Field and classroom initiatives for portable sequence-based monitoring of dengue virus in Brazil.

Brazil experienced a large dengue virus (DENV) epidemic in 2019, highlighting a continuous struggle with effective control and public health preparedness. Using Oxford Nanopore sequencing, we led field and classroom initiatives for the monitoring of DENV in Brazil, generating 227 novel genome sequences of DENV1-2 from 85 municipalities (2015-2019). This equated to an over 50% increase in the number of DENV genomes from Brazil available in public databases. Using both phylogenetic and epidemiological models we retrospectively reconstructed the recent transmission history of DENV1-2. Phylogenetic analysis revealed complex patterns of transmission, with both lineage co-circulation and replacement. We identified two lineages within the DENV2 BR-4 clade, for which we estimated the effective reproduction number and pattern of seasonality. Overall, the surveillance outputs and training initiative described here serve as a proof-of-concept for the utility of real-time portable sequencing for research and local capacity building in the genomic surveillance of emerging viruses.

Características dos primeiros casos de microcefalia possivelmente relacionados ao vírus Zika notificados na Região Metropolitana de Recife, Pernambuco / Características de los primeros casos de microcefalia, posiblemente relacionadas con el virus Zika reportados en la Región Metropolitana de Recife / Characteristics of the first cases of microcephaly possibly related to Zika virus reported in the Metropolitan Region of Recife, Pernambuco State, Brazil

OBJETIVO: descrever os primeiros casos de microcefalia possivelmente relacionados ao vírus Zika em nascidos vivos notificados na Região Metropolitana do Recife, Pernambuco, Brasil. MÉTODOS: estudo descritivo de tipo série de casos (notificados de 1º de agosto a 31 de outubro de 2015), com dados obtidos dos registros médicos e de questionário aplicado às mães. RESULTADOS: foram confirmados 40 casos com microcefalia, distribuídos em oito municípios da Região Metropolitana do Recife, com maior concentração no Recife (n=12); a mediana do perímetro cefálico foi de 29 cm, do perímetro torácico, 31 cm, e do peso, 2.628 gramas; 21/25 casos apresentaram calcificação cerebral, ventriculomegalia ou lisencefalia; entre as 40 mães, 27 referiram exantema na gestação, 20 no primeiro trimestre e sete no segundo, além de prurido, cefaleia, mialgia e ausência de febre. CONCLUSÃO: a maioria dos casos apresentou características de infecção congênita; a maioria das mães apresentou quadro sugestivo de infecção pelo vírus Zika na gestação.

OBJETIVO: describir los primeros casos de microcefalia en nacidos vivos reportados al Departamento de Salud del Estado de Pernambuco, en la región metropolitana de Recife, Pernambuco, 2015. MÉTODOS: estudio epidemiológico descriptivo de serie de casos (reportados de 1 de agosto a 31 de octubre de 2015), con datos obtenidos de registros médicos y cuestionarios aplicados a las madres. RESULTADOS: 40 casos fueron confirmados con microcefalia, en ocho municipios de la región metropolitana de Recife, con mayor concentración de casos en Recife (n=12); la circunferencia media de la cabeza fue 29 cm, perímetro torácico 31 cm y peso 2.628 gramos; exámenes revelaron que 21/25 casos mostraron calcificación, dilatación ventricular o lisencefalia; de las 40 madres, 27 (68%) informan exantema durante la gestación, 20 (74%) en el primer trimestre y siete (26%) en la segunda, además de prurito, dolor de cabeza, mialgia y ausencia de fiebre. CONCLUSIÓN: la mayoría de los casos presenta características de infección congénita; la mayoría de las madres mostró características que sugieren infección por el virus Zika en el embarazo.

OBJECTIVE: to describe the first cases of microcephaly possibly related to Zika virus in live born babies reported in the Metropolitan Region of Recife, Pernambuco State, Brazil. METHODS: this was a descriptive case series study (cases reported between August 1st and October 31st 2015), using medical record data and data from a questionnaire answered by the mothers of the babies. RESULTS: 40 microcephaly cases were confirmed, distributed in eight municipalities within the Metropolitan Region, with Recife itself having the highest concentration of cases (n=12); median head circumference was 29 cm, median chest girth was 31 cm and median weight was 2,628 grams; 21/25 cases had brain calcification, ventriculomegaly or lissencephaly; 27 of the 40 mothers reported rash during pregnancy, 20 in the first trimester and 7 in the second trimester, as well as itching, headache, myalgia and absence of fever. CONCLUSION: the majority of the cases bore the characteristics of congenital infection; the clinical condition of the majority of mothers suggested Zika virus infection during pregnancy.

Characteristics of the first cases of microcephaly possibly related to Zika virus reported in the Metropolitan Region of Recife, Pernambuco State, Brazil. / Características dos primeiros casos de microcefalia possivelmente relacionados ao vírus Zika notificados na Região Metropolitana de Recife, Pernambuco.

OBJECTIVE: to describe the first cases of microcephaly possibly related to Zika virus in live born babies reported in the Metropolitan Region of Recife, Pernambuco State, Brazil. METHODS: this was a descriptive case series study (cases reported between August 1st and October 31st 2015), using medical record data and data from a questionnaire answered by the mothers of the babies. RESULTS: 40 microcephaly cases were confirmed, distributed in eight municipalities within the Metropolitan Region, with Recife itself having the highest concentration of cases (n=12); median head circumference was 29 cm, median chest girth was 31 cm and median weight was 2,628 grams; 21/25 cases had brain calcification, ventriculomegaly or lissencephaly; 27 of the 40 mothers reported rash during pregnancy, 20 in the first trimester and 7 in the second trimester, as well as itching, headache, myalgia and absence of fever. CONCLUSION: the majority of the cases bore the characteristics of congenital infection; the clinical condition of the majority of mothers suggested Zika virus infection during pregnancy.

Microcephaly in Pernambuco State, Brazil: epidemiological characteristics and evaluation of the diagnostic accuracy of cutoff points for reporting suspected cases. / Microcefalia no Estado de Pernambuco, Brasil: características epidemiológicas e avaliação da acurácia diagnóstica dos pontos de corte adotados para notificação de caso.

The increase in the number of reported cases of microcephaly in Pernambuco State, and Northeast Brazil, characterized an epidemic that led the Brazilian Ministry of Health to declare a national public health emergency. The Brazilian Ministry of Health initially defined suspected cases as newborns with gestational age (GA) ≥ 37 weeks and head circumference (HC) ≤ 33cm, but in December 2015 this cutoff was lowered to 32cm. The current study aimed to estimate the accuracy, sensitivity, and specificity of different cutoff points for HC, using ROC curves, with the Fenton and Intergrowth (2014) curves as the gold standard. The study described cases reported in Pernambuco from August 8 to November 28, 2015, according to sex and GA categories. The Fenton and Intergrowth methods provide HC growth curves according to GA and sex, and microcephaly is defined as a newborn with HC below the 3rd percentile in these distributions. Of the 684 reported cases, 599 were term or post-term neonates. For these, the analyses with ROC curves show that according to the Fenton criterion the cutoff point with the largest area under the ROC curve, with sensitivity greater than specificity, is 32cm for both sexes. Using the Intergrowth method and following the same criteria, the cutoff points are 32cm and 31.5cm for males and females, respectively. The cutoff point identified by the Fenton method (32cm) coincided with the Brazilian Ministry of Health recommendation. Adopting Intergrowth as the standard, the choice would be 32cm for males and 31.5cm for females. The study identified the need to conduct critical and on-going analyses to evaluate cutoff points, including other characteristics for microcephaly case definition.