[The present and future prospects in rapid molecular diagnosis of tuberculosis and MDR-TB (First Part)]. / Prezent si perspective în diagnosticul rapid molecular al tuberculozei si al MDR-tB (prima parte).

Tuberculosis is still one of the diseases with a major medical and social impact, and in terms of early diagnosis (which would imply a fair treatment and established at the time), difficulties related to the delay bacilli isolation in culture, decreased susceptibility testing methods to antituberculosis drugs, lack of methods for differentiation of M. Tuberculosis complex germs of non TB Mycobacteria, may have important clinical implications. Traditional testing of anti-TB drug susceptibility on solid Löwenstein-Jensen medium (gold standard) or liquid media can only be performed using grown samples. Determining the time it takes up to 42 days on solid media and 12 days for liquid media. For MDR/XDR TB cases is absolutely essential to reduce the detection time. In these cases prove their usefulness rapid diagnostic methods. Automatic testing in liquid medium, molecular hybridization methods are currently recommended by the current WHO guidelines. Rapid diagnosis of MDR-TB is extremely useful for the early establishment of an effective treatment tailored more accurately on the spectrum of sensitivity of the resistant strain (thus reducing the risk of developing additional resistance to other drugs) and control the spread of these strains. Genetic diagnostic methods, approved and recommended by the WHO, can reduce the time of diagnosis of TB case and, importantly, the case of MDR TB. They do not replace the current standard diagnostic methods and resistance profile, but complete them in selected cases.

[Prudent optimism and the evolution of the main indicators of endemic tuberculosis in Romania in 2012]. / Optimismul prudent si evolutia principalilor indicatori ai endemiei tuberculoase în anul 2012, în România.

The implementation of programmes for Tuberculosis Control (NPTC) in the medium term, starting in 1997, who under the auspices and the coordination of the Ministry of Health, was the guarantor of the achievements in these years in TB control, therapeutic success rate of cases being a constant source of 80%. The global incidence of TB (IG) (new cases and relapses) has decreased in the past 10 years with 42%, from a maximum of 142.2per 100 thousand in 2002, to 79.2 per 100 thousand in 2012. The incidence of TB in children between 0 and 14 years of age has dropped significantly, from 48.2 per 100 thousand in 2002 (1843) a t28.3per 100 thousand in 2011 (770). Mortality declined from 10.8% in 2002 to 6% in 2011. To increase the control of TB, and in accordance with the envisaged country strategy for the period 2013-2017, the anti-TB Programme will give priority to the following measures: gradual introduction of rapid molecular techniques able to identify in the shortest time TB and chemoresistancies; centralized procurement anti-TB drugs; better integration ofpractices of diagnosis and treatment of TB in children with standard practices for tuberculosis control; for a proper diagnosis and treatment to all people suffering from MDR-TB (until 2015).

[Tuberculosis in children in Romania]. / Tuberculoza la copii în Romania.

According to the World Health Organization and Stop TB Partnership, tuberculosis among children often remains undiagnosed, the main reported causes being lack of access to health services or because health professionals unrecognizing the signs and symptoms of tuberculosis in this age group. In Romania, consistent with TB endemic levels, the overall incidence progressively decreased from 142.2%ooo in 2002 to 82.8%ooo in 2011, incidence of TB in children 0-14 years dropped steadily from 47.2 %ooo (1784 cases) in the same "peak year"2002 to 23.6% ooo (766 cases) in 2011. The distribution of TB disease in children by counties shows variations between these, the explanations may be related both to differences in offer of the bacilli between different areas (prevalence of pulmonary patients smear and/or culture positive) and by deficiencies in the detection of cases and lack of rigor in diagnosis (variation in the incidence of TB in 0-14 years from 2.S%ooo in Salaj county up to 53.2%ooo in Maramures county in 2011). The number of serious cases of TB in children (meningoencephalitis, miliary, cavitary) still maintains a constant high annual rate (65 cases in 2011), which demonstrates the severity of endemic TB in our country. Prompt assurance of TB diagnostic and also the accurate management of TB treatment constitute the guarantee of the decrease of this disease, goal applies to all age groups.

[Present and future perspectives for the rapid molecular diagnosis of TB and MDR-TB]. / Prezent si perspective in diagnosticul rapid molecular al tuberculozei si al MDR-TB.

