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Aims: To investigate the seroprevalence of infection with bovine viral diarrhoea (BVD) virus among 75 beef herds and seroconversion in cattle during early pregnancy, and to determine the practices and opinions of farmers towards BVD control and their association with real and perceived herd serological status. Methods: Blood samples were collected before mating in 75 beef herds across New Zealand from 15 unvaccinated heifers that had delivered their first calf that season. Serum samples were tested for BVD antibodies using ELISA individually, and after pooling samples for each farm. Animals that were antibody-negative were retested at either pregnancy diagnosis or weaning. Farmers were asked to complete a detailed survey about herd demographics, BVD testing and vaccination practices, and opinions towards national BVD control. Results: Based on the pooled serum antibody ELISA results, there were 28/75 (37%) negative herds, 15/75 (20%) suspect herds, and 32/75 (43%) positive herds. Of 1,117 animals sampled 729 (65.3%) tested negative for BVD virus antibodies; when retested, 47/589 (8.0%) animals from 13/55 (24%) herds had seroconverted. Among 71 famers providing survey responses 11 (15%) believed their herd was infected with BVD, 24 (34%) were unsure and 36 (51%) did not think their herd was infected. Only 19/71 (18%) farmers had performed any BVD testing within the past 5 years and 50/70 (71%) had not vaccinated any cattle for BVD. Support for national BVD eradication programme was strong in 51/71 (56%) respondents, but the biggest challenge to BVD control was considered to be famer compliance. Compared to farmers who did not think their herd was infected, more farmers who thought BVD was present in their herds had previously tested for BVD, would consider testing all replacement calves, and would support establishing a national BVD database; fewer would consider purchasing BVD tested or vaccinated cattle only. Conclusions and clinical relevance: Only 15% of the beef farmers in this study believed their herds were infected with BVD virus and few of them had undertaken BVD screening. Nevertheless many were supportive of implementing a national BVD control programme. It is likely that the lack of farmer awareness around BVD and the failure of farmers to recognise the potential impacts in their herds are hindering progress in controlling the disease in New Zealand. There are opportunities for New Zealand veterinarians to be more proactive in helping beef farmers explore BVD management options.

Eradicating bovine viral diarrhoea (BVD) from cattle populations requires a clear approach for determining the epidemiological status of individual herds and implementing the appropriate control measures to ensure the transmission cycle is cost-effectively broken. This is particularly important in countries such as New Zealand where there is currently no coordinated national programme and the herd-level decisions to control BVD are left to the discretion of individual farmers and veterinarians. To ensure greater consistency in the information being delivered by different stakeholders, we review the epidemiology of BVD in the context of New Zealand pastoral production systems and provides a series of simplified recommendations for the future control of BVD in beef and dairy herds. Based on analysis of BVD test accession data from commercial diagnostic laboratories, it has been estimated that 40.6% of dairy herds and 45.6% of beef herds tested had positive results for antibodies to BVD virus. While BVD continues to remain widespread and under voluntary control in New Zealand, it is recommended that herds test all individual mixed-age cows and replacement heifers for BVD virus or antigen and remove persistently infected animals from the breeding population. All new breeding animals that have entered the herd either through purchase or birth should also be tested for BVD virus. Biosecurity risks should be managed by reducing contacts with other herds and implementing targeted vaccination programmes. All individual purchased cattle should be tested and confirmed negative for BVD virus before being moved onto the buyer's property, even if the herd of origin had a negative antibody-based screening test. Herds should continue annual antigen or virus testing of all calves as soon as possible after birth to identify any persistently infected animals.

