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Andreas Sandgren and colleagues describe a new comprehensive resource on drug resistance mutations inM. tuberculosis. [ABSTRACT FROM AUTHOR]

Lutte antituberculeuse et recession economique : etude longitudinale des donnees de 21 pays europeens pour la periode de 1991 a 2012 Control de la tuberculosis y recesion economica: estudio longitudinal [...], Objective To investigate whether the economic recession affected the control of tuberculosis in the European Union. Methods Multivariate regression models were used to quantify the association between gross domestic product, public health expenditure and tuberculosis case detection rates, using data from 21 European Union member states (1991-2012). The estimated changes in case detection attributable to the recession were combined with mathematical models of tuberculosis transmission, to project the potential influence of the recession on tuberculosis epidemiology until 2030. Findings Between 1991 and 2007, detection rates for sputum-smear-positive tuberculosis in the European Union were stable at approximately 85%. During the economic recession (2008-2011) detection rates declined by a mean of 5.22% (95% confidence interval, CI: 2.54-7.90) but treatment success rates showed no significant change (P=0.62). A fall in economic output of 100 United States dollars per capita was associated with a 0.22% (95% CI: 0.05-0.39) mean reduction in the tuberculosis case detection rate. An equivalent fall in spending on public health services was associated with a 2.74% (95% CI: 0.31-5.16) mean reduction in the detection rate. Mathematical models suggest that the recession and consequent austerity policies will lead to increases in tuberculosis prevalence and tuberculosis-attributable mortality that are projected to persist for over a decade. Conclusion Across the European Union, reductions in spending on public health services appear to have reduced tuberculosis case detection and to have increased the long-term risk of a resurgence in the disease. [TEXT NOT REPRODUCIBLE IN ASCII] [TEXT NOT REPRODUCIBLE IN ASCII] Objectif Enqueter pour determiner si la recession economique a affecte la lutte antituberculeuse dans l'Union europeenne. Methodes Des modeles de regression multivariee ont ete utilises pour quantifier l'association entre le produit interieur brut, les depenses de sante publique et les taux de detection des cas de tuberculose, a partir de donnees provenant de 21 Etats membres de l'Union europeenne (periode de 1991 a 2012). Les changements estimes dans la detection des cas de tuberculose imputables a la recession ont ete combines a des modeles mathematiques de transmission de la tuberculose afin de faire des projections concernant l'influence potentielle de la recession sur l'epidemiologie dela tuberculose jusqu'a 2030. Resultats Entre 1991 et 2007, les taux de detection des cas de tuberculose a frottis d'expectoration positif dans l'Union europeenne sont restes stables, a environ 85 %. Pendant la recession economique (de 2008 a 2011), les taux de detection ont baisse en moyenne de 5,22 % (intervalle de confiance de 95 %, IC : 2,54-7,90), mais les taux de reussite des traitements n'ont connu aucun changement significatif (P = 0,62). Une baisse de la production economique de 100 dollars US par habitant a ete associee a une reduction moyenne du taux de detection des cas de tuberculose de 0,22% (intervalle de confiance de 95 %, IC : 0,05-0,39). Une reduction equivalente dans les depenses consacreesaux services de sante publique a ete associee a une reduction moyenne du taux de detection de 2,74 % (intervalle de confiance de 95 %, IC: 0,31-5,16). Les modeles mathematiques suggerent que la recession et les politiques d'austerite qui en ont resulte entraineront des augmentations de la prevalence de la tuberculose et de la mortalite imputable a la tuberculose qui, d'apres les projections realisees, devraient durer pendant plus de dix ans. Conclusion Dans l'Union europeenne, les reductions des depenses consacreesaux services de sante publique ont fait decliner la detection des cas de tuberculose et ont majore le risque a long terme de resurgence de cette maladie. [TEXT NOT REPRODUCIBLE IN ASCII] Objetivo Investigar si la recesion economica ha afectado al control de la tuberculosis en la Union Europea. Metodos Se utilizaron modelos de regresion multivariados para cuantificar la asociacion entre el producto interior bruto, el gasto en salud publica y las tasas de deteccion de casos de tuberculosis a partir de los datos de 21 estados miembro de la Union Europea (1991-2012). Los cambios estimados en la deteccion de casos atribuibles a la recesion se combinaron con modelos matematicos de transmision de la tuberculosis para proyectar la influencia potencial de la recesion en la epidemiologia de la tuberculosis hasta el 2030. Resultados Entre 1991 y 2007, las tasas de deteccion de la tuberculosis con resultado positivo en el analisis de esputo en la Union Europea se mantuvieron estables en torno al 85%. Durante la recesion economica (2008-2011), las tasas de deteccion se redujeron en un promedio del 5,22% (intervalo de confianza, IC, del 95%: 2,54-7,90), pero las tasas de exito en el tratamiento no mostraron ningun cambio significativo (P = 0,62). Una caida en los resultados economicos de 100 dolares estadounidenses per capita fue asociada a una reduccion media del 0,22% (IC del 95%: 0,05-0,39) en la tasa de deteccion de casos de tuberculosis. Una caida equivalente en el gasto en los servicios de salud publica se asocio a una reduccion media del 2,74% (IC del 95%: 0,31 -5,16) en la tasa de deteccion. Los modelos matematicos sugieren que la recesion y las politicas de austeridad consiguientes conduciran a un aumento de la prevalencia de la tuberculosis y de la mortalidad atribuible a esta enfermedad que se espera que persista durante mas de una decada. Conclusion En la Union Europea, los recortes en el gasto en servicios de salud publica parecen haber reducido la deteccion de casos de tuberculosis y haber incrementado el riesgo a largo plazo de un resurgimiento de la enfermedad.

