Zika Virus Disease

WERNER SLENCZKA1
1

Philipps-University Marburg, Institute of Virology, 35037 Marburg, Germany

ABSTRACT The history of Zika virus disease serves as a

paradigm of a typical emerging viral infection. Zika virus disease,
a mosquito-borne avivirus, was rst isolated in 1947 in the
Zika forest of Uganda. The same virus was also isolated from
jungle-dwelling mosquitoes (Aedes [Stegomyia] africanus).
In many areas of Africa and South Asia human infections with
Zika virus were detected by both serology and virus isolation.
About 80% of infections are asymptomatic, and in 20% a mostly
mild disease with fever, rash, arthralgia, and conjunctivitis may
occur. Fetal infections with malformations were not recorded in
Africa or Asia. Zika virus was imported to northern Brazil possibly
during the world soccer championship that was hosted by
Brazil in June through July 2014. A cluster of severe fetal
malformations with microcephaly and ocular defects was noted
in 2015 in the northeast of Brazil, and intrauterine infections
with Zika virus were conrmed. The dramatic change in Zika
virus pathogenicity upon its introduction to Brazil has remained
an enigma.

ZIKA VIRUS DISEASE

Zika virus, a avivirus, is an example of an emerging
virus infection (16). The virus was rst isolated in
the Zika Forest, Uganda, in 1947 during a program on
yellow fever research. Rhesus monkeys were housed as
sentinel animals in cages in the rain forest. When one
of the animals developed fever, a lterable and mousepathogenic avivirus, closely related to the yellow fever
virus but not identical, was isolated from its blood.
Mosquitoes (Aedes [Stegomyia] africana) trapped in the
area were found to carry the virus. In tests with experimentally infected mosquitoes feeding on mice and on a
monkey, Zika virus was successfully transmitted (2, 7,
8). Zika virus infection is endemic in many regions of
sub-Saharan Africa and in South Asia (920). Jungle, or
sylvatic, transmission cycles serve as the virus reservoir
(12, 13, 17, 20). Infections with Zika virus are asymptomatic in approximately 80% of cases and cause only
mild illness, if any, in endemic regions (1012, 18, 20,

21). Upon importation to the Americas, where Zika

virus had not been previously reported, the virus caused
outbreaks of mostly asymptomatic mild illness, as
in Africa and Asia (3, 4, 22). The difference between
endemic transmission in the Old World and epidemic transmission in Brazil is the occurrence of prenatal infections with serious malformations in cases
when the mother had Zika virus disease during the rst
trimester of gestation (3).

ETIOLOGY
Zika virus is a avivirus, closely related to yellow fever
virus and classied as a member of the Spondweni group
(23). Flaviviruses are enveloped viruses of about 50 nm
in diameter. They have single-stranded nonsegmented
RNA genomes of positive polarity. In contrast to alphaviruses, translation of avivirus RNA does not include
formation of a subgenomic RNA; instead, a polycistronic polyprotein is made, which is cleaved by specic
proteases to yield three structural and seven nonstructural polypeptides. The C-protein is the capsid protein.
PrM (precursor of M) and E-proteins forming a heterodimer constitute the envelope of immature viruses,
which are released by budding from endoplasmatic
vesicles. During a ripening process prM is split by
Received: 29 February 2016, Accepted: 2 March 2016,
Published: 27 May 2016
Editors: W. Michael Scheld, Department of Infectious Diseases,
University of Virginia Health System, Charlottesville, VA; James M.
Hughes, Division of Infectious Diseases, Department of Medicine,
Emory University School of Medicine, Atlanta, GA; Richard J. Whitley,
Department of Pediatrics, University of Alabama at Birmingham,
Birmingham, AL
Citation: Slenczka W. 2016. Zika virus disease. Microbiol Spectrum
4(3):EI10-0019-2016. doi:10.1128/microbiolspec.EI10-0019-2016.
Correspondence: Werner Slenczka, slenczka-marburg@t-online.de
2016 American Society for Microbiology. All rights reserved.

