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Tracing Spread of Zika Virus in the Americas

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Francis Collins visits Ziika Forest

Caption: Here I am visiting the Ziika Forest area of Uganda, where the Zika virus was first identified in 1947.
Credit: National Institutes of Health

A couple of summers ago, the threat of mosquito-borne Zika virus disease in tropical areas of the Americas caused major concern, and altered the travel plans of many. The concern was driven by reports of Zika-infected women giving birth to babies with small heads and incompletely developed brains (microcephaly), as well as other serious birth defects. So, with another summer vacation season now upon us, you might wonder what’s become of Zika.

While pregnant women and couples planning on having kids should still take extra precautions [1] when travelling outside the country, the near-term risk of disease outbreaks has largely subsided because so many folks living in affected areas have already been exposed to the virus and developed protective immunity. But the Zika virus—first identified in the Ziika Forest in Uganda in 1947—has by no means been eliminated, making it crucial to learn more about how it spreads to avert future outbreaks. It’s very likely we have not heard the last of Zika in the Western hemisphere.

Recently, an international research team, partly funded by NIH, used genomic tools to trace the spread of the Zika virus. Genomic analysis can be used to build a “family tree” of viral isolates, and such analysis suggests that the first Zika cases in Central America were reported about a year after the virus had actually arrived and begun to spread.

The Zika virus, having circulated for decades in Africa and Asia before sparking a major outbreak in French Polynesia in 2013, slipped undetected across the Pacific Ocean into Brazil early in 2014, as established in previous studies. The new work reveals that by that summer, the bug had already hopped unnoticed to Honduras, spreading rapidly to other Central American nations and Mexico—likely by late 2014 and into 2015 [2].

Researchers have become quite adept over the past few decades at parsing genetic information not only to tell people more about their ancestry, but also to track the spread of infectious disease in cities or, in the case of Zika, across continents. While previous studies have offered some clues as to the timing of Zika’s spread, the new study—led by Charles Chiu, University of California, San Francisco, and Oliver Pybus, University of Oxford, United Kingdom—set out in 2016 to fill in additional details. The strategy was to isolate Zika’s RNA-based genetic material from the blood and urine of people who lived or visited Central America or Mexico and later showed symptoms consistent with Zika infection.

Because Zika is detectable in people only for a few days and usually at low levels, collecting enough of the virus’ genetic material to track its spread from country to country has been a real challenge. The team used a newly developed strategy designed to sequence all DNA and RNA present in a sample, while specifically enriching for genetic material from the Zika virus. Such an approach helps to ensure Zika virus was detected without missing other potential viral pathogens, which often produce similar symptoms.

Of 95 specimens collected from January to August 2016, they generated full and partial sequences for 61 Zika virus genomes. To understand the relationships among those 61 Zika virus strains, the researchers combined their new genomic information with existing data for another 298 Zika strains from around the world. They then analyzed that evidence to construct the viruses’ family tree.

That family tree shows, with a few exceptions, the viruses that infected people in Central America or Mexico descended from viruses collected from Brazilians. In fact, based on the analysis, the vast majority of Zika infections in Central America and Mexico traced back to a single importation event from Brazil.

The researchers next used the family trees to estimate when and where particular Zika strains diverged from one another. The genomic evidence suggests that the Central American strains diverged from those in Brazil sometime between July 2014 and December 2014. That’s about three months earlier than previous studies had suggested.

The genomic evidence showed that a Zika strain isolated from a person who fell ill in Honduras was most likely derived from strains circulating in Brazil, suggesting that the virus migrated to Honduras first. From there, Zika spread to Guatemala and Nicaragua and onward to southern Mexico from late 2014 to early 2015.

When the first cases of Zika were reported in Brazil in May 2015, the virus was already widely circulating in Central America and Mexico. While the first outbreak in Mexico was thought to have reached its peak in the middle of 2016, the new evidence suggests an earlier outbreak had gone undetected early in 2015.

The evidence also shows that many locations in Central America and Mexico experienced two waves of Zika infection per year, not just one. To better understand that pattern of infection, peaking approximately every 6 months, the researchers analyzed the environmental suitability in each country for Aedes aegypti mosquitoes that primarily transmit Zika virus to people.

