Outline Basic Ebola Case of Ebola Journals

2. Outline
• Brief discussion of Ebola
• Case of Ebola with Ophthalmic Manifestations
• Journals

3. Ebola
• Discovered in 1976
• Single-stranded negative sense RNA Virus
• Order: Mononegavirales
• Family: Filoviridae
– Viral Hemorrhagic Fever in primates
• Genus: Ebolavirus is 1 of 3 members of the
Filoviridae family (filovirus),
– Marburg virus and Cueva virus

4. SPECIES
• Genus Ebolavirus comprises 5 distinct species:
 Bundibugyo ebolavirus (BDBV)
 Zaire ebolavirus (EBOV)
 most dangerous
 Sudan ebolavirus (SUDV)
 Reston ebolavirus (RESTV)
• Taï Forest ebolavirus (TAFV).
• BDBV, EBOV, and SUDV have been associated with large EVD
outbreaks in Africa, whereas RESTV and TAFV have not.
• The RESTV species, found in Philippines and the People’s Republic
of China, can infect humans, but no illness or death in humans from
this species has been reported to date.
Outbreaks of
AFRICA

6. • The virus is transmitted to people from wild animals and spreads in the human
population through human-to-human transmission.
• EVD outbreaks occur primarily in remote villages in Central and West Africa, near tropical
rainforests.

7. Transmission
•The virus is spread through direct
contact (through broken skin or mucous
membranes) with
i. sick person's blood or body fluids
(urine, saliva, feces, vomit, sweat and
semen)
ii. objects (such as needles) that have
been contaminated with infected
body fluids.
iii. Infected animals.

8. Transmission
Animal to human
• Consumption of
raw meat
• Contact with fruit
bat, pigs, apes-
animal handlers
• Animal products
(blood, urine and
feces.)
Human to human
• Close contact with
infected patients
• Care personnels
of patient
• Health care
workers
Prompt and safe
burial of dead
bodies.
No to Autopsy
Virus contained
in dead body for
a period 4 weeks.

9. Transmission
• Men who have recovered from the illness can
still spread the virus to their partner through
their semen for up to 7 weeks after recovery.

11. Pathophysiology
• Endothelial cells, mononuclear phagocytes,
and hepatocytes are the main targets of infection. After
infection, a secreted glycoprotein (sGP) known as the Ebola
virus glycoprotein (GP) is synthesized.
• Ebola replication overwhelms protein synthesis of infected
cells and host immune defenses.
• The GP forms a trimeric complex, which binds the virus to the
endothelial cells lining the interior surface of blood vessels.

12. Pathophysiology
• The sGP forms a dimeric protein that interferes with
the signaling of neutrophils which allows the virus
to evade the immune system by inhibiting early
steps of neutrophil activation.
• These white blood cells also serve as carriers to
transport the virus throughout the entire body to
places such as the lymph nodes, liver, lungs, and
spleen.

13. Incubation Period: 2-21 days

15. • Morbidity and mortality rates are
very high, and they vary with the
strain of Ebola
• Fatality rate 25% to 90%
• Recovery is slow in those who survive
Prognosis

16. Why Is Ebola So Deadly?
• Virus usually detected late with more severe
signs and symptoms
• Often mistaken for malaria, typhoid fever,
dysentery, influenza, or bacterial infections
• Appears in sporadic outbreaks
• People die from the massive blood loss, not
necessarily from the disease
• 10% Survival rate

17. Treatment

18. Treatment
• No ebola virus Disease-specific
treatment exists.
• Treatment is primarily supportive in nature
and includes minimizing invasive
procedures, balancing fluids and
electrolytes to counter dehydration

19. Treatment
• Administration of anticoagulants early in infection to
prevent or control disseminated intravascular
coagulation
 Administration of procoagulants late in infection to
control bleeding
 Maintaining oxygen levels, pain management, and
the use of medications to treat bacterial or fungal
secondary infections.