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Slenczka

cellular proteases of the furin type into M-protein, and

this process results in a smooth virus surface which is
compared with a golf ball. E-protein is the receptorbinding protein, and in addition it functions as a fusion
protein (type 2 of fusion proteins) (24). The E-protein
contains a group-specic domain (A), a complex-specic
domain (B), and a subtype-specic domain (C) (24, 25).
These domains induce cross-reactive antibodies that
are able to react with antigens from other aviviruses.
Therefore, serologic tests for antibody against any avivirus may show broad reactivity against other aviviruses, especially shortly after infection. Anamnestic
responses from previous avivirus infections can produce enhancing antibodies against consecutive avivirus infections, ergo potentially enhance disease (25).
The pathogenesis of any avivirus disease is determined
by these anamnestic responses resulting from previous
infections or from vaccination.

OCCURRENCE OF ZIKA VIRUS INFECTION

There are only limited data on the seroprevalence of
Zika virus in human populations (1020). Zika virus
has been endemic in Africa and probably in South Asia
for a long time before it was introduced into the New
World, and that endemicity is based on the existence
of rural transmission cycles (9, 12). Prior to its emergence as a new pathogen in South America, Zika virus
activity was detected in several African and South Asian
countries by virus isolation and seroepidemiologic
studies on volunteers using neutralization assays. Zika
virus antibody was found in human sera from Uganda,
Tanzania, Ethiopia, Central African Republic, Gabon,
Sierra Leone, Republic of Nigeria, and in several Asian
countries (1016, 19). Seroepidemiologic studies were
performed in Nigeria between 1964 and 1970 (12, 14).
In one of these studies neutralizing antibody against
Zika virus was found in 40% of the sera (14). In the
course of these studies Zika virus was isolated from four
febrile children aged 10 months to 3 years. Additional
symptoms of Zika virus disease were not noted in these
children. In another case the virus was isolated from
a 10-year-old boy who had fever, headache, and generalized malaise (11, 14). This is probably the rst case
in which Zika virus was associated with specic symptoms. In addition, Zika virus was isolated from human
serum in Senegal and from a mosquito in Cte dIvoire
(18).
In South Asia Zika virus activity was established by
seroepidemiologic studies in India, Indonesia, Malaysia,
Thailand, Vietnam, and the Philippines (18, 19). Seven

cases of clinically apparent Zika virus disease were diagnosed serologically, indicating recent infections (18).
A subsequent seroepidemiologic study was performed on
human volunteers in Lombok, Indonesia, and showed
that 13% were positive (18). In 2007 an outbreak of
Zika virus occurred in Micronesia. Yap Island has approximately 6,300 inhabitants distributed in 10 municipalities. There were 49 conrmed and 59 probable cases
of Zika virus fever in 9 out of 10 municipalities. It was
estimated that 73% of the inhabitants had been recently
infected with Zika virus (5, 6).
The rst cases of locally transmitted Zika virus infections in Brazil were reported in 2015 (4). In December
the Brazilian Ministry of Health estimated that 440,000
to 1,300,000 cases of Zika virus disease had occurred
in Brazil by the end of 2015 (26). By 20 January 2016
locally transmitted Zika virus disease had been reported
to the Pan American Health Organization from 20
countries or territories in the Americas (26). These included Barbados (3 cases), Bolivia (4 cases), Brazil
(1.5 million cases) Columbia (20,000 cases), Ecuador
(33 cases), El Salvador (2,500 cases), French Guyana
(15 cases), Guadeloupe (1 case), Guatemala (68 cases),
Guyana (1 case), Haiti (125 cases), Honduras (3,649
cases), Martinique (47 cases), Mexico (37 cases), Panama (50 cases), Puerto Rico (22 cases), Saint Martin
(1 case), Suriname (6 cases), and Venezuela (4,700
cases). In the United States (80 conrmed cases) as well
as in several other countries of the northern hemisphere
importation of Zika virus infection in returning travelers
has been reported (2729).

