Aileen M. Marty MD 1

Transcription

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 Disclosures: None 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. 3 Aileen M. Marty MD 1

2 Current status of Global Zika Pandemic Epidemiology 4 Status: Zika Outbreak Cumulative # of countries & territories (by WHO region) reporting autochthonous mosquito-borne Zika virus transmission for first time by year ( ), and by year & month from 1 Jan 2015 to 31 March 2017 Since this, India reported autochthonous Zika, May Status: Zika Outbreak WHO Regional Office territory / Country / subnational area Total AFRO Angola; Cabo Verde; Guinea-Bissau 3 Category 1 AMRO/PAHO Anguilla; Antigua and Barbuda; Argentina; Aruba; Bahamas; Barbados; Belize; Bolivia (Plurinational State of); Bonaire, Sint Eustatius and 47 Saba; Brazil; British Virgin Islands; Cayman Islands; Colombia; Costa Rica; Cuba; Curaçao; Dominica; Dominican Republic; Ecuador; El Area with new introduction Salvador; French Guiana; Grenada; Guadeloupe; Guatemala; Guyana; Honduras; Jamaica; Martinique; Mexico; Montserrat; Nicaragua; or re-introduction with Panama; Paraguay; Peru; Puerto Rico; Saint Barthélemy; Saint Kitts and Nevis; Saint Lucia; Saint Martin; Saint Vincent and the Grenadines; ongoing transmission Sint Maarten; Suriname; Trinidad and Tobago; Turks and Caicos Islands; United States of America; United States Virgin Islands; Venezuela (Bolivarian Republic of) SEARO Maldives, India 1 WPRO American Samoa; Fiji; Marshall Islands; Micronesia (Federated States of); Palau; Papua New Guinea; Samoa; Singapore; Solomon Islands; 10 Tonga Countries and Subtotal 62 territories reporting Category 1 AFRO Burkina Faso; Burundi; Cameroon; Central African Republic; Côte d Ivoire; Gabon; Nigeria; Senegal; Uganda 9 autochthonous Either evidence of virus AMRO/PAHO Haiti 1 circulation before 2015 or SEARO Indonesia; Thailand; Bangladesh 3 mosquito-borne Zika with ongoing transmission WPRO Cambodia; Lao People's Democratic Republic; Malaysia; Philippines; Viet Nam 5 virus transmission no longer in new or reintroduction phase, but no evidence of interruption Subtotal countries, Category 3: Interrupted AMRO/PAHO SLA DE PASCUA Chile 1 territories, transmission & potential for WPRO Cook Islands; French Polynesia; New Caledonia; Vanuatu 4 subnational areas future transmission with Vector-borne Subtotal 5 Zika transmission Category 4: Established AFRO Benin; Botswana; Chad; Comoros; Congo; Democratic Republic of the Congo; Equatorial Guinea; Eritrea; Ethiopia; Gambia; Ghana;Guinea; 33 (Sum of categories 1-3) competent vector but no Kenya; Liberia; Madagascar; Malawi; Mali; Mauritius; Mayotte; Mozambique; Namibia; Niger; Réunion; Rwanda; Sao Tome and Principe; known documented past or Seychelles; Sierra Leone; South Africa; South Sudan; Togo; United Republic of Tanzania; Zambia; Zimbabwe current transmission 6 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 ofthe); 12 Tokelau; Tuvalu; Wallis and Futuna 63 TITLE from VIEW and Subtotal SLIDE MASTER October 19, 2017 Total 148 Aileen M. Marty MD 2

3 New detection of autochthonous mosquito-borne Zika virus infections, January 2013 January July 2016 to 07 Oct 2017 Infection Type Infection Count 2016 Infection Count 2017 Total Travel-Related Infections of Zika 1, ,259 Locally Acquired Infections of Zika Zika confirmed in Pregnant women Out of State cases >20 Not reported >20 Undetermined 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 8 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 9 Aileen M. Marty MD 3