Their findings suggest that conditions ripe for the spread of Zika virus occur in different parts of Central America and Mexico at different times of year, depending on elevation and other factors. While more study is needed, this spatial and temporal variability will be an important consideration for programs designed to control mosquitoes and for predicting how the virus is most likely to spread.

Zika virus is just the latest in a long line of viral outbreaks. The hope is that universal surveillance methods like the one employed in this study will help to pick up on the next one more quickly, whether it’s an outbreak of Zika virus or some other virus, known or as-yet unknown.

In the meantime, there’s more encouraging news on the Zika virus front: phase 1 clinical trials of an experimental DNA vaccine developed by scientists at the NIH’s National Institute of Allergy and Infectious Diseases showed that the vaccine is safe and induced an immune response in healthy adults [3]. A phase 2 trial designed to test the vaccine’s ability to protect against Zika virus launched in April 2017 has now enrolled more than 650 of its 2,500 planned participants and is expected to reach completion within a couple of years [4]. Other potentially promising versions of a Zika virus vaccine are also coming along. I’ll keep you posted.

References:

[1] Zika Virus. Centers for Disease Control and Prevention.

[2] Genomic epidemiology reconstructs the introduction and spread of Zika virus in Central America and Mexico. Theze J, Li T, Chiu CY, Pybus OG. Cell Host & Microbe. 2018 May 15, [Epub ahead of publication]

[3] Safety, tolerability, and immunogenicity of two Zika virus DNA vaccine candidates in healthy adults: randomised, open-label, phase 1 clinical trials. Gaudinski MR, Houser KV, Morabito KM, TC, Ledgerwood JE, Chen GL; VRC 319; VRC 320 study teams, et al. Lancet. 2018 Feb 10;391(10120):552-562.

[4] VRC 705: A Zika Virus DNA Vaccine in Healthy Adults and Adolescents (DNA). Clinicaltrials.gov

Links:

Zika Virus (National Institute of Allergy and Infectious Diseases/NIH)

Zika Virus Vaccines (NIAID)

Biomedical Advanced Research and Development Authority (U.S. Department of Health and Human Services)

NIH Support: National Institute of Allergy and Infectious Diseases; National Heart, Lung, and Blood Institute

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4 Comments

  • Mary Therese Millich says:

    Any article about ZIKA virus should include SYMPTOMS so as to EDUCATE the public.

    • Moderator says:

      Thanks for your comment. You raise a good point, and, in the Links section of the post, resources are available about Zika and its symptoms.

  • Linda E Maguire says:

