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The red blood cells of the McLeod phenotype have weak expression of Kell System antigens due to no expression of XK protein.One blood donor reacted as K:-4[Kp(b–)] during a screening assay. Subsequent serologic studies demonstrated weak expression of K:4 and all other high-incidence Kell system antigens tested; however, no expression of Kx antigen was observed.One apparently healthy blood donor demonstrated low expression of K:2, K:4, K:5, K:7, K:14, K:22, and no Kx antigen in his red blood cells. His brother and mother showed the same weak expression, and his father showed normal expression of antigens tested. Flow cytometry studies confirmed the mother's status as a McLeod carrier female. Genotyping determined the presence ofKEL2andKEL4alleles in mother and siblings. Southern blot with an exon-1 probe showed fragments shorter than predicted for the siblings and the mother, suggesting a deletion. Polymerase chain reaction with primers spanning exon 1 and flanking regions displayed a similar pattern. Deoxyribonucleic acid sequence allowed the precise characterization of a deletion of 392 bp, beginning at the 5′ of the coding region up to nucleotide 201 of exon 1, which putatively abrogates the production of XK protein.Two brothers with McLeod phenotype in a Brazilian blood-donor population were identified. The molecular basis for this phenotype is a 392-bp deletion spanning from 5′ of the coding region to exon 1 of theXKgene, never described before. [ABSTRACT FROM AUTHOR]

Pandemic arboviruses have emerged as a major global health problem in the past four decades. Predicting where and when the next arbovirus epidemic will occur is a challenge, but history suggests that arboviral black swan events (epidemics that are difficult to predict and that have an extreme effect) will continue to occur as urban growth and globalisation expand. We briefly review unexpected arbovirus epidemics that have occurred in the past 50 years, with emphasis on the American and Pacific regions, to illustrate their unpredictability, and to highlight the need for improved global preparedness, including laboratory-based surveillance, prevention, and control programmes. [ABSTRACT FROM AUTHOR]

An abstract of the article "Immune Response Characterization in HIV/HCV Coinfected Patients of Medicine Tropical Foundation," by Adriana Malheiro, Liziara Silva Fraporti, Flamir Victoria, Kátia Luz Torres, João Paulo Diniz Pimentel, Andrea Tarragô, Laura Patricia Viana Maia, Felicien Vásquez, José Eduardo Levi and Marilu Victoria is presented.

Background: Previous studies suggest intestinal dysbiosis is associated with metabolic diseases. However, the causal relationship between them is not fully elucidated. Gut microbiota evaluation of patients with congenital generalized lipodystrophy (CGL), a disease characterized by the absence of subcutaneous adipose tissue, insulin resistance, and diabetes since the first years of life, could provide insights into these relationships. Methods: A cross-sectional study was conducted with patients with CGL (n = 17) and healthy individuals (n = 17). The gut microbiome study was performed by sequencing the 16S rRNA gene through High-Throughput Sequencing (BiomeHub Biotechnologies, Brazil). Results: The median age was 20.0 years old, and 64.7% were female. There was no difference between groups in pubertal stage, BMI, ethnicity, origin (rural or urban), delivery, breastfeeding, caloric intake, macronutrient, or fiber consumption. Lipodystrophic patients presented a lower alpha diversity (Richness index: 54.0 versus 67.5; p = 0.008). No differences were observed in the diversity parameters when analyzing the presence of diabetes, its complications, or the CGL subtype. Conclusion: In this study, we demonstrate for the first time a reduced gut microbiota diversity in individuals with CGL. Dysbiosis was present despite dietary treatment and was also observed in young patients. Our findings allow us to speculate that the loss of intestinal microbiota diversity may be due to metabolic abnormalities present since the first years of life in CGL. Longitudinal studies are needed to confirm these findings, clarifying the possible causal link between dysbiosis and insulin resistance in humans. [ABSTRACT FROM AUTHOR]

Summary: Objectives: Human papillomavirus (HPV) infection is a major risk factor for cervical disease. Using baseline data from the HIV-infected cohort of Evandro Chagas Clinical Research Institute at Fiocruz, Rio de Janeiro, Brazil, factors associated with an increased prevalence of HPV were assessed. Methods: Samples from 634 HIV-infected women were tested for the presence of HPV infection using hybrid capture II and polymerase chain reaction. Prevalence ratios (PR) were estimated using Poisson regression analysis with robust variance. Results: The overall prevalence of HPV infection was 48%, of which 94% were infected with a high-risk HPV. In multivariate analysis, factors independently associated with infection with high-risk HPV type were: younger age (<30 years of age; PR 1.5, 95% confidence interval (CI) 1.1–2.1), current or prior drug use (PR 1.3, 95% CI 1.0–1.6), self-reported history of HPV infection (PR 1.2, 95% CI 0.96–1.6), condom use in the last sexual intercourse (PR 1.3, 95% CI 1.1–1.7), and nadir CD4+ T-cell count <100cells/mm3 (PR 1.6, 95% CI 1.2–2.1). Conclusions: The estimated prevalence of high-risk HPV-infection among HIV-infected women from Rio de Janeiro, Brazil, was high. Close monitoring of HPV-related effects is warranted in all HIV-infected women, in particular those of younger age and advanced immunosuppression. [Copyright &y& Elsevier]

Introduction: Solid organ transplant (SOT) recipients are at increased risk of Human Papillomavirus (HPV) persistent infection and disease. This study aimed to evaluate HPV seroprevalence, cervical HPV prevalence, genotype distribution, and frequency of HPV-related cervical lesions in SOT recipients in comparison to immunocompetent women. Methods: Cross-sectional study including SOT and immunocompetent women aged 18 to 45 years who denied previous HPV-related lesions. Cervical samples were screened for HPV-DNA by a polymerase chain reaction (PCR)-based DNA microarray system (PapilloCheck®) and squamous intraepithelial lesions (SIL) by liquid-based cytology. A multiplexed pseudovirion-based serology assay (PsV-Luminex) was used to measure HPV serum antibodies. Results: 125 SOT and 132 immunocompetent women were enrolled. Cervical samples were collected from 113 SOT and 127 immunocompetent women who had initiated sexual activity. HPV-DNA prevalence was higher in SOT than in immunocompetent women (29.6% vs. 20.2%, p = 0.112), but this difference was not statistically significant. High-risk (HR)-HPV was significantly more frequent in SOT than in immunocompetent women (19.4% vs. 7.9%, p = 0.014). Simultaneous infection with ≥2 HR-HPV types was found in 3.1% of SOT and 0.9% of immunocompetent women. HPV seropositivity for at least one HPV type was high in both groups: 63.8% of 105 SOT and 69.7% of 119 immunocompetent women (p = 0.524). Low-grade (LSIL) and high-grade SIL (HSIL) were significantly more frequent in SOT (9.7% and 5.3%, respectively) than in immunocompetent women (1.6% and 0.8%, respectively) (p = 0.001). Conclusions: These results may reflect the increased risk of HPV persistent infection and disease progression in SOT women due to chronic immunosuppression. [ABSTRACT FROM AUTHOR]

