Delayed gametocyte clearance in Plasmodium vivax malaria is associated with polymorphisms in the cytochrome P450 reductase (CPR).

Primaquine (PQ) is the main drug used to eliminate dormant liver stages and prevent relapses in Plasmodium vivax malaria. It also has an effect on the gametocytes of Plasmodium falciparum; however, it is unclear to what extent PQ affects P. vivax gametocytes. PQ metabolism involves multiple enzymes, including the highly polymorphic CYP2D6 and the cytochrome P450 reductase (CPR). Since genetic variability can impact drug metabolism, we conducted an evaluation of the effect of CYP2D6 and CPR variants on PQ gametocytocidal activity in 100 subjects with P. vivax malaria. To determine gametocyte density, we measured the levels of pvs25 transcripts in samples taken before treatment (D0) and 72 hours after treatment (D3). Generalized estimating equations (GEEs) were used to examine the effects of enzyme variants on gametocyte densities, adjusting for potential confounding factors. Linear regression models were adjusted to explore the predictors of PQ blood levels measured on D3. Individuals with the CPR mutation showed a smaller decrease in gametocyte transcript levels on D3 compared to those without the mutation (P = 0.02, by GEE). Consistent with this, higher PQ blood levels on D3 were associated with a lower reduction in pvs25 transcripts. Based on our findings, the CPR variant plays a role in the persistence of gametocyte density in P. vivax malaria. Conceptually, our work points to pharmacogenetics as a non-negligible factor to define potential host reservoirs with the propensity to contribute to transmission in the first days of CQ-PQ treatment, particularly in settings and seasons of high Anopheles human-biting rates.

Monoamine oxidase-A (MAO-A) low-expression variants and increased risk of Plasmodium vivax malaria relapses.

OBJECTIVES: Primaquine is essential for the radical cure of Plasmodium vivax malaria and must be metabolized into its bioactive metabolites. Accordingly, polymorphisms in primaquine-metabolizing enzymes can impact the treatment efficacy. This pioneering study explores the influence of monoamine oxidase-A (MAO-A) on primaquine metabolism and its impact on malaria relapses. METHODS: Samples from 205 patients with P. vivax malaria were retrospectively analysed by genotyping polymorphisms in MAO-A and cytochrome P450 2D6 (CYP2D6) genes. We measured the primaquine and carboxyprimaquine blood levels in 100 subjects for whom blood samples were available on the third day of treatment. We also examined the relationship between the enzyme variants and P. vivax malaria relapses in a group of subjects with well-documented relapses. RESULTS: The median carboxyprimaquine level was significantly reduced in individuals carrying low-expression MAO-A alleles plus impaired CYP2D6. In addition, this group experienced significantly more P. vivax relapses. The low-expression MAO-A status was not associated with malaria relapses when CYP2D6 had normal activity. This suggests that the putative carboxyprimaquine contribution is irrelevant when the CYP2D6 pathway is fully active. CONCLUSIONS: We found evidence that the low-expression MAO-A variants can potentiate the negative impact of impaired CYP2D6 activity, resulting in lower levels of carboxyprimaquine metabolite and multiple relapses. The findings support the hypothesis that carboxyprimaquine may be further metabolized through CYP-mediated pathways generating bioactive metabolites that act against the parasite.

Cooperation for malaria control and elimination in the Guiana Shield.

The Guiana Shield, a small region of South America, is currently one of the main hotspots of malaria transmission on the continent. This Amazonian area is characterised by remarkable socioeconomic, cultural, health, and political heterogeneity and a high degree of regional and cross-border population mobility, which has contributed to the increase of malaria in the region in the past few years. In this context, regional cooperation to control malaria represents both a challenge and an indispensable initiative. This Viewpoint advocates for the creation of a regional cooperative mechanism for the elimination of malaria in the Guiana Shield. This strategy would help address operational and political obstacles to successful technical cooperation in the region and could contribute to reversing the regional upsurge in malaria incidence through creating a functional international control and elimination partnership.

Representação social da malária na perspectiva dos garimpeiros em Boa Vista ­ Roraima / Social representation of malaria from the prespective of miners in Boa Vista ­ Roraima / Representación social de la malaria en la perspectiva de los mineros de Boa Vista ­ Roraima

Objetivo: analisar o núcleo central da representação social acerca da malária na ótica dos garimpeiros e dos indivíduos que exercem atividades laborais em região de garimpo que buscam atendimento no Pronto Atendimento Cosme e Silva em Boa Vista/RR. Método:estudo descritivo exploratório de carácter qualitativo delineado por meio da Teoria das Representações Sociais, formulada por Serge Moscovici em 1961. Foram realizadas 72 entrevistas semiestruturadas com garimpeiros. A análise dos dados ocorreu com o auxílio do software OpenEvoc 0.92 desenvolvido pelo Prof. Dr. Hugo Cristo em 2012. Resultados: foi constatado que as percepções dos garimpeiros acerca da malária está diretamente relacionada com a sintomatologia da doença, principalmente pelos traumas vivenciados devidoa ausência de serviço de saúde disponível no local de trabalho. Enquanto que, as percepções dos garimpeiros sobre o garimpo estão vinculadas a condição econômica deste grupo. Conclusão:observa-se que a busca pelo bem-estar financeiro, faz o garimpeiro se submeter às relações extremamente precárias de trabalho, incluindo a exposição ao vetor da malária.

