Particularités épidémiologiques de l'infection rétrovirale à HTLV-1 en Afrique centrale

L'Afrique subsaharienne est le réservoir le plus important de virus HTLV-1, mais son épidémiologie reste très mal connue. Pour y remédier, les auteurs ont étudié - de 1987 à 1990 - la situation qui prévaut dans six états d'Afrique centrale. Les modalités admises de la transmission sont effectives : voie sanguine par le biais de la transfusion au rôle à moduler selon les régions en fonction de l'importance, souvent faible, de cette pratique; voie hétérosexuelle qui ne paraît pas avoir la place essentielle supposée dans les autres régions d'endémicité du globe et transmission de la mère à l'enfant par l'allaitement au sein. Mais il semble que des facteurs environnementaux - qui restent à préciser - puissent jouer un rôle non négligeable parmi lesquels vecteurs ailés et helminthes pourraient être pris en considération. (Résumé d'auteur

The Glass Transition Temperature of Water: A Simulation Study

We report a computer simulation study of the glass transition for water. To mimic the difference between standard and hyperquenched glass, we generate glassy configurations with different cooling rates and calculate the $T$ dependence of the specific heat on heating. The absence of crystallization phenomena allows us, for properly annealed samples, to detect in the specific heat the simultaneous presence of a weak pre-peak (``shadow transition''), and an intense glass transition peak at higher temperature. We discuss the implications for the currently debated value of the glass transition temperature of water. We also compare our simulation results with the Tool-Narayanaswamy-Moynihan phenomenological model.Comment: submitted to Phys. Re

Deletion of parasite immune modulatory sequences combined with immune activating signals enhances vaccine mediated protection against filarial nematodes

<p>Background: Filarial nematodes are tissue-dwelling parasites that can be killed by Th2-driven immune effectors, but that have evolved to withstand immune attack and establish chronic infections by suppressing host immunity. As a consequence, the efficacy of a vaccine against filariasis may depend on its capacity to counter parasite-driven immunomodulation.</p> <p>Methodology and Principal Findings: We immunised mice with DNA plasmids expressing functionally-inactivated forms of two immunomodulatory molecules expressed by the filarial parasite Litomosoides sigmodontis: the abundant larval transcript-1 (LsALT) and cysteine protease inhibitor-2 (LsCPI). The mutant proteins enhanced antibody and cytokine responses to live parasite challenge, and led to more leukocyte recruitment to the site of infection than their native forms. The immune response was further enhanced when the antigens were targeted to dendritic cells using a single chain Fv-αDEC205 antibody and co-administered with plasmids that enhance T helper 2 immunity (IL-4) and antigen-presenting cell recruitment (Flt3L, MIP-1α). Mice immunised simultaneously against the mutated forms of LsALT and LsCPI eliminated adult parasites faster and consistently reduced peripheral microfilaraemia. A multifactorial analysis of the immune response revealed that protection was strongly correlated with the production of parasite-specific IgG1 and with the numbers of leukocytes present at the site of infection.</p> <p>Conclusions: We have developed a successful strategy for DNA vaccination against a nematode infection that specifically targets parasite-driven immunosuppression while simultaneously enhancing Th2 immune responses and parasite antigen presentation by dendritic cells.</p&gt

The Immunomodulatory Role of Adjuvants in Vaccines Formulated with the Recombinant Antigens Ov-103 and Ov-RAL-2 against Onchocerca volvulus in Mice.

BACKGROUND: In some regions in Africa, elimination of onchocerciasis may be possible with mass drug administration, although there is concern based on several factors that onchocerciasis cannot be eliminated solely through this approach. A vaccine against Onchocerca volvulus would provide a critical tool for the ultimate elimination of this infection. Previous studies have demonstrated that immunization of mice with Ov-103 and Ov-RAL-2, when formulated with alum, induced protective immunity. It was hypothesized that the levels of protective immunity induced with the two recombinant antigens formulated with alum would be improved by formulation with other adjuvants known to enhance different types of antigen-specific immune responses. METHODOLOGY/ PRINCIPAL FINDINGS: Immunizing mice with Ov-103 and Ov-RAL-2 in conjunction with alum, Advax 2 and MF59 induced significant levels of larval killing and host protection. The immune response was biased towards Th2 with all three of the adjuvants, with IgG1 the dominant antibody. Improved larval killing and host protection was observed in mice immunized with co-administered Ov-103 and Ov-RAL-2 in conjunction with each of the three adjuvants as compared to single immunizations. Antigen-specific antibody titers were significantly increased in mice immunized concurrently with the two antigens. Based on chemokine levels, it appears that neutrophils and eosinophils participate in the protective immune response induced by Ov-103, and macrophages and neutrophils participate in immunity induced by Ov-RAL-2. CONCLUSIONS/SIGNIFICANCE: The mechanism of protective immunity induced by Ov-103 and Ov-RAL-2, with the adjuvants alum, Advax 2 and MF59, appears to be multifactorial with roles for cytokines, chemokines, antibody and specific effector cells. The vaccines developed in this study have the potential of reducing the morbidity associated with onchocerciasis in humans

