Cynthia Braga

From re-emergence to hyperendemicity: the natural history of the dengue epidemic in Brazil.

Background Dengue virus (DENV) was reintroduced into Brazil in 1986 and by 1995 it had spread throughout the country. In 2007 the number of dengue hemorrhagic fever (DHF) cases more than doubled and a shift in the age distribution was reported. While previously the majority of DHF cases occurred among adults, in 2007 53% of cases occurred in children under 15 years old. The reasons for this shift have not been determined. Methods and Findings Age stratified cross-sectional seroepidemiologic survey conducted in Recife, Brazil in 2006. Serostatus was determined by ELISA based detection of Dengue IgG. We estimated time-constant and time-varying forces of infection of DENV between 1986 and 2006. We used discrete-time simulation to estimate the accumulation of monotypic and multitypic immunity over time in a population previously completely susceptible to DENV. We projected the age distribution of population immunity to dengue assuming similar hazards of infection in future years. The overall prevalence of DENV IgG was 0.80 (n = 1427). The time-constant force of infection for the period was estimated to be 0.052 (95% CI 0.041, 0.063), corresponding to 5.2% of susceptible individuals becoming infected each year by each serotype. Simulations show that as time since re-emergence of dengue goes by, multitypic immunity accumulates in adults while an increasing proportion of susceptible individuals and those with monotypic immunity are among young age groups. The median age of those monotypically immune can be expected to shift from 24 years, 10 years after introduction, to 13 years, 50 years after introduction. Of those monotypically immune, the proportion under 15 years old shifts from 27% to 58%. These results are consistent with the dengue notification records from the same region since 1995. Interpretation Assuming that persons who have been monotypically exposed are at highest risk for severe dengue, the shift towards younger patient ages observed in Brazil can be partially explained by the accumulation of multitypic immunity against DENV-1, 2, and 3 in older age groups, 22 years after the re-introduction of these viruses. Serotype specific seroepidemiologic studies are necessary to accurately estimate the serotype specific forces of infection.

Prevalence and risk factors of Hepatitis C virus infection in Brazil, 2005 through 2009: a cross-sectional study

BackgroundHepatitis C chronic liver disease is a major cause of liver transplant in developed countries. This article reports the first nationwide population-based survey conducted to estimate the seroprevalence of HCV antibodies and associated risk factors in the urban population of Brazil.MethodsThe cross sectional study was conducted in all Brazilian macro-regions from 2005 to 2009, as a stratified multistage cluster sample of 19,503 inhabitants aged between 10 and 69 years, representing individuals living in all 26 State capitals and the Federal District. Hepatitis C antibodies were detected by a third-generation enzyme immunoassay. Seropositive individuals were retested by Polymerase Chain Reaction and genotyped. Adjusted prevalence was estimated by macro-regions. Potential risk factors associated with HCV infection were assessed by calculating the crude and adjusted odds ratios, 95% confidence intervals (95% CI) and p values. Population attributable risk was estimated for multiple factors using a case–control approach.ResultsThe overall weighted prevalence of hepatitis C antibodies was 1.38% (95% CI: 1.12%–1.64%). Prevalence of infection increased in older groups but was similar for both sexes. The multivariate model showed the following to be predictors of HCV infection: age, injected drug use (OR = 6.65), sniffed drug use (OR = 2.59), hospitalization (OR = 1.90), groups socially deprived by the lack of sewage disposal (OR = 2.53), and injection with glass syringe (OR = 1.52, with a borderline p value). The genotypes 1 (subtypes 1a, 1b), 2b and 3a were identified. The estimated population attributable risk for the ensemble of risk factors was 40%. Approximately 1.3 million individuals would be expected to be anti-HCV-positive in the country.ConclusionsThe large estimated absolute numbers of infected individuals reveals the burden of the disease in the near future, giving rise to costs for the health care system and society at large. The known risk factors explain less than 50% of the infected cases, limiting the prevention strategies. Our findings regarding risk behaviors associated with HCV infection showed that there is still room for improving strategies for reducing transmission among drug users and nosocomial infection, as well as a need for specific prevention and control strategies targeting individuals living in poverty.

