In disease control or elimination programs, diagnostics are essential for assessing the impact of interventions, refining treatment strategies, and minimizing the waste of scarce resources. Although ...high-performance tests are desirable, increased accuracy is frequently accompanied by a requirement for more elaborate infrastructure, which is often not feasible in the developing world. These challenges are pertinent to mapping, impact monitoring, and surveillance in trachoma elimination programs. To help inform rational design of diagnostics for trachoma elimination, we outline a nonparametric multilevel latent Markov modeling approach and apply it to 2 longitudinal cohort studies of trachoma-endemic communities in Tanzania (2000-2002) and The Gambia (2001-2002) to provide simultaneous inferences about the true population prevalence of Chlamydia trachomatis infection and disease and the sensitivity, specificity, and predictive values of 3 diagnostic tests for C. trachomatis infection. Estimates were obtained by using data collected before and after mass azithromycin administration. Such estimates are particularly important for trachoma because of the absence of a true "gold standard" diagnostic test for C. trachomatis. Estimated transition probabilities provide useful insights into key epidemiologic questions about the persistence of disease and the clearance of infection as well as the required frequency of surveillance in the post-elimination setting.
Sensitivity analysis (SA) can aid in identifying influential model parameters and optimizing model structure, yet infectious disease modelling has yet to adopt advanced SA techniques that are capable ...of providing considerable insights over traditional methods. We investigate five global SA methods—scatter plots, the Morris and Sobol’ methods, Latin hypercube sampling-partial rank correlation coefficient and the sensitivity heat map method—and detail their relative merits and pitfalls when applied to a microparasite (cholera) and macroparasite (schistosomaisis) transmission model. The methods investigated yielded similar results with respect to identifying influential parameters, but offered specific insights that vary by method. The classical methods differed in their ability to provide information on the quantitative relationship between parameters and model output, particularly over time. The heat map approach provides information about the group sensitivity of all model state variables, and the parameter sensitivity spectrum obtained using this method reveals the sensitivity of all state variables to each parameter over the course of the simulation period, especially valuable for expressing the dynamic sensitivity of a microparasite epidemic model to its parameters. A summary comparison is presented to aid infectious disease modellers in selecting appropriate methods, with the goal of improving model performance and design.
Trachoma: transmission, infection, and control Gambhir, Manoj, Dr; Basáñez, María-Gloria, PhD; Turner, Felicity, MPH ...
The Lancet infectious diseases,
06/2007, Letnik:
7, Številka:
6
Journal Article
Recenzirano
Summary Mass antibiotic treatment and facial cleanliness are central to WHO's strategy for the elimination of blindness caused by trachoma. Recent studies have highlighted the heterogeneous response ...of communities to mass treatment and the complex relation between infection with Chlamydia trachomatis and clinical disease. It is important to be able to explain these findings to predict and maximise the effect of treatment on active trachoma disease and blindness in the community. Here we review the immunobiology of trachoma and provide a simple conceptual model of disease pathogenesis. We show how incorporating this model into a mathematical framework leads to an explanation of the observed community distribution of infection, bacterial load, and disease with age. The predictions of the model and empirical data show some differences that underscore the importance of individual heterogeneity in response to infection. The implications of disease transmission and pathogenesis for trachoma control programmes are discussed.
Community-wide administration of antibiotics is one arm of a four-pronged strategy in the global initiative to eliminate blindness due to trachoma. The potential impact of more efficient, targeted ...treatment of infected households depends on the relative contribution of community and household transmission of infection, which have not previously been estimated.
A mathematical model of the household transmission of ocular Chlamydia trachomatis was fit to detailed demographic and prevalence data from four endemic populations in The Gambia and Tanzania. Maximum likelihood estimates of the household and community transmission coefficients were obtained.
The estimated household transmission coefficient exceeded both the community transmission coefficient and the rate of clearance of infection by individuals in three of the four populations, allowing persistent transmission of infection within households. In all populations, individuals in larger households contributed more to the incidence of infection than those in smaller households.
Transmission of ocular C. trachomatis infection within households is typically very efficient. Failure to treat all infected members of a household during mass administration of antibiotics is likely to result in rapid re-infection of that household, followed by more gradual spread across the community. The feasibility and effectiveness of household targeted strategies should be explored.
