Ebola: what is happening in Uganda?

The last major epidemic of Ebola virus disease took place in West Africa between 2013 and 2016. Due to the Zaire strain of this virus responsible for terrible hemorrhagic fevers, it caused more than 11 deaths, mainly in Sierra Leone, Liberia and Guinea. Since the beginning of September, an East African country, Uganda, has been dealing with the Ebola virus, but this time the Sudan strain is involved.

The first confirmed patient, a 24-year-old man, fell ill on September 11. Originally from a village in Madudu sub-county, Mubende district, central Uganda, he was seized with a high fever accompanied by various symptoms: tonic convulsions, loss of appetite, pain on swallowing , chest pain, dry cough, bloody diarrhea and vomiting, eye bleeding.

He was admitted to the regional reference hospital on September 15, where he was isolated. On September 19, tests confirmed that he had been infected with the Sudan strain of Ebola virus (SUDV). The patient died the same day. The outbreak was officially declared by Ugandan health authorities on September 20. As of October 9, 2022, 68 cases (including 48 confirmed cases) and 37 deaths (including 17 confirmed) have been identified in connection with this outbreak.

How did she start? What do we know about the Sudanese strain that is responsible for it? Should we fear a major epidemic?

A high national risk according to the WHO

Despite the Ugandan government's quick response and proven experience with Ebola virus disease outbreaks, the World Health Organization (WHO) considers the overall risk from the ongoing outbreak to be high at the national level.

The fact that the epidemic was detected in people living around a local gold mine operating in a forest environment could indeed complicate the situation: the mobility of gold miners and traders is probably high, and the declaration of the epidemic can cause the escape of some people already in the incubation period.

Of the 68 cases identified so far, 48 are confirmed cases and 20 probable cases. There are almost as many men as women among the sick, who have been identified in five districts: Mubende, Kyegegwa, Kasanda, Kagadi and Bunyangabu. One death was notably reported in the capital Kampala. 37 deaths have been recorded, including 17 among the confirmed cases, which means that the fatality rate is, for the moment, 29% (among the confirmed cases).

Preliminary investigations to trace the origin of this contamination revealed that during the first two weeks of September, several deaths due to an unknown disease occurred in communities in Madudu and Kiruma sub-counties. Some of these deceased persons had been in contact with the index patient, and all cases are now considered probable cases of Ebola caused by the Sudan virus. To date, 1 contacts have been listed of which 110 are still being followed, the others having completed their WHO-recommended 657-day follow-up period.

What is the Sudan Ebola virus?

The Sudan Ebola virus belongs, like the other known Ebola viruses, to the Filovirus family, which owes its name to the filamentous appearance of the viruses that compose it.

The first Filovirus was identified in 1967 in Europe: it is Marburg virus. Laboratory workers who had been in contact with green monkeys from Uganda, or with their tissues (particularly in the context of the preparation of cell cultures) then reported symptoms of haemorrhagic fever. Of the 31 people infected, 7 had died.

The Ebola virus was discovered in 1976, during the occurrence of a double epidemic in South Sudan as well as in the Democratic Republic of Congo (DRC, then Republic of Zaire). Six Ebola viruses are known today: the Ebola virus (EBOV), also called the "Ebola Zaire subtype", the Sudan virus subtype (SUDV), the Reston virus subtype (RESTV), the Taï Forest (TAFV), the Bundibugyo subtype (BDBV) and the Bombali subtype (BOMV). With the exception of the Reston and Bombali strains, the other four strains of Ebola are pathogenic for humans.

Ebola viruses pathogenic for humans cause severe and often fatal haemorrhagic fevers: the fatality rate of Ebola virus disease is 50% on average, but depending on the strain incriminated, it can vary from 25% to 90 %. The fatality rate of SUDV is estimated at around 50% according to the United States Centers for Disease Control, while the WHO considers it to be between 41% and 100%.

The incubation period of the disease fluctuates from 2 to 21 days, and the onset of symptoms can be sudden. Due to the similarity of these symptoms to those of other conditions, it can be difficult to clinically distinguish Ebola virus disease from infectious diseases such as malaria, typhoid fever and meningitis.

The disease typically proceeds in two phases. The so-called “dry” phase includes symptoms such as fever, fatigue, muscle aches, headaches and sore throats. This is followed by the so-called “wet” phase which includes vomiting and diarrhoea, skin rashes and symptoms of impaired kidney and liver function. In some cases, the patient may also experience internal and external bleeding. Infected people cannot transmit the disease until they develop symptoms, and they remain infectious as long as their blood contains the virus.

Of the 44 Ebola virus disease outbreaks reported since 1976, 8 have been caused by SUDV, including the current outbreak. The majority of other outbreaks were caused by the Zaire virus, with the largest being the 2014-2016 outbreak in Sierra Leone, Liberia and Guinea (28 cases, 610 deaths).