TRANSMISSION
According to vector usage, aviviruses are subdivided
into three major groups: tick-borne viruses with more
than 10 members, mosquito-borne viruses comprising
about 130 members, and a third group of 20 viruses in
which vectors were not identied. It is important to
know that the host range of arthropod-borne viruses is
determined not only by viral surface proteins but also by
adaptation of the arthropods to their specic vertebrate
hosts. Vector usage has a signicant impact on arbovirus
epidemiology. The difference between urban and rural
infectious cycles is due to different species of vectors,
adapted either to urban or jungle habitats. Most aviviruses, including yellow fever, Dengue, West Nile fever,
and Zika virus, are transmitted by Aedes vectors; however, only a quarter of Aedes species bite humans. All
RNA viruses have a high mutation rate since they lack
proofreading mechanisms. New variants can therefore

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Zika Virus Disease

adapt not only to new hosts but also to new vectors.

Changes in host or vector specicity can result in the
emergence of new human pathogenic viruses.
A critical element in the epidemiology of arboviruses
is the mechanism by which arthropods are infected. The
female arthropod requires blood meals from vertebrates
and if, by chance, the vertebrate is viremic the virus can
infect the arthropod, which will transmit the infection
to another vertebrate host. In rural transmission cycles,
animals may be hosts, but in urban cycles humans are
the hosts.
If vertical infection in the arthropod can be excluded,
only blood meals on vertebrate hosts that have a high
virus titer can infect the arthropod. When viremia is
absent or exists only at a low titer, the infection chain
is aborted. Another prerequisite is that the host animals
should lack neutralizing antibodies. To replicate in different hosts, such as in vertebrates and in arthropods,
the potential for adaptation to both different host cells
and body temperatures is needed. Thus, only a few DNA
viruses are among the arboviruses.
The details of the epidemiology of Zika virus remain
to be elucidated. The virus may be transmitted by several
species of mosquitoes, mainly Aedes spp. Aedes aegypti
is the principal vector, at least in urban cycles. Zika virus
has produced only sporadic cases during a period of
60 years. Perhaps the virus was mainly propagated in
rural cycles between canopy-dwelling mosquitoes and
wild-living vertebrates, and the sporadic occurrence of
human cases resulted as an overspill from the jungle
cycles. Additionally, asymptomatic infections of humans
are frequent, and therefore a high proportion of the population may have acquired immunity. Thus, in endemic
regions Zika virus disease is more or less a childhood
illness, being included in the differential diagnosis of several other exanthemas (measles, rubella, Chikungunya, or
Dengue). In a mild course of a clinical disease no physician
would have ordered virological diagnostic investigations.
Notably, aviviruses are less pathogenic for children than
adults.
Zika virus is endemic in Africa and in South Asian
countries such as India, Indonesia, Thailand, Vietnam,
and Malaysia. Differences exist between African and
Asian strains of Zika virus and can be detected by RNA
sequencing. In respect to biological behavior and pathogenicity, there are no differences between African and
Asian strains. Undeniably, in South America as well as
some Pacic atolls, Zika virus has occurred in populations which had no previous exposure to this virus.
Thus, presumably, rural infectious cycles have not preexisted in South America. However, rural transmission

