Louisville Medicine Volume 64, Issue 4 | Page 21

Zika virus ( ZIkV ) was originally isolated from a primate in Uganda in 1947 . It is a member of the Flaviviridae family which also includes closely related viruses that cause Dengue fever , Yellow fever , Chikungunya infection and West Nile infection . These viruses are primarily transmitted by the Aedes aegypti mosquitos in tropical areas . These mosquitos breed in pools of stagnant water and can survive indoors and outdoors . These mosquitos bite mostly in daylight hours . The mosquitos Aedes albopictus live in temperate climates and can transmit ZIkV as well . Florida health authorities are investigating the first indigenously-acquired ZIkV as of early August .

ZIkV has been associated with mild febrile disease and a maculopapular rash in tropical Africa and some areas in southeast Asia . Outbreaks occurred in several islands in the Pacific ( Micronesia in 2013 ), ( French Polynesia in 2014 ). In 2015 ZIkV outbreaks occurred in South America where it had not been previously identified .
The ZIkV outbreaks in South America are characterized by a dramatically increased risk of intrauterine or perinatal transmission of the virus and a resultant increase in the number of newborns with microcephaly ( 1 ). A recent prospective study showed fetal ultrasonographic abnormalities in 12 of 42 women ( 29 %) with ZIkV infections during pregnancy ; 7 of the 42 fetuses ( 17 %) had microcephaly , cerebral atrophy or brain calcification ( 2 ). Driggers et al reported in detail a case report of a patient and her husband infected by mosquitos in Guatemala at 11 weeks gestation . RNA for ZIkV was detected in maternal serum by reverse-transcriptase polymerase chain reaction ( RT-PCR ). ZIkV Ig M was positive at a titer greater than 1:2560 . A decrease in fetal head circumference from 47 th percentile at 16 weeks to 24 th percentile at 20 weeks was observed . Fetal MRI at 20 weeks showed multiple areas of diffuse brain atrophy , and the pregnancy was terminated at 21 weeks . Microscopic analysis showed abundant apoptoses primarily affecting the intermediately differentiated post migratory neurons in the neo cortex . The highest ZIkV viral loads were found in the fetal brain followed by placenta , fetal membranes and umbilical cord . Amniotic fluid levels were positive for ZIkV RNA in low count numbers . Maternal serum obtained the day before termination was positive for ZIkV RNA ( 10 weeks after initial infection ). ZIkV RNA became negative after delivery . ZIkV RNA in the spouse was negative in the urine at 11 weeks after travel , negative in the serum at 5 and 11 weeks after travel and negative in the semen at 10 and 12 weeks after travel . ( 3 )
The clinical manifestations of ZIkV indicate a short-lived illness lasting 2-12 days following a mosquito bite in 20 percent of patients . Symptoms include some fever 37 - 38C range , maculopapular rash , arthralgias of the hands and feet and non-purulent conjunctivitis . Additional symptoms may be headache , retro-orbital pain , myalgia and rarely abdominal pain , nausea , diarrhea , ulceration of mucus membranes and pruitus . The Guillian-Barre Syndrome ( GBS ), a polyneuropathy has been described in patients with ZIkV but the incidence is not yet known . GBS occurs at an incidence of 1 in 100,000 persons in the general population but could be 5 to 10 times more frequent in ZIkV infections . It is not known why 80 percent of persons bitten by mosquitos are asymptomatic .
Pregnant women are not known to have an increased susceptibility to ZIkV infections as compared to the general population . However , ZIkV-RNA has been detected in blood , amniotic fluid , semen , saliva , cerebrospinal fluid , urine and breast milk .
Pregnant women can be infected in any trimester of pregnancy and maternal-fetal transmission can occur throughout pregnancy . Males who have contracted ZIkV will have ZIkV-RNA in semen for greater than 30 days and in the case described above the pregnant patient was Zika RNA positive for 10 weeks and become Zika RNA negative in the early post-partum period .
Recommendations for pregnant women with a history of travel to areas with ZIkV transmission are seen in Table 1 ( page 20 ). ( 5 ) This table speaks to a variety of ZIKV testing and a more detailed explanation is seen in Table 2 ( page 20 ). ( 6 )
Since the only current method of prevention of ZIkV infection is to prevent mosquito bites , there are several insect repellents available that are safe in pregnancy . These repellents are listed in Table 3 ( page 21 ).
The hope for control of ZIkV infection depends on the development of an effective vaccine . Two recent publications have demonstrated both hope for a vaccine , and a great concern .
The study by Barba-Spaeth et al ( 6 ) assessed the activities of a panel of well-defined antibodies isolated from a patient with dengue that targeted the E protein of all four Dengue types ( DENV ) and found that two of the antibodies EDE1 and EDE2 strongly neutralized ZIkV in vitro . Dejnirattisai ( 7 ) performed studies with plasma collected from patients who had DENV infection and found that anti-DENV antibody neutralization of ZIkV was less efficent than neutralization of DENV . Further studies showed the plasma from patients with DENV infection had antibody-dependent enhancement ( ADE ) for ZIkV producing > 100 fold enhancement of infection of a human myeloid cell line . However , given that ZIkV and DENV are commonly present in the same geographic areas and anti-DENV have antibody enhancing activity for ZIkV , vaccine trials will have to be conducted with caution . The risk for ADE has been a major limiting factor in Dengue vaccine development and could similarly limit ZIkV vaccine development .
The major effects of ZIkV infection seems to occur in pregnant women . The testing protocols in Table 2 apply to all persons while the algorithm in Table 1 applies only to pregnant women . In the first four months of 2016 , there were 265 publications on ZIkV so the interest in this virus and its disease is intense .
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