CLARISSE MARTINS MACHADO
Projetos de Pesquisa
Unidades Organizacionais
Departamento de Moléstias Infecciosas e Parasitárias, Faculdade de Medicina
LIM/52 - Laboratório de Virologia, Hospital das Clínicas, Faculdade de Medicina
LIM/52 - Laboratório de Virologia, Hospital das Clínicas, Faculdade de Medicina
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conferenceObject SARS CoV-2 infection and covid-19 in health care workers from a hematopoietic stem cell transplant (HSCT) unit before and after vaccination: A prospective cohort study(2022) SANTOS, A. C. Ferrari dos; MORENO, J. Do Prado; ZANETTI, L. Perilio; OLIVEIRA, L. C. de; TESTA, L. H. de Almeida; SIMIONE, A. J.; SOUZA, M. P. de; COLTURATO, V. A. Rensi; MACHADO, C.- Respiratory viruses and postoperative hemodynamics in patients with unrestrictive congenital cardiac communications: a prospective cohort study(2023) ABUD, Kelly C. O.; MACHADO, Clarisse M.; BOAS, Lucy S. Vilas S.; MAEDA, Nair Y.; CARVALHO, Eloisa S.; SOUZA, Maria Francilene S.; GAIOLLA, Paula V.; CASTRO, Claudia R. P.; PEREIRA, Juliana; RABINOVITCH, Marlene; LOPES, Antonio AugustoBackgroundPulmonary vascular abnormalities pose a risk for severe life-threatening hemodynamic disturbances following surgical repair of congenital cardiac communications (CCCs). In the distal lung, small airways and vessels share a common microenvironment, where biological crosstalks take place. Because respiratory cells infected by viruses express a number of molecules with potential impact on airway and vascular remodeling, we decided to test the hypothesis that CCC patients carrying viral genomes in the airways might be at a higher risk for pulmonary (and systemic) hemodynamic disturbances postoperatively.MethodsSixty patients were prospectively enrolled (age 11 [7-16] months, median with interquartile range). Preoperative pulmonary/systemic mean arterial pressure ratio (PAP/SAP) was 0.78 (0.63-0.88). The presence or absence of genetic material for respiratory viruses in nasopharyngeal and tracheal aspirates was investigated preoperatively in the absence of respiratory symptoms using real-time polymerase chain reaction (kit for detection of 19 pathogens). Post-cardiopulmonary bypass (CPB) inflammatory reaction was analyzed by measuring serum levels of 36 inflammatory proteins (immunoblotting) 4 h after its termination. Postoperative hemodynamics was assessed using continuous recording of PAP and SAP with calculation of PAP/SAP ratio.ResultsViral genomes were detected in nasopharynx and the trachea in 64% and 38% of patients, respectively. Rhinovirus was the most prevalent agent. The presence of viral genomes in the trachea was associated with an upward shift of postoperative PAP curve (p = 0.011) with a PAP/SAP of 0.44 (0.36-0.50) in patients who were positive versus 0.34 (0.30-0.45) in those who were negative (p = 0.008). The presence or absence of viral genomes in nasopharynx did not help predict postoperative hemodynamics. Postoperative PAP/SAP was positively correlated with post-CPB levels of interleukin-1 receptor antagonist (p = 0.026), macrophage migration inhibitory factor (p = 0.019) and monocyte chemoattractant protein-1 (p = 0.031), particularly in patients with virus-positive tracheal aspirates.ConclusionsPatients with CCCs carrying respiratory viral genomes in lower airways are at a higher risk for postoperative pulmonary hypertension, thus deserving special attention and care. Preoperative exposure to respiratory viruses and post-CPB inflammatory reaction seem to play a combined role in determining the postoperative behavior of the pulmonary circulation.
