Prevalence and clinical consequences of Hepatitis C virus infection in patients undergoing hematopoietic stem cell transplantation

ABSTRACT Hepatitis C virus (HCV) infection is a significant cause of morbidity and mortality among hematopoietic stem cell transplant (HCT) recipients. In Brazil, its occurrence in HCT recipients remains undetermined. We now report on HCV prevalence in HCT recipients and its clinical consequences. The medical records of all HCT recipients seen at Hospital das Clinicas, Sao Paulo University Medical School, from January 2010 to January 2020 were reviewed to determine HCV serostatus. A retrospective analysis of medical charts was undertaken on all seropositive cases to determine HCV genotype, presence of liver fibrosis, co-infections with other viruses, previous treatments, and clinical evolution of liver pathology after HCT. Of the 1,293 HCT recipients included in the study, seven (0.54%) were HCV antibody-positive and five (0.39%) were also viremic for HCV-RNA. Four of these individuals had moderate to severe liver fibrosis (METAVIR F2/F3) and one was cirrhotic. Two of the viremic patients developed acute liver dysfunction following transplantation. All patients had their acute episode of liver dysfunction resolved with no further complications. Four of the viremic patients were treated for HCV infection with direct acting agents (DAA). Information regarding HCV treatment was lacking for one of the viremic HCV patients due to loss of follow up. Sustained anti-virologic responses were observed in three cases after the use of DAA. The detection of HCV in hematological adults undergoing HCT and its successful treatment with DAA highlight the necessity of testing for HCV both prior to and following transplantation.

Lactobacilluscrispatus dominance in the vaginalmicrobiome reduces the occurrence of spontaneouspreterm birth in women with a short cervical length / Dominância de Lactobacillus crispatus no microbioma vaginal reduz a ocorrênciade parto prematuro espontâneo em mulheres com encurtamento do colo uterino

Introduction: The majority of pregnant women with a short cervix will deliver at term and, thus, may unnecessarily receive advanced monitoring and treatment. It is still necessary to define more accurately which sub-population of women with a short cervix is at elevated risk for early delivery. Objective: To determine if vaginal microbiome composition influenced the rate of spontaneous preterm birth in women with a short cervical length. Methods: In an exploratory, observational prospective study, vaginal secretions were obtained from 591 women at 21­24 week gestation. Vaginal microbiome composition was determined by analyzing the V1­V3 region of the bacterial 16S ribosomal RNA gene. Results: Lactobacillus crispatus was numerically dominant in the vagina in 41.7% of subjects, followed by L. iners in 32% and Gardnerella vaginalis in 12%. In women whose cervix was ≤25mm, the sensitivity to predict an spontaneous preterm birth was 11.8%. However, when L. crispatus was not the dominant vaginal bacterium, this sensitivity increased to 81.8%. Similarly, in women with a cervical length ≤30mm, the sensitivity to predict an spontaneous preterm birth increased from 21.7 to 78.3% when L. crispatus was not the dominant vaginal bacterium.In women with a prior spontaneous preterm birth and a cervix ≤25 or ≤30mm, L. crispatus dominance was also associated with a reduced rate of spontaneous preterm birth in the current pregnancy (p<0.001). Conclusion: In pregnant women with a cervix ≤25mm or ≤30mm, the risk for an spontaneous preterm birth is increased if L. crispatus is not dominant in the vagina.

