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Keyword: pneumonia

By Dr. Kate O'Brien

While the political turmoil and violence in Mali occupied headlines earlier this year, we here at IVAC were acutely aware of the situation as we worried daily about our partners there, including Dr. Samba Sow and his team at Center for Vaccine Development (CVD) in Bamako, who lead the Mali site of our Pneumonia Etiology Research for Child Health (PERCH) project. Earlier this month, our team had a chance to return to Mali, now that the situation in the capital has stabilized. We were impressed at CVD’s ability to keep the PERCH project – not to mention their work on the Global Enterics Multi-center Study (GEMS), MenAfriVac, and a few other randomized vaccine trials – up and running during the crisis, and to make the right choices to safely balance the security of their staff and care for patients while maintaining the integrity of the research. The trip got me reflecting on the broader efforts around pneumonia prevention, and three things struck me as worth sharing.

PERCH team with CVD Mali

Kate O'Brien with members of IVAC's PERCH team and CVD-Mali in Bamako.

First, in spite of the progress on PCV, our work is not done on squelching the burden of pneumonia and the problem is not being fully met with the resources needed to tackle it. Much time and many resources are being allocated to global mortality estimates, including for pneumonia, and there is evidence that this burden of mortality has fallen meaningfully over the past decade. Credible disease burden efforts have an important place in the global health landscape and deserve to be done, and done properly, but they are, and will always be, a monitoring and planning tool. They only reflect the progress; they are not the progress itself. These estimates are fully dependent on sound, high-quality fieldwork on pneumonia burden, and the consequent efforts and research on protection, prevention, and treatment of pneumonia. There is too little funding for strategic fieldwork on pneumonia. Being in Bamako, in the hospital, in the clinic, and most importantly visiting communities and households of families who are affected by pneumonia, reminded me that this is where progress is made and this is where we must invest and innovate. 

Second, we have to focus on what will meaningfully make changes in the burden of and mortality from pneumonia. We still don’t have tools that can readily differentiate the children with true pneumonia from those with other lower respiratory diseases that require a different treatment. Families still don’t have the basic understanding of signs of respiratory disease for which they should readily seek care. And hospitals and clinics remain crowded, under-resourced, and fragile with treatment approaches that too often are unable to support children through their illness. This is why children die from pneumonia, still.

PERCH Mali lab staff

CVD-Mali staff demonstrate procedures as Kate O'Brien and other PERCH team members observe.

Third, there are field research sites that have built expertise, infrastructure, and experience to tackle the important unknowns, but they are fragile and will not remain unless investments are made. In spite of the constraints, there is research of the highest quality ongoing in places where child mortality from pneumonia is highest, including in Mali. It is outstanding how the CVD-Mali team managed to keep all of its critical research projects up and running not only through the day-to-day challenges, but also through the political challenges of this past year. It was a great honor to learn from them, to work on solving challenges at the site, and to renew our understanding of where focus and effort is needed to make reductions of pneumonia and diarrhea a reality on the ground, and not just in our computer algorithms and spreadsheets.

 

Kate O’Brien, MD, MPH, is Acting Executive Director of IVAC. A pediatric infectious disease physician, epidemiologist, and vaccinologist, she previously served as Deputy Director of IVAC. She also serves as Associate Director of the Center for American Indian Health.

By Dr. Kate O’Brien

This week scientists came together to declare that we will eradicate polio in 5 years. It’s an achievable goal, and admittedly an aspirational one. But, if we as a global community leverage proven strategies and follow through on commitments made, it will be met. It is amazing to think that this goal, which just two decades ago seemed impossible to many, is now firmly in our sights. It also gives me confidence that we can reach other goals, such as reducing preventable childhood deaths to a degree that any such death is seen as a shocking, rare event rather than predictable and intractable. This challenge, which the global health community laid out in last year’s Promise Renewed initiative may seem daunting, given that despite recent declines, 6.9 million children died in 2011. However, when you consider that worldwide polio cases have dropped by 99% since the Global Polio Eradication Initiative began in 1988, it is clear these problems are surmountable. Like polio eradication, we need a concrete approach to tackling the leading child killers, and we made a big step forward with today’s launch of the Integrated Global Action Plan for Prevention and Control of Pneumonia and Diarrhoea (GAPPD). Released by WHO and UNICEF, GAPPD clearly outlines the steps we must take to eliminate the two leading killers of young children in 20 years.

