Publications by authors named "Clarice N L Morais"

15 Publications

  • Page 1 of 1

Diagnostic performance of anti-Zika virus IgM, IgAM and IgG ELISAs during co-circulation of Zika, dengue, and chikungunya viruses in Brazil and Venezuela.

PLoS Negl Trop Dis 2021 04 19;15(4):e0009336. Epub 2021 Apr 19.

Section Clinical Tropical Medicine, Department for Infectious Diseases, Heidelberg University Hospital, Heidelberg, Germany.

Background: Serological diagnosis of Zika virus (ZIKV) infection is challenging because of the antibody cross-reactivity among flaviviruses. At the same time, the role of Nucleic Acid Testing (NAT) is limited by the low proportion of symptomatic infections and the low average viral load. Here, we compared the diagnostic performance of commercially available IgM, IgAM, and IgG ELISAs in sequential samples during the ZIKV and chikungunya (CHIKV) epidemics and co-circulation of dengue virus (DENV) in Brazil and Venezuela.

Methodology/principal Findings: Acute (day of illness 1-5) and follow-up (day of illness ≥ 6) blood samples were collected from nine hundred and seven symptomatic patients enrolled in a prospective multicenter study between June 2012 and August 2016. Acute samples were tested by RT-PCR for ZIKV, DENV, and CHIKV. Acute and follow-up samples were tested for IgM, IgAM, and IgG antibodies to ZIKV using commercially available ELISAs. Among follow-up samples with a RT-PCR confirmed ZIKV infection, anti-ZIKV IgAM sensitivity was 93.5% (43/46), while IgM and IgG exhibited sensitivities of 30.3% (10/33) and 72% (18/25), respectively. An additional 24% (26/109) of ZIKV infections were detected via IgAM seroconversion in ZIKV/DENV/CHIKV RT-PCR negative patients. The specificity of anti-ZIKV IgM was estimated at 93% and that of IgAM at 85%.

Conclusions/significance: Our findings exemplify the challenges of the assessment of test performance for ZIKV serological tests in the real-world setting, during co-circulation of DENV, ZIKV, and CHIKV. However, we can also demonstrate that the IgAM immunoassay exhibits superior sensitivity to detect ZIKV RT-PCR confirmed infections compared to IgG and IgM immunoassays. The IgAM assay also proves to be promising for detection of anti-ZIKV seroconversions in sequential samples, both in ZIKV PCR-positive as well as PCR-negative patients, making this a candidate assay for serological monitoring of pregnant women in future ZIKV outbreaks.
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http://dx.doi.org/10.1371/journal.pntd.0009336DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8084345PMC
April 2021

The Coutinho index as a simple tool for screening patients with advanced forms of Schistosomiasis mansoni: a validation study.

Trans R Soc Trop Med Hyg 2021 Mar 16. Epub 2021 Mar 16.

Instituto Aggeu Magalhães, Fundação Oswaldo Cruz, Recife-Pernambuco, 50670-420, Brasil.

Background: Periportal fibrosis (PPF) is the major pathological consequence of Schistosoma mansoni infection. The Coutinho index-the alkaline phosphatase (ALP) to platelet ratio ([ALP/upper limit of normality {ULN}]/platelet count [106/L] x 100)-was validated. Validation consisted of modest laboratory tests to predict advanced PPF.

Methods: A total of 378 individuals from an endemic area of Brazil with a previous history of the disease and/or a positive parasitological examination were evaluated. We used ultrasound examination as the gold standard for classification of the PPF pattern and measured the biological markers of the index.

Results: Forty-one individuals (10.8%) without PPF, 291 (77%) with moderate PPF and 46 (12.2%) with advanced PPF, were identified. ALP and platelet count were used for the index. The cut-off point ≥0.228 predicted the presence of fibrosis with an area under the receiver operating characteristic curve (AUROC) of 0.56, sensitivity of 68.6% and specificity of 46.3%. There was an absence of PPF in 46.3% of individuals without fibrosis and the presence of PPF in 68.5% of cases with moderate and advanced ultrasound fibrosis. The identification of advanced fibrosis with a cut-off point ≥0.316 revealed an AUROC curve of 0.70, sensitivity of 67.4% and specificity of 68.3%, thus confirming the advanced phase in 65.2% of cases compared with ultrasound.

