Completeness of tuberculosis case notifications in Germany in 2013–2017: first results of an inventory study

Background Evaluating the completeness of tuberculosis (TB) notification data is important for monitoring of TB surveillance systems. We conducted an inventory study to calculate TB underreporting in Germany in 2013–2017. Methods Acquisition of two pseudonymized case-based data sources (national TB notification data and antibiotic resistance surveillance data) was followed by two-source Capture-recapture (CRC) analysis, as case-based data from a third source was unavailable. Aggregated data on consumption of a key anti-TB drug (pyrazinamide [PZA]) was compared to an estimated need for PZA based on TB notification data to obtain an independent underreporting estimation. Additionally, notified TB incidence was compared to TB rate in an aggregated health insurance fund dataset. Results CRC and PZA-based approaches indicated that between 93 and 97% (CRC) and between 91 and 95% (PZA) of estimated cases were captured in the national TB notification data in the years 2013–2017. Insurance fund dataset did not indicate TB underreporting on the national level in 2017. Conclusions Our results suggest that more than 90% of estimated TB cases are captured within the German TB surveillance system, and accordingly the TB notification rate is likely a good proxy of the diagnosed TB incidence rate. An increase in underreporting and discrepancies however should be further investigated.Peer Reviewe

Severe Cases of Pandemic (H1N1) 2009 in Children, Germany

In a hospital-based observational study in Germany, we investigated children admitted to pediatric intensive care units and deaths caused by confirmed pandemic (H1N1) 2009 to identify risk factors and outcomes in critically ill children. Ninety-three children were eligible for our study, including 9 with hospital-acquired infections. Seventy-five percent had underlying chronic medical conditions; neurodevelopmental disorders were most prevalent (57%). The proportion of patients having >1 risk factor increased with age in years (odds ratio 1.21, p = 0.007). Of 15 deaths, 11 occurred in a pediatric intensive care unit (case-fatality rate 12%, 95% confidence interval 6%–21%). Only 9% of the children had been vaccinated against pandemic (H1N1) 2009; all survived. Our results stress the role of underlying risk factors, especially neurodevelopmental disorders, and the need for improving preventive measures to reduce severe disease and adverse outcomes of pandemic (H1N1) 2009 in children

Vollständigkeit der Tuberkulose-Meldungen in Deutschland in den Jahren 2013 – 2017: Ergebnisse einer Inventurstudie

Für die Evaluation der Qualität von Tuberkulose-Meldesystemen ist die Bewertung der Vollständigkeit der Meldedaten von zentraler Bedeutung, da diese die Basis für eine aussagekräftige Tuberkulose-Surveillance und daraus abgeleitete Maßnahmen sind. Wie das Epidemiologische Bulletin 11/2021 beschreibt, wurde am Robert-Koch-Institut für den Zeitraum 2013-17 eine Inventarstudie zur Schätzung der Tuberkulose-Untererfassung in Deutschland durchgeführt. Das Ergebnis: mit einer Erfassungsquote von über 90% ist die Tuberkulose-Melderate trotz eines leichten Rückgangs innerhalb des untersuchten Zeitraums ein guter Näherungswert für die tatsächliche Tuberkulose-Inzidenz

Epidemiology of Epidemic Ebola Virus Disease in Conakry and Surrounding Prefectures, Guinea, 2014–2015

In 2014, Ebola virus disease (EVD) in West Africa was first reported during March in 3 southeastern prefectures in Guinea; from there, the disease rapidly spread across West Africa. We describe the epidemiology of EVD cases reported in Guinea’s capital, Conakry, and 4 surrounding prefectures (Coyah, Dubreka, Forecariah, and Kindia), encompassing a full year of the epidemic. A total of 1,355 EVD cases, representing ≈40% of cases reported in Guinea, originated from these areas. Overall, Forecariah had the highest cumulative incidence (4× higher than that in Conakry). Case-fatality percentage ranged from 40% in Conakry to 60% in Kindia. Cumulative incidence was slightly higher among male than female residents, although incidences by prefecture and commune differed by sex. Over the course of the year, Conakry and neighboring prefectures became the EVD epicenter in Guinea

