Brazil is the largest and most populated country in Latin America, covering >8 million km² with an estimated 2002 population of 174,632,932 inhabitants. High population density areas and cities (up to 12,901 inhabitants/km²) are located mainly on the Atlantic Coast. Most of Brazil has a tropical climate; in the southern region, the climate is subtropical. The rainy season is observed in the first several months of the year, and the average temperature is >20°C (14).

The epidemiologic pattern of dengue fever in Brazil during the last 20 years can be divided into 2 distinct periods: 1) epidemic waves in localized areas (1986–1993) and 2) epidemic and endemic virus circulation countrywide (1994–2002) (Figure 1 and Table 1). The main dengue-related events occurring in these 2 periods are summarized in Table 1. In 1981, the first laboratory-confirmed cases of dengue (DENV1 and DENV4) occurred in an isolated area in the northwest Amazon region (Roraima State). After a 5-year interval without confirmed dengue fever, an epidemic due to DENV1 occurred in Rio de Janeiro State and was followed by several epidemics in highly populated cities in the southeast and northeast regions of Brazil. The number of dengue fever cases peaked at ≈100,000 in 1987 and 1991, probably because different serotypes (DENV1 and DENV2, respectively; Figure 2) were introduced. From 1986 to 1993, a total of 76.6% of the 294,419 reported dengue cases occurred in the rainy season from December to May, showing a marked seasonal pattern (Figure 1B). A cyclical pattern of 2-year intervals between large outbreaks was observed, which suggested low viral activity in the dry season (June to November).

In the second period (1994–2002), a total of 2,826,948 dengue cases were reported, indicating an upward trend in the incidence from 37 to 454 per 100,000 inhabitants. Although large outbreaks were observed in the rainy season, 482,163 cases were reported in the nonrainy season, which demonstrated increased dengue virus activity during the entire year. The bulk of incident cases were generated from metropolitan areas, although several outbreaks occurred in smaller urban settings in 25 out of 27 states. Two unprecedented epidemics occurred in 1998 and 2002, with 528,388 and 794,219 dengue fever cases reported, respectively. During this second period, vector surveillance to monitor A. aegypti infestation was extended to most of the country, covering 69.7% (n = 3,878) of the municipalities in 1996 and 89.6% (n = 4,985) in 2002. According to this vector information system, the number of infested municipalities ranged from 1,726 (44.5%) in 1996 to 2,905 (58.3%) in 2002. To date, Santa Catarina and Rio Grande do Sul States, located in southernmost Brazil, remain free of autochthonous dengue transmission; they report only imported cases.

The overall age distribution among reported cases during the last 5 years is presented in Figure 3. Approximately 50% of all reported dengue cases occurred in adults 20–40 years of age. During this period, dengue incidence was consistently higher in adults, reaching up to 432.7/100,000 population in the 30- to 49-year-old age group in 2002 (Table 2). The male:female ratio was constant at ≈1.1:1 during this 5-year period. Sex and age group distribution were very similar when the data for the 5 regions of the country were stratified (data not shown).

The first DHF cases were confirmed in 1990, after DENV2 was introduced into Brazil. During the decade that followed, 893 confirmed DHF cases with 44 deaths (rate of 4.9%) occurred; 75% of these deaths occurred in Rio de Janeiro State. During 2001–2002, a striking increase in the number of DHF cases was detected, with incidence rates of 2.9/100,000 population (n = 682) in 2001 and 12.9/100,000 population (n = 2,714) in 2002 (Figure 2). DHF cases increased 45-fold from 2000 to 2002, compared to a 3.3-fold increase in dengue fever cases during the same period. In the epidemic year of 2002, the overall ratio of dengue fever to DHF cases was 292.6; in Rio de Janeiro State, the most affected area, this ratio was 134.8. From 1998 to 2002, the case-fatality rate was 5.4% (195/3,632). During this period, the sex distribution of DHF was similar, and cases occurred mainly in adults (median age 33 years) (Figure 3A). Recently, a different pattern in the age distribution of DHF was observed in Amazonas State, where unlike the national level, a higher proportion of DHF cases occurred among children. In Amazonas State, 30.9% (17/55) and 28.8% (15/52) of DHF cases occurred among children <15 years of age in 2001 and 2003, respectively (Figure 3B).

Countrywide, an upward trend in hospitalized dengue cases has been apparent since 1994, peaking with >54,000 hospitalizations in 2002 (Figures 2 and 4). Hospitalization rates were consistently higher among adults from 1998 to 2002. Comparing the 2 largest epidemic years (1998 and 2002), hospitalization rates in all age groups increased ≈8-fold (Table 2). The ratio of reported to hospitalized cases decreased from 29.4 in 1998 to 10.6 in 2002, which represents 1 hospitalization for every 10 reported dengue cases. Despite this increased proportion of hospitalized cases, >90% of the total reported cases were considered mild or moderate cases by the health system.