A disease of animal origin

Ebola virus disease is a zoonotic disease, that is to say transmitted to humans by animals. fruit bats (Pteropodidae) are suspected to be the natural reservoir of the virus, which can also infect chimpanzees, gorillas, monkeys, forest antelopes or porcupines. Animal-to-human transmission occurs through contact with infected animals during subsistence activities such as hunting or cooking.

Human-to-human transmission occurs through direct contact with the blood or bodily fluids of a person who is sick or has died of Ebola, as well as via objects contaminated by infected body fluids (sheets, clothes, syringes). The Ebola virus can enter the body through skin lesions or mucous membranes. Health professionals are therefore particularly at risk during treatment, and must wear personal protective equipment.

The data shows that sexual transmission from male to female is plausible. Indeed, the virus can persist in the semen of survivors for several months after recovery, and this persistence is associated with a high risk of transmission. Sexual transmission from female to male is also possible, but less likely.

Pregnant women who have acute Ebola and recover from the disease may still carry the virus in breast milk or in pregnancy-related fluids and tissues. In contrast, women who become pregnant after surviving Ebola disease are not at risk of carrying the virus.

No treatment available against the Sudan strain

Two treatments were approved in 2020 by the U.S. Food and Drugs Administration (FDA) for the treatment of Ebola Zaire virus: Inmazeb, a combination of three monoclonal antibodies, and Ebanga, a human monoclonal antibody isolated from a survivor of the Zaire epidemic. 'Ebola.

On the other hand, no treatment currently exists against the Sudan strain: these therapies are indeed ineffective against viruses other than the Zaire strain. The only way to improve the survival rate of patients is to provide them with supportive care – oral or intravenous rehydration – and to treat specific symptoms.

A cocktail of two monoclonal antibodies with a broad neutralizing spectrum seems however to constitute a promising candidate, since it has shown, in ferrets and non-human primates, a high efficiency against infection by the Zaire, Sudan, and Bundibugyo viruses (MBP134). . However, further evaluations will be necessary. Clinical phase trials in humans will be developed thanks to significant funding provided by the Administration for Strategic Preparedness and Response, an operational agency of the United States Public Health Service whose purpose is the prevention and response to disasters that can negatively impact health.

Where are the vaccines?

To date, no approved vaccine against the Sudan strain exists. Conversely, two vaccines against the Zaire virus are authorized by international health authorities: ERVEBO, a live attenuated vaccine containing the surface glycoprotein of the Zaire Ebola virus (produced by Merck Sharp & Dohme BV) and Zabdeno/Mvabea (from the Janssen laboratory ), a vaccine given in two doses.

The second dose of Zabdeno/Mvabea targets not only the Zaire strain, but also other filoviruses, including the Sudan strain and the Marburg virus. However, the protection conferred against these latter viruses has not been demonstrated by clinical data. Furthermore, despite its potential ability to induce a response against SUDV after the second dose, the length of the vaccination schedule (the two doses should be separated by approximately 8 weeks) makes this vaccine unsuitable for use in epidemic contexts where the response must be rapid, as is currently the case in Uganda.

To address this issue, six candidate vaccines targeting the Sudan strain are currently in development, three of which have reached the clinical phase. The WHO is setting up a clinical trial in Uganda to test two of these candidates.

The first is a specific single-dose vaccine against SUDV, developed by GSK, which licensed it in 2019 to the Sabin Vaccine Institute. The second candidate is a bivalent chimpanzee adenovirus vaccine containing Zaire virus and SUDV glycoproteins. This vaccine is developed by the University of Oxford, UK.

The Ugandan trial will be launched by the end of October 2022 at the latest. Until then, many uncertainties remain as to the evolution of the epidemic…

The information contained in this article comes from an ANRS knowledge note on the Ebola disease epidemic due to the Sudan – Uganda virus (coordinated by Yazdan Yazdanpanah, Éric D'Ortenzio and Marion Fanjat, and written by Nicolas Pulik , Erica Telford, and Inmaculada Ortega-Perez).

Nicolas pulik, International development officer - ANRS|Emerging infectious diseases, Inserm; Erica Telford, Project Manager - Dept. Innovation - ANRS | Emerging Infectious Diseases, Inserm; Eric D'Ortenzio, Doctor, Epidemiologist, Head of Strategy & Partnerships Department, ANRS I Emerging infectious diseases, Inserm et Inmaculada Ortega-Perez, Project Manager - Innovation Department ANRS MIE at ANRS, Inserm

This article is republished from The Conversation under Creative Commons license. Read theoriginal article.

Image: Microscopic view of the Ebola virus