20. Vaccines
• No vaccine is currently available for humans.
• Promising candidates are DNA vaccines or
vaccines derived from adenoviruses, vesicular
stomatitis Indian virus (VSIV) or filovirus-like
particles (VLPs)
• Vaccines have protected nonhuman primates
• DNA vaccines, adenovirus-based vaccines, and
VSIV-based vaccines have entered clinical
trials

21. Preventive

23. Case of Ebola

24. Emory Ebola Patient #3
• 43yo male, Physician evacuated from Sierra
Leone
• “sickest patient with Ebola virus that we’ve
cared for at Emory”

25. History of Present Illness
• Day 1: Fever, malaise, fatigue, headache
• Day 2: EVD confirmed by RT-PCR
• Day 3: Petechial rash, 1st dose of TKM-100802
• Day 4: Admission (9/3/14)
• Exam:
• 126/73, 51bpm, 40C 98% O2
• Increased work of breathing, petechial rash -> delirium
• Labs: WBC 2.6 PLT 62 AST:155

26. Hospitalization Course
• Day 6: Severe gastroenteritis and hepatitis
• Day 9: AKI and Respiratory distress
– Intubation and mechanical ventilation
• Day 11: Cardiac arrhythmias and worsening
acidosis
• Day 21: Extubated -> Delirium

27. Hospitalization Course
• Day 29: Improving mental status
– Ambulates with assistance
• Day 35: Dialysis held
– Blood test negative for EBOV by RT-PCR
• Day 40: Discharged
– 30lb weight loss, easy fatigability, muscle
weakness, word-finding difficulties

28. Hospitalization Course
• Experimental Treatments
• TKM-100802
– Day 3-8
• Plasma from a survivor
– Day 8, 9, 11, 12, 14 15

29. Day 70 of Illness
11/14/14
• Improving Symptoms
– Ambulation improving
– Occasional word-finding difficulty
– Gaining weight
• New Symptoms
– Hair loss, coming out in clumps
– Marked decreased hearing L>R
– Low back pain
– Enthesitis: Bilateral Achilles tendons
– Occsional blurry vision bilaterally
• Transient burning lasting for a few seconds, every few days

30. Day 80 of Illness
• Improving symptoms
– Back and joint pains
– Tendinitis
– Word-finding difficulties
• Worsening symptoms
– Blurred vision
– Mild light sensitivity
– Increased need for reading glasses

31. Day 80 of Illness
• PE
• VA 20/15 OU
• IOP OD 10mmHg, OS 9
mmHg
• SLE
– C/S Quiet OU
– K Mild arcus senilis OU
– AC D/Q OU
– Iris WNL OU, Blue irides
OU
– Lens Clear OU
– Ant Vitreous Quiet

32. Posterior Segment Examination

36. Day 80 of Illness
• Posterior Uveitis/Chorioretinitis Inactive
– ? Post inflammatory viral changes
• s/p Ebola Virus Disease convalescent
• Plan
– Observation
– Follow-up 3-4 weeks

37. Day 97 of Illness
12/11/14
• Acute onset of symptoms
– Headache and retro-orbital aching sensation
– Blurred vision and haloes
– Photophobia
• Recommended urgent evaluation
– Diagnosis? Acute angle closure

38. Day 97 of Illness
12/11/14
• VA 20/20 OS
• IOP 44mmHg OS
• SLE OS
– Mild corneal edema, trace cell
• Gonioscopic evaluation
– No evidence of angle closure
• Plan:
– Diamox 250mg and administered ocular hypertensives
decreased 35 mmHg
– Pred forte 1% QID OS
– Systemic and topical ocular hypotensives

41. Day 99 of Illness
12/13/14
• Primary Diagnosis: Hypertensive Anterior Uveitis
• Interval History
– Escalating pain symptoms over next 2 days
– Increasing anterior chamber inflammation
• Differential Diagnosis
– Herpes simplex virus 1 and 2
– Cytomegalovirus
– Varicella zoster virus
– Toxoplasmosis, syphilis, sarcoidosis, HLA-B27 associated
– Ebola virus associated Uveitis

42. Day 99 of Illness
12/13/14
• Plan
– Conjunctiva and tear film specimen taken for
Ebola virus PCR
– Anterior Chamber Paracentesis for PCR testing
– Serologic evaluation for autoimmune/infectious
etiologies
– Referral to infectious disease

