Zika Virus Infection

Zika virus infection
The right clinical information, right where it's needed
Last updated: Aug 09, 2018

Table of Contents
Summary 3
Basics 4
Definition 4
Epidemiology 4
Aetiology 5
Pathophysiology 7
Prevention 8
Primary prevention 8
Screening 10
Secondary prevention 11
Diagnosis 12
Case history 12
Step-by-step diagnostic approach 12
Risk factors 20
History & examination factors 22
Diagnostic tests 25
Differential diagnosis 29
Diagnostic criteria 32
Treatment 34
Step-by-step treatment approach 34
Treatment details overview 35
Treatment options 37
Emerging 40
Follow up 41
Recommendations 41
Complications 43
Prognosis 44
Guidelines 45
Diagnostic guidelines 45
Treatment guidelines 47
Online resources 51
References 53
Images 70
Disclaimer 75
Summary
◊ Majority of patients are asymptomatic; however, about 20% of infections result in a mild, self-limited
illness with fever, rash, arthralgia, and conjunctivitis.
◊ There is strong scientific consensus that Zika virus is a cause of microcephaly and other congenital
abnormalities. The range of abnormalities seen and the likely causal link to the virus suggest a new
congenital syndrome. Pregnant women are advised not to travel to areas with infection risk.
◊ Guillain-Barre syndrome and other neurological disorders are strongly associated with, and
suspected to be caused by, Zika virus but the link is unproven and studies are ongoing, including to
elucidate a possible mechanism.
◊ Treatment of symptomatic infection is supportive and there are no specific antiviral therapies at this
time. Prevention of mosquito bites through individual and public health measures is important to
prevent infections.
Zika virus infection Basics
Definition
A mild, usually self-limited infection when symptomatic (about 20% of infections) caused by the Zika virus
(also known as ZIKV). The virus belongs to the Flaviviridae family (genus Flavivirus ) and is an arbovirus (a
BASICS
virus transmitted by arthropods). It is named after the Zika forest in Uganda where it was first discovered in
1947.[1]
It is transmitted to humans primarily by the Aedes species of mosquito which is also a vector for dengue,
chikungunya, and West Nile viruses. Sexual transmission from person to person is also possible.
Congenital Zika syndrome is a recognised pattern of congenital anomalies in infants (i.e., microcephaly,
intracranial calcifications or other brain anomalies, or eye anomalies, among others) associated with
Zika virus infection during pregnancy.[2] [3] [4] [5] [6] According to the World Health Organization (WHO),
there is strong scientific consensus that Zika virus is a cause of microcephaly and these other congenital
abnormalities.[7] The Centers for Disease Control and Prevention (CDC) has also concluded that there is a
causal relationship between antenatal Zika virus infections and microcephaly/other brain abnormalities.[8]
Preliminary results from a case-control study have also suggested that Zika virus causes microcephaly.[9]
Guillain-Barre syndrome and other neurological disorders are strongly associated with and suspected to
be caused by Zika virus infection but the link is unproven and studies are ongoing, including to elucidate a
possible mechanism.[10] [11] [12] [13]
[CDC: Zika virus]
[WHO: Zika virus disease]
[Pan American Health Organization: Zika virus infection]
Epidemiology
Zika virus was first discovered in the Zika forest of Uganda in 1947 in rhesus monkeys, but was not identified
in humans until 1952 in Tanzania.[18] [19] Since then, outbreaks have occurred sporadically in Africa, the
Americas, Asia, and the Pacific. Until 2007, only 14 cases had been documented in humans worldwide.[20]
The first large outbreak was reported on the island of Yap (Federated States of Micronesia) in 2007.[21]
[22] The most likely source of this outbreak was introduction of the virus by travel or trade involving an
infected person or an infected mosquito.[1] Another large outbreak was seen in the Pacific Islands (French
Polynesia, Easter Island, the Cook Islands, New Caledonia) in 2013 to 2014. This was the first outbreak
where congenital malformations (e.g., microcephaly) and neurological complications, including Guillain-Barre
syndrome (GBS), were linked to the infection, although this association was made retrospectively.[21] [23]
[24]
In the current outbreak, the first reports of locally transmitted infection came from Brazil in May 2015,
although there are data to suggest that the virus originated in the Americas in Brazil between October
2012 and May 2013.[25] Eighty-six countries, territories, and subnational areas have reported evidence of
mosquito-borne Zika virus transmission.[26] Transmission is ongoing in the Americas, the Western Pacific
region, the Southeast Asia region, and Africa.
Cases in returning travellers have been reported in, but not limited to, locations including the UK, Europe,
US, Australia, New Zealand, Israel, Japan, and China.[27] [28] [29] [30] [31] [32] [33] [34] [35] As of
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November 2017, 305 cases were reported in the UK, all of them associated with travel.[36] Between June
2015 and January 2017, 21 countries in the European Union reported 2133 confirmed cases of infection
(106 cases in pregnant women).[37] WHO has warned that the risk of Zika virus transmission in Europe
is low to moderate, although 3 areas are at high risk: the island of Madeira in Portugal, Georgia, and the
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southern part of the Russian Federation.[38]
An association between Zika virus infection and fetal microcephaly, as well as other birth defects, was first
reported in the current outbreak in October 2015.[39] The prevalence of birth defects potentially related
to Zika virus infection was reported to be 3 per 1000 live births in a birth cohort of nearly 1 million births
in 2016.[40]Data from the US Zika Pregnancy Registry found that 10% of pregnancies with laboratory-
confirmed infection resulted in fetuses/infants with birth defects. This figure increases to 15% when restricting
the analysis to the first trimester.[41] This report covered cases reported in US states only. A more robust
study of completed pregnancies in women with laboratory evidence of Zika virus infection in US territories
found approximately 1 in 20 (5%) fetuses or infants had a possible Zika-associated birth defect. When the
analysis was restricted to confirmed infection in the first trimester, the rate increased to 1 in 12 (8%).[42]
An association between Zika virus infection and GBS was first reported in the current outbreak in July 2015.
Current evidence estimates the incidence of GBS to be 24 cases per 100,000 persons infected with Zika.[43]
GBS has not been reported in children.[44]
[CDC: Zika virus case counts in the US]
[WHO: Zika virus classification tables]
[European Centre for Disease Prevention and Control: threats and outbreaks of Zika virus disease]
Aetiology
Zika virus is a single-stranded RNA virus of the Flaviviridae family (genus Flavivirus ), and is related to the
dengue, yellow fever, West Nile, and Japanese encephalitis viruses.[45] A 3-dimensional map of the virus
structure has shown that the Zika virus is similar in structure to the West Nile virus, Japanese encephalitis
virus, and Dengue virus.[46] The structure of non-structural protein 5 (NS5) has also been reported,
providing an important target for future drug therapy.[47] The complete genomes for the Asian- and African-
lineage viruses have been sequenced.[48] [49] There are two major lineages: the African lineage (reported
in Africa only) and the Asian lineage (reported in Asia, the Western Pacific Region, the Americas, and Cabo
Verde).[26] Phylogenetic analysis has revealed that current epidemic strains have accumulated multiple
substitutions from their Asian ancestor which may make the current strains more virulent to humans.[50]
Transmission to humans is primarily through the bite of an infected Aedes species mosquito. It is most
commonly transmitted by the A aegypti species which lives in tropical regions, but can also be carried by
A albopictus which lives in temperate regions.[45] [51] [52] The same species of mosquito transmits the
chikungunya, dengue, and West Nile viruses, although the Culex species of mosquito is the primary vector
for West Nile virus. There is emerging evidence that Zika virus could also be spread by C quinquefasciatus
,[53] although this has been disputed.[54] [55] [56] Non-human and human primates are likely to be the
main reservoirs of the virus, and anthroponotic (human-to-vector-to-human) transmission occurs during
outbreaks.[52]
Non-vector transmission events (e.g., perinatal,[57] in utero,[58] [59] sexual,[57] [60] [61] and transfusion
transmission[62] [63] [64]) have also been reported.[65] Transmission via platelet transfusion has been
This PDF of the BMJ Best Practice topic is based on the web version that was last updated: Aug 09, 2018.
5
reported in Brazil.[66] Infection has been reported in a small series of hepatic and renal transplant
recipients,[67] and infection with Zika was strongly suspected in a paediatric patient who developed Guillain-
Barre syndrome after haematopoietic stem cell transplant in one case report.[68] Further studies are required
to investigate these modes of transmission.[69]
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Nearly all reported cases of sexual transmission involved vaginal or anal sex with men during, shortly before
onset of, or shortly after resolution of symptomatic illness consistent with acute Zika virus infection. However,
there have been 2 cases of asymptomatic male to female transmission.[70] Sexual transmission from women
to their sexual partners has been reported,[71] as has male-to-male sexual transmission.[72] There is the
possibility of oral transmission of the virus through semen.[73]Evidence suggests that the virus is present
in semen and urine for longer periods than in blood or saliva.[74] [75] [76] A cohort study of 184 men with
confirmed symptomatic infection found that Zika virus RNA was detected in 61% of semen samples collected
within 30 days of symptom onset, 43% of samples collected within 31 to 60 days of symptom onset, and 21%
of samples collected within 61 to 90 days of symptom onset. Less than 7% of samples had detectable levels
of Zika virus RNA more than 90 days after symptom onset.[77]
Zika virus RNA has been detected in body fluids other than blood and semen, including amniotic fluid, CSF,
urine, saliva, vaginal secretions, and ocular fluids; however, transmission via these body fluids has not yet
been fully elucidated.[59] [78] [79] [80] [81] [82] [83] The virus may persist for up to 80 days in the blood,[84]
and persists in the blood longer than plasma.[85] The virus has been detected in the genital tract of an
infected woman, which may have implications for vertical transmission.[86] It has also been detected in fetal
tissue. Viraemia has been reported in a newborn at least 67 days after birth.[87] While the virus has been
detected in breast milk, there are no reports of transmission via breastfeeding.[88]
Occupational exposure in healthcare personnel is possible via a percutaneous injury (e.g., needlestick injury)
or direct contact of mucous membrane (or non-intact skin) with blood, tissue, or other body fluids that are
infectious.[89]
The Centers for Disease Control and Prevention (CDC) investigated how a family contact of a patient
who died of Zika virus infection in Utah became infected. The deceased patient had very high levels of
circulating virus, and the family member had close contact with the patient (i.e., kissing and hugging). The
mechanism of transmission remains unknown, but was likely to be from person-to-person contact with the
index patient.[90]
Viraemic travellers (who are often asymptomatic) have introduced the virus into countries where susceptible
Aedes species mosquitoes become infected and initiate and perpetuate local transmission cycles.[91]
Possible co-infection with dengue and chikungunya viruses has been reported; however, this is yet to be
confirmed.[92] [93] [94] [95] There has been a case report of triple co-infection with Zika, chikungunya, and
dengue viruses.[96]
The Brazilian government is investigating whether factors other than Zika virus infection (e.g., poor hygiene,
co-infection with other viruses) are involved in the development of microcephaly because there is an
unexpected and uneven distribution of cases of microcephaly across Brazil.[97]
Pathophysiology
The incubation period after transmission is between 3 and 14 days.[98] The pathogenesis of infection is
unclear; however, flaviviruses in general are thought to replicate initially in dendritic cells near the site of
BASICS
inoculation and spread to the blood and lymph nodes.[99] Viraemia generally lasts up to 1 week in patients
with clinical illness.
Zika virus is a neurotropic virus which has been shown to target neural progenitor cells, as well as neuronal
cells at different states of maturity but to a lesser extent.[7] In one in vitro study, a strain of Zika virus was
serially passaged in monkey and mosquito cells and efficiently infected human neural progenitor cells derived
from induced pluripotent stem cells. Zika virus infection increased cell death and dysregulated cell-cycle
progression, resulting in attenuated cell growth.[100] Another study found that the virus infects human
cortical progenitor cells leading to cell death by apoptosis and autophagy.[101]
Despite mild clinical symptoms, gestational Zika virus infection is associated with fetal death, placental
insufficiency, fetal growth restriction, and CNS injury.[102] Based on an average full-term gestation, the
24-week period from the peak of the Zika virus outbreak to the peak in reported microcephaly occurrence
suggests that the greatest risk for microcephaly is associated with Zika virus infection during the first
trimester and early in the second trimester of pregnancy.[103] However, CNS abnormalities have been
reported with exposure as late as 39 weeks’ gestation.[104] A case report found that fetal microcephaly may
be caused by a loss of intermediately differentiated post-migratory neurons through an apoptotic mechanism
in the mid-gestational fetal brain.[105] It has been suggested that the germinal matrix is the principal target
for the virus.[106] Mouse studies provide evidence for a direct causal link between Zika virus infection and
microcephaly by causing cell-cycle arrest, apoptosis, and inhibition of neural precursor cells.[107] [108]
[109] [110] It appears that the virus triggers cell behaviours that alter normal cell proliferation and survival
of neural progenitor cells during critical periods of brain development.[111] The role of the placenta in fetal
microcephaly is not clear but it has been hypothesised that the placenta might facilitate viral transmission
to the fetus, or alternatively to contribute a damaging immune response.[112] One hypothesis is that the
virus gains access to the fetal compartment by directly infecting placental cells, thereby disrupting the
placental barrier.[113] There are data to suggest that for the virus to enter the fetal compartment, it must
evade trophoblast-derived interferon-lambda-1.[114] Another study found that placental infection induces
proliferation and prominent hyperplasia of Hofbauer cells in the chorionic villi.[115] The virus can continue
to replicate in infants’ brains after birth, and can persist in the placenta for months.[116] Further studies are
required to understand the full spectrum of Zika-associated congenital abnormalities and their pathogenesis,
including systematic examination of fetal and neonatal autopsy tissues and placental tissue from living infants
with microcephaly.[117]
A case report of Guillain-Barre syndrome developing while the Zika virus was still present in serum suggests
that the virus may exert its neurotropic effects by either direct neural injury or a rapid cellular-mediated
response to the virus with cross-reactivity against peripheral nerves. The neuroinvasion processes are not
fully understood and further study is needed.[118] Mouse studies suggest adult neural stem cells are also
vulnerable to Zika neuropathology.[119]
The presence of antibodies against other flaviviruses may enhance Zika infection, resulting in more severe
infection; however, this hypothesis has only been tested in animal models so far, and further research is
warranted.[120]
7
Zika virus infection Prevention
Primary prevention
There are currently no vaccines for prevention, although they are in development. Zika purified inactivated
virus (ZPIV) vaccine, an investigational vaccine, has started clinical trials to test safety and efficacy in the
US.[132]
Primary prevention currently relies on mosquito bite prevention and mosquito population control (e.g.,
removing or modifying breeding sites), as well as the prevention of non-vector transmission (e.g., sexual,
transfusion, nosocomial).
Mosquito bite prevention and population control
• The World Health Organization (WHO) and Centers for Disease Control and Prevention (CDC)
recommend the following bite prevention measures:[133] [134]
• Wearing clothes that cover as much of the body as possible (e.g., long-sleeved shirts and long
trousers); clothes may be treated with permethrin
• Staying in places with air conditioning or that use window and door screens to keep mosquitoes
PREVENTION
outside
• Sleeping under a mosquito net (possibly impregnated with insecticide)
• Using approved insect repellent (if ≥2 months of age); DEET, picaridin, and IR3535 can be
safely used in pregnant and breastfeeding women when used as directed[135]
• Covering cribs, strollers, or baby carriers with a mosquito net
• Emptying, cleaning, or covering containers that can hold water to reduce areas where
mosquitoes can breed including in and around households.
• The main way to prevent congenital Zika virus infection is to prevent maternal infection using mosquito
bite prevention measures.
• Travellers returning from areas of ongoing transmission should use mosquito bite prevention measures
for 3 weeks after returning to prevent spread to uninfected mosquitoes.[134]
• During outbreaks, insecticide spraying (using an insecticide recommended by the WHO) may be
carried out.
• The development of Aedes aegypti mosquitoes that are resistant to arbovirus infection is a preventive
approach that shows promise.[136] [137] The US Food and Drug Administration (FDA) has released
a report concluding that a field trial of genetically modified mosquitoes would pose no significant
environmental impact in Key Haven, Florida; however, further regulatory requirements are needed
before these mosquitoes are approved for commercial use.[138]
Prevention of sexual transmission
• Recommendations for pregnant couples: the CDC recommends that pregnant women with male or
female sex partners who live in or have travelled to an area with active transmission should abstain
from sex (vaginal, anal, oral) or use barriers against infection (e.g., condoms) during sex for the
duration of the pregnancy. Additionally, the CDC recommends that pregnant women talk with their
healthcare providers about their sex partner’s potential exposures to Zika virus and symptoms of Zika-
like illness.[139]
• Recommendations for non-pregnant couples: the CDC recommends that if only the female partner
travels to an area with risk for transmission, the couple should use condoms and abstain from sex
for at least 2 months after the female partner's symptom onset (if symptomatic) or last possible
exposure (if asymptomatic). However, if the male partner (or both partners) travel to an area with risk
for transmission, the couple should use condoms and abstain from sex for at least 3 months after the
male partner's symptom onset (if symptomatic) or last possible exposure (if asymptomatic).[139]
• The WHO still recommends safe sex practices for at least 6 months in men or women returning from
areas with active transmission, regardless of whether they are symptomatic or asymptomatic.[70]
Pregnancy prevention
• Healthcare providers should discuss reproductive life plans (including intention of pregnancy and
timing of pregnancy) with women of reproductive age in the context of the potential risks associated
with Zika virus infection.
• Women living in endemic areas should consult local health authorities for advice before becoming
pregnant.
• Family planning services, including access to contraception to prevent unplanned pregnancy, is
important to prevent Zika-related congenital abnormalities.[140] Access to adequate contraception
may be an issue in some countries.[141]
• In Brazil, there are no formal recommendations to avoid pregnancy because of the Zika virus outbreak;
the choice to get pregnant is regarded as a personal decision.[142]
Prevention while travelling
• Advice varies internationally and travellers should stay informed about Zika virus outbreaks.
• The WHO recommends that pregnant women should not travel to areas of ongoing transmission.[143]
• The CDC recommends that pregnant women should not travel to any area where there is a risk of Zika
virus infection, including:[144]
PREVENTION
• Areas where the virus has been newly introduced or re-introduced and local transmission is
ongoing
• Areas where the virus was endemic (present before 2015) and there is no evidence that
transmission has stopped
• Areas where the virus is likely to be circulating but has not been documented.
• To help pregnant women and others identify areas of Zika risk, the CDC has produced an interactive
map that allows people to search for location-specific information and travel recommendations. [CDC:
world map of areas with risk of Zika]
• Mosquito bite and sexual transmission prevention measures are recommended when travelling to
areas of ongoing transmission.
Prevention of transfusion transmission
• The FDA recommends universal testing of donated whole blood and blood components for Zika virus
in the US and its territories.[126]
• The FDA recommends that people should defer donating blood if they have been to areas with
ongoing Zika virus transmission, have potentially been exposed to the virus, or have confirmed
infection. In areas without active transmission, donors at risk for infection (e.g., those who have had
symptoms suggestive of infection, those who have had sexual contact with a person who has resided
in/travelled to an area with active transmission in the prior 3 months, and those who have travelled to
areas with ongoing transmission in the past 4 weeks) should defer donating blood for 4 weeks.[123]
People with a history of Zika virus infection should not donate blood for 120 days after a positive viral
test or the resolution of symptoms (whichever is longer).[126]
• Patients who develop symptoms within 14 days of giving blood should notify the place of donation.
• An investigational test is available to screen blood donations.[127]
Prevention of nosocomial transmission
• Transmission in a healthcare setting has not been described as yet; however, standard precautions
(e.g., hand hygiene, use of personal protective equipment, respiratory hygiene and cough etiquette,
safe injection practices, safe handling of potentially contaminated equipment or surfaces) are
recommended for the protection of healthcare professionals and patients in healthcare settings and
labour and delivery settings. These precautions are recommended regardless of whether the infection
is suspected or confirmed.[145]
• The CDC has produced interim guidance for the management of healthcare personnel with
occupational exposure. There is currently no post-exposure prophylaxis or vaccination available.[89]
9
[CDC: mosquito bite prevention for travelers]
[CDC: Zika virus prevention]
Screening
There is currently no need to screen for Zika virus infection in non-pregnant, asymptomatic travellers
returning from a country with ongoing transmission.
Pregnant women
The Centers for Disease Control and Prevention (CDC) recommendations for testing symptomatic and
asymptomatic pregnant women are detailed below.[166]
Symptomatic pregnant women
• Testing is recommended in all symptomatic pregnant women with possible Zika virus exposure (i.e.,
travel to, or residence in, an area with risk for mosquito-borne Zika virus transmission, or sex with a
PREVENTION
partner who has travelled to or resides in an area with risk for mosquito-borne Zika virus transmission).
• Concurrent RT-PCR (paired serum and urine specimens) and serological testing (serum) is
recommended in pregnant women as soon as possible up to 12 weeks after symptom onset. If RT-
PCR is positive, infection is confirmed, although further testing may be required if the IgM result is
negative. If RT-PCR and serology are both negative, diagnosis is excluded. If RT-PCR is negative and
serology is either positive or equivocal, PRNT is recommended. A PRNT <10 rules out diagnosis.
• Serological testing may be considered >12 weeks after symptom onset; however, a negative result
does not rule out infection during pregnancy as IgM levels decrease over time. A positive result should
be interpreted in the context of the known limitations of serological testing.
• Dengue virus IgM antibody testing is also recommended in symptomatic pregnant women.
Asymptomatic pregnant women
• Asymptomatic pregnant women with ongoing possible exposure: RT-PCR (serum and urine) is
recommended 3 times during pregnancy (e.g., at the initial antenatal care visit, and then at 2 non-
consecutive antenatal visits). If the result is positive, infection is confirmed. Additional testing is not
recommended in women who have a positive test any time before or during the current pregnancy. IgM
testing is no longer routinely recommended.
• Asymptomatic pregnant women with recent possible exposure but no ongoing possible exposure (e.g.,
travel or sexual exposure): testing is not routinely recommended but may be considered on a case-by-
case basis.
Pregnant women with possible exposure to Zika virus who have a fetus with antenatal ultrasound findings
consistent with congenital Zika virus infection should be tested following the same recommendations for
symptomatic pregnant women. If amniocentesis is performed as part of routine clinical care, RT-PCR
should be performed on amniotic fluid as a positive result may indicate fetal infection. Testing placental
and fetal tissues is not routinely recommended, but may be performed in certain situations (e.g., a woman
without laboratory-confirmed infection who has a fetus or infant with possible Zika virus-associated
abnormalities).[166]
The CDC has produced an algorithm to assist in clinical decision making about testing based on current
recommendations:
• [CDC: pregnancy & Zika testing]
One study found that most asymptomatic pregnant women who were tested in the US who had travelled
to, or moved from, areas with active Zika virus transmission did not have Zika virus infection.[189] A large-
scale antenatal Zika screening programme identified that only 0.2% of pregnant women who were at risk of
infection from recent travel to a Zika-affected area became infected.[190]
Sexual transmission
At this time, the Centers for Disease Control and Prevention (CDC) does not recommend testing of men for
the purpose of assessing risk for sexual transmission.[191]
Secondary prevention
People infected with Zika virus should be protected from further mosquito exposure during the first week of
illness (i.e., the viraemic stage) to prevent other mosquitoes from becoming infected and therefore reduce the
risk of local transmission.[134]
Zika virus infection (and Zika virus congenital infection) is a notifiable disease in many countries. Healthcare
providers should report suspected and confirmed cases to their state or local health department. In the
PREVENTION
US, these departments should report laboratory-confirmed cases to the Centers for Disease Control and
Prevention (CDC) through Arbonet. In other countries, cases should be reported to the relevant national
public health authorities who are then encouraged to inform the World Health Organization (WHO) and Pan
American Health Organization (PAHO) through established International Health Regulations (IHR) channels.
The WHO has produced reporting requirements for cases of Zika virus infection, microcephaly, and Guillain-
Barre syndrome:
• [WHO: surveillance for Zika virus infection, microcephaly and Guillain-Barre syndrome]
However, the definitions for surveillance reporting areas were updated in March 2017:
• [WHO: Zika virus country classification scheme]

