Functional screening of selective mitochondrial inhibitors of Plasmodium.

Phenotypic screening has produced most of the new chemical entities currently in clinical development for malaria, plus many lead compounds active against Plasmodium falciparum asexual stages. However, lack of knowledge about the mode of action of these compounds delays and may even hamper their future development. Identifying the mode of action of the inhibitors greatly helps to prioritise compounds for further development as novel antimalarials. Here we describe a whole-cell method to detect inhibitors of the mitochondrial electron transport chain, using oxygen consumption as high throughput readout in 384-well plate format. The usefulness of the method has been confirmed with the Tres Cantos Antimalarial Compound Set (TCAMS). The assay identified 124 respiratory inhibitors in TCAMS, seven of which were novel anti-plasmodial chemical structures never before described as mitochondrial inhibitors.

[Outbreak of gastroenteritis caused by Norwalk virus at a senior citizens assisted living facility in Granada, Spain]. / Brote de gastroenteritis por virus Norwalk en una residencia de ancianos de Granada.

BACKGROUND: The outbreaks of acute gastroenteritis caused by a virus are currently one of the health problems having the greatest impact on those living in senior citizen facilities. The objective of this study is that of investigating the causes of the start and contagion of an outbreak of acute gastroenteritis caused by a Norwalk-Like virus. METHOD: At a senior citizen living facility with 141 residents and 71 employees exposed, the relations between the disease in question and different independent variables: personal traits, features of location, date of onset of symptoms, clinical pattern of the disease and causal factors (food and drinking water intake). A descriptive study, a contingency table and a hypothesis ?2 test, design of cases and controls with the calculation of the unprocessed and subsequently adjusted Odds Ratio (IC 95%) were carried out using logic regression. RESULTS: No significant differences were found in the personal trait and features of location variables. The attack rate among the residents was 30.1%, being 21.12% among the employees. In the adjusted Odds Ratio calculation, solely the whipped cream mousse showed causal relationship values (adjusted Odds Ratio = 4.66; IC-95% 1.15-18.91; p = 0.031). Ten patient stool samples were sent for analysis, no disease-causing bacteria having been detected, Norwalk-Like virus however having been isolated in three samples. CONCLUSIONS: The whipped cream mousse having been found to possibly have been responsible for the outbreak is a first involving Norwalk virus, but this result is subject to limitations, such as the possible bias of classification due to failing to recall having eaten foods. Even so, this is an element to be taken into account in the control of acute viral gastroenteritis.