Viral Infection Most Common Cause of Pneumonia in Children

Jenni Laidman

February 27, 2015

Respiratory viruses were responsible for most cases of community-acquired pneumonia among hospitalized children, and one in four children studied had multiple pathogens, according to a study published in the February 26 issue of the New England Journal of Medicine. The new findings may redirect clinical decisions and prescriptions, according to one expert.

Seema Jain, MD, medical epidemiologist, Influenza Division, Centers for Disease Control and Prevention (CDC), Atlanta, Georgia, and colleagues enrolled 2638 children younger than 18 years who were diagnosed with pneumonia in the population-based surveillance study. The children were hospitalized in three hospitals in Memphis and Nashville, Tennessee, and Salt Lake City, Utah, between January 2010 and June 2012.

"This is foundational work in pneumonia," Samir S. Shah, MD, MSCE, professor, Department of Pediatrics, University of Cincinnati College of Medicine, Ohio, told <>Medscape Medical News. Dr Shah was not involved in the current research.

"Etiology of pneumonia has historically been very difficult to determine," he continued. "What this paper has done is used the best methods we have available for the identification to help us really understand the etiology of pneumonia overall, and broken down by age." Dr Shah, who is also director of the Division of Hospital Medicine and James M. Ewell Endowed Chair at Cincinnati Children's Hospital Medical Center, is a coauthor of the Pediatric Infectious Disease Society and the Infectious Diseases Society of America clinical practice guidelines for the management of pneumonia in infants older than 3 months.

The researchers found that 70% of the hospitalized children in the Etiology of Pneumonia in the Community (EPIC) study were age 4 years or younger, with a median age of 2 years. Children younger than 2 years made up 45% of those in the study.

Overall, 2358 (89%) children had radiographic evidence of pneumonia. Of those, 497 (21%) required intensive care and 3 (<1%) died. Of the 2222 children with radiographic evidence and specimens for bacterial and viral testing, 66% (1472) were positive for one or more viruses, 8% (175) carried bacterial pathogens, and 7% (155) had both bacterial and viral pathogens.

Pneumonia incidence during the study period was 15.7 per 10,000 in children younger than 18 years, according to US census data from the hospital catchment areas for each of the study years. The incidence in children younger than 2 years was 62.2 per 10,000 children.

The most common viral pathogen was respiratory syncytial virus (RSV), found in 28% of samples. RSV was also the most common cause of pneumonia in children younger than 2 years. In children younger than 5 years, 37% were diagnosed with RSV compared with 8% of older children.

Dr Shah said the study data on Mycoplasma pneumonia were particularly striking. "It accounts for a large portion of cases of pneumonia — 19% in children 5 and older — that's one out of five children," Dr Shah told Medscape Medical News. However, treatment of Mycoplasma pneumonia is controversial because many people who are infected do not get sick or get better without treatment. "Yet there has been some evidence that treatment may offer some benefit," with length of stay decreasing among children treated on the first day of hospitalization compared with those treated later or not at all.

Another important finding, Dr Shah said, was the fact that although 2358 children had a radiologic finding of pneumonia, the vast majority had pneumonia caused by virus. "Right now, children diagnosed with pneumonia because of a chest X-ray end up receiving antibiotics. Now we know that most cases of pneumonia, even those with abnormal X-ray findings, are caused by viruses, it's not clear that all children will need antibiotics."

In a news release, CDC Director Tom Frieden, MD, MPH, called the study "ground-breaking," saying it showed "how badly we need faster, less-expensive diagnostic tests for doctors to accurately diagnose the cause of pneumonia so they can effectively treat it."

Lead author Dr Jain noted in the release that the study underlines the role of viral infections. "The data gathered from this study add to the evidence base that respiratory virus infections lead to pneumonia hospitalizations and complications in children."

Although this study included multiple tests to determine etiology, such as separate polymerase chain reaction tests for a variety of pathogens, "the Holy Grail is a single test that will give us an answer," Dr Shah said.

Two other viruses were also more common in children younger than 5 years: adenovirus (11% overall; 37% among children younger than 5 vs 8% among older children) and human metapneumovirus (13% overall; 15% for children younger than 5 years vs 8% among older children).

Among the whole study population, human rhinovirus was the second most common virus, found in 22% of all cases. However, it also showed up in 17% of asymptomatic controls enrolled at the same three sites during the study period, muddying any interpretation of the role of rhinovirus in pneumonia.

The researchers conclude, "Effective antiviral vaccines or treatments, particularly for RSV infection, could have a mitigating effect on pneumonia in children. The low prevalence of detection of bacterial pathogens probably reflects both the effectiveness of bacterial conjugate vaccines and relatively insensitive diagnostic tests."

Several coauthors report various financial relationships with GlaxoSmithKline, Forest Pharmaceuticals, Cubist Pharmaceuticals, MedImmune, Novartis, Pfizer, Juvaris Bio-Therapeutics, BioFire Diagnostics, BioMerieux, Affinium Pharmaceuticals, Astute Medical, Crucell Holland BV, BRAHMS GmbH, Rapid Pathogen Screening, Venaxis, Cempra Pharmaceuticals, CareFusion, Accelerate Diagnostics, Crucell/Janssen/J&J, Genentech/Roche, Rempex/The Medicines Company, Vical, Cubist, Bayer, and Cerexa. One coauthor has a patent related to reovirus vaccines to be licensed to Vanderbilt University. Another coauthor reports patents related to preparation and use of a recombinant influenza A virus M2 construct vaccine, materials and methods for respiratory disease control in canines, and an effective vaccine against pandemic strains of influenza viruses. Another coauthor reports a patent pending related to a sterile blood culture collection system. The other authors and Dr. Shah have disclosed no relevant financial relationships.

N Engl J Med. 2015;372;835-845. Abstract


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