Microcephaly epidemic related to the Zika virus and living conditions in Recife, Northeast Brazil.

BACKGROUND: Starting in August 2015, there was an increase in the number of cases of neonatal microcephaly in Northeast Brazil. These findings were identified as being an epidemic of microcephaly related to Zika virus (ZIKV) infection. The present study aims to analyse the spatial distribution of microcephaly cases in Recife (2015-2016), which is in Northeast Brazil, and its association with the living conditions in this city. METHODS: This was an ecological study that used data from reported cases of microcephaly from the State Health Department of Pernambuco (August 2015 to July 2016). The basic spatial unit of analysis was the 94 districts of Recife. The case definition of microcephaly was: neonates with a head circumference of less than the cut-off point of -2 standard deviations below the mean value from the established Fenton growth curve. As an indicator of the living conditions of the 94 districts, the percentage of heads of households with an income of less than twice the minimum wage was calculated. The districts were classified into four homogeneous strata using the K-means clustering algorithm. We plotted the locations of each microcephaly case over a layer of living conditions. RESULTS: During the study period, 347 microcephaly cases were reported, of which 142 (40.9%) fulfilled the definition of a microcephaly case. Stratification of the 94 districts resulted in the identification of four strata. The highest stratum in relation to the living conditions presented the lowest prevalence rate of microcephaly, and the overall difference between this rate and the rates of the other strata was statistically significant. The results of the Kruskal-Wallis test demonstrated that there was a strong association between a higher prevalence of microcephaly and poor living conditions. After the first 6 months of the study period, there were no microcephaly cases recorded within the population living in the richest socio-economic strata. CONCLUSION: This study showed that those residing in areas with precarious living conditions had a higher prevalence of microcephaly compared with populations with better living conditions.

Could the erythrocyte indices or serum ferritin predict the therapeutic response to a trial with oral iron during pregnancy? Results from the Accuracy study for Maternal Anaemia diagnosis (AMA).

BACKGROUND: Treatment of maternal iron-deficiency anaemia can reduce risks of prematurity and low birth weight; hence a reliable diagnosis of maternal iron needs is critical. However, erythrocyte indices and serum ferritin have shown a weak correlation with iron status during pregnancy. This study verified the accuracy of those tests to predict the responsiveness to a therapeutic test with oral iron as reference standard for iron deficiency in pregnant women. METHODS: A prospective diagnostic study phase 3 was conducted in a single prenatal care center in Northeast Brazil. Between August 2011 and October 2012 a consecutive sampling included 187 women in their 2(nd)-3(rd) trimesters of low-risk pregnancy and having anaemia (haemoglobin <11.0 g/dL). Until December 2012, 139 women completed a trial with daily pills of ferrous sulfate (40 mg of iron), during 23 to 125 days. Haemoglobin (Hb), other erythrocyte indices and ferritin (index-tests) were assessed pre-treatment by automated analyzers. Hb was performed also post-treatment to assess the therapeutic response by its post-pretreatment differences. We estimated sensitivity (Se), specificity (Sp), predictive values (PV), likelihood ratios (LR), diagnostic Odds Ratio (OR), area under Receiver Operating Characteristic curve (AUC), accuracy ratio and agreement coefficient of the index-tests against an increase of at least 0.55 Hb Z-score (reference standard test). We calculated the Z-scores according to the reference population from Centers for Disease Control and Prevention. RESULTS: Hb had a mean increase of 0.24 Z-score after 30 iron pills (p 0.013). All index-tests demonstrated PV- above 70 %, PV+ around 40 %, LR around 1.0, and AUC of 0.5 to 0.6. Hb and haematocrit had Se of 50 % (95 % CI 40 to 70); and Sp of 59 % (95 % CI 43 to 74) and 47 % (95 % CI 38 to 57), respectively. Ferritin, Mean Corpuscular Volume, Mean Corpuscular Haemoglobin, Mean Corpuscular Haemoglobin Concentration and Red blood cell Distribution Width had Se below 40 % with Sp above 70 %. CONCLUSIONS: Erythrocyte indices and ferritin could not predict the iron needs of anemic pregnant women. Increases of Hb Z-scores after a short treatment with oral iron may be a reliable therapeutic test. TRIAL REGISTRATION: World Health Organization International Clinical Trials Registry Platform U1111-1123-2605; Brazilian Registry of Clinical Trials RBR-237wbg , registered 28 July 2011.

Evaluation of four molecular methods for the diagnosis of tuberculosis in pulmonary and blood samples from immunocompromised patients.

The present study analysed the concordance among four different molecular diagnostic methods for tuberculosis (TB) in pulmonary and blood samples from immunocompromised patients. A total of 165 blood and 194 sputum samples were collected from 181 human immunodeficiency virus (HIV)-infected patients with upper respiratory complaints, regardless of suspicious for TB. The samples were submitted for smear microscopy, culture and molecular tests: a laboratory-developed conventional polymerase chain reaction (PCR) and real-time quantitative PCR (qPCR) and the Gen-Probe and Detect-TB Ampligenix kits. The samples were handled blindly by all the technicians involved, from sample processing to results analysis. For sputum, the sensitivity and specificity were 100% and 96.7% for qPCR, 81.8% and 94.5% for Gen-Probe and 100% and 66.3% for Detect-TB, respectively. qPCR presented the best concordance with sputum culture [kappa (k) = 0.864)], followed by Gen-Probe (k = 0.682). For blood samples, qPCR showed 100% sensitivity and 92.3% specificity, with a substantial correlation with sputum culture (k = 0.754) and with the qPCR results obtained from sputum of the corresponding patient (k = 0.630). Conventional PCR demonstrated the worst results for sputa and blood, with a sensitivity of 100% vs. 88.9% and a specificity of 46.3% vs. 32%, respectively. Commercial or laboratory-developed molecular assays can overcome the difficulties in the diagnosis of TB in paucibacillary patients using conventional methods available in most laboratories.

Diagnostic accuracy of hemoglobin for iron deficiency in pregnancy: disclosing results of a cited clinical trial.

