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Post-Ebola virus syndrome

Post-Ebola virus syndrome
Other namesPost Ebola syndrome
Ebola virus particles (blue) attacking a cell (yellow)
SpecialtyInfectious disease
SymptomsChest pain, fatigue, hearing loss[1]
CausesEVD
Diagnostic methodNeurological observation[2]

Post-Ebola virus syndrome (or post-Ebola syndrome) is a post-viral syndrome affecting those who have recovered from infection with Ebola.[3] Symptoms include joint and muscle pain, eye problems, including blindness, various neurological problems, and other ailments, sometimes so severe that the person is unable to work.[4] Although similar symptoms had been reported following previous outbreaks in the last 20 years, health professionals began using the term in 2014 when referring to a constellation of symptoms seen in people who had recovered from an acute attack of Ebola disease.[5]

Signs and symptoms

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Researchers have been aware of a group of symptoms that frequently followed Ebola virus disease for 20 years, but it became more widely reported with the large number of survivors of the deadly epidemic in West Africa in 2014.[3][6][7][8][2] Post Ebola syndrome may manifest as joint pain, muscle pain, chest pain, fatigue, hearing loss, hair loss, cessation of menstruation, and poor long-term health. Some survivors report neurological issues including memory problems and anxiety attacks. Vision loss is also frequently reported, along with eye pain, inflammation, and blurred vision.[1] Two papers published in the New England Journal of Medicine in 2015 report that symptoms include lethargy, joint pains, hair loss, and vision loss, frequently to the point of near blindness, and uveitis.[9][10]

Mechanism

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Doctors put on protective gear before entering an Ebola treatment ward in Liberia, August 2014.

Although, there is some progress that may potentially help Ebola survivors, adequate funding and further research is required to help provide more answers about post-Ebola syndrome.[11]

Studies from previous outbreaks reveal that the virus is able to survive for months after recovery in some parts of the body such as the eyes and testes, where the immune system cannot reach. It is not known if the neurologic symptoms seen in survivors are a direct result of the virus or, instead, triggered by the immune system's response to the infection. It is known that Ebola can trigger a massive cytokine storm that can cause bleeding throughout the body, including the brain, which may explain various neurological symptoms that have been reported.[12]

Diagnosis

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In terms of diagnosis, the individual may show sensitivity to light or eye redness when ocular problems are suspected. Neurologically the individual's coordination, gait and frontal release signs should be observed.[2]

Management

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Management depends on the symptoms displayed, for example, if the individual indicates muscular-skeletal pain then paracetamol may be administered. If the individual presents with ocular problems, then prednisone and cyclopentolate may be used for treatment, according to the WHO.[2]

Prognosis

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Viral persistence and transmission

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According to a review by Brainard, et al., Ebola virus was identified in almost 3 out of 4 seminal fluid samples (18 survivors) almost 4 months after initial infection, with the last positive samples being more than 6 months (203 days) after infection had occurred.[13] Another aspect of survivors of the Ebola virus, is that it could become sexually transmitted, as the virus is present in semen nine months after the individuals are declared free of Ebola.[14] A 2017 study found the virus in the semen of some men after more than two years following the recovery from the acute infection[15] and in one case, Ebola viral RNA was identified up to 40 months after illness.[16]

At the start of 2021 an outbreak of EVD that caused 18 cases and 9 deaths in Guinea is thought to be due to a West Africa Ebola outbreak survivor. This individual apparently infected a woman more than 5 years after he himself had incurred the infection[17]

Research

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An observational study, done roughly 29 months after the 2007 Bundibugyo outbreak in Uganda, found that long-term sequelae (i.e. consequences) persisted among survivors. Symptoms included eye pain, blurred vision, hearing loss, difficulty swallowing, difficulty sleeping, arthralgias, memory loss or confusion, and "various constitutional symptoms controlling for age and sex".[18]

