Which Mosquito-borne Virus is it?

That may be the “$64,000 Question” facing clinicians in South America and the Caribbean, where 3 viruses linked with the Aedes aegypti mosquito have caused concurrent epidemics, resulting in confusion as efforts are made to diagnose and treat them. The most troubling of these viruses is, of course, Zika, which has been linked with serious birth defects (including microcephaly) in babies born to infected mothers.

Now, research funded by the National Institutes of Health and Abbott Laboratories and published online on July 13 in the Journal of Clinical Microbiology (JCM) has confirmed what many clinicians have seen on the ground in Brazil, the epicenter of the Zika epidemic, and elsewhere: that a coinfection with Zika virus and diseases such as dengue fever and chikungunya, which have also plagued the region recently, may be missed if they fail to “test for more than 1 virus,” said study co-author Charles Chiu, MD, PhD, director of the Abbott Viral Diagnostics and Discovery Center at the University of California-San Francisco, in a statement released in conjunction with the publication of the findings.

“With these viruses, the symptoms associated with acute illness, including fever, rash, joint pains, and conjunctivitis, are non-specific, so it is difficult to make an accurate diagnosis based on clinical findings alone” Dr. Chiu continued. “It’s easy to imagine a physician failing to detect Zika when they instead suspect a different virus that causes similar symptoms, and then their suspicion is confirmed by a diagnostic test designed to detect only that virus—they might easily miss a co-infection if they do not test for more than one virus.”

Dr. Chiu and his team, which included Silvia Sardi, PhD, the Federal University of Bahia (Brazil) researcher credited with being among the first to identify Zika in Brazil, used a single “metagenomic” laboratory test that can detect virtually any known virus to analyze blood samples from patients infected with Zika. They found two cases of co-infection with the chikungunya virus among 15 previously confirmed Zika cases (and none with dengue) from the state of Bahia, Brazil diagnosed between April, 2015 and January, 2016. To date, Bahia is the Brazilian state with the highest number of Zika-associated cases of microcephaly.

In another study that used serum from the same cases, Dr. Chiu and his colleagues confirmed with “molecular clock” sequencing analysis that the Zika strain currently circulating in Bahia likely emerged in mid-2014, more than 8 months before the first documented case of Zika infection in Brazil was reported in March of 2015. This research is scheduled for publication in the October 2016 issue of the journal Emerging Infectious Diseases.

“The failure to identify Zika virus in Brazil in a timely fashion underscores the urgent need for comprehensive diagnostic tests that can rapidly monitor the emergence of outbreak pathogens,” Dr. Chiu said in the UCSF release. “Had these tests been in place, we might have had the opportunity to curtail spread of the outbreak.”

Although the symptoms of Zika, dengue, and chikungunya typically mirror those of severe influenza, the viruses pose significant health consequences to those infected. In addition to microcephaly, Zika infection has also been associated with Guillain-Barré syndrome, while chikungunya infection can cause chronic arthritis and dengue virus infection can cause encephalitis, immune-mediated syndromes, and/or stroke.

According to Dr. Chiu, these and other potential complications make the need for development of comprehensive—and accurate—tests imperative. At present, there is no US Food and Drug Administration-approved test for Zika virus, and the lab tests commonly used, which are designed to detect antibodies to Zika, have been associated with “false-positive” results in cases in which another virus (typically dengue or chikungunya) is present.

“Traditionally, barriers to next-generation sequencing have included high costs, complex instrumentation, and lack of dedicated bioinformatics tools,” Dr. Chiu and colleagues write in JCM. “These barriers are being overcome with the development of rapid computational pipelines for analysis of next-generation sequencing data, and emergence of portable sequencers that can be used in field laboratories and other point of-care settings.”

Brian P. Dunleavy is a medical writer and editor based in New York. His work has appeared in numerous healthcare-related publications. He is the former editor of Infectious Disease Special Edition.