Analysing vaccine efficacy evaluated in phase 3 clinical trials carried out during outbreaks.

In this paper we examine several definitions of vaccine efficacy (VE) that we found in the literature, for diseases that express themselves in outbreaks, that is, when the force of infection grows in time, reaches a maximum and then vanishes. The fact that the disease occurs in outbreaks results in several problems that we analyse. We propose a mathematical model that allows the calculation of VE for several scenarios. Vaccine trials usually needs a large number of volunteers that must be enrolled. Ideally, all volunteers should be enrolled in approximately the same time, but this is generally impossible for logistic reasons and they are enrolled in a fashion that can be replaced by a continuous density function (for example, a Gaussian function). The outbreak can also be replaced by a continuous density function, and the use of these density functions simplifies the calculations. Assuming, for example Gaussian functions, one of the problems one can immediately notice is that the peak of the two curves do not occur at the same time. The model allows us to conclude: First, the calculated vaccine efficacy decreases when the force of infection increases; Second, the calculated vaccine efficacy decreases when the gap between the peak in the force of infection and the peak in the enrollment rate increases; Third, different trial protocols can be simulated with this model; different vaccine efficacy definitions can be calculated and in our simulations, all result are approximately the same. The final, and perhaps most important conclusion of our model, is that vaccine efficacy calculated during outbreaks must be carefully examined and the best way we can suggest to overcome this problem is to stratify the enrolled volunteer's in a cohort-by-cohort basis and do the survival analysis for each cohort, or apply the Cox proportional hazards model for each cohort.

Effects of migration rates and vaccination on the spread of yellow fever in Latin American communities.

Objective: To assess how relevant the flow of people between communities is, compared to vaccination and type of vector, on the spread and potential outbreaks of yellow fever in a disease-free host community. Methods: Using a SEIRV-SEI model for humans and vectors, we applied numerical simulations to the scenarios: (1) migration from an endemic community to a disease-free host community, comparing the performance of Haemagogus janthinomys and Aedes aegypti as vectors; (2) migration through a transit community located on a migratory route, where the disease is endemic, to a disease-free one; and (3) effects of different vaccination rates in the host community, considering the vaccination of migrants upon arrival. Results: Results show no remarkable differences between scenarios 1 and 2. The type of vector and vaccination coverage in the host community are more relevant for the occurrence of outbreaks than migration rates, with H. janthinomys being more effective than A. aegypti. Conclusions: With vaccination being more determinant for a potential outbreak than migration rates, vaccinating migrants on arrival may be one of the most effective measures against yellow fever. Furthermore, H. janthinomys is a more competent vector than A. aegypti at similar densities, but the presence of A. aegypti is a warning to maintain vaccination above recommended levels.

Effects of migration rates and vaccination on the spread of yellow fever in Latin American communities

[ABSTRACT]. Objective. To assess how relevant the flow of people between communities is, compared to vaccination and type of vector, on the spread and potential outbreaks of yellow fever in a disease-free host community. Methods. Using a SEIRV-SEI model for humans and vectors, we applied numerical simulations to the scenarios: (1) migration from an endemic community to a disease-free host community, comparing the performance of Haemagogus janthinomys and Aedes aegypti as vectors; (2) migration through a transit community located on a migratory route, where the disease is endemic, to a disease-free one; and (3) effects of different vaccination rates in the host community, considering the vaccination of migrants upon arrival. Results. Results show no remarkable differences between scenarios 1 and 2. The type of vector and vaccination coverage in the host community are more relevant for the occurrence of outbreaks than migration rates, with H. janthinomys being more effective than A. aegypti. Conclusions. With vaccination being more determinant for a potential outbreak than migration rates, vac- cinating migrants on arrival may be one of the most effective measures against yellow fever. Furthermore, H. janthinomys is a more competent vector than A. aegypti at similar densities, but the presence of A. aegypti is a warning to maintain vaccination above recommended levels.

