Sunday, October 2, 2016

Zika Update 10-2-2016

Aedes aegypti

It's been a busy two weeks with news on Zika. As usual, there is good news and not so good news.

First the best news: The US congress has finally approved the Zika spending bill and the important research that was in danger of running out of funding. However, the delay in funding has allowed Zika to establish a foot hold in the continental US and resulting in money being used to develop strategies to combat Ebola being diverted for the Zika work. 

There is more good news for Zika with a vaccine entering Phase I human trials now. Another piece of good news was the identification of a co-factor that increases the risk of birth defects: prior infection with Herpes simplex virus-2 which I wrote a blog post about here.

Now for some of the bad news. It is now likely that Zika can be transmitted by sweat and tears. This is the result from the case in Utah where someone was infected caring for an infected family member who later died. As a precaution, people who are caring for those who are sick with Zika should make sure that they are careful and not coming into contact with bodily fluids that may contain Zika. Likewise, new recommendations from the CDC advise that those exposed to Zika but aren't showing symptoms wait 6 months before trying to have children (or unprotected sex with a pregnant woman). The previous recommendation was 8 weeks. 

In more bad news, the area of local Zika transmission is expanding with more mosquitoes being found outside of the original area 
that are carrying the virus. Likewise, more cases are being reported in the area from both local sources and from travel. If this news wasn't bad enough, local surveillance of mosquitoes has revealed that Dengue is now in Southern Florida as well. This is bad news because research has revealed that Zika and Dengue are closely related enough that they can cause antibody-dependent enhancement of disease. This means that getting Dengue first could result in a more severe case of Zika infection and that getting Zika first could result in the more severe form of Dengue that can be lethal.  

We are also beginning to discover that Zika causes more lasting damage in children infected in utero than researchers initially thought. The initial reports are just starting to come in, but it may be years before we know the full extent of damage that Zika does. This damage highlights why a vaccine would be warranted even if the rate of birth defects are low. Additionally, cases of birth defects caused by Zika are being seen in other locations, outside of Brazil, where outbreaks are occurring. Two cases of microcephaly have recently been identified in Thailand that have been linked to Zika infection. One argument that is commonly used against Zika causing birth defects is that cases of microcephaly haven't been seen elsewhere. This wasn't the case prior and now that researchers and medical professionals know what to look for, cases are being identified in locations with outbreaks.

Another sad result is the recent fight between researchers over the best test for detection of Zika. In recently released documents, a researcher has been fighting with the CDC over whether using an RT-PCR test (used to detect RNA viruses) in singleplex (targets only one sequence) or a multiplex (targets two or more unique sequences) assay is best. Fights like this only hurt public confidence as the nuances that would be plainly evident to researchers are not known by the general public. Yes, testing for a single target at a time is generally more sensitive than multiplexing several targets; however, multiplex assays can be optimized so that is isn't an issue and should be done prior to releasing the technique to the community. But this fight is something really belongs in a scientific journal and not on the internet.

In an interesting piece of news, a team from KSU recently reported that Culex species of mosquitoes do not transmit Zika. However, there are a number of issues with this report. They didn't actually test for transmission, they just fed mosquitoes infected blood and tested them by RT-PCR after 7 and 14 days. None of the mosquitoes tested positive after 7 days despite being positive immediately after feeding. There are a number of concerns that are raised by the methodology used in this study. The first is that they only tested a small number of mosquitoes (about 30 at each time point for two isolates of C. pipiens and one of C. quinquefasciatus). I reported in the last update that C. pipiens is not a vector as seen in a transmission assay (really the best way to see if an arthropod is a vector or not), so I don't doubt those results. If C. quinquefasciatus is an inefficient vector, it is possible to miss it with those numbers. Another issue here is that there is a conflicting report from Brazil where replication of Zika was detected in several tissues including the salivary glands (which is a prerequisite to transmission for flaviviruses). In the report from Brazil, a total of 99 mosquitoes were tested which could explain the differences between the two studies. Another big difference is the study from Brazil used qRT-PCR as opposed to RT-PCR (qRT-PCR is far more sensitive than RT-PCR). Additionally, electron microscopy was done on the dissected C. quinquefasciatus salivary glands and signs of viral replication were observed. More importantly, this work from Brazil showed that Zika had low titers in C. quinquefasciatus, suggesting that there is the risk of RT-PCR detection resulting in false negatives due to the low starting titer. Certainly more work is needed here, but the results of the Kansas study do not show that C. quinquefasciatus isn't a vector for Zika as they never tested that. That is bad science reporting and could lead to serious repercussions as a potential vector could be ignored.

I didn't want to leave this update on a sour note, so I saved one of the best stories for last. A paper describing two Zika DNA vaccines (see my infographic below) has been published. In addition to these vaccines protecting mice and eliciting a robust neutralizing antibody response in rhesus macaques, the results  give researchers a clue as to the dosage needed in order to prevent viremia (spread of the virus through the bloodstream). One of these DNA vaccines is currently the one that is in clinical trials that I mentioned above. The second DNA vaccine will start Phase I clinical trials soon. 

My infographic on DNA vaccines.