Effect of ionic environment on oxygen uptake and lactate production of myometrium.

The present studies were designed to measure the metabolic cost, in terms of oxygen consumption (QO2) and lactate production, of membrane ion transport, and activation of the contractile apparatus of rat myometrium. The normal QO2 of 16.98 +/- 0.84 mumol/g wet tissue per h was reduced to 15.42 +/- 0.66 in the presence of high-K (127 mM) solution. This was further reduced to 14.05 +/- 0.77 and 13.53 +/- 0.76 by the addition of D-600 (10(-5) M), which inhibits Ca influx or in the presence of Ca-deficient high-K solutions, respectively. Ouabain (10(-3) M) reduced QO2 by an amount similar to that produced by high K. Addition of K+ to Na-rich preparations produced an immediate ouabain-sensitive increase of QO2 whose rate was a linear function of [K+]o up to 30 mM in Ca-deficient solution. In all of the above conditions, changes in lactate release paralleled those in QO2. Isoproterenol (10(-6) M), which causes mechanical inhibition of myometrium, had no effect on the QO2 of muscles in normal solution but reduced the QO2 of muscles in Ca-deficient solution. Lactate release was increased by isoproterenol in both normal and Ca-deficient solutions. These results show that the Na pump is an important site of energy utilization in myometrium. Components which can be interpreted in terms of energy utilization for Ca pumping and the contractile apparatus were also demonstrated.     

The Indian and Nepalese programmes of indoor residual spraying for the elimination of visceral leishmaniasis: performance and effectiveness

Although, when applied under controlled conditions in India and Nepal, indoor residual spraying (IRS) has been found to reduce sandfly densities significantly, it is not known if IRS will be as effective when applied generally in these countries, via the national programmes for the elimination of visceral leishmaniasis. The potential benefits and limitations of national IRS programmes for the control of sandflies were therefore evaluated in the districts of Vaishali (in the Indian state of Bihar), Sarlahi (in Nepal) and Sunsari (also in Nepal). The use of technical guidelines, levels of knowledge and skills related to spraying operations, insecticide bio-availability on the sprayed surfaces, concentrations of the insecticide on the walls of sprayed houses, insecticide resistance, and the effectiveness of spraying, in terms of reducing sandfly densities within sprayed houses (compared with those found in unsprayed sentinel houses or control villages) were all explored. It was observed that IRS programme managers, at district and subdistrict levels in India and Nepal, used the relevant technical guidelines and were familiar with the procedures for IRS operation. The performance of the spraying activities, however, showed important deficiencies. The results of bio-assays and the chemical analysis of samples from sprayed walls indicated substandard spraying and suboptimal concentrations of insecticide on sprayed surfaces. This was particularly obvious at one of the Nepali study sites (Sunsari district), where no significant vector reduction was achieved. Sandfly resistance to the insecticide used in India (DDT) was widespread but the potential vectors in Nepal remained very susceptible towards a pyrethroid similar to the one used there. The overall short-term effectiveness of IRS was found to be satisfactory in two of the three study sites (in terms of reduction in the densities of the sandfly vectors). Unfortunately, the medium-term evaluation, conducted 5 months after spraying, was probably made invalid by flooding or lime plastering in the study areas. Preparation for, and the monitoring of, the IRS operations against sandfly populations in India and Nepal need to be improved.     

Murray Valley encephalitis virus recombinant subviral particles protect mice from lethal challenge with virulent wild-type virus

We report on the development and characterisation of a recombinant Murray Valley encephalitis virus (MVE) envelope glycoprotein expression system that results in the secretion of subviral particles (SVPs) upon transfection of the murine fibroblast (COS-7) cell line. Initially, aspects of the physical and antigenic structure of cell-associated and secreted forms of the MVE envelope glycoproteins (prM and E) are presented. We then show that BALB/c mice inoculated with SVPs purified from pcDNA(3)-prM/E-transfected COS-7 cell supernatants are protected from lethal challenge with the virulent prototype strain MVE-1-51 and that this protection correlates with the development of a neutralising humoral immune response by the host. By contrast, prior immunisation with cell-associated, recombinant MVE envelope glycoproteins did not protect mice from challenge with MVE-1-51 and this was associated with the development of antibody that was unable to neutralise virus infectivity in vitro. These studies demonstrate that SVPs derived from the in vitro expression of recombinant MVE prM and E genes are an effective candidate vaccine for the prevention of encephalitis in the mouse model.     

What does dengue disease surveillance contribute to predicting and detecting outbreaks and describing trends?

Objective To review the evidence on the application of tools for dengue outbreak prediction/detection and trend monitoring in passive and active disease surveillance systems in order to develop recommendations for endemic countries and identify research needs. Method Systematic review of literature in the Cochrane Database of Systematic Reviews, PubMed, EMBASE, Lilacs, WHO library database, manual reference search and grey literature. Two reviewers independently applied pre‐defined inclusion and exclusion criteria and assessed the level of evidence. Studies describing the outcome of dengue disease surveillance with respect to trend monitoring and outbreak prediction/detection based on empirical data were included. Results Twenty‐four studies (of 1804 references) met the eligibility criteria. Different indicators and their respective threshold values were identified as potential triggers for outbreak alerts through retrospective analysis of data from passive and/or active surveillance systems. Some indicators are potentially useful for predicting imminent outbreaks in the low transmission season and others for detecting outbreaks at an early stage. However, the information collected is mainly retrospective and often site‐specific and appropriate levels of sensitivity and specificity of the outbreak indicators/triggers could not be determined. Retrospective and prospective virus surveillance studies were not conclusive regarding the question of whether a newly introduced serotype is an outbreak predictor, but contributed additional indicators for outbreak prediction/detection. Under‐reporting was a major concern. Taking cost and feasibility issues into account, it remains an open question whether dengue surveillance should be passive (based on routine reporting) or active (based on more costly sentinel or other active population based surveillance systems). Adding active surveillance elements to a well‐functioning passive surveillance system improves sensitivity; adding laboratory elements to the system improves specificity. Conclusions In view of the lack of evidence about the most feasible and sustainable surveillance system in a country context, countries could use a stepwise approach to locally adapt their passive routine surveillance system into an improved combined active/passive surveillance approach. Prospective studies are needed to better define the most appropriate dengue surveillance system and trigger for dengue emergency response.