Characteristics and Early Outcomes of Patients With Xpert MTB/RIF-Negative Pulmonary Tuberculosis Diagnosed During Screening Before Antiretroviral Therapy

Comparison of the characteristics of HIV-infected patients with Xpert-positive and Xpert-negative tuberculosis and relationship of Xpert status with subsequent clinical and programmatic outcomes

Predicting the long-term impact of antiretroviral therapy scale-up on population incidence of tuberculosis.

OBJECTIVE: To investigate the impact of antiretroviral therapy (ART) on long-term population-level tuberculosis disease (TB) incidence in sub-Saharan Africa. METHODS: We used a mathematical model to consider the effect of different assumptions about life expectancy and TB risk during long-term ART under alternative scenarios for trends in population HIV incidence and ART coverage. RESULTS: All the scenarios we explored predicted that the widespread introduction of ART would initially reduce population-level TB incidence. However, many modelled scenarios projected a rebound in population-level TB incidence after around 20 years. This rebound was predicted to exceed the TB incidence present before ART scale-up if decreases in HIV incidence during the same period were not sufficiently rapid or if the protective effect of ART on TB was not sustained. Nevertheless, most scenarios predicted a reduction in the cumulative TB incidence when accompanied by a relative decline in HIV incidence of more than 10% each year. CONCLUSIONS: Despite short-term benefits of ART scale-up on population TB incidence in sub-Saharan Africa, longer-term projections raise the possibility of a rebound in TB incidence. This highlights the importance of sustaining good adherence and immunologic response to ART and, crucially, the need for effective HIV preventive interventions, including early widespread implementation of ART

Tuberculosis Incidence Rates during 8 Years of Follow-Up of an Antiretroviral Treatment Cohort in South Africa: Comparison with Rates in the Community

BACKGROUND: Although antiretroviral therapy (ART) is known to be associated with time-dependent reductions in tuberculosis (TB) incidence, the long-term impact of ART on incidence remains imprecisely defined due to limited duration of follow-up and incomplete CD4 cell count recovery in existing studies. We determined TB incidence in a South African ART cohort with up to 8 years of follow-up and stratified rates according to CD4 cell count recovery. We compared these rates with those of HIV-uninfected individuals living in the same community. METHODOLOGY/PRINCIPAL FINDINGS: Prospectively collected clinical data on patients receiving ART in a community-based cohort in Cape Town were analysed. 1544 patients with a median follow-up of 5.0 years (IQR 2.4-5.8) were included in the analysis. 484 episodes of incident TB (73.6% culture-confirmed) were diagnosed in 424 patients during 6506 person-years (PYs) of follow-up. The TB incidence rate during the first year of ART was 12.4 (95% CI 10.8-14.4) cases/100PYs and decreased to 4.92 (95% CI 3.64-8.62) cases/100PYs between 5 and 8 years of ART. During person-time accrued within CD4 cell strata 0-100, 101-200, 201-300, 301-400, 401-500, 501-700 and ≥700 cells/µL, TB incidence rates (95% CI) were 25.5 (21.6-30.3), 11.2 (9.4-13.5), 7.9 (6.4-9.7), 5.0 (3.9-6.6), 5.1 (3.8-6.8), 4.1 (3.1-5.4) and 2.7 (1.7-4.5) cases/100PYs, respectively. Overall, 75% (95% CI 70.9-78.8) of TB episodes were recurrent cases. Updated CD4 cell count and viral load measurements were independently associated with long-term TB risk. TB rates during person-time accrued in the highest CD4 cell count stratum (>700 cells/µL) were 4.4-fold higher that the rate in HIV uninfected individuals living in the same community (2.7 versus 0.62 cases/100PYs; 95%CI 0.58-0.65). CONCLUSIONS/SIGNIFICANCE: TB rates during long-term ART remained substantially greater than rates in the local HIV uninfected populations regardless of duration of ART or attainment of CD4 cell counts exceeding 700 cells/µL

Dynamic instabilities of fracture under biaxial strain using a phase field model

We present a phase field model of the propagation of fracture under plane strain. This model, based on simple physical considerations, is able to accurately reproduce the different behavior of cracks (the principle of local symmetry, the Griffith and Irwin criteria, and mode-I branching). In addition, we test our model against recent experimental findings showing the presence of oscillating cracks under bi-axial load. Our model again reproduces well observed supercritical Hopf bifurcation, and is therefore the first simulation which does so

Effect of antiretroviral therapy on the diagnostic accuracy of symptom screening for intensified tuberculosis case finding in a South African HIV clinic.

