09:13pm Sunday 19 January 2020

Serious lung infections in children jump after introduction of pneumococcus vaccine

(SACRAMENTO, Calif.)A comprehensive national study by UC Davis researchers has found that the introduction of an early childhood vaccine for bacterial pneumonia nearly a decade ago has decreased the incidence of pneumonia, but the drop was accompanied by a dramatic increase in the incidence of a serious and sometimes life-threatening complication.

The researchers conjecture that the doubling of the incidence of the complication, which causes pockets of purulence, or pus, around the lungs, may partly be the result of the vaccine eliminating certain types of pneumococcus, creating the opportunity for other bacteria to take its place.

Published in the January issue of the journal Pediatrics, the study examined the incidence of empyema, a complication of pneumonia that is a severe infection in a cavity between the lung and the chest wall. Despite a 50 percent drop in hospitalizations from pneumonia due to pneumococcus since the introduction of the vaccine in 2000, and an overall decrease in all bacterial pneumonias, the empyema rate jumped 70 percent.

In 2000, the Food and Drug Administration licensed PCV7, a vaccine designed to protect infants and children from the seven serotypes, or strains of microorganisms, most commonly responsible for serious infections from Streptococcus pneumoniae, which is responsible for most community-acquired bacterial pneumonias.

Su-Ting T. Li, the study’s lead author, said that while the study does not directly examine the reason for the increased empyema rate, it may be because the vaccine eliminated competition from the seven targeted pneumococcal serotypes that commonly cause pneumonia, creating opportunities for pneumococcal serotypes not targeted by the vaccine.

Though responsible for less pneumonia overall, those serotypes may lead to more complicated pneumonias, such as empyema, when they do occur. In addition, the incidence of empyemas caused by staphylococcus, another bacterial cause of pneumonia not addressed by pneumococcal vaccines, appears to be increasing. This increase in staphylococcal empyemas may be due to more virulent and antibiotic-resistant forms of staphylococcus, such as methicillin-resistant staphylococcus aureus (MRSA).

“This may be occurring because the vaccine does not affect the types of microorganisms causing empyemas,” said Li, an assistant professor in the Department of Pediatrics at UC Davis Children’s Hospital. “The vaccine may be getting rid of the pneumococcal bacteria that cause most pneumonia and other types of invasive pneumococcal disease. But the bacteria that are left over that it doesn’t protect against that are more likely to cause empyema may increase because they don’t have to compete against the other pneumococcal bacteria anymore.”

The researchers launched the study after learning of conflicting regional data on empyema incidence since the introduction of PCV7. Since its introduction, empyema incidence was reported to have increased by 88 percent in Utah and 400 percent in California. Texas, on the other hand, reported a 55 percent decrease. The incidence in Quebec, Canada, reportedly remained unchanged.

The study employed the nationally representative Kids’ Inpatient Database (KID) to estimate the total annual hospitalizations of children with empyema 18 and under in the United States. The researchers analyzed KID data from 1997, 2000, 2003 and 2006. The estimated counts for these years were then converted into annual incidence rates per 100,000 children using U.S. Census Bureau data. The findings were then compared to incidence rates between 1997 and later years to gauge the impact of the PCV7 vaccine on hospitalizations.

The researchers found that during 2006 an estimated total of 2,898 hospitalizations of children 18 and under in the U.S. were associated with empyema. The empyema-associated hospitalization rate was an estimated 3.7 per 100,000, an increase of almost 70 percent over the 1997 empyema hospitalization rate of 2.2 per 100,000. The rate of complicated pneumonia, which includes empyema, pleural effusion, or bacterial pneumonia requiring a chest tube or decortication, similarly increased 45 percent to 5.5 per 100,000.

While hospitalization rates associated with complications from pneumonia increased, the rate of bacterial pneumonia hospitalizations decreased 13 percent to 244.3 per 100,000. The rate of invasive pneumococcal disease — pneumonia, sepsis or meningitis caused by Streptococcus pneumoniae — decreased 50 percent to 6.3 per 100,000.

The researchers also found that since the introduction of the PCV7 vaccine, the average age of children with empyema is decreasing. In 2006, the mean age for children hospitalized for empyema decreased to just above 6 years, one year younger than the mean age of slightly more than 7 in 1997. For children younger than 5 years old, the rate of empyema hospitalizations increased 100 percent, from 3.8 per 100,000 in 1997 to 7.6 per 100,000 in 2006.

The finding is important because empyemas, though relatively uncommon, can be life-threatening. Empyemas are a collection of pus in the pleural space between the outer surface of the lung and chest wall that sometimes develop from an infection secondary to the pneumonia. Empyemas can impede breathing by pressing against the lung. Early intervention is key to decreasing mortality. Interventions range from antibiotics, to minimally invasive drainage with a catheter, to the riskier open surgical removal of the layer of pus restricting lung expansion.

Li and co-author Daniel Tancredi, an assistant professor in the Department of Pediatrics at UC Davis Children’s Hospital, said parents should continue to immunize their children with the pneumonia vaccine because it has proven highly effective in combating invasive pneumococcal disease.

“They should certainly immunize their kids because the fraction of pneumonia that tends to result in empyema is still low, so there is a huge benefit from immunization,” Tancredi said.

But parents should be watchful for complications from the types of bacterial pneumonia not covered by the vaccine. Each year, empyema causes significant morbidity with prolonged hospitalizations and multiple invasive procedures.

Li said an expanded vaccine that would cover the serotypes associated with empyema is in the works and is expected to be approved and distributed within a few years.

“We’re hoping that once the new vaccine is approved and licensed and distributed to patients we would look at the data again and that we would find decrease in the incidence of empyema,” said Li. “This paper demonstrates the value of nationally representative administrative data sets because they allow researchers and clinicians to address an issue in which regionally specific data sets yielded mixed results,” Tancredi said.

UC Davis Children’s Hospital is the Sacramento region’s only comprehensive hospital for children. From primary care offices to specialty and intensive care clinics, pediatric experts provide compassionate care to more than 100,000 children each year and conduct research on causes and improved treatments for conditions such as autism, asthma, obesity, cancer and birth defects. The hospital also has the only level 1 pediatric trauma center and pediatric emergency room in the region. For more information, visit the UC Davis Children’s Hospital Web site.

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