Zika-the new global pandemic

After dengue and chikungunya, the Aedes mosquito is delivering a new emergency— Zika. Down To Earth looks into the reasons behind the spread and the threat the virus holds

 
By Vibha Varshney, Kundan Pandey
Last Updated: Monday 29 February 2016 | 15:03:36 PM

Sting Chorus

The world is in the throes of yet another infectious disease outbreak. A report released by the World Health Organization (WHO) on February 5 says that the Zika virus has spread to 33 countries. Brazil, the worst affected, has between 0.5 million to 1.5 million suspected cases.

Zika was first isolated from the rhesus monkey in Uganda’s Zika forest in 1947 and in humans in 1952. But in the next five decades only 15 cases were reported from Africa and Southeast Asia. In 2007, there was a massive spread of this zoonotic disease (infections that emerge in animals and jump to humans) in Yap, an island group in the Western Pacific, and things have been getting worse since then. The virus went to other Pacific Islands before reaching Brazil, from where it spread rapidly to other parts of South America, Central America, Mexico, and the Caribbean. Things came to a head on February 1 when the huge number of cases forced WHO to declare it a Public Health Emergency of International Concern. This is only the fourth time WHO has declared a state of emergency.

The Zika virus, spread by Aedes aegypti and Aedes albopictus mosquitoes, usually causes mild fever, aches, rashes and conjunctivitis. But this time, the incidence of microcephaly (a condition of underdeveloped heads and brain defects) in children born to women who suffered from the infection during pregnancy is much higher. Till January 22, the virus had caused 3,893 suspected cases of microcephaly only in Brazil. This is over 30 times the number of suspected cases reported by the country in any given year since 2010. Seven of the 33 Zika-affected countries have reported a rise in cases of microcephaly. The virus also seems to have a link with Guillain-Barré Syndrome, a progressive neurological disease that causes paralysis.

Brazil has decided to
deploy 220,000 workers
to scour sites for
mosquito breeding (Source: AGÉNCIA BRASíLIA)

The possible links have turned the Zika virus from a mild threat to an alarming one. In the Americas, the virus has spread rapidly mainly because the population has never been exposed to this pathogen and has, therefore, not developed immunity. Only two countries in the Americas—Canada and Chile—are completely free of the virus. Governments of Brazil, Colombia, Jamaica, El Salvador and Venezuela have advised women not to plan pregnancies till the virus is controlled. The US Centers for Disease Control and Prevention too has advised pregnant women not to travel to Brazil and other countries with Zika virus outbreaks. Expert say that in order to understand the full impact of the virus, pregnant women and babies will have to be monitored for a long period.

In light of the correlation of the virus with microcephaly and Guillain-Barré Syndrome, WHO got experts together to study the link. The first meeting of the Emergency Committee was convened on February 1 and though no direct link between the Zika virus and microcephaly was established, the observed correlation was strong enough for the committee to call the outbreak a Public Health Emergency of International Concern. David Heymann, chair of the emergency meeting, explained that while the Zika virus per se was not the health emergency, its suspected link to microcephaly and neurological disorders makes it one.



“A coordinated international response is needed to improve surveillance, the detection of infections, congenital malformations and neurological complications, to intensify the control of mosquito populations, and to expedite the development of diagnostic tests and vaccines to protect people at risk, especially during pregnancy,” said WHO Director General Margaret Chan in the meeting. But despite this, the committee did not see the need to recommend restrictions on travel or trade to prevent the spread of Zika, probably because of the financial implications.

And the financial impact is estimated to be huge.

Geraint Johnes, professor of economics, Lancaster University, in his article in The Conversation, an independent news and commentary website, says that with Brazil’s annual carnival and the Rio Summer Olympics (beginning August 5), Brazil is likely to suffer huge losses in tourism. During these events, the earnings in the tourism sector are as big as 10 per cent of the country’s gross domestic product. Using data collected during the 2003 SARS outbreak in Malaysia, Singapore, Hong Kong and China, where losses in tourism sector were as much as 20 per cent, he said Brazil could lose US $47 billion in the year.

Apart from the financial loss, the virus has engendered a debate that has religious undertones. Most of the affected countries are Roman Catholic where contraception and abortions are looked down upon. Though governments of affected countries, such as Brazil, are mulling proposals to allow abortions, the choices women are faced with are tough.

How ready is India?

