Targeted FMD Vaccines for Eastern Africa: The AgResults Foot and Mouth Disease Vaccine Challenge Project

As one of the most infectious livestock diseases in the world, foot and mouth disease (FMD) presents a constant global threat to animal trade and national economies. FMD remains a severe constraint on development and poverty reduction throughout the developing world due to many reasons, including the cost of control measures, closure of access to valuable global FMD-free markets for livestock products, production losses through reduced milk yield, reduced live weight gain, and the inability of infected livestock to perform traction. FMD virus infects a variety of cloven-hoofed animals, including cattle, sheep, goats, swine, all wild ruminants, and suidae, with high morbidity in adult animals. High mortality can occur in young animals due to myocarditis. FMD is endemic in Africa, most of Asia, the Middle East, and parts of South America. The global clustering of FMD viruses has been divided into seven virus pools, where multiple serotypes occur but within which are topotypes that remain mostly confined to that pool. Three pools cover Europe, the Middle East, and Asia; three pools cover Africa; and one pool covers the Americas. The highly infectious nature of FMDV, the existence of numerous continually circulating serotypes and associated topotypes, the potential for wildlife reservoirs, and the frequent emergence of new strains that are poorly matched to existing vaccines all serve to compound the difficulties faced by the governments of endemic countries to effectively control and reduce the burden of the disease at the national and regional levels. This clustering of viruses suggests that if vaccination is to be a major tool for control, each pool could benefit from the use of tailored or more specific vaccines relevant to the topotypes present in that pool, rather than a continued reliance on the currently more widely available vaccines. It should also be noted that, currently, there are varying degrees of effort to identify improved vaccines in different regions. There are relatively few targeted for use in Africa, while the developed world's vaccine banks have a good stock of vaccines destined for emergency outbreak use in FMDV-free countries. The AgResults Foot and Mouth Disease (FMD) Vaccine Challenge Project (the "Project") is an eight-year, US $17.68 million prize competition that supports the development and uptake of high-quality quadrivalent FMD vaccines tailored to meet the needs of Eastern Africa (EA). The Project targets the following Pool Four countries: Burundi, Ethiopia, Kenya, Rwanda, Tanzania and Uganda. The Project is being run in two phases: a development phase, which will encourage the production of regionally relevant vaccines, and a cost-share phase, designed to help to reduce the price of these vaccines in the marketplace to the end users, which is hoped will encourage broader uptake. Manufacturers can submit quadrivalent FMD vaccines containing serotypes A, O, SAT1, and SAT2, which will be assessed as relevant for use in the region through a unique component of the Project requiring the screening of vaccines against the Eastern Africa Foot and Mouth Disease Virus Reference Antigen Panel assembled by the World Reference Laboratory for FMD (WRLFMD), at the Pirbright Institute, UK, in collaboration with the OIE/FAO FMD Reference Laboratory Network. To be eligible for the Project, sera from vaccinated cattle will be used to evaluate serological responses of FMD vaccines for their suitability for use in Eastern African countries. If they pass a determined cut-off threshold, they will be confirmed as relevant for use in the region and will be entered into the Project's cost-share phase.

Biotransformation of pregabalin in surface water matrices and the occurrence of transformation products in the aquatic environment - comparison to the structurally related gabapentin.

The biodegradability of the anticonvulsant pregabalin (PGB) was studied in laboratory incubation experiments in contact with water/sediment systems under different redox conditions. PGB was degraded by biological processes under aerobic conditions reaching half-lives of 8 to 10 d, while inactivated and anaerobic control experiments revealed no significant decrease of PGB concentrations. Within experiments spiked with elevated PGB concentrations, 12 TPs were formed and tentative chemical structures could be proposed by accurate masses and fragmentation pathways detected via measurements with high resolution mass spectrometry (LC-QToF-MS). Four of the proposed TPs were finally confirmed either by authentic reference standards (PGB-Lactam, ISA, TP 157-A (II)) or a self-synthesized standard (NA-PGB). PGB-Lactam was identified as the quantitatively most relevant TP formed via intramolecular cyclization under aerobic conditions, reaching up to 33% of the initial PGB concentration. Incubation experiments spiked with PGB-Lactam revealed three times higher half-lives compared to the parent compound, indicating that PGB-Lactam is more stable than PGB. A comparison with results gained from water/sediment incubation experiments with the structurally related compound gabapentin (GBP) revealed, that the transformation behaviour can be mainly extrapolated to PGB. Most of the observed transformation reactions found for PGB were comparable to the ones found for GBP. The TPs PGB-Lactam and NA-PGB as well as three GBP TPs (GBP-Lactam, NA-GBP and CCHA) have been detected in German wastewater treatment plants (WWTPs) effluents and the river Rhine including some of its tributaries such as Main, Neckar, Moselle and Aare. Moreover, GBP and PGB as well as some of their TPs were detected in German bank filtrates and finished drinking waters up to 260 ng L-1. For that reason these compounds should be monitored in drinking water in the future.

