title: Redefining risk categories for pneumococcal disease in adults: critical analysis of the evidence.
abstract: OBJECTIVE
  To analyze the available published data (2005-2014) describing the prevalence of multimorbidity in adult patients with pneumococcal disease, with a focus on the comorbidities considered by the Advisory Committee on Immunization Practices (ACIP) of the US Centers for Disease Control and Prevention to increase the risk of pneumococcal disease in adults (immunocompetent persons with chronic medical conditions (at risk) and immunocompromised or immunosuppressed persons (high risk)). An analysis of case-control and population-based surveillance studies that have evaluated risk factors for community-acquired pneumonia (CAP) and invasive pneumococcal disease (IPD) was also performed in order to estimate the importance of risk stacking.
  
  
  METHODS
  Studies that established the enrolment procedure for patients and reported the incidence of multimorbidity and risk factors for CAP and/or IPD were included. In order to obtain a risk stacking value based on the at-risk comorbidity odds ratios (OR), the multiplicative method described by Campbell was used.
  
  
  RESULTS
  Thirty-eight articles were selected, 19 for multimorbidity and 19 for risk factors for CAP/IPD. With regard to multimorbidity, the prevalence among adults aged ≥65 years ranged from 23% to 98.7% for two or more comorbidities and from 18% to 89.7% for three or more comorbidities. Diabetes (DBT), chronic heart disease (CHD), and chronic obstructive pulmonary disease (COPD) were the three most frequent comorbidities described (7.6-28.5%, 6.9-25.8%, and 3.8-15.4%, respectively). With regard to risk factors, based on the multiplicative method, the hypothetical scenario of concurrence of the three most frequent at-risk conditions (DBT+CHD+COPD) showed an OR of ≥7.5. In this group of patients, the addition of smoking, another common at-risk factor for CAP (stacking four concurrent conditions) increased the OR from 8.5 to >40. These ORs were generally similar to rates described by other authors in persons with a high risk.
  
  
  CONCLUSIONS
  The ORs for CAP and IPD of patients with two or more comorbidities, with or without smoking, were found to be similar to the ORs for CAP and IPD described in the literature for patients currently classified as high risk. The potential impact of multiple, stacking comorbidities is underestimated and there is a need for the risk categories for pneumococcal disease to be redefined.
authors.affiliation: Latin America/Canada Pfizer Vaccines, Edificio Complejo Thames Office Park, Colectora Panamericana 1804, 1er piso, Sector B Lado Sur, B1607EEV Villa Adelina, Prov. Buenos Aires, Argentina. Electronic address: daniel.curcio@pfizer.com.
authors.forename: Daniel
authors.initials: D
authors.lastname: Curcio
authors.affiliation: Latin America/Canada Pfizer Vaccines, Edificio Complejo Thames Office Park, Colectora Panamericana 1804, 1er piso, Sector B Lado Sur, B1607EEV Villa Adelina, Prov. Buenos Aires, Argentina.
authors.forename: Alejandro
authors.initials: A
authors.lastname: Cané
authors.affiliation: Global Pneumococcal Vaccines, Pfizer Inc., , Collegville, PA, USA.
authors.forename: Raúl
authors.initials: R
authors.lastname: Isturiz
mesh_terms: D000328:Adult; D002908:Chronic Disease; D017714:Community-Acquired Infections / Q000453:epidemiology*; D015897:Comorbidity; D005260:Female; D006331:Heart Diseases / Q000453:epidemiology; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D011018:Pneumonia, Pneumococcal / Q000453:epidemiology*; D011159:Population Surveillance; D015995:Prevalence; D029424:Pulmonary Disease, Chronic Obstructive / Q000453:epidemiology; D012307:Risk Factors; D012907:Smoking / Q000009:adverse effects; D013296:Streptococcus pneumoniae / Q000276:immunology* / Q000302:isolation & purification; D014481:United States; D014611:Vaccination; D055815:Young Adult
keywords: Multimorbidity; Pneumococcal disease; Risk factors; Risk stacking