Tropical Medicine and International Health volume 7 no 9 pp 757–762 september 2002
Dynamics of dengue virus circulation: a silent epidemic in a complex urban area Maria da Glo´ria Teixeira1, Maurı´cio L. Barreto1, Maria da Conceic¸a˜o N. Costa1, Leila Denize A. Ferreira2, Pedro F. C. Vasconcelos3 and Sandy Cairncross4 1 2 3 4
Instituto de Sau´de Coletiva, Universidade Federal da Bahia, Salvador-Bahia, Brazil Department of Statistics, Universidade Federal da Bahia, Salvador, Brazil Instituto Evandro Chagas, FUNASA, Ministry of Health, Bele´m, Brazil London School of Hygiene and Tropical Medicine, UK
Summary
Serotypes of dengue DEN-1 and DEN-2 have been reported in much of Brazil over the last 15 years, and DEN-3 serotype was only recently detected. This prospective study was conducted in Salvador, a large city in north-east Brazil, where two epidemics were previously recorded (DEN-1 and DEN-2). We obtained the seroprevalence and 1-year incidence of dengue infections in the population of 30 sampling areas of Salvador and analysed the relationship between intensity of viral circulation, standard of living and vector density. High seroprevalence (68.7%) and annual incidence (70.6%) of infection for one or both circulating serotypes (DEN-1 and DEN-2) were found. High rates of transmission were observed in all studied areas, from the highest to the lowest socio-economic status. The mean PI (Premise Index) for Aedes aegypti was 7.4% (range 0.27–25.6%). Even in the areas with the lowest PI (£ 3%) the observed seroincidence was 54.6%. These findings highlighted the existence of a silent epidemic during a period perceived by the Health Services as of low endemicity, indicating the strength and speed of dengue transmission in the city of Salvador. keywords dengue, prospective study, serological survey, living conditions, vector density correspondence M. G. Teixeira, Instituto de Sau´de Coletiva, Universidade Federal da Bahia, Rua Padre Feijo´, 29 Canela, 40.110-170 Salvador-Bahia, Brazil. Tel.: +21 245 0544; Fax: +71 237 5856; E-mail:
[email protected]
Introduction The occurrence of epidemics of classical dengue, haemorrhagic dengue and dengue shock syndrome in the America make this vector-borne disease an important public health concern throughout the New World. The serotypes DEN-1 and DEN-2 have been reported in Brazil over the last 15 years, and the DEN-3 serotype was detected only recently. Few cases of dengue haemorrhagic fever have been registered. Since 1995 the virus of dengue (DEN-1 and DEN-2) is circulating in Salvador, a large city in the north-east region of the country, and two previous epidemics have been recorded (Teixeira et al. 2001). A number of factors have been pointed out as contributing to the resurgence of dengue. Demographic and societal changes, increased air travel, decay of the public health infrastructure (Gubler 1998) and the co-circulation of multiple serotypes increase the potential for the emergence of dengue haemorrhagic fever (Halstead 1981). In
ª 2002 Blackwell Science Ltd
the absence of a vaccine, dengue prevention currently depends on effective vector control, but a new research initiative is required because this strategy is not enough to prevent dengue virus transmission (Reiter 1998). One of the controversial aspects about dengue is the relationship between environmental conditions and the risk of infection, which has been related to both good and bad standards of living (Medronho 1995; Vasconcelos et al. 1998). The dynamics of dengue transmission in urban settings are still poorly understood. Better knowledge about the epidemiology of this disease requires epidemiological studies, especially those based on incidence (Kuno 1995). For instance, it would be useful to know the threshold of transmission in terms of vector density, so as to develop new strategies for control of this disease (WHO 1999). Our study of the seroprevalence and incidence of dengue infection in a large Brazilian city examines the relationship between intensity of viral circulation and standard of living, environmental quality and vector density. 757
Tropical Medicine and International Health
volume 7 no 9 pp 757–762 september 2002
M. G. Teixeira et al. Dengue dynamics circulation
Materials and methods This prospective cohort study was analysed both as an ecological study and in terms of risk to individuals. In 1998 the city of Salvador had around 2.3 million inhabitants, with wide differences between specific areas in the socioeconomic status of the population and the quality of their environment. The sampling scheme is described in detail elsewhere (Teixeira et al. 2002). The study population was drawn from a spatial sample of 30 neighbourhoods throughout the city, purposively selected from the census enumeration areas which had been stratified on the basis of sanitation coverage and income level, so as to represent a wide range of living conditions. These included areas where living standards were • High: > 80% of households with sanitation and >50% of households earning more than five times the national minimum wage (US$ 80.00, six areas); • Medium: 50–80% of households with sanitation and over 50% of households earning one to four times the national minimum wage (19 areas); • Low: less than half of households with sanitation and > 50% of households earning less than the national minimum wage (five areas). The data about level of income and population density were supplied by the Brazilian Statistics Institute (Brazil 1996). The association between sanitation coverage and income was such that all census tracts in the city fell into one of the three categories above. For the sample size calculation, a seroprevalence of dengue of 50% was assumed, based on previous surveys in other Brazilian cities (Cunha et al. 1995; Vasconcelos et al. 1998). Assuming a precision of ±3%, a cluster effect of 1.5, a confidence level of 95%, and an inflation of 30% to compensate for those individuals lost gave a final figure of 2149 individuals. Using a previous census as a sampling frame, 2149 residents of the 30 sample areas were selected from the population of 68 749 by random sampling without replacement and with post-stratification (Cochran 1977). A questionnaire which included name, address, sex, age, educational level, income and yellow fever (YF) vaccination status was administered to all participating individuals between May and July 1998. After informed consent was obtained, the first sample of blood was also collected at this time. Three individuals who were vaccinated were excluded to avoid false positives because of cross-reaction. One year later, a second sample of blood was collected from all individuals except those who had tested positive for both serotypes in the first collection. 758
