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We need to talk about CMV

Co-authored by: Professor Paul Griffiths Professor Paul Heath Professor Caroline Hollins Martin Professor Mark Kilby Professor Mike Sharland June 2015 2 We need to talk about Cmv

I am CMV

I have infected 3 out of 5 people you will ever meet Yet most don’t even know that I am there In most people I probably won’t have caused anything more than a mild sniffle before I hide, unnoticed forever Yet to an unborn baby I can cause serious harm I can cause miscarriages. I can cause stillbirths 2 or 3 babies are born every single day in the UK who have been affected by me that’s nearly 1000 every year These babies can have hearing loss, vision loss, cerebral palsy and epilepsy At the moment, you cannot vaccinate against me and in the UK nobody screens for me So you can’t stop me But with greater awareness, I can be outsmarted The more people talk, the more they will know how to reduce their risk of exposure to me The more they know, the more they can identify the babies I have affected But until you realise how vulnerable I really am, I am the stealth

0808 802 0030 [email protected]

Registered charity no: 1147633 cmvaction.org.uk @cmvactionuk With grateful thanks to Professor Paul Griffiths, author ofT he Stealth Virus, available from amazon.co.uk /CMVAction 3 We need to talk about Cmv

Contents

Executive Summary 4

Foreword 6

Case Study: Lyra 7

The changing zeitgeist of CMV 8

Reducing CMV 11

What midwives and childbearing women should know 13

Case Study: Oscar 15

Management in pregnancy 16

What the future holds 18

Conclusion 20 4 We need to talk about Cmv

Executive Summary

Around 1 in 5 babies born with , CMV is a or CMV, will suffer serious consequences such neglected as hearing loss, cerebral palsy and epilepsy. Not only does this put a huge strain on the families affected, but also on the NHS. burden Currently pregnant women receive no advice about reducing their risk of . Educating the general public, as as health care professionals, is fundamental to winning the fight against CMV.T hrough education, we can help babies receive an earlier diagnosis which will allow the opportunity for treatment. More research is also needed to develop an effective CMV .

The ‘We need to talk about CMV’ expert report is calling for more to be done to tackle CMV which affects more babies every year than Down’s syndrome, or listeriosis.

CMV is a neglected public the golden era of vaccine reduce the risk of acquiring health burden despite research has CMV been left CMV in pregnancy. We also representing a very real public behind? In the past it has know that pregnant women health concern. Around 1 been seen as too complex are highly motivated to follow in 5 babies born with CMV a virus. But the zeitgeist has preventative advice and that will have problems such as now changed from ‘if we get British women of childbearing hearing loss, cerebral palsy a CMV vaccine’ to ‘when we age want to know more about and physical impairment – get a CMV vaccine’. CMV. placing considerable burdens on families as well as health, We now know more about In the US, many states are social and educational how CMV is spread. The main legislating to mandate better services. way that pregnant women education and more rapid catch CMV is from the urine diagnostics. Public health and Over past decades, one by and saliva of small children. professional bodies in several one, the scourges of , There is a growing body of countries already recommend , and rubella research that shows that that health professionals began to be eliminated in providing pregnant women discuss CMV with pregnant many countries. So why in with this information can patients. 5 We need to talk about Cmv

So how can this information form of this virus, might the good be delivered effectively in the science now be close to NHS? Midwives are perfectly pensioning it off? news is placed to give pregnant Given the far-reaching there’s women advice about four simple hygiene precautions. consequences for children, plenty that However, many will have families and public services this is a goal that desperately can be done received minimal education on CMV since their initial needs to be achieved. But the right now training. Midwife educators good news is there’s plenty should prioritise continuing that can be done right now professional development on at little or no cost. GPs and CMV to equip midwives with midwives can advise women the knowledge to make a vital about reducing the risks difference. of infection. Obstetricians, sonographers, radiographers Even when infection in and neonatologists can be pregnancy is identified, alert to the potential signs there are many frustrations of CMV infection in a fetus in managing it. Unlike many or newborn so that more other infectious diseases, newborn babies can be there are few prevention diagnosed and treated within and treatment options. the first four weeks of life. There is an urgent need Paediatricians, and other for more research into professionals working with and treatment families, can understand the to prevent the devastating guidelines for managing CMV consequences of fetal so that more families receive infection. In the meantime, the monitoring and support it is important that their child needs. obstetricians and other professionals involved in We realise that it will take antenatal care improve time and collaborative their understanding of working to achieve the vision susceptibility, infection and of fewer babies being born transmission. with CMV and better support in place for those affected. While research into CMV But it can and must be it will take has traditionally lagged achieved if we are to reduce behind other , our the unacceptable burden on time to understanding is now evolving the hundreds of young lives achieve the in more exciting directions blighted each year through than ever before. We also congenital CMV infection. vision of know more about the gaps in fewer babies research that we need to fill and the UK is at the forefront being born of finding the answers. So as with CMV we near the 65th anniversary of the isolation of the human 6 We need to talk about Cmv

Foreword

CMV is a common infection that devastates lives. CMV can infect people of all ages. Most healthy adults and children experience no long-term effects from it. But it is very dangerous to unborn babies and is the most common infection passed from a pregnant woman to her baby.

