Thanks for yet another year of great podcasting.
After last year’s success with the twiebov-episodes (this week in ebola virus), I thought you might like to do some similar episodes on the current big virus news in the media: zika. Other than being interesting, sad and difficult to handle; Twiz has a nice ring to it.
Hello the Twiverers,
A quick question to add to the many I am sure you’re getting on Zika.
At a seminar in our department this week a visiting speaker* pointed out the odd fact that the increase in reported microcephaly is much, much higher in Brazil than elsewhere (for example in Colombia, which also has a high incidence of Zika) and much higher in a few specific regions of Brazil in a way which didn’t obviously correlate with viral incidence.
When pressed on why this might be he pointed out that responses to previous arbovirus outbreaks had led to very high insecticide use in some areas, without the measures to protect humans that he would be comfortable with.
At the time of writing there is a correlation between Zika and microcephaly but no mechanistic link. I would be interested in your thoughts – could the rise in microcephaly be a result of intoxication by insecticides rather than arbovirus infection?
Hopefully by the time you discuss this there will be more data; at the moment everything is worryingly speculative. Thank you,
University of Oxford, UK
*whom I did not contact about this e-mail, so he can be left as a nameless worker in a relevant area
Dear TWIV hosts
Writing from São Paulo, 23oC, cloudy skies, humidity 100%, visibility 3Km, Wind 6.4 Km/h ENE, no autochthonous zika virus transmission in the city yet.
As Vincent requested, I am writing an update on the Zika disease situation in Brazil. Most information is based on official reporting from the Brazilian Government. However, I will take the freedom to bring few perceptions, which the listeners should take with a grain of salt.
The most notorious information is how the media is covering the subject. Every (I mean every) front newspaper or weekly magazine portray something related to Zika virus (ZKV). It has been overwhelming and a good time to teach some virology to the general population. Needless to say that there are many conspiracy theories spreading in social media (wackaloons saying that the virus causes neurologic defects in children up to 7 years-old and the microcephaly cases were caused by an expired vaccine…). These are the front pages for the main two weekly magazines: an arthropod showcase, in a picture I took at the newsstand three days ago.
Figure: Two of the main Brazilian weekly magazines front covers this week.
Updated microcephaly report
The Brazilian Ministry of Health issued another update on January 2nd, with 3,670 suspected cases under investigation, 404 confirmed microcephaly cases probably associated with ZKV and 706 discarded cases. Microcephaly has been detected in 22 out of 26 states. As per the map, Brazil has 5 regions.
Most cases concentrate in the Northeast Region (blue in the map), with 2,995 suspected cases, 401 confirmed.
To date, 17 cases had positive PCR for ZKV RNA (personal communication), which is still a minority.
Seventy six deaths were attributed to microcephaly or other neurological defects at birth. Of those, 15 were confirmed to be probably associated with Zika, 5 of those with identified Zika virus (by RT-PCR). 56 are under investigation and 5 were discarded.
Acute Zika cases
It is very hard to say how the virus is spreading, since the viremia is short-lasting and the access to RT-PCR is quite limited across the country. However, ID colleagues working in the Northeast Region tell me that the number of suggestive acute rash disease cases has dramatically decreased. On the other hand, the North and Central-West regions seem to be having virus circulation at the moment. No case of local transmission has been documented in the City of São Paulo.
My perception is that microcephaly cases is the developing of a picture of the epidemic taken several months before. Therefore, it would not be surprising to see declining number of acute Zika cases where one sees a surge of microcephaly cases. Tracking the virus transmission would be a more efficient way of implementing preventive interventions and counselling for women in reproductive age.
GBS cases continue to be observed, but no report is available with a consolidated number of cases in Brazil. Most seem to be mild, but few severe cases were noted. This perception has been confirmed in other countries. El Salvador just reported an increase in the number of GBS (http://www.who.int/csr/don/21-january-2016-gbs-el-salvador/en/), with 46 cases, including 2 deaths, from 1 December 2015 to 6 January 2016, contrasting to the average yearly number of 169 cases. My clinical team is currently providing care to a 56 y-o woman with Zika-associated GBS. She came from a trip to one of the city capitals in the North Region (Belém, State of Pará) and developed a mild form of GBS after signs and symptoms suggestive of Zika disease. She had a positive ZKV RNA by RT-PCR in the urine in two consecutive days upon admission (days 12 and 13 after onset of symptoms, ran in two independent labs). The plasma samples (days 12 and 13) were negative for ZKV RNA. We are still monitoring the virus shedding. After treatment with IVIG, she is fully recovered and should be discharged tomorrow.
The immunopathology for Zika-related GBS remains unknown. The role of a direct ZKV effect versus the classical immune-mediated mechanism still needs to be investigated.
I will end here, and let the TWIV team and the invited guests peer review this letter. But before last, please allow me to share some pictures I took in a nice library at a hotel on the mountains few weeks ago. Between the books, some craft art pieces separated the books. Made with clay by artisans from the Alagoas State, Northeast Region, they portray what seems to be human figures resembling some of those very unfortunate babies born with microcephaly. These pieces were created long before the current ZKV epidemic and may reflect how we may have been underestimating the problem of microcephaly in Brazil. Perhaps our folk artists have been having a better sense of the problems related to this condition than us.