GAPPD cover

The Integrated Global Action Plan for Pneumonia and Diarrhoea (GAPPD)

Most of my professional life has been spent assessing and applying interventions to reduce pneumonia and diarrhea, both in the United States among American Indian communities and around the world in the communities where most child deaths still occur. I’ve seen the burden of these diseases in the numbers we calculate and on the faces of the patients I’ve treated. I’ve also seen that we have the tools we need to stop children from dying or suffering from severe pneumonia and diarrhea. When I worked in Haiti, the ward was full of children, over a third of whom would die in those beds. Nearly all of the illnesses these children had were fully preventable, mostly through the use of vaccines but also through other simple, sensible interventions. The interventions we have work, and the task we have is to figure out how to use them most effectively, to know if what we are doing is working, and to make adjustments in optimizing their impact. This feedback loop can only be put in place when we can measure the impact of what we’re doing. We may not be able to measure with absolute precision, but with enough precision to know if our time and treasure is being wisely spent.

We know what we need to do to tackle pneumonia and diarrhea, and establishing clear evidence on the burden of disease and on interventions that work creates the platform from which we can prioritize our efforts. A new series published in the Lancet today in conjunction with GAPPD provides updated evidence on this front. One of the papers, led by faculty in our Department of International Health at Johns Hopkins provides updated mortality estimates for pneumonia and diarrhea – together responsible for more than 2 million child deaths in 2011.

We also have a clear understanding of which interventions work, and we know that many of them overlap. As my colleague Bob Black pointed out in the Lancet series launch, while diarrhea and pneumonia have very different symptoms and causes, several risk factors for the two diseases are the same, including under-nutrition, suboptimal breastfeeding, and zinc deficiency, meaning that they can be effectively prevented and treated as part of a coordinated program. We also know that vaccination campaigns will play an important role. A second paper in the Lancet evaluated 15 key interventions using the Lives Saved Tool. It found that nearly one third of severe diarrhea episodes could be prevented by widespread vaccination against rotavirus and cholera, while up to two thirds of pneumonia deaths could be prevented by implementation of pneumococcal and Haemophilus influenzae type b vaccines. With ambitious scale-up – 80% coverage or more – the authors estimated all 15 interventions could effectively eliminate (95% prevented) diarrheal deaths and prevent around two-thirds of pneumonia deaths by 2025. All this at a total cost of just USD6.7 billion.

GAPPD and the Lancet series reflect years of work toward a consensus among all stakeholders that we must target our efforts on proven interventions, and we must work together in an integrated way. Many of the interventions for childhood diseases overlap, and can be delivered more efficiently if all parties work together. This integration will not only result in better care for each child, it is also crucial in resource-poor settings, where countries simply cannot afford to maintain siloed efforts and where partnering countries and organizations are increasingly demanding more impact for their investments.

We have the evidence, and our marching orders are clear. With polio eradication beckoning our efforts, it is the time to leverage this energy, know-how, and confidence by fulfilling our promises and advocating for all stakeholders – donors, governments, civil society, and other leaders – to fulfill theirs. We can all take inspiration and insight from polio eradication efforts and make the end of preventable pneumonia and diarrhea deaths a reality.

 

Kate O’Brien, MD, MPH is Acting Executive Director of IVAC. A pediatric infectious disease physician, epidemiologist, and vaccinologist, she previously served as Deputy Director of IVAC. She also serves as Associate Director of the Center for American Indian Health.

By Dr. Juliet Otieno

This the second blog in a series from the Pneumonia Etiology Research for Child Health or PERCH study team. PERCH is a multi-country case-control study of the etiology of severe and very severe pneumonia in children aged 1-59 months. Led by IVAC and funded by the Bill & Melinda Gates Foundation, PERCH operates seven research sites throughout Africa and Asia.