Aims: To describe temporal trends in bulk milk antibody ELISA and PCR testing for bovine viral diarrhoea (BVD) in New Zealand pastoral dairy herds and to assess the use of historical accession data to predict herd-level BVD incursions. Methods: Data on all diagnostic testing of bulk milk for BVD performed by the Livestock Improvement Corporation (Hamilton, NZ) over eight lactation seasons from 1 June 2010 to 31 May 2018 were analysed. This included anonymised herd identification, geographic location, herd size, sample collection date, sample to positive (S/P) ratio for antibody ELISA results, and cycle threshold values for PCR detecting viral RNA. Multivariable logistic regression was used to explore the relationship between historical accession data and the risk of herds having at least one positive bulk milk PCR test result in the 2017 season. Results: There were 156,034 bulk milk BVD diagnostic testing accessions for 10,495 uniquely identified dairy herds over the 8-season period. The prevalence of tested herds with at least one positive bulk milk PCR test result decreased from 14.6% (407/2,786) in the 2010 season to 5.6% (355/6,309) in the 2017 season with similarly marked declines in S/P ratios. In the 2017 season, 2,961/6,309 (46.9%) herds had S/P ratios greater than the 0.75 cut-off value indicating recent or active BVD virus transmission within the herd while 1,422/6,309 (22.5%) herds were classified as having negative or low S/P ratios. Herds that cleared BVD from the milking herd experienced a mean decline in S/P ratio of 0.11 units per year (min 0.05; max 0.18). In the multivariable analysis, the overall incidence risk of herds experiencing a BVD incursion in the 2017 season was 3.8% (146/3,848) and there were three significant predictors in the final model: herd size, PCR status in the 2014 season, and change in S/P ratio between the 2014 and 2015 seasons. The area under the receiver operating curve for the final model was 0.695 indicating poor discrimination. Conclusions and clinical relevance: The prevalence of dairy herds in New Zealand with positive bulk milk PCR test results and high S/P ratios has decreased over time, suggesting fewer herds are actively infected with BVD and that herd immunity may also be declining. Although monitoring trends in bulk milk test results provides useful information on changes in individual herd status, it is difficult to accurately predict when new incursions will occur and farmers should continue to maintain good biosecurity.

To explore recommendations that New Zealand veterinarians make for diagnosing and managing bovine viral diarrhoea (BVD) in cattle herds under different clinical scenarios and their opinions towards potential barriers and opportunities for implementing BVD control programmes in New Zealand. A cross-sectional survey of registered veterinarians in New Zealand was conducted in 2019. Respondents were asked about the approaches they would use to manage BVD under different clinical scenarios as well as their opinions on national BVD control. A subset of veterinarians completed a more in-depth survey providing additional free-text responses on a range of different BVD topics. Descriptive statistics were provided for all quantitative study variables and the free-text responses were also analysed to generate further insights into veterinarians’ perceptions towards BVD management. The cross-sectional survey was completed by 101 of an estimated 870 (11.6%) cattle veterinarians. Thirty-five veterinarians completed the in-depth survey. There was wide variation in the BVD diagnostic testing and vaccination protocols that respondents recommended under different clinical scenarios. Annual bulk milk BVD testing was perceived as a valuable tool for initiating BVD discussions with dairy farmers. Respondents indicated that beef farmers were more difficult to engage in BVD control largely due to the logistical challenges of yarding cattle at the appropriate times to implement interventions, with many farmers only contacting veterinarians after experiencing a BVD outbreak Most respondents (91/101; 90%) believed it was possible to eradicate BVD from New Zealand, but cited lack of farmer awareness and poor compliance with management recommendations as significant barriers. The measure with the most support for inclusion in a compulsory national eradication programme was requiring farmers to declare the status of their animals prior to sale while the least supported measure was requiring farmers to double fence boundaries to prevent nose-to-nose contact with neighbouring stock. Although respondents highlighted the need for farmers and industry to support any national eradication programme in order for it to be successful, there was also recognition that veterinarians could be more pro-active in engaging with farmers particularly in discussions around the economics of BVD. While the survey respondents appeared to be highly supportive of BVD control, it was perceived that financial and logistical barriers existed that could impede farmer engagement. Further extension efforts may be needed to ensure that veterinarians are presenting clear and consistent recommendations about BVD management to farmers. Abbreviations: BVD: Bovine viral diarrhoea; NAIT: National Animal Identification and Tracing System; PI: Persistently infected

Aims: To determine whether sheep that co-grazed with cattle that were suspected to be positive for bovine viral diarrhoea (BVD) virus had serological evidence of exposure to the virus.Methods: Eighteen commercial farms that routinely co-grazed cattle and sheep in the same paddocks were recruited through purposive sampling. The recruiting veterinarians identified nine farms with cattle herds that were known or highly suspected to be positive for BVD and nine farms that were considered to be free of BVD. Blood samples were taken from 15 ewes aged 1 year on each farm and samples were submitted to a commercial diagnostic laboratory to test for antibodies against pestiviruses using an ELISA. All samples that were positive were then tested using a virus neutralisation test (VNT)for antibodies against BVD virus.Results: Of the 270 blood samples, 17 were positive for pestivirus antibodies by ELISA and these originated from two farms that were known or suspected to have BVD virus-positive cattle. None of the samples from the nine flocks co-grazed with cattle herds that were known or suspected to be BVD virus-negative were positive for pestivirus antibodies. Within the two positive farms, 2/15 samples from the first farm and 15/15 samples from the second farm were antibody-positive. When the 17 positive blood samples were submitted for VNT, all 15 samples from the second farm tested positive for BVD virus antibodies with the highest titre being 1:512.Conclusions and clinical relevance: In this small sample of New Zealand sheep and beef farms with suspected BVD infection in cattle, there was evidence of pestivirus exposure in co-grazed sheep. Although we were unable to confirm the origin of the exposure in these sheep, these findings highlight that farmers who are trying to eradicate BVD from their cattle should be mindful that the infection may also be circulating in sheep, and both populations should be considered a possible risk to each other for generating transient and persistent infections. Further work is needed to estimate the true prevalence of New Zealand sheep flocks that are affected by BVD and the associated economic impacts.