• This was the first randomized, double-blinded, placebo-controlled clinical trial evaluating outpatients with mild COVID-19 • Viral clearance rates within a 9-day period from symptom onset did not change with hydroxychloroquine and azithromycin (HCQ/AZT) treatment • The use of HCQ/AZT combination was safe and not associated with more adverse effects or major cardiovascular events Hydroxychloroquine has shown potential to block viral replication of SARS-CoV-2 in some in vitro studies. This randomised, double-blinded, placebo controlled clinical trial evaluated the efficacy of hydroxychloroquine plus azithromycin (HCQ/AZT) in reducing viral loads in patients with early and mild SARS-CoV-2 infection. A single-centre randomised placebo-controlled clinical trial was conducted with outpatients with early and mild SARS-CoV-2 infection. Inclusion criteria were: patients aged 18–65 years with symptoms suggestive of COVID-19 for < 5 days, no significant comorbidities, and positive nasopharyngeal/oropharyngeal swab screening tests (POCT-PCR). Randomised patients received either hydroxychloroquine for 7 days plus azithromycin for 5 days or placebo. The primary endpoint was viral clearance within a 9-day period. Secondary endpoints included viral load reduction, clinical evolution, hospitalization rates, chest computed tomography evolution, and adverse effects. From 107 potential trial participants, 84 were enrolled following predetermined criteria. Statistical analyses were performed on an intention-to-treat (N = 84) and per-protocol (PP) basis (N = 70). On the PP analysis, the treatment (N = 36) and placebo (N = 34) groups displayed similar demographic characteristics. At 95% CI, no statistically significant between-group differences were found in viral clearance rates within 9 days following enrolment (P = 0.26). This randomised, double-blinded, placebo-controlled clinical trial evaluating outpatients with early and mild COVID-19 showed that viral clearance rates within a 9-day period from enrolment did not change with HCQ/AZT treatment compared with placebo, although no major cardiovascular events were observed in participants without comorbidities. Secondary outcomes were also not significantly improved with HCQ/AZT treatment compared with placebo. These findings do not support use of HCQ/AZT in this setting. [ABSTRACT FROM AUTHOR]

In January 2022, our genomic surveillance network identified a SARS-CoV-2 BA.1 and BA.2 coinfection in a sample from a patient residing in Brazil. Our results suggest that the true number of SARS-CoV-2 coinfections remains largely underestimated. [ABSTRACT FROM AUTHOR]

Introduction: As the leading sexually transmitted infection worldwide, human papillomavirus (HPV) may disproportionately affect transwomen. We aimed to estimate anal HPV prevalence, especially focusing on high‐risk (hr)‐HPV types and evaluate their associated factors among transwomen living in Rio de Janeiro, Brazil. Methods: Transwomen enrolled in a respondent‐driven sampling (RDS)‐based survey conducted between August 2015 and January 2016 self‐collected anal samples, which were promptly stored at minus 80°C. After DNA extraction, HPV detection and genotyping were performed using the PapilloCheck test. We estimated HPV prevalences and evaluated the correlates of anal hr‐HPV infection using a regression logistic model. Results: Out of 345 transwomen, 272 (78.8%) were included in this analysis (122 [44.9%] HIV‐positive). No participant had ever received HPV vaccination. Among participants enrolled, 212 (77.9%) were positive for any anal HPV type and 165 (60.7%) for hr‐HPV. Most common hr‐HPV were as follows: HPV16 (17.6%), HPV68 (14.7%), HPV39 (14.3%), HPV56 (12.5%), HPV51 (11.4%) and HPV52 (11.0%). HIV‐positive transwomen had three times the odds of having an hr‐HPV compared to HIV‐negative transwomen. Participants who had a current rectal Neisseria gonorrhoeae infection had 3.7 times the odds of being coinfected with hr‐HPV. Among HIV‐positive transwomen, neither antiretroviral therapy use, undetectable viral load, current and nadir CD4 counts were associated with anal hr‐HPV infection. Conclusions: Brazilian transwomen in our study exhibit some of the highest population‐specific rates of HPV and hr‐HPV. There is an urgent need to elucidate the burden of HPV infection, prevalence of HPV‐related diseases and access to and uptake of HPV vaccination among transwomen, especially from low‐ and middle‐income settings. [ABSTRACT FROM AUTHOR]

Introduction: The challenges related to the diagnosis of sexually transmitted infections present more complex factors in remote and hard-to-reach areas. The use of self-collection devices that facilitate the obtaining of a biological sample with high quality for sensitive molecular tests have been examined. This study aimed to evaluate the performance and acceptance of the Evalyn® Brush (Rovers® Medical Devices) for detection of T. vaginalis among women living in the riverside communities of Amazonas, Brazil. Methodology: The study included 300 riverside women. They received instructions for self-collection, carried out the task, and then answered a questionnaire on the use of the device. T. vaginalis was detected by Polymerase Chain Reaction, using primers TVK3/TVK7. Results: The mean age of the women was 35.8 years, and most of them presented low schooling, low income, agricultural activity and lived in a marital union. All samples were positive for human genomic DNA (100%) and the prevalence of T. vaginalis infection was 5.6% (n = 17). Of the 300 women, 293 (97.7%) indicated that they liked the use of the device, 287 (95.7%) reported having had no difficulty in handling it, 265 (88.3%) did not feel any type of discomfort and 228 (76%) said they preferred the self-collection to the collection made by the professional, mainly due to privacy and comfort. Conclusions: The Evalyn® Brush proved reliable as a device for the collection of biological samples for molecular analysis and was well-accepted by women. Its use can be indicated in remote and hard to reach places. [ABSTRACT FROM AUTHOR]

