Mosquitos Aedes aegypti UCSF School of Medicine 10 m West Coast - - PowerPoint PPT Presentation

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Mosquitos Aedes aegypti UCSF School of Medicine 10 m West Coast - - PowerPoint PPT Presentation

Apr 05, 2023 135 likes •462 views

12/2/2016 UCSF December Course- 2016 San Francisco, CA Mosquito-Borne Uveitis Emmett T. Cunningham, Jr, MD, PhD, MPH Mosquito Department of Ophthalmology, Proboscis California Pacific Medical Center Department of Ophthalmology, Stanford

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10 μm

Mosquito-Borne Uveitis

Emmett T. Cunningham, Jr, MD, PhD, MPH

Department of Ophthalmology, California Pacific Medical Center Department of Ophthalmology, Stanford University School of Medicine Francis I. Proctor Foundation, UCSF School of Medicine West Coast Retina Medical Group

UCSF December Course- 2016 San Francisco, CA

Mosquito Proboscis

www.gettyimages.com

Mosquitos …

Aedes aegypti Aedes albopictus

Global Distribution of Aedes albopictus Global Distribution of Aedes aegypti

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Global Distribution of Aedes albopictus Global Distribution of Aedes aegypti

Tropics: 36% of the Earth’s Landmass One-Third of the Earth’s Population Tropics: 36% of the Earth’s Landmass One-Third of the Earth’s Population

http://education.nationalgeographic.org/encyclopedia/tropics/

23.5 o N – Tropic of Cancer 23.5 o S – Tropic of Capriocorn Equator

Global Air Travel

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Heavily Interconnected

  • Malaria – 450,000 Deaths/year
  • Measles
  • Mumps
  • Rubella
  • Filariasis
  • Pork tapeworm
  • Hepatitis C
  • Enveloped viruses
  • Icosahedral structures
  • A positive sense, single-strand RNA

genome (~ 12kb)

  • Transcribed as a single polyprotein
  • More than 100 different members
  • Subdivided into:
  • Flavivirus (including Yellow

fever, Japanese Encephalitis, West Nile, dengue, and Zika viruses)

  • Pestivirus
  • Hepacivirus (hepatitis C viruses)

The Flaviviridae Family

http://www.utmb.edu/discoveringdenguedrugs-together/Diseases/Flaviviridae%20Family.asp

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West Nile Virus

West Nile Virus

  • Flavivirus genus
  • Flaviviridae family
  • Positive-sense, single stranded RNA virus
  • ~ 12Kb.

WNV Lifecycle

US Outbreak 1999 Identified in Uganda 1937 Israeli Outbreak 1957

West Nile Virus

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Global Distribution of West Nile Virus

Courtesy Mr. Nicholas Jones, Uveitis, 2nd Edition, 2013 1999 2000 2001 2002

http://www.cdc.gov/westnile/resources/pdfs/wnvguidelines.pdf

West Nile Virus – USA, 1999-2012 CDC ArboNET

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62 21 66 4156 9868 2526 3086 4269 3630 1356 720 1019 712 5674 2469 2205 1566

2000 4000 6000 8000 10000 1999 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013 2014 2015 YTD

Cases of WNV Reported to the CDC by Year < 1 / 100,000 / year Index Cases, NYC

Average Annual Incidence of WNV Human Neuroinvasive Disease by Decile, 1999 – 2012, USA CDC ArboNET More Common in Elderly Number of Cases of WNV Human Neuroinvasive Disease by week, 1999 – 2012, USA CDC ArboNET More Common in Summer / Fall

http://diseasemaps.usgs.gov/mapviewer/ West Nile Virus

Human - 1566 Mosquito 2015 To Date

Cases reported to CDC ArboNET

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Systemic Disease

  • 2 – 14 day incubation
  • 80% asymptomatic
  • 15% symptomatic, WN Fever – self limited, ~ 1 week
  • Fever
  • Headache
  • Myalgia
  • Arthralgia
  • Malaise
  • Nausea
  • Vomiting
  • Skin Rash
  • Pharyngitis
  • 5% WN Encephalitis – Severe headache, meningismus,

confusion, stupor/coma, tremors, convulsions, paralysis, death – typically older or debilitated (diabetes).

