Catheter-directed therapy for acute pulmonary embolism: results of a multicenter national registry.

INTRODUCTION AND OBJECTIVES: Catheter-directed therapy (CDT) for acute pulmonary embolism (PE) is an emerging therapy that combines heterogeneous techniques. The aim of the study was to provide a nationwide contemporary snapshot of clinical practice and CDT-related outcomes. METHODS: This Investigator-initiated multicenter registry aimed to include consecutive patients with intermediate-high risk (IHR) or high-risk (HR), acute PE eligible for CDT. The primary outcome of the study was in-hospital all-cause death. RESULTS: A total of 253 patients were included, of whom 93 (36.8%) had HR-PE, and 160 (63.2%) had IHR-PE with a mean age of 62.3±15.1 years. Local thrombolysis was performed in 70.8% and aspiration thrombectomy in 51.8%, with 23.3% of patients receiving both. However, aspiration thrombectomy was favored in the HR-PE cohort (80.6% vs 35%; P<.001). Only 51 patients (20.2%) underwent CDT with specific PE devices. The success rate for CDT was 90.9% (98.1% of IHR-PE patients vs 78.5% of HR-PE patients, P<.001). In-hospital mortality was 15.5%, and was highly concentrated in the HR-PE patients (37.6%) and significantly lower in IHR-PE patients (2.5%), P<.001. Long-term (24-month) mortality was 40.2% in HR-PE patients vs 8.2% in IHR-PE patients (P<.001). CONCLUSIONS: Despite the high success rate for CDT, in-hospital mortality in HR-PE is still high (37.6%) compared with very low IHR-PE mortality (2.5%).

Value of exercise right heart catheterization in the differential diagnosis of chronic thromboembolic pulmonary disease.

INTRODUCTION AND OBJECTIVES: Chronic thromboembolic disease refers to the presence of chronic thrombotic pulmonary vascular thrombosis without pulmonary hypertension (PH) at rest but with exercise limitation after pulmonary embolism (PE). Our aim was to evaluate the hemodynamic response to exercise in these patients and its correlation with the values reached in cardiopulmonary exercise testing. METHODS: We included symptomatic patients with persistent pulmonary thrombosis after PE. We excluded patients with left heart disease or significant PH (mean pulmonary arterial pressure [mPAP] >25mmHg, pulmonary vascular resistance >3 WU, and pulmonary capillary wedge pressure [PCWP] >15mmHg). Cardiopulmonary exercise testing and exercise right heart catheterization were performed. Exercise-induced precapillary PH was defined as mPAP/CO slope >3 and PCWP/CO slope <2mmHg/l/min. The hemodynamic response and the values obtained in cardiopulmonary exercise testing were compared between patients with and without exercise-induced precapillary PH. RESULTS: We studied 36 patients; 4 were excluded due to incomplete hemodynamic data. Out of the 32 patients analyzed; 3 developed a pathological increase in PCWP. Among the remaining 29 patients (mean age, 49.4±13.7 years, 34.5% women), 13 showed exercise-induced PH. Resting mPAP was higher in those who developed exercise-induced PH (23.3±5.4 vs 19.0±3.8mmHg; P=.012), although CO was similar in the 2 groups. Patients with exercise-induced PH exhibited data of ventilatory inefficiency with reduced values of end-tidal CO2 pressure at the anaerobic threshold (32.8±3.0 vs 36.2±3.3mmHg; P=.021) and a higher Ve/VCO2 slope (34.2±4.8 vs 30.7±5.0; P=.049). CONCLUSIONS: Exercise limitation and ventilatory inefficiency could be attributable to exercise-induced precapillary PH in a subgroup of patients with persistent pulmonary thrombosis and dyspnea.

Initial results of investigator initiated international database on catheter directed therapy of acute pulmonary embolism.

