Availability and affordability of treatment for Human African Trypanosomiasis.

Human African Trypanosomiasis (HAT) is a re-emerging disease whose usual treatments are becoming less efficient because of the increasing parasite resistance. Availability of HAT drugs is poor and their production in danger because of technical, ecological and economic constraints. In view of this dramatic situation, a network involving experts from NGOs, WHO and pharmaceutical producers was commissioned with updating estimates of need for each HAT drug for the coming years; negotiations with potential producers of new drugs such as eflornithine; securing sustainable manufacturing of existing drugs; clinical research into new combinations of these drugs for first and second-line treatments; centralizing drug purchases and their distribution through a unique non-profit entity; and addressing regulatory and legal issues concerning new drugs

Où en est le foyer de trypanosomiase humaine de Mossaka (Congo) ?

Le foyer de Mossaka (sur la basse Sangha, région de la Cuvette au Congo) évolue depuis quelques années de façon inquiétante. En 1989, à la suite d'une prospection que nous avions réalisée dans le foyer, nous avions insisté sur l'urgence des mesures à prendre. Depuis, la situation s'est aggravée tant en ce qui concerne le nombre des malades dépistés (74 en 1987, 171 en 1989, 200 en 1991) qu'en ce qui concerne la population concernée (le foyer s'est étendu ; le nombre des villages ou l'on dépistait des malades est passé de 3 en 1987, à 12 en 1989 et 17 en 1991). Si des mesures ne sont pas prises rapidement, on ne peut que craindre une dramatique extension du foyer de la basse Sangha. (Résumé d'auteur

Dynamic Nuclear Polarization by Thermal Mixing Under Partial Saturation

We describe a low-temperature thermodynamic model for dynamic nuclear polarization (DNP) via continuous-wave partial saturation of electron spin resonance (ESR) lines that are both homogeneously and inhomogeneously broadened. It is a variant of a reasoning proposed by Borghini, which in turn used Redfield's thermodynamic treatment of saturation. Our variant is furthermore based on Provotorov's insight that under partial saturation of a coupled-spin system two distinct spin temperatures should appear in a thermodynamical theory. We apply our model to DNP results obtained at a temperature of 1.2K and in magnetic fields of 3.35 and 5T on 1-13C labeled sodium acetate dissolved in a frozen D2O/ethanol-d6 solution doped with the free radical TEMP

Update on field use of the available drugs for the chemotherapy of human African trypanosomiasis

Despite the fact that eflornithine was considered as the safer drug to treat human African trypanosomiasis (HAT) and has been freely available since 2001, the difficulties in logistics and cost burden associated with this drug meant that the toxic melarsoprol remained the drug of choice. The World Health Organization responded to the situation by designing a medical kit containing all the materials needed to use eflornithine, and by implementing a training and drugs distribution programme which has allowed a transition to this much safer treatment. The introduction of the combination of nifurtimox and eflornithine (NECT) has accelerated the shift from melarsoprol to the best treatment available, due to reduced dosage and treatment time for eflornithine that has significantly lessened the cost and improved the burden of logistics encountered during treatment and distribution. The decrease in the use of more dangerous but cheaper melarsoprol has meant a rise in the per patient cost of treating HAT. Although NECT is cheaper than eflornithine monotherapy, an unexpected consequence has been a continuing rise in the per patient cost of treating HAT. The ethical decision of shifting to the best available treatment imposes a financial burden on HAT control programmes that might render long-term application unsustainable. These factors call for continuing research to provide new safer and more effective drugs that are simple to administer and cheaper when compared to current drug

Dynamic Nuclear Polarization by Thermal Mixing Under Partial Saturation

We describe a low-temperature thermodynamic model for dynamic nuclear polarization (DNP) via continuous-wave partial saturation of electron spin resonance (ESR) lines that are both homogeneously and inhomogeneously broadened. It is a variant of a reasoning proposed by Borghini, which in turn used Redfield's thermodynamic treatment of saturation. Our variant is furthermore based on Provotorov's insight that under partial saturation of a coupled-spin system two distinct spin temperatures should appear in a thermodynamical theory. We apply our model to DNP results obtained at a temperature of 1.2 K and in magnetic fields of 3.35 and 5 T on 1-C-13 labeled sodium acetate dissolved in a frozen D2O/ethanol-d(6) solution doped with the free radical TEMPO

