Cross-border outbreak of extensively drug-resistant tuberculosis linked to a university in Romania.

Extensively drug-resistant (XDR) tuberculosis (TB) poses a threat to public health due to its complicated, expensive and often unsuccessful treatment. A cluster of three XDR TB cases was detected among foreign medical students of a Romanian university. The contact investigations included tuberculin skin testing or interferon gamma release assay, chest X-ray, sputum smear microscopy, culture, drug susceptibility testing, genotyping and whole-genome sequencing (WGS), and were addressed to students, personnel of the university, family members or other close contacts of the cases. These investigations increased the total number of cases to seven. All confirmed cases shared a very similar WGS profile. Two more cases were epidemiologically linked, but no laboratory confirmation exists. Despite all the efforts done, the source of the outbreak was not identified, but the transmission was controlled. The investigation was conducted by a team including epidemiologists and microbiologists from five countries (Finland, Israel, Romania, Sweden and the UK) and from the European Centre for Disease Prevention and Control. Our report shows how countries can collaborate to control the spread of XDR TB by exchanging information about cases and their contacts to enable identification of additional cases and transmission and to perform the source investigation.

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.

Reversing the tuberculosis upwards trend: a success story in Romania.

At present, no published evidence is available on the effectiveness of the DOTS (directly observed treatment, short-course) strategy in reducing the incidence of tuberculosis (TB) within a country in the European "hot spots". The present study aimed to demonstrate the effectiveness of the strategy implementation in reversing the epidemiological TB trend in Romania based on programmatic data analysis. Key programme indicators were analysed from 1998 to 2007, and included DOTS coverage, case-detection rate, treatment success and overall incidence of notified cases. Internationally agreed definitions were used. The key programme indicators began declining and the World Health Assembly targets were reached (79% case-detection of new sputum-smear positive cases and 85.5% success rate in new culture-positive TB cases), 7 yrs after initiation of the DOTS expansion. The success story in Romania suggests that other middle-income, high-incidence countries (i.e. those belonging to the former Soviet Union) might be able to reach the World Health Assembly Targets and curb the burden of tuberculosis.

[260 cases of tuberculosis death at the Institute of Pneumophysiology of Bucharest 1976-1985]. / Etude de 260 cas de tuberculose décédés à l'Institut de Pneumophtisiologie de Bucarest de 1976 à 1985.

The case notes of all deaths due to tuberculosis registered at the Institute of Pneumophysiology at Bucharest have been reviewed. Out of 273 patients registered, the diagnosis of tuberculosis was retrospectively confirmed 260 times on either bacteriology or histology and was not confirmed by analysis of the medical notes on 13 cases. Of the 260 cases (70% males) the ages range from 18 to 75. There was 95 new cases of tuberculosis, 68 were relapses and on 97 occasions it was chronic form. Resistant bacilli were isolated 79 times (63%). Intolérance to treatment was noted in 95 patients (36%) and an incomplete treatment occurred in 84 patients (32%). The death occurred before treatment could be instituted in 33 patients. Tuberculosis was multicavitatory in 192 cases (74%), was bilateral in 214 cases (82%). From the last admission on 140 patients whose bacteriology was available for studies 112 (80%) were positive on direct examination. Compared to another enquiry carried out in Bucarest between 1961 and 1968 on 350 deaths due to tuberculosis, it appeared that the patients in the more recent period were suffering from a more severe form of tuberculosis. The above facts witness the efforts made in Rumania to achieve an early diagnosis and treatment in the management of tuberculosis.

[A surgical cure of inguinal hernias by the Shouldice procedure]. / Cura chirurgicala a herniilor inghinale prin procedeul Shouldice.

Shouldice procedure became an elective technique in inguinal hernia repair as a consequence of the spectacular results of the Shouldice Hospital in Toronto (less 1% recurrence rate) and of other surgical centres in USA or western Europe. In the present study 73 cases of uncomplicated inguinal hernias who underwent a Shouldice herniotomy are analysed within a period of three years. Cremaster resection was routinely performed preserving a one inch proximal fragment which was used to calibrate the inguinal ring after reconstruction. Two continuous nonresorbable stitches were used to reinforce the posterior wall, as described by the author. Short postoperative follow-up showed good results in 64 cases but only 21 patients were reviewed within 6 and 12 month. Nevertheless no recurrence was reported in 3 years by any patient. According to these encouraging results Shouldice procedure might be considered as the procedure of choice in the treatment of inguinal hernias but much more data are necessary for pertinent conclusions.