cycles of Zika virus are established in tropical and subtropical zones of the Americas. The consequence is that
Zika virus will be endemic in the New World in the same
way as has happened before with other arboviruses,
such as yellow fever, Dengue, and Chikungunya.
No data exist as to whether or not ornithophilic
mosquitoes and birds might be involved in the spread of
Zika virus. Considering that the virus took 60 years to
travel to South America and travelled west and not
north, it is unlikely that migrating birds have transported the virus. It is much more likely to assume that
Zika virus traveled to South America in the body of an
infected tourist or in a mosquito as a passenger in an
airplane.
A new development in Zika virus epidemiology is the
observation of vertical transmission and of transmission
in semen results in human infections (30, 31). Prenatal
infections are known to occur with several avivirus
infections such as Dengue, West Nile fever, and yellow
fever, but systematic studies are lacking. Often the consequence is spontaneous abortion or preterm delivery. In
the case of prenatal infections with yellow fever, mother
and child have little chance of survival. With Dengue
the mother and the newborn have severe hemorrhagic
complications. Historically, serious malformations as in
prenatal Zika virus infections have not been observed.
Vertical transmission of Zika virus from mother to fetus
has been proven in many cases. Sexual transmission
(30, 31), intrauterine transmission resulting in congenital infection (3236), intrapartum transmission from
a viremic mother to her child, blood transfusion (37),
and laboratory exposure (21, 34) are known routes of
infection in addition to mosquito bites. Retrospectively,
it will not be possible to conrm to what extent sexual
transmission might have contributed to the spread of
Zika virus in the Brazilian population.
Although Zika virus has been detected in breast milk,
transmission by breast feeding has not yet been reported.
There is concern about the possibility that transmission
might occur through organ transplantation, since many
cases are asymptomatic.
Intrauterine transmission of infection to the fetus is
a new manifestation of Zika virus disease. Likely, it
would have to be explained either by emergence of a new
virus variant or by accepting that in Africa and in South
Asia most women are immunized by asymptomatic infections during childhood. An additional possibility is
that in many countries malformations are not registered and children with serious malformations would
either be aborted or be killed after birth. Notably, enhancing antibodies resulting from previous exposure to

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Slenczka

aviviruses increases pathogenicity. Since an individuals previous exposure to other aviviruses is not
known in Zika virus patients, it can only be speculated
that differences in the gravity of symptoms might be
inuenced by enhancing antibodies. Coinfection with
Dengue and Zika virus occurs and might also increase
the pathogenicity of Zika virus infection (38). Coinfection is relevant not only in South America but also in
Asia and in Africa.
Sexual transmission has only recently been identied. The rst example of sexual transmission was with
Marburg virus disease (39). During the acute phase of
disease some male patients suffered from orchitis. One
of these patients infected his wife 4 months after the
acute phase of his disease. At this time he was no longer
viremic, and in the absence of another possibility, intercourse had to be assumed as the route of infection of
his wife, who fell ill with Marburg virus disease within
5 days after a single event of intercourse. Virus was
detected by injecting undiluted seminal uid into the
peritoneal cavity of guinea pigs. One of the animals fell
ill with fever, and Marburg virus was found in the liver
and spleen; the other animal remained healthy and did
not produce antibody. This means that the probe contained less than one infective dose. Seminal specimens
taken from the other male convalescents were negative.
Three female convalescents became pregnant and
gave birth to children between 1 and 2 years after their
disease. The children had transplacental IgG antibodies
at birth, which were catabolized in the course of several
months.
With Ebola as in Marburg virus seminal virus excretion is not necessarily combined with viremia and is
probably due to virus persisting in the testes. Sexual
transmission of loviruses from viremic people at the
end of incubation and before onset of symptoms is
possible.
As to the sexual transmission of Zika virus, some of
the male partners have had only mild or asymptomatic
infections. The possibility exists that clinical disease may
be preceded by viremia and seminal shedding of virus.
There is at present not enough information to determine
if the donors were viremic at the time of the intercourse
or had any symptoms of orchitis. It is not known
whether Zika virus can be transmitted from the female
partner to the male.
Since vertical virus transmission and sexual transmission of Zika virus can occur in people who are not
aware of their infection even with clinical mild or
asymptomatic illnesses, likely, viremic blood donors can
transmit Zika virus by transfusion (40).