From August through December 2014, a total of 10 patients with Ebola were treated in US hospitals; of these patients, 8 survived. In March 2015, the CDC interviewed the survivors; they all reported having had at least one adverse symptom during their recovery period. The symptoms ranged from mild (e.g. hair loss) to more severe complications requiring re-hospitalisation or treatment. The most frequently reported symptoms were lethargy or fatigue, joint pain, and hair loss. Sixty-three per cent reported having eye problems including two who were diagnosed with uveitis, 75% reported psychological or cognitive symptoms, and 38% reported neural difficulties. Although most symptoms resolved or improved over time, only one survivor reported complete resolution of all symptoms.[19]

A study published in May 2015 discussed the case of Ian Crozier, a Zimbabwe-born physician and American citizen who became infected with Ebola while he was working at an Ebola treatment centre in Sierra Leone. He was transported to the US and successfully treated at Emory University Hospital. However, after discharge Crozier began to experience symptoms including low back pain, bilateral enthesitis of the Achilles tendon, paresthesias involving his lower legs, and eye pain, which was diagnosed as uveitis. His eye condition worsened and a specimen of aqueous humor obtained from his eye tested positive for Ebola. The authors of the study concluded that "further studies to investigate the mechanisms responsible for the ocular persistence of Ebola and the possible presence of the virus in other immune-privileged sites (e.g., in the central nervous system, gonads, and articular cartilage) are warranted." The authors also noted that 40% of participants in a survey of 85 Ebola survivors in Sierra Leone reported having "eye problems", though the incidence of actual uveitis was unknown.[20]

Another study, which was released in August 2015 looked at the health difficulties reported by survivors. Calling the set of symptoms "post-Ebolavirus disease syndrome", the research found symptoms that included "chronic joint and muscle pain, fatigue, anorexia, hearing loss, blurred vision, headache, sleep disturbances, low mood and short-term memory problems", and suggested the "implementation of specialised health services to treat and follow-up survivors".[21]

Researchers from the National Institute of Neurological Disorders and Stroke (NINDS) and Liberian research partners are doing a 5-year follow-up study of 1500 Ebola survivors in Liberia. Survivors will be evaluated every 6 months; as of October 2017, two follow-ups have been performed. Researchers will track relapses and viral persistence, characterize sequelae in various bodily systems, and do clinical studies on pharmacologic interventions and vaccines.[22]

PREVAIL III (Partnership for Research on Ebola Vaccines in Liberia III), a study of survivors and their contacts, a collaboration between NIAID and Liberia, was planned in late 2014.[23] Early results described abdominal, chest, neurologic, musculoskeletal, and ocular[24] challenges faced by survivors.[16]

PREVAIL IV examined if a medication, GS-5734, could help men with persistent Ebola virus RNA in semen to eliminate it,[25] and thereby reduce the potential risk for sexual transmission.

PREVAIL VII examined if survivors of Ebola virus disease had evidence of Ebola virus RNA in aqueous humor and outcomes of cataract surgery relative to the local population.[26]

In 2018, over two years after the resolution of the Ebola outbreak in Eastern Sierra Leone, a study was conducted of Ebola survivors, with their families used as a control group. The study was published in 2021, Looking at the results, the researchers were able to find an underlying process leading to persistent symptoms in some but not all Ebola survivors. One hypothesis suggests "ongoing inflammation due to persistent infection vs autoimmune phenomena." The authors suggest that more study is needed to come to conclusions about why some survivors continue to experience post syndrome ailments.[27]

