Risk of adverse outcomes in offspring with RT-PCR confirmed prenatal Zika virus exposure: An individual participant data meta-analysis of 13 cohorts in the Zika Brazilian Cohorts Consortium.

Background: Knowledge regarding the risks associated with Zika virus (ZIKV) infections in pregnancy has relied on individual studies with relatively small sample sizes and variable risk estimates of adverse outcomes, or on surveillance or routinely collected data. Using data from the Zika Brazilian Cohorts Consortium, this study aims, to estimate the risk of adverse outcomes among offspring of women with RT-PCR-confirmed ZIKV infection during pregnancy and to explore heterogeneity between studies. Methods: We performed an individual participant data meta-analysis of the offspring of 1548 pregnant women from 13 studies, using one and two-stage meta-analyses to estimate the absolute risks. Findings: Of the 1548 ZIKV-exposed pregnancies, the risk of miscarriage was 0.9%, while the risk of stillbirth was 0.3%. Among the pregnancies with liveborn children, the risk of prematurity was 10,5%, the risk of low birth weight was 7.7, and the risk of small for gestational age (SGA) was 16.2%. For other abnormalities, the absolute risks were: 2.6% for microcephaly at birth or first evaluation, 4.0% for microcephaly at any time during follow-up, 7.9% for neuroimaging abnormalities, 18.7% for functional neurological abnormalities, 4.0% for ophthalmic abnormalities, 6.4% for auditory abnormalities, 0.6% for arthrogryposis, and 1.5% for dysphagia. This risk was similar in all sites studied and in different socioeconomic conditions, indicating that there are not likely to be other factors modifying this association. Interpretation: This study based on prospectively collected data generates the most robust evidence to date on the risks of congenital ZIKV infections over the early life course. Overall, approximately one-third of liveborn children with prenatal ZIKV exposure presented with at least one abnormality compatible with congenital infection, while the risk to present with at least two abnormalities in combination was less than 1.0%.

Zika Virus Infection in a Cohort of Pregnant Women with Exanthematic Disease in Manaus, Brazilian Amazon.

The epidemic transmission of Zika virus (ZIKV) in Brazil has been identified as a cause of microcephaly and other neurological malformations in the babies of ZIKV-infected women. The frequency of adverse outcomes of Zika virus infection (ZIKVi) in pregnancy differs depending on the characteristics of exposure to infection, the time of recruitment of research participants, and the outcomes to be observed. This study provides a descriptive analysis-from the onset of symptoms to delivery-of a cohort registered as having maternal ZIKVi in pregnancy, from November 2015 to December 2016. Suspected cases were registered at a referral center for infectious and tropical diseases in Manaus, in the Amazonian region of Brazil. Of 834 women notified, 762 women with confirmed pregnancies were enrolled. Reverse-transcriptase polymerase chain reaction (RT-PCR) confirmed ZIKVi in 42.3% of the cohort. In 35.2% of the cohort, ZIKV was the sole infection identified. Severe adverse pregnancy outcomes (miscarriage, stillbirth, or microcephaly) were observed in both RT-PCR ZIKV-positive (5.0%) and ZIKV-negative (1.8%) cases (RR 3.1; 95% IC 1.4-7.3; p < 0.05), especially during the first trimester of pregnancy (RR 6.2, 95% IC 2.3-16.5; p < 0.001). Although other infectious rash diseases were observed in the pregnant women in the study, having confirmed maternal ZIKVi was the most important risk factor for serious adverse pregnancy events.

Neurological Findings in Children without Congenital Microcephaly Exposed to Zika Virus in Utero: A Case Series Study.

The Zika virus can induce a disruptive sequence in the fetal brain and is manifested mainly by microcephaly. Knowledge gaps still exist as to whether the virus can cause minor disorders that are perceived later on during the first years of life in children who are exposed but are asymptomatic at birth. In this case series, we describe the outcomes related to neurodevelopment through the neurological assessment of 26 non-microcephalic children who had intrauterine exposure to Zika virus. Children were submitted for neurological examinations and Bayley Scales-III (cognition, language, and motor performance). The majority (65.4%) obtained satisfactory performance in neurodevelopment. The most impaired domain was language, with 30.7% impairment. Severe neurological disorders occurred in five children (19.2%) and these were spastic hemiparesis, epilepsy associated with congenital macrocephaly (Zika and human immunodeficiency virus), two cases of autism (one exposed to Zika and Toxoplasma gondii) and progressive sensorineural hearing loss (GJB2 mutation). We concluded that non-microcephalic children with intrauterine exposure to Zika virus, in their majority, had achieved satisfactory performance in all neurodevelopmental domains. One third of the cases had some impairment, but the predominant group had mild alterations, with low occurrence of moderate to severe disorders, similar to other studies in Brazil.

Snakebites as cause of deaths in the Western Brazilian Amazon: Why and who dies? Deaths from snakebites in the Amazon

Snake envenoming represents a major burden for public health worldwide. In the Amazon, the official number of cases and deaths detected is probably underestimated because of the difficulty riverine and indigenous populations have reaching health centers in order to receive medical assistance. Thus, integrated analysis of health information systems must be used in order to improve adequate health policies. The aim of this work is to describe a series of deaths and identify risk factors for lethality from snakebites in the state of Amazonas, Brazil. All deaths from snakebites reported to the Brazilian Notifiable Diseases Surveillance System (SINAN) and to the Mortality Information System (SIM; ICD10-10th revision, X.29), from 2007 to 2015, were included. Variables were assessed by blocks with distal (ecological variables), intermediate (demographics) and proximal (clinical variables) components to identify predictors of case fatality. A total of 127 deaths from snakebites were recorded, with 58 pairs found through linkage of the SINAN and SIM databases (45.7%), 37 (29.1%) deaths found only in SINAN and 32 (25.2%) found only in the SIM. Deaths occurred mostly in males (95 cases; 74.8%) living in rural areas (78.6%). The most affected age group was the >= 61 years old (36 cases; 28.4%). Snakebites were presumably due to Bothrops snakes in 68.5% of the cases and Lachesis in 29.5% based on clinico-epidemiological diagnosis. A proportion of 26.2% of the cases received treatment over 24 h after the bite ocurred. On admission, cases were mostly classified as severe (65.6%). Overall, 28 patients (22.0%). Deceased without any medical assistance Antivenom was given to 53.5%. In the multivariate analysis, a distance from Manaus >300 km [OR = 3.40 (95%Cl = 1.99-5.79); (p < 0.001)1; age >= 61 years [OR = 431 (95%Cl = 1.22-1521); (p = 0.023)] and Indigenous status [OR = 5.47 (95%Cl = 237-12.66); (p < 0.001)1 were independently associated with case fatality from snakebites. Severe snakebites [OR = 16.24 (95%Cl = 4.37-6039); (p < 0.001)] and a lack of antivenom administration [OR = 4.21 (95%Cl = 1.30-13.19); (p = 0.014)] were also independently associated with case fatality. Respiratory failureklyspnea, systemic bleeding, sepsis and shock were recorded only among fatal cases. In conclusion, i) death from snakebites was under-reported in the mortality surveillance system; ii) older age groups living in remote municipalities and indigenous peoples were the population groups most prone to death; iii) lack or underdosage of anti venom resulted in higher case fatality and iv) systemic bleeding, circulatory shock, sepsis and acute respiratory failure were strongly associated to fatal outcome.