Background: Yellow fever virus infection results in death in around 30% of symptomatic individuals. The aim of this study was to identify predictors of death measured at hospital admission in a cohort of patients admitted to hospital during the 2018 outbreak of yellow fever in the outskirts of São Paulo city, Brazil.Methods: In this observational cohort study, we enrolled patients with yellow fever virus from two hospitals in São Paolo-the Hospital das Clínicas, University of São Paulo and the Infectious Diseases Institute "Emilio Ribas". Patients older than 18 years admitted to hospital with fever or myalgia, headache, arthralgia, oedema, rash, or conjunctivitis were consecutively screened for inclusion in the present study. Consenting patients were included if they had travelled to geographical areas in which yellow fever virus cases had been previously confirmed. Yellow fever infection was confirmed by real-time PCR in blood collected at admission or tissues at autopsy. We sequenced the complete genomes of yellow fever virus from infected individuals and evaluated demographic, clinical, and laboratory findings at admission and investigated whether any of these measurements correlated with patient outcome (death).Findings: Between Jan 11, 2018, and May 10, 2018, 118 patients with suspected yellow fever were admitted to Hospital das Clínicas, and 113 patients with suspected yellow fever were admitted to Infectious Diseases Institute "Emilio Ribas". 95 patients with suspected yellow fever were included in the study, and 136 patients were excluded. Three (3%) of 95 patients with suspected yellow fever who were included in the study were excluded because they received a different diagnosis, and 16 patients with undetectable yellow fever virus RNA were excluded. Therefore, 76 patients with confirmed yellow fever virus infection, based on detectable yellow fever virus RNA in blood (74 patients) or yellow fever virus confirmed only at the autopsy report (two patients), were included in our analysis. 27 (36%) of 76 patients died during the 60 day period after hospital admission. We generated 14 complete yellow fever virus genomes from the first 15 viral load-detectable samples. The genomes belonged to a single monophyletic clade of the South America I genotype, sub-genotype E. Older age, male sex, higher leukocyte and neutrophil counts, higher alanine aminotransferase, aspartate transaminase (AST), bilirubin, and creatinine, prolonged prothrombin time, and higher yellow fever virus RNA plasma viral load were associated with higher mortality. In a multivariate regression model, older age, elevated neutrophil count, increased AST, and higher viral load remained independently associated with death. All 11 (100%) patients with neutrophil counts of 4000 cells per mL or greater and viral loads of 5·1 log10 copies/mL or greater died (95% CI 72-100), compared with only three (11%) of 27 (95% CI 2-29) among patients with neutrophil counts of less than 4000 cells per mL and viral loads of less than 5·1 log10 copies/mL.Interpretation: We identified clinical and laboratory predictors of mortality at hospital admission that could aid in the care of patients with yellow fever virus. Identification of these prognostic markers in patients could help clinicians prioritise admission to the intensive care unit, as patients often deteriorate rapidly. Moreover, resource allocation could be improved to prioritise key laboratory examinations that might be more useful in determining whether a patient could have a better outcome. Our findings support the important role of the virus in disease pathogenesis, suggesting that an effective antiviral could alter the clinical course for patients with the most severe forms of yellow fever.Funding: São Paulo Research Foundation (FAPESP). [ABSTRACT FROM AUTHOR]

There is a significant inter-individual heterogeneity of Vel antigen expression which can lead to inaccuracies on Vel phenotyping of blood donors and, potentially, to hemolytic post-transfusion reactions. Our aim was to evaluate the impact of genetic variants in the SMIM 1 intron 2 on the expression of Vel antigen among Brazilian blood donors harboring the c.64 _ 80del17 deletion in heterozygosity. Donors presenting the SMIM1 c.64 _ 80del17 in heterozygosity were included in the study and subjected to SMIM1 intron 2 direct sequencing aiming to genotype the following polymorphisms: rs143702418, rs1181893, rs191041962, rs6673829, rs1175550 and rs9424296. SMIM1 intron 2 sequencing was performed on two hundred donors presenting one c.64 _ 80del17 allele. The rs1175550 polymorphism significantly impacted on Vel antigen expression. Variations in the strength of agglutination on Vel phenotyping were also observed according to the rs6673829 genotype, but this difference did not persist with statistical relevance after multivariate analysis. The presence of the rs1175550A allele of SMIM1 is significantly and independently associated with a decrease in Vel antigen expression. Even though the population in Brazil is intensely mixed, the allele frequencies obtained in the current study were very similar to that reported for Europeans. [ABSTRACT FROM AUTHOR]

Background The complexity of Rh genetic variation among sickle cell disease (SCD) patients is high. Conventional molecular assays cannot identify all genetic variants already described for the RH locus as well as foresee novel alleles. Sequencing RHD and RHCE is indicated to broaden the search for Rh genetic variants. Aims To standardize the Next Generation Sequencing (NGS) strategy to assertively identify Rh genetic variants among SCD patients with serologic suspicion of Rh variants and evaluate if it can improve the transfusion support. Methods Thirty-five SCD patients with unexplained Rh antibodies were enrolled. A NGS-based strategy was developed to genotype RHD and RHCE using gene-specific primers. Genotype and serological data were compared. Results Data obtained from the NGS-based assay were gene-specific. Ten and 25 variant RHD and RHCE alleles were identified, respectively. Among all cases of unexplained Rh antibodies, 62% had been inaccurately classified by serological analysis and, of these, 73.1% were considered as relevant, as were associated with increased risk of hemolytic reactions and shortage of units suitable for transfusion. Conclusion The NGS assay designed to genotype RH coding regions was effective and accurate in identifying variants. The proposed strategy clarified the Rh phenotype of most patients, improving transfusion support. [ABSTRACT FROM AUTHOR]

Objectives: To explore whether HPV-related biomarkers predict oropharyngeal squamous cell cancer (OPSCC) survival similarly across different global regions, and to explore their prognostic utility among non-oropharyngeal (non-OP) head and neck cancers.Methods: Data from 1362 head and neck SCC (HNSCC) diagnosed 2002-2011 was used from epidemiologic studies in: Brazil (GENCAPO study, n=388), U.S. (CHANCE study, n=472), and Europe (ARCAGE study, n=502). Tumors were centrally tested for p16INK4a and HPV16 DNA (by PCR). Risk of mortality was examined using Cox proportional hazard models.Results: There were 517 OPSCC and 845 non-OP HNSCC. Cases were primarily male (81%), ever smokers (91%), with median age of 58yearsandmedian follow-up of 3.1years (IQR=1.4-5.9). Among OPSCC, the risk of mortality was significantly lower among 184 HPV-related (i.e., p16+/HPV16+) compared to 333 HPV-unrelated (p16- and/or HPV16-) cases (HR=0.25, 95%CI=0.18-0.34). Mortality was reduced among HPV-related OPSCC cases from the U.S., Europe, and Brazil (each p⩽0.01) and after adjustment, remained significantly reduced (aHR=0.34, 95%CI=0.24-0.49). Among non-OP HNSCC, neither p16 (aHR=0.83, 95%CI=0.60-1.14), HPV16 DNA (aHR=1.20, 95%CI=0.89-1.63), or p16+/HPV16+ (aHR=0.59, 95%CI=0.32-1.08) was a significantly predictor of mortality. When interaction was tested, the effect of HPV16/p16 was significantly different in OPSCC than non-OP HNSCC (p-interaction=0.02).Conclusion: HPV-related OPSCCs had similar survival benefits across these three regions. Prognostic utility of HPV among non-OP HNSCC is limited so tumor HPV/p16 testing should not be routinely done among non-OP HNSCC. [ABSTRACT FROM AUTHOR]