4 Transmission 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? 10 Aileen M. Marty MD 4

5 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 not warranted b/c Zika virus IgM testing is no longer routinely recommended for asymptomatic pregnant women with ongoing possible Zika virus exposure. 13 Case Definitions WHO ZIKA CASE Definition Suspected Probable Confirmed 14 Suspected case Person presents with: Rash with or without fever * With no evidence of infection with other flaviviruses OR ---- Fever with or without Rash and at least one of the arthralgia; or following signs or symptoms: arthritis; or conjunctivitis (non-purulent/hyperemic). * Epidemiologic link: Contact w/ confirmed case, or Hx of residing in/travelling to area with local ZV Probable case A Suspected case and: IgM antibody against Zika virus and an epidemiological link transmission within 2 weeks prior to symptom onset 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 15 Aileen M. Marty MD 5

6 Clinical Features of ZIKA 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 16 TITLE from VIEW and 2010 SLIDE Team MASTER SA October 19, 2017 Zika Clinical Findings 17 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 18 Et. Al Zika Virus in Skin. International J of Dermatology Aileen M. Marty MD 6

7 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 March 2014: 2 Mothers and their newborns with Zika infections acquired transplacentally in French Polynesia CNS abnormalities WHO Regional Office Country or territory Total 30 Oct 2015: Brazil reports unusual increase in children born with microcephaly Countries and territories that have reported microcephaly and/ or CNS malformation cases potentially associated with ZIKV infection AFRO Cabo Verde 1 AMRO/PAHO Argentina, Bolivia (Plurinational State of), 24 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* EURO Slovenia**, Spain*** 2 SEARO Thailand 1 WRPO French Polynesia, Marshall Islands, Viet Nam 2 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 Total * 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. Zika-infected brain weighing 84 g vs and age-matched control weighing 240 g Zika Virus Associated 21 Micrencephaly ˇStrafela TITLE from VIEW and SLIDE MASTER et al. Arch Pathol October 19, 2017 Lab Med (doi: /arpa SA) Aileen M. Marty MD 7

8 Zika: Retinal Damage to Congenitally infected Infants Knowledge on eye damage 1 st reported: 7 Jan 2016: Ophthalmologists in Brazil: severe ocular malformations in infants w/ microcephaly 22 Neurological Microcephaly Lissencephaly Hydrocephalus Polymicrogyria Agyria Ventriculomegaly Holoprosencephaly Brain calcifications Ocular Retinal disorders Musculoskeletal system abnormalities Arthrogryposis Scoliosis Hip dislocation Craniofacial disproportion Genitourinary 23 TITLE from VIEW and 2010 SLIDE Team MASTER SA October 19, July 2015: Brazil linked GBS & other neurologic changes to Arboviral diseases including Zika 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 Other complications: meningoencephalitis, myelitis, encephalopathy, death And: reported in Puerto Rico: Autoimmune reaction leading to thrombocytopenia 24 Aileen M. Marty MD 8

9 The heart too non-human primate studies and now human cases documented 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 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. 25 Zika and Infertility in adult males 26 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 27 Aileen M. Marty MD 9

10 Best available and future Dx, Rx, and Vaccines Development Development of of Diagnostics, Diagnostics, Therapeutics, Therapeutics, Safe Safe and and effective effective vaccines vaccines for for the the zika zika virus virus 28 FDA is supporting ZIKA Dx test development Test sensitives vary considerably for different NATs 29 Diagnostics 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 30 Aileen M. Marty MD 10