BACKGROUND: Current symptom screening algorithms for intensified tuberculosis case finding or prior to isoniazid preventive therapy (IPT) in patients infected with human immunodeficiency virus (HIV) were derived from antiretroviral-naive cohorts. There is a need to validate screening algorithms in patients on antiretroviral therapy (ART). METHODS: We performed cross-sectional evaluation of the diagnostic accuracy of symptom screening, including the World Health Organization (WHO) algorithm, to rule out tuberculosis in HIV-infected individuals pre-ART and on ART undergoing screening prior to IPT. RESULTS: A total of 1429 participants, 54% on ART, had symptom screening and a sputum culture result available. Culture-positive tuberculosis was diagnosed in 126 patients (8.8%, 95% confidence interval [CI], 7.4%-10.4%). The WHO symptom screen in the on-ART compared with the pre-ART group had a lower sensitivity (23.8% vs 47.6%), but higher specificity (94.4% vs 79.8%). The effect of ART was independent of CD4(+) count in multivariable analyses. The posttest probability of tuberculosis following a negative WHO screen was 8.9% (95% CI, 7.4%-10.8%) and 4.4% (95% CI, 3.7%-5.2%) for the pre-ART and on-ART groups, respectively. Addition of body mass index to the WHO screen significantly improved discriminatory ability in both ART groups, which was further improved by adding CD4 count and ART duration. CONCLUSIONS: The WHO symptom screen has poor sensitivity, especially among patients on ART, in a clinic where regular tuberculosis screening is practiced. Consequently, a significant proportion of individuals with tuberculosis would inadvertently be placed on isoniazid monotherapy despite high negative predictive values. Until more sensitive methods of ruling out tuberculosis are established, it would be prudent to do a sputum culture prior to IPT where this is feasible

Cleaved surface of i-AlPdMn quasicrystals: Influence of the local temperature elevation at the crack tip on the fracture surface roughness

Roughness of i-AlPdMn cleaved surfaces are presently analysed. From the atomic scale to 2-3 nm, they are shown to exhibit scaling properties hiding the cluster (0.45 nm) aperiodic structure. These properties are quantitatively similar to those observed on various disordered materials, albeit on other ranges of length scales. These properties are interpreted as the signature of damage mechanisms occurring within a 2-3 nm wide zone at the crack tip. The size of this process zone finds its origin in the local temperature elevation at the crack tip. For the very first time, this effect is reported to be responsible for a transition from a perfectly brittle behavior to a nanoductile one.Comment: 8 page

Screening for HIV-Associated Tuberculosis and Rifampicin Resistance before Antiretroviral Therapy Using the Xpert MTB/RIF Assay: A Prospective Study

In a prospective study, Stephen Lawn and colleagues find that pre-ART screening with Xpert MTB/RIF increased tuberculosis case detection by 45% compared to smear microscopy in HIV-positive patients at high risk of TB risk. AE competing interests must also pull through to the proof. “The Academic Editor, Madhukar Pai, declares that he consults for the Bill & Melinda Gates Foundation (BMGF). The BMGF supported FIND which was involved in the development of the Xpert MTB/RIF assay. He also co-chairs the Stop TB Partnership's New Diagnostics Working Group that was involved in the WHO endorsement of the Xpert assay.” Linked: Scott pmed.1001061; Evans pmed.1001064; Dowdy pmed.100106

Dynamical stability of the crack front line

Dynamical stability of the crack front line that propagates between two plates is studied numerically using the simple two-dimensional mass-spring model. It is demonstrated that the straight front line is unstable for low speed while it becomes stable for high speed. For the uniform model, the roughness exponent in the slower speed region is fairly constant around 0.4 and there seems to be a rough-smooth transition at a certain speed. For the inhomogeneous case with quenched randomness, the transition is gradual.Comment: 14 pages, 7 figure