Use of infectious disease surveillance reports to monitor the Zika virus epidemic in Latin America and the Caribbean from 2015 to 2017: strengths and deficiencies

Objectives To summarise the occurrence of congenital Zika syndrome (CZS) in Latin America and the Caribbean from 2015 to 2017 using two outcome measures derived from infectious disease surveillance reports and to assess the completeness of these reports.Design Surveillance study.Setting Pan American Health Organization (PAHO)/WHO epidemiology reports on confirmed and suspected Zika virus infection and cases of CZS.Participants Populations of 47 countries in the South and Central Americas, Mexico and the Caribbean.Primary and secondary outcome measures The number of CZS cases per 1000 births (using 2016–2017 births as a denominator) and the number of CZS cases per 1000 births in women with Zika virus infection during pregnancy.Results By 4 January 2018, 548623 suspected and 239063 confirmed Zika virus infections had been reported to PAHO/WHO from 47 countries. In 25 countries, over 80% of infections were reported as suspected. There were 3617 confirmed CZS cases in 25 countries; 2952 (82%) had occurred in Brazil. The number of CZS cases per 1000 births varied considerably with Brazil and several Caribbean island communities (Puerto Rico, St Martin, Martinique, Guadeloupe and Grenada) having the highest CZS prevalence above 0.5 per 1000 births. Analysing the number of CZS cases per 1000 births in women infected with Zika virus during their pregnancy highlighted the inaccuracies of the data, with Venezuela likely to have had severe under-reporting of CZS.Conclusions Expressing data on CZS in relation to total births, rather than as absolute numbers, better illustrates the burden of disease, providing that under-reporting of CZS is not too severe. Data on infections in pregnant women enable potential under-reporting of CZS to be identified. Both measures are recommended for future PAHO/WHO publications. Evidence of severe under-reporting of Zika virus infections and CZS makes interpretation of the data and comparisons between countries challenging

Prevalence and clinical profile of microcephaly in South America pre-Zika, 2005-14: prevalence and case-control study