Every year in the UK, CMV We need to talk about CMV: infection affects almost 1000 • Brings together evidence CMV affects ALMOST babies. It places an extra demonstrating that CMV is burden on the NHS, social a serious public health issue care, welfare and education systems, as well as the children • Sets out, for the first time, 1000 and families who live with the what different professionals babies Every year consequences of the virus. can do now to limit the impact of this virus Lyra is my granddaughter and as an educational professional • Outlines the research needed (I am a Teacher of the Deaf) now, and in the future, I was shocked that so few of including finding a vaccine the healthcare professionals for CMV we met had heard of CMV. CMV Action’s vision for the Even fewer knew how to future is one where fewer manage it. Yet CMV is not babies in the UK are born rare: it is more common than with CMV and better support Down’s syndrome and even is in place for those who are that all pregnant affected. I hope this report women are warned about will raise awareness of CMV such as toxoplasmosis and and inspire readers to listeriosis. support all efforts to educate, CMV Action is committed vaccinate and eradicate this to raising awareness of this devastating virus. virus. Our hope is that this We can reduce the impact report, We need to talk about of CMV. And we need to CMV, will alert prospective start now. parents, families, healthcare professionals and those Jan Pearman running the health service Trustee and Secretary of the threat of CMV. of CMV Action 7 We need to talk about Cmv

CASE STUDY Lyra

Lyra was born to parents who had never heard of CMV. The pregnancy was straightforward but it was evident at birth that Lyra was a very sick baby; her parents were told she might not survive.

The doctors treating Lyra diagnosed CMV infection quickly but admitted they knew little about the infection and were liaising with specialists in London. They started treatment with anti viral drugs the day after she was born. Scans and tests showed chronic liver damage, low platelets and extensive brain damage. Lyra’s parents were told that it was unlikely she would ever walk or talk and would probably never even know they were her mum and dad. They had to come to terms with the knowledge that their daughter was severely mentally and physically disabled and medically fragile. Blood tests showed that Lyra’s mother had contracted the virus early on during the pregnancy but the infection and resulting damage had not been identified. Lyra is now nearly 3 years old. CMV has affected her whole body. She has severe cerebral palsy. She can’t roll, sit or hold her head up. She has chronic liver disease, epilepsy that is complex and difficult to control, damage to her lungs, kidneys and spleen, scoliosis of the spine, dislocated hips, feeding difficulties and more. She can’t fight infection. She is blind. But she can hear and she smiles for her mum and dad. Those smiles are priceless.

Jan Pearman Grandparent 8 We need to talk about Cmv

The changing zeitgeist of CMV vaccines

In 1953 a Nobel Prize was awarded for the discovery of techniques, and from this somewhat obscure and highly technical breakthrough was launched one of the most significant public health interventions in human history – the modern era of vaccination. So why in the golden era of vaccine research was CMV left behind? And how close are we now to finding an answer?

CMV: A neglected public health burden

CMV represents a very real Clearly these problems can the annual recurrent cost public health concern. place considerable burdens of NICE recommended This virus damages more on the affected child and care for ADHD around babies than many better their family. But they also £40million.7 If we add to known infections and every place burdens on health, this the costs of NHS care year one or two in every 200 social and educational for vision loss, cerebral palsy, babies are born with CMV.1 services. The cost to the developmental problems and This makes CMV the most NHS of hearing loss, for the many other conditions common infection passed example, is significant; the caused by CMV, the total from mother to her baby. hearing loss associated burden rises even further. with CMV infection is Sadly, around one in every Of course, eradication of frequently progressive, with five of these babies will have CMV will not completely the commonest severity problems as a result of remove all of these costs— being severe-profound, for congenital CMV infection.2 since they can all be caused which the lifelong cost of a These include vision loss, by other diseases—but cochlear implant is £82,000 cerebral palsy, epilepsy, they would at least remove - £108,000.5 physical impairment, as well an important preventable as behavioural and learning Similarly, the cost of the component of the overall difficulties. In addition, some provision of specialist health total. Health economic 13 per cent of babies born care for other conditions assessments are needed to with CMV develop hearing caused by CMV can be more accurately determine loss,3 and at a quarter of all high. The total cost of care some of these burdens. cases, CMV infection is the for epilepsy conditions is leading cause of preventable around £2billion in direct hearing loss in childhood.4 and indirect costs,6 and 9 We need to talk about Cmv

The future may not be now, but it’s getting very much closer.

