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Zika 10/19/2017 Aileen M. Marty MD 1 Zika Update: Another Great Mimicker Zika Virus 2017 Baptist Health South Florida 8th Biennial Symposium on Infection Prevention and Control October 20, 2017 Joe Scott MD Chair, BHSF Zika Task Force Chair, WKBH Emergency Medicine Joe Scott MD Chair, BHSF Zika Task Force Chair, WKBH Emergency Medicine Disclosures: None TITLE from VIEW and SLIDE MASTER | October 19, 2017 3 | Objectives Objectives Current status of Global Zika Pandemic Patient population at highest risks for infection and complications Case Definition Scope of proximal & long term clinical manifestations and complications of persons infected with Zika. Best available diagnostic methods for Zika and other Arboviral diseases. Development of Diagnostics, Therapeutics, Safe and effective vaccines for the zika virus.

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Page 1: Zika Update: Another Great Mimickercme.baptisthealth.net/infectionsymposium/documents/2017/...Zika 10/19/2017 Aileen M. Marty MD 1 Zika Update: Another Great Mimicker Zika Virus 2017

Zika 10/19/2017

Aileen M. Marty MD 1

Zika Update: Another Great Mimicker

Zika Virus 2017 Baptist Health South Florida 8th Bi ennial Symposium on Infection Prevention and Contro lOctober 20, 2017

Joe Scott MDChair, BHSF Zika Task Force

Chair, WKBH Emergency Medicine

Joe Scott MDChair, BHSF Zika Task Force

Chair, WKBH Emergency Medicine

Disclosures: None

TITLE from VIEW and SLIDE MASTER | October 19, 20173 |

ObjectivesObjectives� Current status of Global Zika Pandemic

� Patient population at highest risks for infection and complications

� Case Definition

� Scope of proximal & long term clinical manifestations and complications of persons infected with Zika.

� Best available diagnostic methods for Zika and other Arboviral diseases.

� Development of

� Diagnostics,

� Therapeutics,

� Safe and effective vaccines for the zika virus.

Page 2: Zika Update: Another Great Mimickercme.baptisthealth.net/infectionsymposium/documents/2017/...Zika 10/19/2017 Aileen M. Marty MD 1 Zika Update: Another Great Mimicker Zika Virus 2017

Zika 10/19/2017

Aileen M. Marty MD 2

TITLE from VIEW and SLIDE MASTER | October 19, 20174 |

� Current status of Global Zika Pandemic � Current status of Global Zika Pandemic

Epidemiology

TITLE from VIEW and SLIDE MASTER | October 19, 20175 |

Cumulative # of countries & territories (by WHO region) reporting autochthonousmosquito-borne Zika virus transmission for first time • by year (2007–2014), and• by year & month from 1 Jan

2015 to 31 March 2017

Status: Zika Outbreak

Since this, India reported autochthonous Zika, May 2017

TITLE from VIEW and SLIDE MASTER | October 19, 20176 |

Countries and territories reporting autochthonousmosquito-borne Zika virus transmission

Status: Zika

Outbreak

85 countries , territories, subnational areas with Vector-borne Zika transmission(Sum of categories 1-3)

WHO Regional Office Country / territory / subnational area Total

AFRO Angola; Cabo Verde; Guinea-Bissau 3

Category 1

Area with new introduction

or re-introduction with

ongoing transmission

AMRO/PAHO Anguilla; Antigua and Barbuda; Argentina; Aruba; Bahamas; Barbados; Belize; Bolivia (Plurinational State of); Bonaire, Sint Eustatius and

Saba; Brazil; British Virgin Islands; Cayman Islands; Colombia; Costa Rica; Cuba; Curaçao; Dominica; Dominican Republic; Ecuador; El

Salvador; French Guiana; Grenada; Guadeloupe; Guatemala; Guyana; Honduras; Jamaica; Martinique; Mexico; Montserrat; Nicaragua;

Panama; Paraguay; Peru; Puerto Rico; Saint Barthélemy; Saint Kitts and Nevis; Saint Lucia; Saint Martin; Saint Vincent and the Grenadines;

