Zika, chikungunya and dengue: the causes and threats of new and re-emerging arboviral diseases.

The recent emergence and re-emergence of viral infections transmitted by vectors-Zika, chikungunya, dengue, Japanese encephalitis, West Nile, yellow fever and others-is a cause for international concern. Using as examples Zika, chikungunya and dengue, we summarise current knowledge on characteristics of the viruses and their transmission, clinical features, laboratory diagnosis, burden, history, possible causes of the spread and the expectation for future epidemics. Arboviruses are transmitted by mosquitoes, are of difficult diagnosis, can have surprising clinical complications and cause severe burden. The current situation is complex, because there is no vaccine for Zika and chikungunya and no specific treatment for the three arboviruses. Vector control is the only comprehensive solution available now and this remains a challenge because up to now this has not been very effective. Until we develop new technologies of control mosquito populations, the globalised and urbanised world we live in will remain vulnerable to the threat of successive arbovirus epidemics

Evaluation of record linkage of two large administrative databases in a middle income country: stillbirths and notifications of dengue during pregnancy in Brazil.

BACKGROUND: Due to the increasing availability of individual-level information across different electronic datasets, record linkage has become an efficient and important research tool. High quality linkage is essential for producing robust results. The objective of this study was to describe the process of preparing and linking national Brazilian datasets, and to compare the accuracy of different linkage methods for assessing the risk of stillbirth due to dengue in pregnancy. METHODS: We linked mothers and stillbirths in two routinely collected datasets from Brazil for 2009-2010: for dengue in pregnancy, notifications of infectious diseases (SINAN); for stillbirths, mortality (SIM). Since there was no unique identifier, we used probabilistic linkage based on maternal name, age and municipality. We compared two probabilistic approaches, each with two thresholds: 1) a bespoke linkage algorithm; 2) a standard linkage software widely used in Brazil (ReclinkIII), and used manual review to identify further links. Sensitivity and positive predictive value (PPV) were estimated using a subset of gold-standard data created through manual review. We examined the characteristics of false-matches and missed-matches to identify any sources of bias. RESULTS: From records of 678,999 dengue cases and 62,373 stillbirths, the gold-standard linkage identified 191 cases. The bespoke linkage algorithm with a conservative threshold produced 131 links, with sensitivity = 64.4% (68 missed-matches) and PPV = 92.5% (8 false-matches). Manual review of uncertain links identified an additional 37 links, increasing sensitivity to 83.7%. The bespoke algorithm with a relaxed threshold identified 132 true matches (sensitivity = 69.1%), but introduced 61 false-matches (PPV = 68.4%). ReclinkIII produced lower sensitivity and PPV than the bespoke linkage algorithm. Linkage error was not associated with any recorded study variables. CONCLUSION: Despite a lack of unique identifiers for linking mothers and stillbirths, we demonstrate a high standard of linkage of large routine databases from a middle income country. Probabilistic linkage and manual review were essential for accurately identifying cases for a case-control study, but this approach may not be feasible for larger databases or for linkage of more common outcomes

Hospitalizações sensíveis à atenção primária em menores de cinco anos

Objetivo: analisar em que medida o coeficiente de incidência das internações sensíveis a atenção primária em menores de cinco anos é influenciada pelo percentual de cobertura da Estratégia de Saúde da Família (ESF). Métodos: trata-se de um estudo ecológico de corte transversal que associa a cobertura da ESF e o coeficiente das internações sensíveis à atenção primária em 2000 e 2010. Utilizaram-se dados do Sistema de Informação Hospitalar (SIH) e o Sistema de Informação da Atenção Básica (SIAB). Resultados: Os dados revelaram que o aumento da cobertura da ESF proporcionou redução dos coeficientes de internação das doenças estudadas. Em 2000 a redução foi maior para as gastroenterites (51% em menores de 01 ano e 30% em crianças de 01 ”“ 04 anos), em 2010 para as doenças respiratórias (51% em menores de 01 ano e 33% em crianças de 01 ”“ 04 anos). Conclusão: constatou-se associação entre a cobertura da ESF e as taxas de internação, entretanto outras variáveis parecem interferir, evidenciando a necessidade de realização de outros estudos

Symptomatic dengue infection during pregnancy and the risk of stillbirth in Brazil, 2006-12: a matched case-control study.

BACKGROUND: Maternal infections during pregnancy can increase the risk of fetal death. Dengue infection is common, but little is known about its role in fetal mortality. We aimed to investigate the association between symptomatic dengue infection during pregnancy and fetal death. METHODS: We did a nested case-control study using obstetrician-collected data from the Brazilian livebirth information system (SINASC), the mortality information system (SIM), and the national reportable disease information system (SINAN). We identified all pregnancies ending in stillbirth and a random sample of livebirths between Jan 1, 2006, and Dec 31, 2012. We did linkage to determine which mothers were diagnosed with dengue infection during pregnancy. By use of stillbirths as cases and a sample of matched livebirths as a control, we calculated matched odds ratios (mORs) using conditional logistic regression adjusted for maternal age and education. FINDINGS: 275 (0·2%) of 162 188 women who had stillbirths and 1507 (0·1%) of 1 586 105 women who had livebirths were diagnosed with dengue infection during pregnancy. Symptomatic dengue infection during pregnancy almost doubled the odds of fetal death (mOR 1·9, 95% CI 1·6-2·2). The increase in risk was similar when analyses were restricted to laboratory-confirmed cases of dengue infection (1·8, 1·4-2·4). Severe dengue infection increased the risk of fetal death by about five times (4·9, 2·3-10·2). INTERPRETATION: Symptomatic dengue infection during pregnancy is associated with an increased risk of fetal death. We recommend further epidemiological and biological studies of the association between dengue and poor birth outcomes to measure the burden of subclinical infections and elucidate pathological mechanisms. FUNDING: Brazilian National Council for Scientific and Technological Development, Horizon 2020

