Exhaustive TORCH Pathogen Diagnostics Corroborate Zika Virus Etiology of Congenital Malformations in Northeastern Brazil
ABSTRACT The Latin American 2015–2016 Zika virus (ZIKV) outbreak was associated with an increase in microcephaly predominantly in northeastern Brazil. To comparatively investigate infectious causes of congenital malformations, we performed a nested case-control study in 32 mothers of cases of suspec...
| Main Authors: | , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
American Society for Microbiology
2018-08-01
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| Series: | mSphere |
| Subjects: | |
| Online Access: | https://journals.asm.org/doi/10.1128/mSphere.00278-18 |
| _version_ | 1828953588430274560 |
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| author | Andres Moreira-Soto Renata Cabral Celia Pedroso Monika Eschbach-Bludau Alexandra Rockstroh Ludy Alexandra Vargas Ignacio Postigo-Hidalgo Estela Luz Gilmara Souza Sampaio Christian Drosten Eduardo Martins Netto Thomas Jaenisch Sebastian Ulbert Manoel Sarno Carlos Brites Jan Felix Drexler |
| author_facet | Andres Moreira-Soto Renata Cabral Celia Pedroso Monika Eschbach-Bludau Alexandra Rockstroh Ludy Alexandra Vargas Ignacio Postigo-Hidalgo Estela Luz Gilmara Souza Sampaio Christian Drosten Eduardo Martins Netto Thomas Jaenisch Sebastian Ulbert Manoel Sarno Carlos Brites Jan Felix Drexler |
| author_sort | Andres Moreira-Soto |
| collection | DOAJ |
| description | ABSTRACT The Latin American 2015–2016 Zika virus (ZIKV) outbreak was associated with an increase in microcephaly predominantly in northeastern Brazil. To comparatively investigate infectious causes of congenital malformations, we performed a nested case-control study in 32 mothers of cases of suspected congenital Zika syndrome (CZS) and 160 age-matched controls from Bahia, northeastern Brazil. We collected clinical and imaging data and assessed past exposure to ZIKV, Chikungunya virus (CHIKV), dengue virus, and 8 established TORCH (Toxoplasma gondii, Treponema pallidum, rubella virus, cytomegalovirus, herpes simplex virus 1 [HSV-1] and HSV-2, varicella-zoster virus, parvovirus B19) pathogens using multiple serological tests. Heterogeneous symptoms prevented unequivocal diagnosis of CZS on clinical grounds. Only ZIKV and CHIKV seroprevalence rates differed significantly between cases and controls (93.8% versus 67.8% for ZIKV [Fisher’s exact text, P = 0.002] and 20.7% versus 8.2% for CHIKV [χ2, P = 0.039]). High ZIKV seroprevalence rates in cases could not be explained by previous dengue virus infections potentially eliciting cross-reactive antibody responses affecting ZIKV serological tests. In conditional logistic regression analyses, only ZIKV was significantly associated with congenital malformations (P = 0.030; odds ratio, 4.0 [95% confidence interval, 1.1 to 14.1]). Our data support an association between maternal ZIKV exposure and congenital malformations. Parallels between the discrepant ZIKV and CHIKV seroprevalence rates between cases and controls and similar seroprevalence rates between cases and controls for the sexually transmitted T. pallidum and HSV-2 may suggest the occurrence of predominantly vector-borne transmission in our study population. High seroprevalence of TORCH pathogens suggests that exhaustive diagnostics will be necessary in the aftermath of the ZIKV outbreak and provides baseline data for longitudinal studies on ZIKV pathogenesis. IMPORTANCE The Latin American Zika virus (ZIKV) outbreak had a major impact on reproductive health worldwide. The reasons for the massively increased reports of neonatal microcephaly in northeastern Brazil are still unclear. Beyond the technical limitations of laboratory diagnostics, unambiguous diagnosis of ZIKV as the cause of congenital malformations is hampered by similar clinical pictures elicited by other pathogens known as TORCH pathogens. We performed a case-control