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To illustrate the usefulness of mathematical models to the microbiology and medical communities, we explain how to construct and apply a simple transmission model of an emerging pathogen. We chose to model, as a case study, a large (>8,000 reported cases) on-going outbreak of community-acquired meticillin-resistant Staphylococcus aureus (CA-MRSA) i...
Contexts in source publication
Context 1
... ranges can be estimated from various sources including empirical data, expert opinion and/ or best estimates from the literature. We have used all three approaches to parameterize the CA-MRSA model; parameter ranges are shown in TAble 1. Data from the LACJ were used to estimate ranges for most of the parameters in the model. ...
Context 2
... uncertainty analysis was used to determine the expected variability (that is, uncertainty) in the predicted incidence that was due to the uncertainty in estimating the values of the model's parameters. To conduct a multivariate uncertainty analy- sis, we first assigned a range of values to each parameter in the model (TAble 1). These parameter ranges were then sampled 1,000 times and used to generate 1,000 scenarios of the model [44][45][46][47][48][49] . ...
Context 3
... and 21 (IQR of 13-44) infected women (data not shown). At the beginning of the outbreak, male and female inmates were incar- cerated for 47 and 33 days on average, respectively (TAble 1), and these parameter values were used in the model. If the model is used to calculate the incarcera- tion times that are required so that R 0 is equal to 1, then these values are found to be substantially larger than the actual incarceration times -the critical incarcera- tion time was calculated to be 83 days for male inmates and 60 days for female inmates (fIG. ...
Context 4
... this stage, the outbreak could have been controlled if a large-scale highly effective screening pro- gramme of entering inmates had been developed to iden- tify both colonized and infected individuals who could then have been treated and/or quickly isolated. However, as the LACJ books hundreds of new inmates each day (TAble 1), this intervention strategy would not have been feasible for economic and logistical reasons. ...
Similar publications
Methicillin-resistant Staphylococcus aureus (MRSA) are causing growing concern in the medical community. The incidence ranges 0.1 -1.8% to 21.6 -33.6% in Europe and USA [1,2]. In Bangladesh, a limited study in 1998 reported 37.2% to 21.6% MRSA among infected hospitalized and non-hospitalized diabetics, respectively [3]. We report here the findings...
Citations
... That is, the assumptions of disease modeling often inadequately address how disease burden manifests in unequal societies . There are, however, examples of studies that have used mathematical modeling to examine phenomena where inequalities manifest, such as the spread of HIV and HCV in persons who inject drugs [19][20][21] or with regards to infectious spread in prisons [22]. More recently, scholars have offered syntheses that have remarked on the need to color mathematical modeling with social forces [23][24][25][26], or commented on how targeting poor populations can lead to better outcomes in tuberculosis [27]. ...
... 2. Infectious individuals in each group have different overall transmission rates (when w 0 0: see Figure S2). Without loss of generality, we assume that group 1 has the higher effective contact rate; hence, w 0 > 0 and β 11 + β 21 > β 12 + β 22 . In this scenario, we also consider subcases similar to the first scenario: where w 1 = w 2 ( Figure S2(a) and (b)), and where w 1 w 2 ( Figure S2(c)). ...
Mathematical modelling has served a central role in studying how infectious disease transmission manifests at the population level. These models have demonstrated the importance of population-level factors like social network heterogeneity on structuring epidemic risk and are now routinely used in public health for decision support. One barrier to broader utility of mathematical models is that the existing canon does not readily accommodate the social determinants of health as distinct, formal drivers of transmission dynamics. Given the decades of empirical support for the organizational effect of social determinants on health burden more generally and infectious disease risk more specially, addressing this modelling gap is of critical importance. In this study, we build on prior efforts to integrate social forces into mathematical epidemiology by introducing several new metrics, principally structural causal influence (SCI). Here, SCI leverages causal analysis to provide a measure of the relative vulnerability of subgroups within a susceptible population, which are crafted by differences in healthcare, exposure to disease, and other determinants. We develop our metrics using a general case and apply it to specific one of public health importance: Hepatitis C virus in a population of persons who inject drugs. Our use of the SCI reveals that, under specific parameters in a multi-community model, the "less vulnerable" community may sustain a basic reproduction number below one when isolated, ensuring disease extinction. However, even minimal transmission between less and more vulnerable communities can elevate this number, leading to sustained epidemics within both communities. Summarizing, we reflect on our findings in light of conversations surrounding the importance of social inequalities and how their consideration can influence the study and practice of mathematical epidemiology.
