Review on the transmission porcine reproductive and respiratory syndrome virus between pigs and farms and impact on vaccination

Porcine reproductive and respiratory syndrome (PRRS) is considered to be one of the most costly diseases affecting intensive pig production worldwide. Control of PRRS is a complex issue and involves a combination of measures including monitoring, diagnosis, biosecurity, herd management, and immunization. In spite of the numerous studies dealing with PRRS virus epidemiology, transmission of the infection is still not fully understood. The present article reviews the current knowledge on PRRSV transmission between and within farm, and the impact of vaccination on virus transmission

Bottlenecks in the transmission of porcine reproductive and respiratory syndrome virus (PRRSV1) to naïve pigs and the quasi-species variation of the virus during infection in vaccinated pigs

This paper describes the results of two experiments regarding porcine reproductive and respiratory syndrome virus (PRRSV1): the first one studied the existence of bottlenecks in an experimental one-to-one model of transmission in pigs; while the second analysed the differences between viral quasi-species in vaccinated pigs that developed shorter or longer viraemias after natural challenge. Serum samples, as well as the initial inoculum, were deep-sequenced and a viral quasi-species was constructed per sample. For the first experiment, the results consistently reported a reduction in the quasi-species diversity after a transmission event, pointing to the existence of bottlenecks during PRRSV1 transmission. However, despite the identified preferred and un-preferred transmitted variants not being randomly distributed along the virus genome, it was not possible to identify any variant producing a structural change in any viral protein. In contrast, the mutations identified in GP2, nsp9 and M of the second experiment pointed to changes in the amino acid charges and the viral RNA-dependent RNA polymerase structure. The fact that the affected proteins are known targets of the immunity against PRRSV, plus the differential level of neutralizing antibodies present in pigs developing short or long viraemias, suggests that the immune response selected those changes.info:eu-repo/semantics/publishedVersio

Transmission of porcine reproductive and respiratory syndrome virus (PRRSV) : assessment of the reproduction rate (R) in different conditions /