The dengue viruses are widespread in Brazil and are a major public health concern. Other flaviviruses also cause diseases in humans, although on a smaller scale. The city of São Paulo is in a highly urbanized area with few green spaces apart from its parks, which are used for recreation and where potential vertebrate hosts and mosquito vectors of pathogenic Flavivirus species can be found. Although this scenario can contribute to the transmission of Flavivirus to humans, little is known about the circulation of members of this genus in these areas. In light of this, the present study sought to identify Flavivirus infection in mosquitoes (Diptera: Culicidae) collected in parks in the city of São Paulo. Seven parks in different sectors of the city were selected. Monthly mosquito collections were carried out in each park from March 2011 to February 2012 using aspiration and traps (Shannon and CD C-CO 2 ). Nucleic acids were extracted from the mosquitoes collected and used for reverse-transcriptase and real-time polymerase chain reactions with genus-specific primers targeting a 200-nucleotide region in the Flavivirus NS5 gene. Positive samples were sequenced, and phylogenetic analyses were performed. Culex and Aedes were the most frequent genera of Culicidae collected. Culex flavivirus (CxFV)-related and Aedes flavivirus (AEFV)- related nucleotide sequences were detected in 17 pools of Culex and two pools of Aedes mosquitoes, respectively, among the 818 pools of non-engorged females analyzed. To the best of our knowledge, this is the first report of CxFV and AEFV in the city of São Paulo and Latin America, respectively. Both viruses are insect- specific flaviviruses, a group known to replicate only in mosquito cells and induce a cytopathic effect in some situations. Hence, our data suggests that CxFV and AEFV are present in Culex and Aedes mosquitoes, respectively, in parks in the city of São Paulo. Even though Flavivirus species of medical importance were not detected, surveillance is recommended in the study areas because of the presence of vertebrates and mosquitoes that could act as amplifying hosts and vectors of flaviviruses, providing the required conditions for circulation of these viruses. [ABSTRACT FROM AUTHOR]

Invasive cervical cancer (ICC) is the third most frequent cancer among women worldwide and is associated with persistent infection by carcinogenic human papillomaviruses (HPVs). The combination of large populations of viral progeny and decades of sustained infection may allow for the generation of intra-patient diversity, in spite of the assumedly low mutation rates of PVs. While the natural history of chronic HPVs infections has been comprehensively described, within-host viral diversity remains largely unexplored. In this study we have applied next generation sequencing to the analysis of intra-host genetic diversity in ten ICC and one condyloma cases associated to single HPV16 infection. We retrieved from all cases near full-length genomic sequences. All samples analyzed contained polymorphic sites, ranging from 3 to 125 polymorphic positions per genome, and the median probability of a viral genome picked at random to be identical to the consensus sequence in the lesion was only 40%. We have also identified two independent putative duplication events in two samples, spanning the L2 and the L1 gene, respectively. Finally, we have identified with good support a chimera of human and viral DNA. We propose that viral diversity generated during HPVs chronic infection may be fueled by innate and adaptive immune pressures. Further research will be needed to understand the dynamics of viral DNA variability, differentially in benign and malignant lesions, as well as in tissues with differential intensity of immune surveillance. Finally, the impact of intralesion viral diversity on the long-term oncogenic potential may deserve closer attention. [ABSTRACT FROM AUTHOR]

Identifying factors, including human papillomavirus (HPV) genotypes, associated with abnormal anal cytology in HIV-infected women have implications for anal squamous cell cancer (SCC) prevention in HIV-infected women. Anal and cervical samples were collected for cytology, and tested for high-(HR-HPV) and low-risk HPV (LR-HPV) genotypes in a cross-sectional analysis of the IPEC Women's HIV Cohort (Rio de Janeiro, Brazil). Multivariate log-binomial regression models estimated prevalence ratios for factors associated with abnormal anal cytology [≥atypical squamous cells of undetermined significance, (ASC-US)]. Characteristics of the 863 participants included: median age 42 years, 57% non-white, 79% current CD4+ T-cell count >350 cells/mm3, 53% HIV-1 viral load <50 copies/mL, median ART duration 5.8 years. Fifty-one percent of anal specimens contained ≥1 HR-HPV genotype; 31% had abnormal anal cytology [14% ASC-US, 11% low-grade squamous intra-epithelial lesion, (LSIL); 2% atypical squamous cells-cannot exclude high-grade SIL (ASC-H); 4% high-grade SIL/cancer (HSIL+)]. In multivariate analysis, cervical LSIL+, nadir CD4+ T-cell count ≤50 cells/mm3, HIV-1 viral load ≥50 copies/mL, and anal HPV 6, 11, 16, 18, 33, 45, 52, 56, and 58 were associated with ≥anal ASC-US ( p<0.05). Abnormal anal cytology and HR-HPV prevalences were high. HIV-infected women with cervical LSIL+, low nadir CD4+ counts, or detectable HIV-1 viral loads should be a particular focus for enhanced anal SCC screening efforts. [ABSTRACT FROM AUTHOR]

Highlights: [•] A broad but unguided cytokine storm is observed in the non-responder HCV patients. [•] SVR was associated with early decrease in the viral load. [•] A time-dependent increase on IL-12 levels was critical to support the SVR. [Copyright &y& Elsevier]

We investigated the clinical impact of human coronaviruses (HCoV) OC43, 229E, HKU1 and NL63 in pediatric patients with cystic fibrosis (CF) during routine and exacerbation visits. A total of 408 nasopharyngeal aspirate samples were obtained from 103 patients over a 1-year period. Samples positive for HCoV were submitted for nucleotide sequencing to determine the species. Nineteen samples (4.65%) were positive for HCoV, of which 8 were positive for NL63, 6 for OC43, 4 for HKU1, and 1 for 229E. Identification of HCoV was not associated with an increased rate of respiratory exacerbations, but NL63-positive patients had higher exacerbation rates than patients who were positive for other HCoV species. [ABSTRACT FROM PUBLISHER]

Abstract: The recovery and stability of DNA for the detection and genotyping of HPV in UCM-containing specimens, after exposure to denaturing reagents and stored for up to 2 years were evaluated. Samples were collected from 60 women who had cervical cytology specimens harboring cervical intraepithelial neoplasia (CIN) 2 or 3. All samples were stored in UCM and had been frozen at −20°C following the addition of the denaturing reagent (sodium hydroxide) and the removal of the aliquot required for Hybrid Capture 2 testing for the identification of HPV DNA. The samples had been stored for 6, 12 and 24 months (20 samples for each storage time). HPV DNA extraction was performed according to a protocol designed specifically and the presence and quality of DNA was confirmed by human β-globin detection using the consensus primers G73 and G74. HPV DNA was amplified using the consensus primers PGMY09 and PGMY11, and reverse line-blot hybridization was used to detect type-specific amplicons for 37 HPV types. The DNA extracted from the denatured specimen was recovered in 57/60 (95%) of the samples. HPV DNA was detected in 56/57 (98%) of the recovered samples. Twenty-six of the 56 samples recovered (48%) were genotyped successfully. [Copyright &y& Elsevier]

