Malaria in Brazil: what happens outside the Amazonian endemic region

Brazil, a country of continental proportions, presents three profiles of malaria transmission. The first and most important numerically, occurs inside the Amazon. The Amazon accounts for approximately 60% of the nation’s territory and approximately 13% of the Brazilian population. This region hosts 99.5% of the nation’s malaria cases, which are predominantly caused by Plasmodium vivax (i.e., 82% of cases in 2013). The second involves imported malaria, which corresponds to malaria cases acquired outside the region where the individuals live or the diagnosis was made. These cases are imported from endemic regions of Brazil (i.e., the Amazon) or from other countries in South and Central America, Africa and Asia. Imported malaria comprised 89% of the cases found outside the area of active transmission in Brazil in 2013. These cases highlight an important question with respect to both therapeutic and epidemiological issues because patients, especially those with falciparum malaria, arriving in a region where the health professionals may not have experience with the clinical manifestations of malaria and its diagnosis could suffer dramatic consequences associated with a potential delay in treatment. Additionally, because the Anopheles vectors exist in most of the country, even a single case of malaria, if not diagnosed and treated immediately, may result in introduced cases, causing outbreaks and even introducing or reintroducing the disease to a non-endemic, receptive region. Cases introduced outside the Amazon usually occur in areas in which malaria was formerly endemic and are transmitted by competent vectors belonging to the subgenus Nyssorhynchus (i.e., Anopheles darlingi, Anopheles aquasalis and species of the Albitarsis complex). The third type of transmission accounts for only 0.05% of all cases and is caused by autochthonous malaria in the Atlantic Forest, located primarily along the southeastern Atlantic Coast. They are caused by parasites that seem to be (or to be very close to) P. vivax and, in a less extent, by Plasmodium malariae and it is transmitted by the bromeliad mosquito Anopheles (Kerteszia) cruzii. This paper deals mainly with the two profiles of malaria found outside the Amazon: the imported and ensuing introduced cases and the autochthonous cases. We also provide an update regarding the situation in Brazil and the Brazilian endemic Amazon.     

An overview of malaria transmission from the perspective of Amazon Anopheles vectors

In the Americas, areas with a high risk of malaria transmission are mainly located in the Amazon Forest, which extends across nine countries. One keystone step to understanding the Plasmodium life cycle in Anopheles species from the Amazon Region is to obtain experimentally infected mosquito vectors. Several attempts to colonise Ano- pheles species have been conducted, but with only short-lived success or no success at all. In this review, we review the literature on malaria transmission from the perspective of its Amazon vectors. Currently, it is possible to develop experimental Plasmodium vivax infection of the colonised and field-captured vectors in laboratories located close to Amazonian endemic areas. We are also reviewing studies related to the immune response to P. vivax infection of Anopheles aquasalis, a coastal mosquito species. Finally, we discuss the importance of the modulation of Plasmodium infection by the vector microbiota and also consider the anopheline genomes. The establishment of experimental mosquito infections with Plasmodium falciparum, Plasmodium yoelii and Plasmodium berghei parasites that could provide interesting models for studying malaria in the Amazonian scenario is important. Understanding the molecular mechanisms involved in the development of the parasites in New World vectors is crucial in order to better determine the interaction process and vectorial competence.     

An ecoregional classification for the state of Roraima, Brazil: the importance of landscape in malaria biology

Understanding the different background landscapes in which malaria transmission occurs is fundamental to understanding malaria epidemiology and to designing effective local malaria control programs. Geology, geomorphology, vegetation, climate, land use, and anopheline distribution were used as a basis for an ecological classification of the state of Roraima, Brazil, in the northern Amazon Basin, focused on the natural history of malaria and transmission. We used unsupervised maximum likelihood classification, principal components analysis, and weighted overlay with equal contribution analyses to fine-scale thematic maps that resulted in clustered regions. We used ecological niche modeling techniques to develop a fine-scale picture of malaria vector distributions in the state. Eight ecoregions were identified and malaria-related aspects are discussed based on this classification, including 5 types of dense tropical rain forest and 3 types of savannah. Ecoregions formed by dense tropical rain forest were named as montane (ecoregion I), submontane (II), plateau (III), lowland (IV), and alluvial (V). Ecoregions formed by savannah were divided into steppe (VI, campos de Roraima), savannah (VII, cerrado), and wetland (VIII, campinarana). Such ecoregional mappings are important tools in integrated malaria control programs that aim to identify specific characteristics of malaria transmission, classify transmission risk, and define priority areas and appropriate interventions. For some areas, extension of these approaches to still-finer resolutions will provide an improved picture of malaria transmission patterns.     