Biological transformation of fexofenadine and sitagliptin by carrier-attached biomass and suspended sludge from a hybrid moving bed biofilm reactor.

Laboratory-scale experiments were conducted to investigate the (bio)transformation of the antidiabetic sitagliptin (STG) and the antihistamine fexofenadine (FXF) during wastewater treatment. As inoculum either attached-growth on carriers or suspended sludge from a hybrid moving bed biofilm reactor (HMBBR) was used. Both target compounds were incubated in degradation experiments and quantified via LC-MS/MS for degradation kinetics. Furthermore transformation products (TPs) were analyzed via high resolution mass spectrometry (HRMS). Structural elucidation of the TPs was based on the high resolution molecular ion mass to propose a molecular formula and on MS2 fragmentation to elucidate the chemical structure of the TPs. In total, 22 TPs (9 TPs for STG and 13 TPs for FXF) were detected in the experiments with STG and FXF. For all TPs, chemical structures could be proposed. STG was mainly transformed via amide hydrolysis and conjugation of the primary amine moiety. In contrast, FXF was predominantly transformed by oxidative reactions such as oxidation (dehydrogenation) and hydroxylation. Furthermore, FXF was removed significantly faster in contact with carriers compared to suspended sludge, whereas STG was degraded slightly faster in contact with suspended sludge. Moreover, the primary TP of FXF was also degraded faster in contact with carriers leading to higher proportions of secondary TPs. Thus, the microbial community of both carriers and suspended sludge catalyzed the same primary transformation reactions but the transformation kinetics of FXF and the formation/degradation of FXF TPs were considerably higher in contact with carrier-attached biomass. The primary degradation of both target compounds in pilot- and full-scale conventional activated sludge (CAS) and MBBR reactors reached 42 and 61% for FXF and STG, respectively. Up to three of the identified TPs of FXF and 8 TPs of STG were detected in the effluents of pilot- and full-scale CAS and MBBR.

Chronic viral infections in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS).

BACKGROUND AND MAIN TEXT: Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a complex and controversial clinical condition without having established causative factors. Increasing numbers of cases during past decade have created awareness among patients as well as healthcare professionals. Chronic viral infection as a cause of ME/CFS has long been debated. However, lack of large studies involving well-designed patient groups and validated experimental set ups have hindered our knowledge about this disease. Moreover, recent developments regarding molecular mechanism of pathogenesis of various infectious agents cast doubts over validity of several of the past studies. CONCLUSIONS: This review aims to compile all the studies done so far to investigate various viral agents that could be associated with ME/CFS. Furthermore, we suggest strategies to better design future studies on the role of viral infections in ME/CFS.

Biotransformation of gabapentin in surface water matrices under different redox conditions and the occurrence of one major TP in the aquatic environment.

Laboratory-scale incubation experiments in water/sediment systems were conducted to test the transformation behavior of the anticonvulsant gabapentin (GBP) under different environmental conditions (aerobic, anaerobic, with abiotic controls). GBP was transformed by biological processes as it was eliminated quickly under aerobic conditions (dissipation time 50% of initial concentration (DT50): 2-7 days) whereas no decrease was observed under anaerobic conditions. Measurements via high resolution mass spectrometry (LC-Orbitrap-MS) revealed eight biological transformation products (TPs). Three of them were identified with reference standards (GBP-Lactam, TP186, TP213), while for the other five TPs tentative structures were proposed from information by MS2/MS3 experiments. Furthermore, the quantitatively most relevant TP GBP-Lactam was formed via intramolecular amidation (up to 18% of initial GBP concentration). Incubation experiments with GBP-Lactam revealed a higher stability against biotic degradation (DT50: 12 days) in contrast to GBP, while it was stable under anaerobic and abiotic conditions. Besides GBP, GBP-Lactam was detected in surface water in the µg L-1 range. Finally, GBP and GBP-Lactam were found in potable water with concentrations up to 0.64 and 0.07 µg L-1, respectively. According to the elevated environmental persistence of GBP-Lactam compared to GBP and its presumed enhanced toxicity, we recommend to involve GBP-Lactam into monitoring programs.