Vaccines for emerging pathogens: prospects for licensure.

Globally, there are a number of emerging pathogens. For most, there are no licensed vaccines available for human use, although there is ongoing research and development. However, given the extensive and increasing list of emerging pathogens and the investment required to bring vaccines into clinical use, the task is huge. Overlaid on this task is the risk of anti-microbial resistance (AMR) acquisition by micro-organisms which can endow a relatively harmless organism with pathogenic potential. Furthermore, climate change also introduces a challenge by causing some of the insect vectors and environmental conditions prevalent in tropical regions to begin to spread out from these traditional areas, thus increasing the risk of migration of zoonotic disease. Vaccination provides a defence against these emerging pathogens. However, vaccines for pathogens which cause severe, but occasional, disease outbreaks in endemic pockets have suffered from a lack of commercial incentive for development to a clinical standard, encompassing Phase III clinical trials for efficacy. An alternative is to develop such vaccines to request US Emergency Use Authorization (EUA), or equivalent status in the United States, Canada and the European Union, making use of a considerable number of regulatory mechanisms that are available prior to licensing. This review covers the status of vaccine development for some of the emerging pathogens, the hurdles that need to be overcome to achieve EUA or an equivalent regional or national status and how these considerations may impact vaccine development for the future, such that a more comprehensive stockpile of promising vaccines can be achieved.

An intensive field trial to assess hazards to birds and mammals from the use of methiocarb as a bird repellent on ripening cherries.

: A field trial was carried out in Kent, UK, in 1980, to assess the possible hazards to wildlife of methiocarb used as a spray to protect ripening cherries from damage by birds. A broad range of studies was undertaken on a single site subjected to a series of five applications. Ground deposition was measured by analysis of strips of chromatography paper and petri dishes placed between lines of trees. Airborne drift was measured on targets up to 11 m above the ground, and methiocarb residues were measured in samples of cherries. Birds were captured by intensive mist-netting throughout the trial, and breeding success was monitored in nest boxes and natural nest sites. Livetraps were set to catch small mammals in the orchard on five occasions during the trial. Systematic searches for possible casualties were made, resulting in the discovery of 21 birds found dead or incapacitated. Levels of activity of plasma, liver and brain esterases were measured in samples taken from several species, and liver slices from House Sparrows, Starlings and Thrushes were examined histologically for signs of cell damage. Samples of breast muscle tissue from Starlings and House Sparrows were analysed by GLC for residues of methiocarb and its principal breakdown product, methiocarb sulfoxide. Overall, the trial revealed that many birds and mammals were exposed to methiocarb, but its effects were largely transient and sublethal. Even a heavy repeated programme of spray applications did not cause any serious hazard to wildlife populations.

Cost analysis and cost justification of automated data processing in the clinical laboratory.

Prospective cost analysis of alternative data processing systems can be facilitated by proper selection of the costs to be analyzed and realistic appraisal of the effect on staffing. When comparing projects with dissimilar cash flows, techniques such as analysis of net present value can be helpful in identifying financial benefits. Confidence and accuracy in prospective analyses will increase as more retrospective studies are published. Several accounts now in the literature describe long-term experience with turnkey laboratory information systems. Acknowledging the difficulty in longitudinal studies, they all report favorable effects on labor costs and recovery of lost charges. Enthusiasm is also expressed for the many intangible benefits of the systems. Several trends suggest that cost justification and cost effectiveness will be more easily demonstrated in the future. These are the rapidly decreasing cost of hardware (with corresponding reduction in service costs) and the entry into the market of additional systems designed for medium to small hospitals. The effect of broadening the sales base may be lower software prices. Finally, operational and executive data management and reporting are destined to become the premier extensions of the LIS for cost justification. Aptly applied, these facilities can promote understanding of costs, control of costs, and greater efficiency in providing laboratory services.

The effects of 1,1-di(p-chlorophenyl)-2-chloroethylene (DDMU) on hepatic morphology of Japanese quail.

The effects of dietary administration of 1,1-di(p-chlorophenyl)-2-chloroethylene (DDMU) to Japanese quail at a concentration of 100 ppm were investigated for periods of up to 32 days. Hepatic morphology was studied by light microscopy. Histologic changes observed included cytoplasmic and nuclear degeneration in the hepatocytes followed by severe lipid accumulation and hepatocellular hypertrophy. There was a progressive increase in cytoplasmic vacuoles containing lipid up to Day 24 followed by a decrease by Day 32 when the numbers of vacuoles remained greater than those in untreated quail livers. The vacuoles showed a distribution which followed the functional acinar units of the liver. Increased numbers and hypertrophy were observed in Kupffer cells and fibrocytes. There was an occasional necrotic hepatocyte observed but this lesion was not a prominent feature. Hepatocellular hyperplasia occurred as the lipid accumulation decreased. The histologic findings are compared with the biphasic response previously described.

Control enzyme levels in the plasma, brain and liver from wild birds and mammals in Britain.

Brain from 47 avian and 17 mammalian species and the liver from 19 avian and 7 mammalian species has been examined for acetyl cholinesterase and nitrophenyl acetate esterase activities. Plasma from 27 avian and 7 mammalian species has been examined for acetyl cholinesterase, cholinesterase, nitrophenyl acetate esterase, glutamate, oxaloacetate transaminase, glutamate pyruvate transaminase, glutamate dehydrogenase, sorbitol dehydrogenase and lactate dehydrogenase activities. The studies have revealed that variations in enzyme activities occur between species but that there are discernible trends within families. The results indicate that comprehensive control enzyme data is necessary in order to assess the effects of exposure to agricultural chemicals in wildlife.

A study on the toxicity and the biochemical effects of ethylene dibromide in the Japanese quail.

1. The acute oral LD50 and chronic LC50 toxicity values for ethylene dibromide (EDB) were estimated for japanese quail. 2. Single sub-acute oral and intraperitoneal doses of EDB (1/2 LD50) and chronic oral doses of EDB (1/3 LC50) were administered to quail in order to characterise the sub-lethal effects of EDB residues. 3. At 24 h after sub-acute dosing, relative liver weight, plasma aspartate aminotransferase (AT) [EC 2.6.1.1] and L-iditol (sorbitol) dehydrogenase (SDH) [EC 1.1.1.14] were elevated and decreases were found in hepatic total lipid, total protein, AT and glutamic dehydrogenase (NAD (P)+) (GDH) and plasma cholinesterase (ChE) [EC 3.1.1.8] and total lipid. 4. Following chronic administration, elevations in relative liver weight, plasma ChE and total lipid, haemoglobin and haematocrit were found and hepatic AT, GDH and total lipid were decreased. 5. The changes in hepatic and plasma enzymes and constituents are discussed in relation to possible biphasic effects resulting from EDB exposure.

Economic analysis in assessing technology in clinical laboratories.

In applying product-oriented cost analysis to economic decisions in the clinical laboratory, one should be especially aware of those areas in which the data used are only approximations. Many cost components are imbedded in accounts that are common to several areas of activity and cannot rationally be separated. Once cast into an elegant study, information of borderline validity may be obscured. the accuracy of the projections will also depend on the stability of the laboratory environment, and the available degree of detail and completeness of the data. Special care must be taken in the areas of supply and personnel since the actual behavior of these items can vary according to laboratory size, population served, service requirements, and management policies.