The CDC has started a US-based Zika pregnancy registry. The data collected through the registry will be
used to update clinical recommendations and improve prevention of infection during pregnancy.
[CDC: US Zika pregnancy and infant registry]
The Puerto Rico Department of Health and CDC have developed a surveillance system to evaluate the
association between Zika virus infection during pregnancy and adverse outcomes during pregnancy,
birth, and early childhood (up to 3 years of age) called the Zika Active Pregnancy Surveillance System
(ZAPSS).[225]
11
Zika virus infection Diagnosis
Case history
Case history #1
A 31-year-old woman (gravida 1 para 0) presents at 12 weeks’ gestation to her obstetrician in London.
Her husband returned about 1 month ago from a business trip to Texas. Although he does not recall any
specific symptoms over the past month, he experienced mosquito bites during the trip. They have had
unprotected vaginal sex since his return.
Case history #2
A 22-year-old woman (gravida 3 para 2) presents at 24 weeks’ gestation (with twins) for a routine
antenatal check-up in Recife, Brazil. The woman reports a history of rash at 12 weeks' gestation,
but she did not seek medical attention for this. An antenatal ultrasound scan shows periventricular
microcalcifications and ventriculomegaly in one of the twins, while the other appears to be normal.
Other presentations
Approximately 80% of people infected with Zika virus are asymptomatic.[14] In those who are
symptomatic, patients generally present with a mild, self-limited illness including fever, maculopapular
(sometimes morbilliform) rash, arthralgia/myalgia, and conjunctivitis. Less common symptoms include
vomiting/diarrhoea, abdominal pain, anorexia, oedema of the lower limbs, and retro-orbital pain.[14]
There have been case reports of sepsis and rapid disease progression in patients with comorbidities.[15]
Atypical presentations (e.g., patients have presented with generalised rash or fever only) have been
reported.[16] Zika-related microcephaly has been reported in both fetuses in a monochorionic diamniotic
twin pregnancy.[17]
People may ask about whether to proceed with planned travel to endemic areas and/or preventive
measures for avoidance of mosquito bites. Women of childbearing age may ask about whether to proceed
DIAGNOSIS
with or to defer a planned pregnancy. People may ask about safe sexual practice, including before or
during pregnancy. Pregnant women who have possibly been exposed to Zika virus through travel or
sexual contact may inquire about Zika virus testing and fetal monitoring.
Step-by-step diagnostic approach

