Weak evidence; high degree of case under-ascertainment. 9 Mexico May 2020 no data available. no d... more Weak evidence; high degree of case under-ascertainment. 9 Mexico May 2020 no data available. no data available. no data available. no data available. 10 Mexico April 2021 CFr: 11% (44,986/407,548) CFr=17% (768/4469) CFrr=1.6 Very high under-ascertainment. Inconclusive data. 3 a peru, total population March 2021 Ar: 3.
for gentagen anvendelse af antigentests til reduktion af smitte på skoler og arbejdspladser. (1 u... more for gentagen anvendelse af antigentests til reduktion af smitte på skoler og arbejdspladser. (1 udg.) Roskilde Universitet.
The West African Ebola (2014-2016) epidemic caused an estimated 11.310 deaths and massive social ... more The West African Ebola (2014-2016) epidemic caused an estimated 11.310 deaths and massive social and economic disruption. The epidemic was comprised of many local outbreaks of varying sizes. However, often local outbreaks recede before the arrival of international aid or susceptible depletion. We modeled Ebola virus transmission under the effect of behavior changes acting as a local inhibitor. A spatial model is used to simulate Ebola epidemics. Our findings suggest that behavior changes can explain why local Ebola outbreaks recede before substantial international aid was mobilized during the 2014-2016 epidemic.
BackgroundThe draconian measures used to control COVID-19 dissemination have been highly effectiv... more BackgroundThe draconian measures used to control COVID-19 dissemination have been highly effective but only at enormous socioeconomic cost. Evidence suggests that “superspreaders” who transmit the virus to a large number of people, play a substantial role in transmission; recent estimates suggest that about 1-20% of people with the virus are the source for about 80% of infections. We used an agent-based model to explore the interplay between social structure, mitigation and superspreading.MethodsWe developed an agent-based model with a subset of “superspreader” agents that transmit disease far more efficiently. These agents act in a social network that allows transmission during contacts in three sectors: “home,” “work/school” and “other”. We simulated the effect of various mitigation strategies that limit contacts in each of these sectors, and used the model to fit COVID-19 mortality data from Sweden.FindingsReducing contacts in the “other” sector had a far greater impact on epidem...
The global malaria burden, including falciparum malaria, has been reduced by 50% since 2000, thou... more The global malaria burden, including falciparum malaria, has been reduced by 50% since 2000, though less so in Sub-Saharan Africa. Regional malaria elimination campaigns beginning in the 1940s, up-scaled in the 1950s, succeeded in the 1970s in eliminating malaria from Europe, North America, the Caribbean (except Haiti), and parts of Asia and South-and Central America. Dengue has grown dramatically throughout the pantropical regions since the 1950s, first in Southeast Asia in the form of large-scale epidemics including severe dengue, though mostly sparing Sub-Saharan Africa. Globally, the WHO estimates 50 million dengue infections every year, while others estimate almost 400 million infections, including 100 million clinical cases. Curiously, despite wide geographic overlap between malaria and dengue-endemic areas, published reports of co-infections have been scarce until recently. Superimposed acute dengue infection might be expected to result in more severe combined disease because both pathogens can induce shock and hemorrhage. However, a recent review found no reports on more severe morbidity or higher mortality associated with co-infections. Cases of severe dual infections have almost exclusively been reported from South America, and predominantly in persons infected by Plasmodium vivax. We hypothesize that malaria infection may partially protect against dengue-in particular falciparum malaria against severe dengue-and that this inter-species cross-protection may explain the near absence of severe dengue from the Sub-Saharan region and parts of South Asia until recently. We speculate that malaria infection elicits cross-reactive antibodies or other immune responses that infer cross-protection, or at least partial cross-protection, against symptomatic and severe dengue. Plasmodia have been shown to give rise to polyclonal B-cell activation and to heterophilic antibodies, while some anti-dengue IgM tests have high degree of cross-reactivity with sera from malaria patients. In the following, the historical evolution of falciparum malaria and dengue is briefly reviewed, and we explore early evidence of subclinical dengue in high-transmission malaria areas as well as conflicting reports on severity of co-morbidity. We also discuss examples of other interspecies interactions.
