Em agosto de 2015, neuropediatras de hospitais públicos do Recife, Pernambuco, Brasil, observaram um aumento do número de casos de microcefalia desproporcional associado a anomalias cerebrais. Esse ...fato gerou comoção social, mobilização da comunidade acadêmica e levou o Ministério da Saúde a decretar emergência de saúde pública nacional, seguida pela declaração de emergência de saúde pública de interesse internacional da Organização Mundial da Saúde. A hipótese formulada para o fenômeno foi a infecção congênita pelo vírus Zika (ZIKV), com base na correlação espaço-temporal e nas características clínico-epidemiológicas das duas epidemias. Evidências se acumularam e no âmbito do raciocínio epidemiológico preencheram critérios que deram sustentação à hipótese. Sua plausibilidade está ancorada no neurotropismo do ZIKV demonstrado em animais, atingindo neurônios progenitores do cérebro em desenvolvimento, e em seres humanos devido às complicações neurológicas observadas em adultos após a infecção. O isolamento do RNA e antígenos virais no líquido amniótico de mães infectadas e em cérebros de neonatos e fetos com microcefalia contribuíram para demonstrar a consistência da hipótese. O critério de temporalidade foi contemplado ao se identificar desfechos desfavoráveis em uma coorte de gestantes com exantema e positivas para o ZIKV. Finalmente, o primeiro estudo caso-controle conduzido demonstrou existir uma forte associação entre microcefalia e infecção congênita pelo ZIKV. O conhecimento construído no âmbito do paradigma epidemiológico recebeu a chancela da comunidade científica, construindo o consenso de uma relação causal entre o ZIKV e a epidemia de microcefalia.
In August 2015, pediatric neurologists at public hospitals in Recife, Pernambuco State, Brazil, observed an increase in the number of disproportional microcephaly cases associated with other congenital anomalies. The fact caused social commotion and mobilization of the academic community and led the Brazilian Ministry of Health to declare a national public health emergency, followed by the declaration of a Public Health Emergency of International Concern by the World Health Organization. The hypothesis for the phenomenon was congenital Zika virus (ZIKV) infection, based on spatial-temporal correlation and the clinical-epidemiological characteristics of the two epidemics. Further evidence accumulated, and within the scope of epidemiologial reasoning fulfilled criteria that gave support to the hypothesis. The plausibility of the hypothesis is based on the neurotropism of ZIKV, demonstrated in animals, affecting neural progenitors in the developing brain, and in humans, due to neurological complications in adults following infection. Isolation of viral RNA and antigens in the amniotic fluid of infected mothers and in brains of newborns and fetuses with microcephaly further demonstrated the consistency of the hypothesis. The criterion of temporality was met by identifying adverse pregnancy outcomes in a cohort of mothers with a history of rash and positive ZIKV serology. Finally, the first case-control study demonstrated a strong association between microcephaly and congenital ZIKV infection. The knowledge built with the epidemiological paradigm was supported by the scientific community, thereby establishing the consensus for a causal relationship between ZIKV and the microcephaly epidemic.
En agosto de 2015, neuropediatras de hospitales públicos de Recife, Pernambuco, Brasil, observaron un aumento desproporcional del número de casos de microcefalia, asociado a anomalías cerebrales. Este hecho generó conmoción social, movilización de la comunidad académica y obligó al Ministerio de Salud a decretar la emergencia de salud pública nacional, seguida de la declaración de interés internacional de la Organización Mundial de la Salud. La hipótesis formulada para este fenómeno fue la infección congénita por el virus Zika (ZIKV), en base a la correlación espacio-temporal y a las características clínico-epidemiológicas de las dos epidemias. Se acumularon evidencias, y en el ámbito del raciocinio epidemiológico se cumplieron los criterios que dieron apoyo a la hipótesis. Su plausibilidad está anclada en el neurotropismo del ZIKV, demostrado en animales, alcanzando progenitores neuronales del cerebro en desarrollo, y en seres humanos, debido a las complicaciones neurológicas observadas en adultos tras la infección. El aislamiento del ARN y antígenos virales en el líquido amniótico de madres infectadas, en cerebros de neonatos y fetos con microcefalia, contribuyeron a demostrar la consistencia de la hipótesis. El criterio de temporalidad se contempló al identificarse desenlaces desfavorables en una cohorte de gestantes con exantema y positivas en ZIKV. Finalmente, el primer estudio caso-control realizado demostró que existía una fuerte asociación entre microcefalia e infección congénita por el ZIKV. El conocimiento construido en el ámbito del paradigma epidemiológico recibió la aprobación de la comunidad científica, existiendo consenso en cuanto a la relación causal entre el ZIKV y la epidemia de microcefalia.
