Effect of adherence to primaquine on the risk of Plasmodium vivax recurrence: a WorldWide Antimalarial Resistance Network systematic review and individual patient data meta-analysis.

BACKGROUND: Imperfect adherence is a major barrier to effective primaquine radical cure of Plasmodium vivax. This study investigated the effect of reduced adherence on the risk of P. vivax recurrence. METHODS: Efficacy studies of patients with uncomplicated P. vivax malaria, including a treatment arm with daily primaquine, published between January 1999 and March 2020 were identified. Individual patient data from eligible studies were pooled using standardized methodology. Adherence to primaquine was inferred from i) the percentage of supervised doses and ii) the total mg/kg dose received compared to the target total mg/kg dose per protocol. The effect of adherence to primaquine on the incidence of P. vivax recurrence between days 7 and 90 was investigated by Cox regression analysis. RESULTS: Of 82 eligible studies, 32 were available including 6917 patients from 18 countries. For adherence assessed by percentage of supervised primaquine, 2790 patients (40.3%) had poor adherence (≤ 50%) and 4127 (59.7%) had complete adherence. The risk of recurrence by day 90 was 14.0% [95% confidence interval: 12.1-16.1] in patients with poor adherence compared to 5.8% [5.0-6.7] following full adherence; p = 0.014. After controlling for age, sex, baseline parasitaemia, and total primaquine dose per protocol, the rate of the first recurrence was higher following poor adherence compared to patients with full adherence (adjusted hazard ratio (AHR) = 2.3 [1.8-2.9]). When adherence was quantified by total mg/kg dose received among 3706 patients, 347 (9.4%) had poor adherence, 88 (2.4%) had moderate adherence, and 3271 (88.2%) had complete adherence to treatment. The risks of recurrence by day 90 were 8.2% [4.3-15.2] in patients with poor adherence and 4.9% [4.1-5.8] in patients with full adherence; p < 0.001. CONCLUSION: Reduced adherence, including less supervision, increases the risk of vivax recurrence.

Influence of trem-1 gene polymorphisms on cytokine levels during malaria by Plasmodium vivax in a frontier area of the Brazilian Amazon.

BACKGROUND: The immunopathology during malaria depends on the level of inflammatory response generated. In this scenario, the TREM-1 has been associated with the severity of infectious diseases and could play an important role in the inflammatory course of malaria. We aimed to describe the allelic and genotypic frequency of four polymorphisms in the trem-1 gene in Plasmodium vivax-infected patients and to verify the association of these polymorphisms with clinical and immunological factors in a frontier area of the Brazilian Amazon. METHODS: We included 76 individuals infected with P. vivax and 144 healthy controls living in the municipality of Oiapoque, Amapá, Brazil. The levels of TNF-α, IL-10, IL-2, IL-4, IL-5, and IFN-γ were measured by flow cytometry, while IL-6, sTREM-1, and antibodies against PvMSP-119 were evaluated by ELISA. The SNPs were genotyped by qPCR technique. Polymorphisms analysis, allelic and genotype, frequencies, and HWE calculation were determined by x2 test in R Software. The association between the parasitemia, gametocytes, antibodies, cytokines, and sTREM-1 with the genotypes of malaria and control groups was performed using the Kruskal-Wallis test, these analyzes were conducted in SPSS Software, at 5% significance level. RESULTS: All SNPs were successfully genotyped. Allelic and genotypic distribution was in Hardy-Weinberg Equilibrium. Furthermore, several associations were identified between malaria and control groups, with increased levels of IL-5, IL-6, IL-10, TNF-α, and IFN-γ in the infected individuals with rs6910730A, rs2234237T, rs2234246T, rs4711668C alleles compared to the homozygous wild-type and heterozygous genotypes of the controls (p-value < 0.05). No association was found for these SNPs and the levels of IL-2, and sTREM-1. CONCLUSIONS: The SNPs on the trem-1 gene are associated with the effector molecules of the innate immunity and may contribute to the identification and effective participation of trem-1 in the modulation of the immune response. This association may be essential for the establishment of immunization strategies against malaria.

Polymorphisms in Toll-Like receptors genes and their associations with immunological parameters in Plasmodium vivax malaria in the Brazil-French Guiana Border.

BACKGROUND: The innate immune response plays an important role during malaria. Toll-like receptors (TLR) are capable of recognizing pathogen molecules. We aimed to evaluate five polymorphisms in TLR-4, TLR-6, and TLR-9 genes and their association with cytokine levels and clinical parameters in malaria from the Brazil-French Guiana border. METHODS: A case-control study was conducted in Amapá, Brazil. P. vivax patients and individuals not infected were evaluated. Genotyping of five SNPs was carried out by qPCR. Circulating cytokines were measured by CBA. The MSP-119 IgG antibodies were performed by ELISA. RESULTS: An association between TLR4 A299G with parasitemia was observed. There was an increase for IFN-ɤ, TNF-ɑ, IL-6, and IL-10 in the TLR-4 A299G and T3911, TLR-6 S249P, and TLR-9 1486C/T, SNPs for the studied malarial groups. There were significant findings for the TLR-4 variants A299G and T3911, TLR-9 1237C/T, and 1486C/T. For the reactivity of MSP-119 antibodies levels, no significant results were found in malaria, and control groups. CONCLUSIONS: The profile of the immune response observed by polymorphisms in TLRs genes does not seem to be standard for all types of malaria infection around the world. This can depend on the human population and the species of Plasmodium.

