Michael Höhle

Universität Greifswald

We describe the design and implementation of a novel automated outbreak detection system in Germany that monitors the routinely collected surveillance data for communicable diseases. Detecting unusually high case counts as early as possible is crucial as an accumulation may indicate an ongoing outbreak. The detection in our system is based on state...

Preprint available as http://www.math.su.se/~hoehle/pubs/Hoehle_SpaMethInfEpiModelling2015.pdf

The availability of geocoded health data and the inherent temporal structure of communicable diseases have led to an increased interest in statistical models and software for spatio-temporal data with epidemic features. The open source R package surveillance can handle various levels of aggregation at which infective events have been recorded: indi...

Public health surveillance aims at lessening disease burden by, e.g., timely recognizing emerging outbreaks in case of infectious diseases. Seen from a statistical perspective, this implies the use of appropriate methods for monitoring time series of aggregated case reports. This paper presents the tools for such automatic aberration detection offe...

Background Globally, since 1 January 2020 and as of 24 January 2023, there have been over 664 million cases of COVID-19 and over 6.7 million deaths reported to WHO. WHO developed an evidence-based alert system, assessing public health risk on a weekly basis in 237 countries, territories and areas from May 2021 to June 2022. This aimed to facilitate...

The real-time analysis of infectious disease surveillance data is essential in obtaining situational awareness about the current dynamics of a major public health event such as the COVID-19 pandemic. This analysis of e.g., time-series of reported cases or fatalities is complicated by reporting delays that lead to under-reporting of the complete num...

We comment the paper by Jahn et al. (On the role of data, statistics and decisions in a pandemic, 2022).

The real-time analysis of infectious disease surveillance data, e.g. time-series of reported cases or fatalities, can help to provide situational awareness about the current state of a pandemic. This task is challenged by reporting delays that give rise to occurred-but-not-yet-reported events. If these events are not taken into consideration, this...

Coronavirus disease 2019 (COVID-19) is associated with a very high number of casualties in the general population. Assessing the exact magnitude of this number is a non-trivial problem, as relying only on officially reported COVID-19 associated fatalities runs the risk of incurring in several kinds of biases. One of the ways to approach the issue i...

Coronavirus disease 2019 (COVID-19) is associated with a very high number of casualties in the general population. Assessing the exact magnitude of this number is a non-trivial problem, as relying only on officially reported COVID-19 associated fatalities runs the risk of incurring in several kinds of biases. One of the ways to approach the issue i...

As several countries gradually release social distancing measures, rapid detection of new localized COVID-19 hotspots and subsequent intervention will be key to avoiding large-scale resurgence of transmission. We introduce ASMODEE (automatic selection of models and outlier detection for epidemics), a new tool for detecting sudden changes in COVID-1...

We analysed the coronavirus disease 2019 epidemic curve from March to the end of April 2020 in Germany. We use statistical models to estimate the number of cases with disease onset on a given day and use back-projection techniques to obtain the number of new infections per day. The respective time series are analysed by a trend regression model wit...

We determined secondary attack rates (SAR) among close contacts of 59 asymptomatic and symptomatic coronavirus disease case-patients by presymptomatic and symptomatic exposure. We observed no transmission from asymptomatic case-patients and highest SAR through presymptomatic exposure. Rapid quarantine of close contacts with or without symptoms is n...

Motivation Permutation tests offer a straightforward framework to assess the significance of differences in sample statistics. A significant advantage of permutation tests are the relatively few assumptions about the distribution of the test statistic are needed, as they rely on the assumption of exchangeability of the group labels. They have great...

To assess the current dynamics of an epidemic, it is central to collect information on the daily number of newly diseased cases. This is especially important in real-time surveillance, where the aim is to gain situational awareness, for example, if cases are currently increasing or decreasing. Reporting delays between disease onset and case reporti...

We analyze the Covid-19 epidemic curve from March to end of April 2020 in Germany. We use statistical models to estimate the number of cases with disease onset on a given day and use back-projection techniques to obtain the number of new infections per day. The respective time series are analyzed by a Poisson trend regression model with change poin...

Motivation Permutation tests offer a straight forward framework to assess the significance of differences in sample statistics. A significant advantage of permutation tests are the relatively few assumptions about the distribution of the test statistic are needed, as they rely on the assumption of exchangeability of the group labels. They have grea...

