Quantifying the Burden and Trends of Isoniazid Resistant Tuberculosis, 1994–2009

Quantifying isoniazid resistant (INH-R) tuberculosis (TB) is important because isoniazid resistance reduces the probability of treatment success, may facilitate the spread of multidrug resistance, and may reduce the effectiveness of isoniazid preventive therapy (IPT).We used data reported to the World Health Organization between 1994-2009 to estimate the INH-R burden among new and retreatment TB cases. We assessed geographical and temporal variation in INH-R and reported levels in high HIV prevalence countries (≥2%) to understand implications for IPT. 131 settings reported INH-R data since 1994. A single global estimate of the percentage of incident TB cases with INH-R was deemed inappropriate due to particularly high levels in the Eastern European region where 44.9% (95% CI: 34.0%, 55.8%) of incident TB cases had INH-R. In all other regions combined, 13.9% (95% CI: 12.6%, 15.2%) of incident cases had INH-R with the lowest regional levels seen in West/Central Europe and Africa. Where trend data existed, we found examples of rising and falling burdens of INH-R. 40% of high HIV prevalence countries reported national data on INH-R and 7.3% (95% CI: 5.5%, 9.1%) of cases in these settings had INH-R.Outside the Eastern European region, one in seven incident TB cases has INH-R, while this rises to nearly half within Eastern Europe. Many countries cannot assess trends in INH-R and the scarcity of data from high HIV prevalence areas limits insight into the implications for IPT. Further research is required to understand reasons for the observed time trends and to determine the effects of INH-R for control of TB

The Duration of the Effects of Repeated Widespread Badger Culling on Cattle Tuberculosis Following the Cessation of Culling

Background: In the British Isles, control of cattle tuberculosis (TB) is hindered by persistent infection of wild badger (Meles meles) populations. A large-scale field trial—the Randomised Badger Culling Trial (RBCT)—previously showed that widespread badger culling produced modest reductions in cattle TB incidence during culling, which were offset by elevated TB risks for cattle on adjoining lands. Once culling was halted, beneficial effects inside culling areas increased, while detrimental effects on adjoining lands disappeared. However, a full assessment of the utility of badger culling requires information on the duration of culling effects. Methodology/Principal Findings: We monitored cattle TB incidence in and around RBCT areas after culling ended. We found that benefits inside culled areas declined over time, and were no longer detectable by three years post-culling. On adjoining lands, a trend suggesting beneficial effects immediately after the end of culling was insignificant, and disappeared after 18 months post-culling. From completion of the first cull to the loss of detectable effects (an average five-year culling period plus 2.5 years post-culling), cattle TB incidence was 28.7% lower (95% confidence interval [CI] 20.7 to 35.8% lower) inside ten 100 km2 culled areas than inside ten matched no-culling areas, and comparable (11.7% higher, 95% CI: 13.0% lower to 43.4% higher, p = 0.39) on lands #2 km outside culled and no-culling areas. The financial costs of culling an idealized 150 km2 area would exceed the savings achieved through reduced cattle TB, by factors of 2 to 3.5. Conclusions/Significance: Our findings show that the reductions in cattle TB incidence achieved by repeated badger culling were not sustained in the long term after culling ended and did not offset the financial costs of culling. These results, combined with evaluation of alternative culling methods, suggest that badger culling is unlikely to contribute effectively to the control of cattle TB in Britain

The burden of latent multidrug-resistant tuberculosis

In the past 10 years, there has been renewed interest in the early phases of the natural history of tuberculosis.1 Estimates suggest that around 25% of the world's population could have latent tuberculosis infection,2 5–10% of whom will develop active disease during their lifetime3 (10% annually among people with HIV).4 Failure to implement effective tuberculosis control measures to manage latent infection threatens elimination goals

Effectiveness of a novel cellular therapy to treat multidrug-resistant tuberculosis

