Zika virus and microcephaly

FlavivirusThree reports have been published that together make a compelling case that Zika virus is causing microcephaly in Brazil.

An epidemic of Zika virus infection began in Brazil in April 2015, and by the end of the year the virus had spread through 19 states, many in the northeastern part of the country. Six months after the start of the outbreak, there was a surge in the number of infants born with microcephaly. It was not known if most of the mothers had been infected with Zika virus, as results of serological tests, virus isolation, or PCR were not available.

An initial report of 35 Brazilian infants with microcephaly born to women who either resided in or traveled to areas where Zika virus is circulating revealed that 74% of mothers had a rash (one sign of Zika virus infection) in the first or second trimester. At the time of this study no laboratory confirmation of Zika infection was available, but the infants did not have other infections associated with birth defects, including syphilis, toxoplasmosis, rubella, cytomegalovirus or herpes simplex virus.

Yesterday the CDC reported on the analysis of tissues from two infants with microcephaly who died within 20 hours of birth, and two miscarriages, all from the state of Rio Grande do Norte in Brazil. The mothers all had rashes typical of Zika virus infection in the first trimester of pregnancy, but were not tested for infection.

All four specimens were positive for Zika virus RNA by polymerase chain reaction (PCR) done with primers from two different regions of the viral RNA. Staining of tissues with anti-viral antibodies revealed the presence of viral antigens in two of the four samples, in the brain of one newborn and in the placenta from one of the miscarriages.

A second report from the University of Sao Paulo documents ocular abnormalities in Brazilian infants (from the state of Bahia) with microcephaly and presumed Zika virus infection. The mothers of 23 of 29 infants (79.3%) with microcephaly reported signs of Zika virus infection (rash, fever, joint pain, headache, itch, malaise). Of these, 18 (78.3%) had symptoms during the first trimester of pregnancy, 4 (17.4%) during the second trimester, and 1 (4.3%) during the third trimester.

No laboratory results were available to confirm Zika virus infections, but toxoplasmosis, rubella, cytomegalovirus, herpes simplex virus, syphilis, and HIV were ruled out.

Abnormalities of the eye were found in 10 of 29 (34.5%) of infants with microcephaly. These included focal pigment mottling, chorioretinal atrophy, optic nerve abnormalities, displacement of the lens, or a hole in the iris.

These observations suggest that Zika virus infection may also cause lesions of the eye, although confirmation of infection needs to be done to prove causation. This uncertainty is reflected in the title of the article: “Ocular findings in infants with microcephaly associated with presumed Zika virus congenital infection in Salvador, Brazil” (italics mine).

The final paper is, in my opinion, the blockbuster. In this single case report, a 25 year old European woman working in Natal, Brazil, became pregnant in February 2015. In the 13th week of gestation she had fever, muscle and eye pain, and rash. Ultrasound in Slovenia at 14 and 20 weeks revealed a normal fetus.

At 28 weeks of gestation fetal abnormalities were detected, including microcephaly, and the pregnancy was aborted. Autopsy revealed severe brain defects, and 42 to 54 nm virus particles were detected in the brain by electron microscopy.

Infection with a variety of microbes was ruled out, but Zika virus RNA was subsequently detected in brain tissue by PCR.

Here is the clincher – the entire Zika virus genome was identified in brain tissue by next-generation sequencing! Analysis of the sequence revealed 99.7% nucleotide identity with a Zika virus strain isolated from a patient from French Polynesia in 2013, and a strain from Sao Paulo from 2015. These findings agree with the hypothesis that the current Brazilian outbreak was triggered by a virus from Asia.

Up to now there have been few data that strongly link Zika virus infection to congenital birth defects. Of these three new studies, the recovery of a full length Zika virus genome from an infant with microcephaly is the most convincing. Given the rapidity by which new data are emerging, it seems likely that additional evidence demonstrating that Zika virus can cause microcephaly will soon be forthcoming.