Sint Maarten; Suriname; Trinidad and Tobago; Turks and Caicos Islands; United States of America; United States Virgin Islands; Venezuela

(Bolivarian Republic of)

47

SEARO Maldives, India 1

WPRO American Samoa; Fiji; Marshall Islands; Micronesia (Federated States of); Palau; Papua New Guinea; Samoa; Singapore; Solomon Islands;

Tonga

10

Subtotal 62

Category 1

Either evidence of virus

circulation before 2015 or

with ongoing transmission

no longer in new or re-

introduction phase, but no

evidence of interruption

AFRO Burkina Faso; Burundi; Cameroon; Central African Republic; Côte d’Ivoire; Gabon; Nigeria; Senegal; Uganda 9

AMRO/PAHO Haiti 1

SEARO Indonesia; Thailand; Bangladesh 3

WPRO Cambodia; Lao People's Democratic Republic; Malaysia; Philippines; Viet Nam 5

Subtotal 18

Category 3: Interrupted

transmission & potential for

future transmission

AMRO/PAHO SLA DE PASCUA – Chile 1

WPRO Cook Islands; French Polynesia; New Caledonia; Vanuatu 4

Subtotal 5

Category 4: Established

competent vector but no

known documented past or

current transmission

AFRO Benin; Botswana; Chad; Comoros; Congo; Democratic Republic of the Congo; Equatorial Guinea; Eritrea; Ethiopia; Gambia; Ghana; Guinea;

Kenya; Liberia; Madagascar; Malawi; Mali; Mauritius; Mayotte; Mozambique; Namibia; Niger; Réunion; Rwanda; Sao Tome and Principe;

Seychelles; Sierra Leone; South Africa; South Sudan; Togo; United Republic of Tanzania; Zambia; Zimbabwe

33

AMRO/PAHO Uruguay 1

EMRO Djibouti; Egypt; Oman; Pakistan; Saudi Arabia; Somalia; Sudan; Yemen 8

EURO Georgia; Região Autónoma da Madeira – Portugal; Russian Federation; Turkey 4

SEARO Bhutan; Myanmar; Nepal; Sri Lanka; Timor-Leste 6

WPRO Australia; Brunei Darussalam; China; Christmas Island; Guam; Kiribati; Nauru; Niue; Northern Mariana Islands (Commonwealth of the);

Tokelau; Tuvalu; Wallis and Futuna

12

Subtotal 63

Total 148

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Zika 10/19/2017

Aileen M. Marty MD 3

TITLE from VIEW and SLIDE MASTER | October 19, 20177 |

New detection of autochthonous mosquito-borne Zika virus infections, January 2013–January 2017

TITLE from VIEW and SLIDE MASTER | October 19, 20178 |

July 2016 to 07 Oct 2017July 2016 to 07 Oct 2017

Infection Type Infection Count 2016 Infection Count 2 017 Total

Travel-Related Infections of Zika 1,112 147 1,259

Locally Acquired Infections of Zika 287 0 287

Zika confirmed in Pregnant women 292 103 395

Out of State cases >20 Not reported >20

Undetermined 43 32 75

Babies born with Congenital Zika Syndrome

Not reported 3 >3

Total 2, 019 (excluding out of state cases)

* Most Cases reported from Dade, Broward, and Orange Counties

TITLE from VIEW and SLIDE MASTER | October 19, 20179 |

Patient population at highest risks for infection and complications.Patient population at highest risks for infection and complications.

Most Susceptible Hosts• People who do NOT protect themselves (from vectors and/or from STDs)• People who are more prone to mosquito bites• People who travel to or reside in places with autochthonous transmission• All age groups are at risk for Zika virus infection;

• in Yap Island outbreak, attack rate for symptomatic Zika virus disease among children (<19 years of age) was lower than for adults

• Fetuses are the most at risk for complications, though vertical transmission risk is ~10%• Among adults, those with underlying disease are at highest risk for complications

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Zika 10/19/2017

Aileen M. Marty MD 4

TITLE from VIEW and SLIDE MASTER | October 19, 201710 |

TransmissionTransmission

� Zika can be spread through:� Mosquito “bites”

� Female Mosquito to her eggs

� Sexually between Mosquitos

� Pregnant woman to her fetus � Sex with an infected person� Blood transfusion � Lab accident� Possibly via organ and tissue

transplant, fertility treatment, and breastfeeding

� Animal to animal via bites, sex?

