European Neolithic societies showed early warning signals of population collapse.

Ecosystems on the verge of major reorganization-regime shift-may exhibit declining resilience, which can be detected using a collection of generic statistical tests known as early warning signals (EWSs). This study explores whether EWSs anticipated human population collapse during the European Neolithic. It analyzes recent reconstructions of European Neolithic (8-4 kya) population trends that reveal regime shifts from a period of rapid growth following the introduction of agriculture to a period of instability and collapse. We find statistical support for EWSs in advance of population collapse. Seven of nine regional datasets exhibit increasing autocorrelation and variance leading up to collapse, suggesting that these societies began to recover from perturbation more slowly as resilience declined. We derive EWS statistics from a prehistoric population proxy based on summed archaeological radiocarbon date probability densities. We use simulation to validate our methods and show that sampling biases, atmospheric effects, radiocarbon calibration error, and taphonomic processes are unlikely to explain the observed EWS patterns. The implications of these results for understanding the dynamics of Neolithic ecosystems are discussed, and we present a general framework for analyzing societal regime shifts using EWS at large spatial and temporal scales. We suggest that our findings are consistent with an adaptive cycling model that highlights both the vulnerability and resilience of early European populations. We close by discussing the implications of the detection of EWS in human systems for archaeology and sustainability science.

Establishing an ICD-10 code based SARI-surveillance in Germany - description of the system and first results from five recent influenza seasons.

BACKGROUND: Syndromic surveillance of severe acute respiratory infections (SARI) is important to assess seriousness of disease as recommended by WHO for influenza. In 2015 the Robert Koch Institute (RKI) started to collaborate with a private hospital network to develop a SARI surveillance system using case-based data on ICD-10 codes. This first-time description of the system shows its application to the analysis of five influenza seasons. METHODS: Since week 40/2015, weekly updated anonymized data on discharged patients overall and on patients with respiratory illness including ICD-10 codes of primary and secondary diagnoses are transferred from the network data center to RKI. Retrospective datasets were also provided. Our descriptive analysis is based on data of 47 sentinel hospitals collected between weeks 1/2012 to 20/2016. We applied three different SARI case definitions (CD) based on ICD-10 codes for discharge diagnoses of respiratory tract infections (J09 - J22): basic CD (BCD), using only primary diagnoses; sensitive CD (SCD), using primary and secondary diagnoses; timely CD (TCD), using only primary diagnoses of patients hospitalized up to one week. We compared the CD with regard to severity, age distribution and timeliness and with results from the national primary care sentinel system. RESULTS: The 47 sentinel hospitals covered 3.6% of patients discharged from all German hospitals in 2013. The SCD comprised 2.2 times patients as the BCD, and 3.6 times as many as the TCD. Time course of SARI cases corresponded well to results from primary care surveillance and influenza virus circulation. The patients fulfilling the TCD had been completely reported after 3 weeks, which was fastest among the CD. The proportion of SARI cases among patients was highest in the youngest age group of below 5-year-olds. However, the age group 60 years and above contributed most SARI cases. This was irrespective of the CD used. CONCLUSIONS: In general, available data and the implemented reporting system are appropriate to provide timely and reliable information on SARI in inpatients in Germany. Our ICD-10-based approach proved to be useful for fulfilling requirements for SARI surveillance. The exploratory approach gave valuable insights in data structure and emphasized the advantages of different CD.

[Consensus-Based Guidelines for Diagnosis, Prevention and Treatment of Tuberculosis in Children and Adolescents - A Guideline on Behalf of the German Society for Pediatric Infectious Diseases (DGPI)]. / S2k-Leitlinie zur Diagnostik, Prävention und Therapie der Tuberkulose im Kindes- und Jugendalter.

Recently, epidemiological data shows an increase of childhood tuberculosis in Germany. In addition to this, drug resistant tuberculosis becomes more frequent. Therefore, diagnosis, prevention and therapy in childhood and adolescence remain a challenge. Adult guidelines do not work for children, as there are age specific differences in manifestation, risk of progression and diagnostic as well as therapeutic pathways.The German Society for Pediatric Infectious Diseases (DGPI) has initiated a consensus-based (S2k) process and completed a paediatric guideline in order to improve and standardize care for children and adolescents with tuberculosis exposure, infection or disease.Updated dosage recommendations take age dependant pharmacokinetics in the treatment of drug sensitive but also drug resistant tuberculosis in account. In addition to this, there is a detailed chapter on perinatal exposure and disease as well as extrapulmonary manifestations.