Since the first report by Perry et al. (1955), most studies affirmed the hypertensive effects of cadmium (Cd) in humans. Nonetheless, conclusions between studies remain inconsistent.
The aim of this ...study was to reevaluate the evidence for a potential relationship between Cd exposure and altered blood pressure and/or hypertension, focusing on studies published between January 2010 and March 2020.
We reviewed all observational studies from database searches (PubMed and SCOPUS) on Cd exposure and blood pressure or hypertension. We extracted information from studies that provided sufficient data on population characteristics, smoking status, exposure, outcomes, and design.
Thirty-eight studies met our inclusion criteria; of those, twenty-nine were cross sectional, three case control, five cohort and one interventional study. Blood or urinary Cd levels were the most commonly used biomarkers.
A positive association between blood Cd levels and blood pressure and/or hypertension was identified in numerous studies at different settings. Limited number of representative population-based studies of never-smokers was observed, which may have confounded our conclusions. The association between urinary Cd and blood pressure and/or hypertension remains uncertain due to conflicting results, including inverse relationships with lack of strong mechanistic support. We point to the urgent need for additional longitudinal studies to confirm our findings.
•We performed a systematic review on the effects of human Cd exposure and altered blood pressure and/or hypertension.•Observational studies were reviewed from database searches published between January 2010 and March 2020.•A positive association between blood Cd levels and blood pressure and/or hypertension was identified.•The association between urinary Cd and blood pressure and/or hypertension remains uncertain.•Future population-wide longitudinal studies, as well as studies in non-smoking populations are needed.
Resumo Objetivo: descrever a melhoria da qualidade do registro da causa básica de morte por causas externas após realização do relacionamento de dados dos setores Saúde, Segurança Pública e imprensa ...no estado do Rio de Janeiro, Brasil, em 2014. Métodos: relacionamento determinístico de dados de óbitos por causas externas de intenção indeterminada e naturais por causa indeterminada do Sistema de Informações sobre Mortalidade (SIM), Instituto Médico Legal, Polícia Civil, Serviço de Atendimento Móvel de Urgência (SAMU) e imprensa. Resultados: dos 13.916 óbitos por causas externas, os óbitos por causas de intenção indeterminada foram reduzida de 5.836 (41,9%) para 958 (6,9%); das 2.069 causas naturais indeterminadas, 222 (10,7%) foram reclassificadas para causas externas; houve aumento na mortalidade por acidentes de transporte (93,0%), agressões (71,6%), intervenção legal (744,7%), lesões autoinfligidas (112%) e outros acidentes (29,9%). Conclusão: houve melhoria da qualidade da informação por tipo de causa básica por causas externas, mediante estratégia que pode ser reproduzida por outros serviços.
Polylysogeny is frequently considered to be the result of an adaptive evolutionary process in which prophages confer fitness and/or virulence factors, thus making them important for evolution of both ...bacterial populations and infectious diseases. The Enterococcus faecalis V583 isolate belongs to the high-risk clonal complex 2 that is particularly well adapted to the hospital environment. Its genome carries 7 prophage-like elements (V583-pp1 to -pp7), one of which is ubiquitous in the species. In this study, we investigated the activity of the V583 prophages and their contribution to E. faecalis biological traits. We systematically analyzed the ability of each prophage to excise from the bacterial chromosome, to replicate and to package its DNA. We also created a set of E. faecalis isogenic strains that lack from one to all six non-ubiquitous prophages by mimicking natural excision. Our work reveals that prophages of E. faecalis V583 excise from the bacterial chromosome in the presence of a fluoroquinolone, and are able to produce active phage progeny. Intricate interactions between V583 prophages were also unveiled: i) pp7, coined EfCIV583 for E. faecalis chromosomal island of V583, hijacks capsids from helper phage 1, leading to the formation of distinct virions, and ii) pp1, pp3 and pp5 inhibit excision of pp4 and pp6. The hijacking exerted by EfCIV583 on helper phage 1 capsids is the first example of molecular piracy in Gram positive bacteria other than staphylococci. Furthermore, prophages encoding platelet-binding-like proteins were found to be involved in adhesion to human platelets, considered as a first step towards the development of infective endocarditis. Our findings reveal not only a role of E. faecalis V583 prophages in pathogenicity, but also provide an explanation for the correlation between antibiotic usage and E. faecalis success as a nosocomial pathogen, as fluoriquinolone may provoke release of prophages and promote gene dissemination among isolates.
