Biomedical subjects

Pontiano Kaleebu

Publications and source records attributed to Pontiano Kaleebu.

5 recordsLinked to original sources

PubMed2026

Emergence of a Bundibugyo virus variant in the 2026 outbreak in the Democratic Republic of the Congo and Uganda.

In May 2026, an outbreak of Ebola disease caused by Bundibugyo virus (BDBV, species Orthoebolavirus bundibugyoense) was declared in the Democratic Republic of the Congo (DRC), with cases originating from DRC and locally transmitted cases reported in Uganda. Bundibugyo virus disease (BVD) outbreaks were previously recorded in 2007-2008 in Bundibugyo District, Uganda, and in 2012 in Isiro, DRC. Here, we generated 22 genomes from samples obtained from individuals with BVD in DRC and Uganda. These genomes form a well-supported phylogenetic cluster separate from BDBV variants associated with the 2007 and 2012 outbreaks, together with evidence for sustained human transmission. This is consistent with the emergence of a new zoonotic spillover event rather than resurgence from previously reported variants. Besides ongoing efforts in strengthening surveillance systems, community engagement, establishing Ebola treatment centers, and developing targeted medical countermeasures; our report advocates to specifically increase decentralized laboratory diagnostics capacity, with pan-Orthoebolavirus assays, including genomic sequencing capacity, for limiting further outbreak expansion, timely detection and control of future outbreaks.

Journal Article↗

PubMed2026

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).

Adult↗

PubMed2026

Saliva versus lesion swabs for PCR diagnosis of acute-phase clade Ib mpox in Uganda: a prospective matched hospital cohort study.

BACKGROUND: As clade Ib mpox expands through HIV-affected populations in east and central Africa, diagnostic specimen selection should balance accuracy, accessibility, and operational feasibility in outbreak settings. Here, we aimed to compare the diagnostic performance of matched plasma, saliva, genital, anal, and skin specimens during the acute rash phase of clade Ib mpox to identify clinically practical and high-yield sampling approaches for outbreak response and clinical care. METHODS: We conducted a prospective cohort study of 155 adults (median age 30 years, IQR 25-36) hospitalised at Uganda's national mpox referral hospital. The specimens were collected between March 3 and April 10, 2025, during the clade Ib outbreak. All participants were admitted with suspected mpox and were subsequently confirmed by MPXV PCR. We collected 836 clinical specimens (acid citrate dextrose plasma, saliva, genital swabs, anal swabs, and skin swabs) during the acute phase (visit 1; 14 days [SD 2] after systemic symptom onset) and at approximately 3 months (visit 2). A matched acute-phase subset (n=80) provided concurrent plasma, saliva, genital, and skin specimens for within-participant comparisons. MPXV DNA was quantified by F3L real-time quantitative PCR, and cycle threshold (Ct) values were compared using paired Wilcoxon signed-rank tests. Whole-genome sequencing of selected acute specimens confirmed clade assignment. FINDINGS: In the matched subset at visit 1, PCR positivity was high in saliva (78 [98%] of 80), skin swabs (78 [98%] of 80), and genital swabs (77 [96%] of 80). Results for the saliva closely mirrored genital and skin swab results, supporting saliva as a high-yield alternative when lesion sampling is painful, operationally difficult, or unacceptable. Plasma had substantially lower sensitivity (34 [43%] of 80) and showed poor agreement with mucocutaneous compartments. At 3 months, persistent MPXV DNA was rare (ten [9%] of 109) and clustered among people with HIV, including the only two participants with persistent plasma positivity. All sequenced genomes clustered within clade Ib. INTERPRETATION: During the established rash phase (14 days [SD 2] after onset), saliva provides diagnostic yield similar to that provided by lesion swabs for clade Ib mpox in this hospitalised cohort. These findings are restricted to this sampling window; further studies are needed to define performance in prodromal, pre-rash, and asymptomatic infection. FUNDING: CEPI through its Centralised Laboratory Network.

Adult↗

PubMed2026

Evolutionary dynamics of HIV-1 recombinants: analysis of contemporary and historical viral populations in East Africa.

BACKGROUND: Understanding the genetic evolution of HIV-1 Transmitted/Founder (T/F) virus is crucial for developing effective treatment and prevention strategies due to its rapid mutation and recombination rates. METHODS: This study compared the genetic diversity of 24 contemporary T/F viruses collected between 2016 and 2021 in Uganda and Kenya with 29 historical T/F sequences sampled between 2006 and 2011. RESULTS: Subtype analysis based on near-full-length (NFL) HIV-1 T/F genomes revealed that 57.1% (12/21) of contemporary viruses were recombinants, predominantly involving Subtype A1, D, and increasing Subtype C, with 33.3% (7/21) being A1D recombinants (A1 > D) and 19% (4/21) classified as complex recombinants involving three or more subtypes. Historical viruses showed a similar overall proportion (69%) but were mainly A1D mosaics (D > A1) with recombination confined primarily to the envelope region. In contrast, contemporary viruses shifted towards more complex recombinant patterns affecting additional genomic regions, including pol and accessory genes. Phylogenetic analysis demonstrated that contemporary viruses clustered into distinct, well-supported (98% bootstrap) sub-branches, suggesting divergency attributed to an imbalance in their proportions of subtype A1 and D sequences as well as a different content of A1 and D segments in the A1/D mosaic recombinants. CONCLUSIONS: These findings underscore the dynamic and shifting nature of HIV-1 genetic diversity in East Africa, highlighting the need for continuous molecular surveillance and region-specific treatment guidelines.

HIV-1↗

PubMed2025

HIV-phyloTSI: subtype-independent estimation of time since HIV-1 infection for cross-sectional measures of population incidence using deep sequence data.

BACKGROUND: Estimating the time since HIV infection (TSI) at population level is essential for tracking changes in the global HIV epidemic. Most methods for determining TSI give a binary classification of infections as recent or non-recent within a window of several months, and cannot assess the cumulative impact of an intervention. RESULTS: We developed a Random Forest Regression model, HIV-phyloTSI, which combines measures of within-host diversity and divergence to generate continuous TSI estimates directly from viral deep-sequencing data, with no need for additional variables. HIV-phyloTSI provides a continuous measure of TSI up to 9 years, with a mean absolute error of less than 12 months overall and less than 5 months for infections with a TSI of up to a year. It performs equally well for all major HIV subtypes based on data from African and European cohorts. CONCLUSIONS: We demonstrate how HIV-phyloTSI can be used for incidence estimates on a population level.

HIV Infections↗