As a Kenyan doctor, having completed my internship at a rural mission hospital and worked as a junior doctor in a paediatric hospital for just over a year, I found myself two years ago in a small rural town, Kilifi, in the heart of a study on the causes of childhood pneumonia, the Pneumonia Etiology Research for Child Health or PERCH. When I began working with the PERCH study, a study on the “causes” of pneumonia initially seemed to me as a rather counter-intuitive approach to the problem at hand. I had spent years cramming the national diagnostic and treatment guidelines for pneumonia and I was pretty confident in the management of children with acute and chronic respiratory illnesses. I did not need the much-cited research to know what pneumonia looks like or to understand its burden on our children.

physicians examine chest x-ray

Physicians from three different PERCH sites, Dr. Juliet Otieno, Dr. Bernard Ebruke, and Dr. David Moore, examine a chest x-ray of a patient with pneumonia during a cross-site visit in South Africa.

Childhood pneumonia is a topic I have always been able to easily relate to, starting from my days as a medical student in the busy paediatric wards where most of the very sick children had respiratory illnesses. While efforts have been instituted to ensure early recognition and treatment of children with pneumonia, unfortunately a child succumbing to death from a respiratory illness is still seen as an unfortunate but inevitable eventuality in most of our hospitals in Kenya.

Two years later, I have had many epiphanies along the way about the importance of investigating the causes of pneumonia, but a recent one has been particularly influential and has changed my mindset completely. I recently had the opportunity to attend a cross-site visit to Chris Hani Baragwanath Hospital in Johannesburg, South Africa – another PERCH study site – where I had a chance to look at a histopathology slide of lung tissue from a child who died of pneumonia. Post-mortem lung biopsy studies are carried out as part of the PERCH study in some of the participating sites because they can give researchers a much more direct, accurate diagnosis of etiology in fatal pneumonia cases. (Learn more in this 2011 article in Clinical Infectious Diseases.)

This particular post-mortem lung specimen we were examining was from a child who presented with clinical features consistent with pneumonia caused by pulmonary tuberculosis and was treated for this condition without success and died. The post-mortem analysis revealed that the child did not have TB, a bacterial infection, but instead the pneumonia had been caused by florid cytomegalovirus infection, a virus that spreads through bodily fluids and is especially dangerous for patients with compromised immune systems. If the doctors caring for him had known this, they would have treated him differently, and he might have lived. Unfortunately, we cannot get such an accurate picture of the pathogens present in the lung with current tests available for patients. It dawned on me just then how important post-mortem results are in defining the epidemiology of pneumonia in a particular setting, made possible through studies like PERCH, and which help doctors see the range of pathogens that are causing child deaths in their hospitals, so they might be more aware and ready to treat them.

I left wondering what definitive pathogens we would find if we carried out post-mortem studies on fatal pneumonia cases in Kilifi, and how this would influence our clinical management of pneumonia. Would we only find the “traditional” bacteria we expect? Or would we be opened to a whole new world of “atypical” bacteria that we occasionally treat as a last ditch resort? Would we see that the recently introduced vaccine against the streptococcal pneumonia bacteria caused a significant reduction in one of the most common “traditional” pneumonia-causing bacteria? Would our very definition of “atypical” pathogens be challenged? Would we be more confident in administering relevant antimicrobial treatment – albeit a non-conventional approach – in a more timely manner? I also wondered how post-mortem findings would compare to the induced sputum test results we gather through PERCH, which get us as close as we can to the lung while the child is living, but are still unproven, and leave us wondering if we’re really getting at the source of the infection. Most importantly, I wondered if all this knowledge could be the answer needed to save lives, reduce unnecessary use of antibiotics that can lead to resistance, and decrease the burden of pneumonia morbidity in our paediatric ward?

Otieno demonstrates NP swab

Dr. Otieno demonstrates a nasopharyngeal swab during a training session.

At a clinical level, results from post-mortem studies are easily interpretable and could improve the outcome of pneumonia cases at our hospital. At the same time, they are often difficult because they require gaining consent from a grieving parent. But because I now understood the value of post-mortem studies in protecting all our children from fatal pneumonia, I went home with a stirring in my heart to test the waters of community acceptance. I was reminded of a common saying, “better the devil you know than the devil you do not know,” for despite the challenges associated with post-mortem studies, knowledge of the bugs causing pneumonia today would give us the best chance at saving lives in the future, rather than continuing to treat what we don’t know or what we only think we know.