Objective To determine which service models and organisational structures are effective and cost-effective for delivering tuberculosis (TB) services to hard-to-reach populations. Design Embase and MEDLINE (1990-2017) were searched in order to update and extend the 2011 systematic review commissioned by National Institute for Health and Care Excellence (NICE), discussing interventions targeting service models and organisational structures for the identification and management of TB in hard-to-reach populations. The NICE and Cochrane Collaboration standards were followed. setting European Union, European Economic Area, European Union candidate countries and Organisation for Economic Co-operation and Development countries. Participants Hard-to-reach populations, including migrants, homeless people, drug users, prisoners, sex workers, people living with HIV and children within vulnerable and hard-to-reach populations. Primary and secondary outcome measures Effectiveness and cost-effectiveness of the interventions. results From the 19 720 citations found, five new studies were identified, in addition to the six discussed in the NICE review. Community health workers from the same migrant community, street teams and peers improved TB screening uptake by providing health education, promoting TB screening and organising contact tracing. Mobile TB clinics, specialised TB clinics and improved cooperation between healthcare services can be effective at identifying and treating active TB cases and are likely to be cost-effective. No difference in treatment outcome was detected when directly observed therapy was delivered at a health clinic or at a convenient location in the community. Conclusions Although evidence is limited due to the lack of high-quality studies, interventions using peers and community health workers, mobile TB services, specialised TB clinics and improved cooperation between health services can be effective to control TB in hard-to-reach populations. Future studies should evaluate the (cost-) effectiveness of interventions on TB identification and management in hard-to-reach populations and countries should be urged to publish the outcomes of their TB control systems. PrOsPErO registration number CRD42015017865. [ABSTRACT FROM AUTHOR]

Background: Latent tuberculosis infection (LTBI) control relies on high initiation and completion rates of preventive treatment to preclude progression to tuberculosis disease. Specific interventions may improve initiation and completion rates. The objective was to systematically review data on determinants of initiation, adherence and completion of LTBI treatment, and on interventions to improve initiation and completion.Methods: A systematic review of the literature (PubMed, Embase) published up to February 2014 was performed. Relevant prospective intervention studies were assessed using GRADE.Results: Sixty-two articles reporting on determinants of treatment initiation and completion were included and 23 articles on interventions. Determinants of LTBI treatment completion include shorter treatment regimen and directly observed treatment (DOT, positive association), adverse events and alcohol use (negative association), and specific populations with LTBI (both positive and negative associations). A positive effect on completion was noted in intervention studies that used short regimens and social interventions; mixed results were found for intervention studies that used DOT or incentives.Conclusion: LTBI treatment completion can be improved by using shorter regimens and social interventions. Specific needs of the different populations with LTBI should be addressed taking into consideration the setting and condition in which the LTBI treatment programme is implemented. [ABSTRACT FROM AUTHOR]

