Zika Virus: Rapid Spread in the Western Hemisphere
Authors: Lin H. Chen, Davidson H. Hamer
Journal: Annals of Internal Medicine (2016)

Ideas and Opinions3 May 2016Zika Virus: Rapid Spread in the Western HemisphereFREELin H. Chen, MD and Davidson H. Hamer, MDLin H. Chen, MDFrom Mount Auburn Hospital, Cambridge, and the Center for Global Health and Development, Boston University School of Public Health, Boston, Massachusetts. and Davidson H. Hamer, MDFrom Mount Auburn Hospital, Cambridge, and the Center for Global Health and Development, Boston University School of Public Health, Boston, Massachusetts.Author, Article, and Disclosure Informationhttps://doi.org/10.7326/M16-0150 SectionsAboutVisual AbstractPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Zika virus, a mosquito-borne flavivirus that causes febrile illness associated with rash, has been rapidly emerging in the Western Hemisphere over the past few months. The virus was rarely identified until outbreaks occurred on Yap Island in the Federated States of Micronesia in 2007, French Polynesia in 2013, and Easter Island in 2014. It was initially detected in Brazil in 2015, in the northeast, and was subsequently identified in other states and several South American countries, including Colombia, Ecuador, Suriname, Venezuela, French Guyana, and Paraguay (1). Local transmission has been documented in Central America (Panama, El Salvador, Honduras, and Guatemala), the Caribbean (Martinique, Puerto Rico, Dominican Republic, and Haiti), and Mexico. Transmission has also occurred in travelers returning from the infected regions to nonendemic countries, including the United States, Canada, Japan, and Western Europe. As of 22 January 2016, a total of 20 countries and territories in the Americas have Zika virus circulation (1). The explosive spread mirrors the emergence of chikungunya, which was first detected in the Americas (St. Martin) in 2013 and rapidly disseminated throughout the region (2).Background and EpidemiologyZika is an RNA virus in the family Flaviviridae, genus Flavivirus. It is related to dengue, yellow fever, West Nile, and Japanese encephalitis viruses. It was initially isolated in the Zika Forest of Uganda in 1947 from a febrile rhesus monkey that was a sentinel for a surveillance project on jungle yellow fever (3). Subsequently isolated from Aedes africanus mosquitoes in the same forest in 1948 and intermittently from humans and mosquitoes since then, Zika virus is predominantly transmitted through the bite of Aedes mosquitoes; however, risk for infection via blood transfusion and sexual activity exists (4–6). Phylogenetic analyses suggest 2 major lineages, African and Asian, arising from a common Zika virus ancestor, possibly in Uganda (4). Numerous Aedes species have been reported to be possible vectors, including Ae. hesilli in Yap, Ae. aegypti and Ae. polynesiensis in French Polynesia (5, 7, 8). Aedes aegypti and Ae. albopictus are present in much of the Americas, including many parts of the Southeastern and Southcentral United States as well as Hawaii (5).Although past serologic surveys suggested the presence of Zika virus infections in Africa and Asia, few human cases were reported until 2007, when an outbreak of fever, rash, conjunctivitis, arthralgia, and arthritis occurred on Yap Island, Micronesia (7). Although initial serologic results were positive for dengue IgM, further testing by reverse transcriptase polymerase chain reaction (RT-PCR) confirmed Zika virus as the cause. An estimated 73% of Yap residents aged 3 years or older were infected with Zika virus; about 80% of infections were subclinical (5, 7).In October 2013, Zika virus was first identified in French Polynesia and suspected to be responsible for an estimated 19 000 cases of a dengue-like syndrome by December of that year; the virus was closest to one isolated in Cambodia in 2010 (8). Circulation of Zika virus was subsequently detected in New Caledonia, Cook Islands, and Easter Island (Chile) in 2014 (1).By March 2015, cases of a dengue-like syndrome reported from Natal in the state of Rio Grande do Norte, Brazil, were confirmed to be Zika by RT-PCR. Thereafter, outbreaks have occurred in several states in Brazil and has spread rapidly in the Americas. As of 22 January 2016, a total of 20 countries and territories in the Americas has reported Zika virus infection (1). The Asian lineage has been responsible for all Zika virus outbreaks in the Pacific and the Americas.Clinical Manifestations and DiagnosisSymptoms develop after a bite by a Zika-infected mosquito following an estimated incubation period of 2 to 7 days, similar to other flaviviruses (1). Patients typically present with a maculopapular rash (duration, 2 to 14 days; median, 6 days), arthralgias (duration, 1 to 14 days; median, 3.5 days), and conjunctivitis (7). Other reported symptoms include