Zika Virus Facing a New Threat

2.0 ANCC CONTACT HOURS Zika virus Facing a new threat

By R. Bryan Simon, BSN, RN, CNOR, FAWM, DiMM, and Tiffany L. Carpenetti, PhD

LIKE DENGUE and chikungunya, the what healthcare professionals need to Zika virus has spread beyond its re- teach patients to minimize risks. gion of origin in Africa to Central and South America and then to the United Epidemiology States.1,2 Worried patients are asking Zika virus was first identified in 1947 their healthcare providers about the in the Zika Forest in Uganda.6 At the virus and its potential for transmis- time, scientists were using caged mon- sion. Concern about this public health keys as sentinels for surveillance of emergency is greatest among expect- yellow fever virus when a previously ant parents: On February 1, 2016, the unidentified virus was isolated from a World Health Organization (WHO) febrile sentinel.7 Since then, the virus declared the association of microceph- has been isolated during outbreaks aly with Zika virus infections to be a throughout Africa and Asia, where it’s Public Health Emergency of Global well established. However, the link to Concern. On April 13, 2016, the microcephaly in infants wasn’t recog- CDC declared that the Zika virus can nized until recently.3,4 cause development of microcephaly Zika’s epidemic potential was first in a developing fetus.3,4 (See Picturing demonstrated in an outbreak on the microcephaly. ) In addition, Zika virus Yap Island of Micronesia in 2007, infection has been linked to Guillain- where about 70% of the population Barré syndrome (GBS) in adults.5 were infected.8 The virus has now However, most people who are in- traveled worldwide, with infections fected don’t have signs and symptoms, identified in patients throughout or experience only mild flulike symp- Africa, Asia, Polynesia (including a toms that are self-limiting. significant outbreak on Easter Island), This article discusses what nurses and the Americas.9 A recent outbreak need to know about Zika virus infec- in Puerto Rico was confirmed with tion, including how it’s transmitted and 1,072 cases of Zika infection identified JAMES GATHANY, CDC

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Copyright © 2016 Wolters Kluwer Health, Inc. All rights reserved. between November 2015 and early tors from endemic regions who St. Louis encephalitis viruses. Two June 2016.10 attended the 2014 World Cup in major lineages, Asian and African, Zika virus is considered endemic Brazil.14,15 The viruses isolated from have been identified, with strains to Africa and Asia, where it’s regularly the outbreak in the Americas most isolated from the outbreak in Brazil found within portions of the popula- closely resemble the strains isolated more closely resembling the Asian tion.11 The virus circulates between from French Polynesia, suggesting lineage.6 Pathogenesis of this virus primates and various Aedes mosquito that it was imported to the region isn’t well understood, but it may species in an enzootic cycle.12 by tourists. initially replicate in dendritic cells This virus has followed a pattern The significant size of the current near the site of the mosquito bite established by other mosquito-borne outbreak in Central and South Amer- and spread to lymph nodes and into viruses such as chikungunya in its ica makes it highly likely that the the bloodstream.12 spread from endemic regions to areas virus is being transported by visitors Zika virus is transmitted by mos- that hadn’t experienced outbreaks in to the region.14 Imported infections quitoes of the Culicidae family, usually the past.9 This is likely due to the occur in people who’ve traveled to of the genus Aedes.6 Aedes aegypti mos- combination of increased global trav- areas with circulating virus who re- quitoes are considered an important el and the expanded range of sus- turn home and then experience signs vector because of their tendency to pected vector species. and symptoms. Such cases have been cohabitate with humans and breed in The foundation for the new inten- documented in Canada, the United small pools of standing water. How- sity of research into the Zika virus States, Australia, Slovenia, and the ever, Aedes albopictus and many