I’m amazed that a flavivirus can cause birth defects – when no flavivirus has done so before*. This is a virus spread by mosquitoes, and to which most of the world is not immune. The Zika virus outbreak will surely test our ability to respond rapidly with substantial mosquito control, diagnostics, antivirals, and a vaccine.

Update 2/11/16: A second paper has been published documenting ocular abnormalities in ten infants born to mothers in Brazil who had symptoms consistent with Zika virus infection.

Update 2/12/16: *Japanese encephalitis virus and West Nile virus have been shown to cross the placenta and infect the fetus. Such events must be rare because a larger association with birth defects has not been reported.

Comments on this entry are closed.

  • chemfreemom

    A much more likely cause of the increase in Microcephaly in Brazil is the fact that their use of Atrazine, Metalachlor, and Glyphosate has skyrocketed, and studies show side effects from these three are restricted fetal growth, small head circumference, and Microcephaly. Not to mention a larvicide added to their drinking water, the release of GM mosquitoes with no long term testing, and a mandate for the DtaP vaccine in all pregnant women though admittedly never tested in pregnant women, all the year before the increase.
    Any correlation between zika and Microcephaly has been miniscule, and even if larger, does not equal causation.

  • chemfreemom

    There is no concrete evidence to blame zika, and yet they are going out of their way to do so. It would be easier to blame a virus rather than an action on the part of the Brazilian government.

  • chemfreemom

    This NPR article says there were 20,000 cases of zika in the French Polynesia outbreak, and only 17 central nervous system abnormalities, which are not named specifically as Microcephaly, and which they said could have been caused by something else. It seems like a lot of people are grasping at straws to blame zika for the increase in Microcephaly in Brazil.

    http://www.npr.org/sections/goatsandsoda/2016/02/09/466152313/zika-in-french-polynesia-it-struck-hard-in-2013-then-disappeared

  • chemfreemom

    I agree that the CDC and WHO are being irresponsible and hasty.

  • sabelmouse

    your english is very good, and yes, you have.

  • 655321

    From the reports I’ve seen, Zika is detected in less than 10% of microcephaly cases…..that’s not even correlation, let alone causation.

  • JGC

    The reports I’ve seen (for example, this from Reuters http://www.reuters.com/article/us-health-zika-brazil-idUSKCN0XN2NP) indicate that as of April 26 in Brazil of 7228 suspected cases of Zika associated microcephaly, 4908 had been confirmed as linked to Zika infection while 2,320 had been ruled out.

    That’s 68% of all cases where linkage has been evaluated, not 10%.

  • 655321

    page not found…..surprise, surprise. seems to be a favorite tactic of paid posters….make false claims then post non-working links as “proof”, hoping no-one will click the link.

  • JGC

    I apologize for the error, and have corrected the typo in the URL in the original post.

  • 655321

    Your own link states that “the link between the virus and the birth defects has not been scientifically established…..”Honestly, do you have psychological issues? No one is this stupid.

  • JGC

    the response was directed to your claim that “Zika is detected in less than 10% of microcephaly cases”, when it has instead been detected in ~68% of cases where attempts at virus detection have been made. Do you have reading comprehension issues?

  • 655321

    Let me guess, you’ll quietly drop Zika posts or change usernames as the CDC quietly backs away from the Zika-microcephaly fraud.

  • JGC

    I’ve used the same user name (or variations on it where the initials JGC are already in use on a forum) for more than a decade so I doubt I’ll change my username at ay time in the future. And I’d see no reason to do so if the continued accumulation of evidence indicated that Zika infection was not causally associated with the increased rates of microcephaly we’ve been observing–once goes wherever the evidence leads, after all, as it become available.

  • 655321

    Science works in that theories are built on accumulation of evidence, not the opposite as you continue to post in complete ignorance of the scientific method.

  • JGC

    Science proceeds from observations to hypotheses to theories to revision, in that order.

    At present we have observations which support a hypothesis that Zika infection is a significant contributor to the increased incidence of microcephaly, If that hypothesis is falsified as new observations are made science will simply move on to revise the hypothesis or discard it to be replaced by hypotheses that encompass both the previous and new observations.

