Most Zika infections are asymptomatic and non-consequential unless the infected person is pregnant or has had unprotected sex while the virus was circulating in the blood or persisting in a human reservoir like semen. Thus, we have seen tragic birth defects, failed or terminated pregnancies, transmission to sexual partners both male and female, and Zika infection following a needlestick.
But perhaps no case of Zika is as strange and alarming as that of the first U.S. death due to the emerging virus in June of this year in Salt Lake City. While hospitalized, the 73-year-old patient apparently transmitted Zika to a visiting acquaintance — possibly through tears — before dying with an incredibly high level of circulating virus in the blood. The secondary case developed symptomatic Zika infection, but subsequently recovered.
It is concerning, but not completely unexpected, that a patient could transmit a virus that was circulating in high titers in his system, but the level of virus was off the charts. At 200 million particles per milliliter, the Zika viral load in the patient was 100,000 times higher than what had been reported in other Zika cases, researchers recently reported.1
As a result, a previously healthy 38-year-old acquaintance of the index case — with no travel history or other Zika risk factors — acquired the virus after having wiped the index patient’s watering eyes and helped a nurse reposition him in the bed.
“It is likely that Patient 2 acquired the infection from Patient 1, since Patient 2 had not traveled to an area in which Zika virus (ZIKV) is endemic in more than 9 months and had not had sex with a partner who had traveled to such areas,” investigators concluded. “Given the very high level of viremia in Patient 1, infectious levels of virus may have been present in sweat or tears, both of which Patient 2 contacted without gloves. Transmission of the infection through a mosquito bite appears to be unlikely, since Aedes species that are known to transmit ZIKV have not been detected in the Salt Lake City area. In addition, the second case occurred 7 to 10 days after contact with the index patient in the hospital, which implicates direct contact during hospitalization. … No healthcare workers who had contact with Patient 1 reported having symptomatic illness.”
No Smoking Gun
There are many unresolved aspects to the case, perhaps none greater than the central question of why the patient developed such a high titer of Zika virus. A variety of host and viral possibilities are being considered, but there is no smoking gun clearly suggesting a mutation that would enhance Zika virulence or an underlying illness that made the man highly susceptible to escalating infection.
One intriguing theory is that treatment for prostate cancer opened the door for Zika to aggressively multiply in the man’s system. Before traveling to Mexico, where he reported being bitten by mosquitoes, the patient had completed radiation therapy for prostate cancer and was still on antiandrogen or “hormone” therapy when hospitalized.
“[R]adiation therapy and androgen blockade may have played a role in enhancing ZIKV virus pathogenicity,” the investigators note. “In that regard, it is of interest that ZIKV persists in seminal fluid after clearance of viremia and may reach levels exceeding those in blood, suggesting that cells in the male reproductive system may provide a milieu particularly suitable for ZIKV persistence and replication. It is possible that radiation therapy may have enhanced ZIKV replication in irradiated tissues, and this may be a suitable area for further research.”
- Swaminathan S, Schlaberg R, Lewis J, et al. Correspondence: Fatal Zika Virus Infection with Secondary Nonsexual Transmission. New Engl Jrl Med September 28, 2016: DOI: 10.1056/NEJMc1610613.