[RESUMEN]. Objetivo. Evaluar la importancia del flujo de personas entre comunidades, en comparación con la vacunación y el tipo de vector, para la propagación y los posibles brotes de fiebre amarilla en una comunidad de acogida libre de la enfermedad. Métodos. Con el empleo de un modelo SEIRV—SEI para personas y vectores, aplicamos simulaciones numéricas a las siguientes situaciones hipotéticas: 1) migración desde una comunidad con endemicidad a una comunidad de acogida libre de la enfermedad, en la que se compararon los resultados producidos por Haemagogus janthinomys y Aedes aegypti como vectores; 2) migración a través de una comunidad de tránsito situada en una ruta migratoria, donde la enfermedad es endémica, hacia otra comunidad libre de la enfermedad; y 3) efectos de tasas de vacunación diferentes en la comunidad de acogida, tomando en consideración la vacunación de las personas migrantes a su llegada. Resultados. Los resultados no muestran diferencias notables entre las situaciones 1 y 2. En cuanto a la aparición de brotes, tanto la cobertura vacunal en la comunidad de acogida como el tipo de vector tienen más importancia que las tasas de migración; y H. janthinomys muestra mayor eficacia que A. aegypti. Conclusiones. Dado que, para determinar la aparición de un posible brote, la vacunación tiene mayor importancia que las tasas de migración, la vacunación de las personas migrantes a su llegada puede ser una de las medidas más eficaces contra la fiebre amarilla. Además, a densidades similares, H. janthinomys es un vector más competente que A. aegypti, por lo que la presencia de A. aegypti constituye una señal de alerta para mantener la vacunación por encima de los niveles recomendados.

[RESUMO]. Objetivo. Avaliar a relevância do fluxo de pessoas entre comunidades em comparação com a vacinação e tipo de vetor para a propagação e potenciais surtos de febre amarela em uma comunidade de destino livre da doença. Métodos. Usando um modelo SEIRV-SEI para humanos e vetores, foram aplicadas simulações numéricas aos seguintes cenários: (1) migração de uma comunidade endêmica para uma comunidade de destino livre da doença, comparando o desempenho de Haemagogus janthinomys e de Aedes aegypti como vetores; (2) migração através de uma comunidade de trânsito localizada em uma rota migratória, onde a doença é endêmica, para uma comunidade de destino livre da doença; e (3) efeitos de diferentes taxas de vacinação na comunidade de destino, considerando-se a vacinação dos migrantes ao chegarem. Resultados. Os resultados não revelaram diferenças marcantes entre os cenários 1 e 2. O tipo de vetor e a cobertura vacinal na comunidade de destino são mais relevantes para a ocorrência de surtos do que as taxas de migração; o vetor H. janthinomys é mais efetivo do que A. aegypti. Conclusões. Na medida em que a vacinação é mais determinante para um potencial surto que as taxas de migração, a vacinação de migrantes na chegada pode ser uma das medidas mais efetivas contra a febre amarela. Além disso, o H. janthinomys é um vetor mais competente do que o A. aegypti em densidades similares, mas a presença de A. aegypti é um alerta para manter a vacinação acima dos níveis recomendados.

Toxoplasma gondii and Neospora caninum antibody seroprevalence and risk factors among dogs treated at Public Veterinary Hospitals in São Paulo, Brazil / Soroprevalência de anticorpos anti-Toxoplasma gondii e Neospora caninum em cães atendidos em Hospitais Públicos Veterinários em São Paulo, Brasil

Abstract Dogs can be infected by Toxoplasma gondii and Neospora caninum, for which they function, respectively, as intermediate, and definitive hosts. In the present study seroprevalence against T. gondii and N. caninum antibodies, were determined by indirect fluorescent antibody test (cut off of 16 and 50, respectively), in dogs that were treated at public veterinary hospitals in the metropolitan region of São Paulo and risk factors were identified. Out of the 1,194 samples 125 (10.5%; 95% CI: 8.8-12.3%) were positive for T. gondii and 9 (0.75%, 95% CI: 0.34-1.4%) for N. caninum. For T. gondii, statistical differences were observed between the proportions of positive dogs and different zones of the municipality (p = 0.025), and age (p = 0.02), higher among older dogs. The keepers were invited to answer an epidemiological questionnaire to analyze risk factors, and 471 (39.4%) agreed to be interviewed, and among their dogs 65 (13.8%) were T. gondii seropositive. Age group above 8 years (OR = 3.63; 95% CI: 1.08-12.23) was a risk factor and having a defined breed (OR = 0.49; 95% CI: 0.25-0.96) was a protective factor for T. gondii infection. Because of the low number of dogs positive for N. caninum, risk factors for this coccidium were not determined.

