To the best of our knowledge, this is the first comprehensive effort to analyze the burden of malaria in Brazil using data from the GBD 2017, comprising a period of 28 years (from 1990 to 2017) and examining both genders at different age groups and in all the Brazilian federated units (both in the Legal Amazon and the Extra-Amazon regions). The present study showed a reduction in all disease burden indicators in the country during the study period, with a 92.0% decrease in the DALYs per 100,000 inhabitants, a 95.0% decrease in mortality, and a 96.4% decrease in disease incidence. Reductions were evidenced for both sexes, at all age groups, and in all the federated units of the country. An important feature associated with this change was the decrease in the contribution of YLLs to the DALYs rate. In 1990, the YLLs contributed with 67.2% of the DALYs rate, a percentage that decreased to 38.2% in 2017, thus reaffirming the substantial reduction in the mortality due to malaria, which was reflected in the decrease of the YLLs.
Altogether, the DALYs, YLLs, and YLDs gather information on mortality and morbidity and allow the estimation of the impact of each disease or injury on the health status of the population. Therefore, these indicators constitute remarkable tools for policy making aimed at reducing the burden of a disease [19, 20, 21, 22, 23, 24, 25].
The fact that Brazil is among the countries with the highest DALYs rates due to malaria in South America  highlights a situation that deserves attention. Despite the decrease in all the disease burden indicators between 1990 and 2017 (and particularly in the YLLs rate, which decreased by 95.4% in the period), we noted that the years of life lost due to disability (YLDs) currently constitute the most representative contribution to the DALYs estimates. This scenario may also be a reflex of the decrease in incidence and mortality rates due to the disease observed in the country over the years of study.
We observed that the DALYs, YLLs, and YLDs values over the years were comparable between genders. However, in some geographic regions, men are at a higher occupational risk of contracting malaria as they frequently work in mines, fields, or forests at times of intense activity of the vectors - mosquitoes of the genus Anopheles that transmit the parasites to humans [15, 41, 42].
Nevertheless, we observed differences when the age groups were analyzed according to gender. The reasons underlying the high rates of DALYs, YLLs, and YLDs observed among children in 1990 are still poorly understood. However, it should be noted that their immune systems are more susceptible to infections, which is likely one of the reasons why children are more affected than other age groups . On the other hand, the higher DALYs rate observed in 2017 among males in the age group of “20 to 24 years old” may be related to the occupational exposure or to the migration of individuals from this age group to high risk areas [43, 44].
Noteworthy, the large contribution of the YLDs to the DALYs rate due to malaria in recent years in Brazil reflects the fact that this disease incapacitates those affected to carry out their routine activities (work, school, among others). Studies have shown that most cases of malaria in Brazil affect the economically productive age groups (individuals between 15 and 45 years old), thus indicating that the disease has an economic impact on the affected families due to the loss of productive hours of the patient. Therefore, greater investments are needed to control malaria, not only to reduce its impacts on individuals’ health but also to minimize the economic pressure that it exerts on the population [45, 46, 47].
Among the Brazilian federated units, Acre, Rondônia, and Roraima, situated in the Amazon region (in the North of Brazil) had the highest incidence and DALYs rates in 1990 and 2017. The Brazilian Amazon, so-called Legal Amazon (Amazônia Legal) since 1953, is formed by the states of Acre, Amapá, Amazonas, Pará, Rondônia, Roraima, Tocantins, and part of the states of Maranhão and Mato Grosso). It presents environments that are favorable to malaria transmission, with risk factors that include poor demographic and socioeconomic conditions, and areas of expansion of the agricultural frontier, logging, road construction, and hydroelectric plants [11, 48, 49, 50, 51].
The estimates of the GBD 2017 showed that in the 1990s the highest DALYs rates were observed in the states of Goiás (Central-West Brazil, in the Extra-Amazon region) and Mato Grosso (Central-West Brazil, within the Legal Amazon region). Both these regions received the highest proportion of cases from the North region of the country . In non-endemic areas, the constant presence of infected individuals, along with the persistence of the vector, represents a continuous risk for the reintroduction of the natural transmission . As observed in other states of the Legal Amazon region, Maranhão (which politically belongs to the Northeast region) has been undergoing a process of expansion of its agricultural frontiers since the 1970s and 1980s. This expansion is occurring particularly in the west and north frontiers of the state, in the pre-Amazonian region in the border with the state of Pará. These conditions helped exacerbate malaria transmission in 1986 and 1987 .