Submitted by Sandra Infurna ([email protected]) on 2017-12-07T10:08:10Z No. of bitstreams: 1 eduardo_castilla_etal_IOC_2017.pdf: 420663 bytes, checksum: 1bda2b904f26e96d052e0b767bc85897 (MD5)Approved for entry into archive by Sandra Infurna ([email protected]) on 2017-12-07T10:25:41Z (GMT) No. of bitstreams: 1 eduardo_castilla_etal_IOC_2017.pdf: 420663 bytes, checksum: 1bda2b904f26e96d052e0b767bc85897 (MD5)Made available in DSpace on 2017-12-07T10:25:41Z (GMT). No. of bitstreams: 1 eduardo_castilla_etal_IOC_2017.pdf: 420663 bytes, checksum: 1bda2b904f26e96d052e0b767bc85897 (MD5) Previous issue date: 2017Universidade Federal do Rio de Janeiro, Rio de Janeiro. Instituto de Biologia. Departamento de Genética. Estudo colaborativo latino-americano de malformações congênitas. Rio de Janeiro, RJ, Brasil / Instituto Nacional de Genética Médica Populacional. Porto Alegre, RS, Brasil.Ulster University. Institute of Nursing and Health Research. Maternal Fetal and Infant Research Centre. Newtownabbey, Northern Ireland, UK.Instituto Nacional de Genética Médica Populacional. Porto Alegre, RS, Brasil / ECLAMC at Center for Medical Education and Clinical Research (CEMIC-CONICET). Buenos Aires, Argentina.Universidade Federal do Rio de Janeiro, Rio de Janeiro. Instituto de Biologia. Departamento de Genética. Estudo colaborativo latino-americano de malformações congênitas. Rio de Janeiro, RJ, Brasil / Instituto Nacional de Genética Médica Populacional. Porto Alegre, RS, Brasil.Instituto Nacional de Genética Médica Populacional. Porto Alegre, RS, Brasil / ECLAMC at Center for Medical Education and Clinical Research (CEMIC-CONICET). Buenos Aires, Argentina.Instituto Nacional de Genética Médica Populacional. Porto Alegre, RS, Brasil / Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Epidemiologia de Malformações Congênitas. Estudo Colaborativo Latino-americano de Malformações Congênitas. Rio de Janeiro, RJ, Brasil.Instituto Nacional de Genética Médica Populacional. Porto Alegre, RS, Brasil / Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Epidemiologia de Malformações Congênitas. Estudo Colaborativo Latino-americano de Malformações Congênitas. Rio de Janeiro, RJ, Brasil.Instituto Nacional de Genética Médica Populacional. Porto Alegre, RS, Brasil / ECLAMC at Center for Medical Education and Clinical Research (CEMIC-CONICET). Buenos Aires, Argentina.Objective To describe the prevalence and clinical spectrum of microcephaly in South America for the period 2005-14, before the start of the Zika epidemic in 2015, as a baseline for future surveillance as the Zika epidemic spreads and as other infectious causes may emerge in future.Design Prevalence and case-control study.Data sources ECLAMC (Latin American Collaborative Study of Congenital Malformations) database derived from 107 hospitals in 10 South American countries, 2005 to 2014. Data on microcephaly cases, four non-malformed controls per case, and all hospital births (all births for hospital based prevalence, resident within municipality for population based prevalence). For 2010-14, head circumference data were available and compared with Intergrowth charts.Results 552 microcephaly cases were registered, giving a hospital based prevalence of 4.4 (95% confidence interval 4.1 to 4.9) per 10 000 births and a population based prevalence of 3.0 (2.7 to 3.4) per 10 000. Prevalence varied significantly between countries and between regions and hospitals within countries. Thirty two per cent (n=175) of cases were prenatally diagnosed; 29% (n=159) were perinatal deaths. Twenty three per cent (n=128) were associated with a diagnosed genetic syndrome, 34% (n=189) polymalformed without a syndrome diagnosis, 12% (n=65) with associated neural malformations, and 26% (n=145) microcephaly only. In addition, 3.8% (n=21) had a STORCH (syphilis, toxoplasmosis, other including HIV, rubella, cytomegalovirus, and herpes simplex) infection diagnosis and 2.0% (n=11) had consanguineous parents. Head circumference measurements available for 184/235 cases in 2010-14 showed 45% (n=82) more than 3 SD below the mean, 24% (n=44) between 3 SD and 2 SD below the mean, and 32% (n=58) larger than -2 SD.Conclusion Extrapolated to the nearly 7 million annual births in South America, an estimated 2000-2500 microcephaly cases were diagnosed among births each year before the Zika epidemic began in 2015. Clinicians are using more than simple metrics to make microcephaly diagnoses. Endemic infections are important enduring causes of microcephaly

Interaction between IRF6 and TGFA Genes Contribute to the Risk of Nonsyndromic Cleft Lip/Palate

Previous evidence from tooth agenesis studies suggested IRF6 and TGFA interact. Since tooth agenesis is commonly found in individuals with cleft lip/palate (CL/P), we used four large cohorts to evaluate if IRF6 and TGFA interaction contributes to CL/P. Markers within and flanking IRF6 and TGFA genes were tested using Taqman or SYBR green chemistries for case-control analyses in 1,000 Brazilian individuals. We looked for evidence of gene-gene interaction between IRF6 and TGFA by testing if markers associated with CL/P were overtransmitted together in the case-control Brazilian dataset and in the additional family datasets. Genotypes for an additional 142 case-parent trios from South America drawn from the Latin American Collaborative Study of Congenital Malformations (ECLAMC), 154 cases from Latvia, and 8,717 individuals from several cohorts were available for replication of tests for interaction. Tgfa and Irf6 expression at critical stages during palatogenesis was analyzed in wild type and Irf6 knockout mice. Markers in and near IRF6 and TGFA were associated with CL/P in the Brazilian cohort (p<10-6). IRF6 was also associated with cleft palate (CP) with impaction of permanent teeth (p<10-6). Statistical evidence of interaction between IRF6 and TGFA was found in all data sets (p = 0.013 for Brazilians; p = 0.046 for ECLAMC; p = 10-6 for Latvians, and p = 0.003 for the 8,717 individuals). Tgfa was not expressed in the palatal tissues of Irf6 knockout mice. IRF6 and TGFA contribute to subsets of CL/P with specific dental anomalies. Moreover, this potential IRF6-TGFA interaction may account for as much as 1% to 10% of CL/P cases. The Irf6-knockout model further supports the evidence of IRF6-TGFA interaction found in humans. © 2012 Letra et al

