Ebola Survivor Details Ongoing Sequelae as Lessons Learned for Future Outbreaks
SAN DIEGO—Ian Crozier, MD, has been described as the sickest person ever to survive Ebola Virus Disease, or EVD. Presenting his story as a survivor at IDWeek 2015, he said he was “happy to be here.”
In fact, he said he was happy to be anywhere. And, as the details of the 40 long days and 40 long nights he spent combating multisystem organ failure at Emory University Hospital and the ongoing sequelae he continues to experience as a result of the disease unfolded, attendees began to grasp that this “dual citizen”—physician and survivor—may provide an ideal “N of 1,” but at a vast personal cost, which they acknowledged with a standing ovation.
Or, as he put it, “it ain't over even when it's over.”
Dr. Crozier, who working as a WHO-deployed clinician at the Kenema Ebola Treatment Unit in Sierra Leone, does not know how he contracted EVD. However, on September 7, 2014, the day he describes as “a change of citizenship,” he had a fever, headache, intense fatigue, and myalgia. Self-isolating in a hotel room, he drew a specimen and, several hours later, found he was positive for EVD.
Since his Emory discharge in October 2014, he has had joint pain, or “reactive arthritis”; central nervous system neurocognitive deficits, including short-term memory loss, word-finding difficulty, and new-onset generalized tonic-clonic seizure; moderate to severe sensorineural hearing loss, now with constant tinnitus in his left ear; chronic disabling fatigue; peripheral neuropathy; insomnia; and hair loss.
Then, on December 11, 2014, he had left eye pain, retro-orbital headache, nausea, blurred vision, and prominent halos. His intraocular pressure was markedly elevated. At Day 4, anterior chamber paracentesis found his eye teeming with Ebola.
This raised “more questions than answers. Was this an active replicating virus? Had Ebola virus ever been found previously in the anterior chamber? What was the virus doing in the eye? How did it get there? How did it avoid systemic immune detection and responses? What role was viral replication and lytic infection playing in pathogenesis in the eye?”
Dr. Crozier hypothesized that the eye and the blood retinal barrier were likely breached during the acute infection at peak viremia. Then, “in the setting of ocular immune privilege,” viral replication was ongoing at low levels before it reached a “tipping point,” causing hypertensive anterior uveitis.
When the Ebola virus in his blood from September 2014 was compared with the December 2014 ocular viral specimen, 5 additional mutations were discovered: 1 silent minor variant, not previously identified; 2 mutations identified in previous Ebola virus outbreaks; and 2 mutations not identified in Ebola outbreaks, either in 2014—2015 or previously.
When Dr. Crozier's clinical sequelae were compared with 277 survivors in Africa, similar trends emerged: 75.8% had arthralgia; 60.3% new ocular symptoms and 18.1%, uveitis; and 24.2% had auditory symptoms. A higher viral load at presentation was independently associated with new ocular symptoms or diagnoses and uveitis.
Based on these findings, the National Institutes of Health has instituted the PREVAIL III study in Monrovia, which is designed to determine the incidence, burden, and natural history of uveitis in West Africa.
As of October 6, 2015, the World Health Organization (WHO) tallied 28,424 total cases of EVD and 11,311 deaths. In the west African countries of Guinea, Liberia, and Sierra Leone, this included 881 cases in health care workers, 513 of whom died.