Understanding the Role of Duration of Vaccine Protection with MenAfriVac: Simulating Alternative Vaccination Strategies.

We previously developed a transmission dynamic model of Neisseria meningitidis serogroup A (NmA) with the aim of forecasting the relative benefits of different immunisation strategies with MenAfriVac. Our findings suggested that the most effective strategy in maintaining disease control was the introduction of MenAfriVac into the Expanded Programme on Immunisation (EPI). This strategy is currently being followed by the countries of the meningitis belt. Since then, the persistence of vaccine-induced antibodies has been further studied and new data suggest that immune response is influenced by the age at vaccination. Here, we aim to investigate the influence of both the duration and age-specificity of vaccine-induced protection on our model predictions and explore how the optimal vaccination strategy may change in the long-term. We adapted our previous model and considered plausible alternative immunization strategies, including the addition of a booster dose to the current schedule, as well as the routine vaccination of school-aged children for a range of different assumptions regarding the duration of protection. To allow for a comparison between the different strategies, we use several metrics, including the median age of infection, the number of people needed to vaccinate (NNV) to prevent one case, the age distribution of cases for each strategy, as well as the time it takes for the number of cases to start increasing after the honeymoon period (resurgence). None of the strategies explored in this work is superior in all respects. This is especially true when vaccine-induced protection is the same regardless of the age at vaccination. Uncertainty in the duration of protection is important. For duration of protection lasting for an average of 18 years or longer, the model predicts elimination of NmA cases. Assuming that vaccine protection is more durable for individuals vaccinated after the age of 5 years, routine immunization of older children would be more efficient in reducing disease incidence and would also result in a fewer number of doses necessary to prevent one case. Assuming that elimination does not occur, adding a booster dose is likely to prevent most cases but the caveat will be a more costly intervention. These results can be used to understand important sources of uncertainty around MenAfriVac and support decisions by policymakers

Risk factors and variations in detection of new bovine tuberculosis breakdowns via slaughterhouse surveillance in Great Britain.

Slaughterhouse surveillance through post-mortem meat inspection provides an important mechanism for detecting bovine tuberculosis (bTB) infections in cattle herds in Great Britain (GB), complementary to the live animal skin test based programme. We explore patterns in the numbers of herd breakdowns detected through slaughterhouse surveillance and develop a Bayesian hierarchical regression model to assess the associations of animal-level factors with the odds of an infected animal being detected in the slaughterhouse, allowing us to highlight slaughterhouses that show atypical patterns of detection. The analyses demonstrate that the numbers and proportions of breakdowns detected in slaughterhouses increased in GB over the period of study (1998-2013). The odds of an animal being a slaughterhouse case was strongly associated with the region of the country that the animal spent most of its life, with animals living in high-frequency testing areas of England having on average 21 times the odds of detection compared to animals living in Scotland. There was also a strong effect of age, with animals slaughtered at > 60 months of age having 5.3 times the odds of detection compared to animals slaughtered between 0-18 months of age. Smaller effects were observed for cattle having spent time on farms with a history of bTB, quarter of the year that the animal was slaughtered, movement and test history. Over-and-above these risks, the odds of detection increased by a factor of 1.1 for each year of the study. After adjustment for these variables, there were additional variations in risk between slaughterhouses and breed. Our framework has been adopted into the routine annual surveillance reporting carried out by the Animal Plant Health Agency and may be used to target more detailed investigation of meat inspection practices.Defra Project SE3133. (Department of Environment and Rural Affairs, UK Government

Prevalence of Bovine Tuberculosis in India: A systematic review and meta-analysis.