Transformation of social networks in the late pre-Hispanic US Southwest.

The late pre-Hispanic period in the US Southwest (A.D. 1200-1450) was characterized by large-scale demographic changes, including long-distance migration and population aggregation. To reconstruct how these processes reshaped social networks, we compiled a comprehensive artifact database from major sites dating to this interval in the western Southwest. We combine social network analysis with geographic information systems approaches to reconstruct network dynamics over 250 y. We show how social networks were transformed across the region at previously undocumented spatial, temporal, and social scales. Using well-dated decorated ceramics, we track changes in network topology at 50-y intervals to show a dramatic shift in network density and settlement centrality from the northern to the southern Southwest after A.D. 1300. Both obsidian sourcing and ceramic data demonstrate that long-distance network relationships also shifted from north to south after migration. Surprisingly, social distance does not always correlate with spatial distance because of the presence of network relationships spanning long geographic distances. Our research shows how a large network in the southern Southwest grew and then collapsed, whereas networks became more fragmented in the northern Southwest but persisted. The study also illustrates how formal social network analysis may be applied to large-scale databases of material culture to illustrate multigenerational changes in network structure.

Recommendations of the German Central Committee against Tuberculosis (DZK) and the German Respiratory Society (DGP) for the Diagnosis and Treatment of Non-tuberculous Mycobacterioses.

Non-tuberculous mycobacterioses comprise a group of diseases caused by mycobacteria which do not belong to the Mycobacterium (M.) tuberculosis-complex and are not ascribed to M. leprae. These mycobacteria are characterized by a broad variety as to environmental distribution and adaptation. Some of the species may cause specific diseases, especially in patients with underlying immunosuppressive diseases, chronic pulmonary diseases or genetic predisposition, respectively. Worldwide, a rising prevalence and significance of non-tuberculous mycobacterioses is recognized. The present recommendations summarise current aspects of epidemiology, pathogenesis, clinical aspects, diagnostics - especially microbiological methods including susceptibility testing -, and specific treatment for the most relevant species. Diagnosis and treatment of non-tuberculous mycobacterioses during childhood and in HIV-infected individuals are described in separate chapters.

Age-related prevalence of cross-reactive antibodies against influenza A(H3N2) variant virus, Germany, 2003 to 2010.

To estimate susceptibility to the swine-origin influenza A(H3N2) variant virus (A(H3N2)v) in the German population, we investigated cross-reactive antibodies against this virus and factors associated with seroprotective titre using sera from representative health examination surveys of children and adolescents (n = 815, 2003­06) and adults (n = 600, 2008­10). Antibodies were assessed by haemagglutination inhibition assay (HI); in our study an HI titre ≥ 40 was defined as seroprotective. We investigated associated factors by multivariable logistic regression. Overall, 41% (95% confidence interval (CI): 37­45) of children and adolescents and 39% (95% CI: 34­44) of adults had seroprotective titres. The proportion of people with seroprotective titre was lowest among children younger than 10 years (15%; 95% CI: 7­30) and highest among adults aged 18 to 29 years (59%; 95% CI: 49­67). Prior influenza vaccination was associated with higher odds of having seroprotective titre (odds ratio (OR) for children and adolescents: 3.4; 95% CI: 1.8­6.5; OR for adults: 2.4; 95% CI: 1.7­3.4). Young children showed the highest and young adults the lowest susceptibility to the A(H3N2)v virus. Our results suggest that initial exposure to circulating seasonal influenza viruses may predict long-term cross-reactivity that may be enhanced by seasonal influenza vaccination.

[Current epidemiology of tuberculosis in Germany]. / Aktuelle Epidemiologie der Tuberkulose in Deutschland.

