Invasive pneumococcal disease in Indigenous people in north Queensland: an update, 2005–2007

The 23-valent pneumococcal polysaccharide vaccine (23vPPV) was made available to eligible Indigenous adults in north Queensland from 1996, and the 7-valent pneumococcal conjugate vaccine (7vPCV) became freely available for Indigenous children aged under 2 years (with a dose of 23vPPV at age 24 months) from the latter part of 2001. This meant that, from 2001, invasive pneumococcal disease (IPD) became preventable not only in Indigenous adults, but also, for the first time, in Indigenous children.

In the 3 years after the introduction of 7vPCV (2002–2004), we documented a rapid decline in the annual incidence of IPD in Indigenous children in north Queensland.1 Furthermore, it appeared that the use of 7vPCV in children was associated with an indirect protective effect in older Indigenous people, who were not eligible for this vaccine.1 This indirect “herd immunity” effect is believed to occur because 7vPCV interrupts the transmission of vaccine-type pneumococci by reducing their acquisition in the nasopharynx of immunised children.2

However, initial enthusiasm about the capacity of 7vPCV to prevent IPD, both directly and indirectly, has recently been dampened:3,4 7vPCV is known to increase the prevalence of nasopharyngeal carriage of non-7vPCV serotype pneumococci in vaccinated children, and several recent studies from the United States have documented increases in the incidence of non-7vPCV serotype IPD in both children and adults.5,6,7 These increases were not so apparent in the first few years after the introduction of 7vPCV, suggesting that the emergence of non-7vPCV serotype IPD is a gradual process.5,6,7

Before the introduction of pneumococcal vaccines, the incidences of IPD in Indigenous children8 and adults were significantly greater than those documented in non-Indigenous people in north Queensland. Furthermore, a considerable proportion of cases in Indigenous children were caused by non-7vPCV serotype pneumococci.1,8 For these reasons, it is essential to continue surveillance of IPD in Indigenous people to determine whether non-7vPCV serotype IPD emerges over time, and, if so, which serotypes are involved.

This study aimed to examine trends in the epidemiology of IPD in Indigenous people in north Queensland over another 3 years (2005–2007) after the introduction of 7vPCV, to determine trends in indirect effects, and to assess whether non-7vPCV serotype IPD is emerging in Indigenous people in north Queensland.

We have used the same methods since our first study began in 1999.1 Briefly, IPD is defined by the isolation of pneumococci from a usually sterile body site. Data on all IPD cases are collected with a standardised questionnaire that requests information on demographic and clinical features. This information is linked with the pneumococcal vaccination status of the patient and the serotype of the infecting pneumococcus. Definitions of “vaccine-preventable” and “vaccine failure” IPD were as used previously1 (Box 1).

Trends were compared over three 3-year periods: 1999–2001 (before the introduction of 7vPCV for Indigenous children), 2002–2004 and 2005–2007. Comparisons were made with the χ2 test for trend.

The population estimates for north Queensland from the 2001 national census were used to determine the average annual incidences during 1999–2001, and similarly 2006 census estimates were used to determine incidences during 2005–2007. Confidence intervals for the incidences were calculated from tabulated 95% significance factors.9

Over the 9 years 1999–2007, there were 273 cases of IPD in Indigenous people in north Queensland (Box 2); the infecting serotype was determined in 264 (97%) of the cases.

From 1999–2001 to 2005–2007, there was a 60% decline in IPD in young Indigenous children in north Queensland, which is consistent with predictions made before the introduction of 7vPCV.8

No 7vPCV failures have yet been documented in north Queensland. However, there have now been three 23vPPV failures in Indigenous children since it was introduced into the immunisation schedule in mid-2001: a serotype 12F vaccine failure occurred in 2003 in a 2.5-year-old child who had received 23vPPV at 21 months of age,1 and two serotype 1 vaccine failures occurred more recently.

There is no evidence yet of an emergence of non-7vPCV serotype IPD in Indigenous children or (contrary to an initial impression1) an indirect protective effect in children aged 5–14 years. Nevertheless, there is now very strong evidence that Indigenous adults are benefiting indirectly from the use of 7vPCV in children. This was shown by a significant decline in 7vPCV serotype IPD in adults over the three periods, but no concurrent decline in IPD caused by serotypes present only in the 23vPPV; these observations are consistent with those from elsewhere.7,10 Children are a significant reservoir of pneumococci, and contact with young children is a recognised risk factor for IPD in adults.11 Because 7vPCV reduces nasopharyngeal carriage of vaccine serotypes, transmission of these pneumococci to close contacts is, in turn, also reduced.11

In contrast, the initial benefits of 23vPPV to Indigenous adults in north Queensland appear to have now plateaued.1 Little is known about the longer-term protection afforded by that vaccine, particularly in populations with a very high prevalence of comorbid conditions.