Modeling the Dynamic Transmission of Dengue Fever: Investigating Disease Persistence

Background Dengue is a disease of great complexity, due to interactions between humans, mosquitoes and various virus serotypes as well as efficient vector survival strategies. Thus, understanding the factors influencing the persistence of the disease has been a challenge for scientists and policy makers. The aim of this study is to investigate the influence of various factors related to humans and vectors in the maintenance of viral transmission during extended periods. Methodology/Principal Findings We developed a stochastic cellular automata model to simulate the spread of dengue fever in a dense community. Each cell can correspond to a built area, and human and mosquito populations are individually monitored during the simulations. Human mobility and renewal, as well as vector infestation, are taken into consideration. To investigate the factors influencing the maintenance of viral circulation, two sets of simulations were performed: (1st) varying human renewal rates and human population sizes and (2nd) varying the house index (fraction of infested buildings) and vector per human ratio. We found that viral transmission is inhibited with the combination of small human populations with low renewal rates. It is also shown that maintenance of viral circulation for extended periods is possible at low values of house index. Based on the results of the model and on a study conducted in the city of Recife, Brazil, which associates vector infestation with Aedes aegytpi egg counts, we question the current methodology used in calculating the house index, based on larval survey. Conclusions/Significance This study contributed to a better understanding of the dynamics of dengue subsistence. Using basic concepts of metapopulations, we concluded that low infestation rates in a few neighborhoods ensure the persistence of dengue in large cities and suggested that better strategies should be implemented to obtain measures of house index values, in order to improve the dengue monitoring and control system.

Effect of aggressive prolonged diethylcarbamazine therapy on circulating antigen levels in bancroftian filariasis.

BACKGROUND Single dose diethylcarbamazine (DEC) as used in control programmes is effectively microfilaricidal for periods of up to a year or more but has incomplete ability to kill Wuchereria bancrofti adult parasites. These regimens can be effective in breaking transmission by suppression of circulating microfilariae available to mosquito vectors. Whether prolonged or aggressive therapy with DEC has a significant effect on adult worms, which may live up to 12 years or more, and is important in the context of the treatment of individual patients, is still incompletely understood.

Choices on contraceptive methods in post-abortion family planning clinic in the northeast Brazil

BackgroundIn Brazil, a Ministry of Health report revealed women who underwent an abortion were predominantly in the use of contraceptive methods, but mentioned inconsistent or erroneously contraceptive use. Promoting the use of contraceptive methods to prevent unwanted pregnancies is one of the most effective strategies to reduce abortion rates and maternal morbidity and mortality. Therefore, providing post-abortion family planning services that include structured contraceptive counseling with free and easy access to contraceptive methods can be suitable. So the objective of this study is to determine the acceptance and selection of contraceptive methods followed by a post-abortion family planning counseling.MethodsA cross-sectional study was carried out from July to October 2008, enrolling 150 low income women to receive post-abortion care at a family planning clinic in a public hospital located in Recife, Brazil. The subjects were invited to take part of the study before receiving hospital leave from five different public maternities. An appointment was made for them at a family planning clinic at IMIP from the 8th to the 15th day after they had undergone an abortion. Every woman received information on contraceptive methods, side effects and fertility. Counseling was individualized and addressed them about feelings, expectations and motivations regarding contraception as well as pregnancy intention.ResultsOf all women enrolled in this study, 97.4% accepted at least one contraceptive method. Most of them (73.4%) had no previous abortion history. Forty of the women who had undergone a previous abortion, 47.5% reported undergoing unsafe abortion. Slightly more than half of the pregnancies (52%) were unwanted. All women had knowledge of the use of condoms, oral contraceptives and injectables. The most chosen method was injectables, followed by oral contraceptives and condoms. Only one woman chose an intrauterine device.ConclusionThe acceptance rate of post-abortion contraceptive methods was greater and the most chosen method was the best-known one. Implementing a specialized family planning post abortion service may promote an acceptance, regardless of the chosen method. Most important is they do receive contraception if they do not wish for an immediate pregnancy.