Asymptomatic infection in individuals from the municipality of Barcelos (Brazilian Amazon) is not associated with the anti-Plasmodium falciparum glycosylphosphatidylinositol antibody response

Anti-glycosylphosphatidylinositol (GPI) antibodies (Abs) may reflect and mediate, at least partially, anti-disease immunity in malaria by neutralising the toxic effect of parasitic GPI. Thus, we assessed the anti-GPI Ab response in asymptomatic individuals living in an area of the Brazilian Amazon that has a high level of malaria transmission. For comparative purposes, we also investigated the Ab response to a crude extract prepared from Plasmodium falciparum, the merozoite surface protein (MSP)3 antigen of P. falciparum and the MSP 1 antigen of Plasmodium vivax (PvMSP1-₁₉) in these individuals and in Angolan patients with acute malaria. Our data suggest that the Ab response against P. falciparum GPI is not associated with P. falciparum asymptomatic infection in individuals who have been chronically exposed to malaria in the Brazilian Amazon. However, this Ab response could be related to ongoing parasitaemia (as was previously shown) in the Angolan patients. In addition, our data show that PvMSP1-₁₉may be a good marker antigen to reflect previous exposure to Plasmodium in areas that have a high transmission rate of P. vivax.     

Urban malaria in the Brazilian Western Amazon Region I: high prevalence of asymptomatic carriers in an urban riverside district is associated with a high level of clinical malaria

Cross sectional studies on malaria prevalence was performed in 2001, 2002, and 2004 in Vila Candelária, an urban riverside area of Porto Velho, Rond?nia, in the Brazilian Western Amazon, followed by longitudinal surveys on malaria incidence. Vila Candelária is a working class district, provided with electricity, water supply, and basic sanitation. Previous preliminary surveys indicated high malaria incidence in this community. At the end of year 2000 regular diagnostic and treatment measures for malaria were introduced, with active search of febrile cases among residents. Despite of both rapid treatment of cases and relative good sanitary and housing conditions, the malaria incidence persisted at high levels during the following years with an annual parasite index of 150 to 300/1000 inhabitants. Parasite surveys in 2001, 2002, and 2004 achieved through microscopy and polymerase chain reaction to diagnose malaria showed a constant high prevalence of asymptomatic carriers for both Plasmodium falciparum and P. vivax parasites. It was concluded that asymptomatic carriers represent an important reservoirs of parasites and that the carriers might contribute to maintaining the high level of transmission. Comparing our findings to similar geo-demographic situations found in other important urban communities of the Brazilian Amazon, we propose that asymptomatic carriers could explain malaria's outbreaks like the one recently observed in Manaus.     

Epidemic and Endemic Malaria Transmission Related to Fish Farming Ponds in the Amazon Frontier

Fish farming in the Amazon has been stimulated as a solution to increase economic development. However, poorly managed fish ponds have been sometimes associated with the presence of Anopheles spp. and consequently, with malaria transmission. In this study, we analyzed the spatial and temporal dynamics of malaria in the state of Acre (and more closely within a single county) to investigate the potential links between aquaculture and malaria transmission in this region. At the state level, we classified the 22 counties into three malaria endemicity patterns, based on the correlation between notification time series. Furthermore, the study period (2003–2013) was divided into two phases (epidemic and post-epidemic). Higher fish pond construction coincided both spatially and temporally with increased rate of malaria notification. Within one malaria endemic county, we investigated the relationship between the geolocation of malaria cases (2011–2012) and their distance to fish ponds. Entomological surveys carried out in these ponds provided measurements of anopheline abundance that were significantly associated with the abundance of malaria cases within 100 m of the ponds (P < 0.005; r = 0.39). These results taken together suggest that fish farming contributes to the maintenance of high transmission levels of malaria in this region.     

