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Background Infection caused by Streptococcus pneumoniae, mainly invasive pneumococcal disease (IPD) and pneumococcal pneumonia (PP), are a major public health problem worldwide. This study investigated population-based incidence and risk of PP among Catalonian persons ≥ 50 years-old with and without specific underlying conditions/comorbidities, examining the influence of single and multi-comorbidities in the risk of suffering PP. Methods Population-based cohort study involving 2,059,645 persons ≥ 50 years-old in Catalonia, Spain, who were retrospectively followed between 01/01/2017-31/12/2018. The Catalonian information system for development of research in primary care (SIDIAP) was used to establish baseline characteristics of the cohort (comorbidities/underlying conditions), and PP cases were collected from discharge codes (ICD-10: J13) of the 68 referral Catalonian hospitals. Results Global incidence rate (IR) was 90.7 PP cases per 100,000 person-years, with a 7.6% (272/3592) case-fatality rate (CFR). Maximum IRs emerged among persons with history of previous IPD or all-cause pneumonia, followed by haematological neoplasia (475.0), HIV-infection (423.7), renal disease (384.9), chronic respiratory disease (314.7), liver disease (232.5), heart disease (221.4), alcoholism (204.8), solid cancer (186.2) and diabetes (159.6). IRs were 42.1, 89.9, 201.1, 350.9, 594.3 and 761.2 in persons with 0, 1, 2, 3, 4 and ≥ 5 comorbidities, respectively. In multivariable analyses, HIV-infection (hazard ratio [HR]: 5.16; 95% CI: 3.57–7.46), prior all-cause pneumonia (HR: 3.96; 95% CI: 3.45–4.55), haematological neoplasia (HR: 2.71; 95% CI: 2.06–3.57), chronic respiratory disease (HR: 2.66; 95% CI: 2.47–2.86) and prior IPD (HR: 2.56; 95% CI: 2.03–3.24) were major predictors for PP. Conclusion Apart of increasing age and immunocompromising conditions (classically recognised as high-risk conditions), history of prior IPD/pneumonia, presence of chronic pulmonary/respiratory disease and/or co-existing multi-comorbidity (i.e., two or more underlying conditions) are major risk factors for PP in adults, with an excess risk near to immunocompromised subjects. Redefining risk categories for PP, including all the above-mentioned conditions into the high-risk category, could be necessary to improve prevention strategies in middle-aged and older adults.
Background Infection caused by Streptococcus pneumoniae, mainly invasive pneumococcal disease (IPD) and pneumococcal pneumonia (PP), are a major public health problem worldwide. This study investigated population-based incidence and risk of PP among Catalonian persons ≥ 50 years-old with and without specific underlying conditions/comorbidities, examining the influence of single and multi-comorbidities in the risk of suffering PP. Methods Population-based cohort study involving 2,059,645 persons ≥ 50 years-old in Catalonia, Spain, who were retrospectively followed between 01/01/2017-31/12/2018. The Catalonian information system for development of research in primary care (SIDIAP) was used to establish baseline characteristics of the cohort (comorbidities/underlying conditions), and PP cases were collected from discharge codes (ICD-10: J13) of the 68 referral Catalonian hospitals. Results Global incidence rate (IR) was 90.7 PP cases per 100,000 person-years, with a 7.6% (272/3592) case-fatality rate (CFR). Maximum IRs emerged among persons with history of previous IPD or all-cause pneumonia, followed by haematological neoplasia (475.0), HIV-infection (423.7), renal disease (384.9), chronic respiratory disease (314.7), liver disease (232.5), heart disease (221.4), alcoholism (204.8), solid cancer (186.2) and diabetes (159.6). IRs were 42.1, 89.9, 201.1, 350.9, 594.3 and 761.2 in persons with 0, 1, 2, 3, 4 and ≥ 5 comorbidities, respectively. In multivariable analyses, HIV-infection (hazard ratio [HR]: 5.16; 95% CI: 3.57–7.46), prior all-cause pneumonia (HR: 3.96; 95% CI: 3.45–4.55), haematological neoplasia (HR: 2.71; 95% CI: 2.06–3.57), chronic respiratory disease (HR: 2.66; 95% CI: 2.47–2.86) and prior IPD (HR: 2.56; 95% CI: 2.03–3.24) were major predictors for PP. Conclusion Apart of increasing age and immunocompromising conditions (classically recognised as high-risk conditions), history of prior IPD/pneumonia, presence of chronic pulmonary/respiratory disease and/or co-existing multi-comorbidity (i.e., two or more underlying conditions) are major risk factors for PP in adults, with an excess risk near to immunocompromised subjects. Redefining risk categories for PP, including all the above-mentioned conditions into the high-risk category, could be necessary to improve prevention strategies in middle-aged and older adults.
Background Although vaccination is recommended for protection against invasive pneumococcal disease, the frequency of pneumococcal pneumonia is still high worldwide. In fact, no vaccines are effective for all pneumococcal serotypes. Fusion pneumococcal surface protein A (PspA) has been shown to induce a broad range of cross-reactivity with clinical isolates and afford cross-protection against pneumococcal challenge in mice. Furthermore, we developed prime-boost-type mucosal vaccines that induce both antigen-specific IgG in serum and antigen-specific IgA in targeted mucosal organs in previous studies. We investigated whether our prime-boost-type immunization with a fusion PspA was effective against pneumococcal infection in mice and cynomolgus macaques. Methods C57BL/6 mice were intramuscularly injected with fusion PspA combined with CpG oligodeoxynucleotides and/or curdlan. Six weeks later, PspA was administered intranasally. Blood and bronchoalveolar lavage fluid were collected and antigen-specific IgG and IgA titers were measured. Some mice were given intranasal Streptococcus pneumoniae and the severity of infection was analyzed. Macaques were intramuscularly injected with fusion PspA combined with CpG oligodeoxynucleotides and/or curdlan at week 0 and week 4. Then, 13 or 41 weeks later, PspA was administered intratracheally. Blood and bronchoalveolar lavage fluid were collected and antigen-specific IgG and IgA titers were measured. Some macaques were intranasally administered S. pneumoniae and analyzed for the severity of pneumonia. Results Serum samples from mice and macaques injected with antigens in combination with CpG oligodeoxynucleotides and/or curdlan contained antigen-specific IgG. Bronchial samples contained antigen-specific IgA after the fusion PspA boosting. This immunization regimen effectively prevented S. pneumoniae infection. Conclusions Prime-boost-type immunization with a fusion PspA prevented S. pneumoniae infection in mice and macaques.
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