Objective: to analyze the central nucleus of the social representation about malaria from the perspective of miners and individuals who carry out work activities in a mining region who seek care at the Cosme e Silva Emergency Room in Boa Vista/RR. Method:descriptiveexploratory study of a qualitative nature outlined through the Theory of Social Representations, formulated by Serge Moscovici in 1961. 72 semi-structured interviews were carried out with miners. Data analysis took place with the aid of the OpenEvoc 0.92 software developed by Prof. Dr. Hugo Cristo in 2012. Results:it was found that the prospectors' perceptions about malaria are directly related to the symptoms of the disease, mainly due to the traumas experienced due to the lack of health services available in the workplace. Meanwhile, the prospectors' perceptions about mining are linked to the economic condition of this group. Conclusion:it is observed that the search for financial well-being makes the prospector submit to extremely precarious work relationships, including exposure to the malaria vector.

Objetivo: analizar el núcleo central de la representación social sobre la malaria en la perspectiva de mineros y personas que ejercen actividades laborales en una región minera que buscan atención en el Servicio de Emergencia Cosme e Silva de Boa Vista/RR. Método:estudio descriptivo exploratorio de carácter cualitativo esbozado a través de la Teoría de las Representaciones Sociales, formulada por Serge Moscovici en 1961. Se realizaron 72 entrevistas semiestructuradas con mineros. El análisis de datos se llevó a cabocon la ayuda del software OpenEvoc 0.92 desarrollado por el Prof. Dr. Hugo Cristo en 2012. Resultados:se encontró que las percepciones de los prospectores sobre la malaria están directamente relacionadas con los síntomas de la enfermedad, principalmente debido a los traumas experimentados por la falta de servicios de salud disponibles en el lugar de trabajo. Por su parte, las percepciones de los buscadores sobre la minería están ligadas a la condición económica de este grupo. Conclusión: se observa que labúsqueda de bienestar económico hace que el prospector se someta a relaciones de trabajo extremadamente precarias, incluida la exposición al vector de la malaria.

Malária: A crise silenciosa em Alto Alegre, Roraima e o fantasma do garimpo na Terra Indígena Yanomami / Malaria: The Silent Crisis in Alto Alegre, Roraima and the Specter of Mining in the Yanomami Indigenous Land / Malaria: La crisissilenciosa en Alto Alegre, Roraima y el fantasma de la minería en la Tierra Indígena Yanomami

Objetivo:analisar a evolução dos casos de malária em Roraima, principalmente no município de Alto Alegre, estratificado por aglomerações por área geográfica habitada -rural, urbana e área indígena no período de 2013 a 2022. Método:Estudo ecológico do tipo série temporal baseado em dados secundários dos casos confirmados de malária em Roraima, no período de 2013 a 2022. Resultados:nesse período foram confirmados 72.828 casos de malária em Roraima, dos quais 78,0% foram por Plasmodium vivax. Além disso, a maior parte dos casos se concentrou no município de Alto Alegre, correspondendo a 41,1%. Portanto, este foi o município que mais produziu malária procedente de garimpo, apesar de existirem outros que registraram aumento da doença nesse período. Conclusão:assim, osmunicípios de Alto Alegre, Amajari, Caracaraí, Iracema e Mucajaí, juntos respondem por 77.8% de toda malária produzida em Roraima. Estes municípios fazem parte da rota do garimpo ilegal na terra indígena Yanomami.

Objective: analyze the evolution of malaria cases in Roraima, especially in the municipality of Alto Alegre, stratified by geographical areas of habitation -rural, urban, and indigenous areas, from 2013 to 2022. Method: A time series ecological study based on secondary data of confirmed malaria cases in Roraima from 2013 to 2022. Results:During this period, 72,828 cases of malaria were confirmed in Roraima, of which 78.0% were due to Plasmodium vivax. Furthermore, the majority of cases were concentrated in the municipality of Alto Alegre, accounting for 41.1%. Therefore, this was the municipality that produced the most malariafrom mining activities, despite others experiencing an increase in the disease during this period. Conclusion: Thus, the municipalities of Alto Alegre, Amajari, Caracaraí, Iracema, and Mucajaí together accounted for 77.8% of all malaria cases produced in Roraima. These municipalities are part of the illegal mining route within the Yanomami indigenous land.

