Mathematical modeling of bovine brucellosis control by vaccination

As fêmeas bovinas, por sua importância na transmissão e na manutenção da brucelose, constituíram o alvo dos inquéritos do Programa Nacional de Controle e Erradicação da Brucelose e da Tuberculose Animal. Com base em informações obtidas em unidades federativas onde foram realizados inquéritos sorológicos e observadas prevalências de animais acima de 2%, elaborou-se um modelo para simular a dinâmica da brucelose em rebanhos bovinos formados exclusivamente por fêmeas, analisando o efeito de estratégias de vacinação. Para baixa cobertura vacinal, da ordem de 30%, o tempo para reduzir a prevalência a 2%, valor adotado como referência, pode ser longo, aproximando-se do dobro do tempo necessário para uma cobertura mais alta, de 90%. De acordo com o modelo, o tempo para reduzir a prevalência a 1% ou 2%, que permitam passar à fase de erradicação, pode chegar a uma década. Recomenda-se a intensificação do esforço para a vacinação de fêmeas, procurando atingir alta cobertura vacinal.Due to the important role played by female bovines in the transmission and maintenance of brucellosis, they were the target of the serological surveys of the Brazilian National Program for the Control and Eradication of Bovine Brucellosis and Tuberculosis. Based on the information obtained in Brazilian states, where the serological surveys were carried out and prevalences higher than 2% were observed, a model to simulate the dynamics of brucellosis in herds of female bovines was developed to analyze the effects of vaccination strategies. For low vaccination coverage (around 30%), the time to reduce the prevalence to 2%, adopted as a reference, may be long, approximately twice as long as the time observed for a higher coverage (90%). According to the model, the time to reduce the prevalence to levels of 1% or 2%, adequate to start the eradication phase, may reach a decade. It is recommended an intensification of the effort to vaccinate females, aiming at attaining high vaccination coverage.FAPESPCNPqMAPA Ministério da Agricultura, Pecuária e Abasteciment

Epidemiological status of bovine brucellosis in the Federal District, Brazil

Realizou-se um estudo para caracterizar a situação epidemiológica da brucelose bovina no Distrito Federal (DF). No total foram amostrados 2.019 animais, provenientes de 278 propriedades. Em cada propriedade visitada aplicou-se um questionário epidemiológico para verificar o tipo de exploração e as práticas de criação e sanitárias que poderiam estar associadas ao risco de infecção pela doença. O protocolo utilizado foi o da triagem com o teste do antígeno acidificado tamponado e a confirmação dos positivos com o teste do 2-mercaptoetanol. O rebanho foi considerado positivo quando pelo menos um animal foi reagente às duas provas sorológicas. A prevalência no DF foi de 2,5% [1,0-5,1%] para propriedades e de 0,16% [0,04-0,28%] para animais. Em razão dos resultados encontrados, que permitem pensar em estratégias de erradicação, recomenda-se que o DF intensifique o diagnóstico de brucelose, tanto na forma de testes sorológicos sistemáticos como pela introdução de mecanismos de detecção rápida em laticínios, em ambos os casos a fim de aumentar o número de propriedades certificadas como livres da doença e melhorar a sensibilidade do sistema de vigilância ativa.A study to characterize the epidemiological status of brucellosis was carried out in the Federal District of Brazil. A total of 2,019 serum samples from 278 herds were collected. In each herd, it was applied an epidemiological questionnaire focused on herd traits as well as husbandry and sanitary practices that could be associated with the risk of infection. The serum samples were screened for antibodies against Brucella spp. by the Rose-Bengal Test (RBT), and all positive sera were re-tested by the 2-mercaptoethanol test (2-ME). The herd was considered positive if at least one animal was positive on both RBT and 2-ME tests. Herd prevalence was estimated as 2.5% [1.0-5.1%] whereas animal prevalence was 0.16% [0.04-0.28%]. Given these results, that may warrant the implementation of eradication strategies, there is a case for intensifying the serological testing in the Federal District, coupled with the introduction of rapid detection methods by the dairy industries, with a view to increasing the number of accredited free herds and improving the sensitivity of the surveillance system..FAPESPCNPqSEAP-DFMAPA Ministério da Agricultura, Pecuária e Abasteciment

