Abstract. We estimate that the global burden of malaria due to Plasmodium vivax is ϳ70-80 million cases annually. Probably ϳ10-20% of the world's cases of P. vivax infection occur in Africa, south of the Sahara. In eastern and southern Africa, P. vivax represents around 10% of malaria cases but Ͻ 1% of cases in western and central Africa. Outside of African, P. vivax accounts for Ͼ 50% of all malaria cases. About 80-90% of P. vivax outside of Africa occurs in the Middle East, Asia, and the Western Pacific, mainly in the most tropical regions, and 10-15% in Central and South America. Because malaria transmission rates are low in most regions where P. vivax is prevalent, the human populations affected achieve little immunity to this parasite; as a result, in these regions, P. vivax infections affect people of all ages. Although the effects of repeated attacks of P. vivax through childhood and adult life are only rarely directly lethal, they can have major deleterious effects on personal well-being, growth, and development, and on the economic performance at the individual, family, community, and national levels. Features of the transmission biology of P. vivax give this species greater resilience than the less robust Plasmodium falciparum in the face of conditions adverse to the transmission of the parasites. Therefore, as control measures become more effective, the residual malaria burden is likely increasingly to become that of P. vivax.

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.

BackgroundIllegal gold miners in French Guiana, a French overseas territory (‘département’) located in Amazonia, often carry malaria parasites (up to 46.8%). While the Guiana Shield Region aims at malaria elimination, the high prevalence of Plasmodium in this hard-to-reach population in conjunction with frequent incorrect use of artemisinin-based anti-malarials could favour the emergence of resistant parasites. Due to geographical and regulatory issues in French Guiana, usual malaria control strategies cannot be implemented in this particular context. Therefore, new strategies targeting this specific population in the forest are required.MethodsNumerous discussions among health institutions and scientific partners from French Guiana, Brazil and Suriname have led to an innovative project based on the distribution of kits for self-diagnosis and self-treatment of Plasmodium infections. The kit-distribution will be implemented at “resting sites”, which are areas across the border of French Guiana regularly frequented by gold miners. The main objective is to increase the appropriate use and complete malaria treatment after a positive malaria diagnosis with a rapid test, which will be evaluated with before-and-after cross-sectional studies. Monitoring indicators will be collected from health mediators at the time of kit distribution and during subsequent visits, and from illegal gold miners themselves, through a smartphone application. The project funding is multisource, including Ministries of Health of the three countries, WHO/PAHO, and the European Union.ResultsThis project will start in April 2018 as a 18 month pilot study led by the Clinical Investigation Centre of Cayenne. Results should be available at the end of 2019.DiscussionThis innovative approach may have several limitations which should be taken into account, as potential side effects, kit misuse or resale, declarative main criteria, or no Plasmodium vivax curative treatment. Close monitoring is thus needed.ConclusionsThis project may be the best available solution to a specific and important public health challenge in the Guiana Shield. If the use of self-diagnosis and self-treatment approach is effective, this strategy could be sustained by health institutions in the region.

Brazil is the largest country of Latin America, with a considerable portion of its territoritory within the malaria-endemic Amazon region in the North. Furthermore, a considerable portion of its territory is located within the Amazon region in the north. As a result, Brazil has reported half of the total malaria cases in the Americas in the last four decades. Recent progress in malaria control has been accompanied by an increasing proportion of Plasmodium vivax, underscoring a need for a better understanding of management and control of this species and associated challenges. Among these challenges, the contribution of vivax malaria relapses, earlier production of gametocytes (compared with Plasmodium falciparum), inexistent methods to diagnose hypnozoite carriers, and decreasing efficacy of available antimalarials need to be addressed. Innovative tools, strategies, and technologies are needed to achieve further progress toward sustainable malaria elimination. Further difficulties also arise from dealing with the inherent socioeconomic and environmental particularities of the Amazon region and its dynamic changes.

4www.scielo.br/rsbmt I www.rsbmt.org.br Revista da Sociedade Brasileira de Medicina Tropical 48(Suppl I):4-11, 2015http://dx.doi. org/10.1590/0037-8682-0275-2014 Review Article ABSTRACT In Brazil, more than 99% of malaria cases are reported in the Amazon, and the State of Amazonas accounts for 40% of this total. However, the accumulated experience and challenges in controlling malaria in this region in recent decades have not been reported. Throughout the fi rst economic cycle during the rubber boom (1879 to 1912), malaria was recorded in the entire state, with the highest incidence in the villages near the Madeira River in the Southern part of the State of Amazonas. In the 1970s, during the second economic development cycle, the economy turned to the industrial sector and demanded a large labor force, resulting in a large migratory infl ux to the capital Manaus. Over time, a gradual increase in malaria transmission was observed in peri-urban areas. In the 1990s, the stimulation of agroforestry, particularly fi sh farming, led to the formation of permanent Anopheline breeding sites and increased malaria in settlements. The estimation of environmental impacts and the planning of measures to mitigate them, as seen in the construction of the Coari-Manaus gas pipeline, proved effective. Considering the changes occurred since the Amsterdam Conference in 1992, disease control has been based on early diagnosis and treatment, but the development of parasites that are resistant to major antimalarial drugs in Brazilian Amazon has posed a new challenge. Despite the decreased lethality and the gradual decrease in the number of malaria cases, disease elimination, which should be associated with government programs for economic development in the region, continues to be a challenge.