I am grateful for the opportunity to visit another PERCH research site in South Africa and learn from my colleagues across the continent. I come away from the experience having realized that the value of postmortem analysis in pneumonia etiology studies cannot be understated.  Working in this multi-site project has brought back the nostalgia of my internship year, including the steep learning curve, but also the accompanying fulfillment at the end of each day.

I also have a deeper appreciation that the PERCH study is indeed a landmark study. Working on this project has been an exciting experience and has given me the unique opportunity to be part of the global effort to protect millions of children around the world from pneumonia, and it has shaped my career trajectory towards pneumonia prevention strategies.

 

Juliet Otieno, MD, is a Clinical Research Training Fellow at Kenya Medical Research Institute (KEMRI) Wellcome Trust Research Programme and a member of the PERCH study team.

This is the first in a series of profiles to help IVAC partners and friends get to know our team. We thought we’d start with Lois Privor-Dumm, a long-time IVAC team member and Director of our Alliances and Information team. We caught up with Lois in between her busy travel schedule to chat about her background, her work at IVAC and what she likes to do in her spare time.

Tell us a bit about your background, what inspired you to work in global health, and how you ended up at IVAC.

Lois_PrivorDumm

Lois Privor-Dumm

I didn’t set out to work in global health, but I’ve always wanted to work internationally. I spent most of my career in the private sector and was fortunate enough to have the opportunity to launch Prevnar®, the first pneumococcal conjugate vaccine (PCV), in the U.S. and then help other countries around the world introduce the vaccine. I had worked with other vaccines and pharmaceuticals, but this experience, coming in direct contact with families impacted by pneumococcal disease, particularly meningitis, made a major impression. I saw the value that the vaccine had for countries that had introduced, but also recognized the severe disparities that existed in vaccine access around the world. I decided I could play a role in helping reduce those disparities. Although I was able to influence some change while working in pharma, I thought I could make a bigger impact by bringing my understanding of the industry and my marketing and operations experience to public health. I was fortunate to be working with experts on PCV, including Orin Levine, Mathu Santosham and Kate O’Brien, who recognized how my perspective – despite my non-traditional background for a public health career – could be beneficial. We shared the vision that new vaccine introductions did not need to see delays of 20 years or more between licensure and introduction in low-income countries, and helping devise and implement a plan to achieve this goal was very intriguing to me. 

So, I first joined Hopkins in 2005 as Director of Communications and Strategy on the Hib Initiative and soon after took on the role of Director of Access and Implementation, and later Communications, for the PneumoADIP. Our approach of addressing the needs of all stakeholders – countries, donors and suppliers – proved to be an effective way to achieve our vision, and we’ve been fortunate that we’ve been able to continue our mission through what is now IVAC. I consider myself very lucky to work with such a diverse, creative and talented team. I think it is the team and the way we work that has enabled us to work on some really tough challenges that have a big impact and achieve success.

I’m also a strong believer that there are always solutions and, at Hopkins, I value the opportunity to help facilitate those solutions, bringing both a manufacturer perspective and that of someone working with global health colleagues and country leaders. There’s been significant progress in vaccine access in the past decade or so, and I hope our work will continue to accelerate greater access and equity for vaccines and other interventions that make such a difference in peoples’ lives and contribute to healthier and more productive societies.

What projects do you work on at IVAC?

PrivorDumm_Nigeria_Vaccine_Summit

Lois Privor-Dumm and a group of children at the 1st National Vaccine Summit in Abuja, Nigeria in April 2012.

I lead the Alliances and Information team at IVAC, which includes projects covering advocacy and communications – both globally and in-country – as well as policy research and supply and access issues. I spend a great deal of time on our country-focused work, namely India, where we have been working to synthesize the evidence base and advocate for interventions for pneumonia and diarrhea at both the national and state level, and Nigeria, where we have helped analyze barriers and solutions to improve routine immunization and continue to provide technical support and encourage government accountability. I’m also excited that we’ve recently added country work with Pakistan.

