SummaryBackground The microcephaly epidemic, which started in Brazil in 2015, was declared a Public Health Emergency of International Concern by WHO in 2016. We report the preliminary results of a case-control study investigating the association between microcephaly and Zika virus infection during pregnancy.

Brazilian Ministry of Health, Pan American Health Organization, and Enhancing Research Activity in Epidemic Situations.

Brazil currently accounts for the majority of dengue cases reported in the Americas, with co-circulation of DENV 1, 2 and 3. Striking variation in the epidemiological pattern of infection within cities has been observed. Therefore, investigation of dengue transmission in small areas is important to formulate control strategies. A population-based household survey was performed in three diverse socio-economic and environmental areas of Recife, a large urban center of Brazil, between 2005 and 2006. Dengue serostatus and individual- and household-level risk factors for infection were collected in residents aged between 5 and 64 years. A total of 2,833 individuals were examined, and their residences were geo-referenced. Anti-dengue IgG antibodies were measured using commercial ELISA. The dengue seroprevalence and the force of infection were estimated in each area. Individual and household variables associated with seropositivity were assessed by multilevel models for each area. A spatial analysis was conducted to identify risk gradients of dengue seropositivity using generalized additive models (GAM). The dengue seroprevalence was 91.1%, 87.4% 74.3%, respectively, in the deprived, intermediate and high socioeconomic areas, inversely related to their socio-economic status. In the deprived area, 59% of children had already been exposed to dengue virus by the age of 5 years and the estimated force of infection was three times higher than that in the privileged area. The risk of infection increased with age in the three areas. Working or studying outside the home area was a risk factor for seropositivity in the deprived area (OR=2.26; 95% CI: 1.18-4.30). Number of persons per room was a risk factor for seropositivity in the intermediate (OR=3.00; 95% CI: 3.21-7.37) and privileged areas (OR=1.81; 95% CI: 1.07-3.04). Living in a house, as opposed to an apartment, was a risk factor for seropositivity in the privileged area (OR=3.62; 95% CI: 2.43-5.41). The main difference between the privileged and other areas could be attributed to the much larger proportion of apartment dwellers. Intensive vector control, surveillance and community education should be considered in deprived urban areas where a high proportion of children are infected by an early age.

BackgroundStarting in August 2015, there was an increase in the number of cases of neonatal microcephaly in Northeast Brazil. These findings were identified as being an epidemic of microcephaly related to Zika virus (ZIKV) infection. The present study aims to analyse the spatial distribution of microcephaly cases in Recife (2015–2016), which is in Northeast Brazil, and its association with the living conditions in this city.MethodsThis was an ecological study that used data from reported cases of microcephaly from the State Health Department of Pernambuco (August 2015 to July 2016). The basic spatial unit of analysis was the 94 districts of Recife. The case definition of microcephaly was: neonates with a head circumference of less than the cut-off point of −2 standard deviations below the mean value from the established Fenton growth curve. As an indicator of the living conditions of the 94 districts, the percentage of heads of households with an income of less than twice the minimum wage was calculated. The districts were classified into four homogeneous strata using the K-means clustering algorithm. We plotted the locations of each microcephaly case over a layer of living conditions.ResultsDuring the study period, 347 microcephaly cases were reported, of which 142 (40.9%) fulfilled the definition of a microcephaly case. Stratification of the 94 districts resulted in the identification of four strata. The highest stratum in relation to the living conditions presented the lowest prevalence rate of microcephaly, and the overall difference between this rate and the rates of the other strata was statistically significant. The results of the Kruskal-Wallis test demonstrated that there was a strong association between a higher prevalence of microcephaly and poor living conditions. After the first 6 months of the study period, there were no microcephaly cases recorded within the population living in the richest socio-economic strata.ConclusionThis study showed that those residing in areas with precarious living conditions had a higher prevalence of microcephaly compared with populations with better living conditions.

A cohort of cases initiating tuberculosis treatment from May 2001 to July 2003 was followed in Recife, Pernambuco State, Brazil, to investigate biological, clinical, social, lifestyle, and healthcare access factors associated with three negative tuberculosis treatment outcomes (treatment failure, dropout, and death) separately and as a group. Treatment failure was associated with treatment delay, illiteracy, and alcohol consumption. Factors associated with dropout were age, prior TB treatment, and illiteracy. Death was associated with age, treatment delay, HIV co-infection, and head of family's income. Main factors associated with negative treatment outcomes as a whole were age, HIV co-infection, illiteracy, alcoholism, and prior TB treatment. We suggest the following strategies to increase cure rates: further training of the Family Health Program personnel in TB control, awareness-raising on the need to tailor their activities to special care for cases (e.g., literacy training); targeting use of directly observed therapy for higher risk groups; establishment of a flexible referral scheme to handle technical and psychosocial problems, including alcoholism; and increased collaboration with the HIV/AIDS program.