The search for a vaccine Signs of progress One by one, the scourges of polio, measles, The results of three studies in particular have mumps and rubella began to be eliminated been reported in recent years8,9,10 and, while none in many countries. In terms of public health, of the vaccines was good enough to yet offer CMV was an obvious early candidate for to the general public, there are at least some a vaccine. It damaged many more babies each signs now that there is the potential for making year than did rubella for example, and the improvements through further development and costs of treating the consequences are high. additional clinical trials. Some of these are so- Unfortunately, for various reasons, a suitable called ‘Phase 1’ (very early) studies, but there is vaccine was not quickly identified and researchers now at least one vaccine in ‘Phase 3’ trials—the turned their attention to making successful type of large-scale study from which regulatory vaccines against viruses like , bodies are able to determine whether the vaccine , rotavirus and chickenpox. should be made available to the general public. So it seems that some progress is being made. Over the decades few researchers showed enthusiasm for tackling the problem of CMV. So is there anything that the public can do to It was seen as too complex a virus because help? The good news is that they can get involved it infected each person more than once and with family members, friends and neighbours to can lie dormant or latent for years before take part in randomised controlled trials. Tens of reawakening to cause recurrent infections in thousands of volunteers will eventually be needed some. The molecular of the virus itself including toddlers, teenagers of both sexes and showed it to be adept at evading the human women of childbearing age. These studies take immune system and many argued it would simply time but they will provide the best way of ensuring be “impossible” to make a vaccine against CMV. that a CMV vaccine is being given a fair chance to demonstrate its safety and efficacy. Nevertheless, some investigators persisted, citing the need for evidence before giving up on such an How long will it take before we have a vaccine important cause of disease. And their persistence to routinely protect against the terrible effects is showing encouraging signs of being rewarded. of congenital CMV, just as we now routinely protect against the effects of measles, mumps, rubella and polio? Realistically, it will need years or even decades, and we don’t know how many vaccine candidates will have to be evaluated before one is found that is good enough to be licensed. But the zeitgeist has definitely changed from when it was deemed “impossible”, we now talk not of “if we get a CMV vaccine” but “when we get a CMV vaccine”. The future may not be now, but it’s getting very much closer.

CMV represents a very real public health

concern Professor Paul Griffiths Professor of Virology, University College London 10 We need to talk about Cmv

Table 1: The Zeitgeist extends beyond vaccines: key international differences between UK and the rest of the world

Key differences in practice in CMV between the UK and other countries

Public education Screening of neonates • In the US, the Centers for Disease Control • Screening programmes for newborns have and Prevention (CDC) recommends doctors not yet been implemented at national level tell pregnant women about CMV and is in the US or Europe but there is increasing investing in a public education programme enthusiasm for this among health care professionals • The state of Utah have made CMV education mandatory and Hawaii’s • In the US, a large study is evaluating legislature recently took the first step whether CMV screening should be routinely in passing their proposed law on implemented and the feasibility of such communicating the dangers of CMV a programme to pregnant women. Similar legislation • In the state of Utah CMV testing is is being considered in a number of other mandatory for newborns who fail their states including Connecticut, Illinois, hearing screen and other states are planning Tennessee and Texas a similar approach • Professional and Public Health bodies across several other countries recommend Other healthcare guidelines that health professionals educate women • In the US, the Institute of Medicine has about CMV. For example, The Australian ranked the development of a CMV vaccine Society for Infectious Diseases (ASID) as one of their highest priorities because of recommends CMV counselling at prenatal the lives it would save and the disabilities it and antenatal appointments. In France, the would prevent. However, it may be a number ANAES (Agence Nationale d’Accréditation et of years before there is a and Drug d’Evaluation en Santé) and CSHPF (Conseil Administration-approved CMV vaccine supérieur d’hygiène publique de France) also • In the UK, health technology assessment recommend giving information to pregnant bodies such as the National Institute for women about CMV infection Health and Care Excellence (NICE) and • There are no recommendations in the the Scottish Medicines Consortium (SMC) UK for antenatal education have no current plans to update guidelines involving CMV Antenatal screening • Testing of pregnant women is controversial and its use is not recommended in the UK or US • However, Israel and eight European countries (France, Belgium, Spain, Italy, Germany, Austria, Portugal and the Netherlands) routinely screen the majority of pregnant women serologically for CMV.11 This routine serologic screening occurs without the recommendations or guidelines of any governmental agency, authority or professional medical society 11 We need to talk about Cmv

Reducing CMV transmission

If you were to ask people what poses the most risk to a pregnant woman and her baby out of a dirty cat litter tray, an unpasteurised cheese or a drooling toddler, most would pick the litter tray or the cheese. And yet they would be completely wrong.