Resumo Cães podem ser infectados por Toxoplasma gondii e Neospora caninum, os quais funcionam, respectivamente, como hospedeiros intermediários e definitivos. Neste estudo, a soroprevalência contra anticorpos anti-T. gondii e N. caninum foi determinada pelo teste de imunofluorescência indireta (ponto de corte de 16 e 50, respectivamente), em cães atendidos em hospitais públicos veterinários da região metropolitana de São Paulo e fatores de risco foram identificados. Das 1.194 amostras, 125 (10,5%; IC 95%: 8,8-12,3%) foram positivas para T. gondii e 9 (0,75%, IC 95%: 0,34-1,4%) para N. caninum. Para T. gondii foram observadas diferenças entre as proporções de cães positivos e diferentes zonas do município (p = 0,025) e idade (p = 0,02), prevalência maior entre os mais velhos. Os tutores foram convidados a responder um questionário epidemiológico para análise de fatores de risco, e 471 (39,4%) concordaram em ser entrevistados, destes 65 cães (13,8%) eram soropositivos para T. gondii. Faixa etária acima de 8 anos (OR = 3,63; IC 95%: 1,08-12,23) foi fator de risco e raça definida (OR = 0,49; IC 95%: 0,25-0,96) foi fator de proteção para a infecção por T. gondii. Devido ao baixo número de positivos para anticorpos anti-N. caninum, fatores de risco para este coccídio não foram determinados.

Effects of migration rates and vaccination on the spread of yellow fever in Latin American communities / Efectos de las tasas de migración y de la vacunación en la propagación de la fiebre amarilla en comunidades de América Latina / Efeitos das taxas de migração e vacinação na propagação da febre amarela em comunidades latino-americanas

ABSTRACT Objective. To assess how relevant the flow of people between communities is, compared to vaccination and type of vector, on the spread and potential outbreaks of yellow fever in a disease-free host community. Methods. Using a SEIRV-SEI model for humans and vectors, we applied numerical simulations to the scenarios: (1) migration from an endemic community to a disease-free host community, comparing the performance of Haemagogus janthinomys and Aedes aegypti as vectors; (2) migration through a transit community located on a migratory route, where the disease is endemic, to a disease-free one; and (3) effects of different vaccination rates in the host community, considering the vaccination of migrants upon arrival. Results. Results show no remarkable differences between scenarios 1 and 2. The type of vector and vaccination coverage in the host community are more relevant for the occurrence of outbreaks than migration rates, with H. janthinomys being more effective than A. aegypti. Conclusions. With vaccination being more determinant for a potential outbreak than migration rates, vaccinating migrants on arrival may be one of the most effective measures against yellow fever. Furthermore, H. janthinomys is a more competent vector than A. aegypti at similar densities, but the presence of A. aegypti is a warning to maintain vaccination above recommended levels.

RESUMEN Objetivo. Evaluar la importancia del flujo de personas entre comunidades, en comparación con la vacunación y el tipo de vector, para la propagación y los posibles brotes de fiebre amarilla en una comunidad de acogida libre de la enfermedad. Métodos. Con el empleo de un modelo SEIRV—SEI para personas y vectores, aplicamos simulaciones numéricas a las siguientes situaciones hipotéticas: 1) migración desde una comunidad con endemicidad a una comunidad de acogida libre de la enfermedad, en la que se compararon los resultados producidos por Haemagogus janthinomys y Aedes aegypti como vectores; 2) migración a través de una comunidad de tránsito situada en una ruta migratoria, donde la enfermedad es endémica, hacia otra comunidad libre de la enfermedad; y 3) efectos de tasas de vacunación diferentes en la comunidad de acogida, tomando en consideración la vacunación de las personas migrantes a su llegada. Resultados. Los resultados no muestran diferencias notables entre las situaciones 1 y 2. En cuanto a la aparición de brotes, tanto la cobertura vacunal en la comunidad de acogida como el tipo de vector tienen más importancia que las tasas de migración; y H. janthinomys muestra mayor eficacia que A. aegypti. Conclusiones. Dado que, para determinar la aparición de un posible brote, la vacunación tiene mayor importancia que las tasas de migración, la vacunación de las personas migrantes a su llegada puede ser una de las medidas más eficaces contra la fiebre amarilla. Además, a densidades similares, H. janthinomys es un vector más competente que A. aegypti, por lo que la presencia de A. aegypti constituye una señal de alerta para mantener la vacunación por encima de los niveles recomendados.