Background The epidemiological impact and cost-effectiveness of social protection and biomedical interventions for tuberculosis-affected households might be improved by risk stratification. We therefore derived and externally validated a household-level risk score to predict tuberculosis among contacts of patients with tuberculosis. Methods In this prospective cohort study, we recruited tuberculosis-affected households from 15 desert shanty towns in Ventanilla and 17 urban communities in Callao, Lima, Peru. Tuberculosis-affected households included index patients with a new diagnosis of tuberculosis and their contacts who reported being in the same house as the index patient for more than 6 h per week in the 2 weeks preceding index patient diagnosis. Tuberculosis-affected households were not included if the index patient had no eligible contacts or lived alone. We followed contacts until 2018 and defined household tuberculosis, the primary outcome, as any contact having any form of tuberculosis within 3 years. We used logistic regression to identify characteristics of index patients, contacts, and households that were predictive of household tuberculosis, and used these to derive and externally validate a household-level score. Findings Between Dec 12, 2007, and Dec 31, 2015, 16 505 contacts from 3 301 households in Ventanilla were included in a derivation cohort. During the 3-year follow-up, tuberculosis occurred in contacts of index patients in 430 (13%, 95% CI 12–14) households. Index patient predictors were pulmonary tuberculosis and sputum smear grade, age, and the maximum number of hours any contact had spent with the index patient while they had any cough. Household predictors were drug use, schooling of the female head of a household, and lower food spending. Contact predictors were if any of the contacts were children, number of lower-weight (body-mass index [BMI]

Aims: To assess the suitability of using existing national diagnostic laboratory testing data to support national bovine viral diarrhoea (BVD) research, surveillance, and control in New Zealand. Methods: Data on laboratory accessions for BVD diagnostic testing in New Zealand from 1 January 2015 to 31 December 2017 were provided by four commercial veterinary diagnostic companies. The data were integrated into a single dataset containing the unique accession number, sample submission date, farm location (territorial authority level), test type (bulk milk antibody-ELISA, bulk milk PCR, serum antibody-ELISA, blood/serum/tissue antigen-ELISA, or blood/serum/tissue PCR), and test results. Estimates for the number of registered cattle farms in each territorial authority were generated from the National Animal Identification and Tracing database. Results were summarised for July 2015 to June 2016 and July 2016 to June 2017. Results: There was a total of 59,007 unique BVD diagnostic test accessions including 39,920 (67.6%) for bulk milk antibody-ELISA, 27,832 (47.2%) for bulk milk PCR, 3,229 (5.5%) for serum antibody-ELISA, 9,132 (15.5%) for blood/serum/tissue antigen-ELISA, and 7,122 (12.1%) for blood/serum/tissue PCR. Of the 17,946 accessions for blood/serum/tissue samples, 4,316 (24.0%) were missing the herd production type and 6,678 (37.2%) were missing the animals age. Approximately 7,000/10,958 (65%) dairy herds and 1,600/43,611 (4%) beef herds were conducting annual BVD screening tests. In 2016/2017, the prevalence of accessions with ≥1 BVD-positive result was 40.6% for bulk milk antibody, 6.4% for bulk milk PCR, 45.6% for serum antibody, and 9.8% for blood/serum/tissue antigen-ELISA or PCR tests. There was substantial regional variation in both the percentage of herds testing for BVD and the prevalence of positive accessions. Following pooled serum antibody-ELISA, only 175/604 (29.0%) beef herds and 177/566 (31.3%) dairy herds had recorded follow-up testing. Conclusions and Clinical Relevance: Laboratory diagnostic accession data has the potential to provide valuable insights about BVD epidemiology in New Zealand, but there are significant limitations in the data collected and discrepancies in the different systems that each laboratory uses to measure, interpret, and record diagnostic data. There is a strong need to develop a more consistent national system for recording and sharing BVD test results to support BVD management at farm and industry levels. Abbreviations: BVD: Bovine viral diarrhoea; Ct: Cycle threshold; NAIT: National Animal Identification and Tracing; NZVP: New Zealand Veterinary Pathology; PI: Persistently infected; S/P: Sample to positive control

