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Keyword: perch

By Dr. Samba Sow

Dr. Samba Sow is Director General of the Center for Vaccine Development – Mali (CVD Mali) and a Professor of Medicine at the University of Maryland School of Medicine. This blog is cross-posted from Lancet Global Health.

Scientific research, by definition, is about process. Scientists must follow carefully developed guidelines and established protocols to make sure research is conducted validly, accurately, and ethically. As any field researcher knows, meticulous attention to detail is challenging at the best of times, when obstacles like staff turnover, equipment shortages or delays, power outages, strikes, security concerns, and disruptive rumours are not out of the ordinary. But these “everyday” logistical challenges of doing research are further compounded when political instability surrounds your research site.

In the past year, my colleagues and I at Center for Vaccine Development (CVD) Mali faced immeasurable challenges in keeping research efforts going when the insurgency that has afflicted our country for decades began moving southward and threatening the capital city of Bamako, where our research centre is located. Read the full blog at the Lancet Global Health.


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. 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.

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.

Accurately diagnosing pneumonia can be very difficult in the resource-challenged settings of developing nations.  IVAC’s PERCH study allows the opportunity to explore a new technology that can help improve the accuracy and speed of pneumonia diagnoses. This type of innovation enables us to reach more children and save more lives, while also furthering our understanding of the epidemiology of this disease. In advance of World Pneumonia Day, marked each year on November 12, we’re excited to offer a look at the digital future of using state-of-the-art technology in diagnosing and treating respiratory illness in the world’s poorest settings.

By Eric D. McCollum, MD    

Digital auscultation in The Gambia

Digital auscultation to record and analyze the breath sounds of a patient, as seen in The Gambia. Photo by Eric D. McCollum.

The scene is familiar, an African healthcare worker with only several months of training but working as the community doctor, is setting up his temporary pediatric clinic in a remote village beneath the shade of a baobab tree. The queue is long, as mothers and their children from this small community and beyond have waited since the early morning for their child to be seen. Some children are sick and need medicine, and some are not and instead need only a weight check and their immunizations. The penetrating tropical sun begins to rise signaling the beginning of the clinic. Fortunately, the girth of the baobab tree provides the necessary relief. “Okay, let’s begin,” the healthcare worker states in the local dialect as his eyes meet with the mother of the first child, a toddling 17 month old girl with only a dirty brown shirt covering her body. “How can I help you?”

“She is sick with fever and cough for four days,” the mother answers, brow tense with concern.

The healthcare worker continues with his routine follow-up questions until this trite scenario takes an unexpected, most interesting turn. He reaches into his pocket and pulls out his mobile phone and attaches to it what looks to be almost a miniature suction cup with fine beads covering its face. Several mothers waiting in the line take notice and turn to each other talking quickly. The worker pushes several buttons on his phone and then presses the device onto the bare chest of the girl, who remains clinging to her mother’s breast. He then sits back, rests against the heavy trunk of the baobab tree, punches a button on his mobile phone, and waits. After several short moments the phone then beeps, and his eyebrows raise up in response. “Your child has pneumonia… and needs antibiotics.”

The continent that skipped over clunky technology like landline phones and large desktop computers in favor of slick mobile phones and the internet may also be leapfrogging what many consider to be the first medical device, the stethoscope.  Learning to interpret the sounds captured by the stethoscope can take years of practice.  Even then, opinions processed by the ears of vastly experienced physicians can still differ.  The stethoscope is quite simply “the art of medicine.” Given these inherent drawbacks of traditional stethoscopes, the World Health Organization’s (WHO) diagnostic criteria for childhood pneumonia intentionally ignores respiratory sounds altogether. This allows healthcare providers with minimal training who work in remote areas, often where childhood pneumonia mortality is greatest, to still diagnose and treat pneumonia. The drawback of the WHO not including respiratory sounds in its diagnostic criteria is that many children with pneumonia are incorrectly diagnosed and thus incorrectly treated, a potential danger to the health of the child and waste of scarce financial resources. 

Digital auscultation

Digital auscultation at work. Photo by Eric D. McCollum.

Art may soon be giving way to cutting edge clinical science and computer technology. Electronic devices exist that act similarly to traditional stethoscopes, except that they generate digital sound waves that can be fed into computer software programs. In fact, they are under active study and continued refinement, such that a small mobile device that contains sophisticated software may soon be able to accurately interpret chest sounds for use in clinical care of children. The Pneumonia Etiology Research for Child Health study, or PERCH, is a large collaborative project funded by The Bill and Melinda Gates Foundation currently ongoing in seven developing countries throughout Africa and Asia.  PERCH is utilizing digital stethoscopes to record chest sounds from children hospitalized with life-threatening pneumonia. These sounds are then uploaded onto local internet servers that can be accessed by co-investigators at The Johns Hopkins School of Public Health International Vaccine Access Center and the Johns Hopkins University Engineering Department. These investigators are in turn creating novel computer software algorithms that can interpret these sounds and therefore accurately diagnose childhood respiratory illness. This could mean more efficient use of childhood pneumonia resources and even better outcomes for children sick with pneumonia, the number one cause of childhood mortality globally.

While digital auscultation devices and computer software able to interpret chest sounds from children may still be in experimental phases, it is not unrealistic to envision a time where healthcare professionals located anyplace and anywhere, even beneath a Baobab tree in a remote African village, can utilize this technology to accurately diagnose and provide life-saving treatments to children with pneumonia. So listen up carefully on this World Pneumonia Day, a revolution is coming.

Dr. Eric D. McCollum is a Post-doctoral Fellow in the Division of Pediatric Pulmonology at the Johns Hopkins School of Medicine, and a member of the PERCH study team.