... Mathematical modeling has been widely used to investigate and understand the transmission dynamics of AMROs (32)(33)(34)(35)(36)(37) and guide the development of intervention measures against HAIs in healthcare systems (22,23,(38)(39)(40)(41)(42). A number of approaches have been developed to estimate population-level transmission characteristics, including nosocomial transmissibility and importation rates from the community (43)(44)(45)(46). ...
Significance
Healthcare-associated infections caused by antimicrobial-resistant agents are hard to eliminate in hospitals partly because of the existence of asymptomatic spreaders who unwittingly transmit these pathogens to others. In practice, identifying asymptomatic patients colonized with antimicrobial-resistant agents is challenging, as only a limited number of carriers are typically observed. Here, we develop an efficient, individual-level inference method capable of estimating the colonization probability for each individual in a hospital network. Using real-world patient-to-patient contact networks and sparse observations of colonization, the proposed method identifies carriers of methicillin-resistant Staphylococcus aureus , a prevalent antimicrobial-resistant pathogen, more accurately than competing approaches informed by hospitalization history and contact tracing. In in silica control experiments, the individual-level inference supports improved, targeted interventions against healthcare-associated infections.
... Mathematical models have long been used to study pathogen dissemination in hospitals and to evaluate infection control strategies. Community models of resistance spread and control are scarce, and are often limited to MRSA [11,12]. Moreover, most of these models were simplified, for example, by ignoring the complex interplay between disease transmission and individual-level risk factors, such as age, patient treatment or the structure of contact networks. ...
Background:
The best strategy to control ESBL-producing Escherichia coli (ESBL-EC) spread in the community is lacking.
Methods:
We developed an individual-based transmission model to evaluate the impact of hand hygiene (HH) improvement and reduction in antibiotic use on the within-household transmission of ESBL-EC. We used data from the literature and incorporated key elements of ESBL-EC transmission such as the frequency and nature of contacts among household members, antibiotic use in the community and hand hygiene behaviour. We introduced in a household a single ESBL-EC colonised person and simulated the transmission dynamics of ESBL-EC over a one-year time horizon.
Results:
The probability of ESBL-EC transmission depended on the household composition and the profile of the initial carrier. In the two-person household, the probability of ESBL-EC transmission was 5.3% (95% CI 5.0-5.6) or 6.6% (6.3-6.9) when the index person was a woman or a man, respectively. In a four-person household, the probability of transmission varied from 61.4% (60.9-62.0) to 68.8% (68.3-69.3) and was the highest when the index patient was the baby. Improving HH by 50% reduced the probability of transmission by 33-62%. Antibiotic restriction by 50% reduced the transmission by 2-6%.
Conclusions:
The transmission of ESBL-EC is frequent in households and especially those with a baby. Antibiotic reduction had little impact on ESBL-EC. Improvement of hygiene in the community could help prevent transmission of ESBL-EC.
... This is in contrast to well-mixed models (e.g. 24 ) and is a consequence of a patient making too many contacts over a period of time, that is not necessarily connected to the length-of-stay (See SI, Fig. S2A-D). ...
... We devise a novel model capturing the main mechanisms of the MRSA contagion dynamics on the empirical networked population. Our model and parameters are based on the literature and adapted to the unique network structure available in our study 22,24,30 . The model is naturally a simplification of the infection dynamics, yet keeping the key features, to make simulations feasible given the complexity of the infection process and the size of the study population. ...
