Saul Levy-Blitchtein， Juana del Valle-Mendoza，3?

1Medicine School， Health Sciences Faculty， Universidad Peruana de Ciencias Aplicadas （UPC）， Lima， Peru

2Research Center and Innovation of the Health Sciences Faculty， Universidad Peruana de Ciencias Aplicadas （UPC）， Lima， Peru

3Instituto de Investigación Nutricional （IIN）， Lima， Peru

?

Zika virus is arriving at the American continent

Saul Levy-Blitchtein1，2， Juana del Valle-Mendoza1，2，3?

1Medicine School， Health Sciences Faculty， Universidad Peruana de Ciencias Aplicadas （UPC）， Lima， Peru

2Research Center and Innovation of the Health Sciences Faculty， Universidad Peruana de Ciencias Aplicadas （UPC）， Lima， Peru

3Instituto de Investigación Nutricional （IIN）， Lima， Peru

ARTICLE INFO

Article history:

in revised form 12 June 2016

Accepted 14 July 2016

Available online 20 October 2016

Zika virus

Arbovirosis

Dengue virus

Chikungunya

Aedes aegypti

Zika virus is the last arbovirosis arriving at the American continent and it is able to produce severe complications due to its neurotropism， such as microcephaly and it is also associated with Guillain-Barre syndrome （GBS）. Presence of Aedes aegypti in many regions of Peru makes it easier to spread and it could be present in population， not being detected because there is a lack of rapid diagnosis methods. It is important to make a quick， effective and combined response to this new threat.

Document heading doi: 10.1016/j.apjtm.2016.07.030

Dear editor，

Zika virus （ZIKV） is the last arbovirosis to arrive to the American continent， following dengue virus （DENV） in 1990， West Nile virus（WNV） in 1999 and chikungunya （CHIK） at 2013. At this time， it represents a pandemic at this continent［1］.

It was first isolated from a rhesus monkey at the Zika forest near Kampala， Uganda in 1947 and from mosquito Aedes africanus in 1948［2］. It is a member of Flaviviridae family， along with yellow fever virus （YFV）， DENV， WNV and Japanese encephalitis virus［1，3］. The first reports of human infection were in Uganda and Tanzania， in 1952［4］. Since then， ZIKV has spread from Africato Southeast Asia and Pacific Islands［1，4，5］. The first epidemic started in 2007 at Yap Islands， Micronesia， which was also the first detection of ZIKV outside of Africa and Asia， with an estimate of 73% population infected and 49 confirmed cases［6］. The second and largest epidemic was at French Polynesia， reaching 28 000 medical attentions which represented about 11% of population［7］ and almost 70% in some islands［8］. Hence it spreads through the Pacific， where it is still actually circulating in New Caledonia， Cook Islands，Vanatu， Solomon Islands， Fiji and Easter Island［7］. It is believed that the last one make the epidemiological entrance of the virus to the Americas， on May 2015 in Brazil［8，9］.

Today ZIKV has autochthonous transmission in 33 countries and regions of the American continent［10］， where the main vector is Aedes aegypti （Ae. aegypti）， also carrier of DENV， YFV and CHIK. In 1947 A. aegypti was eradicated from 18 countries through efforts of Pan-American Health Organization （PHO） and the use of organophosphate DDT. However， DDT use was left in the 1960s and the mosquito returned， so it is present now［11］. There are reports of six countries （Argentina， Chile， France， Italy， New Zealandand United States） without the presence of the vector and local acquisition of the disease， probably by sexual intercourse［10］.

In Peru， Ae. aegypti reemerged in 1984 at Loreto and spread to San Martin region and country's central rainforest zone. Towards 2000 the vector was detected in Lima region， at five districts （La Victoria， El Agustino， Rimac， San Juan de Lurigancho， Cercado de Lima） and later on it spread to other 29 districts. By 2011， the mosquito presence involved 269 districts and 18 regions of Peruvian territory， where about a third of the total population lived［12］. Five haplotypes of Ae. aegypti have been found， which indicates that genetic variability is not only because of its active migration but also because of the passive migration by human activities［13，14］. Also，Ae. aegypti has expanded its habitat due to climate change and El Ni?o phenomenon， both of which increase temperature and humidity［15］.

ZIKV incubation period is estimated between three and seven days（range 3 to 14） after host infection［16］. Course tends to be mild， last days or weeks and it is suspected that individuals acquire immunity after first episode because reinfection has not been reported yet［17，18］. Clinical symptoms， present in 20% of cases， consist in onset of fever and pruriginous maculopapular rash， arthralgia and/or non-purulent conjunctivitis. Common manifestations are nonspecific including fever， malaise， headache and joint pain associated to rash［17-19］. There are neither reports of hemorrhagic complications， nor synergy or increased severity when there is coinfection with DENV or CHIK［20，21］.

