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Title: A MENACE WRAPPED IN A PROTEIN: ZIKA AND THE GLOBAL HEALTH SECURITY AGENDA

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Title: A MENACE WRAPPED IN A PROTEIN: ZIKA AND THE GLOBAL HEALTH SECURITY AGENDA Authors: Helen Epstein, Wilmot James, Ángel G. Muñoz, Lawrence Stanberry & Madeleine C. Thomson. Reference: Columbia GHS&D Working Group Papers 2017-01 Date: September, 2017 Place: Columbia University Medical Center, Morgan Stanley Children’s Hospital, Office 102, 3959 Broadway CHC 1-102, New York City NY 10032, USA. Copyright: This work is licensed under the Creative Commons Attribution-NonCommercial- ShareAlike 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-sa/4.0/.

A MENACE WRAPPED IN A PROTEIN1: ZIKA AND THE GLOBAL HEALTH SECURITY AGENDA

Preface Stephen Nicholas & Marc Grodman… i

1.Zika: Implications for Global Health Security Helen Epstein… 1

2.Zika Pathogenesis, Diagnosis and Vaccines Lawrence Stanberry… 12

3.Climate Change, the Environment and the Zika Outbreak Madeleine C. Thomson & Ángel G. Muñoz… 15

4.Global Health Security and Diplomacy Wilmot James… 25

5.Timeline of the Zika Virus Pandemic 39

6.Zika Reading List 48

7.Conference: Zika and the Global Health Security Agenda 50

Stephen W. Nicholas, M.D., is Senior Associate Dean for Admissions at the College for Physicians and Surgeons and Professor of Pediatrics and Population & Family Health at Columbia University Medical Center and founder/director of The Program for Global and Population Health (established in 1999 as the IFAP Global Health Program).

Marc Grodman, M.D., is an Assistant Professor of Clinical Medicine at Columbia University College of Physicians and Surgeons (P&S) and the Founder Chairman and CEO of BioReference Laboratories Inc. He serves as a member of the CUMC Board of Advisors.

Helen Epstein, Ph.D., is Visiting Professor of Global Health and Human Rights at Bard College.

Lawrence Stanberry M.D. Ph.D., is a leading specialist in congenital infections and authority on viral infections and vaccine development. He is the chief pediatrician at Morgan Stanley Children’s Hospital and Chairman of the Department of Pediatrics at the College of Physicians and Surgeons at Columbia University.

Wilmot James, Ph.D., is Visiting Professor of Pediatrics (non-clinical) and International Affairs and Director of Global Health Security & Diplomacy at The Program for Global and Population Health at Columbia University. He is a former MP and Shadow Health Minister (South Africa).

Madeleine Thomson, Ph.D., is Senior Research Scientist at the International Research Institute for Climate and Society, The Earth Institute, and the Mailman School of Public Health, Department of Environmental Health Sciences, Columbia University. She also leads the WHO/PAHO Collaborating Center for Malaria early warning systems and other climate sensitive diseases.

Ángel G. Muñoz, Ph.D., is a climate scientist at Atmospheric and Oceanic Sciences, Princeton University and the International Research Institute for Climate and Society, The Earth Institute, Columbia University.

1 The title is inspired by Nobel Laureate Peter Medawar’s description of a virus as ‘bad news wrapped in a protein’. PREFACE: GRODMAN & NICHOLAS

Preface Marc Grodman and Stephen Nicholas

Finding simplicity in complexity. That was our aim in holding a one-day meeting in April 2017 to address Global Health Security through the prism of the Zika virus epidemic. This meeting brought together colleagues from across the Columbia University campus, many of us meeting for the first time, from the College of Physicians and Surgeons, the Mailman School of Public Health, the School of International and Public Affairs, the Earth Institute and the International Research Institute for Climate and Society. We were joined by individuals from outside Columbia, bringing together experts from vastly different domains— from academia, government, industry, journalism— specialists in health and public health, policy formulation, sustainable development, climate and earth studies, etymology, informatics, vaccine and drug and diagnostics development— to consider the Zika epidemic, which has swept Latin America and the Caribbean and left damaged babies in its wake. We examined Zika as a means by which to explore the multiple dimensions that must be considered when the health, security and well-being of our world is endangered by such a frightening outbreak. Global threats to well-being don’t fit into one discipline. Understanding the challenges, providing the solutions don’t belong to one profession or share any specific line of training. To be effective, physicians need to understand informatics, public health professionals need to understand policy, climate change scientists need to understand health. These challenges stretch the perspective of all of us. The other reason is that pandemics and global threats that are not limited by borders or boundaries are frightening, not because of what we know about them but rather what we don’t. Zika is an accurate example of this paradigm, since it took time to diagnose the outbreak, time to understand its scope, time to understand the appropriate diagnostics, time to understand the clinical presentations and even more, it will still take a great deal more time to understand its long term effects. This is a threat whose parameters are still being defined. The uncertainty is disturbing, for those of us who want immediate answers. While the Zika epidemic is anything but simple, using it as a way to begin to examine the vastly more complex topic of Global Health Security was a useful exercise. What was most memorable

i PREFACE: GRODMAN & NICHOLAS about this meeting was the high degree of enthusiasm that participants voiced in support of continued broad collaborative relationships. This subsequently has led to the formation of: The Working Group on Global Health Security and Diplomacy at Columbia University (Executive Director, Dr. Wilmot James (P&S, Program for Global and Population Health and SIPA) and Co-Director, Dr. Madeleine Thomson (Earth Institute/IRI). The Working Group’s Steering Committee includes Steven Cohen (Earth Institute), Marc Grodman (P&S, CUMC Board of Advisors), Merit Janow (SIPA), Theresa McGovern (Mailman SPH) and Stephen Nicholas (P&S and Mailman SPH) and Lawrence Stanberry (P&S).

Zika Conference: April 3, 2017, CUMC: Left to Right: K. Modjarrad, M. deWilde, M. Grodman, and P. R. Vagelos

ii 1 EPSTEIN ZIKA: IMPLICATIONS FOR GLOBAL HEALTH SECURITY

1: ZIKA: IMPLICATIONS FOR GLOBAL HEALTH SECURITY

Helen Epstein

Zika and the Urgency of Pandemic Preparedness

Until very recently, Zika, a mosquito-borne virus closely related to the one that causes yellow fever, was unknown outside of Africa and Asia and was thought to be virtually harmless. Then about a decade ago it began island hopping across the Pacific Ocean, and as it did, its terrifying nature gradually became known. First there was an outbreak on tiny Yap Island in Micronesia in 2007, where three quarters of those infected came down with rash, conjunctivitis, fever, and joint pain. In 2013, Zika struck some 20,000 people in French Polynesia, sharply increasing the incidence of Guillain-Barre syndrome, in which the immune system attacks nerve cells, causing weakness and paralysis, which is usually temporary.

In 2015, Zika cases exploded in the New World, landing first in Brazil and sweeping on through all of Latin and Central America, the Caribbean, and into Florida, Texas and other parts of the United States. It was only then that epidemiologists recognized Zika’s most tragic manifestation. Thousands of infants infected with Zika in the womb were born with microcephaly, a condition in which the virus destroys the neuronal scaffolding upon which brain cells travel during early development. The cerebral cortex of microcephalic infants is smaller than normal, and these children suffer severe and lifelong visual and hearing defects as well as delays in speech and learning. Most will never be able to feed or care for themselves or even sit, stand or walk unaided. Microcephaly is found in about one baby in ten born to Zika-infected mothers. Why some pregnancies are more vulnerable than others is not known.

Zika followed fast on the heels of Ebola, and once again raised questions about how governments, university laboratories, pharmaceutical companies and other international partners can best work together to control deadly epidemics, whether natural or created deliberately by hostile nations or terrorists. With this broader question in mind, a group of scientists, doctors, public health specialists and diplomats gathered at Columbia University on April 3, 2017, to review the response

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1 EPSTEIN ZIKA: IMPLICATIONS FOR GLOBAL HEALTH SECURITY to Zika and share insights into the prospects for preventing, tracking and controlling the future spread of infectious threats.

The task is daunting, in part because the universe of infectious diseases appears to be enormous. Using a technique known as VirCapSeq-VERT, Columbia University epidemiologist Ian Lipkin described how he and his colleagues recently identified some 900 previously unknown microbes that are potentially harmful to humans. Lipkin’s team invented a special microchip that carries roughly two million viral signature DNA sequences that can be used to fish for known and unknown viruses in samples of blood or other tissues. The technique has been used to identify previously unknown types of influenza, a novel virus that has been decimating stocks of tilapia fish in the Middle East, and the deadly MERS virus, which has jumped from bats to camels to people and is especially common among the Bedouins of Saudi Arabia. Occasionally new and deadly pathogens are identified when people come down with unexplained illnesses—hotel workers and travel agents are particularly vulnerable. One arenavirus isolated from a Zambian travel agent would have killed 80 percent of its victims if it had spread.

The World Health Organization1 recently identified the following emerging pathogens as those most likely to cause severe outbreaks in the near future:

 Crimean Congo hemorrhagic fever virus;  Filo virus diseases (Ebola and Marburg);  Highly pathogenic emerging coronaviruses relevant to humans (Middle-East Respiratory Syndrome coronaviruses and severe acute respiratory syndrome coronavirus);  Lassa fever virus;  Nipah virus;  Rift Valley fever virus;  Chikungunya;  Severe fever with thrombocytopenia syndrome  Zika virus

1 World Health Organization (WHO), Research and Development Blueprint for action to prevent epidemics, plan of action (May 2016).

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Lipkin estimates, however, that the earth’s roughly 5,500 mammalian species could harbor at least 320,000 microbes that are potentially transmissible to humans. Whether and when any of them will spring from their animal hosts into human populations is impossible to predict, but climate change, migration and war all have the potential to disrupt the fragile ecosystems that ordinarily keep these threats contained.

When it comes to new microbes, New York is America’s Achilles’ heel, Lipkin said, because it is the gateway to the US from all over the world. A few years ago, two monkey heads were confiscated from passengers trying to smuggle them through JFK airport. When Lipkin analyzed them, he found they were riddled with viruses previously unknown to science. New York’s rats are also a trove of novel microbes, to which some New Yorkers carry antibodies, indicating that they can potentially spread. Some forms of chronic Lyme disease may actually be due to as yet unidentified Lyme-like pathogens. Other pathogens might be a hidden cause of stillbirths and even some forms of autism; others found in vaginal flora may actually protect women from infection with HIV.

As if nature and our increasingly stressed environment weren’t enough to worry about, there is also the threat of bioterrorism. Andrew Weber, former US Assistant Secretary of Defense for Nuclear, Chemical & Biological Defense Programs has been involved in shaping America’s response to infectious disease threats for decades. To date, bioterror events are rare, but Weber reminded participants that during the Cold War, Soviet scientists prepared tons of potentially weaponizable anthrax in giant fermenters at a secret lab in Ukraine, and that Al-Qaeda has advertised in its magazine Inspire for recruits with biological expertise.

Weber helped develop the Global Health Security Agenda, an international effort to counter global infectious disease threats, either from nature or terrorism, by conducting surveillance through a network of cooperating agencies around the world and securing laboratories in volatile regions. Launched in February 2014, and given impetus by the deadly West African Ebola outbreak that killed 11,312 people, the GHSA has grown rapidly into a cooperative enterprise that involves more than fifty nations and scores of international and nongovernmental organizations. The GHSA is governed by a steering group of ten countries—Canada, Chile, Finland, India, Indonesia, Italy, Kenya, Kingdom of Saudi Arabia, Republic of Korea and the U. The secretariat is based in the

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Republic of Korea. It is self-funded by member states, although grants are available to assist poorer countries.

The GHSA draws on work in the key areas of immunization, vaccine development, antimicrobial resistance, laboratory security and zoonotic disease outbreaks. The goal is to develop a global network of labs and a real-time surveillance system to detect novel outbreaks before they become epidemics and to construct a similar network of emergency operations centers linking public health with law and rapid response countermeasures.

As former South African Member of Parliament Wilmot James points out in the next chapter, the GHSA is an innovative global partnership that promotes measurable progress in international preparedness to prevent and combat biological threats. The GHSA has already published the first national roadmaps for the implementation of the WHO’s International Health Regulations (IHR) and pandemic preparedness with specific milestones, metrics, and timetables for improvement and for integrating human and animal health. It has galvanized health, security, development, agriculture and defense agencies to work collaboratively and across sectors to achieve common targets.