BACKGROUND: Cough frequency, and its duration, is a biomarker that can be used in low-resource settings without the need of laboratory culture and has been associated with transmission and treatment response. Radiologic characteristics associated with increased cough frequency may be important in understanding transmission. The relationship between cough frequency and cavitary lung disease has not been studied. METHODS: We analyzed data in 41 adults who were HIV negative and had culture-confirmed, drug-susceptible pulmonary TB throughout treatment. Cough recordings were based on the Cayetano Cough Monitor, and sputum samples were evaluated using microscopic observation drug susceptibility broth culture; among culture-positive samples, bacillary burden was assessed by means of time to positivity. CT scans were analyzed by a US-board-certified radiologist and a computer-automated algorithm. The algorithm evaluated cavity volume and cavitary proximity to the airway. CT scans were obtained within 1 month of treatment initiation. We compared small cavities (≤ 7 mL) and large cavities (> 7 mL) and cavities located closer to (≤ 10 mm) and farther from (> 10 mm) the airway to cough frequency and cough cessation until treatment day 60. RESULTS: Cough frequency during treatment was twofold higher in participants with large cavity volumes (rate ratio [RR], 1.98; P = .01) and cavities located closer to the airway (RR, 2.44; P = .001). Comparably, cough ceased three times faster in participants with smaller cavities (adjusted hazard ratio [HR], 2.89; P = .06) and those farther from the airway (adjusted HR, 3.61;, P = .02). Similar results were found for bacillary burden and culture conversion during treatment. CONCLUSIONS: Cough frequency during treatment is greater and lasts longer in patients with larger cavities, especially those closer to the airway.

In this study, 132 patients with lymphadenopathy were investigated. Fifty-two (39.4%) were diagnosed with tuberculosis (TB). The microscopic observation drug susceptibility (MODS) assay provided rapid (13 days), accurate diagnosis (sensitivity, 65.4%) and reliable drug susceptibility testing (DST). Despite its lower sensitivity than that of other methods, its faster results and simultaneous DST are advantageous in resource-poor settings, supporting the incorporation of MODS into diagnostic algorithms for extrapulmonary TB.

In this work we present a density matrix model which considers an infinite quantum cascade laser (QCL) and models transport via a nearest neighbor approximation. We will discuss derivation of output parameters of the model in detail and show the direct mathematical link to semi-classical rate equation approach. This model can be extended to an arbitrary number of states in the QCL period, without a priori specification of upper and lower lasing level. Application of the model to various QCL structures is possible, including bound-to-continuum structures which typically employ a large number of states per period. The model has been applied to a 2 THz bound-to-continuum QCL and a very good agreement with measured V-I characteristics is obtained along with qualitative agreement with measured L-I characteristics in terms of dynamic range.

Background The performance of laboratory tests to diagnose pulmonary tuberculosis is dependent on the quality of the sputum sample tested. The relative merits of sputum collection methods to improve tuberculosis diagnosis are poorly characterised. We therefore aimed to investigate the effects of sputum collection methods on tuberculosis diagnosis. Methods We did a systematic review and meta-analysis to investigate whether non-invasive sputum collection methods in people aged at least 12 years improve the diagnostic performance of laboratory testing for pulmonary tuberculosis. We searched PubMed, Google Scholar, ProQuest, Web of Science, CINAHL, and Embase up to April 14, 2017, to identify relevant experimental, case-control, or cohort studies. We analysed data by pairwise meta-analyses with a random-effects model and by network meta-analysis. All diagnostic performance data were calculated at the sputum-sample level, except where authors only reported data at the individual patient-level. Heterogeneity was assessed, with potential causes identified by logistic meta-regression. Findings We identified 23 eligible studies published between 1959 and 2017, involving 8967 participants who provided 19 252 sputum samples. Brief, on-demand spot sputum collection was the main reference standard. Pooled sputum collection increased tuberculosis diagnosis by microscopy (odds ratio [OR] 1·6, 95% CI 1·3–1·9, p