Anyone who lives in or travels to an area with Zika and has not already been infected with Zika virus can get it.

TITLE from VIEW and SLIDE MASTER | October 19, 201711 |

…and that may be extended

Classification WHO Regional Office

Country / territory Total Countries

Countries with evidence of person-to-person transmission of Zika virus, other than mosquito-borne transmission

AMERO/PAHO Argentina, Canada, Chile, Peru, United States of America

5

EURO France, Germany, Italy, Netherlands, Portugal, Spain, United Kingdom of Great Britain and Northern Ireland

7

WPRO New Zealand 1Total 13

TITLE from VIEW and SLIDE MASTER | October 19, 201712 |

An Asymptomatic Person can Transmit Zika

MMWR: Likely Sexual Transmission of Zika Virus from a Man with No Symptoms of Infection — Maryland, 2016 Early Release / August 26, 2016 / 65

“There is a small potential risk of Zika virus transmission associated with exposure to semen from male residents in the Florida tri-county area of Miami-Dade, Palm Beach and Broward Counties since June 15, 2016,”

MARCH 13, 2017: Centers for Disease Control and Prevention:

Zika Warning Is Issued Over Sperm Banks

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Zika 10/19/2017

Aileen M. Marty MD 5

TITLE from VIEW and SLIDE MASTER | October 19, 201713 |

July 2017, CDC: Interim Guidance for HCW caring for Pregnant women with possible Zika exposure

July 2017, CDC: Interim Guidance for HCW caring for Pregnant women with possible Zika exposure

1. All pregnant women in U.S.A. and its territories should be asked about possible Zika virus exposure before and during current pregnancy, at every prenatal care visit.

2. Pregnant women with recent possible Zika virus exposure and symptoms† of Zika virus disease should be tested to diagnose cause of their symptoms.

3. Asymptomatic pregnant women with ongoing possible Zika virus exposure§ offer Zika virus Nucleic acid-based test (NAT) testing 3- times during pregnancy.

4. Asymptomatic pregnant women with recent¶ possible Zika virus exposure (e.g. travel or sexual exposure) but without ongoing possible exposure are not routinely recommended to have Zika virus testing.

5. Pregnant women with recent possible Zika virus exposure and with fetus with prenatal ultrasound findings c/w congenital Zika virus syndrome should receive Zika virus testing to assist in establishing cause of birth defects. Use both NAT and IgM tests.

6. Comprehensive approach to testing placental and fetal tissues has been updated.

7. Zika virus IgM testing as part of preconception counseling to establish baseline IgM for nonpregnant women with ongoing possible Zika virus exposure is notwarranted b/c Zika virus IgM testing is no longer routinely recommended for asymptomatic pregnant women with ongoing possible Zika virus exposure.

TITLE from VIEW and SLIDE MASTER | October 19, 201714 |

Case DefinitionsCase Definitions

• Suspected• Probable• Confirmed

WHO ZIKA CASE Definition

TITLE from VIEW and SLIDE MASTER | October 19, 201715 |

Suspected case Person presents with:� Rash with or without fever

---- OR ----� Fever with or without Rash

and at least one of the following signs or symptoms:

arthralgia; orarthritis; orconjunctivitis (non-purulent/hyperemic).

Probable case A Suspected case and: IgM antibody against Zika virus and an epidemiological link

Confirmed case Person with laboratory confirmation of recent Zika virus infection:

Presence of Zika virus RNA or antigen in serum or other samples (e.g. saliva, tissues, urine, whole blood, etc.);� Detection of Zika virus nucleic acid in a

clinical specimen; � Detection of Zika virus antigen in a

clinical specimen;� Isolation of Zika virus from a clinical

specimen;

--- OR---Zika virus specific IgM antibodies in serum sample(s) and confirmation by neutralization test; Seroconversion or four-fold increase in the titer of Zika specific antibodies in paired serum samples� IgM antibody against Zika virus positive� and PRNT90 for Zika virus with titer ≥20� and Zika virus PRNT90 titer ratio ≥ 4

compared to other flaviviruses;� and exclusion of other flaviviruses

* With no evidence of infection with other flaviviru ses.

