History and exam
Key diagnostic factors
common
residence in/travel from endemic area
Diagnosis should be suspected in patients who have resided in/traveled from an area where there is ongoing transmission in the 2 weeks prior to symptom onset.
Only 20% of infections are thought to be symptomatic.[14]
fever
Fever is usually low-grade (i.e., <101.3°F [<38.5°C]).[144]
maculopapular rash
Rash (sometimes morbilliform) is characteristic of infection and may be itchy.[14][144][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.[168]
arthralgia
features of congenital Zika syndrome (infants)
Congenital Zika syndrome is a recognized 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, postpartum-onset microcephaly in infants born with a normal head circumference, postpartum-onset hydrocephalus in infants born with microcephaly, sleep electroencephalogram abnormalities, and diaphragmatic paralysis in infants born with microcephaly and arthrogryposis.[2][167]
Infants may present with microcephaly or other manifestations including spasticity, hypertonia, abnormal persistence of primitive reflexes, impaired cognitive development, delayed neuropsychomotor development, seizures, craniofacial disproportion, retrognathia, brainstem dysfunction, ocular abnormalities, hearing loss, speech disorders, impaired language development, alteration in tongue frenulum, absence of stapedial reflexes, findings on neuroimaging (e.g., cortical disorders, calcifications, ventriculomegaly), arthrogryposis (e.g., congenital joint contractures), low birth weight for gestational age, irritability, dysphagia, and feeding difficulties.[147][148][149]
Features consistent with fetal immobility (e.g., dimples, feet malpositions, distal hand/finger contractures) may also be present.[150]
There have been reports of these neurologic abnormalities in infants who have a normal head circumference and with mothers who do not report having a rash during pregnancy.[3][151][152][153][154] It does not appear to be associated with maternal disease severity.[155] Poor head growth with microcephaly developing after birth has been reported in a small number of patients in Brazil.[157]
Eye abnormalities may be the only initial finding; therefore, it is recommended that all infants with potential Zika virus exposure should undergo an eye exam regardless of the presence or absence of other symptoms.[158]
uncommon
features of Guillain-Barre syndrome
Neurologic complications are rare and have been reported in 0.3% of cases, with the most common complication being Guillain-Barre syndrome (GBS).[46]
The clinical phenotype is generally a sensorimotor demyelinating GBS with a severe disease course. The most common features were limb weakness (97%), absent/diminished reflexes (96%), sensory symptoms (82%), and facial palsy (51%). Median time between infectious and neurologic symptoms was 5 to 12 days.[138]
Key diagnostic factors include paresthesias (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 recommends using the Brighton criteria for the case definition of GBS.[143] The Pan American Health Organization has also published a case definition for Zika-related GBS.[144]
Physicians should be vigilant for early signs and symptoms of GBS as it may progress faster than usual in patients with Zika virus infection.[25]
Other diagnostic factors
uncommon
gastrointestinal symptoms
Include vomiting, diarrhea, and/or abdominal pain.[14]
retro-orbital pain
Uncommon symptom reported in some cases.[14]
edema 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.[146]
Risk factors
strong
residence in/travel from endemic area
Diagnosis should be suspected in patients who have resided in/traveled from an area where there is ongoing transmission in the 2 weeks prior to symptom onset. CDC: Yellow Book Opens in new window
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.[47][53] There is emerging evidence that Zika virus could also be spread by Culex quinquefasciatus, although this has been disputed.[54][55][56][57]
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 cases of male to female transmission from asymptomatic men. Sexual transmission from women to their sexual partners has been reported.[70] Male-to-male sexual transmission has also been reported.[71] There is the possibility of oral transmission of the virus through semen.[72]
weak
blood transfusion from infected individual
Transmission is thought to be possible from blood transfusions; however, further investigation is required. Transmission via platelet transfusion has been reported in Brazil.[62][63][64][66]
The overall pooled prevalence of Zika virus RNA and antibodies in blood donations has been reported to be 1%.[125]
Blood donation is not recommended for 1 month following Zika infection or exposure.[126] Some countries may test blood donations for Zika virus.
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 traveled 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 counseled on the risks.
There is the potential for infection at various stages of assisted reproduction, and this should be considered.[127]
exposure to other infected body fluids
Zika virus RNA has been detected in body fluids other than blood or semen including amniotic fluid, cerebrospinal fluid, urine, saliva, vaginal secretions, and ocular fluids; however, transmission via these body fluids has not yet been documented.[60][78][79][80][81][82][83]
While the virus has been detected in breast milk, there are no reports of transmission via breast-feeding.[90] One systematic review found no evidence of perinatal transmission via breast-feeding or breast milk intake based on low-certainty evidence.[91]
The virus has been detected in the genital tract of infected women, sometimes for long periods after clearance from the blood and urine, which may have implications for vertical transmission.[86][87] Viremia has been reported in a newborn at least 67 days after birth.[89]
The Centers for Disease Control and Prevention 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.[93]
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, and infection with Zika was strongly suspected in a pediatric patient who developed Guillain-Barre syndrome after hematopoietic stem cell transplant in one case report.[67][68]
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