RESUMO Objetivo. Avaliar a relevância do fluxo de pessoas entre comunidades em comparação com a vacinação e tipo de vetor para a propagação e potenciais surtos de febre amarela em uma comunidade de destino livre da doença. Métodos. Usando um modelo SEIRV-SEI para humanos e vetores, foram aplicadas simulações numéricas aos seguintes cenários: (1) migração de uma comunidade endêmica para uma comunidade de destino livre da doença, comparando o desempenho de Haemagogus janthinomys e de Aedes aegypti como vetores; (2) migração através de uma comunidade de trânsito localizada em uma rota migratória, onde a doença é endêmica, para uma comunidade de destino livre da doença; e (3) efeitos de diferentes taxas de vacinação na comunidade de destino, considerando-se a vacinação dos migrantes ao chegarem. Resultados. Os resultados não revelaram diferenças marcantes entre os cenários 1 e 2. O tipo de vetor e a cobertura vacinal na comunidade de destino são mais relevantes para a ocorrência de surtos do que as taxas de migração; o vetor H. janthinomys é mais efetivo do que A. aegypti. Conclusões. Na medida em que a vacinação é mais determinante para um potencial surto que as taxas de migração, a vacinação de migrantes na chegada pode ser uma das medidas mais efetivas contra a febre amarela. Além disso, o H. janthinomys é um vetor mais competente do que o A. aegypti em densidades similares, mas a presença de A. aegypti é um alerta para manter a vacinação acima dos níveis recomendados.

Apparent prevalence and risk factors for bovine tuberculosis in the state of Paraná, Brazil: an assessment after 18 years since the beginning of the Brazilian program.

Bovine tuberculosis (bTB) impacts considerably animal production and one health worldwide. To describe the prevalence, risk factors, and spatial pattern of the disease in the state of Paraná, Brazil, a cross-sectional study was conducted from September 2018 to February 2019. The area was divided into seven regions. Within each region, farms were randomly selected, and a predetermined number of cows was selected and tested by a comparative cervical tuberculin test. 17,210 animals were tested across 1757 farms. Herd prevalence of bTB-infected herds in Paraná was 2.5% [1.87-3.00%]. It has varied from 0.8 to 3.98% among seven regions, with clustering being detected in the west, central, and northeast areas. Animal prevalence was 0.35% [0.21-0.59%] and has varied from 0.08 to 0.6% among the pre-set regions. No major shifts in the prevalence of bTB were detected since 2007. Large-sized herds, dairy production, and feeding with whey were detected to be correlated with the presence of bTB. Exclusively among dairy herds, veterinary assistance from cooperatives, possession of self-owned equipment to cool milk, and feeding with whey were correlated with the disease. Considering these results, it is recommended that the state of Paraná seek to implement a surveillance system for the detection of bTB-infected herds transforming them into free ones, if possible, incorporating elements of risk-based surveillance. Health education is also recommended to inform farmers about the risks of introducing animals without testing and of feeding raw whey to calves.

Modelling control strategies against classical swine fever: Influence of traders and markets using static and temporal networks in Ecuador.

Pig farming in Ecuador represents an important economic and cultural sector, challenged by classical swine fever (CSF). Recently, the National Veterinary Service (NVS), has dedicated its efforts to control the disease by implementing pig identification, mandatory vaccination against CSF and movement control. Our objective was to characterise pig premises according to risk criteria, to model the effect of movement restriction strategies and to consider the temporal evolution of the network. Social network analysis (SNA), SIRS (susceptible, infected, recovered, susceptible) network modelling and temporal analysis were used. The network contained 751,003 shipments and 6 million pigs from 2017 to 2019. Participating premises consisted of 144,118 backyard farms, 138 industrial farms, 21,337 traders and 51 markets. The 10 most influential markets, in the Andean highlands, received between 500 and 4600 pigs each week. The 10 most influential traders made about 3 shipments with 17 pigs per week. Simulations without control strategy resulted in an average CSF prevalence of 14.4 %; targeted movement restriction reduced the prevalence to 7.2 %, while with random movement restriction it was 13 %. Targeting the top 10 national traders and markets and one of the high-risk premises in every parish was one of the best strategies with the surveillance infrastructure available, highlighting its major influence and epidemiological importance in the network. When comparing the static network with its temporal counterpart, causal fidelity (c = 0.62) showed a 38 % overestimation in the number of transmission paths, also traversing the network required 4.39 steps, lasting approximately 233 days. In conclusion, NVS surveillance strategies could be more efficient by targeting the most at-risk premises, and in particular, taking into account the temporal information would make the risk assessment much more precise. This information could contribute to implement risk-based surveillance reducing the time to eradicate CSF and other infectious animal diseases.

Network analysis of pig movements in Ecuador: Strengthening surveillance of classical swine fever.