* Epidemiologic link: Contact w/ confirmed case, or Hx of residing in/travelling to area with local ZV transmission within 2 weeks prior to symptom onset

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Zika 10/19/2017

Aileen M. Marty MD 6

TITLE from VIEW and SLIDE MASTER | October 19, 201716 | 2010 Team SA

� Incubation : 3 - 12 days

� Clinical Range– Asymptomatic: common in endemic areas – estimated at 75 to 80%– Mild self-limited disease (most common clinical expression, usually lasts course 2–7 d)– Severe (rare, except for intrauterine infections)

� Clinical Prodrome – Mild (fever + HA for ≤ 48 hrs.), – Moderate (fever, HA, myalgia)

� Classic– Days to a week or so– Rash, H/A, Fever, Conjunctivitis– +/- Lymphadenopathy, Joint pain, muscle pain, nausea

� Prognosis : – Recovery >90%

• may recover rapidly after 3–4 days, or recovery may take > 1 week– GBS

• Autoimmune attack of nervous system causing paralysis – Death – rare, only noted in persons with other pre-existing medical conditions

� Other Complications– Mother to child transmission spatially and geographically linked to infants born with microcephaly,

calcifications in brain, CNS malformations

Clinical Features of ZIKA

TITLE from VIEW and SLIDE MASTER | October 19, 201717 |

Zika – Clinical Findings

TITLE from VIEW and SLIDE MASTER | October 19, 201718 |

Skin lesions &/or rash in >90% of Symptomatic Zika Patients

34-year-old man with slight erythema of face and rash on trunk from Zika

43-year-old woman with worsening of her psoriasis

s/p ZIKV infection

Anderson Et. Al Zika Virus in Skin. International J of Dermatology

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Zika 10/19/2017

Aileen M. Marty MD 7

TITLE from VIEW and SLIDE MASTER | October 19, 201719 |

� Scope of proximal & long term clinical manifestations and complications of persons infected with Zika

� Scope of proximal & long term clinical manifestations and complications of persons infected with Zika

� Established Role in Zika Congenital Syndrome– Zika Congenital Syndrome is REAL, and Risk per Pregnancy ~ 10%

� Multisystem Impact– Cardiovascular Health– Immunological System (Autoimmune complications)– Neurologic System (including GBS)– Dermatologic– Male Fertility and health

Health Impact

TITLE from VIEW and SLIDE MASTER | October 19, 201720 |

CNS abnormalities

WHO Regional Office

Country or territory Total

AFRO Cabo Verde 1

Countries and territories that have reported microcephaly and/ or CNS malformation cases potentially associated with ZIKV infection

AMRO/PAHO Argentina, Bolivia (Plurinational State of), Brazil, Canada*, Colombia, Costa Rica, Dominican Republic, El Salvador, French Guiana, Grenada, Guadeloupe, Guatemala, Haiti, Honduras, Martinique, Mexico, Nicaragua, Panama, Paraguay, Puerto Rico, Saint Martin, Suriname, Trinidad and Tobago, United States of America*

24

EURO Slovenia**, Spain*** 2

SEARO Thailand 1

WRPO French Polynesia, Marshall Islands, Viet Nam

2

Total 31* Probable locations of ZIKV infection are undetermined.** Probable location of ZIKV infection is Brazil. *** Probable locations of ZIKV infection are Colombia or Bolivarian Republic of Venezuela.

