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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.
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Background: Household transmission studies seek to understand the transmission dynamics of a pathogen by estimating the risk of infection from household contacts and community exposures. We estimated within/extra-household SARS-CoV-2 infection risk and associated factors in a household cohort study in one of the most vulnerable neighbourhoods in Rio de Janeiro city. Methods: Individuals ≥1 years-old with suspected or confirmed COVID-19 in the past 30 days (index cases) and household members aged ≥1 year were enrolled and followed at 14 and 28 days (study period November/2020-December/2021). RT-PCR testing, COVID-19 symptoms, and SARS-CoV-2 serologies were ascertained in all visits. Chain binomial household transmission models were fitted using data from 2024 individuals (593 households). Findings: Extra-household infection risk was 74.2% (95% credible interval [CrI] 70.3-77.8), while within-household infection risk was 11.4% (95% CrI 5.7-17.2). Participants reporting having received two doses of a COVID-19 vaccine had lower extra-household (68.9%, 95% CrI 57.3-77.6) and within-household (4.1%, 95% CrI 0.4-16.6) infection risk. Within-household infection risk was higher among participants aged 10-19 years, from overcrowded households, and with low family income. Contrastingly, extra-household infection risk was higher among participants aged 20-29 years, unemployed, and public transportation users. Interpretation: Our study provides important insights into COVID-19 household/community transmission in a vulnerable population that resided in overcrowded households and who struggled to adhere to lockdown policies and social distancing measures. The high extra-household infection risk highlights the extreme social vulnerability of this population. Prioritising vaccination of the most socially vulnerable could protect these individuals and reduce widespread community transmission. Funding: Fundação Oswaldo Cruz, CNPq, FAPERJ, Royal Society, Instituto Serrapilheira, FAPESP.
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Many molecular mechanisms that lead to the host antibody response to COVID-19 vaccines remain largely unknown. In this study, we used serum antibody detection combined with whole blood RNA-based transcriptome analysis to investigate variability in vaccine response in healthy recipients of a booster (third) dose schedule of the mRNA BNT162b2 vaccine against COVID-19. The cohort was divided into two groups: (1) low-stable individuals, with antibody concentration anti-SARS-CoV IgG S1 below 0.4 percentile at 180 days after boosting vaccination; and (2) high-stable individuals, with antibody values greater than 0.6 percentile of the range in the same period (median 9525 [185-80,000] AU/mL). Differential gene expression, expressed single nucleotide variants and insertions/deletions, differential splicing events, and allelic imbalance were explored to broaden our understanding of the immune response sustenance. Our analysis revealed a differential expression of genes with immunological functions in individuals with low antibody titers, compared to those with higher antibody titers, underscoring the fundamental importance of the innate immune response for boosting immunity. Our findings also provide new insights into the determinants of the immune response variability to the SARS-CoV-2 mRNA vaccine booster, highlighting the significance of differential splicing regulatory mechanisms, mainly concerning HLA alleles, in delineating vaccine immunogenicity.
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Vacinas contra COVID-19 , COVID-19 , Humanos , SARS-CoV-2/genética , Vacina BNT162 , Vacinas de mRNA , COVID-19/prevenção & controle , Anticorpos , Imunidade Inata , Anticorpos AntiviraisRESUMO
This study shows that the distribution of CYP3A5 alleles (*1, *3, *6 and *7) and genotype-predicted CYP3A5 phenotypes vary significantly across Latin American cohorts (Brazilians and the One Thousand Genomes Admixed American superpopulation), as well as among subcohorts comprising individuals with the highest proportions of Native, European or sub-Saharan African ancestry. Differences in biogeographical ancestry across the study groups are the likely explanation for these results. The differential distribution of CYP3A5 phenotypes has major pharmacogenomic implications, affecting the proportion of individuals carrying high risk CYP3A5 phenotypes for the immunosuppressant tacrolimus and the number of patients that would need to be genotyped to prevent acute rejection in kidney transplant recipients under tacrolimus treatment.