• RNA extraction-free RT-PCR saliva testing can be used for SARS-CoV-2 detection. • RNA extraction-free RT-PCR saliva testing is useful for SARS-CoV-2 detection, especially in the early phase of symptom onset. • RNA extraction-free RT-PCR saliva testing shows substantial agreement with the oro/nasopharyngeal swabs reference testing. SARS-CoV-2 is the etiologic agent of coronavirus disease 2019 (COVID-19) and is mainly detected by RT-PCR methods from upper respiratory specimens, as recommended by the World Health Organization. Oro/nasopharyngeal swabbing can be discomfortable to the patients, requires trained healthcare personnel and may generate aerosol, increasing the risk of nosocomial infections. In this study, we describe two SARS-CoV-2 RNA extraction-free single RT-PCR protocols on saliva samples and compared the results with the paired oro/nasopharyngeal swab specimens from 400 patients. The two saliva protocols demonstrated a substantial agreement when compared to the oro/nasopharyngeal swab protocol. Moreover, the positivity rate of saliva protocols increased according to the disease period. The 95 % limit of detection of one of the therefore implemented saliva protocol was determined as 9441 copies/mL. Our results support the conclusion that RNA extraction-free RT-PCR using self-collected saliva specimens is an alternative to nasopharyngeal swabs, especially in the early phase of symptom onset. [ABSTRACT FROM AUTHOR]

• Alinity m and Abbott RealTi m e HIV-1, HCV, and HBV assays were highly correlated. • One Alinity m achieved lower total TAT than five m2000 instruments combined. • The average processing time observed for STAT samples on the Alinity m was 4 h. • Overall observed bias for each assay is unlikely to impact clinical decisions. New partially or fully automated molecular diagnostic testing platforms are being developed to address the growing demand for fast, accurate, and cost-effective testing. To evaluate the analytical and clinical performance of the Alinity m system compared to the Abbott RealTi m e m 2000 assay system in a large central molecular laboratory. Alinity m HIV-1, HCV, and HBV assay precision, reproducibility, and sensitivity were assessed using commercial customized dilution panels. Clinical performance of the Alinity m and m 2000 assay systems was compared using standard lab protocols and residual, de-identified patient specimens. A workflow analysis of 1,068 samples compared turnaround times (TATs) on five m2000 systems and one Alinity m system running Alinity m HIV-1, HCV, HBV, HR HPV, and STI assays. The Alinity m assay system demonstrated high detectability and precision at clinical decision points and excellent correlation with Abbott RealTi m e assay results. Processing TAT for 100 % of results was 117 min on Alinity m. Sample onboard TAT, from sample loading to 95 % of results, was 5:15 h for Alinity m and 7:30 h for m 2000. 100 % of STAT samples were processed within 4 h on Alinity m. Total TAT for 100 % of results from all five assays was 80 h for m 2000 versus 9 h for Alinity m. The Alinity m system produces assay results comparable to those of the Abbott RealTime m2000 system, but with significantly faster turnaround times due to continuous loading and the ability to run multiple assays simultaneously on the same sample. [ABSTRACT FROM AUTHOR]

The Zika virus crisis exemplified the risk associated with emerging pathogens and was a reminder that preparedness for the worst-case scenario, although challenging, is needed. Herein, we review all data reported during the unexpected emergence of Zika virus in French Polynesia in late 2013. We focus on the new findings reported during this outbreak, especially the first description of severe neurological complications in adults and the retrospective description of CNS malformations in neonates, the isolation of Zika virus in semen, the potential for blood-transfusion transmission, mother-to-child transmission, and the development of new diagnostic assays. We describe the effect of this outbreak on health systems, the implementation of vector-borne control strategies, and the line of communication used to alert the international community of the new risk associated with Zika virus. This outbreak highlighted the need for careful monitoring of all unexpected events that occur during an emergence, to implement surveillance and research programmes in parallel to management of cases, and to be prepared to the worst-case scenario. [ABSTRACT FROM AUTHOR]

Introduction: Immunocompromised persons are at high risk of persistent Human Papilloma Virus (HPV) infection and associated diseases. Few studies evaluated HPV vaccines in immunocompromised persons. This study aimed to evaluate the quadrivalent HPV vaccine (4vHPV) immunogenicity and safety in solid organ transplant (SOT) recipients, in comparison to immunocompetent women (IC)., Methods: Open-label clinical trial that enrolled SOT recipients and immunocompetent women aged 18 to 45 years. All participants received three doses of 4vHPV vaccine. Blood samples were drawn for evaluation of immune responses at baseline and one month after the third vaccination. Seroconversion rates and antibody geometric mean concentration (GMC) against HPV 6, 11, 16, 18, 31, 35, 52 and 58 were measured with in-house multiplexed serology assay (xMAP technology). Follow-up for the local and systemic adverse events (AEs) continued for seven days after each vaccination. Severe AEs were evaluated throughout the study., Results: 125 SOT and 132 immunocompetent women were enrolled; 105 (84%) SOT and 119 (90%) immunocompetent women completed the study. At baseline, HPV seropositivity was not significantly different between groups. Seroconversion rates were significantly lower in SOT (HPV18, 57%; HPV6 and 16, 69%; and HPV11, 72%) than in immunocompetent women (100% seroconversion to all vaccine types) ( p <0.001). Antibody GMCs of all four HPV vaccine types were also significantly lower in SOT ( p <0.001). Pain in the injection site and headache were the most frequent adverse event in both groups. Local pain was more frequent in immunocompetent women than in SOT recipients. Rates of other AEs were comparable in both groups., Conclusion: 4vHPV vaccine was well-tolerated by SOT recipients. We found strong evidence of lower humoral immune responses to 4vHPV vaccine in SOT compared to immunocompetent women, which strengthen recommendation of routine cervical cancer screening in SOT recipients regardless of HPV vaccination status., Competing Interests: Since June 2020, VI is an employee of Instituto Butantan and since March 2021, KM is an employee of Instituto Butantan producer of 4vHPV vaccine in Brazil, through a technology transfer agreement. CR is an employee of Instituto Butantan since April 2023. AL, AS and CP received grant from Instituto Butantan in 2021-2022, to conduct studies on COVID vaccines. Data collection for this study and analysis were performed before that. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Miyaji, Infante, Picone, Dillner, Kann, Eklund, Levi, de Oliveira, Lara, Kawakami, Tacla, Castanheira, Mayaud and Sartori.)

