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

Anemia em gestantes brasileiras antes e após a fortificação das farinhas com ferro

OBJECTIVE: To compare prevalence of anemia and hemoglobin (Hb) levels in Brazilian pregnant women before and after flour fortification with iron. METHODS: A repeated cross-sectional panel study of public health care centers of municipalities in the five Brazilian regions was conducted. Retrospective data were obtained from 12,119 medical records of pregnant women distributed in two groups: before fortification (delivery prior to June 2004) and after fortification (date of last period after June 2005). Anemia was defined as HbOBJETIVO: Comparar prevalencia de anemia y valores de hemoglobina (Hb) en gestantes brasileñas, antes y después de la fortificación de las harinas con hierro. MÉTODOS: Estudio de evaluación de paneles repetidos, desarrollado en servicios públicos de salud de municipios de las cinco regiones brasileñas. Datos retrospectivos se obtuvieron de 12.119 prontuarios de gestantes distribuidas en dos grupos: antes de la fortificación, con parto anterior a junio de 2004, y posterior a la fortificación, con última menstruación después de junio 2005. Anemia fue definida como HbOBJETIVO: Comparar prevalência de anemia e valores de hemoglobina (Hb) em gestantes brasileiras, antes e após a fortificação das farinhas com ferro. MÉTODOS: Estudo de avaliação de painéis repetidos, desenvolvido em serviços públicos de saúde de municípios das cinco regiões brasileiras. Dados retrospectivos foram obtidos de 12.119 prontuários de gestantes distribuídas em dois grupos: antes da fortificação, com parto anterior a junho de 2004, e após a fortificação, com última menstruação após junho de 2005. Anemia foi definida como Hb < 11,0 g/dL. Valores de Hb/idade gestacional foram avaliados segundo dois referenciais da literatura. Foram utilizados teste qui-quadrado, t de Student e regressão logística, com nível de 5% de significância. RESULTADOS: Na amostra total, anemia caiu de 25% para 20% após fortificação (p < 0,001), com médias de Hb significativamente maiores no grupo "após" (p < 0,001). Observaram-se, entretanto, diferenças regionais importantes: reduções significativas nas regiões Nordeste (37% para 29%) e Norte (32% para 25%), onde as prevalências de anemia eram elevadas antes da fortificação, e reduções menores nas regiões Sudeste (18% para 15%) e Sul (7% para 6%), onde as prevalências eram baixas. Os níveis de Hb/idade gestacional de ambos os grupos se mostraram discretamente mais elevados nos primeiros meses, porém bem mais baixos após o terceiro ou quarto mês, dependendo da referência utilizada para comparação. Análise de regressão logística mostrou que grupo, região geográfica, situação conjugal, trimestre gestacional, estado nutricional inicial e gestação anterior associaram-se com anemia (p < 0,05). CONCLUSÕES: A prevalência de anemia diminuiu após a fortificação, porém continua elevada nas regiões Nordeste e Norte. Embora a fortificação possa ter tido papel nesse resultado favorável, há que se considerar a contribuição de outras políticas públicas implementadas no período estudado

No Difference in Penetrance between Truncating and Missense/Aberrant Splicing Pathogenic Variants in MLH1 and MSH2: A Prospective Lynch Syndrome Database Study

Background. Lynch syndrome is the most common genetic predisposition for hereditary cancer. Carriers of pathogenic changes in mismatch repair (MMR) genes have an increased risk of developing colorectal (CRC), endometrial, ovarian, urinary tract, prostate, and other cancers, depending on which gene is malfunctioning. In Lynch syndrome, differences in cancer incidence (penetrance) according to the gene involved have led to the stratification of cancer surveillance. By contrast, any differences in penetrance determined by the type of pathogenic variant remain unknown. Objective. To determine cumulative incidences of cancer in carriers of truncating and missense or aberrant splicing pathogenic variants of the MLH1 and MSH2 genes. Methods. Carriers of pathogenic variants of MLH1 (path_MLH1) and MSH2 (path_MSH2) genes filed in the Prospective Lynch Syndrome Database (PLSD) were categorized as truncating or missense/aberrant splicing according to the InSiGHT criteria for pathogenicity. Results. Among 5199 carriers, 1045 had missense or aberrant splicing variants, and 3930 had truncating variants. Prospective observation years for the two groups were 8205 and 34,141 years, respectively, after which there were no significant differences in incidences for cancer overall or for colorectal cancer or endometrial cancers separately. Conclusion. Truncating and missense or aberrant splicing pathogenic variants were associated with similar average cumulative incidences of cancer in carriers of path MLH1 and path_MSH2

No Difference in Penetrance between Truncating and Missense/Aberrant Splicing Pathogenic Variants in MLH1 and MSH2: A Prospective Lynch Syndrome Database Study

Background. Lynch syndrome is the most common genetic predisposition for hereditary cancer. Carriers of pathogenic changes in mismatch repair (MMR) genes have an increased risk of developing colorectal (CRC), endometrial, ovarian, urinary tract, prostate, and other cancers, depending on which gene is malfunctioning. In Lynch syndrome, differences in cancer incidence (penetrance) according to the gene involved have led to the stratification of cancer surveillance. By contrast, any differences in penetrance determined by the type of pathogenic variant remain unknown. Objective. To determine cumulative incidences of cancer in carriers of truncating and missense or aberrant splicing pathogenic variants of the MLH1 and MSH2 genes. Methods. Carriers of pathogenic variants of MLH1 (path_MLH1) and MSH2 (path_MSH2) genes filed in the Prospective Lynch Syndrome Database (PLSD) were categorized as truncating or missense/aberrant splicing according to the InSiGHT criteria for pathogenicity. Results. Among 5199 carriers, 1045 had missense or aberrant splicing variants, and 3930 had truncating variants. Prospective observation years for the two groups were 8205 and 34,141 years, respectively, after which there were no significant differences in incidences for cancer overall or for colorectal cancer or endometrial cancers separately. Conclusion. Truncating and missense or aberrant splicing pathogenic variants were associated with similar average cumulative incidences of cancer in carriers of path MLH1 and path_MSH2