OBJECTIVE: To analyze the accuracy of hemoglobin (Hb) concentrations as a diagnostic indicator of iron deficiency in pregnant women and to measure the efficacy of oral iron therapy using Hb z-scores rather than Hb absolute values. METHODS: The sensitivity and specificity of Hb < 11.0 g/dL, and its receiver operating characteristic (ROC) curve, in the diagnosis of iron deficiency (serum ferritin (SF) < 12.0 ng/mL) were determined in 318 women in their second trimester of pregnancy who had been screened for a clinical trial conducted in 2001 in Northeast Brazil. A secondary analysis of iron therapy efficacy was carried out using data from the trial's three different treatments (60 mg of oral iron once per week (n = 46), twice per week (n = 50), and once per day (n = 44)). The mean differences between post- and pre-treatment Hb absolute values (g/dL) and z-scores (standard deviation (SD)) were calculated for the three treatment groups for study participants with and without iron deficiency. RESULTS: Hb sensitivity, specificity, and area under the ROC curve were 60.7%, 44.3%, and 0.54 respectively. Women without iron deficiency showed improvements in Hb absolute values (as in the clinical trial's overall results) but did not have improved Hb z-scores (with scores of - 0.6 SD (95% confidence interval (CI): - 0.99, - 0.28); - 0.2 SD (95% CI: - 0.47, 0.08); and - 0.1 SD (95% CI: - 0.33, 0.18) for weekly, twice-per-week, and daily iron treatment schemes respectively). In contrast, iron-deficient women treated with the intermittent schemes had reductions in both Hb absolute values and Hb z-scores, respectively: weekly = - 0.42 g/dL (95% CI: - 0.72, - 0.12) and - 1.4 SD (95% CI: - 1.74, - 0.99); twice per week = - 0.14 g/dL (95% CI: - 0.46, 0.17) and - 1.1 SD (95% CI: - 1.44, - 0.75). CONCLUSIONS: These analyses revealed that Hb concentrations were not an accurate indicator of either iron needs or iron-therapy response in pregnant women.

Accuracy of erythrogram and serum ferritin for the maternal anemia diagnosis (AMA): a phase 3 diagnostic study on prediction of the therapeutic responsiveness to oral iron in pregnancy.

BACKGROUND: Pregnancy anemia remains as a public health problem, since the official reports in the 70's. To guide the treatment of iron-deficiency anemia in pregnancy, the haemoglobin concentration is the most used test in spite of its low accuracy, and serum ferritin is the most reliable test, although its cutoff point remains an issue. METHODS/DESIGN: The aim of this protocol is to verify the accuracy of erythrocyte indices and serum ferritin (studied tests) for the diagnosis of functional iron-deficiency in pregnancy using the iron-therapy responsiveness as the gold-standard. This is an ongoing phase III accuracy study initiated in August 2011 and to be concluded in April 2013. The subjects are anemic pregnant women (haemoglobin concentration < 11.0 g/dL) attended at a low-risk prenatal care center in the Northeast of Brazil. The sample size (n 278) was calculated to estimate sensitivity of 90% and 80% of specificity with relative error of 10% and power of 95%. This study has a prospective design with a before-after intervention of 80 mg of daily oral iron during 90 days and will be analyzed as a delayed-type cross-sectional study. Women at the second trimester of pregnancy are being evaluated with clinical and laboratorial examinations at the enrollment and monthly. The 'responsiveness to therapeutic test with oral iron' (gold-standard) was defined to an increase of at least 0.55 Z-score in haemoglobin after 4 weeks of treatment and a total dose of 1200 mg of iron. At the study conclusion, sensitivities, specificities, predictive values, likelihood ratios and areas under the ROC (Receiver Operating Characteristic) curves of serum ferritin and erythrocyte indices (red blood cell count, haematocrit, haemoglobin concentration, mean corpuscular volume, mean corpuscular haemoglobin, mean corpuscular haemoglobin concentration, red blood cell distribution width, reticulocyte count) will be tested. The compliance and adverse effects are considered confounding variables, since they are the main obstacles for the iron-therapy responsiveness. DISCUSSION: This study protocol shows a new approach on iron-deficiency anemia in pregnancy from a functional point of view that could bring some insights about the diagnostic misclassifications arising from the dynamic physiologic changes during the gestational cycle. TRIAL REGISTRATION: WHO International Clinical Trials Registry Platform U1111-1123-2605.

Prevalence of hepatitis A in the capitals of the States of North, Southeast and South regions of Brazil: decrease in prevalence and some consequences.

Hepatitis A virus (HAV) infection has been considered one of the leading causes of acute hepatitis. The aim of the present study was to estimate the prevalence of HAV among children and adolescents in a population-based study in the capitals of the States of the North, Southeast and South of Brazil and identify predictive factors for the infection. A multi-stage sampling was used to select subjects aged between 5-9 and 10-19 years. Individual and household levels aside from the level of variables in the areas were collected. The outcome was the total IgG antibodies to HAV levels detected using a commercial Enzyme Immuno Assay (EIA). The associations between HAV and the independent variables were assessed using the odds ratio. A multilevel analysis was performed by GLLAMM using the Stata software. The prevalence of HAV infection in the 5-9 and 10-19 age groups was 28.7% and 67.5%, respectively for the North, 20.6% and 37.7%, for the Southeast and 18.9% and 34.5% for the South Region. The prevalence of HAV increased according to age in all sites. Variables related to education at the individual level (North and South), family and area level (South and Southeast) and family income level (Southeast and South) were independently associated with HAV infection. This emphasizes the need for individualized strategies to prevent the infection.

[Assessment of the impact of prenatal, childbirth, and neonatal care on avoidable neonatal deaths in Pernambuco State, Brazil: an adequacy study]. / Avaliação do impacto de programas de assistência pré-natal, parto e ao recém-nascido nas mortes neonatais evitáveis em Pernambuco, Brasil: estudo de adequação.

This study aimed to assess the impact of programs for prenatal, childbirth, and neonatal care (Mother Owl and Stork Network) on avoidable neonatal mortality in Pernambuco State, Brazil, using the adequacy approach. We analyzed the trend in avoidable neonatal mortality and the impact of these programs on avoidable neonatal mortality in four health regions in the state from 2000 to 2016. The Mortality Information System (SIM) and the Information System on Live Births (SINASC) and official documents were used as the data sources. Deaths were classified according to the Brazilian List of Avoidable Causes of Deaths Via Interventions by the Unified National Health System. Linear regression and joinpoint methods were used to analyze tendencies and identifying turning points in the neonatal mortality curves. There was a sharp drop in avoidable neonatal mortality in the state, especially in early neonatal mortality. Except for the I-Recife region, where there was a downturn in the mortality curves after implementation of the Stork Network, there was no association between the turning points in the curves and the periods with the programs' implementation in the regions. Other factors appear to have led to the improvement of these indicators, such as the expansion of the high-risk network. Strengthening this network can thus help reduce avoidable neonatal deaths, especially early deaths.

