Genomic epidemiology of the SARS-CoV-2 epidemic in Brazil.

The high numbers of COVID-19 cases and deaths in Brazil have made Latin America an epicentre of the pandemic. SARS-CoV-2 established sustained transmission in Brazil early in the pandemic, but important gaps remain in our understanding of virus transmission dynamics at a national scale. We use 17,135 near-complete genomes sampled from 27 Brazilian states and bordering country Paraguay. From March to November 2020, we detected co-circulation of multiple viral lineages that were linked to multiple importations (predominantly from Europe). After November 2020, we detected large, local transmission clusters within the country. In the absence of effective restriction measures, the epidemic progressed, and in January 2021 there was emergence and onward spread, both within and abroad, of variants of concern and variants under monitoring, including Gamma (P.1) and Zeta (P.2). We also characterized a genomic overview of the epidemic in Paraguay and detected evidence of importation of SARS-CoV-2 ancestor lineages and variants of concern from Brazil. Our findings show that genomic surveillance in Brazil enabled assessment of the real-time spread of emerging SARS-CoV-2 variants.

Genomic epidemiology reveals the impact of national and international restrictions measures on the SARS-CoV-2 epidemic in Brazil.

Brazil has experienced some of the highest numbers of COVID-19 cases and deaths globally and from May 2021 made Latin America a pandemic epicenter. Although SARS-CoV-2 established sustained transmission in Brazil early in the pandemic, important gaps remain in our understanding of virus transmission dynamics at the national scale. Here, we describe the genomic epidemiology of SARS-CoV-2 using near-full genomes sampled from 27 Brazilian states and a bordering country - Paraguay. We show that the early stage of the pandemic in Brazil was characterised by the co-circulation of multiple viral lineages, linked to multiple importations predominantly from Europe, and subsequently characterized by large local transmission clusters. As the epidemic progressed under an absence of effective restriction measures, there was a local emergence and onward international spread of Variants of Concern (VOC) and Variants Under Monitoring (VUM), including Gamma (P.1) and Zeta (P.2). In addition, we provide a preliminary genomic overview of the epidemic in Paraguay, showing evidence of importation from Brazil. These data reinforce the usefulness and need for the implementation of widespread genomic surveillance in South America as a toolkit for pandemic monitoring that provides a means to follow the real-time spread of emerging SARS-CoV-2 variants with possible implications for public health and immunization strategies.

Comparative Therapeutic Potential of Cardioactive Glycosides in Doxorubicin Model of Heart Failure.

In the present study, we investigated the cardioactive glycosides oleandrin and ouabain, and compared them to digoxin in a model of cardiotoxicity induced by doxorubicin. Adult rats were distributed into four experimental groups. Each group was challenged with a single intraperitoneal application of doxorubicin at a dose of 12 mg/kg. Then, they were treated with saline solution and the glycosides oleandrin, ouabain, and digoxin at a dose of 50 µg/kg, for 7 days. They underwent echocardiography, electrocardiography, hematologic, biochemical tests, and microscopic evaluation of the heart. All animals presented congestive heart failure, which was verified by a reduction in the ejection fraction. Oleandrin and digoxin were able to significantly reduce (p < 0.05) the eccentric remodeling caused by doxorubicin. Oleandrin and digoxin were significantly lower (p < 0.05) than the control group in maintaining systolic volume and left ventricular volume in diastole. Other parameters evaluated did not show significant statistical differences. All animals showed an increase in erythrocyte count, and an increase in the duration of the QRS complex on the ECG and myocardial necrosis at the histopathological analysis. It is concluded that the glycosides oleandrin, ouabain, and digoxin in the used dosage do not present therapeutic potential for the treatment of congestive heart failure caused by doxorubicin.

Premature Birth in Women with Endometriosis: a Systematic Review and Meta-analysis.

The objective of this study is to verify the association between endometriosis and preterm birth through systematic review and meta-analysis. Is there an increased risk of premature birth in women with endometriosis compared to women without this diagnosis? The databases searched were PubMed, Medline, and LILACS in order to identify all studies published up to April 2020, using the keywords (prematurity OR preterm birth OR premature birth OR premature labor OR obstetric premature labor OR preterm labor OR premature obstetric labor) AND (endometriosis OR adenomyosis OR endometrioma OR endometriomas). A manual research was also performed through the analysis of theses, book chapters, reference references, guidelines, and reviews. All published prospective cohort studies that reported the prevalence of preterm delivery among women with endometriosis, adenomyosis, or endometrioma were included, comparing it to the control group of women without such diagnoses. The random-effects model, the calculation of relative risk, and the confidence interval of 95% were used to perform the meta-analysis. Three studies involving 10,111 patients were included. Compared to women without endometriosis, women with endometriosis present an increased risk of premature birth (RR: 2.68, 95% CI [1.19; 6.02], I2 = 91%). In the subgroup of women with spontaneous conception, endometriosis is also a risk factor for prematurity (RR: 3.26, 95% CI [2.09; 5.09], I2 = 0%, 2 studies, 682 participants). The evidence presented suggests that women with endometriosis should be alerted to a potential risk of preterm birth. PROSPERO registration number, CRD42020189451.

