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Introducción: La provincia de Chincha reportó 4,317 casos de infección por virus Zika (ZIKV) durante el 2017. Debido a que 62% de casos de Zika son asintomáticos es importante estimar el estado de seroprevalencia en la población ya que existen estudios que sugieren protección inmunológica a infecciones futuras. El objetivo del estudio fue estimar la seroprevalencia de ZIKV y sus factores asociados en dos distritos de Chincha. Metodología: Estudio transversal realizado entre marzo y mayo del 2019 en los distritos de Chincha Baja (CB) y Pueblo Nuevo (PN); este último fue el distrito con más casos reportados de Zika en el brote del 2017. La población fueron participantes de ambos sexos, entre 20 a 40 años, residentes de sus distritos mínimo 1 año sin viajes mayores a 1 mes durante dicho periodo. Se registraron variables demográficas, antecedentes, y factores de riesgo para infección por arbovirus y se analizaron las muestras para IgG anti-ZIKV. Resultados: Se enrolaron 400 participantes, siendo 78.8% del sexo femenino. Se encontró una prevalencia de 10.3% para IgG-anti ZIKV entre ambos distritos, siendo 17.6% y 3% en PN y CB, respectivamente. Los residentes de PN tienen 5.83 veces la prevalencia de IgG anti-ZIKV positivo en comparación a la población de CB (IC95% 2.51 - 13.56, p < 0.001). Ingresos mensuales menores al sueldo mínimo (RP: 2.76; IC95% 1.34 - 5.71), antecedente personal y familiar de fiebre y rash (RP:5.49, IC95% 3.16 - 9.55; RP:2.56, IC95% 1.41 - 4.67, respectivamente) se asociaron a títulos de IgG positivo. Conclusiones: La prevalencia en Chincha es similar a la reportada en otro países de Latinoamérica. Se debe fomentar métodos de protección contra vectores y formular estrategias de prevención ante la posibilidad de un futuro brote en CB. 2019-09-05

Background The European Commission (EC) Horizon 2020 (H2020)-funded ZIKAlliance Consortium designed a multicentre study including pregnant women (PW), children (CH) and natural history (NH) cohorts. Clinical sites were selected over a wide geographic range within Latin America and the Caribbean, taking into account the dynamic course of the ZIKV epidemic. Methods Recruitment to the PW cohort will take place in antenatal care clinics. PW will be enrolled regardless of symptoms and followed over the course of pregnancy, approximately every 4 weeks. PW will be revisited at delivery (or after miscarriage/abortion) to assess birth outcomes, including microcephaly and other congenital abnormalities according to the evolving definition of congenital Zika syndrome (CZS). After birth, children will be followed for 2 years in the CH cohort. Follow-up visits are scheduled at ages 1–3, 4–6, 12, and 24 months to assess neurocognitive and developmental milestones. In addition, a NH cohort for the characterization of symptomatic rash/fever illness was designed, including follow-up to capture persisting health problems. Blood, urine, and other biological materials will be collected, and tested for ZIKV and other relevant arboviral diseases (dengue, chikungunya, yellow fever) using RT-PCR or serological methods. A virtual, decentralized biobank will be created. Reciprocal clinical monitoring has been established between partner sites. Substudies of ZIKV seroprevalence, transmission clustering, disabilities and health economics, viral kinetics, the potential role of antibody enhancement, and co-infections will be linked to the cohort studies. Discussion Results of these large cohort studies will provide better risk estimates for birth defects and other developmental abnormalities associated with ZIKV infection including possible co-factors for the variability of risk estimates between other countries and regions. Additional outcomes include incidence and transmission estimates of ZIKV during and after pregnancy, characterization of short and long-term clinical course following infection and viral kinetics of ZIKV. Study registrations clinicaltrials.gov NCT03188731 (PW cohort), June 15, 2017; clinicaltrials.gov NCT03393286 (CH cohort), January 8, 2018; clinicaltrials.gov NCT03204409 (NH cohort), July 2, 2017.