Este estudo teve como objetivo avaliar o impacto de programas voltados à assistência pré-natal, parto e ao recém-nascido (Mãe Coruja Pernambucana e Rede Cegonha) na mortalidade neonatal evitável no Estado de Pernambuco, Brasil, utilizando a abordagem de adequação. Analisou-se a tendência dos coeficientes de mortalidade neonatal evitável, bem como o impacto desses programas na mortalidade neonatal evitável em quatro regiões de saúde do estado, de 2000 a 2016. Sistemas de Informações sobre Mortalidade (SIM) e de Nascidos Vivos (SINASC) e documentos oficiais foram usados como fonte de dados. Os óbitos foram classificados segundo a Lista Brasileira de Causas de Óbitos Evitáveis por Intervenções do SUS. Utilizaram-se métodos de regressão linear e joinpoint para análise das tendências e identificação de pontos de inflexão nas curvas de mortalidade neonatal. Houve acentuada queda da mortalidade neonatal evitável no estado, principalmente a precoce. Excetuando-se a Região I-Recife, onde observou-se inflexão negativa das curvas de mortalidade após a implantação da Rede Cegonha, não houve correspondência das inflexões nas curvas com os períodos de implantação dos programas nas demais regiões. Outros fatores parecem ter atuado na melhoria desses indicadores, como a ampliação da rede de alto risco. Portanto, o fortalecimento dessa rede pode contribuir na redução dos óbitos neonatais evitáveis, particularmente o precoce.

El objetivo de este estudio fue evaluar el impacto de programas dirigidos a la asistencia pre-natal, parto y cuidados al recién nacido (Madre-Búho y Red Cigüeña) en la mortalidad neonatal evitable en el estado de Pernambuco, Brasil, utilizando un abordaje de adecuación. Se analizó la tendencia de los coeficientes de mortalidad neonatal evitable, así como el impacto de estos programas en la mortalidad neonatal evitable en cuatro regiones de salud del estado, de 2000 a 2016. Se utilizaron como fuente de datos los Sistemas de Información sobre Mortalidad (SIM) y de Nacidos Vivos (SINASC), así como documentos oficiales. Los óbitos se clasificaron según la Lista Brasileña de Causas de Óbitos Evitables por Intervenciones del SUS. Se utilizaron métodos de regresión lineal y joinpoint para el análisis de las tendencias e identificación de puntos de inflexión en la curvas de mortalidad neonatal. Hubo una acentuada caída de la mortalidad neonatal evitable en el estado, principalmente la precoz. Exceptuándose la región I-Recife, donde se observó una inflexión negativa de las curvas de mortalidad tras la implantación de la Red Cigüeña, no hubo una correspondencia de las inflexiones en las curvas con los períodos de implantación de los programas en las demás regiones. Otros factores parecen haber actuado en la mejoría de estos indicadores, como la ampliación de la red de alto riesgo. Por tanto, el fortalecimiento de esta red puede contribuir a la reducción de los óbitos neonatales evitables, particularmente el precoz.

The first hundred days of COVID-19 in Pernambuco State, Brazil: epidemiology in historical context. / Cem dias de COVID-19 em Pernambuco, Brasil: a epidemiologia em contexto histórico.

The timeline of the COVID-19 pandemic began on December 31, 2019, in China, with SARS-CoV-2 identified as the etiological agent. This article aims to describe the COVID-19 epidemic's spatial and temporal dynamics in the first hundred days in the State of Pernambuco, Brazil. We present the evolution in cases and deaths according to epidemiological weeks. We analyzed the series of accumulated daily confirmed COVID-19 cases, with projections for the subsequent 15 days, using the JoinPoint app. This software allows identifying turning points, testing their statistical significance. We also analyze the trend in the spread of COVID-19 to the interior of the state, considering the percent distribution of cases in the state capital, Recife, municipalities in Greater Metropolitan Recife, and the state's interior, by sets of three weeks, constructing thematic maps. The first hundred days of the COVID-19 epidemic resulted in 52,213 cases and 4,235 deaths from March 12, or epidemiological week 11, until June 20, 2020 (epidemiological week 25). The peak in the epidemic curve occurred in epidemiological week 21 (May 23), followed by deceleration in the number of cases. We initially detected the spread of cases from the city center to the periphery of the state capital and Metropolitan Area, followed by rapid spread to the state's interior. There was a decrease in the mean daily growth starting in April, but with an average threshold of more than 6,000 weekly cases of COVID-19. At the end of the period, the state's case series indicates the persistence of SARS-CoV-2 circulation and community transmission. Finally, paraphrasing Gabriel Garcia Marques in One Hundred Years of Solitude, we ask whether we are facing "a pause in the storm or a sign of redoubled rain".

A pandemia de COVID-19 iniciou sua linha do tempo em 31 de dezembro de 2019 na China e o SARS-CoV-2 identificado como agente etiológico. O objetivo deste manuscrito é descrever a dinâmica espacial e temporal da epidemia de COVID-19 nos primeiros cem dias, no Estado de Pernambuco, Brasil. Apresentamos a evolução de casos e óbitos segundo semana epidemiológica. Realizamos a análise da série do acumulado diário de casos da COVID-19 confirmados, com projeções para os 15 dias subsequentes, utilizando o aplicativo JoinPoint. Esse programa possibilita identificar pontos de inflexão testando sua significância estatística. Analisamos também a tendência de interiorização da COVID-19 no estado, considerando a distribuição percentual de casos ocorridos no Recife, municípios da Região Metropolitana de Recife e do interior, por conjuntos de três semanas, com construção de mapas temáticos. Os 100 dias da epidemia de COVID-19 resultaram em 52.213 casos e 4.235 óbitos entre 12 de março, correspondendo se 11, até 20 de junho de 2020 (semana epidemiológica 25). O pico da curva epidêmica ocorreu na semana epidemiológica 21 (23 de maio), seguido por desaceleração do número de casos. Detectou-se, inicialmente, a periferização dos casos na capital e região metropolitana, seguida por rápida disseminação para o interior do estado. Houve redução das taxas de crescimento médio diário a partir de abril, mas com patamar de mais de 6.000 casos semanais de COVID-19, em média. Ao final do período, a série de casos do estado indica persistência da circulação e transmissão comunitária do SARS-CoV-2. Finalmente, questiona-se parafraseando Garcia Marques em Cem Anos de Solidão, se estaríamos diante de "uma estiagem ou prenúncio de recrudescimento".