Dental anomaly detection using intraoral photos via deep learning

Children with orofacial clefting (OFC) present with a wide range of dental anomalies. Identifying these anomalies is vital to understand their etiology and to discern the complex phenotypic spectrum of OFC. Such anomalies are currently identified using intra-oral exams by dentists, a costly and time-consuming process. We claim that automating the process of anomaly detection using deep neural networks (DNNs) could increase efficiency and provide reliable anomaly detection while potentially increasing the speed of research discovery. This study characterizes the use of` DNNs to identify dental anomalies by training a DNN model using intraoral photographs from the largest international cohort to date of children with nonsyndromic OFC and controls (OFC1). In this project, the intraoral images were submitted to a Convolutional Neural Network model to perform multi-label multi-class classification of 10 dental anomalies. The network predicts whether an individual exhibits any of the 10 anomalies and can do so significantly faster than a human rater can. For all but three anomalies, F1 scores suggest that our model performs competitively at anomaly detection when compared to a dentist with 8 years of clinical experience. In addition, we use saliency maps to provide a post-hoc interpretation for our model’s predictions. This enables dentists to examine and verify our model’s predictions.Fil: Ragodos, Ronilo. University of Iowa; Estados UnidosFil: Wang, Tong. University of Iowa; Estados UnidosFil: Padilla, Carmencita. University of the Philippines; FilipinasFil: Hecht, Jacqueline T.. University of Texas Health Science Center at Houston; Estados UnidosFil: Poletta, Fernando Adrián. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. CEMIC-CONICET. Centro de Educaciones Médicas e Investigaciones Clínicas "Norberto Quirno". CEMIC-CONICET; ArgentinaFil: Orioli, Ieda Maria. Universidade Federal do Rio de Janeiro; BrasilFil: Buxó, Carmen J.. Universidad de Puerto Rico; Puerto RicoFil: Butali, Azeez. University of Iowa; Estados UnidosFil: Valencia Ramirez, Consuelo. Fundación Clínica Noel; ColombiaFil: Restrepo Muñeton, Claudia. Fundación Clínica Noel; ColombiaFil: Wehby, George. University of Iowa; Estados UnidosFil: Weinberg, Seth M.. University of Pittsburgh; Estados Unidos. University of Pittsburgh at Johnstown; Estados UnidosFil: Marazita, Mary L.. University of Pittsburgh at Johnstown; Estados Unidos. University of Pittsburgh; Estados UnidosFil: Moreno Uribe, Lina M.. University of Iowa; Estados UnidosFil: Howe, Brian J.. University of Iowa; Estados Unido

Global birth defects app: An innovative tool for describing and coding congenital anomalies at birth in low resource settings