Diagnosis of Zika virus infection is based on clinical suspicion along with molecular and serological testing.
Although the majority of infected people are asymptomatic, physicians should have a high index of suspicion
for patients who present with fever, a maculopapular (sometimes morbilliform) rash, arthralgia/myalgia, and
conjunctivitis in the correct epidemiological context (i.e., residence in/travel from an area where there is a
current outbreak or the potential for transmission).
The clinical spectrum of disease overlaps with that caused by other arbovirus infections. As a consequence,
the differential diagnosis is broad and includes dengue and chikungunya infection. It is important to
differentiate between Zika, dengue, and chikungunya virus infection as the 3 diseases can produce similar
symptoms, particularly during the acute phase. The World Health Organization (WHO) has produced a tool
to help physicians differentiate between these 3 diseases.[146] Molecular or serological testing is required to
confirm the diagnosis.
There is strong scientific consensus that Zika virus is a cause of microcephaly and other congenital
abnormalities. The range of abnormalities seen and the likely causal link to Zika virus suggest a new
congenital syndrome which WHO is in the process of defining.[7] Preliminary results from a case-control
study have confirmed that Zika virus causes microcephaly.[9]
Guillain-Barre syndrome and other neurological disorders are strongly associated with and suspected to
be caused by Zika virus infection but the link is unproven and studies are ongoing, including to elucidate a
possible mechanism.[10] [11] [12] [13]
Infection prevention and control

Standard precautions (e.g., hand hygiene, use of personal protective equipment, respiratory hygiene and
cough etiquette, safe injection practices, safe handling of potentially contaminated equipment or surfaces)
are recommended for the protection of healthcare professionals and patients in healthcare settings and
labour and delivery settings. These precautions are recommended regardless of whether the infection is
suspected or confirmed.[145]
Transmission
Diagnosis should be suspected in patients who have resided in/travelled from an area where there is
a current outbreak (or where the Aedes mosquito is present) in the 2 weeks prior to symptom onset.
Non-vector transmission events (e.g., perinatal,[57] in utero,[58] [59] sexual,[57] [60] [61] and transfusion
transmission[62] [63] [64] [66]) have also been reported.[65] Sperm donation is a theoretical concern;
however, there have been no reports as yet.
Clinical presentation
The incubation period after transmission is between 3 and 14 days.[98] Approximately 80% of patients
do not develop symptoms.[14] In those who do, characteristic clinical findings include fever, an
itchy maculopapular (sometimes morbilliform) rash, arthralgia, and non-purulent conjunctivitis. The
DIAGNOSIS
characteristic rash is one of the most distinctive symptoms.[14]
[Fig-1]
Other commonly reported symptoms include myalgia, malaise, and headache.[14] [133] Less common
symptoms include vomiting/diarrhoea, abdominal pain, anorexia, oedema of the lower limbs, and retro-
orbital pain.[14] No differences in clinical presentation have been described between pregnant women
and non-pregnant patients, or between adults and children. Most children have a rash, and more than half
have a fever and rash.[44] Symptoms generally develop within 1 week of infection in 50% of patients, and
within 2 weeks of infection in 99% of patients.[98]
Clinical illness is usually self-limited with mild symptoms lasting 2 to 7 days.[14] [147] Severe disease
requiring hospitalisation is uncommon and the case fatality is low.[14] Immunosuppressed patients may
experience more severe complications; however, data from a small number of case reports suggest that
people with HIV infection are not at an increased risk for severe illness.[148]
Neurological examination should be performed on all patients with suspected GBS. Key diagnostic factors
include paraesthesias (usually of the hands and feet), muscle weakness, pain (usually starts in the back
and legs), and paralysis. Oropharyngeal, facial, and extraocular weakness may also occur. The WHO
13
recommends using the Brighton criteria for the case definition of GBS.[149] The Pan American Health
Organization (PAHO) has also published a case definition for Zika-related GBS.[150] Physicians should
be vigilant for early signs and symptoms of GBS as it may progress faster than usual in patients with Zika
virus infection.[24] Neurological consultation is recommended in patients with suspected GBS.[151]
Congenital Zika syndrome is a recognised pattern of congenital anomalies (i.e., microcephaly, intracranial
calcifications or other brain anomalies, or eye anomalies, among others) in infants associated with
Zika virus infection during pregnancy.[2] [3] [4] [5] [6] Infants may present with microcephaly or
other manifestations including spasticity, seizures, craniofacial disproportion, brainstem dysfunction,
ocular abnormalities, hearing loss, findings on neuro-imaging (e.g., cortical disorders, calcifications,
ventriculomegaly), arthrogryposis (e.g., congenital joint contractures), irritability, dysphagia,[152] and
feeding difficulties. Other presentations include ocular abnormalities in infants without microcephaly or
other brain abnormalities, postnatal-onset microcephaly in infants born with a normal head circumference,
postnatal-onset hydrocephalus in infants born with microcephaly, sleep electroencephalogram (EEG)
abnormalities, and diaphragmatic paralysis in infants born with microcephaly and arthrogryposis.[2]
Features consistent with fetal immobility (e.g., dimples, feet malpositions, distal hand/finger contractures)
may also be present.[153] There have been reports of these abnormalities in infants who have a normal
head circumference and with mothers who do not report having a rash during pregnancy.[3] [154] [155]
[156] [157] The syndrome does not appear to be associated with maternal disease severity.[158] Signs
of congenital brain injury due to Zika virus infection acquired during the third trimester of pregnancy have
been reported.[159] Poor head growth with microcephaly developing after birth has been reported in
a small number of patients in Brazil.[160] Eye abnormalities may be the only initial finding; therefore, it
is recommended that all infants with potential Zika virus exposure should undergo an eye examination
regardless of the presence or absence of other symptoms.[161] Other infectious causes of microcephaly
should be ruled out.[162]
Case definitions
Case definitions have been published by WHO, Centers for Disease Control and Prevention (CDC), and
PAHO:
DIAGNOSIS
• [WHO: Zika virus disease - interim case definition]

• [CDC: arboviral diseases, neuroinvasive and non-neuroinvasive 2015 case definition]
• [Pan American Health Organization: case definitions]
Case definitions vary and their sensitivity has been questioned, particularly in areas where other
arboviruses, such as chikungunya and dengue, circulate. One study found that the symptoms most
strongly associated with Zika virus infection included rash, pruritus, conjunctival hyperaemia, absence of
fever (axillary temperature <37.5°C), no petechiae, and no anorexia.[163]
Investigations
Diagnosis can be confirmed with molecular or serological testing, which includes reverse transcriptase-
polymerase chain reaction (RT-PCR) for viral RNA, and IgM ELISA plus plaque-reduction neutralisation
testing (PRNT) for Zika virus antibodies. PRNT can be performed to measure virus-specific neutralising
antibodies and discriminate between cross-reacting antibodies in primary flavivirus infections (e.g.,
dengue and yellow fever viruses, yellow fever vaccine recipients);[164] however, there are currently few
laboratories that perform this test. Availability of commercial tests depends on location.
Antenatal ultrasound and amniocentesis may be recommended in some pregnant women. Head
circumference measurement, CT/MRI of the head, cranial ultrasound, hearing screen, ophthalmological
screen, and neurological examination may be recommended in infants with suspected congenital Zika
syndrome.
Nerve conduction studies/electromyography and CSF examination should be performed in patients with
suspected GBS if available; however, these investigations are not needed to make a clinical diagnosis
and should not delay treatment.[149] Interpretation of these studies and definitive diagnosis requires
consultation with a neurologist.
[CDC: instructions for submitting diagnostic specimens to the DVBD Arbovirus Diagnostic Laboratory]
Limitations of testing
The duration of typical IgM detectability is about 12 weeks.[165] However, data suggest that Zika virus
IgM can persist beyond 12 weeks in some people; therefore, a positive IgM result may not always indicate
recent infection. Therefore, IgM test results cannot always reliably distinguish between infection that
occurred before or during the current pregnancy, particularly in women with possible Zika exposure before
the current pregnancy. Additionally, as the prevalence of Zika virus disease declines, the likelihood of
false-positive test results increases.[166] Before testing, limitations should be discussed with the patient.
Sensitivity and negative predictive value for all Zika investigations has not been fully established,
especially for asymptomatic people. Consequently, transmission prevention precautions remain important
even when a test is negative. Additionally, it is important to exclude differential diagnoses that may
resemble Zika virus infection, dengue fever, and chikungunya. Other conditions such as malaria or
leptospirosis may require specific and urgent treatment.
Testing in non-pregnant individuals

Testing is recommended in all symptomatic patients with possible exposure. The CDC recommends
RT-PCR on serum or patient-matched serum and urine for specimens collected <14 days after
symptom onset. If RT-PCR is positive, infection is confirmed. If RT-PCR is negative, or the specimen
DIAGNOSIS
is collected ≥14 days after symptom onset, serological testing is recommended. If serological testing is
negative, infection can be ruled out and no further testing is required. If positive (or equivocal), PRNT
is recommended to confirm diagnosis (except in Puerto Rico). A PRNT <10 rules out infection. Plasma,
whole blood, CSF, and amniotic fluid may also be used as test specimens for RT-PCR if necessary.
Dengue and chikungunya testing (RT-PCR or serology) should also be performed in patients at risk of
exposure with clinically compatible illness.[167]
Testing recommendations may differ between guidelines and locations with WHO and PAHO offering
different recommendations:
• [WHO: laboratory testing for Zika virus infection]

• [PAHO: Zika virus surveillance in the Americas - recommendations for laboratory detection and
diagnosis]
Testing in pregnant women

All pregnant women should be asked about possible Zika virus exposure before and during the current
pregnancy, at every antenatal care visit. The CDC recommendations for testing symptomatic and
asymptomatic pregnant women are detailed below.[166]
15
Symptomatic pregnant women
• Testing is recommended in all symptomatic pregnant women with possible Zika virus exposure
(i.e., travel to, or residence in, an area with risk for mosquito-borne Zika virus transmission, or sex
with a partner who has travelled to or resides in an area with risk for mosquito-borne Zika virus
transmission).
• Concurrent RT-PCR (paired serum and urine specimens) and serological testing (serum) is
recommended in pregnant women as soon as possible up to 12 weeks after symptom onset. If
RT-PCR is positive, infection is confirmed, although further testing may be required if the IgM
result is negative. If RT-PCR and serology are both negative, diagnosis is excluded. If RT-PCR is
negative and serology is either positive or equivocal, PRNT is recommended. A PRNT <10 rules
out diagnosis.
• Serological testing may be considered >12 weeks after symptom onset; however, a negative result
does not rule out infection during pregnancy as IgM levels decrease over time. A positive result
should be interpreted in the context of the known limitations of serological testing.
• Dengue virus IgM antibody testing is also recommended in symptomatic pregnant women.
Asymptomatic pregnant women
• Asymptomatic pregnant women with ongoing possible exposure: RT-PCR (serum and urine) is
recommended 3 times during pregnancy (e.g., at the initial antenatal care visit, and then at 2 non-
consecutive antenatal visits). If the result is positive, infection is confirmed. Additional testing is not
recommended in women who have a positive test any time before or during the current pregnancy.
IgM testing is no longer routinely recommended.
• Asymptomatic pregnant women with recent possible exposure but no ongoing possible exposure
(e.g., travel or sexual exposure): testing is not routinely recommended but may be considered on a
case-by-case basis.
Pregnant women with possible exposure to Zika virus who have a fetus with antenatal ultrasound findings
consistent with congenital Zika virus infection should be tested following the same recommendations for
symptomatic pregnant women. If amniocentesis is performed as part of routine clinical care, RT-PCR
DIAGNOSIS
should be performed on amniotic fluid as a positive result may indicate fetal infection. Testing placental
and fetal tissues is not routinely recommended, but may be performed in certain situations (e.g., a woman
without laboratory-confirmed infection who has a fetus or infant with possible Zika virus-associated
abnormalities).[166]
Pregnant women with laboratory evidence of possible Zika virus infection should have serial ultrasounds
every 3 to 4 weeks to monitor fetal anatomy and growth, and be referred to a specialist.[166] Intrauterine
diagnosis of microcephaly is made when the head circumference is ≥2 standard deviations below the
mean for sex and gestational age.[168]
The CDC has produced an algorithm to assist in clinical decision making about testing based on current
recommendations:
• [CDC: pregnancy & Zika testing]
Testing in infants with suspected congenital infection

