Burden of multidrug-resistant tuberculosis in England: a focus on prevalent cases.

The incidence of multidrug-resistant tuberculosis (MDR-TB) is routinely reported by the Public Health England, UK, but prevalence better represents burden. To estimate MDR-TB prevalence, and identify the factors associated with acquired resistance and unsuccessful outcomes in people managed by the health services. We included notified MDR-TB cases prevalent between 2010 and 2014. Multivariable logistic regression was used to identify the factors associated with acquisition of resistance and unsuccessful outcomes. The social risk factors (SRFs) recorded were alcohol, drug misuse, homelessness and incarceration. Between 2010 and 2014, there were 2.3-3.1 times more prevalent than incident cases each year, with an increasing prevalence-to-incidence ratio over time; 86% of prevalent cases were foreign-born, and 15% had an SRF. Overall, 11% of MDR-TB cases acquired resistance, including 18% of those with SRFs and 22% of UK-born MDR-TB cases acquired resistance. Half of the cases completed treatment by 24 months; those with SRFs, extensive drug resistance or acquired resistance were less likely to complete treatment. The number of prevalent cases is higher than incident cases, and increases over time, so a focus on prevalent cases enables better planning for services to support patients. We recommend that additional support be provided for those at risk of acquiring resistance, including those with SRFs. .

Public health outcome of Tuberculosis Cluster Investigations, England 2010-2013.

OBJECTIVES: Tuberculosis (TB) is a serious re-emergent public health problem in the UK. In response to rising case incidence a National TB Strain-Typing Service based on molecular strain-typing was established. This facilitates early detection and investigation of clusters, targeted public health action, and prevention of further transmission. We review the added public health value of investigating molecular TB strain-typed (ST) clusters. METHODS: A structured questionnaire for each ST cluster investigated in England between 1 January 2010 and 30 June 2013 was completed. Questions related to epidemiological links and public health action and the perceived benefits of ST cluster investigation. RESULTS: There were 278 ST cluster investigations (CIs) involving 1882 TB cases. Cluster size ranged from 2 to 92. CIs identified new epidemiological links in 36% of clusters; in 18% STs were discordant refuting transmission thought to have occurred. Additional public health action was taken following 23% of CI. CONCLUSIONS: We found positive benefits of TB molecular ST and CI, in identifying new epidemiological links between cases and taking public health action and in refuting transmission and saving resources. This needs to be translated to a decrease in transmission to provide evidence of public health value in this low prevalence high resource setting.

Delay from symptom onset to treatment start among tuberculosis patients in England, 2012-2015.

Improving access to tuberculosis (TB) care and ensuring early diagnosis are two major aims of the WHO End TB strategy and the Collaborative TB Strategy for England. This study describes risk factors associated with diagnostic delay among TB cases in England. We conducted a retrospective cohort study of TB cases notified to the Enhanced TB Surveillance System in England between 2012 and 2015. Diagnostic delay was defined as more than 4 months between symptom onset and treatment start date. Multivariable logistic regression was used to identify demographic and clinical factors associated with diagnostic delay. Between 2012 and 2015, 22 422 TB cases were notified in England and included in the study. A third (7612) of TB cases had a diagnostic delay of more than 4 months. Being female, aged 45 years and older, residing outside of London and having extra-pulmonary TB disease were significantly associated with a diagnostic delay in the multivariable model (aOR = 1.2, 1.2, 1.2, 1.3, 1.8, respectively). This study identifies demographic and clinical factors associated with diagnostic delay, which will inform targeted interventions to improve access to care and early diagnosis among these groups, with the ultimate aim of helping reduce transmission and improve treatment outcomes for TB cases in England.

The challenge of estimating tuberculosis mortality accurately in England and Wales.

