ETIDIOH - NEW

ABSTRACT A cocktail of human monoclonal antibodies 1C3 and 1C11 previously protected macaques from a lethal exposure to either Ebola virus (EBOV) or Sudan virus (SUDV). 1C3 is of particular interest because its paratope strongly binds with unique stoichiometry to the glycoprotein head of several orthoebolaviruses , resulting in neutralization of EBOV and SUDV . Therefore, we evaluated the protective activity of 1C3 as a standalone therapeutic in macaques exposed to either EBOV or SUDV. Two doses of 1C3 monotherapy, administered 4 and 7 days post-exposure, did not protect SUDV-exposed macaques and partially protected EBOV-exposed macaques . Notably, in a macaque that succumbed to EBOV infection, we identified two mutually exclusive escape mutations that emerged immediately after the first dose and resulted in two amino acid changes at the 1C3 binding site . We also detected a subconsensus treatment-emergent mutation likely affecting the 1C3 binding site in all three deceased SUDV-expose...

Abstract 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...

Abstract The Sudan virus (SUDV) outbreaks in Uganda in 2022 and 2025 created public health concerns in-country and the entire East African region. There are currently no licensed countermeasures against SUDV . We developed a SUDV vaccine candidate based on a nanocarrier (LIONTM) complexed with an alphavirus-based replicon RNA . Here, we compare the protective efficacy of the LION-SUDV vaccine either encoding the SUDV glycoprotein (GP) alone or in combination with the Ebola virus (EBOV) GP (LION-Combination). A LION-EBOV vaccine which is protective against EBOV was also included to determine the potential for cross-protection against SUDV infection . Single-dose vaccinations were conducted three weeks before challenge with a lethal dose of guinea pig-adapted SUDV using a female guinea pig disease model. We demonstrate 100% survival and protection with the LION-SUDV and the LION-Combination vaccines, while the LION-EBOV vaccine achieved 50% protection. Antigen-specific humoral responses ...

{Summary} Situation at a glance On 26 April 2025, the Ministry of Health (MoH) of Uganda declared the end of the Sudan virus disease (SVD) outbreak after two consecutive incubation periods (a total of 42 days) since the last person confirmed with SVD tested negative for the virus on 14 March 2025.  A total of 14 SVD cases (including 12 confirmed cases and two probable cases) including four deaths (two confirmed and two probable) have been reported during this outbreak.  WHO and partners provided technical , operational and financial support to the government to contain the outbreak.  Although the outbreak has been declared over , health authorities are maintaining surveillance to rapidly identify and respond to any re-emergence.  Risk communication and community engagement will also continue to ensure the community stay informed and stigma to those who were affected is minimized. (...) Source: World Health Organization,  https://www.who.int/emergencies/disease-o...

Abstract In 2018, a clinical trial of four investigational therapies for Ebola virus disease (EVD), known as the PALM trial , was conducted in the Democratic Republic of Congo . All patients received either the antiviral remdesivir (RDV) or a monoclonal antibody product : ZMapp, mAb114 (Ebanga), or REGN-EB3 (Inmazeb). The study concluded that both mAb114 and REGN-EB3 were superior to ZMapp and RDV in reducing mortality from EVD. However, the data suggested that some patients in the RDV and ZMapp groups might have been sicker at the time of treatment initiation. Here, we assessed the efficacy of each of these therapies in a uniformly lethal rhesus monkey model of EVD when treatment was initiated 5 days after Ebola exposure. Treatment with RDV, mAb114, REGN-EB3, and ZMapp each resulted in similar survival (approximately 40% ). Survival was associated with circulating viral load at treatment initiation. A trend of more escape mutants in the GP1 and GP2 domains was observed for the mAb114 ...

Abstract In February 2023, the government of Equatorial Guinea declared an outbreak of Marburg virus disease . We describe the response structure and epidemiologic characteristics , including case-patient demographics, clinical manifestations, risk factors , and the serial interval and timing of symptom onset, treatment seeking, and recovery or death . We identified 16 laboratory-confirmed and 23 probable cases of Marburg virus disease in 5 districts and noted several unlinked chains of transmission and a case-fatality ratio of 90% (35/39 cases). Transmission was concentrated in family clusters and healthcare settings . The median serial interval was 18.5 days ; most transmission occurred during late-stage disease . Rapid isolation of symptomatic case-patients is critical in preventing transmission and improving patient outcomes; community engagement and surveillance strengthening should be prioritized in emerging outbreaks. Further analysis of this outbreak and a One Health surveillan...

Abstract Ebola virus (EBOV) and Marburg virus (MARV) are zoonotic filoviruses that cause hemorrhagic fever in humans . Correlative data implicate bats as natural EBOV hosts , but neither a full-length genome nor an EBOV isolate has been found in any bats sampled. Here, we model filovirus infection in the Jamaican fruit bat (JFB), Artibeus jamaicensis, by inoculation with either EBOV or MARV through a combination of oral, intranasal, and subcutaneous routes . Infection with EBOV results in systemic virus replication and oral shedding of infectious virus. MARV replication is transient and does not shed. In vitro, JFB cells replicate EBOV more efficiently than MARV, and MARV infection induces innate antiviral responses that EBOV efficiently suppresses. Experiments using VSV pseudoparticles or replicating VSV expressing the EBOV or MARV glycoprotein demonstrate an advantage for EBOV entry and replication early , respectively, in JFB cells. Overall, this study describes filovirus species-sp...

