In the JournalsPerspective

Ebola detected in eye of US physician months after recovery

An American physician diagnosed with Ebola virus infection in September continued to carry the virus and developed serious ocular complications 14 weeks after his diagnosis, according to research published in the New England Journal of Medicine and presented recently at the 2015 Association for Research in Vision and Ophthalmology Annual Meeting in Denver.

“Among survivors of [Ebola virus disease (EVD)], late complications that include ocular disease can develop during convalescence,” according to Jay B. Varkey, MD, of the department of medicine, division of infectious diseases at Emory University School of Medicine, and colleagues. “However, few systematic studies have been conducted on post-EVD sequelae, so the incidence and clinical manifestations of post-EVD ocular complications are unclear.”

The physician, aged 43 years and previously healthy, was diagnosed with Ebola virus (EBOV) on Sept. 6, 2014, while treating Ebola patients in Sierra Leone. He arrived at Emory University Hospital 4 days after the onset of symptoms, and was treated with an experimental, small interfering RNA antiviral agent, TKM-100802 (TKM-Ebola, Tekmira Pharmaceuticals), convalescent plasma and aggressive supportive care.

On day 44 of illness, and after his blood and urine tested negative for the disease on reverse-transcriptase PCR (RT-PCR) assay, the patient was discharged. Shortly later, however, the patient began experiencing sporadic bilateral ocular burning, photophobia and foreign-body sensation, according to the researchers. The patient, whose ocular history included only myopia, required an adjustment to his prescription reading glasses. After evaluation at the Emory Eye Center, he was diagnosed with posterior uveitis, a likely complication of EVD, the researchers wrote.

One month later — 14 weeks after his Ebola diagnosis — the patient presented with acute redness in his left eye, blurred vision, pain and photophobia. During the next 2 days, his symptoms worsened, and Emory specialists performed paracentesis of the physician’s anterior chamber. He was later diagnosed with acute anterior uveitis that progressed to panuveitis.

Aqueous humor samples sent to Emory University Hospital tested positive for EBOV RNA, but a conjunctival swab and tear-film specimens tested negative for EBOV RNA. Repeat peripheral blood also tested negative, according to Varkey and colleagues.

“It is reassuring that samples of conjunctivae and tears tested negative for EBOV, a finding that supports previous studies suggesting that patients who recover from EVD pose no risk of spreading the infection through casual contact,” the researchers wrote. The patient was treated with multiple interventions including topical and systemic corticosteroids.

At a 3-month follow-up visit, his visual acuity had returned to normal, and follow-up evaluations are ongoing.

Although there have been few confirmed cases where EBOV has been detected in conjunctival samples, it is an issue that should not be ignored, according to the researchers.

“The current outbreak has resulted in the largest number of EVD survivors in history,” Varkey told Infectious Disease News. “EVD survivors require ongoing medical care to manage complications from the infection that may develop during recovery.” – by David Jwanier

Disclosure: Varkey reports no relevant financial disclosures. Please see the full study for a list of all other authors’ relevant financial disclosures.

An American physician diagnosed with Ebola virus infection in September continued to carry the virus and developed serious ocular complications 14 weeks after his diagnosis, according to research published in the New England Journal of Medicine and presented recently at the 2015 Association for Research in Vision and Ophthalmology Annual Meeting in Denver.

“Among survivors of [Ebola virus disease (EVD)], late complications that include ocular disease can develop during convalescence,” according to Jay B. Varkey, MD, of the department of medicine, division of infectious diseases at Emory University School of Medicine, and colleagues. “However, few systematic studies have been conducted on post-EVD sequelae, so the incidence and clinical manifestations of post-EVD ocular complications are unclear.”

The physician, aged 43 years and previously healthy, was diagnosed with Ebola virus (EBOV) on Sept. 6, 2014, while treating Ebola patients in Sierra Leone. He arrived at Emory University Hospital 4 days after the onset of symptoms, and was treated with an experimental, small interfering RNA antiviral agent, TKM-100802 (TKM-Ebola, Tekmira Pharmaceuticals), convalescent plasma and aggressive supportive care.

On day 44 of illness, and after his blood and urine tested negative for the disease on reverse-transcriptase PCR (RT-PCR) assay, the patient was discharged. Shortly later, however, the patient began experiencing sporadic bilateral ocular burning, photophobia and foreign-body sensation, according to the researchers. The patient, whose ocular history included only myopia, required an adjustment to his prescription reading glasses. After evaluation at the Emory Eye Center, he was diagnosed with posterior uveitis, a likely complication of EVD, the researchers wrote.

One month later — 14 weeks after his Ebola diagnosis — the patient presented with acute redness in his left eye, blurred vision, pain and photophobia. During the next 2 days, his symptoms worsened, and Emory specialists performed paracentesis of the physician’s anterior chamber. He was later diagnosed with acute anterior uveitis that progressed to panuveitis.

Aqueous humor samples sent to Emory University Hospital tested positive for EBOV RNA, but a conjunctival swab and tear-film specimens tested negative for EBOV RNA. Repeat peripheral blood also tested negative, according to Varkey and colleagues.

“It is reassuring that samples of conjunctivae and tears tested negative for EBOV, a finding that supports previous studies suggesting that patients who recover from EVD pose no risk of spreading the infection through casual contact,” the researchers wrote. The patient was treated with multiple interventions including topical and systemic corticosteroids.

At a 3-month follow-up visit, his visual acuity had returned to normal, and follow-up evaluations are ongoing.

Although there have been few confirmed cases where EBOV has been detected in conjunctival samples, it is an issue that should not be ignored, according to the researchers.

“The current outbreak has resulted in the largest number of EVD survivors in history,” Varkey told Infectious Disease News. “EVD survivors require ongoing medical care to manage complications from the infection that may develop during recovery.” – by David Jwanier

Disclosure: Varkey reports no relevant financial disclosures. Please see the full study for a list of all other authors’ relevant financial disclosures.

    Perspective
    Christopher W. Woods

    Christopher W. Woods

    Clinical investigators and epidemiologists are increasingly aware of sub-acute and chronic complications from EBOV infection now referred to as post-Ebola syndrome. Many of the manifestations (eg, fatigue, headache, muscle and joint discomfort, and depression) are commonly associated with recovery from a diversity of severe infections and do not necessarily imply failed clearance of the virus. This report by Emory clinicians documents high levels of replicating EBOV in the eye of a recently recovered patient who develops symptomatic pan-uveitis. Considered together with the delayed clearance of EBOV from semen, this finding demonstrates the importance of immune privileged sites where ongoing viral activity may result in new or persistent symptoms or serve as a potential reservoir for delayed transmission.

    The absence of detectable virus from the patient’s tears, conjunctiva, or peripheral blood supports current recommendations regarding infection-control procedures. However, the detection of persistent infection in what appears to be a sanctuary site is remarkable and potentially has important implications for how we handle specimens collected from patients with a history of EBOV infection and provide their routine follow-up care.

    The documentation of viral replication in the eye of the patient in this report is unique, but uveitis has been reported in previous outbreaks of EBOV and other hemorrhagic fever viruses. Ongoing clinical investigations have documented a variety of ophthalmological, auditory and neurological findings among survivors. The unprecedented number of survivors from this outbreak and the frequency of such findings being reported highlight the importance of longitudinal follow up studies. This is essential for appropriate medical care, assurance of the safety of clinical and laboratory personnel, and ultimately the prevention of unnecessary stigma related to these patient’s daily lives.

    • Christopher W. Woods, MD, MPH
    • Infectious Disease News Editorial Board member Professor of medicine and global health Duke University School of Medicine

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