Up to this time viral isolates have been obtained

from the following mosquitoes: A. africanus, Aedes
apicoargenteus, Aedes luteocephalus, A. aegypti, Aedes
vittatus, and Aedes furcifer (2, 12, 20).

CLINICAL MANIFESTATIONS
Zika virus disease is characterized as an inuenza-like
illness. The outbreak of Zika virus disease in Yap Island
in 2007 was the rst outbreak which had occurred at
that time and was characterized by rash, fever, conjunctivitis, and arthralgia. In some patients myalgia,
headache, retro-orbital pain, edema, and vomiting were
noted. None of the patients required hospitalization,
and no deaths resulted (1, 3, 5). Before this event only 14
cases of the disease had been conrmed by viral diagnostic techniques in Africa and in South Asia. The bestconrmed case was an occupationally acquired illness
that was described by the patient himself (21). The disease began with mild headache followed the next day
by a maculopapular rash covering the face, neck, trunk,
and palms and soles. At the same time the patient had
fever and suffered from malaise and back pain. The
general symptoms lasted for only 2 days. By the 2nd day
of disease the patient was afebrile. The rash disappeared
2 days later. Zika virus was isolated from his serum,
which was obtained while febrile. Another case was a
laboratory-acquired infection (37). This patient developed acute onset of fever, headache, and joint pain but
did not develop a rash. Zika virus was isolated from his
serum on the rst day of his illness. About a week after
onset of the symptoms the illness had resolved.
Seven patients were observed in Indonesia (18). All of
them had fever, anorexia, diarrhea, constipation, abdominal pain, and dizziness. None of the patients had
rash; conjunctivitis was found in one case only. As noted,
most Zika virus infections remain clinically inapparent,
and the majority of clinically apparent infections are
characterized by a mild course and short duration. Zika
virus disease in South America remains predominantly
asymptomatic (80%) (35). Clinically apparent courses
had only a mild form of disease. The malformations observed upon intrauterine Zika virus infection include
microcephaly and severe ocular changes. Previously,
intrauterine infections had not been noted in regions
of Africa and South Asia or on Yap Island (6) in spite of
sexual transmission (3, 30, 31).
The dramatic increase in pathogenicity, which is observed in Brazil, would have to be explained either by
emergence of new virus variants or by special features
of the epidemic situation, e.g., changes in vector usage

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Zika Virus Disease

or absence of previous immunologic experience with

the new virus. Virus transmission via the sexual route
shortly before, during, or after the time of conception
might be a conditioning factor of fetal infection. Enhancing antibodies resulting from previous infections
with aviviruses or coinfection with either Dengue or
Chikungunya might also play a role in the pathogenesis
(38). These questions will have to be elucidated in the
future.

COMPLICATIONS OF THE DISEASE

The most serious complications result from prenatal
infection of the fetus during the rst trimester of pregnancy. Microcephaly and eye defects are described and
were conrmed by viral diagnostic tests in about 1% of
suspected cases. In a well-documented case a European
woman became pregnant during a stay in Natal, the
capital of the Rio Grande del Norte state (32). In her
13th week of gestation she fell ill with high fever, musculoskeletal and retro-orbital pain, and a generalized
maculopapular rash. Ultrasonography revealed a normal fetus at 14 and at 20 weeks. Ultrasonography performed at 32 weeks of gestation revealed a placenta with
numerous calcications and a fetus with microcephaly
with numerous intracranial calcications. The pregnancy was terminated at this time and the fetus was
autopsied. Macroscopic inspection of the brain revealed
microcephaly, widely open sylvan ssures, a small cerebellum and brain stem, and almost complete agyria.
Histopathological ndings included multifocal collections of lamentous, granular, and neuron-shaped calcications in the cortex, the subcortical nuclei, and the
subcortical white matter with focal involvement of the
cortical ribbon. Diffuse astrogliosis was present with
focal astrocytic outburst into the subarachnoidal space.
Activated microglia cells and macrophages were present throughout the gray and white matter. Scattered
perivascular inltrates of T-cells and some B-cells were
present. The cerebellum, brain stem, and spinal cord
revealed neither inammation nor dystrophic calcications. However, the brain stem and spinal cord showed
Wallerian degeneration of the lateral corticospinal tract,
whereas ascending dorsal cords were well preserved.
Immunouorescence revealed intracytoplasmic reaction
in destroyed neuronal structures. By electron microscopic examination, clusters of dense virus-like particles
of 50-nm size were found in damaged cytoplasmic vesicles. Positive results for Zika virus RNA were obtained
only in the fetal brain, with 6.5 x 107 copies per milligram of brain tissue. PCR assays for other aviviruses