BACKGROUND: Catheter directed therapies (CDT) are widely used in the treatment of acute pulmonary embolism (PE). A multicenter registry was organized to evaluate their application in real life and to determine efficacy and safety of these procedures. Local experience of participating centers in percutaneous techniques for PE treatment was assessed. METHODS: An internet-based registry was designed to collect clinical, echocardiographic and laboratory data of consecutive PE patients treated with CDT in participating centers between 2017 and 2022. RESULTS: Under analysis were 145 consecutive patients with acute PE, aged 61 ± 15 years, treated with CDT in 7 centers: 50 (34.5%) patients with high-risk PE (HRPE), and 95 (65.5%) patients with intermediate-high risk PE (IHRPE). 100 (69%) patients were treated with dedicated devices, in 45 (31%) subjects a pigtail catheter was used. Total PE or CDT related in-hospital mortality in HRPE reached 14% (7 patients), while in IHRPE 3.2% (3 patients) (p = 0.032). 50% of PE or CDT related deaths occurred in patients treated with a pigtail catheter. All-cause mortality in 145 patients was 9.7%, and it was higher in HRPE than in IHRPE (18% vs. 5.3%, p = 0.019). The use of pigtail catheters compared to dedicated systems was associated with higher mortality (20% vs. 5%, p = 0.01). CONCLUSIONS: Catheter directed therapies is a real option of treating PE. It was used as primary therapy also in patients without contraindication for thrombolysis suggesting that clinical practice does not always follow current PE guidelines. Patients treated with dedicated CDT systems had a higher survival rate than subjects treated with pigtail catheters.

Comparison of the pathological outcome and disease progression of two Mycobacterium caprae experimental challenge models in goats: endobronchial inoculation vs. intranasal nebulization.

Background: Goats are natural hosts of tuberculosis (TB) and are a valid animal model to test new vaccines and treatments to control this disease. In this study, a new experimental model of TB in goats based on the intranasal nebulization of Mycobacterium caprae was assessed in comparison with the endobronchial route of infection. Methods: Fourteen animals were divided into two groups of seven and challenged through the endobronchial (EB) and intranasal (IN) routes, respectively. Clinical signs, rectal temperature, body weight, and immunological responses from blood samples were followed up throughout the experiment. All goats were euthanized at 9 weeks post-challenge. Gross pathological examination, analysis of lung lesions using computed tomography, and bacterial load quantification in pulmonary lymph nodes (LNs) by qPCR were carried out. Results: The IN-challenged group showed a slower progression of the infection: delayed clinical signs (body weight gain reduction, peak of temperature, and apparition of other TB signs) and delayed immunological responses (IFN-γ peak response and seroconversion). At the end of the experiment, the IN group also showed significantly lower severity and dissemination of lung lesions, lower mycobacterial DNA load and volume of lesions in pulmonary LN, and higher involvement of the nasopharyngeal cavity and volume of the lesions in the retropharyngeal LN. Conclusion: The results indicated that the IN challenge with M. caprae induced pathological features of natural TB in the lungs, respiratory LN, and extrapulmonary organs but extremely exaggerating the nasopharyngeal TB pathological features. On the other hand, the EB route oversized and accelerated the pulmonary TB lesion progression. Our results highlight the need to refine the inoculation routes in the interest of faithfully reproducing the natural TB infection when evaluating new vaccines or treatments against the disease.

Outcome of moderate-severe tricuspid regurgitation after pulmonary endarterectomy or balloon pulmonary angioplasty.