myalgias, headache, retro-orbital pain, joint swelling, vertigo, and vomiting. Zika infection is generally mild and self-limited and resolves in a week (5, 7), whereas chikungunya infection can lead to persistent or relapsing arthralgia lasting months or longer (2). However, neurologic and autoimmune complications have been identified in the French Polynesian outbreak, particularly Guillain-Barré syndrome, as well as perinatal transmission. (1, 5). Of great concern, additional cases of Guillain-Barré syndrome and a new association between Zika virus infection and microcephaly have occurred in Brazil, where a dramatic 3530 cases have been recorded as of the first week of 2016 (1, 5).Diagnosis of infection is confirmed by RT-PCR during the first week of illness; viremia has been demonstrated from days 0 to 11 after symptom onset (4). Serologic testing (IgM on enzyme-linked immunosorbent assay) can detect the virus, although dengue may cause false-positive results; therefore, positive results should be confirmed by plaque reduction neutralization assays. Conversely, Zika virus infection can cause false-positive results for dengue. Zika virus RNA can also be detected in saliva and urine and may remain positive in urine for longer than in serum (9, 10). Further complicating diagnosis is the potential for co-infection with dengue (proven) and chikungunya (potential).Treatment, Prevention, and ControlTreatment of Zika fever is supportive and primarily involves acetaminophen for fever, headache, or myalgia. As with treatment for dengue, nonsteroidal anti-inflammatory agents should be avoided if thrombocytopenia is present. Given the worldwide spread of dengue and chikungunya and the wide range of Aedes mosquitoes that can transmit Zika, prevention of infection relies on mosquito avoidance. These preventive measures include DEET- or picaridin-containing insect repellents to minimize risk from day-biting Aedes mosquitoes, drainage of mosquito breeding sites, and application of insecticides. There is no vaccine available.Clinician AdvisoryAfter the recent dissemination of chikungunya in the Western Hemisphere, the rapid spread of Zika virus since its arrival in the Americas reminds us once again of our global interconnectedness. Since Aedes mosquitoes are vectors for Zika as well as chikungunya and dengue, distribution of these infections overlap. Clinicians should advise patients to use antivector measures when traveling to regions with Zika transmission (Figure). Given the possible association between Zika virus and microcephaly, pregnant women should avoid travel to areas that are reporting outbreaks or practice meticulous mosquito avoidance (including repellents containing DEET, picaridin, or IR3535, considered safe in pregnant and breastfeeding women) (5). Clinicians should consider Zika, dengue, and chikungunya in the differential diagnosis of febrile travelers with rash, arthralgia, and myalgia after travel to Central and South America and the Caribbean. Risk for introduction into the United States is substantial given the presence of Ae. aegypti and particularly Ae. albopictus mosquitoes in many states.Figure. Countries that have past or current evidence of Zika virus transmission (as of January 2016).Accessed at www.cdc.gov/zika/geo/index.html on 19 January 2016. Download figure Download PowerPoint References1. Pan American Health Organization. Zika virus infection. Accessed at www.paho.org/hq/index.php?option=com_topics&view=article&id=427&Itemid=41484&lang=en on 19 January 2016. Google Scholar2. Hamer DH, Chen LH. Chikungunya: establishing a new home in the Western Hemisphere. Ann Intern Med. 2014;161:827-8. [PMID: 2524435]. doi:10.7326/M14-1958 LinkGoogle Scholar3. Dick GW, Kitchen SF, Haddow AJ. Zika virus. I. Isolations and serological specificity. Trans R Soc Trop Med Hyg. 1952;46:509-20. [PMID: 12995440] CrossrefMedlineGoogle Scholar4. Lanciotti RS, Kosoy OL, Laven JJ, Velez JO, Lambert AJ, Johnson AJ, et al. Genetic and serologic properties of Zika virus associated with an epidemic, Yap State, Micronesia, 2007. Emerg Infect Dis. 2008;14:1232-9. [PMID: 18680646] doi:10.3201/eid1408.080287 CrossrefMedlineGoogle Scholar5. Hennessey M, Fischer M, Staples JE. Zika virus spreads to new areas—region of the Americas, May 2015–January 2016. Accessed at www.cdc.gov/mmwr/volumes/65/wr/mm6503e1er.htm on 23 January 2016. Google Scholar6. Foy BD, Kobylinski KC, Chilson Foy JL, Blitvich BJ, Travassos da Rosa A. Haddow AD, et al. Probable non-vector-borne transmission of Zika virus, Colorado, USA. Emerg Infect Dis. 2011;17:880-2. [PMID: 21529401] doi:10.3201/eid1705.101939 CrossrefMedlineGoogle Scholar7. Duffy MR, Chen TH, Hancock WT, Powers AM, Kool JL, Lanciotti RS, et al. Zika virus outbreak on Yap Island, Federated States of Micronesia. N Engl J Med. 2009;360:2536-43. [PMID: 19516034] doi:10.1056/NEJMoa0805715 CrossrefMedlineGoogle Scholar8. Cao-Lormeau VM, Roche C, Teissier A, Robin E, Berry AL, Mallet HP, et al. Zika virus, French polynesia, South pacific, 2013 [Letter]. Emerg Infect Dis. 2014;20:1085-6. [PMID: 24856001] doi:10.3201/eid2006.140138 CrossrefMedlineGoogle Scholar9. Gourinat AC, O'Connor O, Calvez E, Goarant C, Dupont-Rouzeyrol M. Detection of Zika virus in urine. Emerg Infect Dis. 2015;21:84-6. [PMID: 25530324] doi:10.3201/eid2101.140894 CrossrefMedlineGoogle Scholar10. Musso D, Roche C, Nhan TX, Robin E, Teissier A, Cao-Lormeau VM. Detection of Zika virus in saliva. J Clin Virol. 