Examining the quality of record linkage process using nationwide Brazilian administrative databases to build a large birth cohort.

BACKGROUND: Research using linked routine population-based data collected for non-research purposes has increased in recent years because they are a rich and detailed source of information. The objective of this study is to present an approach to prepare and link data from administrative sources in a middle-income country, to estimate its quality and to identify potential sources of bias by comparing linked and non-linked individuals. METHODS: We linked two administrative datasets with data covering the period 2001 to 2015, using maternal attributes (name, age, date of birth, and municipally of residence) from Brazil: live birth information system and the 100 Million Brazilian Cohort (created using administrative records from over 114 million individuals whose families applied for social assistance via the Unified Register for Social Programmes) implementing an in house developed linkage tool CIDACS-RL. We then estimated the proportion of highly probably link and examined the characteristics of missed-matches to identify any potential source of bias. RESULTS: A total of 27,699,891 live births were submited to linkage with maternal information recorded in the baseline of the 100 Million Brazilian Cohort dataset of those, 16,447,414 (59.4%) children were found registered in the 100 Million Brazilian Cohort dataset. The proportion of highly probably link ranged from 39.3% in 2001 to 82.1% in 2014. A substantial improvement in the linkage after the introduction of maternal date of birth attribute, in 2011, was observed. Our analyses indicated a slightly higher proportion of missing data among missed matches and a higher proportion of people living in an urban area and self-declared as Caucasian among linked pairs when compared with non-linked sets. DISCUSSION: We demonstrated that CIDACS-RL is capable of performing high quality linkage even with a limited number of common attributes, using indexation as a blocking strategy in larg e routine databases from a middle-income country. However, residual records occurred more among people under worse living conditions. The results presented in this study reinforce the need of evaluating linkage quality and when necessary to take linkage error into account for the analyses of any generated dataset

Zika virus infection in pregnancy and adverse fetal outcomes in São Paulo State, Brazil: a prospective cohort study.

Robust epidemiological and biological evidence supports a causal link between prenatal Zika Virus (ZIKV) infection and congenital brain abnormalities including microcephaly. However, it remains uncertain if ZIKV infection in pregnancy also increases the risk for other adverse fetal and birth outcomes. In a prospective cohort study we investigated the influence of ZIKV on the prevalence of prematurity, low birth weight, small-for-gestational-age, and fetal death as well as microcephaly (i.e., overall and disproportionate) in the offspring of women attending a high-risk pregnancy clinic during the recent ZIKV outbreak in Brazil. During the recruitment period (01 March 2016-23 August 2017), urine samples were tested for ZIKV by RT-PCR from all women attending the high-risk pregnancy clinic at Jundiaí University Hospital and from the neonates after delivery. Of the 574 women evaluated, 44 (7.7%) were ZIKV RT-PCR positive during pregnancy. Of the 409 neonates tested, 19 (4.6%) were ZIKV RT-PCR positive in the first 10 days of life. In this cohort, maternal ZIKV exposure was not associated with increased risks of prematurity, low birth weight, small-for-gestational-age, or fetal death. However, relative to ZIKV-negative neonates, ZIKV-positive infants had a five-fold increased risk of microcephaly overall (RR 5.1, 95% CI 1.2-22.5) and a ten-fold increased risk of disproportionate microcephaly (RR 10.3, 95% CI 2.0-52.6). Our findings provide new evidence that, in a high-risk pregnancy cohort, ZIKV RT-PCR positivity in the neonate at birth is strongly associated with microcephaly. However, ZIKV infection during pregnancy does not appear to influence the risks of prematurity, low birth weight, small-for-gestational-age or fetal death in women who already have gestational comorbidities. The results suggest disproportion between neonatal head circumference and weight may be a useful screening indicator for the detection of congenital microcephaly associated with ZIKV infection

Socioeconomic risk markers of arthropod-borne virus (arbovirus) infections: A systematic literature review and meta-analysis