The SARS-CoV-2 ancestral strain has caused pronounced super-spreading events, reflecting a diseas... more The SARS-CoV-2 ancestral strain has caused pronounced super-spreading events, reflecting a disease characterized by overdispersion, where about 10% of infected people causes 80% of infections. New variants of the disease have different person-to-person variations in viral load, suggesting for example that the Alpha (B.1.1.7) variant is more infectious but relatively less prone to superspreading. Meanwhile, mitigation of the pandemic has focused on limiting social contacts (lockdowns, regulations on gatherings) and decreasing transmission risk through mask wearing and social distancing. Using a mathematical model, we show that the competitive advantage of disease variants may heavily depend on the restrictions imposed. In particular, we find that lockdowns exert an evolutionary pressure which favours variants with lower levels of overdispersion. We find that overdispersion is an evolutionarily unstable trait, with a tendency for more homogeneously spreading variants to eventually dom...
Proceedings of the National Academy of Sciences of the United States of America, Feb 14, 2017
When a new vaccine is introduced, it is critical to monitor trends in disease rates to ensure tha... more When a new vaccine is introduced, it is critical to monitor trends in disease rates to ensure that the vaccine is effective and to quantify its impact. However, estimates from observational studies can be confounded by unrelated changes in healthcare utilization, changes in the underlying health of the population, or changes in reporting. Other diseases are often used to detect and adjust for these changes, but choosing an appropriate control disease a priori is a major challenge. The "synthetic controls" (causal impact) method, which was originally developed for website analytics and social sciences, provides an appealing solution. With this approach, potential comparison time series are combined into a composite and are used to generate a counterfactual estimate, which can be compared with the time series of interest after the intervention. We sought to estimate changes in hospitalizations for all-cause pneumonia associated with the introduction of pneumococcal conjugate...
Although randomized placebo-controlled trials (RCT) are critical to establish efficacy of vaccine... more Although randomized placebo-controlled trials (RCT) are critical to establish efficacy of vaccines at the time of licensure, important remaining questions about vaccine effectiveness (VE)-used here to include individual-level measures and population-wide impact of vaccine programmes-can only be answered once the vaccine is in use, from observational studies. However, such studies are inherently at risk for bias. Using a causal framework and illustrating with examples, we review newer approaches to detecting and avoiding confounding and selection bias in three major classes of observational study design: cohort, case-control and ecological studies. Studies of influenza VE, especially in seniors, are an excellent demonstration of the challenges of detecting and reducing such bias, and so we use influenza VE as a running example. We take a fresh look at the time-trend studies often dismissed as 'ecological'. Such designs are the only observational study design that can measure the overall effect of a vaccination programme [indirect (herd) as well as direct effects], and are in fact already an important part of the evidence base for several vaccines currently in use. Despite the great strides towards more robust observational study designs, challenges lie ahead for evaluating best practices for achieving robust unbiased results from observational studies. This is critical for evaluation of national and global vaccine programme effectiveness.
ABSTRACTBackgroundUnderstanding the real-world impact of pneumococcal conjugate vaccines (PCVs) o... more ABSTRACTBackgroundUnderstanding the real-world impact of pneumococcal conjugate vaccines (PCVs) on pneumonia mortality is critical, given the expectation that PCVs can substantially reduce the burden of pneumonia deaths in children under five years. However, surprisingly few post-vaccine introduction studies have estimated the benefit of PCVs for childhood mortality, and results have been inconsistent.MethodsWe investigated the long-term trends in child pneumonia mortality in Brazil (1980-present) and assessed the impact of PCV10 on childhood pneumonia mortality, both nationally and in municipalities stratified by socioeconomic status (SES), after the vaccine was introduced in Brazil in 2010.FindingsBetween 1980 and 2010, a period when Brazil’s Human Development Index (HDI) rose from 0.55 to 0.71, national pneumonia mortality in children under five decreased 10-fold. Despite rapid uptake of PCV10 following its introduction in 2010, our primary analytical method found no significant ...
