Professionals talk about RSV
Dr. Natalie Mazur on strategies for preventing RSV
Dr. Natalie Mazur has been involved in RSV research for 8 years. Under the supervision of prof. Louis Bont she obtained her PhD, which was focused on, among others, global mortality due to RSV, and the development of vaccines against this virus. Currently s
he is working as postdoctoral researcher, and drawing attention to the importance of making vaccines accessible in the developing world. In addition, she is a paediatric resident in training. She has a passion for global health and the movement of scientific discoveries into clinical applications. We spoke with Natalie about the spreading of RSV and preventive measures that can help to prevent a child from getting a (severe) RSV infection.
Hands are the most important culprit
“RSV is spread through contact with droplets, either through direct contact when there is physical contact with an infected person, for example by kissing someone on the mouth, or indirectly by transmission of infected droplets and snot from your hands to your eyes, nose or mouth. Therefore, hands play a very important role in the transmission of RSV. It depends on the type of surface how long RSV survives: RSV can survive for approximately 7 hours on hard surfaces such as light switches, tables, door knobs and toys. On soft surfaces, such as skin, clothes and tissues, it typically lives for a shorter time, approximately one hour. RSV is spread from person to person. There is a virus that is closely related to RSV, the so-called bovine RSV which can be found in you
ng cows, but as far as we know, this virus cannot infect humans like COVID-19, which can be transferred from minks to people.”
Handwashing and cleaning
“Washing your hands correctly and regularly is the key in RSV prevention. If you are not able to wash your hands, it is important to avoid touching your eyes, nose or mouth. Furthermore, it is best to avoid cuddles and kisses between your baby and people who are having a cold. It can be helpful to regularly disinfect toys and throw away used nose wipes as soon as possible. How often you should clean toys depends on how many strangers touch them, or on if there is snot on them. Toys that are touched by a lot of different children should be cleaned more regularly than those that are only used by your own child.
The most important places to disinfect are, in addition to your hands, hard surfaces that are touched often. RSV lives longest on these surfaces. Hard surfaces that are frequently touched by adults are light switches, pens and door knobs. For children, you should think of toys, bed frames and highchairs.”
Receiving visitors and nurseries
Almost every child will be infected with RSV before the age of 2. After the first infection, you can recurrently get infected. The first 6 months after birth, the risk of developing pneumonia or need for hospital admission is highest. After this age, symptoms of infection are more often less severe, for instance a cold or ear infection. There is no clear cut-off age after which visitors safely hold and touch your baby. Rather, it is most important to ask visitors to wash their hands before touching your baby, and to keep people who are having a cold away until they are not sick anymore.
Certain groups of children are at higher risk of severe disease when they get infected with RSV. These are for instance premature babies or babies with Down’s Syndrome. Nevertheless, the measures to prevent these children from getting RSV are the same as for other children, although it is more important to avoid children in these risk groups from getting RSV.
Parents should decide for their own when they want to take their child to nursery. The risk of getting RSV will be higher, because your child will be in contact with many other children and will therefore more often meet children who have a cold. However, nowadays this risk may be lower, as a lot of children must stay at home when they have a cold. In the first 6 months after birth, the risk of severe RSV infection is highest. A lot of children will go to nursery when they are 3-4 months old, so a risk for severe RSV infection remains between 4-6 months of age. It is up to the parents whether they feel it’s best to keep their child at home for a longer period of time. A nursery is important for the development of a child and the ability to combine work with a family.
Siblings
“Children with siblings are at higher risk of getting RSV, because siblings can be exposed to RSV in school or child-care centers and transmit the virus to other members of the family. The most important measure to prevent siblings from transmitting the virus to you baby is by letting them wash their hands well. Furthermore, it can be helpful to avoid siblings from touching each other’s toys when they have a cold.”
Is exposure to viruses beneficial?
“By being exposed to viruses, children build up their immune system. However, children aged younger than 6 months are most vulnerable for severe RSV infection. Ideally, a child is exposed to the virus after this age, so they can build up immunity against the virus. This would change when a vaccine will become available to protect young children from RSV.
RSV infection is harmless for pregnant women and their unborn babies. Rather, when women in the second or third trimester of their pregnancy are infected with RSV, antibodies will pass through to the unborn baby, which provides protection during the first couple of weeks after birth. It is extremely rare for a pregnant woman to become severely ill after RSV infection. Therefore, you could say that infection during pregnancy has more pros than cons.
