Trial design to estimate the effect of vaccination on tuberculosis incidence in badgers

The principal wildlife reservoir of Mycobacterium bovis in Ireland is the European badger. Studies in the Republic of Ireland (RoI) have shown that badgers culled in association with cattle herd tuberculosis breakdowns (focal culling) have a higher prevalence of infection than the badger population at large. This observation is one rationale for the medium term national strategy of focal badger culling. A vaccination strategy for the control of bovine tuberculosis (bTB) in badgers is a preferred long-term option. The Bacillus Calmette-Guérin (BCG) vaccine has been shown to decrease disease severity in captive badgers under controlled conditions. As the vaccine has been tested in a controlled environment with precise information on infection pressure, it cannot be assumed a priori that the effects of vaccination are similar in the wild, where other environmental and/or ecological factors prevail. For this reason we have designed a vaccine field trial to assess the impact of vaccination on the incidence of TB infection in a wild badger population. The selected study area for the vaccine trial (approximately 755 square kilometers) is divided into three zones each of which has similar characteristics in terms of size, number of main badger setts, cattle herds, cattle and land classification type. Three vaccination levels (100%, 50% and 0%) will be allocated to the three zones in a way that a gradient of vaccination coverage North to South is achieved. The middle zone (zone B) will be vaccinated at a 50% coverage but zone A and C will be randomly allocated with 100% or 0% vaccination coverage. Vaccination within zone B will be done randomly at individual badger level. The objective of this paper is to describe the design of a field tuberculosis vaccination trial for badgers, the epidemiological methods that were used to design the trial and the subsequent data analysis. The analysis will enable us to quantify the magnitude of the observed vaccination effect on M. bovis transmission in badgers under field conditions and to improve our knowledge of the biological effects of vaccination on susceptibility and infectiousness.     

Genetic and immunobiological diversities of porcine reproductive and respiratory syndrome genotype I strains

Genetic diversity of porcine reproductive and respiratory syndrome virus (PRRSV) has been based on ORF5/GP5 and ORF7/N protein variations. Complete viral genome studies are limited and focused on a single or a few set of strains. Moreover, there is a general tendency to extrapolate results obtained from a single isolate to the overall PRRSV population. In the present study, six genotype-I isolates of PRRSV were sequenced from ORF1a to ORF7. Phylogenetic comparisons and the variability degree of known linear B-epitopes were done considering other available full-length genotype-I sequences. Cytokine induction of all strains was also evaluated in different cellular systems. Non structural protein 2 (nsp2) was the most variable part of the virus with 2 out of 6 strains harboring a 74 aa deletion. Deletions were also found in ORF3 and ORF4. Phylogenetic analyses showed that isolates could be grouped differently depending on the ORF examined and the highest similarity with the full genome cluster was found for the nsp9. Interestingly, most of predicted linear B-epitopes in the literature, particularly in nsp2 and GP4 regions, were found deleted or varied in some of our isolates. Moreover, 4 strains, those with deletions in nsp2, induced TNF-α and 3 induced IL-10. These results underline the high genetic diversity of PRRSV mainly in nsp1, nsp2 and ORFs 3 and 4. This variability also affects most of the known linear B-epitopes of the virus. Accordingly, different PRRSV strains might have substantially different immunobiological properties. These data can contribute to the understanding of PRRSV complexity.     

Update on vaccination of cattle and wildlife populations against tuberculosis

A recombinant bovine herpesvirus 5 lacking thymidine kinase and glycoprotein E genes (BoHV-5gEΔTKΔ) was evaluated as a live experimental vaccine. In a first experiment, ten-months-old calves were vaccinated intramuscularly (n=9) or remained as controls (n=8) and 42 days later were challenged with BoHV-5 or BoHV-1 intranasally. The four control calves challenged with BoHV-5 developed severe depression and neurological signs and were euthanized in extremis at days 13 and 14 pos-infection (pi); the five vaccinated animals challenged with BoHV-5 remained healthy. The titers of virus shedding were reduced (p<0.01) from days 3 to 7 post-infection (pi) in vaccinated animals. Control and vaccinated calves challenged with BoHV-1 presented mild transient respiratory signs; yet the magnitude of virus shedding was reduced (p<0.05) in vaccinated animals (days 5, 9 and 11pi). In a second experiment, young calves (100-120 days-old) were vaccinated (n=15) or kept as controls (n=5) and subsequently challenged with a BoHV-1 isolate. Control calves developed moderate to severe rhinitis and respiratory distress; two were euthanized in extremis at days 5 and 9 pi, respectively. In contrast, vaccinated animals were protected from challenge and only a few developed mild and transient nasal signs. The duration and titers of virus shedding after challenge were reduced (p<0.05) in vaccinated animals comparing to controls. In both experiments, vaccinated animals developed antibodies to gE only after challenge. These results demonstrate homologous and heterologous protection and are promising towards the use of the recombinant BoHV-5gEΔTKΔ in vaccine formulations to control BoHV-5 and BoHV-1 infections.     