Conclusion: The Coutinho index was able to predict advanced PPF in most individuals. It is valid as a new tool, uses routine laboratory tests and therefore is more accessible for screening patients with a severe form of the disease in endemic areas.
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http://dx.doi.org/10.1093/trstmh/trab040DOI Listing
March 2021

Follow-Up Household Serosurvey in Northeast Brazil for Zika Virus: Sexual Contacts of Index Patients Have the Highest Risk for Seropositivity.

J Infect Dis 2021 Feb;223(4):673-685

Arthropod-borne and Infectious Diseases Laboratory, Department of Microbiology, Pathology and Immunology, Colorado State University, Fort Collins, Colorado, USA.

Background: Zika virus (ZIKV) is a mosquito-borne virus that is also transmitted sexually; however, the epidemiological relevance of ZIKV sexual transmission in endemic regions is unclear.

Methods: We performed a household-based serosurvey in Northeast Brazil to evaluate the differential exposure to ZIKV and chikungunya virus (CHIKV) among households. Individuals who participated in our previous arboviral disease cohort (indexes) were recontacted and enrolled, and their household members were newly enrolled.

Results: The relative risk of sexual partners being ZIKV-seropositive when living with a ZIKV-seropositive index participant was significantly higher, whereas this was not observed among nonsexual partners of the index. For CHIKV, both sexual and nonsexual partner household members living with a CHIKV-seropositive index had a significantly higher risk of being seropositive. In the nonindex-based dyadic and generalized linear mixed model analyses, the odds of sexual dyads having a concordant ZIKV plaque reduction neutralization test result was significantly higher. We have also analyzed retrospective clinical data according to the participants' exposure to ZIKV and CHIKV.

Conclusions: Our data suggest that ZIKV sexual transmission may be a key factor for the high ZIKV seroprevalence among households in endemic areas and raises important questions about differential disease from the 2 modes of transmission.
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http://dx.doi.org/10.1093/infdis/jiaa563DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7904287PMC
February 2021

The P-MAPA Immunomodulator Partially Prevents Apoptosis Induced by Zika Virus Infection in THP-1 Cells.

Curr Pharm Biotechnol 2021 ;22(4):514-522

Department of Virology and Experimental Therapy, Aggeu Magalhaes Institute, Oswaldo Cruz Foundation/FIOCRUZ, Recife, Brazil.

Background: Zika virus is an emerging arbovirus of global importance. ZIKV infection is associated with a range of neurological complications such as the Congenital Zika Syndrome and Guillain Barré Syndrome. Despite the magnitude of recent outbreaks, there is no specific therapy to prevent or to alleviate disease pathology.

Objective: To investigate the role of P-MAPA immunomodulator in Zika-infected THP-1 cells.

Methods: THP-1 cells were subjected to Zika virus infection (Multiplicity of Infection = 0.5) followed by treatment with P-MAPA for until 96 hours post-infection. After that, the cell death was analyzed by annexin/ PI and caspase 3/ 7 staining by flow cytometry. In addition, virus replication and cell proliferation were accessed by RT-qPCR and Ki67 staining, respectively.

Results: We demonstrate that P-MAPA in vitro treatment significantly reduces Zika virus-induced cell death and caspase-3/7 activation on THP-1 infected cells, albeit it has no role in virus replication and cell proliferation.

Conclusion: Our study reveals that P-MAPA seems to be a satisfactory alternative to inhibit the effects of Zika virus infection in mammalian cells.
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http://dx.doi.org/10.2174/1389201021666200602140005DOI Listing
June 2021

Binding capacity of mannose-binding lectin (MBL) is associated with the severity of chronic Chagas cardiomyopathy.

Parasitol Int 2018 10 24;67(5):593-596. Epub 2018 May 24.

Aggeu Magalhães Institute, IAM-FIOCRUZ, PE, Brazil. Electronic address:

Chagas disease (CD) is a global problem. Currently, it affects approximately 15 million individuals in Latin America. It is well know that the human immune response is related to different clinical manifestations. Mannose binding lectin (MBL) plays an important role in innate immunity, and it mediates the phagocytosis and complement-mediated destruction of pathogens. The binding capacity is enhanced by the oligomerization of MBL. In this study, we evaluated the serum concentration and the binding capacity of MBL in patients with chronic chagasic cardiomyopathy. A total of 77 patients with chronic CD were included with indeterminate (n = 19), mild cardiac (n = 29) and severe cardiac (n = 29) forms. The serum concentration and the binding capacity were measured using enzyme-linked immunosorbent assays (ELISA). There was no significant difference in the serum MBL levels between the groups of patients. However, we found a relationship between the binding capacity and the groups studied. Our results suggest that binding capacity of MBL could be an indicator of clinical manifestation in Chronic Chagas cardiomyopathy. Furthermore, combined with the Mannose Binding Index results in a useful clinical tool for management of Chronic Chagas Patients.
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http://dx.doi.org/10.1016/j.parint.2018.05.009DOI Listing
October 2018

