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Zika virus

Epidemiology: - transmitted by mosquitoes in the genus Aedes (Aedes aegypti) - incubation is 3-14 days [159] - vertebrate hosts of the virus include monkeys & humans - Zika virus circulating in 38 countries & territories, March 2016 [46] - Africa: Uganda, Tanzania, Egypt, Central African Republic, Sierra Leone & Gabon - Asia: India, Malaysia, the Philippines, Thailand, Vietnam, & Indonesia - South America: Brazil - Puerto Rico [3] - 30 cases in Puerto Rico Nov 2015 - Jan 2016 [24] - 680 cases reported in Puerto Rico Nov 2015-April 2016, 1 death related to severe thrombocytopenia [61] - 1% of blood donors in Puerto Rico June 2016 infected with Zika virus [75] - HHS declares a public health emergency in Puerto Rico Aug 2016 [100] - 2400 people in the U.S. contracted Zika virus disease during the first 7 months of 2016 [113] - only 28 were locally acquired, mostly via mosquitoes, the rest were travel-associated - one case of Zika contracted by a laboratory finger stick [113] - Zika virus spreading explosively through Americas [12,13] - map of distribution of Aedes mosquitoes & risk for Zika virus U.S.A. [43] - case reported in Texas [4] - case reported in Hawaii [5] - case reports in Illinois & Florida [8] - case report in Massachusetts resident after travel to Costa Rica [23] - 182 cases of confirmed Zika virus infection in New York City related to travel exposure Jan-June 2016 [76] - a person in Utah contracted the Zika virus after caring for another Zika patient who died in June [85] - possible non-travel related case of Zika infection in Miami-Dade County Florida July 2016 [86] - active transmission of Zika virus expanding in Miami Beach, 4.5 square miles Sept 2016 [115] - 35 non-travel-related Zika cases in Miami Beach, & 93 total in Florida Sept 2016 [115] - active transmission of Zika in new area of Miami-Dade County [122] - FDA requests postponing blood donations in Miami-Dade & Broward counties of Florida until Zika-free blood can be assured [91] - potential risk of Zika Miami-Dade, Broward, & Palm Beach counties March 2017 [139] - Florida's 17th infection Aug 2015 not related to foreign travel [97] - spread of Zika to Florida's gulf coast [104] - 1st confirmed Zika-related death in continental U.S. [80] - infant with Zika-linked microcephaly dies in Texas Aug 2016 [98] - mother infected with Zika in Latin America during pregnancy - Texas resident acquired Zika infection during travel to Miami Aug 2016 [101] - as of May 12, 279 pregnant women in the U.S. have tested positive for Zika [66] - 3 children of U.S. women infected with the Zika virus have been born with birth defects in 2016 [74] - case reports of sexually transmitted Zika virus infection [14,54] - case of Zika transmission from male to male sexual transmission involving anal sex [57] - suspected female to male sexual transmission of Zika [84] - zika virus RNA common in semen of symptomatic men [153] - persistence in semen for 2 months [25] - sexual transmission of Zika virus from an asymptomatic man who traveled to a Zika-affected region to a woman without a travel history [107] - WHO recommend ready access to emergency contraception in Zika-infected areas [30] - confirmed transmission of Zika via blood transfusion [17] - transmission via platelet transfusion reported [102] - maximal length of Zika viremia is thought to be < 28 days - Brazilian researchers at the Oswaldo Cruz Foundation say they have found active Zika virus in urine & saliva [18] - virus found in amniotic fluid associated with microcephaly [28] - Aedes mosquitoes linked to Zika virus not likely in areas above 6,500 feet (2,000 meters) [41] - cancelling or changing the location of the 2016 Olympics will not significantly alter the international spread of Zika virus [65,71] exception of perhaps 4 countries Chad, Djibouti, Eritrea, & Yemen [81] since they don't have significant travel to other countries with local transmission - requests for abortions up in Latin America June 2016 related to concerns of Zika virus [78] - January-November 2016, 476 microcephaly cases were reported in Colombia [131] - 33 Service members have acquired Zika overseas (Aug 2016) - Texas report case of local Zika transmission (Nov 2016) [129] - Texas reports 4 additional cases of suspected locally acquired Zika infection [133] - 5 cases of locally transmitted Zika virus identified in Brownsville, Texas Dec 2016 [137] - Texas reports case of local Zika transmission (July 2017) [145] - prevalence of birth defects potentially related to Zika virus increased from 2.0 to 2.4 per 1000 live births in U.S. areas with local Zika transmission in 2016 [150] - Zika virus outbreak in the Americas will likely diminish by 2019 [83] - Zika remains significant enduring public health challenge but no longer represents a public health emergency (WHO) [127] - 5200 probable or confirmed, noncongenital Zika cases in U.S. states in 2016 [151] - 95% in travelers from Zika-affected areas - 4% from local, mosquito-borne transmissions, all in Florida or Texas - 1% from other transmissions, including sexual contact [151] Pathology: - in humans disease similar to dengue, yellow fever, West Nile virus & Japanese encephalitis virus - Zika virus is neurotropic, preferentially affecting tissues in the brain & brain stem of the developing fetus [40] - Zika virus impairs growth of human neural progenitor cells [60] - microcephaly, diminished cerebral volume, ventriculomegaly, cerebellar hypoplasia, lissencephaly with hydrocephalus [121] - overall pattern of brain atrophy suggests interference in neuronal migration [121] - levels of zika viral RNA in fetal brain tissue are > 1000-fold higher than that found in placental tissue, suggesting zika replication in brain [135] - zika virus genome found in both maternal & neonatal tissues (amniotic fluid, cord blood, placenta, & brain) [121] - high levels of zika virus RNA in placental macrophages which have access to fetal circulation [135] (likely route of entry) - structure of zika virus [49] - male infant born with microcephaly in Brazil Zika viremia at least 67 days after birth; baby's mother had Zika symptoms during her 26th week of pregnancy [106] Genetics: - positive-sense RNA flavivirus in the family Flaviviridae [148] - single genetic mutation S139N in the prM protein of Zika may contribute to fetal microcephaly [147] Clinical manifestations: - most infected persons are asymptomatic [45] - symptoms are typically mild & last < 1 week - micropapular rash (86%), pruritus (82%) often intense [55,140] - rash generally widespread, involving a median of 45% body surface area [140] - common sites of involvement - face & upper limbs (95%), trunk (93%), lower limbs (86%) - palms (30%) & soles (13%) less frequently involved [140] - low-grade fever (56%) - arthralgia - nonpurulent conjunctivitis (56%) - dysethesia (52%) may be accompanied by autonomic symptoms [140] - some patients report this as one of the more bothersome & distinctive aspects of Zika [140] - fever, rash, myalgias, conjunctivitis - eye abnormalities in infants - focal pigment mottling of the retina - chorioretinal atrophy - optic nerve abnormalities [19] - zika tends to be mildly symptomatic in children affected postnatally [119] Laboratory: - zika virus serology* - serum samples should be obtained from the umbilical cord or from the infant within 2 days of birth [10] - Zika virus IgM in serum - first test in symptomatic women presenting 2-12 weeks after symptom onset [87] - followup testing in asymptomatic women in areas of active Zika transmitssion with negative serum Zika virus RNA [87] - IgM antibodies may persist > 12 weeks [144] - asymptomatic pregnant women not recommended unless woman not living in endemic area & > 2 weeks after prior exposure [157] - chikungunya/dengue/Zika serology screening panel FDA approved [44] - Zika virus RNA during 1st week after symptom onset [48,62,64] - Zika virus RNA in urine (test of choice) [64] - Zika virus RNA in serum [64] - Zika virus RNA in saliva [64] - symptomatic women or asymptomatic women in areas of active Zika transmission presenting < 2 weeks after symptom onset [87] - urine & serum Zika virus RNA - followup in symptomatic women with negative zika virus serology - zika viremia up to 8 weeks after symptom onset [130] - cases of pregnant women with Zika viremia 10 weeks [48] & 15 weeks [130] after symptom onset - a negative Zika virus RNA does not rule out Zika infection [69] - Zika serology & dengue serology should be performed [69] - pregnant women who develop symptoms while pregnant or if their sexual partner tests positive [142] - offer Zika RNA testing to pregnant women 3 times during pregnancy [144] - diminished sensitivity if performed > 2 weeks after exposure [156] - consider Zika virus RNA in amniotic fluid if available [142] - dengue + chikungunya + zika virus RNA - blood bank - FDA advises testing all donated blood & blood components for Zika virus [110] - universal screening of donated blood begins Nov 2016 [125] - cost $6-$10 per donation - screening of U.S. blood donations for Zika virus RNA is costly with low yield [154] - ARUP Zika virus consult includes CDC Zika virus testing info [126] * < 1% of asymptomatic people with potential Zika exposure tested for Zika are actually infected [58] * New York Department of Health