The Response to Zika: The Devils in the Details

Since Zika arrived in the Western hemisphere, over 700,000 suspected cases have been reported. Sixty-one countries have ongoing transmission, and thirty-one have reported babies with microcephaly or other Zika-related congenital malformations. In the US, there have been nearly 5,000 travel-related Zika cases. In New York, the first case of Zika microcephaly occurred in a baby whose mother had traveled to the Dominican Republic while pregnant. The much feared second wave of Zika, which was expected in 2017, has so far been mild, with only 185 recorded cases in the US as of August 2017, virtually all travel-related.2

Lawrence Stanberry, head of pediatrics at Columbia University College of Physicians and Surgeons, outlined the CDC’s recommendations for the medical care of infants with Zika-related microcephaly. These children require consultation with a neurologist; an infectious disease

2 https://www.cdc.gov/zika/reporting/2017-case-counts.html

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1 EPSTEIN ZIKA: IMPLICATIONS FOR GLOBAL HEALTH SECURITY specialist; an ophthalmologist; an endocrinologist; an orthopedist, physiatrist, or physical therapist for the management of hypertonia, club foot or contracture conditions; a pulmonologist or otolaryngologist for breathing issues; a lactation specialist, nutritionist, gastroenterologist or speech or occupational therapist for the management of feeding issues; and a geneticist, to determine whether the microcephaly might have resulted from another cause. Obviously, the families of microcephalic infants will also need counseling and other social support services. How this care is to be coordinated and paid for is not currently known.

Also unknown are the long-term medical and developmental outcomes for these infants, or for infants with apparently asymptomatic congenital infection. Zika-positive infants have been shown to shed virus for up to two months after birth, but the risk of transmission to others is also not known. Prevention of Zika infection of pregnant women in particular is therefore crucial.

An assessment of the response to the 2015–16 Zika epidemic underscores the importance of greater cooperation on health security. It also demonstrates the difficulty of identifying every challenge in advance, in part because the greatest ones tend to be political, not technical. The Columbia meeting began with a bracing and frank assessment of the Zika response by New York Times journalist Donald McNeil, who assailed public health agencies such as WHO and the Centers for Disease Control for failing to issue clear warnings to women in Zika-affected countries, especially concerning the delay of pregnancy until mosquito season had passed. Until a Zika vaccine becomes available, prevention of microcephaly must rely on behavior change, specifically birth control and abortion if contraception fails, as well as aggressive mosquito control, which has successfully eliminated other mosquito-borne plagues such as yellow fever and malaria from much of the Western hemisphere. In many Zika-affected countries, none of these tools have been effectively implemented.

Although the CDC did ship contraceptives to Puerto Rico, for example, women there weren’t urged to use them. Instead, as in most countries, including the US, they were advised to consult their doctors concerning pregnancy, contraception and abortion. Even US health officials’ recommendations were vague, and many doctors were confused about what to tell their patients who planned to travel to Zika-affected countries. How many disabled infants were born as a result of the failure to issue loud and unambiguous warnings as soon as the link between Zika and microcephaly was first identified will never be known and McNeil’s bitterness over the

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1 EPSTEIN ZIKA: IMPLICATIONS FOR GLOBAL HEALTH SECURITY politicization of this issue highlights some of the perils and weaknesses of the global health architecture,.

Officials at WHO are in a precarious position: they are unelected and hold their positions at the behest of world leaders, some of whom are not themselves elected. The CDC is similarly vulnerable, and faces a strident backlash if its directives clash with any of the myriad views on contraception and abortion that exist within the increasingly fractured US. Reproductive health is among the most controversial areas these agencies deal with, and their choices are limited by diplomatic imperatives not to provoke Christian leaders and others who object to government promotion of birth control and abortion under any circumstances. Should those nations—or states in the case of the CDC—withdraw support for these agencies, the entire infrastructure of global health could be put at risk. This is the conundrum of the Global Health Security Agenda: it is only achievable as long as all, or most, leaders buy into it. But as those leaders more frequently question the post–World War II liberal consensus concerning international cooperation, this could be an increasingly difficult task.

Susan Wong of the New York State Health Department’s Wadsworth Laboratory provided a fascinating frontline view of fighting Zika and other diseases in the lab. At the Wadsworth Center and at hospitals in western Canada, she has conducted serological studies of infectious diseases for over forty years. During this time she’s witnessed amazing advances in technology allowing for increasingly accurate molecular detection of pathogens, including polymerase chain reaction, MALDI-TOF mass spectrometry, whole genome sequencing and parallel sequencing. Labs can now differentiate minute and unique differences between similar viruses such as Zika versus the four serotypes of closely related dengue viruses. While these methods work well in wealthy countries, however, they often perform poorly in developing countries where new pathogens are most likely to arise.

Wong noted that in poor countries the sophisticated instruments provided by the CDC, WHO and the Clinton Foundation often cease to be useful after the departure of the experts who install the machines and train local staff. Reliable electricity to maintain the cold chain is necessary to keep these machines up and running, as are biomedical engineers who can maintain the equipment and ensure quality control. Dependable communications are needed to transmit lab findings to hospitals or surveillance teams. All these resources are often lacking. The safety and security of

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1 EPSTEIN ZIKA: IMPLICATIONS FOR GLOBAL HEALTH SECURITY laboratory staff is another concern, especially in conflict situations. When Wong was lecturing in an unnamed conflict zone she was whisked away by a security team when explosions occurred nearby, while scientists from that country remained on the job. Often the best-educated people in such circumstances are the ones protected, while dedicated staff left behind carry on at great personal risk.

Diagnostic labs should run more smoothly in the US, but Wong noted that challenges occur here too. In the midst of the 2015–16 Zika outbreak, for instance, the FDA gave emergency-use authorization to two Zika tests, but both have limitations. Meanwhile a far more accurate and useful test still awaits FDA approval, even though it is now being used successfully in many other countries.

Of the two FDA approved tests, one is based on PCR and is only useful in the first week or two after infection. The other is based upon measuring IgM antibodies to the Zika envelope protein. But people who have been previously exposed to the closely related dengue virus—which is also endemic in many Zika-prone regions—have a muted IgM response to Zika, and the antibodies are only detectable for six to eight weeks at most. Such cases of co-infection could be quite common, meaning many infections during the thirty-eight weeks of pregnancy could be missed, giving rise to a potentially large false-negative population. Wong estimates that at least 30 percent of Zika in the US will probably be missed as long as testing facilities rely on IgM and PCR testing alone.

In addition, the IgM test cross-reacts with antibodies to other viruses, including dengue and West Nile, so some women might be told they have Zika when they do not. Roughly 25 to 20 percent of Zika IgM ELISA results are therefore false positives, and some pregnant women may choose to terminate healthy pregnancies.

In the US and Canada, the definitive Zika test is a plaque reduction neutralization assay, but getting results can take weeks. In New York, about 10 percent of such tests identify Zika, 20 percent find dengue and 70 percent find an “undifferentiated flavivirus,” which means the infecting virus cannot be determined with any certainty.

It is known that the immune response to nonstructural proteins of flaviviruses—the inner enzymes that make the virus work—is more virus-specific than the immune response to the structural proteins that give the microbe its shape. Serologic tests based on nonstructural proteins should

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1 EPSTEIN ZIKA: IMPLICATIONS FOR GLOBAL HEALTH SECURITY therefore be more accurate. Companies have made good assays that can rapidly detect IgG—which appears later than IgM and lasts much longer—to one of Zika’s nonstructural proteins. These new IgG tests are able to determine if a woman was infected at any time during pregnancy and are being used in Europe, Brazil and French Polynesia. They have not yet been widely deployed in North America, however, because they lack FDA approval, even though good publications in reputable journals testify to their utility. As far as Wong knows, neither the FDA nor the CDC has explained the delay in approving these tests.

In trying to get around the bottleneck caused by the FDA’s failure to approve the IgG test, Wong developed a multiplex microsphere immunoassay to detect total antibodies to multiple structural and nonstructural Zika proteins, as well as nonstructural proteins from all four dengue serotypes. Her lab at the New York State Health Department can determine which serum has Zika antibodies, dengue antibodies, both or none. In patients with antibodies to both viruses, she can run further tests to determine which infection occurred first. But only a fraction of samples designated for Zika testing come through her lab, so not all patients benefit from this highly sensitive and specific assay.

Vaccines on the Horizon

So far, Zika appears not to be a perennial epidemic. For reasons not currently understood, it has not returned to those areas most severely affected in the past, such as Yap Island and Northeast Brazil. Nor, as yet, does it seem to be affecting the southern US as extensively as last year. But this is no cause for complacency. Fortunately a number of vaccine candidates are currently in the works, not only for Zika but also for Ebola and other emerging infections. Conference participants heard from Kayvon Modjarrad, of the Walter Reed Army Institute of Research, about the remarkably swift progress on the Zika vaccine front. There are now several different “platforms” or types of Zika vaccine under development in labs around the world. Some use genetically engineered proteins from the virus to elicit an immune response, others use sections of Zika DNA, while others use live but weakened strains of the virus or hybrids of other viruses engineered to express Zika proteins. Any live virus platform could be dangerous for pregnant women, Modjarrad cautioned. His lab at WRAIR has made rapid progress on a vaccine made from whole inactivated Zika. Production began three months after the first Zika case in the US and human trials began in

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October last year. The vaccine proved 100 percent effective in protecting rhesus monkeys from Zika infection; since a very similar vaccine for Japanese encephalitis, which resembles Zika, is already on the market, it is highly likely that WRAIR’s vaccine will prove safe as well as effective, and could be available by 2019.

Vaccine production carries considerable risks for pharmaceutical companies, both because of research costs and potential liability. Michel de Wilde of Zanofi Pasteur, which manufactures many vaccines currently on the market, discussed the Coalition for Epidemic Preparedness Innovation (CEPI), an alliance that aims to mitigate these risks by raising money from governments and philanthropists to support the development of vaccines against pathogens with epidemic potential.

Diplomacy, Routine Health Care and Innovation Must Remain Essential Priorities

Jennifer Nuzzo, senior associate at the Johns Hopkins Center for Health Security, summarized five key preparedness and response areas in need of urgent attention:

1. Surveillance: One day, a global health security early warning system may be able to predict outbreaks the way meteorologists predict the weather. The rapid spread of both the 2014/2015 Ebola and Zika epidemics caught the world off guard, but there were actually some warning signs. For example, the bat species known to harbor Ebola-Zaire virus existed in West Africa, and Zika was already spreading east from its African and Asian heartland long before it arrived in Latin America. 2. Basic public health systems: The routine public health care system is the foundation for preparedness and responses to rarer events, but it is weak in many developing countries. The rapid containment of Ebola in Nigeria was made possible in part by the expertise and facilities of the polio eradication and PEPFAR programs, but in the longer term, broader primary health care services must be strengthened everywhere. 3. Better diagnostic and predictive tools: As Susan Wong also noted, the diagnostic tests for Zika and many other diseases currently available in the US are inadequate. We must identify better, faster, more reliable ways of testing for new diseases, but this requires often risky investment. With funding from the Intelligence Advanced Research Projects Activity,

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a US government program that supports high risk/high payoff research, Microsoft is developing an innovative trap that can identify infections in mosquitoes. This device was in development before Zika emerged and could vastly improve surveillance of vector-borne diseases. It would not have been available if it weren’t for this particularly risk-tolerant, forward-looking research and development program, of which there are far too few. 4. Medical countermeasures: A lack of vaccines and medicines for potential infectious threats undermines the ability to implement control measures, increases fear and erodes public trust. All too often, research and development programs don’t produce medical countermeasures until an epidemic is over. 5. Funding: After an initial surge in funding for public health preparedness in the early 2000s, federal and state funding has steadily declined. Political leaders tend to view preparedness as a one-time investment, as if a firehouse built one year could be torn down the next because no more fires had broken out.

Finally, conference participants heard from Lawrence Kerr of the Office of Global Affairs at the US Department of Health and Human Services. He indicated that Trump administration officials have expressed commitment to pandemic preparedness and the Global Health Security Agenda. At the same time, Trump has indicated an intention to cut funds for the National Institutes of Health and the US Agency for International Development and the Centers for Disease Control, and to repeal the Affordable Care Act and replace it with legislation that could leave millions of people without health insurance. These moves seem inconsistent with a commitment to preparedness: cutting research funds and foreign aid for health programs overseas obviously limits America’s ability to prevent and control infectious diseases. The routine health care system within the US provides a crucial sentinel for emerging diseases and will be placed at risk if people find such care unaffordable upon the repeal of the ACA.

It is not clear how or if the Trump administration will reconcile these sharply conflicting policies. It is possible that the administration will place an increasing number of GHSA responsibilities in the hands of the Department of Defense, which took the lead on combating Ebola. In that case the arrival of US soldiers on the streets of Monrovia, Liberia and Freetown, Sierra Leone, helped reassure affected populations and strengthened public health measures. But a lead role for the US

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1 EPSTEIN ZIKA: IMPLICATIONS FOR GLOBAL HEALTH SECURITY military may not be appropriate in every case, especially if threats emerge in countries that are not allies. This is why a role for civilian health officials and diplomats, who are currently facing severe budget cuts, will remain crucial.