Comparison of tests for the detection of circulating filarial antigen (Og4C3-ELISA and AD12-ICT) and ultrasound in diagnosis of lymphatic filariasis in individuals with microfilariae

Significant advances were made in the diagnosis of filariasis in the 1990s with the emergence of three new alternative tools: ultrasound and tests to detect circulating antigen using two monoclonal antibodies, Og4C3 and AD12-ICT-card. This study aimed to identify which of these methods is the most sensitive for diagnosis of infection. A total of 256 individuals, all male and carrying microfilariae (1-15,679 MF/mL), diagnosed by nocturnal venous blood samples, were tested by all three techniques. The tests for circulating filarial antigen concurred 100% and correctly identified 246/256 (96.69%) of the positive individuals, while ultrasound detected only 186/256 (73.44%). Of the circulating antigen tests, ICT-card was the most convenient method for identification of Wuchereria bancrofti carriers. It was easy to perform, practical and quick.

Force of infection of dengue serotypes in a population-based study in the northeast of Brazil.

This study investigated anti-dengue serotype-specific neutralizing antibodies in a random sample of dengue IgG-positive individuals identified in a survey performed in a hyperendemic setting in northeastern Brazil in 2005. Of 323 individuals, 174 (53.8%) had antibodies to dengue virus serotype 1 (DENV-1), 104 (32.2%) to DENV-2 and 301 (93.2%) to DENV-3. Monotypic infections by DENV-3 were the most frequent infection (35.6%). Of 109 individuals aged <15 years, 61.5% presented multitypic infections. The force of infection estimated by a catalytic model was 0.9%, 0.4% and 2.5% person-years for DENV-1, DENV-2 and DENV-3, respectively. By the age of 5 years, about 70%, 30% and 40% of participants were immune to DENV-3, DENV-2 and DENV-1, respectively. The data suggest that infection with DENV-1, -2 and -3 is intense at early ages, demonstrating the need for research efforts to investigate dengue infection in representative population samples of Brazilian children during early infancy.

Sustained Reduction of the Dengue Vector Population Resulting from an Integrated Control Strategy Applied in Two Brazilian Cities

Aedes aegypti has developed evolution-driven adaptations for surviving in the domestic human habitat. Several trap models have been designed considering these strategies and tested for monitoring this efficient vector of Dengue. Here, we report a real-scale evaluation of a system for monitoring and controlling mosquito populations based on egg sampling coupled with geographic information systems technology. The SMCP-Aedes, a system based on open technology and open data standards, was set up from March/2008 to October/2011 as a pilot trial in two sites of Pernambuco -Brazil: Ipojuca (10,000 residents) and Santa Cruz (83,000), in a joint effort of health authorities and staff, and a network of scientists providing scientific support. A widespread infestation by Aedes was found in both sites in 2008–2009, with 96.8%–100% trap positivity. Egg densities were markedly higher in SCC than in Ipojuca. A 90% decrease in egg density was recorded in SCC after two years of sustained control pressure imposed by suppression of >7,500,000 eggs and >3,200 adults, plus larval control by adding fishes to cisterns. In Ipojuca, 1.1 million mosquito eggs were suppressed and a 77% reduction in egg density was achieved. This study aimed at assessing the applicability of a system using GIS and spatial statistic analysis tools for quantitative assessment of mosquito populations. It also provided useful information on the requirements for reducing well-established mosquito populations. Results from two cities led us to conclude that the success in markedly reducing an Aedes population required the appropriate choice of control measures for sustained mass elimination guided by a user-friendly mosquito surveillance system. The system was able to support interventional decisions and to assess the program’s success. Additionally, it created a stimulating environment for health staff and residents, which had a positive impact on their commitment to the dengue control program.

Prevalence and incidence of dengue virus and antibody placental transfer during late pregnancy in central Brazil

