Dye, C.

Clinical prognostic value of RNA viral load and CD4 cell counts during untreated HIV-1 infection - A quantitative review (Article)

2009-06-17T00:00:00Z

Background: The prognostic value of CD4 counts and RNA viral load for identifying treatment need in HIV-infected individuals depends on (a) variation within and among individuals, and (b) relative risks of clinical progression per unit CD4 or RNA difference. Methodology/Principal Findings: We reviewed these measurements across (a) 30 studies, and (b) 16 cohorts of untreated seropositive adults. Median within-population interquartile ranges were 74,000 copies/mL for RNA with no significant change during the course of infection; and 330 cells/μL for CD4, with a slight proportional increase over infection. Applying measurement and physiological fluctuations observed on chronically infected patients, we estimate that 45% of population-level variation in RNA, and 25% of variation in CD4, were due to within-patient fluctuations. Comparing a patient with RNA at upper 75th centile with a patient at median RNA, 5-year relative risks were 1.4 (95% CI 1.2-1.7) for AIDS and 1.5 (1.3-1.9) for death, without change over the course of infection. In contrast, for a patient with CD4 count at the lower 75th centile, relative risks increased from 1.0 at seroconversion to maxima of 6.3 (4.4-8.9) for AIDS and 5.5 (2.7-10.1) for death by year 6, when the population median had fallen to 300 cells/ μL. Below 300 cells/μL, prognostic power did not increase, due to a narrower CD4 range. Conclusions: Findings support the current WHO recommendation (used with clinical criteria) to start antiretroviral treatment in low-income settings at CD4 thresholds of 200-350 cells/μL, without pre-treatment RNA monitoring - while not precluding earlier treatment based on clinical, socio-demographic or public health criteria.

The measurement and estimation of tuberculosis mortality (Article)

2009-01-01T00:00:00Z

Tuberculosis (TB) ranks among the 10 principal causes of death and disability worldwide, largely on the basis of mortality estimates. These estimates have been derived by a variety of methods, from a limited database. Here we review the data and methods used to measure and estimate TB mortality in adults, assess the strengths and weaknesses of each and suggest ways to improve current mortality statistics. In principle, deaths attributable to TB can be obtained directly from national vital registration (VR) systems. However, only 59 of 213 countries in 2005 (including three in the World Health Organization Africa Region and one in the South-East Asia Region) had VR systems that reported TB deaths, corresponding to just 10% of all estimated deaths attributable to TB. Until comprehensive, national VR systems are established, an interim solution is to carry out verbal autopsies within sample VR schemes. The number of TB deaths from VR should ultimately converge with deaths recorded in national TB control programmes. At present, deaths in treatment cohorts cover a small subset of all estimated TB deaths (<13% in 2006), as deaths are missed among patients who are never diagnosed, who default or fail treatment, and among patients with untreated recurrent TB or TB sequelae. In contrast, some deaths recorded during treatment are not due to TB. To ensure convergence between cohort monitoring and VR, definitions of causes of death - including TB as an associate cause in deaths from human immunodeficiency virus/acquired immune-deficiency syndrome - should be standardised, so that both systems adhere to the International Classification of Diseases.

Modeling the impact of immigration on the epidemiology of tuberculosis (Article)

2008-05-01T00:00:00Z

This paper presents two new theoretical frameworks to investigate the impact of immigration on the transmission dynamics of tuberculosis. For the basic model, we present new analysis on the existence and stability of equilibria. Then, we use numerical simulations of the model to illustrate the behavior of the system. We apply the model to Canadian reported data on tuberculosis and observe a good agreement between the model prediction and the data. For the extended model, which incorporated the recruitment of the latent and infectious in immigrants to the basic model, we find that the usual threshold condition does not apply and a unique equilibrium exists for all parameter values. This indicates that the disease does not disappear and becomes endemic in host areas. This finding is also supported by numerical simulations with the extended model. Our study suggests that immigrants have a considerable influence on the overall transmission dynamics behavior of tuberculosis.

Reply to Eisenhut [2] (Article)

2007-05-15T00:00:00Z

Reply to Lawn and Wood [2] (Article)

2007-04-01T00:00:00Z

Cost effectiveness analysis of strategies for tuberculosis control in developing countries (Article)

2005-01-01T00:00:00Z

OBJECTIVE: To assess the costs and health effects of tuberculosis control interventions in Africa and South East Asia in the context of the millennium development goals. DESIGN: Cost effectiveness analysis based on an epidemiological model. SETTING: Analyses undertaken for two regions classified by WHO according to their epidemiological grouping-Afr-E, countries in sub-Saharan Africa with very high adult and high child mortality, and Sear-D, countries in South East Asia with high adult and high child mortality. DATA SOURCES: Published studies, costing databases, expert opinion. MAIN OUTCOME MEASURES: Costs per disability adjusted life year (DALY) averted in 2000 international dollars (dollarsInt). RESULTS: Treatment of new cases of smear-positive tuberculosis in DOTS programmes cost dollarsInt6-8 per DALY averted in Afr-E and dollarsInt7 per DALY averted in Sear-D at coverage levels of 50-95%. In Afr-E, adding treatment of smear-negative and extra-pulmonary cases at a coverage level of 95% cost dollarsInt95 per DALY averted; the addition of DOTS-Plus treatment for multidrug resistant cases cost dollarsInt123. In Sear-D, these costs were dollarsInt52 and dollarsInt226, respectively. The full combination of interventions could reduce prevalence and mortality by over 50% in Sear-D between 1990 and 2010, and by almost 50% between 2000 and 2010 in Afr-E. CONCLUSIONS: DOTS treatment of new smear-positive cases is the first priority in tuberculosis control, including in countries with high HIV prevalence. DOTS treatment of smear-negative and extra-pulmonary cases and DOTS-Plus treatment of multidrug resistant cases are also highly cost effective. To achieve the millennium development goal for tuberculosis control, substantial extra investment is needed to increase case finding and implement interventions on a wider scale.