Zika Conference: April 3, 2017, CUMC: Left to Right: M. Grodman, A. Nolting, L. Stanberry

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2 LAWRENCE STANBERRY: ZIKA PATHOGENESIS, DIAGNOSIS & VACCINES

2: ZIKA PATHOGENESIS, DIAGNOSIS AND VACCINES

Lawrence Stanberry

1. Pathogenesis

Zika virus (ZIKV) is a Flavivirus closely related to West Nile virus, dengue virus, and yellow fever virus. Like other Flaviviruses it is transmitted by the bite of an infected mosquito; unlike other Flaviviruses, the Zika virus can be transmitted from human to human through sexual intercourse or, in the case of an infected pregnant woman, from the woman to her fetus. The majority of ZIKV infected people do not become ill. Those who do generally have a brief mild illness with fever, headache, conjunctivitis, joint pain, and rash. Occasionally the infection can trigger Guillain–Barré syndrome, a neurological disorder. The mechanisms by which ZIKV is sexually transmitted or triggers Guillain–Barré syndrome remain to be elucidated.

The most concerning aspect of ZIKV is its ability to cross the placenta and cause congenital infection with potentially profound consequences, particularly microcephaly and other neurologic abnormalities. The currently available data suggests that ZIKV targets neural progenitor cells in the developing fetus. The infection and related inflammation interferes with cell proliferation and differentiation resulting in cell death, destruction of fetal brain tissue and failure of the fetal brain to develop. The molecular mechanisms responsible for the neurotropism and neuropathology are unknown. There are two Zika families, the African lineage and the Asian lineage. The Zika viruses that are causing microcephaly in the Americas are closely related to the Asian strains. Whether viruses of different lineages or even different strains within a lineage differ in their propensity to cause microcephaly and other neurological abnormalities is unknown.

2. Diagnosis

Because the clinical diagnosis of Zika virus (ZIKV) infection is unreliable, diagnostic testing is necessary to prove an individual is or has been infected. Such testing is challenging: no single test is useful in all clinical settings, and previous or concurrent infection with other flaviviruses, e.g.,

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2 LAWRENCE STANBERRY: ZIKA PATHOGENESIS, DIAGNOSIS & VACCINES dengue and West Nile, can produce antibodies that cross-react with Zika tests, causing them to be falsely positive.

Two types of diagnostic tests have been developed: nucleic acid amplification tests (NAATs) for detection of viral RNA, and immunoassays for detection of immunoglobulin M (IgM) and immunoglobulin G (IgG) antibodies. Detection of ZIKV RNA is indicative of an acute, current infection. Detection of IgM antibodies generally indicates a recently acquired infection (within the past twelve weeks), while detection of immunoglobulin G (IgG) antibodies indicates the individual has been infected with ZIKV sometime in the past. ZIKV immunoassays for the detection of IgG and IgM antibodies to the nonstructural ZIKV protein NS1 are currently available in much of the world with the exception of the United States, where the focus has been on developing assays targeting broadly cross-reactive envelope proteins.

As of August 2017 there are no commercially available diagnostic tests cleared by the US Food and Drug Administration (FDA) for the detection of Zika virus infection, but several tests are available through the FDA’s Emergency Use Authorization Program. Two types of diagnostic tests have received Emergency Use Authorization: NAATs for detection of ZIKV RNA in serum, plasma or urine, and immunoassays for Zika IgM antibody. The FDA has also approved a multiplex NAAT assay that tests for all serotypes of dengue, chikungunya, West Nile, and ZIKV viruses simultaneously. Presently there are no FDA-sanctioned tests to detect Zika IgG.

The development of ZIKV diagnostic tests for use in the US has been hampered by the lack of standardized patient samples for use in validating the new ZIKV diagnostics. In August 2017 the FDA made available to developers a panel of plasma samples from anonymous individuals infected with dengue, West Nile, or Zika viruses. The availability of the standardized samples is expected to facilitate the development of ZIKV serological tests with improved specificity.

The WHO has established target product profiles for these tests. To best serve global needs, tests designed to detect active infection would not require blood collection by phlebotomy or by a sophisticated reference laboratory staffed by trained technicians; instead a minimally trained health care worker would collect blood by finger stick or use saliva or urine and conduct the test at the point of care. The tests would be >99.5 percent specific and >98 percent sensitive.

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3. Vaccines

According to the WHO there are currently forty-five Zika virus (ZIKV) vaccine candidates in development. Six are currently being tested in humans: two inactivated whole ZIKV vaccines (National Institute of Allergy and Infectious Diseases and the Beth Israel Deaconess Medical Center), two DNA vaccines (National Institute of Allergy and Infectious Diseases and Inovio Pharmaceuticals), an mRNA vaccine (Moderna Therapeutics), and a live attenuated recombinant ZIKV vaccine (Themis Bioscience).

Vaccine development involves three stages of clinical testing to insure the vaccine is safe, immunogenic and effective. Phase 1 generally involves a small number of healthy volunteers, is of short duration, and is designed to show that the vaccine is safe and can produce vaccine-specific immune responses. Phase 2 studies have larger numbers of volunteers who are at risk for infection. The studies are longer in duration and are intended to expand the safety and immunogenicity data base and begin to gather evidence that the vaccine is effective. Phase 3 trials normally enroll large numbers of volunteers who are at risk of becoming infected. The trial can take several years, and its goal is to demonstrate the vaccine is safe and efficacious. Presently four of the ZIKV vaccines are in Phase 1 trials and two have entered Phase 2. Given the time required to show safety and efficacy it is unlikely we will have a widely available, effective ZIKV vaccine for several years.

The Phase 3 trials will probably be designed to show that the vaccine can prevent symptomatic Zika infection in the volunteer rather than congenital Zika infection with its dreaded sequelae of microcephaly and other neurological abnormalities. Because congenital infection occurs in a very small percentage of Zika infections, a trial to prove effectiveness against congenital ZIKV infection would require many years and thousands of volunteers. Theoretically studies could be done in high-risk pregnant women, although such studies are fraught with ethical and safety concerns. Once a vaccine has been shown to be safe and effective in nonpregnant women, post- licensure studies will be needed to show the vaccine actually prevents congenital Zika infection.

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3 THOMSON & MUÑOZ CLIMATE, ENVIRONMENT AND ZIKA

3: CLIMATE CHANGE, THE ENVIRONMENT AND THE ZIKA OUTBREAK

Madeleine C. Thomson and Ángel G. Muñoz

Introduction

Any response to Zika must also factor in anthropogenic global warming and natural climate variations. Irrespective of political considerations, the climate will continue to change as key natural and human drivers impact earth systems. Below we outline how such changes have affected and could affect Zika transmission risk in the Americas.

Evidence to date suggests Zika virus (ZIKV) is principally transmitted globally, and in Latin America and the Caribbean (LAC), by the container breeder mosquito Aedes aegypti, with Aedes albopictus identified as a possible significant future vector because of its recent rapid spread.1 Both species also transmit dengue fever, chikungunya, yellow fever viruses, and other diseases, making them a significant public health concern.

Since the fifteenth century, Ae. aegypti has expanded from its ancestral form in the forests of sub- Saharan Africa to become a domesticated vector that is ubiquitous in urban environments in the tropics and subtropics, the home of half the world’s population. Its evolution as an unwanted companion to globalization comes from its preference for ovipositing in both natural and artificial water-filled receptacles, where the eggs can survive even though water contents fluctuate and regularly expose them to drying conditions.2 Suitable containers are common in domestic and peri- domestic urban areas. The survival of the eggs during periods of desiccation is key to the global spread of this mosquito as it can establish itself in new environments should its breeding site be moved. This adaptability accounts for the arrival of Ae. aegypti in the New World, transported by Spanish and Portuguese slave ships, and the subsequent yellow fever epidemics in port cities.

1 J.P. Messina et al., “Mapping global environmental suitability for Zika virus,” eLife, 2016. doi.org/10.7554/eLife.15272.002 2 K.J. Faull et al., “Intraspecific variation in desiccation survival time of Aedes aegypti (L.) mosquito eggs of Australian origin,” Journal of Vector Ecology 40 (2015), pp. 292–300.

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Desiccation-resistant eggs also make controlling Aedes populations particularly difficult because breeding sites are hard to identify when dry. Despite these challenges, however, intensive control programs in the 1950s and 1960s involving social mobilization, house-to-house searches for vector breeding sites, environmental management and insecticide control of adult and juvenile mosquitoes dramatically reduced vector populations and associated disease. Weakening of country vector-control capabilities and insecticide resistance has resulted in resurgence and expansion, bringing this agile vector to preeminence in the globalized twenty-first century.

Although ZIKV transmission depends on several factors, including human behavior, it is well established that vector transmission of the virus is sensitive to variations in environmental temperature and rainfall. Temperature is a significant driver of the development rates of juvenile Ae. aegypti and Ae. albopictus and adult feeding/egg-laying cycles, along with the length of the extrinsic incubation period and viral replication of arboviruses.3 Both excess rainfall and drought have been implicated in the proliferation of breeding sites for Aedes vectors of ZIKV and associated epidemics of dengue and chikungunya. Rain may result in the development of outdoor breeding sites in a wide range of artificial containers,4 and drought may encourage the use of containers (domestic pots, drums and tanks) for water storage. If improperly managed, these vessels become household breeding sites, as happened in Brazil in 2015.5

What was happening to the climate in Brazil in 2015?

At the dawn of 2015, Brazil experienced a combination of climate effects that created suitable environmental conditions for the occurrence of Aedes-borne disease epidemics. The two previous years brought above-normal temperatures to the Amazon basin, with more South American regions

3 O.J. Brady et al., “Global temperature constraints on Aedes aegypti and Ae. albopictus persistence and competence for dengue virus transmission,” Parasit Vectors 47 (2014), p. 388. 4 A.M. Stewart-Ibarra et al., “Spatiotemporal clustering, climate periodicity, and social-ecological risk factors for dengue during an outbreak in Machala, Ecuador, in 2010,” BMC Infect Dis, 14 (2014), p. 610. 5 S. Paz, S. et al., “El Niño and climate change—contributing factors in the dispersal of Zika virus in the Americas?,” Lancet 387, no. 10020 (2016), p. 745. 16

3 THOMSON & MUÑOZ CLIMATE, ENVIRONMENT AND ZIKA exhibiting higher temperatures as time progressed (Figure 1). In fact, by yearend both 2014 and 2015 were reported as the hottest years on record.6

During 2015, Brazil also had its sixth consecutive year of a multiyear drought that is still occurring.7 In addition to temperature anomalies, between 2013 and 2015 a growing number of areas in the country encountered rainfall deficits (Figure 1), with important consequences for society.8

Figure 1. Annual temperature and rainfall anomalies during 2013, 2014 and 2015. Anomalies are computed with respect to the climatological period 1981–2010. Modified from Muñoz et al., 2016.9

6 NOAA, 2015. State of the Climate: Global Analysis for 2014. http://www.ncdc.noaa.gov/sotc/global/201513. Accessed 25 June 2016; NOAA. 2016. State of the Climate: Global Analysis for 2015. http://www.ncdc.noaa.gov/sotc/global/201513. Accessed 25 June 2016. 7 E. Bretan et al., “Drought Preparedness Policies and Climate Change Adaptation and Resilience Measures in Brazil,” in An Institutional Change Assessment. In Evaluating Climate Change Action for Sustainable Development, ed. P. Uitto, and van den Berg (Springer International Publishing, 2017), pp. 305–326. 8 F.E.I. Otto et al., “Factors Other Than Climate Change, Main Drivers of 2014/15 Water Shortage in Southeast Brazil,” Bull Am Meteol Soc 96, no. 12 (2015). 9 A.G. Muñoz et al., “Analyzing climate variations at multiple timescales can guide Zika virus response measures,” GigaScience 41, no. 20165 (2016). 17

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Was it El Niño or climate change?

The year 2015 also marked the start of one of the three most intense El Niño events on record. El Niño tends to bring above-normal temperatures over multiple areas of Brazil, as well as below- normal rainfall conditions, especially in northeastern Brazil (but not necessarily its “Nordeste” region) between October and January. Hence it is tempting to attribute the climate conditions described in the previous section to the occurrence of this very strong El Niño, although such a conclusion would not be entirely warranted a priori.

One way to assess the importance of El Niño and other climate signals to the total observed temperature and rainfall variability is by means of a special filtering process called timescale decomposition.10 This approach divides the variable of interest in signals varying at timescales classified as inter-annual (up to seven to ten years), decadal (ten to sixty years) and long-term climate change (roughly more than sixty years). Once the decomposition is performed, a comparison between the degree of variability of each timescale and the one of the original signal (i.e., the explained variance) provides a measure of the specific importance of each signal.