La cuantificación de la transmisión del Virus del síndrome reproductivo y respiratorio porcino (VSRRP) es crucial para estimar el potencial de la vacunación como medio de control de la infección a escala poblacional. El objetivo de la presente tesis fue determinar la tasa de reproducción (R) del VSRRP en condiciones de campo y experimentalmente, usando como modelo cerdos destetados y de engorde. El primer estudio tuvo como objetivo estimar de forma preliminar de la R del VSRRP en dos granjas de ciclo cerrado (F1 y F2) infectadas de forma endémica. En ambos casos, un lote entero de lechones fue monitoreado desde destete hasta matadero. Basándose en los resultados serológicos, el tiempo necesario para alcanzar el 50% de animales infectados fue de 7 y 3,5 semanas en la F1 y F2, respectivamente. El valor de R para la transmisión del VSRRP fue estimado en 3,53 (CI95%: 2,89-4.18) y 7,11 (CI95%: 3,55-10,68) para F1 y F2, respectivamente. El segundo estudio pretendía determinar la eficacia de la vacunación en un modelo experimental de transmisión por contacto en grupos. Lechones de 3 semanas de edad (n=98) fueron divididos en dos grupos: 1) cerdos V, vacunados con una vacuna comercial atenuada del genotipo 1, y 2) cerdos NV, sin tratamiento. Cinco semanas más tarde, 14 NV (a partir de ahora animales "semillas" (S)) fueron inoculados por vía intranasal (IN) con la cepa 3267 del VSRRP (genotipo 1). Dos días después, un S fue introducido en corrales de 5 V o 5 NV (8 grupos de 1S:5V y 6 grupos de 1S:5NV). Tras 21 días de contacto con el S, todos los NV desarrollaron viremia mientras que solo el 52.5% de V se infectó. El tiempo medio de supervivencia fue de 7 y 21 días para los NV y V, respectivamente (p 0,05). El valor de R fue 2,78 (CI95%: 2,13-3,43) y 0,53 (CI95%: 0,19-0,76) para los NV y V, respectivamente (p 0,05). Además, la vacunación redujo significativamente la duración de la viremia y del periodo de excreción del virus por las vías nasal y fecal. En el tercer estudio, la transmisión del virus y la eficacia vacunal fueron evaluadas en modelo experimental de transmisión por contacto de tipo uno a uno. Como en el estudio anterior, 44 lechones de 3 semanas de vida fueron divididos en dos grupos: V y NV. Cuatro semanas más tarde, 18 NV fueron separados e inoculados IN con el mismo aislado usado en el estudio 2 (animales S). Dos días después, cada S fue reagrupado con un V o un NV formando 12 réplicas de 1S:1V y seis de 1S:1NV. Los animales se siguieron por 21 días. Los V infectados desde el S (Vinf) venían trasladados (en menos de 24 horas) a un nuevo corral donde venían dejados en contacto con un nuevo V no infectado y reservado desde el inicio (Vc ). Todos los NV y V se infectaron tras contacto con el S pero la duración de la viremia se redujo desde 12,5±2,7 días en los NV a 5,5±4,3 días en los V (p 0,005). Además, el tiempo necesario para infectarse fue de 13.6±3 y 5,4±2,7 días en los NV y V, respectivamente. La transmisión desde Vinf a Vc tuvo lugar en 7/8 animales (87.5%), pero la duración de la viremia y el área bajo la curva (AUC) de la carga vírica en suero se redujeron significativamente en los Vc (AUC: 0.98, 0.87, 0.79 para NV, Vinf y Vc, respectivamente, p 0.05). In conclusión, los resultados de la presente tesis indican que para el VSRRP de genotipo 1 y subtipo 1, la vacunación masiva de los animales puede ser una herramienta efectiva para parar o disminuir significativamente la transmisión.The quantification of Porcine reproductive and respiratory syndrome virus (PRRSV) transmission is crucial to foresee the potential of vaccination as a mean of control of the infection at a population level. The aim of the present thesis was to determine the reproduction rate (R) of PRRSV under field and experimental conditions using weaners/growers as a model. Study 1 was directed to preliminary assess R of PRRSV in two endemically infected farrow-to-finish farms (F1 and F2). In both cases, a whole batch of weaners was followed serologically from weaning to slaughtering age. Based on serological data, the average time needed to reach 50% of infected pigs was 7 and 3.5 weeks in F1 and F2, respectively. R value for PRRSV transmission was estimated to be 3.53 (CI95%: 2.89-4.18) and 7.11 (CI95%: 3.55-10.68) for F1 and F2, respectively. The second study was directed to assess the efficacy of the vaccination in an experimental study of transmission by contact in groups. Ninety-eight 3-week-old piglets were divided in two groups: 1) V pigs, vaccinated with a commercial attenuated PRRSV genotype 1 vaccine, and 2) NV piglets, kept as unvaccinated controls. Five weeks later, 14 NV pigs (from now on seeders (S)) were inoculated intranasally (IN) with PRRSV genotype 1 isolate 3267. Two days later, one S was mingled with 5 V or 5 NV pigs (8 groups of 1S:5V and 6 replicas of 1S:5NV). After 21 days of contact with the S, all NV developed viremia while only 52.5% of V pigs were become viremic. The average 50% survival period was 7 and 21 days for NV and V pigs, respectively (p 0.05). The R value was 2.78 (CI95%: 2.13-3.43) and 0.53 (CI95%: 0.19-0.76) for NV and for V pigs, respectively (p 0.05). Moreover, vaccination significantly reduced the biological parameters related to transmission, such as the duration of viremia and shedding of virus by the nasal and fecal routes. In the third study, the transmission of PRRSV and vaccine efficacy were assessed using one-to-one experiments, a scenario where the probability of transmission between animals was the highest possible. Forty-four 3-week-old piglets were divided in 2 groups as above: V and NV. Four weeks later, 18 NV were inoculated IN with the same isolate as in study 2 (S pigs). Two days later, S pigs were mixed in a 1:1 basis with V and NV pigs, namely 1S:1V (n=12) and 1S:1NV (n=6) and were then followed for 21 days. Once a V pig was detected as viremic as a result of the contact with a S, the infected V (Vinf) was transferred (in less than 24 h) to a new pen where it was left in contact with a new V (from now Vc) for at least 14 days. All NV and V pigs became viremic after contacting S pigs; however, the average duration of viremia was reduced from 12.5±2.7 to 5.5±4.3 days comparing V pigs to NV (p 0.05). Also, V animals needed on average 13.6±3 days in order to become infected from the S compared to NV (5.4±2.7 days, p 0.05). Transmission from Vinf to Vc pigs occurred in 7/8 animals (87.5%) but the mean length of viremia as well as the area under the curve (AUC) for viral load in sera of Vc pigs were also significantly reduced (AUC: 0.98, 0.87 and 0.79 for NV, Vinf and Vc, respectively, p 0.05). In conclusion, the data shown in the present thesis indicated that for genotype 1 subtype 1 PRRSV, mass vaccination of pigs can be a tool effective to stop or to significantly reduce the transmission of the virus

T-cell lymphoma in South America and Europe.