BackgroundMaternal dengue antibodies are considered to play a significant role in dengue pathogenesis among infants. Determining the transplacental specific antibody transfer is invaluable for establishing the optimal vaccination age among infants in endemic regions.MethodsWe conducted a cross-sectional study among pairs of maternal and corresponding umbilical cord blood samples in public hospitals. The prevalence and incidence of dengue infection were determined in 505 pairs of pregnant women and neonates during a large outbreak (2009–2010) in central Brazil. The women were interviewed at late pregnancy to assess current or past symptoms of dengue. All parturients and their neonates were screened using Dengue IgG Indirect ELISA (Panbio) to assess previous dengue exposure. A semi-quantitative measurement of the IgG antibody expressed by the index ratio was calculated using optical density (OD) values according to the manufacturer’s instructions. The studied population of parturients and their offspring was also screened for recent dengue infection by the Dengue IgM-capture ELISA (Panbio). Those participants with history of fever and two or more symptoms of dengue at least 10 days before the delivery were also tested for the dengue NS1 antigen using the Dengue Early ELISA (Panbio) and RT-PCR.ResultsThe mean maternal age was 25.8 (SD = 6.4), and 83.6% of deliveries were between 37 and 41 weeks. Approximately half of the 505 women and neonates were IgG-seropositive, yielding 99.3% co-positive mother-child frequency of antibody transfer (Kappa = 0.96). The incidence of dengue infection was 2.8% (95% CI 1.4–4.4%) among the women considering 14 IgM-positive results and one DENV2 detected by RT-PCR. The dengue NS1 antigen was undetectable in the matched pairs.ConclusionThis study provides critical data on the prevalence of transplacental transferred maternal-infant anti-dengue antibodies and incidence of infection. The design of future vaccine trials should consider diverse regional epidemiological scenarios.

Effects of folic acid fortification on the prevalence of neural tube defects

OBJETIVO:Analizar el efecto de alimentos fortificados con acido folico en la prevalencia de defectos del cierre del tubo neural entre nacidos vivos. METODOS: Estudio longitudinal de nacidos vivos del municipio de Recife (Noreste de Brasil), entre 2000 y 2006. Los datos pesquisados fueron obtenidos del Sistema Nacional de Informaciones de Nacidos Vivos. Los defectos del cierre del tubo neural fueron definidos de acuerdo con el Codigos Internacional de Enfermedades- 10a Revision: anencefalia, encefalocele y espina bifida. Se compararon las prevalencias en los periodos anterior (2000 - 2004) y posterior (2005-2006) al periodo obligatorio de fortificacion. Se analizo la tendencia temporal de las prevalencias trimestrales de defectos del cierre del tubo neural por las pruebas de Mann-Kendall y Sens Slope. RESULTADOS: No se identifico tendencia de reduccion en la ocurrencia del hecho (Teste de Mann-Kendall); p= 0,270; Sens Slope = - 0,008) en el periodo estudiado. No hubo diferencia estadisticamente significativa entre las prevalencias de defectos de cierre del tubo neural en los periodos anterior y posterior a la fortificacion de los alimentos con acido folico de acuerdo con las caracteristicas maternas. CONCLUSIONES: A pesar de que no haya sido observada reduccion de los defectos de cierre del tubo neural posterior al periodo obligatorio de fortificacion de alimentos con acido folico, los resultados encontrados no permiten descartar el beneficio del mismo en la prevencion de esta malformacion. Son necesarios estudios evaluando mayor periodo y considerando el nivel de consumo de los productos fortificados por las mujeres en edad fertil.OBJECTIVE To analyze the effect of folic acid-fortified foods on the prevalence of neural tube defects in live newborns. METHODS Longitudinal study with newborns from the city of Recife, Northeastern Brazil, between 2000 and 2006. Data analyzed were obtained from the Sistema Nacional de Informações de Nascidos Vivos (National Information System on Live Births). Neural tube defects were defined in accordance with the International Classification of Diseases, 10th revision (ICD-10): anencephaly, encephalocele, and spina bifida. Prevalences from the periods before (2000-2004) and after (2005-2006) the mandatory fortification period were compared. Time trend of three-month prevalences of neural tube defects were analyzed using Mann-Kendall test and Sens Slope estimator. RESULTS Tendency towards reduction in the occurrence of outcome (Mann-Kendall test; p= 0.270; Sens Slope estimator =-0.008) was not identified in the period studied. The difference between prevalences of neural tube defects in the periods before and after food fortification with folic acid was not statistically significant, according to maternal characteristics. CONCLUSIONS Even though reduction in neural tube defects after the period of mandatory food fortification with folic acid was not observed, results found do not enable its benefit to prevent malformations to be ruled out. Studies assessing longer periods and considering the level of consumption of fortified products by women of fertile age are necessary.