Purpose: To describe a 2019 acute toxoplasmosis outbreak in the city of São Paulo, Brazil, and to evaluate the laboratory serological profile for toxoplasmosis for three consecutive years. The ophthalmological manifestations of the patients involved in the outbreak were also studied., Methods: A cross-sectional descriptive study of a toxoplasmosis outbreak in São Paulo, Brazil, between February and May 2019. Epidemiological data were described, as were the observed ocular manifestations. As part of this study the number of patients with positive IgM toxoplasmosis serology was obtained from a large laboratory network (DASA) for three consecutive years, including the year of the outbreak (2018, 2019, 2020)., Results: Eighty-three individuals were identified in the outbreak and two clusters were studied. The clinical picture of at least 77% of the patients, the epidemiological analysis, and the short incubation period (5-8 days) suggested contamination by oocysts. Serological laboratory data analysis revealed an increase of positive toxoplasmosis IgM in 2019 of 73% compared to the previous year. Ophthalmological examination revealed that at least 4.8% of the patients developed toxoplasmic retinochoroiditis, none of whom had been treated during the acute systemic disease., Conclusion: Our findings indicate vegetable contamination as the possible source of this outbreak, a high prevalence of toxoplasmosis in São Paulo during the outbreak period, and a drop in the number of tests during the COVID-19 pandemic. Retinochoroiditis was observed in at least 4.8% of the cases. We confirm the need to implement effective means for the prevention, diagnosis, and treatment of the disease. This may involve raising awareness among the population of the importance of vegetable hygiene, and improved quality control of food and water.

Hematopoietic stem cell transplant (HSCT) recipients are at -increased risk for severe COVID-19. The aim of this study was to evaluate the burden of COVID-19 in a cohort of HSCT recipients. This retrospective study evaluated a cohort of adult hospitalized HSCT recipients diagnosed with COVID-19 in two large hospitals in São Paulo, Brazil post-HSCT, from January 2020 to June 2022. The primary outcome was all-cause mortality. Of 49 cases, 63.2% were male with a median age of 47 years. Allogeneic-HSCT (51.2%) and autologous-HSCT (48.9%) patients were included. The median time from HSCT to COVID-19 diagnosis was 398 days (IQR: 1211-134), with 22 (44.8%) cases occurring within 12 months of transplantation. Most cases occurred during the first year of the pandemic, in non-vaccinated patients (n=35; 71.4%). Most patients developed severe (24.4%) or critical (40.8%) disease; 67.3% received some medication for COVID-19, primarily corticosteroids (53.0%). The probable invasive aspergillosis prevalence was 10.2%. All-cause mortality was 40.8%, 51.4% in non-vaccinated patients and 14.2% in patients who received at least one dose of the vaccine. In the multiple regression analyses, the variables mechanical ventilation (OR: 101.01; 95% CI: 8.205 - 1,242.93; p = 0.003) and chest CT involvement at diagnosis ≥50% (OR: 26.61; 95% CI: 1.06 - 664.26; p = 0.04) remained associated with all-cause mortality. Thus, HSCT recipients with COVID-19 experienced high mortality, highlighting the need for full vaccination and infection prevention measures.

Since human papillomavirus (HPV) is recognized as the causative agent of cervical cancer and associated with anogenital non-cervical and oropharyngeal cancers, the characterization of the HPV types circulating in different geographic regions is an important tool in screening and prevention. In this context, this study compared four methodologies for HPV detection and genotyping: real-time PCR (Cobas® HPV test), nested PCR followed by conventional Sanger sequencing, reverse hybridization (High + Low PapillomaStrip® kit) and next-generation sequencing (NGS) at an Illumina HiSeq2500 platform. Cervical samples from patients followed at the Family Health Strategy from Juiz de Fora, Minas Gerais, Brazil, were collected and subjected to the real-time PCR. Of those, 114 were included in this study according to the results obtained with the real-time PCR, considered herein as the gold standard method. For the 110 samples tested by at least one methodology in addition to real-time PCR, NGS showed the lowest concordance rates of HPV and high-risk HPV identification compared to the other three methods (67-75 %). Real-time PCR and Sanger sequencing showed the highest rates of concordance (97-100 %). All methods differed in their sensitivity and specificity. HPV genotyping contributes to individual risk stratification, therapeutic decisions, epidemiological studies and vaccine development, supporting approaches in prevention, healthcare and management of HPV infection., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:Marcelo A. Soares reports financial support was provided by Carlos Chagas Filho Foundation for Research Support of Rio de Janeiro State (FAPERJ). Marcelo A. Soares reports financial support was provided by 10.13039/501100003593National Council for Scientific and Technological Development (CNPq)., (© 2024 Published by Elsevier Ltd.)

Introduction: The Colombian National Institute of Health administers the National Information System of Haemovigilance (SIHEVI-INS). Today, SIHEVI-INS constitutes a national blood donor and recipient database, which contains a national deferred donor registry (DDR), allowing blood banks to take acceptance or rejection decisions of a potential donor in real time. The study aimed to determine the rate of people who have made more than one whole blood donation monthly in Colombia, violating the national guideline of intervals between donations (three months for men and four for women), since DDR implementation., Methods: We detected the unique personal identification number of people who, in 30 calendar days, made more than one whole blood donation at any of the 83 blood banks set up in Colombia. There were three comparison periods: 01/01/2018-08/31/2019 (launch of SIHEVI-INS and first national feedback); 09/01/2019-12/31/2020 (second feedback) and 01/01/2021-09/30/2022 (massive incorporation of web services)., Results: For the first period, blood banks accepted 18.0 donations per 1000 people. There was a rate of 28.8 people/10,000 donations who had donated whole blood twice within 30 days. In the second period, there were 17.0 donations/1000 people and a rate of 2.1 people/10,000 donations (OR:14.0 CI95 %:12.2-16.0). For the last period, there were 18.2 donations/1000 people and a rate of 0.9 individuals/10,000 donations (OR:31.3 CI95 %:26.6-36.9, p < 0.001)., Conclusion: DDR reduced by 31 times the acceptance of blood donors who made more than one whole blood donation in the same month. It was necessary to provide periodic feedback and promote web service implementation to reduce this risky behavior., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Emerging and re-emerging viruses are a global health concern. Genome sequencing as an approach for monitoring circulating viruses is currently hampered by complex and expensive methods. Untargeted, metagenomic nanopore sequencing can provide genomic information to identify pathogens, prepare for or even prevent outbreaks. SMART (Switching Mechanism at the 5' end of RNA Template) is a popular approach for RNA-Seq but most current methods rely on oligo-dT priming to target polyadenylated mRNA molecules. We have developed two random primed SMART-Seq approaches, a sequencing agnostic approach 'SMART-9N' and a version compatible rapid adapters  available from Oxford Nanopore Technologies 'Rapid SMART-9N'. The methods were developed using viral isolates, clinical samples, and compared to a gold-standard amplicon-based method. From a Zika virus isolate the SMART-9N approach recovered 10kb of the 10.8kb RNA genome in a single nanopore read. We also obtained full genome coverage at a high depth coverage using the Rapid SMART-9N, which takes only 10 minutes and costs up to 45% less than other methods. We found the limits of detection of these methods to be 6 focus forming units (FFU)/mL with 99.02% and 87.58% genome coverage for SMART-9N and Rapid SMART-9N respectively. Yellow fever virus plasma samples and SARS-CoV-2 nasopharyngeal samples previously confirmed by RT-qPCR with a broad range of Ct-values were selected for validation. Both methods produced greater genome coverage when compared to the multiplex PCR approach and we obtained the longest single read of this study (18.5 kb) with a SARS-CoV-2 clinical sample, 60% of the virus genome using the Rapid SMART-9N method. This work demonstrates that SMART-9N and Rapid SMART-9N are sensitive, low input, and long-read compatible alternatives for RNA virus detection and genome sequencing and Rapid SMART-9N improves the cost, time, and complexity of laboratory work., Competing Interests: No competing interests were disclosed., (Copyright: © 2023 Claro IM et al.)

