Kinetics of Torque Teno Virus Viral Load Is Associated with Infection and De Novo Donor Specific Antibodies in the First Year after Kidney Transplantation: A Prospective Cohort Study.

Torque teno virus (TTV) was recently identified as a potential biomarker for the degree of immunosuppression, and potentially as a predictor of rejection and infection in solid organ transplant patients. We evaluated TTV viral load in kidney transplant (KT) patients during the first year post-transplant to examine overall kinetics and their relationships with deleterious events, including episodes of infection and the formation of de novo donor-specific antibodies (DSAs). In a single-center, prospective observational cohort study, 81 KT patients were monitored at baseline, week 1, and month 1, 3, 6, 9 and 12, post-KT, and whenever required by clinical events. Kidney function, plasma TTV load, immunoglobulins and lymphocyte subpopulations were assessed at each time point. Twenty-six patients (32.1%) presented a total of 38 infection episodes post-KT. Induction immunosuppression with thymoglobulin, compared to basiliximab, was not associated with more infections (p = 0.8093). Patients with infectious events had lower T-cells (p = 0.0500), CD8+ T-cells (p = 0.0313) and B-cells (p = 0.0009) 1 month post-KT, compared to infection-free patients. Patients with infection also showed higher increases in TTV viral loads between week 1- month 1, post-KT, with TTV viral load variations >2.65 log10 cp/mL predicting the development of infectious events during the 12-month study period (p < 0.0001; sensitivity 99.73%; specificity 83.67%). Patients who developed de novo DSAs had lower TTV DNA viral loads at month 12 after KT, compared to patients who did not develop DSA (3.7 vs. 5.3 log10 cp/mL, p = 0.0023). Briefly, evaluating early TTV viremia is a promising strategy for defining infectious risk in the 1st year post-KT. The availability of standardized commercial real-time PCR assays is crucial to further validate this as an effective tool guiding immunosuppression prescription.

Detection of JCV or BKV viruria and viremia after kidney transplantation is not associated with unfavorable outcomes.

Studies analyzing the relationship between BK polyomavirus (BKV) or JC polyomavirus (JCV) infection and kidney transplant (KT) long term clinical outcomes are scarce. Therefore, we evaluated this relationship in a single-center retrospective cohort of 288 KT patients followed for 45.4(27.5; 62.5) months. Detection of BKV viremia in two consecutive analyses led to discontinuation of antimetabolite and initiation of mammalian target of rapamycin inhibitor. Outcome data included de novo BKV and/or JCV viremia and/or viruria after KT, death-censored graft survival and patient survival. BKV viruria and viremia were detected in 42.4% and 22.2% of KT recipients, respectively. BKV viremic patients had higher urinary BKV viral loads at the onset of viruria, when compared to nonviremic patients (7 log10 vs. 4.9 log10 cp/mL, p < 0.001). JCV viruria was identified in 38.5% of KT patients; the 5.9% of KT recipients who developed JCV viremia had higher JCV urinary viral loads at the onset of viruria, when compared to non-viremic patients (5.3 vs. 3.7 log10 cp/mL, p = 0.034). No differences were found in estimated glomerular filtration rate at the end of follow up, when comparing BKV or JCV viruric or viremic patients with nonviremic patients. No association was found between JCV or BKV viruria or viremia and death/graft failure. Therefore, higher BKV urinary viral loads at the onset could serve as an early maker of over immunosuppression. JCV and BKV replication was not associated with inferior clinical outcomes in KT patients with the above-mentioned immunosuppression strategy.

Torquetenovirus viral load is associated with anti-spike antibody response in SARS-CoV-2 mRNA BNT162b2 vaccinated kidney transplant patients.

