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 170,526 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The strategy of directly observed treatment, short course (DOTS) is achieving substantial progress in coverage and quality improvements worldwide. However, the problem of multi-drug-resistant tuberculosis (MDR-TB) has emerged as a new challenge to TB control in both developing and industrialized countries. The effort of various countries of the Pacific Rim to fight this problem, one of the negative progenies from the 20th century, was a major theme of the conference. Asia, WHO's Southwest Asia and Western Pacific Regions, combined, account globally for almost 60% of the newly occurring MDR-TB cases. However, the problem has likely been overlooked, as it was masked by taking averages for countries or wider regions. In this way, we may have lost sight of "hot zones" with extremely high prevalence of MDR-TB in smaller areas or in population segments. The problem was basically a result of the low-quality treatment program, but recently it may be amplified in some areas by the HIV epidemic that is another new challenge to TB strategies. So far, developing countries have not been taking active measures to manage this problem. However, some countries, such as the Philippines and Peru, have undertaken aggressive efforts, supported technically and financially by the new international mechanisms, such as the Stop TB Partnership and the Global Fund to fight AIDS, TB and Malaria. These efforts would be more effective if there were further technical innovation in diagnosis and treatment, supported by a strong political commitment.
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PMID:MDR-TB--its characteristics and control in Asia-Pacific rim symposium in USJCMSP 10th international conference on emerging infectious diseases in the Pacific rim. 1758 96

Tuberculosis (TB) kills about 3 million people per year worldwide. Furthermore, TB is an infectious disease associated with HIV patients, and there is a rise in multidrug-resistant TB (MDR-TB) cases around the world. There is a need for new anti-TB agents. The study evaluated the antimycobacterial activity of nine plants used in Mexican traditional medicine to treat tuberculosis and other respiratory diseases. Nasturtium officinale showed the best activity (MIC = 100 microg/mL) against the sensitive Mycobacterium tuberculosis. The following plants were active also but at 200 microg/mL: Citrus sinensis, Citrus aurantifolia, Foeniculum vulgare, Larrea tridentata, Musa acuminata and Olea europaea. Contrary to the above data, activity against drug-resistant variants of M. tuberculosis was more evident, e.g. N. officinale was the most potent (MIC < or = 100 microg/mL) against the four mono-resistant variants tested; F. vulgare and O. europaea were active against all the resistant variants (MICs < or = 100 microg/mL). The most susceptible variant was the isoniazid resistant, being inhibited by C. aurantifolia, C. sinensis and O. europaea (MIC = 25 microg/mL). These data point to the importance of biological testing of extracts against drug-resistant M. tuberculosis isolates, and the bioguided assay of these extracts for the identification of lead compounds against MDR-TB isolates.
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PMID:Activity against drug resistant-tuberculosis strains of plants used in Mexican traditional medicine to treat tuberculosis and other respiratory diseases. 1772 32

The largest TB control programme in terms of patients treated is India's Revised National Tuberculosis Control Programme (RNTCP). The treatment success of new smear positive TB cases under RNTCP has exceeded the global benchmark of 85%. Also there are some challenges in TB control programme eg, addressing TB in HIV-infected persons and accurate diagnosis and management of multidrug resistant TB (MDR-TB). Diagnosis of MDR-TB requires sophisticated laboratories. If MDR-TB is not managed effectively, then there is possibility to emerge drug-resistant TB which is virtually untreatable. The Public-Private mix initiatives of RNTCP attempt to make quality assured treatment for TB for all patients, regardless of healthcare providers they choose. The International Standards of TB Care (ISTC) is an international effort which has articulated the diagnostic, treatment and public health standards which all providers should hold themselves and their peers accountable to. For providers the path to practise the ISTC is to diagnose and treat patients in collaboration with RNTCP. The IMA has taken up the cause of TB control in India very seriously. This organisation of the doctors (IMA) deserves recognition for becoming the first professional association to endorse the ISTC in India. All health providers should work with and support the RNTCP, so that the programme can be made into a genuine mass movement to fight TB.
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PMID:RNTCP 2007: looking ahead to future challenges. 1782 87

This article analyses the complexity of the age-old battle that the human species has been waging for millions of years against Mycobacterium tuberculosis. We review all of the knowledge available about this disease, and the most important future developments, in order to reach the conclusion that it is indeed possible to dream of eradicating this disease that has caused such harm to humanity. In spite of the human species possessing sufficient knowledge to win the battle against Mycobacterium tuberculosis, important conditioning factors, above all social in character (poverty, immigration, HIV, MDR), are favouring the bacteria in this war. And, in spite of suitably applying all of the positive knowledge acquired for the control of TB (detection and cure of cases, chemoprofilaxis, BCG vaccination, etc.), it will still take several centuries to achieve its eradication. Only by discovering a vaccine that is 100% efficient, or the discovery of new anti-microbial associations that could cure the disease in no longer than 15 days, could accelerate this advance towards its eradication. But, unfortunately, there are no reasons allowing us to dream that either of these two possibilities can be fulfilled in the next 10 to 20 years. Therefore, the dream of eradicating TB is a very old dream, but one that unfortunately remains very distant.
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PMID:[The old battle between the human species and Koch's bacillae. Can one dream of eradicating tuberculosis?]. 1789 35