Man biting rate seasonal variation of malaria vectors in Roraima, Brazil

Malaria control has been directed towards regional actions where more detailed knowledge of local determinants of transmission is of primary importance. This is a short report on range distribution and biting indices for Anopheles darlingi and An. albitarsis during the dry and rainy season that follows river level variation in a savanna/alluvial forest malaria system area in the Northern Amazon Basin. Distribution range and adult biting indices were at their highest during the rainy season for both An. darlingi and An. albitarsis. During the rainy season the neighboring alluvial forest was extensively flooded. This coincided with highest rates in malaria transmission with case clustering near the river. As the river receded, anopheline distribution range and density decreased. This decrease in distribution and density corresponded to a malaria decrease in the near area. An exponential regression function was derived to permit estimations of An. darlingi distribution over specified distances. Anopheline spatio-temporal variations lead to uneven malaria case distribution and are of important implications for control strategies.     

Parity and age composition for Anopheles darlingi root (Diptera: Culicidae) and Anopheles albitarsis Lynch-Arribálzaga (Diptera: Culicidae) of the northern Amazon Basin, Brazil.

Parity and age composition for Anopheles darlingi and Anopheles albitarsis in the northern Amazon Basin, Brazil, were investigated. Anopheline ovaries and ovarioles were examined in order to determine whether hourly and seasonal parity status for the vectors An. albitarsis and An. darlingi would vary in two different landscapes (forest and savanna/forest) where malaria is endemic in the northern Amazon Basin. A total of 1,199 anophelines (535 An. darlingi and 664 An. albitarsis) was dissected for parity status, ovariole dilatations, and follicular stages. The total number of nulliparous and parous females for both species varied by time of collection, locality, and season. During the rainy season for the first two h of collection, more nulliparous An. albitarsis and An. darlingi females were collected in the first hour (18:00-19:00), but during the second hour (19:00-20:00) more parous females of both species were captured. During the dry season in Copaíbas, more parous females of An. albitarsis were observed in the first hour while more nulliparous females were observed in the second hour. Nulliparous and parous females of both species for both hours were not significantly different at Road 19 in the dry season. This location was characterized by a forest malaria pattern of transmission with higher numbers of parous females and population stability in the dry season. In Copaíbas, the density and parity of An. darlingi increased during the rainy season, and it could be classified as an alluvial malaria pattern of transmission. For Copaíbas, control measures would be more successful if adopted at the transition from dry to rainy season. Further investigation on longitudinal spatio-temporal change in longevity and survival rates would help us to clarify differences in vector competence for An. darlingi and An. albitarsis and add to the understanding of differences regarding prevailing landscapes in malaria epidemiology in the northern Amazon Basin.     

Temporal and spatial distribution of malaria within an agricultural settlement of the Brazilian Amazon

Malaria has reemerged in tropical regions with rapid population growth and deforestation. The dynamics of malaria transmission in agricultural settlements of the Amazon have been poorly defined. We studied the spatial distribution of malaria incidence in Roraima, Brazil, using multi regression analysis on 12 parameters that described social, housing, and behavioral variables. Malaria cases were associated with the proximity of Anopheles darlingi breeding sites, the main vector in these areas. During the dry season, transmission was enhanced near a temporary river. Cases occurred throughout the year near fish‐farming dams. Epidemiological models derived from urban or riverine malaria are probably inadequate for describing disease transmission in agricultural settlements, where cases are clustered near breeding sites, while the majority of the population remains unaffected. Identification of these areas, associated with residual insecticide spraying or surveillance, may considerably decrease the costs of control efforts.     

Cross-sectional study defines difference in malaria morbidity in two Yanomami communities on Amazonian boundary between Brazil and Venezuela

It is well established that immunity to malaria is short-lived and is maintained by the continuous contact with the parasite. We now show that the stable transmission of malaria in Yanomami Amerindian communities maintains a degree of immunity in the exposed population capable to reduce prevalence and morbidity of malaria. We examined 508 Yanomami Amerindians living along Orinoco (407) and Mucajaí (101) rivers, on the Venezuelan and Brazilian Amazon region, respectively. At Orinoco villages, malaria was hyperendemic and presented stable transmission, while at Mucajaí villages it was mesoendemic and showed unstable transmission. The frequency of Plasmodium vivax and P. falciparum was roughly comparable in Venezuelan and Brazilian communities. Malaria presented different profiles at Orinoco and Mucajaí villages. In the former communities, malaria showed a lower prevalence (16% x 40.6%), particularly among those over 10 years old (5.2% x 34.8%), a higher frequency of asymptomatic cases (38.5% x 4.9%), and a lower frequency of cases of severe malaria (9.2% x 36.5%). Orinoco villagers also showed a higher reactivity of the immune system, measured by the frequency of splenomegaly (72.4% x 29.7%) and by the splenic index (71.4% over level 1 x 28.6), and higher prevalence (91.1% x 72.1%) and mean titer (1243 x 62) of antiplasmodial IgG antibodies, as well as a higher prevalence (77.4% x 24.7%) and mean titer (120 x 35) of antiplasmodial IgM antibodies. Our findings show that in isolated Yanomami communities the stability of malaria transmission, and the consequent continuous activation of the immune system of the exposed population, leads to the reduction of malaria prevalence and morbidity.     

