Ebola virus, which can persist in certain areas of the body, can re-emerge to cause fatal disease, even long after treatment with monoclonal antibodies, according to a study.
The study, published in the journal Science Translational Medicine, was conducted using a nonhuman primate model of Ebola virus infection.
The research team from US Army Medical Research Institute of Infectious Diseases found that about 20 per cent of monkeys that survived lethal Ebola virus exposure after treatment with monoclonal antibody therapeutics still had persistent Ebola virus infection — specifically in the brain ventricular system, in which cerebrospinal fluid is produced, circulated, and contained — even when Ebola virus was cleared from all other organs.
“Ours is the first study to reveal the hiding place of brain Ebola virus persistence and the pathology causing subsequent fatal recrudescent Ebola virus-related disease in the nonhuman primate model,” explained Xiankun (Kevin) Zeng, from the institute.
In particular, two monkeys that initially recovered from Ebola virus-related disease after treatment with antibody therapeutics had recurrence of severe clinical signs of Ebola virus infection and succumbed to the disease, Zeng said.
Severe inflammation and massive Ebola virus infection were present in the brain ventricular system; no obvious pathology and viral infection were found in other organs.
Previous research using nonhuman primate survivors as a model has showed that the virus, despite being cleared from all other organs, can hide and persist in specific regions of immune-privileged organs, such as the vitreous chamber of eyes, the seminiferous tubules of testes, and the ventricular system of the brain reported in this study.
“The persistent Ebola virus may reactivate and cause disease relapse in survivors, potentially causing a new outbreak,” said Jun Liu, from USAMRIID.
Recurrence of Ebola virus disease has previously been reported in human survivors, according to the researchers.
For example, a British nurse experienced Ebola virus relapse in the brain, suffering from meningoencephalitis nine months after recovering from severe Ebola virus disease.
She had received therapeutic antibodies during the 2013-2016 outbreak in Western Africa, the largest such outbreak to date.
In addition, a vaccinated patient who had been treated with monoclonal antibody therapeutics for Ebola virus disease six months earlier relapsed and died at the end of the 2018-2020 outbreak in the Democratic Republic of the Congo.
Unfortunately, that case also led to many subsequent human-to-human transmissions
Ebola virus causes one of the deadliest infectious diseases known to humankind. It is still a major threat in Africa, and there were three outbreaks in Africa in 2021 alone, according to the World Health Organization.
Two vaccines and two monoclonal antibody therapeutics have been approved to prevent and treat Ebola virus disease in recent years.
“However, our study reinforces the need for long-term follow-up of Ebola virus disease survivors — even including survivors treated by therapeutic antibodies — in order to prevent recrudescence. This will serve to reduce the risk of disease re-emergence, while also helping to prevent further stigmatization of patients,” Zeng said.