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

Berecha Bayissa,Adane Worku,Gobena Ameni,Stefan Berg,Yemisrach Zeleke,Andrew Conlan,The Ethicobots Consortium ,Mahlet Chanyalew,Balako Gumi,H Martin Vordermeier,R Glyn Hewinson,James L N Wood,Aboma Zewude,Asegedech Sirak

doi:10.3389/fvets.2021.702402

Abstract

Bovine tuberculosis (bTB) is prevalent in intensive dairy farms in Ethiopia. Vaccination could be an alternative control approach given the socio-economic challenges of a test-and-slaughter control strategy. The efficacy of the BCG was evaluated on 40 Holstein-Friesian (HF) and zebu crossbred calves recruited from single intradermal cervical comparative tuberculin (SICCT) test negative herds and randomly allocated into two groups. Twenty-two calves were vaccinated within 2 weeks of age, and 18 were kept as a control. Six weeks post-vaccination, the two groups were exposed and kept mixed with known SICCT test positive cows for 1 year. Immune responses were monitored by interferon gamma (IFN-γ) release assay (IGRA), SICCT test, and antibody assay. Vaccinated calves developed strong responses to the SICCT test at the sixth week post-vaccination, but did not respond to ESAT-6/CFP-10 peptide antigen-based IGRA. During the exposure, IFN-γ response to the specific peptide cocktail [F(2.44, 92.67) = 26.96; p < 0.001] and skin reaction to the specific proteins cocktail [F(1.7, 64.3); p < 0.001] increased progressively in both groups while their antibody responses were low. The prevalence of bTB was 88.9% (95% CI: 65.3–98.6) and 63.6% (95% CI: 40.7–83.8) in the control and vaccinated calves, respectively, based on Mycobacterium bovis isolation, giving a direct protective efficacy estimate of 28.4% (95% CI: −2.7 to 50.1). The proportion of vaccinated calves with lesion was 7.0% (34/484) against 11.4% (45/396) in control calves, representing a 38% (95% CI: 5.8–59.4) reduction of lesion prevalence. Besides, the severity of pathology was significantly lower (Mann–Whitney U-test, p < 0.05) in vaccinated (median score = 2.0, IQR = 0–4.75) than in control (median score = 5, IQR = 3.0–6.25) calves. Moreover, survival from M. bovis infection in vaccinated calves was significantly (log-rank test: χ2 = 6.749, p < 0.01) higher than that of the control calves. In conclusion, the efficacy of BCG was low, but the reduced frequency and severity of lesion in vaccinated calves could suggest its potential role in containing onward transmission.

Highlights

In Ethiopia, bTB is an endemic cattle disease [1] characterized by the progressive development of granulomatous lesions in the respiratory tract and other tissues of the infected host [2]
The experiment was undertaken at the National Animal Health Diagnostic and Investigation Center (NAHDIC) at Sebeta, which is located 25 km southwest of Addis Ababa, the capital city of Ethiopia
The IFN-γ response to PPD (BA) increased after vaccination in the vaccinated calves attaining a peak at the third week post-vaccination with median OD450 value of 0.29 (IQR = 0.02–0.67) and remained higher with median

Summary

INTRODUCTION

In Ethiopia, bTB is an endemic cattle disease [1] characterized by the progressive development of granulomatous lesions in the respiratory tract and other tissues of the infected host [2]. 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]. 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]. Further studies are needed to resolve the large difference in reported efficacy of the vaccine and to consider its use in crossbred cattle (HF and zebu cross) preferred in Ethiopia for the expansion of the dairy sector, as no BCG efficacy trial has been conducted in them. We perform a pilot study of a protein cocktail with DIVA (Differentiating Infected from Vaccinated Animal) properties [30] to understand its potential as a skin test in distinguishing BCG vaccination from bovine TB infection in crossbred cattle

MATERIALS AND METHODS

RESULTS

DISCUSSION

CONCLUSION

ETHICS STATEMENT