Background: SDI tracks influenza by collecting clinical, demographic, vaccine status, medical his... more Background: SDI tracks influenza by collecting clinical, demographic, vaccine status, medical history and rapid testing data from ~20,000 patients with influenza-like illness (ILI) seen in ~400 primary physician offices across the US each season. Furthermore, SDI tracks patterns in vaccine dose administration in physician's offices using a large national sample of medical claims. Objectives: To generate near-real time influenza vaccine coverage estimates Methods: We estimated influenza vaccination coverage from the primary surveillance system in the subset of ILI patients seen during November 1 through December 10 2009, and who tested negative for influenza virus. Medical claims data from CMS-1500 forms featuring procedure codes for pandemic and seasonal doses were used to generate temporal uptake patterns and total doses administered in physician's offices. Results: We included 1607 rapid-test negative ILI patients in the study; of these, 431 had received seasonal vaccine, ...
Background: Beginning March 2010, 13-valent pneumococcal conjugate vaccine (PCV13) replaced the 7... more Background: Beginning March 2010, 13-valent pneumococcal conjugate vaccine (PCV13) replaced the 7-valent (PCV7) vaccine for pediatric use in the U.S. We modeled timely ICD9-coded electronic health records from hospital discharges to study the effectiveness of PCV13 in reducing pneumococcal-related disease burden over the first 2 years in all age groups. Method: We accessed a privately held 20% inpatient ICD9-coded database, projected to national figures. We also modeled medical claims data to assess trends in the uptake of PCV13 vaccine doses in children <5. For 2005-2012 we modeled monthly numbers of invasive pneumococcal disease (IPD), lobar pneumonia, empyema and all-cause pneumonia hospitalizations, controlling for influenza incidence. Finally, we computed the PCV13-attributable risk reduction by age: <2, 2-4, 5-17, 18-49, 40-64, and 65+ years. Result: By mid-winter 2011-12 ~50% of all children <5 years had achieved putatively protective PCV13 doses. By then, IPD hospit...
Recent events related to the current outbreak of Ebola virus disease (EVD) in West Africa seeming... more Recent events related to the current outbreak of Ebola virus disease (EVD) in West Africa seemingly indicate inevitable problems that Europe has to face: an individual became symptomatic from Ebola virus disease only after having arrived in a non-affected country [1], and healthcare workers became infected with Ebola while caring for patients, either in West Africa or in non-affected countries where they had been medically evacuated [2-4]. Moreover, media enquiries and reports reveal concern among the general public.
Thousands of millions of injections are delivered every year in developing countries, many of the... more Thousands of millions of injections are delivered every year in developing countries, many of them unsafe, and the transmission of certain bloodborne pathogens via this route is thought to be a major public health problem. In this article we report global and regional estimates of the number of hepatitis B virus (HBV), hepatitis C virus (HCV) and human immunodeficiency virus (HIV) infections that may occur from unsafe injections in the developing world. The estimates were determined using quantitative data on unsafe injection practices, transmission efficiency and disease burden of HBV, HCV and HIV and the prevalence of injection use obtained from a review of the literature. A simple mass-action model was used consisting of a generalized linear equation with variables accounting for the prevalence of a pathogen in a population, susceptibility of a population, transmission efficiency of the pathogen, proportion of injections that are unsafe, and the number of injections received. The...
MMWR. CDC surveillance summaries : Morbidity and mortality weekly report. CDC surveillance summaries / Centers for Disease Control, Jan 31, 1997
CDC conducts active surveillance annually from October through May on the emergence and spread of... more CDC conducts active surveillance annually from October through May on the emergence and spread of influenza virus variants and the impact of influenza-related morbidity and mortality. Influenza activity is also monitored throughout the year by passive surveillance. This report summarizes U.S. influenza surveillance from October 1992 through May 1994. Influenza surveillance comprises four components, three of which provide weekly data from October through May: a) state and territorial epidemiologists provide estimates of local influenza activity; b) approximately 140 sentinel physicians report their total number of patient visits and the number of cases of influenza-like illness; and c) approximately 70 collaborating laboratories of the World Health Organization (WHO) report weekly influenza virus isolations and submit selected influenza isolates to CDC for antigenic analysis. Throughout the year, vital statistics offices of 121 cities report deaths related to pneumonia and influenza...