    That’s how science works.

  • 655321

    You literally stated Aika causing microcephaly needs to be proven otherwise with accumulation of evidence. You’re full of crap.

  • JGC

    Not that I’m aware–can you offer a direct quote from the post where you believe I have?

    I only recall indicating that your claim that “Zika is detected in less than 10% of microcephaly cases” was false and that the evidence is instead that “in Brazil 68% of all cases of microcephaly where a possible linkage to ZIka virus has been confirmed or ruled out were confirmed–not 10%”.

    Perhaps you missed the word “possible” in the phrase “possible linkage has been confirmed”?

  • 655321

    ” And I’d see no reason to do so if the continued accumulation of
    evidence indicated that Zika infection was not causally associated with
    the increased rates of microcephaly”

  • JGC

    Uhhh… where in that quote, exactly, do I argue that a casual association between zika infection and microcephalic had been demonstrated rather than indicate the willingness to accept a causal association has been proven not to exist should new evidence indicating that’s the case be identified?

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  • thaddeus

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  • rtj1211

    Strictly speaking, it states that Zika cannot be THE ONLY CAUSE of microcephaly, unless it acts as a trigger to initiate pathology and is not required for pathological progression in the majority of cases.

    There is a long and extremely undistinguished history of the Western media mis-reporting science on a number of medical conditions, conflating rare presence of one agent with it becoming the sole reason for disease.

    As of now, scientists have not got an animal model for Zika-induced microcephaly, which is necessary to prove that Zika is a microcephaly inducer. Nor do they understand the causes of microcephaly in the majority of cases where Zika is not present. It could be dietary, it could be environmental contamination, it could be medication-associated, it could be anything.

    IN other words, it is impossible to state currently what causes the majority of cases of microcephaly.

    What it is also possible to state is this: ‘until Zika-virus can be shown to be necessary for early stage disease progression but can be absent for further progression, Zika Virus cannot be stated to be the primary cause of microcephaly in the majority of reported cases.’

  • rtj1211

    The most obvious explanation is that, like several other known viruses, it can be an asymptomatic infection in the majority of cases, which in a small number of cases leads on to disease progression.

    The real question is whether anyone has any clue as to the prevalence of Zika Virus in healthy women, including those with normally progressing pregnancies.

    Go look at the historical research on HPV, HSV, EBV etc. You’ll find that they are common asymptomatic infections which may flare up into something more serious in a small percentage of cases.

    Whether that is the case for Zika Virus or not, who knows.

    But the usual media nonsense is saying we understand what is going on long before scientists have a clue.

  • rtj1211

    You’d be amazed. You couldn’t detect an LD50 for thalidomide in laboratory animals, which is why it was licensed back in the 1960s. It all depends on whether a particular chemical targets a protein whose critical target site is sufficiently unique in humans not to affect animals.

    As for an insect GH not having an effect on mammals, you’d hope it had been tested long before being licensed.

  • rtj1211

    The issue may be that a chemical can activate a latent viral infection. It may be that the virus is a trojan horse, sitting quietly doing nothing, but something environmental triggers the small number of cases that actually become pathological.

  • rtj1211

    They are going out of their way to try and punish Brazil for being associated with Russia and China and to try and undermine the Rio 2016 Olympics. That’s what they are going out of the way about……

  • rtj1211

    Don’t know about in foetuses, but go look at HPVs, Herpes simplex viruses, Epstein-Barr virus. They can all reside latently, they can have vegetative cycles and they can shift the types of tissue they infect. They are all also associated with cancers in some sub-types.

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  • Mick Price

    You’re obviously a con man trying to play on ignorant people’s fear. Zika isn’t lethal, so why be afraid that you will die? There is no Zika cure and none is needed since as long as you’re not pregnant during the infection you’ll be fine.

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  • Patricia Nicoll

    Were normal baby’s sampled? In other words, was the Zika virus genome found in normal brains? What about the allegations of a pesticide causing these defects?