other almost 70 years after its discovery was Netherlands.11,14,16,17 Aedes species have also tested positive the sharp increase in reported micro- for Zika virus.7 The virus circulates cephaly cases in Brazil potentially Pathophysiology between viremic humans and mosqui- linked to Zika virus infection. From and transmission toes in densely populated areas. November 2015 until March 2016, Zika virus is a single-stranded, Combined, A. aegypti and A. albo- 6,776 potential cases of microcephaly positive-sense, RNA arbovirus of the pictus currently have a range that (average: 1,355 per month) had been Flaviviridae family.6 (See Glossary of covers the United States as far north reported. As of May 2016, 1,326 con- terms.) This is significant because as New York State and as far west as firmed cases had been documented, the genome of +ssRNA viruses acts Texas, with sporadic populations with at least 208 resulting in an infant’s like mRNA in the cell and therefore appearing in Nevada and Califor- death.5,13 The previous average month- doesn’t have to cross the nuclear nia.18 Predictive models suggest that ly totals from 2001 until 2014 were membrane to be made into protein. these ranges could increase to cover 13.5 cases per month (163 per year).5 It’s most closely related to Spond- most of the United States, even as The Zika outbreak in Brazil may weni virus; its next nearest relatives far north as Canada. If enough cases have originated with infected specta- include Ilhéus virus, Rocio, and are imported to the United States for the virus to become established within vector mosquito populations, Picturing microcephaly the Zika virus could spread across the country. Normal The warmer, wetter climate caused by El Niño, an ongoing pattern that can last for up to 2 years, is Microcephaly likely to increase the population of both significant vector species and their overlapping ranges.19 Warmer temperatures and an increased risk of standing water pose significant challenges to mosquito population

OURCE control and increase the likelihood of S Zika becoming established in local CIENCE

/S mosquito populations. Further com- plicating this issue is the remarkable

CHROEDER “ecological plasticity” of A. albopictus, S as demonstrated by the species’ abil- ONICA

M ity to consistently increase its range

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Copyright © 2016 Wolters Kluwer Health, Inc. All rights reserved. year by year, and also the ability to a region without active vector-borne lay diapausing eggs that survive win- transmission. The recommendations Glossary of terms ter in a dormant state and contribute for nonactive areas include providing • mRNA is messenger RNA, a subtype to the cold-hardiness of this vector.20 educational materials and collecting a of RNA containing portions of To date, no reservoir species for travel and medical history question- DNA code used for transmission to Zika virus has been identified. How- naire from potential blood donors.24 other areas of the cell for protein ever, anti-Zika antibodies have been Areas of active spread of the virus production. • found in some large mammals and require testing of the collected blood Positive-sense means that the RNA can be directly translated into rodents.6 supply. An investigational test has protein by cellular machinery. been authorized by the FDA for • A reservoir species is an animal Sexual, transfusion, and Puerto Rico, the only current area of that maintains blood serum levels prenatal transmissions widespread active transmission with- of virus sufficient to infect biting 25 Besides transmission by mosquitoes, in the United States and its territories. mosquitoes. human-to-human sexual transmission Widespread reports of the inexpli- of the Zika virus has been confirmed cably high number of cases of micro- signs and symptoms include fever, via both vaginal and anal sex with five cephaly in Brazil highlighted the risk maculopapular rash, arthralgia, mal- and one cases reported in published of perinatal transmission of this aise, and conjunctivitis. Other pos- medical literature, respectively, and a pathogen and emphasized the need sible symptoms include myalgia and total of 10 cases confirmed by the for