Tuberculosis (TB) is a devastating disease caused by Mycobacterium tuberculosis that killed an estimated 4000-5000 person each day during 2005. Although infections with drug sensitive strains can be effectively cured with a 6 to 9 month regimen of multiple antibiotics, the inability to deliver and complete appropriate courses of therapy on a global level has led to the selection of resistant strains over the past 50 years. The selection and spread of multiple drug resistant M. tuberculosis continued for decades leading to two operationally distinct forms of the disease, multiple drug resistant (MDR-TB) and extensively drug resistant (XDR-TB). The estimate for MDR-TB and XDR-TB cases for 2005 were 424,000 and 27,000 respectively, and the situation is worst in areas with high incidences of HIV infection. The outcome was predictable based on basic microbiological principles, and the resultant and future epidemic effectively modeled mathematically. This situation was brought to the forefront when an outbreak of XDR-TB occurred in Tugela Ferry, KwaZulu-Natal, South Africa, in 2005 and began to spread. Unfortunately, we do not know the true extent of XDR-TB globally. However, all signs point to an emerging epidemic of TB infections that will be difficult, if not impossible to cure. A few new drugs are in clinical trials, but it is too early to know the final outcome; some may fail, and none will be available for several years. The situation will continue to worsen unless more resources are made available to discover and deliver better treatment options.
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PMID:The evolution of extensively drug resistant tuberculosis (XDR-TB): history, status and issues for global control. 1797 Feb 20

