Joseph Malik Peiris was born in Sri Lanka, and graduated from the University of Ceylon in 1972. He then went to the UK, where he completed his DPhil at the University of Oxford in 1981 followed by his MRCPath at the Royal College of Pathologists in 1982. He returned to Sri Lanka and set up the first virology laboratory at the University of Peradeniya. He returned to the UK in 1988, and worked as a consultant virologist at the Royal Victoria Infirmary in Newcastle Upon Tyne.
In 1995, he joined the University of Hong Kong and has been there since. His research interests are diverse, and have included arboviruses, malaria, and human herpes viruses 6 and 7. He became really interested in influenza, and is a leading authority in the diagnosis, and pathogenesis of human and animal influenza viruses. He is currently a Professor in the Departments of Microbiology at the University of Hong Kong, and Honorary Consultant Microbiologist at the Queen Mary Hospital in Hong Kong. His team of investigators are one of the first groups to isolate and identify the severe acute respiratory syndrome (SARS) virus.
TLID: What drew you into the infectious disease arena?
JMP: I was born Sri Lanka and always had a fascination with microbes. The work of Howard Walter Florey and Ernst Boris Chain interested me a great deal even before I went to university. I wanted to do research right from an early age, so when I finished my medical training, I entered academic medicine. In my own medical faculty a teacher who was really inspirational as a researcher was the professor of microbiology at that time called Chubby Arsculeratne. He was doing good research in Sri Lanka with minimal funding and he served as an example of what was possible, even with limited facilities. I joined his department and received my initiation in to microbiology and to research. I subsequently went to the William Dunn School of Pathology, at Oxford for my postgraduate training. In fact I actually ended up doing my DPhil in the same laboratory as Florey and Chain. James Porterfield, an eminent arbovirologist, was my mentor. I also received much intellectual stimulation from Simon Gordon, a cell biologist with a life-time fascination for the macrophage. It is satisfying that 20 years later, I collaborated with Simon again in a recent paper on macrophages and influenza. After further training in the UK, I returned to Sri Lanka where I set up a cell culture and virology laboratory from scratch. For various reasons in 1988, I moved back to the UK to join Dick Madeley, the professor of virology at Newcastle, another major influence on my career. I worked there as a consultant virologist until 1995, when I received an offer to move to Hong Kong, a place that I found very exciting.
TLID: Is infectious diseases seen as a specialty in Hong Kong?
JMP: Infectious disease consultation is largely provided by clinical microbiologists, as is the case in the UK.
TLID: Your research interests are diverse, and include arboviruses, and virus synergism in disease pathogenesis. Can you tell us briefly about you work in these areas?
JMP: Disease pathogenesis has always fascinated me. My doctoral work was to consolidate the concept of antibody mediated enhancement of viral replication, a controversial proposition at that time put forward by Scott Halstead, to explain the pathogenesis of dengue haemorrhagic fever. Antibodies are supposed to kill viruses. What we showed beyond doubt was that in viruses that replicate in macrophages (such as arboviruses), antibodies actually enhance viral replication, This has susbequently been shown for a number of other viruses including HIV. On my return to Sri Lanka, I continued to work on arbovirus epidemiology. But when I moved back to Newcastle, arboviruses had to be left behind. There are no medically important arboviruses up there in the north of England. So I changed lanes completely, and started to work on some recently discovered herpesviruses, human herpesvirus (HHV) 6 and HHV7, trying to study the role of these viruses in transplant patients. Something we observed was that in transplant patients where cytomegalovirus (CMV) is a major problem, the reactivation of HHV7 appeared to enhance the progression of CMV infection. So we proposed that there may be synergism between those two viruses.
TLID: What have been the major achievements in your career so far?
JMP: One of the greatest highlights of my career was the setting up of a virology laboratory in Sri Lanka on my return there in 1982. We did some very useful research on arboviruses, and in defining antigens of Plasmodium vivax that might be potential vaccine candidates. I suppose the other memorable period was coping with the H5N1 “bird flu” incident in Hong Kong in 1997. In fact it was a very similar situation to what we have now with the severe acute respiratory syndrome (SARS)—a highly pressurised investigation, where we were trying to cope with a potential outbreak that was publicly visible and of huge public concern. After that, I was drawn into working with influenza. I began working on animal influenza viruses that may pose a threat to humans—the animal-human interface of influenza. I was intrigued as to why these H5N1 viruses in 1997 were so lethal to human beings. The mortality was 33% which was unheard of for conventional human flu viruses. Recent work from our group suggests a possible explanation. These viruses are potent inducers of proinflammatory cytokines, which may contribute to the unusual severity of the H5N1 disease in human beings (Lancet 2002; 360: 1831–38).
