Taming infection
“As important as developing new drugs and vaccines is the understanding of the dynamics of virus emergence and transmission because they provide us with opportunity for interventions that can minimise risks of emergence and mitigate transmission of these emerging diseases,” says Dr. Joseph Sriyal Malik Peiris, a renowned virologist who has worked on influenza and coronaviruses.
As a boy in Sri Lanka, Dr Peiris was inspired by a biography of microbiologist Louis Pasteur and was determined to work in the field of infectious disease. He went on to study microorganisms that crossed the animal-human interface to cause diseases. While working on mosquito-borne diseases in Sri Lanka, he applied a holistic ‘One Health’ approach to fighting infections such as Japanese encephalitis by investigating outbreaks within their environmental context. Dr. Peiris, who is now a professor of virology at the University of Hong Kong, says he still applies the same concepts to the study of influenza and coronaviruses.
SARS
Hong Kong was the epicenter of Severe Acute Respiratory Syndrome (SARS) in 2003. Dr. Peiris' team in Hong Kong was able to isolate the virus, decode its genetic information and identify it as a novel coronavirus. It took only a few more days for diagnostic tests for the new infection to be developed, and these ultimately contributed to bringing the SARS outbreak under control.
SARS is a story that reads like a detective novel. What vexed Dr. Peiris was the question of the origin of the virus in the first place, and the conditions that led to its spread. All indications were that the virus was transmitted to humans from animals. One of Dr. Peiris’ colleagues, Guan Yi left for China to look at animal markets where wild game is sold for the restaurant trade. The team found that a range of animal species in these markets were infected by a SARS-like virus, indicating that these markets were the mixing place for the emergence of SARS-like viruses, which crossed to humans, giving rise to repeated small outbreaks.
The natural reservoir of the virus was bats, but the virus was entering the market through other animals on sale, bringing it into contact with humans and enabling the crossing over. Although initially limited to smaller outbreaks in different in parts of Guangdong. The virus later spread to Guangzhou, then to Hong Kong and the rest of the world.
“Our lifestyle today makes it easier for viruses to jump from animals to humans and spread globally. It wouldn’t have been possible 50 years ago,” says Dr. Peiris explaining how a man from Guangdong who had stayed in a Hong Kong hotel for a day initially spread the SARS virus among hotel guests from different countries, who in turn took the disease all over the world. “We can be here in Hong Kong today and in some other part of the world tomorrow, making the spread of newer diseases that much faster.”
Influenza
Seasonal influenza is an annual occurrence and leads to many deaths in the elderly and hospitalisations of children. But influenza viruses also circulate in animals. When an animal influenza virus crosses to humans and starts to transmit, it can give rise to a pandemic because the human population has no prior immunity to such a virus.
The swine flu in the 2009 pandemic that emerged in Mexico in April infected more than 35% of all children in Hong Kong by September, illustrating the speed with which pandemics spread worldwide. Dr Peiris says that the world was fortunate that the 2009 pandemic virus was not the most virulent of viruses, because if it had been, there were no vaccines available in time to mitigate the first wave of the pandemic. “We may not be so lucky with future pandemics” he says.
Most animal viruses can’t easily cross to humans. For example, avian influenza viruses don’t have receptors that bind well on to cells present in the human respiratory tract and have a problem adapting to humans. But occasionally, the virus mutates and can thrive in the human host, and may adapt to transmit efficiently between humans. This is what happened in 2009 and we know this will happen again, says Dr Peiris.
His work also addresses influenza viruses, such as avian flu H5N1 which causes severe sickness in humans. He and his colleagues have discovered that the patient’s own immune response can aggravate the lung injury initiated by the virus. They recently found that H5N1 influenza infection impairs the activity of the sodium and chloride pumps that are responsible for clearing out alveolar fluid in lungs and that this is a major contributor to the severe pneumonia that follows. Dr. Pieris’ team is looking at ways to reverse this damage and prevent lung injury.
MERS
In 2012, there was another report of a coronavirus outbreak, this time in Saudi Arabia. Dubbed MERS, the disease has now been reported in 21 countries, and Dr. Peiris’ team worked contributed to defining the role of camels as a source of human infection and in mapping the geographic range of virus activity.
They showed that the virus responsible for MERS was present only in dromedary (one-humped) camels, which are found abundantly all over the Middle East as well as North, West and East Africa. However, human MERS has so far not been reported in African countries. This intrigued Dr. Peiris, and since then his team has been studying MERS coronaviruses isolated in Nigeria, Morocco, Egypt, and Ethiopia and comparing them with the ones causing MERS in Saudi Arabia to understand the discrepancy in its spread.
Prevention and treatment
Despite advances in modern medicine, it still takes time to develop new vaccines when a new outbreak occurs. The added challenge, in the case of influenza, is that each virus strain requires a specific vaccine and there are multiple types and subtypes (from H1 to H16 and N1 to N9), each capable of causing an epidemic.
