Clinical and microbiological features of critical Clade Ib mpox in adults with HIV during a Ugandan outbreak

OBJECTIVES: Severe mpox in people living with HIV remains poorly characterized in African settings experiencing Clade 1b transmission. We characterized the clinical, virological, microbiological, and immunopathological features of critical illness during the 2025 mpox outbreak in Uganda. METHODS: We conducted a prospective cohort study of 155 consecutively hospitalized adults with mpox in Uganda between 3 March and 10 April 2025 and performed a nested analysis of critically ill participants. Critically ill participants with sequencing-confirmed Clade Ib infection underwent compartment-specific MPXV PCR testing, lesion bacterial culture and antimicrobial susceptibility testing, HIV viral load assessment, and routine hematological and biochemical investigations. RESULTS: Ten of 155 participants (6.5%) developed critical illness, including four deaths, four severe non-ICU cases, and two ICU admissions. All were people living with HIV. MPXV DNA was consistently detected in skin, genital, and oral/saliva specimens, with substantially lower detection in plasma. Purulent lesion cultures were positive in 9/9 participants and yielded Gram-negative bacilli, Staphylococcus aureus, coagulase-negative staphylococci, and Enterococcus species, demonstrating resistance to multiple commonly used antibiotics. Critically ill participants exhibited anemia, neutrophilia, relative lymphopenia, hypoalbuminemia, hyperbilirubinemia, and elevated C-reactive protein. Most survivors cleared MPXV DNA during follow-up, whereas persistent plasma and anal MPXV DNA detection was observed in one participant who subsequently died. CONCLUSION: Critical Clade 1b mpox in adults with HIV was characterized by high mucocutaneous viral burden, frequent bacterial superinfection with antimicrobial resistance, and marked systemic inflammatory abnormalities. These findings support integrated management strategies incorporating mucocutaneous diagnostics, antimicrobial stewardship, inflammatory monitoring, and optimization of HIV care.