Metrics details
Surgical castration of males is carried out on a large scale in the US swine industry and the pain resulting from this procedure can be assessed using the Unesp-Botucatu pig composite acute pain scale (UPAPS)
We aim to propose a short version of UPAPS based on the behaviors best-ranked by a random forest algorithm
We used behavioral observations from databases of surgically castrated pre-weaned and weaned pigs
We trained a random forest algorithm using the pain-free (pre-castration) and painful (post-castration) conditions as target variable and the 17 UPAPS pain-altered behaviors as feature variables
We ranked the behaviors by their importance in diagnosing pain
The algorithm was refined using a backward step-up procedure
The predictive capacity of the original and short version of the UPAPS was estimated by the area under the curve (AUC)
the algorithm with the five best-ranked behaviors had the lowest complexity and predictive capacity equivalent to the algorithm with all behaviors
The AUC of Short UPAPS (89.62%) was statistically equivalent (p = 0.6828) to that of UPAPS (90.58%)
the proposed Short UPAPS might facilitate the implementation of a standard operating procedure to monitor and diagnose acute pain post-castration in large-scale systems
identifying a more concise method to assess pain in pigs is needed intervention analgesia decision making for mitigating acute pain
the random forest can contribute to identifying important behaviors that drive pain assessment outcomes in castrated pigs
The refinement of pain scales to establish an concise version that still maintain accuracy
might facilitate a more realistic pain monitoring protocol for large-scale systems
This short pain scale version might enable on-farm delivery of pain mitigation and improve pig’s welfare
pain-altered behaviors in pigs have not been ranked by random forest yet to propose a short version of the UPAPS
the use of machine learning techniques is a novel approach to refine and to establish short pain scale versions across several species
we aimed to propose a short version of UPAPS based on the pain-altered behaviors best-ranked by the random forest algorithm using pigs before and after surgical castration
Inter-observer reliability of the UPAPS total sum was considered “good” to “very good” according to the intraclass correlation coefficient (ICC) (Table 1)
while the pre-weaned pig database was 0.98
Percentage of the importance of the 17 UPAPS pain-altered behavior based on the random forest algorithm using the pain condition (after castration) and pain-free (before castration) as target variable (UPAPS is Unesp-Botucatu pig composite acute pain scale)
The random forest algorithm had an AUC of 91.38%, which was statistically equivalent (p = 0.8545) to the AUC of UPAPS (90.58%) (Table 2)
The AUC of UPAPS (90.58%) was statistically equivalent (p = 0.4940) to its short version (89.62%) (Table 3)
Short UPAPS total sum ranged from 0 to 5 and had an optimal cut-off point of 2 based on the upper 95% confidence interval
no work to date has ranked these pain-altered behaviors using machine learning techniques to develop a short version of this pain scale
we used five experienced observers in swine pain assessment
who had satisfactory inter-observer reliability for the UPAPS total sum
we assumed behavioral assessments were reliable in the study
the other two of five pain-altered behaviors were different across studies and might be explained by (i) the database used
and (iii) the type of target and feature variables used as input to the algorithm for each study
Further studies should explore new study population of pigs and observers to cover larger individual variability
One novelty of the present study was the Short UPAPS proposal based on the refinement by the random forest algorithm
The Short UPAPS and the original did not significantly differ in discriminatory ability
The optimal cut-off point above 2 on the Short UPAPS total sum determined that the occurrence of only two of the five best-ranked pain-altered behaviors indicates a painful condition
It is worth mentioning that Short UPAPS was effective in identifying acute pain
considering exclusively surgical castration of weaned and pre-weaned pigs
the methodological approach used to refine the algorithm and propose a short version of the UPAPS can be easily translated to pain scales in other species
we identified a ranking of the importance of UPAPS pain-altered behaviors using a random forest algorithm and found that the predictive capacity of the algorithm was equivalent to UPAPS
we determined a short version of the UPAPS based on the five pain-altered behaviors best-ranked by the algorithm that had a discriminatory ability equivalent to the original version of the UPAPS
the proposed Short UPAPS might facilitate implementing acute pain monitoring in surgical castration routines in large-scale systems
Future studies are needed to validate the proposed Short UPAPS based on psychometric properties following the COSMIN guidelines
provided the original author and source were credited
we disregarded both food-related items (Appetite and Nursing item) to combine the two databases
The total sum of the five behavioral items ranged from 0 to 15 and represented the intensity of pain according to UPAPS
Statistical analysis was conducted in the R programming language, in the RStudio integrated development environment77 (Version 4.3.0; RStudio
