Use of DALYs in economic analyses on interventions for infectious diseases: a systematic review.

A systematic literature review was performed on full economic evaluations of infectious disease interventions using disability-adjusted life years (DALY) as outcome measure. The search was limited to the period between 1994 and September 2011 and conducted in Medline, SciSearch and EMBASE databases. We included 154 studies, mostly targeting HIV/AIDS and malaria with most conducted for African countries (40%) and <10% in high-income countries. Third-payer perspective was applied in 29% of the studies, 25% used the societal perspective and 12% used both. Only 16% of the studies took indirect effects (i.e. herd immunity) of interventions into account. Intervention, direct healthcare and indirect non-healthcare costs were taken into account in respectively 100%, 81% and 36% of the studies. The majority of the studies followed the Global Burden of Disease method for DALY estimations, but most studies deviated from WHO cost-effectiveness guidelines. Better adherence to freely accessible guidelines will improve generalizability between full economic evaluations.

The disease burden of hepatitis B, influenza, measles and salmonellosis in Germany: first results of the burden of communicable diseases in Europe study.

Setting priorities in the field of infectious diseases requires evidence-based and robust baseline estimates of disease burden. Therefore, the European Centre for Disease Prevention and Control initiated the Burden of Communicable Diseases in Europe (BCoDE) project. The project uses an incidence- and pathogen-based approach to measure the impact of both acute illness and sequelae of infectious diseases expressed in disability-adjusted life years (DALYs). This study presents first estimates of disease burden for four pathogens in Germany. The number of reported incident cases adjusted for underestimation served as model input. For the study period 2005-2007, the average disease burden was estimated at 33 116 DALYs/year for influenza virus, 19 115 DALYs/year for Salmonella spp., 8708 DALYs/year for hepatitis B virus and 740 DALYs/year for measles virus. This methodology highlights the importance of sequelae, particularly for hepatitis B and salmonellosis, because if omitted, the burden would have been underestimated by 98% and 56%, respectively.

Incidence and mortality of hospital- and ICU-treated sepsis: results from an updated and expanded systematic review and meta-analysis.

PURPOSE: To investigate the global burden of sepsis in hospitalized adults by updating and expanding a systematic review and meta-analysis and to compare findings with recent Institute for Health Metrics and Evaluation (IHME) sepsis estimates. METHODS: Thirteen electronic databases were searched for studies on population-level sepsis incidence defined according to clinical criteria (Sepsis-1, -2: severe sepsis criteria, or sepsis-3: sepsis criteria) or relevant ICD-codes. The search of the original systematic review was updated for studies published 05/2015-02/2019 and complemented by a search targeting low- or middle-income-country (LMIC) studies published 01/1979-02/2019. We performed a random-effects meta-analysis with incidence of hospital- and ICU-treated sepsis and proportion of deaths among these sepsis cases as outcomes. RESULTS: Of 4746 results, 28 met the inclusion criteria. 21 studies contributed data for the meta-analysis and were pooled with 30 studies from the original meta-analysis. Pooled incidence was 189 [95% CI 133, 267] hospital-treated sepsis cases per 100,000 person-years. An estimated 26.7% [22.9, 30.7] of sepsis patients died. Estimated incidence of ICU-treated sepsis was 58 [42, 81] per 100,000 person-years, of which 41.9% [95% CI 36.2, 47.7] died prior to hospital discharge. There was a considerably higher incidence of hospital-treated sepsis observed after 2008 (+ 46% compared to the overall time frame). CONCLUSIONS: Compared to results from the IHME study, we found an approximately 50% lower incidence of hospital-treated sepsis. The majority of studies included were based on administrative data, thus limiting our ability to assess temporal trends and regional differences. The incidence of sepsis remains unknown for the vast majority of LMICs, highlighting the urgent need for improved epidemiological sepsis surveillance.

Copper metabolism in the acute inflammatory process and its possible significance for a novel approach to the therapy of inflammation.

The concentration and the total content of copper were evaluated in plasma, blood cells, liver and kidney of normal rats and in rats inflamed by intrapleural injection of carrageenan. The experimental disease was followed from zero time up to 10 days after the irritant injection. A statistically significant increase of copper concentration in both plasma and blood cells compartments was measured between zero and 72 h, followed by a prompt return to normal copper levels. On the contrary, copper concentration and total copper content of the liver did not vary throughout the experiment, whereas in the kidney both parameters were found slightly higher than normal 6, 8 and 10 days after the injection of the irritant. These observations are briefly discussed, and proposed as a valuable background to outline new strategies for anti-inflammatory therapy.