The declaration of the emergency by WHO has made India take notice of the threat. On February 2, the Union Ministry of Health and Family Welfare issued guidelines on managing the Zika virus and appointed the National Centre for Disease Control in Delhi as the nodal agency for investigating outbreaks in the country.

The ministry has also issued travel advisories and suggested that people avoid non-essential travel to affected countries. According to the guidelines, pregnant women or women who are planning pregnancy should defer travelling to the affected areas. It suggests that travellers diagnosed with fever within two weeks of return from an affected country should report to the nearest health facility.

The guidelines also call for pregnant women who have travelled to Zika-affected areas to mention their travel during antenatal visits in order to be assessed and monitored appropriately. For enhancing surveillance, the ministry has said that the Integrated Disease Surveillance Programme (IDSP), through its community and hospital-based data gathering mechanism, would keep track of areas where a large number of cases of acute fever are reported. IDSP would also advise its state- and district-level units to look for clustering of cases of microcephaly among newborns and reporting of Guillain-Barré Syndrome. The Maternal and Child Health Division (under National Health Mission) would also advise its field units to look for clustering of cases of microcephaly among newborns.

Though, no case of Zika has been reported in India so far, the virus has a history in the country. In reply to Down To Earth, D T Mourya, director of National Institute of Virology (NIV), Pune, said that prevalence studies on the Zika virus had been carried out as early as in 1952-53 by the institute and showed presence of antibodies in humans in several parts of central and western India. He also claimed that India is prepared to deal with any challenge and NIV has the basic diagnostic tools to detect the virus.

The changing dynamics of the mosquito

Climate change and deforestation are fuelling vector growth

Zika virus might have been first isolated in monkeys but we do not need to worry about them anymore because the virus is already moving human to human. The vectors we need to focus on are Aedes aegypti and Aedes albopictus mosquitoes. These are just two of the 3,500 species of mosquitoes on the earth but their impact on human health is catastrophic. For instance, countries have found it difficult to check the spread of chikungunya and dengue, viruses that first emerged in Africa and are spread by the Aedes species. Between 2004 (when there was a major outbreak of the disease) and 2015, around three million cases of chikungunya were reported across the world. Similarly, 350 million cases of dengue, which is spread by the same vectors, are reported every year, as per a recent report by who. Since Zika is associated with microcephaly and the Guillain-Barré Syndrome, its impact could be more deadly and long lasting. Experts says that half the world’s population is susceptible to the bite of Zika vectors.

“Mosquitoes (at least the ones that are major pests) are very well adapted to cope with tough environments,” says Michael Jeffries, teaching fellow, ecology, Northumbria University, UK. Their young tend to be very vulnerable to predators such as a fish and dragonflies but the species survive because some populations escape, he says. “So we can keep hitting them with chemicals, drainage and biocontrol agents,” says Jeffries, and adds that “it only takes a few populations to survive and they soon bounce back.” To make matters worse, climate change is creating new habitats for the vector, say recent studies. It is even adapting to cold climate. A 2016 study by researchers at the University of Notre Dame, USA, found the Aedes mosquitoes have been present in Washington DC for the past four winters. The findings were published in the American Journal of Tropical Medicine and Hygiene. At the executive board meeting at WHO headquarters, director general Margaret Chan too flagged the issue that the impact of El Nio on global weather patterns this year would increase mosquito populations in many areas. The impact would change precipitation patterns and create warmer conditions, which help the vector to thrive.

Apart from climate change, deforestation and urbanisation have created favourable conditions for the vector. A study under Jonathan Patz from the University of Wisconsin—Madison, USA, found a correlation between the extent of forest destruction and the incidence of malaria vector, Anopheles darlingi. The presence of the malaria vector was found to be more in areas which had undergone extensive deforestation. The study was published in the July 2009 issue of the American Journal of Tropical Medicine and Hygiene.

Studies have also found a link between urbanisation and the population increase of the Aedes albopictus mosquito, which spreads Zika, dengue, chikungunya and yellow fever. Aedes albopictus larval population surveys in Guangzhou, China, found that urban areas had the highest and the rural area had the lowest number of aquatic habitats that tested positive for the larvae. The results, published in November 2014 in PLoS Neglected Tropical Diseases, show that urbanisation significantly increases the potential for disease outbreaks.

Emergence of zoonotic diseases

Viral outbreaks like Zika are indicative of the bigger problem—the emergence of zoonotic diseases, which are now a global threat. Since its inception, WHO has declared Public Health Emergency of International Concern four times, and three of these have been due to zoonotic diseases. More importantly, all the three emergencies have been post 2009.