The functions and packages used were described as ‘package::function’ format corresponding to the programming language used
a significance level of 5% (p < 0.05) was considered
Palette colors distinguishable by people with common forms of color blindness were used to construct the figures (ggplot2::scale_colour_viridis_d)
The sample size was estimated using 80% power
and 0.90 of the area under the curve according to a receiver operating characteristic curve test (pROC::power.roc.test)
the minimum sample size estimated was six cases (painful conditions) and six controls (pain-free conditions)
Reliability was conducted using 100% of all databases
The database was separated into a division for training (training base) and another for testing (testing base)
The training base contained 70% of the pigs (31 weaned and 10 pre-weaned) selected randomly
while the testing base had 30% of the remaining pigs (14 weaned and four pre-weaned)
Both training and testing bases remained with five observers
exclusively changing the number of pigs and
each dummy variable represented one UPAPS pain-altered behavior
All trees were based on the Gini coefficient
The list of UPAPS items names andtheir respective dummy variables (pain-altered behaviors) used in the algorithm can be seen in the Table S2
The optimization (tuning) of the algorithm was conducted adjusting the random forest hyperparameters and cross-validation parameters by using the grid search technique
testing (i) two to 17 feature variables in each decision tree
1001 and 2001 decision trees in the forest
(iii) two to 10 folds in k-fold technique and (iv) two to 10 repetitions
3888 algorithms were evaluated with multiple combinations of random forest hyperparameters and cross-validation parameters
and their accuracy was on average 92.07 ± 0.66%
The random forest algorithm with the highest accuracy (94.26%) contained two feature variables in each decision tree
which was assumed as the optimal complexity algorithm to be used in the study
the ranking of the importance of each pain-altered behavior (caret::varImp) according to the classification of the selected algorithm was presented in a bar plot (ggplot2::ggplot)
AUC above 90 is considered ‘good’ and above 95 is ‘excellent’
The ROC curve for each algorithm was constructed using the condition (painful and pain-free) as a predictive variable and the UPAPS total sum or the probability of each pig needing analgesia based each algorithm as a predictive variable (pROC::ROC)
it is necessary to establish an optimal cut-off point for each predictive variable
The YI is estimated based on the sum of specificity and sensitivity subtracted from 1
calculated for each value of the predictive variable
The YI represents the maximum specificity and sensitivity concomitantly
attributing similar importance of specificity and sensitivity to the optimal cut-off point
The algorithms’ AUC were compared with UPAPS’s AUC by the DeLong test (pROC::roc.test)
We use the ranking established by random forest training to reduce the number of pain-altered behaviors in the algorithm based on a step-up backward procedure
an algorithm was built using the training base
with exclusively the 16 best-ranked pain-altered behaviors
and this procedure was repeated sequentially until an algorithm was built with only the two best-ranked pain-altered behaviors
the AUC of all algorithms with different numbers of pain-altered behaviors was compared with the AUC of the algorithm containing all behaviors using the DeLong test
The algorithm with the smallest number of pain-altered behaviors (lowest complexity) having an AUC statistically equivalent to or greater than the algorithm with all pain-altered behaviors was understood as the best refinement
The pain-altered behaviors contained in the algorithm with the best refinement were added together to make the Short UPAPS total sum
with each pain-altered behavior computed value ‘1’ in the total sum regardless of its classification on the original scale
An optimal cut-off point was established for Short UPAPS based on the high 95% confidence interval of the YI
the AUC of the Short UPAPS was compared with the AUC of the UPAPS using the DeLong test
These steps were done with the testing base
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Laboratory of Applied Artificial Intelligence in Health
Beatriz Granetti Peres & Pedro Henrique Esteves Trindade
Department of Veterinary Surgery and Animal Reproduction
School of Veterinary Medicine and Animal Science
Global Production Animal Welfare Laboratory
Department of Population Health and Pathobiology
Monique Danielle Pairis-Garcia & Pedro Henrique Esteves Trindade
Department of Large Animal Clinical Sciences
Writing—original draft and Writing—review & editing; GVS: Investigation and Writing—review & editing; BGP: Writing—review & editing; SPLL: Investigation and Writing—review & editing; MDPG: Investigation and Writing—review & editing; PHET: Conceptualization
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the São Paulo state government reported 4 flood-related fatalities: 3 in Botucatu and 1 in Marília
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This observational study found the effectiveness of ChadOx1-nCoV19 to be 74.5% against COVID-19 disease of any severity, comparable to the efficacy observed in clinical trials (81.3% after dose 2), despite the dominance of the Gamma and Delta VoCs. No COVID-19-related hospitalizations or deaths in fully vaccinated individuals were reported.