Chikungunya, Zika, Mayaro, and Equine Encephalitis virus detection in adult Culicinae from South Central Mato Grosso, Brazil, during the rainy season of 2018.

INTRODUCTION: Several arboviruses causing human disease have been reported in Brazil. In nature, arboviruses maintain a lifecycle involving vertebrates and vectors, which may contribute for periodical reemergence of those of public health concern in tropical regions, as Mato Grosso State (MT). In this study, we searched for arboviruses in mosquito body pools sampled during the rainy season of 2018 in 21 bird watching points of Cuiabá and Varzea Grande, South Central MT. METHODS: In total, 2873 (57%) males and 2167 (43%) females belonging to six urban and sylvatic mosquito genera allocated to 398 pools were subjected to RNA extraction and RT-PCR for arboviruses. Positive pools were subjected to virus isolation in C6/36 cells. RESULTS: A total of 102/398 pools, 66/233 (29.6%) of females, and 36/165 (21.8%) of males, mostly sampled in May (31/102), were positive for arboviruses. Chikungunya virus (CHIKV) was distributed in 19 points, Zika virus (ZIKV) was found in 14 points, Mayaro virus (MAYV) in 10 points, and East Equine encephalitis virus (EEEV) in three points. Culex quinquefasciatus pools (39/89 of females and 24/99 of males) were positive for CHIKV, ZIKV, and MAYV; Aedes (Stg) aegypti pools (11/46 of females and 12/33 of males) for CHIKV, ZIKV, MAYV, and EEEV; Aedes albopictus female pools (8/29) for CHIKV, ZIKV, and EEEV; and Psorophora albigenu (2/12) and Psorophora ferox female pools (4/16) for CHIKV. CONCLUSIONS: Arbovirus molecular detection in mosquito populations varies considerable between geographical regions and epidemics, influenced by genetic characteristics and microbiome interference on virus replication. Although infected females are responsible for the transmission to vertebrates during bloodfeeding, male infection by CHIKV, ZIKV, and MAYV resultant from vertical route could lead to interepidemic maintenance of these arboviruses in their natural reservoirs.

Sialovirome of Brazilian tropical anophelines.

Anophelinae is a widely dispersed Culicidae subfamily that may carry a unique virome. Here we herein report the set of viruses found in 323 salivary glands of 16 anopheline species sampled at Upper Pantanal, Chapada dos Guimarães National Park and Coxipó river basin, South Central Mato Grosso, Brazil, pooled (n = 11) and subjected to high throughput sequencing. Metagenomics revealed the presence of nine viral sequences belonging to novel viruses from seven viral families: Purunga is a putative novel orbivirus sharing 74% and 65% aa identity, respectively, with the VP1 and VP3 segments of Changuinola serogroup, Jaracatiá flavivirus shares 60% amino-acid (aa) identity with Aedes flavivirus. Coxipó dielmovirus and Chapada dielmovirus shared 51% and 39% aa identity with Merida virus. Coloiado-orthomyxo like virus is 57.1-64.8% identical at aa level to Aedes albonnulatus orthomyxo-like virus. Mujica picorna-like virus shares 49% aa identity with Flen picorna-like virus and Chiquitos virus is 50% similar to Ista virus, both from Picornavirales order. Cerrado partiti-like-virus shares 75-86% aa identity with Atrato partiti-like virus 2. We also found the S and L segments of Anopheles triannulatus orthophasmavirus (92% identity) in Anopheles lutzi from Chapada dos Guimarães. The identification of these putative novel viruses underscore the wide dispersion of viruses in culicid hosts contributing to extensions on mosquito virome descriptions.

Value-based care in obstetrics: comparison between vaginal birth and caesarean section.