The analysis of domestic pig movements has become useful to understand the disease spread patterns and epidemiology, which facilitates the development of more effective animal diseases control strategies. The aim of this work was to analyse the static and spatial characteristics of the pig network, to identify its trading communities and to study the contribution of the network to the transmission of classical swine fever. In this regard, we used the pig movement records from the National Veterinary Service of Ecuador (2017-2019), using social network analysis and spatial analysis to construct a network with registered premises as nodes and their movements as edges. Furthermore, we also created a network of parishes as its nodes by aggregating their premises movements as edges. The annual network metrics showed an average diameter of 20.33, a number of neighbours of 2.61, a shortest path length of 4.39 and a clustering coefficient of 0.38 (small-world structure). The most frequent movements were to or from markets (55%). Backyard producers made up 89% of the network premises, and the top 2% of parishes (highest degree) contributed to 50% of the movements. The highest frequencies of movements between parishes were in the centre of the country, while the highest frequency of movements to abattoirs was in the south-west. Finally, the pattern of classical swine fever (CSF) disease outbreaks within the Ecuador network was likely the result of network transmission processes. In conclusion, our results represented the first exploratory analysis of domestic pig movements at premise and parish levels. The surveillance system could consider these results to improve its procedures and update the disease control and management policy, and allow the implementation of targeted or risk-based surveillance.

Dynamics of natural infection by Toxoplasma gondii in goat herds in the semiarid region of northeastern Brazil: transitional antibody observation.

This study aimed to describe the transmission of T. gondii in naturally infected goats in the semiarid region of northeastern Brazil, through evaluating the serological status of these animals from one to 12 months of age. Seven goat farms were selected. During the first visit, an epidemiological questionnaire was applied. Blood samples were collected from pregnant goats and from their female offspring every month, to monitor them for anti-T. gondii antibodies, using the indirect fluorescence antibody test (IFAT). Out of 66 pregnant goats evaluated, 47% (31/66) (95% CI: 34.6% - 59.7%) were positive and out of 93 female offspring, 61.3% (57/93) (95% CI: 52.4% - 69.2%) were positive, in at least one month during the evaluation period. Among the positive female offspring, 43.3% (27/57) (95% CI: 39.7% - 56.9%) presented environmental infection and 56.7% (30/57) (95% CI: 43.4% - 66.3 %) probably had only colostral antibodies or vertical transmission. It was observed that 92,6% (25/27) from environmental infections occurred until reproductive age (six months) (p<0.0001). It was also noted that there is a correlation between the titration of mothers and offspring, until four months of age (p<0.0001). Large fluctuations in the presence of antibodies were observed among the animals over the months monitored. It can be concluded that the prevalence of anti-T. gondii antibodies within the herds was greater than what has been expressed in specific prevalence studies and that most goat become infected up to the six months of life in the studied area.

Seroprevalence and risk factors for bovine brucellosis in the state of Paraná, Brazil: an analysis after 18 years of ongoing control measures.

Seroprevalence and risk factors of bovine brucellosis (Brucella abortus) in herds and cattle were estimated by a cross-sectional study in the state of Paraná, Brazil. The state was divided into seven regions and a random, two-stage sampling was performed on properties and cattle from each region between 2018 and 2019. Serum samples were collected from 11,592 cows over 24 months from 1,757 properties and a questionnaire was applied to identify potential risk factors. As recommended by the National Program for the Control and Eradication of Animal Brucellosis and Tuberculosis (PNCEBT), serological testing for the detection of anti-Brucella antibodies included the buffered plate agglutination test (screening test) and the fluorescence polarization assay (confirmatory test). The seroprevalence of bovine brucellosis on properties and in cattle was 4.87% (95% confidence interval [CI]: 3.98-5.93%) and 2.24% (95% CI: 1.47-3.41%), respectively. Multiple logistic regression analysis identified larger herd size and failure to test for brucellosis as risk factors for the presence of anti-B. abortus antibodies. These results demonstrate no change in the prevalence when comparing initial studies conducted in 2002. Given our findings, it is recommended that policies for brucellosis control include a widespread vaccination program for higher prevalence areas and eradication approach to lower prevalence areas. All steps related to correct immunization of the herds should be verified and improved by training and education. Health education action must be carried out informing farmers about the risks of introducing animals not tested for brucellosis into their herds and the benefits of testing their herds regularly.

Modelling the impact of delaying vaccination against SARS-CoV-2 assuming unlimited vaccine supply.