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Farmacogenética , População da América do Sul , Tacrolimo , Humanos , Citocromo P-450 CYP3A/genética , Citocromo P-450 CYP3A/metabolismo , Genótipo , Rejeição de Enxerto/genética , Imunossupressores/efeitos adversos , América Latina , Fenótipo , Polimorfismo de Nucleotídeo Único/genética , Tacrolimo/efeitos adversos , Povos Indígenas , População Branca , População da África SubsaarianaRESUMO
BACKGROUND: After validation in multiple types of liver disease patients, the MELD score was adopted as a standard by which liver transplant candidates with end-stage liver disease were prioritized for organ allocation in the United States since 2002, and in Brazil, since 2006. AIMS: To analyze the mortality profile of patients on the liver transplant waiting list correlated to MELD score at the moment of transplantation. METHODS: This study used the data from the Secretary of Health of the São Paulo State, Brazil, which listed 22,522 patients, from 2006 (when MELD score was introduced in Brazil) until June 2009. Patients with acute hepatic failure and tumors were included as well. We also considered the mortality of both non-transplanted and transplanted patients as a function of the MELD score at presentation. RESULTS: Our model showed that the best MELD score for patients on the liver transplant waiting list associated to better results after liver transplantation was 26. CONCLUSIONS: We found that the best score for applying to liver transplant waiting list in the State of São Paulo was 26. This is the score that minimizes the mortality in both non-transplanted and liver transplanted patients.
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Doença Hepática Terminal , Transplante de Fígado , Humanos , Brasil , Listas de Espera , Doença Hepática Terminal/cirurgiaRESUMO
OBJECTIVE: To present theoretical-methodological reflections on the elaboration, types, and functions of theoretical models as well as their conceptual and analytic frameworks. METHODS: This is an essay, whose material collection was carried out in a non-systematic way, by electing studies exclusively based on the line of argument and reflection that the authors intend to submit to appreciation and public debate. RESULTS: We present reflections on the types and functions of theoretical models, theoretical foundations in research, and reflections on the importance of theoretical models for public health research and their relation with the process of elaboration, development, and reporting in scientific studies. In addition, we describe types of theoretical models referring to the conceptual and empirical levels and the important elaboration and description of their combination for scientific practice. CONCLUSION: With this article, our intention is to stimulate discussions and reflections on current methods that permeate scientific practice and encourage the use of Theoretical Models as a basis for scientific research in its elaboration, development, and reporting process.
OBJETIVO: Apresentar reflexões teórico-metodológicas sobre elaboraçõo, tipos e funções dos modelos teóricos, bem como suas estruturas conceituais e de análise. MÉTODOS: Trata-se de um ensaio cujo processo de coleta do material foi realizado de forma não sistemática, eleito exclusivamente e baseado na linha de argumentaçõo e reflexão que os autores pretendem submeter à apreciaçõo e ao debate público. RESULTADOS: Este trabalho apresenta reflexões sobre tipos e funções dos modelos teóricos, fundamentaçõo teórica nas pesquisas e reflexões sobre a importância dos modelos teóricos para as pesquisas em saúde pública e sua relaçõo com o processo de elaboraçõo, desenvolvimento e relato nos estudos científicos. Além disso, são descritos tipos de modelos teóricos referentes aos planos conceitual e empírico, e a importante elaboraçõo e descriçõo da junçõo de ambos para o fazer científico. CONCLUSÃO: Espera-se que este artigo levante discussões e reflexões sobre os métodos atuais que permeiam o fazer científico e fomentem a utilizaçõo dos modelos teóricos como base das pesquisas científicas em seu processo de elaboraçõo, desenvolvimento e relato.