IL17A Polymorphism Is Not Associated with Human T-Lymphotropic Virus 1-Associated Myelopathy/Tropical Spastic Paraparesis.

Viral Immunol 2017 05 14;30(4):298-301. Epub 2017 Apr 14.

1 Department of Virology, Centro de Pesquisas Aggeu Magalhães (CPqAM) Research Center , Fundação Oswaldo Cruz (Fiocruz), Recife, Brazil .

The human T-lymphotropic virus 1 (HTLV-1) is the causative agent of HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). The present study investigated the association between the rs2275913 polymorphism in the IL17A gene and the development of HAM/TSP. Peripheral blood samples were collected from 116 patients (29 symptomatic patients with HAM/TSP and 87 asymptomatic) with a positive diagnosis of HTLV-1. The single nucleotide polymorphism genotyping was carried out by real time PCR using TaqMan probes. In addition, serum levels of IL-2, IFN-γ, TNF-α, IL-4, IL-6, IL-10, and IL-17 were measured in 64 infected individuals from the study (47 asymptomatic and 17 HAM/TSP), using cytometric bead array technique. No significant differences were found in genotypic and allelic frequencies between the groups. Analysis of cytokine levels showed highest concentrations of IFN-γ and TNF-α in HAM/TSP patients. The results of the present study, therefore, suggest a lack of association between the rs2275913 polymorphism in the IL17A gene and the presence of HAM/TSP.
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http://dx.doi.org/10.1089/vim.2016.0152DOI Listing
May 2017

Genetic susceptibility to chronic Chagas disease: an overview of single nucleotide polymorphisms of cytokine genes.

Cytokine 2012 Aug 15;59(2):203-8. Epub 2012 May 15.

Department of Immunology, Centro de Pesquisas Aggeu Magalhães, Recife, Brazil.

Chagas disease is a parasitic infection that is a significant public health problem in Latin America. The mechanisms responsible for susceptibility to the infection and the mechanisms involved in the development of cardiac and digestive forms of chronic Chagas disease remain poorly understood. However, there is growing evidence that differences in susceptibility in endemic areas may be attributable to host genetic factors. The aim of this overview was to analyze the genetic susceptibility to human Chagas disease, particularly that of single nucleotide polymorphisms of cytokine genes. A review of the literature was conducted on the following databases: PubMed/MEDLINE and Scopus. The search strategy included using the following terms: "Cytokines", "Single Nucleotide Polymorphisms" and "Chagas Disease". After screening 25 citations from the databases, 19 studies were selected for the overview. A critical analysis of the data presented in the articles suggests that genetic susceptibility to Chagas disease and chronic Chagas cardiomyopathy is highly influenced by the complexity of the immune response of the host. Follow-up studies based on other populations where Chagas disease is endemic (with distinct ethnic and genetic backgrounds) need to be conducted. These should use a large sample population so as to establish what cytokine genes are involved in susceptibility to and/or progression of the disease.
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http://dx.doi.org/10.1016/j.cyto.2012.04.035DOI Listing
August 2012

Immunoglobulin M antibodies against CRA and FRA recombinant antigens of Trypanosoma cruzi in chronic chagasic patients.

Hum Immunol 2011 May 1;72(5):402-5. Epub 2011 Mar 1.

Departamento de Imunologia, Centro de Pesquisas Aggeu Magalhães/Fiocruz, Recife, Brazil.

