Potential Economic Viability of Two Proposed Rifapentine-Based Regimens for Treatment of Latent Tuberculosis Infection

Rationale: Rifapentine-based regimens for treating latent tuberculosis infection (LTBI) are being considered for future clinical trials, but even if they prove effective, high drug costs may limit their economic viability. Objectives: To inform clinical trial design by estimating the potential costs and effectiveness of rifapentine-based regimens for treatment of latent tuberculosis infection (LTBI). Methods: We used a Markov model to estimate cost and societal benefits for three regimens for treating LTBI: Isoniazid/ rifapentine daily for one month, isoniazid/rifapentine weekly for three months (self-administered and directly-observed), and isoniazid daily for nine months; a strategy of ‘‘no treatment’ ’ used for comparison. Costs, quality-adjusted life-years gained, and instances of active tuberculosis averted were calculated for all arms. Results: Both daily isoniazid/rifapentine for one month and weekly isoniazid/rifapentine for three months were less expensive and more effective than other strategies under a wide variety of clinically plausibly parameter estimates. Daily isoniazid/rifapentine for one month was the least expensive and most effective regimen. Conclusions: Daily isoniazid/rifapentine for one month and weekly isoniazid/rifapentine for three months should be studied in a large-scale clinical trial for efficacy. Because both regimens performed well even if their efficacy is somewhat reduced

Risk assessment of plant protection products

<p>EFSA’s Panel on Plant Protection Products and their Residues (PPR Panel) provides independent scientific advice in the field of risk assessment of plant protection products (PPPs, pesticides). Since its establishment in 2003 under Regulation (EC) No 178/2002, it has delivered a series of scientific outputs in support of evaluation of pesticide active substances, establishing scientific principles and guidance documents in the field of pesticide risk assessment and in support of decision making of European Union (EU) law makers. Next to a series of scientific opinions evaluating specific adverse effects of PPPs for human health (like for instance carcinogenicity) the Panel also delivered scientific opinions on general principles in the field of human health risk assessment (like reference value setting) and is, in particular over the last years, very much engaged in development of methodologies to meet new challenges in regulatory risk assessments such as assessment of toxicity of pesticide metabolites and potential cumulative effects of pesticides to human health. Fate, behaviour and transformation of pesticides after their application and consequent release to the environment are a major aspect of pesticide risk assessment. The PPR Panel has achieved major accomplishments by delivering guidance and scientific opinions on degradation in soil, exposure of soil organisms and assessment of environmental risks by use of pesticides in greenhouses or grown under cover. A series of scientific opinions have been delivered also in the field of environmental risk assessment of pesticides. Scientific output covered specific issues arising in the peer review of specific active substances, revision of data requirements, development of risk assessment methodologies and the development of guidance documents. A major milestone of the PPR Panel was the development of the methodological framework for deriving specific protection goals for environmental risk assessment of pesticides in view of the future dialogue between risk managers and risk assessors during the next steps of the revision of the ecotoxicology guidance documents.</p&gt

European scenarios for exposure of soil organisms to pesticides

Standardised exposure scenarios play an important role in European pesticide authorisation procedures (a scenario is a combination of climate, weather and crop data to be used in exposure models). The European Food Safety Authority developed such scenarios for the assessment of exposure of soil organisms to pesticides. Scenarios were needed for both the concentration in total soil and for the concentration in the liquid phase. The goal of the exposure assessment is the 90th percentile of the exposure concentration in the area of agricultural use of a pesticide in each of three regulatory European zones (North, Centre and South). A statistical approach was adopted to find scenarios that are consistent with this exposure goal. Scenario development began with the simulation of the concentration distribution in the entire area of use by means of a simple analytical model. In the subsequent two steps, procedures were applied to account for parameter uncertainty and scenario uncertainty (i.e. the likelihood that a scenario that is derived for one pesticide is not conservative enough for another pesticide). In the final step, the six scenarios were selected by defining their average air temperature, soil organic-matter content and their soil textural class. Organic matter of the selected scenarios decreased in the order North-Centre-South. Because organic matter has a different effect on the concentration in total soil than it has on the concentration in the liquid phase, the concentration in total soil decreased in the order North-Centre-South whereas the concentration in the liquid phase decreased in the opposite order. The concentration differences between the three regulatory zones appeared to be no more than a factor of two. These differences were comparatively small in view of the considerable differences in climate and soil properties between the three zones

Incidence of tuberculosis and the predictive value of ELISPOT and Mantoux tests in Gambian case contacts.

BACKGROUND: Studies of Tuberculosis (TB) case contacts are increasingly being utilised for understanding the relationship between M. tuberculosis and the human host and for assessing new interventions and diagnostic tests. We aimed to identify the incidence rate of new TB cases among TB contacts and to relate this to their initial Mantoux and ELISPOT test results. METHODS AND FINDINGS: After initial Mantoux and ELISPOT tests and exclusion of co-prevalent TB cases, we followed 2348 household contacts of sputum smear positive TB cases. We visited them at 3 months, 6 months, 12 months, 18 months and 24 months, and investigated those with symptoms consistent with TB. Those who were diagnosed separately at a government clinic had a chest x-ray. Twenty six contacts were diagnosed with definite TB over 4312 person years of follow-up (Incidence rate 603/100,000 person years; 95% Confidence Interval, 370-830). Nine index and secondary case pairs had cultured isolates available for genotyping. Of these, 6 pairs were concordant and 3 were discordant. 2.5% of non-progressors were HIV positive compared to 12% of progressors (HR 6.2; 95% CI 1.7-22.5; p = 0.010). 25 secondary cases had initial Mantoux results, 14 (56%) were positive ; 21 had initial ELISPOT results, 11 (52%) were positive; 15 (71%) of 21 tested were positive by one or the other test. Of the 6 contacts who had concordant isolates with their respective index case, 4 (67%) were Mantoux positive at recruitment, 3 (50%) were ELISPOT positive; 5 (83%) were positive by one or other of the two tests. ELISPOT positive contacts, and those with discordant results, had a similar rate of progression to those who were Mantoux positive. Those negative on either or both tests had the lowest rate of progression. CONCLUSIONS: The incidence rate of TB disease in Gambian TB case contacts, after screening for co-prevalent cases, was 603/100,000 person years. Since initial ELISPOT test and Mantoux tests were each positive in only just over half of cases, but 71% were positive by one or other test, positivity by either might be the best indication for preventive treatment. These data do not support the replacement of the Mantoux test by an ELISPOT test in The Gambia or similar settings