Introdução: A maioria das mulheres grávidas com colo do útero curto dará à luz a termo e, portanto, pode receber desnecessariamente monitoramento e tratamento avançados. Permanece a necessidade de definir com mais precisão qual subpopulação de mulheres com colo do útero curto está em risco elevado de parto prematuro. Objetivo: Determinar se a composição do microbioma vaginal influenciou a taxa de parto prematuro espontâneo em mulheres com colo curto. Métodos: Em um estudo prospectivo exploratório observacional, os conteúdos vaginais foram obtidos de 591 mulheres com 21­24 semanas de gestação. A composição do microbioma vaginal foi determinada pela análise da região V1­V3 do gene de RNA ribossômico bacteriano 16S. Resultados: Lactobacilluscrispatus foi numericamente dominante na vagina em 41,7% dos indivíduos, seguido por L. iners em 32% e Gardnerella vaginalis em 12%. Em mulheres cujo colo do útero era <25 mm, a sensibilidade para prever uma taxa de parto prematuro espontâneo foi de 11,8%. No entanto, quando L. crispatus não era a bactéria vaginal dominante, essa sensibilidade aumentou para 81,8%. Da mesma forma, em mulheres com comprimento cervical <30 mm, a sensibilidade para prever uma taxa de parto prematuro espontâneo aumentou de 21,7 para 78,3% quando L. crispatus não era a bactéria vaginal dominante. Em mulheres com taxa de parto prematuro espontâneo anterior e colo do útero <25 ou <30 mm, a dominância de L. crispatus também foi associada a uma taxa reduzida de taxa de parto prematuro espontâneo na gravidez atual (p<0,001). Conclusão: Em mulheres grávidas com colo do útero <25 ou <30 mm, o risco de parto prematuro espontâneo é aumentado se L. crispatus não for dominante na vagina.

Absence of neutralizing antibodies against the Omicron SARS-CoV-2 variant in convalescent sera from individuals infected with the ancestral SARS-CoV-2 virus or its Gamma variant

Abstract Objectives: The aim of the present study was to evaluate if neutralizing antibody responses induced by infection with the SARS-CoV-2 strain that was dominant at the beginning of the pandemic or by the Gamma variant was effective against the Omicron variant. Methods: Convalescent sera from 109 individuals, never exposed to a SARS-CoV-2 vaccine, who had mild or moderate symptoms not requiring hospitalization following either a documented SARS-CoV-2 ancestral strain infection or a Gamma variant infection, were assayed for in vitro neutralizing antibody activity against their original strains and the Omicron variant. Results: Following an infection with the ancestral strain, 56 (93.3%), 45 (77.6%) and 1 (1.7%) serum sample were positive for neutralizing antibodies against the ancestral, Gamma variant, and Omicron variant, respectively. After infection with the Gamma variant, 43 (87.8%) and 2 (4.1%) sera were positive for neutralizing antibodies against the Gamma and Omicron variants, respectively. Conclusions: Neutralizing antibodies generated following mild or moderate infection with the SARS-CoV-2 ancestral strain or the Gamma variant are not protective against the Omicron variant. HIGHLIGHTS Individuals previously infected with SARS-CoV-2 ancestral strain do not develop neutralizing antibodies against the Omicron variant. Omicron variant escapes immune response after SARS CoV-2 previous infection with the SARS CoV-2 Gamma variant. Individuals previously infected with SARS-CoV-2 ancestral strain or with SARS-CoV-2 Gamma variant will likely have little protection if subsequently exposed to the Omicron variant.

Generation of neutralizing antibodies against Omicron, Gamma and Delta SARS-CoV-2 variants following CoronaVac vaccination

ABSTRACT Vaccination is a fundamental tool to prevent SARS-CoV-2 infection and to limit the COVID-19 pandemic. The emergence of SARS-CoV-2 variants with multiple mutations has raised serious concerns about the ability of neutralizing antibody responses elicited by prior vaccination to effectively combat these variants. The neutralizing capacity against the Gamma, Delta and Omicron variants of sera from individuals immunized with the CoronaVac vaccine remains incompletely determined. The present study evaluated 41 health care workers at the Faculdade de Medicina of the Universidade de Sao Paulo, in Sao Paulo, Brazil, naive to previous SARS- CoV-2 infection, who were vaccinated with two doses of the CoronaVac SARS-CoV-2 vaccine 28 days apart. Neutralizing antibody levels against the Gamma, Delta, and Omicron variants were measured at 32 and 186 days after the second vaccination. We also measured neutralizing antibodies against Omicron in 34 of these individuals following a subsequent booster immunization with the Pfizer vaccine. Quantification of neutralizing antibodies was performed using the Cytopathic Effect-based Virus Neutralization test. Neutralization antibody activity against the Gamma, Delta and Omicron variants was observed in 78.0%, 65.9% and 58.5% of serum samples, respectively, obtained at a mean of 32 days after the second immunization. This decreased to 17.1%, 24.4% and 2.4% of sera having activity against Delta, Gamma and Omicron, respectively, at 186 days post-vaccination. The median neutralizing antibody titers at 32 days were 1:40, 1:20 and 1:20 against Gamma, Delta and Omicron, respectively, and decreased to an undetectable median level against all variants at the later time. A booster immunization with the Pfizer vaccine elicited neutralizing antibodies against Omicron in 85% of subjects tested 60 days after vaccination. We conclude that two doses of the CoronaVac vaccine results in limited protection of short duration against the Gamma, Delta and Omicron SARS-CoV-2 variants. A booster dose with the Pfizer vaccine induced antibody neutralizing activity against Omicron in most patients which was measurable 60 days after the booster.