... The model is naturally a simplification of the infection dynamics, yet keeping the key features, to make simulations feasible given the complexity of the infection process and the size of the study population. We thus assume that a single strain circulates in this population and that a patient may be either Susceptible (S), Colonised (C), or Infectious (I) 24 . This is an extension of the standard SIS compartmental model with an extra state C for asymptotic colonised patients. ...
Methicillin-resistant Staphylococcus aureus (MRSA) is a difficult-to-treat infection. Increasing efforts have been taken to mitigate the epidemics and to avoid potential outbreaks in low endemic settings. Understanding the population dynamics of MRSA is essential to identify the causal mechanisms driving the epidemics and to generalise conclusions to different contexts. Previous studies neglected the temporal structure of contacts between patients and assumed homogeneous behaviour. We developed a high-resolution data-driven contact network model of interactions between 743,182 patients in 485 hospitals during 3,059 days to reproduce the exact contact sequences of the hospital population. Our model captures the exact spatial and temporal human contact behaviour and the dynamics of referrals within and between wards and hospitals at a large scale, revealing highly heterogeneous contact and mobility patterns of individual patients. A simulation exercise of epidemic spread shows that heterogeneous contacts cause the emergence of super-spreader patients, slower than exponential polynomial growth of the prevalence, and fast epidemic spread between wards and hospitals. In our simulated scenarios, screening upon hospital admittance is potentially more effective than reducing infection probability to reduce the final outbreak size. Our findings are useful to understand not only MRSA spread but also other hospital-acquired infections.
... Mathematical models have long been used to study pathogen dissemination in hospitals and to evaluate infection control strategies. Community models of resistance spread and control are scarce, and are often limited to MRSA [11,12]. Moreover, most of these models were simplified, for example, by ignoring the complex interplay between disease transmission and individual-level risk factors, such as age, patient treatment or the structure of contact networks. ...
Background The best strategy to control ESBL-producing Escherichia coli (ESBL-EC) spread in the community is lacking.
Methods We developed an individual-based transmission model to evaluate the impact of hand hygiene (HH) improvement and reduction in antibiotic use on the within-household transmission of ESBL-EC. We used data from the literature and incorporated key elements of ESBL-EC transmission such as the frequency and nature of contacts among household members, antibiotic use in the community and hand hygiene behaviour. We introduced in a household a single ESBL-EC colonised person and simulated the transmission dynamics of ESBL-EC over a one-year time horizon.
Results The probability of ESBL-EC acquisition depended on the household composition and the profile of the initial carrier. In the two-person household, the probability of ESBL-EC acquisition by another household member was 5.3% (95% CI 5.0-5.6) and 6.6% (6.3-6.9) when the index person was a woman or a man, respectively. In a four-person household, the probability of acquisition varied from 61.4% (60.9-62.0) to 68.8% (68.3- 69.3) and was the highest when the index patient was the baby. Improving HH by 50% reduced the probability of transmission by 33-62%. Antibiotic restriction by 50% reduced the transmission by 2-6%.
Conclusions The acquisition of ESBL-EC is frequent in households and especially those with a baby. Antibiotic reduction had little impact on ESBL-EC. Improvement of hygiene in the community could help prevent transmission of ESBL-EC.
... Mathematical models have long been used to study pathogen dissemination in hospitals and to evaluate infection control strategies. Community models of resistance spread and control are scarce, and are often limited to MRSA [11,12]. Moreover, most of these models were simpli ed, for example, by ignoring the complex interplay between disease transmission and individual-level risk factors, such as age, patient treatment or the structure of contact networks. ...
Background The best strategy to control ESBL-producing Escherichia coli (ESBL-EC) spread in the community is lacking.
