Biomedical subjects

Mirjam Kretzschmar

Publications and source records attributed to Mirjam Kretzschmar.

12 recordsLinked to original sources

PubMed2006

Determinants of childhood vaccination coverage in Kazakhstan in a period of societal change: implications for vaccination policies.

After the fall of the Soviet Union countries in Central Asia have undergone large changes. In Kazakhstan the vaccination coverage decreased between 1990 and 1995, which resulted in an increased incidence of some vaccine-preventable diseases, e.g. diphtheria and measles. In this study we examined which factors affected the vaccination status of children in Kazakhstan and whether they resemble patterns observed in developing or developed countries. We found a mixed pattern of risk factors, consistent with the status of Kazakhstan as a transitional economy. Especially prominent was the relatively high education of the women and good access to the medical care system.

Adolescent↗

PubMed2006

Using data on social contacts to estimate age-specific transmission parameters for respiratory-spread infectious agents.

The estimation of transmission parameters has been problematic for diseases that rely predominantly on transmission of pathogens from person to person through small infectious droplets. Age-specific transmission parameters determine how such respiratory agents will spread among different age groups in a human population. Estimating the values of these parameters is essential in planning an effective response to potentially devastating pandemics of smallpox or influenza and in designing control strategies for diseases such as measles or mumps. In this study, the authors estimated age-specific transmission parameters by augmenting infectious disease data with auxiliary data on self-reported numbers of conversational partners per person. They show that models that use transmission parameters based on these self-reported social contacts are better able to capture the observed patterns of infection of endemically circulating mumps, as well as observed patterns of spread of pandemic influenza. The estimated age-specific transmission parameters suggested that school-aged children and young adults will experience the highest incidence of infection and will contribute most to further spread of infections during the initial phase of an emerging respiratory-spread epidemic in a completely susceptible population. These findings have important implications for controlling future outbreaks of novel respiratory-spread infectious agents.

Adolescent↗

PubMed2006

Prediction of costs, effectiveness, and disease control of a population-based program using home sampling for diagnosis of urogenital Chlamydia trachomatis Infections.

OBJECTIVE: To estimate the incremental effects and costs of a home sampling screening approach for Chlamydia trachomatis over the current in-office screening practice in Denmark. GOALS: To assess the effect of a new screening strategy. STUDY DESIGN: A dynamic Monte Carlo model estimated prevalence and incidence over 10 years for a home sampling screening program and the current in-office screening. Subsequently, the incremental number of major outcomes averted (MOA) and the related direct and indirect costs were estimated. RESULTS: Infection prevalence after 10 years was 1.0% with a home sampling program and 4.2% with the current in-office screening practice. The total costs per MOA reached 3186 US dollars during the first year of the home sampling strategy, but in year 4, the accumulated indirect costs offset the direct costs, and the program henceforth saved society costs. CONCLUSIONS: Home sampling should be considered a relevant alternative to the current practice of in-office screening.

Adolescent↗

PubMed2006

Frequency of adverse events after vaccination with different vaccinia strains.