Bovine tuberculosis (bTB) is a chronic disease of cattle that impacts productivity and represents a major public health threat. Despite the considerable economic costs and zoonotic risk consequences associated with the disease, accurate estimates of bTB prevalence are lacking in many countries, including India, where national control programmes are not yet implemented and the disease is considered endemic. To address this critical knowledge gap, we performed a systematic review of the literature and a meta-analysis to estimate bTB prevalence in cattle in India and provide a foundation for the future formulation of rational disease control strategies and the accurate assessment of economic and health impact risks. The literature search was performed in accordance with PRISMA guidelines and identified 285 cross-sectional studies on bTB in cattle in India across four electronic databases and handpicked publications. Of these, 44 articles were included, contributing a total of 82,419 cows and buffaloes across 18 states and one union territory in India. Based on a random-effects (RE) meta-regression model, the analysis revealed a pooled prevalence estimate of 7.3% (95% CI: 5.6, 9.5), indicating that there may be an estimated 21.8 million (95% CI: 16.6, 28.4) infected cattle in India-a population greater than the total number of dairy cows in the United States. The analyses further suggest that production system, species, breed, study location, diagnostic technique, sample size and study period are likely moderators of bTB prevalence in India and need to be considered when developing future disease surveillance and control programmes. Taken together with the projected increase in intensification of dairy production and the subsequent increase in the likelihood of zoonotic transmission, the results of our study suggest that attempts to eliminate tuberculosis from humans will require simultaneous consideration of bTB control in cattle population in countries such as India

Structure and consistency of self-reported social contact networks in British secondary schools.

Self-reported social mixing patterns are commonly used in mathematical models of infectious diseases. It is particularly important to quantify patterns for school-age children given their disproportionate role in transmission, but it remains unclear how the structure of such social interactions changes over time. By integrating data collection into a public engagement programme, we examined self-reported contact networks in year 7 groups in four UK secondary schools. We collected data from 460 unique participants across four rounds of data collection conducted between January and June 2015, with 7,315 identifiable contacts reported in total. Although individual-level contacts varied over the study period, we were able to obtain out-of-sample accuracies of more than 90% and F-scores of 0.49-0.84 when predicting the presence or absence of social contacts between specific individuals across rounds of data collection. Network properties such as clustering and number of communities were broadly consistent within schools between survey rounds, but varied significantly between schools. Networks were assortative according to gender, and to a lesser extent school class, with the estimated clustering coefficient larger among males in all surveyed co-educational schools. Our results demonstrate that it is feasible to collect longitudinal self-reported social contact data from school children and that key properties of these data are consistent between rounds of data collection

Effect of Bovine Tuberculosis on Selected Productivity Parameters and Trading in Dairy Cattle Kept Under Intensive Husbandry in Central Ethiopia.

Bovine tuberculosis (BTB) has substantial impact on fertility, milk, and meat productivity in cattle. However, these assumptions are based on outdated data. Recent global studies on the impact of BTB on cattle productivity are scarce and show sometimes inconclusive and/or contradicting results. This pilot study is the first longitudinal study performed in urban upgraded dairy cattle in Ethiopia that are kept under intensive husbandry. We assessed whether BTB has an impact on various animal productivity parameters and animal movement. Animals (N = 890) included in the study were tested for BTB at least once using the comparative intradermal tuberculin test (CIDT). Fertility, mortality, and offtake were assessed in 21 dairy farms where herd follow-ups over 3 years were performed. In addition, an independent abattoir survey was conducted to assess carcass weight and visible TB-like lesions upon meat inspection. Animal movements (purchasing and offtakes) were documented for each farm. The impact of BTB status on the intervals been birth, service, and calving times and the intercalving intervals was analyzed using a Cox proportional hazards model. The hazard ratio associated with BTB-positive animals was smaller than 1 for all fertility parameters, suggesting that BTB status increases the time between events; however, the effect was small and only statistically significant (95% level) for the time between calving and service. Offtakes included a higher percentage of reactor animals (58%) as compared with non-reactor animals (42%) (p = 0.0001). Overall, reactors were eliminated from the farms within 238.6 days after receiving test results, which was 54.9 days faster than for negative animals. The majority of owners purchased animals within their town or its surrounding. Nearly a quarter of reactors were sold directly to other farms. Animals were also sold further away, including other regions, raising the question of disease spread and the need for an animal tracing mechanism. In the abattoir survey, a total of 349 carcasses were weighed, of which 8% showed visible TB-like lesions and 53.6% had fasciolosis. Negative adult bull carcasses were 7.5 kg heavier than reactor bulls.This work was funded by the Biotechnology and Biological Sciences Research Council, the Department for International Development, the Economic and Social Research Council, the Medical Research Council, the Natural Environment Research Council, and the Defence Science and Technology Laboratory, under the Zoonoses and Emerging Livestock Systems (ZELS) programme, ref. BB/L018977/1. The funders were not involved in the design of the study; in the collection, analysis, and interpretation of data; and in writing the manuscript