Models of epidemics: when contact repetition and clustering should be included

Background The spread of infectious disease is determined by biological factors, e.g. the duration of the infectious period, and social factors, e.g. the arrangement of potentially contagious contacts. Repetitiveness and clustering of contacts are known to be relevant factors influencing the transmission of droplet or contact transmitted diseases. However, we do not yet completely know under what conditions repetitiveness and clustering should be included for realistically modelling disease spread. Methods We compare two different types of individual-based models: One assumes random mixing without repetition of contacts, whereas the other assumes that the same contacts repeat day-by-day. The latter exists in two variants, with and without clustering. We systematically test and compare how the total size of an outbreak differs between these model types depending on the key parameters transmission probability, number of contacts per day, duration of the infectious period, different levels of clustering and varying proportions of repetitive contacts. Results The simulation runs under different parameter constellations provide the following results: The difference between both model types is highest for low numbers of contacts per day and low transmission probabilities. The number of contacts and the transmission probability have a higher influence on this difference than the duration of the infectious period. Even when only minor parts of the daily contacts are repetitive and clustered can there be relevant differences compared to a purely random mixing model. Conclusion We show that random mixing models provide acceptable estimates of the total outbreak size if the number of contacts per day is high or if the per-contact transmission probability is high, as seen in typical childhood diseases such as measles. In the case of very short infectious periods, for instance, as in Norovirus, models assuming repeating contacts will also behave similarly as random mixing models. If the number of daily contacts or the transmission probability is low, as assumed for MRSA or Ebola, particular consideration should be given to the actual structure of potentially contagious contacts when designing the model.ISSN:1742-468

Exposure Patterns Driving Ebola Transmission in West Africa:A Retrospective Observational Study

BackgroundThe ongoing West African Ebola epidemic began in December 2013 in Guinea, probably from a single zoonotic introduction. As a result of ineffective initial control efforts, an Ebola outbreak of unprecedented scale emerged. As of 4 May 2015, it had resulted in more than 19,000 probable and confirmed Ebola cases, mainly in Guinea (3,529), Liberia (5,343), and Sierra Leone (10,746). Here, we present analyses of data collected during the outbreak identifying drivers of transmission and highlighting areas where control could be improved.Methods and findingsOver 19,000 confirmed and probable Ebola cases were reported in West Africa by 4 May 2015. Individuals with confirmed or probable Ebola ("cases") were asked if they had exposure to other potential Ebola cases ("potential source contacts") in a funeral or non-funeral context prior to becoming ill. We performed retrospective analyses of a case line-list, collated from national databases of case investigation forms that have been reported to WHO. These analyses were initially performed to assist WHO's response during the epidemic, and have been updated for publication. We analysed data from 3,529 cases in Guinea, 5,343 in Liberia, and 10,746 in Sierra Leone; exposures were reported by 33% of cases. The proportion of cases reporting a funeral exposure decreased over time. We found a positive correlation (r = 0.35, p ConclusionsAchieving elimination of Ebola is challenging, partly because of super-spreading. Safe funeral practices and fast hospitalisation contributed to the containment of this Ebola epidemic. Continued real-time data capture, reporting, and analysis are vital to track transmission patterns, inform resource deployment, and thus hasten and maintain elimination of the virus from the human population

Tuberculosis among people living with HIV/AIDS in the German ClinSurv HIV Cohort: long-term incidence and risk factors

BACKGROUND: Tuberculosis (TB) still presents a leading cause of morbidity and mortality among people living with HIV/AIDS (PLWHA), including those on antiretroviral therapy. In this study, we aimed to determine the long-term incidence density rate (IDR) of TB and risk factors among PLWHA in relation to combination antiretroviral therapy (cART)-status. METHODS: Data of PLWHA enrolled from 2001 through 2011 in the German ClinSurv HIV Cohort were investigated using survival analysis and Cox regression. RESULTS: TB was diagnosed in 233/11,693 PLWHA either at enrollment (N = 62) or during follow-up (N = 171). The TB IDR during follow-up was 0.37 cases per 100 person-years (PY) overall [95% CI, 0.32-0.43], and was higher among patients who never started cART and among patients originating from Sub-Saharan Africa (1.23 and 1.20 per 100PY, respectively). In two multivariable analyses, both patients (I) who never started cART and (II) those on cART shared the same risk factors for TB, namely: originating from Sub-Saharan Africa compared to Germany (I, hazard ratio (HR); [95% CI]) 4.05; [1.87-8.78] and II, HR 5.15 [2.76-9.60], CD4+ cell count <200 cells/μl (I, HR 8.22 [4.36-15.51] and II, HR 1.90 [1.14-3.15]) and viral load >5 log(10) copies/ml (I, HR 2.51 [1.33-4.75] and II, HR 1.77 [1.11-2.82]). Gender, age or HIV-transmission risk group were not independently associated with TB. CONCLUSION: In the German ClinSurv HIV cohort, patients originating from Sub-Saharan Africa, with low CD4+ cell count or high viral load at enrollment were at increased risk of TB even after cART initiation. As patients might be latently infected with Mycobacterium tuberculosis complex, early screening for latent TB infection and implementing isoniazid preventive therapy in line with available recommendations is crucial