[Anatomicoclinical study of fatal cases of pulmonary tuberculosis at the Institute of Phthisiology in 1976-1986 (a preliminary study)]. / Studiul anatomoclinic al cazurilor letale de tuberculoza pulmonara din Institutul de Ftiziologie în perioada 1976-1986 (studiu preliminar).

The paper reports on 95 cases of treated pulmonary and extrapulmonary tuberculosis, deceased during 10 years. In 46 of them necropsy was made. Anatomoclinical examination confirmed in 5 cases pulmonary tuberculosis and intravital neglected tuberculosis in 4 cases. Advanced forms of the disease were found at case-finding in 2/3 of the cases, this explaining the death before the treatment action. Only in 70.5% of cases the cause of death was tuberculosis, in the rest it was due to associated affection. In about half of the cases (47.4% the patients' age was over 60.

[Current aspects of the antitubercular chemotherapy of new patients with tuberculosis and diabetes mellitus]. / Aspecte actuale ale chimioterapiei antituberculoase la bolnavi noi cu tuberculoza si diabet zaharat.

Starting from the published data that demonstrate the annulling of the negative influence of diabetes-tuberculosis morbid association, the authors studied from the clinical, epidemiologic, paraclinical and therapeutical viewpoints 68 diabetic patients with pulmonary tuberculosis (31 men, 37 women) and a control group of 73 patients (57 men and 16 women), both groups were new cases under a first treatment. There was no difference as regards the onset, evolution up to the moment of detection and diagnosis, the presenting clinical and radiologic forms, the gravity of the cases, biologic test and evolution under treatment. These data demonstrate the efficiency of the present day treatment, regardless of the association of the two diseases, the annulling of the negative influence described in previous years, but also the lability of diabetic patients in spite of the control of tuberculosis by tuberculostatics.

[Single-dose administration in the treatment with penicillin G (PG) and metronidazole (Me) in primary pulmonary abscesses (a preliminary study)]. / Administrarea în priza unica a tratamentului cu penicilina G (PG) si metronidazol (Me) în abcesele pulmonare primitive (studiu preliminar).

The anaerobic bacteria play the main role in the etiology of the lung abscesses (Finegold, 1989). From this reason, the administration of the association PG and Me (endovenously or per os) gives a high healing rate in our country; 90.5%. The objective of this work was to study the influence of the drug-administration rhythm on the therapeutical results. The drugs were given once daily, several times daily, or in a combination of those 2 modalities. A lot of 38 patients hospitalized between 1.01.94-31.12.95 in the Institute of Pneumophthisiology, was divided in 3 groups: U (11 cases--28.9%), treated with PG: 5-10 mill and Me: 1.5-2 g in one endovenous perfusion, daily: M (18 cases--47.3%), treated with PG: 5-10 mill, one endovenous perfusion daily and Me: 1.5-2 g, 2-4 times daily: F (9 cases--23.8%), treated with both PG: 5-10 mill and Me: 1.5-2 g, 2-4 times daily. Cases with lung abscess and advanced neoplasia, hepato-renal or cardio-pulmonary insufficiencies, were excluded. The hospitalization period was 15-77 days, with an average of 38.3 +/- 26. The proportion of the therapeutical successes, estimated as the disparition of the clinical suppurative symptomatology and the reduction > or = 90% of the lesions and cavity surfaces on the chest X-ray, was for the group U: 90.9% (10 from 11 cases), for M: 94.4% (17 from 18 cases) and for F: 88.9% (8 from 9 cases), the difference being statistical non-significant.

[The evolution and structure of morbidity from extrarespiratory tuberculosis in the last 15 years in Romania]. / Consideratii privind evolutia si structura morbiditatii prin tuberculoza extrarespiratorie în ultimii 15 ani in România.