BACKGROUND: At the moment we have more than 177 million cases and 3.8 million deaths (as of June 2021) around the world and vaccination represents the only hope to control the pandemic. Imperfections in planning vaccine acquisition and difficulties in implementing distribution among the population, however, have hampered the control of the virus so far. METHODS: We propose a new mathematical model to estimate the impact of vaccination delay against the 2019 coronavirus disease (COVID-19) on the number of cases and deaths due to the disease in Brazil. We apply the model to Brazil as a whole and to the State of Sao Paulo, the most affected by COVID-19 in Brazil. We simulated the model for the populations of the State of Sao Paulo and Brazil as a whole, varying the scenarios related to vaccine efficacy and compliance from the populations. RESULTS: The model projects that, in the absence of vaccination, almost 170 thousand deaths and more than 350 thousand deaths will occur by the end of 2021 for Sao Paulo and Brazil, respectively. If in contrast, Sao Paulo and Brazil had enough vaccine supply and so started a vaccination campaign in January with the maximum vaccination rate, compliance and efficacy, they could have averted more than 112 thousand deaths and 127 thousand deaths, respectively. In addition, for each month of delay the number of deaths increases monotonically in a logarithmic fashion, for both the State of Sao Paulo and Brazil as a whole. CONCLUSIONS: Our model shows that the current delay in the vaccination schedules that is observed in many countries has serious consequences in terms of mortality by the disease and should serve as an alert to health authorities to speed the process up such that the highest number of people to be immunized is reached in the shortest period of time.

Estimating the effects of reopening of schools on the course of the epidemic of COVID-19.

In this paper, we present a method to estimate the risk of reopening of schools illustrated with the case of the State of São Paulo, Brazil. The model showed that, although no death of children would result from the reopening of the schools in the three cities analysed, the risk of asymptomatic and symptomatic cases and secondary cases among teachers, school staff and relatives of the children is not negligible. Although the epidemic hit different regions with different intensities, our model shows that, for regions where the incidence profile is similar to the cities analysed, the risk of reopening of schools is still too high. This in spite of the fact that incidences in these cities were declining in the period of the time considered. Therefore, although we cannot extend the result to the entire country, the overall conclusion is valid for regions with a declining incidence and it is even more valid for regions where incidence is increasing. We assumed a very conservative level of infection transmissibility of children of just 10% as that of adults. In spite of the very low level of transmissibility is assumed, the number of secondary cases caused by infected children among teachers, school staff and relatives varied from 2 to 85. It is, therefore, too soon to have any degree of confidence that reopening of schools before the advent of a vaccine is the right decision to take. The purpose of our model and simulations is to provide a method to estimate the risk of school reopening, although we are sure it could be applied as a guide to public health strategies.

Modelling the impact of contact tracing of symptomatic individuals on the COVID-19 epidemic.

OBJECTIVES: With the declining numbers of coronavirus disease 2019 (COVID-19) cases in the state of São Paulo, Brazil, social distancing measures have gradually been lifted. However, the risk of a surge in the number of cases cannot be overlooked. Even with the adoption of nonpharmaceutical interventions, such as restrictions on mass gatherings, wearing of masks, and complete or partial closure of schools, other public health measures may help control the epidemic. We aimed to evaluate the impact of the contact tracing of symptomatic individuals on the COVID-19 epidemic regardless of the use of diagnostic testing. METHODS: We developed a mathematical model that includes isolation of symptomatic individuals and tracing of contacts to assess the effects of the contact tracing of symptomatic individuals on the COVID-19 epidemic in the state of São Paulo. RESULTS: For a selection efficacy (proportion of isolated contacts who are infected) of 80%, cases and deaths may be reduced by 80% after 60 days when 5000 symptomatic individuals are isolated per day, each of them together with 10 contacts. On the other hand, for a selection efficacy of 20%, the number of cases and deaths may be reduced by approximately 40% and 50%, respectively, compared with the scenario in which no contact-tracing strategy is implemented. CONCLUSION: Contact tracing of symptomatic individuals may potentially be an alternative strategy when the number of diagnostic tests available is not sufficient for massive testing.

Spatio-temporal network analysis of pig trade to inform the design of risk-based disease surveillance.

