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Zika Virus
Thu, 2016-04-07 11:12 — Mohamed SIn 1947, a study of yellow fever yielded the first isolation of a new virus, from the blood of a sentinel rhesus macaque that had been placed in the Zika Forest of Uganda.1 Zika virus remained in relative obscurity for nearly 70 years; then, within the span of just 1 year, Zika virus was introduced into Brazil from the Pacific Islands and spread rapidly throughout the Americas.2 It became the first major infectious disease linked to human birth defects to be discovered in more than half a century and created such global alarm that the World Health Organization (WHO) would declare a Public Health Emergency of International Concern.3 This review describes the current understanding of the epidemiology, transmission, clinical characteristics, and diagnosis of Zika virus infection, as well as the future outlook with regard to this disease.
EPIDEMIOLOGY
Zika virus is a flavivirus, in the family Flaviviridae. Although Zika virus was isolated on several occasions from Aedes africanus mosquitoes after its discovery in 1947,4 there initially was no indication that the virus caused human disease. Nevertheless, a serosurvey involving residents of multiple areas of Uganda revealed a 6.1% seroprevalence of antibodies against Zika virus, which suggested that human infection was frequent.5 Additional serosurveys indicated a much broader geographic distribution of human infection, including Egypt,6 East Africa,7 Nigeria,8 India,9Thailand,10 Vietnam,10 the Philippines,11 and Malaysia (near Kuala Lumpur and in East Malaysia [Sabah and Federal Territory of Labuan]).12
Human illness caused by Zika virus was first recognized in Nigeria in 1953, when viral infection was confirmed in three ill persons.8 Despite recognition that Zika virus infection could produce a mild, febrile illness, only 13 naturally acquired cases were reported during the next 57 years.13-16Thus, it came as a great surprise when a 2007 outbreak on several islands in the State of Yap, Federated States of Micronesia, resulted in an estimated 5000 infections among the total population of 6700.17
Subsequently, an outbreak in French Polynesia in 2013 and 2014 is estimated to have involved 32,000 persons who underwent evaluation for suspected Zika virus infection.18-20 Although most of the illnesses appeared similar to those seen in Yap, cases of Guillain–Barré syndrome were also noted.19,21 Subsequent outbreaks occurred on other Pacific islands, including New Caledonia (in 2014),22 Easter Island (2014),23 Cook Islands (2014),24 Samoa (2015), and American Samoa (2016) (Figure 1FIGURE 1Areas in Which Zika Virus Infections in Humans Have Been Noted in the Past Decade (as of March 2016).). In stark contrast to these outbreaks, in the past 6 years, only sporadic cases of Zika virus infection have been reported in Thailand,25,26 East Malaysia (Sabah),27 Cambodia,28 the Philippines,29 and Indonesia.30,31
Zika virus was first identified in the Americas in March 2015, when an outbreak of an exanthematous illness occurred in Bahia, Brazil.32,33Epidemiologic data indicate that in Salvador, the capital of Bahia, the outbreak had begun in February and extended to June 2015.34 By October, the virus had spread to at least 14 Brazilian states,35 and in December 2015, the Brazil Ministry of Health estimated that up to 1.3 million suspected cases had occurred.36 In October 2015, Colombia reported the first autochthonous transmission of Zika virus outside Brazil,35 and by March 3, 2016, a total of 51,473 suspected cases of Zika virus had been reported in that country.37 By March 2016, the virus had spread to at least 33 countries and territories in the Americas (Figure 1).36,37
By September 2015, investigators in Brazil noted an increase in the number of infants born with microcephaly in the same areas in which Zika virus was first reported,38 and by mid-February 2016, more than 4300 cases of microcephaly had been recorded, although overreporting and misdiagnosis probably inflated this number.39 Subsequently, French Polynesian investigators retrospectively identified an increased number of fetal abnormalities, including microcephaly, after the Zika virus outbreak in that country.40,41
ZIKA VIRUS TRANSMISSION
Mosquito-borne Transmission
In Africa, Zika virus exists in a sylvatic transmission cycle involving nonhuman primates and forest-dwelling species of aedes mosquitoes (Figure 2FIGURE 2Zika Virus Transmission Cycle.). In Asia, a sylvatic transmission cycle has not yet been identified. Several mosquito species, primarily belonging to the stegomyia and diceromyia subgenera of aedes, including A. africanus, A. luteocephalus, A. furcifer, and A. taylori, are likely enzootic vectors in Africa and Asia.42,43