further research. Based on addi- headache.29,30 Severe symptoms indi- CDC within the United States.10,21 In tional investigation, the CDC deter- cating GBS include tingling and one instance, a scientist was infected mined in April that the Zika virus is weakness in the extremities. while traveling to Senegal. When he a cause of microcephaly.3,4 Two pos- Because clinical manifestations returned home, his wife, who hadn’t sible hypotheses have been discussed often resemble those of dengue fever left the United States, exhibited in recent literature, including direct (flavivirus) and chikungunya (alpha- symptoms of a Zika virus infection transfer and placental mediation.26 virus), Zika virus infection is often 9 days after his arrival.11 A man in According to the direct transfer hy- misdiagnosed.12,31,32 These diseases Tahiti demonstrated replicative Zika pothesis, the placenta conveys the can be difficult to distinguish by re- virus in semen samples when he Zika virus to the fetus and is the verse transcriptase-polymerase chain sought treatment for hematosper- primary cause for the resulting reaction (RT-PCR). After the first mia.22 Male-to-male sexual transmis- teratogenic effects.26 The placental week of onset of signs and symp- sion was confirmed in a case reported mediation theory hypothesizes that toms, virus-specific IgM and neutral- in Texas, and the CDC continues to microcephaly results from the pla- izing antibodies begin to develop.33 monitor additional potential cases of centa’s immunoprotective response.26 Because the current geographical sexually transmitted Zika virus within A recent study in French Polynesia distributions of these diseases over- the United States.2,21 highlights two mothers and new- lap, coinfections can occur. Other As with other blood-borne patho- borns with confirmed Zika infections differential diagnoses that should be gens, Zika virus has the potential for that likely passed from viremic moth- considered for patients presenting transmission via blood transfusion. er to child via the placenta or during with a similar cluster of signs and This risk is elevated by the relatively delivery.27 It’s very likely the virus symptoms, with or without travel to high incidence of asymptomatic cas- crosses the placenta given the anec- endemic regions, include malaria, es.23 Historically, other flaviviruses dotal evidence of Zika virus in pla- leptospirosis, rickettsia, group A have been transmitted through blood cental tissue and neural tissue samples streptococcus, rubella, measles, parvo- transfusion. Two possible cases of of stillborn and aborted fetuses from virus, enterovirus, and adenovirus.33 transfusion-derived transmission infected mothers, and evidence of the Providers should be concerned have been reported in Brazil, and virus in amniotic fluid samples of about the links between Zika virus surveillance in French Polynesia is fetuses exhibiting microcephaly.28 and microcephaly in newborns and ongoing.24 to GBS in adults.3,4,27,28 The WHO, Within the United States, the FDA Signs and symptoms the CDC, and medical researchers produced a document for blood col- An estimated 20% of all individuals worldwide are currently investigating lection and transfusion centers with infected with the Zika virus become both neurologic disorders due to the recommendations for areas with and ill, and while most of these cases are increase of Zika-related microcephaly without active vector-borne transmis- very mild and self-limiting, signs and in nine nations, with substantial in- sion. As of June 16, 2016, the conti- symptoms usually last from a few creases in Brazil, and the growing nental United States was considered days to a week. The most common understanding of Zika-related GBS in www.Nursing2016.com August l Nursing2016 l 27