Methods We developed an individual-based transmission model to evaluate the impact of hand hygiene (HH) improvement and reduction in antibiotic use on the within-household transmission of ESBL-EC. We used data from the literature and incorporated key elements of ESBL-EC transmission such as the frequency and nature of contacts among household members, antibiotic use in the community and hand hygiene behaviour. We introduced in a household a single ESBL-EC colonised person and simulated the transmission dynamics of ESBL-EC over a one-year time horizon.
Results The probability of ESBL-EC transmission depended on the household composition and the profile of the initial carrier. In the two-person household, the probability of ESBL-EC transmission was 5.3% (95% CI 5.0-5.6) or 6.6% (6.3-6.9) when the index person was a woman or a man, respectively. In a four-person household, the probability of transmission varied from 61.4% (60.9-62.0) to 68.8% (68.3- 69.3) and was the highest when the index patient was the baby. Improving HH by 50% reduced the probability of transmission by 33-62%. Antibiotic restriction by 50% reduced the transmission by 2-6%.
Conclusions The transmission of ESBL-EC is frequent in households and especially those with a baby. Antibiotic reduction had little impact on ESBL-EC. Improvement of hygiene in the community could help prevent transmission of ESBL-EC.
... Establishing this intake prevalence is critical for understanding the high burden of MRSA that has been observed during incarceration. For example, Kajita et al [35] developed a mathematical model to estimate transmission rates and intervention effects during a large MRSA outbreak at the Los Angeles County Jail. Our calculated intake prevalence may be useful for updating this and similar models, especially to derive estimates that accurately reflect the contribution of intake MRSA colonization. ...
Background:
Jails may facilitate spread of MRSA in urban areas. We examined MRSA colonization at entrance to a large urban jail to determine if there are community transmission networks for MRSA that precede incarceration.
Methods:
Incarcerated males at the Cook County Jail were enrolled-with enrichment for HIV-positive subjects-within 72hours of intake. Surveillance cultures were collected to determine prevalence of MRSA colonization. Genomic analysis and epidemiologic data were used to identify community transmission networks.
Results:
There were 800 incarcerations (718 individuals) enrolled; 58% were HIV-infected. The prevalence of MRSA colonization at intake was 19%. In multivariate analysis, methamphetamine use, unstable housing, current/recent skin infection, and recent injection drug use were predictors of MRSA. Among HIV patients, recent injection drug use, current skin infection, and HIV care at outpatient Clinic A that emphasizes comprehensive care to the LGBTQ community were predictors of MRSA. 14(45%) of 31 detainees with care at Clinic A had colonization. WGS revealed that the high prevalence of MRSA in Clinic A was not due to clonal spread in the clinic but rather an intermingling of distinct community transmission networks. In contrast, genomic analysis supported spread of USA500 strains within a community network. Members of this USA500 network were more likely to be HIV-infected (p<0.01), men who have sex with men (p<0.001), and methamphetamine users (p<0.001).
Conclusion:
A high proportion of individuals enter jail colonized with MRSA. Molecular epidemiology and colonization risk factors provide clues to identify colonized detainees entering jail and potential community reservoirs of MRSA.
... Für Krankenhäuser existieren von mehreren Autoren Daten zur Reproduktionsrate (Anzahl sekundärer Fälle, ausgehend von einem Indexfall pro stationärer Aufnahme) sowie der täglichen Transmissionsrate (Übertragungsrate von einem MRSA-positiven zu einem empfänglichen Patienten pro Tag) [134, [201][202][203][204][205][206]. Die berichteten Reproduktionsraten sind erwartungsgemäß sehr unterschiedlich und liegen zwischen 0,06 und 0, 93 isoliert wurden, eine Reproduktionsrate von 0,06 (95 %-CI 0,02-0,14); während bei Fällen, die nicht sofort nach den niederländischen Empfehlungen behandelt und isoliert wurden, eine Reproduktionsrate von 0,25 (95 %-CI 0,15-0,4) zu verzeichnen war [204,207]. ...