Then earlier this year in February, we heard about an outbreak of atypical pneumonia in the Guangdong province of southern China. In collaboration with colleagues in the hospital authority, and the Department of Health of Hong Kong, we stepped up surveillance of severe atypical pneumonia in Hong Kong because we were concerned that it might come to Hong Kong. We picked something up in early February that happened to be H5N1 influenza again, in a family returning from China to Hong Kong. Two members of that family had H5N1 disease. We thought that the outbreak of pneumonia was probably H5N1 now adapted for human transmission. To some extent that proved to be a red herring because we spent some time trying to pick up further cases along the same line. But it became quite apparent that was not the case. In the meantime some of these unusual pneumonia patients did appear in Hong Kong. They seemed to be in clusters, affecting health care professionals who were in close contact to the infection. It subsequently became apparent that it was not H5N1, nor was it any of the known viruses or bacteria, and casting the net wider using a number of different angles we managed to grow the virus in two patients. It was subsequently identified as a coronovirus independently by ourselves, and the laboratories of the US Centres for Disease Control and Prevention (CDC).
TLID: You have begun studies to look at the disease burden of influenza in Hong Kong, the first such data from a tropical region. What conclusions have you been able to draw?
JMP: Influenza is not really regarded as a big problem in Hong Kong or for that matter in the tropical world in general, such as in Singapore, or China. I believe the reason for this is the lack of a sharp seasonality of influenza circulation in this part of the world. In the UK you have a very sharp winter peak, most of the influenza hits you within about 6 weeks so you really are forced to take notice of it. In Hong Kong, Singapore, and places like that, the virus activity is far more diffuse, it is not so focused. And therefore the clinical effects are not so obvious. In fact people don't actually go round trying to diagnose influenza in people with pneumonia. Together with my paediatric colleagues, we have demonstrated that influenza is really a major problem in childhood hospitalisation (N Engl J Med 2002; 347: 2097–2103), and that influenza is not a trivial disease.
TLID: What kind of surveillance systems and tools are used to monitor infectious diseases in Hong Kong?
JMP: Surveillance of infections in Hong Kong is pretty good. Influenza surveillance in particular is very comprehensive. The human surveillance is done by the Department of Health's virus laboratory. In addition, we work with the Agriculture Department to maintain surveillance in animals, something that is not widely done in many parts of the world. I suppose it is ironic that sometimes when you do intensive surveillance and pick something up, people then think Hong Kong is a terrible place to live. But actually neither H5N1 flu that happened recently, or the recent SARS outbreak really began in Hong Kong. It was just that they were first being picked up in Hong Kong. So the thing is that if you don't look you will not find. Hong Kong—I speak for the whole system here—is looking hard and looking well. So, to quote my predecessor, Ken Shortridge, Hong Kong is really a sentinel post for the region.
TLID: You are involved in the investigation of the worldwide SARS outbreak. At the time of going to press, the primary causative agent looks like it is a coronavirus but other microbes such as metapneumovirus, paramyxovirus, and Chlamydia pneumoniae have also been identified. What from your experience have been the challenges to isolate and identify the pathogen? And do you think the causative agent might be a combination of pathogens?
JMP: The agent that is associated with SARS doesn't grow in the usual cells used to investigate respiratory viral infections. So it was just not picked up in the initial trawl. But on casting the net wider, we were able to grow the virus and to identify it as a coronavirus. Independently, CDC came to the same conclusion. This appears to be a novel coronavirus. But human coronaviruses do not cause disease resembling the magnitude of SARS. From the partial genetic information we have, this is not a human coronavirus and not like any known animal coronavirus either. While we think that this coronavirus-like agent is the primary agent in SARS pathogenesis, there may be a role for other pathogens to act as co-factors. This is something that needs to be investigated further.
TLID: There has been much speculation as to the origins of the SARS outbreak. Is there any direct evidence that it is linked to the epidemic of atypical pneumonia that occurred in the Guangdong province in southern China in early February?
JMP: Clinically, there seem to be many similarities between the reported outbreak in Guangdong and the susbsequent outbreak in Hong Kong.
TLID: What lessons can be learnt from the SARS outbreak
JMP: The fact is that these microbes keep on surprising us, especially in this part of the world. We have had the Nipah outbreak in Malaysia, the enterovirus 71 outbreak in Taiwan, and the H5N1 in Hong Kong. We have had three major problems and this is the fourth. And if you look at the USA, they have had West Nile and the UK has had bovine spongiform encephalopathy. Microbes are far from conquered. We have done a fantastic job controlling smallpox, polio, and other diseases. But at the same time there are many other changes that are going on in the way we live our lives which allows some of these emerging pathogens to hit us with a vengeance. I am sure this type of emerging organism has been happening right through history. But in the past if the SARS virus had popped up somewhere, it might have caused disease in a few people in a village, or killed a few people in a village, and that would of been it; it would have been contained. Now of course, once an outbreak starts in one place modern living means it spreads, and SARS is a perfect example of that.
TLID: Of your many and diverse research interests, what would you most like to find the answer to?
JMP: What I am most interested in is disease pathogenesis. Even in my early work on antibody enhancement in infections with arbovirus I was trying to understand how microbes cause disease. Although that might seem a fairly simple straight forward question, actually it is not; it is far more complicated than just a microbe killing a cell. It is a very complex interaction between the host immune response and the pathogen. Of course H5N1 has fascinated me and we are still working on that. And then there's the new SARS agent, which seems to not be just a case of the virus damaging the host, but very possibly an interaction between the host and the virus that could be an immunological component of the disease. In other words, the severity of the disease may be aggravated by the host's immune system.