43. Ebola virus RT-PCR Positive
(12/14/2014)

44. Ebola virus RT-PCR Positive
(12/14/2014)
• Conjunctival swab and tear film pre and 24 hr
post procedure were EBOV PCR negative

45. Day 102 of Illness
12/16/14
• Interval History
– Worsening vision and eye pain
• VA 20/60 OS, TA 15mmHg
• SLE
– C/S - 3+ episclera;/scleral injection
– K - Diffuse keratic Precipitates
– AC – 2-3+ cells with interspersed RBC
– Iris - WNL
– Lens – Clear
– Vit – No vitreous cell

46. Day 102 of Illness
12/16/14
• Plan
– Start oral prednisone 80mg/day (1mg/kg)
– Topical Prednisolone acetate 1% q2 OS

47. Day 103 of Illness
12/17/14

48. Day 103 of Illness
12/17/14
• VA OS 20/150
• IOP OS 15mmHg
• Hypopion 0.5mm
• Plan
– Continue oral prednisone 80mg/day (1mg/kg)
– Topical Prednisolone acetate 1% q1 OS

49. Day 110 of Illness
12/22/14
• Interval History
– Improving eye pain
• VA OS 20/800 IOP OS 1mmHg
• SLE
– C/S – Quiet conjunctiva
– K -2+ stromal edema w/ decemet folds
– AC – 1+ cells
– Iris - WNL
– Lens – Clear
– Vit – 2+ vitreous haze

50. Day 110 of Illness
12/22/14

52. Day 110 of Illness
12/22/14
• Plan
– Continue oral prednisone 80mg/day (1mg/kg)
– Difluprednate q2 OS

53. Day 110 of Illness
12/22/14
• Current Diagnosis
– Aggressive, acute hypertensive anterior uveitis
progressing to severe panuveitis with hypotony

54. Uncertainty
1. Management and prognosis at this time
• Corticosteroid vs anti-viral
2. Direct viral lytic effect vs immunologic reaction
to Ebola

55. Day 112 of Illness
12/24/14
• Readmission
• Started antiviral
– EBOV specific option
– TKM-Ebola aka T-705

56. Day 117 of Illness
12/29/14
• Steroid Injection

59. Day 118 of Illness
12/30/14

60. Day 118 of Illness
12/30/14
• Discharged
• Poor prognosis

61. Day 122 of Illness
1/3/15
• Febrile episode
• Readmitted

64. Updates
• Explanation for Vision Improvement remains
to be speculations for now.
• On going research and studies

65. Journals

66. What we know about ocular manifestations of Ebola
(Majid Moshirfar,1 Carlton R Fenzl,2 Zhan Li3November 2014)
• Ocular signs observed in both the acute and
late settings
• Conjunctival injection
– 58% of infected patients
– Often presents bilaterally
• Subconjunctival hemorrhage
• Excessive lacrimation
• Unclear pathophysiology of manifestations

67. What we know about ocular manifestations of Ebola
(Majid Moshirfar,1 Carlton R Fenzl,2 Zhan Li3November 2014)
• Subacute/chronic ophthalmic manifestations:
– Two pathways:
• they may rapidly progress to a more intense
hemorrhagic state where death is nearly inevitable
• they may enter a convalescent phase.
– at risk for uveitic episodes.
• Despite the complexity of findings, treatment
required only topical steroids and cycloplegia.

68. Late Ophthalmologic Manifestations in Survivors of the 1995 Ebola Virus
Epidemic in Kikwit, Democratic Republic of the Congo
(Colebunders et at 1999)
• Cumulative total of suspected cases of EBO hemorrhagic fever (EHF)
was 316, of whom 245 (77%) died
• acute phase of EBO infection
– conjunctival injection
• 48% and 58%
• a relatively early sign of EHF
– bilateral conjunctivitis
• acute phase of the epidemic was highly predictive for the diagnosis of an EBO
infection;
– subconjunctival hemorrhages also been reported
– blurred vision or blindness
• etiology of these ocular manifestations remains unclear
• Ophthalmologic examinations considered potentially risky
procedures for health care workers
– the nurse-ophthalmologist died during the EBO epidemic