Volume 10 - 2022 | https://doi.org/10.3389/fpubh.2022.1016402
This article is part of the Research TopicCOVID-19 Vaccine Hesitancy, Safety and EffectivenessView all 32 articles
Introduction: As the COVID-19 pandemic progresses
rapidly emerging variants of concern raise fears that currently licensed vaccines may have reduced effectiveness against these new strains
a mass vaccination campaign using ChadOx1-nCoV19 was initiated on 16th of May 2021
Two vaccine doses were offered 12 weeks apart
with the second delivered on 8th of August
This setting offered a unique opportunity to assess the effectiveness of two ChadOx1-nCoV19 doses in a real-life setting
and vaccination were obtained from the Hospital das Clínicas da Faculdade de Medicina de Botucatu
A test-negative study design was employed; whereby the odds of being vaccinated among cases vs controls were calculated to estimate vaccine effectiveness (VE; 1-OR)
All individuals aged 18–60 who received a PCR test after the 16th of May and were unvaccinated prior to this date were included in the analysis until the study ended in mid-November 2021
Results: 77,683 citizens of Botucatu aged 18–60 received the first dose
and 74,051 received a second ChadOx1-nCoV19 dose 12 weeks later for a vaccination coverage of 84.2 and 80.2%
The VE against any symptomatic infection was estimated at 39.2%
There were no COVID-19-related hospitalizations or deaths among the 74,051 fully vaccinated individuals
The VE against severe disease was estimated at 70.8 and 100% after doses 1 and 2
90.5% of all lineages sequenced between doses 1 and 2 (16th of May−7th of August) were of the Gamma variant
while 83.0% were of the Delta variant during the second period after dose 2 (8th of August−18th of November)
Discussion: This observational study found the effectiveness of ChadOx1-nCoV19 to be 74.5% against COVID-19 disease of any severity
comparable to the efficacy observed in clinical trials (81.3% after dose 2)
despite the dominance of the Gamma and Delta VoCs
No COVID-19-related hospitalizations or deaths in fully vaccinated individuals were reported
Large scale vaccination was core for containing the pandemic
The most used COVID-19 vaccine globally is the vector construct ChadOx1-C0V19 developed by the University of Oxford
As the pandemic progresses, variants of concern (VoCs) of SARS-CoV-2 are constantly emerging; and mutations promoting immune escape have raised questions about the effectiveness of currently licensed COVID-19 vaccines against these emerging VoCs. In January 2021, the P.1 variant (also known as the Gamma variant), designated a VoC by the WHO due to its increased transmissibility, was first identified in Japan in travelers arriving from Manaus, Brazil (3)
the Gamma variant was the dominant strain circulating in Brazil
The city harbors a university hospital that provides tertiary care for surrounding municipalities
The municipal health department adheres to the family health program within Brazil's socialized Unified Health System (SUS); and historically has had high adherence to previous vaccination campaigns
This setting thus offered a unique opportunity to assess the overall effectiveness of 1 and 2 doses of ChadOx1-nCoV19
The Brazilian MoH launched a mass vaccination campaign using ChadOx1-nCoV19 starting on the 16th of May 2021
targeting the population between 18 and 60 years of age
vaccination in the 18–60-years-old population was not yet implemented in Brazil
except for health care workers (HCWs) and high risk citizens
All citizens in this age group (N = 92,349) were eligible for inclusion in the campaign if not yet vaccinated
including those with underlying conditions
Vaccination was offered by qualified HCWs in four school courts and
in 45 election-voting locations with which the vaccinees were familiar
A second dose was planned to be administered 12 weeks after the first dose
Whilst there was no lockdown during the entire study period
mask use was mandatory throughout the study period
The main objective of the study was to determine the vaccine effectiveness (VE) of ChadOx1-nCoV19 against any COVID-19 disease
The VE against severe COVID-19 disease (defined as hospitalization or death) was a secondary objective
All individuals fitting the clinical criteria for COVID-19 as established by the municipal secretary of health according to globally accepted standards received one of three types of tests: a PCR test
PCR positive samples were sequenced upon consent from the participant
All participants who received a positive or negative PCR test result after the 16th of May
and were unvaccinated prior to the same date