(Dengue, yellow fever, West Nile fever, and Central European encephalitis [CEE]) and other viruses (Chikungunya,
lymphocytic choriomeningitis, cytomegalovirus, rubella,
varicella zoster, herpes simplex, and parvovirus B19) and
for Toxoplasma gondii were negative. A complete genome
sequence was recovered from brain tissue and showed
identity with a Zika virus strain isolated in Cambodia
(98.3%) and with a strain from the outbreak in Micronesia
(98.0%).
Ophthalmopathological defects are mostly associated
with microcephaly in children with prenatal Zika virus
infection (3436). They include macular alterations (pigment mottling, and/or chorioretinal atrophy) and optic
nerve abnormalities (hypoplasia with double-ring sign
and/or increased cup-to-disk ratio).
In some cases Zika virus disease is followed immediately by Guillain-Barr syndrome. In a well-documented
case a female patient, 40 years old with a history of
rheumatoid arthritis, succumbed following an inuenzalike illness with paresthesia and tetraplegia, diffuse
myalgia, and peripheral facial palsy (41). Deep tendon
reexes were absent. The patient developed chest pain
with sustained ventricular tachycardia and orthostatic
hypotension. Electrocardiography did not reveal signs of
myocarditis or pericarditis. Treatment with polyvalent
immunoglobulin resulted in improvement. The patient
survived and was discharged on day 13. Blood samples
taken on day 8 after disease onset were negative in a
Zika virus PCR test. Serological analysis revealed IgG
antibodies against Dengue 14 antigens and IgM antibodies against Zika virus antigen.

PATHOGENESIS
It is thought that mosquito-borne aviviruses replicate
immediately after infection in dendritic cells near the
site of inoculation and spread to the lymph nodes and
the bloodstream, where they cause microangiopathy and
rash (25). Invasion of the brain is believed to result from
infection of microglial cells, which serve as a Trojan
horse (42). The pathogenesis of developmental retardation and organ defects is not clear. Hypoxia due to
microvasculitis and thrombosis may also be involved.
With rubella embryopathy is a direct effect of virus
replication, virus-induced apoptosis of noninfected cells,
and inhibition of mitosis. Maternal antiviral immune
reactions, specic and innate, may play a role. IFN-1,
binding to cellular receptors, mediates downregulation
of the enzyme superoxide dismutase, the most powerful intracellular antioxidant. With respect to aviviruscaused embryopathy, there is a decit in knowledge (43).

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Slenczka

The dramatic change in the pathogenesis of Zika virus

disease observed after its importation to Brazil remains
an enigma (3, 3236). While Zika virus infected an immunologically nave population, fetal malformations
were not noted in other previously uninfected populations (3, 5). Zika virus could have been spread both by
mosquitoes and by sexual transmission, facilitating
transmission to the fetus.