BACKGROUND: Accurate estimates of tuberculosis (TB) mortality are required to monitor progress towards the World Health Organization End TB goal of reducing TB deaths by 95% by 2035. We compared TB death data for England and Wales from the national surveillance system (Enhanced Tuberculosis Surveillance System [ETS]) and the vital registration system from the Office for National Statistics (ONS). METHODS: TB cases notified in ETS were matched to deaths in ONS (dONS) with International Classification of Diseases, Tenth Revision (ICD-10) codes indicating that TB caused/contributed to the death (A15-A19). Deaths captured in one but not both systems were assessed to identify if ONS captured all TB deaths and if there was under-notification of TB in ETS. We stratified deaths into active TB, TB sequelae, incidental deaths and not TB. RESULTS: Between 2005 and 2015, there were fewer deaths in ETS (dETS) than dONS with ICD-10 codes A15-A19 (n = 4207 vs. n = 6560); 57% of dETS were recorded as dONS and 53% of dONS were notified to ETS. A total of 9289 deaths were identified from dETS and dONS: 64% were due to active TB, 23% were TB sequelae, 6% were incidental and 7% were not TB. CONCLUSIONS: TB deaths in ETS and ONS differ substantially. Almost one third of TB deaths recorded by ONS are not due to active TB; this can be amended through coding changes.

Investigating a tuberculosis cluster among Filipino health care workers in a low-incidence country.

SETTING: Nearly 8% of adult tuberculosis (TB) cases in England, Wales and Northern Ireland (EW&NI) occur among health care workers (HCWs), the majority of whom are from high TB incidence countries. OBJECTIVES: To determine if a TB cluster containing multiple HCWs was due to nosocomial transmission. METHODS: A cluster of TB cases notified in EW&NI from 2009 to 2014, with indistinguishable 24-locus mycobacterial interspersed repetitive unit-variable number of tandem repeats (MIRU-VNTR) profiles, was identified through routine national cluster review. Cases were investigated to identify epidemiological links, and occupational health (OH) information was collected for HCW cases. To further discriminate strains, typing of eight additional loci was conducted. RESULTS: Of the 53 cases identified, 22 were HCWs. The majority (n = 43), including 21 HCWs, were born in the Philippines. Additional typing split the cluster into three subclusters and seven unique strains. No epidemiological links were identified beyond one household and a common residential area. HCWs in this cluster received no or inadequate OH assessment. CONCLUSIONS: The MIRU-VNTR profile of this cluster probably reflects common endemic strains circulating in the Philippines, with reactivation occurring in the UK. Furthermore, 32-locus typing showed that 24-locus MIRU-VNTR failed to distinguish strain diversity. The lack of OH assessment indicates that latent tuberculous infection could have been identified and treated, thereby preventing active cases from occurring.

Sputum smear microscopy result: a predictor for drug-resistant tuberculosis?

Until countries establish capacity for continuous surveillance systems, representative surveys of tuberculosis (TB) patients continue to improve our understanding of the burden of drug-resistant TB and help ensure appropriate allocation of resources. Although the available data are limited, the current recommendation of restricting surveys to sputum smear-positive patients is justified, given the greatly simplified logistics and only limited evidence in specific settings of an association between drug resistance and sputum smear status. Nonetheless, the relationship between drug resistance and sputum smear microscopy results may vary according to the setting and population under study. With the increasing availability and use of molecular diagnostics and the drive for universal drug susceptibility testing under the World Health Organization's End TB Strategy, substantially more data on drug resistance in the whole TB patient population should become available in the near future.

Evaluation of a nonlinear Hertzian-based model reveals prostate cancer cells respond differently to force than normal prostate cells.

Understanding how the mechanical properties of cells alter with disease may help with the development of novel diagnostics and treatment regimes. The emergence of tools such as the atomic force microscope (AFM) has enabled us to physically measure the mechanical properties of cells. However, suitable models for the analysis of real experimental data are either absent, or fail to provide a simple analysis tool in which experimental data can be analyzed quickly and reliably. The Hertz model has been widely used to study AFM data on living cells, however it makes assumptions that are untrue for cells, namely that cells behave as linear elastic bodies. This article presents and evaluates an alternative nonlinear Hertz model, which allows the Young's modulus to vary according to a second order polynomial function of indentation depth. Evaluation of the model revealed that prostate cancer cells (PC3) responded more uniformly to force compared to the normal PNT2 cells. Also, more energy (J) was needed to deform the normal prostate cells compared to the prostate cancer cells. Finally, the model described here suggests that overall the normal prostate cells behave in a more linear fashion to applied force compared to the prostate cancer cells.