Infection is associated with neurological complications， being the main and most alarming Guillain-Barré syndrome （GBS）. French Polynesia epidemic showed an increase of GBS cases， which was lately associated in a case-control study of 42 patients［22］. Thirteen countries and territories reported raising incidence of GBS while ZIKV was circulating［10］. Also， in Brazil， within the 2014-2015 period， the incidence of microcephaly in newborns increased 20 times［1］， reporting initially 141 suspected cases in Pernambuco，followed by other northeastern states （Paramaiba， Rio Grande do Norte）， alongside spontaneous abortions and miscarriages［23］. First months of pregnancy of the newborns match the highest incidence periods of ZIKV at northeastern Brazil and there was not family history of either genetic diseases or positive tests for other infections［24］.

Causal association was carried out by Instituto Evadro Chagas through isolation of ZIKV from brain tissue and detection of virus in cerebrospinal fluid （CSF） and， brain tissue and fragments of viscera （heart， lungs， liver， spleen， kidney） of a newborn that died shortly after birth［23，24］. In addition， ZIKV IgM was found in CSF of 12 newborns with microcephaly and negative to TORCH test （Toxoplasma gondii， other agents， rubella， cytomegalovirus and herpes simplex virus types 1 and 2）， DENV and CHIK［24］. Two cases reported ZIKV in amniotic fluid and microcephaly by ultrasound［25］. Centre for Disease Control and Prevention （CDC）confirmed the presence of virus in cerebral tissue and placenta using polymerase chain reaction （PCR） and immunohistochemistry methods［26］. Besides neurological damage， there is evidence of ocular compromise as macular atrophy， and both macular and perimacular injuries with optical nerve atrophy［24］. Brazil has reported 739 microcephaly cases and other fetal malformations until 21th November， 2015［9］.

One of the major difficulties is the lack of commercial serological and molecular diagnostic tests. Those now available are limited to reference laboratories and cannot fulfill public health demand. It is necessary to develop fast tests （immunochromatography），and serologic （ELISA IgM， IgG） and molecular methods for early diagnosis of ZIKV infection， according to circumstances of involved countries， most of which are low or middle income countries［1，24］. Use of the diagnosis tests should be prioritized for susceptible population as pregnant women and individuals with chronic or autoimmune diseases［24］. On the other hand， these tests will contribute to a better case manage， preventing and treating the complications according etiology［1］.

ZIKV is not well known comparing to other virus. However， due to its neurotropism it causes microcephaly and is associated with GBS. Presence of Ae. aegypti in many regions of Peru makes it easier to spread and could be present in population， not being detected well timed because there is a lack of diagnosis methods. It is important to take appropriate control measures and lower case numbers for the control of mosquito. A quick， effective and combined response is needed by the World Health Organization （WHO） Member States through financial aid and assistance. Also， a vaccine for this virus should be developed to prevent not only the infection but also its main complications.

Conflict of interest statement

We declare that we have no conflict of interest.

［1］ Fauci AS， Morens DM. Zika virus in the Americas--yet another arbovirus threat. N Engl J Med 2016； 374（7）: 601-604.

［2］ Dick GW， Kitchen SF， Haddow AJ. Zika virus. Ⅰ. isolations andserological specificity. Trans R Soc Trop Med Hyg 1952； 46（5）: 509-520.

［3］ Lucey DR， Gostin LO. The emerging Zika pandemic: enhancing preparedness. JAMA 2016； 315（9）: 865-866.

［4］ Dick GW. Zika virus. Ⅱ. pathogenicity and physical properties. Trans RSoc Trop Med Hyg 1952； 46（5）: 521-534.

［5］ Hennessey M， Fischer M， Staples JE. Zika virus spreads to new areas -region of the Americas， May 2015-January 2016. MMWR Morb Mortal Wkly Rep 2016； 65（3）: 55-58.

［6］ 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（24）: 2536-2543.

［7］ Musso D， Nilles EJ， Cao-Lormeau VM. Rapid spread of emerging Zika virus in the Pacific area. Clin Microbiol Infect 2014； 20（10）: O595-O596.

［8］ Dyer O. Zika virus spreads across Americas as concerns mount over birth defects. BMJ 2015； 351: h6983.

［9］ Gatherer D， Kohl A. Zika virus: a previously slow pandemic spreads rapidly through the Americas. J Gen Virol 2015； 97（2）: 269-273.

［10］ Pan American Health Organization. Zika virus infection. ［Online］. Available from: http://www.paho.org/hq/index.php？option=com_cont ent&view=article&id=11585&Itemid=41688&lan=es ［Accessed 10th March 2016］.