In order to measure VE, a TND was applied, whereby the odds of being vaccinated were compared among cases (testing positive for SARS-CoV-2) and controls (not testing positive). Logistic regression was used to obtain the odds ratio and the VE (1−OR). The VE was calculated from 21 days after dose 1 and 14 days after dose 2, as efficacy has been reported to occur after this interval (5)
Records containing information on COVID-19 testing and vaccination status were entered into case report forms (CRFs)
Individual information was derived from four de-identified databases for the period from the 17th of May to the 18th of November 2021: (1) E-SUS
used for routine influenza-like-illness (ILI) surveillance
adapted for the COVID-19 pandemic and containing information on symptomatic and asymptomatic cases
containing vaccination information on all vaccinated individuals
and (4) a database containing information on testing and sequencing results
Databases were linked using a randomly generated de-identified ID
The analysis was restricted to those that received an RT-PCR test within 10 days of symptom onset, to account for the reduced sensitivity of the PCR test after this time (8)
Multiple tests taken on 1 day were counted as one test
with the positive result counting toward the analysis if one was present
Any tests taken within 21 days of each other were counted as one illness episode
Individuals who received more than two vaccine doses were excluded from the analysis
Individuals who received a positive test result prior to being vaccinated were counted as unvaccinated
VE was also estimated from an intent-to-treat (ITT) perspective
measured from the first day after each dose
The research was approved by the Ethical Committee of Botucatu Medical School/São Paulo State University (FMB/UNESP) and by the Comissao Nacional De Etica em Pesquisa CONEP
Only participants who consented to having their information collected were enrolled in the study
only de-identified data were received for analysis
A total of 65,450 citizens aged 18–60 years received a first dose of ChadOx1-nCoV19 on the first day of the campaign (Sunday
for a total of 77,683 vaccines (84.2% coverage)
60,333 citizens received their second ChadOx1-nCoV19 dose 12 weeks later
with an additional 13,718 citizens over the next 4 weeks
for a total of 74,051 fully vaccinated persons (80.2% coverage)
A total of 10,218 PCR tests were available and successfully linked to vaccination data. After various exclusion criteria were applied, 7,958 PCR results were available for analysis, of which 2,109 positive PCRs were recorded in people 18–60 years old (Figure 1)
Exclusion criteria applied to overall cohort
Table 1 shows the baseline characteristics of the study population
The mean age was 35.7 years for the controls and 37.9 for the confirmed COVID-19 cases
Gender was approximately equally distributed in both groups
The positivity rate of the PCR was highest (48.2%) in the week immediately following the first campaign
and rapidly declined to below 20% following the second campaign and finally below 10% in October
Baseline characteristics of persons 18–60 years old tested for COVID-19
Of the 452 strains with sequencing results, 70.4% were Gamma VoC. The remaining strains were either Delta VoC (27.8%, including B.1.617 or AY variants), or Alpha VoC (1.8%). There was, however, an important shift from Gamma VoC dominance to Delta VoC dominance during the study. Table 2 shows the VoC distribution by time period
Overall VE against any illness was estimated at 39.2% (95% CI 23.7–51.5) as of 3 weeks after dose 1, and 74.5% (95% CI 23.7–51.5) as of 14 days after dose 2 (Table 3)
Vaccine effectiveness against any COVID-19 illness
A total of 73 patients with PCR-confirmed COVID-19 infections had severe COVID-19 disease: 64 hospitalizations and nine deaths
None of the 74,051 citizens who were fully vaccinated with ChadOx1-nCoV2 was hospitalized or died during the 3 months of observation
Ten hospitalizations and two deaths occurred in one-dose recipients
of which eight occurred within the first 3 weeks after the first dose
The remaining 61 severe disease events occurred all in non-vaccines
The VE against severe COVID-19 disease was thus estimated at 70.8% after dose 1 (95% CI 9.6–90.6%) and 100% (95% CI 44.3–100%) after dose 2
The ITT analysis whereby VE was measured as of the day of vaccination showed an overall VE after the first dose of 30.7% (95% CI 18.9–40.8) and after the second dose of 70.2% (95% CI 53.0–80.8)
We had defined severe disease in this observational study as hospitalization or death
In the absence of sufficient hospitalizations or deaths among the much smaller cohort of control
we could not estimate with reasonable precision the VE against severe disease
Two deaths and 10 hospitalizations occurred in one-dose recipients