“New pandemics can spread across the world at a rapid pace but vaccines take much longer to develop. So it is important to understand transmission mechanisms because you can then introduce control measures in an evidence based manner,” Dr. Peiris explained.
Studies have shown that there are common pathways for these zoonotic (animal to human) and pandemic influenza viruses to emerge and spread. Once the virus enters a live poultry market like in Guangdong, for instance, it stays there and never leaves, because new chickens are being introduced every day. However, the lifecycle of the virus can be broken if the market is closed even for a day – hence the concept of “rest days” in poultry markets. Although the viruses may occasionally return, having regular market “rest days” reduces the staying power of the viruses. They found that keeping live poultry markets empty overnight has an even stronger impact in reducing virus persistence. “These are relatively simple measures that can reduce human risk,” says Dr Peiris.
Researchers have found that avian flu like H5N1, H7N9, and H10N8 emerged after viruses from aquatic birds (such as ducks) and chickens mix, giving rise to new “hybrid” viruses. Traditionally, ducks, geese, and chicken are marketed together in common wholesale markets, and when these birds are in close proximity the viruses they carry have ample opportunity to intermingle. Separating the market chains of ducks and geese from that of chickens would significantly reduce the risk of emergence of new influenza viruses that threaten humans.
One of the challenges of influenza vaccines is that the protection they elicit is highly strain specific. Dr. Peiris’ colleague, Leo Poon, is trying to develop a universal influenza vaccine, which will protect against multiple strains and subtypes of influenza viruses. Even if such a vaccine is not as effective as the conventional vaccines, Dr. Peiris says, such universal vaccines have a role as “first responder” vaccines when a new pandemic emerges, and can provide some protection in the first few months until the more specific vaccines are made.
Challenges
Scientists are painfully aware from the SARS and Ebola crises that the identification of a new virus takes time. By the time diagnosis is made and the response mounted, the virus is already out of control.
“We now live in a global village. So, epidemic in one part of the world is a problem for us all,” says Dr Peiris.
The international community has learnt from past outbreaks, and came together to sign up to the International Health Regulations Agreement in 2005 which mandates all countries to develop the capacity to detect, report, and respond to these emerging epidemics.
However, neither local governments nor the international community have invested sufficiently in ensuring the successful compliance and implementation of this agreement, says Dr Peiris. And recent events, for example with Zika, have shown that some things are slow to change.“Once a crisis such as Ebola develops, money and resources are mobilised to respond to it, often too little and too late. And once the crisis is past, forgetfulness sets in until the next epidemic,” explained Dr Peiris, “We should invest so we are all well prepared before the diseases get out of control and also anticipate which organisms might pose a problem next, to be better equipped.”
Additionally, the lesson of the Ebola epidemic is that significant and sustained international investment is needed to bring all countries up to a minimum standard so they can detect and respond rapidly and robustly to emerging infectious diseases.
Apart from prevention measures, new diseases also demand newer technologies to be able to quickly develop treatment and vaccines but Dr. Peiris points out that we cannot rely just on the pharmaceutical industry.
“It is unrealistic to expect the pharmaceutical industry to invest in developing vaccines or drugs that may never be needed – this is financially not viable,” says Dr Peiris, “We need a different funding model to prepare for such unpredictable events.”
But that is precisely why the studies in this field have high significance, so as to be better prepared for the emergence of new diseases.
Dr Peiris is worried about the career opportunities for the next generation of researchers. Infectious disease research in Hong Kong is largely carried out in universities. But funding for academic staff comes on the basis of undergraduate student admission (number of students and courses). This means that some excellent young researchers have no long term career. This is not a model for developing research excellence.
But despite all these adversities, Dr. Peiris hasn’t lost his childhood fascination for the study of viruses and the disease they cause. Scientists need to be one step ahead of mutating microbes, and be able to outwit them because the cost of not doing enough is so serious.
Says Dr. Peiris: “It has been an incredibly rewarding area to work in, and despite the challenges, we have shown that we can make a difference to the community and the world.”
Dr. Peiris was elected a Fellow of the Royal Society of London in 2006. In 2007 he was awarded the Chevalier de la Legion d’Honneur, France and with the Mahathir Science Award, AkademiSains, Malaysia. He was honoured with Silver Bauhinia Star (S.B.S.), Hong Kong SAR in 2008. He was a Croucher Senior Medical Research Fellowship recipient in 2005. He attended St. Anthony’s College in Sri Lanka and later studied medicine at the University of Peradeniya, Sri Lanka. He went to the Sir William Dunn School of Pathology, the University of Oxford, UK for his post-graduate study. He is an investigator of the Centers of Excellence for Influenza Research and Surveillance (CEIRS) program of NIAID, National Institutes of Health, USA. He also co-directs WHO H5 Reference Laboratory at HKU. He’s currently director at the school of Public Health at the University of Hong Kong.
To view Dr Peiris' personal Croucher profile, please click here.