BACKGROUND: In addition to malaria and HIV/AIDS, tuberculosis (TB) is one of the world's most important infectious diseases. Also in Germany tuberculosis still remains a relevant public health problem that needs special attention. OBJECTIVES: This article provides an overview of the tuberculosis epidemiology in Germany with emphasis on drug resistance and population groups that are predominantly affected. METHODS: Based on surveillance data provided in the notification system, the TB-situation in Germany is presented-particularly with respect to drug resistance, origin of patients (country of birth and nationality) and treatment outcome. RESULTS: Since 2009, the continuous decline in case numbers has slowed down and is now stagnating as observed in several other industrialized nations. Since 2007, the proportion of foreign-born patients has continuously increased and accounts for over half of all cases registered in Germany. Special attention deserves the current drug resistance situation: With a proportion of 3.4% in 2013, multidrug-resistant tuberculosis (MDR-TB) has increased significantly compared to the previous year (2.1%) and the rate is therefore higher than in many other European low-incidence countries. Particularly high levels of MDR-TB were observed among foreign-born patients originating from a former Soviet Union country. On average, treatment success was observed in 79% of the cases. Thus, Germany does not reach the WHO target of 85% treatment success. Stagnating case numbers together with the observed drug resistance trend clearly indicate the need for continued efforts in tuberculosis control in Germany including focused strategies for the most affected population groups.

Laboratory diagnosis of paediatric tuberculosis in the European Union/European Economic Area: analysis of routine laboratory data, 2007 to 2011.

Laboratory confirmation of paediatric tuberculosis (TB) is frequently lacking. We reviewed the range of routine laboratory tests and their performance in different biological samples used to diagnose active TB in children. A questionnaire-based survey was conducted among the European Reference Laboratory Network for TB followed by collection of routine laboratory data on 10,549 paediatric samples tested in 2007 to 2011 at six reference laboratories (in Croatia, Germany, Italy, Latvia, Lithuania and the United Kingdom (UK)). The questionnaire showed that all laboratories used rapid assays. Non-respiratory samples were collected more often in Germany (135/275, 49.1%) and the UK (490/2,140, 22.9%) compared with Croatia (138/2,792, 4.9%), Latvia (222/2,401, 9.2%) and Lithuania (76/1,549, 4.9%). Overall laboratory positivity rates (isolation of Mycobacterium tuberculosis complex and/or identification of its nucleic acids in a sample) were higher in lymph node and gastric aspirate samples (14/203 (6.9%) and 43/1,231 (3.5%)) than in sputum samples (89/4,684 (1.9%)). Pooled sensitivity, specificity, positive and negative predictive values and accuracy of molecular assays assessed against solid or liquid culture were 79.2%, 93.6%, 67.1%, 96.5% and 91.6%, respectively. A more intensive approach in obtaining gastric aspirate and non-respiratory samples may increase laboratory confirmation of paediatric TB. Major effort is needed in optimisation and validation of molecular tests in these samples.

Epidemiology of tuberculosis in big cities of the European Union and European Economic Area countries.

This cross-sectional survey aimed to examine the epidemiology of tuberculosis (TB) in European Union (EU) and European Economic Area (EEA) cities with populations greater than 500,000. National TB programme managers were asked to provide data on big city population size, total number of notified TB cases in big cities and national notification rate for 2009. A rate ratio was calculated using the big city TB notification rate as a numerator and country TB notification rate, excluding big city TB cases and population, as a denominator. Twenty of the 30 EU/EEA countries had at least one big city. Pooled rate ratios were 2.5, 1.0, and 0.7 in low-, intermediate- and high-incidence countries respectively. In 15 big cities, all in low-incidence countries, rate ratios were twice the national notification rate. These data illustrate the TB epidemiology transition, a situation whereby TB disease concentrates in big cities as national incidence falls, most likely as a result of the higher concentration of risk groups found there. This situation requires targeted interventions and we recommend that big city TB data, including information about patients' risk factors, are collected and analysed systematically, and that successful interventions are shared.

Tuberculosis control in big cities and urban risk groups in the European Union: a consensus statement.

In low-incidence countries in the European Union (EU), tuberculosis (TB) is concentrated in big cities, especially among certain urban high-risk groups including immigrants from TB high-incidence countries, homeless people, and those with a history of drug and alcohol misuse. Elimination of TB in European big cities requires control measures focused on multiple layers of the urban population. The particular complexities of major EU metropolises, for example high population density and social structure, create specific opportunities for transmission, but also enable targeted TB control interventions, not efficient in the general population, to be effective or cost effective. Lessons can be learnt from across the EU and this consensus statement on TB control in big cities and urban risk groups was prepared by a working group representing various EU big cities, brought together on the initiative of the European Centre for Disease Prevention and Control. The consensus statement describes general and specific social, educational, operational, organisational, legal and monitoring TB control interventions in EU big cities, as well as providing recommendations for big city TB control, based upon a conceptual TB transmission and control model.