all other severe disease events in non-vaccinees
This study aimed to estimate the effectiveness of ChadOx1-nCoV19 following a mass vaccination campaign in Botucatu
during which 84.2% of the eligible population of 18–60-year-old citizens received at least one dose and 80.2% received a second dose 3 months later
The vast majority of the latter received their first and second dose on single Sundays in May and August in a set-up where the 45 voting stations for elections of the city were transformed into vaccination centers
The vaccine showed an overall effectiveness of 39.2% from week 3 after dose 1
which increased to 74.5% 2 weeks after dose 2
against any COVID-19 illness in individuals 18–60 years old
This study adds to the body of evidence of VE during active circulation of emerging VoCs, such as Gamma and Delta which were predominant during the study period. In randomized control trials, the clinical efficacy of ChadOx1-nCoV19 showed a 76.0% reduction in symptomatic illness in the 3 weeks after dose 1, and of 81.3% 14 days after dose 2 (9)
and with the ancestor strain Wuhan as the predominant strain
prior to the emergence of the Gamma and Delta VoCs
We found slightly higher VE estimates against any COVID-19 disease and Gamma following the first dose
Bernal et al. (12) noted a reduced effectiveness against Delta when compared with the Alpha strain with an estimated effectiveness of ChadOx1-nCoV19 for Delta after dose 1 at 30.0% (vs 48.7% for Alpha) and 67.0% (vs 74.5% for Alpha) after dose 2
Our results suggest a slightly higher VE of 76.0% against Delta
comparable to the originally estimated VE against the Alpha strain
We also calculated VE from the ITT perspective
whereby VE was estimated from the date of vaccination
VE was not estimated against severe COVID-19 using the TND case control approach as the recorded number of patients within the respective observation periods was very limited
none of the 74,051 citizens who had received a full priming was hospitalized or died
We restricted the analysis to those that had symptom onset 2 weeks after each of the mass vaccination campaign dates, to avoid that an increase in testing following COVID-like side effects of the vaccine may bias the VE estimates. This finding is supported by an observed increase in Emergency Room attendance and hospitalizations in the 1 week following each campaign, which was noted in our safety results reported elsewhere (13)
The high vaccination coverage achieved in Botucatu (estimated at 84.2% and 80.2% for the first and second doses
for the population between 18 and 60 years old) may bias the estimation of VE to the null
as the unvaccinated may also have been protected through herd immunity
This study would have benefited from a longer follow-up period to detect any of these effects
We attempted to reduce any selection biases; however
as this was an observational study residual bias is still possible
The use of the TND attempted to control for any selection bias in health-seeking behavior among study participants
Only people who received a PCR test within 10 days of symptom onset were included in the analysis; however
misclassification of cases/controls due to low sensitivity/specificity of the PCR test
which may affect one variant more than another
Given that 70.3% of all sequenced sequences were of the Gamma variant
this reduces the possibility of the latter
Vaccine effectiveness against any COVID-19 disease was estimated at 39.2% in the 3 weeks after dose 1
and 74.5% 2 weeks after dose 2 of ChadOx1-nCoV19 following a mass vaccination campaign in Botucatu
with no hospitalizations or deaths in fully vaccinated individuals
These results suggest that the ChadOx1-nCoV19 was also highly effective in preventing COVID-19 disease in a real-life setting with various circulating variants
not studied in the original efficacy studies
Combined with the reassuring results on the safety of the same vaccine studied in the same campaign
these effectiveness results show the highly beneficial effect that has been achieved through this mass campaign in Botucatu
The raw data supporting the conclusions of this article will be made available by the authors
The study was reviewed and approved by Ethical Committee of Botucatu Medical School/São Paulo State University (FMB/UNESP) and by the Comissao Nacional De Etica em Pesquisa CONEP
The patients/participants provided their written informed consent to participate in this study
All authors critically reviewed and approved the final version
All authors confirm that they had full access to all the data in the study and accept responsibility to submit for publication
This research was funded by the Brazilian Council for Scientific and Technological Development (CNPq)