RESUMO: Objetivo: Avaliar a mortalidade por áreas de Belo Horizonte (BH) durante a pandemia de COVID-19 conforme a vulnerabilidade social, visando a uma estratégia de vacinação. Métodos: Estudo ...ecológico com análise de mortalidade, segundo setores censitários classificados pelo índice de vulnerabilidade da saúde, composto de indicadores de saneamento e socioeconômicos. Óbitos por causas naturais e COVID-19 foram obtidos do Sistema de Informação sobre Mortalidade, entre a 10ª e a 43ª semanas epidemiológicas (SE) de 2020. Calculou-se o excesso de mortalidade por modelo de série temporal, considerando-se as mortes observadas por SE entre 2015 e 2019, por setor censitário. Taxas de mortalidade (TM) foram calculadas e padronizadas por idade com base em estimativas populacionais do Instituto Brasileiro de Geografia e Estatística (IBGE). Resultados: Houve 16,1% (n = 1.524) de excesso de mortalidade em BH: 11, 18,8 e 17,3% nas áreas de baixa, média e elevada vulnerabilidade, respectivamente. As diferenças entre TM observadas e esperadas por causas naturais, padronizadas por idade, foi igual a 59/100 mil habitantes em BH, aumentando de 31 para 77 e 95/100 mil, nas áreas de baixa, média e elevada vulnerabilidade, respectivamente. Houve gradiente de aumento com a idade nas TM por COVID-19, variando de 4 a 611/100 mil habitantes entre as idades de 20-39 anos e 75+ anos. A TM por COVID-19 por 100 mil idosos (60+ anos) foi igual a 292, aumentando de 179 para 354 e 476 nos setores de baixa, média e elevada vulnerabilidade, respectivamente. Conclusão: Desigualdades na mortalidade, mesmo entre idosos, aliadas à baixa oferta de doses, demonstram a importância de priorizar áreas socialmente vulneráveis durante a vacinação contra COVID-19.
ABSTRACT: Objective: To assess mortality during the COVID-19 pandemic according to social vulnerability by areas of Belo Horizonte (BH), aiming at strategies for vaccination. Methods: Ecological study with mortality analysis according to census tracts classified by the Health Vulnerability Index, a composite indicator that includes socioeconomic and sanitation variables. Deaths by natural causes and by COVID-19 were obtained from the “Mortality Information System”, between the 10th and 43rd epidemiological weeks (EW) of 2020. Excess mortality was calculated in a time series model, considering observed and expected deaths per EW, between 2015 and 2019, per census tracts. Mortality rates (MR) were calculated and age-standardized using population estimates from the 2010 census, by the Brazilian Institute of Geography and Statistics (IBGE). Results: Excess mortality in BH was 16.1% (n = 1,524): 11, 18.8 and 17.3% in low, intermediate and high vulnerability areas, respectively. The differences between observed and expected age-standardized MR by natural causes were equal to 59/100,000 inhabitants in BH, increasing from 31 to 77 and 95/100,000 inhabitants in the areas of low, intermediate and high vulnerability, respectively. There was an aging gradient in MR by COVID-19, ranging from 4 to 611/100,000 inhabitants among individuals aged 20-39 years and 75+ years. The COVID-19 MR per 100,000 older adults (60+ years) was 292 in BH, increasing from 179 to 354 and 476, in low, intermediate and high vulnerability areas, respectively. Conclusion: Inequalities in mortality, particularly among older adults, combined with the limited supply of doses, demonstrate the importance of prioritizing socially vulnerable areas during vaccination against COVID-19.
Pneumonia plays an important role in children's morbidity and mortality. In Brazil, epidemiological and social changes occurred concomitantly with the universal introduction of the 10-valent ...pneumococcal conjugate vaccine. This study identified risk factors for pneumonia following the implementation of a pneumococcal vaccination program.
A hospital-based, case-control study involving incident cases of pneumonia in children aged 1-59 months was conducted between October 2010 and September 2013 at a tertiary hospital in northeastern Brazil. The diagnosis of pneumonia was based on the World Health Organization (WHO) criteria. The control group consisted of children admitted to the day-hospital ward for elective surgery. Children with comorbidities were excluded. The risk factors for pneumonia that were investigated were among those classified by the WHO as definite, likely and possible. A multivariate analysis was performed including variables that were significant at p ≤ 0.25 in the bivariate analysis.