La pandemia de COVID-19 inicia su línea del tiempo el 31 de dicembre de 2019 en China y el SARS-CoV-2 identificado como agente etiológico. El objetivo de este trabajo original es describir la dinámica espacial y temporal de la epidemia de COVID-19 en los primeros cien días de epidemia, en el estado de Pernambuco, Brasil. Presentamos la evolución de casos y óbitos según las semanas epidemiológicas. Realizamos el análisis de la serie del acumulado diario de casos de COVID-19 confirmados, con proyecciones para los 15 días subsiguientes, utilizándose la aplicación JoinPoint. Este programa posibilita identificar puntos de inflexión, probando su significancia estadística. Analizamos también la tendencia de interiorización de la COVID-19 en el estado, considerándose la distribución porcentual de casos ocurridos en Recife, municipios de la Región Metropolitana de Recife y del interior, por conjuntos de tres semanas, con unas construcciones de mapas temáticos. Los cien días de la epidemia de COVID-19 resultaron en 52.213 casos y 4.235 óbitos entre el 12 de marzo, correspondiendo a la semana epidemiológica 11, hasta el 20 de juno de 2020 (semana epidemiológica 25). El pico de la curva epidémica ocurrió en la semana epidemiológica 21 (23 de mayo), seguido de una desaceleración en el número de casos. Se detectó, inicialmente, la periferización de los casos en la capital y región metropolitana, seguido por la rápida diseminación hacia el interior del estado. Hubo una reducción de las tasas de crecimiento medio diario a partir de abril, pero con un nivel de más de 6.000 casos semanales de COVID-19 de media. Al final del período la serie de casos del estado indica la persistencia de la circulación y transmisión comunitaria del SARS-CoV-2. Finalmente, se cuestiona, parafraseando a García Márquez en Cien Años de Soledad, si estamos ante "un periodo de remisión o la antesala de un recrudecimiento".

[Family screening for HBB*S gene and detection of new cases of sickle cell trait in Northeastern Brazil]. / Triagem familiar para o gene HBB*S e detecção de novos casos de traço falciforme em Pernambuco.

OBJECTIVE: To estimate the additional number of affected individuals based on the prevalence of sickle-cell syndromes among relatives of index cases. METHODS: Cross-sectional study of relatives of a random sample of index cases identified through a neonatal screening program in Northeastern Brazil, between 2001 and 2005. The extended family trial model included 463 relatives of 21 index cases. Relatives were classified as nuclear family (NF: father, mother, and siblings); first degree extended family (N1: grandparents, uncles and aunts, and first cousins); second degree extended family (N2: children of first cousins); extended family (NA: NF+N1+N2); and extended nuclear family (NA1: NF+N1). The presence of HBB*S and other abnormal hemoglobins was confirmed by high-performance liquid chromatography. The association between the presence of HBB*S and other variables was calculated using prevalence ratios and their respective 95% confidence intervals, and differences between means were calculated using Student's t test with a 5% significance level. RESULTS: Of relatives, 81% had no knowledge of sickle-cell anemia and HBB*S was present in 114 family members. A total of 53.3% of the studied population was considered as of reproductive age, and 80% of HBB*S carriers had already had children. Frequency was higher among NF (69%), but was also high in N1 (22.8%). NA1 screening resulted in the detection of 69 carriers additional (a 172% increase). CONCLUSIONS: These results indicate that family screening for the identification of sickle-cell carriers should be extended to first degree relatives.

Factors associated with underreporting of tuberculosis based on data from Sinan Aids and Sinan TB. / Fatores associados à subnotificação de tuberculose com base no Sinan Aids e Sinan Tuberculose.

INTRODUCTION: Tuberculosis (TB) is one of the world's major public health problems. Epidemiological surveillance has proved to be an important tool to assist in the control and prevention of communicable diseases such as TB and AIDS. This study aimed to estimate the rate and factors associated with the underreporting of TB among cases of coinfection with human immunodeficiency virus (HIV)/AIDS in the state of Pernambuco, based on data from the TB and Aids Notifiable Diseases Information System (Sinan TB and Sinan AIDS). METHODS: A cross-sectional study was carried out based on the records of the TB and AIDS Notification System to identify cases of TB underreporting in the study period. In order to identify underreporting, a probabilistic linkage was undertaken using RecLink III software. RESULTS: The rate of TB underreporting was 29%, and the factors associated were: presenting a clinical form of TB as cavitary or unspecified pulmonary TB or having both kinds of TB at the same time; being treated outside the municipality of Recife; and being treated at health services not specialized for HIV/AIDS. DISCUSSION: The proportion of underreporting found in our study was lower than that observed in other Brazilian studies that took into account underreporting from mortality data. CONCLUSION: The variables associated with underreporting of TB were mostly related to the healthcare system rather than to individual characteristics, which points to the need for training of health professionals in order to notify the information systems correctly.

INTRODUÇÃO: A tuberculose (TB) é um dos graves problemas da saúde pública mundial. A vigilância epidemiológica tem se mostrado uma importante ferramenta para auxiliar em ações de controle e prevenção de doenças transmissíveis, como a TB e a aids. O objetivo do presente estudo foi estimar a proporção e os fatores associados à subnotificação da tuberculose em Pernambuco, entre os casos de coinfecção TB/aids, com base nos dados do Sistema de Informação de Agravos de Notificação da TB e da aids. MÉTODOS: Realizou-se um estudo de corte seccional, baseado nos registros dos Sistemas de Notificação de TB e aids, para identificação de casos de subnotificação de TB no período de estudo, mediante a realização de linkage probabilístico utilizando o software RecLink III. Resultados: Verificou-se proporção de 29% de subnotificação de TB, e os fatores associados à subnotificação foram: apresentar forma clínica da TB pulmonar cavitária ou não especificada, ou ter os dois tipos de TB ao mesmo tempo; e ser atendido fora do Recife e em serviços que não são especializados para vírus da imunodeficiência humana (HIV)/aids. DISCUSSÃO: A proporção de subnotificação encontrada em nosso estudo foi menor do que a observada em outras pesquisas brasileiras que levaram em consideração a subnotificação haja vista os dados de mortalidade. CONCLUSÃO: As variáveis associadas à subnotificação de TB referem-se, em sua maioria, à rede de atenção, e não às características individuais, o que aponta para a necessidade de capacitação dos profissionais de saúde para efetuar a notificação aos sistemas de informação.

The microcephaly epidemic and Zika virus: building knowledge in epidemiology. / Epidemia de microcefalia e vírus Zika: a construção do conhecimento em epidemiologia.