Impact of measles national vaccination coverage on burden of measles across 29 Member States of the European Union and European Economic Area, 2006-2011.

BACKGROUND: Challenges in reaching good vaccination coverage against measles emerged in several European Union/European Economic Area Member States (EU/EEA MS) leading to progressive accumulation of susceptible individuals and outbreaks. The Burden of Communicable Diseases in Europe (BCoDE) project developed a methodology for measuring the burden of communicable diseases expressed in Disability-Adjusted Life Years (DALYs) in the EU/EEA MS. The aim of this study was to compare national vaccination coverage and burden of measles across EU/EEA MS. METHODS: Country-specific data on measles national vaccination coverage 2006-2011 from 29 EU/EEA MS (MCV1) were retrieved from Centralized Information System for Infectious Diseases (CISID). DALYs were calculated for each country separately using a disease progression model with a single input parameter (annual measles incidence, adjusted for under-estimation). A software application was used to compute estimated DALYs according to country-specific and year-specific population age-distributions (data retrieved from Eurostat). Log-linear mixed-effect regression modeling approach was used to investigate a linear relation between natural logarithm-transformed DALYs and coverage. RESULTS: The reported annual vaccination coverage ranged from 72.6% to 100%. The estimated national annual burden ranged from 0 to 30.6 DALYs/100,000. Adjusting for year, there was a significant negative relationship between coverage and burden. For a given country there was a decrease in log-transformed DALYs/100,000 of 0.025 (95% confidence interval: -0.047 to -0.003) for every percentage increase in vaccination coverage. The largest effect of calendar time on estimated burden of measles was observed for the year 2011, the smallest was for the year 2007. CONCLUSIONS: This study shows that the degree of success of national measles vaccination programs, when measured by the coverage obtained, is significantly associated with overall impact of measles across EU/EEA MS. In EU/EEA MS each percentage point increase in national vaccination coverage seems to lead to early significant reduction of overall burden of measles.

Metal accumulation and binding protein induction in Mytilus galloprovincialis, Scapharca inaequivalvis, and Tapes philippinarum from the Lagoon of Venice.

Heavy metal pollution is known to be widespread in the sediments of the Lagoon of Venice. Therefore, physiological parameters influenced by this form of contamination were examined. The bivalve molluscs blue mussel (Mytilus galloprovincialis), ark clam (Scapharca inaequivalvis), and Japanese littleneck (Tapes philippinarum) were sampled in two sites (Marghera, Chioggia) every 3 months for 1 year. The digestive gland and gills of each bivalve were analyzed. The concentrations of essential and nonessential metals (including chromium, manganese, iron, cobalt, nickel, copper, zinc, and cadmium) were determined. Because glutathione and metallothioneins (MTs) are involved in metal homeostasis and detoxification, their concentrations were evaluated in relation to metal concentrations. Results show that (1) all three studied species accumulate metals to a considerable extent, with some species-specific differences between the digestive gland and gills; (2) gills are a good tissue to evaluate pollution by examining the MT content. In particular, the correlation between Zn and MT levels in the gills indicates that M. galloprovincialis and S. inaequivalvis are sentinel organisms and can be used specifically for Zn pollution; (3) T. philippinarum accumulates Cu in the digestive gland more readily than the other two bivalves and therefore has the highest MT.

Copper and zinc status during acute inflammation: studies on blood, liver and kidneys metal levels in normal and inflamed rats.

The concentrations of copper and zinc in plasma, blood cells, liver and kidneys were determined in a study performed on normal female rats, and in female rats with carrageenan induced pleurisy. In the normal rat, the total amount of both metals increases, from 51 to 79 days of age, in all the compartments examined. This increase was mostly, and in some case exclusively, dependent upon the growth of the animal, although high individual and day to day variations in both copper and zinc values were observed in all the compartments studied. In the blood of inflamed rats a statistically significant increase in copper was measured during the crucial hours of the experiment (i.e. from 6 to 72 h); over 90% of the increase found was attributable to variations in plasma copper concentration values. In the liver of inflamed rats a statistically significant increase in zinc was measured at 6, 22 and 48 h after the carrageenan injection. The induction of the acute non-infective inflammatory process did not cause quantitative changes of both copper and zinc in all the other compartments considered in the present study. These results seem to suggest that, during acute inflammation, the organism increases its requirement for copper and zinc, and that this demand is fulfilled by enhanced intestinal absorption and/or decreased intestinal excretion of both metals.