INTRODUCTION AND OBJECTIVES: The management of persistent moderate-severe tricuspid regurgitation (TR) in patients with chronic thromboembolic pulmonary hypertension after treatment with pulmonary endarterectomy (PEA) or balloon pulmonary angioplasty (BPA) is not well defined. This study aimed to analyze the progression and predictors of significant persistent postintervention TR and its prognostic impact. METHODS: This single-center observational study included 72 patients undergoing PEA and 20 who completed a BPA program with a previous diagnosis of chronic thromboembolic pulmonary hypertension and moderate-to-severe TR. RESULTS: The postintervention prevalence of moderate-to-severe TR was 29%, with no difference between the PEA- or BPA-treated groups (30.6% vs 25% P=.78). Compared with patients with absent-mild postprocedure TR, those with persistent TR had higher mean pulmonary arterial pressure (40.2±1.9 vs 28.5±1.3mmHg P <.001), pulmonary vascular resistance (472 [347-710] vs 282 [196-408] dyn.s/cm5; P <.001), and right atrial area (23.0 [21-31] vs 16.0 [14.0-20.0] P <.001). The variables independently associated with persistent TR were pulmonary vascular resistance> 400 dyn.s/cm5 and postprocedure right atrial area> 22cm2. No preintervention predictors were identified. The variables associated with increased 3-year mortality were residual TR and mean pulmonary arterial pressure> 30mmHg. CONCLUSIONS: Residual moderate-to-severe TR following PEA-PBA was associated with persistently high afterload and unfavorable postintervention right chamber remodeling. Moderate-to-severe TR and residual pulmonary hypertension were associated with a worse 3-year prognosis.

Effectiveness and Safety of Balloon Pulmonary Angioplasty for the Treatment of Patients with Persistent Pulmonary Hypertension after Pulmonary Endarterectomy.

(1) Background: Pulmonary endarterectomy (PEA) is the "gold standard" treatment for operable patients with chronic thromboembolic pulmonary hypertension (CTEPH). Persistent pulmonary hypertension (PH) after PEA confers a worse prognosis. Balloon pulmonary angioplasty (BPA) could represent a useful therapy in this setting, but evidence about its effectiveness and safety in patients with previous PEA is limited. (2) Methods: A total of 14 patients with persistent PH after PEA were treated with BPA in a single PH center. Hemodynamic and clinical effects of BPA and complications of the procedure were retrospectively collected. (3) Results: After BPA, the mean pulmonary arterial pressure fell from 50.7 ± 15.3 mmHg to 38.0 ± 7.9 mmHg (25.0% decrease; 95% confidence interval (CI) 14.0-35.5%; p = 0.01). Pulmonary vascular resistances were reduced from 8.5 ± 3.6 WU to 5.3 ± 2.2 WU (37.6% decrease; 95% CI 18.8-56.5%; p = 0.01). WHO functional class was also improved with BPA. Severe BPA-related complications were infrequent and no periprocedural deaths were observed. (4) Conclusions: BPA is an effective and safe therapy for patients with CTEPH and persistent PH after PEA.

Influence of Laboring People's Mobility and Positional Changes on Birth Outcomes in Low-Dose Epidural Analgesia Labor: A Systematic Review with Meta-Analysis.

INTRODUCTION: Freedom of movement has been identified as a key issue for pregnant individuals during the birthing process, even if they opt for epidural analgesia, which has relegated people to more static positions during birth for many years. The aims of this systematic review were to evaluate the influence of mobility and positional changes on perinatal and neonatal outcomes in people in labor with epidural analgesia, describe the range of movement interventions used during the first and second stage of labor, and describe the level of motor blockade among people with low-dose epidural analgesia. METHODS: Bibliographic databases (Web of Science, Cochrane, CINAHL) were consulted from December 2020 to January 2021. The articles selected were clinical trials and observational or analytical studies, the subject of which was mobilization during labor in people with epidural analgesia. The outcome measures were mode of birth, duration of labor, and extrauterine adaptation after birth. A narrative synthesis was used to describe the types of movements interventions employed during the stages of labor and the level of motor blockade among people with low-dose epidural analgesia. RESULTS: Ten articles were selected (8 clinical trials, one cross-sectional study, and one quasiexperimental study), with a total sample of 6086 individuals. A meta-analysis showed nonsignificant results between groups for mode of birth (relative risk [RR], 1.00; 95% CI, 0.87-1.14), duration of labor (RR, 1.64; 95% CI, -34.57 to 37.86), and extrauterine adaptation after birth (RR, 0.86; 95% CI, 0.39-1.93). There was heterogeneity among studies in the type of movement interventions used during the first and second stage of labor. DISCUSSION: Although no clear benefit was observed for mobilization in epidural labor, no detrimental effects were found either, so perinatal care providers should encourage mobilization if the laboring person so desires, throughout the entire childbirth process.