20 March 2014 : 2 Mothers and their newborns with Zika infections acquired transplacentally in French Polynesia

30 Oct 2015 : Brazil reports unusual increase in children born with microcephaly

28 Nov 2015 : Brazil detects Zika in blood and tissues of baby born with microcephaly

01 Dec 2015: WHO issues alert on link between Zika & microcephaly

12 Jan 2016 : Brazil & US CDC release lab study strongly lining Zika & microcephaly (soon followed by retrospective French Polynesia study)

12 March 2016 : Overwhelming physical evidence Zika neurotropic and can contribute to / cause fetal brain disruption sequence

TITLE from VIEW and SLIDE MASTER | October 19, 201721 |

Zika-infected brain weighing 84 g vs and age-matche d control weighing 240 g

Zika Virus–Associated Micrencephaly—ˇStrafela et al. Arch Pathol Lab Med (doi: 10.5858/arpa.2016-0341-SA)

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Zika 10/19/2017

Aileen M. Marty MD 8

TITLE from VIEW and SLIDE MASTER | October 19, 201722 |

Zika: Retinal Damage to Congenitally infected Infan ts

Knowledge on eye damage 1st reported: 7 Jan 2016: Ophthalmologists in Brazil: severe ocular malformations in infants w/ microcephaly

TITLE from VIEW and SLIDE MASTER | October 19, 201723 | 2010 Team SA

• Neurological• Microcephaly• Lissencephaly• Hydrocephalus• Polymicrogyria• Agyria• Ventriculomegaly• Holoprosencephaly• Brain calcifications

• Ocular • Retinal disorders

• Musculoskeletal system abnormalities

• Arthrogryposis• Scoliosis• Hip dislocation• Craniofacial disproportion

• Genitourinary

TITLE from VIEW and SLIDE MASTER | October 19, 201724 |

Other complications: meningoencephalitis, myelitis, encephalopathy, deat hAnd: reported in Puerto Rico: Autoimmune reaction lead ing to thrombocytopenia

WHO Regional Office Country or territory Total

Reported increase in incidence of GBS cases, with at least one GBS case with confirmed ZIKV infection

AMRO/PAHO Brazil, Colombia, Curaçao, Dominican Republic, El Salvador*, French Guiana, Guadeloupe, Guatemala, Honduras, Jamaica, Martinique, Puerto Rico, Suriname**, Trinidad and Tobago, Venezuela (Bolivarian Republic of)

15

WRPO French Polynesia 1

No increase in GBS incidence reported, but at least one GBS case with confirmed ZIKV infection

AMRO/PAHO Bolivia (Plurinational State of), Costa Rica, Grenada, Haiti, Mexico, Panama, Saint Martin

7

Total 23

7 July 2015: Brazil linked GBS & other neurologic changes to Arboviral diseases including Zika

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Zika 10/19/2017

Aileen M. Marty MD 9

TITLE from VIEW and SLIDE MASTER | October 19, 201725 |

� A 45-year-old healthy outpatient with a fever that had started 5 days previously; diffuse joint pain, myalgia, headache, and diarrhea. Had been in La Martinique islands from 21 December 2015 to 1 January 2016. On his return he complained of a recent mild throbbing, squeezing mediothoracic pain without any spread to other parts of his body and no dyspnea.

� Initial examination revealed a body temperature of 39°C, bilateral conjunctivitis, and hand edema but no skin rash. His blood pressure was normal, heart rate was 95 bpm; no sign of cardiac failure, no abnormal heart sounds.

� Myocarditis diagnosed, based on an ST-segment elevation in anteroseptal region, electrocardiogram associated with increase in troponin I level (0.49 µg/L, normal <0.04 µg /L) and creatine phosphokinase (CPK) level (213 UI/L, normal <200 UI/L). Echocardiogram estimated left ventricular ejection fraction at 55% and showed an inferior medial wall hypokinesia.

The heart too…non-human primate studies…and now human cases documentedThe heart too…non-human primate studies…and now human cases documented

TITLE from VIEW and SLIDE MASTER | October 19, 201726 |

Zika and Infertility in adult males

TITLE from VIEW and SLIDE MASTER | October 19, 201727 |

Zika and Infertility in adult males

Zika virus permanently damages Sertoli cells, in adults Sertoli cells are non-dividing cells, their number is important since they can only nurture only a finite number of germ cells. Result:

• Decrease Inhibin B• Decrease Testosterone• Malformed and insufficient sperm production

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Zika 10/19/2017

Aileen M. Marty MD 10

TITLE from VIEW and SLIDE MASTER | October 19, 201728 |

Best available and future Dx, Rx, and VaccinesBest available and future Dx, Rx, and Vaccines

