Serotypes 19A and 14 are the most common types of pneumococcal strains found in Italian children aged 5 years and younger, and results of a new study indicate that the 13-valent pneumococcal conjugate vaccine appears to be the most effective means of preventing the disease.
Susanna Esposito, MD, and colleagues, of the Università degli Studi di Milano in Italy, studied 510 children from September 2008 to March 2011 who had a laboratory-confirmed diagnosis of community-acquired pneumonia (CAP).
The researchers said pneumococcal CAP was found in 73 cases, or 14.3% of children, and complicated pneumonia was more frequent in these cases, with empyema as the main complication. The most common serotypes were 19A (17 cases); 14 (10 cases); 4 (five cases); and 3 (four cases).
The researchers compared these rankings with current pneumococcal conjugate vaccine (PCV) strain coverage and estimated that “the theoretical coverage offered by the available pneumococcal conjugate vaccines was calculated to be 31% for PCV7 [Prevnar, Wyeth], 37% for PCV10 and 71% for PCV13 [Prevnar13, Wyeth].”
Because PCV13 is the only vaccine that protects against serotype 19A, it is the best choice for administration in Italy, where only 50% of children are vaccinated, Esposito and colleagues concluded.
“On the basis of these data and the composition of the new vaccines, it can be concluded that PCV13 seems the best solution at the moment available to overcome the limitations of PCV7, whereas the theoretical protection offered by PCV10 against bacteremic CAP is only slightly higher than that of PCV7,” Esposito and colleagues wrote.
Disclosure: This study was funded by a grant from Pfizer, Italy.
The manuscript by Esposito and colleagues describing otherwise healthy children in Italy with clinical symptoms of pneumonia and abnormal X-rays consistent with pneumonia, provides several important insights into pneumococcal colonization/infection. With information on the use of conjugate pneumococcal vaccines (PCV7 in this study) in these children, the serotypes included in the vaccine, and identification of the serotypes colonizing/infecting these children, these investigators have confirmed the lack of high efficacy of the conjugate pneumococcal vaccines for pneumonia (in contrast to the superb efficacy in bacteremia and meningitis), the emergence of non-vaccine serotypes (particularly 19A) during the use of PCV7, as was also noted in the United States, and the existence of other potentially invasive serotypes, not even included in the newer PCV13 vaccine!
Of note, data recently presented by Sheldon Kaplan (Baylor College of Medicine) and an eight-center pneumococcal surveillance group in the US, similar to the Italian group presenting this manuscript, documented that PCV13, launched in the US in 2010, has already decreased the incidence of serotype 19A invasive disease in children (IDSA, Boston, October 2011). However, as pointed out by Esposito and colleagues, eradication of one colonizing serotype is often followed by replacement of another. Newer, even more comprehensive pneumococcal vaccines are likely to be needed in the future.
The extremely sensitive PCR technique that detects fragments of pneumococcal DNA in serum may be a bit too sensitive in diagnosing truly invasive pneumococcal pneumonia, as we learned from trying to extrapolate data from adults on the use of a test for pneumococcal antigen in the urine to diagnose pneumonia. Kids with cough and X-ray changes (many who probably had viral pneumonia) had an unacceptably high false-positive rate of pneumococcal antigenuria, forcing us to abandon this test for diagnosis in children (Dowell S. Clin Infect Dis. 2001;32(5):824-825).
Since pneumococcal antigens from colonizing strains may be present in urine in children with presumed viral pneumonia without the children actually having pneumococcal pneumonia (given the changes in the respiratory tract mucosa that occur with viral infection), it seems logical to speculate that the same movement of pneumococcal components into plasma may be detected with an even more sensitive test, PCR. Perhaps pneumococcal antigenuria (and PCR) might pick up “early” invasive disease that has not yet developed into true pneumonia? Do these kids all require antibiotic treatment, or is there a spontaneous cure rate in healthy kids with very early infection? For children with viral pneumonia (not assessed in the Esposito manuscript), perhaps the plasma PCR test might be able to detect viral/bacterial co-infection?
It is striking that 92% of children were diagnosed solely based on plasma PCR in this population of children with clinical pneumonia. It may be premature to either mandate antibiotics for all children with a positive plasma PCR test, or assume that all of these children had classic “bacteremic pneumococcal pneumonia,” but that should not prevent us from congratulating the authors on their extensive work in moving us much closer to a test that we need desperately: a sensitive and specific rapid test to diagnose invasive pneumococcal pneumonia, particularly in children who have been given antibiotics prior to diagnostic testing.
As recently reviewed (PIDS/IDSA Pediatric CAP Guidelines 2011; www.idsociety.org), the blood culture is sorely lacking in sensitivity, acute inflammatory markers don’t have adequate predictive value, and you just can’t get the 2-year-old to produce sputum!
John S. Bradley, MD
Division of Infectious Diseases, Rady Children's Hospital
Associate Clinical Professor of Pediatrics at University of California San Diego
Disclosure: Dr. Bradley reports no relevant financial disclosures.