This Week in Zika: Clinical and Public Health Updates

— New funding, new research on neurological effects of the virus

MedpageToday

Approved supplemental Zika funding will be allocated to U.S. state and local health departments, and will be used to finance research on a vaccine. Meanwhile, both clinical and basic research continued on the myriad neurological conditions associated with Zika among infants and adults.

Zika $$ to Fund State Prevention Efforts, Vaccine Trials

A large portion of recently approved $1.1 billion in funds for Zika virus will be distributed to U.S. states and territories, in addition to planned additional clinical trials for a Zika vaccine and enhanced surveillance for mosquito-borne diseases, said researchers from the CDC, HHS, and the National Institute for Allergy and Infectious Diseases (NAIAD).

On a conference call with officials from all three government agencies, CDC director Tom Frieden, MD, said that $350 million of recently approved funds will be distributed to U.S. states, local governments, and territories to help "fight Zika more effectively and robustly." This will include sending teams to deal with local outbreaks, such as the type of assistance the CDC provided to the state of Florida.

A portion of these funds will also be put toward funding clinical trials for a Zika virus vaccine. The NIH currently has five clinical trials of a Zika vaccine in development, either alone or in collaboration with other agencies, including the Biomedical Advanced Research and Development Authority (BARDA). This includes the DNA-based vaccine that started human trials last week.

Range of Brain Injuries in Zika Microcephaly

There is phenotypic variability in the microcephaly tied to the Zika virus, with differences in the extent of brain damage and affected brain structures, researchers found.

The results showed, however, a common pattern of brain atrophy, and the changes appeared to be tied to disturbances in neuronal migration, according to an assessment of 11 infants born to mothers in Brazil who were infected with the virus.

The findings were reported online in JAMA Neurology by Amilcar Tanuri, MD, PhD, of the Federal University of Rio de Janeiro in Brazil, and colleagues.

More Evidence Links Zika to Guillain-Barré

A small prospective study found that 40% of patients with Guillain-Barré syndrome tested positive for Zika virus infection during a Zika outbreak in Colombia, further strengthening the association between Guillain-Barré and Zika.

Of the 68 patients with Guillain-Barré, 42 underwent laboratory testing for the presence of Zika virus, and 17 of those patients (40%) had a confirmed positive reverse transcriptase polymerase chain reaction (RT-PCR) test for Zika, reported Beatriz Parra, PhD, of Hospital Universitario del Valle in Colombia, and colleagues.

Notably, half of these patients reported a much shorter time to onset of symptoms than is typical for Guillain-Barré, according to the results published online in the New England Journal of Medicine. In fact, 20 of 42 patients reported neurological symptoms either during or immediately after reporting symptoms of Zika virus infection. For all patients, there was a median period of 7 days from the time they reported Zika infection to reporting of Guillain-Barré symptoms.

Culex Mosquitoes Unlikely to be Zika Vectors

The Culex mosquito, which is common throughout North America, may not susceptible to transmitting the Zika virus, researchers found. There had been reports of Zika virus isolates from Culex mosquitoes, raising the question as to whether they could potentially act as secondary vectors for Zika.

But a study published in Vector-Borne and Zoonotic Diseases suggested otherwise. Researchers fed Culex mosquitoes blood meals containing Zika, but found a high degree of refractoriness, or insensitivity to stimulation to the virus -- even when the mosquitoes were exposed to high-titer blood meals.

The authors concluded that because of their findings, Florida should concentrate mosquito control efforts on both the Aedes aegypti and Aedes albopictus as sources of local transmission of Zika virus.

Zika Persists in Saliva and Semen of Nonhuman Primates

Zika virus RNA was found in the saliva and semen of rhesus and cynomolgus macaques as long as 28 days following infection which was considerably longer than it was detectable in blood or urine. Writing in Nature Medicine, researchers infected these apes with Zika virus and tested the animals for viral RNA as early as a day after infection.

They found Zika virus RNA in saliva and semen 3 weeks after it had cleared from the blood. Zika was detectable in blood serum as early as 1 day following infection, in urine as early as 2 days and saliva in half the subjects 3 days following infection. But it cleared from both blood plasma and urine 10 days after infection.

Researchers also found Zika RNA in tissue samples of the animals, including the brain and both male and female reproductive tissues both during early and late stages of infection. For males, Zika was found in semen, and in the uterus for females -- but little was found in vaginal secretions, potentially shedding more light onto sexual transmission of the virus.

Vaccine Candidates Show Promise in Mice

Mice showed immunity to Zika virus from 2 weeks to 6 weeks following inoculation, researchers found. They developed and tested two vaccines -- one traditional needle delivery and one "micro-needle array" (a Band-Aid-like patch that affixes just below the skin and delivers the vaccine through tiny crystals) -- and reported their results in EBioMedicine.

The mice showed immunity to the needle-based vaccine after two weeks and the micro-needle array vaccine after 6 weeks. Five weeks inoculating the mice with either vaccine or a saline-based solution, researchers mated them and tested the pups for Zika. All of the needle vaccine pups and half of the micro-needle array vaccine pups were immune to Zika, while none of the control pups were.

However, the needle-based vaccine was only a "proof of principle" as its method of delivery (an adenovirus similar to the common cold) would likely not work well in humans. Researchers plan to move ahead on a second-generation of the micro-needle array vaccine.