History and exam

Key diagnostic factors

presence of risk factors

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

Fever is usually low-grade (i.e., <38.5°C [<101.3°F]).[150][169]

maculopapular rash

Rash (sometimes morbilliform) is characteristic of infection and may be itchy.[14][150]com.bmj.content.model.Caption@51929ae4[Figure caption and citation for the preceding image starts]: Characteristic maculopapular rash in a pregnant woman with Zika virus infectionFrom the personal collection of Dr Geraldo Furtado, MD, MSc (used with permission) [Citation ends].

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

Particularly in the small joints of hands and feet.[169]

Peri-articular oedema may be present.[150]

conjunctivitis

Usually non-purulent.[14][150][171]

Conjunctival hyperaemia may be present.[150][171]

features of congenital Zika syndrome (infants)

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 potential Zika virus exposure should undergo an eye examination regardless of the presence or absence of other symptoms.[161]

features of Guillain-Barre syndrome

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

Include malaise, myalgia, and/or headache.[14][133][150]

gastrointestinal symptoms

Include vomiting, diarrhoea, and/or abdominal pain.[14]

retro-orbital pain

Uncommon symptom reported in some cases.[14]

oedema of lower limbs

Uncommon symptom reported in some cases.[14]

transient hearing loss in adults

An association between Zika infection and transient hearing loss has been reported in a small number of cases.[172]

Risk factors

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]

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 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]

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]

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