In August 2015, pediatric neurologists at public hospitals in Recife, Pernambuco State, Brazil, observed an increase in the number of disproportional microcephaly cases associated with other congenital anomalies. The fact caused social commotion and mobilization of the academic community and led the Brazilian Ministry of Health to declare a national public health emergency, followed by the declaration of a Public Health Emergency of International Concern by the World Health Organization. The hypothesis for the phenomenon was congenital Zika virus (ZIKV) infection, based on spatial-temporal correlation and the clinical-epidemiological characteristics of the two epidemics. Further evidence accumulated, and within the scope of epidemiologial reasoning fulfilled criteria that gave support to the hypothesis. The plausibility of the hypothesis is based on the neurotropism of ZIKV, demonstrated in animals, affecting neural progenitors in the developing brain, and in humans, due to neurological complications in adults following infection. Isolation of viral RNA and antigens in the amniotic fluid of infected mothers and in brains of newborns and fetuses with microcephaly further demonstrated the consistency of the hypothesis. The criterion of temporality was met by identifying adverse pregnancy outcomes in a cohort of mothers with a history of rash and positive ZIKV serology. Finally, the first case-control study demonstrated a strong association between microcephaly and congenital ZIKV infection. The knowledge built with the epidemiological paradigm was supported by the scientific community, thereby establishing the consensus for a causal relationship between ZIKV and the microcephaly epidemic.

Em agosto de 2015, neuropediatras de hospitais públicos do Recife, Pernambuco, Brasil, observaram um aumento do número de casos de microcefalia desproporcional associado a anomalias cerebrais. Esse fato gerou comoção social, mobilização da comunidade acadêmica e levou o Ministério da Saúde a decretar emergência de saúde pública nacional, seguida pela declaração de emergência de saúde pública de interesse internacional da Organização Mundial da Saúde. A hipótese formulada para o fenômeno foi a infecção congênita pelo vírus Zika (ZIKV), com base na correlação espaço-temporal e nas características clínico-epidemiológicas das duas epidemias. Evidências se acumularam e no âmbito do raciocínio epidemiológico preencheram critérios que deram sustentação à hipótese. Sua plausibilidade está ancorada no neurotropismo do ZIKV demonstrado em animais, atingindo neurônios progenitores do cérebro em desenvolvimento, e em seres humanos devido às complicações neurológicas observadas em adultos após a infecção. O isolamento do RNA e antígenos virais no líquido amniótico de mães infectadas e em cérebros de neonatos e fetos com microcefalia contribuíram para demonstrar a consistência da hipótese. O critério de temporalidade foi contemplado ao se identificar desfechos desfavoráveis em uma coorte de gestantes com exantema e positivas para o ZIKV. Finalmente, o primeiro estudo caso-controle conduzido demonstrou existir uma forte associação entre microcefalia e infecção congênita pelo ZIKV. O conhecimento construído no âmbito do paradigma epidemiológico recebeu a chancela da comunidade científica, construindo o consenso de uma relação causal entre o ZIKV e a epidemia de microcefalia.

En agosto de 2015, neuropediatras de hospitales públicos de Recife, Pernambuco, Brasil, observaron un aumento desproporcional del número de casos de microcefalia, asociado a anomalías cerebrales. Este hecho generó conmoción social, movilización de la comunidad académica y obligó al Ministerio de Salud a decretar la emergencia de salud pública nacional, seguida de la declaración de interés internacional de la Organización Mundial de la Salud. La hipótesis formulada para este fenómeno fue la infección congénita por el virus Zika (ZIKV), en base a la correlación espacio-temporal y a las características clínico-epidemiológicas de las dos epidemias. Se acumularon evidencias, y en el ámbito del raciocinio epidemiológico se cumplieron los criterios que dieron apoyo a la hipótesis. Su plausibilidad está anclada en el neurotropismo del ZIKV, demostrado en animales, alcanzando progenitores neuronales del cerebro en desarrollo, y en seres humanos, debido a las complicaciones neurológicas observadas en adultos tras la infección. El aislamiento del ARN y antígenos virales en el líquido amniótico de madres infectadas, en cerebros de neonatos y fetos con microcefalia, contribuyeron a demostrar la consistencia de la hipótesis. El criterio de temporalidad se contempló al identificarse desenlaces desfavorables en una cohorte de gestantes con exantema y positivas en ZIKV. Finalmente, el primer estudio caso-control realizado demostró que existía una fuerte asociación entre microcefalia e infección congénita por el ZIKV. El conocimiento construido en el ámbito del paradigma epidemiológico recibió la aprobación de la comunidad científica, existiendo consenso en cuanto a la relación causal entre el ZIKV y la epidemia de microcefalia.

Dengue as a cause of fever during pregnancy: a report of two cases.

Dengue infection has not been routinely investigated among pregnant women and parturients with acute febrile syndrome in endemic settings. Here, we report two cases of dengue fever detected at the time of delivery in parturients enrolled in a cohort prospective study conducted in a hospital in Recife, Brazil. The parturients reported fever onset within seven days prior to delivery, and dengue infection was confirmed upon detection of viral ribonucleic acid (RNA) by using the reverse transcriptase-polymerase chain reaction. Dengue infection should be considered as a diagnostic possibility in cases of fever during pregnancy and labor, especially in endemic areas.

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.

Avaliação do impacto de programas de assistência pré-natal, parto e ao recém-nascido nas mortes neonatais evitáveis em Pernambuco, Brasil: estudo de adequação / Assessment of the impact of prenatal, childbirth, and neonatal care on avoidable neonatal deaths in Pernambuco State, Brazil: an adequacy study / Evaluación del impacto de programas de asistencia pre-natal, parto y cuidados al recién-nacido en las muertes neonatales evitables en Pernambuco, Brasil: estudio de adecuación

Este estudo teve como objetivo avaliar o impacto de programas voltados à assistência pré-natal, parto e ao recém-nascido (Mãe Coruja Pernambucana e Rede Cegonha) na mortalidade neonatal evitável no Estado de Pernambuco, Brasil, utilizando a abordagem de adequação. Analisou-se a tendência dos coeficientes de mortalidade neonatal evitável, bem como o impacto desses programas na mortalidade neonatal evitável em quatro regiões de saúde do estado, de 2000 a 2016. Sistemas de Informações sobre Mortalidade (SIM) e de Nascidos Vivos (SINASC) e documentos oficiais foram usados como fonte de dados. Os óbitos foram classificados segundo a Lista Brasileira de Causas de Óbitos Evitáveis por Intervenções do SUS. Utilizaram-se métodos de regressão linear e joinpoint para análise das tendências e identificação de pontos de inflexão nas curvas de mortalidade neonatal. Houve acentuada queda da mortalidade neonatal evitável no estado, principalmente a precoce. Excetuando-se a Região I-Recife, onde observou-se inflexão negativa das curvas de mortalidade após a implantação da Rede Cegonha, não houve correspondência das inflexões nas curvas com os períodos de implantação dos programas nas demais regiões. Outros fatores parecem ter atuado na melhoria desses indicadores, como a ampliação da rede de alto risco. Portanto, o fortalecimento dessa rede pode contribuir na redução dos óbitos neonatais evitáveis, particularmente o precoce.