Tuberculosis is still one of the diseases with a major medical and social impact, and in terms of early diagnosis (which would imply a fair treatment and established at the time), difficulties related to the delay bacilli isolation in culture, decreased susceptibility testing methods to antituberculosis drugs, lack of methods for differentiation of M. Tuberculosis complex germs of non-TB Mycobacteria, may have important clinical implications. Traditional testing of anti-TB drug susceptibility on solid Löwenstein-Jensen medium (gold standard) or liquid media can only be performed using grown samples. Determining the time it takes up to 42 days on solid media and 12 days for liquid media. For MDR/XDR TB cases itis absolutely essential to reduce the detection time. In these cases rapid diagnostic methods prove their usefulness. Automatic testing in liquid medium, molecular hybridization methods are currently recommended by the current WHO guidelines. Rapid diagnosis of MDR-TBis extremely useful for the early establishment of an effective treatment tailored more accurately on the spectrum of sensitivity of the resistant strain (thus reducing the risk of developing additional resistance to other drugs) and control the spread of these strains. Genetic diagnostic methods, approved and recommended by the WHO, can reduce the time of diagnosis of TB case and, importantly, the case of MDR-TB. They do not replace the current standard diagnostic methods and resistance profile, but complete them in selected cases.

[Mortality of tuberculosis in Romania, a marker for severity of the endemic]. / Mortalitatea prin tuberculoza in România, un marker al gravitatii endemiei.

After reaching the lowest level of tuberculosis mortality rate in 1980, 3.7% hundred thousand (830 deaths), followed by a few years with low levels of mortality, the period following the year 1985 was marked by a gradual increase in the mortality rate and in 1995 it reached 11.3% hundred thousand (2560 deaths). The implementation since 1997 of TB control programmes on medium-term (under technical assistance of WHO experts) has led to a decrease in tuberculosis mortality rate to 1482 deaths, 6.9% hundred thousand, in 2010. Compared to standardized TB mortality rate in Europe, Romania is far from the countries of Western and Central Europe, with a rate 6.6 times greater than in the EU. Standardized mortality rate by sex reveals that the rate for males in Romania, in 2009, was 6.5 times higher than in women. Similar to 2009, in 2010, the deaths have reached a maximum per age group at 45-54 years old. In 2010 the tuberculosis fatality was 4.7% and the lethality was 0.6%. Consistency of tuberculosis control strategy, regarding both measures for early detection of tuberculosis and establishing TB treatment under the direct observation, represent the safety elements in the reduction of tuberculosis mortality rate. It should be reminded that one of the goals of Stop TB Partnership is reducing mortality rate in 2012 at half compared to 1990, Romania being one of the 18 countries included in this plan initiated by the WHO Europe Region Office.

[Proportion and site distribution of extrarespiratory tuberculosis in 2007-2010 in Romania]. / Ponderea si structura pe localizari a tuberculozei extrarespiratorii in perioada 2007-2010 în România.

In the actual context of an increased TB endemia (notification rate of 90.5 per thousand, meaning 21457 cases in 2010, but with a constant decreasing trend in the last 8 years), we wanted to see what is the share and structure of extra-respiratory tuberculosis in the period 2007-2010. In the interval 2007-2010 have been registered annually between 1252-1267 extra-respiratory TB cases. Extra-respiratory TB have been between 30% and 42,1% from all TB cases registered annually with the extra-pulmonary TB. In the descending order of cases recorded with TB extra respiratory in 2010, the first was extra-thoracic ganglionary TB (244 cases), followed by osteo-articulary (233) and those of meningo-encephalitis and CNS TB (133). Location of TB on the spine remains the most common form of skeletal TB, representing 62.2% (145 cases) of all osteo-articulary locations. The number of registered cases of pericardial effusions TB annually remains steady at 40-50 cases. The number still high of meningo encephalitis TB (severe prognosis, epidemiological severity) involves enhanced accountability measures in TB control of the territory. The collaboration between the pulmonologist and the body specialist constitutes compulsory condition of quality assistance in case of TB extra respiratory sites.

[Evaluation of COPD patients using CAT-COPD assessment test]. / CAT-COPD assessment test Testul de evaluare a BPOC.

INTRODUCTION: Purposes and objectives. CAT test is a simple questionnaire that quantifies the impact of COPD on patients and doctor-patient communication; it is a complex questionnaire that evaluates the lung function and the impact on quality of life. The score ranges from 0 to 40. The higher the score, the bigger the health problems are. This questionnaire can be used in any language and country, by all COPD patients. METHOD AND MATERIALS: We evaluated 71 COPD patients from Clinical Hospital "Victor Babes" Craiova between 2010-2011. These patients were included in a respiratory rehabilitation program of 16 sessions of physical exercises and education for 8 weeks. RESULTS AND DISCUSSIONS: The average final score was with 12.86% lower than baseline score. The average CAT score after rehabilitation for COPD stage I recorded the best decrease with 16.23%. The program of respiratory rehabilitation has a positive impact no matter BMI. CONCLUSIONS: CAT questionnaire is a sensitive test, easy to fill in that improves the doctor patient communication with a great impact on quality of life.