Congenital Zika syndrome is a recognised pattern of congenital anomalies (i.e., microcephaly, intracranial
calcifications or other brain anomalies, or eye anomalies, among others) in infants associated with Zika
virus infection during pregnancy.[2] [3] [4] [5] [6] Other presentations include ocular abnormalities in
infants without microcephaly or other brain abnormalities, postnatal-onset microcephaly in infants born
with a normal head circumference, postnatal-onset hydrocephalus in infants born with microcephaly,
sleep electroencephalogram (EEG) abnormalities, and diaphragmatic paralysis in infants born with
microcephaly and arthrogryposis.[2] Suspected cases should be referred to a paediatrician.
Both molecular and serological testing are recommended in:[2]
• Infants with clinical findings consistent with congenital Zika syndrome born to mothers with possible
Zika virus exposure in pregnancy, regardless of maternal testing results
• Infants without clinical findings consistent with congenital Zika virus syndrome who were born to
mothers with laboratory evidence of possible Zika virus infection.
Laboratory testing is not routinely recommended for infants without clinical findings consistent with
congenital Zika syndrome born to mothers with possible Zika exposure during pregnancy but without
laboratory evidence of maternal infection.
Initial samples for testing (i.e., infant serum and urine; whole blood; cord blood is no longer
recommended) should be collected directly from the infant in the first 2 days of life for simultaneous RT-
PCR (on serum and urine) and IgM ELISA testing (note: specimens collected within the first few weeks
to months after birth still may be useful, especially in infants born in areas without risk of Zika). CSF
testing can be considered if CSF is obtained for other purposes.[2] A positive RT-PCR on serum or urine
confirms congenital infection. A negative RT-PCR result with a positive IgM result suggests probable
congenital infection.[2] PRNT can be used to help identify false-positive results, and confirm or rule out
congenital Zika virus infection in children aged ≥18 months.
DIAGNOSIS
17
Interpretation of results of laboratory testing for evidence of congenital Zika virus infection
Centers for Disease Control and Prevention (CDC)
DIAGNOSIS
A standard evaluation is recommended in all infants born to mothers with possible or confirmed infection,
regardless of whether the infant has clinical findings consistent with congenital Zika syndrome. The
evaluation should include:[2]
• Comprehensive physical examination including growth parameters
• Developmental monitoring and screening using validated tools
• Vision screening
• Newborn hearing screen at birth, with automated auditory brainstem response (ABR) if possible.
In addition to this, infants with clinical findings consistent with congenital Zika syndrome, and infants
without clinical findings born to mothers with laboratory evidence of possible Zika virus infection should
have the following investigations:[2]
• Head ultrasound
• Comprehensive ophthalmological examination by 1 month of age
• Automated ABR by 1 month of age (if not already done as part of standard newborn evaluation).
Infants with clinical findings consistent with congenital Zika virus syndrome should also have the
following:[2]
• Referral to a development specialist, early intervention service programmes, and family support
services
• Consultation with infectious disease, clinical genetics, and neurology specialists, as well as any
other clinical specialists based on the infant’s clinical findings (e.g., endocrinologist, lactation
specialist, gastroenterologist, speech or occupational therapist, orthopaedist, physiotherapist,
pulmonologist).
Infants who do not have clinical findings consistent with congenital Zika virus syndrome should be
referred to an appropriate specialist if any clinical findings are noted at follow-up visits.
Follow-up care requires a multidisciplinary team to facilitate coordination of care and will depend on
the clinical findings in the infant. Healthcare providers should be vigilant for other clinical findings (e.g.,
difficulty swallowing, hydrocephaly) or new clinical findings. A standard evaluation should be performed
at subsequent well-child visits in all infants, along with routine paediatric care. Automated ABR testing is
no longer recommended in infants at 4 to 6 months of age if they passed the initial hearing screen with
ABR.[2]
The WHO offers specific guidance for the screening, assessment, and management of neonates and
infants with congenital Zika infection.
[WHO: screening, assessment and management of neonates and infants with complications associated
with Zika virus exposure in utero]
DIAGNOSIS
19
Recommended Zika virus testing and evaluation of infants born to

DIAGNOSIS
mothers with laboratory evidence of Zika virus infection during pregnancy

Risk factors
Strong
residence in/travel from endemic area
• Diagnosis should be suspected in patients who have resided in/travelled from an area where there is
ongoing transmission in the 2 weeks prior to symptom onset. [WHO: Zika virus classification tables]
• Travel-associated cases have been reported in, but not limited to, the US, UK, Europe, Australia, New
Zealand, Israel, Japan, and China.[27] [28] [29] [30] [31] [32] [33] [34] [35]
• Pregnant women who reside in areas with ongoing transmission have an ongoing risk for infection
throughout pregnancy.
mosquito bites in endemic area
• Transmission to humans is primarily through the bite of an infected mosquito. It is most commonly
transmitted by the A aegypti species which lives in tropical regions, but can also be carried by A
albopictus which lives in temperate regions.[45] [51] [52] There is emerging evidence that Zika virus
could also be spread by Culex quinquefasciatus ,[53] although this is has been disputed.[54] [55] [56]
unprotected sexual contact with infected individual

• Nearly all reported cases of sexual transmission involved vaginal or anal sex with men during, shortly
before onset of, or shortly after resolution of symptomatic illness consistent with acute Zika virus
infection. However, there have been 2 cases of asymptomatic male to female transmission.[70]
Sexual transmission from women to their sexual partners has been reported.[71] Male-to-male sexual
transmission has also been reported.[72] There is the possibility of oral transmission of the virus
through semen.[73]
• There are some data to support calls to classify Zika virus infection as a sexually transmitted
infection.[121]
Weak
blood transfusion from infected individual
• Transmission is thought to be possible from blood transfusions;[62] [63] [64] however, further
investigation is required. Transmission via platelet transfusion has been reported in Brazil.[66]
Approximately 1% of blood donors in Puerto Rico have been found to be viraemic with Zika virus.[122]
• Blood donation is not currently recommended for 1 month following Zika infection or exposure.[123]
[124]
• The US Food and Drug Administration (FDA) recommends universal testing of donated whole blood
and blood components for Zika virus in the US and its territories. The cobas Zika test has been
approved for this purpose (as well as for testing specimens from living organ donors) by the FDA.[125]
• People with a history of Zika virus infection should not donate blood for 120 days after a positive viral
test or the resolution of symptoms (whichever is longer).[126] An investigational test is available to
DIAGNOSIS
screen blood donations.[127] Zika-positive donations have been detected in the US during pre-emptive
screening.[128] [129]
sperm donation from infected individual

• While transmission via sperm donation is theoretically possible, there have not been any reports of a
woman or her fetus becoming infected via this mode of transmission as yet.
• Sperm donors who live in, or have travelled to, an area of active transmission should not donate
sperm.
• There is currently no investigation available to test semen for the presence of Zika virus. However, a
comprehensive travel history should be obtained from all donors.
• Women who have been exposed to semen from men potentially infected with Zika virus should be
counselled on the risks.
• There is the potential for infection at various stages of assisted reproduction, and this should be
considered.[130]
21
exposure to other infected body fluids
• Zika virus RNA has been detected in body fluids other than blood or semen including amniotic fluid,
CSF, urine, saliva, vaginal secretions, and ocular fluids; however, transmission via these body fluids
has not yet been documented.[59] [78] [79] [80] [81] [82] [83]
• While the virus has been detected in breast milk, there are no reports of transmission via
breastfeeding.[88]
• The virus has been detected in the genital tract of an infected woman, which may have implications for
vertical transmission.[86] Viraemia has been reported in a newborn at least 67 days after birth.[87]
• The Centers for Disease Control and Prevention (CDC) investigated how a family contact of a patient
who died of Zika virus infection in Utah became infected. The deceased patient had very high levels of
circulating virus. The mechanism of transmission remains unknown, but was likely to be from person-
to-person contact with the index patient.[90]
exposure to infected human cells/tissues

• There is a potential risk for transmission from human (including gestational) cells, tissues, and cellular/
tissue-based products (e.g., corneas, heart valves, bone, skin) that are used as part of medical,
reproductive, or surgical procedures.[69] Infection has been reported in a small series of hepatic
and renal transplant recipients,[67] and infection with Zika was strongly suspected in a paediatric
patient who developed Guillain-Barre syndrome after haematopoietic stem cell transplant in one case
report.[68]
• Deceased donors should be considered ineligible if they were diagnosed with Zika virus infection in the
past 6 months. Living donors should be considered ineligible if they were diagnosed with the infection
in the last 6 months, were in an area with active transmission within the past 6 months, or had sex with
a male with either of those risk factors in the past 6 months.[131]
• Donors of umbilical cord blood, placenta, or other gestational tissues should be considered ineligible
if the birth mother has any of the following risk factors: medical diagnosis of Zika virus infection at
any point during pregnancy; residence in/travel to an area with active transmission at any point during
pregnancy; or sex with a male at any point during the pregnancy who is known to have these risk
factors.[131]
DIAGNOSIS
History & examination factors

Key diagnostic factors
presence of risk factors (common)
• Key risk factors include residence in/travel from an endemic area, and mosquito bites in an endemic
area.
• Only 20% of infections are thought to be symptomatic.[14]
fever (common)
• Fever is usually low-grade (i.e., <38.5°C [<101.3°F]).[150] [169]
maculopapular rash (common)

• Rash (sometimes morbilliform) is characteristic of infection and may be itchy.[14] [150]
[Fig-1]
• Rash was found to involve a median of 45% of the body surface area in one study, with the most
common sites of involvement being the face and upper limbs (95%), trunk (93%), and lower limbs
(86%). Rash on the palms and soles of the feet were less common. Intense pruritus occurred in 82%
of patients.[170]
arthralgia (common)
• Particularly in the small joints of hands and feet.[169]
• Peri-articular oedema may be present.[150]
conjunctivitis (common)
• Usually non-purulent.[14] [150] [171]
• Conjunctival hyperaemia may be present.[150] [171]
features of congenital Zika syndrome (infants) (common)

• Congenital Zika syndrome is a recognised pattern of congenital anomalies (i.e., microcephaly,
intracranial calcifications or other brain anomalies, or eye anomalies, among others) in infants
associated with Zika virus infection during pregnancy.[2] [3] [4] [5] [6]
• Other presentations include ocular abnormalities in infants without microcephaly or other brain
abnormalities, postnatal-onset microcephaly in infants born with a normal head circumference,
postnatal-onset hydrocephalus in infants born with microcephaly, sleep electroencephalogram (EEG)
abnormalities, and diaphragmatic paralysis in infants born with microcephaly and arthrogryposis.[2]
• Infants may present with microcephaly or other manifestations including spasticity, seizures,
craniofacial disproportion, brainstem dysfunction, ocular abnormalities, hearing loss, findings on
neuro-imaging (e.g., cortical disorders, calcifications, ventriculomegaly), arthrogryposis (e.g.,
congenital joint contractures), irritability, dysphagia,[152]and feeding difficulties.
• Features consistent with fetal immobility (e.g., dimples, feet malpositions, distal hand/finger
contractures) may also be present.[153]
• There have been reports of these neurological abnormalities in infants who have a normal head
circumference and with mothers who do not report having a rash during pregnancy.[154] [3] [155] [156]
[157] It does not appear to be associated with maternal disease severity.[158] Poor head growth with
microcephaly developing after birth has been reported in a small number of patients in Brazil.[160]
• Eye abnormalities may be the only initial finding; therefore, it is recommended that all infants with
DIAGNOSIS
potential Zika virus exposure should undergo an eye examination regardless of the presence or
absence of other symptoms.[161]
features of Guillain-Barre syndrome (uncommon)

• Key diagnostic factors include paraesthesias (usually of the hands and feet), muscle weakness, pain
(usually starts in the back and legs), and paralysis. Oropharyngeal, facial, and extraocular weakness
may also occur. The World Health Organization (WHO) recommends using the Brighton criteria for
the case definition of Guillain-Barre syndrome (GBS).[149] The Pan American Health Organization
(PAHO) has also published a case definition for Zika-related GBS.[150]
• Physicians should be vigilant for early signs and symptoms of GBS as it may progress faster than
usual in patients with Zika virus infection.[24]
Other diagnostic factors

other constitutional symptoms (common)
• Include malaise, myalgia, and/or headache.[14] [133] [150]
gastrointestinal symptoms (uncommon)
23
• Include vomiting, diarrhoea, and/or abdominal pain.[14]
retro-orbital pain (uncommon)

• Uncommon symptom reported in some cases.[14]
oedema of lower limbs (uncommon)

• Uncommon symptom reported in some cases.[14]
transient hearing loss in adults (uncommon)