- Endemic or regionally limited parasitic and fungal infections in haematopoietic stem-cell transplantation recipients: a Worldwide Network for Blood and Marrow Transplantation (WBMT) Review(2023) MUHSEN, Ibrahim N.; GALEANO, Sebastian; NIEDERWIESER, Dietger; KOH, Mickey B. C.; LJUNGMAN, Per; MACHADO, Clarisse M.; KHARFAN-DABAJA, Mohamed A.; CAMARA, Rafael de la; KODERA, Yoshihisa; SZER, Jeff; RASHEED, Walid; CESARO, Simone; HASHMI, Shahrukh K.; SEBER, Adriana; ATSUTA, Yoshiko; SALEH, Mostafa F. Mohammed; SRIVASTAVA, Alok; STYCZYNSKI, Jan; ALRAJHI, Abdulrahman; ALMAGHRABI, Reem; ABID, Muhammad Bilal; CHEMALY, Roy F.; GERGIS, Usama; BRISSOT, Eolia; FAKIH, Riad El; RICHES, Marcie; MIKULSKA, Malgorzata; WOREL, Nina; WEISDORF, Daniel; GREINIX, Hildegard; CORDONNIER, Catherine; ALJURF, MahmoudThere is a scarcity of data on endemic and regionally limited fungal and parasitic infections in recipients of haematopoietic stem-cell transplantation (HSCT) outside western Europe and North America. This Worldwide Network for Blood and Marrow Transplantation (WBMT) Review is one of two papers aiming to provide guidance to transplantation centres worldwide regarding prevention, diagnosis, and treatment based on the currently available evidence and expert opinion. These recommendations were created and reviewed by physicians with expertise in HSCT or infectious disease, representing several infectious disease and HSCT groups and societies. In this paper, we review the literature on several endemic and regionally limited parasitic and fungal infections, some of which are listed as neglected tropical diseases by WHO, including visceral leishmaniasis, Chagas disease, strongyloidiasis, malaria, schistosomiasis, histoplasmosis, blastomycosis, and coccidioidomycosis.
- Epidemiology, treatment patterns, and disease burden of cytomegalovirus in hematopoietic cell transplant recipients in selected countries outside of Europe and North America: A systematic review(2023) CHO, Sung-Yeon; AR, Muhlis Cem; MACHADO, Clarisse M.; WU, Depei; SINGH, Inderjeet; SANDHU, Anudeep; DEMUTH, Dirk; SLAVIN, MonicaBackground: Cytomegalovirus (CMV) disease impacts morbidity and mortality in hematopoietic cell transplant (HCT) recipients. This systematic review summarized data on the epidemiology, management, and burden of CMV post-HCT outside of Europe and North America.Methods: The MEDLINE, Embase, and Cochrane databases were searched for observational studies and treatment guidelines in HCT recipients across 15 selected countries from Asia-Pacific, Latin America, and Middle East (search period: 1 January 2011-17 September 2021). Outcomes included incidence of CMV infection/disease, recurrence, risk factors, CMV-related mortality, treatments, refractory, resistant CMV, and burden.Results: Of 2708 references identified, 68 were eligible (67 studies and one guideline; 45/67 studies specific to adult allogeneic HCT recipients). The rates of CMV infection and disease within 1 year of allogeneic HCT were 24.9%-61.2% (23 studies) and 2.9%-15.7% (10 studies), respectively. Recurrence occurred in 19.8%-37.9% of cases (11 studies). Up to 10% of HCT recipients died of CMV-related causes. In all countries, first-line treatment for CMV infection/disease involved intravenous ganciclovir or valganciclovir. Conventional treatments were associated with serious adverse events such as myelosuppression (10.0%) or neutropenia only (30.0%, 39.8%) and nephrotoxicity (11.0%) (three studies), frequently leading to treatment discontinuation (up to 13.6%). Refractory CMV was reported in 2.9%, 13.0%, and 28.9% of treated patients (three studies) with resistant CMV diagnosed in 0%-10% of recipients (five studies). Patient-reported outcomes and economic data were scarce.Conclusion: The incidence of CMV infection and disease post-HCT is high outside of North America and Europe. CMV resistance and toxicity highlight a major unmet need with current conventional treatments.