See also

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References

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  1. ^ a b Carod-Artal FJ (3 October 2015). "Post-Ebolavirus disease syndrome: what do we know?". Expert Review of Anti-Infective Therapy. 13 (10): 1185–7. doi:10.1586/14787210.2015.1079128. PMID 26293407.
  2. ^ a b c d "Clinical care for survivors of Ebola virus disease" (PDF). WHO. World Health Organization. Retrieved 5 August 2016.
  3. ^ a b Scott JT, Sesay FR, Massaquoi TA, Idriss BR, Sahr F, Semple MG (April 2016). "Post-Ebola Syndrome, Sierra Leone". Emerging Infectious Diseases. 22 (4): 641–6. doi:10.3201/eid2204.151302. PMC 4806950. PMID 26983037.
  4. ^ Burki TK (July 2016). "Post-Ebola syndrome". The Lancet. Infectious Diseases. 16 (7): 780–781. doi:10.1016/S1473-3099(15)00259-5. PMID 27352759.
  5. ^ Yasmin S. "Why Ebola Survivors Struggle with New Symptoms". Scientific American. Retrieved 2020-05-27.
  6. ^ Neporent L (2014-09-03). "'Post-Ebola Syndrome' Persists After Virus Is Cured, Doctor Says". ABC news. Retrieved 12 May 2015.
  7. ^ Farge E, Giahyue JH (2015-02-04). "Free from Ebola, survivors complain of new syndrome". Reuters. Dakar, Monrovia. Retrieved 12 May 2015.[dead link‍]
  8. ^ Grady D (2015-05-07). "After Nearly Claiming His Life, Ebola Lurked in a Doctor's Eye". The New York Times. The New York Times. Retrieved 12 May 2015.
  9. ^ Varkey JB, Shantha JG, Crozier I, Kraft CS, Lyon GM, Mehta AK, et al. (June 2015). "Persistence of Ebola Virus in Ocular Fluid during Convalescence". The New England Journal of Medicine. 372 (25): 2423–7. doi:10.1056/NEJMoa1500306. hdl:2328/35704. PMC 4547451. PMID 25950269.
  10. ^ Epstein L, Wong KK, Kallen AJ, Uyeki TM (December 2015). "Post-Ebola Signs and Symptoms in U.S. Survivors". The New England Journal of Medicine. 373 (25): 2484–6. doi:10.1056/NEJMc1506576. PMID 26672870.
  11. ^ "Ebola survivors: What happens next?". Foundation for Biomedical Research. Archived from the original on 10 July 2015. Retrieved 8 July 2015.
  12. ^ Clark DV, Kibuuka H, Millard M, Wakabi S, Lukwago L, Taylor A, et al. (August 2015). "Long-term sequelae after Ebola virus disease in Bundibugyo, Uganda: a retrospective cohort study". The Lancet. Infectious Diseases. 15 (8): 905–12. doi:10.1016/S1473-3099(15)70152-0. PMID 25910637.
  13. ^ Brainard J, Pond K, Hooper L, Edmunds K, Hunter P (February 2016). "Presence and Persistence of Ebola or Marburg Virus in Patients and Survivors: A Rapid Systematic Review". PLOS Neglected Tropical Diseases. 10 (2): e0004475. doi:10.1371/journal.pntd.0004475. PMC 4771830. PMID 26927697.
  14. ^ "Preliminary study finds that Ebola virus fragments can persist in the semen of some survivors for at least nine months". WHO. World Health Organization. Archived from the original on 7 December 2016. Retrieved 5 August 2016.
  15. ^ Fischer WA, Brown J, Wohl DA, Loftis AJ, Tozay S, Reeves E, et al. (2017). "Ebola Virus Ribonucleic Acid Detection in Semen More Than Two Years After Resolution of Acute Ebola Virus Infection". Open Forum Infectious Diseases. 4 (3): ofx155. doi:10.1093/ofid/ofx155. PMC 5897835. PMID 29670927.
  16. ^ a b Sneller MC, Reilly C, Badio M, Bishop RJ, Eghrari AO, Moses SJ, et al. (March 2019). "A Longitudinal Study of Ebola Sequelae in Liberia". The New England Journal of Medicine. 380 (10): 924–934. doi:10.1056/NEJMoa1805435. PMC 6478393. PMID 30855742.