Efficient Protein Trans-Splicing at Low Vector Doses

Funding Information: Author Mariana V. Ferreira acknowledges Fundação para a Ciência e Tecnologia for PH.D. fellowship UI/BD/151256/2021 within the scope of the Ph.D. Program in Bioengineering—Cell Therapies and Regenerative Medicine. This work was funded by Fundação para a Ciência e Tecnologia/Ministério da Ciência, Tecnologia e Ensino Superior (FCT/MCTES, Portugal) through national funds to iNOVA4Health (UIDB/04462/2020 and UIDP/04462/2020) and the Associate Laboratory LS4FUTURE (LA/P/0087/2020). Publisher Copyright: © 2023 by the authors.Adeno-associated viral (AAV) vectors represent one of the leading platforms for gene delivery. Nevertheless, their small packaging capacity restricts their use for diseases requiring large-gene delivery. To overcome this, dual-AAV vector systems that rely on protein trans-splicing were developed, with the split-intein Npu DnaE among the most-used. However, the reconstitution efficiency of Npu DnaE is still insufficient, requiring higher vector doses. In this work, two split-inteins, Cfa and Gp41-1, with reportedly superior trans-splicing were evaluated in comparison with Npu DnaE by transient transfections and dual-AAV in vitro co-transductions. Both Cfa and Gp41-1 split-inteins enabled reconstitution rates that were over two-fold higher than Npu DnaE and 100% of protein reconstitution. The impact of different vector preparation qualities in split-intein performances was also evaluated in co-transduction assays. Higher-quality preparations increased split-inteins’ performances by three-fold when compared to low-quality preparations (60–75% vs. 20–30% full particles, respectively). Low-quality vector preparations were observed to limit split-gene reconstitutions by inhibiting co-transduction. We show that combining superior split-inteins with higher-quality vector preparations allowed vector doses to be decreased while maintaining high trans-splicing rates. These results show the potential of more-efficient protein-trans-splicing strategies in dual-AAV vector co-transduction, allowing the extension of its use to the delivery of larger therapeutic genes.publishersversionpublishe

Tuberculosis determined by Mycobacterium bovis in captive waterbucks (Kobus ellipsiprymnus) in São Paulo, Brazil

Two waterbucks from São Paulo Zoo Foundation exhibited respiratory symptoms in July 2004. After euthanasia, granulommas in lungs and mediastinic lymph nodes were observed. Acid-fast bacilli isolated were identified as Mycobacterium bovis spoligotype SB0121 by PRA and spoligotyping. They were born and kept in the same enclosure with the same group, without any contact to other species housed in the zoo. This is the first detailed description of M. bovis infection in Kobus ellipsiprymnus.FAPES

Epidemiological situation of bovine brucellosis in the State of Rondônia, Brazil

Realizou-se um estudo para caracterizar a situação epidemiológica da doença no Estado de Rondônia. O Estado foi estratificado em três circuitos produtores. Em cada circuito produtor foram amostradas aleatoriamente cerca de 300 propriedades e, dentro dessas, foi escolhido, de forma aleatória, um número pré-estabelecido de animais, dos quais foi obtida uma amostra de sangue. No total, foram amostrados 9.717 animais, provenientes de 927 propriedades. Em cada propriedade amostrada foi aplicado um questionário epidemiológico para verificar o tipo de exploração e as práticas zootécnicas e sanitárias que poderiam estar associadas ao risco de infecção pela doença. O protocolo de testes utilizado foi o da triagem com o teste do antígeno acidificado tamponado e o reteste dos positivos com o teste do 2-mercaptoetanol. O rebanho foi considerado positivo, se pelo menos um animal foi reagente às duas provas sorológicas. As prevalências de focos e de animais infectados do Estado foram de 35,2% [32,1-38,4%] e 6,2% [4,9-7,6%], respectivamente. Os resultados para os circuitos pecuários foram: circuito 1, 41,9% [36,3-47,6%] e 8,3% [5,9-10,8%]; circuito 2, 31,7% [26,5-37,2%] e 5,9% [4,3-7,6%]; circuito 3, 31,9% [26,7-37,4%] e 4,6% [2,5-6,6%]. Os fatores de risco (odds ratio, OR) associados à condição de foco foram: histórico de aborto (OR= 1,42 [1,04-1,95]) e exploração de corte (OR= 1,75 [1,30-2,38]). ______________________________________________________________________________________________________________ ABSTRACTA study to characterize the brucellosis epidemiological situation in the State of Rondônia was carried out. The State was divided into three regions. Three hundred herds were randomly sampled in each region. A pre-established number of animals were sampled in each of these herds. From 927 herds and 9,717 serum samples were collected. In each herd, it was applied an epidemiological questionnaire regarding herd features and also husbandry and sanitary practices that could be associated with risk of infection. The serum samples were screened for antibodies to Brucella spp. by the Rose-Bengal Test (RBT), and all RBT-positive sera were re-tested by the 2-mercaptoethanol test (2-ME). The herd was considered positive if at least one animal was positive on both RBT and 2-ME tests. The prevalences of infected herds and animals in Rondônia State were 35.2% [32.1-38.4%] and 6.2% [4.9-7.6%], respectively. In the regions, the prevalences of infected herds and animals were, respectively: region 1, 41.9% [36.3-47.6%] and 8.3% [5.9-10.8%]; region 2, 31.7% [26.5-37.2%] and 5.9% [4.3-7.6%]; and region 3, 31.9% [26.7-37.4%] and 4.6% [2.5-6.6%]. The risk factors (odds ratio, OR) associated with the presence of the infection were: recent history of abortion (OR= 1.42 [1.04-1.95]) and beef herd (OR=1.75 [1.30-2.38])

