What Is the Cost of Diagnosis and Management of Drug Resistant Tuberculosis in South Africa?

What is the Cost of Diagnosis and Management of Drug Resistant Tuberculosis in South Africa?

Filed under: Drug and Alcohol Rehabilitation

PLoS One. 2013; 8(1): e54587
Pooran A, Pieterson E, Davids M, Theron G, Dheda K

Drug-resistant tuberculosis (DR-TB) is undermining TB control in South Africa. However, there are hardly any data about the cost of treating DR-TB in high burden settings despite such information being quintessential for the rational planning and allocation of resources by policy-makers, and to inform future cost-effectiveness analyses.We analysed the comparative 2011 United States dollar ($ ) cost of diagnosis and treatment of drug sensitive TB (DS-TB), MDR-TB and XDR-TB, based on National South African TB guidelines, from the perspective of the National TB Program using published clinical outcome data.Assuming adherence to national DR-TB management guidelines, the per patient cost of XDR-TB was $ 26,392, four times greater than MDR-TB ($ 6772), and 103 times greater than drug-sensitive TB ($ 257). Despite DR-TB comprising only 2.2% of the case burden, it consumed ?32% of the total estimated 2011 national TB budget of US $ 218 million. 45% and 25% of the DR-TB costs were attributed to anti-TB drugs and hospitalization, respectively. XDR-TB consumed 28% of the total DR-TB diagnosis and treatment costs. Laboratory testing and anti-TB drugs comprised the majority (71%) of MDR-TB costs while hospitalization and anti-TB drug costs comprised the majority (92%) of XDR-TB costs. A decentralized XDR-TB treatment programme could potentially reduce costs by $ 6930 (26%) per case and reduce the total amount spent on DR-TB by ?7%.Although DR-TB forms a very small proportion of the total case burden it consumes a disproportionate and substantial amount of South Africa’s total annual TB budget. These data inform rational resource allocation and selection of management strategies for DR-TB in high burden settings.
HubMed – drug


Altered network communication following a neuroprotective drug treatment.

Filed under: Drug and Alcohol Rehabilitation

PLoS One. 2013; 8(1): e54478
Vincent K, Tauskela JS, Mealing GA, Thivierge JP

Preconditioning is defined as a range of stimuli that allow cells to withstand subsequent anaerobic and other deleterious conditions. While cell protection under preconditioning is well established, this paper investigates the influence of neuroprotective preconditioning drugs, 4-aminopyridine and bicuculline (4-AP/bic), on synaptic communication across a broad network of in vitro rat cortical neurons. Using a permutation test, we evaluated cross-correlations of extracellular spiking activity across all pairs of recording electrodes on a 64-channel multielectrode array. The resulting functional connectivity maps were analyzed in terms of their graph-theoretic properties. A small-world effect was found, characterized by a functional network with high clustering coefficient and short average path length. Twenty-four hours after exposure to 4-AP/bic, small-world properties were comparable to control cultures that were not treated with the drug. Four hours following drug washout, however, the density of functional connections increased, while path length decreased and clustering coefficient increased. These alterations in functional connectivity were maintained at four days post-washout, suggesting that 4-AP/bic preconditioning leads to long-term effects on functional networks of cortical neurons. Because of their influence on communication efficiency in neuronal networks, alterations in small-world properties hold implications for information processing in brain systems. The observed relationship between density, path length, and clustering coefficient is captured by a phenomenological model where connections are added randomly within a spatially-embedded network. Taken together, results provide information regarding functional consequences of drug therapies that are overlooked in traditional viability studies and present the first investigation of functional networks under neuroprotective preconditioning.
HubMed – drug


HIV-1 Fusion Is Blocked through Binding of GB Virus C E2D Peptides to the HIV-1 gp41 Disulfide Loop.

Filed under: Drug and Alcohol Rehabilitation

PLoS One. 2013; 8(1): e54452
Eissmann K, Mueller S, Sticht H, Jung S, Zou P, Jiang S, Gross A, Eichler J, Fleckenstein B, Reil H

A strategy for antiviral drug discovery is the elucidation and imitation of viral interference mechanisms. HIV-1 patients benefit from a coinfection with GB Virus C (GBV-C), since HIV-positive individuals with long-term GBV-C viraemia show better survival rates than HIV-1 patients without persisting GBV-C. A direct influence of GBV-C on HIV-1 replication has been shown in coinfection experiments. GBV-C is a human non-pathogenic member of the flaviviridae family that can replicate in T and B cells. Therefore, GBV-C shares partly the same ecological niche with HIV-1. In earlier work we have demonstrated that recombinant glycoprotein E2 of GBV-C and peptides derived from the E2 N-terminus interfere with HIV entry. In this study we investigated the underlying mechanism. Performing a virus-cell fusion assay and temperature-arrested HIV-infection kinetics, we provide evidence that the HIV-inhibitory E2 peptides interfere with late HIV-1 entry steps after the engagement of gp120 with CD4 receptor and coreceptor. Binding and competition experiments revealed that the N-terminal E2 peptides bind to the disulfide loop region of HIV-1 transmembrane protein gp41. In conjunction with computational analyses, we identified sequence similarities between the N-termini of GBV-C E2 and the HIV-1 glycoprotein gp120. This similarity appears to enable the GBV-C E2 N-terminus to interact with the HIV-1 gp41 disulfide loop, a crucial domain involved in the gp120-gp41 interface. Furthermore, the results of the present study provide initial proof of concept that peptides targeted to the gp41 disulfide loop are able to inhibit HIV fusion and should inspire the development of this new class of HIV-1 entry inhibitors.
HubMed – drug


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