• An association between Zika infection and transient hearing loss has been reported in a small number
of cases.[172]
DIAGNOSIS
Diagnostic tests
1st test to order
Test Result
reverse transcriptase-polymerase chain reaction (RT-PCR) on positive for Zika virus
serum and urine RNA
• Non-pregnant: the Centers for Disease Control and Prevention
(CDC) recommends testing serum or patient-matched serum and
urine specimens collected <14 days after onset of symptoms in
all symptomatic patients with possible exposure.[167] If result is
negative, serological tests are recommended.
• Pregnant and symptomatic: CDC recommends testing paired serum
and urine specimens as soon as possible up to 12 weeks after onset
of symptoms in all symptomatic patients with possible exposure.
Concurrent serological testing is recommended; further testing may
be required if RT-PCR is positive and IgM result is negative.[166]
• Pregnant and asymptomatic: CDC recommends testing paired serum
and urine specimens 3 times during pregnancy (e.g., at the initial
antenatal care visit, and then at 2 non-consecutive antenatal visits) in
patients with ongoing possible exposure only.[166]
• Pregnant women with possible exposure to Zika virus who
have a fetus with antenatal ultrasound findings consistent with
congenital Zika virus infection should be tested following the same
recommendations for symptomatic pregnant women.[166]
• Infants: CDC recommends testing in infants with clinical findings
consistent with congenital Zika syndrome born to mothers with
possible Zika virus exposure in pregnancy (regardless of maternal
testing results), or infants without clinical findings consistent with
congenital Zika virus syndrome who were born to mothers with
laboratory evidence of possible Zika virus infection. Serum and urine
should be collected from the infant in the first 2 days of life if possible
(note: specimens collected within the first few weeks to months after
birth still may be useful, especially in infants born in areas without risk
DIAGNOSIS
of Zika).[2]
• CSF testing can be considered in infants with clinical findings of
possible congenital Zika syndrome but whose initial laboratory tests
on serum and urine are negative.[2]
• Availability of commercial tests depends on location.
• Testing recommendations may differ between guidelines and
locations.[74] [173]
•
25
Test Result
serology positive for Zika virus
antibodies; PRNT ≥10
• Non-pregnant: CDC recommends testing serum specimens collected
≥14 days after onset of symptoms in all symptomatic patients
with possible exposure (or if RT-PCR on specimens collected <14
days after onset of symptoms is negative).[167] If result is positive
or equivocal, plaque-reduction neutralisation testing (PRNT) is
recommended (except in Puerto Rico) to confirm diagnosis.
• Pregnant and symptomatic: CDC recommends testing serum
specimens as soon as possible up to 12 weeks after onset of
symptoms in all symptomatic patients with possible exposure.
Concurrent RT-PCR is recommended; if RT-PCR is negative and
serology is either positive or equivocal, PRNT is recommended
(except in Puerto Rico) to confirm diagnosis.[166] May be considered
>12 weeks after symptom onset; however, result should be
interpreted in the context of known limitations.
• Pregnant and asymptomatic: CDC no longer routinely recommends
IgM testing in these patients.[166]
• Pregnant women with possible exposure to Zika virus who
have a fetus with antenatal ultrasound findings consistent with
congenital Zika virus infection should be tested following the same
recommendations for symptomatic pregnant women.[166]
• Infants: CDC recommends testing in infants with clinical findings
consistent with congenital Zika syndrome born to mothers with
possible Zika virus exposure in pregnancy (regardless of maternal
testing results), or infants without clinical findings consistent with
congenital Zika virus syndrome who were born to mothers with
laboratory evidence of possible Zika virus infection. Serum should
be collected from the infant in the first 2 days of life if possible (note:
specimens collected within the first few weeks to months after birth
still may be useful, especially in infants born in areas without risk
of Zika). A positive result (with positive RT-PCR) confirms infection.
A non-negative result (with negative RT-PCR) indicates probable
infection.[2]
• Availability of commercial tests depends on location.
DIAGNOSIS
• Sensitivity and specificity of commercial serology assays is uncertain

and should be interpreted with caution. The FDA has released a
caution about a higher than expected incidence of false-positive
results with the ZIKV Detect IgM Capture ELISA. Positive results from
this test are only presumptive and must be confirmed by additional
testing.[174]
testing for other arboviruses depends on test and
• It is important to differentiate between Zika, dengue, and chikungunya organism
virus infection as the 3 diseases can produce similar symptoms,
particularly during the acute phase.
• RT-PCR or serology for dengue and/or chikungunya is recommended
in patients at risk of exposure with clinically compatible illness.[167]
[166]
Other tests to consider
Test Result
antenatal ultrasound may show microcephaly,
intracranial
• Microcephaly can sometimes be diagnosed on antenatal ultrasound,
calcifications, or brain/
especially if performed in late pregnancy. Intrauterine diagnosis of
eye abnormalities
microcephaly is made when the head circumference is ≥2 standard
deviations below the mean for gender and gestational age.[168]
• Pregnant women with laboratory evidence of possible Zika virus
infection should have serial ultrasounds every 3 to 4 weeks to monitor
fetal anatomy and growth, and be referred to a specialist.[166]
• In Brazil, 3 ultrasounds are recommended during low-risk
pregnancies, with monthly ultrasounds recommended in pregnant
women with confirmed infection.[175]
• A systematic review and meta-analysis found that overall diagnostic
test accuracy of ultrasound for predicting microcephaly at birth is
limited as it varies with the applied cut-offs, and that it appears more
accurate at detecting the absence of microcephaly rather than its
presence.[176]
amniocentesis positive for Zika virus
RNA
• If amniocentesis is performed as part of routine clinical care, RT-
PCR should be performed on amniotic fluid as a positive result may
indicate fetal infection.[166]
head circumference measurement (newborn) third percentile or ≥2
standard deviations
• Infant’s head circumference should be measured at birth, 24 hours
after birth, and then regularly during early infancy using standardised below the mean (for age
and gender)
methods and compared with growth standards.[168] [177]
• The Centers for Disease Control and Prevention (CDC) defines
definite microcephaly as head circumference at birth in the third
percentile for gestational age and gender, or head circumference in
the third percentile for age and gender within the first 6 weeks of life
(if head circumference at birth is not available).[178]
• The World Health Organization (WHO) defines microcephaly as a
DIAGNOSIS
head circumference of ≥2 standard deviations below the mean for
age and gender, and severe microcephaly as a head circumference
of ≥3 standard deviations below the mean for age and gender. WHO
Child Growth Standards or the INTERGROWTH-21 Size at Birth
Standards should be used to interpret measurements.[177]
• Some infants may present with craniofacial disproportion (i.e., the
head appears disproportionately small relative to the face).[177]
• Poor head growth with microcephaly developing after birth has been
reported in a small number of patients in Brazil.[160]
• [CDC: measuring infant head circumference: an instructional video for
healthcare providers]
27
Test Result
newborn further evaluation abnormalities consistent
with congenital Zika virus
• A standard evaluation is recommended in all infants born to mothers
infection
with possible or confirmed infection, regardless of whether the infant
has clinical findings consistent with congenital Zika syndrome. The
evaluation should include: a comprehensive physical examination
including growth parameters; developmental monitoring and
screening using validated tools; vision screening; and newborn
hearing screen at birth, with automated auditory brainstem response
(ABR) if possible.[2]
• In addition to this, infants with clinical findings consistent with
congenital Zika syndrome, and infants without clinical findings
born to mothers with laboratory evidence of possible Zika virus
infection, should have the following investigations: head ultrasound;
comprehensive ophthalmological examination by 1 month of age;
and automated ABR by 1 month of age (if not already done as part of
standard newborn evaluation).[2]
• Infants with clinical findings consistent with congenital Zika virus
syndrome should also have the following: referral to a development
specialist, early intervention service programmes, and family support
services; and consultation with infectious disease, clinical genetics,
and neurology specialists, as well as any other clinical specialists
based on the infant’s clinical findings (e.g., endocrinologist, lactation
specialist, gastroenterologist, speech or occupational therapist,
orthopaedist, physiotherapist, pulmonologist).[2]
CT/MRI head (newborn) may show intracranial
calcifications,
• Recommended in infants with microcephaly (or craniofacial
ventriculomegaly,
disproportion) where Zika infection is suspected in the mother during
cerebellar hypoplasia,
pregnancy, or if any neurological signs/symptoms are present in the
infant.[177] callosal abnormalities, or
ocular findings
• Either CT or MRI can be performed; however, an MRI may provide
more detail and can potentially detect other conditions.[177]
• The most common feature found on CT is brain calcifications in the
junction between the cortical and subcortical white matter, often
DIAGNOSIS
with a simplified gyral pattern and predominance of pachygyria

or polymicrogyria in the frontal lobes. These calcifications often
resolve; therefore, the absence of calcifications should not exclude
the diagnosis, and the presence of calcifications should not be
consIdered a major criterion for diagnosis.[179]
• Other findings include abnormalities of the corpus callosum
(hypogenesis or hypoplasia), enlarged cisterna magna,
ventriculomegaly, delayed myelination, and hypoplasia of the
cerebellum and brainstem.[180] [181]
• Some infants have been found to have vision-threatening eye findings
(e.g., macular and perimacular lesions, pigmentary retinopathy and
atrophy, torpedo maculopathy, haemorrhagic retinopathy).[182]
[183] [184] [185] [186] [187] Ocular findings were seen more often
in infants with smaller cephalic diameter at birth, and infants born to
mothers who reported symptoms in the first trimester.[188]
• Signs of congenital brain injury (e.g., subependymal cysts,
lenticulostriate vasculopathy) due to Zika virus infection acquired
during the third trimester of pregnancy have been reported.[159]
• [Fig-4]
Test Result
tests for Guillain-Barre syndrome slowing of nerve
conduction velocities;
• Nerve conduction studies/electromyography and CSF examination
elevated CSF protein
should be performed in patients with suspected Guillain-Barre
syndrome if available; however, these investigations are not needed
to make a clinical diagnosis and should not delay treatment.[149]
• Interpretation of these studies and definitive diagnosis requires
consultation with a neurologist.
Differential diagnosis
Condition Differentiating signs / Differentiating tests

symptoms
Dengue fever • Residence in/travel from • Reverse transcriptase-
dengue-endemic region. polymerase chain reaction
• Biphasic fever and rash. (RT-PCR): positive for
• Signs of haemorrhage dengue virus RNA.
(e.g., petechiae, purpura, • Non-structural protein 1
epistaxis, gingival bleeding, (NS1) detection: positive.
haematemesis, melena, • The World Health
vagina bleeding) or Organization (WHO) has
plasma leakage in dengue produced a tool to help
haemorrhagic fever. physicians differentiate
• Diffuse skin flushing of face, between Zika, dengue,
neck, and chest early in and chikungunya virus
infection course. infection.[146]
• Milder cases may be difficult
to distinguish from Zika virus
infection without diagnostic
testing.
Chikungunya virus • Residence in/travel from • ELISA/indirect fluorescent
DIAGNOSIS
chikungunya-endemic antibody (IFA): positive for
region. chikungunya antibodies.
• Almost always symptomatic. • RT-PCR: positive for
• Prominent joint symptoms. chikungunya viral RNA.
• Hyperpigmentation of skin • WHO has produced a tool to
and intertriginous lesions are help physicians differentiate
common. between Zika, dengue,
• Difficult to distinguish from and chikungunya virus
Zika virus infection without infection.[146]
diagnostic testing.
West Nile virus • Residence in/travel from • West Nile virus-specific IgM
West Nile virus-endemic in serum or CSF: positive.
region.
• Visual disturbances are
common.
• Rarely causes neuroinvasive
disease (e.g., encephalitis,
meningitis, flaccid paralysis
syndrome).
29

symptoms
Yellow fever • Residence in/travel from • Serology: positive for yellow
Yellow fever virus-endemic fever virus antibodies.
region.
• Absence of Yellow fever
vaccination.
• Also transmitted by
Haemagogus species of
mosquito.
• Relative bradycardia (Faget's
sign) may be present.
• Haemorrhagic signs.
• Biphasic course: after a
remission period lasting
up to 24 hours, some
patients develop a period of
intoxication with jaundice,
liver and kidney failure,
coagulopathy, shock, and
death.
• High mortality rate.
Malaria infection • Residence in/travel from • Giemsa-stained blood film:

malaria-endemic region. positive for Plasmodium
• Inadequate or absent species.
malaria chemoprophylaxis. • Rapid diagnostic tests:
positive for Plasmodium
species.
Leptospirosis • Zoonosis transmitted by • Darkfield examination: direct

direct or indirect contact with visualisation of spirochete in
urine of infected animals. blood or urine.
• Residence in/travel from • Blood/CSF culture: positive
endemic region. for leptospires.
DIAGNOSIS
• History of water sports. • RT-PCR: positive Leptospira

• Outbreaks during flooding RNA.
and natural disasters. • Serology (indirect
• High remitting fever and haemagglutination test,
biphasic course of illness. microagglutination test, or
• Bilateral conjunctival dipstick test): positive.
suffusion pathognomonic for • Antigen detection in urine:
leptospirosis. positive.
• Pulmonary symptoms.
• Affected individuals can
present with an extensive
spectrum of clinical
manifestations ranging
from subclinical illness
in approximately 90% of
cases to renal and hepatic
failure and pulmonary
haemorrhages.

symptoms
Rubella • Incomplete or absence of • Anti-rubella IgM: positive.
rubella vaccination.
• Exposure to infectious
contact.
• Rash is erythematous,
discrete, maculopapular, and
sometimes mildly pruritic,
and may be accentuated by
heat. Usually begins on face
and spreads to head and
feet. May be petechial.
• Lymphadenopathy may
precede rash.
• Mild upper respiratory
symptoms are common.
• Maternal infection during
pregnancy may cause
spontaneous abortion, fetal
death, or multiple congenital
anomalies (congenital
rubella syndrome).
Erythema infectiosum • Exposure to infectious • Diagnosis is usually clinical.