Defining cases of Zika virus (ZIKV) infection is a critical challenge for epidemiological research. Due to ZIKV’s overlapping clinical features and potential immunologic cross-reactivity with other flaviviruses and the current lack of an optimal ZIKV-specific diagnostic assay, varying approaches for identifying ZIKV infections have been employed to date. This paper presents the laboratory results and diagnostic criteria developed by the Microcephaly Epidemic Research Group for defining cases of maternal ZIKV infection in a cohort of pregnant women with rash (N = 694) recruited during the declining 2015–2017 epidemic in northeast Brazil. For this investigation, we tested maternal sera for ZIKV by quantitative reverse transcription polymerase chain reaction (qRT-PCR), Immunoglobulin (Ig) M and IgG3 enzyme-linked immunosorbent assays (ELISAs), and Plaque Reduction Neutralization Test (PRNT50). Overall, 23.8% of participants tested positive by qRT-PCR during pregnancy (range of detection: 0–72 days after rash onset). However, the inter-assay concordance was lower than expected. Among women with qRT-PCR-confirmed ZIKV and further testing, only 10.1% had positive IgM tests within 90 days of rash, and only 48.5% had ZIKV-specific PRNT50 titers ≥20 within 1 year of rash. Given the complexity of these data, we convened a panel of experts to propose an algorithm for identifying ZIKV infections in pregnancy based on all available lines of evidence. When the diagnostic algorithm was applied to the cohort, 26.9% of participants were classified as having robust evidence of a ZIKV infection during pregnancy, 4.0% as having moderate evidence, 13.3% as having limited evidence of a ZIKV infection but with uncertain timing, and 19.5% as having evidence of an unspecified flavivirus infection before or during pregnancy. Our findings suggest that integrating longitudinal data from nucleic acid and serologic testing may enhance diagnostic sensitivity and underscore the need for an on-going dialogue regarding the optimization of strategies for defining cases of ZIKV in research.

Background Since 2015, the arthropod-borne viruses (arboviruses) Zika and chikungunya have spread across the Americas causing outbreaks, accompanied by increases in immune-mediated and infectious neurological disease. The spectrum of neurological manifestations linked to these viruses, and the importance of dual infection, are not known fully. We aimed to investigate whether neurological presentations differed according to the infecting arbovirus, and whether patients with dual infection had a different disease spectrum or severity. Methods We report a prospective observational study done during epidemics of Zika and chikungunya viruses in Recife, Pernambuco, a dengue-endemic area of Brazil. We recruited adults aged 18 years or older referred to Hospital da Restauração, a secondary-level and tertiary-level hospital, with suspected acute neurological disease and a history of suspected arboviral infection. We looked for evidence of Zika, chikungunya, or dengue infection by viral RNA or specific IgM antibodies in serum or CSF. We grouped patients according to their arbovirus laboratory diagnosis and then compared demographic and clinical characteristics. Findings Between Dec 4, 2014, and Dec 4, 2016, 1410 patients were admitted to the hospital neurology service; 201 (14%) had symptoms consistent with arbovirus infection and sufficient samples for diagnostic testing and were included in the study. The median age was 48 years (IQR 34–60), and 106 (53%) were women. 148 (74%) of 201 patients had laboratory evidence of arboviral infection. 98 (49%) of them had a single viral infection (41 [20%] had Zika, 55 [27%] had chikungunya, and two [1%] had dengue infection), whereas 50 (25%) had evidence of dual infection, mostly with Zika and chikungunya viruses (46 [23%] patients). Patients positive for arbovirus infection presented with a broad range of CNS and peripheral nervous system (PNS) disease. Chikungunya infection was more often associated with CNS disease (26 [47%] of 55 patients with chikungunya infection vs six [15%] of 41 with Zika infection; p=0·0008), especially myelitis (12 [22%] patients). Zika infection was more often associated with PNS disease (26 [63%] of 41 patients with Zika infection vs nine [16%] of 55 with chikungunya infection; p≤0·0001), particularly Guillain-Barré syndrome (25 [61%] patients). Patients with Guillain-Barré syndrome who had Zika and chikungunya dual infection had more aggressive disease, requiring intensive care support and longer hospital stays, than those with mono-infection (median 24 days [IQR 20–30] vs 17 days [10–20]; p=0·0028). Eight (17%) of 46 patients with Zika and chikungunya dual infection had a stroke or transient ischaemic attack, compared with five (6%) of 96 patients with Zika or chikungunya mono-infection (p=0·047). Interpretation There is a wide and overlapping spectrum of neurologica...

Objective To estimate the incidence of epilepsy in children with Zika‐related microcephaly in the first 24 months of life; to characterize the associated clinical and electrographic findings; and to summarize the treatment responses. Methods We followed a cohort of children, born during the 2015‐2016 Zika virus (ZIKV) epidemic in Brazil, with congenital microcephaly and evidence of congenital ZIKV infection on neuroimaging and/or laboratory testing. Neurological assessments were performed at ≤3, 6, 12, 15, 18, 21, and 24 months of life. Serial electroencephalograms were performed over the first 24 months. Results We evaluated 91 children, of whom 48 were female. In this study sample, the cumulative incidence of epilepsy was 71.4% in the first 24 months, and the main type of seizure was infantile spasms (83.1%). The highest incidence of seizures occurred between 3 and 9 months of age, and the risk remained high until 15 months of age. The incidence of infantile spasms peaked between 4 and 7 months and was followed by an increased incidence of focal epilepsy cases after 12 months of age. Neuroimaging results were available for all children, and 100% were abnormal. Cortical abnormalities were identified in 78.4% of the 74 children evaluated by computed tomography and 100% of the 53 children evaluated by magnetic resonance imaging. Overall, only 46.1% of the 65 children with epilepsy responded to treatment. The most commonly used medication was sodium valproate with or without benzodiazepines, levetiracetam, phenobarbital, and vigabatrin. Significance Zika‐related microcephaly was associated with high risk of early epilepsy. Seizures typically began after the third month of life, usually as infantile spasms, with atypical electroencephalographic abnormalities. The seizure control rate was low. The onset of seizures in the second year was less frequent and, when it occurred, presented as focal epilepsy.