Mass spectrometry based method to increase throughput for kinome analyses using ATP probes.

Protein kinases play critical roles in many biological and pathological processes, making them important targets for therapeutic drugs. Here, we desired to increase the throughput for kinome-wide profiling. A new workflow coupling ActivX ATP probe (AAP) affinity reagents with isotopic labeling to quantify the relative levels and modification states of kinases in cell lysates is described. We compared the new workflow to a classical proteomics approach in which fractionation was used to identify low-abundance kinases. We find that AAPs enriched approximately 90 kinases in a single analysis involving six cell lines or states in a single run, an 8-fold improvement in throughput relative to the classical approach. In general, AAPs cross-linked to both the active and inactive states of kinases but performing phosphopeptide enrichment made it possible to measure the phospho sites of regulatory residues lying in the kinase activation loops, providing information on activation state. When we compared the kinome across the six cell lines, representative of different breast cancer clinical subtypes, we observed that many kinases, particularly receptor tyrosine kinases, varied widely in abundance, perhaps explaining the differential sensitivities to kinase inhibitor drugs. The improved kinome profiling methods described here represent an effective means to perform systematic analysis of kinases involved in cell signaling and oncogenic transformation and for analyzing the effect of different inhibitory drugs.

The burden of extrapulmonary and meningitis tuberculosis: an investigation of national surveillance data, Germany, 2002 to 2009.

Tuberculosis (TB) surveillance commonly focuses on pulmonary (PTB) where the main organ affected is the lung. This might lead to underestimate extrapulmonary TB (EPTB) forms, where in addition to the lung other sites are affected by TB. In Germany, TB notification data provide the main site and the secondary site of disease. To gain an overview of all the different EPTB forms, we analysed German TB notification data between 2002 and 2009 using information on both main and secondary disease site to describe all individual EPTB forms. Further, we assessed factors associated with meningitis using multivariable logistic regression. Solely analysing the main site of disease, lead to one third of EPTB manifestations being overlooked. Case characteristics varied substantially across individual extrapulmonary forms. Of 46,349 TB patients, 422 (0.9%) had meningitis as main or secondary site. Of those, 105 (25%) of the 415 with available information had died. Multivariable analysis showed that meningitis was more likely in children younger than five years and between five and nine years-old (odds ratio (OR): 4.90; 95% confidence interval (CI): 3.40­7.07 and OR: 2.65; 95% CI: 1.40­5.00), in females (OR: 1.42; 95% CI: 1.17­1.73), and in those born in the World Health Organization (WHO) regions of south-east Asia (OR: 2.38; 95% CI: 1.66­3.43) and eastern Mediterranean (OR: 1.51; 95% CI: 1.02­2.23). Overall, EPTB manifestations, including meningitis, which is often fatal, were underestimated by routine analysis. We thus recommend using all information on disease manifestation generated by surveillance to monitor severe forms and to transfer the gained knowledge to TB case management where awareness of EPTB is most important.

Challenges in diagnosing extrapulmonary tuberculosis in the European Union, 2011.

In the European Union (EU) 72,334 tuberculosis (TB) cases were notified in 2011, of which 16,116 (22%) had extrapulmonary tuberculosis (EPTB). The percentage of TB cases with EPTB ranged from 4% to 48% in the reporting countries. This difference might be explained by differences in risk factors for EPTB or challenges in diagnosis. To assess the practices in diagnosis of EPTB we asked European Union/European Economic Area (EU/EEA) countries to participate in a report describing the diagnostic procedures and challenges in diagnosing EPTB. Eleven EU Member States participated and reports showed that in the majority EPTB is diagnosed by a pulmonologist, sometimes in collaboration with the doctor who is specialised in the organ where the symptoms presented. In most countries a medical history and examination is followed by invasive procedures, puncture or biopsy, to collect material for confirmation of the disease (by culture/histology/cytology). Some countries also use the tuberculin skin test or an interferon-gamma-release-assay. A wide variety of radiological tests may be used. Countries that reported challenges in the diagnosis of EPTB reported that EPTB is often not considered because it is a rare disease and most medical professionals will not have experience in diagnosing EPTB. The fact that EPTB can present with a variety of symptoms that may mimic symptoms of other pathologies does pose a further challenge in diagnosis. In addition, obtaining an appropriate sample for confirmation of EPTB was frequently mentioned as a challenge. In summary, diagnosis of EPTB poses challenges due to the diversity of symptoms with which EPTB may present, the low level of suspicion of clinicians, and due to the difficulty in obtaining an adequate sample for confirmation.