Structure and consistency of self-reported social contact networks in British secondary schools

Self-reported social mixing patterns are commonly used in mathematical models of infectious diseases. It is particularly important to quantify patterns for school-age children given their disproportionate role in transmission, but it remains unclear how the structure of such social interactions changes over time. By integrating data collection into a public engagement programme, we examined self-reported contact networks in year 7 groups in four UK secondary schools. We collected data from 460 unique participants across four rounds of data collection conducted between January and June 2015, with 7,315 identifiable contacts reported in total. Although individual-level contacts varied over the study period, we were able to obtain out-of-sample accuracies of more than 90% and F-scores of 0.49-0.84 when predicting the presence or absence of social contacts between specific individuals across rounds of data collection. Network properties such as clustering and number of communities were broadly consistent within schools between survey rounds, but varied significantly between schools. Networks were assortative according to gender, and to a lesser extent school class, with the estimated clustering coefficient larger among males in all surveyed co-educational schools. Our results demonstrate that it is feasible to collect longitudinal self-reported social contact data from school children and that key properties of these data are consistent between rounds of data collection

Effectiveness of isolation, testing, contact tracing, and physical distancing on reducing transmission of SARS-CoV-2 in different settings: a mathematical modelling study.

BACKGROUND: The isolation of symptomatic cases and tracing of contacts has been used as an early COVID-19 containment measure in many countries, with additional physical distancing measures also introduced as outbreaks have grown. To maintain control of infection while also reducing disruption to populations, there is a need to understand what combination of measures-including novel digital tracing approaches and less intensive physical distancing-might be required to reduce transmission. We aimed to estimate the reduction in transmission under different control measures across settings and how many contacts would be quarantined per day in different strategies for a given level of symptomatic case incidence. METHODS: For this mathematical modelling study, we used a model of individual-level transmission stratified by setting (household, work, school, or other) based on BBC Pandemic data from 40 162 UK participants. We simulated the effect of a range of different testing, isolation, tracing, and physical distancing scenarios. Under optimistic but plausible assumptions, we estimated reduction in the effective reproduction number and the number of contacts that would be newly quarantined each day under different strategies. RESULTS: We estimated that combined isolation and tracing strategies would reduce transmission more than mass testing or self-isolation alone: mean transmission reduction of 2% for mass random testing of 5% of the population each week, 29% for self-isolation alone of symptomatic cases within the household, 35% for self-isolation alone outside the household, 37% for self-isolation plus household quarantine, 64% for self-isolation and household quarantine with the addition of manual contact tracing of all contacts, 57% with the addition of manual tracing of acquaintances only, and 47% with the addition of app-based tracing only. If limits were placed on gatherings outside of home, school, or work, then manual contact tracing of acquaintances alone could have an effect on transmission reduction similar to that of detailed contact tracing. In a scenario where 1000 new symptomatic cases that met the definition to trigger contact tracing occurred per day, we estimated that, in most contact tracing strategies, 15 000-41 000 contacts would be newly quarantined each day. INTERPRETATION: Consistent with previous modelling studies and country-specific COVID-19 responses to date, our analysis estimated that a high proportion of cases would need to self-isolate and a high proportion of their contacts to be successfully traced to ensure an effective reproduction number lower than 1 in the absence of other measures. If combined with moderate physical distancing measures, self-isolation and contact tracing would be more likely to achieve control of severe acute respiratory syndrome coronavirus 2 transmission. FUNDING: Wellcome Trust, UK Engineering and Physical Sciences Research Council, European Commission, Royal Society, Medical Research Council

Inferring Mycobacterium bovis transmission between cattle and badgers using isolates from the Randomised Badger Culling Trial.

