Early epilepsy in children with Zika-related microcephaly in a cohort in Recife, Brazil: Characteristics, electroencephalographic findings, and treatment response.

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.

From re-emergence to hyperendemicity: the natural history of the dengue epidemic in Brazil.

BACKGROUND: dengue virus (DENV) was reintroduced into Brazil in 1986 and by 1995 it had spread throughout the country. In 2007 the number of dengue hemorrhagic fever (DHF) cases more than doubled and a shift in the age distribution was reported. While previously the majority of DHF cases occurred among adults, in 2007 53% of cases occurred in children under 15 years old. The reasons for this shift have not been determined. METHODS AND FINDINGS: age stratified cross-sectional seroepidemiologic survey conducted in Recife, Brazil in 2006. Serostatus was determined by ELISA based detection of Dengue IgG. We estimated time-constant and time-varying forces of infection of DENV between 1986 and 2006. We used discrete-time simulation to estimate the accumulation of monotypic and multitypic immunity over time in a population previously completely susceptible to DENV. We projected the age distribution of population immunity to dengue assuming similar hazards of infection in future years. The overall prevalence of DENV IgG was 0.80 (n = 1427). The time-constant force of infection for the period was estimated to be 0.052 (95% CI 0.041, 0.063), corresponding to 5.2% of susceptible individuals becoming infected each year by each serotype. Simulations show that as time since re-emergence of dengue goes by, multitypic immunity accumulates in adults while an increasing proportion of susceptible individuals and those with monotypic immunity are among young age groups. The median age of those monotypically immune can be expected to shift from 24 years, 10 years after introduction, to 13 years, 50 years after introduction. Of those monotypically immune, the proportion under 15 years old shifts from 27% to 58%. These results are consistent with the dengue notification records from the same region since 1995. INTERPRETATION: assuming that persons who have been monotypically exposed are at highest risk for severe dengue, the shift towards younger patient ages observed in Brazil can be partially explained by the accumulation of multitypic immunity against DENV-1, 2, and 3 in older age groups, 22 years after the re-introduction of these viruses. Serotype specific seroepidemiologic studies are necessary to accurately estimate the serotype specific forces of infection.

A dynamic analysis of tuberculosis dissemination to improve control and surveillance.

BACKGROUND: Detailed analysis of the dynamic interactions among biological, environmental, social, and economic factors that favour the spread of certain diseases is extremely useful for designing effective control strategies. Diseases like tuberculosis that kills somebody every 15 seconds in the world, require methods that take into account the disease dynamics to design truly efficient control and surveillance strategies. The usual and well established statistical approaches provide insights into the cause-effect relationships that favour disease transmission but they only estimate risk areas, spatial or temporal trends. Here we introduce a novel approach that allows figuring out the dynamical behaviour of the disease spreading. This information can subsequently be used to validate mathematical models of the dissemination process from which the underlying mechanisms that are responsible for this spreading could be inferred. METHODOLOGY/PRINCIPAL FINDINGS: The method presented here is based on the analysis of the spread of tuberculosis in a Brazilian endemic city during five consecutive years. The detailed analysis of the spatio-temporal correlation of the yearly geo-referenced data, using different characteristic times of the disease evolution, allowed us to trace the temporal path of the aetiological agent, to locate the sources of infection, and to characterize the dynamics of disease spreading. Consequently, the method also allowed for the identification of socio-economic factors that influence the process. CONCLUSIONS/SIGNIFICANCE: The information obtained can contribute to more effective budget allocation, drug distribution and recruitment of human skilled resources, as well as guiding the design of vaccination programs. We propose that this novel strategy can also be applied to the evaluation of other diseases as well as other social processes.

Selection bias: neighbourhood controls and controls selected from those presenting to a Health Unit in a case control study of efficacy of BCG revaccination.

BACKGROUND: In most case control studies the hardest decision is the choice of the control group, as in the ideal control group the proportion exposed is the same as in the population that produced the cases. METHODS: A comparison of two control groups in a case control study of the efficacy of BCG revaccination. One group was selected from subjects presenting to the heath unit the case attended for routine prevention and care; the second group was selected from the neighbourhood of cases. All Health Units from which controls were selected offered BCG revaccination. Efficacy estimated in a randomized control trial of BCG revaccination was used to establish that the neighbourhood control group was the one that gave unbiased results. RESULTS: The proportion of controls with scars indicating BCG revaccination was higher among the control group selected from Health Unit attenders than among neighbourhood controls. This excess was not removed after control for social variables and history of exposure to tuberculosis, and appears to have resulted from the fact that people attending the Health Unit were more likely to have been revaccinated than neighbourhood controls, although we can not exclude an effect of other unmeasured variables. CONCLUSION: In this study, controls selected from people presenting to a Health Unit overrepresented exposure to BCG revaccination. Had the results from the HU attenders control group been accepted this would have resulted in overestimation of vaccine efficacy. When the exposure of interest is offered in a health facility, selection of controls from attenders at the facility may result in over representation of exposure in controls and selection bias.

Avaliação de indicador sócio-ambiental utilizado no rastreamento de áreas de tansmissão de filariose linfática em espaços urbanos

O artigo narra um estudo realizado no Município de Olinda, Pernambuco, em áreas com diferentes riscos de transmissão da filariose bancroftiana. Após um mapeamento da área a ser avaliada, foram identificados todos os moradores com idade entre 5 e 65 anos para realização de um inquérito parasitológico. Arquivo em PDF. Requer o Adobe Acrobat Reader