AbstractBackground/objectiveWe urgently need novel treatments for multidrug-resistant tuberculosis (MDR-TB). Autologous mesenchymal stromal cell (MSC) infusion is one such possibility due to its potential to repair damaged lung tissue and boost immune responses. We aimed to assess the safety and effectiveness of MSC to improve treatment outcomes among MDR-TB patients.MethodsWe analyzed treatment outcomes for 108 Belarusian MDR-TB patients receiving chemotherapy. Thirty-six patients (cases) also had MSCs collected, extracted, cultured, and reinfused (average time from chemotherapy start to infusion was 49days) in optimal dose; another 36 patients (without MSC treatment) were “study controls”. We identified another control group: 36 patients from the Belarusian national surveillance database (surveillance controls) 1:1 matched to cases.ResultsSuccessful outcomes were observed in 81% of cases, 42% of surveillance controls, and 39% of study controls. After adjusting for age, odds of a successful outcome were 6.5 (95% confidence interval, 1.2–36.2, p=0.032) times greater for cases than surveillance controls. Adjusting for other potential confounders increased the effect estimate while maintaining statistical significance. Cases were less likely (p=0.01) to be culture negative at 2months than surveillance controls, indicating a poorer initial prognosis in cases before (or shortly after) infusion. Radiological improvement was more likely in cases than in study controls.ConclusionMSC treatment could vastly improve treatment outcomes for MDR-TB patients. Our findings could revolutionize therapy options and have strong implications for future directions of MDR-TB therapy researc

Detection of a CMB decrement towards a cluster of mJy radiosources

We present the results of radio, optical and near-infrared observations of the field of TOC J0233.3+3021, a cluster of milliJansky radiosources from the TexOx Cluster survey. In an observation of this field with the Ryle Telescope (RT) at 15 GHz, we measure a decrement in the cosmic microwave background (CMB) of $-675 \pm 95 \mu$Jy on the RT's $\approx$ 0.65 k$\lambda$ baseline. Using optical and infrared imaging with the McDonald 2.7-m Smith Reflector, Calar Alto 3.5-m telescope and UKIRT, we identify the host galaxies of five of the radiosources and measure magnitudes of $R \approx 24$, $J \approx 20$, $K \approx 18$. The CMB decrement is consistent with the Sunyaev-Zel'dovich (SZ) effect of a massive cluster of galaxies, which if modelled as a spherical King profile of core radius $\theta_C = 20^{\prime\prime}$ has a central temperature decrement of $900 \mu$K. The magnitudes and colours of the galaxies are consistent with those of old ellipticals at $z \sim 1$. We therefore conclude that TOC J0233.3+3021 is a massive, high redshift cluster. These observations add to the growing evidence for a significant population of massive clusters at high redshift, and demonstrate the effectiveness of combining searches for AGN `signposts' to clusters with the redshift-independence of the SZ effect.Comment: Six pages; accepted for publication in MNRAS. Version with full-resolution UV plot available from http://www.mrao.cam.ac.uk/~garret/MB185.p

Clinical manifestations and epidemiology of adolescent tuberculosis in Ukraine

BACKGROUND: During adolescence, childhood and adult forms of tuberculosis (TB) overlap, resulting in diverse disease manifestations. Knowing which patient characteristics are associated with which manifestations may facilitate diagnosis and enhance understanding of TB pathophysiology. METHODS: In this cross-sectional study, we included 10-19-year-olds in Ukraine\u27s national TB registry who started TB treatment between 2015 and 2018. Using multivariable regression, we estimated associations between patient characteristics and four presentations of TB: pleural, extrathoracic, cavitary and rifampicin-resistant (RR). We also described the epidemiology of adolescent TB in Ukraine. RESULTS: Among 2491 adolescent TB cases, 88.4% were microbiologically confirmed. RR-TB was confirmed in 16.9% of new and 29.7% of recurrent cases. Of 88 HIV-infected adolescents, 59.1% were not on antiretroviral therapy at TB diagnosis. Among 10-14-year-olds, boys had more pleural disease (adjusted OR (aOR) 2.12, 95% CI: 1.08-4.37). Extrathoracic TB was associated with age 15-19 years (aOR 0.26, 95% CI: 0.18-0.37) and HIV (aOR 3.25, 95% CI: 1.55-6.61 in 10-14-year-olds; aOR 8.18, 95% CI: 3.58-17.31 in 15-19-year-olds). Cavitary TB was more common in migrants (aOR 3.53, 95% CI: 1.66-7.61) and 15-19-year-olds (aOR 4.10, 95% CI: 3.00-5.73); among 15-19-year-olds, it was inversely associated with HIV (aOR 0.32, 95% CI: 0.13-0.70). RR-TB was associated with recurrent disease (aOR 1.87, 95% CI: 1.08-3.13), urban residence (aOR 1.27, 95% CI: 1.01-1.62) and cavitation (aOR 2.98, 95% CI: 2.35-3.78). CONCLUSIONS: Age, sex, HIV and social factors impact the presentation of adolescent TB. Preventive, diagnostic and treatment activities should take these factors into consideration