Epidemiological situation of bovine brucellosis in the State of Bahia, Brazil

O trabalho consistiu em estratificar o Estado da Bahia em quatro regiões com características homogêneas (circuitos produtores) para que fossem amostradas aleatoriamente, em cada uma delas, 300 propriedades. Em cada propriedade foram escolhidas, de forma aleatória, 10 a 15 fêmeas bovinas adultas, das quais foi obtida uma amostra de sangue. No total, foram amostrados 10.816 animais, provenientes de 1.413 propriedades. O protocolo de testes utilizado foi o da triagem com o teste do antígeno acidificado tamponado (Rosa Bengala) e a confirmação dos positivos com o teste do 2-mercaptoetanol. O rebanho foi considerado positivo se pelo menos um animal reagiu às duas provas sorológicas. As prevalências de focos e a de fêmeas adultas soropositivas do Estado foram de 4,2% [3,1-5,3%] e 0,66% [0,41-0,93%], respectivamente. Para os circuitos produtores foram: circuito 1, 5,8% [3,6-8,7%] e 0,86% [0,41-1,3%]; circuito 2, 3,1% [1,5-5,6%] e 1,2% [0,25-2,1%]; circuito 3, 6,3% [4,0-9,3%] e 1,7% [0,66-2,7%]; e circuito 4, 0,60% [0,07-2,2%] e 0,07 [0,00-0,21%]. Para a análise de fatores de riscos associados à doença foi aplicado um questionário epidemiológico em cada propriedade visitada. Os fatores de risco (odds ratio, OR) associados à condição de foco foram: compra de reprodutores (OR= 2,27) e presença de áreas alagadiças (OR= 1,76). A vacinação de fêmeas de três até oito meses de idade foi um fator de proteção (OR= 0,53). ____________________________________________________________________________________________________________________ ABSTRACTA study to characterize the epidemiological situation of bovine brucellosis in the State of Bahia was carried out in 2004. The State was divided into four similar production regions, 300 herds were randomly sampled in each region, and 10 to 15 adult bovine females were sampled in each of these herds. A total of 10,816 serum samples from 1,413 herds were collected. The serum samples were screened for antibodies to Brucella spp. by the Rose-Bengal Test (RBT), and all RBT-positive sera were re-tested by the 2-mercaptoethanol test (2-ME) for confirmation. A herd was considered positive if at least one animal was positive on both RBT and 2-ME tests. The prevalence of infected herds and seropositive adult bovine females in Bahia State were: 4.2% [3.1-5.3%] and 0.66% [0.41-0.93%], respectively. In the production regions, prevalence of infected herds and animals were, respectively: region 1, 5.8% [3.6-8.7%] and 0.86% [0.41-1.3%]; region 2, 3.1% [1.5-5.6%] and 1.2% [0.25-2.1%]; region 3, 6.3% [4.0-9.3%] and 1.7% [0.66-2.7%]; and region 4, 0.60% [0.07-2.2%] and 0.07%[0.00-0.2%]. In each herd, an epidemiological questionnaire was applied. The risk factors (odds ratio, OR) associated with the presence of the infection were: purchase of breeding animals (OR = 2.27) and presence of flood areas (OR= 1.76). Vaccination of heifers from three to eight months of age was a protective factor (OR=0.53)

Epidemiologic situation of bovine brucellosis in the State of Mato Grosso, Brazil