The year of 2021 was marked by the emergence and dispersal of a number of SARS-CoV-2 lineages, resulting in the "third wave" of COVID-19 in several countries despite the level of vaccine coverage. Soon after the first confirmed cases of COVID-19 by the Delta variant in Brazil, at least seven Delta sub-lineages emerged, including the globally spread AY.101 and AY.99.2. In this study we performed a detailed analysis of the COVID-19 scenario in Brazil from April to December 2021 by using data collected by the largest private medical diagnostic company in Latin America (Dasa), and SARS-CoV-2 genomic sequences generated by its SARS-CoV-2 genomic surveillance project (GENOV). For phylogenetic and Bayesian analysis, SARS-CoV-2 genomes available at GISAID public database were also retrieved. We confirmed that the Brazilian AY.99.2 and AY.101 were the most prevalent lineages during this period, overpassing the Gamma variant in July/August. We also estimated that AY.99.2 likely emerged a few weeks after the entry of the B.1.617.2 in the country, at some point between late April and May and rapidly spread to other countries. Despite no increased fitness described for the AY.99.2 lineage, a rapid shift in the composition of Delta SARS-CoV-2 lineages prevalence in Brazil took place. Understanding the reasons leading the AY.99.2 to become the dominant lineage in the country is important to understand the process of lineage competitions that may inform future control measures., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Romano, de Oliveira, da Silva and Levi.)

Brazil is the country with the second-largest number of deaths due to the coronavirus disease-2019 (COVID-19). Two variants of concern (VOCs), Alpha (B.1.1.7) and Gamma (P.1), were first detected in December 2020. While Alpha expanded within an expected rate in January and February 2021, its prevalence among new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) cases started to decrease in March, which coincided with the explosion of Gamma variant incidence all over the country, being responsible for more than 95% of the new cases over the following months. A significantly higher viral load [i.e., mean cycle threshold (Ct) values] for Gamma in comparison to non-VOC samples was verified by the analysis of a large data set of routine reverse transcription-PCR (RT-PCR) exams. Moreover, the rate of reinfections greatly increased from March 2021 onward, reinforcing the enhanced ability of Gamma to escape the immune response. It is difficult to predict the outcomes of competition between variants since local factors like frequency of introduction and vaccine coverage play a key role. Genomic surveillance is of uttermost importance for the mitigation of the pandemic., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Levi, Oliveira, Croce, Telles, Lopes, Romano, Lira, Resende, Lopes, Ruiz and Campana.)

In December 2020, research surveillance detected the B.1.1.7 lineage of severe acute respiratory syndrome coronavirus 2 in São Paulo, Brazil. Rapid genomic sequencing and phylogenetic analysis revealed 2 distinct introductions of the lineage. One patient reported no international travel. There may be more infections with this lineage in Brazil than reported.

Objectives: To investigate the association between selected single nucleotide polymorphisms (SNPs) with cervical insufficiency and its relationship with obstetric history., Methods: Twenty-eight women with cervical insufficiency (case group) and 29 non-pregnant women (control group) were included. The SNPs sequenced included rs2586490 in collagen type I alpha 1 chain ( COL1A1 ), rs1882435 in collagen type IV alpha 3 chain ( COL4A3 ), rs2277698 in metallopeptidase inhibitor 2 ( TIMP2 ), and rs1800468 in transforming growth factor beta 1 ( TGFB1 )., Results: We found a higher frequency of the normal allele in the control group (65.5%) and the homozygous mutated genotype in the case group (64.3%) for rs2586490 in COL1A1 (p=0.023). An unplanned finding in the cervical insufficiency group was a higher gestational age of delivery (median≥38 weeks) in the mutated allele than in the wild-type genotype (median of 28.2 weeks) for rs2857396, which is also in the COL1A1 gene (p=0.011)., Conclusions: The findings of the present study corroborate the hypothesis that cervical insufficiency has a genetic component and probably involves genes encoding proteins in the extracellular matrix, in addition to inflammatory processes., (© 2021 Walter de Gruyter GmbH, Berlin/Boston.)

Brazil currently has one of the fastest-growing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) epidemics in the world. Because of limited available data, assessments of the impact of nonpharmaceutical interventions (NPIs) on this virus spread remain challenging. Using a mobility-driven transmission model, we show that NPIs reduced the reproduction number from >3 to 1 to 1.6 in São Paulo and Rio de Janeiro. Sequencing of 427 new genomes and analysis of a geographically representative genomic dataset identified >100 international virus introductions in Brazil. We estimate that most (76%) of the Brazilian strains fell in three clades that were introduced from Europe between 22 February and 11 March 2020. During the early epidemic phase, we found that SARS-CoV-2 spread mostly locally and within state borders. After this period, despite sharp decreases in air travel, we estimated multiple exportations from large urban centers that coincided with a 25% increase in average traveled distances in national flights. This study sheds new light on the epidemic transmission and evolutionary trajectories of SARS-CoV-2 lineages in Brazil and provides evidence that current interventions remain insufficient to keep virus transmission under control in this country., (Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)

Introduction: Cervical cancer remains an important burden for HIV-infected women in the era of combination antiretroviral therapy. Recommendations for cervical screening in these women diverge and may include high-risk HPV (HRHPV) testing. We aimed to evaluate the clinical usefulness of a single HRHPV testing for cervical screening of HIV-infected women., Methods: 723 HIV-infected women from a Brazilian prospective cohort were included between 1996 and 2012. Inclusion criteria were: normal cervical cytology at baseline and having a HRHPV-test at baseline. We calculated incidence rates of any squamous intraepithelial lesion (SIL) and high grade SIL+ (HSIL+) and negative predictive values (NPV) within 12 and 36 months. Hazard Ratios were obtained using Cox proportional hazards regression models., Results: Incidence rate for both outcomes was low (9.9 cases per 100 PY [95% CI 8.8-11.0] for any SIL and 1.3 cases per 100 PY [95% IC 0.9-1.8] for HSIL+). Women with a HRHPV positive status at baseline had 1.7-fold (95% CI 1.3-2.2) and 3.2-fold (95% CI 1.5-7.1) increased risk of presenting any SIL and HSIL+, respectively, during follow-up. Negative-HRHPV test presented high NPV for both periods and outcomes (any SIL: 92.4% [95% CI 89.7-94.6] for 12 months and 80.9% [95% CI 77.2-84.3] for 36 months; and HSIL+: 99.8% [95% CI 98.9-100.0] for 12 months and 99.0 [95% CI 97.6-99.7] for 36 months)., Conclusions: Incidence of any and high grade cytological abnormality was significantly higher among HIV-infected women with positive-HRHPV test. A single negative-HRHPV test helped reassure follow-up free of cytological abnormalities through three years of follow-up in HIV-infected women with negative cytology., (Copyright © 2017 Sociedade Brasileira de Infectologia. Published by Elsevier Editora Ltda. All rights reserved.)