Our work is varied, and there is never a dull moment. Our efforts have helped others become advocates and add their voice to important issues in child health. For instance, we’ve run advocacy workshops and collaborated with a network of trained experts to address child pneumonia and diarrhea in their countries. We support the efforts of experts including the ROTA Council, a dedicated council of scientific experts working to accelerate the introduction of rotavirus vaccines, and the Global Coalition Against Child Pneumonia. With the help of key partners, we established World Pneumonia Day to call for action on protection, prevention and treatment of the leading global killer of children. Our team also coordinates closely with IVAC’s Epidemiology and Economics & Finance teams to help communicate the results of their work and highlight the work of other researchers that relates to vaccines and child health.

Last but not least, I spend much of my time on our supply and access work, which is also very important. One of our more recent projects centers around primary container decision making and building awareness of how these seemingly straightforward decisions have significant impact on not only cold-chain space and procurement cost, but also wastage and other costs, vaccine coverage, and safety. We’ve developed a framework and have been working with various experts to help advocate for a more robust approach to considering all the implications of these decisions.

I’d be remiss not to mention, that none of this, of course, could be done without the great team of hard working and very capable individuals and students on the A&I team.

What have been some of your most rewarding or memorable experiences at IVAC?

One of my most memorable experiences was my first week at Johns Hopkins. I was working with the Hib Initiative and went to the Gambia and Bangladesh to film the BBC World Kill or Cure: Hib documentary, which highlighted the impact of the disease and efforts needed to bring a vaccine to developing countries. I remember meeting people at the labs and families that had been affected by meningitis and seeing how dedicated they were to finding the solution. I have great memories from that trip, for example touring the lab at MRC and then having tea with a family in the Gambia with little kids around very curious about all of our cameras. Bangladesh was no different, although it was tough seeing a child and her mother who did not know whether her daughter would survive the night or succumb to a severe case of pneumonia.

Another big moment was the first World Pneumonia Day in 2009 and seeing that kick off not only in the U.S. but probably more importantly around the world. That sense of pride continues when I see how many other people have taken up the cause. As we move into World Pneumonia Day’s fifth year, I am increasingly impressed by the level and volume of activities that take place – creating a global community of sorts. The fact that people are talking about antibiotic access, bringing new vaccines into countries, improving breastfeeding rates – it is very gratifying.

What is the most interesting place you’ve traveled to? Anyone who has seen your passport will know this will be a tough question to answer.

Yes, it is. Everywhere I’ve gone has been interesting. Large countries hold a lot of interest for me simply because of the level of contrast you see within the same country. I’m always struck by the disparities within the countries, but at the same time, the level of hope and generosity of those that don’t have much. I am fascinated by the diverse modes of transportation like the trucks that are brightly painted with “honk please” signs in India and Bangladesh, navigating the same roads as people walking with bundles of firewood on their heads or families piled three or four onto a small motorbike seat. In Nigeria I’ve been captivated by the people and the diversity of just about every aspect from dress to food, language and density of the population. And in some countries you’ve got such a long history that can’t help but impact you – Angkor Watt in Cambodia, Petra in Jordan, and slave quarters in Africa – it reminds me of how far the countries have come, yet how much more is still to be achieved.

Since you spend a lot of time in India and Nigeria, what similarities and differences do you see between the two?

India_National_Course

Lois Privor-Dumm and fellow participants at a national course on pneumonia and diarrhea prevention in Delhi in December 2012.

That’s a great question. I’d love to hear the perspective from those who live in one of the two countries. From my perspective though, they are similar in that they both have some wonderful, high caliber people. Both have large bureaucracies and complex environments, and I’m always impressed by

individuals who’ve been great champions of children who’ve successfully been able to navigate the environment and overcome some real barriers to getting things done. The real heroes are the ones who’ve been able to not just talk about change, but have been able to see things through, and there have been examples in both places. Another similarity is that health is very much a state subject, and implementation and sustainable change is highly dependent on the individual states. As different as priorities and ways of life are between these countries, the same can be said of individual states, and it is important to understand the priorities and players in each.

Both countries obviously have had to tackle an ongoing challenge of polio, and the related challenges and opportunities of an enormous vaccine effort. India has now gotten ahead of the curve with no cases of wild-type polio for the past two years. Nigeria still faces many challenges with polio, but has moved ahead to strengthen routine immunization and add new vaccines. 