In urban and suburban environments, Zika virus is transmitted in a human–mosquito–human transmission cycle (Figure 2). Two species in the stegomyia subgenus of aedes — A. aegypti and, to a lesser extent, A. albopictus44 — have been linked with nearly all known Zika virus outbreaks, although two other species, A. hensilli and A. polynesiensis, were thought to be vectors in the Yap45 and French Polynesia46 outbreaks, respectively. A. aegypti and A. albopictus are the only known aedes (stegomyia) species in the Americas. Despite the association of A. aegypti and A. albopictus with outbreaks, both were found to have unexpectedly low but similar vector competence (i.e., the intrinsic ability of a vector to biologically transmit a disease agent) for the Asian genotype Zika virus strain, as determined by a low proportion of infected mosquitoes with infectious saliva after ingestion of an infected blood meal.47 However, A. aegyptiis thought to have high vectorial capacity (i.e., the overall ability of a vector species to transmit a pathogen in a given location and at a specific time) because it feeds primarily on humans, often bites multiple humans in a single blood meal, has an almost imperceptible bite, and lives in close association with human habitation.48
Both A. aegypti and A. albopictus bite primarily during the daytime and are widely distributed throughout the tropical and subtropical world. A. albopictus can exist in more temperate areas thanA. aegypti, thus extending the potential range where outbreaks may occur. In the United States, A. aegypti is endemic throughout Puerto Rico and the U.S. Virgin Islands and in parts of the contiguous United States and Hawaii (Figure 3FIGURE 3Approximate Ranges of A. aegypti and A. albopictus in the United States (as of March 2016).).49 A. albopictus is widely distributed in the eastern United States and Hawaii. Nevertheless, in the contiguous United States, contemporary outbreaks of dengue, which has a transmission cycle similar to that of Zika virus, have occurred only in areas in which A. aegypti is endemic, which suggests that the potential for the transmission of Zika virus elsewhere is limited. In contrast, Hawaii has experienced contemporary dengue outbreaks in which A. albopictus was the vector.50,51
Zika virus has infrequently been identified in other mosquito species, such as A. unilineatus, Anopheles coustani, and Mansonia uniformis; however, vector-competence studies have indicated that these species have a low potential for transmission of the virus. It is notable that Zika virus has been reported only once in any culex species, which suggests that mosquitoes in this genus have a low vectorial capacity.42
Nonmosquito Transmission
Substantial evidence now indicates that Zika virus can be transmitted from the mother to the fetus during pregnancy. Zika virus RNA has been identified in the amniotic fluid of mothers whose fetuses had cerebral abnormalities detected by ultrasonography,40,52-54 and viral antigen and RNA have been identified in the brain tissue and placentas of children who were born with microcephaly and died soon after birth,55 as well as in tissues from miscarriages.54,55 The frequency of and risk factors for transmission are unknown.
Two cases of peripartum transmission of Zika virus have been reported among mother–infant pairs.56 Zika virus RNA was detected in both infants; one infant had a mild rash illness and thrombocytopenia, whereas the other was asymptomatic.
Sexual transmission to partners of returning male travelers who acquired Zika virus infection abroad has been reported.57-59 In one instance, sexual intercourse occurred only before the onset of symptoms, whereas in other cases sexual intercourse occurred during the development of symptoms and shortly thereafter. The risk factors for and the duration of the risk of sexual transmission have not been determined. Replicative viral particles, as well as viral RNA — often in high copy numbers — have been identified in sperm, and viral RNA has been detected up to 62 days after the onset of symptoms.60-62
Although the transmission of Zika virus through a blood transfusion has yet to be reported, it is likely to occur, given the transmission of other, related flaviviruses through this route.63 During the Zika virus outbreak in French Polynesia, 3% of donated blood samples tested positive for Zika virus by reverse-transcriptase polymerase chain reaction (RT-PCR).64
One case of Zika virus transmission occurred after a monkey bite in Indonesia, although mosquito-borne transmission could not be ruled out.65 Two infections in laboratories have been reported.16,66A volunteer became infected after subcutaneous injection of infected mouse brain suspension.67Transmission through breast milk has not been documented, although the breast milk of a woman who became symptomatic with Zika virus infection on the day of delivery contained infective Zika viral particles in high titer.68
to read the full article click on:http://www.nejm.org/doi/full/10.1056/NEJMra1602113
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