It is of considerable concern that there has been a significant increase in the number of IPD cases in Indigenous adults caused by serotypes not present in either vaccine. Similarly, the repertoire of serotypes not present in either vaccine that caused IPD in Indigenous adults has expanded from seven in 1999–2001 to 13 in 2002–2007 (Box 4).

Although these could be coincidental findings, an increase in the nasopharyngeal carriage of serotypes not present in either vaccine (“replacement colonisation”12) was seen in Native Alaskan adults after the introduction of childhood 7vPCV.12 In addition, a 44% increase in IPD caused by non-vaccine serotypes was recently reported in HIV-infected adults in the US.13 If we assume an association between the increase in IPD caused by non-vaccine serotypes and the introduction of 7vPCV, then this increase has offset the decrease in IPD caused by 7vPCV serotypes, as has also been seen in Native Alaskan adults.12

Although the relatively small numbers of cases in our study do not allow definitive conclusions about particular pneumococcal serotypes, some observations are nevertheless warranted. Serotype 1 has long been recognised as a cause of occasional outbreaks of IPD, but was recently suggested to cause an ongoing cyclical pattern of IPD in some settings.14 “Outbreaks” of serotype 1 IPD occurred in Indigenous populations in north Queensland in 1992–1995, 1999–2001 and 2005–2007, supporting the hypothesis that serotype 1 is endemic in the region and causes a cyclical pattern of IPD.

Following the introduction of 7vPCV, serotypes 6A and 33F have become prominent causes of IPD in Indigenous children less than 5 years of age in north Queensland (Box 3). The former is surprising, as a case–control study in the US showed that 7vPCV was 76% effective (95% CI, 39%–90%) in preventing serotype 6A IPD in children,15 leading to a comment that the vaccine was effectively an “eight-valent” product.16 Certainly, serotype 6A IPD declined significantly in most children in the US after the introduction of 7vPCV,7 but the nasopharyngeal carriage of this serotype increased in vaccinated Native American children,2 and it has emerged as a prominent cause of IPD in Native Alaskan children.5 A recent increase in serotype 33F IPD among children in the US has also been documented.10,17

Serotypes 22F, 10F and 18A appear to have become more prominent causes of IPD in Indigenous adults in north Queensland following the vaccination of children with 7vPCV (Box 4). For this to have occurred, the nasopharyngeal carriage of these non-7vPCV serotypes would have had to increase in adults.11 A recent non-significant increase in the carriage of serotype 22F has been noted among Native Alaskan adults.12 Increases in IPD in adults caused by these serotypes do not appear to have been described elsewhere.

There is no clear evidence yet that serotype 19A IPD has recently increased in either Indigenous children or adults in north Queensland since the introduction of 7vPCV. The US case–control study showed that 7vPCV was not effective in protecting children against serotype 19A IPD,15 and there has been a recent marked increase in IPD caused by this non-7vPCV serotype in children6,7 and adults7,10,13 elsewhere, including Native Alaskan children and adults.5 Of note, 36% of the cases of IPD that occurred in children less than 5 years of age in the US in 2005 were caused by serotype 19A.18

Several mechanisms for the emergence of serotype 19A IPD have been proposed,18 but it is unclear why this serotype has not become a more prominent cause of IPD among Indigenous people in north Queensland, as it was present in the region before the introduction of 7vPCV.1,8 It is unlikely that 23vPPV has played a significant role in preventing the emergence of this serotype, as this vaccine is not scheduled for Indigenous children in Queensland until they reach 24 months of age. All six cases of serotype 19A IPD that occurred between 1999 and 2007 in children less than 5 years of age occurred before 24 months; presumably any recent emergence of this serotype would be apparent before this age, as seen in Native Alaskan children.5

Newer conjugate vaccines, including a 13-valent vaccine (which includes serotypes 1, 3, 5, 6A, 7F and 19A) are under clinical development.19 Such vaccines will be necessary to eradicate apparently endemic serotype 1 IPD in Indigenous people in north Queensland, and could prevent a considerable amount of the persisting IPD caused by other serotypes, both directly and indirectly. Continued surveillance will be essential.