What is Sudan virus disease and how does it differ from other forms of Ebola?

On 30 January 2025, Uganda declared an outbreak of Sudan virus disease after a 32-year-old nurse in Kampala presented with signs and symptoms. Laboratory tests soon confirmed Sudan virus infection. The patient subsequently died.

As of 6 February, six further cases have been identified; all close contacts of the index case, including healthcare workers who attended to him. Their close contacts have been traced and are currently being followed up, and the nurse has since died.

Sudan virus disease is a type of Ebola disease, and the current outbreak is the ninth to have occurred since the virus was first identified in southern Sudan in June 1976.

Although no licensed vaccine exists, a trial of a new vaccine has already been launched, while a trial of a therapeutic monoclonal antibody is expected to start within days.

So, what exactly is Sudan virus, and what does this vaccine candidate have in common with existing vaccines against Ebola virus (formerly known as Zaire ebolavirus)?

Causes of Ebola disease

There are six known species of Orthoebolaviruses; four of which can cause Ebola disease in humans: Ebola virus, Sudan virus, Taï Forest virus and Bundibugyo virus.

Since their discovery in 1976, there have been at least 38 outbreaks of Ebola disease and more than 34,000 cases – most of them associated with the 2014–16 West Africa outbreak and 2018–20 outbreak in the Democratic Republic of the Congo (DRC), which were caused by Ebola virus.

Sudan virus is closely related to Ebola virus, but while they have many similarities, they have different genetic material and different proteins, which means their antigenic profile – the substances that trigger an immune response – is different.

“This means an immune response against one virus does not protect against the other virus, so you need a vaccine that is specific for that species,” says Dr Daniela Manno, a clinical epidemiologist at the London School of Hygiene & Tropical Medicine in London, UK, who was involved in trials of the Ad26.ZEBOV, MVA-BN-Filo (Zabdeno/Mvabea) vaccine against Ebola virus.

They also cause similar symptoms, beginning with non-specific ones such as fever, aches, pains and fatigue, which can then progress to diarrhoea, vomiting and unexplained bleeding.

They are both spread through contact with the body fluids of an infected sick or dead person, or contact with an infected or sick animal, such as a bat or primate.

Both also have a high case fatality rate, killing approximately half of those who are infected.

The current outbreak in Uganda is the sixth outbreak of Sudan virus disease to have occurred in the country, with the other three occurring in Sudan. The last Ugandan outbreak was in 2022, but genetic testing suggests the virus that caused it is different to the one implicated in the current outbreak.

Because of this history, Uganda is well prepared for dealing with such incidents, as is the wider WHO Africa region: “One of the advantages we have had with all these multiple emergencies is that we have been building capacity in countries [to deal with them],” says Dr Otim Patrick Ramadan, WHO’s Regional Incident Manager for Filoviruses.

Vaccine development

Scientists have been trying to develop Ebola vaccines and therapeutics – including candidates against Sudan virus – for several decades.

By the time the West Africa epidemic erupted in Guinea, Liberia and Sierra Leone in 2014, there were ten vaccines and treatments in various stages of research, development and clinical testing. “That outbreak really shook the research field and people really put all their efforts together to try to develop a vaccine specifically against Ebola virus,” Manno says.

Gavi, the Vaccine Alliance was also involved in these efforts, offering an advance purchase commitment including a pre-payment to all manufacturers with an Ebola vaccine in phase 1 clinical trials or beyond, committing to purchase doses as and when a WHO-prequalified vaccine became available, provided they agreed to certain conditions – including creating and maintaining a stockpile of investigational doses available in case of an outbreak prior to licensure.

Gavi’s Advanced Purchase Commitment (APC) sent a clear signal to the market and incentivised manufacturers to continue investing in vaccine research and development of a vaccine as there would be a guaranteed market.

MSD agreed to these terms in 2016, and their vaccine, known as rVSV-ZEBOV, was the first against Ebola disease to be approved in 2019, followed by Johnson and Johnson’s Zabdeno/Mvabea vaccine in 2020.

Gavi now funds a global stockpile of licensed vaccines against Ebola virus disease.

Unfortunately, these existing vaccines are not cross-protective for Sudan virus, and, because it hasn’t caused as many outbreaks, or such big outbreaks as Ebola virus, there hasn’t been quite the same impetus to drive vaccine candidates through clinical trials. Even so, there are a few Sudan virus vaccine candidates in development, including some that have already entered clinical trials.

Sudan virus vaccine

The current trial, launched on 3 February in Uganda, involves a candidate provided by nonprofit research organisation the International AIDS Vaccine Initiative (IAVI).

It is based on the same recombinant vesicular stomatitis virus (rVSV) viral vector platform as the ERVEBO vaccine, but encodes a surface protein from Sudan virus, rather than Ebola virus.

Initial results from a Phase 1 trial of this vaccine candidate suggested that it was well tolerated and triggered an immune response in healthy adults. Some 2,160 doses of it were already prepositioned in Kampala, as they’d been delivered during the 2022 outbreak, but arrived too late to be used as the country had already contained the outbreak using other measures

A key challenge for proving the efficacy of rare disease vaccine candidates is starting the trial early enough during an outbreak for the people who need protection to receive it and therefore to demonstrate its protection.

Fortunately, in this case, doses were available and there was a pre-approved protocol in place. “It meant that they could move very quickly. It also helped that they already had the vaccine in country, because sometimes producing and shipping the vaccine takes time, and this can slow down trial initiation,” says Manno.

Contacts of cases who are at elevated risk of infection will be prioritised for inclusion in the trial, as part of a ring vaccination strategy – the same strategy that brought an end to smallpox and has successfully been used in past outbreaks of Ebola virus disease.

Another challenge will be having enough people with whom to test the vaccine. Obviously, the hope is that Uganda will swiftly bring the outbreak under control, but if this happens there may not be enough cases to demonstrate whether or not the vaccine is effective.

“In this case, they will probably need to wait until the next outbreak and do a cumulative analysis – combining data from different outbreaks, to estimate the efficacy of the vaccine,” Manno says.