title: Pneumocystis pneumonia in HIV-positive patients in Spain: epidemiology and environmental risk factors.
abstract: BACKGROUND
  Specific environmental factors may play a role in the development of Pneumocystis pneumonia (PCP) in HIV-positive patients. The aim of this study was to estimate the PCP incidence and mortality in hospitalized HIV-positive patients in Spain during the combination antiretroviral therapy (cART) era (1997 to 2011), as well as to analyze the climatological factors and air pollution levels in relation to hospital admissions and deaths.
  
  
  METHODS
  We carried out a retrospective study. Data were collected from the National Hospital Discharge Database and the State Meteorological Agency of Spain. A case-crossover analysis was applied to identify environmental risk factors related to hospitalizations and deaths. For each patient, climatic factors and pollution levels were assigned based on readings from the nearest meteorological station to his or her postal code.
  
  
  RESULTS
  There were 13,139 new PCP diagnoses and 1754 deaths in hospitalized HIV-positive patients from 1997 to 2011. The PCP incidence (events per 1000 person-years) dropped from 11.6 in 1997 to 2000, to 5.4 in 2004 to 2011 (p<0.001). The mortality (events per 10,000 person-years) also decreased from 14.3 in 1997 to 2000, to 7.5 in 2004 to 2011 (p<0.001). Most hospital admissions and deaths occurred in the winter season and the fewest occurred in the summer, overlapping respectively with the lowest and highest temperatures of the year in Spain. Moreover, lower temperatures prior to PCP admission, as well as higher concentrations of NO2 and particulate matter up to 10 m in size (PM10) at the time of admission were associated with higher likelihoods of hospital admission due to PCP when two weeks, one month, 1.5 months or two months were used as controls (p<0.01). Furthermore, higher concentrations of ozone at one month (p=0.007), 1.5 months (p<0.001) and two months (p=0.006) prior to admission were associated with higher likelihoods of hospital admission with PCP. For PCP-related deaths, lower temperatures prior to admission and higher concentrations of atmospheric PM10 at the time of admission were related to higher likelihood of death when two weeks, one month and 1.5 months were used as controls (p<0.05).
  
  
  CONCLUSIONS
  PCP was a significant health problem in the cART era (1997 to 2011), and PCP epidemiology was adversely influenced by colder climatological factors and higher ambient air pollution levels.
authors.affiliation: Department of Preventive Medicine & Public Health, Rey Juan Carlos University, Madrid, Spain; alejandro.alvaro@urjc.es.
authors.forename: Alejandro
authors.initials: A
authors.lastname: Alvaro-Meca
authors.affiliation: Department of Preventive Medicine & Public Health, Rey Juan Carlos University, Madrid, Spain.
authors.forename: Ines
authors.initials: I
authors.lastname: Palomares-Sancho
authors.affiliation: Unit of HIV Surveillance and Behavioural Monitoring, National Centre of Epidemiology, Institute of Health Carlos III, Madrid, Spain.|Network of Biomedical Research Centres Epidemiology and Public Health (Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública (CIBERESP), Madrid, Spain.
authors.forename: Asuncion
authors.initials: A
authors.lastname: Diaz
authors.affiliation: Department of Human Geography, Faculty of Geography and History, Complutense University of Madrid, Madrid, Spain.
authors.forename: Rosa
authors.initials: R
authors.lastname: Resino
authors.affiliation: Department of Preventive Medicine & Public Health, Rey Juan Carlos University, Madrid, Spain.
authors.forename: Angel Gil
authors.initials: AG
authors.lastname: De Miguel
authors.affiliation: Unit of Viral Infection and Immunity, National Centre for Microbiology, Institute of Health Carlos III, Majadahonda, Madrid, Spain; sresino@isciii.es.
authors.forename: Salvador
authors.initials: S
authors.lastname: Resino
mesh_terms: D000328:Adult; D018592:Cross-Over Studies; D005260:Female; D006679:HIV Seropositivity / Q000150:complications*; D006760:Hospitalization; D006801:Humans; D015994:Incidence; D008297:Male; D011020:Pneumonia, Pneumocystis / Q000453:epidemiology*; D012189:Retrospective Studies; D012307:Risk Factors; D013030:Spain / Q000453:epidemiology
keywords: AIDS; Pneumocystis; air pollution; epidemiology; seasonality