Objetivo: analizar la evolución de los casos de malaria en Roraima, principalmente en el municipio de Alto Alegre, marcado por aglomeraciones por área geográfica habitada -rural, urbana, en el área indígena en el período comprendido desde 2013 hasta 2022. Método: Estudio ecológico de tipo serie temporal basado en datos secundarios de los casos confirmados de malaria en Roraima, en el periodo de 2013 hasta 2022. Resultados: Durante este periodo fueron confirmados 72.828 casos de malaria en Roraima, de los cuales 78,0% correspondieron a Plasmodium Vivax. Además, la mayor parte de los casos estaban concentrados en el municipio de Alto Alegre, correspondiendo a 41,1%. Por lo tanto, este fue el condado que más produjo malaria proveniente de la minería, a pesar de existir otros que registraron aumentos de la enfermedad durante este periodo. Conclusión: Siendo así, los condados de Alto Alegre, Amajari, Caracaraí, Iracema y Mucajaí, juntos representan el 77.8% de toda la malaria existente en Roraima. Estos condados hacen parte de la ruta de minería ilegal en tierras indígenas Yanomam.

The impact of imported malaria by gold miners in Roraima: characterizing the spatial dynamics of autochthonous and imported malaria in an urban region of Boa Vista

BACKGROUND The number of malaria cases in Roraima nearly tripled from 2016 to 2018. The capital, Boa Vista, considered a low-risk area for malaria transmission, reported an increasing number of autochthonous and imported cases. OBJECTIVES This study describes a spatial analysis on malaria cases in an urban region of Boa Vista, which sought to identify the autochthonous and imported cases and associated them with Anopheles habitats and the potential risk of local transmission. METHODS In a cross-sectional study at the Polyclinic Cosme e Silva, 520 individuals were interviewed and diagnosed with malaria by microscopic examination. Using a global positional system, the locations of malaria cases by type and origin and the breeding sites of anopheline vectors were mapped and the risk of malaria transmission was evaluated by spatial point pattern analysis. FINDINGS Malaria was detected in 57.5% of the individuals and there was a disproportionate number of imported cases (90.6%) linked to Brazilian coming from gold mining sites in Venezuela and Guyana. MAIN CONCLUSIONS The increase in imported malaria cases circulating in the west region of Boa Vista, where there are positive breeding sites for the main vectors, may represent a potential condition for increased autochthonous malaria transmission in this space.

Abordagem crítico-interpretativa das fragilidades e potencialidades do trabalho de enfermagem aos ianomâmis, Amazonas

Este estudo analisa as fragilidades e potencialidades do processo de trabalho de enfermagem desenvolvido nas comunidades indígenas ianomâmis, dos municípios de Barcelos e Santa Isabel do Rio Negro, estado do Amazonas. Trata-se de uma pesquisa qualitativa, de abordagem crítico-interpretativa, realizada em 2006. Informantes-chave: três enfermeiros e 17 técnicos de enfermagem. As informações foram obtidas por meio de entrevistas. Para a interpretação, optou-se pelo método da análise de conteúdo, com emprego da técnica analítica de enunciação com transversalidade temática constituinte de duas categorias – fragilidades e potencialidades. As fragilidades desvelam o gerenciamento do serviço de enfermagem em área indígena e a escassez de recursos humanos e de materiais. As potencialidades revelam o trabalho em equipe e a presença dos agentes indígenas de saúde nas aldeias. Conclui-se que a situação dos trabalhadores de enfermagem descrita nos discursos dos entrevistados requer atenção dos gestores da saúde indígena, para dar condições mais dignas de trabalho...

This study analyzes the fragilities and the potentialities of nursing working process developed in autochthonous yanomamis communities, at municipal districts of Barcelos and Santa Isabel do Rio Negro, Amazon state. That is a qualitative investigation with a critical-interpretive approaching, accomplished in 2006. Main informers: three nurses and seventeen nursing assistants. The informations were obtained by means of interviews. To the interpretation, it was opted for the method of the analysis of the content, by using the enunciation analytical technique with thematic transverse, constituting two categories that are fragilities and potentialities. The fragilities discoveries show: the management of the nursing service in autochthonous area, the shortage of human resources and of materials. The potentialities reveal the team work and the presence of indigenous Agents of health in the villages. It is concluded that the situation of the nursing workers described in the speeches of the interviewed requires attention of the indigenous health managers, giving them better conditions of work...

El estudio analiza las debilidades y las potencialidades del proceso del trabajo que la enfermería desarrolló en las comunidades autóctonas yanomamis, de los distritos municipales de Barcelos y Santa Isabel do Rio Negro, Amazonas. Se trata de una investigación cualitativa, de enfoque crítico-interpretativo con desenrollo en el año de 2006. Informante-clave: tres enfermeras y diecisiete técnicos de enfermería. Las informaciones fueron obtenidas por entrevista. Para la interpretación se optó por el método del análisis del contenido, con el trabajo de la técnica analítica de la enunciación con componente transversal temático de dos debilidades de categorías y potencialidades. Las debilidades muestran: el gerenciamiento del servício de enfermería en la área indígena, la escasez de recursos humanos y de materiales. Las potencialidades revelan el trabajo en equipo, la presencia de los agentes indígenas de salud en las comunidades. Se concluye que la situación descrita de los trabajadores de enfermería en los discursos de los entrevistados requiere atención de los administradores de la salud indígena ofreciendoles condiciones más dignas de trabajo...