A Meta-Analysis of the Effect of Bacillus Calmette-Guérin Vaccination Against Bovine Tuberculosis: Is Perfect the Enemy of Good?

Abstract

More than 50 million cattle are likely exposed to bovine tuberculosis (bTB) worldwide, highlighting an urgent need for bTB control strategies in low- and middle-income countries (LMICs) and other regions where the disease remains endemic and test-and-slaughter approaches are unfeasible. While Bacillus Calmette-Guérin (BCG) was first developed as a vaccine for use in cattle even before its widespread use in humans, its efficacy against bTB remains poorly understood. To address this important knowledge gap, we conducted a systematic review and meta-analysis to determine the direct efficacy of BCG against bTB challenge in cattle, and performed scenario analyses with transmission dynamic models incorporating direct and indirect vaccinal effects (“herd-immunity”) to assess potential impact on herd level disease control. The analysis shows a relative risk of infection of 0.75 (95% CI: 0.68, 0.82) in 1,902 vaccinates as compared with 1,667 controls, corresponding to a direct vaccine efficacy of 25% (95% CI: 18, 32). Importantly, scenario analyses considering both direct and indirect effects suggest that disease prevalence could be driven down close to Officially TB-Free (OTF) status (<0.1%), if BCG were introduced in the next 10-year time period in low to moderate (<15%) prevalence settings, and that 50–95% of cumulative cases may be averted over the next 50 years even in high (20–40%) disease burden settings with immediate implementation of BCG vaccination. Taken together, the analyses suggest that BCG vaccination may help accelerate control of bTB in endemic settings, particularly with early implementation in the face of dairy intensification in regions that currently lack effective bTB control programs.

Evaluation of the Efficacy of BCG in Protecting Against Contact Challenge With Bovine Tuberculosis in Holstein-Friesian and Zebu Crossbred Calves in Ethiopia

“…Similar to the study in New Zealand, the infection pressure was low as contact challenge was conducted in a herd with bTB prevalence of 24%. Although the efficacy value recorded by the present study was within the range of BCG efficacy (0 and 75%) reported from experimental studies and field trials in cattle by different researchers from different countries [reviewed by ( 19 , 21 )], the use of 100% positive seeders as a source of infection could have contributed to the lower efficacy value recorded, as compared with those studies conducted in Mexico, New Zealand, and Chile.…”

“…The animal and public health risks dictate that controls warrant implementation. The lack of funding to underpin a test and slaughter control program in Ethiopia, in common with other low-and middle-income countries (16), means that vaccination is an attractive alternative where the disease is endemic at high prevalence (17)(18)(19).…”

“…BCG could be a potential vaccine candidate for the control of tuberculosis in cattle (19)(20)(21). Several evaluations have been undertaken to determine a protective capacity of BCG in cattle since 1911 (20)(21)(22)(23).…”

“…Several explanations were given for the observed variability of efficacy of BCG including variation in the strain and dose of BCG used [reviewed by (21)], challenge model (5,24), previous exposure to environmental mycobacteria (25,26), and breed and health status of study animals (11,(27)(28)(29). In general, a recent meta-analysis reported a relatively low direct protection of BCG against infection with a pooled efficacy estimate of 25%, and significant reduction in the frequency and severity of pathology of bTB in vaccinated animals (19).…”

Cellular and Cytokine Responses in Lymph Node Granulomas of Bacillus Calmette Guérin (BCG)-Vaccinated and Non-vaccinated Cross-Breed Calves Naturally Infected With Mycobacterium bovis

“…But in general, it was observed that both gross and microscopic pathology were relatively less severe in vaccinated calves than in non-vaccinated calves. Substantiating this observation, a recently conducted meta-analysis suggested that BCG vaccination may help in accelerate control of bTB in endemic settings by inducing immunity against M. bovis and also limiting the progress TB lesion at the site of infection ( 33 ).…”