INTRODUCTION: Kidney transplant patients (KT) are at high risk for severe COVID-19 and presented attenuated antibody responses to vaccination when compared to immunocompetent individuals. Torquetenovirus (TTV) has recently gained attention as a potential surrogate marker of the net state of immunosuppression. We evaluated the association between pre-vaccination TTV viral load and anti-spike total antibody response to SARS-CoV-2 vaccination in KT. MATERIAL AND METHODS: The 114 adult KT recipients enrolled in this prospective single-center cohort study received two doses of SARS-CoV-2 mRNA BNT162b2 vaccine. Serum samples were collected immediately before vaccination at the days when patients received both the first (T0) and the second dose (T1) and 16-45 days after the second dose (T2). Primary endpoint was the development of anti-spike total antibodies after vaccination. Demographic, clinical, and laboratorial parameters were compared between patients with and without detectable SARS-CoV-2 antibodies at T2. RESULTS: Ninety-nine patients (86.8%) were naïve for SARS-CoV-2 before vaccination. Fifty-six (56.6%) patients developed anti-spike total antibodies at T2. The use of mTOR inhibitors was associated with a favorable response (p = .005); conversely, mycophenolic acid (MPA) was associated with a negative response (p = .006). In a multivariable model, the presence of TTV at T0 ≥ 3.36 log10 cp/ml was associated with unfavorable vaccine response (OR: 5.40; 95% CI: 1.47-19.80; p = .011), after adjusting for age and eGFR at T0. CONCLUSIONS: Higher TTV viral loads before vaccination are associated with reduced anti-spike total antibody response in SARS-CoV-2 mRNA BNT162b2 vaccinated KT patients. The association between TTV viral load and vaccine response may be an added-value in the optimization of vaccination regimens in KT.

Antimicrobial Resistance and Biofilms Underlying Catheter-Related Bloodstream Coinfection by Enterobacter cloacae Complex and Candida parapsilosis.

Biofilm-associated infections are a public health concern especially in the context of healthcare-associated infections such as catheter-related bloodstream infections (CRBSIs). We evaluated the biofilm formation and antimicrobials resistance (AMR) of Enterobacter cloacae complex and Candida parapsilosis co-isolated from a CRBSI patient. Antimicrobial susceptibility of central venous catheters (CVCs) and hemoculture (HC) isolates was evaluated, including whole genome sequencing (WGS) resistome analysis and evaluation of gene expression to obtain insight into their AMR determinants. Crystal violet assay was used to assess dual biofilm biomass and microscopy was used to elucidate a microorganism's distribution within biofilms assembled on different materials. Bacteria were multidrug-resistant including resistance to colistin and beta-lactams, likely linked to the mcr-9-like phosphoethanolamine transferase and to an ACT family cephalosporin-hydrolyzing class C beta-lactamase, respectively. The R398I and Y132F mutations in the ERG11 gene and its differential expression might account for C. parapsilosis resistance to fluconazole. The phenotype of dual biofilms assembled on glass, polystyrene and polyurethane depends on the material and how biofilms were initiated by one or both pathogens. Biofilms assembled on polyurethane were denser and richer in the extracellular polymeric matrix, and microorganisms were differently distributed on the inner/outer surface of the CVC.

COVID-19-Associated Invasive Pulmonary Aspergillosis in the Intensive Care Unit: A Case Series in a Portuguese Hospital.

Invasive pulmonary aspergillosis (IPA) has become a recognizable complication in coronavirus disease 2019 (COVID-19) patients admitted to intensive care units (ICUs). Alveolar damage in the context of acute respiratory distress syndrome (ARDS) appears to be the culprit in facilitating fungal invasion in COVID-19 patients, leading to a COVID-19-associated pulmonary aspergillosis (CAPA) phenomenon. From November 2020 to 15 February 2021, 248 COVID-19 patients were admitted to our ICUs, of whom ten patients (4% incidence) were classified as either probable (six) or possible (four) CAPA cases. Seven patients had positive cultural results: Aspergillus fumigatus sensu stricto (five), A. terreus sensu stricto (one), and A. welwitschiae (one). Five patients had positive bronchoalveolar lavage (BAL) and galactomannan (GM), and two patients had both positive cultural and GM criteria. All but two patients received voriconazole. Mortality rate was 30%. Strict interpretation of classic IPA definition would have resulted in eight overlooked CAPA cases. Broader diagnostic criteria are essential in this context, even though differentiation between Aspergillus colonization and invasive disease might be more challenging. Herein, we aim to raise awareness of CAPA in view of its potential detrimental outcome, emphasizing the relevance of a low threshold for screening and early antifungal treatment in ARDS patients.

Outcomes of Living Kidney Donor Candidates and Living Kidney Recipient Candidates with JC Polyomavirus and BK Polyomavirus Viruria.

