Immune Response to Tick-Borne Hemoparasites: Host Adaptive Immune Response Mechanisms as Potential Targets for Therapies and Vaccines.

Tick-transmitted pathogens cause infectious diseases in both humans and animals. Different types of adaptive immune mechanisms could be induced in hosts by these microorganisms, triggered either directly by pathogen antigens or indirectly through soluble factors, such as cytokines and/or chemokines, secreted by host cells as response. Adaptive immunity effectors, such as antibody secretion and cytotoxic and/or T helper cell responses, are mainly involved in the late and long-lasting protective immune response. Proteins and/or epitopes derived from pathogens and tick vectors have been isolated and characterized for the immune response induced in different hosts. This review was focused on the interactions between tick-borne pathogenic hemoparasites and different host effector mechanisms of T- and/or B cell-mediated adaptive immunity, describing the efforts to define immunodominant proteins or epitopes for vaccine development and/or immunotherapeutic purposes. A better understanding of these mechanisms of host immunity could lead to the assessment of possible new immunotherapies for these pathogens as well as to the prediction of possible new candidate vaccine antigens.

First data on microflora of loggerhead sea turtle (Caretta caretta) nests from the coastlines of Sicily.

Caretta caretta is threatened by many dangers in the Mediterranean basin, but most are human-related. The purposes of this research were: (i) to investigate microflora in samples from six loggerhead sea turtle nests located on the Sicilian coast and (ii) to understand microbial diversity associated with nests, with particular attention to bacteria and fungi involved in failed hatchings. During the 2016 and 2018 summers, 456 eggs and seven dead hatchling from six nests were collected. We performed bacteriological and mycological analyses on 88 egg samples and seven dead hatchlings, allowing us to isolate: Fusarium spp. (80.6%), Aeromonas hydrophila (55.6%), Aspergillus spp. (27.2%) and Citrobacter freundii (9%). Two Fusarium species were identified by microscopy and were confirmed by PCR and internal transcribed spacer sequencing. Statistical analyses showed significant differences between nests and the presence/absence of microflora, whereas no significant differences were observed between eggs and nests. This is the first report that catalogues microflora from C . caretta nests/eggs in the Mediterranean Sea and provides key information on potential pathogens that may affect hatching success. Moreover, our results suggest the need for wider investigations over extensive areas to identify other microflora, and to better understand hatching failures and mortality related to microbial contamination in this important turtle species.

Changes in cardiac Aquaporin expression during aortic valve replacement surgery with cardiopulmonary bypass.

OBJECTIVES: Cardiopulmonary bypass (CPB) use is an essential strategy for many cardiovascular surgeries. However, its use and duration have been associated with a higher rate of postoperative complications, such as low cardiac output syndrome due to myocardial oedema and dysfunction. Though Aquaporin water channels have been implicated in myocardial water balance, their specific role in this clinical scenario has not been established. METHODS: In a consecutive study of 17 patients with severe aortic stenosis undergoing aortic valve replacement surgery, 2 myocardial biopsies of the left ventricle were taken: 1 before and 1 after CPB use. Sociodemographic, clinical and laboratory data were collected. Western blot and immunohistochemistry studies were performed. RESULTS: After CPB use, there was a mean increase of ∼62% in Aquaporin 1 protein levels (P = 0.001) and a mean reduction of ∼38% in Aquaporin 4 protein levels (P = 0.030). In immunohistochemistry assays, Aquaporin 1 was found lining small blood vessels, while Aquaporin 4 formed a circular label in cardiomyocytes. There were no changes in the localization of either protein following CPB use. During the observed on-pump time interval, there was a 1.7%/min mean increase in Aquaporin 1 (P = 0.021) and a 2.5%/min mean decrease in Aquaporin 4 (P = 0.018). Myocardial interstitial oedema increased by 42% (95% confidence interval 31-54%) after CPB use. Patients who developed low cardiac output syndrome were in the upper half of the median percentage change of Aquaporin expression. CONCLUSION: Time-dependent changes in cardiac Aquaporin expression may be associated with myocardial oedema and dysfunction related to CPB use.

Incidental catch of loggerhead sea turtles (Caretta caretta) along the Sicilian coasts by longline fishery.

It has been estimated that 44,000 Caretta caretta turtles die every year due to anthropomorphic activity in the Mediterranean Sea, and that longline fishing is one of the most significant causes of mortality. A total of 482 specimens of C. caretta were rescued from different parts of the Sicilian coast (Mediterranean Sea) from 2014 to 2016. The most numerous stranding was recorded during the spring and summer seasons, mainly along the north and eastern coasts of Sicily. The curved carapace length for all the specimens ranged from between 19 and 95 cm and most of these were young or sub adults. The highest number of strandings was recorded in 2014 and 2015, with 206 and 169 individuals, respectively. A total of 66 live specimens out of 239 were successfully rehabilitated and released after surgery or drug therapy; fishing hooks were found in 129 specimens in different parts of the digestive tract with greater frequency in the oesophagus (47.3%) followed by the gut (24.8%), stomach (14.7%), and mouth (13.2%). This paper will highlight the incidence of the incidental catch by longline fishing of C. caretta along the Sicilian coasts and also relate the size of ingested hooks to the size of examined specimens.

