Navajo Indian children remain at risk for invasive pneumococcal disease

Rates of invasive pneumococcal disease caused by 7-valent pneumococcal conjugate vaccine serotypes may have been eliminated in Navajo Indian populations, according to recently published findings.

However, Navajo children continue to have a threefold to fivefold risk for all serotypes of invasive pneumococcal disease compared with children in the general U.S. population.

Before introduction of PCV7 (Prevnar, Wyeth), Navajo populations had significantly higher rates of invasive pneumococcal disease than the general U.S. population, and about half of cases in children involved PCV7 serotypes.

The researchers documented case characteristics of invasive disease and serotyped isolates among Navajos from 1995 to 2006.

Of 1,508 cases of invasive pneumococcal disease in the analysis, 447 occurred in children younger than 5 years.

From 1995 to 1997, per 100,000 Navajo population, there were 210 cases of invasive pneumococcal disease among children aged younger than 1 year, 263 cases among children aged 1 to 2 years and 51 cases among children aged 2 to 5 years; there were zero cases per 100,000 population in those age groups during 2004 to 2006 (P<.001).

An 81% decrease in rates of invasive pneumococcal disease because of vaccine serotypes was observed among adults aged 65 years and older (95% CI, -98% to -9%).

The rate of nonvaccine serotype disease decreased by 35% among adults aged 18 to 39 years (95% CI, -57% to -1%). In all other age groups, rates of nonvaccine vaccine serotype disease remained unchanged. – by Rob Volansky

Weatherholtz and colleagues demonstrate significant benefits in reduction of PCV7 serotypes in young children and provide evidence of herd immunity in children too young to receive vaccine. They also demonstrate these phenomena in adults.

Given the high incidence of nonvaccine types in the community (only 13% of cases of invasive disease in the elderly at baseline were vaccine types), they point out that a significant burden of nonvaccine serotype disease remains.

Did the vaccine lead to an increase in nonvaccine type disease? This is difficult to determine in an observational study. The authors believe that the “lack of significant replacement disease where PCV7 has been in use now for >12 years is an important finding.”

The devil is unfortunately, as usual, in the details. At baseline, the single biggest serotype contributor to invasive pneumococcal disease in children was serotype 5, an epidemic serotype, rarely carried in the nasopharynx for long prior to disease, and generally far less common in the rest of the United States; when the reduction in serotype 5 is removed from the analysis, then replacement was significant in most age groups. Further, serotype 6A, to which the vaccine confers both direct and indirect protection through interruption of carriage, was also included as a nonvaccine type. This type also almost disappeared over time. The largest significant replacement by rate was type 19A, which predominates now in most of the rest of the United States, followed by another carried strain, serotype 3. Increases in the rarely carried types 1 and 7F were also observed, but these epidemic types may have varied upward as a secular trend in epidemic types, just as serotype 5 went down.

The authors make the point that these rarely carried epidemic type changes have not yet been causally linked to PCV7 introduction. It is incontrovertible, however, that PCV7 leads to complete replacement in carriage of vaccine types with nonvaccine type, and it is also now as incontrovertible that the replacing carriage types following PCV7 introduction leads to an increase in invasive pneumococcal disease, albeit to a lesser degree than the replacement in the nasopharynx.

The data from this study are consistent with these observations. Replacement has occurred among certain commonly carried nonvaccine types, leading to an increase in disease due to those types, following PCV7 introduction, in this community. Fortunately, the benefits in reduction of invasive pneumococcal disease due to vaccine type pneumococci outweigh the small increases in disease due to those nonvaccine types for most communities.

– Keith P. Klugman, MD, PhD
– William H. Foege Professor of Global Health at Rollins School of Public Health, Emory University

Weatherholtz R et al. Clin Infect Dis. 2010;50:1238–1246.