Improving Drug Uptake and Penetration Into Tumors: Current and Forthcoming Opportunities.

Improving drug uptake and penetration into tumors: current and forthcoming opportunities.

Front Oncol. 2013; 3: 161
Marcucci F, Berenson R, Corti A

HubMed – drug


Allergen specific immunotherapy induced multi-organ failure.

Pan Afr Med J. 2013; 14: 155
Sana A, Ben Salem C, Ahmed K, Abdelbeki A, Jihed S, Imene BS, Mohamed B

Allergen specific immunotherapy (ASI) is a well-documented treatment for allergic asthma, rhinitis and allergy to bee venoms. Immunotherapy with subcutaneous injections of allergens extracts has proved beneficial in reducing symptoms of allergic rhinitis and asthma. Side effects due to specific immunotherapy in short term have been largely documented. These effects were various but were usually mild. Fatal reactions are less frequent. We reported a case of a woman, with a history of allergic asthma under specific desensitization protocol who developed an acute multi-organ failure (MOF) consecutive to administration of ASI (Alustal(®) Stallergenes SA, France). This fatal reaction has never been described as adverse event of specific immunotherapy. We aimed to describe this dramatic reaction, expose the arguments to define the relationship between the administration of allergen extract and the occurrence of this fatal reaction. HubMed – drug


Impact of three rounds of mass drug administration on lymphatic filariasis in areas previously treated for onchocerciasis in sierra leone.

PLoS Negl Trop Dis. 2013 Jun; 7(6): e2273
Koroma JB, Sesay S, Sonnie M, Hodges MH, Sahr F, Zhang Y, Bockarie MJ

1974-2005 studies across Sierra Leone showed onchocerciasis endemicity in 12 of 14 health districts (HDs) and baseline studies 2005-2008 showed lymphatic filariasis (LF) endemicity in all 14 HDs. Three integrated annual mass drug administration (MDA) were conducted in the 12 co-endemic districts 2008-2010 with good geographic, programme and drug coverage. Midterm assessment was conducted 2011 to determine impact of these MDAs on LF in these districts.The mf prevalence and intensity in the 12 districts were determined using the thick blood film method and results compared with baseline data from 2007-2008. Overall mf prevalence fell from 2.6% (95% CI: 2.3%-3.0%) to 0.3% (95% CI: 0.19%-0.47%), a decrease of 88.5% (p?=?0.000); prevalence was 0.0% (100.0% decrease) in four districts: Bo, Moyamba, Kenema and Kono (p?=?0.001, 0.025, 0.085 and 0.000 respectively); and seven districts had reductions in mf prevalence of between 70.0% and 95.0% (p?=?0.000, 0.060, 0.001, 0.014, 0.000, 0.000 and 0.002 for Bombali, Bonthe, Kailahun, Kambia, Koinadugu, Port Loko and Tonkolili districts respectively). Pujehun had baseline mf prevalence of 0.0%, which was maintained. Only Bombali still had an mf prevalence ?1.0% (1.58%, 95% CI: 0.80%-3.09%)), and this is the district that had the highest baseline mf prevalence: 6.9% (95% CI: 5.3%-8.8%). Overall arithmetic mean mf density after three MDAs was 17.59 mf/ml (95% CI: 15.64 mf/ml-19.55 mf/ml) among mf positive individuals (65.4% decrease from baseline of 50.9 mf/ml (95% CI: 40.25 mf/ml-61.62 mf/ml; p?=?0.001) and 0.05 mf/ml (95% CI: 0.03 mf/ml-0.08 mf/ml) for the entire population examined (96.2% decrease from baseline of 1.32 mf/ml (95% CI: 1.00 mf/ml-1.65 mf/ml; p?=?0.000)).The results show that mf prevalence decreased to <1.0% in all but one of the 12 districts after three MDAs. Overall mf density reduced by 65.0% among mf-positive individuals, and 95.8% for the entire population. HubMed – drug


Mass Treatment with Azithromycin for Trachoma: When Is One Round Enough? Results from the PRET Trial in The Gambia.