A cluster of multidrug-resistant Mycobacterium tuberculosis among patients arriving in Europe from the Horn of Africa: a molecular epidemiological study

SummaryBackground The risk of tuberculosis outbreaks among people fleeing hardship for refuge in Europe is heightened. We describe the cross-border European response to an outbreak of multidrug-resistant tuberculosis among patients from the Horn of Africa and Sudan. Methods On April 29 and May 30, 2016, the Swiss and German National Mycobacterial Reference Laboratories independently triggered an outbreak investigation after four patients were diagnosed with multidrug-resistant tuberculosis. In this molecular epidemiological study, we prospectively defined outbreak cases with 24-locus mycobacterial interspersed repetitive unit-variable number tandem repeat (MIRU-VNTR) profiles; phenotypic resistance to isoniazid, rifampicin, ethambutol, pyrazinamide, and capreomycin; and corresponding drug resistance mutations. We whole-genome sequenced all Mycobacterium tuberculosis isolates and clustered them using a threshold of five single nucleotide polymorphisms (SNPs). We collated epidemiological data from host countries from the European Centre for Disease Prevention and Control. Findings Between Feb 12, 2016, and April 19, 2017, 29 patients were diagnosed with multidrug-resistant tuberculosis in seven European countries. All originated from the Horn of Africa or Sudan, with all isolates two SNPs or fewer apart. 22 (76%) patients reported their travel routes, with clear spatiotemporal overlap between routes. We identified a further 29 MIRU-VNTR-linked cases from the Horn of Africa that predated the outbreak, but all were more than five SNPs from the outbreak. However all 58 isolates shared a capreomycin resistance-associated tlyA mutation. Interpretation Our data suggest that source cases are linked to an M tuberculosis clone circulating in northern Somalia or Djibouti and that transmission probably occurred en route before arrival in Europe. We hypothesise that the shared mutation of tlyA is a drug resistance mutation and phylogenetic marker, the first of its kind in M tuberculosis sensu stricto. Funding The Swiss Federal Office of Public Health, the University of Zurich, the Wellcome Trust, National Institute for Health Research (NIHR) Oxford Biomedical Research Centre (BRC), the Medical Research Council, BELTA-TBnet, the European Union, the German Center for Infection Research, and Leibniz Science Campus Evolutionary Medicine of the Lung (EvoLUNG)

Risk-based surveillance of avian influenza in switzerland : insights into poultry farm determinants and contact networks

This dissertation explores new potentials for a risk-based surveillance of highly pathogenic avian influenza (HPAI) in domestic poultry in an outbreak-free situation in Switzerland, 2007 to 2009. Its focus is on risk factors for HPAI spread related to the host population, namely poultry farms. In Part 1, poultry keepers’ disease awareness, potential contagious contacts amongst poultry farms, and the issue of organizing basic demographic data are addressed. In Part 2, emphasis is placed on the interplay between population data, namely contact structures, and mathematical models of epidemics, in general, and on the specific case of the Swiss poultry population. Part1 Using a mixed methods research design, consisting of a countrywide cross-sectional survey among 3,978 poultry keepers and interviews with experts from the poultry industry, revealed that: (i) risks perceived by the poultry keepers well reflected the officially communicated ones; (ii) having a non-commercial poultry farm was associated with low knowledge scores; (iii) both commercial and non-commercial farms were involved with remote between-farm contacts, which was in contrast to commonly presumed small poultry movement ranges in the non-commercial sector. Organizing demographic and epidemiological information in a relational poultry farm database would allow for considering more than one farm site per poultry keeper and facilitate multi-criteria queries. Part 2 Computer simulations comparing two types of individual-based models for the total outbreak size showed that: (i) models assuming a randomly mixed population provided acceptable estimates of the total outbreak size if the number of contacts per day was high or if the per-contact transmission probability was high; as well as for diseases with very short infectious periods; yet (ii) models considering the structure and stability of potentially contagious contacts were superior if the number of daily contacts or the transmission probability were low. Extrapolating the measured contact profiles on all poultry farms in Switzerland resulted in a synthetic poultry farm population characterized by heterogeneously distributed contacts with most farms having no or one contact and 4% of the farms, including non-commercial ones, having 4 or more different contacts. Overall, a particular need was identified to integrate non-commercial farms in HPAI surveillance. Surveillance intensity would ideally be based on multiple criteria risk weighting and rating, and always be high in poultry and farm dense areas. Epidemic models at the between-farm level for HPAI should take the realistic arrangement of contacts into account. A contact network model for the Swiss poultry farm population is feasible although computationally and labor intensive. A complete and flexible poultry farm database is required for both, targeting surveillance and epidemic modeling. While this dissertation was written the legal basis for a complete poultry register on a federal level has been created in Switzerland