Mycobacterium tuberculosis is one of the most successful bacterial parasites of humans, infecting over one-third of the population of the world as latent infection without clinical manifestations. Over 8.8 million new cases and nearly 2 million deaths by tuberculosis (TB) occur annually. TB poses a significant health threat to the world population. The goal of this symposium is to open new avenues for combating tuberculosis. The speakers have presented their data and provided control strategies against tuberculosis and pulmonary disease due to M. avium complex (MAC) from aspects of molecular epidemiology, pathogenesis, serodiagnosis, new anti-TB drugs, and vaccine development. Drs. Maeda and Murase have reported that the 12-locus VNTR analysis is very useful for molecular epidemiology of M. tuberculosis strains isolated in Japan better than IS6110-RFLP and suggested that the analysis is powerful tool for the molecular epidemiology. Drs. Matsumoto and Kobayashi have discovered a protein, mycobacterial DNA-binding protein 1 (MDPl), overproduced in dormant M. tuberculosis that plays key roles in latent/ persistent infection, disease progression, and host protection. They have concluded that MDP1 may be a possible target for anti-tuberculosis drugs and vaccines. Drs. Kitada and Maekura have developed serodiagnosis of MAC disease based on enzyme immunoassay (EIA) by detecting anti-glycopeptidolipid (GPL) antibody in sera of human patients. GPL is specific for MAC. The EIA is a simple, rapid and accurate measure with high sensitivity and specificity. The levels of antibody also reflect disease activity. A large-scale clinical multicenter study is currently in progress. Dr. Makoto Matsumoto has discovered an innovative new anti-TB drug, OPC-67683 that is a derivative of nitroimidazole compounds. OPC-67683 inhibited mycolic acid synthesis and exerted potent antimycobacterial activity, including multidrug-resistant M. tuberculosis. Multidrug therapy using OPC-67683 could also shorten the course of chemotherapy. The drug is clearly the most promising new anti-TB agent that has been identified in many years. Dr. Okada has presented the vaccine candidates for TB, such as HVJ-liposome/HSP65 DNA+IL-12 DNA and HVJ-envelope/HSP65 DNA+IL-12 DNA. The candidates exhibited an excellent protective efficacy in mice compared to current BCG vaccine, and improved histopathologic lesions induced by M. tuberculosis infection. The candidates also exerted the therapeutic effect in mice against both drugsusceptible TB and extensively drug-resistant TB. Using the cynomolgus monkey model (similar to human TB), HVJ-liposome/ HSP65 DNA+IL-12 DNA provided higher protective efficacy than BCG assessed by mortality. The combination of BCG and HVJ-liposome/HSP65 DNA+IL-12 DNA by the prime-booster procedure could lead to a synergistic effect of 100% survival in infected monkeys. These data suggest that the novel DNA vaccine is a possible candidate for human clinical trials. This symposium has highlighted new advances in our understanding of molecular epidemiology and pathogenesis of "Mycobacteriology" and development of new serodiagnostics, anti-TB drugs, and vaccines. 1. The establishment of the quick genotyping method for TB in Japan using the variable numbers of tandem repeats (VNTR): Shinji MAEDA, Yoshiro MURASE (Research Institute of Tuberculosis, Japan Anti-Tuberculosis Association) The 12-locus VNTR analysis that we have established optimally for Mycobacteriun tuberculosis in Japan was superior to the proposed 15-locus VNTR method in European countries. The discriminatory power of our system was also higher than that of IS6110-based restriction fragment length polymorphism analysis. In future, we will investigate the stability of copy number in each locus by using the strains that suspected epidemiological links in contact investigations. 2. A virulence factor of Mycobacterium tuberculosis, which contributes to persistent infection, reactivation, and host protection: Sohkichi MATSUMOTO (Department of Host Defense, Osaka City University Graduate School of Medicine), Kazuo KOBAYASHI (Department of Immunology, National Institute of Infectious Diseases) Majority of adult tuberculosis is caused by reactivation of previously implanted Mycobacterium tuberculosis. During latent infection, some bacilli are in dormant state, which confers some survival advantage to not only bacteria but also the host. We presented that a protein overproduced in dormant M. tuberculosis plays key roles in persistent infection, disease progression, and host protection. We also presented utility of this protein, such as development of anti-tuberculosis drug and vaccine. 3. Serodiagnosis of Mycobacterium avium complex pulmonary disease by enzyme immunoassay using glycopeptidolipid antigen: Seigo KITADA, Ryoji MAEKURA (Department of Internal Medicine, National Hospital Organization National Toneyama Hospital) The diagnosis of Mycobacterium avium complex pulmonary disease (MAC-PD) and/or its discrimination from pulmonary tuberculosis is sometimes complicated and time consuming. We have developed serological test by enzyme immunoassay that detect serum antibody to glycopeptidolipid antigen. The serodiagnosis is useful for the rapid diagnosis of MAC-PD and differential diagnosis from pulmonary TB. The antibody levels reflected the disease activity including radiographic severity. 4. A novel antituberculous agent, OPC-67683: Research and development: Makoto MATSUMOTO (Microbiological Research Institute, Otsuka Pharmaceutical Co., Ltd.) We initiated a program to screen new antituberculous agents that have potential to shorten the total duration of treatment, provide improved efficacy against MDR-TB, be useful in treating HIV co-infected patients, and target latent TB infections. Our efforts led to the discovery of OPC-67683, a novel oxazo-imidazole derivative with a distinctive characteristic as a subclass mycolic acid inhibitor. Our evaluation studies confirmed OPC-67683 to possess potent in vitro and in vivo antituberculous activity, suggesting potential usefulness in alleviating the current TB problems. 5. The development of novel vaccines against M. tuberculosis: Masaji OKADA (Clinical Research Center, National Hospital Organization Kinki-Chuo Chest Medical Center) We have developed a novel tuberculosis (TB) vaccine (HVJ-liposome/ or HVJ-envelope/HSP65 DNA+ IL-12 DNA). The vaccine provided remarkable protective efficacy in mouse compared to BCG vaccine, and improved the histopathological tuberculosis lesions. This vaccine also exerted therapeutic effect in vivo against XDR-TB as well as drug-sensitive TB in mice. Furthermore, by using the cynomolgus monkey (similar to human tuberculosis), this novel vaccine provided higher protective efficacy (mortality) than BCG mortality. Furthermore, the combination of HSP65+IL-12/HVJ and BCG by the priming-booster method showed a synergistic effect in the TB-infected cynomolgus monkey (100% survival). These data indicate that our novel DNA vaccine might be useful against TB for human clinical trials.
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PMID:[Recent progress in mycobacteriology]. 1801 2

Multidrug-resistant tuberculosis (MDR-TB) with bacillary resistance to at least isoniazid and rifampicin in vitro is a worldwide phenomenon. Hot spots of the disease are found scattered in different continents. Prevention of its development through good tuberculosis control programmes operating under the directly observed therapy, short-course (DOTS) strategy is of paramount importance. However, with established MDR-TB, treatment with alternative and specific chemotherapy is necessary to achieve a beneficial outcome. Such an approach on a programme basis is currently known as the 'DOTS-Plus' strategy. Second-line (reserve) drugs utilized in the treatment of MDR-TB are generally less potent and more toxic, perhaps with the notable exceptions of some fluoroquinolones and injectable agents. Surgery has a distinct adjunctive role for the management of MDR-TB in selected patients. The emergence of extensively drug-resistant tuberculosis (XDR-TB), that is, MDR-TB with additional bacillary resistance to the fluoroquinolones and injectables, has provided a very alarming challenge to global health, as the disease currently has a low cure rate and high mortality. In order to combat XDR-TB, strengthening of DOTS and DOTS-Plus programmes is mandatory, especially in the face of surging HIV infection. Furthermore, more attention needs to be focused on developing new drugs with potent bactericidal and sterilizing activities and low side-effects, and above all, drugs that are affordable for communities worldwide.
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PMID:Management of multidrug-resistant tuberculosis: Update 2007. 1819 9

