Mirjam Kretzschmar

Disability weights for the Global Burden of Disease 2013 study

BACKGROUND The Global Burden of Disease (GBD) study assesses health losses from diseases, injuries, and risk factors using disability-adjusted life-years, which need a set of disability weights to quantify health levels associated with non-fatal outcomes. The objective of this study was to estimate disability weights for the GBD 2013 study. METHODS We analysed data from new web-based surveys of participants aged 18-65 years, completed in four European countries (Hungary, Italy, the Netherlands, and Sweden) between Sept 23, 2013, and Nov 11, 2013, combined with data previously collected in the GBD 2010 disability weights measurement study. Surveys used paired comparison questions for which respondents considered two hypothetical individuals with different health states and specified which person they deemed healthier than the other. These surveys covered 183 health states pertinent to GBD 2013; of these states, 30 were presented with descriptions revised from previous versions and 18 were new to GBD 2013. We analysed paired comparison data using probit regression analysis and rescaled results to disability weight units between 0 (no loss of health) and 1 (loss equivalent to death). We compared results with previous estimates, and an additional analysis examined sensitivity of paired comparison responses to duration of hypothetical health states. FINDINGS The total analysis sample consisted of 30 230 respondents from the GBD 2010 surveys and 30 660 from the new European surveys. For health states common to GBD 2010 and GBD 2013, results were highly correlated overall (Pearsons r 0·992 [95% uncertainty interval 0·989-0·994]). For health state descriptions that were revised for this study, resulting disability weights were substantially different for a subset of these weights, including those related to hearing loss (eg, complete hearing loss: GBD 2010 0·033 [0·020-0·052]; GBD 2013 0·215 [0·144-0·307]) and treated spinal cord lesions (below the neck: GBD 2010 0·047 [0·028-0·072]; GBD 2013 0·296 [0·198-0·414]; neck level: GBD 2010 0·369 [0·243-0·513]; GBD 2013 0·589 [0·415-0·748]). Survey responses to paired comparison questions were insensitive to whether the comparisons were framed in terms of temporary or chronic outcomes (Pearsons r 0·981 [0·973-0·987]). INTERPRETATION This study substantially expands the empirical basis for assessment of non-fatal outcomes in the GBD study. Findings from this study substantiate the notion that disability weights are sensitive to particular details in descriptions of health states, but robust to duration of outcomes. FUNDING European Centre for Disease Prevention and Control, Bill and Melinda Gates Foundation.

Perspective: human contact patterns and the spread of airborne infectious diseases

Networks of social contacts channel the transmission of airborne infections. Emerging insights from fields of science as diverse as mathematics, population biology and the social sciences are beginning to reveal how the contact pattern of the hosts determines the spread and evolution of airborne infectious agents.

The contribution of steady and casual partnerships to the incidence of HIV infection among homosexual men in Amsterdam

Objective: To assess the relative contribution of steady and casual partnerships to the incidence of HIV infection among homosexual men in Amsterdam, and to determine the effect of increasing sexually risky behaviours among both types of partners in the era of highly active antiretroviral therapy (HAART). Methods: A mathematical model was developed for the spread of HIV infection among young homosexual men in Amsterdam after the introduction of HAART. The model describes the formation of both steady and casual partnerships. Behavioural parameters were estimated separately for steady and casual partners from the Amsterdam Cohort Study among young homosexual men. HIV incidence and the fraction of new infections attributed to casual contacts were calculated from the model, allowing for uncertainty in the increases in risky behaviour, the effect of HAART, and levels of HIV testing and HAART administration. Results: Currently, 86% (range 74–90%) of new HIV infections occur within steady partnerships. A reduction of 75–99% in infectivity caused by HAART will be counterbalanced by increases of 50% (range 30–80%) in risky behaviour with steady partners, but not by increases of up to 100% with casual partners. If HIV testing is increased from 42 to 80% and HAART administration from 70 to 85%, then even an increase of 100% in risk-taking with steady partners will not outweigh the effect of HAART. Conclusion: Most new HIV infections among homosexual men in Amsterdam occur within steady relationships. Prevention measures should address risky behaviour, specifically with steady partners, and the promotion of HIV testing.

Social contacts of school children and the transmission of respiratory-spread pathogens

Empirical data about contact frequencies of children is needed for estimating parameters in mathematical modelling studies that investigate the effect of targeting influenza intervention to children. A survey about the social contacts of school children was conducted in a primary school in Germany. The distribution of the daily numbers of contacts was stratified by age of the contacted person and by weekday. A negative binomial regression analysis was performed to investigate factors that influence contact behaviour. Using logistic regression analysis we examined the relationship between the numbers of private contacts and having been ill in the last 6 months. We computed effective contact numbers to take the heterogeneity in contact behaviour into account in assessing the contribution of childrens contacts to the overall transmission of an infection. The possible effects of intervention measures such as school closure and vaccination on the transmission of respiratory-spread agents to other age groups are discussed.

