Suchergebnisse

Fungal infections, such as candidiasis caused by Candida, pose a problem of growing medical concern. In developed countries, the incidence of Candida infections is increasing due to the higher survival of susceptible populations, such as immunocompromised patients or the elderly. Existing treatment options are limited to few antifungal drug families with efficacies that vary depending on the infecting species. In this context, the emergence and spread of resistant Candida isolates are being increasingly reported. Understanding how resistance can evolve within naturally susceptible species is key to developing novel, more effective treatment strategies. However, in contrast to the situation of antibiotic resistance in bacteria, few studies have focused on the evolutionary mechanisms leading to drug resistance in fungal species. In this review, we will survey and discuss current knowledge on the genetic bases of resistance to antifungal drugs in Candida opportunistic pathogens. We will do so from an evolutionary genomics perspective, focusing on the possible evolutionary paths that may lead to the emergence and selection of the resistant phenotype. Finally, we will discuss the potential of future studies enabled by current developments in sequencing technologies, in vitro evolution approaches, and the analysis of serial clinical isolates. ; TG group acknowledges support from the Spanish Ministry of Economy, Industry, and Competitiveness (MEIC) for the EMBL partnership, and grants 'Centro de Excelencia Severo Ochoa 2013–2017' SEV-2012-0208, and BFU2015-67107 cofounded by European Regional Development Fund (ERDF); from the CERCA Programme/Generalitat de Catalunya; from the Catalan Research Agency (AGAUR) SGR857, and grant from the European Union's Horizon 2020 research and innovation programme under the grant agreement ERC-2016-724173 the Marie Sklodowska-Curie grant agreement No H2020-MSCA-ITN-2014-642095.

Background: The Global Project on Anti-Tuberculosis Drug Resistance has been gathering data since 1994. This study provides the latest data on the extent of drug resistance worldwide. Methods: Data for drug susceptibility were gathered from 90 726 patients in 83 countries and territories between 2002 and 2007. Standardised collection of results enabled comparison both between and within countries. Where possible, data for HIV status and resistance to second-line drugs were also obtained. Laboratory data were quality assured by the Supranational Tuberculosis Reference Laboratory Network. Findings: The median prevalence of resistance to any drug in new cases of tuberculosis was 11·1% (IQR 7·0-22·3). The prevalence of multidrug resistance in new tuberculosis cases ranged from 0% in eight countries to 7% in two provinces in China, 11·1% in Northern Mariana Islands (although reporting only two cases), and between 6·8% and 22·3% in nine countries of the former Soviet Union, including 19·4% in Moldova and 22·3% in Baku, Azerbaijan (median for countries surveyed 1·6%, IQR 0·6-3·9). Trend analysis showed that between 1994 and 2007, the prevalence of multidrug-resistant (MDR) tuberculosis in new cases increased substantially in South Korea and in Tomsk Oblast and Orel Oblast, Russia, but was stable in Estonia and Latvia. The prevalence of MDR tuberculosis in all tuberculosis cases decreased in Hong Kong and the USA. 37 countries and territories reported representative data on extensively drug-resistant (XDR) tuberculosis. Five countries, all from the former Soviet Union, reported 25 cases or more of XDR tuberculosis each, with prevalence among MDR-tuberculosis cases ranging between 6·6% and 23·7%. Interpretation: MDR tuberculosis remains a threat to tuberculosis control in provinces in China and countries of the former Soviet Union. Data on drug resistance are unavailable in many countries, especially in Africa, emphasising the need to develop easier methods for surveillance of resistance in tuberculosis. Funding: Global Project: United States Agency for International Development and Eli Lilly and Company. Drug resistance surveys: national tuberculosis programmes, the Government of the Netherlands, the Global Fund to Fight AIDS, Tuberculosis and Malaria, Japan International Cooperation Agency, and Kreditanstalt für Wiederaufbau. © 2009 Elsevier Ltd. All rights reserved.

History of Medicine is not a discipline destined to culturally enrich only those who work in the health sector. All historians know very well how some medical events have influenced the course of history. In particular, infectious diseases, being interconnected with political, social, economic and war issues, have an important historical significance.Microbial agents are invisible enemies ready to undermine mankind and to find prosperity in human misery.Tuberculosis, better than other, is well suited to study the epistemological path of medical thought, from its origins to the present day.From the Hippocratic and Galenic thought to the anatomo-clinical method, from the advent of microbiology to the antibiotic era up to the postantibiotic era, recognizing the timeless need to implement valid social policies and effective preventive medicine actions to achieve satisfactory results.

