Analysis of 2021 Ebola outbreak reveals long-term dormant infections

Guinea recently experienced its second outbreak of the Ebola virus disease within the last decade. This outbreak began when a case was reported in January 2021 in a town named Gouéké, located over 100 miles from the epicenter of the 2013-2016 outbreak.

In a recent Nature study, the source of this most recent outbreak is investigated by next-generation sequencing, finding evidence that eliminates sustained human-to-human transmission or zoonotic transfer as explanations. This study also suggests that the virus could have been dormant or latent since the conclusion of the previous outbreak.

Study: Resurgence of Ebola virus in 2021 in Guinea suggests a new paradigm for outbreaks. Image Credit: David Perieras /

Characterizing the outbreak

The index case appeared on January 21st, 2021 when a 51-year-old woman was admitted to the hospital. Unfortunately, she was misdiagnosed with malaria at this time and discharged two days later. This patient subsequently died at home three days later.

In the following week, four family members who had attended her funeral fell ill and died, while her husband was hospitalized in another city after having traveled more than 400 miles before recognizing that he was ill. He and three other suspected cases were tested, at which point Ebola was detected and the Guinea national epidemic alert system activated. The epidemic was declared over after a period of 25 days with no new cases, but not before a total of 14 confirmed cases were discovered, 9 of which led to death.

Extensive diagnostic and therapeutic measures have been put in place in Guinea against another Ebola outbreak. Additionally, a qualitative reverse-transcriptase polymerase chain reaction (qRT-PCR) assay was specifically developed to detect Ebola strains and was utilized to confirm infection.

Taken together, 11 complete and 8 partial genomic sequences were collected from 12 of the 14 confirmed cases of Ebola in the 2021 outbreak. These samples were obtained by three different laboratories using differing next-generation sequencing methods. In total, 12 high-quality genomes representing 12 infections were then reconstructed by the authors from these data, covering 82.9 – 99.9% of the genome.

What was the origin of the 2021 Ebola outbreak?

Phylogenetic reconstruction revealed that all of the 2021 cases were of similar genetic origin, matching a single cluster from the 2013-2016 outbreak. A total of 10 substitution mutations that had been accumulated by this cluster during the earlier outbreak were noted. These included a mutation known to have been acquired when the virus had previously spread to Sierra Leone.

Only 12 novel mutations were noted in Ebola sampled in 2021 as compared to samples collected in 2016, which the authors state is far fewer than would be expected during a six-year period if the sustained human-to-human transmission had occurred. This would equate to an approximately 6.4-fold lower rate of mutation than expected and is 5.5 fold lower than observed in one patient who bore a sustained infection for over 500 days.

The 12 patients in the 2021 outbreak were sampled over a one-month period; thus, mutations to the virus between these patients over this period could be used to estimate the date of outbreak inception. Using this method, the researchers estimate that the outbreak began on January 22, 2021, which coincides almost perfectly with the date that the probable index case reported symptoms. Therefore, the mutation rate now observed in the 2021 outbreak correlates with the hypothesis of a dormant infection having been reactivated.

It has previously been assumed that the majority of Ebola outbreaks have been the result of repeat independent zoonotic transmission from reservoir species. Notably, this paper has demonstrated that new outbreaks can also be the result of human-to-human transmission from individuals infected many years earlier. The limited genetic change observed in 2021 compared to 2016 may be the result of slow long-term mutation, though the group suggests that a period of latency may be more likely, with the virus persisting at low levels in one or more humans since the last outbreak.

In the probable index case, a 51-year-old nurse, and her close family were all in good health immediately before the outbreak began in 2021. None of the patients who she treated were found to have been infected with Ebola before or after her diagnosis. It is possible that the nurse was not the true index case, was infected with Ebola by a third unrecognized party, or that her latent infection was reactivated at this time.


This paper highlights the importance of continuous monitoring of Ebola virus disease survivors, as well as the development of effective antiviral therapies that can combat latent virus reservoirs.

Transmission between humans is usually by direct contact of bodily fluids from symptomatic or deceased individuals, and transmission has also been noted by breast milk and cervicovaginal fluids. Transmission has also been associated with the viral presence in the semen of 50% of male survivors 6 months after recovery, with persistent detection up to 700 days in some cases.

This recent resurgence 5 years later further reinforces the need for long-term care of Ebola virus disease survivors, both to detect early re-emergence and to alleviate any social stigma they may receive in light of their status as a carrier. A vaccine against Ebola virus disease was approved by the United States Food and Drug Administration (FDA) in late 2019 and is recommended for distribution to those likely to encounter Ebola by the United States Centers for Disease Control and Prevention (CDC).

The economics and logistics of widespread vaccine distribution in West Africa make it an unlikely prospect, though thorough contact tracing may allow vaccines to be strategically administered.

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