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Impact of infant 13-valent pneumococcal conjugate vaccine on serotypes in adult pneumonia

Chamira Rodrigo, Thomas Bewick, Carmen Sheppard, Sonia Greenwood, Tricia M. Mckeever, Caroline L. Trotter, Mary Slack, Robert George, Wei Shen Lim
European Respiratory Journal 2015 45: 1632-1641; DOI: 10.1183/09031936.00183614
Chamira Rodrigo
1Dept of Respiratory Medicine, City Hospital Campus, Nottingham University Hospitals NHS Trust, Nottingham, UK
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Thomas Bewick
1Dept of Respiratory Medicine, City Hospital Campus, Nottingham University Hospitals NHS Trust, Nottingham, UK
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Carmen Sheppard
2Respiratory and Vaccine Preventable Bacteria Reference Unit, Public Health England, Microbiology Services Division, London, UK
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Sonia Greenwood
1Dept of Respiratory Medicine, City Hospital Campus, Nottingham University Hospitals NHS Trust, Nottingham, UK
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Tricia M. Mckeever
3Division of Epidemiology and Public Health, University of Nottingham, Nottingham, UK
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Caroline L. Trotter
4Disease Dynamics Unit, Dept of Veterinary Medicine, University of Cambridge, Cambridge, UK
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Mary Slack
2Respiratory and Vaccine Preventable Bacteria Reference Unit, Public Health England, Microbiology Services Division, London, UK
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Robert George
2Respiratory and Vaccine Preventable Bacteria Reference Unit, Public Health England, Microbiology Services Division, London, UK
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Wei Shen Lim
1Dept of Respiratory Medicine, City Hospital Campus, Nottingham University Hospitals NHS Trust, Nottingham, UK
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  • FIGURE 1
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    FIGURE 1

    Variation in the incidence of adult pneumococcal community-acquired pneumonia (CAP) and CAP by year, according to serotype categories. PCV7 CAP: CAP due to serotypes included in the 7-valent pneumococcal conjugate vaccine; additional PCV13 CAP: CAP due to additional serotypes included in PCV13; other CAP: CAP due to “other” serotypes.

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    FIGURE 2

    Variation in individual serotype numbers by study year among adults with pneumococcal community-acquired pneumonia.

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  • TABLE 1

    Baseline characteristics, disease severity and outcomes of community-acquired pneumonia (CAP) cohort and pneumococcal cohort

    CAP cohortPneumococcal cohort
    Patients2229653
    Demographics
     Age years71.0 (55.1–80.5)69.2 (50.2–79.8)
     Male1237 (55.5)326 (49.9)
     Nursing home residence93 (4.2)30 (4.6)
     WHO performance status ≥2346 (15.5)57 (16.0)
    Comorbid illness
     Charlson Comorbidity Index4.0 (3.0–6.0)4.0 (2.0–6.0)
     Malignancy170 (7.6)40 (6.1)
     Liver disease22 (1.0)10 (1.5)
     Congestive cardiac failure144 (6.5)36 (5.5)
     Ischaemic heart disease396 (17.8)112 (17.2)
     Chronic kidney disease155 (7.0)48 (7.4)
     Asthma265 (11.9)85 (13.0)
     COPD475 (21.3)117 (17.9)
     Diabetes307 (13.8)84 (12.9)
     Stroke201 (9.0)68 (10.4)
     Dementia47 (2.1)21 (3.2)
     HIV11 (0.5)4 (0.6)
    Disease severity
     CURB-65 0–11042 (46.8)272 (41.7)
     CURB-65 2673 (30.2)199 (30.5)
     CURB-65 3–5514 (23.1)182 (27.9)
    Outcomes
     ICU admission267 (12.0)95 (14.5)
     30-day in-patient mortality183 (8.2)41 (6.3)
    • Data are presented as n, median (interquartile range) or n n (%). WHO: World Health Organization; COPD: chronic obstructive pulmonary disease; CURB-65: confusion, urea >7 mmol·L−1, respiratory rate >30 breaths·min−1, blood pressure <90 mmHg (systolic) ≤60 mmHg (diastolic), age ≥65 years; ICU: intensive care unit.

  • TABLE 2

    Incidence rates of community-acquired pneumonia (CAP), pneumococcal CAP, and CAP due to 7-valent pneumococcal conjugate vaccination (PCV7), additional PCV13 and other serotypes by study year