Peripheral T-cell lymphomas are a group of rare neoplasms originating from clonal proliferation of mature post-thymic lymphocytes with different entities having specific biological characteristics and clinical features. As natural killer cells are closely related to T-cell, natural killer-cell lymphomas are also part of the group. The current World Health Organization classification recognizes four categories of T/natural killer-cell lymphomas with respect to their presentation: disseminated (leukemic), nodal, extranodal and cutaneos. Geographic variations in the distribution of these diseases are well documented: nodal subtypes are more frequent in Europe and North America, while extranodal forms, including natural killer-cell lymphomas, occur almost exclusively in Asia and South America. On the whole, T-cell lymphomas are more common in asia than in western countries, usually affect adults, with a higher tendency in men, and, excluding a few subtypes, usually have an aggressive course and poor prognosis. Apart from anaplastic lymphoma kinase-positive anaplastic large cell lymphoma, that have a good outcome, other nodal and extranodal forms have a 5-year oversall survival of about 30%. According to the principal prognostic indexes, the majority of patients are allocated to the unfavorable subset. In the past, the rarity of these diseases prevented progress in the understanding of their biology and improvements in the efficaciousness of therapy. Recently, international projects devoted to these diseases created networks promting investigations on T-cell lymphomas. These projects are the basis of forthcoming cooperative, large scale trials to detail biologic characteristics of each sub-entity and to possibly individuate targets for new therapies

T-Cell Lymphomas in South America and Europe

Peripheral T-cell lymphomas are a group of rare neoplasms originating from clonal proliferation of mature post-thymic lymphocytes with different entities having specific biological characteristics and clinical features. As natural killer cells are closely related to T-cells, natural killer-cell lymphomas are also part of the group. The current World Health Organization classification recognizes four categories of T/natural killer-cell lymphomas with respect to their presentation: disseminated (leukemic), nodal, extranodal and cutaneous. Geographic variations in the distribution of these diseases are well documented: nodal subtypes are more frequent in Europe and North America, while extranodal forms, including natural killer-cell lymphomas, occur almost exclusively in Asia and South America. On the whole, T-cell lymphomas are more common in Asia than in western countries, usually affect adults, with a higher tendency in men, and, excluding a few subtypes, usually have an aggressive course and poor prognosis. Apart from anaplastic lymphoma kinase-positive anaplastic large cell lymphoma, that have a good outcome, other nodal and extranodal forms have a 5-year overall survival of about 30%. According to the principal prognostic indexes, the majority of patients are allocated to the unfavorable subset. In the past, the rarity of these diseases prevented progress in the understanding of their biology and improvements in the efficaciousness of therapy. Recently, international projects devoted to these diseases created networks promoting investigations on T-cell lymphomas. These projects are the basis of forthcoming cooperative, large scale trials to detail biologic characteristics of each sub-entity and to possibly individuate targets for new therapies.424

In vitro and in vivo single-agent efficacy of checkpoint kinase inhibition in acute lymphoblastic leukemia

Background: Although progress in children, in adults, ALL still carries a dismal outcome. Here, we explored the in vitro and in vivo activity of PF-00477736 (Pfizer), a potent, selective ATP-competitive small-molecule inhibitor of checkpoint kinase 1 (Chk1) and with lower efficacy of checkpoint kinase 2 (Chk2). Methods: The effectiveness of PF-00477736 as single agent in B-/T-ALL was evaluated in vitro and in vivo studies as a single agent. The efficacy of the compound in terms of cytotoxicity, induction of apoptosis, and changes in gene and protein expression was assessed using different B-/T-ALL cell lines. Finally, the action of PF-00477736 was assessed in vivo using leukemic mouse generated by a single administration of the tumorigenic agent n-ethyl-n-nitrosourea. Results: Chk1 and Chk2 are overexpressed concomitant with the presence of genetic damage as suggested by the nuclear labeling for \u3b3-H2A.X (Ser139) in 68 % of ALL patients. In human B-and T-ALL cell lines, inhibition of Chk1/2 as a single treatment strategy efficiently triggered the Chk1-Cdc25-Cdc2 pathway resulting in a dose-and time-dependent cytotoxicity, induction of apoptosis, and increased DNA damage. Moreover, treatment with PF-00477736 showed efficacy ex vivo in primary leukemic blasts separated from 14 adult ALL patients and in vivo in mice transplanted with T-ALL, arguing in favor of its future clinical evaluation in leukemia. Conclusions: In vitro, ex vivo, and in vivo results support the inhibition of Chk1 as a new therapeutic strategy in acute lymphoblastic leukemia, and they provide a strong rationale for its future clinical investigation