INTRODUCTION: Arthropod-borne viruses (arboviruses) are of notable public health importance worldwide, owing to their potential to cause explosive outbreaks and induce debilitating and potentially life-threatening disease manifestations. This systematic review and meta-analysis aims to assess the relationship between markers of socioeconomic position (SEP) and infection due to arboviruses with mosquito vectors. METHODS: We conducted a systematic search on PubMed, Embase, and LILACS databases to identify studies published between 1980 and 2020 that measured the association of SEP markers with arbovirus infection. We included observational studies without geographic location or age restrictions. We excluded studies from grey literature, reviews and ecological studies. Study findings were extracted and summarised, and pooled estimates were obtained using random-effects meta-analyses. RESULTS: We identified 36 observational studies using data pertaining to 106 524 study participants in 23 geographic locations that empirically examined the relationship between socioeconomic factors and infections caused by seven arboviruses (dengue, chikungunya, Japanese encephalitis, Rift Valley fever, Sindbis, West Nile and Zika viruses). While results were varied, descriptive synthesis pointed to a higher risk of arbovirus infection associated with markers of lower SEP, including lower education, income poverty, low healthcare coverage, poor housing materials, interrupted water supply, marital status (married, divorced or widowed), non-white ethnicities and migration status. Pooled crude estimates indicated an increased risk of arboviral infection associated with lower education (risk ratio, RR 1.5 95% CI 1.3 to 1.9); I CONCLUSION: Evidence from this systematic review suggests that lower SEP increases the risk of acquiring arboviral infection; however, there was large heterogeneity across studies. Further studies are required to delineate the relationship between specific individual, household and community-level SEP indicators and arbovirus infection risks to help inform targeted public health interventions. PROSPERO REGISTRATION NUMBER: CRD42019158572

The achievements of the SUS in tackling the communicable diseases

Apresenta-se a evolução da situação epidemiológica de algumas das principais Doenças transmissíveis (DT) no Brasil, assinalando as intervenções proporcionadas pelo SUS e outras políticas sociais. Dados e informações foram levantados do Datasus e Boletins epidemiológicos do Ministério da Saúde e de artigos científicos sobre o tema. A universalização, a descentralização e a ampliação das ações de vigilância, controle e prevenção de DT produziram impacto sobre a morbimortalidade dessas doenças, principalmente das imunopreveníveis. A emergência e reemergência de três arboviroses, para as quais não se dispõe de instrumentos de controle efetivos, interromperam a evolução decrescente no perfil de morbidade das DT no Brasil. Outros programas sociais e econômicos, voltados para a população brasileira mais carente, também contribuíram para a melhoria dos indicadores de saúde analisados. Contudo, a universalização do acesso aos serviços de atenção à saúde, ao lado do aperfeiçoamento do escopo de atuação da vigilância sobre doenças e riscos à saúde, vem desempenhando papel fundamental na melhoria das condições de saúde e qualidade de vida da população, bem como contribuindo para o processo de democratização do país.This article presents the development of the epidemiological situation of some of the major communicable diseases (CD) in Brazil, with emphasis on the interventions by the SUS and other social policies. The data and information were collected from Datasus, epidemiological newsletters from the Brazilian Ministry of Health, and scientific articles on the issue. The universalization, decentralization and expansion of the surveillance, control and prevention of CD has produced an impact on the morbidity and mortality of these diseases, mainly those which are vaccine-preventable. The emergence and re-emergence of three arboviruses, for which there are no effective control instruments, interrupted the downward trend in the morbidity profile of CD in Brazil. Other social and economic programs, which are geared to the needier sectors of the Brazilian population, have also contributed to the improvement of the analyzed health indicators. However, the universalization of access to healthcare services, as well as improvements in the scope of the surveillance of diseases and health risks, has played a key role in improving the health and quality of life of the population, as well as contributing to the process of the democratization of Brazil

Validating linkage of multiple population-based administrative databases in Brazil.

BACKGROUND: Linking routinely-collected data provides an opportunity to measure the effects of exposures that occur before birth on maternal, fetal and infant outcomes. High quality linkage is a prerequisite for producing reliable results, and there are specific challenges in mother-baby linkage. Using population-based administrative databases from Brazil, this study aimed to estimate the accuracy of linkage between maternal deaths and birth outcomes and dengue notifications, and to identify potential sources of bias when assessing the risk of maternal death due to dengue in pregnancy. METHODS: We identified women with dengue during pregnancy in a previously linked dataset of dengue notifications in women who had experienced a live birth or stillbirth during 2007-2012. We then linked this dataset with maternal death records probabilistically using maternal name, age and municipality. We estimated the accuracy of the linkage, and examined the characteristics of false-matches and missed-matches to identify any sources of bias. RESULTS: Of the 10,259 maternal deaths recorded in 2007-2012, 6717 were linked: 5444 to a live birth record, 1306 to a stillbirth record, and 33 to both a live and stillbirth record. After identifying 2620 missed-matches and 124 false-matches, our estimated sensitivity was 72%, specificity was 88%, and positive predictive value was 98%. Linkage errors were associated with maternal education and self-identified race; women with more than 7 years of education or who self-declared as Caucasian were more likely to link. Dengue status was not associated with linkage error. CONCLUSION: Despite not having unique identifiers to link mothers and birth outcomes, we demonstrated a high standard of linkage, with sensitivity and specificity values comparable to previous literature. Although there were no differences in the characteristics of dengue cases missed or included in our linked dataset, linkage error occurred disproportionally by some social-demographic characteristics, which should be taken into account in future analyses