One major difference may be in the way vaccines are portrayed in the press in each country. Although the dialogue is changing and more and more positive stories emerge surrounding vaccines, media in both countries still often like to report on sensationalist stories that do not hold scientific muster, and controversy reigns. Politicians and bureaucrats often do not recognize how political capital can be built by improving routine immunization. In Nigeria, although there are anti-vaccine sentiments, particularly surrounding polio in certain areas, health is an important issue, and leaders will take advantage of reporting on the steps they’ve taken to combat disease.

On a related note, what progress have you seen in vaccine access in India and Nigeria recently, and what do you expect to see in the next few years?

I think there is much more recognition in both countries that the systems must be strengthened, infrastructure for delivering polio immunization can be leveraged, and that a focus on bringing up routine immunization coverage will benefit new vaccines and vice versa. There has been a greater level of engagement at the state level, and I expect that this will become increasingly important moving forward. As states are implementers and must ultimately ensure that there is both adequate demand and supply, their engagement in the planning and decision-making process is key. Another area that should see improvement over the next few years is surveillance, not only to be able to measure the impact of the vaccines but also to be able to monitor any adverse events that may happen and to quickly determine if they are related to the vaccine. This has especially been a challenge in India, where activists and media have questioned whether adverse events are due to vaccine and have treated government assurances with suspicion. Good surveillance with baseline measures of child health statistics prior to introduction will make it easier to assess claims and address concerns that may be unfounded, as well as provide a basis for measuring the trends and impact that are so important to communicate to sustain public and policy maker support for vaccines.

On a personal note, when not traveling internationally, you split your time between Baltimore and West Chester. What do you like about each?

Yes, both places are great. West Chester is where I’ve lived for a long time, and where I spend a part of the week with my husband and dog. It is a historic city with brick sidewalks, and a small town where I’ve gotten to know a lot of people over the years. I consider it home, although I am originally from upstate NY. Baltimore is a great city. I love where I live in Fells Point, right by the water. I’ve got great colleagues and friends in the city, and the ability to walk to work is a huge bonus!

Do you have any interesting hobbies?

I like doing things outside, including spending time gardening, hiking and exploring different places old and new. But, there is no place I’d rather be than under the water diving (although on safari is a close second). I’ve been diving since 1992 and try to go every year. One of my favorite places is the South Pacific where you have just an amazing range of color and variety of marine life – sharks and eels and all sorts of different things. I think I like it because I’m an explorer at heart, and you never know what you’re going to find down there, and it’s a way to really relax.

What is the most recent book you’ve read?

I just read Cutting for Stone about a doctor from Ethiopia and am now reading Behind the Beautiful Forevers – Life, Death and Hope in a Mumbai Undercity. I like reading about places I’ve been or would like to go. I also have been reading some of the excerpts from an international thriller novel a friend of mine is working on publishing – can’t wait to see that in print.

Ok, just one last question. If you could have dinner with anyone, alive or dead, who would you pick and why?

That is a really tough question. Can I just throw a party?! I’d love to meet famous women who have made a difference – like Aung San Suu Kyi or, closer to home, Hillary Clinton. They are role models for how you can help change the world. And then there are people who I’m just starting to hear about who are doing some cool things with social innovation – not as well known of course, but just as inspirational. Coming from a business background, I’m interested in hearing about new ways to solve the world’s problems.

By Nick Fancourt

This the first blog in a series from the Pneumonia Etiology Research for Child Health or PERCH study team. PERCH is a multi-country case-control study of the etiology of severe and very severe pneumonia in children aged 1-59 months. Led by IVAC and funded by the Bill & Melinda Gates Foundation, PERCH operates seven research sites throughout Africa and Asia.

 

You’ve probably heard that pneumonia kills more children than any other disease, but have you ever wondered how we ‘count’ pneumonia cases? As we look at disease burden figures from around the world, how do we distinguish pneumonia from other illnesses? There are several ways to count cases, but as it turns out, it’s harder than you might imagine.

Participants at PERCH CXR workshop

Participants learned the subtleties of interpreting chest x-rays at PERCH workshop.

