Vaccines | Free Full-Text | Mortality of Invasive Pneumococcal Disease following Introduction of the 13-Valent Pneumococcal Conjugate Vaccine in Greenland
The aim of this study was to describe changes in IPD-related mortality and fatality after the introduction of the PCV13 in 2010 in Greenland, and how this varies by age, sex, region, ethnicity, and pneumococcal serotype.
Of the entire cohort of 295 IPD patients, 66 died within 31 days after IPD hospitalization representing a CFR of 22.4%. During the pre-PCV13 period (January 1995–September 2010), 49 out of 206 (CFR 23.8%) IPD patients died within 31 days after IPD hospitalization, while 17 out of 89 (CFR 19.1%) IPD patients died within 31 days after IPD hospitalization during the post-PCV13 period (September 2010–October 2020). This difference was not significant (p = 0.463).
The average length of hospitalization for all IPD cases was 14 days. This includes 15 cases who had a length of hospitalization more than 40 days. The average length of hospitalization was 14 days (range 0 to 121 days) for the pre-PCV13 period and 15 days (range 0 to 138 days) for the post-PCV13 period.
3.1. Mortality Rates
Although there was a statistically significant change in crude all-cause mortality in Greenland from the pre- to the post-PCV13 period (9.1 per 1000 PYRS to 9.7 per 1000 PYRS) (p < 0.05), the mortality rates were similar. However, after age-standardization, all-cause mortality rates in Greenland decreased from pre- to the post-PCV13 period (16.4 per 1000 PYRS to 12.8 per 1000 PYRS), which was statistically significant (p < 0.05).
For the whole period, crude IPD-related mortality rate was up to 350-times higher than the crude all-cause mortality rate for the population in Greenland. This rate decreased from the pre- to the post-PCV13 period (3589 per 1000 PYRS to 2658 per 1000 PYRS), but after age-standardization, IPD-related mortality rates increased from the pre- to the post-PCV13 period (3347 per 1000 PYRS to 4441 per 1000 PYRS).
IPD patients with meningitis, compared to IPD patients with non-meningitis, had a higher 31-day IPD-related mortality both during the pre- and the post-PCV13 period, but this was only statistically significant for the post-PCV13 period.
Patients with VT-IPD had a lower 31-day IPD-related mortality during both periods compared to patients with NVT-IPD.
There were no IPD-related deaths in non-Inuits during the post-PCV13 period. Inuits had almost the same 31-day IPD-related mortality during the pre-PCV13 period as non-Inuits. Females had a lower 31-day IPD-related mortality compared to males during both the pre- and the post-PCV13 periods.
3.2. Mortality by Serotypes
Of the total 295 IPD patients in the entire study period, only 185 IPD patients had their isolates serotyped. Of these 185 isolates, 115 (55.8%) were serotyped during the pre-PCV13 period and 70 (78.6%) were serotyped during the post-PCV13 period.
In this register-based study of all IPD cases in Greenland 1995–2020, we found that CFR for IPD decreased with 24.5% from the pre- (1995–2010) to the post-PCV13 (2010–2020) period. The SMR decreased significantly in IPD patients from the pre- to the post-PCV13 period (0.43, 95% CI 0.25–0.75), regardless of sex, ethnicity, comorbidity, and age. More so, there was no IPD-related death in patients up to 39 years of age in the post-PCV13 period.
For IPD patients in the post-PCV13 period, 31-day survival probability was higher, but not significant, compared to IPD patients in the pre-PCV13 period, also after adjusting for sex, age, and CCI score. In addition, there was no difference in length of hospital stay between the two periods.
IPD is a disease that carries a significant mortality in Greenland, which is reflected by the 350-times higher risk of IPD-related mortality when compared with all-cause mortality. However, crude IPD-related mortality rates decreased from the pre- to the post-PCV13 period with 26% (p = 0.291). On that note, the reason for the 33% (p = 0.232) increase in IPD-related mortality after age-standardization from the pre- to the post-PCV13 period is because the elderly IPD cases in the post-PCV13 period are very few but have a high mortality rate, affecting the world-weighted deaths.
The above findings suggest that while PCV13 has a direct effect on mortality of the vaccinated persons, and a herd protection of the adults, there is no effect of PCV13 introduction for children on mortality of the elderly above 60 years of age.
There were clear differences in SMR overall, and over time, between the regions of Greenland; North and South regions of Greenland had the highest SMR of IPD in the pre-PCV13 period which decreased in the post-PCV13 period, while IPD SMR in the East and West regions were lowest during the pre-PCV13 period but increased in the post-PCV13 period. The highest decrease in IPD SMR from the pre- to the post-PCV13 period was, however, observed in Nuuk (0.17, 95% CI: 0.06–0.44). Reasons for these opposite results between regions are unclear, but as diagnostic and treatment possibilities differ markedly between the regions (mainly between Nuuk and coastal hospitals) we believe that such differences over time and place may explain the observations.
Obviously, a temporal association between PCV13 introduction and reduced mortality may not incur causality. Other factors may also account for the reduced mortality, such as better access to health facilities and to laboratory diagnostic testing, and more timely hospital treatment. The finding of a markedly reduced mortality from IPD in the capital Nuuk, where the central hospital in Greenland is located, compared to other regions, can suggest that improved medical treatment can play a role in the reduced mortality following PCV13 introduction.
The strengths of this study are that our population was well-defined, and the study period was long, enabling us to identify long-term association between PCV13 introduction and mortality. We were able to obtain exact demographic information of the study population as we can uniquely identify case patients on a personal identifiable level. Moreover, we were able to obtain a full background population size.
There are a number of limitations in this study. First, the number of observed deaths is small and therefore estimates of, e.g., rates may be interpreted with care. Second, a temporal association between PCV13 introduction and reduction in mortality may not reflect causality as discussed above. Third, IPD-related mortality was defined as deaths within 31 days after hospital admission for IPD, irrespectively of the actual cause of death as we did not have access to information of causes of death for the majority of patients. Fourth, by censoring 31 days after IPD hospitalization we exclude potential cases that might have died from IPD beyond 31 days after hospitalization. Finally, information on serotypes was incomplete for the majority of our study population, and the sample sizes for each specific serotype was small.
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