- Use of live viral vaccines after HCT: Still a lot to learn(2023) SABAINI, Paula Moreira da Silva; MACHADO, Clarisse M.Revaccination program after HCT is necessary due to the loss of lifelong immunity acquired by previous vaccination or infections. The program is complex and even in a favourable scenario, it takes more than 2 years to be completed. As the complexity of HCT increases (alternative donors, diversity of monoclonal antibodies), studies evaluating the response to vaccination in this population are welcome, especially those that evaluate live attenuated vaccines given their scarcity. Furthermore, measles, mumps, rubella and even yellow fever, and poliomyelitis outbreaks have perplexed infectious diseases clinicians and epidemiologists globally, most of them due to the decline in vaccination coverage rates in children and adults, because of the growth of antivaccine movements around the world. The study of Lin et al. adds important information about measles, mumps and rubella vaccination after HCT.
- Thymopoiesis in Pre- and Post-Hematopoietic Stem Cell Transplantation(2018) ROCHA, Luis Klaus A. da; BARROS, Samar Freschi de; BANDEIRA, Francine; BOLLINI, Alexia; TESTA, Lucia Helena de A.; SIMIONE, Anderson Joao; SOUZA, Marina de O. e; ZANETTI, Lilian P.; OLIVEIRA, Leila Cibele S. de; SANTOS, Ana Claudia F. dos; SOUZA, Mair Pedro de; COLTURADO, Vergilio Antonio R.; KALIL, Jorge; MACHADO, Clarisse M.; GUILHERME, LuizaHematopoietic stem cell transplantation (HSCT) is an important therapeutic option for some hematological diseases. However, patients who undergo HSCT acquire a state of immunodeficiency that causes significant mortality. Reconstitution of thymic function is needed to support the immune system. One way to measure thymic function is through T-cell receptor excision circle (TREC) quantification. TRECs are generated by T-cell receptor gene rearrangements during T-cell maturation in the thymus and represent a reliable marker for thymic output. In this study, we aimed to assess aging and malignant hematological diseases as two important factors that may influence thymic output before HSCT. We observed that patients before HSCT presented signal joint TREC (sjTREC) numbers lower than 606.55 copies/mu g DNA (low values) compared with healthy individuals, with an odds ratio (OR) of 12.88 [95% confidence interval (CI): 5.26-31.53; p < 0.001]. Our results showed that a group of older individuals (>= 50 years old), comprising both healthy individuals and patients, had an OR of 10.07 (95% CI: 2.80-36.20) for low sjTREC values compared with younger individuals (<= 24 years old; p < 0.001). Multiple logistic regression analysis confirmed that both older age (>= 50 years old) and malignant hematological diseases and their treatments were important and independent risk factors related to thymic function impairment (p < 0.001). The median sjTREC value for patients of all ages was significantly lower than the sjTREC median for the subgroup of older healthy individuals (>= 50 years old; p < 0.001). These data suggested that patients before HSCT and healthy individuals exhibited age-dependent thymic impairment, and that prior treatment for hematological diseases may exacerbate aging-related deterioration of natural thymic function. Furthermore, we analyzed these patients 9 months post-HSCT and compared patients who underwent autologous HSCT with those who underwent allogeneic HSCT. Both groups of patients achieved sjTREC copy numbers similar to those of healthy individuals. We did not find a close relationship between impaired thymic function prior to HSCT and worse thymic recovery after HSCT.