Asymptomatic Symptomatic Encephalitis

80% 15% 5%

Retina 2003; 23(1):97-99 Arch Ophthalmol 2003; 121:205-207

Ocular Disease

  • AC inflammation
  • Vitreous inflammation
  • Retinal vasculitis
  • Retinitis
  • Choroiditis (ICGA)
  • Multifocal chorioretinitis

curvilinear pattern

Courtesy Prof. Moncef Khairallah Early Lesions Deep, Yellow-White Courtesy Prof. Moncef Khairallah Multifocal Chorioretinitis Often Curvilinear Pattern

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Ophthalmol 2003; 110:1732-1736

http://www.westcoastretina.com/WestCoastRetina/Feb-2014.html Courtesy West Coast Retina

West Nile Virus Chorioretinitis

Courtesy K. Bailey Freund

West Nile Virus Chorioretinitis

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Courtesy Prof. Moncef Khairallah FA ICGA Multifocal Chorioretinitis Often Curvilinear Pattern More on ICGA

West Nile Virus Lesions Nerve Fiber Layer Distribution? Spurious . . .?

Courtesy Prof. Moncef Khairallah Multifocal Chorioretinitis Often Curvilinear Pattern FA

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00:56.19 05:45.96

20/20

Courtesy Dr. Steve Bennett

  • Retina. 2006 Mar;26(3):365-7.

Courtesy Prof. Rathinam Sivakumar

Neuroretinitis – Retinitis Vascular Occlusion

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Dengue Virus

Dengue

  • Flavivirus genus
  • Flaviviridae family
  • Positive-sense, single stranded RNA virus
  • ~ 11Kb.

Global Distribution of Dengue Virus

Courtesy Mr. Nicholas Jones, Uveitis, 2nd Edition, 2013 50-100M New Cases per Year

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10969 1552 6169 8253 551 33 642 243 554 772 654 364

2000 4000 6000 8000 10000 12000 2010 2011 2012 2013 2014 2015 YTD

Cases of Dengue Reported to the CDC by Year

Imported Locally Aquired

< 1 / 100,000 / year

Mostly Florida and Texas

http://diseasemaps.usgs.gov/mapviewer/ Dengue

Locally Acquired 33 Cases Imported 364 2015 To Date

Cases reported to CDC ArboNET

Systemic Disease

  • 2 – 14 day incubation
  • Asymptomatic
  • Non-specific febrile illness
  • Classic Dengue fever
  • High Fever
  • Severe Headache
  • Myalgia
  • Arthralgia
  • Malaise
  • Nausea
  • Vomiting
  • Maculopapular Skin Rash
  • 10% - Dengue Hemorrhagic Fever

Shock Syndrome

https://viraldiseasesd.wikispaces.com/Dengue+Fever https://microbewiki.kenyon.edu/index.php/Dengue_transmission

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Ocular Disease

75% Bilateral May be Serotype Specific

  • Subconjunctival hemorrhage
  • AC inflammation
  • Vitreous inflammation
  • Retinal hemorrhage
  • Retinal vasculitis
  • Retinal vascular occlusion
  • Retinitis
  • Deep retinal spots / foveolitis
  • RPE mottling
  • Serous retinal detachment
  • Choroiditis (ICGA)

Hemorrhage Yellow-White Lesions Dengue Virus Subconjunctival Hemorrhage Platelet Counts < 50,000/ul

https://openi.nlm.nih.gov/detailedresult.php?img=2566568_1757-1626-1-204-1&req=4

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Courtesy Dr. Stephen Teoh Dengue Virus Active Lesions Dengue Virus Active Lesions Courtesy Dr. Stephen Teoh FA FA Courtesy Dr. Stephen Teoh Dengue Virus Active Lesions ICGA ICGA Dengue Virus Active Lesions Courtesy Dr. Stephen Teoh

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Dengue Virus Active Lesions “Foveolitis” Courtesy Dr. Stephen Teoh Courtesy Dr. Padmamalini Mahendradas

Dengue Virus Infection

20/40 CF

Dengue Virus Active Lesions

Courtesy Prof. Khalid Tabbara Dengue Virus Inactive Lesions Courtesy Prof. Khalid Tabbara

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12/2/2016 16 Dengue Virus Active Lesions

Courtesy Dr. Srinivasan Sanjay

Dengue Virus + 9 Months, Inactive

Courtesy Dr. Srinivasan Sanjay

Dengue Virus Active Lesions – Retinitis / Intraretinal Hemorrhage

Courtesy Prof. Chee Soon Phaik

Dengue Virus Active Lesions – Retinitis / Intraretinal Hemorrhage

Courtesy Prof. Chee Soon Phaik

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12/2/2016 17 Dengue Virus Active Lesions – Vasculitis

Courtesy Prof. Chee Soon Phaik

Dengue Virus Active Lesions – Vasculitis

Courtesy Prof. Chee Soon Phaik

Dengue Virus Active Lesions – Foveolitis

Courtesy Prof. Chee Soon Phaik

Chikungunya

  • Alphavirus genus
  • Togaviridae family.
  • Positive-sense, single stranded RNA virus
  • ~ 12Kb.
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Described in 1953, East Africa

Tanzania Mozambique In “Makonde,” Chikungunya means “to walk bent over.” A reference to the stooped posture of many sufferers.