Background: Control of latent tuberculosis infection (LTBI) is an important step towards tuberculosis elimination. Preventive treatment will prevent the development of disease in most cases diagnosed with LTBI. However, low initiation and completion rates affect the effectiveness of preventive treatment. The objective was to systematically review data on initiation rates and completion rates for LTBI treatment regimens in the general population and specific populations with LTBI.Methods: A systematic review of the literature (PubMed, Embase) published up to February 2014 was performed.Results: Forty-five studies on initiation rates and 83 studies on completion rates of LTBI treatment were found. These studies provided initiation rates (IR) and completion rates (CR) in people with LTBI among the general population (IR 26-99 %, CR 39-96 %), case contacts (IR 40-95 %, CR 48-82 %), healthcare workers (IR 47-98 %, CR 17-79 %), the homeless (IR 34-90 %, CR 23-71 %), people who inject drugs (IR 52-91 %, CR 38-89 %), HIV-infected individuals (IR 67-92 %, CR 55-95 %), inmates (IR 7-90 %, CR 4-100 %), immigrants (IR 23-97 %, CR 7-86 %), and patients with comorbidities (IR 82-93 %, CR 75-92 %). Generally, completion rates were higher for short than for long LTBI treatment regimens.Conclusion: Initiation and completion rates for LTBI treatment regimens were frequently suboptimal and varied greatly within and across different populations. [ABSTRACT FROM AUTHOR]

A recent systematic review concluded that there is insufficient evidence on the effectiveness to support or reject preventive therapy for treatment of contacts of patients with multidrug resistant tuberculosis (MDR-TB). Whether preventive therapy is favorable depends both on the effectiveness and the adverse events of the drugs used. We performed a systematic review to assess adverse events in healthy individuals and MDR-TB contacts treated with anti-tuberculosis drugs potentially effective for preventing development of MDR-TB. We searched MEDLINE, EMBASE, and other databases (August 2011). Record selection, data extraction, and study quality assessment were done in duplicate. The quality of evidence was assessed using the GRADE approach. Of 6,901 identified references, 20 studies were eligible. Among the 16 studies in healthy volunteers (a total of 87 persons on either levofloxacin, moxifloxacin, ofloxacin, or rifabutin, mostly for 1 week), serious adverse events and treatment discontinuation due to adverse events were rare (<1 and <5%, respectively), but mild adverse events frequently occurred. Due to small sample sizes of the levofloxacin and ofloxacin studies an increased frequency of mild adverse events compared to placebo could not be demonstrated or excluded. For moxifloxacin the comparative results were inconsistent. In four studies describing preventive therapy of MDR-TB contacts, therapy was stopped for 58-100% of the included persons because of the occurrence of adverse events ranging from mild adverse events such as nausea and dizziness to serious events requiring treatment. The quality of the evidence was very low. Although the number of publications and quality of evidence are low, the available evidence suggests that shortly after starting treatment the occurrence of serious adverse events is rare. Mild adverse events occur more frequently and may be of importance because these may provoke treatment interruption. [ABSTRACT FROM AUTHOR]

Siderocalin is a secreted protein that binds to siderophores to prevent bacterial iron acquisition. While it has been shown to inhibit the growth of Mycobacterium tuberculosis ( M.tb) in extracellular cultures, its effect on this pathogen within macrophages is not clear. Here, we show that siderocalin expression is upregulated following M.tb infection of mouse macrophage cell lines and primary murine alveolar macrophages. Furthermore, siderocalin added exogenously as a recombinant protein or overexpressed in the RAW264.7 macrophage cell line inhibited the intracellular growth of the pathogen. A variant form of siderocalin, which is expressed only in the macrophage cytosol, inhibited intracellular M.tb growth as effectively as the normal, secreted form, an observation that provides mechanistic insight into how siderocalin might influence iron acquisition by the bacteria in the phagosome. Our findings are consistent with an important role for siderocalin in protection against M.tb infection and suggest that exogenously administered siderocalin may have therapeutic applications in tuberculosis. [ABSTRACT FROM AUTHOR]