and the Bill and Melinda Gates Foundation (BMGF)
The investigators acknowledge the support of the Brazil Ministry of Health for donating the vaccines
in-kind support from Oxford University and Fiocruz
and the Bill and Melinda Gates Foundation for financial support
The investigators have special gratitude and acknowledgment to the mayor and the population of the city of Botucatu
Campos and all the health professionals of Botucatu who helped and supported us throughout the study
The authors are grateful to Maxim Blum for help with the analyses
to Alejandra Gonzalez for editorial support
and Somsuvro Basu for help with submission (all at P95 Epidemiology & Pharmacovigilance)
Author CF received funding from the Brazilian Council for Scientific and Technological Development
Authors MC and TV were employed by P95 Epidemiology & Pharmacovigilance
The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest
All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations
Any product that may be evaluated in this article
or claim that may be made by its manufacturer
is not guaranteed or endorsed by the publisher
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Comparing real-life effectiveness of various COVID-19 vaccine regimens during the delta variant-dominant pandemic: a test-negative case-control study
Effectiveness of COVID-19 vaccines against SARS-CoV-2 variants of concern: a systematic review and meta-analysis
Effectiveness of covid-19 vaccines against the B.1.617.2 (Delta) variant
Safety of the fiocruz ChAdOx covid-19 vaccine used in a mass vaccination campaign in Botucatu
National Study Group for COVID-19 Vaccination
Waning mRNA-1273 vaccine effectiveness against SARS-CoV-2 infection in Qatar
Effectiveness of mRNA vaccines and waning of protection against SARS-CoV-2 infection and severe covid-19 during predominant circulation of the delta variant in Italy: retrospective cohort study
COVID-19 vaccine waning and effectiveness and side-effects of boosters: a prospective community study from the ZOE COVID study
Verstraeten T and Clemens R (2022) Effectiveness of the Fiocruz recombinant ChadOx1-nCoV19 against variants of SARS-CoV-2 in the Municipality of Botucatu-SP
Received: 10 August 2022; Accepted: 15 September 2022; Published: 13 October 2022
Copyright © 2022 Costa Clemens, Fortaleza, Crowe, Tasca, Spadaro, Souza-Neto, Grotto, Sider, Jimeno, Verstraeten and Clemens. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY)
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*Correspondence: Ralf Clemens, Y2xlbWVucy5yYWxmQG91dGxvb2suY29t
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The factory is scheduled to go live in 2025 (photo: Karina Toledo/Agência FAPESP)
the plant will perform outsourced medical drug development and production services for pharmaceutical companies
complying with best manufacturing practices
By Karina Toledo | Agência FAPESP – A factory with the infrastructure needed to produce pilot batches of pharmaceuticals for use in clinical trials was unveiled on June 13 on the Botucatu campus of São Paulo State University (UNESP)
Built with funding from the Brazilian health ministry and the university
it will focus on biologics – medical drugs produced using biotechnology and biological sources – especially monoclonal antibodies
which are proteins similar to those secreted by human immune cells but produced in a laboratory to help diagnose and treat various diseases
Part of UNESP’s Center for Studies of Venom and Venomous Animals (CEVAP), the plant will produce inputs for research conducted at the Center for Translational Science and Development of Biopharmaceuticals, which is supported by FAPESP under the aegis of its Science for Development Center (CCD) Program (read more at: agencia.fapesp.br/41208)
it will act as a contract development and manufacturing organization (CDMO)
performing outsourced medical drug development and production services for pharmaceutical companies
biotechs and other research institutions to lower costs and risks for these organizations
increase the flexibility and scalability of production
and assure the quality and conformity of pilot batches of experimental drugs
“This will be Brazil’s first CDMO and the first Latin American center dedicated to the production of biologics for clinical research,” Rui Seabra Ferreira Júnior
Between 100 and 120 patents on biologics are about to expire in the next few years
adding that the possibility of developing biosimilars represents a strategic opportunity for Brazil
“Our focus will be meeting the priorities of the SUS [Sistema Único de Saúde
The importance of increasing Brazil’s capacity to develop and produce vaccines and other biologics became evident during the COVID-19 pandemic.”