Mycobacterium bovis (M. bovis) is a causative agent of bovine tuberculosis, a significant source of morbidity and mortality in the global cattle industry. The Randomised Badger Culling Trial was a field experiment carried out between 1998 and 2005 in the South West of England. As part of this trial, M. bovis isolates were collected from contemporaneous and overlapping populations of badgers and cattle within ten defined trial areas. We combined whole genome sequences from 1,442 isolates with location and cattle movement data, identifying transmission clusters and inferred rates and routes of transmission of M. bovis. Most trial areas contained a single transmission cluster that had been established shortly before sampling, often contemporaneous with the expansion of bovine tuberculosis in the 1980s. The estimated rate of transmission from badger to cattle was approximately two times higher than from cattle to badger, and the rate of within-species transmission considerably exceeded these for both species. We identified long distance transmission events linked to cattle movement, recurrence of herd breakdown by infection within the same transmission clusters and superspreader events driven by cattle but not badgers. Overall, our data suggests that the transmission clusters in different parts of South West England that are still evident today were established by long-distance seeding events involving cattle movement, not by recrudescence from a long-established wildlife reservoir. Clusters are maintained primarily by within-species transmission, with less frequent spill-over both from badger to cattle and cattle to badger

Prevalence of bovine tuberculosis and its associated risk factors in the emerging dairy belts of regional cities in Ethiopia.

Bovine tuberculosis (BTB) has become an economically important disease in dairy herds found in and around Addis Ababa City and is emerging in regional cities like Gondar, Hawassa and Mekelle because of the establishment of dairy farms in the milk sheds of these cities. A cross-sectional study to estimate the prevalence of BTB and identify associated risk factors was conducted between February 2016 and March 2017. A total of 174 herds comprising of 2,754 dairy cattle in the cities of Gondar, Hawassa and Mekelle were tested using the Single Intradermal Comparative Cervical Tuberculin (SICCT) test. Data on herd structure, animal origin, body condition, housing condition, farm hygiene, management and biosecurity practices were collected using a pre-tested structured questionnaire. Generalized Linear Models (GLM) and Generalized Linear Mixed Models (GLMM) were used to analyze the herd and animal level risk factors, respectively. The herd prevalence was 22.4% (95% CI: 17-29%) while the animal prevalence was 5.2% (95% CI: 4-6%) at the cut-off >4 mm. The herd prevalence rose to 65.5% (95% CI: 58-72%) and the animal prevalence rose to 9% (95% CI: 8-10%) when the severe interpretation of >2 mm cut-off was applied. The mean within-herd prevalence in positive farms at the cut-off >4 mm was 22.7% (95% CI: 15-31%). At the herd level, the analysis showed that herd size, farm hygiene, feeding condition and biosecurity were significantly associated with BTB status, while new cattle introductions showed only borderline significance and that age of farm, housing condition, farmers' educational status and animal health care practice were not significant. At the animal level, the results showed that age and animal origin were identified as significant predictors for BTB positivity but sex and body condition score were not related to BTB status. Descriptive analysis revealed that herds having 'BTB history' showed slightly higher likelihood of being BTB positive compared to farms having no previous BTB exposure. In conclusion, this study showed relatively lower average prevalence in the emerging dairy regions as compared to the prevalence observed in and around Addis Ababa City, warranting for implementation of control program at this stage to reduce or possibly stop further transmission of BTB.This work was funded by the Biotechnology and Biological Sciences Research Council, the Department for International Development, the Economic & Social Research Council, the Medical Research Council, the Natural Environment Research Council and the Defence Science & Technology Laboratory, under the Zoonoses and Emerging Livestock Systems (ZELS) programme, ref: BB/L018977/1