When researchers first identified CMV in the 1950s— the same decade as the chickenpox and measles viruses were discovered—it heralded a golden era of viral research. But whilst this research has led to effective treatments and vaccines that are now routinely used to combat many viral illnesses, research into CMV has often lagged behind. And perhaps most worryingly, only 14 per cent of British women know what CMV is.12

So how is a virus that three in every five people13 have caught at some point in their lives, actually spread?

the main Surprisingly, CMV is not that CMV can be spread through easily transmitted as it is spread all bodily fluids—including way only through close contact with sexual contact and medical pregnant bodily fluids. In fact, the main way treatments such as blood pregnant women catch CMV is or organ transplantation— women from the urine or saliva of young however, saliva is a particular catch children. Younger children pose risk. This is because CMV is a greater transmission risk than present at higher levels in CMV is older children: there are higher saliva than urine. Also, many levels of virus found in their bodily of the behaviours that increase from the fluids and they are more likely exposure—such as sharing urine or to spread these around, through food and utensils, kissing on drooling, mouthing toys and so the mouth, and wiping the saliva of on. And the virus can remain face—are very common practice young present in a child’s bodily fluids among mothers and their young for many months or even years children. And these activities children after they have recovered from also allow for direct transfer of the initial infection.14 CMV to mucous membranes. 12 We need to talk about Cmv

Exposure through contact We also know that pregnant with urine mainly occurs women are a highly motivated during nappy changing. group who are more likely However, it is less likely to be to follow CMV preventative transmitted this way than via measures than non-pregnant 14% saliva, as most women say women,16 and that women only 14 per they already clean their hands of childbearing age in the cent of British after a nappy change.15 UK want to know more about CMV: in a survey of women know Aren’t all the people who’ve over 1,000 British women what CMV is caught it already immune aged between 18 and 44 from it? Unfortunately, people 9 out of 10 (91 per cent) think who have already caught that pregnant women should CMV do not have guaranteed be given advice about CMV protection. You can still catch infection during pregnancy.12 a different strain or have a And after reading advice flare-up of the virus that’s about how to prevent already in your body. infection, three quarters So how does this knowledge (75%) of British women of of the rather messy childbearing age think that transmission of CMV help us? it is easy to prevent CMV.12 Although there is as yet no CMV can be prevented. vaccine against CMV infection, While we wait for vaccines there is a growing body of and other interventions to research that suggests risks become available, we have can be reduced. evidence that CMV education Research studies from the may be able to effectively US, France and Italy have prevent CMV infection in all provided evidence that pregnancy. We know that providing pregnant women pregnant women want this with counselling and clear information and are willing information can reduce the risk to take appropriate measures of acquiring CMV in pregnancy to reduce their risk of – in some cases reducing the acquiring CMV infection. risk of acquiring CMV by up to Our immediate priority 85 per cent.16,17,18 Despite this, therefore, should be finding information about avoidance ways in which this education of CMV infection is not can be effectively delivered to routinely provided in the NHS. pregnant women in the NHS, There is a long history of at the point at which they evidence that educational most need it. interventions can prevent congenital diseases. For Our immediate example, efforts aimed at preventing fetal alcohol priority syndrome have reduced maternal alcohol consumption should be to in pregnancy,19 prenatal vitamin effectively and folic acid supplementation have lowered rates of neural Professor Paul Heath educate tube defects,20 and antiviral Professor of Paediatric pregnant use in pregnancy has been Infectious Diseases, shown to reduce mother to St George’s University Hospitals women child transmission of HIV.21 NHS Foundation Trust 13 We need to talk about Cmv

what midwives and childbearing women should know

The risks of childbearing women contracting CMV raises significant responsibilities for health and social care professionals in terms of prevention and management. Humans are desirable hosts and bodily fluids are a keen source of transmission of CMV.

