TheEpidemiology,ClinicalCharacteristic,TransmissionPotentialandControlMeasuresofZikaViru

1、The Epidemiology ， Clinical Characteristic ， Transmission Potential and Control Measures of Zika Virus InfectionZika virus （ ZIKV） is a single-stranded RNA virus，anarthropod-borne Flavivirus distributed throughout much ofAfrica and Asia.The virus is transmitted by Aedesmosquitoes and potentially by

2、transfusion ， perinatal and sexual transmission. The potential for spread into countries where Aedesmosquitoes are endemic is high. Concern hasbeen heightened further in the face of upcoming mass gatherings in regions where the virus iscurrently endemic ， such as the Umrah and Haji pilgrimagesin Sau

3、di Arabia ， where local mosquito populations represent the potential for new outbreaks1. The current lackofspecifictreatments or vaccines and complications in diagnosis of ZIKV further underscorethe urgency of developing a global approach toresearching this virus.International interest in the Zika v

4、irus（ ZIKV）hasbeen sparked by the current outbreak in Braziland other countries in the Americas， which led thePan AmericanHealth Organization to issuean alertfor northeast Brazilon 7 May 2015. The World Health Organization（ WH）Ostrongly suspects that the concomitance of a sharp increaseof microcepha

5、ly and/or GBS incidence in sevencountries in the Americas and the ZIKV out-break indicates a relationship.This possibilityhas led them todeclare a Public Health Emergency of International Concern on February 1 ， 20162.History and EpidemiologyZika virus was first isolated from afebrile sentinel monke

6、y in the Zika forest in Ugandain1947 and subsequently from Aedes africanusmosquitoes in the same forest3. Isolationof ZIKV from Aedes africanus mosquitoes and otherAedes species including Aedes aegypti in Africa andMalaysia.Many other Aedes species， including Aedesluteocephalus ， Aedes albopictus ，

7、Aedes furcifer ， Aedes vittatus ，Aedes taylori ， Aedes dalzieli ， Aedes hirsutus ， Aedes. metallICUs ， Aedes hensilii and Aedes unilineatus 3.Since 1947 ， when Zika virus was first isolated in Uganda， it was confined for thefirst60 years to an equatorial zone across Africa and Asia.However ， it was

8、not until2007 that the virus was recognized as a clinically important pathogen capable of causing disease epidemics . The 2007 outbreak ， on Yap Island in Micronesia ， was the worlds first major outbreak of Zika virus disease in humans. No hospitalization or deaths were reportedduringthis outbreak ，

9、 and the clinical features observed were similar to those described in earlier case reports ： mild fever ， malaise ， headache ， arthralgia and rash.During 2013 and 2014 ， the second and major ZIKV outbreak was reported in French Polynesia ， the febrile cohort of Zika was estimated at 28 ，000 . Affec

10、ted Countries by Recent OutbreakAS of May 2015， ZIKV has spread to at least 20 countries in the Americas. As of July 2016 ， ZIKV has been reported in 65 countries whereas microcephaly and other neural defects have been documented in 13 countries.There was increase in incidence of Guillain-Barr syndr

11、ome haveconfirmed in 15 countries. ZIKV was reported in Brazil ， Caribbean ， several Central and South American states by May 2015. About 30 000 cases of ZIKV infection were confirmed in Brazil by 30 January， 2016. A recentlypublished study reported 1 474 cases of the Guillain- Barrsyndrome and 164

12、237 confirmed and suspected cases of ZIKV disease from Bahia ， Venezuela ， Brazil ， the Dominican Republic ， Honduras ， Colombia ， and Suriname during April 1， 2015 ， to March 31 ， 2016 4. Recent report by Defense Armed Forces Health Surveillance Branch released on 25th January confirmed 198 346 cas

13、es of ZIKVand 2 569 cases ofmicrocephaly during January 2015 to January 2017 in Western Hemisphere countries .VIROLOGIC CHARACTERISTICSZIKV has single-stranded positive-sense RNA genome about 10.7 kb in length enclosed in a capsid and surrounded by a membrane. Single polypeptide that is encoded by t

14、he genome of Zika virus experience post translational chopping done by viral and host proteases leading to formation of seven non-structural proteins that are NS1 ， NS2A， NS2B， NS3， NS4A NS4B， NS5 along with three structural proteins such as envelope （ E）， pre-membrane （ prM）， and capsid （C） .On the

15、 based nucleotide sequences，there are threelineages of ZIKV according to NS5 gene：（ 1） East African （one strain examined），（ 2） Asian （one strain examined）， （3） and West African （three strains examined ） . Whilebased on phylogenetic analysis of entire genomes， twogenetic lineages exist for ZIKV that