In this paper we present AceMod, an agent-based modelling framework for studying influenza epidemics in Australia. The simulator is designed to analyse the spatiotemporal spread of contagion and ...influenza spatial synchrony across the nation. The individual-based epidemiological model accounts for mobility (worker and student commuting) patterns and human interactions derived from the 2006 Australian census and other national data sources. The high-precision simulation comprises 19.8 million stochastically generated software agents and traces the dynamics of influenza viral infection and transmission at several scales. Using this approach, we are able to synthesise epidemics in Australia with varying outbreak locations and severity. For each scenario, we investigate the spatiotemporal profiles of these epidemics, both qualitatively and quantitatively, via incidence curves, prevalence choropleths, and epidemic synchrony. This analysis exemplifies the nature of influenza pandemics within Australia and facilitates future planning of effective intervention, mitigation and crisis management strategies.
Mass drug administration (MDA) is part of the current trachoma control strategy, but it can be costly and results in many uninfected individuals receiving treatment. Here we explore whether ...alternative, targeted approaches are effective antibiotic-sparing strategies.
We analysed data on the prevalence of ocular infection with Chlamydia trachomatis and of active trachoma disease among 4,436 individuals from two communities in The Gambia (West Africa) and two communities in Tanzania (East Africa). An age- and household-structured mathematical model of transmission was fitted to these data using maximum likelihood. The presence of active inflammatory disease as a marker of infection in a household was, in general, significantly more sensitive (between 79% 95%CI: 60%-92% and 86% 71%-95% across the four communities) than as a marker of infection in an individual (24% 16%-33%-66% 56%-76%). Model simulations, under the best fit models for each community, showed that targeting treatment to households has the potential to be as effective as and significantly more cost-effective than mass treatment when antibiotics are not donated. The cost (2007US$) per incident infection averted ranged from 1.5 to 3.1 for MDA, from 1.0 to 1.7 for household-targeted treatment assuming equivalent coverage, and from 0.4 to 1.7 if household visits increased treatment coverage to 100% in selected households. Assuming antibiotics were donated, MDA was predicted to be more cost-effective unless opportunity costs incurred by individuals collecting antibiotics were included or household visits improved treatment uptake. Limiting MDA to children was not as effective in reducing infection as the other aforementioned distribution strategies.
Our model suggests that targeting antibiotics to households with active trachoma has the potential to be a cost-effective trachoma control measure, but further work is required to assess if costs can be reduced and to what extent the approach can increase the treatment coverage of infected individuals compared to MDA in different settings.
The pathogenicity of norovirus is definitively established. However, norovirus is frequently detected in the stool of healthy individuals. To gain understanding of the apparent high prevalence of ...asymptomatic infection, we analyzed a dynamic transmission model of norovirus infection, disease, and immunity. We simulated norovirus epidemiology in low- and high-transmission settings by varying the basic reproduction number (R0). We predicted annual disease incidence values in children aged 0-4 years of 25% with a low R0 and 29% with a high R0. However, the point prevalence of asymptomatic infection rose sharply from 3% to 48% from the low to high R0 settings. Among older children and adults, the models projected that incidence of disease would rise from 6% to 16% from the low to high R0 settings, whereas asymptomatic infection prevalence was lower in this age group. Asymptomatic prevalence of norovirus can change dramatically with small changes in R0. The ratio of prevalence in cases to controls could be high in a developed country and close to or even less than 1 in a high-exposure setting, despite similar disease incidence. These findings highlight an important limitation of case-control studies for pathogens for which there is suboptimal diagnostic specificity.
Despite some success in controlling trachoma with repeated mass drug administration (MDA), some hyperendemic regions are not responding as fast as anticipated. Available data suggests that ...individuals with higher bacterial infection loads are less likely to resolve infection following a single dose of treatment, and thus remain a source of re-emergent infection following treatment. We assessed the potential impact of a new double-dose antibiotic distribution strategy in addition to enhanced facial cleanliness (F) and environmental improvements (E).
Using a within-community mathematical model of trachoma transmission we assessed the impact of a new double-dose antibiotic distribution strategy given 2 weeks apart, with and without enhanced F&E. We compared the annual double-dose strategy to single-dose annual MDA treatment in hyper-, meso- and hypoendemic settings, and to biannual MDA at 6-monthly intervals in hyperendemic communities.
The findings from our mathematical model suggest that implementing the new double-dose strategy for 5 years or less was predicted to control infection more successfully than annual or 6-monthly treatment. Infection was controlled more readily if treatment was combined with enhanced F&E. The results appeared robust to variation in a number of key epidemiological parameters. To have long-term impact on transmission, enhanced F&E is essential for high transmission settings.
Our current findings are based on simualtion modelling only, due to lack of epidemilogical data, however they do suggest that the annual double-dose treatment strategy is encouraging for trachoma control. In high transmission settings, both MDA and enhanced F&E are needed for sustained control.
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