Purpose of the studyMonitoring of primary resistance in HIV‐1 variants circulating in Russia and FSU countries is the important task of HIV infection molecular epidemiology. The data of HIV molecular epidemiology are absent or limited in many FSU countries. IDU‐A variant of HIV‐1 subtype A has been dominating in Russia (>90%) and other FSU countries since 1996. Additionally, the Central Asian region (e.g. Kazakhstan and Uzbekistan) is characterized by relatively wide spread of CRF02_AG recombinant. The aim of our study was the analysis of HIV primary drug resistance in HIV‐1 variants from Kazakhstan.MethodsBlood collection from the HIV‐infected naïve patients was carried out by local specialists. The study was performed with the informed consent of patients. All sequences of pol gene were analyzed by COMETv0.1 and HIVdb on‐line programs. The phylogenetic analysis and tropism testing were carried out by MEGA4.0 and geno2pheno.Summary of results51 PBMC samples were analyzed. According to pol gene phylogenetic analysis and genotyping 24 (47.0%) samples belonged to recombinant CRF02_AG; 25 (49.0%)‐to subtype A1; 2 (3.9%)‐to CRF03_AB circulating in Russia and some FSU countries. Only one subtype A1 sample had D30N mutation in Pro‐region that cause high‐level resistance to NFV. All AG‐samples had K20I substitution which is characteristic for HIV‐1 subtype A and G and is believed to be associated with resistance to LPV and NFV. In addition, we found that 2 AG‐samples had L10V and L76I substitutions, accordingly. Two A1‐subtype samples studied had L10I and K43T, accordingly. A62V characteristic mutation in RT‐region was found in 12 (48%) subtype A1‐samples. One of them had M184I mutation as well. Besides, we found 3 A1‐samples harboring NNRTIs resistance mutations‐K103N, G190S, K238N, accordingly. Further we analyzed IN region of pol‐gene in 16 and env‐gene in 23 samples studied. We found only one E157Q mutation (in CRF03_AB sample) in IN region. As to tropism, only two subtype A1 and 1 CRF03_AB samples belonged to X4/X4R5 variant, all these A1‐subtype samples harbored A62V and one of them‐G190S in RT region of pol‐gene; the other samples were treated as R5 variants.ConclusionsOur data demonstrated the low level of HIV primary drug resistance in Kazakhstan. HIV‐1 subtype A variant dominates on this territory, but CRF02_AG recombinant is rather widespread as well. CRF02_AG variant studied has characteristic features in Pro region compared with IDU‐A.

A History of Drugs details the history of the relationship between drugs and freedom over the last two hundred years; thus disturbing and unravelling the 'naturalness' of the 'drug question', as it traces the multiple and heterogeneous lines of development out of which it has been assembled.

BACKGROUND: Increasing access to drugs for the treatment of multidrug-resistant (MDR) tuberculosis is crucial but could lead to increasing resistance to these same drugs. In 2000, the international Green Light Committee (GLC) initiative began to increase access while attempting to prevent acquired resistance. METHODS: To assess the GLC's impact, we followed adults with pulmonary MDR tuberculosis from the start to the end of treatment with monthly sputum cultures, drug susceptibility testing, and genotyping. We compared the frequency and predictors of acquired resistance to second-line drugs (SLDs) in 9 countries that volunteered to participate, 5 countries that met GLC criteria, and 4 countries that did not apply to the GLC. RESULTS: In total, 832 subjects were enrolled. Of those without baseline resistance to specific SLDs, 68 (8.9%) acquired extensively drug-resistant (XDR) tuberculosis, 79 (11.2%) acquired fluoroquinolone (FQ) resistance, and 56 (7.8%) acquired resistance to second-line injectable drugs (SLIs). The relative risk (95% confidence interval [CI]) of acquired resistance was lower at GLC-approved sites: 0.27 (.16-.47) for XDR tuberculosis, 0.28 (.17-.45) for FQ, and 0.15 (.06-.39) to 0.60 (.34-1.05) for 3 different SLIs. The risk increased as the number of potentially effective drugs decreased. Controlling for baseline drug resistance and differences between sites, the odds ratios (95% CIs) were 0.21 (.07-.62) for acquired XDR tuberculosis and 0.23 (.09-.59) for acquired FQ resistance. CONCLUSIONS: Treatment of MDR tuberculosis involves substantial risk of acquired resistance to SLDs, increasing as baseline drug resistance increases. The risk was significantly lower in programs documented by the GLC to meet specific standards. Published by Oxford University Press on behalf of the Infectious Diseases Society of America 2014. This work is written by (a) US Government employee(s) and is in the public domain in the US. ; open