So, what should health and social care professionals Don’t Share, be doing to play their part in reducing the number of Wash with Care infants affected by the virus? Given the devastating Avoid placing objects consequences for the neonate from contracting 1 in your mouth that have previously been congenital CMV in utero, it is imperative that both in an infant’s mouth health care professionals and women receive e.g. avoid food, cup and utensil sharing, education about reducing the risks of transmission. or sucking a child’s dummy to clean it after with advice to reduce their it has been dropped. Education risk of contamination by CMV. Routine provision of health avoid kissing young The simple and most effective information is a pivotal step children on the mouth education that midwives 2 in encouraging childbearing or cheek. Instead, kiss can offer couples planning women to understand how them on the head or or already pregnant involves to avoid CMV transmission. give them a big hug. four very simple hygiene Transmission of CMV occurs precautions. Wash your hands via bodily fluids, e.g. urine, 3 thoroughly with soap saliva, vaginal , Education costs little and and water after coming semen, breastmilk, blood is key to reducing the into contact with any transfusions and organ spread of CMV. Education bodily fluids. This transplants. Primary infection regarding CMV is aimed includes after a nappy of childbearing women occurs at reducing infant risk of change, or after wiping a in around 0.15-2.0% of all developing Intrauterine toddler’s nose or mouth. pregnancies22 and can lead Growth Retardation thoroughly cleanse to catastrophic consequences (IUGR), hyperbilirubinemia, items that have been for the infant who contracts hepatosplenomegaly, 4 in contact with bodily CMV in utero. Hence, as part thrombocytopenia, and fluids and may have of routine preconception and microcephaly, all of which become contaminated. antenatal care, midwives must cause serious morbidity provide childbearing women problems and often death. 14 We need to talk about Cmv

Discussing CMV with childbearing women may make some feel anxious. Nevertheless, given the catastrophic consequences for Education the infant of contracting congenital CMV in utero, it is imperative that both health care professionals and women receive carefully programmes measured educational messages about its prevention.23 that extend Education could be further strengthened by widening general public health messages about how to prevent the spread of CMV infection. midwives For example, by teaching adults and older children thorough methods of hand hygiene and how to avoid spread between children knowledge in day care facilities. Education programmes that extend midwives about CMV knowledge about CMV are clearly required, e.g. organising study sessions for all grades of staff and increasing the amount and level are clearly of CMV education in the midwifery curriculum. Further training in prevention and management of CMV would profoundly improve required long-term and morbidity. It is the responsibility of midwives to deliver information about CMV in a balanced way so as not to cause alarm. The spread of CMV can be avoided and whilst it is hard for busy women to avoid every potential exposure, simply improving hygiene measures can markedly reduce the risk of transmission. To this effect, CMV Action has developed a range of educational literature for childbearing women (cmvaction.org.uk).

Midwife education is key to reducing CMV midwives understanding spread. With this in mind, as well as increasing their The midwife is perfectly placed midwifery educators in the UK confidence to counsel to increase delivery of CMV should consider advancing women about CMV and education to both staff and education for midwives as its serious consequences. childbearing families, yet part of continuing professional Evidence supports that high many have received minimal development. For example, quality training in prevention education on the topic since content of curriculum should and management of CMV their initial training. Despite include: markedly reduces mortality the growing body of published and morbidity of fragile • How to prevent CMV evidence that emphasises infant lives. the importance of increasing infection spread (Don’t health education in attempts Share, Wash with Care) To conclude, educating women to diminish CMV to reduce CMV transmission • Provide a clear definition 2,11,22,23,24, 25,26,27,28 risk is enormously important , in many and description of CMV if midwives are to make a countries there lacks provision of directives to vital health difference. Clearly a lot is care professionals, such as • Discuss prevalence of CMV yet to be tackled if we are general practitioners, midwives, • Discuss brutal consequences to eradicate CMV risk and neonatal paediatricians and for a fetus who has spread. In essence, the nurses about this subject. This contracted congenital CMV key variable for reducing finding sharply contrasts with CMV transmission involves education designed for delivery CMV Action and The Royal straightforward hygiene in relation to other teratogenic College of Midwives have measures. infections in pregnancy, e.g. developed an e-learning listeriosis and toxoplasmosis, training module to promote which represent far less support further education Professor Caroline danger to the infant. Improving for midwives on CMV. Hollins Martin education that teaches people (ilearn.rcm.org.uk). It Professor in Maternal Health, how to avoid contamination is aimed at enhancing Edinburgh Napier University 15 We need to talk about Cmv