Primary HIV infection as source of HIV transmission within steady and casual partnerships among homosexual men

Objective: To assess the contribution of primary or acute HIV infection to the transmission of HIV among homosexual men in Amsterdam and to investigate how the initiation of treatment during primary HIV infection (PHI) can affect the incidence of HIV infection. Methods: A mathematical model describing HIV transmission among homosexual men was developed. In the model, men are involved in both steady and casual partnerships. Infectivity is higher during PHI than during chronic HIV infection. Highly active antiretroviral therapy reduces infectivity and increases the time to the development of AIDS. Its effect is enhanced if treatment is initiated during PHI. HIV incidence and the fraction of transmission attributed to PHI were calculated for different levels of treatment efficacy. Results: Primary infections account for 35% of HIV transmissions from casual partners and 6% of transmissions from steady partners. Among all new infections, only 11% occurs during PHI. Therefore, the effect of treatment during PHI on the incidence of HIV is limited. However, in a community with higher risky behaviour among casual partners, the fraction of transmission attributed to PHI increases to 25%. Conclusion: Primary infections play a more important role in transmission from casual partners than in transmission from steady partners. Therefore, in communities in which steady partners account for the majority of new infections and the epidemic is at an advanced phase, the contribution of PHI to the transmission of HIV is rather small and the effect of early treatment on the incidence of HIV is limited.

Ring Vaccination and Smallpox Control

We present a stochastic model for the spread of smallpox after a small number of index cases are introduced into a susceptible population. The model describes a branching process for the spread of the infection and the effects of intervention measures. We discuss scenarios in which ring vaccination of direct contacts of infected persons is sufficient to contain an epidemic. Ring vaccination can be successful if infectious cases are rapidly diagnosed. However, because of the inherent stochastic nature of epidemic outbreaks, both the size and duration of contained outbreaks are highly variable. Intervention requirements depend on the basic reproduction number R0, for which different estimates exist. When faced with the decision of whether to rely on ring vaccination, the public health community should be aware that an epidemic might take time to subside even for an eventually successful intervention strategy.

Incidence and Reproduction Numbers of Pertussis: Estimates from Serological and Social Contact Data in Five European Countries

Analyses of serological and social contact data from several European countries by Miriam Kretzschmar and colleagues show that vaccination against pertussis has shifted the burden of infection from children to adolescents and adults.

Dynamic transmission modeling: A report of the ISPOR-SMDM modeling good research practices task force-5

Abstract The transmissible nature of communicable diseases is what sets them apart from other diseases modeled by health economists. The probability of a susceptible individual becoming infected at any one point in time (the force of infection) is related to the number of infectious individuals in the population, will change over time, and will feed back into the future force of infection. These nonlinear interactions produce transmission dynamics that require specific consideration when modeling an intervention that has an impact on the transmission of a pathogen. Best practices for designing and building these models are set out in this article.

Effectiveness of yearly, register based screening for chlamydia in the Netherlands: controlled trial with randomised stepped wedge implementation

Objective To evaluate the effectiveness of register based, yearly chlamydia screening. Design Controlled trial with randomised stepped wedge implementation in three blocks. Setting Three regions of the Netherlands: Amsterdam, Rotterdam, and South Limburg. Participants 317 304 women and men aged 16-29 years listed on municipal registers at start of trial. Intervention From March 2008 to February 2011, the Chlamydia Screening Implementation programme offered yearly chlamydia screening tests. Postal invitations asked people to use an internet site to request a kit for self collection of samples, which would then be sent to regional laboratories for testing. Treatment and partner notification were done by the general practitioner or at a sexually transmitted infection clinic. Main outcome measures Primary outcomes were the percentage of chlamydia tests positive (positivity), percentage of invitees returning a specimen (uptake), and estimated chlamydia prevalence. Secondary outcomes were positivity according to sex, age, region, and sociodemographic factors; adherence to screening invitations; and incidence of self reported pelvic inflammatory disease. Results The participation rate was 16.1% (43 358/269 273) after the first invitation, 10.8% after the second, and 9.5% after the third, compared with 13.0% (6223/48 031) in the control block invited at the end of round two of the intervention. Chlamydia positivity in the intervention blocks at the first invitation was the same as in the control block (4.3%) and 0.2% lower at the third invitation (odds ratio 0.96 (95% confidence interval 0.83 to 1.10)). No substantial decreases in positivity were seen after three screening rounds in any region or sociodemographic group. Among the people who participated three times (2.8% of all invitees), positivity fell from 5.9% to 2.9% (odds ratio 0.49 (0.47 to 0.50)). Conclusions There was no statistical evidence of an impact on chlamydia positivity rates or estimated population prevalence from the Chlamydia Screening Implementation programme after three years at the participation levels obtained. The current evidence does not support a national roll out of this register based chlamydia screening programme. Trial registration NTR 3071 (Netherlands Trial Register, www.trialregister.nl).

Cost-effectiveness of screening programs for Chlamydia trachomatis: a population-based dynamic approach.

BACKGROUND Models commonly used for the economic assessment of chlamydial screening programs do not consider population effects. GOAL To develop a novel dynamic approach for the economic evaluation of chlamydial prevention measures and to determine the cost-effectiveness of a general practitioner-based screening program. STUDY DESIGN The dynamic approach was used to estimate the cost-effectiveness of a screening program for the first 10 years of screening in The Netherlands. Screening involved a ligase chain reaction test on urine followed by standardized therapies and partner referral. Eligible persons were sexually active, 15 to 24 years, visited a general practitioner, and had no symptoms of sexually transmitted diseases. The heterosexual model population, which consisted of persons 15 to 64 years, had a total chlamydial prevalence of 4.1% before screening. Screening effects on chlamydial incidence were computed by using a population-based stochastic simulation model. Incidence data were connected with a decision analysis model to determine the health effects of the program. The net costs of the program were calculated (investment costs minus averted costs, in 1997 US