This study aimed to assess the impact of programs for prenatal, childbirth, and neonatal care (Mother Owl and Stork Network) on avoidable neonatal mortality in Pernambuco State, Brazil, using the adequacy approach. We analyzed the trend in avoidable neonatal mortality and the impact of these programs on avoidable neonatal mortality in four health regions in the state from 2000 to 2016. The Mortality Information System (SIM) and the Information System on Live Births (SINASC) and official documents were used as the data sources. Deaths were classified according to the Brazilian List of Avoidable Causes of Deaths Via Interventions by the Unified National Health System. Linear regression and joinpoint methods were used to analyze tendencies and identifying turning points in the neonatal mortality curves. There was a sharp drop in avoidable neonatal mortality in the state, especially in early neonatal mortality. Except for the I-Recife region, where there was a downturn in the mortality curves after implementation of the Stork Network, there was no association between the turning points in the curves and the periods with the programs' implementation in the regions. Other factors appear to have led to the improvement of these indicators, such as the expansion of the high-risk network. Strengthening this network can thus help reduce avoidable neonatal deaths, especially early deaths.

El objetivo de este estudio fue evaluar el impacto de programas dirigidos a la asistencia pre-natal, parto y cuidados al recién nacido (Madre-Búho y Red Cigüeña) en la mortalidad neonatal evitable en el estado de Pernambuco, Brasil, utilizando un abordaje de adecuación. Se analizó la tendencia de los coeficientes de mortalidad neonatal evitable, así como el impacto de estos programas en la mortalidad neonatal evitable en cuatro regiones de salud del estado, de 2000 a 2016. Se utilizaron como fuente de datos los Sistemas de Información sobre Mortalidad (SIM) y de Nacidos Vivos (SINASC), así como documentos oficiales. Los óbitos se clasificaron según la Lista Brasileña de Causas de Óbitos Evitables por Intervenciones del SUS. Se utilizaron métodos de regresión lineal y joinpoint para el análisis de las tendencias e identificación de puntos de inflexión en la curvas de mortalidad neonatal. Hubo una acentuada caída de la mortalidad neonatal evitable en el estado, principalmente la precoz. Exceptuándose la región I-Recife, donde se observó una inflexión negativa de las curvas de mortalidad tras la implantación de la Red Cigüeña, no hubo una correspondencia de las inflexiones en las curvas con los períodos de implantación de los programas en las demás regiones. Otros factores parecen haber actuado en la mejoría de estos indicadores, como la ampliación de la red de alto riesgo. Por tanto, el fortalecimiento de esta red puede contribuir a la reducción de los óbitos neonatales evitables, particularmente el precoz.

Population-Based Multicentric Survey of Hepatitis B Infection and Risk Factors in the North, South, and Southeast Regions of Brazil, 10-20 Years After the Beginning of Vaccination.

A population-based hepatitis survey was carried out to estimate the prevalence of hepatitis B virus (HBV) infection and its predictive factors for the state capitals from the north, south, and southeast regions of Brazil. A multistage cluster sampling was used to select, successively, census tracts, blocks, households, and residents in the age group 10-69 years in each state capital. The prevalence of hepatitis B surface antigen (HBsAg) was lower than 1% in the north, southeast, and south regions. Socioeconomic condition was associated with HBV infection in north and south regions. Variables related to the blood route transmission were associated with HBV infection only in the south whereas those related to sexual behavior were associated with HBV infection in the north and south regions. Drug use was associated in all regions, but the type of drug differed. The findings presented herein highlight the diversity of the potential transmission routes for hepatitis B transmission in Brazil. In one hand, it reinforces the importance of national control strategies of large impact already in course (immunization of infants, adolescents, and adults up to 49 years of age and blood supply screening). On the other hand, it shows that there is still room for further control measures targeted to different groups within each region.

Cem dias de COVID-19 em Pernambuco, Brasil: a epidemiologia em contexto histórico / Cien días de COVID-19 en Pernambuco, Brasil: la epidemiología en contexto histórico / The first hundred days of COVID-19 in Pernambuco State, Brazil: epidemiology in historical context

Resumo: A pandemia de COVID-19 iniciou sua linha do tempo em 31 de dezembro de 2019 na China e o SARS-CoV-2 identificado como agente etiológico. O objetivo deste manuscrito é descrever a dinâmica espacial e temporal da epidemia de COVID-19 nos primeiros cem dias, no Estado de Pernambuco, Brasil. Apresentamos a evolução de casos e óbitos segundo semana epidemiológica. Realizamos a análise da série do acumulado diário de casos da COVID-19 confirmados, com projeções para os 15 dias subsequentes, utilizando o aplicativo JoinPoint. Esse programa possibilita identificar pontos de inflexão testando sua significância estatística. Analisamos também a tendência de interiorização da COVID-19 no estado, considerando a distribuição percentual de casos ocorridos no Recife, municípios da Região Metropolitana de Recife e do interior, por conjuntos de três semanas, com construção de mapas temáticos. Os 100 dias da epidemia de COVID-19 resultaram em 52.213 casos e 4.235 óbitos entre 12 de março, correspondendo se 11, até 20 de junho de 2020 (semana epidemiológica 25). O pico da curva epidêmica ocorreu na semana epidemiológica 21 (23 de maio), seguido por desaceleração do número de casos. Detectou-se, inicialmente, a periferização dos casos na capital e região metropolitana, seguida por rápida disseminação para o interior do estado. Houve redução das taxas de crescimento médio diário a partir de abril, mas com patamar de mais de 6.000 casos semanais de COVID-19, em média. Ao final do período, a série de casos do estado indica persistência da circulação e transmissão comunitária do SARS-CoV-2. Finalmente, questiona-se parafraseando Garcia Marques em Cem Anos de Solidão, se estaríamos diante de "uma estiagem ou prenúncio de recrudescimento".

