Tuberculosis diagnostics and biomarkers: needs, challenges, recent advances, and opportunities

Tuberculosis is unique among the major infectious diseases in that it lacks accurate rapid point-of-care diagnostic tests. Failure to control the spread of tuberculosis is largely due to our inability to detect and treat all infectious cases of pulmonary tuberculosis in a timely fashion, allowing continued Mycobacterium tuberculosis transmission within communities. Currently recommended gold-standard diagnostic tests for tuberculosis are laboratory based, and multiple investigations may be necessary over a period of weeks or months before a diagnosis is made. Several new diagnostic tests have recently become available for detecting active tuberculosis disease, screening for latent M. tuberculosis infection, and identifying drug-resistant strains of M. tuberculosis. However, progress toward a robust point-of-care test has been limited, and novel biomarker discovery remains challenging. In the absence of effective prevention strategies, high rates of early case detection and subsequent cure are required for global tuberculosis control. Early case detection is dependent on test accuracy, accessibility, cost, and complexity, but also depends on the political will and funder investment to deliver optimal, sustainable care to those worst affected by the tuberculosis and human immunodeficiency virus epidemics. This review highlights unanswered questions, challenges, recent advances, unresolved operational and technical issues, needs, and opportunities related to tuberculosis diagnostics

Antihypertensive therapy, new-onset diabetes, and cardiovascular disease

Type 2 diabetes mellitus is a worldwide epidemic with considerable health and economic consequences. Diabetes is an important risk factor for cardiovascular disease, which is the leading cause of death in diabetic patients, and decreasing the incidence of diabetes may potentially reduce the burden of cardiovascular disease. This article discusses the clinical trial evidence for modalities associated with a reduction in the risk of new-onset diabetes, with a focus on the role of antihypertensive agents that block the renin–angiotensin system. Lifestyle interventions and the use of antidiabetic, anti-obesity, and lipid-lowering drugs are also reviewed. An unresolved question is whether decreasing the incidence of new-onset diabetes with non-pharmacologic or pharmacologic intervention will also lower the risk of cardiovascular disease. A large ongoing study is investigating whether the treatment with an oral antidiabetic drug or an angiotensin-receptor blocker will reduce the incidence of new-onset diabetes and cardiovascular disease in patients at high risk for developing diabetes

'Issues of equity are also issues of rights': Lessons from experiences in Southern Africa

BACKGROUND: Human rights approaches to health have been criticized as antithetical to equity, principally because they are seen to prioritise rights of individuals at the expense of the interests of groups, a core tenet of public health. The objective of this study was to identify how human rights approaches can promote health equity. METHODS: The Network on Equity in Health in Southern Africa undertook an exploration of three regional case studies – antiretroviral access, patient rights charters and civic organization for health. A combination of archival reviews and stakeholder interviews were complemented with a literature review to provide a theoretical framework for the empirical evidence. RESULTS: Critical success factors for equity are the importance of rights approaches addressing the full spectrum from civil and political, through to socio-economic rights, as well as the need to locate rights in a group context. Human rights approaches succeed in achieving health equity when coupled with community engagement in ways that reinforce community capacity, particularly when strengthening the collective agency of its most vulnerable groups. Additionally, human rights approaches provide opportunities for mobilising resources outside the health sector, and must aim to address the public-private divide at local, national and international levels. CONCLUSION: Where it is clear that rights approaches are predicated upon understanding the need to prioritize vulnerable groups and where the way rights are operationalised recognizes the role of agency on the part of those most affected in realising their socio-economic rights, human rights approaches appear to offer powerful tools to support social justice and health equity

Evaluation of tuberculosis diagnostics: establishing an evidence base around the public health impact.

The limitations of existing tuberculosis diagnostic tools are significantly hampering tuberculosis control efforts, most noticeably in areas with high prevalence of human immunodeficiency virus (HIV) infection and antituberculosis drug resistance. However, renewed global interest in tuberculosis research has begun to bear fruit, with several new diagnostic technologies progressing through the development pipeline. There are significant challenges in building a sound evidence base to inform public health policies because most diagnostic research focuses on the accuracy of individual tests, with often significant limitations in the design, conduct, and reporting of diagnostic accuracy studies. Diagnostic accuracy studies may not be appropriate to guide public health policies, and clinical trials may increasingly be required to determine the incremental value and cost-effectiveness of new tools. The urgent need for new diagnostics should not distract from pursuing rigorous scientific evaluation focused on public health impact

Long-term effects of the Diabetes Prevention Program interventions on cardiovascular risk factors: A report from the DPP Outcomes Study

AIMS: Whether long-term cardiovascular risk is reduced by the Diabetes Prevention Program interventions is unknown. The aim of this study was to determine the long-term differences in cardiovascular disease risk factors and the use of lipid and blood pressure medications by the original Diabetes Prevention Program intervention group. METHODS: This long-term follow-up (median 10 years, interquartile range 9.0–10.5) of the three-arm Diabetes Prevention Program randomized controlled clinical trial (metformin, intensive lifestyle and placebo), performed on 2766 (88%) of the Diabetes Prevention Program participants (who originally had impaired glucose tolerance), comprised a mean of 3.2 years of randomized treatment, approximately 1-year transition (during which all participants were offered intensive lifestyle intervention) and 5 years follow-up (Diabetes Prevention Program Outcomes Study). During the study, participants were followed in their original groups with their clinical care being provided by practitioners outside the research setting. The study determined lipoprotein profiles and blood pressure and medication use annually. RESULTS: After 10 years’ follow-up from Diabetes Prevention Program baseline, major reductions were seen for systolic (2–3 mmHg) and diastolic (5–6 mmHg) blood pressure, and for LDL cholesterol (0.47–0.54 mmol/l) and triglycerides (0.18–0.32 mmol/l) in all groups, with no between-group differences. HDL cholesterol also rose significantly (0.13–0.16 mmol/l) in all groups. Lipid (P < 0.012) and blood pressure (P < 0.09) medication use, however, were lower for the lifestyle group during the Diabetes Prevention Program Outcomes Study. CONCLUSION: Overall, intensive lifestyle intervention achieved, with less medication, a comparable long-term effect on cardiovascular disease risk factors, to that seen in the metformin and placebo groups. (Clinical Trials Registry No; NCT 00038727)

Reducing cardiovascular disease risk in type 2 diabetes: is the focus on glycaemia warranted?

Cardiovascular disease remains a major source of morbidity and mortality in type 2 diabetes mellitus. This article examines the recent evidence from trials and related meta-analyses on the effects of glycaemic control on cardiovascular disease (and, to a lesser extent, microvascular outcomes) in diabetes, and compares this with evidence accrued from blood pressure and statin trials. On the basis of such evidence, as well pragmatic considerations, it is clear that clinicians should place stronger emphasis on lipid, blood pressure management and lifestyle changes to lessen cardiovascular risks. At the same time, cardiovascular disease benefits of glycaemia reduction appear less pronounced, with patient characteristics critically influencing risk to benefit ratio. Recent guidelines now reflect recent observations on glycaemic control (with relaxed targets in specific patient groups), whereas future guidelines should encourage physicians to prioritise lipid-lowering and blood pressure management in patients with diabetes