Chikungunya

Global Distribution of Chikungunya

Courtesy Mr. Nicholas Jones, Uveitis, 2nd Edition, 2013

http://diseasemaps.usgs.gov/mapviewer/ Chickunugnya

Locally Acquired 152 Imported 538 2015 To Date

Cases reported to CDC ArboNET

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https://www.sciencenews.org/article/chikungunya-move June 2, 2015 https://www.sciencenews.org/article/chikungunya-move June 2, 2015

Systemic Disease

  • 2 – 14 day incubation
  • Acute
  • Fever
  • Headache
  • Low back pain
  • Severe joint pain
  • Myalgia
  • Malaise
  • Nausea
  • Vomiting
  • Severe – multi-organ failure, CNS involvement, death

In “Makonde,” Chikungunya means “to walk bent over.”

Ocular Disease

  • AC inflammation +/- high IOP
  • Vitreous inflammation
  • Retinal hemorrhage
  • Retinal vasculitis
  • Retinal vascular occlusion
  • Retinitis
  • Neuroretinitis
  • Serous retinal detachment
  • Choroiditis (ICGA)

Courtesy Dr. Padmamalini Mahendradas

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Am J Ophthalmol 2007; 144:552-556

Common

  • AC / Vitreous cell
  • Neuritis
  • Retinitis +/- SRD

Courtesy Prof. Richard Rosen

20/30 20/50

Chikungunya Fever

Courtesy Prof. Richard Rosen

20/30 20/50

1:11 2:16

Chikungunya Fever

Courtesy Prof. Richard Rosen

20/20 20/20

+ Two Months

Oral CST, Topical CST, Topical Cyloplegic / Mydriatic

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Courtesy Prof. Rathinam Sivakumar

Chikungunya Fever

Courtesy Dr. Padmamalini Mahendradas

4 WEEKS

16 WEEKS

20/30 20/40 20/20 20/20

Presentation

Courtesy Dr. Annie Mathai and Dr. Nidhi Relhan

Chikungunya Fever

Am J Ophthalmol 2007; 144:552-556

Vision at Last Visit Variable

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Zika Virus

Zika Virus

  • Flavivirus genus
  • Flaviviridae family
  • Positive-sense, single stranded RNA virus
  • ~ 12Kb.

Uganda 1947 - Monkeys

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How Zika Spread – 70-year Migration

Africa Southeast Asia Pacific Islands Americas

1947 2007 2016 1970s

New England Journal of Medicine; January 13, 2016 DOI: 10.1056/NEJMp1600297

Systemic Disease

  • 1 in 5 symptomatic
  • 2 to 10 day incubation
  • Non-specific febrile illness
  • Fever
  • Arthralgias
  • Maculopapular Skin Rash

https://en.wikipedia.org/wiki/Zika_virus#/media/File:Zika.Virus.Rash.Arm.2014.jpg

Maculopapular Rash

http://www.memeornah.com/trending/zika-virus-rash/887/

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Testing

  • Serum PCR within 7 days
  • Thereafter serum PRNT

(Plaque Reduction Neutralization Technique) assay.

  • Antibody crossreactivity

with Dengue, WNV, etc

http://www.medscape.com/viewarticle/862671

Areas Susceptible to Spread of Zika

http://www.nytimes.com/interactive/2016/02/06/science/air-travel-from-countries-affected-by-zika.html

Risk of Local Zika Transmission: Year Round Seasonal

http://www.nytimes.com/interactive/2016/02/06/science/air-travel-from-countries-affected-by-zika.html

US – Brazil Travel Routes

Zika Risk

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Zika Risk

Maculopapular Rash Conjunctivitis

www.eurosurveillance.com

Child with Microcephaly, Recife, Brazil

http://www.who.int/emergencies/zika-virus/situation-report-26-02-2016.pdf

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“Severe Macular Neuroretinal Atrophy”