Figure 2 shows a timescale decomposition for the average annual rainfall and temperature (in black) observed in Brazil during the period 1901 to 2014. Each temporal component is represented by colors: blue for inter-annual, green for decadal, red for long-term climate change. The superposition of the different signals results in the originally observed time series. The percentages in parentheses in the legend of the figure indicate the explained variances mentioned in the previous paragraph, giving an idea of the specific weight of each signal.

Using this approach, previous research11 concluded that the warming observed in 2015 is not only due to El Niño but is an outcome of positive temperature anomalies at the year-to-year and decadal timescales, superimposed on a long-term positive warming trend that is consistent with climate change. This superposition of signals may have helped to set the climate scenario for local ZIKV transmission via Ae. aegypti and other less significant vectors. This analysis by itself does not shed

10 A.M. Greene et al., “Web tool deconstructs variability in twentieth-century climate,” EOS Transactions American Geophysical Union 92, no. 45 (2011), p. 397. 11 A.G. Muñoz et al., 2016. 18 3 THOMSON & MUÑOZ CLIMATE, ENVIRONMENT AND ZIKA light directly on the behavior of the potential risk of transmission of Aedes-borne diseases, but rather on key contributing climate signals.

Figure 2. Timescale decomposition for rainfall (top panel) and temperature (bottom panel). Numbers in parentheses show explained variance for each timescale. Period of analysis: 1901–2014 (after Muñoz et al., 2016).

A common way to assess the potential risk of occurrence of Aedes-borne epidemics is to estimate the basic reproduction number, R0. Using a two-vector-one-host model, recent work1213 has analyzed the evolution of the spatially-averaged R0 standardized anomalies for LAC (Figure 3). The unfiltered time series (black curve in Figure 3) exhibits a clear trend between 1950 and 2015 consistent with the persistent increase in temperatures observed in the region (Figure 2, bottom panel). Once the longer-term signals are filtered out, the inter-annual component of the R0

12 C. Caminade et al., “Global risk model for vector-borne transmission of Zika virus reveals the role of El Niño 2015,” PNAS 114, no. 1 (2017): pp. 119–124. 13 A.G. Muñoz et al., “Could the Recent Zika Epidemic Have Been Predicted?,” Frontiers 8, no. 1291 (2017). 19

3 THOMSON & MUÑOZ CLIMATE, ENVIRONMENT AND ZIKA standardized anomalies (filled curve in Figure 3) shows a peak in 2015, the second-highest on record after 1998.

The difference observed in Figure 3 between the inter-annual (filled curve in Figure 3) and the raw component (black line in the same figure) indicates that a year-to-year signal cannot be the only one responsible for the record-high values in the time series; in other words, a combination of signals acting at multiple timescales, probably related to the climate signals analyzed in Figure 3, was present during the recent ZIKV epidemic. Neither El Niño nor climate change can be independently blamed for this event.

14 Figure 3. Standardized anomalies of R0 using the two-vector-one-host model of Caminade et al. (2017). The total (unfiltered) time series is presented in black, while the inter-annual component is shown in the filled curve; red and blue correspond to positive and negative standardized anomalies respectively. Units are standard deviations. Period of analysis: 1950–2015.15

Could future ZIKV epidemics be predicted?

Due to the confounding effect of multiple environmental and non-environmental agents, it is extremely difficult to skillfully predict ZIKV epidemics. Nonetheless, it has been recently shown that it is possible to provide skillful forecasts of suitable environmental conditions that are conducive to transmission of Aedes-borne diseases, like ZIKV, dengue and chikungunya.16

14 C. Caminade et al., 2017. 15 Á.G. Muñoz et al., 2017. 16 Ibid., 2017. 20

3 THOMSON & MUÑOZ CLIMATE, ENVIRONMENT AND ZIKA

This new experimental forecast system uses the basic reproduction number model of Caminade and colleagues, mentioned in the previous section, to assess the potential risk of occurrence of generic Aedes-borne diseases. The model uses both ento-epidemiological and environmental information and is forced by observed climate and state-of-the-art operational forecasts from the North American Multi Model Ensemble project (NMME). This approach allows probabilistic predictions of above-normal, normal or below-normal risk for at least the following season (three months), information deemed useful for health practitioners and decision -makers.

Figure 4. Seasonal predictive skill maps for the basic reproductive number, R0, for Latin America and the Caribbean. Units are in percentage. A value of 100 percent represents perfect skill (forecast and observations are equal), a value of 50 percent indicates the same skill as the long-term observed averages (climatological values); values lower than 50 percent indicate places where skill is worse than climatological values. Period of analysis: 1982–2010.19

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The analysis of real-time skill of the potential risk model suggests that the predictive capacity is highest for multiple countries in LAC during the December–February and March–May seasons (Figure 4), and it is slightly lower—although still of potential use to decision-makers—for the rest of the year.

It is important to emphasize that although it is possible to forecast suitable environmental conditions at seasonal timescale for the potential risk of transmission of Aedes-borne diseases, this does not mean that actual transmission or even epidemic events are predictable with this type of forecast system.

What are the long-term implications of climate change?

Climate change implies changes in the climatological characteristics of different variables, both in their mean and extreme values. At a global scale, there is irrefutable observable evidence of warming, something that is reproducible by state-of-the-art climate models. Unfortunately, models are not perfect and the climate information provided by them always has uncertainties, whose magnitudes depend on the model considered, location on the planet, the season and variable of interest as well as the availability of observed climate data from ground stations.

Generally speaking, temperature fields have less uncertainty than rainfall-related fields. Due to global warming, it is expected that larger areas of the planet will experience warmer-than-present temperatures, which tend to provide the conditions for both increased virus replication and mosquito proliferation rates. On the other hand, if temperatures on the order of 40oC or above become more frequent, it is also possible that some places will exhibit a decrease in the vector density, because at such temperatures mosquito mortality increases rapidly.

As indicated, climate change rainfall projections have high uncertainty. Nonetheless, several regions are expected to observe a more extreme rainfall distribution, which may provide suitable conditions for mosquito reproduction, depending on the intensity and frequency of the precipitation.

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As happened in 2015, the occurrence of high temperatures due to an in-phase synchronization of the climate change, decadal and inter-annual signals could reoccur, with likely more extreme consequences. Climate change will therefore affect disease and pathogen distribution and probably epidemic occurrence as well as risks of climate-sensitive epidemics. This is why health has been an important argument for climate-change mitigation. It must be noted, however, that climate change may also affect other societal process that are conducive to vector-borne disease epidemics. These include but are not limited to impacts on local livelihoods, social unrest, impacts on infrastructure and services.

How should climate information be integrated into ZIKV control?

The use of climate information, along with other relevant indicators of population vulnerability, in support of vector-borne disease control programs is not new. Malaria control in the Punjab at the turn of the twentieth century included an early-warning system based on monitoring of unusual weather and the state of food stocks.17 In recent years an extensive literature has emerged on the predictive relationship of observed and forecasted climate events and the seasonal, year-to-year and longer-term shifts in infectious diseases included those transmitted by mosquitoes.18 Significant challenges need to be overcome, however, before such relationships can be exploited in operational decision-making; for now the use of climate information by the health sector is limited. In particular, access to relevant climate and disease data at the appropriate space and time scales, with known indications of uncertainty, is needed. In addition, modeling approaches, whether statistical or dynamical, need to be developed with users in mind. Trust is at the heart of decision-making and “black box” analysis, which provide early warning information but not the clear causal pathway between input data and expected outcome, are of limited use. Health policy makers and practitioners are often not familiar with the data, methodologies and tools required for

17 C.A. Gill, “The prediction of malaria epidemics: with special reference to an actual forecast in 1921,” Indian Journal of Medical Research 10 (1923), pp. 1136–1143. 18 L.A. Kelly-Hope et al., Climate and Infectious Disease in Seasonal Forecasts, Climatic Change, and Human Health, ed. M.C. Thomson, R. Garcia-Herrera, and M. Beniston (Dordrecht: Springer Science+Business Media, 2008), pp. 31–70. 23

3 THOMSON & MUÑOZ CLIMATE, ENVIRONMENT AND ZIKA an effective integration of climate information into predictive disease models and this needs to change.

Conclusion

Climate is an important driver of vector-borne diseases including those, such as Zika, that are transmitted primarily by Aedes mosquitoes.

 Both climate variability and change may increase environmental conditions conducive to Zika vectors and pathogens;  Climate may disrupt social systems in a way that favors disease distribution and epidemics;  Climate-change mitigation may help minimize future risks of vector-borne diseases in regions where the climate (especially temperature) is not yet conducive for those risks;  Knowledge about the climate, its impacts and its predictability may help mitigate some of the risks and enhance health security.

Zika Conference: April 3, 2017, CUMC: Left to Right: L. Kerr, S. Barrett, and P. Hwang

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4 James: Global Health Security and Diplomacy

4: Global Health Security and Diplomacy

Wilmot James

Humanity’s Shared Concern

In the age of globalization, it is health security, a Lancet editorial stated, that “is now the most important foreign policy issue of our time.” The rapid emergence and re-emergence of pathogenic infectious disease, the slow but steady cumulative acts of nature associated with climate change (aggravated often by human actions), forced migration caused by desperation and war, the creeping reality of biochemical terror and the threat of nuclear attacks—all these propel human survival and well-being to the frontline of what today must be everybody’s concern.

The field of health diplomacy provides an unprecedented opportunity to build human solidarity. It is an area of concern and human endeavor that cuts through inherited antagonisms. Governments that offer health improvements as part of aid to nations with whom they wish to develop stronger diplomatic links succeed in cultivating deeper cultural relationships precisely because of their direct benefit to citizens. To advance health diplomacy requires health leaders with an inclusive global vision.

Traditional health diplomacy involved negotiations over intellectual property (IP), access to medicines, trade and donor assistance. Zika, Ebola and other infectious disease outbreaks have focused attention on new areas of negotiations involving rapid inter-governmental emergency responses, the role of the military in building infrastructure, the efficient movement of health professionals, medical therapies, innovative diagnostic and surveillance technologies, intervention methodologies and technical partnerships across regions and continents.

A new paradigm, one that places less emphasis on aid and more on local partnerships and domestic ownership of health regimes has replaced the dated twentieth-century terms “foreign aid” and “donor-recipient” relations. Jimmy Kolker, a former assistant secretary for global affairs at the U.S. Department of Health and Human Services (HSS) and a pioneer in health diplomacy, observed that a new doctrine is being built on partnerships based on trust rooted in evidence, data,

25 4 James: Global Health Security and Diplomacy interventions, people and institutions, and is forged by diplomacy, soft power and mutual interests in health security.1

The emergent “all-risks, one health” approach brings together human and animal health, agriculture, wildlife, finance, defense, security, environment, communication, disaster management, transportation, customs, civil aviation, universities and research institutes, and political leadership. At universities, research and teaching draw on the disciplines of medicine, public health, climate and geographical science, international affairs, law, economics, anthropology, sociology, political science, engineering and journalism to provide expertise and practical field applications.

The deliberate release of dangerous chemicals in theaters of war such as in Syria reminds us of the importance of making every effort possible to stop governments and nonstate actors from poisoning people. No less critical is the need to take appropriate security measures and heighten vigilance over laboratory and health science biosafety protocols when it comes to the accidental or deliberate release of killer chemicals. The specter of a less secure nuclear environment also looms.

Accelerating Compliance: The Global Health Security Agenda

The World Health Organization (WHO), a specialized United Nations agency that serves as the directing and coordinating authority for international health matters, revised its International Health Regulations (IHR) and published reworked and updated specifications and targets in 2005. A decade later 80 percent of the WHO member states had failed to comply with the new regulations, putting them at risk of epidemics, the West African Ebola outbreak being one tragic consequence.

To accelerate compliance, the Global Health Security Agenda (GHSA) was established in 2014 with the goal of assisting countries with the weakest health systems to rapidly scale up disease outbreak prevention methodologies. The ravaging course of the Ebola virus added urgency to the

1 Jimmy Kolker, “HHS and Global Health in the Second Obama Administration” (Center for Strategic and International Studies: Global Health Policy Center, April 2017), p.1.