BACKGROUND: Surveillance programs in low- and middle-income countries (LMICs) have difficulty in obtaining accurate information about congenital anomalies. METHODS: As part of the ZikaPLAN project, an International Committee developed an app for the description and coding of congenital anomalies that are externally visible at birth, for use in low resource settings. The “basic” version of the app was designed for a basic clinical setting and to overcome language and terminology barriers by providing diagrams and photos, sourced mainly from international Birth Defects Atlases. The “surveillance” version additionally allows recording of limited pseudonymized data relevant to diagnosis, which can be uploaded to a secure server, and downloaded by the surveillance program data center. RESULTS: The app contains 98 (88 major and 10 minor) externally visible anomalies and 12 syndromes (including congenital Zika syndrome), with definitions and International Classification of Disease v10 -based code. It also contains newborn examination videos and links to further resources. The user taps a region of the body, then selects among a range of images to choose the congenital anomaly that best resembles what they observe, with guidance regarding similar congenital anomalies. The “basic” version of the app has been reviewed by experts and made available on the Apple and Google Play stores. Since its launch in November 2019, it has been downloaded in 39 countries. The "surveillance” version is currently being field-tested. CONCLUSION: The global birth defects app is a mHealth tool that can help in developing congenital anomaly surveillance in low resource settings to support prevention and care

Cyclopia: An epidemiologic study in a large dataset from the International Clearinghouse of Birth Defects Surveillance and Research

Cyclopia is characterized by the presence of a single eye, with varying degrees of doubling of the intrinsic ocular structures, located in the middle of the face. It is the severest facial expression of the holoprosencephaly (HPE) spectrum. This study describes the prevalence, associated malformations, and maternal characteristics among cases with cyclopia. Data originated in 20 Clearinghouse (ICBDSR) affiliated birth defect surveillance systems, reported according to a single pre-established protocol. A total of 257 infants with cyclopia were identified. Overall prevalence was 1 in 100,000 births (95%CI: 0.89-1.14), with only one program being out of range. Across sites, there was no correlation between cyclopia prevalence and number of births (r=0.08; P=0.75) or proportion of elective termination of pregnancy (r=-0.01; P=0.97). The higher prevalence of cyclopia among older mothers (older than 34) was not statistically significant. The majority of cases were liveborn (122/200; 61%) and females predominated (male/total: 42%). A substantial proportion of cyclopias (31%) were caused by chromosomal anomalies, mainly trisomy 13. Another 31% of the cases of cyclopias were associated with defects not typically related to HPE, with more hydrocephalus, heterotaxia defects, neural tube defects, and preaxial reduction defects than the chromosomal group, suggesting the presence of ciliopathies or other unrecognized syndromes. Cyclopia is a very rare defect without much variability in prevalence by geographic location. The heterogeneous etiology with a high prevalence of chromosomal abnormalities, and female predominance in HPE, were confirmed, but no effect of increased maternal age or association with twinning was observed.Fil: Orioli, Ieda Maria. Instituto de Biologia; Brasil. Instituto Nacional de Genética Médica Populacional; BrasilFil: Amar, Emmanuelle. Rhone-alps Registry Of Birth Defects Remera; FranciaFil: Bakker, Marian K.. University of Groningen; Países BajosFil: Bermejo Sánchez, Eva. Instituto de Salud Carlos III; Brasil. Centro de Investigación Biomédica En Red de Enfermedades Raras; BrasilFil: Bianchi, Fabrizio. Consiglio Nazionale delle Ricerche; ItaliaFil: Canfield, Mark A.. Texas Department Of State Health Services; Estados UnidosFil: Clementi, Maurizio. Università di Padova; ItaliaFil: Correa, Adolfo. Centers for Disease Control and Prevention; BrasilFil: Csáky Szunyogh, Melinda. National Center for Healthcare Audit and Inspection; HungríaFil: Feldkamp, Marcia L.. Utah Department Of Health; Estados Unidos. University Of Utah Health Sciences; Estados UnidosFil: Landau, Danielle. Soroka University Medical Center; IsraelFil: Leoncini, Emanuele. Centre Of The International Clearinghouse For Birth Defects Surveillance And Research; ItaliaFil: Li, Zhu. Peking University Health Science Center; ChinaFil: Lowry, R. Brian. Alberta Congenital Anomalies Surveillance System; CanadáFil: Mastroiacovo, Pierpaolo. Centre Of The International Clearinghouse For Birth Defects Surveillance And Research; ItaliaFil: Morgan, Margery. the Congenital Anomaly Register for Wales; Reino UnidoFil: Mutchinick, Osvaldo M.. Instituto Nacional de la Nutrición Salvador Zubiran; MéxicoFil: Rissmann, Anke. Otto-von-Guericke-Universität Magdeburg; AlemaniaFil: Ritvanen, Annukka. National Institute For Health And Welfare; FinlandiaFil: Scarano, Gioacchino. General Hospital G. Rummo Benevento; ItaliaFil: Szabova, Elena. Slovak Medical University; EslovaquiaFil: Castilla, Eduardo Enrique. Instituto Nacional de Genética Médica Populacional; Brasil. Centro de Educación Medica E Invest.clinicas; Argentina. Fundación Oswaldo Cruz; Brasil. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin

