Fundação Carlos Chagas Filho de Amparo à Pesquisa do Estado de Rio de Janeiro, The Brazilian National Council for Scientific and Technological Development (CNPq), JSPS Grant-in-Aid for scientific research, Secretary for Health Surveillance of the Brazilian Ministry of Health, Global Fund, Fundaçao de amparo à pesquisa do estado de Minas Gerais (Fapemig), and PRONEX Program of the CNPq.

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.

The evolution of malaria in Brazil, its morbidity, the malaria control programs, and the new challenges for these programs in the light of the emergence of asymptomatic infection in the Amazon region of Brazil were reviewed. Rondônia and, in our group, in If a mean of 25% is taken for the asymptomatic infection caused by Plasmodium sp. in the Amazon region of Brazil, malaria control will be difficult to achieve in that region with the measures currently utilized for such control. At least six Brazilian research groups have demonstrated that asymptomatic infection by Plasmodium is an important impediment to malaria control, among mineral prospectors in Mato Grosso and riverside communities in Key words: malaria -asymptomatic infection -control -Brazilian AmazonMalaria is the most widespread and most serious parasitic disease in the world. Forty percent of the world's population (2.4 billion people) is exposed to the infection, especially people who live in tropical and subtropical countries. In these regions, between 300 and 500 million cases are diagnosed every year, causing 1.5 to 2.7 million deaths per year, mostly among African children (WHO 2002). In 2001, according to a review by Hay et al. (2004), the overall incidence of malaria in the areas at risk in the world was 396 million cases, of which more than 80% were on the African continent, leading to the death of 1,123,000 cases, mostly children (Hay et al. 2004).In the Americas and in the Caribbean, 38% of the population (308 million people), in 21 countries, live in areas with malaria transmission, with a mean of 1.3 million cases per year. Thirty-six percent of these are in Brazil (OPS 1997, 1998, WHO 2002.Since 1970, when just over 52,000 cases were recorded in Brazil, malaria has gradually been increasing in this country. In the 1990s, the number of cases surpassed 500,000. In 1999, there were 610,000 notified cases of malaria in Brazil, and 99% of them were in the Amazon region (Ministério da Saúde 2003). Taking into account possible underreporting and cases of asymptomatic infection , Alves et al. 2002, Suárez-Mutis et al. 2004, Ladeia-Andrade 2005, it may be considered that more than 600,000 cases are occurring in Brazil every year (personal estimation). The number of cases of malaria re- show the areas at risk (Fig. 1) and the number of malaria cases notified in Brazil from 1970 to 2005 (Fig. 2).The course followed by malaria usually takes the form of a feverish acute systemic disease. The severity of the disease varies according to the parasite species (Plasmodium falciparum, P. vivax, P. malariae, and P. ovale; the last of these is not found in Brazil), the inoculum, the strain of the parasite, and the degree of previous immunity. Since the time of Hippocrates (460-377 BC), cases of infection of greater or lesser severity have been known. In 1900, Robert Koch first recognized cases of asymptomatic Plasmodium infection among patients in Papua New Guinea (Harrison 1978). This characteristic of malaria has been of concern for some time, particula...

Our findings indicate that the TLR-1 and TLR-6 variants are significantly associated with mild malaria, whereas the TLR-9-1486C/T variants are associated with high parasitemia. These discoveries may bring additional understanding to the pathogenesis of malaria.

Purpose of Review Following Paraguay and Argentina, several countries from the Amazon region aim to eliminate malaria. To achieve this, all key affected and vulnerable populations by malaria, including people working on gold mining sites, must be considered. What is the situation of malaria in these particular settings and what are the challenges? This literature review aims to compile knowledge to answer these questions. Recent FindingsThe contexts in which gold miners operate are very heterogeneous: size and localization of mines, links with crime, administrative status of the mines and of the miners, mobility of the workers or national regulations. The number of malaria cases has been correlated with deforestation (Brazil, Colombia), gold production (Colombia), gold prices (Guyana), or location of the mining region (Peru, Colombia, Venezuela, Guyana). The burden of malaria in gold mines differs between territories: significant in Guyana, French Guiana, or Venezuela; lower in Brazil. Although Plasmodium vivax causes 75% of malaria cases in the Americas, P. falciparum is predominant in several gold mining regions, especially in the Guiana Shield. Because of the remoteness from health facilities, self-medication with under-the-counter antimalarials is frequent. This constitutes a significant risk for the emergence of new P. falciparum parasites resistant to antimalarial drugs. Summary Because of the workers' mobility, addressing malaria transmission in gold mines is essential, not only for miners, but also to prevent the (re-)emergence of malaria. Strategies among these populations should be tailored to the context because of the heterogeneity of situations in different territories. The transnational environment favoring malaria transmission also requires transborder and regional cooperation, where innovative solutions should be considered and evaluated.