The swiftness with which Zika and the Zika virus have gained notoriety is nearly unprecedented. The fear of a not-well-characterized disease, including transmission, symptoms, and infection sequelae, has lead to dire warnings and even the spread of misinformation. Scientists are moving as quickly as they can to secure funding and prevent further spread of this arbovirus.
One of the first challenges is in properly diagnosing Zika infection. Diagnosis is challenging for several reasons: first, many infected individuals don’t suffer severe symptoms. Those that do have relatively non-specific symptoms of low-grade fever, headaches, and muscle soreness that are sometimes seen with conjunctivitis or retro-orbital pain. These general symptoms mean many people infected with Zika may not even go to the doctor, and those that do may be misdiagnosed. Patients with Zika are often suspected of having Dengue fever or a mild case of Chikagunya, and can also be mistaken for Plasmodium, herpes virus, or West Nile virus infection cases.
The second challenge for Zika infection is technical: we don’t have good tools for diagnosis of this disease. This is in part because of the newness of the wide-spread viral distribution (although the virus itself is not newly discovered; it was first described in 1947). This is also in part because of the similarity of Zika virus to another flavivirus, Dengue virus. Serology testing examines whether a patient has mounted an immune response to a particular pathogen (although it doesn't differentiate whether that pathogen, such as the virus, is still in the patient’s system). The Zika virus and Dengue virus are similar enough that IgM antibodies used to diagnose Dengue virus infection have given false positive results for patients actually infected with Zika virus. Proper treatment and conditional associations (such as risk of microcephaly and Guillain-Barré syndrome) can only be determined with correct diagnoses, emphasizing the importance of these tools.
- Viral culture: Although this technique is not generally used for clinical purposes, Zika virus can be passaged in several primate cell lines as well as a mosquito cell line.
- Antibody detection: Cross-reactivity with other flaviviruses is an issue, as discussed above. Development of Zika-specific serology tests is important to assess the risk to developing fetuses for congenital infections that are associated with microcephaly.
- Antigen Detection: Not yet available for Zika virus.
- RNA Detection: This is the best way to diagnose an ongoing infection, and the CDC has both a real-time and standard RT-PCR assay to detect viral RNA genomes present in patient samples, including serum, plasma, saliva, and amniotic fluid. Commercial tests are becoming available but have yet to be clinically assessed.
Differentiating Zika from Dengue virus infection is one of the top priorities for diagnostic toolmakers, since Dengue virus is endemic in the regions Zika has been spreading (compare the Zika map, with purple, to the Dengue map, with orange, above). People living in those regions could well have subsequent, or even simultaneous, infection with both Dengue and Zika virus, and differentiating those who have experienced both from those who have experienced only one is an important priority with both clinical and epidemiological implications. An additional upside of improved diagnostics for Zika is that they may also lead to improved diagnostics for Dengue, another important mosquito-borne disease that affects millions of people worldwide.
For more information on Zika virus, please check out the American Society of Microbiology’s Zika Resources website, which is updated as articles such as this Journal of Clinical Microbiology review are published.
-- Julie Wolf