ZIKA VIRUS Dr.L.Davoodi

virus first isolated in 1947 from a macaque in Zika forest of Uganda first human case reported in Nigeria in 1954

multiple epidemics reported to date * first large-scale outbreak spread in 2007 on Yap Island,Micronesia total of 49 confirmed and 59 probable cases

* second major outbreak reported in French Polynesia in total of 8,510 suspected cases reported

present outbreak began in Brazil in 2015 estimated 500,000 to 1.5 million persons in Brazil active transmission subsequently reported in neighboring regions and countries in South America, Mexico and Central America, and the Caribbean international spread of Zika virus from Brazil likely to occur due to high volume of tourism and wide distribution of Aedes mosquito vectors

in United States first case of Zika virus infection reported in January 2016 in a traveler returning from Latin America to Texas 1 case of sexual transmission reported in Febuary 2016 in Dallas, Texas in a person who had sexual contact with an ill person returning from Zika virus-active region

Risk factors residence in or travel to affected areas mosquito exposure

Associated conditions coinfection with other viral illnesses transmitted by same mosquito vector may occur coinfection with dengue and chikungunya reported in 49-year-old man in Colombia

Pathogen Zika virus is a single-stranded RNA virus of the Flaviviridae family, genus Flavivirus

Transmission transmitted primarily via bite of infected Aedes mosquito main reservoirs are likely human and nonhuman primates anthroponotic (human-to-vector-to-human) transmission occurs during outbreaks incubation period likely about 3 to 12 days but not precisely determined

maternal fetal transmission documented during pregnancy viral RNA detected in fetuses and placenta of infected women increased rate of microcephaly in fetuses and infants of infected women suggests virus is teratogenic

other potential modes of transmission * blood or blood products detection of Zika viral RNA in 3% of 1,505 blood donors who were asymptomatic at time of donation between November 2013 and February 2014 during outbreak in French Polynesia

sexual transmission 1 case of sexual transmission reported in February 2016 in Dallas, Texas in a person who had sexual contact with an ill person returning from Zika virus-active region) 1 case of possible spread of virus through sexual contact in 2008 has been reporteddetection of Zika virus in semen samples of 44- year-old man who presented with hematospermia during 2013 outbreak in French Polynesia

Zika can be passed from a man with symptoms to his sex partners before his symptoms start, while he has symptoms, and after his symptoms end. Men with Zika who never develop symptoms may also be able to pass the virus to their sex partners

breast feeding viral RNA has been detected in breast milk of infected women,no cases of transmission reported but this route of transmission not yet well evaluated

Pathogenesis virus infects and replicates in skin cells including dermal fibroblasts, epidermal keratinocytes, and immature dendritic cells infected epidermal keratinocytes rapidly undergo apoptotic cell death,viral replication induce innate immune response and production of type I interferons in infected cells virus disseminates likely via blood and infected persons typically remain viremic for a few days

Chief presentation about 20%-25% of infected persons develop symptoms when present, common symptoms include *acute-onset fever *rash, typically maculopapular *arthralgias and myalgias *conjunctivitis *headache

frequency of reported symptoms: fever in 73.2% maculopapular rash in 78% arthritis and arthralgia in 58.5% headache in 46.3% conjunctivitis in 46.3% fatigue or myalgia in 44% retro-orbital pain in 31.7% malaise in 22% joint swelling or edema in 19.5% abdominal pain in 14.6% chills and dizziness each in 12.2% anorexia and vomiting each in 10%

Making the diagnosis consider the diagnosis of Zika virus infection in patients with an acute febrile illness with one or more of the following symptoms maculopapular rash arthralgias conjunctivitis -a history of travel to an area with active transmission within 2 weeks of illness onset

ZIKV Serological Diagnosis  Flavivirus serology is complex due to extensive cross-reactivity between antibodies triggered by different flavivirus infections or vaccination.  Although some cross-reactivity can still occur, the most specific serology test for flaviviruses are virus neutralization tests.

Testing overview suspected cases should be reported to local health departments testing options include serum reverse transcriptase-polymerase chain reaction (RT-PCR) used during the first week of illness serum virus-specific immunoglobulin M (IgM) and neutralizing antibodies greater sensitivity at end of first week of illness cross-reacts with other flavivirus (such as dengue or Yellow fever) plaque-reduction neutralization assays, which can be used to distinguish among crossreacting flavivirus antibodies

Sample preservation  Keep refrigerated (2-8 °C) if it is to be processed (or sent to a reference laboratory) within 48 hours.  Keep frozen (-10 to -20 °C) if it is to be processed after the first 48 hours or within 7 days.  Keep frozen (-70 °C) if it is to be processed after a week. The sample can be preserved for extended periods.