Though in comparison with the overall lethality of tuberculosis the extra-respiratory localizations of the disease showed a markedly less weight than the respiratory ones during the past 15 years (12.8% in 1975 and 6.7% in 1989), this pathology chapter is still essential due to the diversity of Tb forms and localizations. The annual average rate of the decrease in extra-respiratory tuberculosis incidence was of 4.8% between 1975-1989, so the incidence value reached 4.2%000 at the end of the last year of study. Just like 15 years ago, in 1989 the extra-respiratory tuberculosis incidence was dominated by the localizations on the peripheral lymph nodes (1.2%000), on bones and joints (1.0%000), urogenital apparatus (0.7%000), meninges and central nervous system (0.5%000). The prevalence of patients with extra-respiratory Tb localizations was gradually diminished so that only 3415 cases were registered in the IIIrd group of the active case-index in 1989 (13,524 in 1975). More than half of the number of deaths through extra-respiratory tuberculosis were still due to tuberculous meningitis, particularly in children aged 0-4 years (82% of deaths in 1989). A further diminution up to a total elimination of extra-respiratory Tb localizations (still about 1,000 new cases a year) can be reached only by a restriction and liquidation at the same time of both primary and secondary pulmonary tuberculoses.

[The results of the chemotherapy of a patient cohort with pulmonary tuberculosis followed-up for a 3-year period]. / Rezultatele obtinute prin chimioterapie la o cohorta de bolnavi cu tuberculoza pulmonara, urmariti timp de 3 ani.

In 1992, in the fourth district of Bucharest 184 news adult patients with pulmonary tuberculosis were registered, and they received specific chemotherapy. The initial sputum bacteriological examination was M+C+ in 63.1% of these patients, M-C+ in 21.7% and M-C- in 15.2%. After three years of surveillance the results of the treatment were evaluated. 27 patients were excluded from the initial group, because they failed to be controlled. The final results were influenced by the sex and the initial bacteriological examination of sputum: the persistent negativation of sputum was obtained in 96.2% of the women, and only in 89.5% of men; depending on the initial bacteriological sputum examination, 100% of the M-C+ cases were negated, but only 86.4% of the M+C+ group.

[Tuberculosis in the elderly: sociomedical aspects]. / Tuberculoza la varstnici; aspecte medico-sociale.

A study on a group of 100 tb patients aged over 60 years registered between 1987-1991 in the district 4 of Bucharest has been carried out aiming at the evaluation of medical and social aspects. In order to increase the relevance of the obtained data, these were compared with a group of young tb patients aged 20-39 years, in the same territory and period of time. The results show: the case-finding predominantly passive, extrarespiratory forms in 25%, high contamination risk (63% acid fast bacilli eliminators on microscopy) non-compliance to treatment in 1/5 of cases. These aspects could be explained by psychic particular features in aged persons, associated diseases a.s.o., leading to treatment failures. The analysis of social and epidemiological aspects of tb in aged subjects evidences some lack of good results in this important public health problem of people.

[The exclusively outpatient treatment of pulmonary tuberculosis under the conditions in Romania]. / Tratamentul exclusiv ambulator al tuberculozei pulmonare în conditiile tarii noastre.

In order to demonstrate the possibility of an exclusively outpatient treatment of pulmonary tuberculosis in the present conditions in our country, a study was performed on 140 cases in Bucharest. The admission criteria were as follows: sputum negative patients (M-C-); paubacillary cases, sputum positive only in culture (M-C+); Tb pleuritis; patients refusing hospitalization, regardless their bacteriological status, and sputum positive cases also at smear examination (M+C+), if they had no household contacts under 20 years of age or with a good social economic standard of life. The patients were given the intensive chemotherapy regimen HSRZ 2/7 for 6 months, that was prolonged to 9 months in specified cases. A number of 31 patients were non-bacillary (M-C-) out of which 14 cases with pleuritis; 70 were paucibacillary (M-C+), and 39 were smear positive (M+C+). Out of 109 patients which were bacteriologically confirmed, sputum reversion in culture was obtained in 71.6% of cases at 2 months and in 89.0% at 3 months. At treatment end, sputum negativation was not obtained in a single patient (0.9%). Case follow-up for 6-41 months after treatment end led to the registration of 8 therapeutical failures and bacteriological relapses (5.7%). Five cases recovered through re-treatment, 1 patient (0.7%) died through tuberculosis, and 2 (1.4%) became chronic case. Periodical control of the 95 contact children in the respective households revealed a single conversion of the tuberculin reaction and no Tb case after treatment start in index cases, which proves the epidemiological reliability of the method.