Objective: Estimate the prevalence of cervical HPV infection among women assisted by the Family Health Strategy and identify the factors related to the infection., Methods: A cross-sectional study involving 2,076 women aged 20-59 years old residing in Juiz de Fora, State of Minas Gerais, who were asked to participate in an organized screening carried out in units were the Family Health Strategy had been implemented. Participants answered the standardized questionnaire and underwent a conventional cervical cytology test and HPV test for high oncogenic risk. Estimates of HPV infection prevalence were calculated according to selected characteristics referenced in the literature and related to socioeconomic status, reproductive health and lifestyle., Results: The overall prevalence of HPV infection was 12.6% (95%CI 11.16-14.05). The prevalence for the pooled primer contained 12 oncogenic HPV types (31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66, and 68) was 8.6% (95%CI 7.3-9.77). In the multivariate analysis, it was observed that the following variables were significantly associated with a higher prevalence of HPV infection: marital status (single: adjusted PR = 1.40, 95%CI 1.07-1.8), alcohol consumption (any lifetime frequency: adjusted PR = 1.44, 95%CI 1.11-1.86) and number of lifetime sexual partners (≥ 3: adjusted PR = 1.35, 95%CI 1.04-1.74)., Conclusions: The prevalence of HPV infection in the study population ranges from average to particularly high among young women. The prevalence of HPV16 and HPV18 infection is similar to the worldwide prevalence. Homogeneous distribution among the pooled primer types would precede the isolated infection by HPV18 in magnitude, which may be a difference greater than the one observed. The identification of high-risk oncogenic HPV prevalence may help identify women at higher risk of developing preneoplastic lesions.

Objectives:: Quantitative fluorescence polymerase chain reaction (QF-PCR) is a rapid and reliable method for screening aneuploidies, but in Brazil, it is not used in public services. We investigated the accuracy of QF-PCR for the prenatal recognition of common aneuploidies and compared these results with cytogenetic results in our laboratory., Method:: A ChromoQuant QF-PCR kit containing 24 primer pairs targeting loci on chromosomes 21, 13, 18, X and Y was employed to identify aneuploidies of the referred chromosomes., Results:: A total of 162 amniotic fluid samples analyzed using multiplex QF-PCR were compared with karyotyping analysis. The QF-PCR results were consistent with the results of cytogenetic analysis in 95.4% of all samples., Conclusion:: QF-PCR was demonstrated to be efficient and reliable for prenatal aneuploidy screening. This study suggests that QF-PCR can be used as a rapid diagnostic method. However, rearrangements and some mosaic samples cannot be detected with this test; thus, those exceptions must undergo cytogenetic analysis.

Human papillomavirus (HPV) causes oropharyngeal squamous cell carcinoma (OPSCC), although strongly divergent results have been reported regarding the prevalence of HPV16 in different countries, whether this represents important differences in etiology remains unclear. Applying rigorous protocols for sample processing, we centrally evaluated 1,420 head and neck tumors (533 oropharynx, 395 oral cavity and 482 larynx) from studies conducted in the US, Europe and Brazil for mucosal HPV DNA and p16 INK4a expression to evaluate regional heterogeneity in the proportion of HPV16-associated OPSCC and other head and neck cancer, and to assess covariates associated with the risk of HPV16-positive OPSCC. While majority of OPSCC in the US (60%) were HPV16-positive, this proportion was 31% in Europe and only 4% in Brazil (p < 0.01). Similar differences were observed for other head and neck tumors, ranging from 7% in the US and 5% in Europe, to 0% in South America. The odds of HPV16-positive OPSCC declined with increasing pack years of smoking (OR: 0.75; 95% CI: 0.64-0.87) and drink years of alcohol use (OR: 0.64; 95% CI: 0.54-0.76). These results suggest that while the contribution of HPV16 is substantial for the oropharynx, it remains limited for oral cavity and laryngeal cancers., (© 2017 IARC/WHO.)

Objectives: To explore whether HPV-related biomarkers predict oropharyngeal squamous cell cancer (OPSCC) survival similarly across different global regions, and to explore their prognostic utility among non-oropharyngeal (non-OP) head and neck cancers., Methods: Data from 1362 head and neck SCC (HNSCC) diagnosed 2002-2011 was used from epidemiologic studies in: Brazil (GENCAPO study, n=388), U.S. (CHANCE study, n=472), and Europe (ARCAGE study, n=502). Tumors were centrally tested for p16 INK4a and HPV16 DNA (by PCR). Risk of mortality was examined using Cox proportional hazard models., Results: There were 517 OPSCC and 845 non-OP HNSCC. Cases were primarily male (81%), ever smokers (91%), with median age of 58yearsandmedian follow-up of 3.1years (IQR=1.4-5.9). Among OPSCC, the risk of mortality was significantly lower among 184 HPV-related (i.e., p16+/HPV16+) compared to 333 HPV-unrelated (p16- and/or HPV16-) cases (HR=0.25, 95%CI=0.18-0.34). Mortality was reduced among HPV-related OPSCC cases from the U.S., Europe, and Brazil (each p⩽0.01) and after adjustment, remained significantly reduced (aHR=0.34, 95%CI=0.24-0.49). Among non-OP HNSCC, neither p16 (aHR=0.83, 95%CI=0.60-1.14), HPV16 DNA (aHR=1.20, 95%CI=0.89-1.63), or p16+/HPV16+ (aHR=0.59, 95%CI=0.32-1.08) was a significantly predictor of mortality. When interaction was tested, the effect of HPV16/p16 was significantly different in OPSCC than non-OP HNSCC (p-interaction=0.02)., Conclusion: HPV-related OPSCCs had similar survival benefits across these three regions. Prognostic utility of HPV among non-OP HNSCC is limited so tumor HPV/p16 testing should not be routinely done among non-OP HNSCC., (Copyright © 2016 Elsevier Ltd. All rights reserved.)