[Present and future in the use of anti-tubercular drugs]. / Prezent si perspectiva în utilizarea de noi medicamente antituberculoase.

After several decades without any notable progress, there are encouraging results in research and development of anti-TB drugs, the result of a large number of projects now in competition. Along with developing new drugs to treat tuberculosis (TMC207, SQ109, LL3858) are being reassessed others to optimize their effectiveness in order to shorten and simplify therapy (rifampin and rifapentine) and three other drugs, currently used for other indications, were forwarded towards TB (gatifloxacin and moxifloxacin, linezolid). Time to approval as a antiTB drug is 10-15 years, consisting of phases of preclinical and clinical research. Substitution of moxifloxacin for isoniazid during intensive phase treatment of pulmonary tuberculosis resulted in a small but statistically nonsignificant increase in 8th- week culture negativity. TMC207, a diarylquinoline with a unique way to address Mycobacterial ATP synthetase, shows high activity in vitro against Mycobacterial strains sensitive or resistant to all drugs in the first and second line, including fluoroquinolones, demonstrating exceptional qualities in vivo against several species of mycobacteria, in various animal models. TMC207 was added to a basic standard regimen in a study of MDR-TB patients. After two months and satisfactory tolerability, sputum conversion rate in culture was 48% (versus 9% in the placebo group). Two nitroimidazole (PA-824 and OPC-67683) are currently in clinical development. PA-824 demonstrated good safety and tolerability in adult patients with pulmonary TB in South Africa, when given once daily for 7 days. Associating isoniazid, would prevent the selection of mutants resistant to Isoniazid. Linezolid 600 mg is currently being tested in a Phase II for treatment of XDR-TB in the Republic of Korea. PNU-100480, analogous to the previous one, has the potential to significantly shorten the treatment in cases where there is sensitivity and in those with resistance to drugs. 300 mg dose is under investigation in a phase II pilot study in MDR-TB in South Africa. With this interest and commitment, it appears that there is a chance of having a new drug available soon.

[Expecting the antinicotine vaccine]. / In asteptarea, cu sperante, a vaccinului antinicotinic.

The last decade is marked by a number of studies regarding the conception of an antinicotine vaccine. There are research studies waiting to be done (Switzerland, USA, Sweden). The principle is represented by the fact that nicotine has a small molecule which can cross the blood-brain barrier resulting in psychic effects and dependence. Vaccination against nicotine produces in the blood an amount of antibodies that prevent the nicotine from generating the feeling of pleasure when the person tries to smoke again. The research studies are advanced and the specialists are hoping to introduce the vaccine against nicotine on the market at the beginning of 2010.

[Tuberculosis in Romania between 2006-2008]. / Tuberculoza in România intre anii 2006-2008.

The high level of TB incidence places Romania among first places in Europe and on the first place in European Union; in the last years a slowly, but hopefully descending trend can be observed (from 114.2 per hundred thousand in 2006 to 109.8 per hundred thousand in 2007 and 108 per hundred thousand in 2008). TB incidence in children has also decreased from 31.6 per hundred thousand in 2006 to 30.8 per hundred thousand in 2007 and 28.5 per hundred thousand in 2008. TB mortality decreased to 7.8 per hundred thousand in 2006 and 7.4 per hundred thousand in 2007. Every year, 800 cases with MDR TB are notified in Romania. The results obtained in the cohort of new patients with pulmonary SS(+) tuberculosis: the success rate reached in 2003 was 79.5% and 83.9% in 2006. The success rate was greater in pulmonary patients confirmed by culture: 82% in 2003 and 85.5% in 2006. In conclusion, the results of NTP implementation in Romania, reflected by the evolution of the principal epidemio-metrical indicators (decrease of the global incidence, TB incidence at children, TB mortality and increase of therapeutical successes) confirms the TB control activities efficacy.

[Clinical and epidemiological aspects of TB cases registered in persons aged > or =65 between 2002-2006, at the TB dispensary of sector 4, Bucharest]. / Aspecte clinico-epidemiologice ale cazurilor de tuberculoza înregistrate la persoanele de > or =65 ani în perioada 2002-2006 la dispensarul de pneumoftiziologie al sectorului 4, Bucuresti.

