Patrick Gérardin

The 2024–25 chikungunya epidemic in Reunion Island illustrates the challenge of translating early warning into timely public-health action during fas

Chikungunya virus infection is considered to confer prolonged immunity. During the 2024–2025 outbreak in Reunion Island, we identified a confirmed and a probable reinfection in patients with systemic lupus erythematosus. These findings challenge this paradigm, underly a complex pathophysiology, and suggest that reinfection may occur, particularly in specific populations.

Background and hypothesis: Dengue fever and chronic kidney disease (CKD) are growing health concerns. However, the features and indicators of severe dengue (SD) in CKD patients remain poorly understood. This study aimed to describe dengue in CKD patients, test the relationship between CKD and SD and identify indicators of SD during the 2019 dengue epidemic in La Réunion Island, a region with high prevalence of metabolic diseases and dengue transmission. Methods: A retrospective cohort study was conducted on patients aged ≥15 years with dengue who presented to the University Hospital of La Réunion between January and June 2019. CKD was defined according to Kidney Disease: Improving Global Outcomes criteria. Clinical, biological, and outcome data were extracted from the EPIDENGUE database. We used nonconditional logistic regression models to identify dengue-specific indicators in CKD patients and indicators of SD [World Health Organization (WHO)-2009 definition] and conditional models to assess the relationship between CKD and SD. Results: Of 1498 confirmed dengue cases, 105 (7%) had CKD. CKD patients were older (median age 77 vs 51 years) with more comorbidities, especially diabetes and hypertension. They displayed a distinct dengue phenotype, with fewer classic symptoms (myalgia and rash) but more dyspnea, encephalopathy, anemia, inflammation, and neutrophil-to-platelet ratios. CKD patients were more likely to develop SD (46% vs 18%, P < .001; conditional odds ratio 1.93; 95% confidence interval 1.21–3.06) and mortality (6.7% vs 1.6%). Severe renal involvement was the main driver of severity. WHO warning signs were poor indicators of SD in CKD patients. In multivariate analysis, insulin-treated diabetes, afebrile presentation, and early cardiorespiratory involvement indicated SD. Conclusion: CKD alters the presentation and worsens the prognosis of dengue independently of confounders. Classical warning signs are insufficient in predicting SD among CKD patients. Diabetes, afebrile presentation, and early cardiorespiratory symptoms require closer monitoring and early hospitalization. CKD patients are a high-risk group needing tailored diagnostic and preventive strategies.

We report a fatal case of febrile encephalopathy in an 84-year-old man following administration of the live-attenuated chikungunya vaccine IXCHIQ® (VLA1553, Valneva SE) during the 2025 outbreak in Réunion Island. The patient, previously autonomous with stable comorbidities, developed fever, asthenia, and polyarthralgia 3 days post-vaccination. His condition rapidly deteriorated, with confusion, acute kidney injury, and hemodynamic instability requiring intensive care. Chikungunya virus RNA was detected in both serum and cerebrospinal fluid, with sequencing confirming the presence of the vaccine strain in both compartments. Despite broad-spectrum antimicrobials, antiviral therapy targeting herpesviruses, and hemodialysis, his neurological status worsened and he died 14 days after symptom onset. This case is the first fatal adverse event officially recognized by French health authorities as plausibly related to VLA1553 vaccine. It raises concerns regarding potential neuroinvasive disease following vaccination in elderly individuals and highlights the importance of close clinical and virological evaluation in post-vaccination adverse events during outbreak settings.

In this cohort study, we evaluated the cognitive and learning difficulties of school-age children perinatally infected with Chikungunya virus (CHIKV) on Reunion Island using the Evaluation of Cognitive Functions and Learning in Children (EDA) battery screening test compared to the healthy children cohort used for EDA development. Of the 19 infected children, 11 (57.9%) exhibited subnormal or abnormal scores, of whom 3 were classified as high risk, and 8 were classified as at risk for cognitive and learning difficulties. Children who had encephalopathy were at higher risk for displaying at least one difficulty than non-encephalopathic children (relative risk 2.13; 95% CI 1.05–4.33). The difficulties observed affected verbal functions, non-verbal functions, and learning abilities, such as phonology, lexical evocation and comprehension, graphism, selective visual attention, planning, visual–spatial reasoning, dictation and mathematics, as well as core executive functions, such as inhibitory control, shifting, and working memory. Neurocognitive dysfunctions could be linked to severe brain damage, as evidenced by severe white matter reduction mainly in the frontal lobes and corpus callosum and potentially in all functional networks involved in difficulties. These results should motivate further investigation of intellectual and adaptive functioning to diagnose intellectual deficiency and severe maladaptive behaviour in children perinatally infected with Chikungunya virus.

Aim: In 2005-2006, a chikungunya epidemic of unprecedented magnitude hit Reunion Island, which raised a public health concern through the substantial proportions of long-lasting manifestations. To understand the pathophysiology underlying chronic chikungunya (CC), we designed the CHIKGene cohort study and collected blood samples from 133 subjects diagnosed with CC and from 86 control individuals that had recovered within 3 months, 12-to-15 years after exposure. Methods: We conducted bulk RNAseq analysis on peripheral blood mononuclear cells to find differentially expressed genes (DEGs), gene set enrichment analysis (GSEA) and gene ontologies to uncover top-level enriched terms associated with DEGs, and weighted gene correlation network analysis (WGCNA) to elucidate underlying cellular processes. Results: Among 1549 DEGs, gene expression analysis identified 10 top genes including NR4A2 and TRIM58 (upregulated in CC), IGHG3 and IGHV3-49 (downregulated in CC) linked to immune regulation, OSBP2 (upregulated in CC) and SEMA6B (downregulated in CC) linked to neuronal homeostasis and axon guidance, respectively. GSEA and WGCNA unveiled cellular processes such as "Metabolism of RNA" and "Cell Cycle”. Conclusions: This study uncovers a shift in gene expression of CC subjects. IGHG3 and IGHV3-49 gene shut-offs spotlight the importance of neutralizing antibodies against chikungunya virus in the progression to chronic disease. Human diseases associations highlight connections to rheumatoid arthritis, nervous and cardiac systems. GSEA and WGCNA bounce the hypotheses of a persistent viral reservoir or an increased susceptibility to RNA viral pathogens with new onset infections. Together, our findings might offer potential targets for therapeutic options aimed at alleviating chronic chikungunya.