Infection and exposure to vector-borne pathogens in rural dogs and their ticks, Uganda.

BACKGROUND: In rural parts of Africa, dogs live in close association with humans and livestock, roam freely, and usually do not receive prophylactic measures. Thus, they are a source of infectious disease for humans and for wildlife such as protected carnivores. In 2011, an epidemiological study was carried out around three conservation areas in Uganda to detect the presence and determine the prevalence of vector-borne pathogens in rural dogs and associated ticks to evaluate the risk that these pathogens pose to humans and wildlife. METHODS: Serum samples (n = 105), blood smears (n = 43) and blood preserved on FTA cards (n = 38) and ticks (58 monospecific pools of Haemaphysalis leachi and Rhipicephalus praetextatus including 312 ticks from 52 dogs) were collected from dogs. Dog sera were tested by indirect immunofluorescence to detect the presence of antibodies against Rickettsia conorii and Ehrlichia canis. Antibodies against R. conorii were also examined by indirect enzyme immunoassay. Real time PCR for the detection of Rickettsia spp., Anaplasmataceae, Bartonella spp. and Babesia spp. was performed in DNA extracted from FTA cards and ticks. RESULTS: 99% of the dogs were seropositive to Rickettsia spp. and 29.5% to Ehrlichia spp. Molecular analyses revealed that 7.8% of the blood samples were infected with Babesia rossi, and all were negative for Rickettsia spp. and Ehrlichia spp. Ticks were infected with Rickettsia sp. (18.9%), including R. conorii and R. massiliae; Ehrlichia sp. (18.9%), including E. chaffeensis and Anaplasma platys; and B. rossi (1.7%). Bartonella spp. was not detected in any of the blood or tick samples. CONCLUSIONS: This study confirms the presence of previously undetected vector-borne pathogens of humans and animals in East Africa. We recommend that dog owners in rural Uganda be advised to protect their animals against ectoparasites to prevent the transmission of pathogens to humans and wildlife.

Control of tick infestations and pathogen prevalence in cattle and sheep farms vaccinated with the recombinant Subolesin-Major Surface Protein 1a chimeric antigen.

BACKGROUND: Despite the use of chemical acaricides, tick infestations continue to affect animal health and production worldwide. Tick vaccines have been proposed as a cost-effective and environmentally friendly alternative for tick control. Vaccination with the candidate tick protective antigen, Subolesin (SUB), has been shown experimentally to be effective in controlling vector infestations and pathogen infection. Furthermore, Escherichia coli membranes containing the chimeric antigen composed of SUB fused to Anaplasma marginale Major Surface Protein 1a (MSP1a) (SUB-MSP1a) were produced using a simple low-cost process and proved to be effective for the control of cattle tick, Rhipicephalus (Boophilus) microplus and R. annulatus infestations in pen trials. In this research, field trials were conducted to characterize the effect of vaccination with SUB-MSP1a on tick infestations and the prevalence of tick-borne pathogens in a randomized controlled prospective study. METHODS: Two cattle and two sheep farms with similar geographical locations and production characteristics were randomly assigned to control and vaccinated groups. Ticks were collected, counted, weighed and classified and the prevalence of tick-borne pathogens at the DNA and serological levels were followed for one year prior to and 9 months after vaccination. RESULTS: Both cattle and sheep developed antibodies against SUB in response to vaccination. The main effect of the vaccine in cattle was the 8-fold reduction in the percent of infested animals while vaccination in sheep reduced tick infestations by 63%. Female tick weight was 32-55% lower in ticks collected from both vaccinated cattle and sheep when compared to controls. The seroprevalence of Babesia bigemina was lower by 30% in vaccinated cattle, suggesting a possible role for the vaccine in decreasing the prevalence of this tick-borne pathogen. The effect of the vaccine in reducing the frequency of one A. marginale msp4 genotype probably reflected the reduction in the prevalence of a tick-transmitted strain as a result of the reduction in the percent of tick-infested cattle. CONCLUSIONS: These data provide evidence of the dual effect of a SUB-based vaccine for controlling tick infestations and pathogen infection/transmission and provide additional support for the use of the SUB-MSP1a vaccine for tick control in cattle and sheep.

Persistent atrial fibrillation is associated with inability to recover atrial contractility after MAZE IV surgery in rheumatic disease.

