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2. Zika virus epidemic in Brazil. I. Fatal disease in adults: Clinical and laboratorial aspects

Author

Azevedo, Raimunda S.S., Araujo, Marialva T., Martins Filho, Arnaldo J., Oliveira, Consuelo S., Nunes, Bruno T.D., Cruz, Ana C.R., Nascimento, Ana G.P.A.C., Medeiros, Rita C., Caldas, Cezar A.M., Araujo, Fernando C., Quaresma, Juarez A.S., Vasconcelos, Barbara C.B., Queiroz, Maria G.L., da Rosa, Elizabeth S. Travassos, Henriques, Daniele F., Silva, Eliana V.P., Chiang, Jannifer O., Martins, Lívia C., Medeiros, Daniele B.A., Lima, Juliana A., Nunes, Márcio R.T., Cardoso, Jedson F., Silva, Sandro P., Shi, Pei-Yong, Tesh, Robert B., Rodrigues, Sueli G., and Vasconcelos, Pedro F.C.

Published
2016
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5. Zika Virus Epidemic in Brazil. II. Post-Mortem Analyses of Neonates with Microcephaly, Stillbirths, and Miscarriage

Author

Azevedo, Raimunda S.S., primary, Araujo, Marialva T., additional, Oliveira, Consuelo S., additional, Filho, Arnaldo Jorge Martins, additional, Nunes, Bruno T.D., additional, Henriques, Daniele F., additional, Silva, Eliana V.P., additional, Carvalho, Valéria L., additional, Chiang, Jannifer O., additional, Martins, Lívia C., additional, Vasconcelos, Barbara C.B., additional, Sousa, Jorge R., additional, Araujo, Fernanda Montenegro C., additional, Ribeiro, Erlane M., additional, Castro, Andrezza R.P., additional, de Queiroz, Maria G. L., additional, Verotti, Mariana P., additional, Nunes, Márcio R.T., additional, Cruz, Ana C.R., additional, Rodrigues, Sueli G., additional, Shi, Pei-Yong, additional, Quaresma, Juarez A.S., additional, Tesh, Robert B., additional, and Vasconcelos, Pedro F.C., additional

Published
2018
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6. In situ immune response and mechanisms of cell damage in central nervous system of fatal cases microcephaly by Zika virus

Author

Azevedo, Raimunda S. S., primary, de Sousa, Jorge R., additional, Araujo, Marialva T. F., additional, Martins Filho, Arnaldo J., additional, de Alcantara, Bianca N., additional, Araujo, Fernanda M. C., additional, Queiroz, Maria G. L., additional, Cruz, Ana C. R., additional, Vasconcelos, Beatriz H. Baldez, additional, Chiang, Jannifer O., additional, Martins, Lívia C., additional, Casseb, Livia M. N., additional, da Silva, Eliana V., additional, Carvalho, Valéria L., additional, Vasconcelos, Barbara C. Baldez, additional, Rodrigues, Sueli G., additional, Oliveira, Consuelo S., additional, Quaresma, Juarez A. S., additional, and Vasconcelos, Pedro F. C., additional

Published
2018
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7. A human inferred germline antibody binds to an immunodominant epitope and neutralizes Zika virus

Author

Magnani, Diogo M., primary, Silveira, Cassia G. T., additional, Rosen, Brandon C., additional, Ricciardi, Michael J., additional, Pedreño-Lopez, Núria, additional, Gutman, Martin J., additional, Bailey, Varian K., additional, Maxwell, Helen S., additional, Domingues, Aline, additional, Gonzalez-Nieto, Lucas, additional, Avelino-Silva, Vivian I., additional, Trindade, Mateus, additional, Nogueira, Juliana, additional, Oliveira, Consuelo S., additional, Maestri, Alvino, additional, Felix, Alvina Clara, additional, Levi, José Eduardo, additional, Nogueira, Mauricio L., additional, Martins, Mauricio A., additional, Martinez-Navio, José M., additional, Fuchs, Sebastian P., additional, Whitehead, Stephen S., additional, Burton, Dennis R., additional, Desrosiers, Ronald C., additional, Kallas, Esper G., additional, and Watkins, David I., additional

Published
2017
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8. Correlation between Apoptosis and in SituImmune Response in Fatal Cases of Microcephaly Caused by Zika Virus

Author

de Sousa, Jorge R., Azevedo, Raimunda S.S., Martins Filho, Arnaldo J., Araujo, Marialva T.F., Moutinho, Ermelinda R.C., Baldez Vasconcelos, Barbara C., Cruz, Ana C.R., Oliveira, Consuelo S., Martins, Lívia C., Baldez Vasconcelos, Beatriz H., Casseb, Livia M.N., Chiang, Jannifer O., Quaresma, Juarez A.S., and Vasconcelos, Pedro F.C.

