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The association between Zika virus infection and microcephaly in Brazil 2015-2017: An observational analysis of over 4 million births.

ABSTRACT: BACKGROUND:In 2015, high rates of microcephaly were reported in Northeast Brazil following the first South American Zika virus (ZIKV) outbreak. Reported microcephaly rates in other Zika-affected areas were significantly lower, suggesting alternate causes or the involvement of arboviral cofactors in exacerbating microcephaly rates. METHODS AND FINDINGS:We merged data from multiple national reporting databases in Brazil to estimate exposure to 9 known or hypothesized causes of microcephaly for every pregnancy nationwide since the beginning of the ZIKV outbreak; this generated between 3.6 and 5.4 million cases (depending on analysis) over the time period 1 January 2015-23 May 2017. The association between ZIKV and microcephaly was statistically tested against models with alternative causes or with effect modifiers. We found no evidence for alternative non-ZIKV causes of the 2015-2017 microcephaly outbreak, nor that concurrent exposure to arbovirus infection or vaccination modified risk. We estimate an absolute risk of microcephaly of 40.8 (95% CI 34.2-49.3) per 10,000 births and a relative risk of 16.8 (95% CI 3.2-369.1) given ZIKV infection in the first or second trimester of pregnancy; however, because ZIKV infection rates were highly variable, most pregnant women in Brazil during the ZIKV outbreak will have been subject to lower risk levels. Statistically significant associations of ZIKV with other birth defects were also detected, but at lower relative risks than that of microcephaly (relative risk < 1.5). Our analysis was limited by missing data prior to the establishment of nationwide ZIKV surveillance, and its findings may be affected by unmeasured confounding causes of microcephaly not available in routinely collected surveillance data. CONCLUSIONS:This study strengthens the evidence that congenital ZIKV infection, particularly in the first 2 trimesters of pregnancy, is associated with microcephaly and less frequently with other birth defects. The finding of no alternative causes for geographic differences in microcephaly rate leads us to hypothesize that the Northeast region was disproportionately affected by this Zika outbreak, with 94% of an estimated 8.5 million total cases occurring in this region, suggesting a need for seroprevalence surveys to determine the underlying reason.

SUBMITTER: Brady OJ

PROVIDER: S-EPMC6400331 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature

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The association between Zika virus infection and microcephaly in Brazil 2015-2017: An observational analysis of over 4 million births.

Brady Oliver J OJ Osgood-Zimmerman Aaron A Kassebaum Nicholas J NJ Ray Sarah E SE de Araújo Valdelaine E M VEM da Nóbrega Aglaêr A AA Frutuoso Livia C V LCV Lecca Roberto C R RCR Stevens Antony A Zoca de Oliveira Bruno B de Lima José M JM Bogoch Isaac I II Mayaud Philippe P Jaenisch Thomas T Mokdad Ali H AH Murray Christopher J L CJL Hay Simon I SI Reiner Robert C RC Marinho Fatima F

PLoS medicine 20190305 3

<h4>Background</h4>In 2015, high rates of microcephaly were reported in Northeast Brazil following the first South American Zika virus (ZIKV) outbreak. Reported microcephaly rates in other Zika-affected areas were significantly lower, suggesting alternate causes or the involvement of arboviral cofactors in exacerbating microcephaly rates.<h4>Methods and findings</h4>We merged data from multiple national reporting databases in Brazil to estimate exposure to 9 known or hypothesized causes of micro ...[more]