Background: Cough is the major determinant of tuberculosis transmission. Despite this, there is a paucity of information regarding characteristics of cough frequency throughout the day and in response to tuberculosis therapy. Here we evaluate the circadian cycle of cough, cough frequency risk factors, and the impact of appropriate treatment on cough and bacillary load. Methods: We prospectively evaluated human immunodeficiency virus-negative adults (n = 64) with a new diagnosis of culture-proven, drug-susceptible pulmonary tuberculosis immediately prior to treatment and repeatedly until treatment day 62. At each time point, participant cough was recorded (n = 670) and analyzed using the Cayetano Cough Monitor. Consecutive coughs at least 2 seconds apart were counted as separate cough episodes. Sputum samples (n = 426) were tested with microscopic-observation drug susceptibility broth culture, and in culture-positive samples (n = 252), the time to culture positivity was used to estimate bacillary load. Results: The highest cough frequency occurred from 1 pm to 2 pm, and the lowest from 1 am to 2 am (2.4 vs 1.1 cough episodes/hour, respectively). Cough frequency was higher among participants who had higher sputum bacillary load (P < .01). Pretreatment median cough episodes/hour was 2.3 (interquartile range [IQR], 1.2-4.1), which at 14 treatment days decreased to 0.48 (IQR, 0.0-1.4) and at the end of the study decreased to 0.18 (IQR, 0.0-0.59) (both reductions P < .001). By 14 treatment days, the probability of culture conversion was 29% (95% confidence interval, 19%-41%). Conclusions: Coughs were most frequent during daytime. Two weeks of appropriate treatment significantly reduced cough frequency and resulted in one-third of participants achieving culture conversion. Thus, treatment by 2 weeks considerably diminishes, but does not eliminate, the potential for airborne tuberculosis transmission.

Background. Use of tuberculosis preventive therapy (PT) must be urgently scaled up and provided to people at high-risk of developing tuberculosis disease (TB). In high-burden settings, PT is poorly utilised and rarely offered to adult household contacts. Furthermore, the tests for tuberculosis infection used to guide prescription are unreliable for predicting disease, fraught with logistical challenges and unavailable in many settings. In low- and middle-income countries a TB risk score could be used to prioritise PT for contacts most likely to benefit. We therefore aimed to develop a risk score to predict TB disease among adult household contacts of patients with TB in urban Callao, Perú. Methods. We identified index-cases with pulmonary TB (n=715), recruited their household contacts aged ≥15 years (n=2,017) and followed them for TB for a total of 18,988 person-years (PY). Cox proportional-hazards models were fitted to investigate factors associated with TB. 1,009 contacts were selected as a derivation cohort from which a risk score was created. Scores were calculated for each contact and low, intermediate and high-risk groups defined. The score was subsequently validated in the remaining 1,008 contacts. Results. Eight predictors formed the score: age 15-30 or ≥50; history of TB; body-mass-index; prolonged exposure to the index-case; poverty; exposure to indoor air pollution; male index-case and high index-case smear-positivity. In the derivation cohort the incidence rates in the low-, intermediate- and high-risk groups were 331/100,000PY (95%CI:200-550); 942/100,000PY (95%CI: 650-1363) and 2038/100,000PY (95%CI:1501-2768) respectively (p

Single-mode (SM) operation of terahertz (THz)-frequency quantum cascade lasers (QCLs) is essential for gas sensing and for their use as local oscillators. Whilst such SM operation has been demonstrated previously using distributed feedback gratings and photonic lattices (PLs), an ability to tune SM THz QCLs electronically would be highly desirable for many applications. This work investigates the electronic properties of multiple segment QCLs, and explores possible electronic tuning mechanisms. We have fabricated THz QCLs with PL gratings. Our THz QCLs, based on a bound-to-continuum active region design, were processed into 150-μm-wide surface-plasmon ridge waveguides with lengths 2.5–4.5 mm. The upper waveguide was then patterned into three sections. The outer sections were fully metallised with gold. In the central 530-μm-long section, however, the top n-doped layer was etched away and metallic PLs fabricated using electron-beam lithography, with grating pitch between 14.60 and 15.65 μm. In each device, both the PL and the outer sections were bonded separately to allow independent biasing. Devices were cooled in a continuous-flow helium cryostat and emission spectra measured using a Fourier-transform infrared spectrometer. Standard (unpatterned) devices lased with multiple Fabry–Pérot modes in the range 2.70–2.83 THz, whilst single mode emission was observed for devices patterned with a PL (Fig. 2). The emission spectra recorded from devices with PLs of different grating pitch showed stop-band behaviour, with the experimentally-determined stop-band bandwidth of around 25 GHz agreeing with the value of 23 GHz calculated using finite-element modelling. Light-output–current–voltage (LIV) characteristics were acquired under different configurations, including the central PL sections both biased and unbiased. An equivalent circuit model describing the electronic properties of the three-section devices was developed, and was found to reproduce the experimental observations well.