Network analysis is a powerful tool to describe, estimate, and predict the role of pig trade in the spread of pathogens and generate essential patterns that can be used to understand, prevent, and mitigate possible outbreaks. This study aimed to describe the network between premises such as production herds, slaughterhouses, and traders of pig movements and identify heterogeneities in the connectivity of premises in the state of Santa Catarina, Brazil, using social network analysis (SNA). We used static and temporal network approaches to describe pig trade in the state by quantifying network attributes using SNA parameters, such as causal fidelity, loyalty, the proportion of node-loyalty, resilience of outgoing contact chains, and communities. Two indexes were implemented, the first one is a normalized index based on SNA-farm level measures and other index-based SNA-farm level measures considering the swineherd population size from all premises, both indexes were summarized by a municipality to target and rank surveillance activities. Within Santa Catarina, the southwest region played a key role in that 80 % of trade was concentrated in this region, and thus acted as a hub in the network. Besides, nine communities were found. The results also showed that premises were highly connected in the static network, with the network exhibiting low levels of fragmentation and loyalty. Also, just 11 % of the paths in the static network existed in the temporal network which accounted for the order in which edges occurred. Therefore, the use of time-respecting-paths was essential to not overestimate potential transmission pathways and outbreak sizes. Compared to static networks, the application of temporal network approaches was more suitable to capture the dynamics of pig trade and should be used to inform the design of riskbased disease surveillance.

Modelling the test, trace and quarantine strategy to control the COVID-19 epidemic in the state of São Paulo, Brazil.

Testing for detecting the infection by SARS-CoV-2 is the bridge between the lockdown and the opening of society. In this paper we modelled and simulated a test-trace-and-quarantine strategy to control the COVID-19 outbreak in the State of São Paulo, Brasil. The State of São Paulo failed to adopt an effective social distancing strategy, reaching at most 59% in late March and started to relax the measures in late June, dropping to 41% in 08 August. Therefore, São Paulo relies heavily on a massive testing strategy in the attempt to control the epidemic. Two alternative strategies combined with economic evaluations were simulated. One strategy included indiscriminately testing the entire population of the State, reaching more than 40 million people at a maximum cost of 2.25 billion USD, that would reduce the total number of cases by the end of 2020 by 90%. The second strategy investigated testing only symptomatic cases and their immediate contacts - this strategy reached a maximum cost of 150 million USD but also reduced the number of cases by 90%. The conclusion is that if the State of São Paulo had decided to adopt the simulated strategy on April the 1st, it would have been possible to reduce the total number of cases by 90% at a cost of 2.25 billion US dollars for the indiscriminate strategy but at a much smaller cost of 125 million US dollars for the selective testing of symptomatic cases and their contacts.

The optimal age of vaccination against dengue in Brazil based on serotype-specific forces of infection derived from serological data.

In this paper, we study a single serotype transmission model of dengue to determine the optimal vaccination age for Dengvaxia. The transmission dynamics are modelled with an age-dependent force of infection. The force of infection for each serotype is derived from the serological profile of dengue in Brazil without serotype distinction and from serotype-specific reported cases. The risk due to an infection is measured by the probability of requiring hospitalization based on Brazilian Ministry of Health data. The optimal vaccination age is determined for any number and combination of the four distinct dengue virus serotypes DENv1-4. The lifetime expected risk is adapted to include antibody dependent enhancement (ADE) and permanent cross-immunity after two heterologous infections. The risk is assumed to be serostatus-dependent. The optimal vaccination age is computed for constant, serostatus-specific vaccine efficacies. Additionally, the vaccination age is restricted to conform to the licence of Dengvaxia in Brazil and the achievable and minimal lifetime expected risks are compared. The optimal vaccination age obtained for the risk of hospitalization varies significantly with the assumptions relating to ADE and cross-immunity. Risk-free primary infections lead to higher optimal vaccination ages, as do asymptomatic third and fourth infections. Sometimes vaccination is not recommended at all, e.g. for any endemic area with a single serotype if primary infections are risk-free. Restricting the vaccination age to Dengvaxia licensed ages mostly leads to only a slightly higher lifetime expected risk and the vaccine should be administered as close as possible to the optimal vaccination age.

Modelling the impact of delaying vaccination against SARS-CoV-2 assuming unlimited vaccine supply

Background At the moment we have more than 177 million cases and 3.8 million deaths (as of June 2021) around the world and vaccination represents the only hope to control the pandemic. Imperfections in planning vaccine acquisition and difficulties in implementing distribution among the population, however, have hampered the control of the virus so far. Methods We propose a new mathematical model to estimate the impact of vaccination delay against the 2019 coronavirus disease (COVID-19) on the number of cases and deaths due to the disease in Brazil. We apply the model to Brazil as a whole and to the State of Sao Paulo, the most affected by COVID-19 in Brazil. We simulated the model for the populations of the State of Sao Paulo and Brazil as a whole, varying the scenarios related to vaccine efficacy and compliance from the populations. Results The model projects that, in the absence of vaccination, almost 170 thousand deaths and more than 350 thousand deaths will occur by the end of 2021 for Sao Paulo and Brazil, respectively. If in contrast, Sao Paulo and Brazil had enough vaccine supply and so started a vaccination campaign in January with the maximum vaccination rate, compliance and efficacy, they could have averted more than 112 thousand deaths and 127 thousand deaths, respectively. In addition, for each month of delay the number of deaths increases monotonically in a logarithmic fashion, for both the State of Sao Paulo and Brazil as a whole. Conclusions Our model shows that the current delay in the vaccination schedules that is observed in many countries has serious consequences in terms of mortality by the disease and should serve as an alert to health authorities to speed the process up such that the highest number of people to be immunized is reached in the shortest period of time.