Situation at a glance On 13 March 2025, the Ministry of Health of the United Republic of Tanzania declared the end of the Marburg virus disease (MVD) outbreak.  This declaration came after two consecutive incubation periods (a total of 42 days) since the last person confirmed with MVD died on 28 January 2025 and was given a safe and dignified burial, in accordance with WHO recommendations.  No new confirmed cases were reported since then.  The outbreak was declared on 20 January 2025 . As of 12 March 2025, two confirmed and eight probable cases were reported by the Ministry of Health from Biharamulo district in Kagera region. All 10 cases died (case fatality ratio 100%), including eight who died before the confirmation of the outbreak. A total of 272 contacts that were listed for monitoring completed their 21-day follow-up as of 10 February 2025. WHO, through its country office, and partners provided technical, operational and financial support to the government to contai...

Situation at a glance Since the outbreak of Sudan virus disease (SVD) was declared in Uganda on 30 January 2025, and as of 5 March 2025, a total of 14 cases (including 12 confirmed cases and two probable cases) including four deaths (two confirmed and two probable) have been reported.  On 1 March 2025, the Ministry of Health released a press statement confirming the tenth case . The patient was a child under 5 years old who presented and died in the Mulago hospital on 23 February 2025.  As of 5 March, two additional confirmed cases and two probable deaths have been reported that are linked to this case. Both of these cases are currently admitted to treatment facilities.  Eight confirmed cases received care at treatment centres in the capital Kampala and in Mbale and were discharged on 18 February 2025.  As of 5 March 2025, 192 new contacts have been identified and are under follow-up in Kampala, Ntoroko and Wakiso. In the absence of licensed vaccines and therapeutics...

{Excerpt} Situation at a glance As of 20 February 2025, a total of nine confirmed cases of Sudan virus disease, including one death have been reported from Uganda , since the outbreak was declared on 30 January 2025. Eight cases received care at treatment centres in the capital Kampala and in Mbale and were discharged on 18 February after two negative tests 72 hours apart.  As of 20 February 2025, 58 contacts that have been identified are still under follow up in designated quarantine facilities located in Jinja, Kampala,and Mbale .  Sudan virus disease belongs to the same family as Ebola virus disease . It is caused by Sudan virus (SUDV). It is a severe disease with high case fatality ranging from 41% to 70% in past outbreaks. In the absence of licensed vaccines and therapeutics for the prevention and treatment of SVD, the risk of potential serious public health impact is high. Early detection, diagnosis, and optimized supportive care may increase the chance of survival. Desc...

 {Excerpt} Situation at a glance Since the declaration of the Marburg Virus Disease (MVD) outbreak on 20 January 2025 in the United Republic of Tanzania, one additional confirmed death was reported by the Ministry of Health from the epicentre of the outbreak in Biharamulo district in Kagera region .  As of 10 February 2025, a cumulative of two confirmed and eight probable cases were reported by the Ministry of Health.  All 10 cases have died , including eight who died before the confirmation of the outbreak.  As of 10 February 2025, all 281 contacts that were listed and under monitoring have completed the 21-day follow-up.  The Ministry of Health developed a national response plan to guide activities. Additionally, a national rapid response team was deployed to the affected region to enhance outbreak investigation and response, with technical and operational support from WHO and health partners. Description of the situation Since the previous Disease Outbreak Ne...

{Excerpt} On 30 January 2025, the Ministry of Health of Uganda declared an outbreak of Sudan Ebola virus (SUDV). The outbreak was declared just 3 hours after laboratory confirmation at two national reference laboratories, consistent with International Health Regulations. The index case was detected at Mulago Specialized National Hospital in Kampala, Uganda1. (...) Source: Nature Medicine,  https://www.nature.com/articles/d41591-025-00012-0 _____

{Excerpt} In a global first, Uganda’s Ministry of Health, the World Health Organization (WHO) and other partners today launched a first ever vaccine trial for Ebola from the Sudan species of the virus, and at an unprecedented speed for a randomized vaccine trial in an emergency . The principal investigators from Makerere University and the Uganda Virus Research Institute (UVRI), with support from WHO and other partners, have worked tirelessly to get the trial ready in 4 days since the outbreak was confirmed on 30 January. It is the first trial to assess the clinical efficacy of a vaccine against Ebola disease due to Sudan virus . The speed was achieved through advanced research preparedness, while ensuring full compliance with national and international regulatory and ethical requirements. The candidate vaccine was donated by IAVI , with financial support from WHO, the Coalition for Epidemic Preparedness Innovations (CEPI), Canada’s International Development Research Centre (IDRC), and...

Situation at a glance On 30 January 2025, the Ministry of Health of Uganda declared an outbreak of Sudan virus disease (SVD) following confirmation from three national reference laboratories.  The case presented with signs and symptoms between 20 and 21 January and died on 29 January at the National Referral Hospital in Kampala.  As of 30 January 2025, 45 contacts have been identified , including 34 healthcare workers and 11 family members.  Sudan virus disease belongs to the same family as Ebola virus disease. It is caused by Sudan virus (SUDV). It is a severe disease with high case fatality from 41% to 70% in past outbreaks.  In the absence of licensed vaccines and therapeutics for the prevention and treatment of SVD, the risk of potential serious public health impact is high.  Early supportive patient care and treatment may increase the chance of survival from severe disease. Description of the situation On 30 January 2025, the Ministry of Health of Uganda de...