Five Questions: PERCH

This month we interviewed Dr. Laura Hammitt who is an Associate Professor at the Johns Hopkins Bloomberg School of Public Health. She served as a co-author of a recent Lancet paper on the Pneumonia Etiology Research for Child Health (PERCH) study, a study conducted in seven countries that found that the majority of cases of pneumonia in children are caused by viruses and not bacteria. This finding is important because over 100 million cases of pneumonia are reported worldwide every year in children five years old or younger — killing 900,000. Researchers say their study highlights the growing need for new vaccines to protect children from this dangerous infection. Additionally, scaling up the technique used to determine the cause of childhood pneumonia may also help reduce the global overuse of antibiotics and provide guidance on appropriate antibiotic prescribing in suspected pneumonia cases. Read our five-questions interview to learn more about this fascinating study.

1. Can you please tell us a little bit about the aims of this study and how it was conceived?

Globally, pneumonia sickens about 150 million children every year, hospitalizes at least 11 million and remains a leading killer of children. About 900,000 children died of pneumonia in 2015 according to the latest estimates—more children than from HIV, TB, Zika, Ebola, and malaria combined. Most of the existing knowledge on the causes of childhood pneumonia comes from studies done in the 1980s and 1990s. The main causes of pneumonia now are not the same as they were in past decades, in part due to highly effective vaccines. H. influenzae type b (Hib) and pneumococcal disease used to be top causes of pneumonia but are now much less common thanks to widespread use of highly effective vaccines to prevent these diseases. New data on the causes of severe pneumonia are critical for decision makers involved in the fight against pneumonia. Quantitative information about etiology allows researchers, policy makers, funders, and pharmaceutical manufacturers to strategically target the bacterial and viral causes of pneumonia that are most significant.

2. How has this study addressed the challenges that previous studies have faced and what added value does it provide to existing evidence on the causes of pneumonia?

The PERCH study methods were rigorous and standardized across all study sites, giving us confidence in the findings. Any variation (or lack of variation) in results across sites represents true differences rather than differences in the way the study was conducted at each site. PERCH also used a novel analytic method. It's very hard to identify the causes of pneumonia in children because it is difficult to access the lung itself. Therefore, scientists and clinicians look for bacteria and viruses in samples from a child's nose, throat, blood, and other body fluids that may indicate what is infecting the lung. PERCH solved an analytical problem that limited previous studies by devising a new way to combine evidence from test results from multiple samples. The Bayesian Analysis Kit for Etiology Research, or BAKER, method factors in the limitations and strengths of each laboratory test to estimate what’s causing pneumonia in each child. BAKER is now “open source” and has already been used to help answer other challenging questions like the causes of infection in newborns.

3. This study highlights the need for new vaccines to tackle respiratory syncytial virus (RSV) and other viruses. What exactly is RSV and why is it important? What role would such vaccines against it play in the fight against antibiotic overuse and antibiotic resistance?

RSV is a common and contagious respiratory virus that usually causes mild, cold-like symptoms. Nearly all children will have an RSV infection at least once by their second birthday. While most people recover quickly, RSV can be serious, especially for infants and older adults. In infants, especially those less than six months old, RSV infection can cause inflammation of the airways, which may require hospitalization. In the PERCH study, RSV was the leading cause of pneumonia. Given the importance of RSV as a cause of pneumonia, finding an effective intervention to prevent RSV is a priority. Preventing RSV – and thereby reducing the number of cases of pneumonia - would result in fewer courses of antibiotics prescribed for pneumonia treatment, thereby aiding in the fight against antibiotic overuse and antibiotic resistance.

4. The World Health Organization guidelines recommend giving antibiotics to children suspected of having pneumonia. Does the PERCH study provide any insight into the appropriateness of these recommendations or future directions in pneumonia treatment?

Bacterial pneumonia is still found across the world and is more likely to result in more serious disease, so antibiotics still play an important role in treating pneumonia and preventing death. But strategies to limit unnecessary antibiotic use are needed. Targeted improvements in diagnostics and testing can aid us in that pursuit, and some of this was explored in PERCH (such as automated chest x-ray reading and digital auscultation). Ultimately we would like to use pneumonia etiology data and clinical/lab measurements to identify children that almost certainly do/do not need antibiotics.

5. What are some important implications of this study’s findings, and what opportunities does it present for antibiotic stewardship and public health in general?

Respiratory syncytial virus (RSV) and other viruses (totaling 61%) now appear to be the main causes of severe childhood pneumonia in low- and middle-income countries, highlighting the need for vaccines against these pathogens. RSV was the leading pathogen (31%) at all sites. Although we studied over 30 pathogens, only 10 pathogens were responsible for the vast majority (about 8 in 10 cases): RSV, rhinovirus, human metapneumovirus (hMPV), parainfluenza, pneumococcus, Haemophilus influenzae, TB, Staphylococcus aureus (Staph), influenza, and Pneumocystis jirovecii. Because most pediatric cases of pneumonia are now viral, needless administration of antibiotics in those cases promotes the march of antibiotic resistance. PERCH lays the groundwork to be able to develop and evaluate clinical decision support tools that predict each child’s need for antibiotics from readily obtainable clinical data.