Breastfeeding protects children against severe airway infections, including RSV. It has been shown that children who are on formula are at higher risk of getting severe airway infections. Especially in the critical period of the first 6 months after birth breastfeeding is important. However, this is a recommendation, and of course dependent of the feasibility to breastfeed.”
Smoking
“Research has shown that if someone smokes in a child’s environment , the risk of hospital admission due to RSV infection increases, and that there is a higher risk of a severe illness. The exact mechanism is unclear, but it could be due to inflammation of the airways, that could make the lungs more susceptible for RSV infection. Mothers who smoke during pregnancy are at increased risk of having a child with a severe RSV infection, because smoking affects development of the lungs.”
Arthur Stigt
Since November 2018, Arthur van Stigt (Medical Doctor and PhD-candidate), has been working in the research groups of Professor Louis Bont, Dr. Jeanette Leusen and Dr. Belinda van ‘t Land. During his Master’s in Medicine, Arthur started at the PRIMA study. PRIMA is an acronym for ‘Protecting against Respiratory Infections through human Milk Analysis’. The aim of this study is to look into the substances in human breast milk that could potentially protect against respiratory infections.
‘It is known that human breast milk protects very well against respiratory infections. Children that have been breastfed get sick less frequently and are less frequently hospitalised because of respiratory infections. Currently, there are various assumptions about what the cause of this. Presumably, many different substances present in breast milk (like antibodies and sugar chains) play a role. What we do not know, is how they function amongst each other and what substances are the most important in protecting children against respiratory infections. Does a combination of these substances play a dominant role? And what makes that combination so powerful? Currently, we do not have the answers to these questions. That is why this study was started.’
Recent developments
‘A new part of our research is nutrition. If wediscover which specific substances protect against respiratory infections, we could try to adjust the breast milk on this aspect. For example, by suggesting a certain diet or certain nutrients to breastfeeding mothers. If mothers do not breastfeed but give formula, we could try to optimise the formula.’
The study in practice
‘For the PRIMA study breast milk is collected from participating mothers and brought to University Medical Centre Utrecht (UMCU). These mothers are asked to respond to questions about how often their child gets sick and what kind of nutrition their child receives. Currently, we have included 300 children in this study. In the future we would like to include a 1000 of children. This group will eventually be divided into two study groups: one group will consist of children that have hardly ever been sick, the other group will consist of children who were frequently or severely sick. The first step is to compare the milk that these two different groups have received. The milk is then examined to see what exact antibodies and sugar chains are present. In this way, a favourable profile of breast can be determined. In the laboratory, we will try to identify and extract a substance with protective properties out of the breastmilk. Due to the current pandemic we have some delay in our study, but fortunately we were able to catch up again.
Relation to RSV
‘If a favourable substance can successfully be extracted out of the breast milk, it could also be determined if this substance protects against Respiratory Syncytial Virus (RSV), or if it makes an RSV infection less severe. Currently, we think a sugar chain (which is also known as an oligosacharide) or an antibody, or a combination of these two, protects against RSV. It is not certain yet which one of these is responsible for this effect, but that is what we hope to find out with our research.’
Do you want to read more about the PRIMA study, or are you interested in participating in this study? See https://prima.hetwkz.nl/ for more information.
Dr Simon Drysdale
Paediatric infectious diseases consultant at St George’s University Hospital NHS Foundation Trust and St George’s, University of London, London, UK.
‘My interest in RSV began when I was offered the opportunity to do a PhD project on the impact of RSV in preterm babies when I was a junior doctor in training. An important reason for me to get involved in this project was the fact that RSV is such a massive problem for children. After obtaining my PhD, I did a clinical training in paediatric infectious diseases in London and in Oxford. Three years ago I started at my current position as a paediatric infectious diseases consultant at St. George’s Hospital in London. During my career I have done a variety of work on RSV, ranging from lab-based studies to surveillance projects and interventional studies. I am also involved in RESCEU.’
‘During the nearly 20 years that I have been involved in paediatrics, I have seen hundreds of children with RSV infection. Many children stick in your mind for some reason. I can recall families where several members were affected by the virus: either twins at the same time or one child followed by another the next year. Parents consenting for their babies to be included in clinical trials also make a big impact on me. In particular those involved in interventional studies, when a new medicine or vaccine is being tested. It takes a leap of faith for parents to let their child participate in such studies and I have the utmost respect for those parents.’
‘Regarding RSV, I think it is most important for (future) parents to be aware of RSV and know how to avoid passing the virus on from one individual to another. In the current era of the COVID pandemic we have shown that if you wash your hands, wear a mask and cover your face, you can essentially almost wipe out RSV. While vaccines and treatments will inevitably have a role, these simple actions can significantly help to avoid spread of the virus and reduce infections.’