Abstract

Zika virus (ZIKV) is a single-stranded positive-sense RNA flavivirus that possesses a genome approximately 10.7 Kb in length. Although pro-inflammatory and anti-inflammatory cytokines and apoptotic markers belonging to the extrinsic and intrinsic pathways are suggested to be involved in fatal cases of ZIKV-induced microcephaly, their exact roles and associations are unclear. To address this, brain tissue samples were collected from 10 individuals, five of whom were diagnosed as ZIKV positive with microcephaly and a further five were flavivirus-negative controls that died because of other causes. Examination of material from the fatal cases of microcephaly revealed lesions in the cerebral cortex, edema, vascular proliferation, neuronal necrosis, gliosis, neuronophagy, calcifications, apoptosis, and neuron loss. The expression of various apoptosis markers in the neural parenchyma, including FasL, FAS, BAX, BCL2, and caspase 3 differed between ZIKV-positive cases and controls. Further investigation of type 1 and 2 helper T-cell cytokines confirmed a greater anti-inflammatory response in fatal ZIKV-associated microcephaly cases. Finally, an analysis of the linear correlation between tumor necrosis factor-α, IL-1β, IL-4, IL-10, transforming growth factor-β, and IL-33 expression and various apoptotic markers suggested that the immune response may be associated with the apoptotic phenomenon observed in ZIKV-induced microcephaly.

Published
2018
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9. Nutritional status in relation to the efficacy of the rhesus-human reassortant, tetravalent rotavirus vaccine (RRV-TV) in infants from Belém, Pará State, Brazil

Author

LINHARES, Alexandre C., CARMO, Kênea B. do, OLIVEIRA, Krynssya K., OLIVEIRA, Consuelo S., FREITAS, Ronaldo B. de, BELLESI, Newton, MONTEIRO, Talita A.F., GABBAY, Yvone B., and MASCARENHAS, Joana D'Arc P.

Subjects
Rotavirus, Nutritional status, Vaccine
Abstract

The rhesus-human reassortant, tetravalent rotavirus vaccine (RRV-TV) was licensed for routine use in the United States of America but it was recently withdrawn from the market because of its possible association with intussusception as an adverse event. The protective efficacy of 3 doses of RRV-TV, in its lower-titer (4 x 10(4) pfu/dose) formulation, was evaluated according to the nutritional status of infants who participated in a phase III trial in Belém, Northern Brazil. A moderate protection conferred by RRV-TV was related to weight-for-age Z-scores (WAZ) greater than -1 only, with rates of 38% (p = 0.04) and 40% (p = 0.04) for all- and- pure rotavirus diarrhoeal cases, respectively. In addition, there was a trend for greater efficacy (43%, p = 0.05) among infants reaching an height-for-age Z-score (HAZ) of > -1. Taking WAZ, HAZ and weight-for-height Z-score (WHZ) indices 0.05) if both placebo and vaccine groups are compared. There was no significant difference if rates of mixed and pure rotavirus diarrhoeal cases are compared in relation to HAZ, WAZ and weight-for-height Z-score (WHZ) indices. Although a low number of malnourished infants could be identified in the present study, our data show some evidence that malnutrition may interfere with the efficacy of rotavirus vaccines in developing countries. A vacina tetravalente contra rotavírus de origem símio-humana, geneticamente rearranjada (RRV-TV), foi licenciada para uso rotineiro nos Estados Unidos da América do Norte; entretanto, tal imunizante foi removido do mercado, uma vez que a intussuscepção emergiu como possível evento adverso vacinal. A eficácia da RRV-TV - em sua formulação menos concentrada (10 x 10(4) pfu/dose) - foi avaliada no tocante ao estado nutricional das crianças que integraram estudo caracterizado como de fase III, levado a efeito em Belém, região norte do Brasil. Observou-se proteção (moderada) apenas entre os indivíduos com escore "Z" (peso-por-idade, WAZ) superior a -1, com eficácias de 38% (p = 0,04) e 40% (p = 0,04) para todos os episódios de diarréia por rotavírus e os caracterizados como "puros" (sem outro enteropatógeno identificado no espécime clínico), respectivamente. A par disso, denotou-se tendência a mais elevados níveis protetores (43%, p = 0.05) entre crianças que apresentavam escore "Z" (estatura-por-idade, HAZ) > -1. Considerando-se conjuntamente os escores "Z" [WAZ, HAZ e peso-por-estatura (WHZ)] menores ou iguais a -1, não se registrou proteção significativa (p > 0,05), uma vez comparadas as crianças que receberam placebo àquelas vacinadas. Também não resultaram expressivas as diferenças, se as infecções "puras" e "mistas" por rotavírus são comparadas relativamente às variáveis antropométricas HAZ, WAZ e WHZ. Não obstante o reduzido número de infantes desnutridos no presente estudo, os resultados disponíveis oferecem evidências de que o estado nutricional pode interferir na eficácia das vacinas contra rotavírus nos países em desenvolvimento.