conferenceObject PRE-EMPTIVE RITUXIMAB FOR EBV REACTIVATION IN TIMES OF COVID-19: IS IT REALLY NECESSARY?(2023) SANTOS, Ana Claudia Ferrari dos; SIMIONE, Anderson Joao; SOUZA, Anna Beatriz Coelho de; MORENO, Juliana Ribeiro do Prado; ZANETTI, Lilian Perilio; OLIVEIRA, Leila Cibele Serra; COLTURATO, Iago; BARBIERI, Fernanda Rodrigues; SANTOS, Juliana Silva; DELATTRE, Erika Rodrigues Pontes; MASCARENHAS, Carolina Ferreira; PEGORARI, Leticia Galbier Ricetto; SOUZA, Mair Pedro de; COLTURATO, Vergilio Antonio Rensi; MACHADO, Clarisse Martins- Salivary SARS-CoV-2 load reduction with mouthwash use: A randomized pilot clinical trial(2021) EDUARDO, Fernanda de Paula; CORREA, Luciana; HELLER, Debora; DAEP, Carlo Amorin; BENITEZ, Carlos; MALHEIROS, Zilson; STEWART, Bernal; RYAN, Maria; MACHADO, Clarisse Martins; HAMERSCHLAK, Nelson; PINHO, Joao Renato Rebello; BEZINELLI, Leticia MelloThe saliva of patients with COVID-19 has a high SARS-CoV-2 viral load. The risk of spreading the virus is high, and procedures for viral load reduction in the oral cavity are important. Little research to date has been performed on the effect of mouthwashes on the salivary SARS-CoV-2 viral load. This pilot randomized single-center clinical trial investigated whether three types of mouthwash with solutions containing either 0.075% cetylpyridinium chloride plus 0.28% zinc lactate (CPC + Zn), 1.5% hydrogen peroxide (HP), or 0.12% chlorhexidine gluconate (CHX) reduce the SARS-CoV-2 viral load in saliva at different time points. Sixty SARS-CoV-2-positive patients were recruited and randomly partitioned into a placebo (oral rinsing with distilled water) group and other groups according to the type of mouthwash. Saliva samples were collected from the participants before rinsing (T0), immediately after rinsing (T1), 30 min after rinsing (T2), and 60 min after rinsing (T3). The salivary SARS-CoV-2 viral load was measured by qRT-PCR assays. Rinsing with HP and CPC + Zn resulted in better reductions in viral load, with 15.8 +/- 0.08- and 20.4 +/- 3.7-fold reductions at T1, respectively. Although the CPC + Zn group maintained a 2.6 +/- 0.1-fold reduction at T3, this trend was not observed for HP. HP mouthwash resulted in a significant reduction in the SARS-CoV-2 viral load up to 30 min after rinsing (6.5 +/- 3.4). The CHX mouthwash significantly reduced the viral load at T1, T2, and T3 (2.1 +/- 1.5-, 6.2 +/- 3.8-, and 4.2 +/- 2.4-fold reductions, respectively). In conclusion, mouthwash with CPC + Zinc and CHX resulted in significant reductions of the SARSCoV-2 viral load in saliva up to 60 mins after rinsing, while HP mouthwash resulted in a significant reduction up to 30 mins after rinsing. Despite this transitory effect, these results encourage further studies and suggest that these products could be considered as risk-mitigation strategies for patients infected with SARS-CoV-2.
- Chikungunya, Dengue, and Zika in Immunocompromised Hosts(2018) DARRIGO JR., Luiz Guilherme; CARVALHO, Alexandre Machado de Sant'Anna; MACHADO, Clarisse MartinsPurpose of Review Describe the characteristics of chikungunya, dengue, and Zika in transplant recipients and immunocompromised hosts. Recent Findings Stem cell/bone marrow grafts, organs, and blood transfusions can transmit CHIKV/DENV/ZIKV infections, which are clinically similar, resembling influenza-like illness. Laboratory confirmation is necessary. In the acute phase, RT-PCR is preferred. DENV and ZIKV serology may cross-react. Delayed engraftment and extended viruria is observed in ZIKV+/HSCT recipients, while longer viremia is observed in DENV+/HSCT patients. Arbovirus persistence in organ tissues is generally unknown. Vaccine development is in early stages for CHIKV/ZIKV. No data is available to recommend the licensed DENV vaccine in transplant recipients. Summary In endemic areas, the assessment of epidemiological risk is mandatory. Donor deferral for 120 days in suspected or confirmed ZIKV+ has been recommended, while CHIKV+ donors should wait 30 days. No deferral is recommended for DENV+ donors. CHIKV/DENV/ZIKV tests should be included in the differential of febrile neutropenia and other transplant syndromes. Reassessment of DENV serology is urgently needed. Prospective studies are necessary to determine the impact of CHIKV/DENV/ZIKV in this special population.
conferenceObject Epidemiology of Cytomegalovirus Infection and Disease in Hematopoietic Stem Cell Transplant Recipients in Selected Countries Outside of North America and Europe: A Systematic Review(2022) MACHADO, Clarisse M.; CHO, Sung-Yeon; SLAVIN, Monica; SINGH, Inderjeet; SANDHU, Anudeep; DEMUTH, Dirk; WU, Depei