    Patient age yearsYear 1, 2008–2009Year 2, 2009–2010Year 3, 2010–2011Year 4, 2011–2012Year 5, 2012–2013
    nIncidence# (95% CI)nIncidence# (95% CI)nIncidence# (95% CI)nIncidence# (95% CI)nIncidence# (95% CI)
    CAP50690.7 (83.0–99.0)43978.7 (71.5–86.4)35964.4 (57.9–71.4)560100.4 (92.3–109.1)36565.4 (58.9–72.5)
    16–241614.0 (8.0–22.7)65.3 (1.9–11.4)119.6 (4.8–17.2)2320.1 (12.8–30.2)1513.1 (7.4–21.6)
    25–445027.9 (20.7–36.7)6033.4 (25.5–43.0)5128.4 (21.2–37.4)6134.0 (26.0–43.7)4927.3 (20.2–36.1)
    45–649759.7 (48.4–72.8)9156.0 (45.1–68.7)8250.4 (40.1–62.6)13180.6 (67.4–95.6)9558.4 (47.3–71.4)
    65–74113201.4 (166.0–242.2)89158.7 (127.4–195.2)77137.2 (108.3–171.6)107190.7 (156.3–230.5)77137.2 (108.3–171.6)
    75–84129360.3 (300.8–428.1)111310.1 (255.1–373.4)91254.2 (204.7–312.1)148413.4 (349.5–485.6)88245.8 (197.2–302.8)
    >851011052.1 (856.9–1278.4)82854.2 (679.3–1060.2)47489.6 (359.7–651.0)90937.5 (753.9–1152.3)41427.1 (306.5–579.4)
    Pneumococcal CAP19635.1 (30.4–40.4)15026.9 (22.8–31.6)10017.9 (14.6–21.8)9216.5 (13.3–20.2)11520.6 (17.0–24.8)
    16–2465.2 (1.9–11.4)43.5 (1.0–9.0)32.6 (0.5–7.7)32.6 (0.5–7.7)65.2 (1.9–11.4)
    25–442212.3 (7.7–18.6)2614.5 (9.5–21.2)2212.3 (7.7–18.6)105.6 (2.7–10.2)1910.6 (6.4–16.5)
    45–644024.6 (17.6–33.5)3119.1 (13.0–27.1)2414.8 (9.5–22.0)2012.3 (7.5–19.0)2616.0 (10.4–23.4)
    65–743969.5 (49.4–95.0)2849.9 (33.2–72.1)2239.2 (24.6–59.4)2035.6 (21.8–55.1)2341.0 (26.0–61.5)
    75–8449136.9 (101.3–181.0)3495.0 (65.8–132.7)1850.3 (29.8–79.5)2467.0 (43.0–99.8)2569.8 (45.2–103.1)
    >8540416.7 (297.7–567.4)27281.2 (185.3–409.2)11114.6 (57.2–205.0)15156.2 (87.4–257.7)16166.7 (95.3–270.7)
    PCV7 CAP6211.1 (8.5–14.2)91.6 (0.7–3.1)81.4 (0.6–2.8)20.4 (0.0–1.3)132.3 (1.2–4.0)
    16–240010.9 (0.0–4.9)000000
    25–4442.2 (0.6–5.7)0010.6 (0.0–3.1)0031.7 (0.3–4.9)
    45–64127.4 (3.8–12.9)31.8 (0.4–5.4)21.2 (0.0–4.4)10.6 (0.0–3.4)10.6 (0.0–3.4)
    65–741526.7 (15.0–44.1)11.8 (0.0–9.9)35.3 (1.1–15.6)11.8 (0.0–9.9)47.1 (1.9–18.3)
    75–841439.1 (21.4–65.6)12.8 (0.1–15.6)12.8 (0.1–15.6)0025.6 (0.7–20.2)
    >8517177.1 (103.2–283.5)331.2 (6.4–91.3)110.4 (0.3–58.0)00331.2 (6.4–91.3)
    Additional PCV13 CAP5910.6 (8.0–13.6)6411.5 (8.8–14.6)458.1 (5.9–10.8)447.9 (5.7–10.6)356.3 (4.4–8.7)
    16–2410.9 (0.0–4.9)18.7 (4.2–16.1)21.7 (0.2–6.3)32.6 (0.5–7.7)32.6 (0.5–7.7)
    25–4495.0 (2.3–9.5)158.4 (4.7–13.8)137.2 (3.9–12.4)42.2 (0.6–5.7)63.3 (1.2–7.3)
    45–64106.2 (3.0–11.3)169.8 (5.6–16.0)116.7 (3.4–12.1)127.4 (3.8–12.9)95.5 (2.5–10.5)
    65–741323.2 (12.3–39.6)1119.6 (9.8–35.1)1017.8 (8.6–32.8)1323.2 (12.3–39.6)712.5 (5.0–25.7)
    75–841644.7 (25.6–72.6)1130.7 (15.3–55.0)411.2 (3.0–28.6)719.6 (7.9–40.3)822.3 (9.6–44.0)
    >8510104.2 (50.0–191.6)10104.2 (50.0–191.6)552.1 (16.9–121.6)552.1 (16.9–121.6)220.8 (2.5–75.3)
    Other CAP244.3 (2.8–6.4)234.1 (2.6–6.2)152.7 (1.5–4.4)122.1 (1.1–3.8)213.8 (2.3–5.8)
    16–240010.9 (0.0–4.9)000000
    25–4473.9 (1.6–8.0)31.7 (0.3–4.9)21.1 (0.1–4.0)21.1 (0.1–4.0)42.2 (0.7–5.7)
    45–6474.3 (1.7–8.9)74.3 (1.7–8.9)42.5 (0.7–6.3)42.5 (0.7–6.3)74.3 (1.7–8.9)
    65–7423.6 (0.4–12.9)47.1 (1.9–18.3)47.1 (1.9–18.3)11.8 (0.0–9.9)58.9 (2.9–20.8)
    75–84616.8 (6.2–36.5)616.8 (6.2–36.5)411.2 (3.0–28.6)38.4 (1.7–24.5)38.4 (1.7–24.5)
    >85220.8 (2.5–75.3)220.8 (2.5–75.3)110.4 (0.2–58.0)220.8 (2.5–75.3)220.8 (2.5–75.3)
    • PCV7 CAP: CAP due to serotypes included in PCV7; additional PCV13 CAP: CAP due to additional serotypes included in PCV13; other CAP: CAP due to “other” serotypes. #: per 100 000.

