Veterinary Epidemiology

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Browsing Veterinary Epidemiology by Author "Abebe Fromsa"

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    Bovine Tuberculosis in Central Ethiopia: Epidemiology, BCG Efficacy in Reducing Transmission, and Performance of Defined Antigen Cocktails for Differentiating Infected from Vaccinated Crossbred Cattle
    (Addis Abeba University, 2025) Abebe Fromsa; Prof. Balako Gumi; Prof. Gobena Ameni
    : Bovine tuberculosis (bTB) is a threat to animal health, the livestock economy,food security, and human safety. Although animal level prevalence ranges from 25% to 39% and herd prevalence exceeds 50% in intensive dairy farms in central Ethiopia, control measures are lacking. The conventional test-and-slaughter strategy is resource-intensive and unaffordable for low- and middle-income countries (LMICs) such as Ethiopia. This necessitates a cost-effective alternative control strategy. Bacillus Calmette-Guérin (BCG) vaccination may constitute a cost-effective approach to control bTB in LMICs and regions with wildlife reservoirs. A meta-analysis of previous BCG vaccine evaluation studies demonstrated limited overall direct efficacy of 25% and additional partial protection by reducing the frequency and severity of disease pathology. Whether this partial protective effect translates into indirect protection through a reduction in the infectiousness of vaccinated animals has not been evaluated. Besides, since the interference of the BCG vaccine with the tuberculin skin testing is a major hindrance to the deployment of BCG vaccination for cattle, there is also a need to adopt a diagnostic test that differentiates infected from vaccinate animals (DIVA). On top of these, a slaughterhouse survey was conducted to identify hotspots of bTB in central Ethiopia to prioritize targeted control measures. Objectives: The objectives of this study include to quantify the direct and indirect efficacies of BCG vaccination in crossbred cattle, evaluate the diagnostic performance of defined peptide antigen cocktails (ESAT-6, CFP10, and Rv3615c) in differentiating infected from vaccinated animals (DIVA), assess the practical implications of routine vaccination on the spread of bTB in the emerging dairy sector, and estimate the prevalence and identify the causative agents of bTB in cattle in central Ethiopia. Methodology: A natural transmission experiment was conducted using a crossover design in two phases, each lasting for one year to evaluate both the direct and indirect effects of BCG vaccination in reducing the transmission of bTB. Sixty-seven unvaccinated control and 67 vaccinated calves were exposed to an equal number of respective seeders eight weeks postvaccination and maintained in contact for twelve months during each phase. Sixty-five unvaccinated control and 62 vaccinated calves underwent postmortem tests. Skin and IGRA tests were conducted using tuberculin and DIVA antigen cocktails every four and two months, respectively. For efficacy evaluation, calves that ever tested positive for DIVA antigens in the IGRA test were considered infected and potentially infectious. Then a mechanistic transmission model calibrated using within-herd basic reproduction number (Ro) and empirical cattle movement data was used to explore the long-term effect of routine BCG vaccination in controlling bTB in the Ethiopian dairy sector. The performance of DIVA antigen cocktails was compared to tuberculin in both IGRA and skin test formats. A slaughterhouse survey was conducted in Central Ethiopia to assess the prevalence, risk factors, and causative agents of bTB. The causative agents were identified using multiplex quantitative PCR (m-qPCR) in all culture-positive samples. Result: The study found a significantly lower total visible lesion score in vaccinated animals compared to unvaccinated controls and a reduction in bTB transmission of 74% (95% CI: 46– 89%) among vaccinated animals compared to unvaccinated controls. The direct efficacy was 58% (95% CI: 34%–73%). The combined direct and indirect effects resulted in a total vaccine efficacy of 89% (95% CI, 74–96%). The estimated Ro, representing the average number of secondary cases per infectious individual was 3.1 (95% CI: 2–4) in unvaccinated group while it was 0.3 (95% CI: 0.1–0.7) in the vaccinated group. A mechanistic transmission model suggests that routine neonatal calf vaccination has the potential to reduce the average population Ro to below 1 within 10 years, presenting significant opportunities for the control and elimination of bTB in cattle. Eight weeks after vaccination, but before exposure to infected seeder animals, the specificities of IGRA and skin test-based defined antigen cocktails were 98.5% and 94.0%, respectively. However, at the end of the experiment, the sensitivities of these tests were 46% and 47%, respectively, which were similar with 45% sensitivity of the comparative tuberculin test (CCT). A slaughterhouse survey revealed the ongoing challenge of bTB in Central Ethiopia, with a prevalence of 2.3% bTB-related lesions and an eleven-fold greater risk in crossbred cattle than in local zebu cattle. All mycobacterial species isolated from experimental and slaughterhouse cattle were identified as M. bovis, except for two cases from the slaughterhouse. One of these cases exhibited co-infection with M. bovis and M. tuberculosis, while the other was co-infected with M. bovis and M. caprae. However, no positive M. orygis was detected in any of culture-positive samples. Conclusions: The study revealed previously unrecognized superior indirect effects of BCG on bTB transmission compared to its direct protective effect against infection. Scenario analyses using mechanistic models indicate that BCG vaccination may enable effective control of bTB and contribute to elimination efforts. DIVA antigens demonstrated high specificity in BCGvaccinated cattle, highlighting their importance for potential integration into BCG vaccination programs for bTB control. These findings hold significant implications for resource-limited settings where the test-and-slaughter strategy is not feasible, while vaccination combined with DIVA testing remains a beneficial and effective approach. The higher risk of bTB in crossbred cattle underscores the necessity for targeted interventions, particularly in crossbred cattle predominantly raised in intensive dairy production systems.