Estimating the effects of reopening schools on the course of the epidemic of COVID-19

In this paper we present a method do estimate the risk of reopening schools illustrated with the case of the State of São Paulo, Brazil. The model showed that, although no death of children would result from the reopening of the schools in the three cities analyzed, the risk of asymptomatic and symptomatic cases and secondary cases among teacher, school staff and relatives of the children is not negligible. Although the epidemic hit different regions with different intensity, our model shows that, for regions where the incidence profile is similar to the cities analysed, the risk of reopening schools is still too high. This in spite of the fact that incidence in these cities were declining in the period of time considered. Therefore, although we cannot extend the result for the entire country, the overall conclusion is valid for regions with declining incidence and it is even more valid for regions where incidence is increasing. We assumed a very conservative level of infection transmissibility of children of just 10% as that of adults. In spite of this very low level of transmissibility assumed, the number of secondary cases caused by infected children among teachers, school staff a relatives varied from 2 to 85. It is therefore too soon to have any degree of confidence that reopening school before the advent of a vaccine is the right decision to take. The purpose of our model and simulations is to provide a method to estimate the risk of schools reopening, although we are sure it could be applied as a guide to public health strategies.

Modelling the impact of contact tracing of symptomatic individuals on the COVID-19 epidemic

OBJECTIVES: With the declining numbers of coronavirus disease 2019 (COVID-19) cases in the state of São Paulo, Brazil, social distancing measures have gradually been lifted. However, the risk of a surge in the number of cases cannot be overlooked. Even with the adoption of nonpharmaceutical interventions, such as restrictions on mass gatherings, wearing of masks, and complete or partial closure of schools, other public health measures may help control the epidemic. We aimed to evaluate the impact of the contact tracing of symptomatic individuals on the COVID-19 epidemic regardless of the use of diagnostic testing. METHODS: We developed a mathematical model that includes isolation of symptomatic individuals and tracing of contacts to assess the effects of the contact tracing of symptomatic individuals on the COVID-19 epidemic in the state of São Paulo. RESULTS: For a selection efficacy (proportion of isolated contacts who are infected) of 80%, cases and deaths may be reduced by 80% after 60 days when 5000 symptomatic individuals are isolated per day, each of them together with 10 contacts. On the other hand, for a selection efficacy of 20%, the number of cases and deaths may be reduced by approximately 40% and 50%, respectively, compared with the scenario in which no contact-tracing strategy is implemented. CONCLUSION: Contact tracing of symptomatic individuals may potentially be an alternative strategy when the number of diagnostic tests available is not sufficient for massive testing.

Modelling the test, trace and quarantine strategy to control the COVID-19 epidemic in the state of São Paulo, Brazil

Testing for detecting the infection by SARS-CoV-2 is the bridge between the lockdown and the opening of society. In this paper we modelled and simulated a test-trace-and-quarantine strategy to control the COVID-19 outbreak in the State of São Paulo, Brasil. The State of São Paulo failed to adopt an effective social distancing strategy, reaching at most 59% in late March and started to relax the measures in late June, dropping to 41% in 08 August. Therefore, São Paulo relies heavily on a massive testing strategy in the attempt to control the epidemic. Two alternative strategies combined with economic evaluations were simulated. One strategy included indiscriminately testing the entire population of the State, reaching more than 40 million people at a maximum cost of 2.25 billion USD, that would reduce the total number of cases by the end of 2020 by 90%. The second strategy investigated testing only symptomatic cases and their immediate contacts – this strategy reached a maximum cost of 150 million USD but also reduced the number of cases by 90%. The conclusion is that if the State of São Paulo had decided to adopt the simulated strategy on April the 1st, it would have been possible to reduce the total number of cases by 90% at a cost of 2.25 billion US dollars for the indiscriminate strategy but at a much smaller cost of 125 million US dollars for the selective testing of symptomatic cases and their contacts.