(parvovirus B19 infection) contact. • Serology: positive for
• Classic bright red macular parvovirus B19 antibodies.
erythema of bilateral cheeks
sparing the nasal ridge and
perioral areas.
• Infection in pregnant
women may result in fetal
anaemia, hydrops fetalis, or
intrauterine death.
DIAGNOSIS
Rock y Mountain spot ted • Transmitted by tick bite. • Serology: positive for
fever • Rash may be petechial. Rickettsia species.
• Nausea/vomiting common.
Group A streptococcal • May manifest as sepsis, • Blood or tissue cultures:

infection cutaneous conditions such positive.
as cellulitis, or pharyngitis. • Rapid antigen detection
tests: allow immediate point-
of-care assessment of group
A streptococcal pharyngitis.
Other alphavirus • Includes Mayaro virus • Antibody detection for

infections disease, Ross River fever, specific virus.
Barmah Forest virus,
O'nyong-nyong virus, and
Sindbis virus.
• Residence in/travel from
endemic region.
• Difficult to distinguish from
Zika virus infection without
diagnostic testing.
31

symptoms
Other causes of fetal • There may be a history of in • Targeted testing for
microcephaly utero drug/toxin exposure, suspected aetiologies.
family history of genetic
factor, or other pregnancy-
associated infection (such as
CMV or syphilis).
Diagnostic criteria
World Health Organization (WHO): interim case definition
An interim case definition has been published by the WHO for the purpose of global standardisation of
classification and reporting.[171]
Suspected case:
• A person presenting with rash and/or fever and at least one of the following signs or symptoms:
• Arthralgia
• Arthritis
• Conjunctivitis (non-purulent/hyperaemic).
Probable case:
• A suspected case with the presence of IgM antibodies against Zika virus and no evidence of infection
with other flaviviruses, plus an epidemiological link (i.e., contact with a confirmed case, or a history of
residence in or travelling to an area with local transmission of Zika virus within 2 weeks prior to onset
of symptoms).
DIAGNOSIS
Confirmed case:
• A person with laboratory confirmation of recent Zika virus infection:
• Presence of Zika virus RNA or antigen in serum or other samples (e.g., saliva, tissues, urine,
whole blood)
• IgM antibody against Zika virus is positive and plaque reduction neutralisation test (PRNT) for
Zika virus with titre ≥20 and Zika virus PRNT titre ratio ≥4 compared with other flaviviruses.
[WHO: Zika virus disease - interim case definition]
Pan American Health Organization (PAHO): interim Zika virus case

definition
An interim case definition has been published by the PAHO.[150]
Suspected case:
• Patient with rash (usually pruritic and maculopapular) plus 2 or more of the following:
• Fever (usually <38.5°C [<101.3°F])

• Conjunctivitis (non-purulent/hyperaemic)
• Arthralgia
• Myalgia
• Peri-articular oedema.
• In geographical areas without autochthonous transmission and where there are no vectors present,
patients who meet the criteria above and who:
• in the 2 weeks prior to onset, travelled to/resided in a geographical area where there is known
local transmission of the Zika virus or there is known vector presence; or
• had unprotected sex in the 2 weeks prior to onset with a person who travelled in the previous
8 weeks to a geographical area with known local transmission of the Zika virus or an area with
known vector presence.
Probable case:
• Patient who meets the criteria of a suspected case and has Zika IgM antibodies with no evidence of
infection with other flaviviruses.
Confirmed case:
• Patient who meets the criteria of a suspected case and has laboratory confirmation of recent Zika virus
infection:
• RNA or Zika virus antigen in any specimen (i.e., serum, urine, saliva, tissue, or whole blood); or
• Positive Zika IgM antibodies and PRNT for Zika virus titres ≥20 and 4 or more times greater
than the titres for other flaviviruses, as well as exclusion of other flaviruses; or
• Detection of viral genome (in fresh or paraffin tissue) in autopsy specimens by molecular
techniques, or detection by immunochemistry.
DIAGNOSIS
PAHO have also published case definitions for Guillain-Barre syndrome or a congenital syndrome associated
with Zika virus, as well as definitions for Zika virus-associated abortion or still birth and vertical transmission
(without congenital syndrome).
[Pan American Health Organization: case definitions]
Centers for Disease Control and Prevention (CDC): arboviral

diseases case definition
The CDC includes Zika virus infection in their arboviral diseases (neuroinvasive and non-neuroinvasive) case
definition:
[CDC: arboviral diseases, neuroinvasive and non-neuroinvasive 2015 case definition]
33
Zika virus infection Treatment
Step-by-step treatment approach

Treatment for symptomatic infection is generally supportive as there is no specific antiviral treatment
available. Because of similar geographical distribution and symptoms, patients with suspected Zika virus
infections should also be evaluated and managed for possible dengue or chikungunya virus infection. It
is also important to rule out other serious, but potentially treatable, infections (e.g., malaria, leptospirosis,
yellow fever, West Nile virus).
Advice for women possibly exposed to Zika virus infection during pregnancy, or for possibly affected
infants, is evolving but generally includes serological testing where warranted, plus antenatal and postnatal
monitoring.
Physicians in areas where there is local transmission should consult with local health authorities for up-to-
date guidance.
Supportive therapies for symptomatic patients

These include rest, fluids, and use of analgesics and/or antipyretics (e.g., paracetamol). Aspirin and other
non-steroidal anti-inflammatory drugs (NSAIDs) should be avoided until dengue virus infection can be
ruled out to reduce the risk of haemorrhage. Calamine lotion may be used for the itch associated with the
rash.
The same general advice is given for symptoms in pregnant and non-pregnant women. Non-drug
measures may be recommended (e.g., damp cloths, lukewarm baths/showers) to reduce fever during
pregnancy. However, if these measures fail, paracetamol can be used safely in pregnant women.
Infection prevention and control

In order to prevent transmission of infection, contact between an infected person and mosquitoes should
be avoided. Mosquito bite prevention strategies should be instituted, particularly during the first week of
infection.[14] Healthcare workers caring for patients should protect themselves from mosquito bites by
using repellents and wearing long sleeves and long trousers.
Standard precautions (e.g., hand hygiene, use of personal protective equipment, respiratory hygiene and
cough etiquette, safe injection practices, safe handling of potentially contaminated equipment or surfaces)
are recommended for the protection of healthcare professionals and patients in healthcare settings and
labour and delivery settings. These precautions are recommended regardless of whether the infection is
suspected or confirmed.[145]
Pregnant women with possible mosquito-borne or sexual

exposure
Pregnant women who may have been exposed to Zika virus should have recommended laboratory
testing and regular fetal ultrasounds to assess the fetus for the presence of microcephaly or other
abnormalities. All pregnant women should be encouraged to attend scheduled antenatal visits.[14]
Appropriate psychological support for the woman and her family is recommended.[192]
TREATMENT
[CDC: updated interim guidance for health care providers caring for pregnant women with possible Zika
virus exposure - United States (including US territories), July 2017]
Congenital Zika syndrome
There is no specific treatment, and management will depend on the individual and the presence of
specific symptoms and neurodevelopmental problems (e.g., seizures, intellectual disability, cerebral palsy,
hearing/vision problems). Supportive therapies should be started. Children should start rehabilitation as
soon as possible. This rehabilitation process must include multidisciplinary support with a physiotherapist,
speech therapist, and occupational therapist. A co-ordinated approach, with ongoing psychosocial
support for families and caregivers, is recommended.[2] [177]
The Centers for Disease Control and Prevention (CDC) has produced detailed guidance for the initial
evaluation and outpatient management of infants with possible congenital Zika virus infection during the
first 12 months of life.
[CDC: interim guidance for the diagnosis, evaluation and management of infants with possible congenital
Zika virus infection]
The WHO also offers specific guidance for the screening, assessment, and management of neonates and
infants with congenital Zika infection.
Breastfeeding is still recommended, even in areas where a Zika virus infection outbreak is occurring
as transmission through breast milk is only a theoretical concern at this point and the benefits of
breastfeeding outweigh the risk of transmission.[193] [194] [195] [88]
Guillain-Barre syndrome
There are few data on the treatment of Guillain-Barre syndrome (GBS) in the context of Zika virus
infection.
All patients should be admitted to hospital and monitored closely for at least 5 days or until clinically
stable. Some patients may require a higher level of care in the ICU (e.g., patients with rapid progression
of motor weakness, respiratory distress, bulbar symptoms, or autonomic dysfunction). Patients should be
monitored closely for complications.[149]
Management should be based on symptoms according to usual treatment protocols for GBS and involves
supportive therapy (e.g., airway management, cardiovascular management, pain management, plasma
exchange, intravenous immunoglobulin, rehabilitation, deep vein thrombosis prophylaxis, nutritional
support, bowel and bladder care, prevention of bed sores, prevention of corneal ulceration if facial
weakness present) as well as psychosocial support and early initiation of a rehabilitation programme.[149]
[151]
Treatment details overview

TREATMENT
Please note that formulations/routes and doses may differ between drug names and brands, drug
formularies, or locations. Treatment recommendations are specific to patient groups: see disclaimer
Acute ( summary )
symptomatic: non-pregnant
35
Acute ( summary )
1st supportive therapy
pregnant: with possible mosquito-

borne or sexual exposure
1st supportive therapy plus monitoring
congenital Zika syndrome
1st evaluation plus monitoring
Zika-associated Guillain-Barre
syndrome
1st supportive therapy plus immunotherapy

TREATMENT
Treatment options
Please note that formulations/routes and doses may differ between drug names and brands, drug
formularies, or locations. Treatment recommendations are specific to patient groups: see disclaimer
Acute
symptomatic: non-pregnant
1st supportive therapy

Primary options
» paracetamol: children: 10-15 mg/kg orally

every 4-6 hours when required, maximum 75
mg/kg/day; adults: 500-1000 mg orally every
4-6 hours when required, maximum 4000 mg/
day
» Treatment for symptoms includes rest, fluids,

and use of analgesics and/or antipyretics (e.g.,
paracetamol).
» Aspirin and other non-steroidal anti-

inflammatory drugs (NSAIDs) should be avoided
until dengue virus infection can be ruled out to
reduce the risk of haemorrhage.
» Calamine lotion may be used for the itch

associated with the rash.
pregnant: with possible mosquito-
borne or sexual exposure
1st supportive therapy plus monitoring

Primary options
» paracetamol: children: 10-15 mg/kg orally

every 4-6 hours when required, maximum 75
mg/kg/day; adults: 500-1000 mg orally every
4-6 hours when required, maximum 4000 mg/
day
» Pregnant women who may have been exposed

to Zika virus should have recommended
laboratory testing and regular fetal ultrasounds
to assess the fetus for the presence of
microcephaly or other abnormalities. All
pregnant women should be encouraged to
attend scheduled antenatal visits.[14]
» If symptomatic, supportive therapies include

rest, fluids, and use of analgesics and/or
antipyretics (e.g., paracetamol). Aspirin and
TREATMENT
other non-steroidal anti-inflammatory drugs

(NSAIDs) should be avoided. Non-drug
measures may be recommended (e.g., damp
cloths, lukewarm baths/showers) to reduce fever
during pregnancy. However, if these measures
37
Acute
fail, paracetamol can be used safely in pregnant
women. Calamine lotion may be used for the itch
associated with the rash.
» Appropriate psychological support for the

woman and her family is recommended.[192]
» [CDC: updated interim guidance for health

care providers caring for pregnant women with
possible Zika virus exposure - United States
(including US territories), July 2017]
congenital Zika syndrome
1st evaluation plus monitoring
» There is no specific treatment, and

management will depend on the individual
and the presence of specific symptoms and
neurodevelopmental problems (e.g., seizures,
intellectual disability, cerebral palsy, hearing/
vision problems). Supportive therapies should
be started. Children should start rehabilitation
as soon as possible. This rehabilitation process
must include multidisciplinary support with
a physiotherapist, speech therapist, and
occupational therapist.
» The Centers for Disease Control and

Prevention (CDC) has produced detailed
guidance for the initial evaluation and outpatient
management of infants with possible congenital
Zika virus infection during the first 12 months of
life. [CDC: interim guidance for the diagnosis,
evaluation and management of infants with
possible congenital Zika virus infection]
» The World Health Organization (WHO) also

offers specific guidance for the screening,
assessment, and management of neonates
and infants with congenital Zika infection.
[WHO: screening, assessment and management
of neonates and infants with complications
associated with Zika virus exposure in utero]
» A co-ordinated approach, with ongoing

psychosocial support for families and caregivers,
is recommended.[2] [177]
» Breastfeeding is still recommended, even in

areas where a Zika virus infection outbreak is
occurring as transmission through breast milk is
only a theoretical concern at this point and the
TREATMENT
benefits of breastfeeding outweigh the risk of

transmission.[193] [194] [195] [88]
Zika-associated Guillain-Barre
syndrome
Acute
1st supportive therapy plus immunotherapy
» There are few data on the treatment of