In the Extra-Amazon region, the state of Piauí (Northeast Brazil) presented the highest incidence rate of malaria in both 1990 and 2017. With the exception of Maranhão, which has part of its territory in the Legal Amazon, the sates in the Northeast of Brazil are considered non-endemic and generally report only sporadic imported cases of malaria. Piauí state records an average of 40 cases of malaria per year, half of which are probably autochthonous. These autochthonous cases are possibly from regions bordering the state of Maranhão .
Some authors have pointed out that the spread of malaria to areas outside the Amazon region in Brazil, and particularly to urbanized and industrialized states, is of major concern since these highly populated areas present favorable conditions for the spread of parasites and vectors [13, 54, 55].
In American countries, P. vivax is the predominant parasite species and accounted for 74.1% of the cases of malaria in 2017. P. falciparum is generally considered the most important etiological agent of malaria in terms of mortality, while P. vivax is responsible for the majority of the infections, causing the disease in large areas of the world, including Brazil. An increasing number of reports has argued that the number of deaths due to infections by P. vivax is underestimated [7, 56, 57]. It is important to consider the parasite species when estimating disease burden because each species lead to different clinical manifestations of the disease [43, 58]. In this sense, indicators of YLLs due to incapacity and premature death may greatly vary depending on the region evaluated and the predominant parasite species.
Three species of the genus Plasmodium were responsible for the 11,327,462 cases of malaria in Brazil between 1990 and 2017. P. vivax accounted for 73.5% of the reports, followed by P. falciparum (25.5%). One percent of the cases were caused by other species. Noteworthy, P. vivax has been increasingly associated with severe malaria, leading to complications that include respiratory distress, shock, and anemia [59, 60, 61, 62]. In Brazil, the cases of malaria are seldom caused by P. malariae, and those are usually restricted to specific Amazon regions and its surroundings [58, 63]. Therefore, the burden of the disease in the country is a result of the infections by P. vivax and P. falciparum. What should be emphasized is that each of these two species generates different burdens for malaria [58, 64, 65]. Additionally, factors such as the immunological and genetic characteristics of the exposed population, the climate and environmental conditions, the presence of vector control policies, and the use of antimalarial drugs can influence the burden of the disease [43, 58, 65].
The main goals of the National Malaria Control Program (Programa Nacional de Controle da Malária - PNCM)  of the Brazilian Ministry of Health are to reduce the case fatality rate and severity of cases, reduce the incidence of the disease, eliminate transmission in urban areas, and maintain the disease controlled in areas where the transmission has already been interrupted. The current scenario in the Amazon region is promising but still requires new approaches to eliminate transmission in the municipalities where it persists. The treatment for malaria adopted by the Brazilian Public Health System (Sistema Único de Saúde - SUS) is based on the use of active principles such as chloroquine and primaquine, among others .
Even though substantial progress has been made in reducing the burden of malaria in Brazil, planning actions for controlling the disease remains a priority, especially in the Legal Amazon. The risk of death due to malaria results from a combination of environmental, demographic, and others factors, which may result in highly localized risk patterns.
Although the GBD 2017 generated important estimates of the global burden of diseases, the study presents critical limitations regarding the coverage and quality of the Brazilian databases used. Another important limitation resides in the fact that their estimates do not consider the malaria burden caused by P. falciparum, P. vivax, and P. malariae separately. This may be taken into account in future studies, as the three parasite species cause different clinical manifestations, present distinct geographic distributions, and, therefore, should have their specific disease burden estimates [58, 68]. P. vivax, for example, can cause multiple relapses, recrudescence or reinfection following the elimination of infection from the blood due to its stage of hypnozoites in the liver [64, 65, 69, 70]. Thus, it leads to a burden that is different from that caused by the other two parasite species.
Despite these limitations, based on the GBD 2017 estimates, our study showed a declining trend in malaria burden in Brazil during the 27 year study period. However, the disease persists as an important cause of loss of years of healthy life due to premature mortality and disability in the country. Understanding the geographic and temporal distribution of the risk of death and disability is essential for the planning, implementation, and refinement of control strategies aiming to eliminate the diseases.