recommends testing anyone > 5 years of age presenting with fever, generalized skin rash, arthralgias & conjunctivitis (3 of 4) for Zika virus [99] CDC recommendations in areas where both Zika & dengue are endemic [157] - nucleic acid amplification testing (NAAT) for dengue & Zika on serum samples collected <= 7 days after symptoms begin. - when NAAT results are negative, or serum samples are collected > 7 days after symptom onset, IgM antibody testing should be performed - if IgM antibody results are positive & NAAT results are negative, neutralizing antibody testing as indicated - for pregnant women: - serum & urine samples should be collected as soon as possible within 12 weeks of symptom onset for simultaneous NAAT & IgM serology for dengue & Zika - if IgM antibody results are positive & NAAT results are negative, neutralizing antibody testing as indicated [157] Special laboratory: - infants - hearing test - auditory brainstem response at 4-6 months if infant fails hearing screen - ophthalmoloscopy by 1 month of age if mom tests + [19,148] - neurologic examinations Radiology: - neuroimaging - cranial ultrasound if severe microcephaly [34] - intracranial calcifications in affected infants - CT & MRI findings [56]; (images & videos [105]) Complications: - fetal abnormalities in ~ 29% of pregnant women [39] - 6% of infants with birth defects [134,136] - 5% of infants with possible Zika infection in U.S. territories with birth defects [143] - brain abnormalities & microcephaly are the most common birth defects (89%) [143] - 10% of U.S. pregnancies with lab-confirmed Zika result in infants or fetuses with birth defects [141] - intrauterine growth restriction with or without microcephaly - central nervous system lesions - congenital contractures, craniofacial malformations, craniosynostosis, pulmonary hypoplasia [79] - fetal death after 30 weeks' gestation - abnormalities occur regardless of which trimester mother was infected [39] - miscarriage (Zika persists in fetal tissue > 21 days) [91] - 2% of Zika infected pregnancies [152] - microcephaly in affected infants - case reports in zika-infected pregnant women [2,22] - 1% in pregnant women infected with Zika virus in first trimester (French Polynesia Sept 2013 - July 2015) [42] - risk of microcephaly is 1-13% in 1st trimester [67] - 4% overall in zika-infected pregnant women [134,136] - severe brain malformations in infants with Zika-related microcephaly [50,53] - intracranial calcifications, primarily in frontal lobe & parietal lobe - white matter hypodensity [50] - 20% of definite or probable cases with head circumference within the normal range [79] - some infants without microcephaly have hydrocephalus [124] - a normal head circumference at birth can mask complications that only become apparent months later [128] - neuroimaging reveals malformations; all show decreased brain volume - of 19 infants born in Brazil with microcephaly, at 24 months - 15 with severe motor impairment [149] - 11 with seizures - 13 with hearing impairment - 11 with vision impairment - 10 with sleep disorder [149] - 14% of infants exposed to Zika in utero have health problems at 1 year of age [155] - not all health problems related to zika apparent at birth [155] - arthrogryposis multiplex congenita may occur in infants also born with microcephaly [97,121] - Guillain-Barre syndrome (GBS) in adults [9,108,109,112] - WHO reports 6-fold increases in Guillain-Barre syndrome in the state of Alagoas, Brazil near the center of the Zika- related microcephaly outbreak [20] - 86 cases of GBS in Columbia Jan 30 - Feb 2, 2016, all with symptoms compatible with Zika virus [26] - 252 cases of GBS cases reported in Venezuela Jan 2016, frequently with Zika symptoms [26] - 34 cases in Puerto Rico in 1st 1/2 of 2016 [108,109] - 0.24 cases of GBS/1000 Zika virus infections during Zika virus outbreak in 2013-2014 in French Polynesia [37] - median interval between viral syndrome & onset of neurological symptoms: 6 days - Zika IgM positive in 93% of GBS patients - RT-PCR for Zika virus negative in all GBS patients - findings confounded by edemic dengue virus [37] - 12 of 38 countries reporting Zika virus have also reported an increase in Guillain-Barre syndrome (GBS) or laboratory evidence of Zika among GBS patients [46] - autommune acute disseminated encephalomyelitis (ADEM) associated with demyelination in the brain & spina cord similar to multiple sclerosis - recovery within 6 months possible [51] - ocular abnormalities - hemorrhagic retinopathy - abnormal retinal vasculature - torpedo maculopathy [68] - sensorineural hearing loss in 6% of infants born with microcephaly [111] - neurologic or ocular defects