Spontaneous coronary artery dissection and ST-segment elevation myocardial infarction: Does clinical presentation matter?

BACKGROUND: Some patients with spontaneous coronary artery dissection (SCAD) present as ST-segment-elevation myocardial infarction (STEMI). This study evaluates the characteristics, management and outcomes of SCAD patients presenting as STEMI compared to non-ST-segment elevation myocardial infarction (NSTEMI). METHODS: We analysed data from consecutive patients included in the prospective Spanish Registry on SCAD. All coronary angiograms were centrally reviewed. All adverse events were adjudicated by an independent Clinical Events Committee. RESULTS: Between June 2015 to December 2020, 389 patients were included. Forty-two percent presented with STEMI and 56% with NSTEMI. STEMI patients showed a worse distal flow (TIMI flow 0-1 38% vs 19%, p < 0.001) and more severe (% diameter stenosis 85 ± 18 vs 75 ± 21, p < 0.001) and longer (42 ± 23 mm vs 35 ± 24 mm, p = 0.006) lesions. Patients with STEMI were more frequently treated with percutaneous coronary intervention (PCI) (31% vs 16%, p < 0.001) and developed more frequently left ventricular systolic dysfunction (21% vs 8%, p < 0.001). No differences were found in combined major adverse events during admission (7% vs 5%, p = 0.463), but in-hospital reinfarctions (5% vs 1.4%, p = 0.039) and cardiogenic shock (2.6% vs 0%, p = 0.019) were more frequently seen in the STEMI group. At late follow-up (median 29 months) no differences were found in the incidence of major adverse cardiac and cerebrovascular events (13% vs 13%, p-value = 0.882) between groups. CONCLUSIONS: Patients with SCAD and STEMI had a worse angiographic profile and were more frequently referred to PCI compared to NSTEMI patients. Despite these disparities, both short and long-term prognosis were similar in STEMI and NSTEMI SCAD patients.

Multivessel spontaneous coronary artery dissection: Clinical features, angiographic findings, management, and outcomes.

BACKGROUND: Spontaneous coronary artery dissection (SCAD) is a rare cause of acute coronary syndrome. Multivessel (MV) SCAD is a challenging clinical presentation that might be associated to a worse prognosis compared with patients with single-vessel (SV) involvement. METHODS: The Spanish multicentre nationwide prospective SCAD registry included 389 consecutive patients. Patients were classified, according to the number of affected vessels, in SV or MV SCAD. Major adverse events (MAE) were analyzed during hospital stay and major cardiac or cerebrovascular adverse events (MACCE) at long-term clinical follow-up. RESULTS: A total of 41 patients (10.5%) presented MV SCAD. These patients had more frequently a previous history of hypothyroidism (22% vs 11%, p = 0.04) and anxiety disorder (32% vs 16%, p = 0.01). MV SCAD patients presented more often as non-ST segment elevation myocardial infarction (73% vs 52%, p = 0.01) and showed less frequently type 1 angiographic lesions (12% vs 21%, p = 0.04). An impaired initial Thrombolysis In Myocardial Infarction (TIMI) flow 0-1 was less frequent (14% vs 29%, p < 0.01) in MV SCAD. In both groups, most patients were treated conservatively (71% vs 79%, p = NS). No differences were found regarding in-hospital MAE or MACCE at late follow-up (median 29 ± 11 months). However, the rate of stroke was higher in MV SCAD patients, both in-hospital (2.4% vs 0%, p < 0.01) and at follow-up (5.1% vs 0.6%, p = 0.01). CONCLUSIONS: Patients with MV SCAD have some distinctive clinical and angiographic features. Although composite clinical outcomes, in-hospital and at long-term follow-up, were similar to those seen in patients with SV SCAD, stroke rate was significantly higher in patients with MV SCAD.