Transmission of porcine reproductive and respiratory syndrome virus (PRRSV): assessment of the reproduction rate (R) in different conditions

La cuantificación de la transmisión del Virus del síndrome reproductivo y respiratorio porcino (VSRRP) es crucial para estimar el potencial de la vacunación como medio de control de la infección a escala poblacional. El objetivo de la presente tesis fue determinar la tasa de reproducción (R) del VSRRP en condiciones de campo y experimentalmente, usando como modelo cerdos destetados y de engorde. El primer estudio tuvo como objetivo estimar de forma preliminar de la R del VSRRP en dos granjas de ciclo cerrado (F1 y F2) infectadas de forma endémica. En ambos casos, un lote entero de lechones fue monitoreado desde destete hasta matadero. Basándose en los resultados serológicos, el tiempo necesario para alcanzar el 50% de animales infectados fue de 7 y 3,5 semanas en la F1 y F2, respectivamente. El valor de R para la transmisión del VSRRP fue estimado en 3,53 (CI95%: 2,89-4.18) y 7,11 (CI95%: 3,55-10,68) para F1 y F2, respectivamente. El segundo estudio pretendía determinar la eficacia de la vacunación en un modelo experimental de transmisión por contacto en grupos. Lechones de 3 semanas de edad (n=98) fueron divididos en dos grupos: 1) cerdos V, vacunados con una vacuna comercial atenuada del genotipo 1, y 2) cerdos NV, sin tratamiento. Cinco semanas más tarde, 14 NV (a partir de ahora animales “semillas” (S)) fueron inoculados por vía intranasal (IN) con la cepa 3267 del VSRRP (genotipo 1). Dos días después, un S fue introducido en corrales de 5 V o 5 NV (8 grupos de 1S:5V y 6 grupos de 1S:5NV). Tras 21 días de contacto con el S, todos los NV desarrollaron viremia mientras que solo el 52.5% de V se infectó. El tiempo medio de supervivencia fue de 7 y 21 días para los NV y V, respectivamente (p<0,05). El valor de R fue 2,78 (CI95%: 2,13-3,43) y 0,53 (CI95%: 0,19-0,76) para los NV y V, respectivamente (p<0,05). Además, la vacunación redujo significativamente la duración de la viremia y del periodo de excreción del virus por las vías nasal y fecal. En el tercer estudio, la transmisión del virus y la eficacia vacunal fueron evaluadas en modelo experimental de transmisión por contacto de tipo uno a uno. Como en el estudio anterior, 44 lechones de 3 semanas de vida fueron divididos en dos grupos: V y NV. Cuatro semanas más tarde, 18 NV fueron separados e inoculados IN con el mismo aislado usado en el estudio 2 (animales S). Dos días después, cada S fue reagrupado con un V o un NV formando 12 réplicas de 1S:1V y seis de 1S:1NV. Los animales se siguieron por 21 días. Los V infectados desde el S (Vinf) venían trasladados (en menos de 24 horas) a un nuevo corral donde venían dejados en contacto con un nuevo V no infectado y reservado desde el inicio (Vc ). Todos los NV y V se infectaron tras contacto con el S pero la duración de la viremia se redujo desde 12,5±2,7 días en los NV a 5,5±4,3 días en los V (p<0,005). Además, el tiempo necesario para infectarse fue de 13.6±3 y 5,4±2,7 días en los NV y V, respectivamente. La transmisión desde Vinf a Vc tuvo lugar en 7/8 animales (87.5%), pero la duración de la viremia y el área bajo la curva (AUC) de la carga vírica en suero se redujeron significativamente en los Vc (AUC: 0.98, 0.87, 0.79 para NV, Vinf y Vc, respectivamente, p<0.05). In conclusión, los resultados de la presente tesis indican que para el VSRRP de genotipo 1 y subtipo 1, la vacunación masiva de los animales puede ser una herramienta efectiva para parar o disminuir significativamente la transmisión.The quantification of Porcine reproductive and respiratory syndrome virus (PRRSV) transmission is crucial to foresee the potential of vaccination as a mean of control of the infection at a population level. The aim of the present thesis was to determine the reproduction rate (R) of PRRSV under field and experimental conditions using weaners/growers as a model. Study 1 was directed to preliminary assess R of PRRSV in two endemically infected farrow-to-finish farms (F1 and F2). In both cases, a whole batch of weaners was followed serologically from weaning to slaughtering age. Based on serological data, the average time needed to reach 50% of infected pigs was 7 and 3.5 weeks in F1 and F2, respectively. R value for PRRSV transmission was estimated to be 3.53 (CI95%: 2.89-4.18) and 7.11 (CI95%: 3.55-10.68) for F1 and F2, respectively. The second study was directed to assess the efficacy of the vaccination in an experimental study of transmission by contact in groups. Ninety-eight 3-week-old piglets were divided in two groups: 1) V pigs, vaccinated with a commercial attenuated PRRSV genotype 1 vaccine, and 2) NV piglets, kept as unvaccinated controls. Five weeks later, 14 NV pigs (from now on seeders (S)) were inoculated intranasally (IN) with PRRSV genotype 1 isolate 3267. Two days later, one S was mingled with 5 V or 5 NV pigs (8 groups of 1S:5V and 6 replicas of 1S:5NV). After 21 days of contact with the S, all NV developed viremia while only 52.5% of V pigs were become viremic. The average 50% survival period was 7 and 21 days for NV and V pigs, respectively (p<0.05). The R value was 2.78 (CI95%: 2.13-3.43) and 0.53 (CI95%: 0.19-0.76) for NV and for V pigs, respectively (p<0.05). Moreover, vaccination significantly reduced the biological parameters related to transmission, such as the duration of viremia and shedding of virus by the nasal and fecal routes. In the third study, the transmission of PRRSV and vaccine efficacy were assessed using one-to-one experiments, a scenario where the probability of transmission between animals was the highest possible. Forty-four 3-week-old piglets were divided in 2 groups as above: V and NV. Four weeks later, 18 NV were inoculated IN with the same isolate as in study 2 (S pigs). Two days later, S pigs were mixed in a 1:1 basis with V and NV pigs, namely 1S:1V (n=12) and 1S:1NV (n=6) and were then followed for 21 days. Once a V pig was detected as viremic as a result of the contact with a S, the infected V (Vinf) was transferred (in less than 24 h) to a new pen where it was left in contact with a new V (from now Vc) for at least 14 days. All NV and V pigs became viremic after contacting S pigs; however, the average duration of viremia was reduced from 12.5±2.7 to 5.5±4.3 days comparing V pigs to NV (p<0.05). Also, V animals needed on average 13.6±3 days in order to become infected from the S compared to NV (5.4±2.7 days, p< 0.05). Transmission from Vinf to Vc pigs occurred in 7/8 animals (87.5%) but the mean length of viremia as well as the area under the curve (AUC) for viral load in sera of Vc pigs were also significantly reduced (AUC: 0.98, 0.87 and 0.79 for NV, Vinf and Vc, respectively, p<0.05). In conclusion, the data shown in the present thesis indicated that for genotype 1 subtype 1 PRRSV, mass vaccination of pigs can be a tool effective to stop or to significantly reduce the transmission of the virus