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Saúde Pública , Humanos , BrasilRESUMO
The innate immune system is the first line of defense against pathogens such as the acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The type I-interferon (IFN) response activation during the initial steps of infection is essential to prevent viral replication and tissue damage. SARS-CoV and SARS-CoV-2 can inhibit this activation, and individuals with a dysregulated IFN-I response are more likely to develop severe disease. Several mutations in different variants of SARS-CoV-2 have shown the potential to interfere with the immune system. Here, we evaluated the buffy coat transcriptome of individuals infected with Gamma or Delta variants of SARS-CoV-2. The Delta transcriptome presents more genes enriched in the innate immune response and Gamma in the adaptive immune response. Interactome and enriched promoter analysis showed that Delta could activate the INF-I response more effectively than Gamma. Two mutations in the N protein and one in the nsp6 protein found exclusively in Gamma have already been described as inhibitors of the interferon response pathway. This indicates that the Gamma variant evolved to evade the IFN-I response. Accordingly, in this work, we showed one of the mechanisms that variants of SARS-CoV-2 can use to avoid or interfere with the host Immune system.
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COVID-19 , Interferon Tipo I , Coronavírus Relacionado à Síndrome Respiratória Aguda Grave , Humanos , Interferon Tipo I/genética , SARS-CoV-2 , Transcriptoma , COVID-19/genéticaRESUMO
Brazil has the second-highest COVID-19 death rate worldwide, and Rio de Janeiro is among the states with the highest rate in the country. Although vaccine coverage has been achieved, it is anticipated that COVID-19 will transition into an endemic disease. It is concerning that the molecular mechanisms underlying clinical evolution from mild to severe disease, as well as the mechanisms leading to long COVID-19, are not yet fully understood. NMR and MS-based metabolomics were used to identify metabolites associated with COVID-19 pathophysiology and disease outcome. Severe COVID-19 cases (n = 35) were enrolled in two reference centers in Rio de Janeiro within 72 h of ICU admission, alongside 12 non-infected control subjects. COVID-19 patients were grouped into survivors (n = 18) and non-survivors (n = 17). Choline-related metabolites, serine, glycine, and betaine, were reduced in severe COVID-19, indicating dysregulation in methyl donors. Non-survivors had higher levels of creatine/creatinine, 4-hydroxyproline, gluconic acid, and N-acetylserine, indicating liver and kidney dysfunction. Several changes were greater in women; thus, patients' sex should be considered in pandemic surveillance to achieve better disease stratification and improve outcomes. These metabolic alterations may be useful to monitor organ (dys) function and to understand the pathophysiology of acute and possibly post-acute COVID-19 syndromes.
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BACKGROUND: Men who have sex with men (MSM) in Brazil remain disproportionately affected by HIV. We estimated the potential incidence reduction by five years with increased uptake of publicly-funded, daily, oral tenofovir/emtricitabine (TDF/FTC) for HIV pre-exposure prophylaxis (PrEP) among MSM using the Cost Effectiveness of Preventing AIDS Complications microsimulation model. We used national data, local studies, and literature to inform model parameters for three cities: Rio de Janeiro, Salvador, and Manaus. RESULTS: In Rio de Janero, a PrEP intervention achieving 10% uptake within 60 months would decrease incidence by 2.3% whereas achieving 60% uptake within 24 months would decrease incidence by 29.7%; results were similar for Salvador and Manaus. In sensitivity analyses, decreasing mean age at PrEP initiation from 33 to 21 years increased incidence reduction by 34%; a discontinuation rate of 25% per year decreased it by 12%. CONCLUSION: Targeting PrEP to young MSM and minimizing discontinuation could substantially increase PrEP's impact.
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Infecções por HIV , Profilaxia Pré-Exposição , Minorias Sexuais e de Gênero , Masculino , Humanos , Homossexualidade Masculina , Brasil , EmtricitabinaRESUMO
In this paper we calculate the variation of the estimated vaccine efficacy (VE) due to the time-dependent force of infection resulting from the difference between the moment the Clinical Trial (CT) begins and the peak in the outbreak intensity. Using a simple mathematical model we tested the hypothesis that the time difference between the moment the CT begins and the peak in the outbreak intensity determines substantially different values for VE. We exemplify the method with the case of the VE efficacy estimation for one of the vaccines against the new coronavirus SARS-CoV-2.