PMID: 30835728

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Project description:The Zika virus (ZIKV) has rapidly reached epidemic proportions, especially in northeastern Brazil, and has rapidly spread to other parts of the Americas. A recent increase in the prevalence of microcephaly in newborn infants and vision-threatening findings in these infants is likely associated with the rapid spread of ZIKV.To evaluate the ocular findings in infants with microcephaly associated with presumed intrauterine ZIKV infection in Salvador, Bahia, Brazil.Case series at a tertiary hospital. Twenty-nine infants with microcephaly (defined by a cephalic circumference of ≤32 cm) with a presumed diagnosis of congenital ZIKV were recruited through an active search and referrals from other hospitals and health unities. The study was conducted between December 1 and December 21, 2015.All infants and mothers underwent systemic and ophthalmic examinations from December 1 through December 21, 2015, in the Roberto Santos General Hospital, Salvador, Brazil. Anterior segment and retinal, choroidal, and optic nerve abnormalities were documented using a wide-field digital imaging system. The differential diagnosis included toxoplasmosis, rubella, cytomegalovirus, herpes simplex virus, syphilis, and human immunodeficiency virus, which were ruled out through serologic and clinical examinations.Ocular abnormalities associated with ZIKV.Twenty-three of 29 mothers (79.3%) reported suspected ZIKV infection signs and symptoms during pregnancy, 18 in the first trimester, 4 in the second trimester, and 1 in the third trimester. Of the 29 infants (58 eyes) examined (18 [62.1%] female), ocular abnormalities were present in 17 eyes (29.3%) of 10 children (34.5%). Bilateral findings were found in 7 of 10 patients presenting with ocular lesions, the most common of which were focal pigment mottling of the retina and chorioretinal atrophy in 11 of the 17 eyes with abnormalities (64.7%), followed by optic nerve abnormalities in 8 eyes (47.1%), bilateral iris coloboma in 1 patient (2 eyes [11.8%]), and lens subluxation in 1 eye (5.9%).Congenital infection due to presumed ZIKV exposure is associated with vision-threatening findings, which include bilateral macular and perimacular lesions as well as optic nerve abnormalities in most cases.

Project description:Background:Zika virus (ZIKV) is an emerging mosquito-borne disease that can cause severe birth defects if contracted congenitally. Since late 2015, there has been a large increase in the number of travel-related cases of Zika virus infection in Canada. Objective:The objective of this study was to describe the epidemiology of travel-related Zika cases in Canada from October 2015 to June 2017 and review them in the context of the international outbreak in the Americas. Methods:Zika virus infections were confirmed by polymerase chain reaction (PCR) detection of viral RNA and/or the serological identification of ZIKV-specific antibodies in serum. Cases of ZIKV infection were identified by provincial and territorial health authorities, and reported on a regular basis to the Public Health Agency of Canada (PHAC). Case information requested included date of illness onset, age category, sex, pregnancy status, and location(s) and dates of travel. Estimates for the monthly number of Canadians travelling outside of Canada to other countries in the Americas were obtained from Statistics Canada and the International Air Transport Association (IATA). Data to produce the epidemic curves of autochthonous cases for each region of the Americas were extracted from country-specific epidemic curves on the Pan American Health Organization website. Results:As of June 7, 2017, 513 laboratory confirmed cases and two Zika-related birth/fetal anomalies were reported across all 10 provinces. Illness in Canadian travellers generally coincided with outbreak intensity in the country of exposure rather than travel volume. There has been no evidence of autochthonous (local) transmission in Canada. Currently, cases are on the decline both in Canada and internationally. Conclusion:The surge in Canadian ZIKV infections in 2016 was directly related to the incursion and spread of ZIKV into the Americas. Although cases are now on the decline worldwide, it remains to be seen whether a resurgence of cases in previously affected or new areas will occur. Both outbreak intensity and seasonality of ZIKV transmission should be monitored over time in order to inform the timing of public health education campaigns, as some may turn out to be more effective in the off-peak travel season when the risk of disease transmission may be higher. Ongoing education and awareness among travellers, particularly for pregnant women and those planning pregnancies, is still indicated.

Dataset Information

The association between Zika virus infection and microcephaly in Brazil 2015-2017: An observational analysis of over 4 million births.

Publications

The association between Zika virus infection and microcephaly in Brazil 2015-2017: An observational analysis of over 4 million births.

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