Blood samples were collected in sterilized vacuum tubes of 10 ml, the serum was separated by centrifugation and stored at )20 C. These samples were sent in thermal boxes containing ice to the Arbovirus Laboratory of the Evandro Chagas Institute, where the Haemagglutination Inhibition/HI test (Clark & Casals 1958), modified by Shope (1963), was carried out using antigens for the four serotypes of the dengue virus and four other flaviviruses: YF, Rocio, Ilhe´us and St Louis Encephalitis, although these do not circulate in Salvador. Serological response to flaviviruses is of controversial interpretation and differs between the first (primary) infection and any subsequent (secondary) infection with another flavivirus or serotype, as flaviviruses show an increasingly strong response on subsequent infection and serological cross-reaction is frequently observed. Thus, the criterion adopted was that defined by World Health Organization (1997): titres by HI of 1:20 or higher, exclusively to a specific dengue serotype, or titres four times higher for one serotype than for another (DEN-1 or DEN-2) were considered positive and specific for that serotype (primary response). Titres indicative of secondary response were also as defined by WHO (1997). These were confirmed by IgG–enzyme-linked immunosorbent assay (Chungue et al. 1989), and considered positive to both serotypes meaning that infection with both DEN-1 and DEN-2 had occurred. Crude and age-standardized seroprevalence and incidence of infection for dengue were calculated by the direct method (Rothman 1986) for each sampling area and all the categories of living standards, using the overall studied population as the reference population. Since the survey were 1 year apart, seroincidences were all expressed as yearly rates in percentage. The prevalence ratios (PR) and relative risks (RR) of infection with dengue virus were calculated, as well as 95% confidence intervals. The chisquare test for trend was used. Exploratory analysis was performed to characterize the study population and to verify the association among the variables using the Pearson correlation coefficient. An exploratory analysis was also performed at the individual level. Risk factors for occurrence of infection by the dengue virus were analysed by logistic regression, thereby obtaining the measures of association (PR and RR) by the Delta method (Armitage & Berry 1987), setting the thresholds so that the ÔexposedÕ individuals were those ‡ 15 years, with less than 8 years of schooling and with an income of less than twice the minimum wage. The Premise Index (PI) was obtained for each sampling area as the percentage of all inspected premises which were found with at least one positive breeding site for Aedes aegypti larvae. Using ancova (Montgomery 1991) the incidence of infection for the neighbourhood in each range
ª 2002 Blackwell Science Ltd
Tropical Medicine and International Health
volume 7 no 9 pp 757–762 september 2002
M. G. Teixeira et al. Dengue dynamics circulation
of PI ( £ 3%; 3.1% to 5%; 5.1% to 10%; and > 10%) was calculated and adjusted for age and mean seroprevalence. The preventable fraction (PF) was also calculated by treating ÔunexposedÕ individuals as if they lived in areas where the PI was 3% or less. Data were entered in Epi-Info 6.0 (Atlanta, Center for Disease Control, 1994) and further analysis was performed using SAS and STATA. The study protocol was approved by the ethics commission for scientific research of the Oswaldo Cruz Institute (FIOCRUZ). Results Of the 2149 selected individuals, 1515 (70%) participated in this study with complete data. However, this did not prejudice the power of the study because the sample size had been inflated by 30% and there were no major demographic differences between the studied and the missing cases. The age distribution of the studied cases showed that 5.1% were aged < 5 years; 20.9% were 5–14 years old, and 74% were ‡ 15 years old. A total of 57.9% were females. Sixty-eight per cent of the adults (age > 15) had less than 8 years of schooling. Around 25% of the population reported a household income lower (< 160 US$ per month) and 50% had an income between two and five times the minimum wage. The overall seroprevalence was 68.7%, varying from 16.2% to 97.6% between the 30 areas. The overall seroprevalence of infection with two serotypes of dengue was 43.2%, varying from 0% to 87.9% across the 30 study areas. In two areas, no individuals with double infections were found. Seroprevalence values were lower in younger age groups: 39.0% among 0–4 year olds and reaching a maximum of 76.4% in the 30–39-year-old age group. The incidence of infection was lower in the group aged 0–4 (46.2%), but showed a sharp increase in the next age group (5–9 years old) (78.3%) and maintained levels between 62.7% and 82.8% in the older age groups. Between the age groups of ‡ 15 and < 15-year-old there was a statistically significant
difference both in seroprevalence (57.4% vs. 76.1%; P < 0.001) and in seroincidence (73.3% vs. 81.0%; P ¼ 0.03). Neither the seroprevalence nor the incidence of dengue infection was associated with education, income or sex. Ecological analysis No significant correlation was found between seroprevalence and the proportion of individuals with lower levels of education or the mean income in the 30 sampling areas (Table 1). On the other hand, seroprevalence showed a strong positive correlation with population density (r ¼ +0.49; P < 0.01). Table 2 shows that the overall seroprevalence increased with worsening living standards (v2for trend ¼ 8.386; P < 0.01). Incidence Of the 860 individuals who tested negative or positive for only one serotype in the first survey, 595 participated in the seroincidence survey, meaning a loss of 30.8%, primarily because of address changes of the individuals. However, the social and demographic characteristics of the sample remained similar to those in the first survey. Table 1 Correlation coefficients for age-standardized seroprevalence and seroincidence for one or two dengue serotypes with several selected variables related to the 30 sampling areas, Salvador, Brazil 1998–99
Variable
Seroprevalence (1998)
Seroincidence (1998–99)
r
P
r
P
0.14 0.76