Previous works of our research group have demonstrated aspects of the humoral immune response of chronic Chagas disease using the cytoplasmatic repetitive antigen (CRA) and the flagellar repetitive antigen (FRA) of Trypanosoma cruzi. The aim of this work was to analyze the presence of specific immunoglobulin M (IgM) antibodies in chronic chagasic patients using these recombinant antigens of T. cruzi. The positivity of IgM in chronic chagasic patients against CRA and FRA antigens was determined by indirect enzyme-linked immunosorbent assay. We reported no statistical significant differences between the levels of IgM for both recombinant antigens and the different chronic clinical forms of Chagas disease. However, a small proportion of chronic chagasic patients analyzed in this study was positive for this antibody isotype. The findings of this study indicate that the IgM antibodies cannot be used to elucidate the differences in the profile of humoral immune response among chronic chagasic patients with different clinical forms using the CRA and FRA recombinant antigens of T. cruzi.
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http://dx.doi.org/10.1016/j.humimm.2011.02.015DOI Listing
May 2011

Increased levels of IgA antibodies against CRA and FRA recombinant antigens of Trypanosoma cruzi differentiate digestive forms of Chagas disease.

Hum Immunol 2010 Oct 24;71(10):964-7. Epub 2010 Jul 24.

Departamento de Imunologia, Instituto Aggeu Magalhães/Fiocruz, Recife, Pernambuco, Brazil.

In the chronic phase of Chagas disease, individuals infected by Trypanosoma cruzi may be asymptomatic or may present cardiac and/or digestive complications. Our aim here was to analyze the relationship between the presence of specific immunoglobulin A antibodies and the different chronic clinical forms of Chagas disease using two recombinant antigens of Trypanosoma cruzi, cytoplasmatic repetitive antigen and flagellar repetitive antigen. The association of this immunoglobulin isotype with the digestive and cardio-digestive forms of the disease determined by indirect enzyme-linked immunosorbent assay, strongly suggests that IgA antibodies against these recombinant antigens of T. cruzi can be used as an immunological marker of the digestive alterations caused by Chagas disease. The tests performed in this study show that it is possible to differentiate digestive forms of Chagas disease. The knowledge provided by these results may help physicians to manage early alterations in the digestive tract of patients with the indeterminate or cardiac forms of Chagas disease. Prospective studies, however, with follow-up of the patients that presenting with high levels of immunoglobulin A against cytoplasmatic repetitive antigen and flagellar repetitive antigen recombinant antigens, need to be conducted to confirm this hypothesis.
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http://dx.doi.org/10.1016/j.humimm.2010.07.004DOI Listing
October 2010

[Serum globulin levels and intensity of hepatic fibrosis in patients with mansonic schistosomiasis].

Arq Gastroenterol 2009 Jul-Sep;46(3):194-8

Estudo desenvolvido no Ambulatório de Esquistossomose e no Laboratório Central do Hospital das Clínicas da Universidade Federal de Pernambuco, Recife, PE.

Background: A correlation between the levels of serum globulins and the hepatic fibrosis degree in chronic hepatitis was described, but reports in schistosomiasis mansoni have not been found.

Objective: To evaluate the serum globulins and IgG levels, and periportal fibrosis intensity measured by ultrasound in patients with schistosomiasis mansoni.

Methods: Between November, 2006 and February 2007, 41 patients which were eligible, filled them a questionnaire and had their levels of serum IgG measured by immunoturbidimetry and globulins indirectly measured by the Biuret method. The ultrasound was carried out by a single researcher, according to the Cairo and Niamey protocols.

Results: The average age was 41 years old and 25 female patients (61%). Ten patients (24%) from 41 showed serum globulins levels raised and 21 (51%) presented elevated IgG levels. According to the Cairo classification, 21 patients showed grade I of fibrosis, 18 grade II and 2 grade III; and by the Niamey classification 8 showed standard C, 20 D, and 13 E. Those with grade II or III of fibrosis had higher IgG levels than the ones with grade I (P = 0.047), as well as those who showed standards D and E as compared to C (P = 0.011). There was no association between the globulins levels and the intensity of fibrosis.

Conclusion: In patients with schistosomiasis mansoni, an increase of the IgG serum levels was observed according to the progression from periportal fibrosis intensity, but the same was not founded with globulins levels.
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http://dx.doi.org/10.1590/s0004-28032009000300010DOI Listing
March 2010

Treatment of human acute schistosomiasis with oxamniquine induces an increase in interferon-gamma response to Schistosoma mansoni antigens.

Mem Inst Oswaldo Cruz 2007 May;102(2):225-8

Departamento de Bioquímica, Universitária, 52020-020 Recife, PE, Brasil.

