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Background. Sudan virus (SUDV) has caused multiple outbreaks in Uganda over the past two decades, leading to significant morbidity and mortality. The recent outbreaks in 2022 and 2025 highlight the ongoing threat posed by SUDV and the challenges in its containment. This study aims to characterize the epidemiological patterns and phylogenomic evolution of SUDV outbreaks in Uganda, identifying key factors influencing transmission and disease severity. Methods. We conducted a retrospective observational study analyzing epidemiological and genomic data from SUDV outbreaks in Uganda between 2000 and 2025. Epidemiological data were collected from official sources, including the Ugandan Ministry of Health and the World Health Organization, supplemented with reports from public health organizations. Genomic sequences of SUDV were analyzed to investigate viral evolution and identify genetic variations associated with pathogenicity and transmissibility. Results. The 2022 outbreak involved 164 confirmed cases and a case fatality rate (CFR) of 33.5%, with significant geographic variation in case distribution. The 2025 outbreak, still ongoing, was first detected in Kampala, with evidence of both nosocomial and community transmission. Phylogenomic analysis revealed the presence of two main genetic groups, representing Sudan and Uganda, respectively. The genetic variability of the Ugandan cluster is higher than that observed in Sudan, suggesting a greater expansion potential, which aligns with the current outbreak. Epidemiological findings indicate that human mobility, weaknesses in the health system, and delays in detection contribute to the amplification of the outbreak. Conclusions. Our findings underscore the importance of integrated genomic and epidemiological surveillance in understanding SUDV transmission dynamics. The recurrent emergence of SUDV highlights the need for improved outbreak preparedness, rapid response mechanisms, and international collaboration. Strengthening real-time surveillance and enhancing healthcare system resilience are critical to mitigating the impact of future outbreaks.

In 2022, a Sudan Ebola virus outbreak was confirmed in Uganda. Within 1 month of the outbreak's onset, we developed an individual-based modeling platform to estimate the unfolding outbreak's burden of cases and deaths, as well as its duration, using different scenarios. Modeled projections were within the range of observed cases.

After the 2022-2023 Sudan virus (SUDV) disease outbreak in Uganda, we studied SUDV persistence in nonhuman primates that had survived acute infection without therapeutic intervention. We identified SUDV persistence in the vitreous chamber and immediately adjacent tissue in the eyes as well as in the seminiferous tubules in the testes but not in common target organs typically infected during the acute phase of disease. Specifically, SUDV persists primarily in macrophages in the eyes and Sertoli cells in the testes. Ocular and testicular SUDV persistence in nonhuman primates is accompanied by tissue damage, including inflammatory cell invasion. Our study suggests that long-term follow-up efforts are needed to reduce possible recrudescent disease and reignition of outbreaks caused by virus persistence in human survivors of SUDV infection.

Currently there is no FDA-licensed vaccine or therapeutic against Sudan ebolavirus (SUDV) infections. The largest ever reported 2014–2016 West Africa outbreak, as well as the 2021 outbreak in the Democratic Republic of Congo, highlight the critical need for countermeasures against filovirus infections. A well-characterized small animal model that is susceptible to wild-type filoviruses would greatly add to the screening of antivirals and vaccines. Here, we infected signal transducer and activator of transcription-1 knock out (STAT-1 KO) mice with five different wildtype filoviruses to determine susceptibility. SUDV and Marburg virus (MARV) were the most virulent, and caused 100% or 80% lethality, respectively. Zaire ebolavirus (EBOV), Bundibugyo ebolavirus (BDBV), and Taï Forest ebolavirus (TAFV) caused 40%, 20%, and no mortality, respectively. Further characterization of SUDV in STAT-1 KO mice demonstrated lethality down to 3.1 × 101 pfu. Viral genomic material was detectable in serum as early as 1 to 2 days post-challenge. The onset of viremia was closely followed by significant changes in total white blood cells and proportion of neutrophils and lymphocytes, as well as by an influx of neutrophils in the liver and spleen. Concomitant significant fluctuations in blood glucose, albumin, globulin, and alanine aminotransferase were also noted, altogether consistent with other models of filovirus infection. Finally, favipiravir treatment fully protected STAT-1 KO mice from lethal SUDV challenge, suggesting that this may be an appropriate small animal model to screen anti-SUDV countermeasures.

