Genomic, virologic, and epidemiologic surveillance to track intrafamilial Mpox, Brazil

co-infection during the 2022 mpox epidemic in Brazil. Clinical, serologic, molecular, viral isolation, and genomic investigations revealed intrafamilial transmission within a multigenerational household, including older women and children. Notably, a 3-year-old child without direct contact with the index case developed clinical signs of mpox and tested positive for MPV by PCR and viral isolation. Genomic sequencing and phylogenetic analyses confirmed the B.1.9 lineage and showed that all viral sequences clustered within the same transmission chain. Serologic assays detected OPV-neutralizing antibodies in an older woman. These findings underscore the potential for prolonged MPV replication and household spread beyond traditionally recognized risk groups, emphasizing the need for strengthened genomic and epidemiologic surveillance, particularly for immunocompromised individuals and their families and caregivers. IMPORTANCE: Mpox expanded globally in 2022, but pediatric and household transmission remains poorly defined. We report a fatal infection in an immunocompromised patient with advanced HIV/AIDS during the epidemic in Brazil. Integrated clinical and genomic investigations revealed intrafamilial spread within a multigenerational household, including a 3-year-old child who had no direct contact with the index case. Viral genomes clustered in lineage B.1.9, and neutralizing antibodies were detected in an older woman and domestic animals. These findings highlight the potential for household transmission beyond recognized risk groups and underscore the need for strengthened surveillance.