Whole Blood Interferon γ Release Is a More Sensitive Marker of Prior Exposure to Than Are Antibody Responses.

For the zoonotic disease Q fever, serological analysis plays a dominant role in the diagnosis of infection and in pre-screening for past exposure prior to vaccination. A number of studies suggest that assessment of -specific T-cell IFNγ responses may be a more sensitive tool to assess past exposure. In this study, we assessed the performance of a whole blood IFNγ release assay in comparison to serological detection in an area of high Q fever incidence in 2014, up to seven years after initial exposure during the Dutch Q fever outbreak 2007-2010.

Repurposing isoxazoline veterinary drugs for control of vector-borne human diseases.

Isoxazolines are oral insecticidal drugs currently licensed for ectoparasite control in companion animals. Here we propose their use in humans for the reduction of vector-borne disease incidence. Fluralaner and afoxolaner rapidly killed , , and mosquitoes and sand flies after feeding on a drug-supplemented blood meal, with IC values ranging from 33 to 575 nM, and were fully active against strains with preexisting resistance to common insecticides.

Modelling mosquito infection at natural parasite densities identifies drugs targeting EF2, PI4K or ATP4 as key candidates for interrupting malaria transmission.

Eradication of malaria requires a novel type of drug that blocks transmission from the human to the mosquito host, but selection of such a drug is hampered by a lack of translational models. Experimental mosquito infections yield infection intensities that are substantially higher than observed in natural infections and, as a consequence, underestimate the drug effect on the proportion of mosquitoes that become infected. Here we introduce a novel experimental and computational method to adequately describe drug efficacy at natural parasite densities.

EARLY CRT MONITORING USING TIME-DOMAIN OPTICAL COHERENCE TOMOGRAPHY DOES NOT ADD TO VISUAL ACUITY FOR PREDICTING VISUAL LOSS IN PATIENTS WITH CENTRAL RETINAL VEIN OCCLUSION TREATED WITH INTRAVITREAL RANIBIZUMAB: A Secondary Analysis of Trial Data.

Purpose: Our primary purpose was to assess the clinical (predictive) validity of central retinal thickness (CRT) and best corrected visual acuity (BCVA) at 1 week and 1 month after starting treatment with ranibizumab for central retinal vein occlusion. The authors also assessed detectability of response to treatment.

Methods: The authors used data from 325 participants in the CRUISE study, which included measurement of time-domain CRT and BCVA at baseline, 1 week, 1 month, and 6 months postrandomization.

Relationship between Histological and Clinical Course of Psoriasis: A Pilot Investigation by Reflectance Confocal Microscopy during Goeckerman Treatment.

Alterations of the skin microvasculature are known to play an important role in the development and maintenance of psoriatic skin lesions. In this study, we investigated lesional skin in 11 psoriatic patients during a modified Goeckerman treatment using reflectance confocal microscopy (RCM) to study the relationship between clinical clearance and histological normalization of psoriatic skin and the significance of histological abnormalities on the course of disease. The treatment regimen resulted in a significant reduction of the Psoriasis Area and Severity Index (PASI) as well as capillary and papillary diameters (p < 0.

Model-based investigations of different vector-related intervention strategies to eliminate visceral leishmaniasis on the Indian subcontinent.

The elimination of infectious diseases requires reducing transmission below a certain threshold. The Visceral Leishmaniasis (VL) Elimination Initiative in Southeast Asia aims to reduce the annual VL incidence rate below 1 case per 10,000 inhabitants in endemic areas by 2015 via a combination of case management and vector control. Using a previously developed VL transmission model, we investigated transmission thresholds dependent on measures reducing the sand fly density either by killing sand flies (e.

Treatment of visceral leishmaniasis: model-based analyses on the spread of antimony-resistant L. donovani in Bihar, India.

Background: Pentavalent antimonials have been the mainstay of antileishmanial therapy for decades, but increasing failure rates under antimonial treatment have challenged further use of these drugs in the Indian subcontinent. Experimental evidence has suggested that parasites which are resistant against antimonials have superior survival skills than sensitive ones even in the absence of antimonial treatment.

Methods And Findings: We use simulation studies based on a mathematical L.