Caracterizou-se a brucelose bovina em Mato Grosso por meio de um estudo transversal realizado em 2003 para auxiliar na implementação do Programa Nacional de Controle e Erradicação da Brucelose e Tuberculose. No Estado, estratificado em quatro circuitos pecuários, foram amostrados 13.684 animais, provenientes de 1.152 rebanhos. O protocolo de testes utilizado foi o da triagem com o teste do antígeno acidificado tamponado e os soros reagentes foram testados pelo 2-mercaptoetanol (ME) e concomitantemente retestados pelo teste de Rosa Bengala para resultado conclusivo. As prevalências de focos e de animais infectados foram: 41,2% [38,0-44,4%] e 10,2% [7,4-13,1%], respectivamente. Nos circuitos produtivos, as prevalências de focos foram 36,9% [29,2-45,2%], 27,2% [22,8-32,1%], 40,4% [38,8-46,2%] e 50,3% [44,5-56,1%]; e as prevalências de animais 7,9% [3,0-12,9%], 4,1% [2,8-5,4%], 8,1% [5,2-11,1%] e 15,3% [9,2-21,3%], respectivamente, para os circuitos 1, 2, 3 e 4. Os fatores de risco (odds ratio, OR) associados à condição de foco no Estado foram: exploração de gado de corte (OR= 1,8 [1,2-2,5]), exploração mista (OR=1,8 [1,2-2,7]), número de fêmeas no rebanho de 11 a 50 (OR=4,8 [1,1-20,8]), número de fêmeas no rebanho acima de 51 (OR=6,8 [1,6-29,0]), ocorrência de aborto (OR=1,7 [1,3-2,2]). A brucelose está homogeneamente distribuída no Estado, o que permite uniformidade de medidas sanitárias. Adicionalmente, sugere-se a intensificação da vacinação de fêmeas para todo o Estado. _______________________________________________________________________________________________________ ABSTRACTA study to characterize bovine brucellosis in the State of Mato Grosso was carried out in 2003 in order to support the implementation of the National Program for the Control and Eradication of Bovine Brucellosis. The State was divided into four productive regions, and 13,684 bovines from 1,152 herds were sampled. The serum samples were screened for antibodies to Brucella spp. by the Rose-Bengal test (RBT) and all RBT-positive sera were re-tested by the 2-mercaptoethanol test (2-ME), and again by RBT for confirmation. The prevalence of infected herds and animals in the State of Mato Grosso were 41.2% [38.0-44.4%] and 10.2% [7.4-13.1%], respectively. In the productive regions, the prevalence of infected herds were 36.9% [29.2-45.2%], 27.2% [22.8-32.1%], 40.4% [38.8-46.2%], and 50.3% [44.5-56.1%], respectively; and the prevalence of infected animals were 7.9% [3.0-12.9%], 4.1% [2.8-5.4%], 8.1% [5.2-11.1%], and 15.3% [9.2-21.3%], respectively, for regions 1, 2, 3, and 4. The risk factors (odds ratio, OR) associated with the presence of the infection in the State were: beef cattle farming (OR=1.8 [1.2-2.5]), mixed (beef and dairy) cattle farming (OR=1.8 [1.2-2.7]), farms with 11 to 50 females (OR=4.8 [1.1-20.8]), farms with more than 51 females (OR=6.8 [1.6-29.0]), and occurrence of abortion (OR=1.7 [1.3-2.2]). Given that brucellosis is homogeneously distributed in the State, uniform sanitary measures might be adopted. As a homogeneous additional measure for the State, the intensification of female vaccination is suggested

Epidemiological situation of bovine brucellosis in the State of São Paulo, Brazil

Realizou-se um estudo para caracterizar a situação epidemiológica da brucelose bovina no Estado de São Paulo. O Estado foi estratificado em sete circuitos produtores de bovinos, e 150 rebanhos com atividade reprodutiva foram aleatoriamente selecionados em cada um deles. No total, foram amostrados 1.073 rebanhos. Foram aletoriamente coletadas amostras de soro de 10 ou 15 fêmeas bovinas com idade ³24 meses, totalizando 8.761 animais. Os soros foram submetidos a um protocolo de testes em série, tendo o teste do antígeno acidificado tamponado como método de triagem e o da fixação de complemento como confirmatório. A prevalência estimada de rebanhos com pelo menos um animal soropositivo foi de 9,7% [7,8-11,6%], enquanto a prevalência estimada de animais soropositivos foi de 3,8% [0,7-6,9%], no Estado. Em cada rebanho foi aplicado um questionário epidemiológico para avaliar o grau de associação de possíveis fatores de risco (odds ratio, OR) com a doença. Propriedades com 87 ou mais bovinos (OR= 2,25) e compra de reprodutores (OR= 1,56) foram as variáveis mais associadas à condição de foco de brucelose. ____________________________________________________________________________________________________________ ARQUIVOA study to characterize the epidemiological situation of bovine brucellosis in the State of São Paulo was carried out. The state was stratified in seven cattle production regions and 150 herds with reproductive activity were randomly selected within each one. A total of 1,073 herds were sampled. In a second stage, 10 or 15 cows older than 24 month age (in herds with <100 cows and herds ≥100 cows, respectively) were bled at random. A total of 8,761 animals were bled. Sera were tested using a serial testing procedure with the Rose Bengal test as the screening method and the Complement Fixation as the confirmatory method. The estimated prevalence of herds with at least one positive animal was 9.7% [7.8-11.6%], whereas the estimated prevalence of positive cattle was 3.8% [0.7-6.9%] in São Paulo State. An epidemiological questionnaire was applied in each farm, allowing the evaluation of the association of selected risk factors with the disease. The characteristics associated with the brucellosis infected herds were farms with more than 87 bovines (OR= 2.25) and introduction of breeding cattle (OR= 1.56)