We present a method for adjusting the observed epidemic curve of daily new COVID-19 onsets for possible misclassification in infection diagnostics. We discuss different assumptions for specificity and sensitivity of the person-specific COVID-19 diagnostics based on PCR-tests, which are the basis for the daily reported case counts. A specificity of...

As several countries gradually release social distancing measures, rapid detection of new localised COVID-19 hotspots and subsequent intervention will be key to avoiding large-scale resurgence of transmission. We introduce ASMODEE (Automatic Selection of Models and Outlier Detection for Epidemics), a new tool for detecting sudden changes in COVID-1...

To assess the current dynamic of an epidemic it is central to collect information on the daily number of newly diseased cases. This is especially important in real-time surveillance, when one aims at evaluating the effects of interventions on disease spread. Reporting delays between disease onset and case reporting hamper our ability to understand...

We analyze the epidemic Covid-19-curve using the daily number cases with symptom onset on a given day based on official data. We find 4 breakpoints, which relate to different stages of the epidemic (in German)

Background Reporting delays in disease surveillance impair the ability to assess the current dynamic of an epidemic. In continuously updated epidemic curves, case numbers for the most recent epidemic week or day usually appear to be lower than the previous, suggesting a decline of the epidemic. In reality, the epidemic curve may still be on the ris...

Revisions of hip and knee arthroplasty implants and cardiac pacemakers pose a large medical and economic burden for society. Consequently, the identification of health care providers with potential for quality improvements regarding the reduction of revision rates is a central aim of quality assurance in any healthcare system. Even though the time...

Despite the wide application of dynamic models in infectious disease epidemiology, the particular modeling of variability in the different model components is often subjective rather than the result of a thorough model selection process. This is in part because inference for a stochastic transmission model can be difficult since the likelihood is o...

A scan statistic is proposed for the prospective monitoring of spatiotemporal count data with an excess of zeros. The method that is based on an outbreak model for the zero‐inflated Poisson distribution is shown to be superior to traditional scan statistics based on the Poisson distribution in the presence of structural zeros. The spatial accuracy...

An expectation-based scan statistic is proposed for the prospective monitoring of spatio-temporal count data with an excess of zeros. The method, which is based on an outbreak model for the zero-inflated Poisson distribution, is shown to be superior to traditional scan statistics based on the Poisson distribution in the presence of structural zeros...

Early identification of contaminated food products is crucial in reducing health burdens of food-borne disease outbreaks. Analytic case-control studies are primarily used in this identification stage by comparing exposures in cases and controls using logistic regression. Standard epidemiological analysis practice is not formally defined and the com...

We address the question “does digital epidemiology represent an epistemic shift in infectious disease epidemiology” from a statistician’s viewpoint. Our main argument is that infectious disease epidemiology has not changed fundamentally as it always has been data-driven. However, as the data aspect has become more prominent, we discuss the statisti...

This chapter surveys univariate and multivariate methods for infectious disease outbreak detection. The setting considered is a prospective one: data arrives sequentially as part of the surveillance systems maintained by public health authorities, and the task is to determine whether to 'sound the alarm' or not, given the recent history of data. Th...

Soon-to-be parents, souvenir mug producers and onomatologists are all equally fascinated by baby name statistics. But end-of-year lists of the most popular names fail to account for uncertainty says Michael Höhle. Can we trust the rankings?.

The availability of geocoded health data and the inherent temporal structure of communicable diseases have led to an increased interest in statistical models and software for spatio-temporal data with epidemic features. The open source R package surveillance can handle various levels of aggregation at which infective events have been recorded: indi...

Infectious disease surveillance data often provides only partial information about the progression of the disease in the individual while disease transmission is often modelled using complex mathematical models for large populations, where variability only enters through a stochastic observation process. In this work it is shown that a rather simpl...

Background Swine can harbor influenza viruses that are pathogenic to humans. Previous studies support an increased risk of human influenza cases among individuals with swine contact. North Carolina has the second-largest swine industry in the United States. Methods We investigated the spatiotemporal association between influenza-like illnesses (IL...

One use of infectious disease surveillance systems is the statistical aberration detection performed on time series of counts resulting from the aggregation of individual case reports. However, inherent reporting delays in such surveillance systems make the considered time series incomplete, which can be an impediment to the timely detection and th...