INTRODUCTION: Recent data have emerged about a protective association between JCV viruria and chronic kidney disease (CKD). Material and Methods. Single-center retrospective cohort study; 230 living kidney donors (LKD) candidates and 59 potential living kidney receptors (LKR) were enrolled. Plasma and urinary JCV and BKV viral loads were measured in all LKD candidates and in nonanuric LKR candidates. Twenty-six living kidney transplant surgeries were performed. LKR were followed in order to evaluate BKV and JCV viremia and urinary viral shedding after KT. RESULTS: In LKD candidates, JCV viruria was negatively associated with proteinuria of >200 mg/24 hours (JC viruric LKD: 12.5% vs JCV nonviruric LKD: 26.7%, p=0.021, OR:0.393; 95% CI: 0.181-0.854). In a multivariate analysis, LKD candidates with JCV viruria had a lower risk of proteinuria of >200 mg/24 hours (p=0.009, OR: 0.342, 95% CI: 0.153-0.764), in a model adjusted for age, gender, presence of hypertension, and eGFR <80 mL/min. Prevalence of JCV viruria was higher in LKD candidates when compared with LKR candidates (40.0% vs 1.7%, p < 0.001). Among the 26 LKR, 14 (53.8%) KT patients evolved with JCV viruria; 71.4% received a graft from a JCV viruric donor. CONCLUSION: Our data corroborate the recent findings of an eventual protective association between JCV viruria and kidney disease, and we extrapolated this concept to a South European population.

Transcontinental Dissemination of the L2b/D-Da Recombinant Chlamydia trachomatis Lymphogranuloma venereum (LGV) Strain: Need of Broad Multi-Country Molecular Surveillance.

Previously, we identified a Chlamydia trachomatis lymphogranuloma venereum (LGV) recombinant strain possessing a non-LGV ompA genotype. Here, culture-independent genome sequencing confirms its circulation in Europe, Middle East, and North America, and unveils emergence of antibiotic resistance. Broad surveillance is needed.

Kinetics of torquetenovirus DNA load in a recent kidney transplant recipient with mild SARS-CoV-2 infection and a failed antibody response.

Kidney transplant (KT) recipients are at an increased risk for severe COVID-19 because of their immunosuppressed state. A 42-year-old KT patient was diagnosed with COVID-19 three months after KT. Despite lymphopenia and several risk factors, he had a mild disease course. Nasopharyngeal real-time reverse transcriptase polymerase chain reaction for SARS-CoV-2 became negative 48 days after detection. SARS-CoV-2 IgG antibodies became negative after day 40. TTV DNA load increased with the onset COVID-19 and reduced after its resolution. This is the first report where TTV DNA load was measured during the course of COVID-19.

Congenital SARS-CoV-2 Infection in a Neonate With Severe Acute Respiratory Syndrome.

Coronavirus disease, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is mainly transmitted through droplets, but other ways of transmission have been hypothesized. We report a case of vertical transmission of SARS-CoV-2 in a preterm born to an infected mother, confirmed by the presence of the virus in the neonatal blood, nasopharyngeal and oropharyngeal swabs collected in the first half an hour of life. The neonate presented with acute respiratory distress, similar to the findings in severely affected adults. This case highlights the importance of pregnancy, labor and neonatal period surveillance of affected mothers and their newborns.

Epidemiology and genetic variability of respiratory syncytial virus in Portugal, 2014-2018.

INTRODUCTION: Respiratory syncytial virus (RSV) is associated with substantial morbidity and mortality since it is a predominant viral agent causing respiratory tract infections in infants, young children and the elderly. Considering the availability of the RSV vaccines in the coming years, molecular understanding in RSV is necessary. OBJECTIVE: The objective of the present study was to describe RSV epidemiology and genotype variability in Portugal during the 2014/15-2017/18 period. MATERIAL AND METHODS: Epidemiological data and RSV-positive samples from patients with a respiratory infection were collected through the non-sentinel and sentinel influenza surveillance system (ISS). RSV detection, subtyping in A and B, and sequencing of the second hypervariable region (HVR2) of G gene were performed by molecular methods. Phylogenetic trees were generated using the Neighbor-Joining method and p-distance model on MEGA 7.0. RESULTS: RSV prevalence varied between the sentinel (2.5%, 97/3891) and the non-sentinel ISS (20.7%, 3138/16779), being higher (P < 0.0001) among children aged <5 years. Bronchiolitis (62.9%, 183/291) and influenza-like illness (24.6%, 14/57) were associated (P < 0.0001) with RSV laboratory confirmation among children aged <6 months and adults ≥65 years, respectively. The HVR2 was sequenced for 562 samples. RSV-A (46.4%, 261/562) and RSV-B (53.6%, 301/562) strains clustered mainly to ON1 (89.2%, 233/261) and BA9 (92%, 277/301) genotypes, respectively, although NA1 and BA10 were also present until 2015/2016. CONCLUSION: The sequence and phylogenetic analysis reflected the relatively high diversity of Portuguese RSV strains. BA9 and ON1 genotypes, which have been circulating in Portugal since 2010/2011 and 2011/2012 respectively, predominated during the whole study period.