16、corresponds to Asian and African geographical areas. African strains are further categorized into two groups ：（1） Nigerian cluster MR766 prototype cluster（ isolated in Uganda ） whereas ，（ 2） Asian clade is also classified into two groups Malaysian and Micronesian strains.Transmission Dynamics of ZIK

17、VThere are many routs for the transmission of the Zika virus to human ， such as1- Vector TransmissionZIKV is an arthropod-borne virus （arbovirus ） that is transmitted bymosquito vectors ， with two distinct transmission cycles ： （i ） a sylvatic cycle ， involved in themaintenance of ZIKV betweennon-hu

18、man primates and arboreal mosquitoes in forests ； and （ ii ） anurban cycle ， involved in the transmission of ZIKV between humansand urban mosquitoes in towns . In an urban cycle ， the transmission of ZIKV is believed to be mediatedpredominantly by two Aedes species mosquitoes ： Aedes. aegypti ， reco

19、gnizedby a bright lyre-shaped dorsal pattern with white bands on itslegs， and Aedes.albopictus ， characterized by a single longitudinal dorsalstripewithwhite bands on its legs.Both Aedes aegypti and Aedes albopictus are usually active during daylighthours andare widelydistributed throughout the trop

20、ical and subtropical regionsof the world. But Aedes albopictus also present incool temperate regions.2- Transmission Through BloodBlood-borne transmission of Zika virus has been reported ，about 2%?C8% blood donors were tested positive for ZIKV during French Polynesia outbreak.In Brazil，twomore cases

21、 of ZIKV were reported by the transfusion of blood .AABB ( American Association of Blood Banks) hasdeclared ZIKV as high risk agent and introduced precautionary measures such as NAT( nucleic acid test)or pathogen inactivation of blood products to control transfusion-transmitted ZIKV. Blood safety au

22、thorities have been alerted regarding The post-transfusion Zika fever was reported in 42 out of 1505 in recipient from blood donors positive for ZIKV by PCR 5.3- Transmission Through Breast MilkZIKV has been detected in breast milk of threelactating mothers and two of three newborns showed symptoms

23、of ZIKV. More evidence is still needed to support this conclusion of transmission of ZIKV through breast milk and other perinatal transmission routes6.4- Transmission Trough SalivaZIKV has been isolated from the salivary sample of person by cell-culture with febrile illness who had returned from Dom

24、inican Republic to Italy on January 2016. About 29 days after the onset of symptoms， viral load was found to be higher in saliva and urine than in blood . During the largest ZIKV outbreak of French Polynesia that occurred from October 2013 to March 2014 ， 1067 salivary and blood samples （ only blood

25、 ， only saliva or both samples together ） were collected from 855 patients and were tested for ZIKV using RT-PCR. Results showed that ZIKV was more frequently confirmed in saliva samples than blood samples. For 182 individuals with both samples collected ， tests were positive for 16 （ 8.8%） in blood

26、 while negative in saliva whereas tests were positive for 35 （ 19.2%） in saliva while negative in blood.5- Transmission Through UrineThe presence of Zika virus in urine is supported by many evidences of the research.During the acute phase of Zikavirus infection， five saliva samples and nine urinesam

27、ples were collected from nine patients and tested by RT-PCR， RT-qPCR， and NAT-Zika in Rio de Janeiro. ZIKV was isolated one from saliva and one from urine sample. Viral load was found to be higher in urine samples than saliva samples. 6-Sexual TransmissionThere are several evidences that show sexual

28、 transmission of ZIKV is possible. In outbreak of French Polynesia that occurred in December 2013， high ZIKV RNAload was confirmed in semen of patient 7.The New York City （ NYC） Department of Health and Mental Hygiene（ DOHM）Hwas reported that the transmission of ZIKV from female to male is possible

29、because a women returened from ZIKV epidemic area and rRT-PCR of woman， was positive for ZKIV. During the condom-less intercourse ZIKV transferred to male.7-Vertical TransmissionThere are lot of evidences that provide basis of vertical transmission of ZIKV and its association with fetal brain develo

30、pment. During French Polynesia epidemic in 2013 ， two cases of ZIKV have been documented and in Brazil outbreak in 2015， pregnant women found to deliver babies with congenital teratogenic disorders specially microcephalyZIKV was confirmed in Brazilian woman during 8th week of pregnancy and also dete

31、cted in amniotic fluid during 17th week of pregnancy in Spain.PathogenesisThere is insufficient data available to understand the pathogenesis of ZIKA virus. TheAXL， DC-SIGN， TIM-1 and Tyro entry/adhesion factors allow the entry of ZIKA virus.After the eatery ， immature dendritic cells ， epidermal ke