    Dr. Collins, I respect and admire your work, especially the big bang analyses in “The Language of God” book. As a Cognitive and Behavioral neuroscientist (GMU ’13, Hopkins ’14), I study spirituality (as also found through music – or Prescription iPods) and explore religion as a platform for discovering the “DNA-God” (oxygenation, meditation, biblical stories, traditional practices, music, metaphors and analogies). I do hope to discuss this with you in person one day soon. Regarding Zika, I have been following the microcephaly crisis from Day 1 when I attended the first conference on Feb 17th, 2016. At the time, I was studying transition metals and oxygen metabolism and needs in the brain. Arnaud Fontanet, from the Institut Pasteur recently published an interesting graph of trimester causality in a microcephaly report. My research shows that it is actually at the 4month point in gestation where Iron and Manganese (used in iron ore mining but embryo-toxic during 0 -16 wk gestation period) is progressively (and gregariously) welcome in human biological and brain development (solely to support mitochondria health). Nearly 6000 cases are in NE Brazil – causality that may involve investigation of and following the Samarco iron ore mining pollution (2008-2016) disaster, plus a record drought 2015-2016 when iron ore run off was recklessly released into surrounding topical areas, then follow Sao Francisco water basin (and expansion), that is sole drinking water source leading directly to the 6000 NE microcephaly cases. Zika virus is very similar to the human cell’s iron chelator “ferritin”. Ferritin stores and disposes of excess iron in the brain in humans – Zika may be a Trojan horse, as it were (but does not mop up excess iron) and allowed into a 6x thick, protecter embryo environment as faux-Ferritin. Zika can then set up shop and do further damage. Iron is not needed in early pregnancy, is paramagnetic – toxic to the developing embryo. Manganese (co-localized with iron for iron ore mining purposes) causes tornado-like reactivity that will wreak havoc on many delicacies of brain tissue embryogenesis and brain pathogenesis. Rather, during 0-16 weeks gestation period, zinc and copper are the primary operative transition metals at work, that then dramatically reduce in fetal development. Zinc/ copper (0-8wks), then copper/ zinc (8-16 weeks are the operative transition metals during neurogenesis. Zinc primarily whips the embryonic cell into (mostly) brain matter during first 8 weeks, while copper protects the integrity of the developing pathways during second 8 weeks – or during 0-16 weeks brain differentiation / gestation period. Minimal/ no iron allowed during 0-16 weeks gestation in our current stage of human evolution). It is zero gravitational environment (that iron tilts and twists). After brain pathways are differentiated, (namely 16 weeks gestation to end-of-life), all that really matters is iron and manganese for mitochondrial health – Iron – for transport of oxygen to mitochondria (mitochondria “eat” oxygen and excrete nuclear-level fuel, or ATP, for brain cells) and Manganese – (Mitochondria use manganese to pry oxygen out of H2O (water) during low oxygen levels (from high stress, anxiety, or otherwise low-oxygen environmental conditions). Iron ore mining also adds Aluminum to the mix that cloaks red appearance of the iron ore run off pollution – and just makes toxicity all the worse. Zinc mining areas seem to be protective from microcephaly (zinc is good in 1st trimester) and we would probably see similar findings in copper area birth statistics (possibly healthier children in either of these mining areas where water seepage has occurred). I recently came across gold mining areas that are now reporting small pockets of microcephaly cases (gold staining used to detect non-DNA tissue in mitochondria studies?). Scientific implications of transition metals that are directly involved in our evolutionary development is game changing and really inform genesis of life science. The traditional trimester paradigm of embryonic development could now be re-sectioned to reflect pre-mitochondria (0-16 weeks where they only hover around in diploid “shells”) and full-mitochondria development (16 weeks to life where they are very similiar to the iron-manganese bacteria “Gallionella”). Mitochondria also signal for our cell health and natural cell death, as well as beta amyloid (low oxygen) and tau (low fluid) issues that contribute to Alzheimer’s plaque formation. Mitochondria have their own DNA and, in reality, host our lives (rather than the traditional assumption that we host them). There is such a vast amount of science in this (tragic) microcephaly disease model of brain development. We need to move from vague, inaccurate, surface Zika talk and get down to the pollution and transition metal science here. My question (and educated guess) is the 2nd trimester microcephaly numbers are really in the 4th month only of gestation, not related to zika (beyond the trojan horse hypothesis and inappropriate access to protective embryonic environment that is laced with iron and seeking ferritin) and related to transition metals that do not belong in the 0-16 week (moreso the first half, to include ovulation period) of pregnancy. Sorry for the long comment but I specialize in aging brain health, completing my PhD dissertation now in Health Communication and hope to discuss some of my findings with you and your staff at NIH. I wish you a peaceful and blessed day.

  • Linda E Maguire says:

    What are the metabolic demands of the Zika virus and the host mosquito ?? This was my original question to Dr. Espinal, director the PAHO, who presented at the Johns Hopkins Zika microcephaly conference on the morning of Feb 17, 2016. Before the conference even began, I spoke with Dr. Espinal, who told me he did not think Zika was involved – because the hundreds of cases were so focal (many thousands now in NE Brazil). I was studying manganese and mitochondrial health (and mtc’s role in beta amyloid and tau production leading to plaque formation in Alzheimer’s). I worked in a transition metals lab (studying Fe, Zn, Cu and oxygen) and quickly followed the mountains of evidence that led to environmental metal pollutants that may be directly involved in the microcephaly mutations. Where there is causation, all one finds is more and more hard evidence. There is so much compelling evidence and game changing science in the transition metals theory developed from the NE Brazil microcephaly cases. Unfortunately, this is a tragic disease-model for groundbreaking transition metals neurogenesis science. Thank you for your insight or comment on this new avenue of scientific investigation. My late, dear friend, Harold Morowitz got me interested in genesis of life science, as has your book “The Language of God”, so I am trying to follow my ongoing work in the Brazil microcephaly (comparative with other mining pollutant areas) and share with interested colleagues! It would be nice to have a grand symposium on this and take it from there. Zika is only a confederate/ accomplice in a much scientific picture, I have concluded.

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