Knowledge of Hepatitis C virus vertical transmission and subsequent pregnancy outcome in virus-positive female blood donors

ABSTRACT Introduction Hepatitis C virus (HCV) can be vertically transmitted from mother to fetus. We evaluated knowledge about HCV vertical transmission in female blood donors who became pregnant following detection of HCV in their donated blood. Methods This was a retrospective descriptive study of females seen at a single blood bank in Sao Paulo, Brazil who were diagnosed with HCV infection in their donated blood. HCV-infected donors who subsequently became pregnant were invited to participate through letters or phone calls. Individuals who agreed to participate were interviewed by questionnaire to evaluate their knowledge on HCV vertical transmission. Results Among 282 HCV-positive female blood donors, 69 reported becoming pregnant after their HCV diagnosis in donated blood. While 24 of these women were successful treated for their infection prior to becoming pregnant, 45 (65.2%) were at risk for vertical HCV transmission either because they had never been treated for HCV, were pregnant before treatment or became pregnant after unsuccessful treatment. Of the 59 women who responded to the question of whether they were informed about the risk of HCV vertical transmission, 58 (98.3%) reported never receiving this information either after obtaining their blood donation results or during their pregnancy. Conclusion The lack of knowledge of HCV-infected women on the possibility for mother-to-child transmission of this virus highlights the critical need to improve communication about pregnancy-related risks between health professionals and HCV-infected women of childbearing age.

Characterization of insect-specific Culex flavivirus (Flaviviridae) nucleotide sequences in mosquitoes from urban parks in São Paulo, Brazil

ABSTRACT Background: Despite their worldwide occurrence, the distribution and role of insect-specific flaviviruses (ISFs) remain unclear. Methods: We evaluated the presence of ISFs in mosquitoes collected in São Paulo, Brazil, using reverse transcription and semi-nested polymerase chain reaction (PCR). Some of the positive samples were subjected to nanopore sequencing. Results: Twelve mosquito pools (2.8%) tested positive for flavivirus infection. Nanopore sequencing was successfully performed on six samples. Phylogenetic analysis grouped these sequences into genotype 2 of Culex flavivirus (CxFV). Conclusions: The identification of CxFV genotype 2 at new locations in São Paulo highlights the importance of understanding the role of ISFs in mosquito vector competence.

Prevalence and diagnostic accuracy of microcephaly in a pediatric cohort in Brazil: a retrospective cross-sectional study

Abstract Objective We sought to describe the prevalence of microcephaly and to compare the different cutoff points established by the Brazilian Ministry of Health at various times during a Zika virus epidemic. As a secondary aim, we investigated the possible etiology of the microcephaly. Method This retrospective study utilized newborn participants in the Zika Cohort Study Jundiaí. Newborns from the Zika Cohort Study Jundiaí with an accurate gestational age determination and complete anthropometric data were analyzed, and microcephaly was diagnosed according to the INTERGROWTH-21st curve. At delivery, fluids were tested for specific antibodies and for viruses. Brain images were evaluated for microcephaly. Receiver Operating Characteristic curves were plotted to define the accuracy of different cutoff points for microcephaly diagnosis. Results Of 462 eligible newborns, 19 (4.1%) were positive for microcephaly. Cutoff points corresponding to the curves of the World Health Organization yielded the best sensitivity and specificity. Three of the microcephaly cases (15.8%) were positive for Zika virus infections; nine (47.4%) had intrauterine growth restriction; one had intrauterine growth restriction and was exposed to Zika virus; three had a genetic syndrome (15.8%); and three had causes that had not been determined (15.8%). Conclusions Microcephaly prevalence was 4.1% in this study. Cutoff values determined by the World Health Organization had the highest sensitivity and specificity in relation to the standard IG curve. The main reason for microcephaly was intrauterine growth restriction. All possible causes of microcephaly must be investigated to allow the best development of an affected baby.