  17. ^ Kupferschmidt, Kai (12 March 2021). "New Ebola outbreak likely sparked by a person infected 5 years ago". Science. doi:10.1126/science.abi4876. Retrieved 19 March 2021.
  18. ^ Steve E Bellanemail; Juliet R C Pulliam; Jonathan Dushoff; Lauren Ancel Meyers (15 October 2015). "Ebola control: effect of asymptomatic infection and acquired immunity". The Lancet. 384 (9953): 1499–1500. doi:10.1016/S0140-6736(14)61839-0. PMC 4829342. PMID 25390569.
  19. ^ Epstein, Lauren; Wong, Karen K; Kallen, Alexander J; Uyeki, Timothy M (17 December 2015). "Post-Ebola Signs and Symptoms in U.S. Survivors". New England Journal of Medicine. 373 (25): 2484–2486. doi:10.1056/NEJMc1506576. PMID 26672870.
  20. ^ Varkey, JB; Shantha, JG; Crozier, I; Kraft, CS; Lyon, GM; Mehta, AK; Kumar, G; Smith, JR; Kainulainen, MH; Whitmer, S; Ströher, U; Uyeki, TM; Ribner, BS; Yeh, S (Jun 2015). "Persistence of Ebola Virus in Ocular Fluid during Convalescence". New England Journal of Medicine. 372 (25): 2423–2427. doi:10.1056/NEJMoa1500306. hdl:2328/35704. PMC 4547451. PMID 25950269.
  21. ^ Carod-Artal FJ (2015). "Post-Ebolavirus disease syndrome: what do we know?". Expert Rev Anti Infect Ther. 13 (10): 1185–7. doi:10.1586/14787210.2015.1079128. PMID 26293407.
  22. ^ Jagadesh S, Sevalie S, Fatoma R, Sesay F, Sahr F, Faragher B, et al. (January 2018). "Disability Among Ebola Survivors and Their Close Contacts in Sierra Leone: A Retrospective Case-Controlled Cohort Study". Clinical Infectious Diseases. 66 (1): 131–133. doi:10.1093/cid/cix705. PMC 5833946. PMID 29020205.
  23. ^ Massaquoi MB, Kennedy SB, Tegli JK, Bolay FK, Kateh FN (April 2016). "Fostering collaboration on post-Ebola clinical research in Liberia". The Lancet. Global Health. 4 (4): e239. doi:10.1016/S2214-109X(15)00323-X. PMID 27013310.
  24. ^ Eghrari AO, Bishop RJ, Ross RD, Davis B, Larbelee J, Amegashie F, et al. (January 2021). "Characterization of Ebola Virus-Associated Eye Disease". JAMA Network Open. 4 (1): e2032216. doi:10.1001/jamanetworkopen.2020.32216. PMC 7786253. PMID 33399856.
  25. ^ "PREVAIL treatment trial for men with persistent Ebola viral RNA in semen opens in Liberia". National Institutes of Health (NIH). 2016-07-05. Retrieved 2021-01-27.
  26. ^ Eghrari, Allen O.; Shantha, Jessica G.; Ross, Robin D.; Ryn, Collin Van; Crozier, Ian; Hayek, Brent; Gradin, Dan; Roberts, Ben; Prakalapakorn, S. Grace; Amegashie, Fred; Nishant, Kumar (2021-01-04). "Efficacy and Safety Outcomes of Cataract Surgery in Survivors of Ebola Virus Disease: 12-Month Results From the PREVAIL VII Study". Translational Vision Science & Technology. 10 (1): 32. doi:10.1167/tvst.10.1.32. ISSN 2164-2591. PMC 7838547. PMID 33520427.
  27. ^ Bond, N. G.; Grant, D. S.; Himmelfarb, S. T.; Engel, E. J.; Al-Hasan, F.; Gbakie, M.; Kamara, F.; Kanneh, L.; Mustapha, I.; Okoli, A.; Fischer, W.; Wohl, D.; Garry, R. F.; Samuels, R.; Shaffer, J. G.; Schieffelin, J. S. (2021). "Post-Ebola Syndrome Presents With Multiple Overlapping Symptom Clusters: Evidence From an Ongoing Cohort Study in Eastern Sierra Leone". Clinical Infectious Diseases. 73 (6): 1046–1054. doi:10.1093/cid/ciab267. PMC 8442780. PMID 33822010.

Further reading

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Scholia has a topic profile for Post-Ebola virus syndrome.