BACKGROUND: MAZE IV surgery is effective in restoring sinus rhythm (SR) and atrial contraction (AC) in patients with nonrheumatic persistent atrial fibrillation (AF). However, there is less information on its effectiveness to restore AC in patients with rheumatic disease. AIMS: To assess the effectiveness of the MAZE IV surgery in restoring AC in patients with rheumatic disease and long persistent AF. METHODS: Prospective, consecutive study in patients who underwent cardiovascular surgery and had long persistent AF in whom MAZE IV surgery was performed. The presence of AC was assessed by lateral mitral annulus tissue Doppler. RESULTS: A total of 75 patients were included. Mean age 60 years (±11.7); 27 men (36%). AF duration was 63 months (±34.1). Primary indication for surgery: rheumatic mitral stenosis 67 patients and mitral insufficiency eight patients. Mean left ventricular ejection fraction (LVEF) was 51.8% (±12.1) and mean left atrial area was 37 cm(2) (±10.3). After a mean follow-up of 28 months (±9.3), 69 patients remained alive and 59 were in SR. AC was detected in 37.3% (Group A) and absent in 62.7% (Group B). The mean difference between groups was the high prevalence of AF longer than 5 years in group B (P = 0.000001). There were no differences related to left atrial size, LVEF, and age. CONCLUSIONS: In patients with rheumatic disease, the absence of correlation between SR recovery and AC recovery post MAZE IV surgery is significant. A history of long persistent AF lasting more than 5 years was a strong predictor for the absence of AC.

Recuperación de la contracción auricular luego de la cirugía de MAZE III izquierdo / Atrial Contraction Recovery After Left MAZE III Surgery

Introducción La cirugía de MAZE III izquierdo demostró una efectividad elevada en la restauración a ritmo sinusal. Sin embargo, la efectividad en la restauración de la sístole auricular en poblaciones con cardiopatía estructural y el predominio de enfermedad reumática resultan áreas de incertidumbre. Objetivo Evaluar la efectividad de la cirugía de MAZE en la restauración de la sístole auricular en pacientes con cardiopatía estructural. Material y métodos Estudio prospectivo, consecutivo de 27 pacientes portadores de fibrilación auricular crónica persistente con indicación de cirugía cardiovascular y en los que se realizó la técnica de MAZE como tratamiento de la arritmia. La presencia de sístole auricular se evaluó mediante Doppler tisular del anillo mitral lateral. Resultados En una población caracterizada por predominancia de cardiopatía reumática (41%) y tiempo prolongado de evolución de la arritmia (61 meses promedio), al final del seguimiento el 87% se encontraba en ritmo sinusal en el 80% de los casos con actividad mecánica. El antecedente de cardiopatía reumática, una duración de la arritmia mayor de 5,5 años, el sexo femenino y el reemplazo de válvula mitral fueron variables estadísticamente significativas en cuanto a la ausencia de sístole auricular. No tuvieron significación la edad, la fracción de eyección del ventrículo izquierdo y el tamaño de la aurícula izquierda. Conclusiones En esta población es significativa la falta de correspondencia entre ritmo sinusal y sístole auricular. El Doppler tisular es un método útil para identificar a aquellos pacientes sin contracción auricular. El impacto clínico de este hallazgo está vinculado con la decisión en la continuidad del tratamiento anticoagulante.

Introduction Left MAZE III surgery has proven a high level of effectiveness in restoring the sinus rhythm. However, the effectiveness in restoring the atrial systole in individuals with structural cardiopathy and the prevalence of rheumatic disease are still uncertain areas. Objective To assess the effectiveness of the MAZE surgery in restoring the atrial systole in patients with structural cardiopathy. Material and Methods Prospective, consecutive study in 27 patients with persistent or chronic atrial fibrillation and recommendation for cardiovascular surgery, who underwent the MAZE technique for treating the arrhythmia. The presence of atrial systole was assessed by lateral mitral annular tisular Doppler. Results In a population characterized by rheumatic cardiopathy predominance (41%) and long arrhythmia evolution (61 months on average), 87% individuals had sinus rhythm and 80% of them had mechanical activity at the end of the follow- up. A history of rheumatic cardiopathy, an arrhythmia lasting more than 5.5 years, the fact of being female, and the mitral valve replacement were statistically significant variables, considering the absence of atrial systole. Factors like age, left ventricle ejection fraction, and left atrial size were not significant. Conclusions In this population, the absence of correlation between the sinus rhythm and the atrial systole is significant. The tisular Doppler is a useful method to identify those patients with no atrial contraction. The clinical impact of this finding is related to the decision on continuing the anticoagulant therapy.