［11］ Dick OB， San Martín JL， Montoya RH， del Diego J， Zambrano B， Dayan GH. The history of dengue outbreaks in the Americas. Am J Trop Med Hyg 2012； 87（4）:584-593.

［12］ Peru， Ministerio de Salud. Aprendiendo de la experiencia: lecciones aprendidas para la preparacion y respuesta en el control vectorial ante brotes de dengue en el Peru. Lima: MINSA； 2011.

［13］ Yanez P， Mamani E， Valle J， García MP， León W， Villaseca P， et al. Variabilidad genetica del Aedes aegypti determinada mediante el analisis del gen mitocondrial ND4 en once areas endemicas para dengue en el Peru. Rev Peru Med Exp Salud Publica 2013； 30（2）: 246-250.

［14］ Leiva N， Cáceres O. Variabilidad genetica de Aedes aegypti en algunas areas del Peru usando Single Stranded Conformational Polymorphism（SSCP）. Rev Peru Med Exp Salud Publica 2004； 21（3）: 157-166.

［15］ Paz S， Semenza JC. El Ni?o and climatechange--contributingfactors in the dispersal of Zika virus in the Americas？ Lancet 2016； 387（10020）: 745.

［16］ Rudolph KE， Lessler J， Moloney RM， Kmush B， Cummings DA. Incubation periods of mosquito-borne viral infections: a systematic review. Am J Trop Med Hyg 2014； 90（5）: 882-891.

［17］ Simpson DI. Zika virus infection in man. Trans R Soc Trop Med Hyg 1964； 58: 335-338.

［18］ Centers for Disease Control and Prevention. Zika virus: for health care providers: clinical evaluation & disease. ［Online］. Available from: http:// www.cdc.gov/zika/hc-providers/clinicalevaluation.html ［Accessed 13th January 2016］.

［19］ Filipe AR， Martins CM， Rocha H. Laboratory infection with Zika virus after vaccination against yellow fever. Arch Gesamte Virusforsch 1973；43（4）: 315-319.

［20］ Villamil-Gómez WE， González-Camargo O， Rodriguez-Ayubi J， Zapata-Serpa D， Rodriguez-Morales AJ. Dengue， chikungunya and Zika coinfection in a patient from Colombia. J Infect Public Health 2016； 9（5）: 684-686. doi:10.1016/j.jiph.2015.12.002.

［21］ Dupont-Rouzeyro M， O'Connor O， Calvez E， Daurès M， John M，Grangeon JP， et al. Co-infection with Zika and dengue viruses in 2 patients， New Caledonia， 2014. Emerg Infect Dis 2015； 21（2）: 381-382.

［22］ Cao-Lormeau VM， Blake A， Mons S， Lastère S， Roche C， Vanhomwegen J， et al. Guillain-Barré syndrome outbreak associated with Zika virus infection in French Polynesia: a case-control study. Lancet 2016；387（10027）: 1531-1539.

［23］ Kindhauser MK， Allen T， Frank V， Santhana RS， Dye C. Zika: the origin and spread of a mosquito-borne virus. Bull World Health Organ 2016. doi: http://dx.doi.org/10.2471/BLT.16.171082.

［24］ de Oliveira CS， da Costa Vasconcelos PF. Microcephaly and Zika virus. J Pediatr （Rio J） 2016: 92 （2）: 103-105.

［25］ de Paula Freitas B， de Oliveira Dias JR， Prazeres J， Sacramento GA，Ko AI， Maia M， et al. Ocular findings in infants with microcephaly associated with presumed Zika virus congenital infection in Salvador，Brazil. JAMA Ophthalmol 2016； 134（5）: 529-535. doi: 10.1001/ jamaophthalmol.2016.0267.

［26］ Martines RB， Bhatnagar J， Keating MK， Silva-Flannery L， Muehlenbachs A， Gary J， et al. Notes from the field: evidence of Zika virus infection in brain and placental tissues from two congenitally infected newborns and two fetal losses--Brazil， 2015. MMWR Morb Mortal Wkly Rep 2016； 65（6）: 159-160.

11 May 2016

Saul Levy-Blitchtein， Universidad Peruana de Ciencias Aplicadas-UPC，Av. Primavera 2390， Monterrico， Lima， Peru.

E-mail: levysaul45@hotmail.com

Tel: +5113133333 ext 2704

Juana del Valle-Mendoza， Universidad Peruana de Ciencias Aplicadas-UPC， Av. Primavera 2390， Monterrico， Lima， Peru.

E-mail: jdelvall@upc.edu.pe

Tel : +5113133333 ext 2704

Fax: +5113496025