Discriminatory ability of hypervariable variable number tandem repeat loci in population-based analysis of Mycobacterium tuberculosis strains, London, UK

To address conflicting results about the stability of variable number tandem repeat (VNTR) loci and their value in prospective molecular epidemiology of Mycobacterium tuberculosis, we conducted a large prospective population-based analysis of all M. tuberculosis strains in a metropolitan setting. Optimal and reproducible conditions for reliable PCR and fragment analysis, comprising enzymes, denaturing conditions, and capillary temperature, were identified for a panel of hypervariable loci, including 3232, 2163a, 1982, and 4052. A total of 2,261 individual M. tuberculosis isolates and 265 sets of serial isolates were analyzed by using a standardized 15-loci VNTR panel, then an optimized hypervariable loci panel. The discriminative ability of loci varied substantially; locus VNTR 3232 varied the most, with 19 allelic variants and Hunter-Gaston index value of 0.909 . Hypervariable loci should be included in standardized panels because they can provide consistent comparable results at multiple settings, provided the proposed conditions are adhered to

The Directly Observed Therapy Short-Course (DOTS) strategy in Samara Oblast, Russian Federation

BACKGROUND: The World Health Organisation (WHO) defines Russia as one of the 22 highest-burden countries for tuberculosis (TB). The WHO Directly Observed Treatment Short Course (DOTS) strategy employing a standardised treatment for 6 months produces the highest cure rates for drug sensitive TB. The Russian TB service traditionally employed individualised treatment. The purpose of this study was to implement a DOTS programme in the civilian and prison sectors of Samara Region of Russia, describe the clinical features and outcomes of recruited patients, determine the proportion of individuals in the cohorts who were infected with drug resistant TB, the degree to which resistance was attributed to the Beijing TB strain family and establish risk factors for drug resistance. METHODS: prospective study RESULTS: 2,099 patients were recruited overall. Treatment outcomes were analysed for patients recruited up to the third quarter of 2003 (n = 920). 75.3% of patients were successfully treated. Unsuccessful outcomes occurred in 7.3% of cases; 3.6% of patients died during treatment, with a significantly higher proportion of smear-positive cases dying compared to smear-negative cases. 14.0% were lost and transferred out. A high proportion of new cases (948 sequential culture-proven TB cases) had tuberculosis that was resistant to first-line drugs; (24.9% isoniazid resistant; 20.3% rifampicin resistant; 17.3% multidrug resistant tuberculosis). Molecular epidemiological analysis demonstrated that half of all isolated strains (50.7%; 375/740) belonged to the Beijing family. Drug resistance including MDR TB was strongly associated with infection with the Beijing strain (for MDR TB, 35.2% in Beijing strains versus 9.5% in non-Beijing strains, OR-5.2. Risk factors for multidrug resistant tuberculosis were: being a prisoner (OR 4.4), having a relapse of tuberculosis (OR 3.5), being infected with a Beijing family TB strain (OR 6.5) and having an unsuccessful outcome from treatment (OR 5.0). CONCLUSION: The implementation of DOTS in Samara, Russia, was feasible and successful. Drug resistant tuberculosis rates in new cases were high and challenge successful outcomes from a conventional DOTS programme alone

Differentiation of Tuberculosis Strains in a Population with Mainly Beijing-family Strains

A new panel of 25 VNTR-MIRU loci differentiates Beijing-family TB strains better than a panel of 15

Mycobacterium tuberculosis and Rifampin Resistance, United Kingdom

A national diagnostic service identified M. tuberculosis and rifampin resistance in primary clinical specimens faster than conventional techniques

