2024-03-28 ペンシルベニア州立大学(PennState)
<関連情報>
- https://www.psu.edu/news/research/story/vaccine-protects-cattle-bovine-tuberculosis-may-eliminate-disease/
- https://www.science.org/doi/10.1126/science.adl3962
BCGワクチン接種により牛の結核感染が減少し、撲滅への見通しが向上 BCG vaccination reduces bovine tuberculosis transmission, improving prospects for elimination
ABEBE FROMSA, KATRIINA WILLGERT, SREENIDHI SRINIVASAN, GETNET MEKONNEN, […], AND VIVEK KAPUR
Science Published:29 Mar 2024
DOI:https://doi.org/10.1126/science.adl3962
Editor’s summary
In industrialized countries, tuberculosis control in cattle is routinely done by test-and-slaughter, but for most of the world, this strategy is unacceptable. As the dairy industry develops in low- and middle-come countries, there is a risk of uncontrolled bovine tuberculosis and a risk of cross-infections with humans. Fromsa et al. exploited developments in diagnostic tests that distinguish vaccinated from naturally infected animals to measure the effectiveness of Bacillus Calmette-Guérin (BCG) vaccination (see the Perspective by Michel). BCG does not fully prevent infection, and its effectiveness is contested in cattle and humans. A mechanistic transmission model calibrated using estimates of the within-herd reproduction rate and empirical cattle movement data from four regions of Ethiopia showed that a 1-year end point efficacy of 24% could be achieved. Although not eliminating disease, BCG vaccination could potentially reduce transmission of bovine tuberculosis by 89% over ensuing decades of consistent vaccination. —Caroline Ash
Structured Abstract
INTRODUCTION
Bovine tuberculosis (bTB) poses a substantial global threat to animal health, food security, and human well-being. Although proven effective in many high-income countries, the traditional test-and-slaughter approach for bTB control is expensive and impractical for socioeconomic reasons in many regions where the disease remains endemic. This has necessitated a need for alternative bTB control strategies, with Bacille Calmette-Guérin (BCG) vaccination presenting a promising option. However, the effectiveness of BCG in controlling bTB by reducing onward transmission remains unclear. This study investigated both the direct and previously unexplored indirect effects of BCG vaccination on bTB transmission in cattle, thereby providing key missing insights for control.
RATIONALE
Traditional vaccine efficacy evaluations cannot measure the impact of vaccination on reducing onward transmission from infected individuals. This mode of action of vaccination is critical for the evaluation of BCG in cattle because the primary effect is to reduce the extent and rate of progression of lesions rather than to provide sterilizing protection. Our study addresses this gap by performing a natural transmission experiment with bTB in cattle, using a crossover design approach. This method enabled a more realistic and robust assessment of BCG’s true impact on bTB transmission, quantifying both the direct efficacy of BCG as well as its effect on reducing transmission. We developed a mechanistic transmission model to explore the potential of using BCG vaccination in Ethiopia, where the transmission risk of bTB varies considerably between herds and the relatively infrequent trading of animals is projected to contribute to a gradual yet substantial increase in prevalence.
RESULTS
The natural transmission study showed a 74% reduction in bTB transmission [95% credible interval (CrI): 46 to 89%] in vaccinated as compared with unvaccinated animals. This substantial indirect effect of BCG vaccination exceeded the observed direct protection against infection (58%; 95% CrI: 34 to 73%), and the combined effects translated to a total vaccine efficacy of 89% (95% CrI: 74 to 96%).
Vaccinated animals exhibited substantially lower total visible lesion scores compared with unvaccinated controls, which is consistent with the notion that BCG vaccination reduces disease severity and potentially infectiousness.
A stochastic metapopulation transmission model, calibrated with data from Ethiopia, suggests that routine calfhood BCG vaccination has the potential to prevent the predicted expansion of bTB in dairy herds and bring the population average reproduction ratio below 1 within as few as 10 years, resulting in a substantial decrease in predicted bTB prevalence as compared with baseline scenarios without vaccination. The results highlight the critical importance of the combined direct and indirect effects of BCG vaccination in enabling bTB elimination.
The findings suggest that BCG vaccination represents an important tool for bTB control, particularly in resource-limited settings where traditional methods are impractical. The results also suggest that achieving elimination through vaccination alone would require a long-term commitment, as the full benefits may take decades to be realized. Our studies highlight a need for further research on the duration of efficacy, including the potential for extending protection through revaccination, as well as the impact on cross-species transmission.
CONCLUSION
Our study demonstrates remarkable and previously unrecognized indirect effects of BCG vaccination on bTB transmission, extending beyond its direct protective effect. Scenario analyses with mechanistic models for transmission in Ethiopia suggest that implementation of BCG vaccination may enable effective bTB control and progress toward elimination. Moreover, these findings suggest that BCG may provide an effective method of control in resource-limited settings where current test-and-slaughter approaches are unfeasible. Lastly, the crossover trial design incorporating natural transmission provides a general framework for studying other vaccines and interventions aimed at reducing onward transmission of TB, with broad applicability to other infectious diseases of animals, including humans.
Quantifying BCG vaccination’s total efficacy against bovine tuberculosis.
Sentinel calves, both BCG-vaccinated and unvaccinated, were exposed to seeder cattle to measure direct efficacy through IGRA-conversion times over 12 months. Subsequently, these sentinels were used to determine BCG’s indirect transmission-reducing effects, and the results helped inform development of models for evaluating TB elimination strategies.
Abstract
Bacillus Calmette-Guérin (BCG) is a routinely used vaccine for protecting children against Mycobacterium tuberculosis that comprises attenuated Mycobacterium bovis. BCG can also be used to protect livestock against M. bovis; however, its effectiveness has not been quantified for this use. We performed a natural transmission experiment to directly estimate the rate of transmission to and from vaccinated and unvaccinated calves over a 1-year exposure period. The results show a higher indirect efficacy of BCG to reduce transmission from vaccinated animals that subsequently become infected [74%; 95% credible interval (CrI): 46 to 98%] compared with direct protection against infection (58%; 95% CrI: 34 to 73%) and an estimated total efficacy of 89% (95% CrI: 74 to 96%). A mechanistic transmission model of bovine tuberculosis (bTB) spread within the Ethiopian dairy sector was developed and showed how the prospects for elimination may be enabled by routine BCG vaccination of cattle.