Balloon pulmonary angioplasty can be an effective and safe therapeutic option in non-surgical elderly patients.

Background: Advanced age, frailty, and age-related comorbidities are the major causes of pulmonary endarterectomy disqualification in patients with chronic thromboembolic pulmonary hypertension (CTEPH). Balloon pulmonary angioplasty (BPA) is an attractive and less invasive therapy for elderly patients. However, information about the safety, procedure tolerance, and effectiveness of BPA in elderly patients is limited. Objective and methods: We aimed to analyze the safety, tolerance, and efficacy of BPA in CTEPH patients aged ≥70 years. This observational, descriptive, and retrospective series included consecutive patients aged ≥70 years, who underwent completed or interrupted BPA programs at a pulmonary hypertension reference center between May 2013 and May 2022. Results: We enrolled 155 patients in our institution's BPA program. Among these, 33 patients were aged ≥70 years (mean age, 76.4 years; women, 75.8%) and had finished or interrupted BPA programs. In this cohort, we performed 116 BPA procedures (average, 3.6 ± 1.8 sessions/patient). Among the 33 patients, 19 (57.6%) completed treatment for all lobes, while the BPA program was interrupted in the remaining 14 (42.4%). Among all 33 patients, BPA was associated with a significant reduction in mean pulmonary arterial pressure (39.2 ± 9.3 vs. 32.8 ± 8.8 mmHg; p < 0.001) and pulmonary vascular resistance (6.7 ± 3.1 vs. 4.4 ± 2.0 WU; p < 0.001), along with an improvement in the cardiac index (2.5 ± 0.6 vs. 2.8 ± 0.7 L/min/m2; p = 0.04) with significant reductions in the N-terminal prohormone of brain natriuretic peptide level (pre-BPA, 353 pg/mL [207-1,960 pg/mL] vs. post-BPA, 167 pg/mL [73-629 pg/mL]; p = 0.03). The patients' functional class improved, and pulmonary hypertension-targeting drug requirements were significantly reduced. The pulmonary injury appeared in 3.4% of the 116 procedures, of which 50% were of grade 2. No patient of ≥70 years had grade 5 pulmonary injury. One periprocedural mortality was recorded (3%), and the median follow-up period was 2.8 years. The survival rate of the entire cohort at 1 and 3 years was 90.5 and 82.8%, respectively. Conclusion: BPA is an effective and safe approach in patients aged ≥70 years. It significantly improves patients' functional class, hemodynamic, and biomarkers, and reduces their pulmonary hypertension-targeting medical therapy requirements. These successes were achieved even though a significant percentage of patients did not complete the therapy. The rates of procedural complications and periprocedural mortality were low. Survival at 1 and 3 years was good in comparison to that of younger patients undergoing BPA.

Clinical outcomes in spontaneous coronary artery dissection.

OBJECTIVE: Spontaneous coronary artery dissection (SCAD) is an infrequent cause of acute coronary syndrome. Our aim was to assess adverse events at follow-up from a nationwide prospective cohort. METHODS: The Spanish Registry on SCAD (SR-SCAD) included patients from 34 hospitals. All coronary angiograms were analysed by two experts. Those cases with doubts regarding the diagnosis of SCAD were excluded. The angiographic SCAD classification by Saw et al was followed. Major adverse cardiovascular and cerebrovascular event (MACCE) was predefined as composite of death, myocardial infarction, unplanned revascularisation, SCAD recurrence or stroke. All events were assigned by a Clinical Events Committee. RESULTS: After corelab evaluation, 389 patients were included. Most patients were women (88%); median age 53 years (IQR 47-60). Most patients presented as non-ST-segment-elevation myocardial infarction (54%). A type 2 intramural haematoma (IMH) was the most frequent angiographic pattern (61%). A conservative initial management was selected in 78% of patients. At a median time of follow-up of 29 months (IQR 17-38), 46 patients (13%) presented MACCE, mainly driven by reinfarctions (7.6%) and unplanned revascularisations (6.2%). Previous history of hypothyroidism (HR 3.79; p<0.001), proximal vessel involvement (HR 2.69; p=0.009), type 2 IMH (HR 2.12; p=0.037) and dual antiplatelet therapy (DAPT) at discharge (HR 2.18; p=0.042) were independent predictors of MACCE. CONCLUSIONS: In this large prospective cohort of patients with SCAD, prognosis was overall favourable, with events mainly driven by reinfarctions or unplanned revascularisations. History of hypothyroidism, proximal vessel involvement, type 2 IMH and DAPT at discharge were associated with MACCE. TRIAL REGISTRATION NUMBER: NCT03607981.