Surveillance of hemorrhagic fever and/or neuroinvasive disease: challenges of diagnosis

ABSTRACT OBJECTIVE To evaluate the performance of post mortem laboratory analysis in identifying the causes of hemorrhagic fever and/or neuroinvasive disease in deaths by arbovirus infection. METHODS Retrospective cross-sectional study based on the differential analysis and final outcome obtained in patients whose samples underwent laboratory testing for arboviruses at the Pathology Center of the Adolfo Lutz Institute, in São Paulo, Brazil. RESULTS Of the 1355 adults clinically diagnosed with hemorrhagic fever and/or neuroinvasive disease, the most commonly attributed cause of death and the most common final outcome was dengue fever. Almost half of the samples tested negative on all laboratory tests conducted. CONCLUSION The failure to identify the causative agent in a great number of cases highlights a gap in the diagnosis of deaths of unknown etiology. Additional immunohistochemical and molecular assessments need to be added to the post-mortem protocol if all laboratory evaluations performed fail to identify a causative agent. While part of our findings may be due to technical issues related to sample fixation, better information availability when making the initial diagnosis is crucial. Including molecular approaches might lead to a significant advancement in diagnostic accuracy.

Surveillance of hemorrhagic fever and/or neuroinvasive disease: challenges of diagnosis

OBJECTIVE: To evaluate the performance of post mortem laboratory analysis in identifying the causes of hemorrhagic fever and/or neuroinvasive disease in deaths by arbovirus infection. METHODS: Retrospective cross-sectional study based on the differential analysis and final outcome obtained in patients whose samples underwent laboratory testing for arboviruses at the Pathology Center of the Adolfo Lutz Institute, in São Paulo, Brazil. RESULTS: Of the 1355 adults clinically diagnosed with hemorrhagic fever and/or neuroinvasive disease, the most commonly attributed cause of death and the most common final outcome was dengue fever. Almost half of the samples tested negative on all laboratory tests conducted. CONCLUSION: The failure to identify the causative agent in a great number of cases highlights a gap in the diagnosis of deaths of unknown etiology. Additional immunohistochemical and molecular assessments need to be added to the post-mortem protocol if all laboratory evaluations performed fail to identify a causative agent. While part of our findings may be due to technical issues related to sample fixation, better information availability when making the initial diagnosis is crucial. Including molecular approaches might lead to a significant advancement in diagnostic accuracy. DESCRIPTORS: Autopsy. Hemorrhagic Fevers, Viral, etiology. Arbovirus Infections, mortality

Validation of a formula predictive of peripheral blood stem cell yield and successful collection in healthy allogeneic donors

ABSTRACT Background: An efficient mobilization and collection of peripheral blood stem cells (PBSCs) are crucial to optimize engraftment in the recipient. We aim to validate a formula that predicted CD34+ cell yield and to describe variables that correlated with high yield mobilization and collection in healthy donors. Methods: We retrospectively analyzed clinical and laboratory data from healthy donors who underwent PBSC collection from 2006 to 2015. The predicted number of collected cells was calculated using the following formula: Total number of CD34+ (cells × 106/kg) yield = [(peripheral CD34+ cells/µL) × (0.43)/recipient body weight (kg)] × total liters processed. Results: We evaluated 338 collections from 307 allogeneic PBSC donors. The predicted versus the observed number of CD34+ cells/kg collected yielded an r-value of 0.775 (0.726-0.816; p < 0.0001). Overall, 55.7% donors had an acceptable mobilization level. Donors with a body weight <67 kg were less likely to yield a satisfactory CD34+ cell count (OR = 0.44; 95% CI 0.24-0.81), while a white blood cell (WBC) count >40 × 109/L (OR = 3.69; 2.11-6.46) and platelet count ≥200 × 109/L (OR = 2.09; 1.26-3.47) on the day of collection predicted a good level of mobilization. Predictors of a CD34+ cell yield/kg of ≥4 × 106 with only one apheresis session were: circulating CD34+ cells/µL >40 (OR = 16; 6.94-36.93), hemoglobin ≥14 g/dL (OR = 3.40; 1.53-7.57), WBC >40 × 109/L (OR = 4.61; 2.10-10.10) on the first collection day, and a positive delta weight between donor and recipient (OR = 3.10; 1.36-7.06). Conclusion: The formula for predicting CD34+ cell yield is accurate and suggests the optimal length of time for successful leukapheresis. Validation of the predictors of successful mobilization will help to further refine PBSC leukapheresis procedures.