study comparing mothers of children with congenital malformations to age-matched controls from Salvador, Brazil, one of the areas most extensively affected by the ZIKV outbreak. The ZIKV and Chikungunya virus seroprevalence rates differed significantly, whereas the levels of maternal exposure to TORCH pathogens were similar between cases and controls. Our data support a link between maternal ZIKV infection and congenital malformations and suggest the occurrence of predominantly vector-borne ZIKV transmission in these cases. In addition, some highly prevalent TORCH pathogens may be misinterpreted as representative of ongoing ZIKV activity in the absence of exhaustive diagnostics in northeastern Brazil. |
| first_indexed | 2024-12-14T07:13:36Z |
| format | Article |
| id | doaj.art-8ae7b50686594092a83c13f183c72aee |
| institution | Directory Open Access Journal |
| issn | 2379-5042 |
| language | English |
| last_indexed | 2024-12-14T07:13:36Z |
| publishDate | 2018-08-01 |
| publisher | American Society for Microbiology |
| record_format | Article |
| series | mSphere |
| spelling | doaj.art-8ae7b50686594092a83c13f183c72aee2022-12-21T23:11:46ZengAmerican Society for MicrobiologymSphere2379-50422018-08-013410.1128/mSphere.00278-18Exhaustive TORCH Pathogen Diagnostics Corroborate Zika Virus Etiology of Congenital Malformations in Northeastern BrazilAndres Moreira-Soto0Renata Cabral1Celia Pedroso2Monika Eschbach-Bludau3Alexandra Rockstroh4Ludy Alexandra Vargas5Ignacio Postigo-Hidalgo6Estela Luz7Gilmara Souza Sampaio8Christian Drosten9Eduardo Martins Netto10Thomas Jaenisch11Sebastian Ulbert12Manoel Sarno13Carlos Brites14Jan Felix Drexler15Institute of Virology, University of Bonn Medical Centre, Bonn, GermanyMaternidade Climério de Oliveira, Universidade Federal da Bahia, Salvador, BrazilComplexo Hospitalar Universitário Professor Edgard Santos, Universidade Federal de Bahia, Salvador, BrazilInstitute of Virology, University of Bonn Medical Centre, Bonn, GermanyDepartment of Immunology, Fraunhofer Institute for Cell Therapy and Immunology, Leipzig, GermanyComplexo Hospitalar Universitário Professor Edgard Santos, Universidade Federal de Bahia, Salvador, BrazilCharité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Institute of Virology, Berlin, GermanyComplexo Hospitalar Universitário Professor Edgard Santos, Universidade Federal de Bahia, Salvador, BrazilComplexo Hospitalar Universitário Professor Edgard Santos, Universidade Federal de Bahia, Salvador, BrazilCharité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Institute of Virology, Berlin, GermanyComplexo Hospitalar Universitário Professor Edgard Santos, Universidade Federal de Bahia, Salvador, BrazilGerman Centre for Infection Research (DZIF)Department of Immunology, Fraunhofer Institute for Cell Therapy and Immunology, Leipzig, GermanyMaternidade Climério de Oliveira, Universidade Federal da Bahia, Salvador, BrazilComplexo Hospitalar Universitário Professor Edgard Santos, Universidade Federal de Bahia, Salvador, BrazilCharité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Institute of Virology, Berlin, GermanyABSTRACT The Latin American 2015–2016 Zika virus (ZIKV) outbreak was associated with an increase in microcephaly predominantly in northeastern Brazil. To comparatively investigate infectious causes of congenital malformations, we performed a nested case-control study in 32 mothers of cases of suspected congenital Zika syndrome (CZS) and 160 age-matched controls from Bahia, northeastern Brazil. We collected clinical and imaging data and assessed past exposure to ZIKV, Chikungunya virus (CHIKV), dengue virus, and 8 established TORCH (Toxoplasma gondii, Treponema pallidum, rubella virus, cytomegalovirus, herpes simplex virus 1 [HSV-1] and HSV-2, varicella-zoster virus, parvovirus B19) pathogens using multiple serological tests. Heterogeneous symptoms prevented unequivocal diagnosis of CZS on clinical grounds. Only ZIKV