Reubicación de los vasos del cuello y exclusión endovascular de las disecciones y los aneurismas del arco aórtico / Replacement of Neck Vessels and Endovascular Exclusion of Aortic Arch Dissections and Aneurysms

El tratamiento endovascular de la aorta descendente le brinda a un grupo de pacientes seleccionados de alto riesgo una alternativa para resolver un problema grave de manera segura y efectiva. Sólo el 15% de los enfermos tiene un cuello adecuado para el implante respetando la integridad de la arteria subclavia izquierda y su oclusión intencional origina en hasta un 30% isquemia del brazo, síndrome vertebrobasilar o leaks. Además, los pacientes que presentan compromiso del arco aórtico (extensión retrógrada de la disección, porque ésta se origina allí o por aneurisma de ese sector) constituyen una población aún más seleccionada y de mayor riesgo para el tratamiento quirúrgico habitual. Entre noviembre de 2005 y diciembre de 2006 incluimos 10 pacientes que se presentaban con: 1) disecciones con compromiso de la arteria subclavia izquierda o retrodisecciones hacia el cayado aórtico (n = 7) y 2) aneurismas del cayado aórtico (n = 3). Fueron tratados dentro del período agudo (14 días), todos con un puntaje de riesgo anestésico (ASA) igual a 3 o mayor. Se utilizó una técnica híbrida, de un solo acto en dos etapas (quirúrgica/endovascular) realizadas en el mismo día. En la fase quirúrgica no se requirió paro cardíaco, circulación extracorpórea ni hipotermia profunda y durante la etapa endovascular se utilizaron prótesis autoexpandibles y es aquí donde se notaron las dificultades técnicas que debieron sortearse para llevar adelante el implante. Todos los procedimientos resultaron técnicamente exitosos. Dos pacientes fallecieron, uno en el primer día (taponamiento cardíaco) otro por sepsis en el día 27. No se registraron complicaciones neurológicas ni vasculares. La técnica fue factible y efectiva, con una morbimortalidad adecuada para la población en estudio y similar a la de publicaciones con pacientes de las mismas características.

Endovascular treatment of the descendant aorta is a safe and effective alternative to solve a severe condition in a selected group of high-risk patients. In only 15% of patients the anatomical relations of the aneurysm neck with the left subclavian artery are adequate for the implant, and the incidence of arm ischemia, vertebrobasilar artery syndrome or leaks related to the left subclavian artery intentionally occluded reaches 30%. In addition, patients with compromise of the aortic arch (due to dissections or aneurysms of the aortic arch) are still a more selected high-risk population for surgical treatment. Between November 2005 and December 2006 we included 10 patients with: 1) dissections with compromise of the left subclavian artery or dissections towards the aortic arch (n=7) and, 2) aneurisms of the aortic arch (n=3). All patients had ASA class III or greater, and they were all treated during the acute phase (14 days). A two-stage (surgical/endovascular) hybrid technique was performed during the same day. The surgical approach was carried out without the need for circulatory arrest, extracorporeal circulation, and deep hypothermia, but endovascular self-expanding stent-graft placement presented a few technical difficulties. All procedures were technically successful. Two patients died, one at day 1 (cardiac tamponade) and the other at day 27 (sepsis). No neurologic or vascular complications were reported. The procedure was feasible and effective, with morbidity and mortality rates according to the study population and similar to those reported in other studies performed on comparable patients.

Disección coronaria espontánea: evolución intrahospitalaria y conducta terapéutica / Spontaneous coronary dissection: its evolution and treatment

Se presenta el caso de una paciente de 69 años de edad que ingresa a la Unidad Coronaria con diagnóstico de infarto agudo de miocardio no Q lateral, y que al quinto día de su evolución presenta reinfarto no Q del mismo territorio. La coronariografía mostró la presencia de una disección coronaria espontánea de la arteria circunfleja, planificándose una angioplastia con stent. A las 48 horas los estudios previos al implante del dispositivo demuestran disección retrógrada con compromiso del tronco de la coronaria izquierda y la descendente anterior. La paciente es enviada a cirugía de revascularización miocárdica. Se analizan la etiología, incidencia, fisiopatología, los factores predisponentes y desencadenantes, así como el tratamiento y el pronóstico de esta patología poco frecuente

Disección coronaria espontánea: evolución intrahospitalaria y conducta terapéutica / Spontaneous coronary dissection: its evolution and treatment

Se presenta el caso de una paciente de 69 años de edad que ingresa a la Unidad Coronaria con diagnóstico de infarto agudo de miocardio no Q lateral, y que al quinto día de su evolución presenta reinfarto no Q del mismo territorio. La coronariografía mostró la presencia de una disección coronaria espontánea de la arteria circunfleja, planificándose una angioplastia con stent. A las 48 horas los estudios previos al implante del dispositivo demuestran disección retrógrada con compromiso del tronco de la coronaria izquierda y la descendente anterior. La paciente es enviada a cirugía de revascularización miocárdica. Se analizan la etiología, incidencia, fisiopatología, los factores predisponentes y desencadenantes, así como el tratamiento y el pronóstico de esta patología poco frecuente (AU)