Characteristics of a hepatitis C patient cohort at a specialized tertiary care facility: Identifying criteria to improve the allocation of public health resources

OBJECTIVES: Our objective was to analyze, in a population treated for hepatitis C infection at a tertiary care treatment unit, the prevalence of comorbidities and extrahepatic manifestations, the range and degree of the clinical complexity and the associations between advanced liver disease and clinical variables. METHODS: Medical records from chronically infected hepatitis C patients seen at a dedicated treatment facility for complex cases in the Infectious Diseases Division of Hospital das Clínicas in Brazil were analyzed. Clinical complexity was defined as the presence of one or more of the following conditions: advanced liver disease (Metavir score F3 or F4 and/or clinical manifestations or ultrasound/endoscopy findings consistent with cirrhosis) or hepatocellular carcinoma and/or 3 or more extrahepatic manifestations and/or comorbidities concomitantly. RESULTS: Among the 1574 patients analyzed, only 41% met the definition of being clinically complex. Cirrhosis or hepatocarcinoma was identified in 22.2% and 1.8% of patients, respectively. According to multiple logistic regression analysis, male sex (p=0.007), age>40 years (p<0.001) and the presence of metabolic syndrome (p=0.008) were independently associated with advanced liver disease. CONCLUSION: The majority of patients did not meet the criteria for admittance to this specialized tertiary service, reinforcing the need to reevaluate public health policies. Enhanced utilization of existing basic and intermediate complexity units for the management of less complex hepatitis C cases could improve care and lower costs.

Ureaplasma urealyticum e mycoplasma hominis no parto pré-termo / Ureaplasma urealyticum and mycoplasma hominis in preterm labor

Mycoplasma hominis and Ureaplasma urealyticum are considered genital mycoplasmas, because infection occurs through sexual contact. The presenceof these bacteria has been associated with non gonococcal urethritis, cervicitis, vaginitis, pelvic inflammatory disease (PID) and pathology of pregnancyand newborns.Complications of genital mycoplasmas on the outcome of pregnancy include ectopic pregnancy, premature birth and preterm premature rupture of membranes (PPROM), chorioamnionitis, post partum endometritis, salpingitis, low weight and late abortion. This review article focuses on theim portance of these microorganisms leading to preterm labor.

Mycoplasma hominis e Ureaplasma urealyticum são considerados micoplasmas genitais, pois a infecção ocorre através do contato sexual. A presença dessas bactérias tem sido associada A uretrite não gonocócica, cervicite, vaginite, doença inflamatória pélvica (DIP) e patologia da gravidez e de recém-nascidos.As complicações de micoplasmas genitais sobre os resultados da gravidez incluem gravidez ectópica, parto prematuro e ruptura prematura das membranas ovulares (PPROM), corioamnionite, endometrite pós-parto, salpingite, baixo peso e abortamento tardio. Este artigo de revisão concentra-se na importância destes microrganismos, levando a trabalho de parto prematuro.