26 4 James: Global Health Security and Diplomacy rapid growth of a voluntary and cooperative enterprise of more than fifty governments and nongovernmental organizations in support of WHO’s global functions.2

GHSA’s agenda set up an International Health Regulations Monitoring and Evaluation Framework (IHR-MEF) that underscored mutual accountability, transparency, experience sharing, dialogue and diplomacy between WHO member states devoted to the purpose of advancing health security. Through annual reporting, joint peer assessments, simulation exercises, systematic follow-ups and the development of easily available standardized measurements (or metrics), the GHSA provided a multi-sectoral picture of a country’s capabilities in detecting, notifying and responding to public health emergencies. These steps contributed to identifying the strengths, gaps and priorities that are further addressed in every country’s National Action Plans for Health Security. “The voluntary, peer to peer, fully collaborative and multi-sectoral approach to external evaluation” that Nirmal Kandel and others wrote about in the Lancet “has led to strong country ownership,” a prerequisite for lasting success.3

______

Joint External Evaluation (JEE)

GHSA teams have led JEE exercises that assessed countries against the following targets:

 An adequate legal framework so state parties can support and enable the implementation of all of their obligations and rights in order to comply with and carry out the International Health Regulations (IHR);  Multi-sectoral/multidisciplinary approaches through national partnerships for effective alert and response systems;  Support work coordinated by the WHO, the Food and Agriculture Organization of the United Nations (FAO) and the World Organization for Animal Health (OIE) to develop an integrated global package of activities to combat antimicrobial resistance, spanning human, animal, agricultural, food and environmental aspects, i.e., a “one health” approach;

2 Mark Siedner and John Kraemar, “The end of the Ebola virus disease epidemic: Has the work just begun?,” Lancet 5, no. 4 (April 2017), pp. e381–e382. 3 Nirmal Kandel, Rajesh Sreedharan, Stella Chungong, Karen Sliter, Simo Nikkari, Kashef ljaz and Guenael RM Rodier, “Joint external evaluation process: bringing multiple sectors together for global health security,” Lancet 5, no. 9 (September 2017), e857–8.

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 Measures, behaviors, policies and/or practices that minimize the transmission of zoonotic diseases from animals to human populations;  Surveillance and response capacity by state parties for food and water-borne disease risks or events;  A whole-government national biosafety and biosecurity system to ensure that especially dangerous pathogens are identified, held, secured and monitored in a minimal number of facilities according to best practices and biological risk management training and outreach are conducted;  A functional national vaccine delivery system able to respond to new disease threats;  Real-time biosurveillance with a national laboratory system and effective modern point- of-care and laboratory diagnostics;  Surveillance systems that detect events of significance for public heath, animal health and health security;  Timely and accurate disease reporting according to WHO requirements and consistent coordination with FAO and OIE;  Skilled and competent health personnel for sustainable and functional public health surveillance and response at all levels of the health system and the effective implementation of the IHR;  Development and maintenance of national, intermediate and local or primary public health emergency response plans for relevant biological, chemical, radiological and nuclear hazards;  Public health emergency operation centers (EOC) that function according to minimum common standards;  In the event of a biological event of suspected or confirmed deliberate origin, the capacity for a country to conduct a rapid, multi-sectoral response, including linking public health and law enforcement and requesting international assistance;  A national framework for transferring medical countermeasures and public health and medical personnel among international partners during public health emergencies;  Risk communication that is multi-level and multi-faced and includes real-time exchange of information, advice and opinion between experts and officials or people who face a threat or hazard to their survival, health or economic or social well-being;

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 The designation and maintenance by state parties of core capacities at international airports—or designated ground crossings—that implement specific public health measures;  Surveillance and response capacity by state parties for chemical risk or events;  Surveillance and response capacity for radio-nuclear hazards or other emergencies.

Financing the GHSA

When the GHSA was launched in February 2014, all participating countries were asked to make a commitment to assist—either in their own country, on a regional basis, or globally. Some countries have pledged money, others are helping to recruit other countries into the GHSA community, while still others are supporting the implementation of the Action Packages first developed by the Atlanta-based Center for Disease Control and Prevention (CDC) to conform with targets set out in the Joint External Evaluation (JEE) methodology.

The US commitment is the most significant. Following the Ebola epidemic, the US Congress allocated $1 billion in new funding over five years, ending in 2019. This money has and is being used to help thirty-one countries and the region of Caribbean Community (CARICOM) meet GHSA targets. Each country/region is creating a five-year national plan to achieve the targets and undergo a JEE as well. In addition, the US Congress appropriated another approximately $400 million annually to the following agencies to carry out GHSA activities: CDC, USAID, DoD Cooperative Threat Reduction, State Biosecurity Engagement Program, the FBI and USDA.

In 2016, G7 leaders agreed to essentially match America’s contribution by assisting seventy-six countries and regions including the thirty-one countries already receiving US help. The monetization and specifics of that commitment, however, have yet to be fully spelled out.

Successful GHSA Projects

 Building community resilience in Vietnam to identify potential outbreaks earlier to shorten response times and avert epidemics;

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 Moving Congolese contact-tracing experts to Guinea to assist with disease and prevention detection efforts;  Training engineers to maintain the 120-plus biosafety cabinets at Ethiopia’s national laboratories;  Acute laboratory testing for pathogens in foodborne outbreaks in India to enable public health experts to link people with similar results;  Developing a special public health approach to deal with the Hindu pilgrimage of Kumbh Mela in India, the largest gathering—sixty million people—on earth;  Modernizing Kazakhstan’s outdated laboratories using a step-wise improvement approach;  Joint WHO–Mali Ministry of Health training program of subject experts in surveillance for viral hemorrhagic fevers, polio and yellow fever;  Training disease detectives in Pakistan to stop vaccine-preventable diseases like measles, diphtheria, pertussis, tetanus, hepatitis B and Hib disease;  Post-Ebola development of Sierra Leone’s Integrated Disease Surveillance and Response System providing timely health data to decision-makers;  Community-based disease surveillance training for volunteer community workers and health workers in Tanzania to investigate and report community-level outbreaks.

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At the 28 July 2017 meeting of the GHSA steering group countries—Canada, Chile, Finland, India, Indonesia, Italy, Kenya, Saudi Arabia, South Korea and the United States—forty-three countries reported the completion of the Joint External Evaluations (JEE) and thirty were underway. Thirty- four countries held simulation exercises and two had After Action Reviews (AAR). Most of the countries from the more vulnerable regions where outbreaks originate, such as Southeast Asia and Central and East Africa participated—and did so early on. Along the way, an ever-growing community of health experts from a diverse set of countries developed professional relationships around the bedrock concepts and processes at the heart of the science enterprise: trust in data, evidence, processes, systems and institutions—all essential requirements for joint action to stem disease and prevent death.

The GHSA arrived after the Ebola outbreak had peaked, too late to make a real difference. The Zika outbreak in Brazil became an early test of the reformed post-Ebola WHO global response.

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Brazil has a sophisticated capacity for surveillance and response. Even so, an international team of experts was assembled at Brazil’s request to develop a fourteen-point action plan giving responsibility to participating countries to follow up. An unprecedented degree of sample, diagnostic, blood test and vaccine development sharing essential for fighting Zika globally became the norm. 4 Beyond Zika, the Nuclear Threat Initiative’s (NTI) Beth Cameron wrote, the GHSA/WHO collaboration provided “tangible support that improved response to the recent Ebola outbreak in the Congo, cholera outbreak in Cameroon, measles outbreak in Pakistan and yellow fever outbreak in Uganda.”5

The funding environment for global health security shifted during 2017 and raised concerns about the GHSA’s viability. Sam Loewenberg remarked that “in the wake of the Ebola crisis, the global health security agenda and the implementation of the IHR became major US priorities. Whether that will continue is uncertain. Although it might seem to be an area that the Trump administration wants to protect for self-interested reasons, the administration could easily go the other way and try to take an isolationist stance, such as (simply) imposing travel bans.”6

Though it has the status of a proposal, the fear of budget slashing is real. The CDC, likely the most important GHSA serving institution, may see a shift toward block grant funding to support domestic state needs. Former CDC Director Tom Frieden said that block grants are often a precursor to funding cuts. He estimates that the CDC will lose $1.8 billion from its $7 billion budget, a 25.7 percent cut. In his experience, block grant funding is naïve and shortsighted. He cites the fact that “block grants for TB control programmes gave rise to deadly outbreaks of drug- resistant TB that cost more than a billion dollars to deal with.” Furthermore, at the NIH, a proposed 18 percent cut including the complete elimination of the Fogarty International Center for Global Health is huge. Taken together, with cuts that will affect both the State Department and Health and Human Services (HHS), funding for global health diplomacy will face serious constraints.

HHS (in which the CDC resides as an agency), the State, Defense, and Agriculture Departments and USAID have led US efforts using a farsighted one-health policy approach. Specific programs

4 Kolker, “HHS and Global Health in the Second Obama,” p.6. 5 Beth Cameron, “Statement in support of extending the Global Health Security Agenda Beyond 2019” (Global Health Security Agenda Consortium, July 2017). 6 Sam Loewenberg, “Trump’s foreign aid proposal rattles global health advocates,” Lancet 389, no. 10073 (11 March 2017), pp. 994–5.

31 4 James: Global Health Security and Diplomacy include the Global Disease Detection Centers, Field Epidemiology Training, Emerging Pandemics Threat, Cooperative Biological Engagement, Biosecurity Engagement and the Global Emerging Infections Surveillance and Response System, but there are others.

The CDC developed the eleven initial Action Packages that provided countries with the tools to help:

 Prevent the emergence and spread of antimicrobial drug-resistant organisms and emerging zoonotic diseases, and strengthen international regulatory frameworks governing food safety;  Promote national biosafety and biosecurity systems;  Reduce the number and magnitude of infectious disease outbreaks;  Launch, strengthen and link global networks for real-time bio surveillance;  Strengthen the global norm of rapid reporting and sample sharing;  Develop and deploy novel diagnostics and strengthen laboratory systems;  Train and deploy an effective biosurveillance workforce;  Develop an interconnected global network of emergency operations centers and multi- sectoral response to biological incidents;  Improve global access to medical and nonmedical countermeasures during health emergencies.

With militaries playing an important role in rapid response logistics and infrastructure development during health emergencies, defense authorities have become involved more and more in frontline public health services, which may carry risks if managed poorly for nonpartisan neutrality in foreign locations. With the Trump administration’s goal of expanding the budget of the defense authorities, spending on military-driven health security may well increase, which is good for the cause.

The US military has made the understanding, preventing and treating of infectious diseases a priority throughout its history. To protect its service personnel from infectious disease the world over, it has invested in infectious disease efforts that have led to a number of scientific, medical and public health contributions. The Department of Defense organizes its support in three ways: (1) medical research and development; (2) health surveillance; and (3) education and training of

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US personnel.7 There are highly specialized programs supported by Defense, among which the medical biological defense research and development effort is of significance, as it addresses naturally occurring and emerging infectious diseases that have the potential to be used as biological agents, such as anthrax and novel influenza viruses.

Defense expenditure on health security under the Trump administration may give more momentum to the securitization of health worldwide, to the possible detriment of diplomatic efforts led by the State Department and Health and Human Services. Many if not most of the difficult and complex issues in health security are solved by diplomacy and negotiations requiring highly skilled health attachés (there are six attached to the Geneva, Beijing, Brasilia, Mexico City, Pretoria and New Delhi US missions), nearly 2,000 HHS staff and foreign CDC stations. Under the GHSA, a fundamental principle has always been that, whether it be a naturally occurring outbreak, a laboratory accident or bioterrorist attack, the first response has to be led by the health system.

To see the US vacate its leadership role in global health would be deeply regrettable. As the saying goes, it takes years to build a community of practice and mere days to destroy it. Still, other major powers must also rise to the occasion, and all countries, rich and poor, must turn promises into practice by seriously investing in strengthening their health systems. The signs are promising. The G7 and G20, focused normally on economic matters, prioritized health as a key component to sustainable development and placed topics such as anti-microbial resistance and lessons learned from the Ebola crisis on their agenda for the G20 Heads of State Summit in Hamburg, 7-8 July 2017. Not coincidentally the meeting was addressed by recently elected WHO Director-General Tedros Adhanom, who spoke about WHO’s priorities under his leadership. But the G20’s commitment to the GHSA has not been adequately costed and turned into a funding stream. China plays an increasingly role in health development globally, but it could do more.8 Finally, ordinary citizens, civic bodies and international organizations like the Inter-Parliamentary Union (IPU) and the Global Organization for Parliamentarians Against Corruption (GOPAC) must fight the disgraceful corruption that diverts public funds for health care into the pockets of parasitic elites.

7 Kellie Moss and Josh Michaud, The U.S. Department of Defense and Global Health: Infectious Disease Efforts (The Henry J. Kaiser Family Foundation, October 2013). 8 Liu Peilong, Yemane Berhane and Wafaie Fawzi, “China, Africa, and US academia join hands to advance global health,” Lancet 390, no. 10096 (19 August 2017), pp. 733–4.

33 4 James: Global Health Security and Diplomacy

From the perspective of the developing world (for the most part), health should not be seen in security terms but, in the words of the Médecins Sans Frontières (MSF), as a “right, an enabler of human potential and a precondition for growth in prosperity.” Instead of only focusing on “crisis management” and “pandemic preparedness,” though those are certainly critically important, nations must invest in universal health coverage, stronger health systems, solutions to antimicrobial resistance, more research and development, the eradication of epidemics of poverty- related diseases, and completion of the unfinished business of the Millennium Development Goals (MDGs). The MSF said specifically that the G20 countries should “strengthen the WHO to enable a coherent global health policy that is adequately financed.”