Patients with acute schistosomiasis were studied before and after oxamniquine treatment. They had been exposed to cercariae 5 to 9 weeks before, and presented compatible clinical manifestations, eosinophilia, and high levels of total IgE. Interferon-gamma (IFN-gamma) and interleukin-4 were measured by ELISA in whole blood samples under soluble egg antigen or soluble adult worm preparation stimulation. After treatment, the reduction of leukocytosis and eosinophilia were not significant, but total IgE levels decreased significantly, in contrast to IFN-gamma levels that were significantly increased. The oxamniquine treatment of acute schistosomiasis patients is followed by an improvement of a Th1 response in vitro. If this response has a protective aspect is unknown, and some investigations need to be realized.
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http://dx.doi.org/10.1590/s0074-02762007005000002DOI Listing
May 2007

Preliminar evaluation of cytokines in the hepatitis C-schistosomiasis co-infection.

Mem Inst Oswaldo Cruz 2006 Sep;101 Suppl 1:353-4

Centro de Pesquisas Aggeu Magalhães-Fiocruz, Av. Prof. Moraes Rego, 52020-020 Recife, PE, Brazil.

Evaluation of hepatic fibrosis is usually performed by histopathological examination of biopsies. However, this is an invasive and potentially dangerous procedure. Several studies have proposed serum biological markers of hepatic fibrosis. This communication evaluates the use of serum cytokines as markers of hepatic fibrosis in hepatitis C, schistosomiasis, and co-infection.
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http://dx.doi.org/10.1590/s0074-02762006000900057DOI Listing
September 2006

Immunopathogenic mechanisms in schistosomiasis: what can be learnt from human studies?

Trends Parasitol 2006 Feb 27;22(2):85-91. Epub 2005 Dec 27.

Departamento de Imunologia, Centro de Pesquisas Aggeu Magalhães, Fundação Oswaldo Cruz, Avenida Professor Moraes Rego s/n, Cidade Universitária, 50670-420 Recife, Brazil.

Studies in mice indicate that schistosome egg-induced granuloma formation and hepatic fibrosis depend markedly on cytokine regulation, with interleukin 10 having a central role. There is no clear consensus about the pattern of cytokine production and regulation that causes a minority of chronically exposed patients to develop severe hepatosplenic (HS) disease, which is characterized by periportal fibrosis and portal hypertension. HS disease and the progression of hepatic fibrosis are associated with the production of profibrotic type 2 cytokines in the early stages of infection with Schistosoma mansoni. However, other studies indicate that HS disease is characterized by a predominant T helper 1 profile. Until new tools and approaches are developed to study human disease in endemic areas, investigators must either speculate about indirect evidence from human studies or rely more heavily on findings generated from experimental models of the disease.
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http://dx.doi.org/10.1016/j.pt.2005.12.004DOI Listing
February 2006

Enhanced interleukin-12 and CD40 ligand activities but reduced Staphylococcus aureus Cowan 1-induced responses suggest a generalized and progressively impaired type 1 cytokine pattern for human schistosomiasis.

Infect Immun 2002 Nov;70(11):5903-12

Departamento de Imunologia, Centro de Pesquisas Aggeu Magalhães-FIOCRUZ. Universidade Federal de Pernambuco, Recife, Brazil.

Whole-blood-cell cultures from schistosomiasis patients were stimulated with a variety of T-cell-dependent and T-cell-independent stimuli to determine whether the defect in type 1 cytokine expression observed following helminth infection is associated with alterations in interleukin-12 (IL-12) or CD40 ligand (CD40L) responsiveness. Cultures from uninfected individuals produced abundant gamma interferon in response to Staphylococcus aureus Cowan 1 (SAC), while patients with intestinal and hepatosplenic disease displayed intermediate and weak responses, respectively. Importantly, the decrease in type 1 cytokine expression was not attributed to defects in IL-12- or CD40L-induced activity. Indeed, schistosomiasis patients displayed heightened responses and even produced more biologically active IL-12 when stimulated with SAC and CD40L than did uninfected controls. Finally, additional studies suggested only a partial role for IL-10, since intestinal patients were the only group that overproduced this downregulatory cytokine. Together, these studies demonstrate that the type 1 deficiency in chronic hepatosplenic schistosomiasis is not related to specific defects in IL-12, IL-10, or CD40L activity, although changes in the functional status of antigen-presenting cells appear to be involved.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC130279PMC
http://dx.doi.org/10.1128/IAI.70.11.5903-5912.2002DOI Listing
November 2002
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