According to Benedito Barraviera
a professor at the Botucatu Medical School who founded CEVAP 30 years ago and is now the head of FAPESP’s new CCD
its chief mission will be to accelerate the process of developing and commercializing novel biologics
The CEVAP group became aware of the need for a facility of this kind during the three decades spent prospecting for molecules derived from animal toxins that could give rise to biological medications
Two products developed during this period – a fibrin sealant derived from buffalo blood and snake venom for use as a surgical adhesive
and an antivenom against the sting of Apis mellifera bees – are currently awaiting the investment required for Phase 3 clinical trials
the researchers can apply for registration of the products by ANVISA
the federal agency responsible for regulating drugs and clinical practices
“These products have been under development for some 30 years at a public university and have succeeded in surviving ‘death valley’ [a phase of clinical research when most projects die without reaching the market]
Bringing them to market and society will be a major win for Brazilian science,” Barraviera said
The new factory will have a space reserved for biotech startups
and will also house a school to enable students to train in best manufacturing practices and earn professional qualifications
The initiative is being coordinated by UNESP in partnership with the University of São Paulo (USP)
the State University of Campinas (UNICAMP)
and Oxford University in the United Kingdom
The project has received BRL 20 million in seed investment for construction of the plant
via an agreement between UNESP and the Ministry of Health
A further injection of BRL 60 million is expected for equipment purchasing
UNESP was responsible for hiring all the professionals who are working for the CDMO
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CoronaVac and Covishield effectiveness tested in Serrana and Botucatu, two towns in the state of São Paulo
The researchers compared Serrana with 16 nearby municipalities, including Brodowski, Jardinópolis, and Cravinhos. “We see the result of an uncontrolled epidemic in the region. In general, the microregion of Ribeirão Preto is suffering enormously, but this does not true in Serrana,” highlights Palacios.
When the results were published at the end of May, eight COVID-19 deaths had been recorded among those vaccinated. Seven of them, however, had only received the first dose. From 15 days after the second dose, no deaths were recorded and only two people were hospitalized due to COVID-19. An immunological survey of the population carried out before the study began revealed that 25.7% of residents had already been exposed to the virus.
The situation in Ribeirão Preto remained critical in early June and monitoring of Serrana is ongoing—the study is planned to last a year. “We are showing, at least for the time being, that vaccination is capable of controlling the epidemic,” says Borges. According to him, the research is intended to reveal how long the immunity conferred by the vaccine lasts. Genetic sequencing of samples from patients who test positive will also ensure quick detection of possible new mutations in the virus.
The primary results have been presented to the media and the general public, while the researchers continue to analyze the data generated by the study for a scientific article. “What we have disclosed so far was a more descriptive analysis, such as the effectiveness. Now we need to create a mathematical model to describe our findings. We hope that this will be ready in the next few weeks,” Borges told Pesquisa FAPESP.
Lucas Martins /Fotoarena A volunteer is given the COVID-19 vaccine in Botucatu in early MayLucas Martins /Fotoarena
Although Serrana continues to follow the rules established in São Paulo’s State COVID-19 Plan
Borges believes restrictions in the municipality may be lifted earlier than in other places
“It is only natural that some will activities return to normality sooner in Serrana
a higher percentage of students at school maybe
It makes no sense for a town not to lift restrictions when almost everyone is vaccinated and the pandemic is under control
But this would require central coordination and any easing to be linked to the State Plan.”
which used the Covishield vaccine produced by the Oswaldo Cruz Foundation (FIOCRUZ)
Those involved in the research are currently currently monitoring cases while preparing for a new round of immunization
with the target audience set to receive their second doses over two days in August
67,000 people were vaccinated in a single day on May 16
Another 7,000 received their first dose the following week
People aged over 60 and health professionals had already been vaccinated under the National Immunization Program (PNI)
Pregnant women and new mothers are not participating in the study
“Everyone on the electoral register with proof of address was vaccinated in a single day
such as students at UNESP’s Botucatu campus or people who have lived in the town for years and can prove it but are not on the electoral register
These cases were analyzed with the help of the Brazilian Bar Association and the Public Prosecutor’s Office to ensure they really were residents,” says Fortaleza
“This was important because the risk of people from elsewhere trying to fraudulently gain access to the program was high
I can’t say that we avoided it completely
but we greatly reduced the likelihood with this strategy.”