Copyright © 2016 Wolters Kluwer Health, Inc. All rights reserved. 13 nations.5,34 (See Nations with re- In late February 2016, the FDA ported microcephaly cases and Nations issued an Emergency Use Authoriza- Nations with with incidence of GBS after confirmed tion (EUA) that authorized the use of incidence of GBS Zika infection.) The causal relation- a CDC-developed test called the Zika after confirmed ship between Zika and microcephaly IgM antibody capture enzyme-linked Zika infection and GBS isn’t clearly understood and immunosorbent assay (Zika MAC- continues to be a primary concern of ELISA) for use on drawn serum or Cases in these countries are potentially medical research.5 CSF. Because these tests can often associated with the Zika virus, as of 5 result in false positives, any positive April 2, 2016. • Brazil* Diagnosis and testing or inconclusive test should be fol- • Colombia* Until recently, no commercially avail- lowed up with the submission of ad- • Dominican Republic* able, FDA-authorized diagnostic tests ditional serum samples to the CDC • El Salvador* 35 were available for the Zika virus. The lab in Ft. Collins for RT-PCR testing. • French Guiana preferred diagnostic test is the RT- On March 17, 2016, the CDC re- • French Polynesia* PCR, which can be performed on ceived a second EUA that allows • Haiti serum, urine, amniotic fluid, and urine, amniotic fluid, and CSF testing • Honduras* cerebrospinal fluid (CSF) ideally using the Trioplex Real-time rRT-PCR • Martinique drawn within 7 days of the presenta- assay for patients suspected of having • Panama tion of signs and symptoms. Zika. Although serum is preferred for • Suriname* Throughout the early stages of the accuracy, any tests conducted on • Venezuela* crisis, the CDC Arbovirus Diagnostic urine, amniotic fluid, or CSF should • United States (Puerto Rico) Laboratory (Division of Vector Borne be accompanied by a serum sample.36 *These locations have reported an increase in GBS cases since the Zika virus was identified. Diseases—DVBD) located in Fort Both of these tests may be conducted Collins, Colo., and several other at the CDC lab or select qualified labs state-level labs throughout the Unit- across the United States. Diagnostics test called cobas Zika to ed States were the only facilities On April 28, 2016, the FDA issued detect and screen for the virus within available to conduct this test.33 Ad- an additional EUA to Quest Diagnos- the donated blood supply in Puerto ditional information about specimen tics to allow use of their RT-PCR test Rico.25,37 This IND may be approved collection and handling can be found at approved Focus Diagnostic labora- for use in the United States if active at the CDC website; see the CDC tories. This temporary authorization transmission is identified in the future. 50.34, Data and Specimen Handing allows providers to conduct the test (DASH) form, which should be used for patients who have signs and Treatment and prevention by healthcare providers to properly symptoms suggestive of Zika and At this time, treatment is supportive collect and handle samples.33 asymptomatic pregnant women who and consists of resting, maintaining have a history of travel to an endemic hydration, and using acetamino- region or have had a male sexual phen for joint and muscle pain and Nations with partner who’s recently traveled to an headaches. Aspirin and nonsteroidal reported endemic region. As with the other anti-inflammatory drugs aren’t recom- microcephaly cases tests described, false negatives may mended until a definitive diagnosis of occur and additional samples should Zika virus infection is confirmed These cases are potentially associated be sent to CDC laboratories for because these medications can exac- with the Zika virus, as of May 13, 2016.5 follow-up analysis. erbate the risk of hemorrhagic fever Because it’s a nationally notifiable if the patient has dengue instead of Country Cases condition, providers must report any Zika virus infection.33 Brazil 1,326 cases of suspected Zika virus to state Due to concerns about microceph- Cape Verde 3 Colombia 7 and local health departments. They aly and other severe fetal brain de- French Polynesia 8 should follow the most recent in- fects caused by maternal Zika virus Martinique 2 structions for submission of serum, infection, fetuses and infants of Marshall Islands 1 urine, amniotic fluid, or CSF samples women infected with Zika virus dur- Panama 1 for RT-PCR or other tests listed on ing pregnancy should be evaluated Slovenia 1* the CDC website.33 for possible congenital infection and United States 2* In March 2016, the FDA approved neurologic abnormalities.30 *Likely acquired in Brazil, Mexico, Belize, or an investigational new drug (IND) If a patient develops signs and Guatemala. application for a Roche Molecular symptoms of GBS, treatment protocols