Koos Korsten
Medical Doctor and epidemiologist
For medical doctor and epidemiologist Koos Korsten (31), RSV (Respiratory Syncytial Virus) has played an important role throughout the past 10 years of his career. He has been working under supervision of Professor Louis Bont at the department of Paediatric Infectious Diseases at Wilhelmina Children’s Hospital since he was in his second year as a medical student. He also did his research internship at this department. After finishing his medical studies, Koos continued as a PhD student in the research group of Professor Bont. During this period, he conducted two clinical studies of the RESCEU project: one on RSV in children and another on RSV in older adults. This April, he will obtain his doctorate for the latter.
The reason for a RSV study in the elderly
‘It is known that people go through multiple RSV infections in life. Severe RSV infection usually affects small children. The reason for this is that young children’s airways are still small, making them more prone for airway obstruction. However, reinfection can also cause complications later in life, when the immune system becomes more vulnerable, for example. Many complications of RSV infection in older adults are similar to those of Influenza. The infection can cause pneumonia, which can even be fatal in some cases. As the elderly are rarely being tested for RSV, little is known about the potential impact of RSV infection in this age group, especially among general practitioners. The aim of this study was to learn more about the burden of RSV disease in this part of the population.’
Study set-up
‘In this study we studied the effects of RSV infection in adults aged 60 years and older who are still living at home. We investigated how often respiratory symptoms were caused by RSV and how ill these patients became. And if these patients with RSV became ill, how many of them had to be hospitalized? In total, 1040 people from three countries (Belgium, The Netherlands and the UK) were included in this study. About two-thirds of this group became ill with respiratory symptoms. In about 60 people of this group the respiratory symptoms were caused by an infection with RSV. About one-third of these 60 people went to see their General Practitioner, but none of these patients developed pneumonia and nobody had to be admitted to the hospital. The majority of RSV infections in the elderly, with the exception of these patients who required secondary care, therefore appears to be mild. In other studies, however, it was found that elderly people with heart failure, COPD or immune deficiencies, as well as people living in nursing homes have a higher risk of developing a severe RSV infection.’
Relation to RSV in children
‘Another aim of the study was to investigate which age group should be vaccinated first when a vaccine becomes available. We also looked at how many of the respiratory infections in older adults were caused by children. Based on this, we estimate that roughly 10% of all respiratory infections in the elderly can be explained by their contacts with children under the age of 5. So, one could argue that when the burden of RSV among children is being reduced by a vaccine, elderly people would also benefit from it and be indirectly protected against the virus.’
Steps for the future
‘A vaccine against severe RSV infection is on the way. Once children are protected against RSV, it will be good to reassess the disease burden of RSV-infections in older adults to see the effects on this age group.’
Prof. Federico Martinón-Torres
Professor Federico Martinón-Torres is currently head of Pediatrics and Director of Translational Pediatrics and Infectious Diseases at the Hospital Clínico Universitario de Santiago in Spain, Academic of the Royal Academy of Medicine and Surgery of Galicia, and Associate professor in Pediatrics. What initially raised his interest in RSV infections, was the fact that these were so common among children, while the treatment options were very scarce. He obtained his PhD on the use of heliox in infants with bronchiolitis and got involved in many more research topics on RSV. Nowadays he is involved in studies concerning all aspects of RSV: from studies on diagnosis and treatment, to pathophysiology and prognosis.
The child will have to do the fighting
‘Unfortunately, currently we can only offer children supportive care when they suffer from RSV infection. There is no cure, which means the child will have to do the fighting against the infection. A lot of young children get RSV and can overcome this infection on their own, but for those children who are at risk for a severe infection, it is crucial that we offer enough supportive care and work on the development of therapeutics and preventive options. We are working very hard on this, but vaccine development in RSV is difficult. The good news is however, that as RSV is such a common disease, from a political perspective treatment and vaccine development is very important. Therefore, there is more investment in RSV research, which speeds up the process.
Awareness
I think there is still much room in improvement of the awareness on RSV among parents. Some parents have heard about bronchiolitis, but considering RSV, there are many parents who have never heard of it. Apart from the parents who have experiences with their child having a severe RSV infection, there are few people fully aware of the impact of RSV.
It is important to realize that any child can suffer from a severe RSV infection. In previous studies we have identified categories of patients that are extra vulnerable for a severe infection (for instance premature babies, or children who also suffer from a pulmonary or cardiac disease), but more than 90% of severe RSV infections occur in healthy infants. It is very difficult to predict how the child will respond to an RSV infection. In previous studies we have identified some genetic variations which are common in infants who are prone to RSV, but we can’t use this information during clinical bedside examination of a child.
