Top: Baby with microcephaly. Bottom: Baby with normal head size. Source: CDC, National Center on Birth Defects and Developmental Disabilities.
Based on the typical clinical features, the differential diagnosis for Zika virus infection is broad. In addition to Dengue, other considerations include leptospirosis, malaria, rickettsia, group A streptococcus, rubella, measles, parvovirus, enterovirus, adenovirus, and alphavirus infections (eg, Chikungunya, Mayaro, Ross River, Barmah Forest, O’nyong-nyong, and Sindbis viruses) (CDC, 2016a).
Preliminary diagnosis is based on the patient’s clinical features, places and dates of travel, and activities. Laboratory diagnosis is generally accomplished by testing serum or plasma to detect virus, viral nucleic acid, or virus-specific immunoglobulin M (IgM) and neutralizing antibodies (CDC, 2016a).
A suspected case of Zika requires the presence of rash and/or fever with either arthralgia, arthritis, or non-purulent conjunctivitis. A probable case requires these symptoms in conjunction with the presence of anti-Zika IgM antibodies and an epidemiologic link within two weeks prior to symptom onset to a region with local transmission (Malone et al., 2016).
A confirmed case of Zika virus disease requires laboratory confirmation of recent Zika virus infection by either the presence of Zika virus RNA or antigen in serum or other samples (e.g. saliva, tissues, urine, whole blood); or IgM antibody against Zika virus positive and PRNT90 for Zika virus with titre ≥20 and Zika virus PRNT90 titre ratio ≥ 4 compared to other flaviviruses; and exclusion of other flaviviruses (Malone et al., 2016). The PRNT90 is considered the "gold standard" for detecting and measuring antibodies that can neutralize a virus.
Microcephaly is defined as occipitofrontal circumference less than the third percentile, based on standard growth charts for sex, age, and gestational age at birth. The occipitofrontal circumference should be disproportionately small in comparison with the length of the infant and not explained by other etiologies or congenital disorders. If an infant’s occipitofrontal circumference is equal to or greater than the third percentile but is notably disproportionate to the length of the infant, or if the infant has deficits that are related to the central nervous system, additional evaluation for Zika virus infection might be considered (Staples et al., 2016).
In 2016 Zika virus disease became a nationally notifiable condition. Healthcare providers are encouraged to report suspected cases to their state or local health departments to facilitate diagnosis and mitigate the risk of local transmission. State health departments are encouraged to report laboratory-confirmed cases to CDC through ArboNET, the national surveillance system for arboviral disease (CDC, 2016a).