CASE STUDY Oscar

After trying for a baby for two That’s when my world crumbled. years, we luckily became pregnant I had contracted CMV at some with out first child just two days point during the first trimester, before we signed the paperwork meaning my baby could be to undergo IVF treatment. A lucky infected, although the doctors miracle I called it. reassured us our baby may not be ‘affected’. Whilst I’d heard of I’d spent so much time looking it, I had never known anyone who into fertility and how difficult had had cmv. How on earth had I getting pregnant can actually be! picked this up? Where had it come I’m also a midwife of eleven years, from? This was my fault. Of course with experience mostly on the I’ve since gone on to read about labour ward but also in teaching how it is contracted and with all and more recently community, so my work with families and children, seeing people everyday and them who knows where it came from? telling me their ‘lucky’ stories of We started googling and found falling pregnant made my two that he may have some learning years very long indeed. disabilities or mild hearing loss, However, we were lucky, we had not a problem we thought. no bleeding, no blood pressure The consultant suggested an issues, the Down’s syndrome amniocentesis, which we had screening came back very low at 33+1 weeks. We also had a and, despite sickness that lasted brain scan which now showed until 22 weeks and horrendous ventriculomegaly, some brain heartburn, I couldn’t complain! abnormalities. We then went onto My midwife started measuring me have an MRI scan at the John at 26 weeks when she picked up Radcliffe Hospital in Oxford. Our that I was SFD (small for dates.) I baby was disagnosed with severe also never felt my baby move. CMV, there was poor growth, enlarged liver / abdomen, a small I started undergoing serial growth head and no brain activity at all. scans. I send my own patients for these all the time and they Our beautiful baby, Oscar William, generally come back fine, so I was stillborn at 33+6 weeks, on wasn’t worried. My consultant 9th March 2015, my shining star. did a TORCH blood screen for His death is still, obviously, fresh infections. The TORCH screen is and everyday is a struggle, from a group of blood tests that check simply watching baby adverts on for several different infections TV, to seeing friends with babies or in a newborn. TORCH stands looking through Oscars’ photos. for toxoplasmosis, rubella, I’m now on maternity leave and cytomegalovirus, , want to raise more awareness and and HIV, but it can also include support CMV Action as much as other newborn infections. I can. Well I knew I was fit and healthy and didn’t have any infections, but Sharon Robinson it’s only a blood test, so why not? Midwife 16 We need to talk about Cmv

Management in pregnancy

Clearly there is a need for more research into vaccination and treatment to prevent the devastating consequences of this infection to the unborn baby. In the meantime it is important that obstetricians and other professionals involved in antenatal care improve their understanding of this infection, and counsel pregnant women accordingly.

There are many frustrations in the management of CMV infection in pregnancy. Unlike many other infectious diseases—such as rubella (German Measles), toxoplasmosis and chickenpox—there are few prevention and treatment options for CMV.

CMV is the largest of the This leaves around two in Herpes virus family. Like every five pregnant women all Herpes viruses, a first or susceptible to a primary ‘primary’ infection can occur infection, and between one at any time, but it may also and four out of every hundred remain ‘latent’ to be re- pregnancies will see a mother activated later in life. This infected by CMV for the first can happen for example in time.29 Of those who become someone whose immune infected when pregnant, system is suppressed, or almost a third (32 per cent)30 if they have experienced will transmit the infection a stressful stimulus, in to their unborn baby. Once which case it is known as a infected, up to 15 per cent2 ‘secondary’ infection. of unborn babies will show signs of disease, and a similar Estimates vary by ethnic proportion of babies who have group, but overall around no symptoms at all will go on 13 three out of every five people to develop permanent in the UK have been infected problems,2 of which the most with CMV at some point in common is hearing loss. their life, usually early on. 17 We need to talk about Cmv

CMV infection during Routine screening for pregnancy is most often CMV during pregnancy is suspected and diagnosed not performed in the UK. when an ultrasound scan The National Screening 32% shows suspicious features. Committee has recommended will transmit the These include the baby being against CMV screening infection to their small, with low amniotic fluid in the antenatal period, unborn baby. (oligohydramnios), echogenic because there is uncertainty (bright) kidneys and in some about the risk to the baby cases brain abnormality when maternal infection is (usually water on the brain diagnosed and because the or hydrocephalus). Such effectiveness of treatment cases are usually referred to has not been confirmed. a specialist fetal medicine However, the consequences centre where a detailed of this infection in pregnancy scan can be performed by can be devastating. Public an expert. Since testing the health measures are urgently mother’s blood can produce needed to reduce the risks inconclusive results, the of infection in high risk majority of experts will want individuals in particular (for to perform an amniocentesis example pregnant health care test to identify CMV DNA, and workers, teachers, and women also look for other signs such with young children), and all as a low platelet count in the pregnant women should be baby’s blood. routinely counselled about the need for hygiene and In such cases, treatment avoidance of contact with options are limited, and small children’s saliva and even when treatment is urine during pregnancy. administered it may not prevent damage to the baby. In reality, however, it is hard The use of antiviral medicines to avoid every possible such as ganciclovir (either by exposure, and there is treating the mother or directly certainly a need for more into the baby by in-utero research into the development transfusion) may reduce the of vaccines which could amount of circulating virus, be safe and effective in and improve platelet count women of reproductive and liver function tests in the age. In the meantime, baby. However once damage more understanding of the has occurred it is unlikely to pathogenesis of susceptibility, be reversed. Currently there is infection and transmission little high quality or definitive to the unborn baby during Public health evidence on the most effective pregnancy can only help in measures ways to treat CMV infection in improving outcomes in this pregnancy. There have been little-known but potentially are urgently no randomised controlled devastating disease process. needed to trials proving that antiviral treatment works and reduces reduce the handicap rates, and more Professor Mark Kilby risks of research studies are urgently Clinical Scientist and Honorary needed. Consultant in Fetal Medicine, infection Birmingham Women’s Foundation Trust 18 We need to talk about Cmv what the future holds