Why? Because we do not often get samples from the infected site (the lung) as this is very invasive. Instead, we can look at children who meet a clinical definition such as “rapid, shallow breathing,” but we know that kind of definition overestimates pneumonia cases – in other words, you get many false positives. We can also look to see if any bacteria grows in a blood sample from a child with likely pneumonia, but we miss many cases that way too, this time because of many false negatives, because bacteria aren’t always found in the blood and bacteria are not the only cause of pneumonia. The best approach has traditionally been looking at a chest X-ray or CXR, which is a frequently used tool for identifying pneumonia in clinical studies. But this leaves us with another not-so-simple question: what, exactly, does pneumonia look like on a CXR?

This is an important question for the Pneumonia Etiology Research for Child Health (PERCH) study team. With seven sites across Africa and Asia, PERCH is enrolling hospitalized children with severe and very severe respiratory symptoms according to WHO clinical definitions. The study aims to better understand which infectious pathogens are now causing childhood pneumonia in a variety of settings – rural, urban, HIV prevalent or not, differing vaccine coverage levels, and limited resource availability – so we can better plan for the interventions to prevent and treat pneumonia in the future. But to do this, we first need to know which children we think have pneumonia actually do, and which do not. 

Defining pneumonia on a CXR can be more troublesome than it sounds. First, interpretation of a CXR involves subtleties of skill and experience than can make it a somewhat subjective process when comparing two doctors’ results. Doctors in different countries, or even just on different floors of the same hospital, may read CXRs differently. So, it is important that we have a standardized approach to radiologic diagnosis. In research (and for PERCH in particular) we are also very interested in those children who definitely do not have pneumonia, as understanding what pathogens are carried by sick children both with and without pneumonia helps us to know which pathogens are causing the greatest burden of disease. So we aim for specificity in our CXR interpretations, which is different from day-to-day clinical practice, where the focus is to identify definite cases of pneumonia in order to quickly treat the child.

Participants examine chest x-rays

Participants examined chest x-rays on laptops during the workshop.

To help achieve the goal of a uniform diagnosis, the WHO developed a methodology for the standardized interpretation of pediatric CXRs. The methodology encourages simple definitions for pneumonia and aims for a high level of agreement between CXR readers. This approach was developed for vaccine impact studies, however, which are importantly different from PERCH’s questions relating to the causes of disease. Beyond PERCH there is continued demand for radiological standardization in environmental studies, antibiotic treatment studies, and epidemiologic studies of pneumonia.

Although a complete review of the WHO methodology is not a primary objective of the PERCH project, the PERCH team knew it was important to organize a comprehensive training program before we began interpreting CXRs in the study. In late August 2012, 14 physicians and radiologists (each associated with one of the seven study sites) met in London, along with collaborating colleagues from the CDC’s International Emerging Infections Program, the Drakenstein Child Health Lung Study in South Africa, and the PCV (Pneumococcal Conjugate Vaccine) Impact Study in Kenya. They were joined by members of the PERCH core team and four technical experts from Australia, Kenya, and the United Kingdom, who served as trainers for the meeting. The purpose of this meeting was to realign the WHO methodology to current study goals, identify ways in which it can be optimized, and ensure PERCH CXR readers have a harmonized approach to diagnosing radiological pneumonia.

X-rays may be one of medicine’s oldest technologies, but our challenge was to improve their interpretation to help a very contemporary study. This gathering allowed the team to think critically about how CXR diagnosis can best serve PERCH’s needs, and the outcomes will help not only the PERCH project, but broader pneumonia diagnosis and research efforts as well. We were able to refine the outcomes we are gathering from CXRs, to be clear on which children have normal CXRs and which definitely have pneumonia, while at the same time calibrate CXRs from PERCH against the WHO methodology to extend these definitions beyond the vaccine impact setting. We now have a group of highly trained CXR readers who will be providing assessments on all of the CXRs from cases within the PERCH study, and we have established a feedback mechanism so that the quality and safety of CXRs at each site is maximized both within the study and beyond.

With this important step now complete, we are armed to interpret the subtle CXR findings that a study like PERCH may identify. So now, for PERCH, the ‘counting’ begins.

 

Nick Fancourt is a PhD candidate at the Johns Hopkins Bloomberg School of Public Health and member of the PERCH study team. He is also an International Fulbright Science and Technology Fellow.

The views and information expressed within this blog are the author’s alone and do not represent the Fulbright Program or the U.S. Department of State.