A recording photoelastic stress meter

An instrument for automatically making photoelastic measurements of stress is described. It may be used for recording transient stresses at a point or for scanning spatial stress distributions. Its use is illustrated by an application entailing the measurement of transient thermal stresses in a viscoelastic material.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/43936/1/11340_2006_Article_BF02327237.pd

Modelling the impact of larviciding on the population dynamics and biting rates of Simulium damnosum (s.l.): implications for vector control as a complementary strategy for onchocerciasis elimination in Africa

Background: In 2012, the World Health Organization set goals for the elimination of onchocerciasis transmission by 2020 in selected African countries. Epidemiological data and mathematical modelling have indicated that elimination may not be achieved with annual ivermectin distribution in all endemic foci. Complementary and alternative treatment strategies (ATS), including vector control, will be necessary. Implementation of vector control will require that the ecology and population dynamics of Simulium damnosum sensu lato be carefully considered. Methods: We adapted our previous SIMuliid POPulation dynamics (SIMPOP) model to explore the impact of larvicidal insecticides on S. damnosum (s.l.) biting rates in different ecological contexts and to identify how frequently and for how long vector control should be continued to sustain substantive reductions in vector biting. SIMPOP was fitted to data from large-scale aerial larviciding trials in savannah sites (Ghana) and small-scale ground larviciding trials in forest areas (Cameroon). The model was validated against independent data from Burkina Faso/Côte d’Ivoire (savannah) and Bioko (forest). Scenario analysis explored the effects of ecological and programmatic factors such as pre-control daily biting rate (DBR) and larviciding scheme design on reductions and resurgences in biting rates. Results: The estimated efficacy of large-scale aerial larviciding in the savannah was greater than that of ground-based larviciding in the forest. Small changes in larvicidal efficacy can have large impacts on intervention success. At 93% larvicidal efficacy (a realistic value based on field trials), 10 consecutive weekly larvicidal treatments would reduce DBRs by 96% (e.g. from 400 to 16 bites/person/day). At 70% efficacy, and for 10 weekly applications, the DBR would decrease by 67% (e.g. from 400 to 132 bites/person/day). Larviciding is more likely to succeed in areas with lower water temperatures and where blackfly species have longer gonotrophic cycles. Conclusions: Focal vector control can reduce vector biting rates in settings where a high larvicidal efficacy can be achieved and an appropriate duration and frequency of larviciding can be ensured. Future work linking SIMPOP with onchocerciasis transmission models will permit evaluation of the impact of combined anti-vectorial and anti-parasitic interventions on accelerating elimination of the disease

Model-based geostatistical mapping of the prevalence of onchocerca volvulus in West Africa.

Background: The initial endemicity (pre-control prevalence) of onchocerciasis has been shown to be an important determinant of the feasibility of elimination by mass ivermectin distribution. We present the first geostatistical map of microfilarial prevalence in the former Onchocerciasis Control Programme in West Africa (OCP) before commencement of antivectorial and antiparasitic interventions. Methods and Findings: Pre-control microfilarial prevalence data from 737 villages across the 11 constituent countries in the OCP epidemiological database were used as ground-truth data. These 737 data points, plus a set of statistically selected environmental covariates, were used in a Bayesian model-based geostatistical (B-MBG) approach to generate a continuous surface (at pixel resolution of 5 km x 5km) of microfilarial prevalence in West Africa prior to the commencement of the OCP. Uncertainty in model predictions was measured using a suite of validation statistics, performed on bootstrap samples of held-out validation data. The mean Pearson’s correlation between observed and estimated prevalence at validation locations was 0.693; the mean prediction error (average difference between observed and estimated values) was 0.77%, and the mean absolute prediction error (average magnitude of difference between observed and estimated values) was 12.2%. Within OCP boundaries, 17.8 million people were deemed to have been at risk, 7.55 million to have been infected, and mean microfilarial prevalence to have been 45% (range: 2–90%) in 1975. Conclusions and Significance: This is the first map of initial onchocerciasis prevalence in West Africa using B-MBG. Important environmental predictors of infection prevalence were identified and used in a model out-performing those without spatial random effects or environmental covariates. Results may be compared with recent epidemiological mapping efforts to find areas of persisting transmission. These methods may be extended to areas where data are sparse, and may be used to help inform the feasibility of elimination with current and novel tools