Weak evidence; high degree of case under-ascertainment. 9 Mexico May 2020 no data available. no d... more Weak evidence; high degree of case under-ascertainment. 9 Mexico May 2020 no data available. no data available. no data available. no data available. 10 Mexico April 2021 CFr: 11% (44,986/407,548) CFr=17% (768/4469) CFrr=1.6 Very high under-ascertainment. Inconclusive data. 3 a peru, total population March 2021 Ar: 3.
for gentagen anvendelse af antigentests til reduktion af smitte på skoler og arbejdspladser. (1 u... more for gentagen anvendelse af antigentests til reduktion af smitte på skoler og arbejdspladser. (1 udg.) Roskilde Universitet.
The West African Ebola (2014-2016) epidemic caused an estimated 11.310 deaths and massive social ... more The West African Ebola (2014-2016) epidemic caused an estimated 11.310 deaths and massive social and economic disruption. The epidemic was comprised of many local outbreaks of varying sizes. However, often local outbreaks recede before the arrival of international aid or susceptible depletion. We modeled Ebola virus transmission under the effect of behavior changes acting as a local inhibitor. A spatial model is used to simulate Ebola epidemics. Our findings suggest that behavior changes can explain why local Ebola outbreaks recede before substantial international aid was mobilized during the 2014-2016 epidemic.
BackgroundThe draconian measures used to control COVID-19 dissemination have been highly effectiv... more BackgroundThe draconian measures used to control COVID-19 dissemination have been highly effective but only at enormous socioeconomic cost. Evidence suggests that “superspreaders” who transmit the virus to a large number of people, play a substantial role in transmission; recent estimates suggest that about 1-20% of people with the virus are the source for about 80% of infections. We used an agent-based model to explore the interplay between social structure, mitigation and superspreading.MethodsWe developed an agent-based model with a subset of “superspreader” agents that transmit disease far more efficiently. These agents act in a social network that allows transmission during contacts in three sectors: “home,” “work/school” and “other”. We simulated the effect of various mitigation strategies that limit contacts in each of these sectors, and used the model to fit COVID-19 mortality data from Sweden.FindingsReducing contacts in the “other” sector had a far greater impact on epidem...
The global malaria burden, including falciparum malaria, has been reduced by 50% since 2000, thou... more The global malaria burden, including falciparum malaria, has been reduced by 50% since 2000, though less so in Sub-Saharan Africa. Regional malaria elimination campaigns beginning in the 1940s, up-scaled in the 1950s, succeeded in the 1970s in eliminating malaria from Europe, North America, the Caribbean (except Haiti), and parts of Asia and South-and Central America. Dengue has grown dramatically throughout the pantropical regions since the 1950s, first in Southeast Asia in the form of large-scale epidemics including severe dengue, though mostly sparing Sub-Saharan Africa. Globally, the WHO estimates 50 million dengue infections every year, while others estimate almost 400 million infections, including 100 million clinical cases. Curiously, despite wide geographic overlap between malaria and dengue-endemic areas, published reports of co-infections have been scarce until recently. Superimposed acute dengue infection might be expected to result in more severe combined disease because both pathogens can induce shock and hemorrhage. However, a recent review found no reports on more severe morbidity or higher mortality associated with co-infections. Cases of severe dual infections have almost exclusively been reported from South America, and predominantly in persons infected by Plasmodium vivax. We hypothesize that malaria infection may partially protect against dengue-in particular falciparum malaria against severe dengue-and that this inter-species cross-protection may explain the near absence of severe dengue from the Sub-Saharan region and parts of South Asia until recently. We speculate that malaria infection elicits cross-reactive antibodies or other immune responses that infer cross-protection, or at least partial cross-protection, against symptomatic and severe dengue. Plasmodia have been shown to give rise to polyclonal B-cell activation and to heterophilic antibodies, while some anti-dengue IgM tests have high degree of cross-reactivity with sera from malaria patients. In the following, the historical evolution of falciparum malaria and dengue is briefly reviewed, and we explore early evidence of subclinical dengue in high-transmission malaria areas as well as conflicting reports on severity of co-morbidity. We also discuss examples of other interspecies interactions.