The study evaluated 407 children in the case group and 407 children in the control group. Household crowding (OR = 2.15; 95 % CI, 1,46-3,18) and not having been vaccinated against the influenza virus (OR = 3.59; 95 % CI, 2,62-4.91) were the only factors found to increase the likelihood of pneumonia. Male gender constituted a protective factor (OR = 0.53; 95 % CI, 0,39-0,72).
Changes on risk factors for pneumonia were most likely associated with the expansion of the vaccination program and social improvements; however, these improvements were insufficient to overcome inequalities, given that household crowding remained a significant risk factor. The protection provided by the influenza vaccine must be evaluated new etiological studies. Furthermore, additional risk factors should be investigated.
Hepatotoxicity is frequently reported as an adverse reaction during the treatment of tuberculosis. The aim of this study was to determine the incidence of hepatotoxicity and to identify predictive ...factors for developing hepatotoxicity after people living with HIV/AIDS (PLWHA) start treatment for tuberculosis. This was a prospective cohort study with PLWHA who were monitored during the first 60 days of tuberculosis treatment in Pernambuco, Brazil. Hepatotoxicity was considered increased levels of aminotransferase, namely those that rose to three times higher than the level before initiating tuberculosis treatment, these levels being associated with symptoms of hepatitis. We conducted a multivariate logistic regression analysis and the magnitude of the associations was expressed by the odds ratio with a confidence interval of 95%. Hepatotoxicity was observed in 53 (30.6%) of the 173 patients who started tuberculosis treatment. The final multivariate logistic regression model demonstrated that the use of fluconazole, malnutrition and the subject being classified as a phenotypically slow acetylator increased the risk of hepatotoxicity significantly. The incidence of hepatotoxicity during treatment for tuberculosis in PLWHA was high. Those classified as phenotypically slow acetylators and as malnourished should be targeted for specific care to reduce the risk of hepatotoxicity during treatment for tuberculosis. The use of fluconazole should be avoided during tuberculosis treatment in PLWHA.
Since 2015, the arthropod-borne viruses (arboviruses) Zika and chikungunya have spread across the Americas causing outbreaks, accompanied by increases in immune-mediated and infectious neurological ...disease. The spectrum of neurological manifestations linked to these viruses, and the importance of dual infection, are not known fully. We aimed to investigate whether neurological presentations differed according to the infecting arbovirus, and whether patients with dual infection had a different disease spectrum or severity.
We report a prospective observational study done during epidemics of Zika and chikungunya viruses in Recife, Pernambuco, a dengue-endemic area of Brazil. We recruited adults aged 18 years or older referred to Hospital da Restauração, a secondary-level and tertiary-level hospital, with suspected acute neurological disease and a history of suspected arboviral infection. We looked for evidence of Zika, chikungunya, or dengue infection by viral RNA or specific IgM antibodies in serum or CSF. We grouped patients according to their arbovirus laboratory diagnosis and then compared demographic and clinical characteristics.
Between Dec 4, 2014, and Dec 4, 2016, 1410 patients were admitted to the hospital neurology service; 201 (14%) had symptoms consistent with arbovirus infection and sufficient samples for diagnostic testing and were included in the study. The median age was 48 years (IQR 34–60), and 106 (53%) were women. 148 (74%) of 201 patients had laboratory evidence of arboviral infection. 98 (49%) of them had a single viral infection (41 20% had Zika, 55 27% had chikungunya, and two 1% had dengue infection), whereas 50 (25%) had evidence of dual infection, mostly with Zika and chikungunya viruses (46 23% patients). Patients positive for arbovirus infection presented with a broad range of CNS and peripheral nervous system (PNS) disease. Chikungunya infection was more often associated with CNS disease (26 47% of 55 patients with chikungunya infection vs six 15% of 41 with Zika infection; p=0·0008), especially myelitis (12 22% patients). Zika infection was more often associated with PNS disease (26 63% of 41 patients with Zika infection vs nine 16% of 55 with chikungunya infection; p≤0·0001), particularly Guillain-Barré syndrome (25 61% patients). Patients with Guillain-Barré syndrome who had Zika and chikungunya dual infection had more aggressive disease, requiring intensive care support and longer hospital stays, than those with mono-infection (median 24 days IQR 20–30 vs 17 days 10–20; p=0·0028). Eight (17%) of 46 patients with Zika and chikungunya dual infection had a stroke or transient ischaemic attack, compared with five (6%) of 96 patients with Zika or chikungunya mono-infection (p=0·047).