Published
2002

10. Oral live attenuated human rotavirus vaccine (RotarixTM) offers sustained high protection against severe G9P[8] rotavirus gastroenteritis during the first two years of life in Brazilian children

Author

Justino, Maria Cleonice A, primary, Araújo, Eliete C, additional, van Doorn, Leen-Jan, additional, Oliveira, Consuelo S, additional, Gabbay, Yvone B, additional, Mascarenhas, Joana D'Arc P, additional, Miranda, Yllen S, additional, Guerra, Sylvia de Fátima S, additional, Silva, Veronilce B da, additional, and Linhares, Alexandre C, additional

Published
2012
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11. Segurança, imunogenicidade e eficácia protetora de duas doses da vacina RIX4414 contendo rotavírus atenuado de origem humana

Author

Araujo, Eliete C., primary, Clemens, Sue Ann C., additional, Oliveira, Consuelo S., additional, Justino, Maria Cleonice A., additional, Rubio, Pilar, additional, Gabbay, Yvone B., additional, Silva, Veronilce B. da, additional, Mascarenhas, Joana D. P., additional, Noronha, Vânia L., additional, Clemens, Ralf, additional, Gusmão, Rosa Helena P., additional, Sanchez, Nervo, additional, Monteiro, Talita Antônia F., additional, and Linhares, Alexandre C., additional

Published
2007
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12. Safety, immunogenicity, and protective efficacy of two doses of RIX4414 live attenuated human rotavirus vaccine in healthy Brazilian infants

Author

Araujo, Eliete C., primary, Clemens, Sue Ann C., additional, Oliveira, Consuelo S., additional, Justino, Maria Cleonice A., additional, Rubio, Pilar, additional, Gabbay, Yvone B., additional, Silva, Veronilce B. da, additional, Mascarenhas, Joana D. P., additional, Noronha, Vânia L., additional, Clemens, Ralf, additional, Gusmão, Rosa Helena P., additional, Sanchez, Nervo, additional, Monteiro, Talita Antônia F., additional, and Linhares, Alexandre C., additional

Published
2007
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15. Prospective study of rotavirus infections in Belém, Pará, Brazil: clinical and epidemiological features

Author

Linhares, Alexandre C., primary, Gabbay, Yvone B., additional, Mascarenhas, Joana D’Arc P., additional, Freitas, Ronaldo B. de, additional, Oliveira, Consuelo S., additional, Bellesi, Newton, additional, Monteiro, Talita F., additional, Lins-Lainson, Zéa, additional, Ramos, Francisco L. P., additional, and Valente, Sebastião A., additional

Published
1994
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18. Risk of Zika virus-associated birth defects in congenital confirmed cases in the Brazilian Amazon.

Author

de Oliveira CS, de Matos HJ, Ramos FLP, Pinto AYDN, Graim PNDS, Guimarães VPR, Gomes LTS, Serra EMF, Cruz AC, Leal A, Henriques DF, Lima JA, Anjos MV, Pinto EV, de Souza AW, and Vasconcelos PFDC

Abstract

Objective: To establish the risk of microcephaly in neonates born to women infected with ZIKV during pregnancy., Methods: A cohort of laboratory-confirmed ZIKV cases of congenital infections (109 mothers infected during pregnancy and 101 newborns) among 308 suspect cases was followed in Belem, Pará, Brazil, from October 2015 to December 2017., Results: A microcephaly risk of 1.98% (95% CI 0.54-6.93%) was found, or 2 cases among the 101 neonates infected with ZIKV during pregnancy. 72% of the pregnant women had ZIKV infection confirmed by RT-qPCR during gestation., Conclusions: Results showed a low incidence of ZIKV-associated birth defects, stillbirth, and miscarriage, which contrasts with previous studies in other Brazilian regions. Previous exposure to yellow fever vaccine and/or multiserotype DENV infection could be implicated in the protection from ZIKV congenital infection.

Published
2020
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19. Safety, immunogenicity, and protective efficacy of two doses of RIX4414 live attenuated human rotavirus vaccine in healthy infants.