  • TABLE 3

    Linear trends and year to year variation in community-acquired pneumonia (CAP), pneumococcal CAP, CAP due to serotype groups and “untyped” pneumococcal CAP

    Year 1, 2008–2009Year 2, 2009–2010Year 3, 2010–11Year 4, 2011–2012Year 5, 2012–13Change in IRR per yearp-value for trend
    CAP1.000.9 (0.8–1.0)0.7 (0.6–0.8)1.1 (1.0–1.2)0.7 (0.6–0.8)0.96 (0.94–0.99)0.016
    Pneumococcal CAP1.000.8 (0.6–0.9)0.5 (0.4–0.6)0.5 (0.4–0.6)0.6 (0.5–0.7)0.84 (0.80–0.89)<0.001
    PCV7 CAP1.000.15 (0.07–0.29)0.13 (0.06–0.27)0.03 (0.01–0.13)0.21 (0.12–0.38)0.52 (0.43–0.62)<0.001
    Additional PCV13 CAP1.001.08 (0.76–1.54)0.76 (0.52–1.12)0.75 (0.50–1.50)0.59 (0.39–0.90)0.87 (0.80–0.95)0.002
    Other CAP1.000.95 (0.54–1.70)0.62 (0.33–1.19)0.50 (0.25–1.00)0.88 (0.49–1.57)0.91 (0.79–1.05)0.218
    Untyped pneumococcal CAP1.001.04 (0.70–1.54)0.65 (0.42–1.01)0.67 (0.43–1.04)0.90 (0.60–1.34)0.94 (0.85–1.03)0.171
    • Data are presented as incidence rate ratio (95% confidence interval) unless otherwise stated. PCV7 CAP: CAP due to serotypes included in the 7-valent pneumococcal conjugate vaccine; additional PCV13 CAP: CAP due to additional serotypes included in PCV13; other CAP: CAP due to “other” serotypes. Bold indicates statistically significant.

  • TABLE 4

    Comparison of incidence rates pre-13-valent pneumococcal conjugate vaccine (PCV13)# and post-PCV13¶ introduction

    Overall incidence+IRR (95%CI)p-value
    Pre-PCV13Post-PCV13
    CAP90.7 (83.0–99.0)76.7 (72.6–81.0)0.85 (0.76–0.94)0.001
    Pneumococcal CAP35.1 (30.4–40.4)18.3 (16.3–20.5)0.52 (0.44–0.62)<0.001
    PCV7 CAP11.1 (8.5–14.2)1.4 (0.9–2.1)0.12 (0.08–0.20)<0.001
    Additional PCV13 CAP10.6 (8.0–13.6)7.4 (6.2–8.8)0.70 (0.51–0.96)0.024
    Other CAP4.3 (2.8–6.4)2.9 (2.1–3.8)0.67 (0.41–1.09)0.105
    • Data are presented as incidence rates (interquartile range), unless otherwise stated. IRR: incidence rate ratio; CAP: community-acquired pneumonia; PCV7 CAP: CAP due to serotypes included in the PCV7 vaccine; additional PCV13 CAP: CAP due to serotypes included in the PCV13 vaccine; other CAP: CAP due to “other” serotypes. #: years 2008–2009; ¶: years 2010–2013; +: per 100 000 population. Bold indicates statistically significant.

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Impact of infant 13-valent pneumococcal conjugate vaccine on serotypes in adult pneumonia
Chamira Rodrigo, Thomas Bewick, Carmen Sheppard, Sonia Greenwood, Tricia M. Mckeever, Caroline L. Trotter, Mary Slack, Robert George, Wei Shen Lim
European Respiratory Journal Jun 2015, 45 (6) 1632-1641; DOI: 10.1183/09031936.00183614

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Impact of infant 13-valent pneumococcal conjugate vaccine on serotypes in adult pneumonia
Chamira Rodrigo, Thomas Bewick, Carmen Sheppard, Sonia Greenwood, Tricia M. Mckeever, Caroline L. Trotter, Mary Slack, Robert George, Wei Shen Lim
European Respiratory Journal Jun 2015, 45 (6) 1632-1641; DOI: 10.1183/09031936.00183614
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