BACKGROUND: Healthcare costs have substantially increased in recent years, threatening the population health. Obstetric care is a significant contributor to this scenario since it represents 20% of healthcare. The rate of cesarean sections (C-sections) has escalated worldwide. Evidence shows that cesarean delivery is not only more expensive, but it is also linked to poorer maternal and neonatal outcomes. This study assesses which type of delivery is associated with a higher healthcare value in low-risk pregnancies. RESULTS: A total of 9345 deliveries were analyzed. The C-section group had significantly worse rates of breastfeeding in the first hour after delivery (92.57% vs 88.43%, p < 0.001), a higher rate of intensive unit care (ICU) admission both for the mother and the newborn (0.8% vs 0.3%, p = 0.001; 6.7% vs 4.5%, p = 0.0078 respectively), and a higher average cost of hospitalization (BRL14,342.04 vs BRL12,230.03 considering mothers and babies). CONCLUSION: Cesarean deliveries in low-risk pregnancies were associated with a lower value delivery because in addition to being more expensive, they had worse perinatal outcomes.

Insect-specific viruses and arboviruses in adult male culicids from Midwestern Brazil.

Viruses were identified from male anthropophilic mosquitoes from Mato Grosso (MT) State, Midwest Brazil from February 2017 to January 2018. Mosquitoes tested included Aedes (Stegomyia) aegypti (1139 males; 84 pools), Culex quinquefasciatus (9426 males; 179 pools), Culex sp. (3 males; 3 pools) and Psorophora albigenu (1 male; 1 pool) collected from four cities of MT. Pools were subjected to viral RNA extraction followed by RT-PCRs specific for ten flaviviruses, five alphaviruses and Simbu serogroup of orthobunyaviruses. Positive pools were passaged three times in VERO cells (alphavirus and orthobunyavirus) or C6/36 cells (flavivirus), with isolates confirmed through RT-PCR and nucleotide sequencing. We detected pools positive for Ilhéus (1 pool), dengue serotype 4 (1), Mayaro (12), equine encephalitis virus (1) yellow fever (1), Oropouche (2), Zika (4) and chikungunya (12) viruses. High throughput sequencing of arbovirus positive pools identified 35 insect-specific viruses (ISVs) from the families Circoviridae (2), Parvoviridae (2), Totiviridae (1), Flaviviridae (1), Iflaviridae (2), Mesoniviridae (4), Nodaviridae (2), Luteoviridae (1), Phasmaviridae (1) Phenuiviridae (2), Rhabdoviridae (2), Orthomyxoviridae (1), Xinmoviridae (1), and unclassified Bunyavirales (1), unclassified Picornavirales (3), unclassified Riboviria (4) and taxon Negevirus (5). From these, five novel viruses were tentatively named Mojica circovirus, Kuia iflavirus, Muxirum negevirus, Lambada picorna-like virus and Tacuru picorna-like virus. Our findings underscore the diversity and wide geographical distribution of ISVs and arboviruses infecting male culicids.

Zika Virus Surveillance at the Human-Animal Interface in West-Central Brazil, 2017-2018.

Zika virus (ZIKV) was first discovered in 1947 in Uganda but was not considered a public health threat until 2007 when it found to be the source of epidemic activity in Asia. Epidemic activity spread to Brazil in 2014 and continued to spread throughout the tropical and subtropical regions of the Americas. Despite ZIKV being zoonotic in origin, information about transmission, or even exposure of non-human vertebrates and mosquitoes to ZIKV in the Americas, is lacking. Accordingly, from February 2017 to March 2018, we sought evidence of sylvatic ZIKV transmission by sampling whole blood from approximately 2000 domestic and wild vertebrates of over 100 species in West-Central Brazil within the active human ZIKV transmission area. In addition, we collected over 24,300 mosquitoes of at least 17 genera and 62 species. We screened whole blood samples and mosquito pools for ZIKV RNA using pan-flavivirus primers in a real-time reverse-transcription polymerase chain reaction (RT-PCR) in a SYBR Green platform. Positives were confirmed using ZIKV-specific envelope gene real-time RT-PCR and nucleotide sequencing. Of the 2068 vertebrates tested, none were ZIKV positive. Of the 23,315 non-engorged mosquitoes consolidated into 1503 pools tested, 22 (1.5%) with full data available showed some degree of homology to insect-specific flaviviruses. To identify previous exposure to ZIKV, 1498 plasma samples representing 62 species of domestic and sylvatic vertebrates were tested for ZIKV-neutralizing antibodies by plaque reduction neutralization test (PRNT90). From these, 23 (1.5%) of seven species were seropositive for ZIKV and negative for dengue virus serotype 2, yellow fever virus, and West Nile virus, suggesting potential monotypic reaction for ZIKV. Results presented here suggest no active transmission of ZIKV in non-human vertebrate populations or in alternative vector candidates, but suggest that vertebrates around human populations have indeed been exposed to ZIKV in West-Central Brazil.