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COVID-19 , Humanos , COVID-19/prevenção & controle , SARS-CoV-2 , Eficácia de Vacinas , Surtos de DoençasAssuntos
Endometriose , Humanos , Feminino , Citocromo P-450 CYP2C19/genética , Brasil/epidemiologia , Fenótipo , EstrogêniosRESUMO
Background: Brazil started the COVID-19 mass vaccination in January 2021 with CoronaVac and ChAdOx1, followed by BNT162b2 and Ad26.COV2.S vaccines. By the end of 2021, more than 317 million vaccine doses were administered in the adult population. This study aimed at estimating the effectiveness of the primary series of COVID-19 vaccination and booster shots in protecting against severe cases and deaths in Brazil during the first year of vaccination. Methods: A cohort dataset of over 158 million vaccination and severe cases records linked from official national registries was analyzed via a mixed-effects Poisson model, adjusted for age, state of residence, time after immunization, and calendar time to estimate the absolute vaccine effectiveness of the primary series of vaccination and the relative effectiveness of the booster. The method permitted analysis of effectiveness against hospitalizations and deaths, including in the periods of variant dominance. Findings: Vaccine effectiveness against severe cases and deaths remained over 25% and 50%, respectively, after 19 weeks from primary vaccination of BNT162b2, ChAdOx1, or CoronaVac vaccines. The boosters conferred greater protection than the primary series of vaccination, with heterologous boosters providing marginally greater protection than homologous. The effectiveness against hospitalization during the Omicron dominance in the 60+ years old population started at 61.7% (95% CI, 26.1-86.2) for ChAdOx1, 95.6% (95% CI, 82.4-99.9) for CoronaVac, and 72.3% (95% CI, 51.4-87.4) for the BNT162b2 vaccine. Interpretation: This study provides real-world evidence of the effectiveness of COVID-19 vaccination in Brazil, including during the Omicron wave, demonstrating protection even after waning effectiveness. Comparisons of the effectiveness among different vaccines require caution due to potential bias effects related to age groups, periods in the pandemic, and eventual behavioural changes. Funding: Fundação Oswaldo Cruz (FIOCRUZ), Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), Fundação de Amparo a Pesquisa do Estado do Rio de Janeiro (FAPERJ), Pan American Health Organization (PAHO), Departamento de Ciência e Tecnologia da Secretaria de Ciência, Tecnologia, Inovação e Insumos Estratégicos em Saúde do Ministério da Saúde do Brasil (DECIT/SCTIE/MS).
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After the outbreak of COVID-19, the interaction of infectious disease systems and social systems has challenged traditional infectious disease modeling methods. Starting from the research purpose and data, researchers improved the structure and data of the compartment model or used agents and artificial intelligence based models to solve epidemiological problems. In terms of modeling methods, the researchers use compartment subdivision, dynamic parameters, agent-based model methods, and artificial intelligence related methods. In terms of factors studied, the researchers studied 6 categories: human mobility, nonpharmaceutical interventions (NPIs), ages, medical resources, human response, and vaccine. The researchers completed the study of factors through modeling methods to quantitatively analyze the impact of social systems and put forward their suggestions for the future transmission status of infectious diseases and prevention and control strategies. This review started with a research structure of research purpose, factor, data, model, and conclusion. Focusing on the post-COVID-19 infectious disease prediction simulation research, this study summarized various improvement methods and analyzes matching improvements for various specific research purposes.