Management of multiple drug-resistant tuberculosis

AbstractThere has been a worldwide increase in multiple drug-resistant tuberculosis (MDR-TB) which has in the past been associated with a poor prognosis. In the U.K., about half of the cases live in the London area and we have set out to obtain further information on their treatment and outcome. We examined the risk factors, drug resistance, drug treatment, sputum conversion, and outcome in patients with MDR-TB at three hospitals in South London and diagnosed during the period June 1995–January 1999. Human Immunodeficiency Virus (HIV)-positive patients were excluded. There were 760 patients resident in Lambeth, Southwark and Lewisham Health Authority (LSLHA) who were notified as tuberculosis (TB) during the time period and who were of negative or unknown HIV status. (The population of LSLHA is approx. 750 000.) There was a total of 13 patients with MDR-TB, known or presumed to be HIV negative. Their median age was 28 years (range 15–53); nine (69%) were born outside the U.K. and 11 had pulmonary disease; they had organisms resistant to a median of two first-line drugs (range 2–4) and to a median of four of all drugs tested (range 2–10). They received treatment with a median of six drugs (range 3–9). Eight were followed up for at least 3 years (range 3–6) after the completion of treatment; at their last assessment none had features of active TB and all were sputum negative (smear and culture). Two returned to their countries of origin during treatment; they were sputum negative at that time. Two patients are well and continue on treatment in the U.K. One patient (known HIV negative) died following treatment failure. In conclusion, we obtained disease-free survival in eight cases of MDR-TB, known or presumed to be HIV negative and followed up for 3 years or more. The prognosis for patients treated at specialised centres is good (and better than is generally believed). We describe a new protocol for the detection and management of MDR-TB

Integration geodätischer und geotechnischer Beobachtungen und Strukturinformationen für eine 3D-Strainanalyse

Für die geodätische Überwachung dreidimensionaler Objekte fehlen in der Regel Informationen zur vollständigen Beschreibung der räumlichen Deformation. Um dieses Informationsdefizit zu beheben, können geotechnische Beobachtungen genutzt werden. In der Dissertation wird die Integration dieser Relativmessungen durch ein erweitertes Krigingverfahren gelöst. Dazu werden für den Signal- und Trendanteil der Beobachtungen die nötigen Kovarianz- und Trendmatrizen hergeleitet. Darüberhinaus wird durch die Darstellung der Beobachtungen als lineare Funktionale des Verschiebungsfeldes die Möglichkeit eröffnet, nicht nur das Verschiebungsfeld zu schätzen sondern auch beliebige lineare Funktionale des Verschiebungsfeldes. Das hergeleitete Verfahren wird an zwei praktischen Beispielen demonstriert

Rates of Latent Tuberculosis in Health Care Staff in Russia

BACKGROUND: Russia is one of 22 high burden tuberculosis (TB) countries. Identifying individuals, particularly health care workers (HCWs) with latent tuberculosis infection (LTBI), and determining the rate of infection, can assist TB control through chemoprophylaxis and improving institutional cross-infection strategies. The objective of the study was to estimate the prevalence and determine the relative risks and risk factors for infection, within a vertically organised TB service in a country with universal bacille Calmette-Guérin (BCG) vaccination. METHODS AND FINDINGS: We conducted a cross-sectional study to assess the prevalence of and risk factors for LTBI among unexposed students, minimally exposed medical students, primary care health providers, and TB hospital health providers in Samara, Russian Federation. We used a novel in vitro assay (for gamma-interferon [IFN-γ]) release to establish LTBI and a questionnaire to address risk factors. LTBI was seen in 40.8% (107/262) of staff and was significantly higher in doctors and nurses (39.1% [90/230]) than in students (8.7% [32/368]) (relative risk [RR] 4.5; 95% confidence interval [CI] 3.1–6.5) and in TB service versus primary health doctors and nurses: respectively 46.9% (45/96) versus 29.3% (34/116) (RR 1.6; 95% CI 1.1–2.3). There was a gradient of LTBI, proportional to exposure, in medical students, primary health care providers, and TB doctors: respectively, 10.1% (24/238), 25.5% (14/55), and 55% (22/40). LTBI was also high in TB laboratory workers: 11/18 (61.1%). CONCLUSIONS: IFN-γ assays have a useful role in screening HCWs with a high risk of LTBI and who are BCG vaccinated. TB HCWs were at significantly higher risk of having LTBI. Larger cohort studies are needed to evaluate the individual risks of active TB development in positive individuals and the effectiveness of preventive therapy based on IFN-γ test results