Mortality
Unfortunately, during my career as a pediatrician I have also lost children due to RSV. They were mostly children with other problems, such as children with cardiac malformations or children who were born extremely preterm. In well-developed countries we can offer a lot of supportive care, but these options are very limited in low-income countries. Although the mortality of RSV is not as high in well-developed countries as in these countries, a severe RSV infection remains a traumatic period for children and parents to go through.
Although there is no cure or vaccine, we can prevent the spread of RSV and protect children against this virus. Therefore, it is crucial that together we raise more awareness on RSV. We all are concerned about SARS-CoV-2, but as a paediatrician I am much more concerned about RSV and its potential impact on young children.’
Prof. Dr. Louis Bont
Paediatrician, infectiologist immunologist at UMC Utrecht
“Unfortunately, few parents know about RSV. RSV infections cause a heavy burden on children and their parents. Every winter, paediatric wards and intensive care units are filled with babies infected with the virus. However, RSV does not only affect young children, the elderly are also more susceptible to severe RSV disease, especially if they suffer from heart or lung disease. RSV patients have trouble breathing because the virus damages
the airways, but also because of the immune response against the virus.
RSV is very unfair, because most children dying from RSV infection live in developing countries due to lack of intensive care facilities. There is no vaccine or medicine to treat RSV yet, but WHO and pharmaceutical industry are
working hard at it. Currently, there are two important developments in preventing serious RSV disease in children:
1. a maternal vaccine. Pregnant women are vaccinated to generate antibodies against the virus which are subsequently transmitted to the baby through the umbilical cord and breast milk. This vaccine is similar to the maternal vaccine against Whooping cough (Pertussis). It protects the child from severe RSV infection during the first months of life.
2. a new antibody. This antibody is given by injection to new-borns and – like the maternal vaccine – protects them from severe RSV infection for several months.
We expect these new preventive immunisation methods to be available within the next 5 years. In the meantime it is important to raise public awareness about RSV. This will improve care for infected children and accelerate vaccine development.
Anne Teirlinck
Epidemiologist respiratory infections at RIVM (Dutch National Institute for Public Health and the Environment)
At RIVM I work at the Centre for Infectious Diseases, Epidemiology and Surveillance. We analyse and monitor the occurrence and trends in infectious diseases in the Netherlands. The focus of my work is on respiratory infections. One of the things we do is register the number of people in the Netherlands with flu or flu like symptoms on a weekly basis. The symptoms of RSV infections are quite similar to those of the flu and lab tests are necessary to distinguish the RSV cases. Because the severity of infection varies a lot, we collect RSV incidence data at hospitals as well as GP practices.
RSV Vaccine
Unfortunately, there is no vaccine against RSV yet. However, there are quite a few vaccines in development. If one of them makes it to the market, it is important to know who needs it most. In order to prepare for potential vaccine introduction we need to learn more about the risks groups of severe RSV. That is why we are actively involved in the RESCEU study on the RSV burden of disease in Europe. Once the vaccine is introduction we need also need to monitor the effects of the vaccine. Again, we will do this together with various healthcare partners like GP practices and hospitals.
To improve RSV surveillance in general we cooperate with international public health institutions, mainly in Europe but also in other parts of the world. We need each other to gain better understanding of RSV, to share knowledge and expertise and to follow global developments in the field of RSV.
My personal experience with RSV
I do not work with RSV patients directly, but from the experiences of others I know about the impact severe RSV disease can have on patients and their families. I am therefore happy that through my work I can make a contribution to generate more knowledge and understanding about RSV.
Mwanajuma Ngama
Clinical Officer at KEMRI-Wellcome Trust Kilifi in Kenya.
RSV in Kenya
I have been working as a clinical officer for 20 years, and have been involved in the RSV project at the KEMRI-Wellcome Trust Research Programme in Kilifi, Kenya, since it started in 2002. Across Kenya we mainly see high numbers of children admitted to the hospital diagnosed with pneumonia or bronchiolitis caused by an RSV infection during two seasonal outbreaks that occur at times that differ from the East to the West of the country. On the coast of Kenya, where our hospital is located, the RSV season starts during the second rainy season and usually peaks in January and February, when it is hot and dry. Elsewhere further west it occurs during the first rainy season around March to July. Many people are not aware of RSV infections and the impact of this disease; it is the biggest cause of hospital admissions with pneumonia in children under 5 years of age worldwide. When a child is diagnosed with an RSV infection parents get some information from the general practitioner or pediatrician, but in public health facilities they are often too busy to properly educate parents on this condition, due to the high workload.