PLoS Negl Trop Dis. 2013 Jun; 7(6): e2115
Harding-Esch EM, Sillah A, Edwards T, Burr SE, Hart JD, Joof H, Laye M, Makalo P, Manjang A, Molina S, Sarr-Sissoho I, Quinn TC, Lietman T, Holland MJ, Mabey D, West SK, Bailey R,

The World Health Organization has recommended three rounds of mass drug administration (MDA) with antibiotics in districts where the prevalence of follicular trachoma (TF) is ?10% in children aged 1-9 years, with treatment coverage of at least 80%. For districts at 5-10% TF prevalence it was recommended that TF be assessed in 1-9 year olds in each community within the district, with three rounds of MDA provided to any community where TF?10%. Worldwide, over 40 million people live in districts whose TF prevalence is estimated to be between 5 and 10%. The best way to treat these districts, and the optimum role of testing for infection in deciding whether to initiate or discontinue MDA, are unknown.In a community randomized trial with a factorial design, we randomly assigned 48 communities in four Gambian districts, in which the prevalence of trachoma was known or suspected to be above 10%, to receive annual mass treatment with expected coverage of 80-89% (“Standard”), or to receive an additional visit in an attempt to achieve coverage of 90% or more (“Enhanced”). The same 48 communities were randomised to receive mass treatment annually for three years (“3×”), or to have treatment discontinued if Chlamydia trachomatis (Ct) infection was not detected in a sample of children in the community after mass treatment (stopping rule(“SR”)). Primary outcomes were the prevalence of TF and of Ct infection in 0-5 year olds at 36 months.The baseline prevalence of TF and of Ct infection in the target communities was 6.5% and 0.8% respectively. At 36 months the prevalence of TF was 2.8%, and that of Ct infection was 0.5%. No differences were found between the arms in TF or Ct infection prevalence either at baseline (Standard-3×: TF 5.6%, Ct 0.7%; Standard-SR: TF 6.1%, Ct 0.2%; Enhanced-3×: TF 7.4%, Ct 0.9%; and Enhanced-SR: TF 6.2%, Ct 1.2%); or at 36 months (Standard-3×: TF 2.3%, Ct 1.0%; Standard-SR TF 2.5%, Ct 0.2%; Enhanced-3× TF 3.0%, Ct 0.2%; and Enhanced-SR TF 3.2%, Ct 0.7% ). The implementation of the stopping rule led to treatment stopping after one round of MDA in all communities in both SR arms. Mean treatment coverage of children aged 0-9 in communities randomised to standard treatment was 87.7% at baseline and 84.8% and 88.8% at one and two years, respectively. Mean coverage of children in communities randomized to enhanced treatment was 90.0% at baseline and 94.2% and 93.8% at one and two years, respectively. There was no evidence of any difference in TF or Ct prevalence at 36 months resulting from enhanced coverage or from one round of MDA compared to three.The Gambia is close to the elimination target for active trachoma. In districts prioritised for three MDA rounds, one round of MDA reduced active trachoma to low levels and Ct infection was not detectable in any community. There was no additional benefit to giving two further rounds of MDA. Programmes could save scarce resources by determining when to initiate or to discontinue MDA based on testing for Ct infection, and one round of MDA may be all that is necessary in some settings to reduce TF below the elimination threshold. HubMed – drug


Effect of the deletion of genes encoding proteins of the extracellular virion form of vaccinia virus on vaccine immunogenicity and protective effectiveness in the mouse model.

PLoS One. 2013; 8(6): e67984
Meseda CA, Campbell J, Kumar A, Garcia AD, Merchlinsky M, Weir JP

Antibodies to both infectious forms of vaccinia virus, the mature virion (MV) and the enveloped virion (EV), as well as cell-mediated immune response appear to be important for protection against smallpox. EV virus particles, although more labile and less numerous than MV, are important for dissemination and spread of virus in infected hosts and thus important in virus pathogenesis. The importance of the EV A33 and B5 proteins for vaccine induced immunity and protection in a murine intranasal challenge model was evaluated by deletion of both the A33R and B5R genes in a vaccine-derived strain of vaccinia virus. Deletion of either A33R or B5R resulted in viruses with a small plaque phenotype and reduced virus yields, as reported previously, whereas deletion of both EV protein-encoding genes resulted in a virus that formed small infection foci that were detectable and quantifiable only by immunostaining and an even more dramatic decrease in total virus yield in cell culture. Deletion of B5R, either as a single gene knockout or in the double EV gene knockout virus, resulted in a loss of EV neutralizing activity, but all EV gene knockout viruses still induced a robust neutralizing activity against the vaccinia MV form of the virus. The effect of elimination of A33 and/or B5 on the protection afforded by vaccination was evaluated by intranasal challenge with a lethal dose of either vaccinia virus WR or IHD-J, a strain of vaccinia virus that produces relatively higher amounts of EV virus. The results from multiple experiments, using a range of vaccination doses and virus challenge doses, and using mortality, morbidity, and virus dissemination as endpoints, indicate that the absence of A33 and B5 have little effect on the ability of a vaccinia vaccine virus to provide protection against a lethal intranasal challenge in a mouse model. HubMed – drug