Urban and suburban malaria in Rondônia (Brazilian Western Amazon) II. Perennial transmissions with high anopheline densities are associated with human environmental changes

Longitudinal entomological surveys were performed in Vila Candelária and adjacent rural locality of Bate Estaca concomitantly with a clinical epidemiologic malaria survey. Vila Candelária is a riverside periurban neighborhood of Porto Velho, capital of the state of Rond?nia in the Brazilian Amazon. High anopheline densities were found accompanying the peak of rainfall, as reported in rural areas of the region. Moreover, several minor peaks of anophelines were recorded between the end of the dry season and the beginning of the next rainy season. These secondary peaks were related to permanent anopheline breeding sites resulting from human activities. Malaria transmission is, therefore, observed all over the year. In Vila Candelária, the risk of malaria infection both indoors and outdoors was calculated as being 2 and 10/infecting bites per year per inhabitant respectively. Urban malaria in riverside areas was associated with two factors: (1) high prevalence of asymptomatic carriers in a stable human population and (2) high anopheline densities related to human environmental changes. This association is probably found in other Amazonian urban and suburban communities. The implementation of control measures should include environmental sanitation and better characterization of the role of asymptomatic carriers in malaria transmission.     

Effect of artesunate-mefloquine fixed-dose combination in malaria transmission in amazon basin communities

ABSTRACT: BACKGROUND: Studies in South-East Asia have suggested that early diagnosis and treatment with artesunate (AS) and mefloquine (MQ) combination therapy may reduce the transmission of Plasmodium falciparum malaria and the progression of MQ resistance. METHODS: The effectiveness of a fixed-dose combination of AS and MQ (ASMQ) in reducing malaria transmission was tested in isolated communities of the Jurua valley in the Amazon region. Priority municipalities within the Brazilian Legal Amazon area were selected according to pre-specified criteria. Routine national malaria control programmatic procedures were followed. Existing health structures were reinforced and health care workers were trained to treat with ASMQ all confirmed falciparum malaria cases that match inclusion criteria. A local pharmacovigilance structure was implemented. Incidence of malaria and hospitalizations were recorded two years before, during, and after the fixed-dose ASMQ intervention. In total, between July 2006 and December 2008, 23,845 patients received ASMQ. Two statistical modelling approaches were applied to monthly time series of P. falciparum malaria incidence rates, P. falciparum/Plasmodium vivax infection ratio, and malaria hospital admissions rates. All the time series ranged from January 2004 to December 2008, whilst the intervention period span from July 2006 to December 2008. RESULTS: The ASMQ intervention had a highly significant impact on the mean level of each time series, adjusted for trend and season, of 0.34 (95%CI 0.20 [EN DASH] 0.58) for the P. falciparum malaria incidence rates, 0.67 (95%CI 0.50 [EN DASH] 0.89) for the P. falciparum/P. vivax infection ratio, and 0.53 (95%CI 0.41 [EN DASH] 0.69) for the hospital admission rates. There was also a significant change in the seasonal (or monthly) pattern of the time series before and after intervention, with the elimination of the malaria seasonal peak in the rainy months of the years following the introduction of ASMQ. No serious adverse events relating to the use of fixed-dose ASMQ were reported. CONCLUSIONS: In the remote region of the Jurua valley, the early detection of malaria by health care workers and treatment with fixed-dose ASMQ was feasible and efficacious, and significantly reduced the incidence and morbidity of P. falciparum malaria.     

Costs Associated with Malaria in Pregnancy in the Brazilian Amazon,a Low Endemic Area Where Plasmodium vivax Predominates

BackgroundInformation on costs associated with malaria in pregnancy (MiP) in low transmission areas where Plasmodium vivax predominates is so far missing. This study estimates health system and patient costs of MiP in the Brazilian Amazon.ConclusionDespite being an area of low risk malaria transmission, MiP is responsible for a significant economic burden in Manaus. Especially when multiple infections are considered, costs associated with P. vivax are higher than costs associated with P. falciparum. The information generated may help health policy decisions for the current control and future elimination of malaria in the area.     