Guillain-Barre syndrome (GBS) in the context of
Zika virus infection.
» All patients should be admitted to hospital

and monitored closely for at least 5 days or until
clinically stable. Some patients may require a
higher level of care in the ICU (e.g., patients with
rapid progression of motor weakness, respiratory
distress, bulbar symptoms, or autonomic
dysfunction). Patients should be monitored
closely for complications.[149]
» Management should be based on symptoms

according to usual treatment protocols for GBS
and involves supportive therapy (e.g., airway
management, cardiovascular management, pain
management, plasma exchange, intravenous
immunoglobulin, rehabilitation, deep vein
thrombosis prophylaxis, nutritional support,
bowel and bladder care, prevention of bed
sores, prevention of corneal ulceration if facial
weakness present) as well as psychosocial
support and early initiation of a rehabilitation
programme.[149] [151]
TREATMENT
39
Emerging
Antiviral agents and vaccines
Various vaccines are in development, including purified inactivated viral (PIV) particles, purified virus-like
particles (VLPs) and viral subunit proteins, live-attenuated vaccines, chimeric vaccines, and viral and nonviral
vectors encoding Zika virus structural proteins.[196] [197] [198] Zika purified inactivated virus (ZPIV) vaccine,
an investigational vaccine, has started clinical trials to test safety and efficacy in the US.[132] A synthetic
DNA vaccine (GLS-500) has shown promise in a phase I trial.[199] A live-attenuated vaccine has also shown
promise in animal studies.[200] While there are currently no specific antiviral treatments available for Zika
virus infection, various candidates are being trialled in early-stage trials.[201] [202] Antiviral agents effective
against the hepatitis C virus are being tested and have shown activity against Zika virus polymerase.[203]
Selected antimalarial drugs have shown activity against Zika virus.[204] A new mouse model may help in
exploring the potential activity of Zika virus vaccines and therapeutics.[205]
TREATMENT
Zika virus infection Follow up
Recommendations
Monitoring
FOLLOW UP
Pregnant women with suspected or confirmed Zika virus infection should have regular fetal ultrasounds to
assess the fetus for the presence of microcephaly or other abnormalities. All pregnant women should be
encouraged to attend scheduled antenatal visits.[14]
Infants with congenital Zika syndrome should be followed up at 1, 3, 6, 9, 12, 18, and 24 months of age.
Additional follow-up may be required if there are other complications. Follow-up beyond 24 months will
depend on the child's individual needs.[177]
Assessment should include:[2] [177]
• Head circumference measurement

• Neurodevelopmental assessment
• Hearing screen
• Ophthalmological assessment
• Feeding and growth
• Endocrine assessment
• Psychological well-being of families and caregivers.
Infants with laboratory evidence of congenital infection who do not have any apparent abnormalities
consistent with congenital infection should have ongoing developmental monitoring and screening,
including hearing tests, by a primary care physician.[2]
The World Health Organization (WHO) offers specific guidance for the screening, assessment, and
management of neonates and infants with congenital Zika infection.
Patients with Guillain-Barre syndrome should be followed up for sequelae and multidisciplinary
rehabilitation therapy.[149]
Patient instructions
General information
• The Centers for Disease Control and Prevention (CDC) has produced a useful overview page:
• [CDC: about Zika]

• The World Health Organization (WHO) has produced a questions and answers page:
• [WHO: Zika virus and complications - questions and answers]
Mosquito bite prevention
• Patients should be advised to avoid mosquito bites in at least the first week of illness by using the
following measures:[133] [134]
• Wearing clothes that cover as much of the body as possible (e.g., long-sleeved shirts and
long trousers); clothes may be treated with permethrin
41
• Staying in places with air conditioning or that use window and door screens to keep
mosquitoes outside
• Sleeping under a mosquito net (possibly impregnated with insecticide)
FOLLOW UP
• Using approved insect repellent (if ≥2 months of age); can be used safely in pregnant and
breastfeeding women when used as directed [EPA: find the insect repellent that is right for
you]
• Covering cribs, strollers, or baby carriers with a mosquito net
• Emptying, cleaning, or covering containers that can hold water to reduce areas where
mosquitoes can breed including in and around households.
• [CDC: mosquito bite prevention for travelers]
• Travellers returning from areas of ongoing transmission should use mosquito bite prevention
measures for 3 weeks after returning to prevent spread to uninfected mosquitoes.[134]
Sexual health
• Recommendations for pregnant couples: the CDC recommends that pregnant women with male or
female sex partners who live in or have travelled to an area with active transmission should abstain
from sex (vaginal, anal, oral) or use barriers against infection (e.g., condoms) during sex for the
duration of the pregnancy. Additionally, the CDC recommends that pregnant women talk with their
healthcare providers about their sex partner’s potential exposures to Zika virus and symptoms of
Zika-like illness.[139]
• Recommendations for non-pregnant couples: the CDC recommends that if only the female partner
travels to an area with risk for transmission, the couple should use condoms and abstain from sex
for at least 2 months after the female partner's symptom onset (if symptomatic) or last possible
exposure (if asymptomatic). However, if the male partner (or both partners) travel to an area
with risk for transmission, the couple should use condoms and abstain from sex for at least 3
months after the male partner's symptom onset (if symptomatic) or last possible exposure (if
asymptomatic).[139]
• The WHO still recommends safe sex practices for at least 6 months in men or women
returning from areas with active transmission, regardless of whether they are symptomatic or
asymptomatic.[70]
Zika and pregnancy
• Women living in endemic areas should consult local health authorities for advice before becoming
pregnant. In Brazil, there are no formal recommendations to avoid pregnancy because of the Zika
virus outbreak; the choice to get pregnant is regarded as a personal decision.[142]
• The CDC has produced information for pregnant women and Zika virus infection:
• [CDC: Zika virus - pregnancy]
Travel advice
• The CDC recommends that pregnant women should not travel to any area where there is a risk of
Zika virus infection, including:[144]
• Areas where the virus has been newly introduced or re-introduced and local transmission is
ongoing
• Areas where the virus was endemic (present before 2015) and there is no evidence that
transmission has stopped
• Areas where the virus is likely to be circulating but has not been documented.
• To help pregnant women and others identify areas of Zika risk, the CDC has produced an
interactive map that allows people to search for location-specific information and travel
recommendations:
• [CDC: world map of areas with risk of Zika]

• Advice varies internationally and travellers should stay informed about Zika virus outbreaks:
FOLLOW UP
• [CDC: Zika travel information]
• [WHO: information for travellers visiting Zika affected countries]
• [Public Health England: Zika virus - travel advice]
Complications
Complications Timeframe Likelihood

Guillain-Barre syndrome and/or other neurological short term low
disorders
Guillain-Barre syndrome (GBS) and other neurological disorders are strongly associated with, and
suspected to be caused by, Zika virus infection but the link is unestablished and studies are ongoing,
including to elucidate a possible mechanism.[10] [11] [12] [13]
Current evidence estimates the incidence of GBS to be 24 cases per 100,000 persons infected with
Zika.[43]
Cases of acute myelitis, meningoencephalitis, and acute disseminated encephalomyelitis have been
reported in patients with Zika virus infection.[26] [213] [214] [215] [216]
A case of rapidly developing acute demyelinating polyneuropathy while the Zika virus was still present in
the serum of the patient has been reported.[118]
Acute sensory polyneuropathy has been reported in one patient during the active infectious phase.[217]
miscarriage short term low
Miscarriage has been reported in some women with Zika virus infection.[218]
uveitis short term low
May be a potential manifestation of Zika virus infection according to case reports.[219] [220] Aqueous
humour from the patient’s eye was positive for Zika virus RNA in reverse-transcription polymerase chain
reaction (RT-PCR). Two cases of Zika-related bilateral hypertensive anterior acute uveitis have been
reported.[221]
cardiovascular complications variable low
A case of transient myocarditis has been associated with Zika virus infection.[222] Other possible
cardiac complications related to Zika virus infection include arrhythmias, heart failure, and pericardial
effusion.[223]
One study suggests that congenital Zika virus infection may be associated with an increased risk of
congenital heart disease, although further research is required.[224]
43
Prognosis
FOLLOW UP
Approximately 80% of patients are asymptomatic, and those with symptoms generally experience a mild,
self-limited illness lasting 2 to 7 days.[14] [147] Severe disease requiring hospitalisation is uncommon and
the case fatality is low.[14] The presence of comorbidities may increase the risk of a fatal outcome, based on
a few case reports.[15] However, fatal outcomes have been reported in healthy individuals.[206] No fatalities
have been reported in children.[44]The Centers for Disease Control and Prevention (CDC) confirmed the
first Zika-related death in the Continental US in an elderly resident of Utah who contracted the virus during
travel to an area with active transmission. The patient also had an undisclosed health condition and the exact
cause of death is unknown.[207]
Prognosis for infants born with microcephaly is unclear; however, microcephaly due to other causes is
associated with a range of neurodevelopmental issues. An estimate of the case fatality rate for infants with
microcephaly associated with Zika virus infection is 8.3%.[208] A study in 19 infants born with microcephaly
in Brazil found that most infants had severe motor impairment and other functional difficulties at 19 to 24
months of age, including seizure disorders, respiratory disorders, hearing/vision impairment, and sleeping/
feeding difficulties. These outcomes often occur together.[209]
A study of 1450 infants that used data from a US Zika registry found that 14% of 1-year-old children who
were exposed to Zika virus in utero had health issues potentially related to virus exposure. Of these infants,
6% had at least one Zika-associated birth defect, 9% had at least one neurodevelopmental abnormality
possibly associated with Zika virus exposure, and 1% had both. However, the authors noted that most
children did not have evidence of all recommended evaluations, and therefore, additional anomalies may
exist.[210]
Once people have recovered from infection, they are likely to be protected from future infections.[211]There is
no evidence to suggest that prior Zika virus infection poses a risk for birth defects in future pregnancies.[212]
Zika virus infection Guidelines
Diagnostic guidelines
Europe
Zika virus (ZIKV): clinical and travel guidance

Published by: Public Health England Last published: 2018
Zika virus infection and pregnancy

Published by: Royal College of Obstetricians and Gynaecologists Last published: 2017
International
WHO toolkit for the care and support of people affected by complications
associated with Zika virus
GUIDELINES
Published by: World Health Organization Last published: 2017
Zika virus country classification scheme

Tool for the diagnosis and care of patients with suspected arboviral diseases
Published by: Pan American Health Organization; World Health Last published: 2017
Organization
Identification and management of Guillain-Barre syndrome in the context of

Zika virus
Laboratory testing for Zika virus infection

Provisional remarks on Zika virus infection in pregnant women: document for

health care professionals
Organization
Preliminary guidelines for the surveillance of microcephaly in newborns in

set tings with risk of Zika virus circulation
Organization
Zika virus (ZIKV) surveillance in the Americas: recommendations for

laboratory detection and diagnosis
Organization
45
North America
Guidance for areas with local Zika virus transmission in the continental
United States and Hawaii
Published by: Centers for Disease Control and Prevention Last published: 2018
Revised recommendations for reducing the risk of Zika virus transmission by

blood and blood components
Published by: US Food and Drug Administration Last published: 2018
Interim guidance for health care providers caring for pregnant women with
possible Zika virus exposure - United States (including US territories)
Guidance for US laboratories testing for Zika virus infection

GUIDELINES
Laboratory safety when working with Zika virus

Practice advisory on Zika virus

Published by: American Congress of Obstetricians and Gynecologists Last published: 2017
CDC Health Information for International Travel (the Yellow Book): Zika
Donor screening recommendations to reduce the risk of transmission of Zika

virus by human cells, tissues, and cellular and tissue-based products
Published by: US Food and Drug Administration Last published: 2016
Interim guidance for interpretation of Zika virus antibody test results

Interim guidance for the diagnosis, evaluation and management of infants

with possible congenital Zika virus infection
Preventing transmission of Zika virus in labor and delivery set tings through
implementation of standard precautions
SOGC recommendation on Zika virus exposure for clinicians caring for

pregnant women and those who intend to get pregnant
Published by: Society of Obstetricians and Gynaecologists of Canada Last published: 2016
Latin America
Protocolo Clínico e Epidemiológico para investigação de casos de

microcefalia no estado de Pernambuco
Published by: Secretaria Estadual de Saúde de Pernambuco Last published: 2015
Oceania
Zika virus: interim guidance information for LMCs (midwives), GPs and other
health professionals dealing with Zika virus in pregnancy
Published by: Ministry of Health New Zealand Last published: 2017
Zika virus - information for clinicians and public health practitioners

Published by: Australian Government Department of Health Last published: 2016
GUIDELINES
Treatment guidelines
Europe
Zika virus (ZIKV): clinical and travel guidance

Published by: Public Health England Last published: 2018
Zika virus infection and pregnancy

Published by: Royal College of Obstetricians and Gynaecologists Last published: 2017
International
WHO toolkit for the care and support of people affected by complications
associated with Zika virus
Tool for the diagnosis and care of patients with suspected arboviral diseases
Organization
Infant feeding in areas of Zika virus transmission