Ulcus cruris venosum, Dekubitus, Malum perforans — dies sind häufige chronische Wunden in der Hausarztpraxis. Das Erkennen bzw. richtige Zuordnen und eine effiziente, oft langwierige Therapie stellen große Herausforderungen dar.
... We evaluate trypanosome drug resistance using three different transmission rates (low 4%, medium 7.5% and high 11%) that reflect differences in drug resistant disease point prevalence values established at two different endemic sampling locales (Kizibe 4%, and Mbegani 11%), which are distant and proximal to the Shimba Hill National Reserve, Kwale -Kenya, respectively. Pathogen transmission and prevalence are strongly correlated; with pathogen prevalence increasing commensurately with transmission (Lipsitch and Moxon, 1997;Kajita et al., 2007;Weinberger et al., 2008). Simulations with discrete time-steps of one day for a period of 3 years highlight differences in a range of drug regimens, and changes in compartment size for host and vector population infected with resistant trypanosomes. ...
Trypanocide resistance remains a huge challenge in the management of animal African trypanosomiasis. Paucity of data on the prevalence of multi-drug resistant trypanosomes has greatly hindered optimal veterinary management practices. We use mathematical model predictions to highlight appropriate drug regimens that impede trypanocide resistance development in cattle. We demonstrate that using drugs in decreasing resistance order results in a negligible increase in number of cattle with resistant infection, in contrast to a more pronounced increase from trypanocide use in increasing resistance order. We demonstrate that the lowest levels of trypanocide resistance are achieved with combination therapy. We also show that increasing the number of cattle treated leads to a progressive reduction in the number of cattle with drug resistant infections for treatments of up to 80% of the cattle population for the combination treatment strategy. Our findings provide an initial evidence-based framework on some essential practices that promote optimal use of the handful of trypanocides. We anticipate that our modest forecasts will improve therapeutic outcomes by appropriately informing on the best choice, and combination of drugs that minimize treatment failure rates.
... As a result, accurate representation of actual contact patterns is crucial for modeling MRSA transmission. Many previous studies have formulated transmission models using ordinary differential equations (ODEs) (Cooper et al., 2004a;Kajita et al., 2007;D'Agata et al., 2009) or stochastic processes (Forrester et al., 2007;Kypraios et al., 2010). To account for heterogeneity among different settings, several studies have included multiple facilities in a single-model construct, incorporating prior information on facility type in order to characterize and differentiate transmission dynamics (Bootsma et al., 2006;Forrester et al., 2007). ...
... Outside the study hospitals, the transmission process is not explicitly simulated; instead, two additional parameters are introduced to represent transmission intensity. For Sources for parameter rangesa: (Cooper et al., 2004a;Bootsma et al., 2006;Eveillard et al., 2006;Wang et al., 2013;Macal et al., 2014;Jarynowski and Liljeros, 2015); p: (Kajita et al., 2007;Jarynowski and Liljeros, 2015); : (D' Agata et al., 2009;Wang et al., 2013); b: Prior; I 0 : Prior; C 0 : Prior, (Hidron et al., 2005;Eveillard et al., 2006;Jarvis et al., 2012). For each individual, the infection progress rate p is drawn after a is specified. ...
Methicillin-resistant Staphylococcus aureus (MRSA) is a continued threat to human health in both community and healthcare settings. In hospitals, control efforts would benefit from accurate estimation of asymptomatic colonization and infection importation rates from the community. However, developing such estimates remains challenging due to limited observation of colonization and complicated transmission dynamics within hospitals and the community. Here, we develop an inference framework that can estimate these key quantities by combining statistical filtering techniques, an agent-based model, and real-world patient-to-patient contact networks, and use this framework to infer nosocomial transmission and infection importation over an outbreak spanning 6 years in 66 Swedish hospitals. In particular, we identify a small number of patients with disproportionately high risk of colonization. In retrospective control experiments, interventions targeted to these individuals yield a substantial improvement over heuristic strategies informed by number of contacts, length of stay and contact tracing.