Courtesy Dr. Camila Ventura of the Altino Ventura Foundation in Recife, Brazil

25% 10% 15% 10% 10% 75% 25% 40% 15% 15%

10 Microcephalic Infants

  • 40% Exopharia
  • 20% Esophoria
  • 10% Horizontal Nystagmus
  • 65% RPE Alterations
  • 25% Optic Disc Hypoplasia
  • 15% RPE Atrophy
  • 15% Optic Disc Pallor

Courtesy Dr. Camila Ventura of the Altino Ventura Foundation in Recife, Brazil

RPE Alterations Atophic Lesion

Courtesy Dr. Camila Ventura of the Altino Ventura Foundation in Recife, Brazil

RPE Alterations Atrophic Lesions

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Courtesy Dr. Camila Ventura of the Altino Ventura Foundation in Recife, Brazil

RPE Alterations Atrophic Lesions

http://www.nature.com/eye/journal/v19/n5/images/6701857f15.jpg

Optic Disc Hypoplasia - Signs 1) Small disc (Disc-foveal distance > 3 DD) 2) “Double-ring sign” 3) +/- Vascular tortuosity

JAMA Ophthalmol. 2016 Aug 1;134(8):912-918.

40 Infants with Microcephaly Zika + Mothers (64% symptomatic) 37 eyes (46%) of 22 patients (55%) with findings Increased Frequency

  • First Trimester Exposure
  • Smaller Cephalic Perimeter
  • RPE Mottling (28%)
  • Optic Disc Hypoplasia (18%)
  • Increased cip/Disc (11%)
  • RPE Atrophy (8%)
  • Optic Disc Pallor (8%)

RPE Alterations RPE Atrophy Tortuosity Vaso- Obliteration

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39-year-old Male Physician

  • Known Zika Infection
  • Blurred vision one week later
  • 20/40 OU
  • IOP 40 mmHg OD; 28 mmHg OS
  • 1+ AC reaction OU
  • Cleared with topical CST and cycloplegic/mydriatic

N Engl J Med. 2016 Jul 28;375(4):394-396.

40s-year-old man

  • Rash and Conjunctivitis x 2 days
  • Serum PCR, IgM, PRNT +; AC PCR + Zika
  • 20/20 OD; 20/40 OS
  • IOP normal
  • Tr + AC reaction OD; 2+ OS
  • Cleared with topical CST and cycloplegic/mydriatic

Courtesy Dr. João M. Furtado, MD

Ophthalmology 2016; Jul 27. pii: S0161-6420(16)30507-3. doi: 10.1016/j.ophtha.2016.06.039. [Epub ahead of print]

64-year-old man erythematous rash / arthritis for 10 days after mission work in Haiti Courtesy Dr. Will Parke

February, 2016 20/20

Courtesy Dr. Will Parke

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February, 2016 3/200 for 3 days IOP Normal

“Ring of Gray Perifoveal Coloration in Roughly a ‘Bull’s-Eye’ shape” Courtesy Dr. Will Parke

February, 2016 3/200 for 3 days RPE Alterations

Courtesy Dr. Will Parke

00:28.36

Courtesy Dr. Will Parke

02:33.14

Courtesy Dr. Will Parke

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April, 2016 20/20

Courtesy Dr. Will Parke

20/20

Courtesy Dr. Will Parke

3/200

Presentation + 2 Months

Unilateral Acute Idiopathic Maculopathy (+Coxsackie)

Courtesy Dr. J. Michael Jumper, West Coast Retina

RPE Alterations

Ocular Disease

  • Conjunctivitis
  • AC inflammation (+/-hypertensive)
  • RPE Alterations / Atrophy
  • Optic Disc Hypoplasia (Neonates)
  • UAIM-like outer retinal inflammation

Anterior Uveitis Conjunctivitis UAIM

Adults Neonates

RPE Alterations RPE Atrophy Disc Hypoplasia

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12/2/2016 31 Zika Ophthalmic Images Courtesy of

Camila V. Ventura, MD Racife, Brazil Rubens Belfort, Jr, MD São Paulo, Brazil

Darius Moshfeghi, MD Stanford, CA, USA

João M. Furtado, MD São Paulo, Brazil

  • D. Wilkin (Will) Parke, III, MD

Minneapolis, MN, USA

emmett_cunningham@yahoo.com

West Coast Retina, San Francisco, CA