Vector control operations framework for Zika virus

Prevention of sexual transmission of Zika virus

47
International
Screening, assessment and management of neonates and infants with

complications associated with Zika virus exposure in utero
Identification and management of Guillain-Barre syndrome in the context of

Zika virus
Pregnancy management in the context of Zika virus infection

Breast feeding in the context of Zika virus

GUIDELINES
Maintaining a safe and adequate blood supply during Zika virus outbreaks
Psychosocial support for pregnant women and for families with microcephaly
and other neurological complications in the context of Zika virus
Provisional remarks on Zika virus infection in pregnant women: document for

health care professionals
Organization
North America
Interim guidance for preconception counseling and prevention of sexual

transmission of Zika virus for men with possible Zika virus exposure - United
States
Interim guidance for health care providers caring for pregnant women with
possible Zika virus exposure - United States (including US territories)
Interim guidance for managing occupational exposures to Zika virus for

healthcare personnel
Practice advisory on Zika virus

Published by: American Congress of Obstetricians and Gynecologists Last published: 2017
North America
CDC Health Information for International Travel (the Yellow Book): Zika
Interim guidance for the diagnosis, evaluation and management of infants

with possible congenital Zika virus infection
Interim guidance for protecting workers from occupational exposure to Zika

virus
Published by: Occupational Safety and Health Administration; National Last published: 2017
Institute for Occupational Safety and Health
Interim guidance for preconception counseling and prevention of sexual

transmission of Zika virus for persons with possible Zika virus exposure
GUIDELINES
Interim recommendations for Zika vector control in the continental United

States
SOGC recommendation on Zika virus exposure for clinicians caring for

pregnant women and those who intend to get pregnant
Published by: Society of Obstetricians and Gynaecologists of Canada Last published: 2016
Latin America
Management of infection by the Zika virus

Published by: Brazilian Infectious Diseases Society Last published: 2016
Atualização das definições operacionais para notificação e investigação

epidemiológica refrente à ocorrência de casos de microcefalia e/ou alterações
do sistema nervoso central (SNC)
Protocolo Clínico e Epidemiológico para investigação de casos de

microcefalia no estado de Pernambuco
Oceania
Zika virus: interim guidance information for LMCs (midwives), GPs and other
health professionals dealing with Zika virus in pregnancy
Published by: Ministry of Health New Zealand Last published: 2017
49
Oceania
Zika virus - information for clinicians and public health practitioners

Published by: Australian Government Department of Health Last published: 2016
GUIDELINES
Zika virus infection Online resources
Online resources
1. CDC: Zika virus (external link)
2. WHO: Zika virus disease (external link)
3. Pan American Health Organization: Zika virus infection (external link)
4. CDC: Zika virus case counts in the US (external link)
5. WHO: Zika virus classification tables (external link)
6. European Centre for Disease Prevention and Control: threats and outbreaks of Zika virus disease
(external link)
7. CDC: world map of areas with risk of Zika (external link)
8. CDC: mosquito bite prevention for travelers (external link)
9. CDC: Zika virus prevention (external link)
10. WHO: Zika virus disease - interim case definition (external link)
11. CDC: arboviral diseases, neuroinvasive and non-neuroinvasive 2015 case definition (external link)
12. Pan American Health Organization: case definitions (external link)
13. CDC: instructions for submitting diagnostic specimens to the DVBD Arbovirus Diagnostic Laboratory
ONLINE RESOURCES
(external link)
14. WHO: laboratory testing for Zika virus infection (external link)
15. PAHO: Zika virus surveillance in the Americas - recommendations for laboratory detection and
diagnosis (external link)
16. CDC: pregnancy & Zika testing (external link)
17. WHO: screening, assessment and management of neonates and infants with complications
associated with Zika virus exposure in utero (external link)
18. CDC: measuring infant head circumference: an instructional video for healthcare providers (external
link)
19. CDC: updated interim guidance for health care providers caring for pregnant women with possible Zika
virus exposure - United States (including US territories), July 2017 (external link)
51
Zika virus infection Online resources
20. CDC: interim guidance for the diagnosis, evaluation and management of infants with possible
congenital Zika virus infection (external link)
21. CDC: about Zika (external link)
22. WHO: Zika virus and complications - questions and answers (external link)
23. EPA: find the insect repellent that is right for you (external link)
24. CDC: Zika virus - pregnancy (external link)
25. CDC: Zika travel information (external link)
26. WHO: information for travellers visiting Zika affected countries (external link)
27. Public Health England: Zika virus - travel advice (external link)
28. WHO: surveillance for Zika virus infection, microcephaly and Guillain-Barre syndrome (external link)
29. WHO: Zika virus country classification scheme (external link)
30. CDC: US Zika pregnancy and infant registry (external link)

ONLINE RESOURCES
Zika virus infection References
Key articles
• Kindhauser MK, Allen T, Frank V, et al. Zika: the origin and spread of a mosquito-borne virus. Bull
REFERENCES
World Health Organ. 2016 Sep 1; 94(9): 675–686C. Full text Abstract
• Adebanjo T, Godfred-Cato S, Viens L, et al. Update: interim guidance for the diagnosis, evaluation,
and management of infants with possible congenital Zika virus infection - United States, October 2017.
MMWR Morb Mortal Wkly Rep. 2017 Oct 20;66(41):1089-99. Full text Abstract
• França GV, Schuler-Faccini L, Oliveira WK, et al. Congenital Zika virus syndrome in Brazil: a case
series of the first 1501 livebirths with complete investigation. Lancet. 2016 Aug 27;388(10047):891-7.
Abstract
• de Araújo TV, Rodrigues LC, de Alencar Ximenes RA, et al. Association between Zika virus infection
and microcephaly in Brazil, January to May, 2016: preliminary report of a case-control study. Lancet
Infect Dis. 2016 Dec;16(12):1356-1363. Full text Abstract
• Pan American Health Organization; World Health Organization. Provisional remarks on Zika virus
infection in pregnant women: document for health care professionals. January 2016 [internet
publication]. Full text
• Delaney A, Mai C, Smoots A, et al. Population-based surveillance of birth defects potentially related
to Zika virus infection - 15 states and U.S. territories, 2016. MMWR Morb Mortal Wkly Rep. 2018 Jan
26;67(3):91-96. Full text Abstract
• Petersen LR, Jamieson DJ, Powers AM, et al. Zika virus. N Engl J Med. 2016 Apr 21;374(16):1552-63.
Full text Abstract
• Polen KD, Gilboa SM, Hills S, et al. Update: interim guidance for preconception counseling and
prevention of sexual transmission of Zika virus for men with possible Zika virus exposure — United
States, August 2018. MMWR Morb Mortal Wkly Rep. ePub: 7 August 2018. Full text
• Oduyebo T, Polen KD, Walke HT, et al. Update: interim guidance for health care providers caring for
pregnant women with possible Zika virus exposure - United States (including US territories), July 2017.
MMWR Morb Mortal Wkly Rep. 2017 Jul 28;66(29):781-93. Full text Abstract
• Fleming-Dutra KE, Nelson JM, Fischer M, et al. Interim guidelines for health care providers caring
for infants and children with possible Zika virus infection. MMWR Morb Mortal Wkly Rep. 2016 Feb
• Elfiky AA. Zika viral polymerase inhibition using anti-HCV drugs both in market and under clinical trials.
J Med Virol. 2016 Dec;88(12):2044-51. Abstract
References
53
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World Health Organ. 2016 Sep 1; 94(9): 675–686C. Full text Abstract
REFERENCES
2. Adebanjo T, Godfred-Cato S, Viens L, et al. Update: interim guidance for the diagnosis, evaluation,
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MMWR Morb Mortal Wkly Rep. 2017 Oct 20;66(41):1089-99. Full text Abstract
3. França GV, Schuler-Faccini L, Oliveira WK, et al. Congenital Zika virus syndrome in Brazil: a case
series of the first 1501 livebirths with complete investigation. Lancet. 2016 Aug 27;388(10047):891-7.
Abstract
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IMAGES Zika virus infection Images
Zika virus infection Images
Images
IMAGES
Figure 1: Characteristic maculopapular rash in a pregnant woman with Zika virus infection
From the personal collection of Dr Geraldo Furtado, MD, MSc (used with permission)
71
Figure 2: Interpretation of results of laboratory testing for evidence of congenital Zika virus infection
Zika virus infection Images
IMAGES
Figure 3: Recommended Zika virus testing and evaluation of infants born to mothers with laboratory evidence
of Zika virus infection during pregnancy
73
Figure 4: CT scan of the head of an infant with Zika virus infection showing a clear distribution of
periventricular calcifications
From the personal collection of Dr Geraldo Furtado, MD, MSc (used with permission)
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Contributors:
// Authors:
Geraldo Furtado, MD, MSc

Clinical Director
Microcephaly Working Group, Instituto de Medicina Integral Professor Fernando Figueira (IMIP), Recife,
Brazil
DISCLOSURES: GF declares that he has no competing interests.
Adriana Scavuzzi, MD, MSc, PhD

Coordinator Obstetrics/Gynecology
Microcephaly Working Group, Instituto de Medicina Integral Professor Fernando Figueira (IMIP), Recife,
Brazil
DISCLOSURES: AS declares that she has no competing interests.
// Peer Reviewers:
William A. Petri, Jr., MD, PhD

Chief
Division of Infectious Diseases and International Health, University of Virginia, Charlottesville, VA
DISCLOSURES: WAP declares that he has no competing interests.
Dominic Dwyer, BSc (Med), MBBS, MD, FRACP, FRCPA

Director
Institute of Clinical Pathology and Medical Research, Pathology West, Westmead Hospital, Sydney,
Australia
DISCLOSURES: DD is a member of Advisory Boards for bioCSL and GSK in antivirals and vaccines.
Chad Achenbach, MD, MPH

Assistant Professor
Division of Infectious Diseases, Northwestern University Feinberg School of Medicine, Chicago, IL
DISCLOSURES: CA declares that he has no competing interests.
Henry Wu, MD, DTM&H

Assistant Professor of Medicine
TravelWell Center, Division of Infectious Diseases, Atlanta, GA
DISCLOSURES: HW declares that he has no competing interests.

Zika Virus Infection

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Zika Virus Infection

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Zika virus infection

The right clinical information, right where it's needed

Last updated: Aug 09, 2018

[CDC: Zika virus]

[WHO: Zika virus disease]

[Pan American Health Organization: Zika virus infection]

[CDC: Zika virus case counts in the US]

[WHO: Zika virus classification tables]

Mosquito bite prevention and population control

[CDC: Zika virus prevention]

Symptomatic pregnant women

Asymptomatic pregnant women

• [CDC: pregnancy & Zika testing]

• [WHO: Zika virus country classification scheme]

[CDC: US Zika pregnancy and infant registry]

Step-by-step diagnostic approach

Infection prevention and control

• [WHO: Zika virus disease - interim case definition]

Testing in non-pregnant individuals

• [WHO: laboratory testing for Zika virus infection]

Testing in pregnant women

• [CDC: pregnancy & Zika testing]

Testing in infants with suspected congenital infection

Both molecular and serological testing are recommended in:[2]

• Comprehensive physical examination including growth parameters

• Developmental monitoring and screening using validated tools

• Comprehensive ophthalmological examination by 1 month of age

Recommended Zika virus testing and evaluation of infants born to

mothers with laboratory evidence of Zika virus infection during pregnancy

unprotected sexual contact with infected individual

sperm donation from infected individual

exposure to infected human cells/tissues

History & examination factors

maculopapular rash (common)

features of congenital Zika syndrome (infants) (common)

features of Guillain-Barre syndrome (uncommon)

Other diagnostic factors

gastrointestinal symptoms (uncommon)

retro-orbital pain (uncommon)

oedema of lower limbs (uncommon)

transient hearing loss in adults (uncommon)

• Sensitivity and specificity of commercial serology assays is uncertain

Other tests to consider

with a simplified gyral pattern and predominance of pachygyria

Condition Differentiating signs / Differentiating tests

Chikungunya virus • Residence in/travel from • ELISA/indirect fluorescent

Condition Differentiating signs / Differentiating tests

Malaria infection • Residence in/travel from • Giemsa-stained blood film:

Leptospirosis • Zoonosis transmitted by • Darkfield examination: direct

• History of water sports. • RT-PCR: positive Leptospira

Condition Differentiating signs / Differentiating tests

Erythema infectiosum • Exposure to infectious • Diagnosis is usually clinical.

Group A streptococcal • May manifest as sepsis, • Blood or tissue cultures:

Other alphavirus • Includes Mayaro virus • Antibody detection for

Condition Differentiating signs / Differentiating tests

• A person with laboratory confirmation of recent Zika virus infection:

[WHO: Zika virus disease - interim case definition]

Pan American Health Organization (PAHO): interim Zika virus case

• Fever (usually <38.5°C [<101.3°F])

[Pan American Health Organization: case definitions]

Centers for Disease Control and Prevention (CDC): arboviral

[CDC: arboviral diseases, neuroinvasive and non-neuroinvasive 2015 case definition]