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During the past year and a half, Zika virus has been spreading rapidly throughout Latin America. In this letter, evidence for the Guillain–Barré syndrome being temporally associated with Zika virus transmission is presented. To the Editor: Zika virus (ZIKV) disease had been described as a mild, self-limiting illness associated with fever, rash, joint pain, and conjunctivitis. 1 However, during the outbreak in French Polynesia, 42 patients with ZIKV disease were found to have the Guillain–Barré syndrome, which represented a marked increase from the approximately 5 cases detected annually during the previous 4 years. 2 A connection with the Guillain–Barré syndrome had previously been described in association with other flavivirus illnesses 3 , 4 but not with ZIKV infection. From April 1, 2015, to March 31, 2016, a total of 164,237 confirmed and suspected cases of ZIKV disease . . .

In November, 2015, an epidemic of microcephaly was reported in Brazil, which was later attributed to congenital Zika virus infection. 7830 suspected cases had been reported to the Brazilian Ministry of Health by June 4, 2016, but little is known about their characteristics. We aimed to describe these newborn babies in terms of clinical findings, anthropometry, and survival. We reviewed all 1501 liveborn infants for whom investigation by medical teams at State level had been completed as of Feb 27, 2016, and classified suspected cases into five categories based on neuroimaging and laboratory results for Zika virus and other relevant infections. Definite cases had laboratory evidence of Zika virus infection; highly probable cases presented specific neuroimaging findings, and negative laboratory results for other congenital infections; moderately probable cases had specific imaging findings but other infections could not be ruled out; somewhat probable cases had imaging findings, but these were not reported in detail by the local teams; all other newborn babies were classified as discarded cases. Head circumference by gestational age was assessed with InterGrowth standards. First week mortality and history of rash were provided by the State medical teams. Between Nov 19, 2015, and Feb 27, 2015, investigations were completed for 1501 suspected cases reported to the Brazilian Ministry of Health, of whom 899 were discarded. Of the remainder 602 cases, 76 were definite, 54 highly probable, 181 moderately probable, and 291 somewhat probable of congenital Zika virus syndrome. Clinical, anthropometric, and survival differences were small among the four groups. Compared with these four groups, the 899 discarded cases had larger head circumferences (mean Z scores −1·54 vs −3·13, difference 1·58 [95% CI 1·45–1·72]); lower first-week mortality (14 per 1000 vs 51 per 1000; rate ratio 0·28 [95% CI 0·14–0·56]); and were less likely to have a history of rash during pregnancy (20·7% vs 61·4%, ratio 0·34 [95% CI 0·27–0·42]). Rashes in the third trimester of pregnancy were associated with brain abnormalities despite normal sized heads. One in five definite or probable cases presented head circumferences in the normal range (above −2 SD below the median of the InterGrowth standard) and for one third of definite and probable cases there was no history of a rash during pregnancy. The peak of the epidemic occurred in late November, 2015. Zika virus congenital syndrome is a new teratogenic disease. Because many definite or probable cases present normal head circumference values and their mothers do not report having a rash, screening criteria must be revised in order to detect all affected newborn babies. Brazilian Ministry of Health, Pan American Health Organization, and Wellcome Trust.

Zika virus has spread rapidly throughout the Americas and has been associated with fetal abnormalities and a variety of neurologic disorders. This report updates the epidemiologic findings over the past 2 years. To the Editor: The first cases of a new illness involving fever and rash that was deemed to have been caused by Zika virus (ZIKV) infection in Brazil were reported in 2014, and the presence of the virus was confirmed in April 2015. In October 2015, an unusual increase in the number of cases of microcephaly among newborn infants was reported in Brazil; this disorder was apparently linked to ZIKV infection. From the first investigations of microcephaly, and from subsequent studies in Brazil and elsewhere, it is now clear that ZIKV is a cause of a range of neurologic disorders, . . .

The co-circulation of different arboviruses in the same time and space poses a significant threat to public health given their rapid geographic dispersion and serious health, social, and economic impact. Therefore, it is crucial to have high quality of case registration to estimate the real impact of each arboviruses in the population. In this work, a Vector Autoregressive (VAR) model was developed to investigate the interrelationships between discarded and confirmed cases of dengue, chikungunya, and Zika in Brazil. We used data from the Brazilian National Notifiable Diseases Information System (SINAN) from 2010 to 2017. There were three peaks in the series of dengue notification in this period occurring in 2013, 2015 and in 2016. The series of reported cases of both Zika and chikungunya reached their peak in late 2015 and early 2016. The VAR model shows that the Zika series have a significant impact on the dengue series and vice versa, suggesting that several discarded and confirmed cases of dengue could actually have been cases of Zika. The model also suggests that the series of confirmed and discarded chikungunya cases are almost independent of the cases of Zika, however, affecting the series of dengue. In conclusion, co-circulation of arboviruses with similar symptoms could have lead to misdiagnosed diseases in the surveillance system. We argue that the routinely use of mathematical and statistical models in association with traditional symptom-surveillance could help to decrease such errors and to provide early indication of possible future outbreaks. These findings address the challenges regarding notification biases and shed new light on how to handle reported cases based only in clinical-epidemiological criteria when multiples arboviruses co-circulate in the same population.

