Impact of pneumococcal conjugate vaccine on pneumococcal disease, carriage and serotype distribution : comparative studies in Sweden and Uganda

Background: Streptococcus pneumoniae is a leading infectious cause of child deaths worldwide. Pneumococcal conjugate vaccine (PCV) was first introduced in the US in the year 2000, and included the major seven pneumococcal serotypes (PCV7) causing invasive pneumococcal disease (IPD) there. Current PCVs include 10 or 13 of the more than 97 known pneumococcal serotypes. In Stockholm County, Sweden, PCV7 was introduced for infants born from July 2007, at 3, 5, and 12 months of age and in 2010 it was changed to PCV13. Uganda started national PCV10 implementation in 2014.

Aims: To study the effects of the introduction of PCV in the childhood vaccination program in Stockholm on incidence, serotypes and antibiotic resistance patterns of IPD, hospitalization due to severe sinusitis and pneumonia in children, and pneumococcal carriage. Also, to study pneumococcal carriage and serotype distribution in healthy children <5 years prior to PCV introduction in Uganda, and estimate the potential effectiveness of PCV.

Methods: All cases of IPD in Stockholm registered in the national mandatory reporting system from 2005 to 2014 were included (n=2519). The pneumococcal isolates were characterized with serotyping (n=2336), including some with molecular typing and antibiotic resistance pattern. All hospitalizations from 2003 to 2012 in Stockholm, ICD-10 coded as sinusitis or pneumonia (N=678, 5051, respectively) in children, were collected from hospital registries. Nasopharyngeal pneumococcal isolates from children <5 years in Stockholm were collected at regular visits to Child Health Centers from 4 to 8 years after PCV introduction from 2011 to 2015 (N=916). Pneumococcal carriage was compared to carriage data in children attending day-care centers in 2004 (N=246), which was before vaccine introduction. OR for invasive disease potential of the pneumococcal isolates in carriage was calculated using data on IPD in all ages from 2011 to 2015. Nasopharyngeal carriage of pneumococci in children <5 in Uganda was assessed through collecting isolates at the Health and Demographic Surveillance Site in Iganga/Maygue districts (N=1761).

Results: We show that PCV introduction in Stockholm has been successful in decreasing the incidence of IPD, from 28.4 to 10.3 cases /100,000 children <2 years (RR 0.36, 95% CI 0.2-0.6) when comparing the time periods 2005-2007 to 2009-2014, Serotypes included in the PCV7 decreased from 22.7 to 0 cases/ 100,000 in this age group (RR 0.0, 95% CI 0.0-0.1). The IPD incidence also decreased in older children and adults, excluding the elderly. However, PCV7 serotypes have decreased in all age groups. There was a decrease in hospitalizations due to severe sinusitis (RR 0.34, 95% CI 0.2-0.5) and pneumonia (RR 0.81, 95% CI 0.7-0.9) in children <2 years. A near elimination of most vaccine serotypes with a high invasiveness potential was seen in carriage. Emerging both in carriage among children and as cause of IPD (all ages) were instead non-vaccine types of lower invasive potential. Carriage data before PCV introduction in Uganda shows that vaccine serotypes were much less prevalent in children <5 years old (PCV10 for 42% and PCV13 for 54%) than what was observed in children <5 years old in Sweden before the PCV implementation (PCV10 63%, PCV13 82%), which may reduce potential vaccine effectiveness in Uganda.

Conclusions: PCV introduction in Stockholm has had a positive overall impact on pneumococcal morbidity in young children, and serotypes included in the vaccine are decreasing in IPD and carriage. PCVs have the potential to save many children’s lives in the coming years, both in Sweden and Uganda. The extent of the impact is still not known, as PCV effectiveness depends on factors such as pneumococcal serotype distribution in carriage before and after PCV implementation, the extent of serotype replacement in carriage as well as in IPD in different age groups following PCV, vaccination coverage, and the serotype content of future pneumococcal vaccines, which may cover more or all pathogenic serotypes.

List of scientific papers

I. Galanis I , Lindstrand A, Darenberg J , Browall S, Nannapaneni P, Sjöström K, Morfeldt E, Wilson J, Naucler P, Blennow M, Örtqvist Å, Henriques-Normark B. Effect of PCV7 and PCV13 on Pneumococcal Invasive Disease and Carriage in Stockholm, Sweden. European Respiratory Journal. January 21, 2016. [Epub ahead of print]
https://doi.org/10.1183/13993003.01451-2015

II. Lindstrand A, Bennet R, Galanis I, Blennow M, Schollin Ask L, Hultman Dennison S, Ryd Rinder M, Eriksson M, Henriques-Normark B, Örtqvist Å, Alfvén T. Sinusitis and Pneumonia Hospitalization after Introduction of Pneumococcal Conjugate Vaccine. Pediatrics. 2014;134(6):1-9.
https://doi.org/10.1542/peds.2013-4177

III. Lindstrand A, Galanis I, Darenberg J, Morfeldt E, Alfvén T, Blennow M, Naucler P, Henriques Normark B, Örtqvist Å. Unaltered Pneumococcal Carriage Prevalence Due to Expansion of Non-vaccine Serotypes of Low Invasive Potential Eight Years after Pneumococcal Conjugate Vaccine Introduction in Stockholm, Sweden. [Submitted]

IV. Lindstrand A, Kalyango J, Alfvén T, Darenberg J, Bwanga F, Kadobera D, Peterson S, Henriques Normark B, Källander K. Pneumococcal Carriage in Children Under Five Years in Uganda - Will Present Pneumococcal Conjugate Vaccines Be Appropriate? [Submitted]