The legacy of ZikaPLAN: a transnational research consortium addressing Zika

Global health research partnerships with institutions from high-income countries and low- and middle-income countries are one of the European Commission's flagship programmes. Here, we report on the ZikaPLAN research consortium funded by the European Commission with the primary goal of addressing the urgent knowledge gaps related to the Zika epidemic and the secondary goal of building up research capacity and establishing a Latin American-European research network for emerging vector-borne diseases. Five years of collaborative research effort have led to a better understanding of the full clinical spectrum of congenital Zika syndrome in children and the neurological complications of Zika virus infections in adults and helped explore the origins and trajectory of Zika virus transmission. Individual-level data from ZikaPLAN`s cohort studies were shared for joint analyses as part of the Zika Brazilian Cohorts Consortium, the European Commission-funded Zika Cohorts Vertical Transmission Study Group, and the World Health Organization-led Zika Virus Individual Participant Data Consortium. Furthermore, the legacy of ZikaPLAN includes new tools for birth defect surveillance and a Latin American birth defect surveillance network, an enhanced Guillain-Barre Syndrome research collaboration, a de-centralized evaluation platform for diagnostic assays, a global vector control hub, and the REDe network with freely available training resources to enhance global research capacity in vector-borne diseases

ZikaPLAN: addressing the knowledge gaps and working towards a research preparedness network in the Americas.

Zika Preparedness Latin American Network (ZikaPLAN) is a research consortium funded by the European Commission to address the research gaps in combating Zika and to establish a sustainable network with research capacity building in the Americas. Here we present a report on ZikaPLAN`s mid-term achievements since its initiation in October 2016 to June 2019, illustrating the research objectives of the 15 work packages ranging from virology, diagnostics, entomology and vector control, modelling to clinical cohort studies in pregnant women and neonates, as well as studies on the neurological complications of Zika infections in adolescents and adults. For example, the Neuroviruses Emerging in the Americas Study (NEAS) has set up more than 10 clinical sites in Colombia. Through the Butantan Phase 3 dengue vaccine trial, we have access to samples of 17,000 subjects in 14 different geographic locations in Brazil. To address the lack of access to clinical samples for diagnostic evaluation, ZikaPLAN set up a network of quality sites with access to well-characterized clinical specimens and capacity for independent evaluations. The International Committee for Congenital Anomaly Surveillance Tools was formed with global representation from regional networks conducting birth defects surveillance. We have collated a comprehensive inventory of resources and tools for birth defects surveillance, and developed an App for low resource regions facilitating the coding and description of all major externally visible congenital anomalies including congenital Zika syndrome. Research Capacity Network (REDe) is a shared and open resource centre where researchers and health workers can access tools, resources and support, enabling better and more research in the region. Addressing the gap in research capacity in LMICs is pivotal in ensuring broad-based systems to be prepared for the next outbreak. Our shared and open research space through REDe will be used to maximize the transfer of research into practice by summarizing the research output and by hosting the tools, resources, guidance and recommendations generated by these studies. Leveraging on the research from this consortium, we are working towards a research preparedness network