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Copyright © 2016 Wolters Kluwer Health, Inc. All rights reserved. for this syndrome should be followed true also for children, although the and a detailed recent history should be EPA advises a restriction on the use obtained. An autoimmune condition of oil of lemon eucalyptus for chil- that affects components of the periph- dren under age 3.44 Measures should eral nervous system, GBS is often be taken to reduce mosquito breed- characterized by the gradual spread of ing grounds by eliminating areas of weakness or tingling in the legs that standing water near the home. Using progresses upward to the arms and screens in windows and doors to face. Severe weakness or paralysis of prevent mosquito entry to indoor chest muscles can result in respiratory living spaces is recommended.45 difficulty. Some patients require ven- Prevention of sexual transmission of tilator support until their respiratory the Zika virus begins with the use of muscle strength returns. Although it condoms or abstinence. The CDC rec- can be life-threatening, GBS is usually ommends that any male living in an self-limiting and most patients recover endemic area or returning from travel fully with no long-term sequelae. to an area with widespread incidence Preventing mosquito bites begins of Zika virus should either abstain with choosing the proper clothing from sexual activity or use a condom and wearing it night and day. Wear- during vaginal, anal, or oral sex due ing light-colored cotton clothing to the potential for disease transmis- that’s loose fitting and fully covers sion.22 At this time, the duration of arms and legs is an outstanding pre- presence of the virus within semen ventive measure.38 Because its signs and isn’t definitively known, but virus has Using synthetic and plant-derived symptoms often resemble been observed to be present for up to oil repellents on exposed areas of those of dengue fever 10 weeks in isolated cases.22,46 skin is also recommended. The use of and chikungunya, Zika All women of childbearing poten- 24% DEET (N,N-diethyl-m-tolumide/ tial should observe the prevention N, N-diethyl-3-methylbenzamide) on virus infection is often recommendations described in this exposed skin effectively reduces bites misdiagnosed. article. The CDC recommends cau- from the A. aegypti mosquito for an tion when traveling to regions with average of 5 hours, especially when Plant-derived products that are effec- active vector-borne transmission of used in conjunction with proper tive repellents include permethrin, oil Zika. Those considering traveling to clothing.38 Picaridin (1-piperidinecar- of lemon eucalyptus, and citronella. the Caribbean, Central America, and boxylic acid, 2-[2-hydroxyethyl]- Permethrin, approved by the EPA for South America should consider and 1-methylpropylester) has been found use only on clothing and gear, is pro- understand the risks for both the to be equally effective against the Ae- tective due to its toxic effect on mos- mother and the fetus.47 For pregnant des mosquito and one study showed quitoes. It’s the active ingredient in women with a history of travel to a it to be more effective against a strain most commercially available clothing- region with ongoing Zika virus trans- of A. aegypti mosquito.39-41 It’s also based repellents.42 A study in 2005 mission, the CDC recommends approved by the CDC and U.S. Envi- found that the use of permethrin on RT-PCR testing.47 ronmental Protection Agency (EPA) tents reduced mosquito bites on oc- and is the active ingredient in some cupants by 36%.43 Citronella (3,7-di- Ongoing research and commercial products.10 IR3535 methyloct-6-en-1-al) is the least effec- vaccine development (3-[N-butyl-N-acetyl]-amino-propi- tive of all products against the Aedes Looking ahead, the major topics of onic acid ethyl ester) is approved by mosquito, but it does confer some concern about Zika virus will be the the CDC and the EPA for use on the protection and is found in most insect development and deployment of a skin.42 