The WHO does need strengthening. Internal and external assessments of its performance during the West Africa Ebola outbreak were damning. Its in-country representation in the affected nations was weak. Its officials enabled rather than challenged national government under-reporting. Mistrust and poor communication defined the relationships between West Africa and Geneva. Domestic coordination of the emergency response was bad to shocking. Cooperation with non- WHO organizations, the UN and international humanitarian organizations was not much better.

In Zika: The Emerging Epidemic, Donald McNeil wrote that during the initial Zika outbreak the

WHO laid low and deferred to the Pan American Health Organization (PAHO) to take the lead.9 Because it is a UN agency, as McNeil puts it, of “big member club” governments, the WHO resisted issuing travel advisories—especially in Brazil, which was about to host the Olympics— because of the economic harm they invariably cause, By the time the WHO declared an international emergency it was a little too late. Because it did not want to offend the governments of Catholic countries who were its members, the organization failed to confront the abortion question head-on and therefore failed to provide women who wanted to become pregnant with assertive contraceptive advice,

Some adjustments were made by Margaret Chan after the Ebola outbreak. Director-General Adhanom has committed the WHO to much deeper reform. It is a challenge. The WHO does not have an army of doctors or an emergency fund. To act it relies on technical bodies such as the CDC and the volunteer doctors such as the MSF. But the WHO has global legitimacy, and it

9 Donald McNeil, Zika: The Emerging Epidemic (New York: W.W. Norton, 2016), pp. 77–79.

34 4 James: Global Health Security and Diplomacy provides diplomatic cover to anyone wishing to contribute to global health regardless of what country that person is coming from.

Adhanom’s great concern must be the future of Africa-CDC. Launched in Addis Ababa, Ethiopia, on 31 January 2017, it is Africa’s first continent-wide public health agency. The CDC, facing budget cuts, was a major force in setting it up. The Africa-CDC’s principal purpose is to develop early warning and response surveillance systems, emergency response, specialist health professional capacity and appropriate technical expertise. Five regional Africa-CDC centers located in Egypt, Gabon, Kenya, Nigeria and Zambia will be required to develop the capacity to rapidly detect pathogens and serve as regional reference centers. In turn, every African country is expected to develop a public health institute. But, as the Lancet editorializes, “insufficient funding is the key element that could hamper implementation. Despite receiving funding from both the African Union and China, there is uncertainty regarding the impact that a change in the commitment of the new US government to support the Global Health Security Agenda could have on the Africa CDC.”10

The GHSA’s mandate—and the $1 billion set aside for it—runs out in 2019. At the 28 July 2017 meeting of the GHSA Steering Group, it renewed its commitment to a world safe and secure from infectious diseases and noted that much unfinished business and many undone tasks lie ahead. But the point of focus may have narrowed. The US delegation said their government’s commitment to achieve all GHSA targets is undiminished, but a working group will consider how the GHSA can better catalyze global preparedness to biological threats. A new biodefense strategy, long in the making, is an opportunity for the Trump administration to incorporate its priorities into the ongoing efforts of the GHSA.11

But the future is uncertain. Trump’s homeland security and counterterrorism advisor Thomas Bossert assured a recent Aspen Institute meeting that the “administration plans to give ‘full- throated support’ to the GHSA.” HHS Secretary Timothy Price similarly declared to the WHO’s 70th Assembly, worth quoting in full, that “the United States affirms its support for the GHSA. The US is dedicated to building capacity to comply with the IHR and to find and stop disease

10 Editorial, “A new day for African public health,” Lancet Infectious Diseases 17, no. 3, p. 237. 11 “Biological Defense: Additional information that Congress may find useful as it considers DOD’s advanced development and manufacturing capability” (US Government Accountability Office GAO-17-701, 17 July 2017, https://www.gao.gov/assets/190/ 685889.pdf).

35 4 James: Global Health Security and Diplomacy outbreaks around the world, whether they are naturally occurring, accidental, or deliberate in nature. We are also committed to realizing multi-sectoral partnerships with other nations, international organizations and nongovernmental stakeholders, including the private sector. WHO cannot succeed in its mission without incorporating the perspectives of extra-governmental entities.” But whether the Trump administration will underwrite the commitment with funding at the level required is another matter altogether, and that just about frames the challenge to our efforts ahead.

Conclusion: Children and Global Health Security

The world today is trying to manage health risks associated with population growth, climate change, deforestation, institutional collapse, state failure, accidents, human error, war and terrorism. The full range of risks is presented in the concept map below and includes infectious disease outbreaks, biological, chemical, radiological and nuclear spillovers or attacks, multiple hazards, food insecurity, state fragility and cyber-security failure or attacks. This is a breathtaking range of risks and no single institution can tackle them alone. They truly are humanity’s common concern.

In response to infectious disease outbreaks, initiatives like the GHSA have emerged to support the WHO in accelerating country compliance with its International Health Regulations so that countries can deal more effectively with emergencies when they arise. There is the grim prospect that beyond emergencies with natural causes, new technologies enable the deliberate release of pathogenic substances that add to an existing arsenal of chemical, biological and radiological weapons that could decimate human populations.

The challenge to universities is whether they are making their research expertise available for the management of health risks—and in a form that makes a practical difference. Columbia University has taken on the challenge by establishing a health diplomacy and security program that will draw on three kinds of intellectual resources for which it has a global reputation: (1) medicine, public health, dentistry and nursing at the Columbia University Medical Center (CUMC); (2) climate and environmental change at the Earth Institute’s International Research Institute for Climate and

36 4 James: Global Health Security and Diplomacy

Society (IRI); and (3) international and global affairs at the School for International and Public Affairs (SIPA).

The initiative will focus on the education of the next generation of health security and diplomacy professionals and leaders. Research, education and policy efforts will give priority to innovations in diagnostics, bio-surveillance, medical countermeasures and emergency medicine in response to pandemic infectious outbreaks and biological, chemical, radiological spillovers or attacks, as well as the climate and environmental impacts on infectious disease outbreaks, forced migration, community fragility and food security risks. New diplomatic tools and international and model domestic law will be used to better detect, prevent and respond to potentially catastrophic threats to health security within a human rights framework. To translate its expertise into practice, the initiative will partner with the GHSA as a nongovernmental stakeholder and other institutions that share our values, principles and sense of urgent purpose.

The welfare of children is a special interest of the initiative, in part because some of its founders are pediatricians who have made major contributions to child health. But there is also a disturbing realization that adults have not acted on an important duty. Moral philosophy distinguishes between the moral standing and moral agency of human beings: children may well have the same moral standing as the rest of humanity, but they rarely ever have the agency—the ability or legal opportunity to act in their own interests to change a law, a practice or a policy. The International Health Regulations do not make adequate provision for children. Vaccines and other medicines have different applications for babies, kids and adolescents. Children suffer disproportionately during epidemic and pandemic outbreaks. They are often targeted during war and civil strife. To bring about the changes necessary to safeguard the lives of all children will require adults to act on their behalf.

37

5 ZIKA TIMELINE

5: Timeline of the Zika Virus Pandemic

1947 Scientists identify a new virus in a rhesus monkey in the Zika Forest of Uganda and name it the Zika virus. 1948 The virus is then recovered from the mosquito Aedes Africanus caught in the Zika Forest. 1952 The first human cases of Zika are detected in Uganda and the United Republic of Tanzania. 1964 A researcher in Uganda is infected with Zika while working on the virus, confirming that Zika virus causes human disease. He reports the illness as “mild.” 1960s–1980s Human cases are confirmed through blood tests. No deaths or hospitalizations are reported, but studies consistently show widespread human exposure to the virus. 1969–1983 Zika virus is detected in mosquitoes found in equatorial Asia, including India, Indonesia, Malaysia and Pakistan. 2007 First large Zika outbreak in humans in the Pacific Island of Yap in the Federated States of Micronesia. Prior to this, no outbreaks and only fourteen cases of human Zika virus disease had been documented anywhere in the world. An estimated 73 percent of Yap residents are infected. The Yap Island outbreak also suggests a lack of immunity in the island’s population. Regular exposure to infection by populations in Africa and Asia may have prevented the large outbreaks seen on Pacific Islands and in the Americas. Underreporting due to the clinical similarities of (mild) illness symptoms associated with Zika, dengue and chikungunya infections might also account for previous Zika outbreaks being overlooked. 2008 A US scientist conducting field work in Senegal falls ill with Zika infection. On his return home to Colorado he infects his wife in what is the first documented case of sexual transmission of a disease usually transmitted by insects. 2012 Researchers identify two distinct lineages of the virus, African and Asian. 2013–2014 Outbreaks occur in four other groups of Pacific Islands: French Polynesia, Easter Island, the Cook Islands and New Caledonia. Thousands of suspected infections are investigated in French Polynesia. Results reveal possible associations between Zika virus and congenital malformations and severe neurological and autoimmune complications.

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20 March 2014 During the outbreak of Zika virus in French Polynesia, two mothers and their newborns are found to have Zika virus infection within four days of birth. The infants’ infections appear to have been acquired by trans- placental transmission or during delivery. 31 March 2014 During the same outbreak of Zika virus in French Polynesia, 1,505 asymptomatic blood donors are reported to be positive for Zika as tested using polymerase chain reaction (PCR) methods. These findings alert authorities that Zika virus can be transmitted through blood transfusion. 29 March 2015 Brazil notifies WHO of an illness characterized by skin rash in northeastern states. From February 2015 to 29 April 2015, nearly 7,000 mild cases are reported, with no reported deaths. Of 425 blood samples taken for differential diagnosis, 13 percent are positive for dengue. Tests for chikungunya, measles, rubella, parvovirus B19 and enterovirus are negative. Zika is not suspected and no tests for Zika are carried out. 7 May 2015 Brazil’s National Reference Laboratory confirms Zika virus is circulating in the country. This is the first report of locally acquired Zika disease in the Americas. WHO/PAHO release an epidemiological alert for possible Zika virus infection in Brazil. The organization recommends that countries establish and maintain Zika virus infection detection and establish clinical management and community engagement strategies to reduce transmission of the virus. 17 July 2015 Brazil reports neurological disorders associated with a history of infection, primarily from the northeastern state of Bahia. Among these reports, forty- nine cases are confirmed as Guillain-Barre syndrome. Of these cases, all but two have a prior history of infection with Zika, chikungunya or dengue. October 2015 Cape Verde confirms the country’s first outbreak of Zika infection. Colombia confirms, through laboratory testing, 156 cases of Zika in 13 municipalities. 30 October 2015 Brazil reports an unusual increase in the number of cases of microcephaly among newborns. November 2015 In the month of November, Suriname, El Salvador, Guatemala, Mexico, Paraguay and the Bolivarian Republic of Venezuela all report laboratory- confirmed cases of locally acquired Zika infection. 6 November 2015 Zika virus is highlighted in WHO’s Weekly Epidemiological Record: “Recent outbreaks of ZIKV infection in different regions of the world underscore the potential for the virus to spread further in the Americas and beyond, wherever the vector is present.”

