Zika Response
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Perhaps the biggest challenge with Zika is recognize it for what it is: a new disease which does not fit the epidemiology or response paradigm of past outbreaks and which will demand effort, resources, unparalleled collaboration, and above all open mindedness in formulating responses.

robert w malone, md, ms / february 2016

 
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How we work

The zika response group

With the sudden emergence of Zika virus as an evolving epidemic we are confronted with the need to simultaneously study and understand a new disease and to develop countermeasures. In many ways Zika presents a much more complex challenge than Ebola, and it may impact more lives. It is vector borne, and therefore its range of transmission will be determined by vector ecosystem. It cannot be significantly contained by limiting movement or contact of people. Acute infection may be unapparent, so patients cannot be quarantined. It exerts its most devastating effects on the unborn fetus with a delay to diagnosis. The transplacental pathology is not understood. Zika virus associated disease has an autoimmune component.  It is epidemic in a region with a high degree of global connectivity; cases will be widely disseminated. The Zika epidemic is moving very rapidly.  Research reagents, animal models, and fundamental science knowledge are much less well developed than they were for Ebola.  On the other hand, decades of experience with dengue, yellow fever, and West Nile have equipped us with familiarity with ADE and flavivirus vaccine development strategies. Zika virus is likely a harbinger of future diseases driven by ecosystem change and global interconnectedness.

Perhaps the biggest challenge with Zika will be to recognize it for what it is: a new disease which does not fit the epidemiology or response paradigm of Ebola or dengue and which will demand effort, resources, unparalleled collaboration, and above all open mindedness in formulating responses.

 
 

“While we were calling them neglected tropical diseases, the 'tropical' part is probably a misnomer, most of the world's neglected tropical diseases are in wealthy countries. It's the poor living among the wealthy.”

Peter Hotez, MD, PHD |  2016

 

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iORG began in the winter of 2016.  News of Zika was rapidly spreading and the founders of iORG, Dr's Robert and Jill Malone wanted to do something to really make a difference.  Having worked in infectious disease outbreak response teams for many years, they realized that the usual governmental response was slow and inefficient.  The usual response time just was not a good solution to solve the spread of Zika and to develop a better understanding of the disease, so that treatments could be developed.  Robert spoke to many colleagues and the response was overwhelming.  together, they founded the Zika Response Group with iORG as the parent organizations.  The was goal was simply to impact on the public health response to make it more efficient and to make a difference.  The team of people assembled worked night and day - and accomplished amazing things. 

Some of the early successes are:

  • Zika Response Working Group wrote a comprehensive meta analysis of Zika and available medical countermeasure options that has helped guide government officials, clinicians and front line public health workers as they are responding to the virus outbreak in January 2016.
  • Zika Response Working Group wrote an extensive review paper on Zika that has helped guide scientists about the virus.  Published in PLoS NTD.  The paper now has over 40,000 readers and is one of the most cited Zika references.
  • Members of the Zika Response Group have performed epitope mapping and computational biology analyses, showing the evolution of the virus - which will lead to a better vaccine and a better understanding of how the disease is causing damage to fetuses, as well as the mechanisms of action of GBS.  This effort culminated in two peer reviewed papers being published.  The Evolution of the Zika Virus paper, published in the fall of 2016, is one of Wiley's most read scientific articles, and is in the  99% of their top publications-  with 72,000 readers having already viewed the paper.
  • Members of our team have extensively consulted with USG and Brazilian government officials on how to control the pandemic.
  • Members of our team have consulting with the World Health Organization, and foreign public health officials on how to control the pandemic.
  • A member of the Zika Response Working Group is  working in South America on GBS. 
  • Members of our team have discovered possible anti-viral drugs that are safe for pregnant women and designed clinical trials, and are in the process of procuring funding and building partners in Latin America to move forward with clinical trials!

The relationship between infection with Zika virus and primary microcephaly meets most accepted criteria for causality, and it has become clear that Zika infection during pregnancy is associated with a cluster of birth defects known as Zika Fetal Syndrome as well as Guillain–Barré syndrome (GBS), kidney disease and other reproductive tract infections.

The Zika Response Working Group, under the non-profit non-governmental organization iOrg (Infectious Outbreak Response Group), rapidly responded to critical needs.  Our activities focused on;

·        Threat and risk assessment and determination

·        Identifying existing licensed drugs likely to have anti-Zika activity

·        Modeling the outbreak to help inform government and corporate planning

·        Geo-spatial tracking and sequence analysis

·        Computational immunology and comparative proteome analysis including epitope mapping

·        Using surveys and alternative media to track the spread of Zika virus, Zika disease, Zika communication, and to identify the unmet needs of medical caregivers and their patients

·        Diagnostics and diagnostic technology research and development

·        Development, manufacturing and production of medical countermeasures for Zika disease (devices, drugs, biologicals, and vaccines)

·        Facilitating clinical trial design/clinical protocol development for rapid testing of preventative and therapeutic treatments

·        Expediting clinical development to licensure of diagnostics, devices, drugs, biotherapies and vaccines to prevent Zika Fetal syndrome and GBS

Our group is united by a commitment to enable rapid responses to the global human threat posed by Zika virus.  

We also believe that, while speed is essential when managing an emerging infectious disease outbreak, it is also important to first observe, analyze, think, discuss, and then to act.

The Zika Response Working Group (iORG) developed threat assessments, that went to the highest levels in government.  Those assessments translated into critically important papers that have influenced the science and research into the Zika virus.

THESE PEER REVIEWED PUBLICATIONS INCLUDE: 

Molecular evolution of Zika virus as it crossed the Pacific to the Americas. Cladistics. 2016

Zika Virus: Medical Countermeasure Development Challenges. PLoS Negl Trop Dis. 2016

Zika Fetal Neuropathogenesis: Etiology of a Viral Syndrome. PLoS Negl Trop Dis. 2016

Antibody mediated epitope mimicry in the pathogenesis of Zika virus related disease. BioRx. 2016.

Of note, the Molecular evolution of Zika virus paper (Cladistics) has been read almost 73,000 times, and is in the 99th percentile: it's in the top 5% of all research outputs ever tracked by Altmetric (Wiley online).

The Zika Virus Countermeasures paper has been read over 40,000 times.

The Zika Fetal Neuropathogenesis paper has been read over 8,500 times.

 

OUR PRESIDENT, ROBERT W MALONE HAS BEEN SPEAKER OR CHAIRPERSON AT THE FOLLOWING CONFERENCES:

  • Chairperson, Repurposing drugs. International Conference on Zika Virus. Washington, DC Feb 22-25, 2017.
  • Accelerated Discovery and Development of re-purposed licensed drugs for Zika virus outbreak antiviral prophylaxis and therapy. International Conference on Zika Virus. Washington, DC Feb 22-25, 2017.
  • Bridging the Sciences: Zika Virus. Speaker. Zika Virus: Accelerating Development of Medical Countermeasures by Re-purposing Licensed Drugs, Emery, Atlanta, GA 1-3 May, 2016
  • World Vaccine Conference. Speaker/Round table- Zika virus: Challenges for Medical Countermeasure Development Washington, DC. 29-31 March, 2016
  •  The World Health Organization (WHO) Consultation for Zika Virus: Research and Development. Presentation of Drug Development TPP. Geneva, Switzerland. 12-14 March, 2016