p. 1-15 Submitted by Edileide Reis (leyde-landy@hotmail.com) on 2014-08-19T14:50:24Z No. of bitstreams: 1 Ricardo Khouri.pdf: 730046 bytes, checksum: 97e66f8a63252afb3abb035fbba7cc97 (MD5) Approved for entry into archive by Delba Rosa (delba@ufba.br) on 2014-08-22T14:38:43Z (GMT) No. of bitstreams: 1 Ricardo Khouri.pdf: 730046 bytes, checksum: 97e66f8a63252afb3abb035fbba7cc97 (MD5) Made available in DSpace on 2014-08-22T14:38:43Z (GMT). No. of bitstreams: 1 Ricardo Khouri.pdf: 730046 bytes, checksum: 97e66f8a63252afb3abb035fbba7cc97 (MD5) Previous issue date: 2012-07 Background Clear therapeutic guidelines for HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) are missing due to the lack of randomized double-blind controlled clinical trials. Moderate yet similar clinical benefit has been demonstrated for IFN-α and high-dose ascorbic acid (AA) monotherapy in a large open clinical trial. However, there is a lack of in vivo and in vitro studies exploring and comparing the effects of high-dose AA and IFN-α treatment in the context of HAM/TSP. Therefore, we performed the first comparative analysis of the ex vivo and in vitro molecular and cellular mechanisms of action of IFN-α and high-dose AA in HAM/TSP. Principal Findings Through thymidine incorporation and quantification of Th1/Th2/Th17 cytokines, we demonstrate that high-dose AA displays differential and superior antiproliferative and immunomodulatory effects over IFN-α in HAM/TSP PBMCs ex vivo. In addition, high-dose AA, but not IFN-α, induced cell death in both HAM/TSP PBMCs and HTLV-1-infected T-cell lines MT-2 and MT-4. Microarray data combined with pathway analysis of MT-2 cells revealed AA-induced regulation of genes associated with cell death, including miR-155. Since miR-155 has recently been demonstrated to up-regulate IFN-γ, this microRNA might represent a novel therapeutic target in HAM/TSP, as recently demonstrated in multiple sclerosis, another neuroinflammatory disease. On the other hand, IFN-α selectively up-regulated antiviral and immune-related genes. Conclusions In comparison to IFN-α, high-dose AA treatment has superior ex vivo and in vitro cell death-inducing, antiproliferative and immunomodulatory anti-HTLV-1 effects. Differential pathway activation by both drugs opens up avenues for targeted treatment in specific patient subsets.

p. 1-15 Submitted by Edileide Reis (leyde-landy@hotmail.com) on 2014-08-19T14:50:24Z No. of bitstreams: 1 Ricardo Khouri.pdf: 730046 bytes, checksum: 97e66f8a63252afb3abb035fbba7cc97 (MD5) Approved for entry into archive by Delba Rosa (delba@ufba.br) on 2014-08-22T14:38:43Z (GMT) No. of bitstreams: 1 Ricardo Khouri.pdf: 730046 bytes, checksum: 97e66f8a63252afb3abb035fbba7cc97 (MD5) Made available in DSpace on 2014-08-22T14:38:43Z (GMT). No. of bitstreams: 1 Ricardo Khouri.pdf: 730046 bytes, checksum: 97e66f8a63252afb3abb035fbba7cc97 (MD5) Previous issue date: 2012-07 Background Clear therapeutic guidelines for HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) are missing due to the lack of randomized double-blind controlled clinical trials. Moderate yet similar clinical benefit has been demonstrated for IFN-α and high-dose ascorbic acid (AA) monotherapy in a large open clinical trial. However, there is a lack of in vivo and in vitro studies exploring and comparing the effects of high-dose AA and IFN-α treatment in the context of HAM/TSP. Therefore, we performed the first comparative analysis of the ex vivo and in vitro molecular and cellular mechanisms of action of IFN-α and high-dose AA in HAM/TSP. Principal Findings Through thymidine incorporation and quantification of Th1/Th2/Th17 cytokines, we demonstrate that high-dose AA displays differential and superior antiproliferative and immunomodulatory effects over IFN-α in HAM/TSP PBMCs ex vivo. In addition, high-dose AA, but not IFN-α, induced cell death in both HAM/TSP PBMCs and HTLV-1-infected T-cell lines MT-2 and MT-4. Microarray data combined with pathway analysis of MT-2 cells revealed AA-induced regulation of genes associated with cell death, including miR-155. Since miR-155 has recently been demonstrated to up-regulate IFN-γ, this microRNA might represent a novel therapeutic target in HAM/TSP, as recently demonstrated in multiple sclerosis, another neuroinflammatory disease. On the other hand, IFN-α selectively up-regulated antiviral and immune-related genes. Conclusions In comparison to IFN-α, high-dose AA treatment has superior ex vivo and in vitro cell death-inducing, antiproliferative and immunomodulatory anti-HTLV-1 effects. Differential pathway activation by both drugs opens up avenues for targeted treatment in specific patient subsets.