Real-time fringe pattern demodulation with a second-order digital phase-locked loop.

The use of a second-order digital phase-locked loop (DPLL) to demodulate fringe patterns is presented. The second-order DPLL has better tracking ability and more noise immunity than the first-order loop. Consequently, the second-order DPLL is capable of demodulating a wider range of fringe patterns than the first-order DPLL. A basic analysis of the first- and the second-order loops is given, and a performance comparison between the first- and the second-order DPLL's in analyzing fringe patterns is presented. The implementation of the second-order loop in real time on a commercial parallel image processing system is described. Fringe patterns are grabbed and processed, and the resultant phase maps are displayed concurrently.

Spatiotemporal phase unwrapping for the measurement of discontinuous objects in dynamic fringe-projection phase-shifting profilometry.

A spatiotemporal phase-unwrapping method is presented that combines the dynamic fringe-projection method and the phase-shifting technique and extends the phase-unwrapping method, which measures two phase maps at different sensitivities. The most important feature of the method is that it makes possible the automatic three-dimensional shape measurement of discontinuous objects with large dynamic range limits and high precision because the effective wavelength of the fringe-projection profilometry can be continuously varied over several orders of magnitude by rotation of the projection grating in its own plane. Only one grating and several steps of rotating the grating are required; therefore the method is inherently simple, fast, and robust. In the experiment, choosing the rotation angle was crucial for optimizing the measurement speed and the measurement accuracy. A criterion is presented for the choice of the minimum number of rotational steps for a given accuracy. The experimental results demonstrate the validity of the proposed method.

Robust, simple, and fast algorithm for phase unwrapping.

Phase unwrapping has been and still is a cumbersome concern that involves the resolution of several different problems. When dealing with two-dimensional phase unwrapping in fringe analysis, the final objective is, in many cases, the realization of that analysis in real time. Many algorithms have been developed to carry out the unwrapping process, with some giving satisfactory results even when high levels of noise are present in the image. However, these algorithms are often time consuming and far removed from the goal of real-time fringe analysis. A new approach to the construction of a simple and fast algorithm for two-dimensional unwrapping that has considerable potential for parallel implementation is presented.

Three-map absolute moiré contouring.

In the shadow-moiré system, the period of the grating is varied by rotation of the grating, so the phase of the moiré pattern is changed as well. By the selection of suitable rotation angles, three images at different positions of the grating are acquired to obtain the absolute distance from the object to the grating. A theoretical analysis is presented for the method, and some experiments have been done to verify the theoretical analysis. The results show that the method is fast and the accuracy is better than 10 µm. The measurable range is directly proportional to the period of the grating and inversely proportional to the angles at which the grating is rotated.

Multichannel Fourier fringe analysis as an aid to automatic phase unwrapping.

We describe a technique termed multichannel Fourier fringe analysis and its application to the problem of automatic phase unwrapping in the presence of surface discontinuities. The technique is especially useful for the analysis of fringe projection contour maps in order to measure surface height distributions. Use is made of multiple fringe patterns that are separated in the frequency space of the Fourier transform by means of a set of bandpass filters. We also describe the design of a special fiber-optic interferometer with features particularly important in the case of this technique: easily adjustable fringe spacing and rotation. Fringe production by the interferometer is analyzed, and the relationship between the fringe phase and the height distribution of an illuminated surface is derived. A method for measuring phase in the case of multichannel Fourier fringe analysis is presented. The application of the technique to automatic phase unwrapping is shown. An example of the technique in operation is given, and a discussion of implementation of the technique is included.

Laser techniques for the evaluation of wear in Class II restorations.

A technique for the quantitative determination of the changes in surface topography of restorations during wear has been developed. This involves the optical contouring of the surface using a laser, and the generation of contour maps. Several different methods for interpreting these maps are discussed. A computer-aided method is the most consistently accurate and measures wear volume to an accuracy of 2--5%.