University of Sao Paulo
How Scared Should You Be About Zika?
By MICHAEL T. OSTERHOLM
JAN. 29, 2016
“..…Some believe we need more scientific data to confirm these more severe manifestations. I don’t agree; I believe the evidence is already compelling.…”
# # #
The main point of the essay — prevention through the elimination of vectors and the development of vaccines — of course is very good. My concern is that effort without sound science will be a windmill tilt.
Hi TWiV Team,
Thanks again for a great series of podcasts and I’m very much looking forward to the planned one on Zika. I’d just like to comment on something Vincent said in TWiV 374 regarding antivirals against Zika virus. Vincent predicted that researchers will be “testing every known antiviral against Zika, and finding ones that work, and then they can be used in compassionate use.” I was wondering who these antivirals would be used in ? The relationship between Zika virus and microcephaly is currently unclear. Even the demonstration of Zika virus sequences in microcephalic brain tissue doesn’t necessarily indicate that infection is causative. Even if Zika turns out to be an aetiological agent of microcephaly, and antivirals with activity against Zika virus are identified, are they likely to be administered to women of child-bearing age, or women who are already pregnant ? There is an understandable reluctance to administer drugs to women who are, or could become pregnant because of the fear of causing foetal damage, and we do not want to increase that risk over that from Zika virus. Furthermore, it is unlikely that we will be able to administer a live viral vaccine to women who are, or could become pregnant, so this should be considered when planning the development of a vaccine against Zika.
Christopher Ring MSc PhD FIBMS FHEA
Senior Lecturer in Microbiology.
Department of Natural Sciences,
School of Science & Technology,
Steve Bachenhemier writes:
You mentioned in your latest blog post on Zika virus that…”We do have a safe and effective vaccine against another flavivirus, yellow fever virus. Substituting the gene encoding the yellow fever (YF) E glycoprotein with that from Zika virus might be a good approach to quickly making a Zika vaccine.”
In principle yes, except for the potential for antibody-dependent enhancement (ADE) of infectivity of related Flaviviruses. As is well documented, antibodies produced following infection with one of the 4 strains of Dengue, are of two types: neutralizing, homotypic; and non- or partially-neutralizing, but heterotypic for the other three strains [it’s slightly more complicated because there are also short-lived (a few months to a few years) heterotypic, neutralizing antibodies produced].
These non-neutralizing heterotypic antibodies have the ability to enhance infection by one or more of the other Dengue strains. There is already some speculation that the high prevalence of these non-neutralizing Dengue antibodies in individuals within hyper-endemic areas might be propelling the spread of the related Zika virus. So if cross-ADE between Dengue and Zika were to be documented, use of a YF-based vaccine platform to produce Zika neutralizing antibodies directed at the Zika E glycoprotein, might have the unintended consequence of enhancing subsequent Dengue infections. And of course, alternatively, wide-spread adoption of one of the Dengue vaccines currently being developed, could potentially enhance Zika virus infection.
Steven Bachenheimer, Ph.D.
Professor emeritus, Microbiology and Immunology
UNC Chapel Hill
Any truth to this?
Vincent and the Twivvers,
A proposed link has been circulating in the leftist paranoiasphere for some weeks now, noting the correlation among the first appearance of the Zika epidemic in Brazil with an area where GM mosquitoes were released in a population control experiment several years ago, and the appearance in Brazil of the microcephaly complication in pregnant women.
I had dismissed the possibility of this correlation-as-causation as being quite unlikely until I came across this article in the leftist press. It does, indeed, propose a plausible mechanism by which this may have occurred.
With you and your highly esteemed Twivvers being experts in this field, I am wondering if you could kindly look this article over and see if there is a chance that this mechanism is sufficiently plausible to merit further investigation.
[ks: use “do not link” for the following
Here in Costa Rica, we’ve just had our second known case of Zika, in an American tourist, diagnosed last week – it may be our first confirmed case of domestic transmission. But I suspect that it is already epidemic and has simply been going unnoticed amidst our H1N1 outbreak – a few weeks ago, I had a rash that lasted a week or so, with a bit of pinkeye in one eye, and a very mild fever for one day. So I suspect I’ve already had it. And I suspect many other Costa Ricans have had it as well, given that Aedes egypti is very common here, and the country has been battling a dengue outbreak for a couple of years now.
Regards from sunny Costa Rica (72º),
Cartago, Costa Rica
We are experiencing a balmy 49 degrees and raining here in Portland Oregon. The balmy- ness of our January has got me thinking about mosquitoes. Usually our winters would kill mosquitoes but I fear a mild winter is only going to fuel the fire of mosquito outbreaks and potential Chikunguya Northward. I cover current events in my science classes. Lately my zoology class and I have been discussing Zika and they have brought up some interesting questions.