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11 November 2015 Brazil declares a national public health emergency as cases of suspected microcephaly continue to increase. 15 November 2015 WHO/PAHO issue an epidemiological alert asking countries to report increases of congenital microcephaly and other central nervous system malformations. Brazil reports the detection of Zika in amniotic fluid samples from two pregnant women, whose fetuses are confirmed by ultrasound examinations to have microcephaly. 28 November 2015 Brazil detects virus genome in the blood and tissue samples of a baby with microcephaly and other congenital anomalies; the baby dies within five minutes of birth. Brazil reports three deaths among two adults and a newborn associated with Zika infection. 30 November 2015 WHO/PAHO send a mission to Brazil to review epidemiological information and clinical data, provide input on a case-control study, and assess lab capacity and infrastructure. December 2015 Panama, Honduras, French Guiana, Martinique and the Commonwealth of Puerto Rico all report laboratory-confirmed cases of locally acquired Zika infection. 1 December 2015 WHO/PAHO issue an alert on the association of Zika virus infection with neurological syndrome and congenital malformations in the Americas. The alert includes guidelines for laboratory detection of the virus. January 2016 The Maldives reports that a Finnish national who worked in the country became ill upon his return to Finland, where he tested positive, by PCR, for Zika infection. Guyana, Ecuador, Barbados, the Plurinational State of Bolivia, Haiti, Saint Martin, the Dominican Republic, St. Croix (US Virgin Islands), Nicaragua, Curacao and Jamaica all report laboratory confirmed cases of locally acquired Zika infection. 5January 2015 Researchers report the first diagnosis of intrauterine transmission of the Zika virus in two pregnant women in Brazil whose fetuses are diagnosed with microcephaly, including severe brain abnormalities, by ultrasound. Although tests of blood samples from both women are negative, Zika virus is detected in amniotic fluid. 7January 2016 Ophthalmologists in Brazil report severe ocular malformations in three infants born with microcephaly. 12 January 2016 In collaboration with health officials in Brazil, the United States Centers for Disease Control and Prevention (CDC) release laboratory findings of four microcephaly cases in Brazil (two newborns who died in the first twenty- four hours of life and two miscarriages) that indicate the presence of Zika virus RNA, detected by PCR and by immunohistochemistry of brain tissue

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samples of the two newborns. In addition, placenta of the two fetuses that miscarried during the first twelve weeks of pregnancy test positive by PCR. Clinical and epidemiological investigations in Brazil confirm that all four women presented fever and rash during their pregnancies. The findings are considered the strongest evidence to date of an association between Zika infection and microcephaly. 15January 2016 The Hawaii Department of Health reports a baby with microcephaly in Hawaii, born to a woman who had resided in Brazil early in her pregnancy. 19 January 2016 El Salvador reports an unusual increase in Guilain-Barre syndrome. From 1 December 2015 to 6 January 2016, forty-six cases of the syndrome are reported, including two deaths. 21January 2016 Brazil reports 3,893 suspected cases of microcephaly, including 49 deaths. Of these, 3,381 are under investigation. In 6 cases, Zika virus is detected in samples from newborns or stillbirths. 22 January 2016 Brazil reports that 1,708 cases of Guilain-Barre syndrome have been registered by hospitals between January and November 2015. Most states reporting cases are experiencing simultaneous outbreaks of Zika, chikungunya and dengue. 27 January 2016 French Polynesia reports retrospective data on its Zika outbreak, which coincided with a dengue outbreak. During the outbreak, forty-two cases of Guilain-Barre syndrome were diagnosed—a twenty-fold increase over previous years. All forty-two cases tested positive for Zika and dengue. The investigation concluded that successive dengue and Zika virus infections might be a predisposing factor for developing Guillain-Barre syndrome. February 2016 Samoa, Bonaire, Aruba, Trinidad and Tobago, Saint Maarten, Saint Vincent and the Grenadines, and Argentina all report cases of Zika infection. 1 February 2016 WHO declares that the recent association of Zika infection with clusters of microcephaly and other neurological disorders constitutes a Public Health Emergency of International Concern. 2 February 2016 The United States reports a case of sexual transmission of Zika infection in Texas. Venezuela reports an increase in cases of Guillain-Barre syndrome since the second week of January 2016. By the end of January, 252 GBS cases, associated in time and place with Zika, are reported. 4 February 2016 Brazilian health officials confirm a case of Zika virus infection transmitted by transfused blood from an infected donor. 7 February 2016 Suriname reports an increase in Guillain-Barre syndrome, beginning in 2015, with ten cases of the syndrome positive for Zika.

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10 February 2016 A case report describes severe fetal brain injury associated with Zika virus infection in a woman who became pregnant in Brazil in February 2015. No virus or pathological changes were found in any other organs, suggesting that the virus is strongly neurotropic, which means it preferentially attacks the nervous system. Honduras reports at least thhirty-seven Guilain-Barre syndrome cases in 2016. The report brings the number of countries detecting an increase in GBS associated with Zika virus circulation to eight: French Polynesia, Brazil, El Salvador, the French territory of Martinique, Colombia, Suriname, Venezuela, and Honduras. 26 February 2016 The United States reports two sexually transmitted cases of Zika virus. March 2016 First locally acquired cases are reported from Federated States of Micronesia, Dominica and Cuba. 3 March 2016 A case report published online in the Lancet describes a fifteen-year-old Zika-positive girl in Guadeloupe who developed acute myelitis (inflammation of the spinal cord), which caused severe back pain, numbness and bladder dysfunction. This association further suggests that the Zika virus preferentially affects the nervous system. 4 March 2016 A study in Brazil of eighty-eight pregnant women found that seventy-two women tested positive for Zika virus in their blood and/or urine. Abnormalities of the fetus were detected by ultrasound in twelve Zika- positive women. These findings add to the growing body of evidence linking Zika virus infection to fetal abnormalities. 9 March 2016 Venezuela provides an epidemiological update of its Zika outbreak. A total of 16,942 suspected cases have been reported. Of 801 samples tested, 352 (44 percent) were positive for Zika virus. 10 March 2016 The US reports two GBS cases with confirmed Zika virus infection. The first case, an elderly man with a recent history of travel to El Salvador, died from sudden subarachnoid hemorrhage caused by a ruptured aneurysm. The second case, a male resident of Haiti in his thirties, was diagnosed after he travelled to the US and was treated in hospital. 14–15 March 2016 WHO convenes the Vector Control Advisory Group to review tools to effectively control the Aedes mosquito populations capable of transmitting Zika virus. Two new tools are recommended for pilot deployment. 15 March 2016 Panama reports its first case of GBS with confirmed Zika virus infection in a thirteen-year-old girl. 22 March 2016 WHO expert meetings have identified gaps in knowledge about Zika virus, potentially related complications, effective interventions, and areas of

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needed research and technologies. Dr. Margaret Chan highlights findings and next steps in the fight against Zika. 24 March 2016 Martinique reports its first case of Zika virus infection in a fetus with microcephaly. The findings allow an estimation of the state of pregnancy at which the mother and the fetus became infected. It also shows that a fetus can be PCR-positive for Zika virus months after the mother’s initial infection. 26 March 2016 Chile notifies WHO/PAHO of a confirmed case of sexually transmitted virus. This is the first case acquired in continental Chilean territory where Aedes mosquitoes are not present. 5 April 2016 Vietnam notifies WHO of the first two confirmed cases of locally acquired Zika virus infection. 29 April 2016 French authorities report the detection of local vector-borne transmission of Zika virus on the island of Saint Barthelemy. Authorities from Peru report the first confirmed cases of Zika virus disease. 7 May 2016 One year since Brazil informed WHO/PAHO of its first laboratory- confirmed cases of Zika virus. 8 May 2016 Cabo Verde reports three cases of microcephaly with one case reported by the US CDC after the baby was delivered in the United States. 20 May 2016 Sequencing of the Zika virus in Cabo Verde by Institut Pasteur, Dakar, confirms that the Zika virus circulating in Cabo Verde is the same as the one circulating in the Americas—the Asian type—which was most likely imported from Brazil. 28 May 2016 WHO issues public health advice regarding the Olympic Games, including advice on preventing transmission of Zika virus. Based on the current assessment of Zika virus circulating in almost sixty countries globally and thirty-nine countries in the Americas at the time, WHO decides that cancelling or changing the location of the 2016 Olympics would not significantly alter the international spread of Zika virus. 3 June 2016 Emerging evidence suggests possible complications for babies born to women affected by the Zika virus could go beyond microcephaly to other brain abnormalities. 4 June 2016 In its third meeting, the Emergency Committee on Zika and associated complications announces that the current clusters of Zika and its neurological complications continue to be a PHEIC. 17 June 2016 WHO/PAHO and partners launch a revised Zika Strategic Response Plan, July 2016 to December 2017. The plan places a greater focus on preventing

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and managing the medical complications caused by the Zika virus infection. WHO requests funds to implement the plan. 1 July 2016 Guinea-Bissau in the African Region reports its first cases of mosquito- borne Zika virus transmission. July 2016 WHO publishes a Target Product Profile for Zika vaccines that defines the desired characteristics of optimal vaccines, covering safety, period of protection, shelf life and number of doses required to protect against Zika. 22 July 2016 Fiocruz Institute Pernambuco announces that it has detected Zika virus in Clux quinquefasciatus mosquitoes collected in houses in the city of Recife, Brazil. 27 July 2016 Dr. Peter Salama takes up his new post of executive director of WHO’s new Health Emergencies Programme. 2 August 2016 WHO releases educational videos on Zika risk communication and community engagement. 11 August 2016 Guinea-Bissau reports two cases of microcephaly in the Western region of Gabu.

15–16 August 2016 Brazil and a few other countries are scaling up new WHO-approved vector control tools such as Wolbachia-infected Aedes mosquitoes, genetically modified mosquitoes and traps for surveillance.

25 August 2016 At least thirty entities, including eight public sector institutions, are involved in the development of a Zika vaccine.

26 August 2016 WHO publishes updated interim guidance on the assessment and management of GBS in the context of the Zika virus infection.

29 August 2016 Since February WHO/PAHO has received $14.4 million in direct contributions from twelve donors out of the $122.1 million requested in the Zika Strategic Response Plan (July 2016 to December 2017).

WHO maps social science research for the Zika response. Knowledge, Attitudes and Practice (KAP) surveys and other social science research allows responders to better address people’s needs at the community level, thereby contributing to the overall public health response to Zika virus and associated complications.

30 August 2016 Updated guidance on management of children born to mothers with possible exposure to Zika virus, expanding beyond microcephaly to the range of complications it may cause.

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2015–2016 Since the outbreak, more than fifty-five Zika diagnostic tests have been developed and some have received regulatory approval.

1 September 2016 WHO Director-General Dr. Margaret Chan convenes the fourth meeting of the IHR Emergency Committee on Zika virus and associated complications. Based on its advice, the PHEIC is continued.

6 September 2016 WHO publishes interim guidelines on the prevention of sexual transmission of the Zika virus. The recommendation for both men and women is to practice safer sex or abstinence for a period of six months, whether they show Zika symptoms or not.

7 September 2016 Based on a systematic science literature review (up to 30 May 2016), WHO concludes that the Zika virus infection during pregnancy is a cause of congenital brain abnormalities, including microcephaly, and that the Zika virus is a trigger of GBS.

29 September 2016 Members of the Association of Southeast Asian Nations (ASEAN) identify key areas of the response to Zika: disease surveillance and risk assessment, relevant and timely sharing of data, regional surveillance and response, vector control, diagnostic testing, laboratory networks, risk communication, and sharing knowledge and best practices. Countries in the Western Pacific Region continue to report new cases as seen in Singapore, Philippines, Malaysia and Vietnam. Thailand, in the South-East Asia Region, also reports Zika cases.

1 October 2016 Thailand notifies WHO of two babies born with microcephaly associated with Zika virus, the first such cases in the Southeast Asia Region.

5 October 2016 The WHO/PAHO received $23.9 million in direct contributions from thirteen donors between February and October. This support has been pivotal in enabling a rapid and effective response to Zika and related complications. An additional amount of $3.8 million was allocated to the Zika response from the WHO Contingency Fund for Emergencies.

25 October 2016 WHO launches the Zika Virus Research Agenda. It identifies critical areas of research. The Agenda’s goal is to support the generation of evidence needed to strengthen essential public health guidance and actions to prevent and limit the impact of the Zika virus and its potential implications.

26 October 2016 WHO issued the first quarterly update of the Zika Strategic Response Plan (July 2016 to December 2017).

18 November 2016 WHO’s Dr. Margaret Chan declares the end of PHEIC regarding microcephaly, other neurological disorders and the Zika virus.

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1 February 2017 WHO updates information on vaccine research and development. More than forty Zika vaccine candidates are in the pipeline and five are entering Phase 1 trials.

7 September 2017 Drugmaker Sanofi SA announces the termination of the development of two Zika virus vaccines, citing a decline in new infections and limits on U.S. government funding.

Principal Source: World Health Organisation (WHO) (http://www.who.int/emergencies/zika- virus/ timeline/en/).

47 6 FURTHER READING LIST

6: Further Reading List

Zika Spread/Timeline:

Cao-Lormeau, V.M. et al., ‘Zika Virus, French Polynesia, South Pacific’, Emerging Infectious Diseases, v.20, no.6 (June 2014), pp. 1084-1086.

Chang, C. et al., ‘The Zika Outbreak of the 21st Century’, The Journal of Autoimmunity v.68 (April 2016), pp. 1-13.

Paixão, E.S. et al., ‘History, Epidemiology, and Clinical Manifestation of Zika: A Systemic Review’, The American Journal of Public Health, v.106, no.4 (April 2016), pp. 606-612.

Wikan, N. and D. Smith, ‘Zika Virus: History of a Newly Emerging Arbovirus’, The Lancet Infectious Diseases, v.16, no.7 (July 2016), pp. 119-126.

Zika Pathogenesis:

Faye, O. et al., ‘Molecular Evolution of Zika Virus During its Emergence in the 20th Century’, PLoS Neglected Tropical Diseases, v.8, no.1 (January 2014), pp. 2636.

Klase, Z.A. et al., ‘Zika Fetal Neuropathogenesis: Etiology of a Viral Syndrome’, PLoS Neglected Tropical Diseases, v.10, no. 8 (August 2016), pg. 4877.

Morrison, T.E., and M.S. Diamond, ‘Animal Models of Zika Virus Infection, Pathogenesis, and Immunity’, Journal of Virology, v.91, no.8 (March 2017), p. 9-17.