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Background: A nationwide Severe Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) vaccination campaign was initiated in Brazil in January 2021 with CoronaVac (Sinovac Biotech) and ChAdOx1 nCoV-19 (AstraZeneca) followed by BNT162b2 mRNA (Pfizer-BioNTech) and Ad26.COV2.S (Johnson & Johnson-Janssen) vaccines. Here we provide estimates of the number of severe cases and deaths due to coronavirus disease (COVID-19) averted during the first year of the mass vaccination campaign in Brazil. Methods: Data on COVID-19 vaccination and COVID-19-related illness and death were obtained from the Brazilian Ministry of Health and used to estimate the direct effects of the vaccination campaign on the number of severe cases and deaths due to COVID-19 occurring between January 17, 2021 and January 31, 2022. To this end, we compared the daily age-specific rates between the unvaccinated population and the "at least partly vaccinated" population (received at least one dose of a two-dose vaccine), as well as other two vaccination subgroups, "fully vaccinated" (completed the one- or two-dose vaccine schedule), and "boosted-vaccinated" (fully vaccinated and recipients of booster dose) populations. Findings: We estimated that 74% (n = 875,846; 95% confidence interval, CI 843,383-915,709) of total expected cases of severe COVID-19 and 82% (n = 303,129; 95% CI 284,019-321,681) of total expected deaths due to COVID-19 were averted in the first year of the national vaccination campaign. The averted burden was heterogeneous between age groups and higher in the more populous states. However, outcome rate differences between vaccinated and unvaccinated groups were higher in the less populated states. Interpretation: The first year of the COVID-19 vaccination program in Brazil saved the lives of at least 303,129 adults. The results highlight the need for future vaccination campaigns, including those required in the current pandemic, to rapidly achieve high uptake, particularly among the elderly and residents of the least populous regions. Funding: Ministry of Health (Brazil).
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Gestational diabetes mellitus (GDM) is the most common medical complication of pregnancy and a severe threat to pregnant people and offspring health. The molecular origins of GDM, and in particular the placental responses, are not fully known. The present study aimed to perform a comprehensive characterisation of the lipid species in placentas from pregnancies complicated with GDM using high-resolution MS lipidomics, with a particular focus on sphingolipids and acylcarnitines in a semi-targeted approach. The results indicated that despite no major disruption in lipid metabolism, placentas from GDM pregnancies showed significant alterations in sphingolipids, mostly lower abundance of total ceramides. Additionally, very long-chain ceramides and sphingomyelins with twenty-four carbons were lower, and glucosylceramides with sixteen carbons were higher in placentas from GDM pregnancies. Semi-targeted lipidomics revealed the strong impact of GDM on the placental acylcarnitine profile, particularly lower contents of medium and long-chain fatty-acyl carnitine species. The lower contents of sphingolipids may affect the secretory function of the placenta, and lower contents of long-chain fatty acylcarnitines is suggestive of mitochondrial dysfunction. These alterations in placental lipid metabolism may have consequences for fetal growth and development.
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Diabetes Gestacional , Placenta , Gravidez , Feminino , Humanos , Placenta/metabolismo , Diabetes Gestacional/metabolismo , Esfingolipídeos/metabolismo , Carnitina/metabolismo , Ceramidas/metabolismoRESUMO
ABSTRACT BACKGROUND: After validation in multiple types of liver disease patients, the MELD score was adopted as a standard by which liver transplant candidates with end-stage liver disease were prioritized for organ allocation in the United States since 2002, and in Brazil, since 2006. AIMS: To analyze the mortality profile of patients on the liver transplant waiting list correlated to MELD score at the moment of transplantation. METHODS: This study used the data from the Secretary of Health of the São Paulo State, Brazil, which listed 22,522 patients, from 2006 (when MELD score was introduced in Brazil) until June 2009. Patients with acute hepatic failure and tumors were included as well. We also considered the mortality of both non-transplanted and transplanted patients as a function of the MELD score at presentation. RESULTS: Our model showed that the best MELD score for patients on the liver transplant waiting list associated to better results after liver transplantation was 26. CONCLUSIONS: We found that the best score for applying to liver transplant waiting list in the State of São Paulo was 26. This is the score that minimizes the mortality in both non-transplanted and liver transplanted patients.