� Development of

� Diagnostics,

� Therapeutics,

� Safe and effective vaccines for the zika virus

�Development of

�Diagnostics,

�Therapeutics,

�Safe and effective vaccines for the zika virus

TITLE from VIEW and SLIDE MASTER | October 19, 201729 |

FDA is supporting ZIKA Dx test developmentFDA is supporting ZIKA Dx test development

Test sensitives vary considerably for different NATs

TITLE from VIEW and SLIDE MASTER | October 19, 201730 |

DiagnosticsDiagnostics

� Serologic Test for Zika Virus– Zika MAC-ELISA*

• FDA authorized CDC Zika MAC-ELISA* under an Emergency Use

Authorization

• Detects IgM in serum

– Other Anti-Zika virus ELISAs (IgA, IgG, or IgM) – Biochip methods detect DENV, CHIKV, & ZIKA

� NAT: – Trioplex Real-time RT-PCR Assay*

• FDA authorized under an Emergency Use Authorization

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Zika 10/19/2017

Aileen M. Marty MD 11

TITLE from VIEW and SLIDE MASTER | October 19, 201731 |

Interpretation of results of nucleic acid and antibody testing for suspected Zika virus infection*,†, §, ¶— United States, 2017Interpretation of results of nucleic acid and antibody testing for suspected Zika virus infection*,†, §, ¶— United States, 2017

Zika NAT (serum)** Zika NAT (urine)**Zika virus and dengue virus IgM ††

Zika virus PRNT

Dengue virus PRNT Interpretation and recommendations

Positive Positive Any result Not indicated Not indicated Acute Zika virus infectionNegative Positive Positive Not indicated Not indicated Acute Zika virus infectionNegative Positive Negative Not indicated Not indicated Suggests acute Zika virus infection

Repeat testing on original urine specimen.If repeat NAT result is positive, interpret as evidence of acute Zika virus infectionIf repeat NAT result is negative, repeat Zika virus IgM antibody testing on a serum specimen collected ≥2 weeks after onset or possible exposure or specimen collection date.If repeat IgM antibody result is positive

§§, interpret as evidence of acute Zika virus infection.

If repeat IgM result is not positive, interpret as no evidence of Zika virus infection.Positive Negative or not

performedPositive Not indicated Not indicated Acute Zika virus infection

Positive Negative or not performed

Negative Not indicated Not indicated Suggests Acute Zika virus infectionRepeat testing on original serum specimen.If repeat NAT result is positive, interpret as evidence of acute Zika virus infection.If repeat NAT result is negative, repeat Zika virus IgM antibody testing on a serum specimen collected ≥2 weeks after onset or possible exposure or specimen collection date.If repeat IgM antibody result is positive

§§, interpret as evidence of acute Zika virus infection.

If repeat IgM antibody result is not positive, interpret as no evidence of Zika virus infection.Negative Negative or not

performedAny non-negative result

¶¶≥10 <10 Zika virus infection, timing of infection cannot be determined. For persons without prior Zika

virus exposure, a positive IgM result represents recent Zika virus infection.Negative Negative or not

performedAny non-negative result

¶¶<10 Any result No evidence of Zika virus infection.

Negative Negative or not performed

Any non-negative result¶¶

≥10 ≥10 Flavivirus infection; specific virus cannot be identified, timing of infection cannot be determined. For persons without prior Zika virus exposure, a positive IgM result represents recent unspecified flavivirus infection.

For areas where PRNT is not recommended ¶

Negative Negative or not performed

Positive for Zika virus AND negative for dengue virus

Not performed because PRNT is not recommended

Presumptive Zika virus infection; timing of infection cannot be determined. ***

Negative Negative or not performed

Positive for Zika virus AND positive for dengue virus

Not performed because PRNT is not recommended

Presumptive flavivirus infection; specific virus cannot be identified; timing of infection cannot be determined. ***

Negative Negative or not performed

Equivocal (either or both assays)

Not performed because PRNT is not recommended

Insufficient information for interpretation. Consider repeat testing.

Negative Negative or not performed

Negative on both assays Not performed because PRNT is not recommended

No laboratory evidence of Zika virus infection.

TITLE from VIEW and SLIDE MASTER | October 19, 201732 |

Treatment of Zika

� There is no specific licensed medicine or vaccine for Zika virus.