Coronary Compression Following Percutaneous Pulmonary Valve Implantation Despite a Negative Balloon Sizing Test: Lessons Learnt From This Unusual Complication.

A 16-years-old male with prior diagnosis of situs inversus totalis and pulmonary atresia with interventricular communication underwent percutaneous pulmonary valve implantation 3 months after successful RVOT stenting following a negative balloon sizing test. Once finished the procedure, after consciousness recovery in the intensive care unit, the patient developed oppressive chest pain with very subtle electrocardiographic changes over his basal right bundle branch block. An urgent coronary angiography showed a severe stenosis in the proximal right coronary artery with TIMI 2 distal flow. Intravascular ultrasound imaging confirmed extrinsic compression. A 4 × 21 mm drug-eluting stent was successfully implanted relieving symptoms immediately. TIMI 3 flow was restored and good apposition and expansion were confirmed with intravascular ultrasound. A carefully review of the procedure showed that the pitfall responsible for this complication was the oversizing of the valve with respect to the size of the balloon used for the sizing test.

Phylogenetic relationships investigation of Mycobacterium caprae strains from sympatric wild boar and goats based on whole genome sequencing.

Tuberculosis (TB) in wildlife challenges epidemiological surveillance and disease control. An outbreak of TB was detected in a free-ranging wild boar population of a Natural Park in Catalonia (Spain) and the outbreak investigation was conducted in the area. During the study period (2015-2020), 278 wild boars were analysed by gross pathology, histopathology, mycobacterial culture and DVR-spoligotyping. In addition, all cattle (49) and goat (47) herds of the area were tested with tuberculin skin test. TB compatible lesions were detected in 21 wild boars, and Mycobacterium caprae was isolated in 17 of them with two different spoligotypes: SB0415 (13) and SB1908 (4). Only two goat herds showed TB positive animals that were subsequently slaughtered. M. caprae with the spoligotypes SB0416 and SB0415 were isolated from these animals. To investigate the phylogenetic relationships and the transmission chain of the outbreak, nine strains isolated from six wild boars and three goats of the study area were analysed by whole genome sequencing (WGS) followed by single nucleotide polymorphism (SNP) analysis by maximum likelihood and median-joining network inference methods. Results indicated that infected wild boars maintained M. caprae strains circulation in their own population and have likely transmitted the infection to goats, thus acting as TB reservoirs, compromising the success of livestock TB eradication campaigns and posing a risk for public health. The results also highlighted the usefulness of WGS followed by SNP analysis in providing relevant epidemiological information when detailed contact data are missing.

Clinical relevance of adding intravascular ultrasound to coronary angiography for the diagnosis of extrinsic left main coronary artery compression by a pulmonary artery aneurysm in pulmonary hypertension.