“Biodiversity hot spots are not just full of rare and cute mammals and birds. Diseases too lurk there. Globalisation is getting them out,” says Jeffries. This is also corroborated by Soumya Swaminathan, Director General, Indian Council of Medical Research. “Many pathogens are crossing into human habitat. There is more intermingling of animals and human beings,” she says.

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Scientists estimate that more than six of every 10 infectious diseases in humans are spread from animals. A 2012 report by the Department for International Development, UK, says that zoonotic diseases are responsible for over 2.7 million deaths and over 2.5 billion cases of human illness every year.

Even the Food and Agriculture Organization (FAO) has recently come up with recommendations regarding infectious animal-borne diseases. FAO suggests that to better assess and manage such outbreaks, policymakers must foster an integrated research programme to map out both what is and what is not known about the transmission dynamics.

Zoonotic diseases are hard to model or predict since they don’t follow an observable pattern. In between randomly occurring epidemics, the disease is contained within unknown reservoirs, where it lies dormant. In an effort to understand the ecological drivers that contribute to the spread of a zoonotic disease, a team led by Colorado State University biologist Daniel Salkeld studied the spread of plague in Prairie dogs, a rodent found in North America. The study found that the disease transmission occurs through a number of pathways, such as interaction with infected rodent groups, inter-group disputes, and interactions between colonies.

The authors compared the data with the recent Ebola outbreaks and said that when searching for a reservoir species for the Ebola virus, most surveys were conducted in the aftermath or during outbreaks. They recommend monitoring of zoonotic diseases within wildlife populations before, during and after outbreaks in humans for developing some sort of predictive capacity. The study was published in Bioscience in January.

The lack of information on such emerging infectious diseases is quite evident in the case of the Zika virus. While we have some information on the role of Aedes mosquitoes in transmitting the disease, we are clueless about other transmission routes. The virus has been traced in human semen and a case of possible person-to-person sexual transmission has also been reported. Transmission of the infection through saliva and urine have also been established. It is also possible that Zika is transmitted through blood. Evidence on mother-to-child transmission of Zika during pregnancy or childbirth is suspected.

To answer some of these questions, WHO is coordinating four kinds of research to understand the virus: case investigation, case control studies, cohort studies and ecological studies. But as microcephaly is a rare event, the studies would be complicated and are likely to take time to yield results, says Heymann.

When asked if the world, at the current level of understanding, is equipped to deal with the outbreaks of zoonotic diseases, Duane J Gubler, Professor and Founding Director of the Signature Research Program in Emerging Infectious Disease of the Duke-NUS Graduate Medical School, Singapore, simply said “no”.

`Prediction will never be perfect'
 
Olivier Restif, epidemiologist at the University of Cambridge, studies the dynamics of infectious diseases. He spoke to Down To Earth on zoonotic diseases. Excerpts

What challenges do researchers in the field of zoonotic diseases face?

It often takes several years of painstaking field research to identify the animal species that acted as the reservoir of a particular disease. In the case of Ebola fever, the virus has been found in apes, bats, rodents and more. In each case, it was only in one or a few animals, making it very hard to decide if these were just anecdotal cases or whether we had found the main source of disease. And when you're dealing with a deadly virus, researchers have to take extreme precautions to protect themselves and the people around them.

What are the roadblocks to the accurate prediction of occurrence, size or frequency of outbreaks?

Once an outbreak has started, we have epidemiological models to help us predict how much they are going to spread and guide interventions. However, just like weather forecast, they are notoriously unreliable in the longer term because we are dealing with very complex systems: it takes just one person getting on a plane to start a pandemic. On a more optimistic note, we are getting much better at estimating risk, so we can direct preventative effort on the regions or the animal species that we have identified as being more "risky", even if we don't know which disease is going to emerge next.

Do you foresee the development of such predictive capabilities in near future?

Major international programmes are already in place to fill the gaps in our knowledge of the chains of transmission that can result in zoonotic outbreaks. This involves the identification of viruses already present in wildlife, and a better understanding of how people may come in contact with those viruses. But prediction will never be perfect, so we must learn from recent outbreaks to improve the response.

Has there been any noticeable change in the funding available in this field after the international attention the Ebola epidemic received last year?

Fortunately, the funding effort in this area had already increased before the latest Ebola outbreak. But emerging diseases, just like climate change or antibiotic resistance, are global threats that require international collaborations, and every country must contribute. Funding for research is important, but we urgently need to see investment in front-line public health infrastructure so that lives can be saved when the next outbreak occurs.