repellent candles.39 All these products fast and reliable method of detection, The effectiveness of DEET and are effective against mosquitoes, and, further research on microcephaly and other repellents deteriorates with when used in conjunction with prop- GBS related to this pathogen, and time, while swimming, or when er clothing choices, act as a substan- development of an effective vaccine. used in conjunction with sunscreen. tive barrier to mosquito bites.42 Currently, the only reliable method Reapplication is recommended to All EPA-approved insect repellents of detection in clinical samples is ensure protective coverage while are safe for use by pregnant women RT-PCR. This method is expensive outdoors. without added precautions. This is and requires specialized equipment in www.Nursing2016.com August l Nursing2016 l 29

Copyright © 2016 Wolters Kluwer Health, Inc. All rights reserved. addition to sample sizes sufficient for large numbers of males to be re- 11. Foy BD, Kobylinski KC, Chilson Foy JL, et al. Probable non-vector-borne transmission of Zika RNA extraction. An assay is currently leased, has shown promise in trials virus, Colorado, USA. Emerg Infect Dis. 2011; under development by the CDC that in the Caribbean and Central Ameri- 17(5):880-882. will simultaneously test for Zika, chik- ca. Local culture and popular opin- 12. Hayes EB. Zika virus outside Africa. Emerg ungunya, and dengue virus RNA.10 ion about genetically modified or- Infect Dis. 2009;15(9):1347-1350. 13. World Health Organization. Zika Situation Unfortunately, the development of ganisms can limit the use of this Report. Zika virus, microcephaly and Guillain-Barré vaccines to combat RNA virus infec- technology. syndrome. June 2, 2016. www.who.int/emergencies/ zika-virus/situation-report/2-june-2016/en/. tions, especially arboviruses, is dif- Information about the identifica- 14. Goorhuis A, von Eije KJ, Douma RA, et al. Zika ficult and complicated. Due to the tion, diagnosis, treatment, and pre- virus and the risk of imported infection in returned highly unstable nature of RNA, these vention of the Zika virus and its links travelers: implications for clinical care. Travel Med Infect Dis. 2016;14(1):13-15. viruses mutate rapidly and exist as to microcephaly and GBS continue 15. Salvador FS, Fujita DM. Entry routes for Zika “quasi-species” rather than as true to evolve with weekly and sometimes virus in Brazil after 2014 World Cup: new species.48 This complicates not only daily updates by the WHO and possibilities. Travel Med Infect Dis. 2016;14(1): 49-51. the development of effective vac- CDC. Healthcare professionals must 16. Fonseca K, Meatherall B, Zarra D, et al. First cines, but also the creation of reliable stay abreast of these developments case of Zika virus infection in a returning Canadian traveler. Am J Trop Med Hyg. 2014;91(5): diagnostic tests. Rapid changes in the and be prepared to assist patients 1035-1038. genome of the Zika virus as it who are concerned or who present 17. Pyke AT, Daly MT, Cameron JN, et al. Imported spreads across the globe should be with signs and symptoms of this Zika virus infections from the Cook Islands into Australia, 2014. PLoS Currents Outbreak. 2014. expected, as should changes in signs most recent public health emergen- http://currents.plos.org/outbreaks/article/imported- and symptoms associated with this cy. More investigation is needed to zika-virus-infection-from-the-cook-islands-into- infection. determine the method of transmis- australia-2014/. 18. Kraemer MU, Sinka ME, Duda KA, et al. The As with other arboviruses, control sion and preventive measures to global distribution of the arbovirus vectors Aedes should be approached with a com- inhibit further Zika-related micro- aegypti and Ae. albopictus. Elife. 2015;4:e08347. bination of vector reduction and cephaly birth defects. ■ 19. Stewart-Ibarra AM, Lowe R. Climate and non- 48 climate drivers of dengue epidemics in southern vaccine development. In the past, coastal Ecuador. Am J Trop Med Hyg. 2013;88(5): mosquito-borne diseases were effec- REFERENCES 971-981. tively controlled with a combination 1. Musso D, Cao-Lormeau VM, Gubler DJ. Zika 20. Erguler K, Smith-Unna SE, Waldock J, et al. virus: following the path of dengue and Large-scale modelling of the environmentally-driven of breeding-site reduction and insec- chikungunya? Lancet. 