Contact investigation of a case of human novel coronavirus infection treated in a German hospital, October-November 2012.

On 24 October 2012, a patient with acute respiratory distress syndrome of unknown origin and symptom onset on 5 October was transferred from Qatar to a specialist lung clinic in Germany. Late diagnosis on 20 November of an infection with the novel Coronavirus (NCoV) resulted in potential exposure of a considerable number of healthcare workers. Using a questionnaire we asked 123 identified contacts (120 hospital and three out-of-hospital contacts) about exposure to the patient. Eighty-five contacts provided blood for a serological test using a two-stage approach with an initial immunofluorescence assay as screening test, followed by recombinant immunofluorescence assays and a NCoV-specific serum neutralisation test. Of 123 identified contacts nine had performed aerosol-generating procedures within the third or fourth week of illness, using personal protective equipment rarely or never, and two of these developed acute respiratory illness. Serology was negative for all nine. Further 76 hospital contacts also tested negative, including two sera initially reactive in the screening test. The contact investigation ruled out transmission to contacts after illness day 20. Our two-stage approach for serological testing may be used as a template for similar situations.

[Recommendations for diagnosis and treatment of nontuberculous mycobacterioses of the German Central Committee against tuberculosis and the German Respiratory Society]. / Empfehlungen zur Diagnostik und Therapie nichttuberkulöser Mykobakteriosen des Deutschen Zentralkomitees zur Bekämpfung der Tuberkulose (DZK) und der Deutschen Gesellschaft für Pneumologie und Beatmungsmedizin (DGP).

Nontuberculous mycobacterioses comprise a group of diseases caused by mycobacteria which do not belong to the Mycobacterium (M.) tuberculosis complex and are not ascribed to M. leprae. These mycobacteria are characterized by a broad variety as to environmental distribution and adaptation. Some of the species may cause specific diseases, especially in patients with underlying immunosuppressive diseases, chronic pulmonary diseases or genetic predisposition, respectively. Worldwide a rising prevalence and significance of nontuberculous mycobacterioses can be recognized. The present recommendations summarise actual aspects of epidemiology, pathogenesis, clinical aspects, diagnostics - especially microbiological methods including susceptibility testing -, and specific treatment for the most relevant species. Diagnosis and treatment of nontuberculous mycobacterioses during childhood and in HIV-infected individuals are described in separate chapters.

[Tuberculosis infection control - recommendations of the DZK]. / Infektionsprävention bei Tuberkulose - Empfehlungen des DZK.

The epidemiological situation of tuberculosis (TB) in Germany has improved considerably during the past few years. However, those in unprotected contact with infectious tuberculosis patients frequently and/or over longer periods of time and/or intensively continue to have a higher risk for TB infection. Rapid diagnosis, prompt initiation of effective treatment, and adequate infection control measures are of particular importance to prevent infection. The present recommendations depict the essentials of infection control as well as specific measures in the hospital (isolation, criteria for its duration and technical requirements, types of respiratory protection, disinfection measures, waste disposal). The specific requirements for outpatients (medical practice), at home, for ambulance services, and in congregate settings, including prisons, are also addressed. Compared with the previous recommendations the pattern of respiratory protection measures has been simplified. As a rule, hospital staff and those visiting infectious tuberculosis patients are advised to wear respiratory protection that satisfies the criteria of FFP2-masks (DIN EN 149), while patients should wear mouth-nose protectors (surgical masks) in the presence of others and outside the isolation room. A detailed depiction of criteria for isolation and its duration in smear positive and only culturally confirmed pulmonary tuberculosis has been added.

[Tuberculosis infection control--recommendations of the DZK]. / Infektionsprävention bei Tuberkulose--Empfehlungen des DZK.

The epidemiological situation of tuberculosis (TB) in Germany has improved considerably during the past few years. However, those in unprotected contact with infectious tuberculosis patients frequently and/or over longer periods of time and/or intensively continue to have a higher risk for TB infection. Rapid diagnosis, prompt initiation of effective treatment, and adequate infection control measures are of particular importance to prevent infection. The present recommendations depict the essentials of infection control as well as specific measures in the hospital (isolation, criteria for its duration and technical requirements, types of respiratory protection, disinfection measures, waste disposal). The specific requirements for outpatients (medical practice), at home, for ambulance services, and in congregate settings, including prisons, are also addressed. Compared with the previous recommendations the pattern of respiratory protection measures has been simplified. As a rule, hospital staff and those visiting infectious tuberculosis patients are advised to wear respiratory protection that satisfies the criteria of FFP2-masks (DIN EN 149), while patients should wear mouth-nose protectors (surgical masks) in the presence of others and outside the isolation room. A detailed depiction of criteria for isolation and its duration in smear positive and only culturally confirmed pulmonary tuberculosis has been added.