Visceral leishmaniasis in the Indian subcontinent: modelling epidemiology and control.

Background: In the Indian subcontinent, about 200 million people are at risk of developing visceral leishmaniasis (VL). In 2005, the governments of India, Nepal and Bangladesh started the first regional VL elimination program with the aim to reduce the annual incidence to less than 1 per 10,000 by 2015. A mathematical model was developed to support this elimination program with basic quantifications of transmission, disease and intervention parameters.

Influenza--insights from mathematical modelling.

Background: When the first cases of a new infectious disease appear, questions arise about the further course of the epidemic and about the appropriate interventions to be taken to protect individuals and the public as a whole. Mathematical models can help answer these questions. In this article, the authors describe basic concepts in the mathematical modelling of infectious diseases, illustrate their use with a simple example, and present the results of influenza models.

Effects of interventions on the demand for hospital services in an influenza pandemic: a sensitivity analysis.

Principles: The evaluation of the capacity of a country's public health system in case of an influenza pandemic is essential for preparedness planning. Only few studies compare existing medical resources with those required during a severe pandemic.

Methods: We perform a sensitivity analysis with the freely available simulation tool InfluSim to explore the expected number of outpatient visits and the hospital bed occupancy in an influenza pandemic in Switzerland.

Antiviral prophylaxis during pandemic influenza may increase drug resistance.

Background: Neuraminidase inhibitors (NI) and social distancing play a major role in plans to mitigate future influenza pandemics.

Methods: Using the freely available program InfluSim, the authors examine to what extent NI-treatment and prophylaxis promote the occurrence and transmission of a NI resistant strain.

Results: Under a basic reproduction number of R0 = 2.

Modeling the effects of drug resistant influenza virus in a pandemic.

Neuraminidase inhibitors (NI) play a major role in plans to mitigate future influenza pandemics. Modeling studies suggested that a pandemic may be contained at the source by early treatment and prophylaxis with antiviral drugs. Here, we examine the influence of NI resistant influenza strains on an influenza pandemic.

Impact of public health interventions in controlling the spread of SARS: modelling of intervention scenarios.

A variety of intervention measures exist to prevent and control diseases with pandemic potential like SARS or pandemic influenza. They differ in their approach and effectiveness in reducing the number of cases getting infected. The effects of different intervention measures were investigated by a mathematical modelling approach, with comparisons based on the effective reproduction number (R(e)).

Blood transfusion and spread of variant Creutzfeldt-Jakob disease.

Variant Creutzfeldt-Jakob disease (vCJD) may be transmissible by blood. To prevent secondary transmission through blood components, several countries have started to exclude as donors persons who have received a blood transfusion. We investigated the effectiveness of this measure by using a dynamic age-structured model.

The influenza pandemic preparedness planning tool InfluSim.

Background: Planning public health responses against pandemic influenza relies on predictive models by which the impact of different intervention strategies can be evaluated. Research has to date rather focused on producing predictions for certain localities or under specific conditions, than on designing a publicly available planning tool which can be applied by public health administrations. Here, we provide such a tool which is reproducible by an explicitly formulated structure and designed to operate with an optimal combination of the competing requirements of precision, realism and generality.

Determinants of the eradicability of filarial infections: a conceptual approach.

Lymphatic filariasis and onchocerciasis are subject to major intervention programs by the WHO. The Onchocerciasis Control Programme in West Africa was launched 30 years ago and has led to considerable insights into the control of this infection. The Global Alliance to Eliminate Lymphatic Filariasis is a relatively recent control program with ambitious targets concerning its efficacy and its schedule.

Modeling senescence in hypotrichous ciliates.

A sexually reproducing hypotrichous ciliates undergo senescence which is in general attributed to degenerative processes in the macronucleus, assuming that loss of viability is based on loss of genetic elements. It is generally accepted that the genetic elements in the macronucleus of hypotrichs segregate randomly, a process which potentially can lead to aneuploid imbalances in the distribution of gene copies. It is, however, unclear whether there are mechanisms which compensate for such imbalances such that each genetic element regains its predetermined copy number (regulatory model, conserving euploidy), or whether the genetic elements only double, so that genetic imbalances can be inherited to further generations (stochastic model, allowing aneuploidy).