Author

Araujo EC, Clemens SA, Oliveira CS, Justino MC, Rubio P, Gabbay YB, da Silva VB, Mascarenhas JD, Noronha VL, Clemens R, Gusmão RH, Sanchez N, Monteiro TA, and Linhares AC

Subjects
Brazil, Double-Blind Method, Gastroenteritis virology, Humans, Infant, Mexico, Rotavirus immunology, Rotavirus Vaccines, Severity of Illness Index, Vaccines, Attenuated adverse effects, Vaccines, Attenuated immunology, Venezuela, Antibodies, Viral blood, Gastroenteritis prevention & control, Rotavirus Infections prevention & control, Vaccines, Attenuated administration & dosage
Abstract

Objective: To determine the safety, immunogenicity and efficacy of two doses of rotavirus vaccine in healthy Brazilian infants., Methods: A randomized, multicenter, double-blind, placebo-controlled trial was conducted in Brazil, Mexico and Venezuela. Infants received two oral doses of vaccine or placebo at 2 and 4 months of age, concurrently with routine immunizations, except for oral poliomyelitis vaccine (OPV). This paper reports results from Belém, Brazil, where the number of subjects per group and the viral vaccine titers were: 194 (10(4.7) focus forming units - FFU), 196 (10(5.2) FFU), 194 (10(5.8) FFU) and 194 (placebo). Anti-rotavirus (anti-RV) antibody response was assessed in 307 subjects. Clinical severity of gastroenteritis episodes was measured using a 20-point scoring system with a score of >or= 11 defined as severe GE., Results: The rates of solicited general symptoms were similar in vaccine and placebo recipients. At 2 months after the second dose, a serum IgA response to RV occurred in 54.7 to 74.4% of vaccinees. No interference was seen in the immunogenicity of routine vaccines. Vaccine efficacy against any rotavirus gastroenteritis (RVGE) was 63.5% (95%CI 20.8-84.4) for the highest concentration (10(5.8) FFU). Efficacy was 81.5% (95%CI 44.5-95.4) against severe RVGE. At its highest concentration (10(5.8) FFU), RIX4414 provided 79.8% (95%CI 26.4-96.3) protection against severe RVGE by G9 strain., Conclusions: RIX4414 was highly immunogenic with a low reactogenicity profile and did not interfere with seroresponse to diphtheria, tetanus, pertussis, hepatitis B and Hib antigens. Two doses of RIX4414 provided significant protection against severe GE caused by RV.

Published
2007
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20. Nutritional status in relation to the efficacy of the rhesus-human reassortant, tetravalent rotavirus vaccine (RRV-TV) in infants from Belém, pará state, Brazil.

Author

Linhares AC, Carmo KB, Oliveira KK, Oliveira CS, Freitas RB, Bellesi N, Monteiro TA, Gabbay YB, and Mascarenhas JD

Subjects
Animals, Anthropometry, Brazil, Developed Countries, Diarrhea prevention & control, Diarrhea virology, Double-Blind Method, Gastroenteritis prevention & control, Gastroenteritis virology, Humans, Infant, Infant, Newborn, Reassortant Viruses immunology, Vaccines, Attenuated therapeutic use, Nutritional Status, Rotavirus immunology, Rotavirus Infections prevention & control, Rotavirus Vaccines therapeutic use
Abstract

The rhesus-human reassortant, tetravalent rotavirus vaccine (RRV-TV) was licensed for routine use in the United States of America but it was recently withdrawn from the market because of its possible association with intussusception as an adverse event. The protective efficacy of 3 doses of RRV-TV, in its lower-titer (4 x 10(4) pfu/dose) formulation, was evaluated according to the nutritional status of infants who participated in a phase III trial in Belém, Northern Brazil. A moderate protection conferred by RRV-TV was related to weight-for-age Z-scores (WAZ) greater than -1 only, with rates of 38% (p = 0.04) and 40% (p = 0.04) for all- and- pure rotavirus diarrhoeal cases, respectively. In addition, there was a trend for greater efficacy (43%, p = 0.05) among infants reaching an height-for-age Z-score (HAZ) of > -1. Taking WAZ, HAZ and weight-for-height Z-score (WHZ) indices 0.05) if both placebo and vaccine groups are compared. There was no significant difference if rates of mixed and pure rotavirus diarrhoeal cases are compared in relation to HAZ, WAZ and weight-for-height Z-score (WHZ) indices. Although a low number of malnourished infants could be identified in the present study, our data show some evidence that malnutrition may interfere with the efficacy of rotavirus vaccines in developing countries.

Published
2002
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