highest when Zika infection occurs during 1st trimester (12.7%) vs 2nd (3.6%) or 3rd (5.3%) trimester [152] - transient hearing loss in adults [132] Differential diagnosis: - dengue incubation time 4-10 days - Chikungunya incubation is 48-72 hours [159] - rash of dengue not as prominent as Chikungunya or Zika - myalgia of dengue more prominent than Chikungunya or Zika - arthralgia of dengue less prominent than Chikungunya or Zika - severe, disabling arthralgias with high fevers suggest chikungunya - bleeding not a feature of Chikungunya or Zika - hemorrhagic complications suggest dengue [140] - shock not a feature of Chikungunya or Zika - conjunctivitis not a feature of dengue or Chikungunya [16] Management: - avoid mosquito bites so as to prevent transmission [45] - use mosquito repellant, protective clothing etc [45] - all pregnant women should be asked if they have recently traveled to areas with active Zika virus transmission - pregnant women with recent travel to areas with active Zika virus transmission & with symptoms of fever, rash, myalgias, or conjunctivitis during or within 2 weeks of travel should be tested for Zika virus - pregnant women who test positive for Zika, should have ultrasound every 3-4 weeks to monitor the fetus's growth - women with Zika virus should breastfeed their infants [33] - pregnant women should avoid 2016 summer Olympics in Brazil [36] - couples in Zika-affected areas should consider delaying pregnancy [70] - asymptomatic persons with possible exposure to Zika (travel to areas with active Zika virus transmission) should wait at least 8 weeks before trying to conceive [47] - women infected with Zika should wait at least 8 weeks after symptom onset before trying to conceive; men should wait at least 6 months [47] - progressive Guillain-Barre syndrome - IV immune globulin or plasma exchange [35] - 38% require intensive care - 29% need respiratory assistance - potential blood donors should defer giving blood for 28 dqys after visiting areas with Zika transmission [15,16,29], having symptoms suggestive of Zika virus in the past 4 weeks, or having sexual contact with a person who has traveled to, or resided in, an area with active Zika virus transmission during the prior 3 months [29] - potential blood donors living in Zika-affected donors are eligible for blood donation within the affected area [31] - donors should be deferred if Zika symptoms noted within the past 28 days [31] - people who develop Zika symptoms within 14 days of donating blood should contact the Red Cross so their donation can be quarantined - human cell & tissue donations if donor in past 6 months - has not been diagnosed with Zika - has not been in an area of active Zika transmission - has not had sex with a male having either of the above 2 risk factors [38] - standard precautions for health care providers [45] Prevention: - first vaccine candidate expected in September 2016 [52] - aerial insecticide spraying helped limit spread of Zika in Miami's Wynwood neighborhood [117] - WHO is exploring the release of genetically modified Aedes aegypti mosquitoes for control of Zika virus - release of sterile male mosquitoes or males with the naturally occurring Wolbachia bacteria - in both instances, when females mate with affected males, the eggs don't hatch [27] - infecting mosquitoes with Wolbachia, an endosymbiotic bacterium found in insects, may help limit spread of the Zika virus - pregnant women with partner possibly exposed to Zika should use barrier contraception or abstain from sex during pregnancy [88] - delay pregnancy for 9 months after possible Zika exposure [89] - asymptomatic men with possible zika exposure should wait at least 6 months before attempting conception [118] - abstinence or use of condoms for 6 months after zika exposure - long-acting reversible contraception (LARC) recommended - in states with Aedes mosquitoes capable transmitting Zika, use of LARC is low [94] - pregnant women who have been to Miami-Dade county Florida since Aug 21, 2016 should be tested for Zika virus [123] - pregnant women should avoid non-essential travel to 11 countries in southeast Asia (Sept 2016) [119] Pharmacology: - zika has oncolytic activity against glioblastoma stem cells [146] Comparative biology: - mouse model described [59,82] Notes: - Zika persistence in body fluids - plasma: median = 14 days, <5% > 54 days - urine: median = 8 days, <5% > 39 days - semen: median = 34 days, <5% 81 days [138]

General

flavivirus

Properties

KINGDOM: virus GENOME-TYPE: RNA SINGLE-STRANDED NEGATIVE-STRAND GENOME-SIZE: 10 kB ENVELOPE: PRESENT CAPSID-SYMMETRY: ICOSAHEDRAL

References

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