While research into CMV infection has traditionally lagged somewhat behind that of other viruses, our understanding is now evolving in more exciting directions than ever before. In addition, we know more about the gaps in research that we need to fill. So as we near the 65th anniversary of the isolation of the human form of this virus, might science now be near to pensioning it off?

Recent years have seen important steps forward in CMV research, both in the UK and around the world, with studies planned or underway across the entire spectrum of the infection, from diagnosis and screening, through to transmission, treatment and prevention. Yet important gaps in our understanding still exist and the UK is very much at the forefront of finding the answers.

Identifying and integrating testing for CMV within the existing newborn treating CMV infection hearing screening programme. Much of the research in the Results from these studies UK has focussed on diagnosis have shown that testing for and treatment. Hearing loss CMV is both acceptable to at birth is one of the most 97 per cent of parents, and common symptoms of CMV. feasible in ‘real life’ practice.31 Yet some CMV babies who fail Newborn hearing screeners felt their newborn hearing screen confident in performing the are not diagnosed with CMV in tests and were able to screen time to start antiviral treatment, around eight out of every ten which must happen in the first babies referred for further month of life in order to limit hearing assessment.32 further deterioration of hearing. Research in this area is To address this issue, a series emerging in ever more of studies in the UK (BEST1 innovative directions, including and BEST2) has explored development of an easy to the benefits and feasibility of use test to diagnose CMV that 19 We need to talk about Cmv

uses nanotechnology – a high or re-infected. We also need educating tech yet low cost device that to know which babies with could enable even more babies infection at birth are more likely pregnant to be tested and diagnosed. to have long-term disease, can we predict those destined for The picture on CMV treatment women hearing loss? And do babies for newborns is evolving with less severe symptoms about CMV rapidly. A US/UK collaboration of disease receive the same reporting in 2013 published benefits from treatment as can reduce evidence on the benefits those who do not? infection in and risks of oral antiviral medicines and showed that We know that, ultimately, pregnancy longer treatment could result preventing CMV depends on in improved outcomes developing a vaccine. There is compared to shorter a clear need for more clinical treatment.33 In addition, further trials of potential vaccine research is now underway that candidates. will explore the benefits of oral So while we wait for the antiviral treatment for children answers to these questions, our with sensorineural hearing focus should be on two things: loss and congenital CMV up diagnosis and education. to the age of 4 years. This could mean that more children First, we have shown that have the option of treatment, babies who are at risk of which is especially important CMV-related hearing loss can for those who develop hearing be tested for CMV quickly problems later on. and easily within the NHS. We now need a larger-scale implementation study to fully Where to next? assess the potential costs Research has come a long and savings, so that NHS way in recent years, yet some commissioners have the important knowledge gaps information they need to make remain. Currently several decisions about improving early studies are looking at neonatal pathways. new approaches in treatment, Second, there exists such as immunoglobulins and a substantial body of antiviral medicines,34,35,36 as international evidence showing well as the ways of reducing that educating pregnant transmission from an infected women about CMV can reduce mother to her unborn child.34 infection in pregnancy. We Clearly, while some of this know education works, we now research appears promising, need to explore how CMV we need results from larger education can most effectively Research randomised studies to confirm be delivered within the NHS. has come a initial findings. In addition, we need to know long way in more about the overall impact of this infection and where recent years, we should focus our efforts yet some in combating it. The Life Study—the largest ever UK- important wide cohort study of babies Professor Mike Sharland knowledge and young children—will look Professor of Paediatric at the burden of disease of Infectious Diseases, gaps remain. congenital CMV and assess St George’s University Hospitals which women get infected NHS Foundation Trust 20 We need to talk about Cmv conclusion

As the evidence in this report shows, the burden of CMV infection is high and the consequences far reaching. There is much that needs to be done if we are to achieve CMV Action’s vision of fewer babies born with CMV and better support in place for those affected. But the good news is there’s plenty that can be done right now at little or no cost.