BackgroundUganda has experienced seven laboratory-confirmed Ebola virus disease (EBOD) outbreaks from 2000 to 2022, with reported case‐fatality ratios (CFRs) varying widely. The influence of diagnostic and response delays on outbreak‐level mortality has not been systematically assessed. We conducted a rapid systematic review and meta-analysis to quantify the effect of diagnostic and response delays on outbreak-level mortality.MethodsWe registered the review on OSF and adhered to PRISMA-2020 guidelines. We searched PubMed, Embase, Scopus, Web of Science, WHO Global Index Medicus, and grey literature through 30 April 2025. Eligible reports described laboratory-confirmed human EBOD in Uganda (2000–2022) and reported case counts, deaths, or quantitative timeliness metrics. Outbreak-level CFRs were meta-analyzed using random-effects models with Freeman–Tukey transformation (metafor package in R). Mixed-effects meta-regression assessed the association between continuous delay metrics and transformed CFR.ResultsFifteen reports met inclusion criteria, spanning 741 confirmed cases and 358 deaths. The pooled CFR was 45.4% (95% CI: 26.2%–65.2%; I² = 87.8%) across seven outbreaks. By species, Sudan ebolavirus outbreaks (n = 5) had a CFR of 44.6% (95% CI: 33.7%–55.6%), Bundibugyo ebolavirus (n = 1) 24.8% (95% CI: 18.2%–32.1%), and Zaire ebolavirus (n = 1) 100% (95% CI: 61.2%–100.0%). In meta-regression, each additional day from first case report to specimen collection was associated with a significant increase in CFR (β = 0.142 on the transformed scale; p = 0.025; R² = 62%), translating to an approximate absolute increase of 3.8% points in CFR per day at a baseline risk of 45%. Conversely, longer delays from symptom onset in the index case to national outbreak declaration were linked to a slight decrease in CFR (β = − 0.00765; p = 0.047).ConclusionsUganda’s EBOD outbreaks exhibit high and variable mortality, with diagnostic delays substantially amplifying case-fatality. Rapid specimen collection and prompt public health responses are critical to reducing EBOD mortality. Strengthening laboratory networks and accelerating declaration protocols should be central to future outbreak preparedness in Uganda and similar contexts.

Sudan virus (SUDV) causes severe lethal hemorrhagic fever in humans and nonhuman primates. The most effective and economical way to protect against Sudan ebolavirus disease is prophylactic vaccination. However, there are no licensed vaccines to prevent SUDV infections. In this study, a bacterium-like particle (BLP)-based vaccine displaying the extracellular domain of the SUDV glycoprotein (eGP) was developed based on a gram-positive enhancer matrix-protein anchor (GEM-PA) surface display system. Expression of the recombinant GEM-displayed eGP (eGP-PA-GEM) was verified by Western blotting and immunofluorescence assays. The SUDV BLPs (SBLPs), which were mixed with Montanide ISA 201VG plus Poly (I:C) combined adjuvant, could induce high SUDV GP-specific IgG titers of up to 1:40,960 and robust virus-neutralizing antibody titers reached 1:460. The SBLP also elicited T-helper 1 (Th1) and T-helper 2 (Th2) cell-mediated immunity. These data indicate that the SBLP subunit vaccine has the potential to be developed into a promising candidate vaccine against SUDV infections.

Sudan ebolavirus (SUDV) is one of four members of the Ebolavirus genus known to cause Ebola Virus Disease (EVD) in humans, which is characterized by hemorrhagic fever and a high case fatality rate. While licensed therapeutics and vaccines are available in limited number to treat infections of Zaire ebolavirus, there are currently no effective licensed vaccines or therapeutics for SUDV. A well-characterized animal model of this disease is needed for the further development and testing of vaccines and therapeutics. In this study, twelve cynomolgus macaques (Macaca fascicularis) were challenged intramuscularly with 1000 PFUs of SUDV and were followed under continuous telemetric surveillance. Clinical observations, body weights, temperature, viremia, hematology, clinical chemistry, and coagulation were analyzed at timepoints throughout the study. Death from SUDV disease occurred between five and ten days after challenge at the point that each animal met the criteria for euthanasia. All animals were observed to exhibit clinical signs and lesions similar to those observed in human cases which included: viremia, fever, dehydration, reduced physical activity, macular skin rash, systemic inflammation, coagulopathy, lymphoid depletion, renal tubular necrosis, hepatocellular degeneration and necrosis. The results from this study will facilitate the future preclinical development and evaluation of vaccines and therapeutics for SUDV.