69. Late Ophthalmologic Manifestations in Survivors of the 1995 Ebola Virus
Epidemic in Kikwit, Democratic Republic of the Congo
(Colebunders et at 1999)
• Twenty (28%) of the 71 EBO survivors were enrolled in a 3-month
follow-up study
• Three participants (15%) presented with ocular manifestations
during the convalescent period of their infection
• fourth EBO survivor outside this cohort, who also had ocular
problem
• all 20 EBO survivors and the additional noncohort patient met the
clinical definition for infection with EBO that was used during the
epidemic. Moreover, serologic results (ELISA) were positive for EBO
infection for all 21 patients
• The clinical features of the 4 EHF cases during the acute EHF illness
were similar to the clinical features observed in other EHF patients.

70. Late Ophthalmologic Manifestations in Survivors of the 1995 Ebola Virus
Epidemic in Kikwit, Democratic Republic of the Congo
(Colebunders et at 1999)
• 15% or 3/20 survivors of the 1995 Ebola outbreak
in the Democratic Republic of the Congo enrolled
in a follow-up study and 1 other survivor
• Developed ocular manifestations after being
asymptomatic for 1 month.
– Complained of ocular pain, photophobia,
hyperlacrimation, and loss of visual acuity.
• Ocular examination revealed uveitis in all 4
patients.

71. Late Ophthalmologic Manifestations in Survivors of the 1995 Ebola Virus
Epidemic in Kikwit, Democratic Republic of the Congo
(Colebunders et at 1999)
• 4 cases, the diagnosis of uveitis was confirmed
by an ophthalmologist.
• The pathogenesis of this uveitis may be a
delayed hypersensitivity reaction to viral
antigens
• All patients improved with a topical treatment
of 1% atropine and steroids

72. Ocular Manifestations of Ebola Virus Disease: An
Ophthalmologist’s Guide to Prevent Infection and Panic
(Enzo Maria Vingolo et al. 11 March 2015)
• The main problem in assessing human-to-
human Ebola virus transmission
• Minimum infectious dose of the
microorganisms is unknown
• EVD patients
– unlikely seek specialized healthcare, as
ophthalmologic care
– likely to seek emergency services and
hospitalization

73. Ocular Manifestations of Ebola Virus Disease: An
Ophthalmologist’s Guide to Prevent Infection and Panic
(Enzo Maria Vingolo et al. 11 March 2015)
• Conjunctivitis
– key early EVD sign
– typically bilateral, asymptomatic, and nonicteric
– appear even 6-7 days before patients seek EVD-related
care
• Persistent and nonhemorrhagic conjunctivitis in EVD
– good prognostic factor
• Summarizing, bilateral, asymptomatic, and nonicteric
conjunctivitis is one of the earliest and most frequent
signs of EVD and has an important prognostic value.

74. Ocular Manifestations of Ebola Virus Disease: An
Ophthalmologist’s Guide to Prevent Infection and Panic
(Enzo Maria Vingolo et al. 11 March 2015)
• Uveitis:
– Late Ophthalmologic Symptom
– 20% of convalescent patients
– asymptomatic for up to 1-2 months
– characterized by ocular pain, photophobia, hyperlacrimation,
and loss of visual acuity
• Pathogenesis of uveitis
– delayed hypersensitivity reaction to RNA viral antigens
• Uveitis can be treated with topical steroids
• patients are considered safe and not infectious
– Even with detectable in tears of acute-phase EVD patients
• Nevertheless, PPE must always be adopted in patients with
ascertained epidemiological risk.

75. Ebola warning for ophthalmologists
(Rose Scneider, May 09, 2015)
• “Ebola virus can remain viable in some body fluids for
an extended period of time after the initial onset of the
disease”
• “If the Ebola epidemic continues, ophthalmologists
throughout the world will be seeing patients with post-
Ebola uveitis, will need to recognize and treat this
condition, and will need to take appropriate increased
precautions in performing surgical procedures on these
patients,”
– Russell N. Van Gelder, AAO president