Wastewater-Based Epidemiology of Hepatitis A in Mexico: Temporal Association with Hospital Admissions and Clinical-Environmental Phylogenetic Relatedness.

Hepatitis A (HepA) is a viral hepatitis caused by the hepatitis A virus (HAV), and currently Mexico is considered to have an intermediate-HAV endemicity. Wastewater-based epidemiology (WBE) is a tool for monitoring infectious diseases but has been poorly evaluated in intermediate-HAV-endemicity settings. From June 2024 to June 2025, 24-hour composite wastewater samples were collected twice a week from three wastewater treatment plants in the metropolitan area of San Luis Potosí, Mexico. Wastewater samples were ultracentrifuged, RNA was extracted, and HAV and crAssphage (for normalization) were detected by qPCR and weighted by the wastewater treatment plant's inflow. We compared these results with HepA hospital admissions from eight public hospitals in the city during the same period. We compared HAV genotype sequences obtained from wastewater and patients. We processed 244 wastewater samples over 46 weeks, of which 35.1% tested positive for HAV. Seventy-three HepA hospital admissions were reported during this period. The Spearman correlation between HAV viral load and hospital admissions, along with its displacement over 10 weeks, showed the strongest correlation between Lag 4 to Lag 6. We genotyped six HAV strains from wastewater samples and two from HepA patients. Phylogenetic analysis revealed that the patient strains were distinct but identical or closely related to the circulating wastewater strains. In conclusion, WBE HAV surveillance may predict an increase in HepA admissions four to six weeks in advance. Diverse, but closely related HAV strains constantly circulate in intermediate HAV-endemicity settings.