11 Interpretation of results of nucleic acid and antibody testing for suspected Zika virus infection *,,, United States, 2017 Zika virus and dengue Zika virus Dengue virus Zika NAT (serum)** Zika NAT (urine)** virus IgM PRNT PRNT Interpretation and recommendations Positive Positive Any result Not indicated Not indicated Acute Zika virus infection Negative Positive Positive Not indicated Not indicated Acute Zika virus infection Negative 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 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 result is not positive, interpret as no evidence of Zika virus infection. Positive Negative or not Positive Not indicated Not indicated Acute Zika virus infection performed Positive Negative or not Negative Not indicated Not indicated Suggests Acute Zika virus infection performed Repeat 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 Any non-negative 10 <10 Zika virus infection, timing of infection cannot be determined. For persons without prior Zika result performed virus exposure, a positive IgM result represents recent Zika virus infection. Negative Negative or not Any non-negative result <10 Any result No evidence of Zika virus infection. performed Negative Negative or not Any non-negative result Flavivirus infection; specific virus cannot be identified, timing of infection cannot be determined. performed 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 Positive for Zika virus AND Not performed because PRNT is not Presumptive Zika virus infection; timing of infection cannot be determined. *** performed negative for dengue virus recommended Negative Negative or not Positive for Zika virus AND Not performed because PRNT is Presumptive flavivirus infection; specific virus cannot be identified; timing of infection cannot be performed positive for dengue virus not recommended determined. *** Negative Negative or not Equivocal (either or both Not performed because PRNT is not Insufficient information for interpretation. Consider repeat testing. performed assays) recommended Negative 31 TITLE from Negative VIEW and or not SLIDE MASTER Negative October on both assays 19, 2017 Not performed because PRNT is not No laboratory evidence of Zika virus infection. performed recommended 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 32 Treatment of Zika 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 ? Suramin? Tiazofurin? Ribavirin? (doubt it) Viral Polymerase inhibitors? (e.g. T-705, T-1105) Alpha & Gamma interferon? (doubt it) 33 TITLE from VIEW and 2010 SLIDE Team MASTER SA October 19, 2017 Aileen M. Marty MD 11

12 Mind Map for Zika Research Goals for Florida 34 TITLE from VIEW and 2010 SLIDE Team MASTER SA October 19, 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 preexposed 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 Florida Atlantic University, $199,280 Florida International University, $2,169,675 Florida State University $2,169, ZIKA RESEARCH GRANT AWARDS Development of a diagnostic for rapid detection of Zika - $199,280 Development of nanoscale approaches for Zika virus and therapeutics - $1,984,536 Identifying molecular targets for spatial mosquito repellent design - $198,468 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 Cellular targets of Zika-encoded proteins and microcephaly - $199,280 Moffitt Cancer Center, $199,280 Nova Southeastern University Comparative analysis of Zika induced antiviral response mechanisms in $198,886 understudied cell populations - $198,886 The Scripps Research Development of screening tools to search for compounds inhibiting the essential Institute $199,280 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 TITLE from VIEW and SLIDE MASTER October disorders 19, 2017 caused by Zika virus - $199,254 Point of care diagnostic platform based on visual split deoxyribozyme sensors - $200,000 ZIKA RESEARCH GRANT AWARDS (Continued) University of Florida, $2,922,999 University of Miami, $13,170,784 University of South Florida, $2,458, 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 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 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 Aileen M. Marty MD 12

13 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 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 AGS-v: Synthetic peptide for any mosquito-borne disease using mosquito salivary proteins (NIAID) 1 Phase I trial, ECD: Dec 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 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-ZKADNA 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 ( 38 A final comment Knowledge is Power! Personal Protection Home and Business Protection Personal Arthropod Repellents EPA approved Biologicals and other Holistic Methods Drain & Cover and other Home Protection Methods 39 Aileen M. Marty MD 13

14 Surveillance and Education 40 Mosquito Repellants 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) Clothing and Gear: Products containing Permethrin recommended for clothing, shoes, bed nets, and camping gear, and are registered with EPA for this use. Picaridin (KBR 3023, Chemical Name: 2-(2- hydroxyethyl)-1- piperidinecarboxylic acid 1- methylpropyl ester ) 41 TITLE from VIEW and 2010 SLIDE Team MASTER SA October 19, Aileen M. Marty MD 14