Resumen: La pandemia de COVID-19 inicia su línea del tiempo el 31 de dicembre de 2019 en China y el SARS-CoV-2 identificado como agente etiológico. El objetivo de este trabajo original es describir la dinámica espacial y temporal de la epidemia de COVID-19 en los primeros cien días de epidemia, en el estado de Pernambuco, Brasil. Presentamos la evolución de casos y óbitos según las semanas epidemiológicas. Realizamos el análisis de la serie del acumulado diario de casos de COVID-19 confirmados, con proyecciones para los 15 días subsiguientes, utilizándose la aplicación JoinPoint. Este programa posibilita identificar puntos de inflexión, probando su significancia estadística. Analizamos también la tendencia de interiorización de la COVID-19 en el estado, considerándose la distribución porcentual de casos ocurridos en Recife, municipios de la Región Metropolitana de Recife y del interior, por conjuntos de tres semanas, con unas construcciones de mapas temáticos. Los cien días de la epidemia de COVID-19 resultaron en 52.213 casos y 4.235 óbitos entre el 12 de marzo, correspondiendo a la semana epidemiológica 11, hasta el 20 de juno de 2020 (semana epidemiológica 25). El pico de la curva epidémica ocurrió en la semana epidemiológica 21 (23 de mayo), seguido de una desaceleración en el número de casos. Se detectó, inicialmente, la periferización de los casos en la capital y región metropolitana, seguido por la rápida diseminación hacia el interior del estado. Hubo una reducción de las tasas de crecimiento medio diario a partir de abril, pero con un nivel de más de 6.000 casos semanales de COVID-19 de media. Al final del período la serie de casos del estado indica la persistencia de la circulación y transmisión comunitaria del SARS-CoV-2. Finalmente, se cuestiona, parafraseando a García Márquez en Cien Años de Soledad, si estamos ante "un periodo de remisión o la antesala de un recrudecimiento".

Abstract: The timeline of the COVID-19 pandemic began on December 31, 2019, in China, with SARS-CoV-2 identified as the etiological agent. This article aims to describe the COVID-19 epidemic's spatial and temporal dynamics in the first hundred days in the State of Pernambuco, Brazil. We present the evolution in cases and deaths according to epidemiological weeks. We analyzed the series of accumulated daily confirmed COVID-19 cases, with projections for the subsequent 15 days, using the JoinPoint app. This software allows identifying turning points, testing their statistical significance. We also analyze the trend in the spread of COVID-19 to the interior of the state, considering the percent distribution of cases in the state capital, Recife, municipalities in Greater Metropolitan Recife, and the state's interior, by sets of three weeks, constructing thematic maps. The first hundred days of the COVID-19 epidemic resulted in 52,213 cases and 4,235 deaths from March 12, or epidemiological week 11, until June 20, 2020 (epidemiological week 25). The peak in the epidemic curve occurred in epidemiological week 21 (May 23), followed by deceleration in the number of cases. We initially detected the spread of cases from the city center to the periphery of the state capital and Metropolitan Area, followed by rapid spread to the state's interior. There was a decrease in the mean daily growth starting in April, but with an average threshold of more than 6,000 weekly cases of COVID-19. At the end of the period, the state's case series indicates the persistence of SARS-CoV-2 circulation and community transmission. Finally, paraphrasing Gabriel Garcia Marques in One Hundred Years of Solitude, we ask whether we are facing "a pause in the storm or a sign of redoubled rain".

Validating a scoring system for the diagnosis of smear-negative pulmonary tuberculosis in HIV-infected adults.

BACKGROUND: The challenge of diagnosing smear-negative pulmonary TB (tuberculosis) in people living with HIV justifies the use of instruments other than the smear test for diagnosing the disease. Considering the clinical-radiological similarities of TB amongst HIV-infected adults and children, the proposal of this study was to assess the accuracy of a scoring system used to diagnose smear-negative pulmonary TB in children and adolescents, in HIV-infected adults suspected of having smear-negative pulmonary TB. METHODS: A Phase III validation study aiming to assess the diagnostic accuracy of a scoring system for diagnosing smear-negative pulmonary TB in HIV-infected adults. The study assessed sensitivity, specificity, positive and negative likelihood ratios, and positive and negative predictive values of the scoring system. Three versions of the scoring system were tested. RESULTS: From a cohort of 2,382 (HIV-infected adults), 1276 were investigated and 128 were diagnosed with pulmonary TB. Variables associated with the diagnosis of TB were: coughing, weight loss, fever, malnutrition, chest X-ray, and positive tuberculin test. The best diagnostic performance occurred with the scoring system with new scores, with sensitivity = 81.2% (95%-CI 74.5% -88%), specificity = 78% (75.6% -80.4%), PPV = 29.2% (24.5% -33.9%) and NPV = 97.4% (96.4% -98.4%), LR+ = 3.7 (3.4-4.0) and LR- = 0.24 (0.2-0.4). CONCLUSION: The proposed scoring system (with new scores) presented a good capacity for discriminating patients who did not have pulmonary TB, in the studied population. Further studies are necessary in order to validate it, thus permitting the assessment of its use in diagnosing smear-negative pulmonary TB in HIV-infected adults.

Fatores associados à subnotificação de tuberculose com base no Sinan Aids e Sinan Tuberculose / Factors associated with underreporting of tuberculosis based on data from Sinan Aids and Sinan TB

RESUMO: Introdução: A tuberculose (TB) é um dos graves problemas da saúde pública mundial. A vigilância epidemiológica tem se mostrado uma importante ferramenta para auxiliar em ações de controle e prevenção de doenças transmissíveis, como a TB e a aids. O objetivo do presente estudo foi estimar a proporção e os fatores associados à subnotificação da tuberculose em Pernambuco, entre os casos de coinfecção TB/aids, com base nos dados do Sistema de Informação de Agravos de Notificação da TB e da aids. Métodos: Realizou-se um estudo de corte seccional, baseado nos registros dos Sistemas de Notificação de TB e aids, para identificação de casos de subnotificação de TB no período de estudo, mediante a realização de linkage probabilístico utilizando o software RecLink III. Resultados: Verificou-se proporção de 29% de subnotificação de TB, e os fatores associados à subnotificação foram: apresentar forma clínica da TB pulmonar cavitária ou não especificada, ou ter os dois tipos de TB ao mesmo tempo; e ser atendido fora do Recife e em serviços que não são especializados para vírus da imunodeficiência humana (HIV)/aids. Discussão: A proporção de subnotificação encontrada em nosso estudo foi menor do que a observada em outras pesquisas brasileiras que levaram em consideração a subnotificação haja vista os dados de mortalidade. Conclusão: As variáveis associadas à subnotificação de TB referem-se, em sua maioria, à rede de atenção, e não às características individuais, o que aponta para a necessidade de capacitação dos profissionais de saúde para efetuar a notificação aos sistemas de informação.