2015;386(9990):243-244. population dynamics of temperate Aedes albopictus (Skuse). PLoS One. 2016;11(2):e0149282. ticide application, especially DDT. 2. Centers for Disease Control and Prevention. Over time, however, the use of DDT Emergency Preparedness and Response. Health 21. Deckard DT, Chung WM, Brooks JT, et al. Alert Network. Update: Interim Guidelines for Male-to-male sexual transmission of Zika virus— has fallen out of favor because of its Prevention of Sexual Transmission of Zika Virus— Texas, January 2016. MMWR Morb Mortal Wkly United States, 2016. February 23, 2016. http:// Rep. 2016;65(14):372-374. http://dx.doi.org/ impact on the environment, and 10.15585/mmwr.mm6514a3. modern alternatives have proven less emergency.cdc.gov/han/han00388.asp. 3. Rasmussen SA, Jamieson DJ, Honein MA, 22. Musso D, Roche C, Robin E, Nhan T, Teissier effective. Habitat reduction is still an Petersen LR. Zika virus and birth defects— A, Cao-Lormeau VM. Potential sexual transmission integral part of reducing disease reviewing the evidence for causality. N Engl J Med. of Zika virus. Emerg Infect Dis. 2015;21(2):359-361. 2016;374(20):1981-1987. transmission. 23. Musso D, Nhan T, Robin E, et al. Potential for 4. Centers for Disease Control and Prevention. Zika virus transmission through blood transfusion As an alternative to the use of in- CDC concludes Zika causes microcephaly and demonstrated during an outbreak in French secticides, some groups have devel- other birth defects. April 13, 2016. www.cdc.gov/ Polynesia, November 2013 to February 2014. media/releases/2016/s0413-zika-microcephaly.html. Euro Surveill. 2014;19(14). pii:20761. oped genetically modified mosquitoes 5. World Health Organization. Situation Report. 24. Food and Drug Administration. Recommenda- to combat the spread of mosquito- Zika virus, microcephaly and Guillain-Barré tions for donor screening, deferral, and product syndrome. May 12, 2016. http://apps.who.int/iris/ management to reduce the risk of transfusion- borne disease. Current techniques bitstream/10665/206311/1/zikasitrep_12May2016_ transmission of Zika virus. Guidance for industry. involve releasing large numbers of eng.pdf. February 2016. www.fda.gov/downloads/ BiologicsBloodVaccines/GuidanceCompliance male mosquitoes with lethal traits, 6. Ioos S, Mallet HP, Leparc Goffart I, Gauthier V, RegulatoryInformation/Guidances/Blood/ Cardoso T, Herida M. Current Zika virus UCM486360.pdf. including genes that make females epidemiology and recent epidemics. Med Mal Infect. unable to fly and mate, and genes 2014;44(7):302-307. 25. Food and Drug Administration. Emergency Preparedness and Response. Zika virus updates that kill mosquito larvae before they 7. Grard G, Caron M, Mombo IM, et al. Zika virus in from FDA. May 18, 2016. www.fda.gov/ complete the pupal life stage.50 Male Gabon (Central Africa)—2007: a new threat from EmergencyPreparedness/Counterterrorism/ Aedes albopictus? PLoS Negl Trop Dis. 2014;8(2):e2681. 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Copyright © 2016 Wolters Kluwer Health, Inc. All rights reserved. 28. Calvet G, Aguiar RS, Melo AS, et al. Detection Centres under FDA Investigational New Drug 46. Atkinson B, Hearn P, Afrough B, et al. and sequencing of Zika virus from amniotic fluid Application protocol. March 30, 2016. http:// Detection of Zika virus in semen [letter]. Emerg of fetuses with microcephaly in Brazil: a case study. molecular.roche.com/News/LocalNews/Pages/ Infect Dis. 2016;22(5):940. http://dx.doi.org/ Lancet Infect Dis. 2016. pii:S1473-3099(16)00095-5. Roche-to-initiate-testing-for-Zika-virus-at-US- 10.3201/eid2205.160107. 29. Kutsuna S, Kato Y, Takasaki T, et al. Two cases Blood-Centres-under-FDA-Investigational-New- 47. Oduyebo T, Petersen EE, Rasmussen SA, of Zika fever imported from French Polynesia to Drug-Application-protocol.aspx. et al. Update: interim guidelines for health care Japan, December 2013 to January 2014 [corrected]. 38. Kanzaria HK, Hsia RY. Mosquitoes and providers caring for pregnant women and women Euro Surveill. 