Zika's Rapid Rise and the Limp Global Response Reveal Dire Global Health Challenges

How much of a game do we want to play with something so dangerous to humanity?

With cases rising in Florida, Singapore, Vietnam and Trinidad and Tobago, the Zika virus pandemic is raising public concern in regions across the globe, including the U.S., where about 80 percent of Americans are aware of it but only 40 percent understand how it is actually transmitted. This raises a host of questions not only about the clinical and epidemiological scope of the outbreak, but also about the ability of citizens, public health authorities and politicians at all levels to adequately deal with it. 

So far, the response has been slow and the challenge remains serious and unpredictable. We need to understand an organism that the director of the Centers for Disease Control’s division of vector-borne diseases called “the most complicated issue CDC has ever faced.”

Zika is linked to the mosquito vector, which received a new lease on life about 5,000 years ago when water storage enabled mosquitos to live closer to people. Our knowledge of Zika starts in 1947 in Uganda when the virus was first cultured from a monkey. Surprisingly there were only 14 human cases identified until 2007 when the virus unexpectedly started rapidly moving through Southeast Asia and the Pacific, stopping in Indonesia, Micronesia, French Polynesia, the Cook Islands, New Caledonia and Easter Island before reaching northeastern Brazil and eventually every country in South America.

The most complicated issue CDC has ever faced. Dr. Lyle Petersen, director of the Centers for Disease Control’s division of vector-borne diseases

From Brazil it headed north to Central America and the southern United States. Puerto Rico was especially hard hit ― 25 percent of the population is estimated to have been infected. It quickly became apparent that there are two distinct strains: the Asian strain that produces complications like microcephaly in the Americas, and the African strain, which is possibly without significant complications and is seen mostly in Southeast Asia. 

In mid-2015, global concerns finally heated up. The Pan American Health Organization issued its first alert for Brazil on May 7. But the CDC activated its emergency operations center only a full eight months later, at the end of January 2016. The World Health Organization declared a “public health emergency of international concern” on February 1. PHEICs have only ever been issued for Influenza H1N1, polio and Ebola. President Obama asked Congress for $1.8 billion to fight Zika a week later, setting off protracted political haggling. The House and the Senate finally passed a $1.1 billion bill to fund the government and the federal response to Zika on Sept. 28, a whopping 233 days after the first request was made.

Why is Zika so different? It boils down to its unusual transmission and it’s complications. The transmission of Zika virus is primarily by the bite of the Aedes mosquito which, in the Western Hemisphere, is found as far north as Canada. We have also discovered that transmission is possible via semen, vaginal secretions, blood transfusion and maybe from person to person. Unlike influenza and colds, Zika is not transmissible by coughing, touching or sneezing.

An Aedes aegypti mosquito known to carry the Zika virus is photographed through a microscope at the Fiocruz institute in Reci
An Aedes aegypti mosquito known to carry the Zika virus is photographed through a microscope at the Fiocruz institute in Recife, Brazil, on Jan. 27.

There are very unusual and severe complications from the virus attacking neural progenitor (originating) cells. This causes a variety of deformities in newborns including but not limited to microcephaly. It’s also been established that infected adults have about a 500 percent higher rate of Guillain-Barre syndrome, a serious progressive neuromuscular impairment. More subtle neurological complications that may not be apparent for years are suspected but not fully studied. From mice experiments we know that men might experience low testosterone levels and low sperm counts which could affect fertility by killing cells located at the barrier of the bloodstream and the testes.

We now know that there are neonatal neurodevelopment effects besides microcephaly that are all now called “Congenital Zika Syndrome,” which covers a wider scope of fetal brain disruptions. The Zika virus is attracted to all neural and glia (supporting) brain cells, specifically radial glia cells. Zika has a stunning affinity for these cells, the progenitor cells of the developing fetal brain. These are the cells that give rise to nerve cells and other proliferating brain cells that serve as the scaffolding of the developing embryonic brain, enabling the migration of nerve cells to other parts of the brain during embryonic development. If you infect and lose these radial glial cells, the number of nerve cells is reduced and the supporting lattice structure is lost.

For Zika to take hold in a community, a number of factors have to fit into place. Infected people must enter the area. An Aedes mosquito then has to bite the infected person when the virus is still in the person’s blood, typically during the first week of infection. All of South and Central America and about half the U.S. has these mosquitos. The infected mosquito then has to live long enough for the virus to multiply, and it has to bite another person. The cycle has to continue over and over again, along with sexual transmission, which is estimated to contribute only about 3 percent additional cases. Aedes mosquitos only have a range of up to 800 meters, so outbreaks separated by just a few miles are not caused by the same mosquitos. The biting Aedes mosquitos, all female, only live about 30 days. Once infected they stay infected for life, but their eggs can survive for up to eight months.

Why are authorities so reluctant to act quickly?

Why is there a sudden rise in cases? Inadequate public health response has been blamed for the rapid spread. But the Zika spread can’t be blamed entirely on inadequate public health measures, as seen in northeastern Brazil and Central America. Singapore and the U.S., with excellent public health systems, have not yet been able to fully contain transmission. Thus, other factors ― like host immunity, the genetics of the virus, a changing environment and mosquito adaptation ― might also play roles. The extremely high incidence of microcephaly, specifically in northeastern Brazil, has not been explained. 

As cases keep increasing in the Americas and Southeast Asia, different strains of Zika virus have to be evaluated as more than merely routine re-emerging viral diseases. Emerging and re-emerging infectious diseases come along all the time. For example, varying strains of influenza occur every year and vary in both contagiousness and transmissibility. One worry is a repeat of the Spanish flu pandemic of 1918-1919 that resulted in approximately 50 million deaths worldwide. 