Solid-state 1H spin polarimetry by 13CH3 nuclear magnetic resonance

Abstract. Dissolution dynamic nuclear polarization is used to prepare nuclear spin polarizations approaching unity. At present, 1H polarization quantification in the solid state remains fastidious due to the requirement of measuring thermal equilibrium signals. Line shape polarimetry of solid-state nuclear magnetic resonance spectra is used to determine several useful properties regarding the spin system under investigation. In the case of highly polarized nuclear spins, such as those prepared under the conditions of dissolution dynamic nuclear polarization experiments, the absolute polarization of a particular isotopic species within the sample may be directly inferred from the characteristics of the corresponding resonance line shape. In situations where direct measurements of polarization are complicated by deleterious phenomena, indirect estimates of polarization using coupled heteronuclear spins prove informative. We present a simple analysis of the 13C spectral line shape of [2-13C]sodium acetate based on the normalized deviation of the centre of gravity of the 13C peaks, which can be used to indirectly evaluate the proton polarization of the methyl group moiety and very likely the entire sample in the case of rapid and homogeneous 1H–1H spin diffusion. For the case of positive microwave irradiation, 1H polarization was found to increase with an increasing normalized centre of gravity deviation. These results suggest that, as a dopant, [2-13C]sodium acetate could be used to indirectly gauge 1H polarizations in standard sample formulations, which is potentially advantageous for (i) samples polarized in commercial dissolution dynamic nuclear polarization devices that lack 1H radiofrequency hardware, (ii) measurements that are deleteriously influenced by radiation damping or complicated by the presence of large background signals and (iii) situations where the acquisition of a thermal equilibrium spectrum is not feasible. </jats:p

Trypanosomiase humaine africaine : étude d'un score de présomption de diagnostic au Congo

Une enquête cas-témoins a été réalisée au Congo afin de définir une grille de score de présomption de la maladie du sommeil à #T.b. gambiense$, basée sur une sélection de critères cliniques et épidémiologiques de la trypanosomiase, utilisable par les structures sanitaires périphériques. L'enquête a été réalisée sur 163 cas et 326 témoins. Les signes cliniques et les symptômes retenus sont :fièvre, céphalées, prurit et lésions de grattage, diarrhée, oedèmes, adénopathies cervicales, troubles du sommeil, troubles de l'appétit, troubles sexuels, psychisme, signes neurologiques et autres troubles cliniques mineurs. Les autres critères retenus sont les antécédents de trypanosomiase humaine africaine (THA) et l'existence d'un cheptel dans la concession. L'analyse des résultats confirme qu'il n'existe pas de critère ou groupe de critères pathognomoniques. Aucun des critères sélectionnés n'est suffisamment discriminant pour permettre une sélection des trypanosomés parmi les consultants. Une grille de score de présomption semble donc de peu d'utilité au niveau périphérique; ceci est d'autant plus vrai si l'on considère l'augmentation de la charge de travail. Le faible pouvoir discriminant des signes cliniques et des symptômes ainsi que des autres paramètres de la trypanosomiase africaine met en évidence la difficulté de mise en place d'une stratégie d'intégration efficiente en tant qu'outil diagnostique précoce. (Résumé d'auteur

The journey towards elimination of gambiense human African trypanosomiasis: not far, nor easy

Considering the epidemic situation of gambiense human African trypanosomiasis (HAT) at the end of the twentieth century, the World Health Organization (WHO) and partners strengthened disease control and surveillance. Over the last 15 years, the activities implemented through the National Control Programmes have brought gambiense HAT under control and now its elimination is deemed as an achievable goal. In 2012, WHO targeted gambiense HAT for elimination as a public health problem by 2020. The final goal will be the sustainable disease elimination by 2030, defined as the interruption of the transmission of gambiense HAT. The elimination is considered feasible, because of the epidemiological vulnerability of the disease, the current state of control, the availability of strategies and tools and international commitment and political will. Integration of activities in the health system is needed to ensure the sustainability of the elimination. The development of user-friendly diagnostic and treatment tools will facilitate the integration process. Adequate funding is needed to implement activities, but also to support research that will make the elimination sustainable. A long-term commitment by donors is needed and ownership of the process by endemic countries is critica

Three-dimensional quantitative evaluation method of nonrigid registration algorithms for adaptive radiotherapy

Purpose: Current radiotherapy is progressing to the concept of adaptive radiotherapy, which implies the adaptation of planning along the treatment course. Nonrigid registration is an essential image processing tool for adaptive radiotherapy and image guided radiotherapy, and the three-dimensional (3D) nature of the current radiotherapy techniques requires a 3D quantification of the registration error that existing evaluation methods do not cover appropriately. The authors present a method for 3D evaluation of nonrigid registration algorithms’ performance, based on organ delineations, capable of working with near-spherical volumes even in the presence of concavities. Methods: The evaluation method is composed by a volume shape description stage, developed using a new ad hoc volume reconstruction algorithm proposed by the authors, and an error quantification stage. The evaluation method is applied to the organ delineations of prostate and seminal vesicles, obtained by an automatic segmentation method over images of prostate cancer patients treated with intensity modulated radiation therapy. Results: The volume reconstruction algorithm proposed has been shown to accurately model complex 3D surfaces by the definition of clusters of control points. The quantification method, inspired by the Haussdorf–Chebysev distance, provides a measure of the largest registration error per control direction, defining a valid metric for concave-convex volumes. Summarizing, the proposed evaluation methodology presents accurate results with a high spatial resolution in a negligible computation time in comparison with the nonrigid registration time. Conclusions: Experimental results show that the metric selected for quantifying the registration error is of utmost importance in a quantitative evaluation based on measuring distances between volumes. The accuracy of the volume reconstruction algorithm is not so relevant as long as the reconstruction is tight enough on the actual volume of the organ. The new evaluation method provides a smooth and accurate volume reconstruction for both the reference and the registered organ, and a complete 3D description of nonrigid registration algorithms’ performance, resulting in a useful tool for study and comparison of registration algorithms for adaptive radiotherapy