In Brazil, the chronology of the appearance of DENV serotypes occurred in the following sequence: DENV1 in 1986, DENV2 in 1990, and DENV3 in 2000 (Figure 2). The simultaneous circulation of these three serotypes was first detected in multiple states during the last 2 years. Molecular epidemiology of DENV in Brazil has identified the Caribbean, Jamaican, and Sri Lankan genotypes for the DENV1, DENV2, and DENV3 viruses, respectively (21).

Analysis of 20 years of dengue/DHF surveillance data showed 2 distinct periods: an initial phase from 1986 to 1993, characterized by localized, sporadic epidemic waves in urban centers, and a nationwide endemic and epidemic pattern from 1994 to 2002. In this latter period, several epidemics of dengue progressed towards hyperendemicity in multiple urban centers. Since 1999, dramatic increases in both the incidence and hospitalizations due to dengue fever and DHF have occurred, indicating a likely increase in disease severity in recent years. Changes in surveillance coverage might explain part of this increase, but this explanation seems unlikely since no major changes were made in surveillance definitions. The current intense virus transmission pattern can be explained by the number of municipalities infested with A. aegypti mosquitoes, the mobility of the population, and the introduction and cocirculation of 3 different virus serotypes (DENV1, 2, and 3).

The epidemiology of dengue in Brazil presents some unusual features, characterized by dengue/DHF affecting mainly adults, with a predominance of milder infection in persons treated at outpatient clinics. In contrast, severe forms of the disease among children requiring hospitalization have been described in DHF epidemics in South and Central American countries (3,22,23). This endemic pattern has also been reported from Southeast Asia in recent decades (24,25). Cuban children with secondary infection by DENV2 showed a higher frequency of DHF and DHF-related deaths during the epidemic of 1981, which had been preceded by a DENV1 outbreak 4 years earlier (26). Apparently, similar events in Brazil, which also experienced the sequential introduction of DENV1 (during 1986) followed by DENV2 4 years later, led to a different outcome: most reported dengue/DHF occurred in adults. These findings may be explained by the distinct DENV2 strains circulating in Cuba (New Guinea) and Brazil (Jamaica) (21,27,28). Another possibility is the underdiagnosis of DHF in children in Brazil, although it seems unlikely that severe clinical manifestations would not likely be misdiagnosed or fail to draw the attention of public health authorities.

During the 20-year period examined, dengue/DHF in Brazil most commonly affected the adult population, even with the observed increase of dengue/DHF cases. Despite these findings, current data underscore a different pattern in the Amazon region, where an increased proportion of severe cases occurs among children. This finding represents a warning to pediatric practitioners and health officials. In the future, if the current intense DENV circulation persists, Brazil could resemble Southeast Asia, with DHF occurring mainly in younger age groups.

In 2002, the absolute number of deaths due to DHF (N = 150) exceeded malaria deaths for the first time in Brazil, demonstrating that malaria is not the only major endemic vector-borne disease in this tropical region. During that year, the largest epidemic yet recorded, including 250,000 dengue cases in the metropolitan area of Rio de Janeiro, caused major public health and political concern (7,8). Hemorrhagic fever and dengue-related deaths also clustered in this city. These findings probably reflect the recent introduction and predominance of DENV3, which suggests a possible role of this serotype in disease severity and the potential for additional DHF epidemics in the future (29). Another possible explanation for the increase in DHF is the association between secondary infection with disease severity (10); however, routine surveillance data only indicate patients’ immune status. In addition, some highly urbanized areas have substantial proportions of the population living in crowded, impoverished areas with poor sanitation (30). These complex urban settings are present in many regions in Brazil, resulting in a major challenge for vector control activities (8).

Several seroepidemiologic studies in Brazil have shown that up to 70% of urban populations had previous dengue infection, outnumbering reported cases. These results suggest that seroprevalence increases with age and that subclinical outcomes are a common feature of DENV exposure (31,32). Access to health services is considered nearly universal in Brazil, particularly in urban settings; therefore, dengue/DHF reports should be representative of the disease in the population. Incidence and hospitalization rates by age group showed similar patterns when surveillance system and hospitalization database were analyzed. The consistent patterns of age and sex distribution for all regions during epidemic and nonepidemic periods also suggest reliability of these surveillance data.

The high case-fatality rate for DHF observed in the last 5 years may be due to difficulties in classifying case severity according to the standard World Health Organization/PAHO dengue case definition (33). The Brazilian Ministry of Health has been strongly committed to improving surveillance and patient care in a major effort to reduce dengue-related deaths (34). The aim of this policy is to rapidly identify patients at risk of developing DHF and to initiate prompt, adequate treatment (e.g., intravenous fluid infusion) to prevent DSS. As result of this early and effective replacement of plasma loss, hemoconcentration (one of the classification criteria for DHF) has become a less frequently observed event during the course of the disease, and therefore, a proportion of these cases may not fulfill DHF criteria. Different applications or interpretations of this case definition by countries may limit the ability to make valid comparisons, particularly in Latin America compared to Southeast Asia (23,33).

The current epidemiologic trend underscores the importance of dengue/DHF and the need for long-term improvements in disease control and surveillance in Brazil. We have described the changing patterns and epidemiologic profile of dengue/DHF during the last 20 years in one of the most severely affected countries in the Americas, highlighting the recent increase in disease severity.