Ebola sparked worldwide interest several years ago and eventually gave us about 25,000 cases, with a very high mortality in three countries in West Africa. We learned about unusual transmission via semen that had only been seen in the past with the related Marburg virus. Like Ebola, Zika is also transmitted by semen and, also like Ebola, has several strains with differing effects. As today with Zika, the slow international response to Ebola and national, misguided, self-serving, uneducated priorities were very apparent. The MERS and SARS viruses have had limited geographic distribution ― primarily in the Middle East and Korea for MERS and Southeast Asia and Canada for SARS ― but they carry a high mortality rate. And there is MERS concern every year at the Hajj pilgrimage when millions of Muslims converge on Mecca. Another concern is with so-called “super-spreaders” ― individuals that for unknown reasons spread the MERS and SARS viruses like wildfire before they are detected and quarantined. 

A health ministry worker fumigates a house to kill mosquitoes in Managua, Nicaragua, on Oct. 27.
A health ministry worker fumigates a house to kill mosquitoes in Managua, Nicaragua, on Oct. 27.

All this presents many public policy challenges. In addition to the routine clinical and public health considerations given to all harmful emerging infections, for Zika there are socioeconomic, psychological and public policy issues that might actually predominate since 80 percent of those infected are asymptomatic. Policy issues such as abortion, birth control, changing prior inattention to the science of vector-borne infections, travel and tourism implications, constantly changing federal guidelines, confusion with related Chikungunya and dengue carried by the same mosquitos, the possible augmenting role of sentinel events such as the Olympics and the Hajj and appropriate timely funding from local, regional, national and international sources ― all this need to be addressed in a much more interconnected world.

But why are authorities so reluctant to act quickly? In the U.S., this was due partly to a misunderstanding by policy-makers of the severity of the problem and attempts at political maneuvering. Other countries don’t want to disrupt tourism or abortion laws. Politics and science too often don’t mix, especially in a background of a general mistrust of science and leadership.

What can and should be done? Just as we’ve done with antiretroviral medications for HIV, we need to speed up the process of drug and vaccine development. But with the decline in Ebola cases there was also a decline in vaccine manufacturer interest in investing hundreds of millions of dollars in a new product. Routine aerial spraying may not be effective since the mosquitos live in close proximity to homes and may be developing immunity to naled, the pesticide most commonly used. Naled is already banned in Europe and Puerto Rico. Naled aerial spraying disperses an ultra-low volume of less than 1 ounce per acre in tiny micron-sized droplets that are designed to get underneath bushes and leaves, where it breaks down quickly in the environment. After initial aerial spraying with naled, officials saw an encouraging drop in mosquito populations, but levels bounced back rapidly. Better education of the public, politicians, even scientists and public health officials is urgently needed. Surveillance systems and registries need to be set up and expanded not only to monitor human cases, but also to monitor the mosquitos and the clinical complications.

How much of a game do we want to play with something so dangerous to humanity?

In addition to more innovative countermeasures, we need better spraying techniques and enhanced surveillance. For example, officials saw mosquito levels plummet and remain low after they followed naled spraying with additional spraying of Bacillus thuringiensis israelensis, a bacterial strategy that attacks both adult mosquitoes and their larvae. Zika will need enhanced surveillance techniques utilizing, for example, innovative predictive modeling with interconnecting temperature profiles, air travel routes, Google trends and social media databases. Social networking was effective in the early tracking of H1N1 influenza during the 2009 outbreak, for example.

We need to study the implications of genetic manipulation and engineering like introducing sterile male mosquitos. Only more research will enable us to understand the profound long-term neurological consequences like microcephaly, or more subtle ones not yet clinically identified. We need to understand the role of “antibody-dependent enhancement,” where a prior infection with dengue, for example, might exacerbate Zika infection or its complications. Prediction markets such as the Iowa Electronic Market and PredictIt at the Victoria University in New Zealand have been successfully utilized in areas ranging from political elections to influenza spread, but are limited in the U.S. by the Gaming Enforcement Act. The complex interactive roles of human immunity, the virus, the mosquito and the changing environment all need much more study.

An emerging disease is only a flight and an incubation period away. Human populations are encroaching more and more in habitats where animals spread these viruses. Poverty gets hit hard. Social norms such as attitudes about abortion may be questioned. Political, social or economic decisions may predominate over scientific ones. The increasing population density in many third-world cities may cause an illness to spread more rapidly (Ebola), as does global travel (SARS and MERS) or natural disasters (cholera in Haiti). And climate change brings disease-spreading insects to new places (West Nile virus and malaria).

Cleane Stephanie with Maria Eduarda, only 11 months old, who has microcephaly caused by Zika virus. Olinda, Brazil,
Cleane Stephanie with Maria Eduarda, only 11 months old, who has microcephaly caused by Zika virus. Olinda, Brazil, Oct. 24.

How much of a game do we want to play with something so dangerous to humanity? There are too many unanswered clinical questions, many bizarre complications, an odd complex transmission pattern, delayed funding by a U.S. Congress playing political games and a very slow international response by a poorly funded WHO emergency response team. There is a need to re-evaluate many social questions, like abortion.

Ever since the time of Hippocrates, the practice of medicine has been improving. But public health has only been studied for a few hundred years. Even with the accomplishments of giants like Paul Farmer and D.A. Henderson, we’re only at the very beginning of our understanding of what to do with very complex global health threats such as Zika, Ebola, MERS and influenza. But we have better and better tools to accomplish this. And with each encounter hopefully we learn more and more about handling the next big one.

As Albert Einstein once said, “Out yonder there was this huge world, which exists independently of us human beings and which stands before us like a great, eternal riddle, at least partially accessible to our inspection and thinking.”

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