Background. The incidence and severity of invasive group A streptococcal infection demonstrate great variability over time, which at least, in part, seems to be related to group A streptococcal type distribution among the human population. Methods. An enhanced surveillance study of invasive group A streptococcal infection (746 isolates) was performed in Sweden from April 2002 through December 2004. Non-invasive isolates from either the throat or skin (773 isolates) were collected in parallel for comparison. Clinical and epidemiological data were obtained from 88% of patients with invasive disease and were related to isolate characteristics, including T type, emm sequence type, and the presence of 9 superantigen genes, as well as pulsed-field gel electrophoresis pattern comparisons of selected isolates. Results. The annual incidence was 3.0 cases per 100,000 population. Among the patients with invasive disease, 11% developed streptococcal toxic shock syndrome, and 9.5% developed necrotizing fasciitis. The overall case fatality rate was 14.5%, and 39% of the patients with streptococcal toxic shock syndrome died ( P<.001). The T3/13/B3264 cluster accounted for 33% of invasive and 25% of noninvasive isolates. Among this most prevalent type cluster, emm types 89 and 81 dominated. Combined results from pulsed-field gel electrophoresis, emm typing, and superantigen gene profiling identified subgroups within specific emm types that are significantly more prone to cause invasive disease than were other isolates of the same type. Conclusions. This study revealed a changing epidemiology of invasive group A streptococcal infection in Sweden, with emergence of new emm types that were previously not described. The results also suggest that some clones may be particularly prone to cause invasive disease. [ABSTRACT FROM AUTHOR]

Toll-like receptor 9 (TLR9) induces an inflammatory response by recognition of unmethylated CpG dinucleotides, mainly present in prokaryotic DNA. So far, TLR9-deficient mice have been shown to be more sensitive than wild-type mice to viral, but not to bacterial infections. Here, we show that mice deficient in TLR9 but not in TLR1, TLR2, TLR4 and TLR6 or IL-1R/IL-18R are more susceptible to a respiratory tract bacterial infection caused by Streptococcus pneumoniae. Intranasal challenge studies revealed that TLR9 plays a protective role in the lungs at an early stage of infection prior to the entry of circulating inflammatory cells. Alveolar as well as bone marrow-derived macrophages deficient in either TLR9 or the myeloid adaptor differentiation protein MyD88 were impaired in pneumococcal uptake and in pneumococcal killing. Our data suggest that in the airways, pneumococcal infection triggers a TLR9 and MyD88-dependent activation of phagocytic activity from resident macrophages leading to an early clearance of bacteria from the lower respiratory tract. [ABSTRACT FROM AUTHOR]

The Toll-like receptors (TLRs) and the myeloid differentiation factor 88 (MyD88) are key players in the activation of the innate immune defence during microbial infections. Using different murine infection models, we show that MyD88-dependent signalling is crucial for the activation of the innate immune defence against Streptococcus pneumoniae. Our data demonstrate that both local and systemic inflammatory response to S. pneumoniae depends on the presence of MyD88 to clear bacterial colonization of the upper respiratory tract and to prevent pulmonary and systemic infection in mice. Finally, we described a strong correlation between enhanced bacterial growth in the bloodstream of MyD88-deficient mice and the inability to lower the serum iron concentration in response to infection. [ABSTRACT FROM AUTHOR]

In the article, the author discusses the public health needs of individuals who are applying for asylum or refugee status in Europe as of June 2016. Also cited are the country of origin of the majority of applicants, namely, Syria, Afghanistan and Iraq, the assessment made by the European Centre for Disease Prevention and Control (ECDC) on the health needs of the applicants, and the shelter conditions of the refugees.