The SARS-CoV-2 ancestral strain has caused pronounced super-spreading events, reflecting a diseas... more The SARS-CoV-2 ancestral strain has caused pronounced super-spreading events, reflecting a disease characterized by overdispersion, where about 10% of infected people causes 80% of infections. New variants of the disease have different person-to-person variations in viral load, suggesting for example that the Alpha (B.1.1.7) variant is more infectious but relatively less prone to superspreading. Meanwhile, mitigation of the pandemic has focused on limiting social contacts (lockdowns, regulations on gatherings) and decreasing transmission risk through mask wearing and social distancing. Using a mathematical model, we show that the competitive advantage of disease variants may heavily depend on the restrictions imposed. In particular, we find that lockdowns exert an evolutionary pressure which favours variants with lower levels of overdispersion. We find that overdispersion is an evolutionarily unstable trait, with a tendency for more homogeneously spreading variants to eventually dom...
Proceedings of the National Academy of Sciences of the United States of America, Feb 14, 2017
When a new vaccine is introduced, it is critical to monitor trends in disease rates to ensure tha... more When a new vaccine is introduced, it is critical to monitor trends in disease rates to ensure that the vaccine is effective and to quantify its impact. However, estimates from observational studies can be confounded by unrelated changes in healthcare utilization, changes in the underlying health of the population, or changes in reporting. Other diseases are often used to detect and adjust for these changes, but choosing an appropriate control disease a priori is a major challenge. The "synthetic controls" (causal impact) method, which was originally developed for website analytics and social sciences, provides an appealing solution. With this approach, potential comparison time series are combined into a composite and are used to generate a counterfactual estimate, which can be compared with the time series of interest after the intervention. We sought to estimate changes in hospitalizations for all-cause pneumonia associated with the introduction of pneumococcal conjugate...
Although randomized placebo-controlled trials (RCT) are critical to establish efficacy of vaccine... more Although randomized placebo-controlled trials (RCT) are critical to establish efficacy of vaccines at the time of licensure, important remaining questions about vaccine effectiveness (VE)-used here to include individual-level measures and population-wide impact of vaccine programmes-can only be answered once the vaccine is in use, from observational studies. However, such studies are inherently at risk for bias. Using a causal framework and illustrating with examples, we review newer approaches to detecting and avoiding confounding and selection bias in three major classes of observational study design: cohort, case-control and ecological studies. Studies of influenza VE, especially in seniors, are an excellent demonstration of the challenges of detecting and reducing such bias, and so we use influenza VE as a running example. We take a fresh look at the time-trend studies often dismissed as 'ecological'. Such designs are the only observational study design that can measure the overall effect of a vaccination programme [indirect (herd) as well as direct effects], and are in fact already an important part of the evidence base for several vaccines currently in use. Despite the great strides towards more robust observational study designs, challenges lie ahead for evaluating best practices for achieving robust unbiased results from observational studies. This is critical for evaluation of national and global vaccine programme effectiveness.
ABSTRACTBackgroundUnderstanding the real-world impact of pneumococcal conjugate vaccines (PCVs) o... more ABSTRACTBackgroundUnderstanding the real-world impact of pneumococcal conjugate vaccines (PCVs) on pneumonia mortality is critical, given the expectation that PCVs can substantially reduce the burden of pneumonia deaths in children under five years. However, surprisingly few post-vaccine introduction studies have estimated the benefit of PCVs for childhood mortality, and results have been inconsistent.MethodsWe investigated the long-term trends in child pneumonia mortality in Brazil (1980-present) and assessed the impact of PCV10 on childhood pneumonia mortality, both nationally and in municipalities stratified by socioeconomic status (SES), after the vaccine was introduced in Brazil in 2010.FindingsBetween 1980 and 2010, a period when Brazil’s Human Development Index (HDI) rose from 0.55 to 0.71, national pneumonia mortality in children under five decreased 10-fold. Despite rapid uptake of PCV10 following its introduction in 2010, our primary analytical method found no significant ...