Are we more likely to see mosquito-borne diseases like Zika in future?

These are the diseases which we expect would increase in response to climate change. Although insect vectors have been travelling from tropical to temperate regions onboard ships and planes for many years, they are now more likely to survive and become established in temperate regions as winters become milder.

Prevention is the only solution

Mosquito control requires a coordinated approach

Prevention is the only defence against zoonotic diseases because the world is not prepared to deal with full-blown epidemics spread by mosquitoes. “While many countries have increased their preparedness over the past decade, as the MERS outbreak in South Korea demonstrated, even high-income countries with good health systems can struggle to contain disease outbreaks. This shows certainly a lot more work needs to be done,” says Adam Kamradt-Scott, associate professor at the Centre for International Security Studies, Department of Government and International Relations, University of Sydney.

WHO is supposed to help member states deal with zoonotic diseases. But in July 2015, the Ebola Interim Assessment Panel concluded that the organisation “does not have the capacity or organisational culture to deliver a full emergency public health response”. It decided that a new entity would be created within WHO to address health emergency preparedness and response. The first phase of the roll-out, scheduled from February to May 2016, will include the changes needed to respond to health risks and emergencies at the WHO Headquarters and in the Eastern Mediterranean and African regions. An evaluation of the implementation of the first phase will also be undertaken and the results studied by the World Health Assembly in May 2016. This is good news, considering the increasing number of emerging infectious diseases that the world has to grapple with.

Till the time WHO sets its system in place, individual countries can try to control mosquito population. Checking mosquito population helped the US eliminate mosquito-borne diseases, such as malaria and yellow fever, says Kristen Healy, assistant professor at Louisiana State University, College of Agriculture, and public health expert. Newer tools have been developed which have greatly improved our ability to deal with vector-borne pathogens, she says, and adds that well-funded programmes can help surveillance of vector-borne pathogens, and suggest the most appropriate control strategies. In 2015, Healy and her colleagues published a study in PLoS One on the role of communities in vector control. The study says that once areas with high density of mosquitoes are identified, the government can undertake mosquito control measures and provide personal protection products like nets and repellents to the people. “Having community involvement can help sustain the efforts,” says Healy.

WHO is also looking into other options, such as developing vaccines, but these will take time because of the long-drawn trial process. “Our best strategy at the moment remains having strong local health systems,” says Kamradt-Scott. These can ensure that we not only detect outbreaks faster but also allow ourselves to respond and contain them before they spread, he adds. The long-term strategies would include tackling climate change and reducing greenhouse gas emissions, he concludes.

Additional reporting by Aparajita Singh

Technological fixes
 
Butantan institute in Sao Paulo, Brazil, is the world's leading research centre on the Zika virus. The institute is planning to develop a vaccine but has warned that it may take up to five years. British drugmaker GlaxoSmithKline and French company Sanofi have said they are checking the feasibility of using existing technologies to limit to spread of the virus. There are several other vaccines for viruses of the same family, like dengue, being developed worldwide. Experts say that they may be helpful in containing Zika too.

Hyderabad-based Bharat Biotech Ltd has claimed to have made a vaccine. The Indian Council of Medical Research (ICMR) plans to invite them for more information, says ICMR Director General Soumya Swaminathan. Once the vaccine is approved, its trials on animals and humans will be done.

Some companies, such as the UK-based firm Oxitec Ltd, are also considering the use of genetic modification technologies for vector-control to check the spread of the virus. The concept involves engineering male Aedes aegypti in such a way that the mosquito's offsprings die before reaching maturity. This has already been used commercially in Brazil in 2014. Oxitec ran trials of their genetically modified (GM) mosquitoes in an area in Brazil where Zika is now particularly prevalent. This has now caused a controversy with some saying that the GM mosquitoes are now responsible for spreading the Zika virus. But others refute this."Without both data and a causal explanation, there is no evidence—or even plausible grounds for evidence—that the trials were in any way related to the outbreak," says Andrew D Maynard, Director, Risk Innovation Lab, Arizona State University, USA.

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IEP Resources:

Detection of Autochthonous Zika Virus transmission in Sincelejo, Colombia

Zika virus associated with microcephaly

Detection and sequencing of Zika virus from amniotic fluid of fetuses with microcephaly in Brazil: a case study

Anticipating the international spread of Zika virus from Brazil

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