There is a wide and overlapping spectrum of neurological manifestations caused by Zika or chikungunya mono-infection and by dual infections. The possible increased risk of acute cerebrovascular disease in patients with dual infection merits further investigation.
Fundação do Amparo a Ciência e Tecnologia de Pernambuco (FACEPE), EU's Horizon 2020 research and innovation programme, National Institute for Health Research.
For the Portuguese and Spanish translations of the abstract see Supplementary Materials section.
Forty enterococci isolated along the production chains of three traditional cheeses (PDO Pecorino Siciliano, PDO Vastedda della Valle del Belìce, and Caciocavallo Palermitano) made in Sicily ...(southern Italy) were studied for the assessment of their antibiotic resistance and virulence by a combined phenotypic/genotypic approach. A total of 31 Enterococcus displayed resistance to at least one or more of the antimicrobials tested. The strains exhibited high percentages of resistance to erythromycin (52.5%), ciprofloxacin (35.0%), quinupristin–dalfopristin (20.0%), tetracycline (17.5%), and high-level streptomycin (5.0%). The presence of tet(M), cat(pC221), and aadE genes for resistance to tetracycline, chloramphenicol, and streptomycin, respectively, was registered in all strains with resistance phenotype. The erm(B) gene was not detected in any erythromycin-resistant strain. The Enterococcus strains were further tested by PCR for the presence of virulence genes, namely, gelE, asa1, efaA, ace, and esp. Twenty strains were positive for all virulence genes tested. Among the enterococci isolated from final cheeses, three strains (representing 33.3% of total cheese strains) were sensible to all antimicrobials tested and did not carry any virulence factor. Although this study confirmed that the majority of dairy enterococci are vectors for the dissemination of antimicrobial resistance and virulence genes, only two strains showed a high resistance to aminoglycosides, commonly administered to combat enterococci responsible for human infections. Furthermore, the presence of the strains E. casseliflavus FMAC163, E. durans FMAC134B, and E. faecium PON94 without risk determinants, found at dominating levels over the Enterococcus populations in the processed products, stimulates further investigations for their future applications in cheese making. All strains devoid of the undesired traits were isolated from stretched cheeses. Thus, this cheese typology represents an interesting environment to deepen the studies on the risk/benefit role of enterococci in fermented foods for their qualified presumption of safety (QPS) assessment.
•31 Enterococcus were resistant to at least one antimicrobial.•tet(M), cat(pC221), and aadE genes were detected in all resistant phenotypes.•20 strains were positive for virulence (gelE, asa1, efaA, ace, and esp) genes.•All strains devoid of risk factors were isolated from stretched cheeses.
This study aimed to describe the demographic and clinical characteristics of cancer patients with COVID-19, exploring factors associated with adverse outcomes.
This retrospective cohort study ...methodically extracted and curated data from electronic medical records (EMRs) of numerous healthcare institutions on cancer patients diagnosed with a confirmed SARS-CoV-2 infection between May 2020 and August 2021, to identify risk factors linked to extended hospitalization and mortality. The retrieved information encompassed the patients' demographic and clinical characteristics, including the incidence of prolonged hospitalization, acute complications, and COVID-19-related mortality.
A total of 1446 cancer patients with COVID-19 were identified (mean Standard deviation age, 59.2 14.3 years). Most patients were female (913 63.1%), non-white (646 44.7%), with non-metastatic (818 56.6%) solid tumors (1318 91.1%), and undergoing chemotherapy (647 44.7%). The rate of extended hospitalization due to COVID-19 was 46% (n = 665), which was significantly impacted by age (p = 0.012), sex (p = 0.003), race and ethnicity (p = 0.049), the presence of two or more comorbidities (p = 0.006), hematologic malignancies (p = 0.013), metastatic disease (p = 0.002), and a performance status ≥ 2 (p = 0.001). The COVID-19-related mortality rate was 18.9% (n = 273), and metastatic disease (<0.001), performance status ≥2 (<0.001), extended hospitalization (p = 0.028), renal failure (p = 0.029), respiratory failure (p < 0.001), sepsis (p = 0.004), and shock (p = 0.040) significantly and negatively influenced survival.
The rate of extended hospitalization and COVID-19-specific death in cancer patients was notably high and could be influenced by comorbidities, cancer treatment status, and clinical fragility. These observations may aid in developing risk counseling strategies regarding COVID-19 in individuals diagnosed with cancer.
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