BACKGROUND: Large quantities of smallpox vaccine have been stockpiled to protect entire nations against a possible reintroduction of smallpox. Planning for an appropriate use of these stockpiled vaccines in response to a smallpox outbreak requires a rational assessment of the risks of vaccination-related adverse events, compared to the risk of contracting an infection. Although considerable effort has been made to understand the dynamics of smallpox transmission in modern societies, little attention has been paid to estimating the frequency of adverse events due to smallpox vaccination. Studies exploring the consequences of smallpox vaccination strategies have commonly used a frequency of approximately one death per million vaccinations, which is based on a study of vaccination with the New York City Board of Health (NYCBH) strain of vaccinia virus. However, a multitude of historical studies of smallpox vaccination with other vaccinia strains suggest that there are strain-related differences in the frequency of adverse events after vaccination. Because many countries have stockpiled vaccine based on the Lister strain of vaccinia virus, a quantitative evaluation of the adverse effects of such vaccines is essential for emergency response planning. We conducted a systematic review and statistical analysis of historical data concerning vaccination against smallpox with different strains of vaccinia virus. METHODS AND FINDINGS: We analyzed historical vaccination data extracted from the literature. We extracted data on the frequency of postvaccinal encephalitis and death with respect to vaccinia strain and age of vaccinees. Using a hierarchical Bayesian approach for meta-analysis, we estimated the expected frequencies of postvaccinal encephalitis and death with respect to age at vaccination for smallpox vaccines based on the NYCBH and Lister vaccinia strains. We found large heterogeneity between findings from different studies and a time-period effect that showed decreasing incidences of adverse events over several decades. To estimate death rates, we then restricted our analysis to more-recent studies. We estimated that vaccination with the NYCBH strain leads to an average of 1.4 deaths per million vaccinations (95% credible interval, 0-6) and that vaccination with Lister vaccine leads to an average of 8.4 deaths per million vaccinations (95% credible interval, 0-31). We combined age-dependent estimates of the frequency of death after vaccination and revaccination with demographic data to obtain estimates of the expected number of deaths in present societies due to vaccination with the NYCBH and Lister vaccinia strains. CONCLUSIONS: Previous analyses of smallpox vaccination policies, which rely on the commonly assumed value of one death per million vaccinations, may give serious underestimates of the number of deaths resulting from vaccination. Moreover, because there are large, strain-dependent differences in the frequency of adverse events due to smallpox vaccination, it is difficult to extrapolate from predictions for the NYCBH-derived vaccines (stockpiled in countries such as the US) to predictions for the Lister-derived vaccines (stockpiled in countries such as Germany). In planning for an effective response to a possible smallpox outbreak, public-health decision makers should reconsider their strategies of when to opt for ring vaccination and when to opt for mass vaccination.

Age Distribution↗

PubMed2005

The incidence of Bordetella pertussis infections estimated in the population from a combination of serological surveys.

OBJECTIVES: Bordetella pertussis circulates even in highly vaccinated populations. There is a considerable amount of infection in adults. For designing more effective vaccination schedules it is important to quantify the age-dependent relation between the number of notified cases and the number of infections. METHODS: We used a statistical relationship between the time since infection and the IgG antibody titers against pertussis toxin, derived from a longitudinal data set, to estimate time since infection for all individuals in a cross-sectional population-based study (1995-1996) based on their titers. Age-specific incidence of infection with B. pertussis was calculated and compared with the age-distribution of notified cases of pertussis in 1994-1996. RESULTS: Estimated incidence of infection was 6.6% per year for 3-79-year olds, annual incidence of notified cases 0.01%. Estimated age-specific incidence of infection was lowest for 3-4-year olds (3.3%) and increased gradually up to the age of 20-24 years (10.8%). The number of notified cases was highest for 3-9-year olds. CONCLUSIONS: In the Dutch population B. pertussis infections occur more frequently and in elder age-categories then suggested by notifications. Mathematical modeling could explore what booster vaccination strategies are most effective in reducing severe disease among not (completely) vaccinated infants.

Adolescent↗

PubMed2005

A measles epidemic threshold in a highly vaccinated population.