A comparative analysis of high-throughput platforms for validation of a circulating microRNA signature in diabetic retinopathy

MicroRNAs are now increasingly recognized as biomarkers of disease progression. Several quantitative real-time PCR (qPCR) platforms have been developed to determine the relative levels of microRNAs in biological fluids. We systematically compared the detection of cellular and circulating microRNA using a standard 96-well platform, a high-content microfluidics platform and two ultrahigh content platforms. We used extensive analytical tools to compute inter- and intra-run variability and concordance measured using fidelity scoring, coefficient of variation and cluster analysis. We carried out unprejudiced next generation sequencing to identify a microRNA signature for Diabetic Retinopathy (DR) and systematically assessed the validation of this signature on clinical samples using each of the above four qPCR platforms. The results indicate that sensitivity to measure low copy number microRNAs is inversely related to qPCR reaction volume and that the choice of platform for microRNA biomarker validation should be made based on the abundance of miRNAs of interest

Bermuda’s tale of two time series : Hydrostation S and BATS

Author Posting. © American Meteorological Society, 2007. This article is posted here by permission of American Meteorological Society for personal use, not for redistribution. The definitive version was published in Journal of Physical Oceanography 37 (2007): 554–571, doi:10.1175/JPO2997.1.This paper describes the oceanic variability at Bermuda between 1989 and 1999, recorded in two overlapping hydrographic time series. Station S and Bermuda Atlantic Time Series Study (BATS), which are 60 km apart, both show that a multidecadal trend of deep warming has reversed, likely as a result of the increased production of Labrador Sea Water since the early 1980s. In addition to recording similar changes in watermass properties, the two time series show similar mean vertical structure and variance as a function of pressure for temperature, salinity, and density above 1500 dbar. The seasonal cycles of these water properties at the two sites are statistically indistinguishable. The time series differ in the individual eddy events they record and in their variability below 1500 dbar. The two time series are used to investigate the propagation of eddy features. Coherence and phase calculated from the low-mode variability of density show westward propagation at 3 cm s−1 of wavelengths around 300–500 km. Satellite altimeter data are used to provide a broader spatial view of the eddy (or wave) field near Bermuda.We acknowledge support from NSF Grant OCE-0219644, the Australian Greenhouse Office, and CSIRO

Early life social incongruities, health risk factors and chronic disease

This study tested specific hypotheses concerned with the relationships between three early life stress variables occurring between 0 and 16 yr of age and a variety of adult health status measures ascertained some 20-60 yr later in a 40% sample of the Tecumseh Community Health Study population 35-69 yr of age. The hypotheses stated that each of the following characteristics, relatively greater residential geographic mobility during childhood, being deprived of one or both natural parents for one or more years during this early formative period, and experiencing parental status incongruence, would be associated with higher levels of nine risk factors, greater prevalence of five chronic diseases, and a greater rate of mortality. The risk factors were systolic and diastolic blood pressure, blood glucose level, serum cholesterol, serum uric acid, the F.E.V.1.0 measure of lung function; adiposity, number of cigarettes smoked currently, and amount of alcohol consumed currently. The chronic conditions were CHD, hypertension, diabetes, chronic bronchitis and asthma. Also measured were the aggregation of these chronic conditions and whether or not the respondents ever smoked cigarettes or drank alcohol.Five mobility measures and an index were developed. As predicted, in general, significant relationships were found among women between the five separate mobility variables and the health measures. Specifically, all five separate measures of mobility were related to CHD among older women, and most were related to cigarette smoking and alcohol consumption among all women. Various of the five mobility measures were related to various other specific health measures. In general, mobility was not related to the health measures studied among men. The hypotheses concerning parental deprivation and parental status incongruency were not substantiated by the data.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/22946/1/0000513.pd