Hydrodynamische Lyapunov-Moden in mehrkomponentigen Lennard-Jones-Flüssigkeiten

Die Charakterisierung hochdimensionaler Systeme mit Lyapunov-Instabilität wird durch das Lyapunov-Spektrum und die zugehörigen Lyapunov-Vektoren ermöglicht. Für eine Vielzahl von derartigen Systemen (Coupled-Map-Lattices, Hartkugel-Systeme, Systeme mit ausgedehnten Potentialen ...) konnte durch die Untersuchung der Lyapunov-Vektoren die Existenz von hydrodynamischen Lyapunov-Moden nachgewiesen werden. Diese kollektiven Anregungen zeigen sich in Lyapunov-Vektoren, deren Lyapunov-Exponenten dem Betrage nach am kleinsten sind. Da Lyapunov-Exponenten charakteristische Zeitskalen innerhalb der Systeme repräsentieren, ist durch die Lyapunov-Moden eine Untersuchung des Langzeitverhaltens möglich. In dieser Arbeit werden die hydrodynamischen Lyapunov-Moden durch Molekulardynamiksimulationen von mehrkomponentigen Lennard-Jones-Flüssigkeiten untersucht. Die Charakterisierung der Lyapunov-Moden zeigt im weiteren eine Ähnlichkeit zu Dispersionsrelationen von Phononen

Clinical and ultrasonographic features of abdominal tuberculosis in HIV positive adults in Zambia

Background: The diagnosis of abdominal tuberculosis (TB) is difficult, especially so in health care facilities in developing countries where laparoscopy and colonoscopy are rarely available. There is little information on abdominal TB in HIV infection. We estimated the prevalence and clinical features of abdominal (excluding genitourinary) TB in HIV infected adults attending the University Teaching Hospital, Zambia. Methods: We screened 5,609 medical inpatients, and those with fever, weight loss, and clinical features suggestive of abdominal pathology were evaluated further. A clinical algorithm was used to specify definitive investigations including laparoscopy or colonoscopy, with culture of biopsies and other samples. Results: Of 140 HIV seropositive patients with these features, 31 patients underwent full evaluation and 22 (71%) had definite or probable abdominal TB. The commonest presenting abdominal features were ascites and persistent tenderness. The commonest ultrasound findings were ascites, para-aortic lymphadenopathy (over 1 cm in size), and hepatomegaly. Abdominal TB was associated with CD4 cell counts over a wide range though 76% had CD4 counts <100 cells/μL. Conclusion: The clinical manifestations of abdominal TB in our HIV-infected patients resembled the well-established pattern in HIV-uninfected adults. Patients with fever, weight loss, abdominal tenderness, abdominal lymphadenopathy, ascites and/or hepatomegaly in Zambia have a high probability of abdominal TB, irrespective of CD4 cell count. © 2009 Sinkala et al; licensee BioMed Central Ltd

The importance of recent infection with Mycobacterium tuberculosis in an area with high HIV prevalence: a long-term molecular epidemiological study in Northern Malawi.

BACKGROUND: The proportion of cases of tuberculosis due to recent infection can be estimated in long-term population-based studies using molecular techniques. Here, we present what is, to our knowledge, the first such study in an area with high human immunodeficiency virus (HIV) prevalence. METHODS: All patients with tuberculosis in Karonga District, Malawi, were interviewed. Isolates were genotyped using restriction-fragment-length polymorphism (RFLP) patterns. Strains were considered to be "clustered" if at least 1 other patient had an isolate with an identical pattern. RESULTS: RFLP results were available from 83% of culture-positive patients from late 1995 to early 2003. When strains with <5 bands were excluded, 72% (682/948) were clustered. Maximum clustering was reached using a 4-year window, with an estimated two-thirds of cases due to recent transmission. The proportion clustered decreased with age and varied by area of residence. In older adults, clustering was less common in men and more common in patients who were HIV positive (adjusted odds ratio, 5.1 [95% confidence interval, 2.1-12.6]). CONCLUSIONS: The proportion clustered found in the present study was among the highest in the world, suggesting high rates of recent transmission. The association with HIV infection in older adults may suggest that HIV has a greater impact on disease caused by recent transmission than on that caused by reactivation