Background: Rotavirus (RV) infection is the primary cause of severe gastroenteritis in children aged <5 years in Germany and worldwide. In 2013 the German Standing Committee on Vaccination (STIKO) developed a national recommendation for routine RV-immunization of infants. To support informed decision-making we predicted the epidemiological impact...

A Bayesian approach to the prediction of occurred-but-not-yet-reported events is developed for application in real-time public health surveillance. The motivation was the prediction of the daily number of hospitalizations for the hemolytic-uremic syndrome during the large May-July 2011 outbreak of Shiga toxin-producing Escherichia coli (STEC) O104:...

The investigation of infectious disease outbreaks relies on the analysis of increasingly complex and diverse data, which offer new prospects for gaining insights into disease transmission processes and informing public health policies. However, the potential of such data can only be harnessed using a number of different, complementary approaches an...

The investigation of infectious disease outbreaks relies on the analysis of increasingly complex and diverse data, which offer new prospects for gaining insights into disease transmission processes and informing public health policies. However, the potential of such data can only be harnessed using a number of different, complementary approaches an...

Understanding infectious disease dynamics using epidemic models based on ordinary differential equations requires the calibration of model parameters from data. A commonly used approach in practice to simplify this task is to fix many parameters on the basis of expert or literature information. However, this not only leaves the corresponding uncert...

Laboratory-confirmed norovirus illness is reportable in Germany since 2001. Reported case numbers are known to be undercounts, and a valid estimate of the actual incidence in Germany does not exist. An increase of reported norovirus illness was observed simultaneously to a large outbreak of Shiga toxin-producing E. coli O104:H4 in Germany in 2011 -...

From 20 September through 5 October 2012, the largest recorded food-borne outbreak in Germany occurred. Norovirus was identified as the causative agent. We conducted four analytical epidemiological studies, two case–control studies and two surveys (in total 150 cases) in secondary schools in three different federal states. Overall, 390 institutions...

https://cran.r-project.org/package=DescTools

New aerial cameras and new advanced geo-processing tools improve the generation of urban land cover maps. Elevations can be derived from stereo pairs with high density, positional accuracy, and efficiency. The combination of multispectral high-resolution imagery and high-density elevations enable a unique method for the automatic generation of urba...

The clinical spectrum following infection with Shiga toxin-producing Escherichia coli (STEC) is wide ranging and includes hemorrhagic colitis and life-threatening hemolytic uremic syndrome (HUS). Severity of STEC illness depends on patients' age and strongly on the infecting strains' virulence. Serogroup O157 is often assumed to be more virulent th...

Background Assessing the mortality impact of the 2009 influenza A H1N1 virus (H1N1pdm09) is essential for optimizing public health responses to future pandemics. The World Health Organization reported 18,631 laboratory-confirmed pandemic deaths, but the total pandemic mortality burden was substantially higher. We estimated the 2009 pandemic mortali...

We pooled data on adults who reported diarrhea or developed life-threatening hemolytic uremic syndrome (HUS) in any of 6 closed cohorts from 4 countries (1 cohort each in Denmark, France, and Sweden and 3 in Germany) that were investigated during a large outbreak of Shiga toxin-producing Escherichia coli (STEC) O104:H4 infection in 2011. Logistic r...

In infectious disease epidemiology, statistical methods are an indispensable component for the automated detection of outbreaks in routinely collected surveillance data. So far, methodology in this area has been largely of frequentist nature and has increasingly been taking inspiration from statistical process control. The present work is concerned...

Background Foodborne Yersinia enterocolitica infections continue to be a public health problem in many countries. Consumption of raw or undercooked pork is the main risk factor for yersiniosis in Germany. Small children are most frequently affected by yersiniosis. In older children and young adults, symptoms of disease may resemble those of appendi...

In October and November 2012 residents and tourists in the Autonomous Region of Madeira, Portugal, were affected by dengue fever. The outbreak waned during the unusually dry winter. Using a Monte Carlo test we investigated the hypothesis that rainy weather conveyed increased risk of dengue virus infection among tourists. Results confirmed the hypot...

To prevent accidents caused by unexploded bombs from the Second World War, high-risk zones need to be determined. We introduce two statistical methods to determine such zones by considering patterns of exploded and unexploded bombs as realizations of inhomogeneous spatial Poisson point processes. The first method is based on the intensity of the po...