� Treat the symptoms.– Plenty of rest.

– Fluids to prevent dehydration.– Over-the-counter meds e.g. acetaminophen to reduce fever & pain

– Avoid aspirin & other NSAIDS until dengue can be ruled out to reduce risk of bleeding

– Avoid secondary infections

– Assure patient’s current meds do interfere &/or are not affected by use of any additional meds

� Infants with Zika Congenital Symptoms: – Manage symptoms

TITLE from VIEW and SLIDE MASTER | October 19, 201733 | 2010 Team SA

• Future Drugs? :• Maybe?

• CRISPR directed targeting of critical proteases (e.g. viral NS2B-NS3 protease?

• Ig targeting key viral protease?• Niclosamide ? • Emricasan ?• Epigallocatechin-3-gallate (EGCG)?• PHA-690509 ?• Suramin?• Tiazofurin ?• Ribavirin ? (doubt it)• Viral Polymerase inhibitors? (e.g. T-705, T-1105)• Alpha & Gamma interferon ? (doubt it)

Treatment of Zika

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Zika 10/19/2017

Aileen M. Marty MD 12

TITLE from VIEW and SLIDE MASTER | October 19, 201734 | 2010 Team SA

Mind Map for Zika ���� Research Goals for Florida1. Support Development of Vaccine or Other

Methods• Participate in Phase II clinical trials

2. Innovative Diagnostic Testing or Therapeutics• Predictive • Serologic • Point of service testing • Genetic screening • Screening and treatment, including barriers and

opportunities (e.g., longitudinal studies with children who do not have overt signs of microcephaly but may have other long-term disabilities).

• Multiplexed assays • Subtractive or reductive diagnostics for flavivirus pre-

exposed populations • Therapeutic approaches for viral clearance and treatment

post-infection

3. Health Effects of Zika Virus • hearing and vision; • neurodevelopment, neurocognition in children,

effects on central nervous system, neuromuscular diseases, peripheral nervous system;

• cognitive effects in adults; and, • organ damage• Treatment options and effects

TITLE from VIEW and SLIDE MASTER | October 19, 201735 |

ZIKA RESEARCH GRANT AWARDS

Florida Atlantic University, $199,280

Development of a diagnostic for rapid detection of Zika - $199,280

Florida International University, $2,169,675

Development of nanoscale approaches for Zika virus and therapeutics - $1,984,536 • Identifying molecular targets for spatial mosquito repellent design - $198,468

Florida State University $2,169,675

• Human pharmacokinetics of niclosamide - $1,113,645 • Mechanism of centrosome activation by Zika and the evaluation of targeted pharmacological interventions -$856,750 • Fetal brain exosomes in the maternal circulation for the detection of Zika virus infected fetuses - $199,280

Moffitt Cancer Center, $199,280

• Cellular targets of Zika-encoded proteins and microcephaly - $199,280

Nova Southeastern University $198,886

• Comparative analysis of Zika induced antiviral response mechanisms in understudied cell populations - $198,886

The Scripps Research Institute $199,280

• Development of screening tools to search for compounds inhibiting the essential Zika virus NS3 protease - $199,280

University of Central Florida, $1,297,817

• Point of care assay development for diagnosis of Zika viremia - $199,280 • Universal nucleic acid recognition platform for detection of Zika - $198,875 • Zika virus activation and inhibition of human complement immunity - $500,408 • Utilization of in utero diffusion tensor magnetic resonance imaging to evaluate neurological disorders caused by Zika virus - $199,254 • Point of care diagnostic platform based on visual split deoxyribozyme sensors - $200,000

TITLE from VIEW and SLIDE MASTER | October 19, 201736 |

ZIKA RESEARCH GRANT AWARDS (Continued)

University of Florida, $2,922,999

• Identification of potent neutralizing Zika virus antibodies using single-cell analysis technology - $868,744 • Rapid detection of Zika and other mosquito borne pathogens -$199,144 • Rapid diagnostic test for Zika virus in dried blood - $198,812 • Multiplexed detection platform for point-of-service testing of Zika - $515,377 • Identification of antiviral therapies for the treatment of Zika using existing drugs - $1,140,922