Facemasks and intensified hand hygiene in a German household trial during the 2009/2010 influenza A(H1N1) pandemic: adherence and tolerability in children and adults.

Non-pharmaceutical interventions (NPI) such as facemasks and intensified hand hygiene may be effective in preventing influenza infections in households. It may be equally important that household members, especially children, can learn to use, maintain and tolerate these measures. We monitored adherence and tolerability of these NPI within a cluster-randomized trial in households with influenza index patients. We recruited 147 participants in 41 households, 39 (95%) out of 41 index patients were children (aged <14 years). In households assigned to wear facemasks, their use peaked on day 4 after symptom onset of the index patient at 73% and at 65% for children and adults, respectively. Mean daily frequency of hand disinfection in households assigned to intensified hand hygiene measures peaked at 7·7 (day 6) for children and at 10·1 (day 5) for adults. The majority of participants reported no problems with mask wearing. Data suggest that usage of NPI can be taught and that measures are well tolerated by adults and even sick children alike.

Avian influenza A(H5N1) in humans: new insights from a line list of World Health Organization confirmed cases, September 2006 to August 2010.

The threat of avian influenza (AI) viruses to humans in Europe in 2005 prompted the Robert Koch Institute to establish a routine monitoring instrument condensing information on all human AI cases worldwide reported from the World Health Organization (WHO) and other sources into a line list for further analysis. The 235 confirmed AI cases captured from September 2006 to August 2010 had a case fatality rate of 56% (132/235), ranging from 28% (27/98) in Egypt to 87% (71/82) in Indonesia. In a multivariable analysis, odds of dying increased by 33% with each day that passed from symptom onset until hospitalisation (OR: 1.33, p=0.002). In relation to children of 0­9 years, odds of fatal outcome were more than six times higher in 10­19 year-olds and 20­29 year-olds (OR: 6.06, 95% CI: 1.89­19.48, p=0.002 and OR: 6.16, 95% CI: 2.05­ 18.53, p=0.001, respectively), and nearly five times higher in patients of 30 years and older (OR: 4.71, 95% CI: 1.56­14.27, p=0.006) irrespective of the country, which had notified WHO of the cases. The situation in Egypt was special in that case number and incidence in children were more than twice as high as in any other age group or country. With this study, we show that data from the public domain yield important epidemiological information on the global AI situation. This approach to establish a line list is time-consuming but a line list is a prerequisite to such evaluations. We thus would like to encourage the placing of a publicly accessible line list of anonymised human AI cases, e.g. directly by WHO. This might enhance our understanding of AI in humans and permit the rapid detection of changes in its epidemiology with implications for human health.

[New recommendations for contact tracing in tuberculosis]. / Neue Empfehlungen für die Umgebungsuntersuchungen bei Tuberkulose*1.

In 2007, the German Central Committee against Tuberculosis (DZK) published recommendations for contact tracing that introduced the new interferon gamma release assays (IGRAs). Meanwhile, substantial progress has been made in documenting the utility of IGRAs. Because IGRAs are usually superior to the tuberculin skin test (TST) in detecting latent TB infection (LTBI) with respect to sensitivity and specificity in adult contact populations that are at least partially BCG vaccinated, it is now recommended that instead of two-step testing only IGRAs be used.[nl]As the literature does not yet provide sufficient data on the accuracy of IGRAs in children younger than 5 years, the TST remains the method of choice in that age group. To date, also, no clear body of data exists to substantiate better performance for IGRAs than for the TST in older children, thus in this age group using of either test is recommended. The new recommendations also underscore the importance of a diligent preselection of close contacts in order to achieve a high probability that positive test results represent recent infection and to thus increase the benefit of chemopreventive treatment for those identified as requiring it. In a third point of update, it is noted that re-testing of contacts individuals found positive for LTBI may produce a considerable number of false-negative results and should thus be avoided in case of documented exposure.