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.

Rapid scale-up of a community-based HIV treatment service: programme performance over 3 consecutive years in Guguletu, South Africa.

BACKGROUND: Despite rapid expansion of antiretroviral therapy (ART) in sub-Saharan Africa there are few longitudinal data describing programme performance during rapid scale-up. METHODS: We compared mortality, viral suppression and programme retention in 3 consecutive years of a public sector community-based ART clinic in a South African township. Data were collected prospectively from establishment of services in October 2002 to the censoring date in September 2005. Viral load and CD4 counts were monitored at 4-monthly intervals. Community-based counsellors provided adherence and programme support. RESULTS: During the study period 1139 ART-naïve patients received ART (161, 280 and 698 in the 1st, 2nd and 3rd years respectively). The median CD4 cell counts were 84 cells/microl (interquartile range (IQR) 42-139), 89 cells/microl (IQR 490-149), and 110 cells/microl (IQR 55-172), and the proportions of patients with World Health Organization (WHO) clinical stages 3 and 4 were 90%, 79% and 76% in each sequential year respectively. The number of counsellors increased from 6 to 28 and the median number of clients allocated to each counsellor increased from 13 to 33. The overall loss to follow-up was .9%. At the date of censoring, the Kaplan-Meier estimates of the proportion of patients still on the programme were 82%, 86% and 91%, and the proportion who were virally suppressed (< 400 copies/ml) were 100%, 92% and 98% for the 2002, 2003 and 2004 cohorts respectively. CONCLUSIONS: While further operational research is required into optimal models of care in different populations across sub-Saharan Africa, these results demonstrate that a single community-based public sector ART clinic can extend care to over 1000 patients in an urban setting without compromising programme performance.