DIAGNOSIS
Flavivirus serology is complicated by group-specic,
complex-specic, and subtype-specic cross-reactivities
associated with domains A, B, and C of the viral E-protein.
Neutralization tests are believed to be the most specic
tests, but even in these tests, antigenically related viruses
should be included as controls. All seroepidemiological
results in which other avivirus antigens are not included
are at least subject to criticism.
Virus can be isolated in mosquito cells, but reverse
transcription PCR (RT-PCR) is the technique of choice
for detection of the virus (44, 45). A real-time RT-PCR
for amplication of the NS5 coding regions is recommended (44). Primers are designed from conserved regions, and for identication the amplication product
must be sequenced and compared with GenBank. Quantitative analysis allows determination of the titer of viremia. A problem is the cocirculation with other aviviruses,
which may result in coinfection with another virus (38).

antiviral therapy, since most patients have mild courses

of illness. Supportive treatment should include rest and
uids. Analgesics and antipyretics may be allowed, but
aspirin or other nonsteroidal anti-inammatory drugs
(NSAIDs) should be avoided until Dengue can be ruled
out to reduce the risk of hemorrhagic disease. For febrile
pregnant women acetaminophen is recommended. Patients with Zika virus, Chikungunya, Dengue, or other
arboviral disease must be protected from mosquitoes to
avoid transmission to other people (3).

PROPHYLAXIS

Zika virus infection should be considered in cases with

inuenza-like disease with acute onset of fever, maculopapular rash, arthralgia, and/or conjunctivitis, especially
when the patient has traveled to areas with ongoing Zika
virus transmission in the 14 days preceding onset of the
illness. Dengue and Chikungunya viruses share the same
geographic prevalence with Zika virus, and they produce
clinical pictures resembling Zika virus disease. Therefore,
Dengue and Chikungunya are differential diagnostic
considerations. Coinfection of Zika virus with Dengue or
with Chikungunya may occur, confounding diagnosis
(38). Other diseases to be considered are malaria, rubella,
measles, parvovirus B19, adenovirus, enterovirus, leptospirosis, rickettsiae, and group A streptococcal infections.

A vaccine against Zika virus is not available. In avivirus infections, the value of antiviral immunoglobulins
for therapy or prophylaxis is controversial. In some
reports it was judged to be helpful, while other reports
suggest an unfavorable outcome. Specic experience
with immunoglobulins in Zika virus disease does not
exist. The best way to avoid Zika virus infection is to
prevent mosquito bites by using air conditioning, closed
windows, or window and door screens when indoors.
For outdoor activities it is recommendable to wear long
sleeves and pants and permethrin-treated clothing and
to use insect repellents (3, 46, 47). Most repellents, including N,N-diethyl-m-toluamide (DEET), which is registered by the Environmental Protection Agency (EPA),
are safe and can be used on children >2 months old.
When used according to the product label, EPA-registered repellents are also safe for pregnant and lactating
women. All travelers, and especially pregnant women,
should take measures to avoid insect bites and arboviral
infections (3, 47, 48). Zika virusinfected people may
appear healthy and asymptomatic although they have
viremia and may shed the virus (49). To avoid transmission of Zika virus via blood donations, blood banks will
have to explore the travel anamnesis of their donors (49).
Assuming that sexual transmission might be relevant
in the epidemiology and to prevent fetal infection, protection by using condoms is recommended. Application
of vaginal rings shedding an antiviral substance such as
Dapivirine could be useful but is not yet approved for
this purpose (50).
In addition, public health measures should control the
reservoirs of drinking water to destroy mosquitoes
breeding places (51).

THERAPY

CONCLUSIONS

Specic antiviral therapeutics are not yet available for

avivirus infections. Principally, there is no need for

Zika virus, a avivirus of African origin was introduced

to the Americas about 70 years after its discovery.

DIFFERENTIAL DIAGNOSIS

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Zika Virus Disease

Control of this new emerging pathogen will require new

strategies to prevent sexual transmission, prenatal infections with serious malformations, and Guillain Barr
syndrome in addition to measures against its arthropod
vectors Aedes aegypti and Aedes albopictus. Since antiviral therapeutics and a vaccine are not yet available, the
population can only be protected by individual prophylaxis and by elimination of the larvae in the breeding
places.
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