2015;68:53-5. [PMID: 26071336] doi:10.1016/j.jcv.2015.04.021 CrossrefMedlineGoogle Scholar Comments0 CommentsSign In to Submit A Comment Prof. Enrique Sanchez-Delgado, MDHospital Metropolitano Vivian Pellas, Managua2 February 2016 Ivermectin to reduce Zika transmission and other diseases by mosquito bite Ivermectin to reduce Zika transmission and other diseases by mosquito biteThe Nobel Prize winner antiparasitary medicine Ivermectin has achieved the reduction of about a third of transmissions of malaria in Africa thanks to its ectoparasitizide effect that kills the mosquitoes after they bite the patients.It has the potential to reduce the enormous impact of Zika, Chikungunya, Dengue and Malaria in Latin America and elsewhere if is administered in one dosage to the appropriate affected patients and family circle, with minimal costs and minimal side effects.This can be done together with the other known methods to reduce the propagation of mosquitos and the transmission of these diseases.I propose the responsible authorities at the WHO/PAHO to analyze the possibilities of success for this strategy.Prof. Dr. Enrique Sánchez-Delgado, MDInternal Medicine-Clinical Pharmacology and TherapeuticsDirector of Medical EducationHospital Metropolitano Vivian Pellas, Managua Carlos PolancoFaculty of Sciences, UNAM 2 February 2016 About diseases that share reservoir and signs The Chen and Hammer's article (1) [Zika Virus: Rapid Spread in the Western Hemisphere, Annals of Internal Medicine], particularly describes the geographic dissemination of the Zika virus disease. It is remarkable to observe a natural reservoir of climate monsoon, located in a geographic zone around the planet, between the tropics of Cancer and Capricorn, and also identifying important diseases: dengue (2), malaria (3), and ebola (4).In my view it is possible to use drones which identify the density of mosquitoes and individuals, as criteria for selecting the areas where these same devices automatically spread repellents containing DEET, picaridin, or IR3535, considered safe in pregnant and breastfeeding women (1).The population growth and the insufficiency of medical/preventive services in underdeveloped countries, well might benefit from this technology.Sincerely yours,Carlos Polanco, Ph.D., D.Sc.Faculty of Sciences, Universidad Nacional Autónoma de México, México City, 04510. México.Carlos Polanco is an Associate Professor in the Facuty of Sciences at Universidad Nacional Autónoma de México, México City, México. ([email protected]).References(1) Chen LH, Hamer DH. Zika Virus: Rapid Spread in the Western Hemisphere. Ann Intern Med (2016) DOI:10.7326/M16-0150. (2) Snow RW, Guerra CA, Noor AM, Myint HY, Hay SI. The global distribution of clinical episodes of Plasmodium falciparum malaria. Nature 434 (7030), 214-217 (2015).(3) Rogers DJ, Wilson AJ, Hay SI, Graham AJ. The Global Distribution of Yellow Fever and Dengue. Advances in parasitology 62, 181-220. (2006).(4)Polanco C, and Castañón González JA. (letter) Check-Hayden E. Ebola teaches tough lessons about rapid research. Nature 521, 405-406 (2015). Author, Article, and Disclosure InformationAffiliations: From Mount Auburn Hospital, Cambridge, and the Center for Global Health and Development, Boston University School of Public Health, Boston, Massachusetts.Disclosures: Disclosures can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M16-0150.Corresponding Author: Lin H. Chen, MD, Mount Auburn Hospital, 330 Mount Auburn Street, Cambridge, MA 02138; e-mail, [email protected]harvard.edu.Current Author Addresses: Dr. Chen: Division of Infectious Diseases, Mount Auburn Hospital, 330 Mount Auburn Street, South 2, Cambridge, MA 02138.Dr. Hamer: Center for Global Health and Development, 801 Massachusetts Avenue, Crosstown Third Floor, Boston, MA 02118.Author Contributions: Conception and design: L.H. Chen, D.H. Hamer.Analysis and interpretation of the data: L.H. Chen, D.H. Hamer.Drafting of the article: L.H. Chen, D.H. Hamer.Critical revision of the article for important intellectual content: L.H. Chen, D.H. Hamer.Final approval of the article: L.H. Chen, D.H. Hamer.Administrative, technical, or logistic support: L.H. Chen.This article was published at www.annals.org on 2 February 2016. 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