What are the chances we will put together a vaccine or cure for Zika before the Olympics in Rio? What implications could the Olympics have for the travel of this virus. Only 20% show symptoms and it is long lasting in the body, this seems like a recipe for disaster.
The only hope I have is a story in the Wall street journal today citing a birth of twins where the mother had Zika and only one child had Zika. Could the drugs they give HIV positive mothers to prevent the virus crossing placental barriers work for this virus?
Science teacher, Oregon
I am a first year medical student hoping to specialize in infectious disease and tropical medicine. I spent a few years of my life in Latin America but now live in the New Haven, Connecticut area. I have been listening to the show since summer of 2010. Due to my personal connection with Latin America as well as my personal interest in infectious disease, the emergence of the Zika virus is extremely pertinent to me and to my future studies.
Like many first year medical students, I have a few months off from studies this summer to do research. I figure that there would be few better ways to introduce and possibly begin to establish myself in the field of infectious disease medicine than by trying to work with teams that are already investigating and trying to prevent the spread of this new infection. I am curious if you or any of your illustrious co-hosts have any suggestions about organizations that might be willing to take on medical students. I have already investigated a few such groups, but those that I have found that take medical student already want a proposed independent project outline. Though I have quite a bit of bench science experience, I quite frankly don’t know where to begin when it comes to trying to design a feasible project that could be completed by a medical student with the majority of the work being completed over a few month period. I figure there would be few people who could offer some useful suggestions of where to begin. I have a strong basic research background and speak Spanish and Portuguese.
Thank you for putting on a fun and informative show week after week. Here in New Haven, the temperature is a sizzling 39 degrees F or 4 degrees C.
Thank you for your time,
Medical Student Year 1
Quinnipiac Frank Netter School of Medicine
Looking forward to the Zika Virus show this week and hope you would discuss this question:
Presuming a link between Zika and microencephaly can be found in Brazil, do you think the reason other regions haven’t reported this, is that here, more people have seroconverted before pregnancy?
All the best,
here comes my questions about Zikavirus.
What is the evidence that Zika causes microcephalia? Do they register microcephalia at the same manner than previously, can better registration explain the part of the its rise? What is estimated risk of microcephalia in pregnant woman in the endemic area? Pregnant women who became infected (diagnosed clinically, by PCR or serologically)? Is the risk lower if infection is without symptoms? Is the risk lower later in pregnancy? How soon can we detect microcephalia with obstetrical ultrasound, how long time does it need to develop? How does “natural history” of the fetal impairment look like, does it progress over the time or reach any plateau and when? Any other consequences for fetus/children except microcepalia? How should we consult women for the future health/intellect of this children? What are expectations about the development of the epidemia?
Thank you in advance,
Julia Savchenko, MD, Sweden
I’m really looking forward the next episode and very happy you gonna talk again about this big insidious threat – ZIKV. How could be different anyway?
A big concern for us, from Public Health, is the appropriate diagnosis. Even with Dengue, a well-known disease with a improved diagnosis there are potential problems to identify correctly. According to a Letter published at Emerging infectious Disease this month, here in Brazil for every 20 dengue patients, only 1 is reported
If we imagine this scenario for Zika, usually oligosymptomatic with a difficult clinical diagnosis and test effective only during the initial infection, what can we expect?
At least, we have some good news today with the announcement by brazilian authorities of a serological test, from Eurimmun. Some brazilian scientists are questioning the cross reactivity with dengue. The CDC did not refer this test at CDC “Testing algorythm”
Regarding the explosive aspect of the epidemics, seems to me (and my opinion it’s just a opinion) that information about the vector and the virus have yet to be completely understood. At the following paper no virus was isolated from any species of mosquito collected during the outbreak at Yap Island. Aedes hensilli was implicated as a probable vector for ZIKV.
But I believe we are on right way
Brazilian people are very resilient and optimistic, and this weekend starts Carnaval celebration. So, at least until next wednesday the ZIKV sadness will be underestimated and Carnaval happiness overestimated, and everything is gonna be fine. And at some point, in the nearest future, everything is gonna be real fine.
Thanks a lot for sharing with everyone so good information
Aline Campos, MV
Vigilância dos Riscos e Agravos Ambientais Biológicos
Vigilância Ambiental em Saúde
Nucleo Regional de Vigilância em Saúde – 9ª CRS
Secretaria de Estado da Saúde-Rio Grande do Sul
Cruz Alta, RS
Hello TWiV crew,
Like Alan in the last episode, I’ve received my Go Viral kit and, strangely, I must say this is the most eager I’ve ever been to actually get ill….Nobody enjoys getting the cold or flu but the promise of getting sequencing data back makes it almost desirable and interesting to this fellow virologist.
Mainly I’m writing to suggest a Listener Pick of the Week. Back in November my sister got me hooked on crossword puzzles. Whenever I got stuck on a difficult question I would lament, “Arg, I wish they made a crossword puzzle for microbiologists”.
A couple months later, for Christmas, she bought me a copy of “Crossword Puzzles for the Microbiology Savvy” by Dana Perkins.
The puzzles are challenging, but fun even for someone who is trained in microbiology.
Anyways, hope all is well.