BackgroundControl of vivax malaria in endemic areas requires management of recurrence. The Brazilian National Malaria Surveillance System (SIVEP-Malária) records every case of malaria in Brazil, but is not designed to differentiate between primary and recurrent infections. The aim of this study was to explore whether the information provided by SIVEP-Malária could be used to identify Plasmodium vivax recurrences, its risk factors and evaluate the effectiveness of short course primaquine (7–9 days: total dose 3–4.2 mg/kg) in preventing relapses.MethodsIn this observational retrospective cohort study, data matching of SIVEP-Malária records was undertaken using bloom filters to identify potential recurrences defined as microscopically-confirmed P. vivax episodes from the same individual occurring within a year. Generalized Estimation Equation (GEE) models were used to determine predictors of recurrence. Extended Cox-based conditional Prentice–Williams–Peterson models (PWP) models were used to evaluate time to recurrence.ResultsBetween June 1, 2014 and May 31, 2015, 26,295 episodes fulfilled the criteria of potential recurrence among 154,970 reported malaria episodes. Age ≤ 3 years, being male, literate, not-indigenous and having domestic working activities were identified as risk factors for recurrence. There was no difference in time to recurrence or recurrence frequency between patients treated with 14-day or 7–9 day primaquine regimens (HR = 1.02, 0.96–1.09) and RR = 0.97 (0.90–1.04), respectively. The use of chloroquine alone was associated with a 1.43 (1.29–1.58, p < 0.0001) increased risk of P. vivax recurrence compared to patients who used chloroquine combined with short-course primaquine, the Brazilian standard of care. This was RR = 2.06 (1.48–2.86, p < 0.0001), RR = 1.90 (1.60–2.25, p = 0.0001) and RR = 1.14 (1.00–1.29, p = 0.05) for recurrences occurring between 3–28, 29–60 and > 60 days, respectively. PWP models showed that the time to recurrence was longer in recipients of both primaquine and artemisinin-based combination therapy (ACT) compared to patients treated with chloroquine alone or with concomitant primaquine, HR = 2.2 (1.62–2.99, p < 0.0001), HR = 1.27 (0.97–1.66, p = 0.08), respectively.ConclusionShort course primaquine was as effective as 14-day regimens and associated with a halving of the risk and delay in time to recurrence of P. vivax infections in comparison to chloroquine alone. The study demonstrates the feasibility of using record linkage on routine surveillance data to identify potential P. vivax recurrences, associated risk factors and impact of treatment.Electronic supplementary materialThe online version of this article (10.1186/s12936-019-2644-y) contains supplementary material, which is available to authorized users.

Background As malaria endemic countries strive towards elimination, intensified spatial heterogeneities of local transmission could undermine the effectiveness of traditional intervention policy. Methods The dynamic nature of large-scale and long-term malaria heterogeneity across Brazilian Amazon basin were explored by (1) exploratory analysis of Brazil’s rich clinical malaria reporting database from 2004 to 2018, and (2) adapting Gini coefficient to study the distribution of malaria cases in the region. Results As transmission declined, heterogeneity increased with cases clustering into smaller subpopulations across the territory. In 2004, the 1% of health units with the greatest number of cases accounted for 46% of all reported Plasmodium vivax cases, whereas in 2018 52% of P. vivax cases occurred in the top 1% of health units. Plasmodium falciparum had lower levels of transmission than P. vivax, and also had greater levels of heterogeneity with 75% of cases occurring in the top 1% of health units. Age and gender stratification of cases revealed peri-domestic and occupational exposure settings that remained relatively stable. Conclusion The pathway to decreasing incidence is characterized by higher proportions of cases in males, in adults, due to importation, and caused by P. vivax. Characterization of spatio-temporal heterogeneity and risk groups can aid stratification for improved malaria control towards elimination with increased heterogeneity potentially allowing for more efficient and cost-effective targeting. Although distinct epidemiological phenomena were clearly observed as malaria transmission declines, the authors argue that there is no canonical path to malaria elimination and a more targeted and dynamic surveillance will be needed if Brazil decides to adopt the elimination target.

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