Intravenous (IV) administration of antiviral monoclonal antibodies (mAbs) can be challenging, particularly during an ongoing epidemic, due to the considerable resources required for performing infusions. An ebolavirus therapeutic administered via intramuscular (IM) injection would reduce the burdens associated with IV infusion and allow rapid treatment of exposed individuals during an outbreak. Here, we demonstrate how MBP134, a cocktail of two pan-ebolavirus mAbs, reverses the course of Sudan ebolavirus disease (Gulu variant) with a single IV or IM dose in non-human primates (NHPs) as late as five days post-exposure. We also investigate the utility of adding half-life extension mutations to the MBP134 mAbs, ultimately creating a half-life extended cocktail designated MBP431. When delivered as a post-exposure prophylactic or therapeutic, a single IM dose of MBP431 offered complete or significant protection in NHPs challenged with Zaire ebolavirus. In conjunction with previous studies, these results support the use of MBP431 as a rapidly deployable IM medical countermeasure against every known species of ebolavirus.

Background. The 2013-2016 Ebola epidemic in West Africa resulted in accelerated development of rapid diagnostic tests for emergency outbreak preparedness. We describe the development and evaluation of the Idylla™ prototype Ebola virus test, a fully automated sample-to-result molecular diagnostic test for rapid detection of Zaire ebolavirus (EBOV) and Sudan ebolavirus (SUDV). Methods. The Idylla™ prototype Ebola virus test can simultaneously detect EBOV and SUDV in 200 of whole blood. The sample is directly added to a disposable cartridge containing all reagents for sample preparation, RNA extraction, and amplification by reverse-transcription polymerase chain reaction analysis. The performance was evaluated with a variety of sample types, including synthetic constructs and whole blood samples from healthy volunteers spiked with viral RNA, inactivated virus, and infectious virus. Results. The 95% limits of detection for EBOV and SUDV were 465 plaque-forming units (PFU)/mL (1010 copies/mL) and 324 PFU/mL (8204 copies/mL), respectively. In silico and in vitro analyses demonstrated 100% correct reactivity for EBOV and SUDV and no cross-reactivity with relevant pathogens. The diagnostic sensitivity was 97.4% (for EBOV) and 91.7% (for SUDV), the specificity was 100%, and the diagnostic accuracy was 95.9%. Conclusions. The Idylla™ prototype Ebola virus test is a fast, safe, easy-to-use, and near-patient test that meets the performance criteria to detect EBOV in patients with suspected Ebola.

The cynomolgus monkey (Macaca fascicularis) non-human primate (NHP) is widely used for filovirus vaccine testing. To use limited BSL-4 resources efficiently and minimize NHP usage, Simon’s two-stage design was adapted to screen candidate Ebola virus (EBOV) vaccines in up to six NHPs with two (optimal), three, or four NHPs in Stage 1. Using the optimal design, two NHPs were tested in Stage 1. If neither survived, the candidate was rejected. Otherwise, it was eligible for Stage 2 testing in four NHPs. Candidates advanced if four or more NHPs were protected over both stages. An 80% efficacious candidate vaccine had 88.5% probability of advancing, and a 40% efficacious candidate vaccine had 83% probability of rejection. Simon’s two-stage design was used to screen 27 EBOV vaccine candidates in 43 candidate regimens that varied in dose, adjuvant, formulation, or schedule. Of the 30 candidate regimens tested using two NHPs in Stage 1, 15 were rejected, nine were withdrawn, and six were tested in Stage 2. All six tested in Stage 2 qualified to advance in the product development pipeline. Multiple regimens for the EBOV vaccines approved by the European Medicines Agency (EMA) and the US Food and Drug Administration (FDA) in 2019 were tested in this program. This approach may also prove useful for screening Sudan virus (SUDV) and Marburg virus (MARV) vaccine candidates.