Current concepts: host-pathogen interactions in cystic fibrosis airways disease.

Chronic infection and inflammation are defining characteristics of cystic fibrosis (CF) airway disease. Conditions within the airways of patients living with CF are conducive to colonisation by a variety of opportunistic bacterial, viral and fungal pathogens. Improved molecular identification of microorganisms has begun to emphasise the polymicrobial nature of infections in the CF airway microenvironment. Changes to CF airway physiology through loss of cystic fibrosis transmembrane conductance regulator functionality result in a wide range of immune dysfunctions, which permit pathogen colonisation and persistence. This review will summarise the current understanding of how CF pathogens infect, interact with and evade the CF host.

Cryptococcal Antigenemia in Immunocompromised Human Immunodeficiency Virus Patients in Rural Tanzania: A Preventable Cause of Early Mortality

Background.  Cryptococcal meningitis is a leading cause of death in people living with human immunodeficiency virus (HIV)/acquired immune deficiency syndrome. The World Health Organizations recommends pre-antiretroviral treatment (ART) cryptococcal antigen (CRAG) screening in persons with CD4 below 100 cells/µL. We assessed the prevalence and outcome of cryptococcal antigenemia in rural southern Tanzania. Methods.  We conducted a retrospective study including all ART-naive adults with CD4 <150 cells/µL prospectively enrolled in the Kilombero and Ulanga Antiretroviral Cohort between 2008 and 2012. Cryptococcal antigen was assessed in cryopreserved pre-ART plasma. Cox regression estimated the composite outcome of death or loss to follow-up (LFU) by CRAG status and fluconazole use. Results.  Of 750 ART-naive adults, 28 (3.7%) were CRAG-positive, corresponding to a prevalence of 4.4% (23 of 520) in CD4 <100 and 2.2% (5 of 230) in CD4 100-150 cells/µL. Within 1 year, 75% (21 of 28) of CRAG-positive and 42% (302 of 722) of CRAG-negative patients were dead or LFU (P<.001), with no differences across CD4 strata. Cryptococcal antigen positivity was an independent predictor of death or LFU after adjusting for relevant confounders (hazard ratio [HR], 2.50; 95% confidence interval [CI], 1.29-4.83; P = .006). Cryptococcal meningitis occurred in 39% (11 of 28) of CRAG-positive patients, with similar retention-in-care regardless of meningitis diagnosis (P = .8). Cryptococcal antigen titer >1:160 was associated with meningitis development (odds ratio, 4.83; 95% CI, 1.24-8.41; P = .008). Fluconazole receipt decreased death or LFU in CRAG-positive patients (HR, 0.18; 95% CI, .04-.78; P = .022). Conclusions.  Cryptococcal antigenemia predicted mortality or LFU among ART-naive HIV-infected persons with CD4 <150 cells/µL, and fluconazole increased survival or retention-in-care, suggesting that targeted pre-ART CRAG screening may decrease early mortality or LFU. A CRAG screening threshold of CD4 <100 cells/µL missed 18% of CRAG-positive patients, suggesting guidelines should consider a higher threshold.

Estimating HIV Incidence, Time to Diagnosis, and the Undiagnosed HIV Epidemic Using Routine Surveillance Data.

BACKGROUND Estimates of the size of the undiagnosed HIV-infected population are important to understand the HIV epidemic and to plan interventions, including "test-and-treat" strategies. METHODS We developed a multi-state back-calculation model to estimate HIV incidence, time between infection and diagnosis, and the undiagnosed population by CD4 count strata, using surveillance data on new HIV and AIDS diagnoses. The HIV incidence curve was modelled using cubic splines. The model was tested on simulated data and applied to surveillance data on men who have sex with men in The Netherlands. RESULTS The number of HIV infections could be estimated accurately using simulated data, with most values within the 95% confidence intervals of model predictions. When applying the model to Dutch surveillance data, 15,400 (95% confidence interval [CI] = 15,000, 16,000) men who have sex with men were estimated to have been infected between 1980 and 2011. HIV incidence showed a bimodal distribution, with peaks around 1985 and 2005 and a decline in recent years. Mean time to diagnosis was 6.1 (95% CI = 5.8, 6.4) years between 1984 and 1995 and decreased to 2.6 (2.3, 3.0) years in 2011. By the end of 2011, 11,500 (11,000, 12,000) men who have sex with men in The Netherlands were estimated to be living with HIV, of whom 1,750 (1,450, 2,200) were still undiagnosed. Of the undiagnosed men who have sex with men, 29% (22, 37) were infected for less than 1 year, and 16% (13, 20) for more than 5 years. CONCLUSIONS This multi-state back-calculation model will be useful to estimate HIV incidence, time to diagnosis, and the undiagnosed HIV epidemic based on routine surveillance data.

Domains of importance to the quality of life of older people from two Swiss regions

BACKGROUND Quality of life (QoL) is a subjective perception whose components may vary in importance between individuals. Little is known about which domains of QoL older people deem most important. OBJECTIVE This study investigated in community-dwelling older people the relationships between the importance given to domains defining their QoL and socioeconomic, demographic and health status. METHODS Data were compiled from older people enrolled in the Lc65+ cohort study and two additional, population-based, stratified random samples (n = 5,300). Principal components analysis (PCA) was used to determine the underlying domains among 28 items that participants defined as important to their QoL. The components extracted were used as dependent variables in multiple linear regression models to explore their associations with socioeconomic, demographic and health status. RESULTS PCA identified seven domains that older persons considered important to their QoL. In order of importance (highest to lowest): feeling of safety, health and mobility, autonomy, close entourage, material resources, esteem and recognition, and social and cultural life. A total of six and five domains of importance were significantly associated with education and depressive symptoms, respectively. The importance of material resources was significantly associated with a good financial situation (β = 0.16, P = 0.011), as was close entourage with living with others (β = 0.20, P = 0.007) and as was health and mobility with age (β = -0.16, P = 0.014). CONCLUSION The importance older people give to domains of their QoL appears strongly related to their actual resources and experienced losses. These findings may help clinicians, researchers and policy makers better adapt strategies to individuals' needs.