Diversity of <Emphasis Type="Italic">Anopheles</Emphasis> spp. (Diptera: Culicidae) in an Amazonian Urban Area

The genus Anopheles encompasses several species considered as vectors of human infecting Plasmodium. Environmental changes are responsible for behavior changes in these vectors and therefore the pattern of malaria transmission. To better understand the dynamics of malaria transmission, this study aimed at identify the species of adult anophelines found in a malaria endemic urban area of the Amazon region, Mâncio Lima, located in the Acre State Brazil. Using Shannon-type light traps installed at 11 collection points near fish ponds, a total of 116 anophelines were collected belonging to nine species. Anopheles darlingi Root 1926 and An. albitarsis s.l. Lynch-Arribalzaga 1878 were the most abundant and predominant species. Despite the low number of captured adult anophelines, the occurrence of An. darlingi throughout all urban area and the presence of secondary vectors reinforce the need of a permanent and continuous entomological surveillance.     

Frequency of the HFE C282Y and H63D polymorphisms in Brazilian malaria patients and blood donors from the Amazon region

Malaria is an endemic parasitosis and its causitive agent, Plasmodium, has a metabolism linked to iron supply. HFE is a gene with the polymorphisms C282Y and H63D, which are associated with a progressive iron accumulation in the organism leading to a disease called hereditary hemochromatosis. The aim of the present study was to determine the allelic and genotypic frequencies of the HFE gene polymorphisms in malaria patients and blood donors from the Brazilian Amazon region. We screened 400 blood donors and 400 malaria patients for the HFE C282Y and H63D polymorphisms from four states of the Brazilian Amazon region by polymerase chain reaction and restriction fragment length polymorphism analysis. We did not find any C282Y homozygous individuals, and the only five heterozygous individuals detected were from Pará State. The most frequent genotype in the North region of Brazil was the H63D heterozygote, in both study groups. Our results contribute to the concept that the Brazilian Amazon region should not be regarded as a single entity in South America. These polymorphisms did not influence the symptoms of malaria in the population studied, as neither severe signs nor high parasitemia were observed. Therefore, different hereditary hemochromatosis diagnostic and control measures must be developed and applied within its diverse locations. Investigations are currently being carried out in our laboratory in order to determine the importance of the coexistence of hereditary hemochromatosis in patients affected by parasitic diseases, such as malaria.     

Malaria control in an agro-industrial settlement of Rondônia (Western Amazon region, Brazil)

A malaria control pilot project was developed in the Urupá agro-industrial farm that is situated in the State of Rond?nia (Western Amazon Region, Brazil). Around 180 inhabitants had been surveyed for the past five years. The control measures were based on (1) training a community agent to perform on the spot microscopical diagnosis of malaria and to treat the uncomplicated cases of malaria; (2) limiting the use of insecticides to a short period before the high transmission season. This resulted in a significant reduction in the time between the onset of clinical symptoms and specific chemotherapy which fell from 3.5 to 1.3 days. In relation to the previous three reference years the total number of malaria cases was reduced to 50% in the first year and to 25% in the second year. The introduction of these measures coincided with pronounced reduction in the frequency of Plasmodium falciparum infections but this was less marked for P. vivax infections. In the second year of the pilot experiment there was no P. falciparum transmission on the farm. During the last decade there was a general decrease in the endemicity of malaria in the State of Rond?nia. The linear regression coefficient values indicate that the decline was more pronounced in Urupá than in the general municipality and that the falciparum malaria API in Urupá farm is significantly lower than in the general municipality of Candeias were the farm is situated.     

