neurological failure (66.7% vs. 18.5%; p = 0.034) and renal impairment (50.0% vs. 7.4%; p = 0.031). No deaths or relapses occurred. At one year, patient-reported outcomes (n = 14) showed persistent symptoms in 8/14, chiefly fatigue and cognitive complaints. Conclusions: In a high-resource, non-endemic setting, renal and neurological sequelae after severe imported malaria are frequent at D28 and persist in nearly one-fifth of cases during post-discharge follow-up. Neurological failure, metabolic acidosis, renal impairment at presentation, older age and D3 blood smear positivity identify patients at risk and support risk-stratified post-discharge follow-up.