The incidence of invasive pneumococcal disease among children younger than 5 years with sickle cell disease plummeted during 2001–2004, according to a new study which suggests that credit belongs to the 7-valent pneumococcal conjugate vaccine introduced in 2000.
“Our study clearly demonstrates that the incidence of invasive pneumococcal disease dramatically decreased after the introduction of pneumococcal conjugate vaccine into the routine childhood immunization schedule,” Dr. Natasha B. Halasa and colleagues wrote.
The data were derived from the follow-up of 2,026 individuals with sickle cell disease (SCD) enrolled in Tennessee Medicaid (TennCare) from Jan. 1, 1995, through Dec. 31, 2004 (Clin. Infect. Dis. 2007;44:1428–33).
During the study period, 37 individuals (0.6–44 years) with SCD had invasive pneumococcal disease (IPD), and no individuals with SCD had more than one episode of IPD during the study period.
In a comparison of the pre-PCV period (1995–1999) with the post-PCV period (2001–2004), the IPD rate decreased 91% in children aged less than 2 years (from 3,600 to 335 cases per 100,000 person-years) and by 93% in children under 5 years (from 2,044 to 134 cases per 100,000 person-years). In the post-PCV era, a mean 69% of children less than 2 years had evidence of receiving one or more doses of PCV during the prior year.
Although penicillin prophylaxis and pneumococcal polysaccharide vaccine have decreased the rate of invasive pneumococcal disease (IPD) in this high-risk population, breakthrough disease still occurs—most commonly among children younger than 3 years—and IPD continues to be a leading cause of death in children with SCD, the researchers explained.
This study, which showed a mean 92% drop in infection after 2000 among children younger than 5 years, raises important questions about the continued use of penicillin, according to Dr. Martin H. Steinberg, whose accompanying editorial poses the question, “Is prophylactic penicillin needed if conjugate vaccination is so effective?”
“Widespread penicillin use is not risk free. Penicillin-resistant strains of S. pneumoniae are increasing in number, and about 40% of isolates associated with sickle cell disease have some measure of resistance,” said Dr. Steinberg, with the departments of medicine, pediatrics, and pathology and laboratory medicine at Boston University (Clin. Infect. Dis. 2007;44:1434–5).
Dr. Steinberg believes that the susceptibility of S. pneumoniae to penicillin might be decreasing, and he points out that prophylaxis is less effective in carriers of intermediate-resistant and resistant serotypes.
In North America, the 7-valent conjugate vaccine protects against greater than 70% of the serotypes isolated from patients in the preconjugate vaccine era, he said. “However, two-thirds of the serotypes not included in the vaccine were susceptible to penicillin, and the use of this vaccine appeared to decrease the number of antibiotic-resistant, pneumococcal infections (N. Engl. J. Med. 2006;354:1455–63).”
Pending the arrival of a more efficacious 13-valent vaccine, antibiotic prophylaxis could be useful, Dr. Steinberg explained, adding that suboptimal compliance with preventive treatment limits penicillin's effectiveness.
In the Tennessee cohort, only 25% to 30% of the children with SCD who were younger than 5 years had their penicillin prescriptions filled for more than 270 days of a 1-year period. These numbers are similar to those found in an earlier study (JAMA 2003;290:1057–61), Dr. Halasa and colleagues said.
Because ongoing penicillin prophylaxis is difficult to sustain, the effectiveness of this approach in practice appears to be less than that demonstrated in the landmark randomized, clinical trial in which the antibiotic produced an 84% reduction in the rate of IPD among children with SCD the researchers said (N. Engl. J. Med. 1986;314:1593–9).
This study has several limitations, according to Dr. Halasa and her team: The number of individuals with SCD and IPD was small and consisted of patients who lived in surveillance counties in Tennessee and who were enrolled in the Tennessee Medicaid program.
“The pre-PCV era IPD rates in individuals with SCD in this study, however, were nearly identical to those reported from other locations, suggesting that these results are generalizable to others with SCD in the United States,” they argue.
A second limitation was that vaccination records, especially from the period prior to the introduction of PCV, may not have captured receipt of all pneumococcal vaccines by persons enrolled in TennCare.
With the universal administration of PCV to all children, both with and without SCD, it is expected that the rates of IPD will continue to decrease among all children, the authors wrote.
“However, ongoing monitoring of these rates and serotyping of all invasive pneumococcal isolates must remain an important priority to monitor whether serotype replacement will occur under continued vaccine pressure. Despite this caution, our data indicate that PCV is effective for reducing the rate of IPD, especially among vulnerable populations,” they concluded.