BACKGROUND: Mass vaccination against measles has successfully lowered the incidence of the disease and has changed the epidemic pattern from a roughly biennial cycle to an irregular sequence of outbreaks. A possible explanation for this sequence of outbreaks is that the vaccinated population is protected by solid herd immunity. If so, we would expect to see the fraction of susceptible individuals remaining below an epidemic threshold. An alternative explanation is the occurrence of occasional localised lapses in herd immunity that allow for major outbreaks in areas with a low vaccine coverage. In that case, we would expect the fraction of susceptible individuals to exceed an epidemic threshold before outbreaks occur. These two explanations for the irregular sequence of measles outbreaks can be tested against observations of both the fraction of susceptible individuals and infection attack rates. METHODS AND FINDINGS: We have estimated both the fraction of susceptible individuals at the start of each epidemic year and the infection attack rates for each epidemic year in the Netherlands over a 28-y period. During this period the vaccine coverage averaged 93%, and there was no sustained measles transmission. Several measles outbreaks occurred in communities with low vaccine coverage, and these ended without intervention. We show that there is a clear threshold value for the fraction of susceptible individuals, below which only minor outbreaks occurred, and above which both minor and major outbreaks occurred. A precise, quantitative relationship exists between the fraction of susceptible individuals in excess of this threshold and the infection attack rate during the major outbreaks. CONCLUSION: In populations with a high but heterogeneous vaccine coverage, measles transmission can be interrupted without establishing solid herd immunity. When infection is reintroduced, a major outbreak can occur in the communities with low vaccine coverage. During such a major outbreak, each additional susceptible individual in excess of the threshold is associated with almost two additional infections. This quantitative relationship offers potential for anticipating both the likelihood and size of future major outbreaks when measles transmission has been interrupted.

Disease Outbreaks↗

PubMed2005

Pathogen adaptation under imperfect vaccination: implications for pertussis.

Mass vaccination campaigns have drastically reduced the burden of infectious diseases. Unfortunately, in recent years several infectious diseases have re-emerged. Pertussis poses a well-known example. Inspired by pertussis, we study, by means of an epidemic model, the population and evolutionary dynamics of a pathogen population under the pressure of vaccination. A distinction is made between infection in immunologically naive individuals (primary infection) and infection in individuals whose immune system has been primed by vaccination or infection (secondary infection). The results show that (i) vaccination with an imperfect vaccine may not succeed in reducing the infection pressure if the transmissibility of secondary infections is higher than that of primary infections; (ii) pathogen strains that are able to evade the immunity induced by vaccination can only spread if escape mutants incur no or only a modest fitness cost and (iii) the direction of evolution depends crucially on the distribution of the different types of susceptibles in the population. We discuss the implications of these results for the design and use of vaccines that provide temporary immunity.

Adaptation, Biological↗

PubMed2005

Competition of pathogen strains leading to infection with variable infectivity and the effect of treatment.

A model for the spread of two strains of a pathogen leading to an infection with variable infectivity is considered. The course of infection is described by two stages with different infectivity levels. The model is extended to account for treatment by including a third stage with different infectivity and survival for those treated. The contribution of each stage to incidence and prevalence is investigated and the effect of infectivity and survival on the basic reproduction ratio is examined. Standard equilibrium analysis is performed for both models, revealing that the successful strain is the one with highest reproduction ratio. If therapy, however, is more effective against the strain that wins in the absence of treatment and its reproduction ratio is sufficiently reduced, it might be outcompeted by the other strain after treatment becomes widely available. In this case, early introduction of treatment can prevent a major outbreak.

Communicable Diseases↗

PubMed2005

Costs and effects of chlamydial screening: dynamic versus static modeling.

OBJECTIVE: The objective of this study was to assess the impact of modeling type on the economic evaluation of screening programs for asymptomatic Chlamydia trachomatis infections. STUDY: We compared a stochastic network simulation model (dynamic model) with a decision analysis model (static model) for estimating the cost-effectiveness of an opportunistic screening program. The influence of the model type on the required data, the computed results, and the sensitivity of model parameters were investigated. RESULTS: When compared with static modeling, dynamic modeling yielded different cost-effectiveness ratios and identified other optimal screening strategies as it considers changes in the force of infection caused by screening. However, it is more complex, data- and time-demanding, and more sensitive to some parameters affecting the force of infection than static modeling. CONCLUSIONS: Dynamic models should be applied for the economic evaluation of prevention measures that have the potential to lower the force of infection such as large-scale chlamydial screening programs.

Adolescent↗

PubMed2004

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.

Acute Disease↗

PubMed2004

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.

Contact Tracing↗

PubMed2003

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.

Adult↗