Symptomatic dengue infection during pregnancy and livebirth outcomes in Brazil, 2007-13: a retrospective observational cohort study.

BACKGROUND: Dengue is a major public health challenge in Brazil. We assessed the relationship between symptomatic dengue infection during pregnancy and adverse birth outcomes in the country between 2007 and 2013. METHODS: We did a retrospective observational cohort study using information reported in the Brazilian national reportable disease information system (SINAN) and the livebirth information system (SINASC) databases. We probabilistically linked confirmed dengue-positive and dengue-negative pregnancies with live childbirths using Fine-Grained Record Integration and Linkage (FRIL) software. We also included an external reference population of randomly selected newborn babies. Pregnancy was adopted as the unit of analysis. We assessed the relationship between symptomatic dengue infection during pregnancy and adverse birth outcomes, using multivariable logistic regression adjusted for relevant covariates. FINDINGS: 3898 dengue-positive pregnant women, 3165 dengue-negative women, and 3898 newborn babies from the reference population were included in the analysis. Preterm birth occurred in 322 (8·4%) of 3821 cases in the dengue-positive group versus 324 (10·4%) of 3101 in the dengue-negative group (unadjusted analysis: relative risk [RR] 0·81, 95% CI 0·70-0·93; adjusted analysis: odds ratio [OR] 1·26, 95% CI 1·06-1·49, p=0·006) and 349 (9·1%) of 3818 in the reference population (RR 0·92, 0·80-1·07; OR 0·98, 0·83-1·16, p=0·84). The prevalence of low birthweight (<2500 g) was similar for dengue-positive women and dengue-negative women (8·3% [322 of 3897] vs 9·8% [310 of 3163]; OR 1·17, 95% CI 0·99-1·39, p=0·07), and in the reference population (8·3% vs 9·0% [350 of 3895]; OR 1·00, 0·85-1·17, p=0·97). The prevalence of malformations did not differ significantly for the dengue-positive group (27 [0·7%] of 3789) versus the dengue-negative group (27 [0·9%] of 3059, p=0·51) or versus the reference population (32 [0·9%] of 3738, p=0·56). INTERPRETATION: In the adjusted analysis, the risk of preterm birth seems to be increased in women with symptomatic dengue infection during pregnancy. However, symptomatic dengue infection during pregnancy does not appear to be associated with congenital malformations or low birthweight. FUNDING: Sanofi Pasteur.

Age and regional differences in clinical presentation and risk of hospitalization for dengue in Brazil, 2000-2014.

OBJECTIVES: Dengue cases range from asymptomatic to severe, eventually leading to hospitalization and death. Timely and appropriate management is critical to reduce morbidity. Since 1980, dengue has spread throughout Brazil, affecting an increasing number of individuals. This paper describes age and regional differences in dengue's clinical presentation and associated risk of hospitalization based on more than 5 million cases reported to the Brazilian Ministry of Health from 2000-2014. METHODS: We performed a retrospective analysis of ∼5,450,000 dengue cases, relating clinical manifestations and the risk of hospitalization to age, gender, previous infection by dengue, dengue virus serotype, years of formal education, delay to first attendance and the occurrence of dengue during outbreaks and in different Brazilian regions. RESULTS: Complicated forms of dengue occurred more frequently among those younger than 10 years (3.12% vs 1.92%) and those with dengue virus 2 infection (7.65% vs 2.42%), with a delay to first attendance >2 days (3.18% vs 0.82%) and with ≤4 years of formal education (2.02% vs 1.46%). The risk of hospitalization was higher among those aged 6-10 years old (OR 4.57; 95% CI 1.43-29.96) and those who were infected by dengue virus 2 (OR 6.36; 95% CI 2.52-16.06), who lived in the Northeast region (OR 1.38; 95% CI 1.11-2.10) and who delayed first attendance by >5 days (composite OR 3.15; 95% CI 1.33-8.9). CONCLUSIONS: In Brazil, the occurrence of severe dengue and related hospitalization is associated with being younger than 10 years old, being infected by dengue virus 2 or 3, living in the Northeast region (the poorest and the second most populated) and delaying first attendance for more than 2 days.