p. 1-15 Submitted by Edileide Reis (leyde-landy@hotmail.com) on 2014-07-16T11:52:51Z No. of bitstreams: 1 Achiléa Bittencourt.pdf: 1561034 bytes, checksum: 891e9491b8c19acf3073a5c4c4d4eecf (MD5) Approved for entry into archive by Flávia Ferreira (flaviaccf@yahoo.com.br) on 2014-08-11T15:38:05Z (GMT) No. of bitstreams: 1 Achiléa Bittencourt.pdf: 1561034 bytes, checksum: 891e9491b8c19acf3073a5c4c4d4eecf (MD5) Made available in DSpace on 2014-08-11T15:38:05Z (GMT). No. of bitstreams: 1 Achiléa Bittencourt.pdf: 1561034 bytes, checksum: 891e9491b8c19acf3073a5c4c4d4eecf (MD5) Previous issue date: 2012 Background IFN-α contributes extensively to host immune response upon viral infection through antiviral, pro-apoptotic, antiproliferative and immunomodulatory activities. Although extensively documented in various types of human cancers and viral infections, controversy exists in the exact mechanism of action of IFN-α in human immunodeficiency virus type 1 (HIV-1) and human T-lymphotropic virus type 1 (HTLV-1) retroviral infections. Results IFN-α displayed strong anti-HIV-1 effects in HIV-1/HTLV-1 co-infected MT-4 cells in vitro, demonstrated by the dose-dependent inhibition of the HIV-1-induced cytopathic effect (IC50 = 83.5 IU/ml, p

Dengue virus (DENV) is the causative agent of dengue fever (DF), the most prevalent arthropod-borne viral disease worldwide. DF presents with non-specific symptoms similar to other febrile diseases that overlap geographically. Therefore, diagnosis cannot be made on clinical and epidemiological data alone and thus require laboratory techniques for case confirmation. Antibody-based assays are simple, affordable, applicable at the point of care and offer a wide diagnostic window. However, the high genetic similarity of DENV serotypes and also with other flaviviruses such as Zika, results in cross-reactive (CR) antibodies complicating serological diagnostics. Consequently, the search for and selection of appropriate biomaterials that enable capturing of highly specific anti-DENV antibodies is crucial to improve dengue diagnosis. The main objective of this PhD thesis was to (1) delineate the dynamics of the antibody responses against DENV at epitope level, (2) to identify regions able to capture DENV-specific Abs, and (3) investigate the value of these biomaterials for diagnostic purposes. The characterization of the temporal evolution of the IgG and IgM response following dengue infection was done using a high-density peptide microarray spanning the entire proteomes and diversity of DENV1-4, Zika (ZIKV) and yellow fever virus (YFV). Sera from a cohort of dengue infected individuals from Peru, as representatives for secondary infections, and overseas travelers, as representatives for primary infections, were used. We found that reactive linear epitopes were located across the proteome both in structural proteins and in non-structural proteins and were targeted by either IgM and/or IgG antibodies. Subsequent analysis of the antibody response against the peptide libraries from DENV, ZIKV and YFV and the further alignment of the highly immunoreactive regions onto the DENV proteome allowed the identification of 15 and 12 DENV-type-specific epitopes and 13 and 12 flavivirus-CR epitopes, targeted by IgM and IgG antibodies, respectively. The diagnostic potential of 20 peptides was further assessed using a bead-based multiplex peptide immunoassay on a large panel of carefully selected human serum samples. Individual peptides offered satisfactory diagnostic performance, but the combination of multiple peptides and using a machine learning algorithm substantially improved the sensitivity and specificity of the assay. In summary, this work has mapped in great detail the immunodominant linear epitopes across the DENV polyprotein and provided proof-of-concept that this approach offers clear potential for the development of highly accurate next-generation dengue serological tests.