Zika Virus: The Struggle is Still Real

Well, even though the groundhog has predicted another 6 weeks of winter, it’s not too early to start thinking about those summer pests – mosquitos – and the diseases they bring with them. Zika virus, in particular. Even though the winter weather has dulled our sensitivity to this emerging threat, it remains a significant problem. The virus is now circulating in 65 countries, mostly in the Americas (1). Currently, the CDC has issued travel alerts to areas where Zika is spreading including Miami-Dade, Florida, Puerto Rico, American Samoa, and the US Virgin Islands (2). Laboratory professionals should be aware of Zika virus because the diagnosis of Zika Virus Disease (ZKD) relies on the laboratory, and many healthcare professionals require guidance from the laboratory on how to proceed with diagnostic testing.

Zika is a flavivirus borne by the Aedes mosquito. Symptoms of ZKD usually last 2-7 days and include mild fever, skin rash, conjunctivitis, muscle and joint pain, malaise or headache. There is scientific consensus that Zika virus infection during pregnancy is the cause of congenital brain abnormalities of the fetus, including microcephaly. This devastating effect of the virus sets it apart from the other Aedes-borne viruses dengue, chikungunya, and yellow fever.

Diagnosis of Zika virus relies on laboratory testing, and yet, there are no FDA approved assays for Zika virus currently available. There are however a number of assays that have been given approval for emergency use, including: Real-Time PCR, MAC-ELISA, and a plaque neutralization reduction test. In the United States, these tests are available from the CDC and some state health labs. An algorithm describing the appropriate use of these tests can be found here. Unfortunately, in developing countries where Zika is endemic, access to the appropriate diagnostic test can be very difficult.

Impediments to accurate diagnosis of ZKD in developing countries include lack of education and access to quality laboratories that offer the right test. Lack of education encompasses not only transmission and prevention of the virus, but also who should seek medical attention and when and who should be tested and when. In many countries where visiting a medical professional is a financial burden to a family, it is less likely that a family will seek medical attention for a disease that has such mild symptoms symptoms as ZKD. While most cases of ZKD don’t require medical attention beyond comfort care, if patients don’t report to clinics or health centers, it is difficult to track and confirm cases if no one presents with a suspected case! Also, there is a need for consensus about what should be called a suspected ZKD case and then how to proceed with confirmatory testing. Some countries, including Brazil, the respective Ministries of Health have issued definitions of a suspected Zika case. The Brazilian definition includes: “patients who present with pruriginous maculopapular exanthema accompanied by two or more of the following signs and symptoms: fever, conjunctival hyperemia without secretion and pruritus, polyathralgia, and periarticular edema” (3). Suspected cases can be confirmed with diagnostic testing, but this is another challenge. The easiest and least expensive test for a clinic in the developing world is a Ig-M based rapid diagnostic test. There are several of these available commercially, mostly from European markets. However, these demonstrate significant cross-reactivity with other flaviruses such as dengue and chikungunya, which are also endemic in areas where Zika is now circulating. The most appropriate tests – RT-PCR, MAC-ELISAs, and plaque reduction tests – are only available in national laboratories it at all. The combination of lack of patients reporting Zika-like symptoms, lack of consensus of what constitutes a suspected case, and limited availability of confirmatory testing means that there is a significant likelihood that the number of Zika cases in many developing countries are underreported.

In January 2016, the WHO presented the Strategic Response Framework and Joint Operations Plan in response to the growing Zika virus epidemic. In October 2016, a quarterly update was released that described the goals and scope of the plan through December 2017. The plan is Strategic Response Plan comprised of four areas: 1) Detection, 2) Prevention, 3) Care and Support, and 4) Research. $10.9 million are dedicated to the detection arm of the strategic plan, which in addition to laboratory testing and diagnosis includes assessment and implementation of preparedness measures, and surveillance and monitoring in it’s scope. $41.2 million are dedicated to the research arm of the plan, which includes the “fast track and scale up of research development and availability of diagnostic tests.”

Hopefully in the next year we will see not only new diagnostic testing, but also medical interventions such as vaccines. In the meantime, it is important that we as laboratory professionals continue to be apprised of available testing, to educate our healthcare partners on the use of lab testing for ZKD, and to support research and development of Zika diagnostics.

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