Differential diagnosis

other DDX: malaria leptospirosis rickettsial infections influenza infectious mononucleosis acute HIV infection meningococcal disease measles rubella parvovirus B19 infection enteroviral infections scarlet fever (Group A Streptococcus) other alphavirus infections, which vary with geography Ross River virus disease (Australia and Oceania) Mayaro virus (South America) Barmah forest virus (Australia) O'nyong'nyong (Africa) Sindbis virus (Africa, Asia, Scandinavia, Russia) Semliki Forest virus (Africa)

Treatment overview no specific antiviral treatment for Zika virus is available supportive care is recommended, focused on rest, hydration, pain control, and fever Control,acetaminophen is generally preferred aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs) should be avoided until dengue, which carries risk of hemorrhage, can be ruled out most patients recover in about 5-7 days severe disease and need for hospitalization is uncommon infected patients should be advised to avoid mosquito exposure during first week of illness to reduce risk of local transmission

Guidelines for evaluation and management of pregnant women (CDC, 2016) ask all pregnant women about recent travel advise pregnant women to consider postponing travel to areas of active transmission if travel undertaken, advise strict adherence to mosquito avoidance strategies test any pregnant women who travelled to an area with active transmission in the past 2 weeks who has ≥ 2 of the following symptoms during or within 2 weeks of travel fever maculopapular rash arthralgias conjunctivitis or who has ultrasound findings of fetal microcephaly or intracranial calcifications

testing options include maternal serum antibody testing and reverse- transcriptase PCR (RT-PCR) amniotic fluid analysis via RT-PCR, for pregnant women who test positive perform serial ultrasounds to monitor fetal growth and anatomy

supportive care is the recommended treatment for pregnant,including rest,fluids,fever control,acetaminophen is preferred aspirin and other (NSAIDs) should generally be avoided in pregnancy and specifically avoided when dengue is a consideration as dengue diagnosis carries risk of hemorrhage for infants born to mother who had Zika virus infection during pregnancy or fetuses diagnosed with Zika virus in pregnancy obtain histopathology of the placenta and umbilical cord test frozen placental tissue and cord tissue for Zika virus RNA test cord serum for Zika and dengue virus immunoglobulin M (IgM) and neutralizing antibodies obtain immunohistochemical staining on fetal tissue, including placenta and umbilical cord in cases of fetal loss when Zika virus infection is suspected

Guidelines for evaluation and management of infants CDC infants with microcephaly or intracranial calcifications born to mothers who have traveled to or resided in an area with active transmission of Zika virus while pregnant infants born to mothers with positive or inconclusive test results for Zika virus test infant's serum sample for Zika virus RNA and IgM and neutralizing antibodies dengue virus IgM and neutralizing antibodies collect initial sample either from umbilical cord or directly from the infant within 2 days of birth, if possible cerebrospinal fluid may also be tested if available consider histopathologic examination of placenta and umbilical cord with immunohistochemical staining and reverse transcription-polymerase chain reaction (RT-PCR) on fixed or frozen tissue

General complications complications in the general adult population are rare Guillain-Barre syndrome Zika virus infection complicated by Guillain-Barre syndrome reported in 26 of 42 confirmed cases of Guillain-Barre syndrome in Brazil as of July 13, cases reported among 8,746 patients with suspected Zika virus infection during outbreak in French Polynesia

Prognosis most patients recover fully in 5-7 days severe disease and need for hospitalization is uncommon no reports of hemorrhagic fever reported to date disease-related mortality appears uncommon 3 deaths reported due to Zika virus infection in Brazil (1 in a newborn with microcephaly)

Prevention -no vaccine or preventive medications are available -mosquito avoidance to preventing illness when travelling to endemic -advise patients to avoid mosquitoes during viremic phase (first week of illness) to prevent local transmission -condom use -additional considerations for pregnant women or women trying to become pregnant

Recommendations for Travellers: There is no medicine or vaccine available Mosquito bite avoidance is strongly recommended for all travelers To help prevent others from getting sick, avoid mosquito bites during the first week of illness. Cannot donate blood for 4 weeks after return if you had no symptoms, or 6 months if you had symptoms of Zika.

Cover tightly with a lid all water tanks, cisterns, barrels, rubbish containers, etc. Remove or empty water in old tyres, tin cans, bottles, trays, etc. Check and clean out clogged gutters and flat roofs where water may have settled. Change water regularly in pet water dishes, birdbaths and plant trays. Introduce larvivorous fish (e.g., guppy) to ornamental water features as these eat the mosquito larvae. Trim weeds and tall grasses as adult mosquitoes seek these for shade on hot days.

Using sterile insects for population control The basic technique is to dose male insects with radiation, which makes them sterile. The sterile males are then released into the environment, where they mate with wild females. Females usually only mate once, so a female which mates with a sterile male doesn’t produce any offspring.

Sexual control Sexual activity or consistently and correctly use condoms during sex (i.e., vaginal intercourse, anal intercourse) for the duration of the pregnancy. Sexual precautions (Women who are not pregnant) should consider using contraception during travel and for 28 days on return to avoid an unplanned pregnancy occurring. – Men should consider using barrier contraception during travel and for 28 days on return to avoid the risk of sexual transmission of Zika virus and unplanned pregnancy. If symptoms of Zika develop in a man, barrier contraception should be used for 6 months after the infection has resolved to avoid the risk of sexual transmission of Zika virus and unplanned pregnancy.