Wastewater discharge into the environment in resource-poor countries poses a threat to public health. Studies in this area within these countries are limited, and the use of high-throughput whole-genome sequencing technologies is lacking. Therefore, understanding of environmental impacts is inadequate. The present study investigated the antibiotic resistance profiles and diversity of beta-lactamases in Escherichia coli strains isolated from environmental water sources in Accra, Ghana. Microbiological analyses were conducted on wastewater samples from three hospitals, a sewage and wastewater treatment plant, and water samples from two urban surface water bodies. Confirmed isolates (N = 57) were selected for phenotypic antibiotic resistance profiles. Multi-drug-resistant isolates (n = 25) were genome sequenced using Illumina MiSeq sequencing technology and screened for sequence types, antibiotic resistance, virulence and beta-lactamase genes, and mobile genetic elements. Isolates were frequently resistant to ampicillin (63%), meropenem (47%), azithromycin (46%), and sulfamethoxazole-trimethoprim (42%). Twenty different sequence types (STs) were identified, including clinically relevant ones such as ST167 and ST21. Five isolates were assigned to novel STs: ST14531 (n = 2), ST14536, ST14537, and ST14538. The isolates belonged to phylogroups A (52%), B1 (44%), and B2 (4%) and carried β-lactamase (TEM-1B, TEM-1C, CTX-M-15, and blaDHA-1) and carbapenemase (OXA-1, OXA-181) resistance genes. Dominant plasmid replicons included Col440I (10.2%) and IncFIB (AP001918) (6.8%). Polluted urban environments in Accra are reservoirs for antibiotic-resistant bacteria, posing a substantial public health risk. The findings underscore the need for targeted public health interventions to mitigate the spread of antibiotic-resistant bacteria and protect public health. [ABSTRACT FROM AUTHOR]

Tuberculosis (TB) is a global infectious threat that is intensified by an increasing incidence of highly drug-resistant disease. Whole-genome sequencing (WGS) studies of Mycobacterium tuberculosis, the causative agent of TB, have greatly increased our understanding of this pathogen. Since the first M. tuberculosis genome was published in 1998, WGS has provided a more complete account of the genomic features that cause resistance in populations of M. tuberculosis, has helped to fill gaps in our knowledge of how both classical and new antitubercular drugs work, and has identified specific mutations that allow M. tuberculosis to escape the effects of these drugs. WGS studies have also revealed how resistance evolves both within an individual patient and within patient populations, including the important roles of de novo acquisition of resistance and clonal spread. These findings have informed decisions about which drug-resistance mutations should be included on extended diagnostic panels. From its origins as a basic science technique, WGS of M. tuberculosis is becoming part of the modern clinical microbiology laboratory, promising rapid and improved detection of drug resistance, and detailed and real-time epidemiology of TB outbreaks. We review the successes and highlight the challenges that remain in applying WGS to improve the control of drug-resistant TB through monitoring its evolution and spread, and to inform more rapid and effective diagnostic and therapeutic strategies. [ABSTRACT FROM AUTHOR]

Background: Social determinants may influence the incidence and control of tuberculosis (TB). The aim of this study was to evaluate the correlation between social determinants and pulmonary TB (PTB) incidence and treatment outcomes in different regions in Brazil.Methods: In this ecological study, PTB incidence and treatment outcome rates as well as HIV incidence for all 5560 Brazilian cities as reported to the Brazilian Tuberculosis Program in 2010 were correlated with two social indicators, the Human Development Index (HDI) and Gini Index (GI). Cities were stratified into six groups based on location (metropolitan region or not) and size (small, medium, and large cities), and according to the regions of the country to which they belong. The Spearman correlation coefficient was used to assess the association between variables.Results: In 2010, 68,729 new PTB cases were reported in Brazil, with an incidence rate of 36 cases per 100,000 inhabitants. Incidence rates and PTB mortality demonstrated a weak negative correlation with HDI and a positive correlation with GI. The correlation between HDI and GI with cure, relapse, and lost to follow-up of treatment greatly varied in the different groups of cities and regions of the country evaluated.Conclusions: There is a weak correlation between HDI and GI and PTB incidence and mortality rate. However, there is great variation between the HDI and GI and cure, relapse, and lost to follow-up in the different groups of cities and regions of the country. This suggests that for TB determination, these outcome variables might be more related to the quality of healthcare provided by services than to social determinants in the general population. [ABSTRACT FROM AUTHOR]