2014;19(4). pii:20683. mosquito-borne diseases. In: Auerbach PS, ed. of reproductive age with possible Zika virus 30. Centers for Disease Control and Prevention. Wilderness Medicine. 6th ed. Philadelphia, PA: exposure—United States, 2016. MMWR Morb Zika virus: clinical evaluation and disease. April Mosby Elsevier; 2012. Mortal Wkly Rep. 2016;65(5):122-127. 19, 2016. www.cdc.gov/zika/hc-providers/ 39. Diaz JH. Chemical and plant-based insect 48. Duarte EA, Novella IS, Weaver SC, et al. RNA clinicalevaluation.html. repellents: efficacy, safety, and toxicity. Wilderness virus quasispecies: significance for viral disease and 31. Zanluca C, Melo VC, Mosimann AL, Santos GI, Environ Med. 2016;27(1):153-163. epidemiology. Infect Agents Dis. 1994;3(4):201-214. Santos CN, Luz K. First report of autochthonous 40. Licciardi S, Herve JP, Darriet F, Hougard JM, 49. Christofferson RC, Mores CN. A role for vector transmission of Zika virus in Brazil. Mem Inst Corbel V. Lethal and behavioural effects of three control in dengue vaccine programs. Vaccine. Oswaldo Cruz. 2015;110(4):569-572. synthetic repellents (DEET, IR3535 and KBR 3023) 2015;33(50):7069-7074. 32. Kwong JC, Druce JD, Leder K. Zika virus on Aedes aegypti mosquitoes in laboratory assays. 50. McGraw EA, O’Neill SL. Beyond insecticides: infection acquired during brief travel to Indonesia. Med Vet Entomol. 2006;20(3):288-293. new thinking on an ancient problem. Nat Rev Am J Trop Med Hyg. 2013;89(3):516-517. 41. Badolo A, Ilboudo-Sanogo E, Ouédraogo AP, Microbiol. 2013;11(3):181-193. 33. Centers for Disease Control and Prevention. Costantini C. Evaluation of the sensitivity of Aedes aegypti and Anopheles gambiae complex mosquitoes R. Bryan Simon, a contract cardiothoracic surgical Zika virus: diagnostic testing. April 05, 2016. nurse based in Fayetteville, W.Va., is owner/partner of www.cdc.gov/zika/hc-providers/diagnostic.html. to two insect repellents: DEET and KBR 3023. Trop Vertical Medicine Resources in Portland, Ore., and a Med Int Health. 2004;9(3):330-334. 34. Oehler E, Watrin L, Larre P, et al. Zika virus director of Appalachian Mountain Rescue Team. He’s 42. U.S. Environmental Protection Agency. Find also a member of the Nursing2016 editorial board. infection complicated by Guillain-Barre syndrome– Tiffany L. Carpenetti, who has a PhD in entomology, case report, French Polynesia, December 2013. the insect repellent that is right for you. April 27, is the macromolecular science and engineering grad- Euro Surveill. 2014;19(9). pii:20720. 2016. http://cfpub.epa.gov/oppref/insect/. uate degree program coordinator at Virginia Poly- technic Institute and State University in Blacksburg, 35. Centers for Disease Control and Prevention. 43. Boulware DR, Beisang AA 3rd. Passive prophylaxis with permethrin-treated tents Va. She’s also a freelance/contract technical science Fact Sheet for Health Care Providers: Interpreting writer in Christiansburg, Va. Zika MAC-ELISA Results. 2016. www.cdc.gov/ reduces mosquito bites among North American zika/pdfs/zika-mac-elisa-fact-sheet-for-hcp.pdf. summer campers. Wilderness Environ Med. 2005; Except where otherwise indicated, the information in 16(1):9-15. this article was current on June 2, 2016. For updated in- 36. Centers for Disease Control and Prevention. formation, refer to these websites: www.cdc.gov/zika/ Trioplex Real-time rRT-PCR Assay: Instructions for 44. Centers for Disease Control and Prevention. and www.who.int/mediacentre/factsheets/zika/en/. Use. For use under an Emergency Use Authoriza- Insect repellent use and safety. Which mosquito tion only. May 17, 2016. www.fda.gov/downloads/ repellents work best? 2015. www.cdc.gov/westnile/ Dr. Carpenetti has received a grant from Radford MedicalDevices/Safety/EmergencySituations/ faq/repellent.html. University to study local populations of mosquitoes. UCM491592.pdf. The authors and planners have disclosed no other 45. Centers for Disease Control and Prevention. potential conflicts of interest, financial or otherwise. 37. Roche Molecular Diagnostics. Media Release. Avoid mosquito bites. May 27, 2016. www.cdc.gov/ Roche to initiate testing for Zika virus at U.S. Blood features/stopmosquitoes/. DOI-10.1097/01.NURSE.0000484957.70486.d0

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