Background: SDI tracks influenza by collecting clinical, demographic, vaccine status, medical his... more Background: SDI tracks influenza by collecting clinical, demographic, vaccine status, medical history and rapid testing data from ~20,000 patients with influenza-like illness (ILI) seen in ~400 primary physician offices across the US each season. Furthermore, SDI tracks patterns in vaccine dose administration in physician's offices using a large national sample of medical claims. Objectives: To generate near-real time influenza vaccine coverage estimates Methods: We estimated influenza vaccination coverage from the primary surveillance system in the subset of ILI patients seen during November 1 through December 10 2009, and who tested negative for influenza virus. Medical claims data from CMS-1500 forms featuring procedure codes for pandemic and seasonal doses were used to generate temporal uptake patterns and total doses administered in physician's offices. Results: We included 1607 rapid-test negative ILI patients in the study; of these, 431 had received seasonal vaccine, ...
Background: Beginning March 2010, 13-valent pneumococcal conjugate vaccine (PCV13) replaced the 7... more Background: Beginning March 2010, 13-valent pneumococcal conjugate vaccine (PCV13) replaced the 7-valent (PCV7) vaccine for pediatric use in the U.S. We modeled timely ICD9-coded electronic health records from hospital discharges to study the effectiveness of PCV13 in reducing pneumococcal-related disease burden over the first 2 years in all age groups. Method: We accessed a privately held 20% inpatient ICD9-coded database, projected to national figures. We also modeled medical claims data to assess trends in the uptake of PCV13 vaccine doses in children <5. For 2005-2012 we modeled monthly numbers of invasive pneumococcal disease (IPD), lobar pneumonia, empyema and all-cause pneumonia hospitalizations, controlling for influenza incidence. Finally, we computed the PCV13-attributable risk reduction by age: <2, 2-4, 5-17, 18-49, 40-64, and 65+ years. Result: By mid-winter 2011-12 ~50% of all children <5 years had achieved putatively protective PCV13 doses. By then, IPD hospit...
Recent events related to the current outbreak of Ebola virus disease (EVD) in West Africa seeming... more Recent events related to the current outbreak of Ebola virus disease (EVD) in West Africa seemingly indicate inevitable problems that Europe has to face: an individual became symptomatic from Ebola virus disease only after having arrived in a non-affected country [1], and healthcare workers became infected with Ebola while caring for patients, either in West Africa or in non-affected countries where they had been medically evacuated [2-4]. Moreover, media enquiries and reports reveal concern among the general public.
Thousands of millions of injections are delivered every year in developing countries, many of the... more Thousands of millions of injections are delivered every year in developing countries, many of them unsafe, and the transmission of certain bloodborne pathogens via this route is thought to be a major public health problem. In this article we report global and regional estimates of the number of hepatitis B virus (HBV), hepatitis C virus (HCV) and human immunodeficiency virus (HIV) infections that may occur from unsafe injections in the developing world. The estimates were determined using quantitative data on unsafe injection practices, transmission efficiency and disease burden of HBV, HCV and HIV and the prevalence of injection use obtained from a review of the literature. A simple mass-action model was used consisting of a generalized linear equation with variables accounting for the prevalence of a pathogen in a population, susceptibility of a population, transmission efficiency of the pathogen, proportion of injections that are unsafe, and the number of injections received. The...
MMWR. CDC surveillance summaries : Morbidity and mortality weekly report. CDC surveillance summaries / Centers for Disease Control, Jan 31, 1997
CDC conducts active surveillance annually from October through May on the emergence and spread of... more CDC conducts active surveillance annually from October through May on the emergence and spread of influenza virus variants and the impact of influenza-related morbidity and mortality. Influenza activity is also monitored throughout the year by passive surveillance. This report summarizes U.S. influenza surveillance from October 1992 through May 1994. Influenza surveillance comprises four components, three of which provide weekly data from October through May: a) state and territorial epidemiologists provide estimates of local influenza activity; b) approximately 140 sentinel physicians report their total number of patient visits and the number of cases of influenza-like illness; and c) approximately 70 collaborating laboratories of the World Health Organization (WHO) report weekly influenza virus isolations and submit selected influenza isolates to CDC for antigenic analysis. Throughout the year, vital statistics offices of 121 cities report deaths related to pneumonia and influenza...
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Papers by Lone Simonsen