CMV Action are Over the longer term it is also • Managing CMV after recommending a number important to address other diagnosis: Health of minimum standards of aspects of CMV: professionals such care for pregnant women as audiologists, • Managing infection in and babies affected by paediatricians and pregnancy: The UK National CMV (see box). These neurologists, who are Screening Committee minimum standards of working with families, recommends against care can be introduced should ensure that systematic population as soon as today. Experts monitoring appointments screening for CMV in attending an international occur at recommended pregnancy. However CMV conference in intervals. individual cases will still be Brisbane in May 2015 identified in the course of • Identifying late-onset agreed unanimously that routine antenatal care. problems: Early years CMV counseling should Each health community professionals and support be given to all pregnant should therefore develop workers must be aware women. Government and and implement local of the particular risk CMV professional bodies in guidelines for: brings of late-onset and many countries such as progressive hearing loss. the US, France, Australia --Testing for CMV should They need to know how and the Netherlands there be suspicion of and when to monitor, already recommend that infection. and how they can assess this happens. However --Management and whether hearing loss is advice on CMV prevention monitoring when infection caused by CMV. is not routinely given within during pregnancy is the NHS. detected. • Tracking longer-term outcomes: Most of the minimum • Diagnosing CMV in Our understanding standards of care that newborns: Research into of congenital CMV families with a baby treatment and diagnostic is still limited and there affected by CMV should technology is underway. is an urgent need to expect from health As new evidence emerges monitor treatment and professionals can also be the National Screening longer-term outcomes introduced immediately. Committee should review on a central UK its position on universal database. newborn screening. 21 We need to talk about Cmv

There are also steps that Minimum standards of care for pregnant can be taken at a national level. Public Health England women should recognise CMV as a serious public health issue and GPs should: support work on public and • Advise women trying to conceive on how to reduce the risk professional education, in the of CMV infection in the same way as they recommend folic same way that the Centers for acid before conception Disease Control and Prevention • Advise pregnant women on how to reduce the risk of CMV (CDC) does in the US. infection in the same way they give advice on reducing the Research from other countries risk of food and animal-borne infections shows that implementation of Midwives should: guidelines can be hampered • Alert all the women booking with them to the dangers by lack of detailed knowledge of CMV infection: how it spreads and how to reduce the of CMV. This is why, alongside risks, in the same way as they already advise about food this report, CMV Action is and animal-borne infections launching training for midwives and will invest in training for • Support women with specific concerns about CMV enabling doctors and other professionals them to access support locally in future. Bodies responsible Radiographers, sonographers and obstetricians should: for professional training should • Be alert to indicators that suggest a higher risk of CMV, also do more to ensure that such as fetal anomalies, and take appropriate action doctors and midwives are confident in their knowledge of CMV prevention, transmission and management. The National Institute for Minimum standards of care for babies Health Research should affected by CMV support research into the prevention, detection and Local health systems should ensure that guidelines and optimal management of pathways are in place for testing, diagnosis and management congenital CMV. of CMV. These would include: • Midwives, obstetricians and neonatologists should know the We would also like to see an potential signs of congenital CMV in a newborn baby increase in research to develop an effective CMV vaccine. • A CMV test should take place as soon as hearing loss is confirmed and systems must be in place that make it We recognise that our vision possible to confirm or exclude CMV diagnosis within the first cannot be realised overnight, four weeks of life, so that treatment can be considered that it will take time and • The standard newborn hearing screen therefore needs collaborative working to to take place within a timeframe which allows diagnosis deliver. But it can and must be of congenital CMV within the first four weeks of life achieved if we are to reduce the unacceptable burden on • Following a diagnosis of CMV, families should have access the hundreds of young lives to a paediatric infectious diseases specialist to discuss blighted each year through treatment congenital CMV infection. • Newborn Screening Laboratories should retain Guthrie cards (dried blood spots) for as long as possible but Let’s start that process now. at least the minimum period of five years.T his is to enable the diagnosis of congenital CMV in children who may present with problems during childhood, adolescence and as a young adult • The healthcare professional that is a family’s key point of contact must have knowledge of the evidence-based guidelines for managing CMV Caroline Star CMV Action Chair 22 We need to talk about Cmv

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