Despite improvements in HIV treatment, the prevalence of multidrug resistance and full class resistance is still reported to be increasing. However, to investigate whether current treatment strategies are still selecting for multidrug and full class resistance, the incidence, instead of the prevalence, is more informative. Temporal trends in multidrug resistance (MDR defined as at most 1 drug fully susceptible) and full class resistance (FCR defined as no drug in this class fully susceptible) in Portugal based on 3394 viral isolates genotyped from 2000 to 2006 were examined using the Rega 6.4.1 interpretation system. From July 2001 to July 2006 there was a significant decreasing trend of MDR with 5.7%, 5.2%, 3.8%, 3.4% and 2.7% for the consecutive years (P = 0.003). Multivariate analysis showed that for every consecutive year the odds of having a new MDR case decreased with 20% (P = 0.003). Furthermore, a decline was observed for NRTI- and PI-FCR (both P < 0.001), whereas for NNRTI-FCR a parabolic trend over time was seen (P < 0.001), with a maximum incidence in 2003-'04. Similar trends were obtained when scoring resistance for only one drug within a class or by using another interpretation system. In conclusion, the incidence of multidrug and full class resistance is decreasing over time in Portugal, with the exception of NNRTI full class resistance which showed an initial rise, but subsequently also a decline. This is most probably reflecting the changing drug prescription, the increasing efficiency of HAART and the improved management of HIV drug resistance. This work was presented in part at the Eighth International Congress on Drug Therapy in HIV Infection, Glasgow (UK), 12-16 November 2006 (PL5.5); and at the Fifth European HIV Drug Resistance Workshop, Cascais (Portugal), 28-30 March 2007 (Abstract 1).
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PMID:The incidence of multidrug and full class resistance in HIV-1 infected patients is decreasing over time (2001-2006) in Portugal. 1824 28

Tuberculosis (TB) is a major public health problem in eastern Europe. Since 1990, the incidence rates of TB have continued to increase in Belarus, the Russian Federation, the Ukraine and the central Asian republics of Kazakhstan, Kyrgyzstan, Tajikistan and Uzbekistan. Eastern Europe, and in particular the Russian Federation and the Ukraine, also face the public health challenge of an escalating multidrug-resistant tuberculosis (MDR-TB) epidemic. Of the 17 283 global MDR-TB cases reported in 2004, over 60% (10 595) were from the European region and the vast majority of these from eastern Europe, including the Baltic states of Estonia, Latvia and Lithuania. Of particular concern is the fact that, along with Africa, treatment success for DOTS in eastern Europe is substantially below average when compared with other regions of the world, and DOTS coverage and smear-positive case detection rate remain the lowest in the world. Collectively, along with Africa, these problems in eastern Europe remain the principal obstacle to meeting the Millennium Development Goals for TB in Europe. The Ukraine has worsening epidemics of TB, MDR-TB and HIV, against a background of epidemics of sexually transmitted illness (STI) and injecting drug users (IDUs). The TB and HIV epidemics are converging. In spite of attempts, the Ukraine has failed to implement DOTS policy due to health systems organization, financing and provider payment systems that created disincentives to change while opposition by policy-makers and clinicians to DOTS strategy hindered implementation efforts.
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PMID:Resistance to implementing policy change: the case of Ukraine. 1829 70

P-glycoprotein (PGP) is a membrane protein and product of the MDR-1 gene, which acts as an efflux pump for several drugs, such as protease inhibitors (PI) used in HIV. Numerous studies in vitro, in experimental animals, and in patients have analyzed the relationships between PGP and the pharmacokinetic and pharmacodynamic properties of antiretroviral agents, with differing conclusions. In addition, studies focusing on the impact of single nucleotide polymorphisms in the MDR-1 gene, mainly C3435T in exon 26 and G2677A/G2677T in exon 21, on antiretroviral plasma concentrations, efficacy and adverse effects, have reported varying results, which have been attributed to the influence of other polymorphisms, such as cytochrome P450.
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PMID:[P-glycoprotein and human immunodeficiency virus infection]. 1835 14


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