OBJECTIVES: We sought to assess the clinical value of adding intravascular ultrasound (IVUS) evaluation to coronary angiography (CA) to guide extrinsic left main coronary artery (LMCA) compression diagnosis and treatment in pulmonary hypertension (PH). BACKGROUND: LMCA compression due to a pulmonary artery aneurysm (PAA) is a severe complication of PH. Although guidelines encourage the use of IVUS for LMCA disease evaluation, it has hardly been used in this scenario. METHODS: We analyzed morbimortality of type 1 and 4 PH patients with clinically suspected LMCA compression by a PAA between 2010 and 2018 in a reference unit. LMCA compression was prospectively assessed with CA ± IVUS. Angiographic-LMCA compression was considered conclusive when LMCA stenosis>50% was present in four predetermined projections; inconclusive, when LMCA stenosis>50% was present in <4 projections and negative if no stenosis>50% was present. Patients with conclusive and inconclusive CA underwent IVUS. IVUS-LMCA compression was defined as systolic minimum lumen area < 6 mm2 . RESULTS: LMCA compression was suspected in 23/796 patients (3%). CA was conclusive for compression in 7(30.5%), inconclusive in 9(39%), and negative in 7(30.5%). IVUS confirmed LMCA compression in 6/7(86%) patients with conclusive CA and in 2/9(22%) with inconclusive CA. Patients fulfilling IVUS criteria for LMCA compression underwent stent implantation. At 20 months follow-up a composite end-point of death, stent restenosis/thrombosis, or lung transplant was reported in three patients (13%). CONCLUSIONS: CA can misdiagnose LMCA extrinsic compression. IVUS discriminates better whether significant compression by a PAA exists or not, avoiding unnecessary LMCA stenting. Patients treated following this strategy show a low rate of major clinical events at 20 months follow-up.

Immunogenicity and Protection against Mycobacterium caprae Challenge in Goats Vaccinated with BCG and Revaccinated after One Year.

Vaccination has been proposed as a supplementary tool for the control of tuberculosis in livestock. The long-term immunogenicity elicited by bacillus Calmette-Guerin (BCG) and the efficacy of revaccination were investigated in thirty goat kids distributed into three groups: unvaccinated controls, BCG (vaccinated at week 0) and BCG-BCG (vaccinated at weeks 0 and 56). Sixty-four weeks after the first vaccination, all animals were challenged with Mycobacterium caprae and examined post-mortem (pathology and bacterial load) at week 73. Antigen-specific interferon-gamma (IFN-γ) release was measured throughout the experiment. At week 59, peripheral blood mononuclear cells were stained for CD4, CD45RO and IFN-γ to determine the presence of antigen-specific cells secreting IFN-γ. The BCG-BCG group showed reductions in rectal temperatures, M. caprae DNA load in pulmonary lymph nodes (LN), the volume of lesions in pulmonary LN, mineralization in lungs, and higher weight gains compared to unvaccinated controls. IFN-γ responses were undetectable from 32 weeks after primary vaccination until revaccination, when the BCG-BCG group showed detectable IFN-γ production and a greater percentage of antigen-specific CD4+CD45RO+IFNγ+ and CD4-CD45RO+IFNγ+ cells compared to the BCG and control groups, which may be an indicator of the mechanisms of protection. Thus, re-vaccination of goats with BCG appears to prolong protection against infection with M. caprae.

Long-term efficacy of BCG vaccination in goat herds with a high prevalence of tuberculosis.

Vaccination of goats against tuberculosis (TB) has been promoted as an ancillary tool for controlling the disease in infected livestock herds. A three-year trial to assess the efficacy of BCG vaccine was carried out in five goat herds. At the beginning of the trial (month 0), all animals were tested for TB using thee different diagnostic tests. Animals negative to all tests were vaccinated with BCG and all replacement goat kids were also systematically vaccinated throughout the trial. All animals were tested by Interferon-gamma release assay (IGRA) using vaccine compatible reagents at months 6, 12, 24, and 36. The risk factors for TB infection were also evaluated. At the end of the study, four out of five farms showed variable reductions of the initial prevalence (93.5%, 28.5%, 23.2%, and 14.3% respectively), and an overall incidence reduction of 50% was observed in BCG vaccinated goats, although adult vaccinated goats showed higher incidences than vaccinated goat kids. The unvaccinated positive animals remaining in herds and adult BCG vaccinated goats significantly enhanced the risk of infection in vaccinated animals. A systematic vaccination of goats with BCG, together with the removal of positive unvaccinated animals, may contribute to reducing the TB prevalence in goat herds.