University of Miami, $13,170,784

• Development of antibody-based Zika diagnostics - $1,141,585 • Development and testing of novel secreted GP96-Ig Zika virus vaccine - $981,901 • Prospective longitudinal assessment of infants of mothers with Zika infection in pregnancy - $1,989,654 • Rapid RNA test for Zika - $199,280 • Longitudinal brain MRI characterization of Zika-positive and exposed children - $1,141,457 • Early diagnosis and rehabilitation for craniofacial disorders in congenital Zika - $1,140,125 • Evaluation of novel Zika vaccines - $1,141,582 • Investigation into cardiovascular complications related to Zika infections - $963,109 • Evaluation of infants for Zika-related organ damage - $1,989,654 • Identification of the duration of Zika persistence to guide reproductive health decisions - $1,141,582 • Development of Nano -formulations of anti-heminthic drugs for Zika therapy and prevention -$1,141,582 • Development of rapid diagnostic assay for Zika virus infection - $199,273

University of South Florida, $2,458,995

• USF Integrated Clinical Trial Network structuring and enhancement of for execution of Zika virus vaccine and diagnostic clinical trials - $1,117,413 • Cellular and molecular mediators of Zika virus replication and mechanisms of transmission - $1,141,582 • Rapid identification of natural products with antiviral activity against Zika - $200,000

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WHO Zika Vaccine Tracker

• Most Vaccine Candidates still in non-clinical status• Phase I status for

1. ZIKV PIV : Whole Virus Vaccine (WRAIR/BIDMC/Harvard/NIAD/Sanofi Pasteur)• 3 Phase I trials, ECD range: Feb-May 2018

2. VRC ZIKV DNA: DNA vaccine (VRC/NIAID)• 1 Phase I trial, ECD: Dec 2018 * UM participating

3. mRNA-1325: mRNA vaccine (Valera of Moderna)• 1 Phase I trial, ECD: Sept 2018

4. AGS-v: Synthetic peptide for any mosquito-borne disease using mosquito salivary proteins (NIAID)• 1 Phase I trial, ECD: Dec 2019

5. GLS-5700: DNA vaccine (Inovio/ GeneOne Life Science, Inc.)• 1 Phase I trial in 2 parts, ECD: Nov 2017 & May

2018

* NIAID DNA vaccine scheduled for Phase II June 2017

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Oct 2017: WHO Monitored Health Product Pipeline for Zika vaccines

Oct 2017: WHO Monitored Health Product Pipeline for Zika vaccines

Disease Name Product Type Product Name Phase

Zika Virus Infection Vaccines AGS-v Phase I

GLS-5700 Phase I

mRNA-1325 Phase II

MV-Zika Phase I

VRC-ZKADNA090-00-VP Phase II

ZIKA PIV Phase I

R & D Phase Clinical Phase

Phase I 4

Phase 2 2

Phase 3 0

Total 6

© World Health Organization 2017 Source : Global Observatory on Health R&D (http://who.int/research-observatory/en/)

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A final commentA final comment

� Knowledge is Power!

� Personal Arthropod Repellents – EPA approved– Biologicals and other Holistic Methods

� Drain & Cover and other Home Protection Methods

Personal ProtectionHome and Business Protection

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Surveillance and EducationSurveillance and Education

TITLE from VIEW and SLIDE MASTER | October 19, 201741 | 2010 Team SA

� DEET (Chemical Name: N,N-diethyl-m-toluamide or N,Ndiethyl-3-methyl-benzamide)

� Oil of Lemon Eucalyptus * or PMD (Chemical Name: paraMenthane-3,8-diol) the synthesized version of oil of lemon eucalyptus

� IR3535 (Chemical Name: 3-[N-Butyl-N-acetyl]-aminopropionic acid, ethyl ester)

� Picaridin (KBR 3023, Chemical Name: 2-(2-hydroxyethyl)-1- piperidinecarboxylic acid 1-methylpropyl ester )

Clothing and Gear:Products containing Permethrin recommended for clothing, shoes, bed nets, and camping gear, and are registered with EPA for this use.

Mosquito Repellants

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