Malaria transmission structure in the Peruvian Amazon through antibody signatures to Plasmodium vivax

BackgroundThe landscape of malaria transmission in the Peruvian Amazon is temporally and spatially heterogeneous, presenting different micro-geographies with particular epidemiologies. Most cases are asymptomatic and escape routine malaria surveillance based on light microscopy (LM). Following the implementation of control programs in this region, new approaches to stratify transmission and direct efforts at an individual and community level are needed. Antibody responses to serological exposure markers (SEM) to Plasmodium vivax have proven diagnostic performance to identify people exposed in the previous 9 months.MethodologyWe measured antibody responses against 8 SEM to identify recently exposed people and determine the transmission dynamics of P. vivax in peri-urban (Iquitos) and riverine (Mazán) communities of Loreto, communities that have seen significant recent reductions in malaria transmission. Socio-demographic, geo-reference, LM and qPCR diagnosis data were collected from two cross-sectional surveys. Spatial and multilevel analyses were implemented to describe the distribution of seropositive cases and the risk factors associated with exposure to P. vivax.Principal findingsLow local transmission was detected by qPCR in both Iquitos (5.3%) and Mazán (2.7%); however, seroprevalence indicated a higher level of (past) exposure to P. vivax in Mazán (56.5%) than Iquitos (38.2%). Age and being male were factors associated with high odds of being seropositive in both sites. Higher antibody levels were found in individuals >15 years old. The persistence of long-lived antibodies in these individuals could overestimate the detection of recent exposure. Antibody levels in younger populations (<15 years old) could be a better indicator of recent exposure to P. vivax.ConclusionsThe large number of current and past infections detected by SEMs allows for detailed local epidemiological analyses, in contrast to data from qPCR prevalence surveys which did not produce statistically significant associations. Serological surveillance will be increasingly important in the Peruvian Amazon as malaria transmission is reduced by continued control and elimination efforts.     

The Duffy binding protein as a key target for a Plasmodium vivax vaccine: lessons from the Brazilian Amazon

Plasmodium vivax infects human erythrocytes through a major pathway that requires interaction between an apical parasite protein, the Duffy binding protein (PvDBP) and its receptor on reticulocytes, the Duffy antigen/receptor for chemokines (DARC). The importance of the interaction between PvDBP (region II, DBPII) and DARC to P. vivax infection has motivated our malaria research group at Oswaldo Cruz Foundation (state of Minas Gerais, Brazil) to conduct a number of immunoepidemiological studies to characterise the naturally acquired immunity to PvDBP in populations living in the Amazon rainforest. In this review, we provide an update on the immunology and molecular epidemiology of PvDBP in the Brazilian Amazon - an area of markedly unstable malaria transmission - and compare it with data from other parts of Latin America, as well as Asia and Oceania.     

How can malaria rapid diagnostic tests achieve their potential? A qualitative study of a trial at health facilities in Ghana

Malaria is still a major public health problem in Brazil, with approximately 306 000 registered cases in 2009, but it is estimated that in the early 1940s, around six million cases of malaria occurred each year. As a result of the fight against the disease, the number of malaria cases decreased over the years and the smallest numbers of cases to-date were recorded in the 1960s. From the mid-1960s onwards, Brazil underwent a rapid and disorganized settlement process in the Amazon and this migratory movement led to a progressive increase in the number of reported cases. Although the main mosquito vector (Anopheles darlingi) is present in about 80% of the country, currently the incidence of malaria in Brazil is almost exclusively (99,8% of the cases) restricted to the region of the Amazon Basin, where a number of combined factors favors disease transmission and impair the use of standard control procedures. Plasmodium vivax accounts for 83,7% of registered cases, while Plasmodium falciparum is responsible for 16,3% and Plasmodium malariae is seldom observed. Although vivax malaria is thought to cause little mortality, compared to falciparum malaria, it accounts for much of the morbidity and for huge burdens on the prosperity of endemic communities. However, in the last few years a pattern of unusual clinical complications with fatal cases associated with P. vivax have been reported in Brazil and this is a matter of concern for Brazilian malariologists. In addition, the emergence of P. vivax strains resistant to chloroquine in some reports needs to be further investigated. In contrast, asymptomatic infection by P. falciparum and P. vivax has been detected in epidemiological studies in the states of Rondonia and Amazonas, indicating probably a pattern of clinical immunity in both autochthonous and migrant populations. Seropidemiological studies investigating the type of immune responses elicited in naturally-exposed populations to several malaria vaccine candidates in Brazilian populations have also been providing important information on whether immune responses specific to these antigens are generated in natural infections and their immunogenic potential as vaccine candidates. The present difficulties in reducing economic and social risk factors that determine the incidence of malaria in the Amazon Region render impracticable its elimination in the region. As a result, a malaria-integrated control effort - as a joint action on the part of the government and the population - directed towards the elimination or reduction of the risks of death or illness, is the direction adopted by the Brazilian government in the fight against the disease.