RESUMO RACIONAL: Desde 2002, após validação em múltiplos tipos de hepatopatias, o escore MELD foi adotado como padrão pelo qual os candidatos a transplante de fígado com doença hepática terminal têm sido priorizados para alocação de órgãos nos Estados Unidos, e em 2006 no Brasil. OBJETIVOS: Analisar a mortalidade de pacientes em lista de espera para transplante de fígado correlacionando com o MELD, no momento do transplante. MÉTODOS: Foram utilizados os dados da Secretaria de Saúde do Estado de São Paulo, Brasil, onde foram listados 22.522 pacientes, desde 2006 (quando o escore MELD foi introduzido no Brasil) até junho de 2009. Foram incluídos pacientes com falência hepática e tumores. A mortalidade de pacientes não transplantados e transplantados também foi considerada em função do escore MELD. RESULTADOS: Nosso modelo mostrou que o melhor valor do MELD, em pacientes em lista de espera para transplante e com melhores resultados, foi de 26. Este valor minimiza mortalidade em pacientes não transplantados bem comem pacientes na lista de espera para transplante de fígado. CONCLUSÕES: O escore MELD ótimo para entrar na lista de espera para transplante de fígado, no estado de São Paulo, é em torno de 26. Esse é o valor que minimiza a mortalidade tanto dos pacientes não transplantados em lista de espera, quanto dos submetidos à transplante de fígado.
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RESUMO Objetivo: Apresentar reflexões teórico-metodológicas sobre elaboraçõo, tipos e funções dos modelos teóricos, bem como suas estruturas conceituais e de análise. Métodos: Trata-se de um ensaio cujo processo de coleta do material foi realizado de forma não sistemática, eleito exclusivamente e baseado na linha de argumentaçõo e reflexão que os autores pretendem submeter à apreciaçõo e ao debate público. Resultados: Este trabalho apresenta reflexões sobre tipos e funções dos modelos teóricos, fundamentaçõo teórica nas pesquisas e reflexões sobre a importância dos modelos teóricos para as pesquisas em saúde pública e sua relaçõo com o processo de elaboraçõo, desenvolvimento e relato nos estudos científicos. Além disso, são descritos tipos de modelos teóricos referentes aos planos conceitual e empírico, e a importante elaboraçõo e descriçõo da junçõo de ambos para o fazer científico. Conclusão: Espera-se que este artigo levante discussões e reflexões sobre os métodos atuais que permeiam o fazer científico e fomentem a utilizaçõo dos modelos teóricos como base das pesquisas científicas em seu processo de elaboraçõo, desenvolvimento e relato.
ABSTRACT Objective: To present theoretical-methodological reflections on the elaboration, types, and functions of theoretical models as well as their conceptual and analytic frameworks. Methods: This is an essay, whose material collection was carried out in a non-systematic way, by electing studies exclusively based on the line of argument and reflection that the authors intend to submit to appreciation and public debate. Results: We present reflections on the types and functions of theoretical models, theoretical foundations in research, and reflections on the importance of theoretical models for public health research and their relation with the process of elaboration, development, and reporting in scientific studies. In addition, we describe types of theoretical models referring to the conceptual and empirical levels and the important elaboration and description of their combination for scientific practice. Conclusion: With this article, our intention is to stimulate discussions and reflections on current methods that permeate scientific practice and encourage the use of Theoretical Models as a basis for scientific research in its elaboration, development, and reporting process.
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By the peak of COVID-19 restrictions on April 8, 2020, up to 1.5 billion students across 188 countries were affected by the suspension of physical attendance in schools. Schools were among the first services to reopen as vaccination campaigns advanced. With the emergence of new variants and infection waves, the question now is to find safe protocols for the continuation of school activities. We need to understand how reliable these protocols are under different levels of vaccination coverage, as many countries have a meager fraction of their population vaccinated, including Uganda where the coverage is about 8%. We investigate the impact of face-to-face classes under different protocols and quantify the surplus number of infected individuals in a city. Using the infection transmission when schools were closed as a baseline, we assess the impact of physical school attendance in classrooms with poor air circulation. We find that (i) resuming school activities with people only wearing low-quality masks leads to a near fivefold city-wide increase in the number of cases even if all staff is vaccinated, (ii) resuming activities with students wearing good-quality masks and staff wearing N95s leads to about a threefold increase, (iii) combining high-quality masks and active monitoring, activities may be carried out safely even with low vaccination coverage. These results highlight the effectiveness of good mask-wearing. Compared to ICU costs, high-quality masks are inexpensive and can help curb the spreading. Classes can be carried out safely, provided the correct set of measures are implemented.