Urinary incontinence and vaginal squeeze pressure two years post-cesarean delivery in primiparous women with previous gestational diabetes mellitus

OBJECTIVE: To assess the prevalence of urinary incontinence and associated vaginal squeeze pressure in primiparous women with and without previous gestational diabetes mellitus two years post-cesarean delivery. METHODS: Primiparous women who delivered by cesarean two years previously were interviewed about the delivery and the occurrence of incontinence. Incontinence was reported by the women and vaginal pressure evaluated by a Perina perineometer. Sixty-three women with gestational diabetes and 98 women without the disease were screened for incontinence and vaginal pressure. Multiple logistic regression models were used to evaluate the independent effects of gestational diabetes. RESULTS: The prevalence of gestational incontinence was higher among women with gestational diabetes during their pregnancies (50.8 percent vs. 31.6 percent) and two years after a cesarean (44.8 percent vs. 18.4 percent). Decreased vaginal pressure was also significantly higher among women with gestational diabetes (53.9 percent vs. 37.8 percent). Maternal weight gain and newborn weight were risk factors for decreased vaginal pressure. Maternal age, gestational incontinence and decreased vaginal pressure were risk factors for incontinence two years after a cesarean. In a multivariate logistic model, gestational diabetes was an independent risk factor for gestational incontinence. CONCLUSIONS: The prevalence of incontinence and decreased vaginal pressure two years post-cesarean were elevated among women with gestational diabetes compared to women who were normoglycemic during pregnancy. We confirmed an association between gestational diabetes mellitus and a subsequent decrease of vaginal pressure two years post-cesarean. These results may warrant more comprehensive prospective and translational studies.

Influence of human papillomavirus infection and sexual intercourse on endocervical epithelial cell immune activity

Células epiteliais no cérvix humano produzem e liberam citoquinas em resposta a estímulos externos, na mesma forma que à presença de citoquinas exógenas de defesa da mucosa dentro do trato genital feminino. Infecçäo de células epiteliais cervicais com papilomavírus humano e a transformaçäo maligna dessas células alteram sua capacidade de proteçäo e resposta a citoquinas. Semelhantemente, a exposiçäo do sêmen também mudaa capacidade imune modular das células epiteliais. Relaçöes sexuais induzem a transcriçäo do código genético para 70 quilo-daltons - kDa - heart shock protein no cérvix humano. Isto mais a produçäo interlenkin-10 em células linfóides, regulam a defesa imune do trato genital

Immunity to the 60kD heat shock proteins

A brief review on the role of the heat shock proteins (hsp), their common properties and possible consequences for early pregnancy development is described. The 60kD hsp plays an important role as immunogenic antigen of many microbial pathogens and possibly in postinfectious autoimmunity. The immune responce to hsp may cause pregnancy failure. The consequences of previous sensitization to microbial hsp and the effects of human autoantibodies to hsp, are demonstrated in a mouse embryo culture model.

Vaginal Candidiasis: An incomprehensible Challege

A infecçäo recorrente da mucosa vaginal pela Candida albicans foi abordada realçando-se os mecanismos de interaçäo entre o fungo e o epitélio vaginal, com ênfase para os aspéctos imunológicos que controlam a proliferaçäo fúngica. Destaca-se o papel da imunidade celular mediada neste processo de eqüilibrio entre agente e hospedeiro, reforçando a importância via Th1, de resposta imune, onde há uma liberaçäo de citocinas como interferon-gama, interleucina-1 e 12. Por outro lado, a via Th2 que libera citocinas estimulantes da produçäo de anticorpos (interleucinas-4, 5 and 10) tera valor limitado na defesa da mucosa contra este agente. Comenta-se também o aspécto fisiopatogênico envolvendo resposta imune ligada aos processos alérgicos individuais e em decorrência de interaçäo como parceiro sexual. O diagnóstico principal "arma" para o tratamento adequado, é enfocado com ênfase na prática, reforçando-se o uso de bacterioscopias simples, sem esquecer que técnicas sofisticadas, como PCR, podem vir a ser útil para determinados casos. O tratamento da fase aguda e de manutençäo foi sugerido na tentativa de diminuir as recorrências, alertando-se principalmente para necessidade de tomar atitudes que visem näo somente o combate ao fungo, mas que também e fudamentalmente, priorize a identificaçäo e eliminaçäo de possíveis alérgenos