People were vaccinated in their electoral zones and at defined times according to their age
About 2,500 people volunteered to work as administrative staff and vaccinators
“We were supported by students from the School of Medicine
and people from other areas who performed administrative duties
The project sparked great public enthusiasm,” says Fortaleza
The study is being led by UNESP with funding from the local government
which donated the FIOCRUZ vaccines and around R$10 million to purchase reagents and genetic sequencing machines
and the Bill & Melinda Gates Foundation
It is being carried out in partnership with the University of Oxford and the Federal University of São Paulo (UNIFESP)
Two molecular biology labs at UNESP have been sequencing the genomes of virus samples from positive cases in the town and 12 other smaller municipalities in the region
built up over the years with funding from FAPESP
that we are able to take on this challenge,” says Fortaleza
the team was still awaiting funds promised by the Ministry of Health for the genome sequencing
first identified in Manaus and renamed as the gamma variant
Although it used a different methodology to Project S
with vaccination taking place over eight weeks
Fortaleza does not hide his admiration for the Butantan Institute’s work
But we did not base our research on any previous experience
independent methodology,” stresses the researcher
highlighting the decision to vaccinate the target audience all at once
With extensive experience of vaccination campaigns in Brazil
from the Santa Casa de Sao Paulo School of Medical Sciences
is following the Brazilian effectiveness studies with interest
as well as those carried out in other countries
“The Serrana study is important and promising
but so far we only have early data,” says Moraes
a member of the Epidemiology Commission of the Brazilian Association of Collective Health (ABRASCO)
He believes the research has to answer the question of whether the variants circulating in Brazil are capable of reducing the protection conferred by the vaccine
where vaccination is progressing very slowly
“The PNI easily has the capacity to vaccinate 2 million people a day
the entire population of Brazil could be given two doses,” he says
And we started the process late,” he points out
Project Development of a COVID-19 vaccine (nº 20/10127-1); Grant Mechanism Research in Public Policy; Principal Investigator Dimas Tadeu Covas (Butantan Institute); Investment R$32,501,477
© Revista Pesquisa FAPESP - All rights reserved
The main aim is to foster engagement in advanced veterinary and human medicine (photo: Fernando Zhiminaicela/Pixabay)
Most of the courses and other activities will be held at São Paulo State University’s Institute of Biosciences in Botucatu
Agência FAPESP – The São Paulo School of Advanced Science in Precision Health is receiving applications until March 17
The School will take place at São Paulo State University’s Institute of Biosciences (IBB-UNESP) on July 18-29
The event is being funded by FAPESP under the aegis of its São Paulo School of Advanced Science (SPSAS) program
A series of interdisciplinary activities will be conducted to integrate multiple knowledge areas so that master’s and PhD students as well as postdocs and early-career researchers from several countries can discuss and engage in advanced veterinary and human medicine
The purpose of the event is to provide in-depth learning in areas relevant to precision health
The focus will be translational and comparative
with emphasis on the One Health approach and the state of the art in precision health
The program will feature lectures by renowned scientists from Brazil and abroad
and presentations by founders of health startups
intensifying the participants’ experience of innovation
The program will also include technical visits to research centers on UNESP’s Botucatu campus
and to Albert Einstein Teaching and Research Center
Students will have opportunities to interact with the speakers and organizers by taking part in small groups and presenting summaries orally or in poster sessions
For more information and to apply, visit: eventos.ibb.unesp.br/precisionhealthschool/
Doctors found spiralling tapeworm larvae inside a patient who came to visit the hospital complaining cough
He was shocked to learn that he was hosting numerous tapeworms inside his lungs
An X-ray on Twitter was shared by Dr Vitor Borin P
a practitioner at the Hospital das Clínicas Botucatu in São Paulo
saying the patient had come in for help with his persistent cough
But it was learned later that he was suffering from cysticercosis in which tapeworm larvae — that live in humans' intestines — come out elsewhere
World Health Organisation (WHO) noted that "this condition
can be caused by a lot of different tapeworms
The larvae form hard lumps called cysts to keep themselves alive for the short term which can be felt through the skin
they can come out of the intestine and go to the brain
and spinal cord and cause epileptic seizures
and blindness in what one expert called the "most common parasitic disease of the human nervous system."
The cysts can be removed easily through surgery or medicines
The doctor showed the X-ray to the patient with countless white dots — cysts created by tapeworms
The doctor said: "Cysticercosis is acquired from ingestion of tapeworm eggs [present in the faeces of humans with tapeworms]
Dr de Souza wrote on Twitter — in the threat which was deleted later — that the patient was awaiting an MRI scan to check for the location of a cyst in his brain
"If you don't have any injury inside the head
you don't even need to treat," Dr de Souza said
"These lesions are calcified so they are not viable cysticerci [tapeworm larvae]."
WHO said: "About 2,500,000 people are thought to be infected with neurocysticercosis each year."
"Taenia solium is the cause of 30% of epilepsy cases in endemic regions where pigs tend to roam
This can swell to as much as seven in 10 cases for high-risk communities," the WHO added
"Although 70% of patients with epilepsy could lead a normal life if treated correctly
cause 75% of people with this condition to be treated poorly if treated at all,” it said
"If it doesn’t cause any discomfort life goes on," Dr de Souza said
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