Lesion viral burden, multidrug-resistant superinfection, and HIV-associated haematological vulnerability in hospitalised clade Ib mpox: a prospective cohort study in Uganda.

BACKGROUND

Mpox has shifted to sustained human-to-human transmission across Africa, yet integrated triage incorporating viral burden, bacterial co-infection, antimicrobial resistance (AMR), HIV status, and routine biomarkers remain scarce.

METHODS

At Uganda's national mpox referral hospital, we prospectively enrolled 155 adults at 14 ± 2 days post-symptom onset; mpox was confirmed by lesion-swab qPCR (F3L), with clade assignment by whole-genome sequencing in a prespecified subset (March-April 2025). Lesion viral DNA burden was estimated using qPCR cycle threshold (Ct) values. Purulent lesions underwent EUCAST-standardised culture and susceptibility testing. Routine laboratory assessments included complete blood counts, C-reactive protein, serum chemistries, HIV serostatus, and plasma HIV-1 RNA.

FINDINGS: Median age was 30 years, and 73/155 (47%) had HIV infection. Multisite pain, particularly anogenital, was highly prevalent. Among 80 participants with purulent lesions selected for clinically suspected bacterial superinfection, all yielded bacterial growth; 35/80 (43.8%) were polymicrobial and predominantly multidrug-resistant Gram-negative bacilli. Susceptibility to first-line β-lactams and fluoroquinolones was low, whereas meropenem retained activity (51/61, 84%). Lesion viral burden did not differ by HIV serostatus and showed weak correlation with HIV-1 viraemia; higher burden was associated with leucocytosis, neutrophilia with left shift, elevated CRP, and hypoalbuminaemia. Genomes clustered within Clade Ib, without segregation by HIV status or clinical severity.

INTERPRETATION: Hospitalised adults with acute Clade Ib mpox in Uganda exhibited high lesion viral burden, frequent multidrug-resistant bacterial co-isolation, and an inflammatory haematological profile accentuated in participants living with HIV-1. These findings support consideration of integrating diagnostic microbiology, HIV viral load assessment, and antimicrobial stewardship into mpox case-management in endemic settings.

FUNDING: This study was supported by the Coalition for Epidemic Preparedness Innovations (CEPI; Project ID PRJ-8284).