Abstract Childhood obesity and the investigation of its risk factors has become an important public health issue. Our work is based on and motivated by a German longitudinal study including 2,226 children with up to ten measurements on their body mass index (BMI) and risk factors from birth to the age of 10 years. We introduce boosting of structure...

Background: In May-July 2011, Germany experienced a large food-borne outbreak of Shiga toxin 2-producing Escherichia coli (STEC O104:H4) with 3842 cases, including 855 cases with hemolytic uremic syndrome (HUS) and 53 deaths. Methods: A multicenter study was initiated in 5 university hospitals to determine pathogen shedding duration. Diagnostics...

Background: From May through July 2011, Germany experienced a large outbreak of Shiga toxin-producing Escherichia coli (STEC) O104:H4 infection. Our objective was to identify the prevalence of STEC O104:H4 carriers in households in highly affected areas, the rate of secondary household transmissions, and the duration of long-term shedding. Method...

We assessed hepatitis E virus (HEV) antibody seroprevalence in a sample of the adult population in Germany. Overall HEV IgG prevalence was 16.8% (95% CI 15.6%-17.9%) and increased with age, leveling off at >60 years of age. HEV is endemic in Germany, and the lifetime risk for exposure is high.

Details of mathematical methods used to compute the yearly incidence from the seroprevalence data in the manuscript.

Background: Socioeconomic factors are increasingly recognised as related to health inequalities in Germany and are also identified as important contributing factors for an increased risk of acquiring infections. The aim of the present study was to describe in an ecological analysis the impact of different social factors on the risk of acquiring in...

Yersinia enterocolitica is an important cause of acute gastrointestinal disease and post-infectious complications. In Germany, incidence of reported yersiniosis is relatively high compared with other countries of the European Union. Children aged <5 years are most frequently affected. The aim of our study was to identify risk factors for sporadic y...

A large outbreak of the hemolytic-uremic syndrome caused by Shiga-toxin-producing Escherichia coli O104:H4 occurred in Germany in May 2011. The source of infection was undetermined. We conducted a matched case-control study and a recipe-based restaurant cohort study, along with environmental, trace-back, and trace-forward investigations, to determi...

A novel point process model continuous in space-time is proposed for quantifying the transmission dynamics of the two most common meningococcal antigenic sequence types observed in Germany 2002-2008. Modeling is based on the conditional intensity function (CIF), which is described by a superposition of additive and multiplicative components. As an...

Number and proportion of observations with reactive antibody titre ≥10 by age groups in pre- and post-pandemic samples (DOC)

GMT by three birth cohorts in pre- and post-pandemic samples (DOC)

Distribution in age groups and sex in general population and in the study population (n = 1179) (DOC)

GMT by age groups in pre- and post-pandemic samples by age groups (DOC)

Number and proportion of observations with reactive antibody titre ≥40 by three birth cohorts in pre-pandemic and post-pandemic samples and difference in proportions between pre- and post-pandemic samples (DOC)

In order to detect levels of pre-existing cross-reactive antibodies in different age groups and to measure age-specific infection rates of the influenza A (H1N1) 2009 pandemic in Germany, we conducted a seroprevalence study based on samples from an ongoing nationwide representative health survey. We analysed 845 pre-pandemic samples collected betwe...

Since early May 2011, a large outbreak of haemolytic uraemic syndrome (HUS) and bloody diarrhoea related to infections with Shiga toxin-producing Escherichia coli (STEC) has been observed in Germany. The outbreak is focused in the north, but cases have been reported from all German states and other countries. Since our report last week, the number...

Since early May 2011, an increased incidence of haemolytic uraemic syndrome (HUS) and bloody diarrhoea related to infections with Shiga toxin-producing Escherichia coli (STEC) has been observed in Germany, with most cases in the north of the country. Cases reported from other European countries had travelled to this area. First results of a case–co...

A multivariate time-series regression model was developed in order to describe the 2005-2008 age-specific time-course of varicella sentinel surveillance data following the introduction of a varicella childhood vaccination programme in Germany. This ecological approach allows the assessment of vaccine effectiveness under field conditions by relating...

A novel point process model continuous in space-time is proposed for infectious disease data. Modelling is based on the conditional intensity function (CIF) and extends an additive-multiplicative CIF model previously proposed for discrete space epidemic modelling. Estimation is performed by means of full maximum likelihood and a simulation algorith...