ABSTRACT: Introduction: Tuberculosis (TB) is one of the world's major public health problems. Epidemiological surveillance has proved to be an important tool to assist in the control and prevention of communicable diseases such as TB and AIDS. This study aimed to estimate the rate and factors associated with the underreporting of TB among cases of coinfection with human immunodeficiency virus (HIV)/AIDS in the state of Pernambuco, based on data from the TB and Aids Notifiable Diseases Information System (Sinan TB and Sinan AIDS). Methods: A cross-sectional study was carried out based on the records of the TB and AIDS Notification System to identify cases of TB underreporting in the study period. In order to identify underreporting, a probabilistic linkage was undertaken using RecLink III software. Results: The rate of TB underreporting was 29%, and the factors associated were: presenting a clinical form of TB as cavitary or unspecified pulmonary TB or having both kinds of TB at the same time; being treated outside the municipality of Recife; and being treated at health services not specialized for HIV/AIDS. Discussion: The proportion of underreporting found in our study was lower than that observed in other Brazilian studies that took into account underreporting from mortality data. Conclusion: The variables associated with underreporting of TB were mostly related to the healthcare system rather than to individual characteristics, which points to the need for training of health professionals in order to notify the information systems correctly.

Epidemia de microcefalia e vírus Zika: a construção do conhecimento em epidemiologia / Epidemia de microcefalia y virus Zika: la construcción del conocimiento en epidemiología / The microcephaly epidemic and Zika virus: building knowledge in epidemiology

Em agosto de 2015, neuropediatras de hospitais públicos do Recife, Pernambuco, Brasil, observaram um aumento do número de casos de microcefalia desproporcional associado a anomalias cerebrais. Esse fato gerou comoção social, mobilização da comunidade acadêmica e levou o Ministério da Saúde a decretar emergência de saúde pública nacional, seguida pela declaração de emergência de saúde pública de interesse internacional da Organização Mundial da Saúde. A hipótese formulada para o fenômeno foi a infecção congênita pelo vírus Zika (ZIKV), com base na correlação espaço-temporal e nas características clínico-epidemiológicas das duas epidemias. Evidências se acumularam e no âmbito do raciocínio epidemiológico preencheram critérios que deram sustentação à hipótese. Sua plausibilidade está ancorada no neurotropismo do ZIKV demonstrado em animais, atingindo neurônios progenitores do cérebro em desenvolvimento, e em seres humanos devido às complicações neurológicas observadas em adultos após a infecção. O isolamento do RNA e antígenos virais no líquido amniótico de mães infectadas e em cérebros de neonatos e fetos com microcefalia contribuíram para demonstrar a consistência da hipótese. O critério de temporalidade foi contemplado ao se identificar desfechos desfavoráveis em uma coorte de gestantes com exantema e positivas para o ZIKV. Finalmente, o primeiro estudo caso-controle conduzido demonstrou existir uma forte associação entre microcefalia e infecção congênita pelo ZIKV. O conhecimento construído no âmbito do paradigma epidemiológico recebeu a chancela da comunidade científica, construindo o consenso de uma relação causal entre o ZIKV e a epidemia de microcefalia.

En agosto de 2015, neuropediatras de hospitales públicos de Recife, Pernambuco, Brasil, observaron un aumento desproporcional del número de casos de microcefalia, asociado a anomalías cerebrales. Este hecho generó conmoción social, movilización de la comunidad académica y obligó al Ministerio de Salud a decretar la emergencia de salud pública nacional, seguida de la declaración de interés internacional de la Organización Mundial de la Salud. La hipótesis formulada para este fenómeno fue la infección congénita por el virus Zika (ZIKV), en base a la correlación espacio-temporal y a las características clínico-epidemiológicas de las dos epidemias. Se acumularon evidencias, y en el ámbito del raciocinio epidemiológico se cumplieron los criterios que dieron apoyo a la hipótesis. Su plausibilidad está anclada en el neurotropismo del ZIKV, demostrado en animales, alcanzando progenitores neuronales del cerebro en desarrollo, y en seres humanos, debido a las complicaciones neurológicas observadas en adultos tras la infección. El aislamiento del ARN y antígenos virales en el líquido amniótico de madres infectadas, en cerebros de neonatos y fetos con microcefalia, contribuyeron a demostrar la consistencia de la hipótesis. El criterio de temporalidad se contempló al identificarse desenlaces desfavorables en una cohorte de gestantes con exantema y positivas en ZIKV. Finalmente, el primer estudio caso-control realizado demostró que existía una fuerte asociación entre microcefalia e infección congénita por el ZIKV. El conocimiento construido en el ámbito del paradigma epidemiológico recibió la aprobación de la comunidad científica, existiendo consenso en cuanto a la relación causal entre el ZIKV y la epidemia de microcefalia.

In August 2015, pediatric neurologists at public hospitals in Recife, Pernambuco State, Brazil, observed an increase in the number of disproportional microcephaly cases associated with other congenital anomalies. The fact caused social commotion and mobilization of the academic community and led the Brazilian Ministry of Health to declare a national public health emergency, followed by the declaration of a Public Health Emergency of International Concern by the World Health Organization. The hypothesis for the phenomenon was congenital Zika virus (ZIKV) infection, based on spatial-temporal correlation and the clinical-epidemiological characteristics of the two epidemics. Further evidence accumulated, and within the scope of epidemiologial reasoning fulfilled criteria that gave support to the hypothesis. The plausibility of the hypothesis is based on the neurotropism of ZIKV, demonstrated in animals, affecting neural progenitors in the developing brain, and in humans, due to neurological complications in adults following infection. Isolation of viral RNA and antigens in the amniotic fluid of infected mothers and in brains of newborns and fetuses with microcephaly further demonstrated the consistency of the hypothesis. The criterion of temporality was met by identifying adverse pregnancy outcomes in a cohort of mothers with a history of rash and positive ZIKV serology. Finally, the first case-control study demonstrated a strong association between microcephaly and congenital ZIKV infection. The knowledge built with the epidemiological paradigm was supported by the scientific community, thereby establishing the consensus for a causal relationship between ZIKV and the microcephaly epidemic.

Dengue as a cause of fever during pregnancy: a report of two cases

Abstract: Dengue infection has not been routinely investigated among pregnant women and parturients with acute febrile syndrome in endemic settings. Here, we report two cases of dengue fever detected at the time of delivery in parturients enrolled in a cohort prospective study conducted in a hospital in Recife, Brazil. The parturients reported fever onset within seven days prior to delivery, and dengue infection was confirmed upon detection of viral ribonucleic acid (RNA) by using the reverse transcriptase-polymerase chain reaction. Dengue infection should be considered as a diagnostic possibility in cases of fever during pregnancy and labor, especially in endemic areas.