Elimination of onchocerciasis in Ecuador: findings of post-treatment surveillance.

BACKGROUND: The Esmeraldas focus of onchocerciasis in Ecuador expanded geographically during the 1980s and was associated with severe ocular and skin disease. Mass drug administration (MDA) with ivermectin started in 1991, initially once but later twice a year, in the principle endemic focus followed by all satellite foci. Treatment was stopped in 2009 when entomological assessments determined that transmission of Onchocerca volvulus had been interrupted. METHODS: Three years after the cessation of ivermectin treatment in 2012, as defined by the WHO guidelines for onchocerciasis elimination, blackfly collections were done in four sentinel sites in former hyperendemic areas. The presence of infective larvae in local vectors, Simulium exiguum and Simulum quadrivittatum, was assessed by detection of O. volvulus DNA by PCR. Additional flies captured in four extra-sentinel sites located in former hyper- and mesoendemic dispersed isolated areas were also assessed. RESULTS: The results from 68,310 captured blackflies, 40,114 from four sentinel villages in the previously hyperendemic areas (Corriente Grande, El Tigre, San Miguel on Río Cayapas and Naranjal on Río Canandé) and 28,197 from extra-sentinel locations, were all negative for the presence of O. volvulus. These extra-sentinel sites (Hualpí on Río Hoja Blanca, Capulí on Río Onzole, La Ceiba on Río Tululví and Medianía on Río Verde) were included to provide additional evidence of the impact of MDA on the transmission of O. volvulus in isolated endemic areas. CONCLUSIONS: Our data indicate that transmission of O. volvulus has been stopped in all endemic areas in Ecuador, including all satellite foci outside the main focus. These findings indicate that a strategy of ivermectin distribution twice a year to over 85% of the treatment-eligible population was effective in eliminating the infection from Ecuador in a focus with a highly competent primary vector, S. exiguum, and where the infection rates were equal to or greater than observed in many onchocerciasis foci in Africa

Relationship between hippocampal structure and memory function in elderly humans

With progressing age, the ability to recollect personal events declines, whereas familiarity-based memory remains relatively intact. It has been hypothesized that age-related hippocampal atrophy may contribute to this pattern because of its critical role for recollection in younger humans and after acute injury. Here, we show that hippocampal volume loss in healthy older persons correlates with gray matter loss (estimated with voxel-based morphometry) of the entire limbic system and shows no correlation with an electrophysiological (event-related potential [ERP]) index of recollection. Instead, it covaries with more substantial and less specific electrophysiological changes of stimulus processing. Age-related changes in another complementary structural measure, hippocampal diffusion, on the other hand, seemed to be more regionally selective and showed the expected correlation with the ERP index of recollection. Thus, hippocampal atrophy in older persons accompanies limbic atrophy, and its functional impact on memory is more fundamental than merely affecting recollection

Graph neural networks for reconstruction and classification in KM3NeT

Instrumentatio

Enhancement of Stochastic Resonance in distributed systems due to a selective coupling

Recent massive numerical simulations have shown that the response of a "stochastic resonator" is enhanced as a consequence of spatial coupling. Similar results have been analytically obtained in a reaction-diffusion model, using "nonequilibrium potential" techniques. We now consider a field-dependent diffusivity and show that the "selectivity" of the coupling is more efficient for achieving stochastic-resonance enhancement than its overall value in the constant-diffusivity case.Comment: 10 pgs (RevTex), 4 figures, submitted to Phys.Rev.Let

Stochastic Resonance in an Extended FitzHugh-Nagumo System: the Role of Selective Coupling

Here we present a study of stochastic resonance in an extended FitzHugh-Nagumo system with a field dependent activator diffusion. We show that the system response (here measured through the output signal-to-noise ratio) is enhanced due to the particular form of the non-homogeneous coupling. Such a result supports previous ones obtained in a simpler scalar reaction-diffusion system and shows that such an enhancement, induced by the field dependent diffusion -or selective coupling-, is a robust phenomenon.Comment: 14 pages, 19 figure

Stochastic resonance between dissipative structures in a bistable noise-sustained dynamics

We study an extended system that without noise shows a monostable dynamics, but when submitted to an adequate multiplicative noise, an effective bistable dynamics arise. The stochastic resonance between the attractors of the \textit{noise-sustained dynamics} is investigated theoretically in terms of a two-state approximation. The knowledge of the exact nonequilibrium potential allows us to obtain the output signal-to-noise ratio. Its maximum is predicted in the symmetric case for which both attractors have the same nonequilibrium potential value.Comment: RevTex, 13 pages, 6 figures, accepted in Physical Review

Journal of nanobiotechnology

BACKGROUND: Nanosuspensions are an important class of delivery system for vaccine adjuvants and drugs. Previously, we developed a nanosuspension consisting of the synthetic TLR4 ligand glucopyranosyl lipid adjuvant (GLA) and dipalmitoyl phosphatidylcholine (DPPC). This nanosuspension is a clinical vaccine adjuvant known as GLA-AF. We examined the effects of DPPC supplier, buffer composition, and manufacturing process on GLA-AF physicochemical and biological activity characteristics. RESULTS: DPPC from different suppliers had minimal influence on physicochemical and biological effects. In general, buffered compositions resulted in less particle size stability compared to unbuffered GLA-AF. Microfluidization resulted in rapid particle size reduction after only a few passes, and 20,000 or 30,000 psi processing pressures were more effective at reducing particle size and recovering the active component than 10,000 psi. Sonicated and microfluidized batches maintained good particle size and chemical stability over 6 months, without significantly altering in vitro or in vivo bioactivity of GLA-AF when combined with a recombinant malaria vaccine antigen. CONCLUSIONS: Microfluidization, compared to water bath sonication, may be an effective manufacturing process to improve the scalability and reproducibility of GLA-AF as it advances further in the clinical development pathway. Various sources of DPPC are suitable to manufacture GLA-AF, but buffered compositions of GLA-AF do not appear to offer stability advantages over the unbuffered composition

Design, Development and Evaluation of rK28-Based Point-of-Care Tests for Improving Rapid Diagnosis of Visceral Leishmaniasis

Visceral Leishmaniasis caused by Leishmania donovani is endemic in several parts of South Asia, East Africa, South and Central America. It is a vector-borne disease transmitted by bites of infected sand flies and often fatal in the absence of chemotherapy. Timely diagnosis is an essential first step in providing proper patient care and in controlling transmission. VL diagnosis in East Africa and Latin America are currently based on microscopic confirmation of parasites in tissue aspirates. The Kalazar Detect rapid test is widely used as a confirmatory test in India with very high accuracy, but sensitivity issues have severely limited its usefulness in the African sub-continent. Direct Agglutination Test is another confirmatory test used widely in East Africa and offers high sensitivity but is not field-friendly. We report on the design of a novel synthetic fusion protein capable of sequestering antibodies against three different Leishmania donovani antigens and the development of point-of-care tests for improving VL diagnosis. We believe the ease of use of these rapid tests and their high accuracy in detecting VL cases could make them useful as a first-line test, thereby eliminating the need for painful biopsies and ensuring better patient care