The study objectives were to find clinical and epidemiological aspects of TB cases registered between 2002-2006 in persons aged > or =65 years that belong to the TB Dispensary of the Sector 4-Bucharest. TB incidence in Romania at age group 265 years was in 2006 94% per hundred thousand (68.6% per hundred thousand in Sector 4-Bucharest). 153 new cases and 28 relapses were registered during 2002-2006, the highest percentage was between 68 and 78 years old. In 96.7% the tracking was passive and relatively delayed, with a 2.5 month mean from the onset of symptoms. The anatomical-radiological forms, caseous-extended and cavitary, represented 36% of the cases and the peripheral lymphatic node TB was the most frequent between the extrapulmonary forms--9.8%. The bacteriological confirmation was 81.7% in new TB cases. DOT strategy was applied in 76.8% of cases (139). The success rate of the therapy in the all cohort was 73.9% and the mortality was 20.4%. The introduction of a clinical surveillance system of the persons aged 65 years with a risk to develop the disease remain to be realised along with the application of the National Programme for TB Control 2007-2011.

[Evolution of the tuberculosis epidemic in Oltenia, between 1980-2006]. / Evolutia endemiei de tuberculoza in Oltenia, in perioada 1980-2006.

The analyze of TB epidemic in Romania and, particularly, in Oltenia, in the condition of national applying of WHO strategy of prevention and control of TB, as the only way of achieving as main objective, the cure of 85% of source cases, represents the main way able to bring the base for adopting optimal solutions for correcting deficiencies. For the evaluation of the tendencies of evolution of the tuberculosis epidemic in Oltenia, the authors carried out a retrospective study over a period of more than 25 years, by the analysis of the main epidemiological indices of tuberculosis epidemic in this Romanian region: global incidence both in adults and children, for new cases and relapses apart, incidence of new cases of pulmonary and extra-respiratory TB, mortality through tuberculosis. In 1980, the TB global incidence was 71.07%000 and doubled this value in 2006. The distribution of new cases on regions in 2005 reflects the fact that Oltenia was on the first place, with a rate of 132.45%000, compared with national value of 105.7%000 in the same year. The incidence of new cases in children in 2006 (33.45%000) was higher than national level (31.6%000). The improvement of the living level of the population, following of the correct application of directly observed treatment and efficient anti-tuberculosis actions can determine a decrease of the TB epidemic in Oltenia.

[Multidrug resistant tuberculosis in Romania in the last years (2004-2007)--an extremely important social phenomenon]. / Tuberculoza multidrog rezistenta în România în ultimii ani (2004-2007)--un fenomen social de maxima importanta.

The emergence of resistance to drugs used to treat tuberculosis (TB), and particularly multidrug resistant (MDR-TB) strains, has become a significant public health problem in a number of countries and an obstacle to effective global TB control. In many other countries, the extent of drug resistance is unknown and the management of the patients with MDR-TB is inadequate. In countries where drug resistance has been identified, specific measures need to be taken within TB control programmes to address the problem through appropriate management of patients and adoption of strategies to prevent the propagation and dissemination of drug resistant TB, including MDR-TB. In Romania there are two centers for the management of MDR-TB cases: one in Bucharest at The National Pneumology Institute "Marius Nasta" and the other at Bisericani (Neamt district). The comparative analysis of MDR-TB cases and under treatment evolution was done, in the two excellence centers Bucharest and Bisericani from 2004 to 2007. This is a retrospective study of MDR-TB patients enrolled in Romania between 2004-2007. All patients evaluated were managed under The National Tuberculosis Programme approved protocols and had the opportunity to receive more than 24 months of treatment. In addition, follow-up data on successfully treated patients were collected at the beginning of 2007. This study is based on an MDR register, and a software collecting information on MDR-TB cases. In order to be accepted in one of the two MDR centers, patients need to fulfill certain criteria to improve the treatment results. A total number of 305 MDR-TB patients were registered at the beginning of 2007 in Bucharest MDR center; this study used a number of 170 MDR-TB patients from Bucharest who fulfilled the study's criteria in oppose to the 294 MDR-TB patients from Bisericani. 184 patients from the first cohort of DOTS-Plus project were evaluated until the end of the study: 55 were completed treatment and 54 cured, which means 59,23% succes rate. The conversion rate of culture at 4 months (for the first cohort) in MDR excellence centers was: Bucharest--72,5% and Bisericani--64%.