Background: The clinical manifestations of microcephaly/congenital Zika syndrome (microcephaly/CZS) have harmful consequences on the child’s health, increasing vulnerability to childhood morbidity and mortality. This study analyzes the case fatality rate and child–maternal characteristics of cases and deaths related to microcephaly/CZS in Brazil, 2015–2017. Methods: Population-based study developed by linkage of three information systems. We estimate frequencies of cases, deaths, case fatality rate related to microcephaly/CZS according to child and maternal characteristics and causes of death. Multivariate logistic regression models were applied. Results: The microcephaly/CZS case fatality rate was 10% (95% CI 9.2–10.7). Death related to microcephaly/CZS was associated to moderate (OR = 2.15; 95% CI 1.63–2.83), and very low birth weight (OR = 3.77; 95% CI 2.20–6.46); late preterm births (OR = 1.65; 95% CI 1.21–2.23), Apgar < 7 at 1st (OR = 5.98; 95% CI 4.46–8.02) and 5th minutes (OR = 4.13; 95% CI 2.78–6.13), among others. Conclusions: A high microcephaly/CZS case fatality rate and important factors associated with deaths related to this syndrome were observed. These results can alert health teams to these problems and increase awareness about the factors that may be associated with worse outcomes.

Zika virus was responsible for the microcephaly epidemic in Brazil which began in October 2015 and brought great challenges to the scientific community and health professionals in terms of diagnosis and classification. Due to the difficulties in correctly identifying Zika cases, it is necessary to develop an automatic procedure to classify the probability of a CZS case from the clinical data. This work presents a machine learning algorithm capable of achieving this from structured and unstructured available data. The proposed algorithm reached 83% accuracy with textual information in medical records and image reports and 76% accuracy in classifying data without textual information. Therefore, the proposed algorithm has the potential to classify CZS cases in order to clarify the real effects of this epidemic, as well as to contribute to health surveillance in monitoring possible future epidemics.

This study aimed to assess the impact of the Zika epidemic on the registration of birth defects in Brazil. We used an interrupted time series analysis design to identify changes in the trends in the registration of congenital anomalies. We obtained monthly data from Brazilian Live Birth Information System and used two outcome definitions: 1) rate of congenital malformation of the brain and eye (likely to be affected by Zika and its complications) 2) rate of congenital malformation not related to the brain or eye unlikely to be causally affected by Zika. The period between maternal infection with Zika and diagnosis of congenital abnormality attributable to the infection is around six months. We therefore used September 2015 as the interruption point in the time series, six months following March 2015 when cases of Zika started to increase. For the purposes of this analysis, we considered the period from January 2010 to September 2015 to be \"pre-Zika event,\" and the period from just after September 2015 to December 2017 to be \"post-Zika event.\" We found that immediately after the interruption point, there was a great increase in the notification rate of congenital anomalies of 14.9/10,000 live births in the brain and eye group and of 5.2/10,000 live births in the group not related with brain or eye malformations. This increase in reporting was in all regions of the country (except in the South) and especially in the Northeast. In the period \"post-Zika event\", unlike the brain and eye group which showed a monthly decrease, the group without brain or eye malformations showed a slow but significant increase (relative to the pre-Zika trend) of 0.2/10,000 live births. These findings suggest an overall improvement in the registration of birth malformations, including malformations that were not attributed to Zika, during and after the Zika epidemic.

Objective This study aims to describe clinical findings and determine the medium-term survival of congenital zika syndrome (CZS) suspected cases. Methods A retrospective cohort study using routine register-based linked data. It included all suspected cases of CZS born in Brazil from January 1, 2015, to December 31, 2018, and followed up from birth until death, 36 months, or December 31, 2018, whichever came first. Latent class analysis was used to cluster unconfirmed cases into classes with similar combinations of anthropometry at birth, imaging findings, maternally reported rash, region, and year of birth. Kaplan–Meier curves were plotted, and Cox proportional hazards models were fitted to determine mortality up to 36 months. Results We followed 11,850 suspected cases of CZS, of which 28.3% were confirmed, 9.3% inconclusive and 62.4% unconfirmed. Confirmed cases had almost two times higher mortality when compared with unconfirmed cases. Among unconfirmed cases, we identified three distinct clusters with different mortality trajectories. The highest mortality risk was observed in those with abnormal imaging findings compatible with congenital infections (HR = 12.6; IC95%8.8–18.0) and other abnormalities (HR = 11.6; IC95%8.6–15.6) compared with those with normal imaging findings. The risk was high in those with severe microcephaly (HR = 8.2; IC95%6.4–10.6) and macrocephaly (HR = 6.6; IC95%4.5–9.7) compared with normal head size. Conclusion Abnormal imaging and head circumference appear to be the main drivers of the increased mortality among suspected cases of CZS. We suggest identifying children who are more likely to die and have a greater need to optimise interventions and resource allocation regardless of the final diagnoses.

Zika virus (ZIKV) became a worldwide public health emergency after its introduction in the Americas. Brazil was implicated as central in the ZIKV dispersion, however, a better understanding of the pathways the virus took to arrive in Brazil and the dispersion within the country is needed. An updated genome dataset was assembled with publicly available data. Bayesian phylogeography methods were applied to reconstruct the spatiotemporal history of ZIKV in the Americas and with more detail inside Brazil. Our analyses reconstructed the Brazilian state of Pernambuco as the likely point of introduction of ZIKV in Brazil, possibly during the 2013 Confederations Cup. Pernambuco played an important role in spreading the virus to other Brazilian states. Our results also underscore the long cryptic circulation of ZIKV in all analyzed locations in Brazil. Conclusions: This study brings new insights about the early moments of ZIKV in the Americas, especially regarding the Brazil-Haiti cluster at the base of the American clade and describing for the first time migration patterns within Brazil.