32、ratinocytes ， and human dermal fibroblasts have been found to be permissive to ZIKV infection. TheReplication of ZIKV triggers an antiviral immune response and produce type I interferon in infected cells8. During the acute phase of ZIKA infection ， T cells such as （Th1， Th2， Th9， and Th17 ） are acti

33、vated.According to one study ， there is infection in radial glial cells of dorsal ventrICUlar zone in response to intraperitonial injection of ZIKV strain in pregnant mice. Therefore ， significant reduction of cortex founder cells in neonates was observed after vertical transmission of Zika virus wh

34、ich leading to brain anomalies in fetus .Brazilian ZIKV （ ZIKVBR） strain has been shown to cause birth defects such as intrauterine growth restrictionandmicrocephaly. ZIKVBR cross the placenta ， target cortical progenitor cells， induce cell death and impairneurodevelopment . ZIKV promotes cells deat

35、h by inhibiting cell-cycle progression and cause death of human cortical progenitor cells（ hCNPC）s .Clinical Manifestations of Zika Virus DiseaseIncubation PeriodIncubation duration is usually between（3?C12）days.Approximately 25% of infected patients develop symptoms （2?C10） days after illness9.Sign

36、s andSymptomsSymptoms associated with ZIKV infection arevariable.It is asymptomatic in up to 80% ofcases ， and when symptoms do occur ，they are typically mild and non-specific.The symptoms typically occur approximately2 to 12 days after the mosquito bite ， presenting mostcommonly with fever ， maculo

37、papular rash ， conjunctivitis ， andjoint pain ， and the clinical illness lasts for several days to aweek. Other symptoms include muscle pain and headache ， butabdominal pain ， nausea ， diarrhea ， mucus membraneu lceration ，andpruritus are rarely observed10.According to Pan America Health Organizatio

38、n ( PAHO)， commonly reported clinical symptoms in ZIKV infected individuals of America are exanthema ( skin rash ) and mild fever often accompanied by joint or muscle pain as well as conjunctivitiswhereas ，autoimmune and neurological complications.The Zika infection is more serious as it is associat

39、ed with two neurological conditions ：1- MicrocephalyAbout 4 000 cases of microcephaly were reported in Brazil with ZIKV infection and this incidence is 20-fold more than 2010 to 2014. Microcephaly has been considered as an irreversible and most serious neurological complications caused by ZIKA virus

40、. According to evidences of study ， the virus has been found in the placenta and amniotic fluid of mothers and in the brains of newborns. The first domestic case of microcephaly in fetus was observed in Hawaii on January 15， 2016 ， whose mother had lived in Brazil. After that many other cases of mic

41、rocephaly in new born were reported in Texas， Illinois ， and Florida in womenw ho were back from international tour 11.2- Guillain-Barre SyndromeGuillain-Barre syndrome is an autoimmune disease inwhich the immunesystemattacks the peripheral nervous system ， causing tingling，muscle weakness ， paralys

42、is ，and even death. Previously， this neuromuscularcomplicationhad been associated with infection by other arboviruses ， such as DENV and chikungunya virus .The temporal and geographic association ofZIKV with Guillain-Barre syndrome was initially observed during the2013?C2014 outbreak reported in Fre

43、nch Polynesia andsubsequently during the2015?C2016 outbreak in the Americas. During the previousFrench Polynesia outbreak，the incidence of Guillain-Barre syndromewas estimated to be 20-fold higher than itsbasal incidence of 1?C2casesper 100 ， 000 population per year .Laboratory Diagnosis of Zika Vir

44、usThere is no widely available test for Zika infection. In most people ， diagnosis is based on clinical symptoms and epidemiological circumstances ( such as Zika outbreak in the patient s area or trips to areaswhere the virusincludeis circulating ) . Diagnostic tests for ZIKV infection1- Polymerase

45、Chain ReactionNucleic acid detection by reverse transcript-polymerase chain reaction （RT-PCR） targeting the non-structural protein 5 genomic region is the primary means of diagnosis. It is useful in the first 3-5 days after the onset of symptoms.2- Serological TestAn ELISA has been developed to dete

46、ct IgM to ZIKV only after five days. Because it is closely related to dengue and yellow fever ， it may cross-react with antibody tests for those viruses.3- Neuclic Acid Amplification TestNucleic acid amplification test （ NAT） for detection of viral RNA can also be performed.4- Plaque Reduction Neutralization TestThe Plaque reduction neutralization assay generally has improved specificityover immunoassays， but may stillyield cross-reactive results in secondary Flavivirus infections.Management of Zika Virus DiseaseThere is presently no vaccine and no specific antiviraltreatment for ZIKV infect