RESUMEN
From a country with one of the highest SARS-CoV-2 morbidity and mortality rates, Brazil has implemented one of the most successful vaccination programs. Brazil's first model city vaccination program was performed by the CoronaVac vaccine (Sinovac Biotech) in the town of Serrana, São Paulo State. To evaluate the vaccination effect on the SARS-CoV-2 molecular dynamics and clinical outcomes, we performed SARS-CoV-2 molecular surveillance on 4375 complete genomes obtained between June 2020 and April 2022 in this location. This study included the period between the initial SARS-CoV-2 introduction and during the vaccination process. We observed that the SARS-CoV-2 substitution dynamics in Serrana followed the viral molecular epidemiology in Brazil, including the initial identification of the ancestral lineages (B.1.1.28 and B.1.1.33) and epidemic waves of variants of concern (VOC) including the Gamma, Delta, and, more recently, Omicron. Most probably, as a result of the immunization campaign, the mortality during the Gamma and Delta VOC was significantly reduced compared to the rest of Brazil, which was also related to lower morbidity. Our phylogenetic analysis revealed the evolutionary history of the SARS-CoV-2 in this location and showed that multiple introduction events have occurred over time. The evaluation of the COVID-19 clinical outcome revealed that most cases were mild (88.9%, 98.1%, 99.1% to Gamma, Delta, and Omicron, respectively) regardless of the infecting VOC. In conclusion, we observed that vaccination was responsible for reducing the death toll rate and related COVID-19 morbidity, especially during the gamma and Delta VOC; however, it does not prevent the rapid substitution rate and morbidity of the Omicron VOC.
Asunto(s)
COVID-19 , SARS-CoV-2 , Humanos , SARS-CoV-2/genética , Brasil/epidemiología , Filogenia , COVID-19/epidemiología , COVID-19/prevención & control , VacunaciónRESUMEN
Toxoplasma gondii causa uma infecção comumente assintomática, porémpode se apresentar de forma grave durante a gravidez e em pacientesimunocomprometidos. A terapia atual para a toxoplasmose é restrita contrataquizoítos, e possuem pouco ou nenhum efeito sobre bradizoítos, que são mantidosem cistos teciduais como fonte recrudescente da infecção. Com isso, novasalternativas terapêuticas vêm sendo propostas, como o uso da Atovaquona, queapresentou alguma eficácia sobre taquizoítos e bradizoítos em cistos teciduais.Neste trabalho, foi estudado o efeito de 3-BrPA, um composto utilizado em testessobre células cancerígenas, durante a interação de células LLC-MK2 infectadas comtaquizoítos da cepa RH de T. gondii. Quanto à célula hospedeira não se observouefeito do composto sobre a proliferação e viabilidade celular. A avaliação dainterferência de 3-BrPA sobre o crescimento in vitro do T. gondii evidenciou umaredução na proliferação intracelular do parasito de cerca de 55 por cento após 24 h detratamento e 61 por cento após 48 h. O desenvolvimento intracelular do parasito, analisadopor MEV, apresentou características morfológicas comumente encontradas emcistos teciduais. A incubação das culturas com lectina DBA confirmou odesenvolvimento de cistos e por MET se evidenciou a presença de bradizoítos. Alémdisso, foram revelados parasitos degradados e a influência do composto sobre aendodiogenia. Outra abordagem adotada foi o tratamento de culturas infectadas coma combinação de 3-BrPA e Atovaquona, que resultou em uma redução de parasitosintracelulares de 73 por cento após 24 h de tratamento e 71 por cento após 48 h, em comparação aocontrole, além da ausência da formação de parede cística nessas culturas...
Toxoplasma gondii usually causes an asymptomatic infection, but it can present severityduring pregnancy and in immunocompromised patients. Current therapies fortoxoplasmosis are restricted only against tachyzoites, and have little or no effect onbradyzoites, which are kept in tissue cysts like source of the infection recrudescent.Consequently, new therapeutic alternatives have been proposed, as the use ofAtovaquone that showed some efficacy against tachyzoites and bradyzoites in tissuecysts. In this work, we propose to study the effect of 3-BrPA, a compound that is beingtested against cancer cells, on the infection of LLC-MK2 cells with tachyzoites of T.gondii (RH strain). No effect of 3-BrPAon host cell proliferation and viability wasobserved. Evaluation of 3-BrPA interference on in vitro growth of T. gondii showed areduction in intracellular parasite proliferation about 55 por cento after 24 h of treatment, and61 por cento after 48 h. Intracellular development of parasite, analyzed by SEM, showedmorphological characteristics commonly found in tissue cysts. Incubation of cultureswith DBA lectin confirmed the development of cysts and TEM showed the presence ofbradyzoites. Moreover, we revealed the presence of degraded parasites and theinfluence of compound on endodyogeny. Another approach used was the treatment ofinfected cultures with combination of 3-BrPA and Atovaquone. This resulted in thereduction of intracellular parasites of 73 por cento after 24 h of treatment and 71 percent after 48 h,compared to control, besides the absence of cyst wall formation in these cultures...