Treatment with limited resources
Our hospital in Kilifi has a high dependency unit, which is not the same as an intensive care unit (ICU), with access to ventilator machines. In Kenya there are only around 10 public hospitals with an ICU. There are also private and mission hospitals which offer ventilator machines, but most parents can’t afford to go to these facilities. In Kilifi, when a child with pneumonia or bronchiolitis is in urgent need for oxygen support they are managed at the high dependency unit where we can offer high oxygen flow by use of a ventilation mask. When this is not enough, we could transfer the child to a hospital with an ICU at one hour drive away, but we prefer to continue treatment of the child at our hospital and optimize the treatment of comorbidities. Before transfer is possible we first have to stabilize the child and inquire if there is an available ICU bed. During stabilization often children either improve and continue management at our hospital, or get more ill and pass away.
Not only are our treatment options limited, but also the preventive measures. In Europe children at high risk (i.e. premature babies) for RSV bronchiolitis can get Palivizumab to prevent an RSV infection, but it is very expensive. Because many parents can’t afford it this is not being offered at our hospital.
Awareness and education
By use of community engagement activities the KEMRI Wellcome Trust Research Programme tries to create more awareness on RSV among the public. There is a weekly radio program (Jukwaa la Utafiti) in the local radio station where health issues and health research are discussed, and people can call in and ask questions. We also try to engage with the community via a network of community representatives, elected by the community, who create a bridge between the community and the research that is being done at the KEMRI Wellcome Trust.
There is much room for improvement in the education of the general public on RSV. As doctors often lack time to provide information during sick visits, it would be useful to give this information during the Maternal and Child Health clinic visits and at the health centers and dispensaries, which provide outpatient services for simple ailments such as a common cold.
Steve Cunningham, professor of pediatric respiratory medicine at the University of Edinburgh
RSV raised my interest as I saw the big impact of RSV on patients, parents and the health service during my ward rounds as a paediatrician. I chaired the national guideline on bronchiolitis for Scotland (SIGN 91), which were published in 2006, and I subsequently chaired the National Institute for Health and Care Excellence (NICE) guideline on bronchiolitis in 2015. I’ve also been involved in more clinical research topics on RSV, such as the optimal oxygen saturation for patients, the development of new treatments and vaccines, and studies on the mechanistic side of RSV.
Phase I trials
Early phase and Phase 1 clinical trials especially raise my interest. The Children’s Clinical Research Facility embedded within the Royal Hospital for Sick Children in Edinburgh is the only children’s hospital in the UK with a paediatric Phase I accreditation. A phase I trial is the first stage of research, for RSV potential treatments are tested in infants with RSV, after being tested first in young healthy adults. Of course we have to work carefully, utilsing the knowledge of many people from the drug company and our staff to understand from the laboratory work and testing in adults what might be the risks and benefits of the new medicine, and what kind of adverse effects we might expect. From this we can provide parents with extensive information on all the knowledge we have gained thus far from the drug. It always has a big impact on me when parents are willing to let their child participate in these trials; it is incredibly altruistic.
Vaccine and Antiviral development
There are two big challenges in vaccine and antiviral development for RSV: we have to recruit sufficient patients at speed, and we have to correctly evaluate the effects, which is difficult as RSV is a variable disease that can lead to symptoms varying from a very mild cold to severe breathing difficulties. We can expect a vaccine and an antiviral to become available in the next 3-5 years, and hopefully it will be more than one. Of course we hope to develop a vaccine that is perfectly safe, so we can give it to all children as part of a routine schedule.
I think the coronavirus will definitely have an impact on the development of new treatments and vaccines for RSV. A lot of resources we need for our research are unavailable because of COVID-19, also social distancing impairs the monitoring process and follow up which is needed to safely provide these experimental therapies. It is difficult to say how big the impact will be, but as we expect COVID-19 to be a long-term issue, we will have to adjust to it. Luckily we have technology to help us out, for example by enabling us to acquire informed consent by use of photographs, and to do follow-up digitally where possible.
Awareness
The awareness among the public about RSV is variable. Many people know about bronchiolitis, but are unaware of RSV. However, the coronavirus pandemic might change this. I expect people will be more aware of the large impact of viruses, including RSV.
My take home message for parents is: If you are worried about your child, don’t hesitate to reassure yourself early by contacting your health service or going to see a doctor.