Epidemiological situation of bovine brucellosis in the State of Rio Grande do Sul, Brazil

Realizou-se um estudo para caracterizar a situação epidemiológica da brucelose bovina. O Estado foi dividido em sete regiões. Em cada região foram amostradas aleatoriamente cerca de 300 propriedades, e dentro dessas foi escolhido de forma aleatória um número pré-estabelecido de animais, dos quais foi obtida uma amostra de sangue. No total foram amostrados 16.072 animais, provenientes de 1.957 propriedades. Em cada propriedade amostrada foi aplicado um questionário epidemiológico para verificar o tipo de exploração e as práticas zootécnicas e sanitárias que poderiam estar associadas ao risco de infecção pela doença. O protocolo de testes utilizado foi o da triagem com o teste do antígeno acidificado tamponado e o reteste dos positivos com o teste do 2-mercaptoetanol. O rebanho foi considerado positivo se pelo menos um animal foi reagente às duas provas sorológicas. Para o Estado, as prevalências de focos e de animais infectados foram, respectivamente, 2,1% [1,5-2,6%] e 1,0% [0,60-1,4%]. Para os circuitos, a prevalência de focos e a de animais foram, respectivamente: circuito 1, 3,1% [1,4-5,7%] e 0,95% [0,0-2,0%]; circuito 2, 7,7% [4,9-11,3%] e 1,0% [0,40-1,7%]; circuito 3, 5,7% [3,4-8,8%] e 2,1% [0,41-3,8%]; circuito 4, 0,66% [0,08-2,4%] e 0,66% [0,0-1,8%]; circuito 5, 0,66% [0,08-2,4%] e 0,05% [0,0-0,13%]; circuito 6, 0,0% [0,0-1,3%] e 0,0% [0,0-0,25%]; circuito 7, 5,4% [2,5-10,1%] e 2,9% [0,49-5,3%]. Os fatores de risco (odds ratio, OR) associados à condição de foco foram: exploração de corte (OR= 4,27 [1,82-10,01]) e histórico de aborto (OR=3,27,1,71-6,25]). ____________________________________________________________________________________________________________ ABSTRACTA study to characterize the epidemiological status of bovine brucellosis was carried out in the State of Rio Grande do Sul. The State was divided in seven regions. Three hundred herds were randomly sampled in each region and a pre-established number of animals were sampled in each of these herds. A total of 16,072 serum samples from 1,957 herds, were collected. In each herd, it was applied an epidemiological questionnaire focused on herd traits as well as husbandry and sanitary practices that could be associated with the risk of infection. The serum samples were screened for antibodies against Brucella spp. by the Rose-Bengal Test and all positive sera were re-tested by the 2-mercaptoethanol test. The herd was considered positive if at least one animal was positive on both tests. The prevalences of infected herds and animals in the State were, respectively 2.1% [1.5-2.6%] and 1.0% [0.60-1.4%]. In the regions, the prevalences of infected herds and animals were, respectively: region 1, 3.1% [1.4-5.7%] and 0.95% [0.0-2.0%]; region 2, 7.7% [4.9-11.3%] and 1.0% [0.40-1.7%]; region 3, 5.7% [3.4-8.8%] and 2.1% [0.41-3.8%]; region 4, 0.66% [0.08-2.4%] and 0.66% [0.0-1.8%]; region 5, 0.66% [0.08-2.4%] and 0.05% [0.0-0.13%]; region 6, 0.0% [0.0-1.3%] and 0.0% [0.0-0.25%]; and region 7, 5.4% [2.5-10.1%] and 2.9% [0.49-5.3%]. The risk factors (odds ratio, OR) associated with the presence of infection were: beef herd (OR= 4.27 [1.82-10.01]) and recent history of abortion (OR= 3.27-1.71-6.25])