and CHIKV seroprevalence rates differed significantly between cases and controls (93.8% versus 67.8% for ZIKV [Fisher’s exact text, P = 0.002] and 20.7% versus 8.2% for CHIKV [χ2, P = 0.039]). High ZIKV seroprevalence rates in cases could not be explained by previous dengue virus infections potentially eliciting cross-reactive antibody responses affecting ZIKV serological tests. In conditional logistic regression analyses, only ZIKV was significantly associated with congenital malformations (P = 0.030; odds ratio, 4.0 [95% confidence interval, 1.1 to 14.1]). Our data support an association between maternal ZIKV exposure and congenital malformations. Parallels between the discrepant ZIKV and CHIKV seroprevalence rates between cases and controls and similar seroprevalence rates between cases and controls for the sexually transmitted T. pallidum and HSV-2 may suggest the occurrence of predominantly vector-borne transmission in our study population. High seroprevalence of TORCH pathogens suggests that exhaustive diagnostics will be necessary in the aftermath of the ZIKV outbreak and provides baseline data for longitudinal studies on ZIKV pathogenesis. IMPORTANCE The Latin American Zika virus (ZIKV) outbreak had a major impact on reproductive health worldwide. The reasons for the massively increased reports of neonatal microcephaly in northeastern Brazil are still unclear. Beyond the technical limitations of laboratory diagnostics, unambiguous diagnosis of ZIKV as the cause of congenital malformations is hampered by similar clinical pictures elicited by other pathogens known as TORCH pathogens. We performed a case-control study comparing mothers of children with congenital malformations to age-matched controls from Salvador, Brazil, one of the areas most extensively affected by the ZIKV outbreak. The ZIKV and Chikungunya virus seroprevalence rates differed significantly, whereas the levels of maternal exposure to TORCH pathogens were similar between cases and controls. Our data support a link between maternal ZIKV infection and congenital malformations and suggest the occurrence of predominantly vector-borne ZIKV transmission in these cases. In addition, some highly prevalent TORCH pathogens may be misinterpreted as representative of ongoing ZIKV activity in the absence of exhaustive diagnostics in northeastern Brazil.https://journals.asm.org/doi/10.1128/mSphere.00278-18BrazilTORCHZika virusmicrocephalyparturient |
| spellingShingle | Andres Moreira-Soto Renata Cabral Celia Pedroso Monika Eschbach-Bludau Alexandra Rockstroh Ludy Alexandra Vargas Ignacio Postigo-Hidalgo Estela Luz Gilmara Souza Sampaio Christian Drosten Eduardo Martins Netto Thomas Jaenisch Sebastian Ulbert Manoel Sarno Carlos Brites Jan Felix Drexler Exhaustive TORCH Pathogen Diagnostics Corroborate Zika Virus Etiology of Congenital Malformations in Northeastern Brazil mSphere Brazil TORCH Zika virus microcephaly parturient |
| title | Exhaustive TORCH Pathogen Diagnostics Corroborate Zika Virus Etiology of Congenital Malformations in Northeastern Brazil |
| title_full | Exhaustive TORCH Pathogen Diagnostics Corroborate Zika Virus Etiology of Congenital Malformations in Northeastern Brazil |
| title_fullStr | Exhaustive TORCH Pathogen Diagnostics Corroborate Zika Virus Etiology of Congenital Malformations in Northeastern Brazil |
| title_full_unstemmed | Exhaustive TORCH Pathogen Diagnostics Corroborate Zika Virus Etiology of Congenital Malformations in Northeastern Brazil |
| title_short | Exhaustive TORCH Pathogen Diagnostics Corroborate Zika Virus Etiology of Congenital Malformations in Northeastern Brazil |
| title_sort | exhaustive torch pathogen diagnostics corroborate zika virus etiology of congenital malformations in northeastern brazil |
| topic | Brazil TORCH Zika virus microcephaly parturient |
| url | https://journals.asm.org/doi/10.1128/mSphere.00278-18 |
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