Risk factors for the nasopharyngeal carriage of respiratory pathogens by Portuguese children: phenotype and antimicrobial susceptibility of Haemophilus influenzae and Streptococcus pneumoniae.

Between 1997 and 2000 nasopharyngeal specimens were obtained from 466 children < or = 12 years old attending the Pediatric Emergency Department at S. Francisco Xavier Hospital, Lisbon, to evaluate risk factors for nasopharyngeal carriage of Haemophilus influenzae and Streptococcus pneumoniae and to characterize their phenotype and antimicrobial susceptibility. The attending pediatrician completed written questionnaires about the children's demographic and clinical histories. Over half the children (52.8%) carried H. influenzae and/or S. pneumoniae. Forty-one percent of these children had H. influenzae, 22.8% had S. pneumoniae and 36.2% had both. Risk factors identified for carriage of respiratory pathogens were: age below 3 years (p < 0.05), black race (p < 0.01), attending a daycare center (p < 0.05), and having a lower respiratory infection (p < 0.05). Asthmatic children were less likely to be carriers (p = 0.004). About two-thirds of H. influenzae isolates were susceptible to all antibiotics tested, 7.9% were beta-lactamase producers, 16.4% were nonsusceptible to trimethoprim, and 6.9% were intermediately resistant to clarithromycin. Over half (57.1%) of S. pneumoniae isolates were susceptible to all antibiotics tested, 21.1% were multiresistant, 23.3% were nonsusceptible to penicillin, and about 20% were resistant to macrolides. Low-level resistance to third-generation cephalosporins was detected in 2.3%. The data reflect the controversy surrounding risk factors of nasopharyngeal colonization. These may have significant implications on clinical practice and on antimicrobial strategies to prevent the appearance of further resistant strains. Our findings highlight the importance to investigate the relationship between asthma and carriage.

Desafios de ser um Sanitarista nos tempos atuais - Mesa de abertura

Mesa de abertura foi composta por: Antônio Ivo de Carvalho, diretor da Ensp, do vice-diretor de Escola de Governo em Saúde, Carlos Machado de Freitas, da coordenadora da Especialização em Saúde Pública, Marina Noronha e da coordenadora das Residências, Maria Alice Pessanha. O arquivo está disponível para audição e/ou download no ícone ao lado.

Formatura da Segunda turma do Curso de Especialização em Saúde da Família nos Moldes da Residência

A coordenadora geral do curso de Especialização em Saúde da Família nos Moldes da Residência, Maria Alice Pessanha, acredita que de alguma maneira tanto os professores quanto os alunos estão contribuindo para as mudanças do modelo apresentado pelo atual sistema de saúde. Outro ponto destacado por ela foi na questão do aprendizado, saindo das salas de aula e indo diretamente para os serviços, onde os alunos aprendem na prática com as dificuldades do dia-a-dia enfrentados nas unidades de saúde. O arquivo está disponível para leitura e/ou download por meio do ícone ao lado.

PAC Saúde: política pública para territórios negligenciados? - Mesa de Abertura.

A abertura do IV Ciclo de Debates contou com as presenças do vice-diretor da Escola de Governo em Saúde, Carlos Machado, representando a Direção da Escola, da coordenadora do Curso de Especialização em Saúde da Família nos moldes da Residência, Maria Alice Pessanha e da chefe do Centro de Saúde Escola Germano Sinval Faria, Else Griebel, que coordenou essa primeira atividade. O arquivo está disponível para leitura e/ou download por meio do ícone ao lado.

Do hospital escola ao Centro Saúde Escola.

Resgatar, explorar e expor o papel do Centro de Saúde Escola Germano Sinval Faria com um espaço de pesquisa, produtor de conhecimento, um Centro formador. Além disso, refletir sobre como articular o exercício da profissão com o exercício da formação na área da saúde. Estes foram os principais objetivos da sessão científica de quinta-feira (09/08), que debateu os caminhos para a preceptoria do Centro de Saúde Escola e teve como palestrantes as pesquisadoras Maria Alice Pessanha, do departamento de Ciências Sociais da ENSP, e Margareth Rose G. Garcia, do Centro de Saúde.