Lead Isotopic and Metallic Pollution Record in Tree Rings from the Copperbelt Mining�CSmelting Area, Zambia

The composition of tree rings and soils was studied at several locations affected by smelting and transportation in the vicinity of Kitwe (Copperbelt, Zambia). The contents of cobalt (Co), copper (Cu), manganese (Mn), and lead (Pb) and the ²⁰⁶Pb/²⁰⁷Pb isotope ratios in the tree rings were interpreted in relation to potential sources of contamination such as smelter production, acidification of the environment, soil composition, raw material processing, and atmospheric suspended particulate matter (SPM). The highest Co contents in the tree rings correspond to maximum ore production in the mid-1970s. Acidification through SO₂ emissions is documented in the increased Mn contents from the mid-1980s. The isotopic composition of the tree rings of the studied tree species varies in the interval 1.16?C1.34 and the youngest parts of all the studied trees exhibit a low ²⁰⁶Pb/²⁰⁷Pb ratio (<1.17). The soil isotope composition varies in the range ²⁰⁶Pb/²⁰⁷Pb?=?1.18?C1.35. The Pb isotope composition in the soils and tree rings was formed by a combination of lithogenic Pb (²⁰⁶Pb/²⁰⁷Pb????1.3), Pb in processed ores (²⁰⁶Pb/²⁰⁷Pb????1.2), and SPM (automobile) Pb (²⁰⁶Pb/²⁰⁷Pb??1.1). As the soils in the distant region have high ²⁰⁶Pb/²⁰⁷Pb ratios (>1.3) in the whole profile and simultaneously the youngest parts of the tree rings of tree species growing in this soil have a low ²⁰⁶Pb/²⁰⁷Pb ratio (<1.17), it can be assumed that the Pb in the youngest parts of the tree species is derived from absorption of SPM Pb through the bark rather than root uptake. The absence of Pb with a low ²⁰⁶Pb/²⁰⁷Pb ratio in soils in the distant area is probably affected by fires in the herbaceous and bush undergrowth and plant litter, which prevents Pb from biomass from entering the soil and mobilize it back into the atmosphere.     

Mercury (Hg) Transport in a High Arctic River in Northeast Greenland

In a warming climate, mercury (Hg) pathways in the Arctic can be expected to be affected. The Hg transport from the high arctic Zackenberg River Basin was assessed in 2009 in order to describe and estimate the mercury transported from land to the marine environment. A total of 95 water samples were acquired and filtered (0.4 ??m pore size), and Hg concentrations were determined in both the filtered water and in the sediment. A range of other elements were also measured in the water samples. Hg concentrations in the filtered water were in general highest in the beginning of the season when the water came mainly from melted snow. THg concentrations in the sediment were in general relatively constant or slightly decreasing until mid-August, where after the concentrations increased. A principal component analysis separated the samples into spring, summer and autumn samples indicating seasonal characteristics of the patterns of element concentrations. The total amount of Hg in the sediment transported was estimated to 2.6 kg. Approximately 60% of the sediment-transported Hg occurred during a 24-h flood in the beginning of August caused by a glacial lake outburst flood. The total amount of transported dissolved Hg was estimated to 46 g, and 13% of this transport occurred during the 24-h flood. If it is assumed that the Hg transport by Zackenberg River is representative for the general glacial rivers in East Greenland, the total Hg transport into the North Atlantic from Greenland alone is approximately 4.6 tons year^?1 with an estimated annual freshwater discharge of ??440 km³.     

Epidemiology and cost of Lyme disease‐related hospitalizations among patients with employer‐sponsored health insurance—United States, 2005–2014

An estimated 300,000 cases of Lyme disease occur in the United States annually. Disseminated Lyme disease may result in carditis, arthritis, facial palsy or meningitis, sometimes requiring hospitalization. We describe the epidemiology and cost of Lyme disease‐related hospitalizations. We analysed 2005–2014 data from the Truven Health Analytics MarketScan Commercial Claims and Encounters Databases to identify inpatient records associated with Lyme disease based on International Classification of Diseases, Ninth Revision, Clinical Modification (ICD‐9‐CM) codes. We estimated the annual number and median cost of Lyme disease‐related hospitalizations in the United States in persons under 65 years of age. Costs were adjusted to reflect 2016 dollars. Of 20,983,165 admission records contained in the inpatient databases during the study period, 2,823 (0.01%) met inclusion criteria for Lyme disease‐related hospitalizations. Over half of the identified records contained an ICD‐9‐CM code for meningitis (n = 614), carditis (n = 429), facial palsy (n = 400) or arthritis (n = 377). Nearly 60% of hospitalized patients were male. The median cost per Lyme disease‐related hospitalization was $11,688 (range: $140–$323,613). The manifestation with the highest median cost per stay was carditis ($17,461), followed by meningitis ($15,177), arthritis ($13,012) and facial palsy ($10,491). Median cost was highest among the 15‐ to 19‐year‐old age group ($12,991). Admissions occurring in January had the highest median cost ($13,777) for all study years. Based on extrapolation to the U.S. population, we estimate that 2,196 Lyme disease‐related hospitalizations in persons under 65 years of age occur annually with an estimated annual cost of $25,826,237. Lyme disease is usually treated in an outpatient setting; however, some patients with Lyme disease require hospitalization, underscoring the need for effective prevention methods to mitigate these serious cases. Information from this analysis can aid economic evaluations of interventions that prevent infection and advances in disease detection.