Musso, D., and D.J. Gubler, ‘Zika Virus’, Clinical Microbiology Review, v.29, no.3 (July 2016), pp. 487-524.

Ramaiah, A.A., ‘Comparative Analysis of Protein Evolution in the Genome of Pre-Epidemic and Epidemic Zika Virus’, Infection, Genetics and Evolution, v.51 (July 2017), pp. 74-85.

Wang, A. et al.. ‘Zika Virus Genome Biology and Molecular Pathogenesis’, Emerging Microbes & Infections, v.6, no. 3 (March 2017), p.13.

Zika Diagnostics:

Landry, M.L. and K. St George, ‘Laboratory Diagnosis of Zika Virus Infection’, Archives of Pathology & Laboratory Medicine, v.141, no.1 (January 2017), pp. 60-67.

48 6 FURTHER READING LIST

Musso, D. et al. ‘Detection of Zika Virus in Saliva’, The Journal of Clinical Virology, v.68 (July 2015), pp.53-55.

Tsakiri, S. et al., ‘Cranial Asymmetry versus Microcephaly: Implications of Practice During the Zika Virus Epidemic’, Texas Medical Association, v.113, no. 8 (August 2017). Wang, Q. et al., ‘Monoclonal Antibodies Against Zika Virus: Therapeutics and their Implications for Vaccine Design’, Journal of Virology, v.91, no.16 (August 2017).

Zika Impact:

Cao-Lormeau, V.M. et al. ‘Guillain-Barré Syndrome Outbreak Associated with Zika Virus Infection in French Polynesia: A Case-Control Study’, The Lancet, v.387, no.10027 (April 2016), pp.1531-1539.

Coelho, A.V.C., and S. Crovella, ‘Microcephaly Prevalence in Infants Born to Zika Virus- Infected Women: A Systemic Review and Meta-Analysis’, International Journal of Molecular Sciences, v.18, no.8 (August 2017), p.1714.

Faizan, M.I. et al. ‘Zika Virus-Induced Microcephaly and its Possible Molecular Mechanism’, Intervirology: The International Journal of Fundamental and Medical Virology, v.59, no.3 (January 2016), pp. 152-158.

Lessler, J. et al. ‘Assessing the Global Threat from Zika Virus’, Science, v.353, no.6300 (August 2016).

Compiled by Zane Grodman.

49 7 ZIKA CONFERENCE APRIL 3, 2017

7: Conference: A Pediatric Menace Wrapped in a Protein: Zika and the Global Health Security Agenda April 3, 2017 Columbia University Medical Center

1. Welcome and Opening Remarks Stephen W. Nicholas, M.D., Senior Associate Dean for Admissions at the College of Physicians and Surgeons (P&S), Columbia University; Marc D. Grodman, M.D., Assistant Professor of Clinical Medicine at Physicians and Surgeons and Member of the Board of Advisors of the Columbia University Medical Center; and Lee Goldman, M.D., Dean of the Faculties of Health Sciences and Medicine and Chief Executive of Columbia University Medical Center. 2. Introduction: The Global Health Security Agenda and its Friends. The Honorable Wilmot James, Ph.D., M.P. (South Africa). 3. Global Zika: What went wrong in Year One and can we avoid a repeat in Year Two? Donald G. McNeil, Jr., New York Times. Discussant: Laura Nogueira da Cruz, Ph.D. 4. What preventing Zika really means? Jennifer Nuzzo, Dr.P.H., Center for Health Security at Johns Hopkins University. Discussants: Madeleine Thompson, Ph.D., Earth Institute, Columbia University, and Dickson Despommier, Ph.D., Emeritus Environmental Health Sciences, Columbia University. 5. The Business of Zika: Implications for Diagnostics and Vaccine Development. Kayvon Modjarrad, M.D. Ph.D., Walter Reed Army Institute of Research. Discussants: Michel De Wilde, Ph.D., Director of VBI Vaccines and Board Member of the Infectious Disease Research Institute (IDRI); P. Roy Vagelos, M.D., Chair: CUMC Board of Advisors, Chair: Regeneron Pharmaceuticals, Inc.; and Marc Grodman, M.D., Assistant Professor, Columbia University. 6. Pediatric Menace: Zika’s clinical management and impact Lawrence Stanberry, M.D. Ph.D., Reuben S. Carpentier Professor and Chair of Pediatrics, Columbia University Medical Center Discussants: Ellen Lee, M.D., New York City Department of Health; Vince Racienello, Ph.D., Higgins Professor of Microbiology and Immunology, Columbia University. 7. Global Health Security Diplomacy. Lawrence Kerr, Ph.D., Office of Global Affairs, Department of Health and Human Services.

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Discussants: Scott Barrett, Ph.D., Lenfest-Earth Institute Professor of Natural Resource Economics, School of International and Public Affairs, Columbia University; Phyllis Hwang, Office of the Special Adviser on the 2030 Agenda for Sustainable Development and Climate Change. 8. The Science and Art of Zika Detection. Ian Lipkin, M.D., John Snow Professor of Epidemiology, Columbia University Medical Center. Discussants: Susan Wong, Ph.D., NYS DOH Wadsworth Center; Yanis Ben Amor, Ph.D., Earth Institute, Columbia University. 9. Looking Ahead at the Global Health Security Agenda: Promise and Reality. Honorable Andrew Weber, Senior Fellow, Belfer Center for Science and International Affairs, John. F. Kennedy School of Government, Harvard University.

Speakers and Discussants: Areas of Interest. Barrett, Scott, is a leading scholar on transnational and global challenges, ranging from climate change to disease eradication. His research focuses on how norms, customary law, resolutions and treaties can be used to promote international cooperation. Ben Amor, Yanis, is currently investigating the critical role of new diagnostics in the control of HIV/AIDS and Tuberculosis in developing countries. He analyzes new, rapid diagnostic tools being investigated and develops ways to allow their implementation in resource-poor settings. Despommier, Dickson, is a microbiologist, an ecologist and emeritus professor of public and environmental health. For 27 years he conducted research on cellular and molecular parasitism. He is the author of the widely acclaimed book, The Vertical Farm (New York, St. Martin’s Press). De Wilde, Michel, started his career in the vaccine industry at GlaxoSmithKline Biologicals and was among the first to apply recombinant DNA technology in industry, contributing to the development of several vaccines at Sanofi Pasteur VaxDesign Corporation. Grodman, Marc, was the Founder, Chairman and CEO of BioReference Laboratories Inc. He has created innovative programs in the areas of cancer, genetics and women’s health. His companies offered the broadest genetics testing of any commercial laboratory worldwide. Hwang, Phyllis, is Senior Legal Officer with the United Nations Office of Legal Affairs and a Member of the Global Ebola Coalition Core Group. James, Wilmot, started his career as a University-based sociologist, led the premier non-governmental organisation that facilitated South Africa’s transition to democracy and most recently served as South Africa’s Shadow Health Minister focusing on the politics of dealing with catastrophic health risks. Kerr, Lawrence, is the Director of the Office Global Health Security at the Department of Health and Human Services. He served as Director for Medical Preparedness Policy at the White House National Security Council Staff and contributed to the development of biodefense policy.

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Lipkin, W. Ian, is an internationally recognized authority on the use of molecular methods for pathogen discovery. He and his team implicated the West Nile virus as the cause of the encephalitis epidemic in New York in 1999 and have discovered or characterized more 500 infectious agents. McNeil Jr., Donald G., is a science and health reporter specializing in plagues and pestilences for the New York Times. He covers the diseases of the world’s poor including AIDS, Ebola, malaria, swine and bird flu, mad cow diseases and SARS. He is the author of Zika: The Emerging Epidemic (W.W.Norton, 2016). Modjarrad, Kayvon, has worked to develop, test and advance vaccine candidates against multiple pathogens of global importance, including Ebola, HIV, RSV and MERS. He assisted the WHO with Ebola response efforts in West Africa. Nicholas, Stephen W., a pediatrician, started in the 1980s to care for HIV-infected children and their families in Harlem and developed the first program to prevent mother-to-child transmission in the Dominican Republic. He is the founder and director of The Program for Global and Population Health (formerly IFAP Global Health Program). Nogueira da Cruz, Laura, a parasitologist, is especially interested in elucidating biological mechanisms in neglected tropical diseases. She is a full-time technologist and member of Brazil’s National Program Coordination for the Control and Prevention of Malaria and diseases transmitted by the Aedes mosquito. Nuzzo, Jennifer, an epidemiologist, focuses on international and domestic disease surveillance, infectious disease diagnostics and disease mitigation strategies. She has worked on issues related to the Affordable Care Act, tuberculosis control, foodborne outbreaks and water security. Lee, Ellen, is with the Division of Disease Control at the New York City Department of Health. Thomson, Madeleine, an entomologist, conducts research on the development of new data, methodologies and tools for improving climate-sensitive health interventions with a focus on vector-born diseases. Her more recent interests include air and water-borne infections, nutrition and disaster related health challenges. Racienello, Vince, established a laboratory at Columbia University in 1982 and worked on the fundamental principles of virus biology. His laboratory identified the poliovirus cell receptor which helped elucidate the means by which the polio infection is initiated. With polio’s decline, he has taken a particular interest in the Zika virus. Stanberry, Lawrence, a pediatrician, is a leading specialist in congenital infections and an authority on viral infections and vaccine development. He is the chief pediatrician at Morgan Stanley Children’s Hospital and Chairman of Physicians and Surgeons’ Department of Pediatrics. Vagelos, P. Roy, a surgeon and comparative biochemist, after spending his initial years at Washington University School of Medicine, devoted more than three decades of his career as a distinguished leader in biomedical research, retiring as Chairman and CEO of Merck & Co., Inc. Wong, Susan, runs a laboratory specializing in the diagnostic serology of human infections, which tests for evidence of infection by bacteria, fungi, parasites and viruses. Zoonoses, infections of animals communicable to humankind, are a special focus of her research. Weber, Andrew, a renowned expert on countering global threats, helped led the U.S. government’s Ebola response efforts in West Africa. He played a key role in the Nunn-Lugar Cooperative Threat Reduction program. He is developing a biosecurity project with NTI at Harvard’s Belfer Center.

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Conference Organizer: The Program for Global and Population Health (Columbia University College of Physicians and Surgeons), formerly known as the IFAP Global Health Program. Lead Sponsor: The Grodman Dual Degree Program Sponsors: Brenthurst Foundation, Johannesburg Columbia University College of Physicians and Surgeon’s Dean’s Office The Program for Global and Population Health (Columbia University College of Physicians and Surgeons) Columbia University Department of Pediatrics Columbia University School of International and Public Affairs Columbia University Earth Institute

Zika Conference: April 3, 2017, CUMC: Back Row (Left to Right): M. deWilde, L. Stanberry, S. Nicholas, W. James, A. Weber, D. McNeil, Jr., I. Lipkin. Front Row (Left to Right): K. Modjarrad, J. Nuzzo, M. Grodman, M. Thomson, L. Nogueira da Cruz, S. Wong

53 Working Group on Global Health Security and Diplomacy at Columbia University Executive Director: Wilmot James Ph.D.

Program for Global and Population Health College of Physicians and Surgeons (P&S) School of International and Public Affairs Co-Director: Madeleine Thomson Ph.D., Earth Institute – International Research Institute on Climate and Society (EI IRI)

Steering Committee Steven Cohen Ph.D., Earth Institute Marc Grodman M.D. P&S, CUMC Board of Advisors Merit Janow Ph.D., Dean, School of International and Public Affairs (SIPA) Terry McGovern J.D., Interim Chair, Population and Family Health, Mailman School of Public Health (MSPH) Stephen Nicholas M.D., P&S and MSPH Lawrence Stanberry M.D., Ph.D., Chairman, Department of Pediatrics, P&S

Working Group Members Helma Al-Marhini Columbia Global Centers (CGC), Douglas Almond SIPA, Scott Barrett SIPA, Yanis Ben Amor Earth Institute (EI), David Brenner P&S, Remi Cousin EI IRI, Katelynn Devinney, NYC Department of Health, Ruth de Vries, Arts and Sciences (A&S), Dannie Dinh EI IRI, Maria Duik-Wasser A&S, Francesco Fiorella EI IRI, John Furlow EI IRI, Lisa Goddard EI IRI, Luis Gravano A&S, Frederick Harris A&S, George Hripcsak P&S, Erik Kantor EI, Colin Kelly EI IRI, Andrew Kruczkiewicz EI IRI, Marc Levy EI, Ian Lipkin MSPH, Terry McGovern MSPH, Kathleen McKeown A&S, Rachel Moresky MSPH, Stephen Morse MSPH, Aisha Owusu EI IRI, Xin Peng CGC, Kiki Pop-Eleches SIPA, Irwin Redlener P&S E, Victoria Rosner, School of General Studies, Jeff Shaman MSPH, Eric Verhoogen, SIPA. View publication stats