Short intermittent taekwondo test to assess athlete's physiological and metabolic profile

Background: The aim of this study was to assess the effectiveness of a new Short Intermittent Taekwondo Test (SITT) in 17 black belt athletes. Methods: Maximal oxygen uptake (V̇O2max), carbon dioxide production (V̇CO2), respiratory exchange ratio (RER), heart rate (HR), and blood lactate concentration [La]+ during treadmill cardiopulmonary exercise test (CPET) and SITT were compared. SITT started with 10 sec of all-out kicks, alternating legs, and progressively increasing 5 s on each stage until the 4th stage. After the 4th stage the participants performed 25 s of turning kicks (Dolleo chagi), on each stage until the last (10th stage). The passive recovery phase after the 4th and the 7th stage lasted 30 s. Results: V̇O2max and maximal HRmax were not significantly different (P=0.85 vs P=0.76) between tests, while RER and [La]+ were significantly higher in SITT than in CPET (P=0.002 vs. P=0.001). No difference in RPE (P=0.84) was found. A significant positive correlation between two tests for V̇O2max and HRmax was found. Conclusions: Our findings showed that SITT induces physiological responses like CPET suggesting that it can be used to assess aerobic power in national taekwondo athletes, thus helping coaches to select correctly training intensities and monitor athletes' aerobic performance along the training phases