Multicentre prospective study on dengue classification in four South-east Asian and three Latin American countries.

OBJECTIVE: To evaluate the existing WHO dengue classification across all age groups and a wide geographical range and to develop a revised evidence-based classification that would better reflect clinical severity. METHODS: We followed suspected dengue cases daily in seven countries across South-east Asia and Latin America and then categorised them into one of three intervention groups describing disease severity according to the overall level of medical and nursing support required. Using a pre-defined analysis plan, we explored the clinical and laboratory profiles characteristic of these intervention categories and presented the most promising options for a revised classification scheme to an independent group of WHO dengue experts for consideration. Potential warning signs were also evaluated by comparing contemporaneous data of patients who progressed to severe disease with the data of those who did not. RESULTS: A total of 2259 patients were recruited during 2006-2007 and 230 (13%) of the 1734 laboratory-confirmed patients required major intervention. Applying the existing WHO system, 47/210 (22%) of patients with shock did not fulfil all the criteria for dengue haemorrhagic fever. However, no three-tier revision adequately described the different severity groups either. Inclusion of readily discernible complications (shock/severe vascular leakage and/or severe bleeding and/or severe organ dysfunction) was necessary to devise a system that identified patients requiring major intervention with sufficient sensitivity and specificity to be practically useful. Only a small number of subjects (5%) progressed to severe disease while under observation; several warning signs were identified, but much larger studies are necessary to fully characterize features associated with disease progression. CONCLUSIONS: Based on these results, a revised classification system comprised of two entities, 'Dengue' and 'Severe Dengue', was proposed and has now been incorporated into the new WHO guidelines.

Cost of dengue cases in eight countries in the Americas and Asia: a prospective study.

Despite the growing worldwide burden of dengue fever, the global economic impact of dengue illness is poorly documented. Using a common protocol, we present the first multicountry estimates of the direct and indirect costs of dengue cases in eight American and Asian countries. We conducted prospective studies of the cost of dengue in five countries in the Americas (Brazil, El Salvador, Guatemala, Panama, and Venezuela) and three countries in Asia (Cambodia, Malaysia, and Thailand). All studies followed the same core protocol with interviews and medical record reviews. The study populations were patients treated in ambulatory and hospital settings with a clinical diagnosis of dengue. Most studies were performed in 2005. Costs are in 2005 international dollars (I$). We studied 1,695 patients (48% pediatric and 52% adult); none died. The average illness lasted 11.9 days for ambulatory patients and 11.0 days for hospitalized patients. Among hospitalized patients, students lost 5.6 days of school, whereas those working lost 9.9 work days per average dengue episode. Overall mean costs were I$514 and I$1,394 for an ambulatory and hospitalized case, respectively. With an annual average of 574,000 cases reported, the aggregate annual economic cost of dengue for the eight study countries is at least I$587 million. Preliminary adjustment for under-reporting could raise this total to $1.8 billion, and incorporating costs of dengue surveillance and vector control would raise the amount further. Dengue imposes substantial costs on both the health sector and the overall economy.

Household survey of dengue infection in central Brazil: spatial point pattern analysis and risk factors assessment.

Urban dengue fever is now considered a major public health threat in most American countries. A household survey was conducted in the city of Goiania in central Brazil in 2001 to assess prevalence of dengue infection and individual and area-based risk factors. Spatial point pattern analysis was performed using the dual Kernel method. A total of 1,610 households were surveyed; 1,585 individuals more than five years old had blood and data collected. Sera were tested for IgM/IgG antibodies by an enzyme-linked immunoassay. Area-based indicators derived from census data were linked to geocoded residential address. The seroprevalence of dengue was 29.5% and the estimate prevalence surface reached 50% in the outskirts areas. The risk of infection was significantly associated with older age (P < 0.01), low education (odds ratio [OR] = 3.45, 95% confidence interval [CI] = 1.82-6.55), and low income (OR = 1.32, 95% CI = 1.02-1.71) in multivariate analysis. This study highlighted the heterogeneity of dengue transmission within the city and can assist in spatial targeting control interventions.