Sexually transmitted infections on the border between Brazil and French Guiana.

Purpose: The border between the State of Amapa, Brazil, and French Guiana is mostly primary forest. In the Oyapock basin, socioeconomic circumstances have fueled sex work, gold mining and the circulation of sexually transmitted infections. Given the lack of comprehensive data on this border area, we describe the different sexually transmitted infections along the Brazil/French Guiana border and the testing and care activity. Methods: We conducted a review of the available scientific and technical literature on sexually transmitted infections in this complex border area. Temporal trends were graphed and for Human Immunodeficiency Virus (HIV) we estimated incidence using the European Center for prevention and Disease Control modeling tool. Results: Until 2019, 26 of the 46 HIV-infected patients followed and treated in Saint Georges de l'Oyapock were residing on the Brazilian side in Oiapoque. Virological suppression was only achieved for 75% of treated patients; but dropped to 62% during the COVID-19 epidemic. In 2019, cooperation efforts allowed HIV care in Oiapoque, resulting in the transfer of Brazilian patients previously followed on the French side and a substantial increase in the number of patients followed in Oiapoque. The average yearly HIV serological testing activity at the health center in Saint Georges was 16 tests per 100 inhabitants per year; in Camopi it was 12.2 per 100 inhabitants. Modeling estimated the number of persons living with HIV around 170 persons, corresponding to a prevalence of 0.54% and about 40 undiagnosed infections. The model also suggested that there were about 12 new infections per year in Saint Georges and Oiapoque, representing an HIV incidence rate of 3.8 cases per 10,000 per year. HPV prevalence in Saint Georges ranges between 25 and 30% and between 35 and 40% in Camopi. Testing activity for other sexually transmitted infections markedly increased in the past 5 years; the introduction of PCR for chlamydiasis and gonorrhea also had a substantial impact on the number of diagnoses. Conclusions: The ongoing cooperation between multiple partners on both sides of the border has led to remarkable progress in primary prevention, in testing efforts, in treatment and retention on both sides of the border. In a region with intense health professional turnover, nurturing cooperation and providing accurate assessments of the burden of sexually transmitted infections is essential to tackle a problem that is shared on both sides of the border.

Contrasted life trajectories: reconstituting the main population exposomes in French Guiana.

In French Guiana, life expectancy is between 2 and 3 years below that of France, reflecting differences in mortality rates that are largely sensitive to primary healthcare and thus preventable. However, because poverty affects half of the population in French Guiana, global measurements of life expectancy presumably conflate at least two distinct situations: persons who have similar life expectancies as in mainland France and persons living in precariousness who have far greater mortality rates than their wealthier counterparts. We thus aimed to synthesize what is known about statistical regularities regarding exposures and sketch typical French Guiana exposomes in relation to health outcomes. We conducted a narrative review on common exposures in French Guiana and made comparisons between French Guiana and mainland France, between rich and poor in French Guiana, and between urban and rural areas within French Guiana. The most striking fact this panorama shows is that being a fetus or a young child in French Guiana is fraught with multiple threats. In French Guiana, poverty and poor pregnancy follow-up; renouncing healthcare; wide variety of infectious diseases; very high prevalence of food insecurity; psychosocial stress; micronutrient deficiencies; obesity and metabolic problems; and frequent exposure to lead and mercury in rural areas constitute a stunningly challenging exposome for a new human being to develop into. A substantial part of the population's health is hence affected by poverty and its sources of nutrition.

Fatores de risco relacionados à ocorrência da síndrome de burnout em profissionais de saúde que atuam em maternidades públicas durante a pandemia do Coronavírus / Factors related to the occurrence of burnout syndrome in healthcare professionals working in public maternities during the Coronavirus pandemic

Introdução: os desafios da atual pandemia impuseram aos profissionais de saúde a adequação do processo de trabalho, inclusive nas maternidades, que muitas vezes estava em contradição direta com as evidências de humanização da assistência. Isso pode resultar em níveis crescentes de danos ocupacionais. Objetivo: analisar os fatores associados à Síndrome de Burnout (SB) entre profissionais de saúde que atuam na assistência às gestantes, puérperas e recém-nascidos nas maternidades públicas de Aracaju durante a pandemia do coronavírus. Metodologia: trata-se de um estudo descritivo com abordagem quantitativa, realizado com profissionais de saúde que atuavam na assistência materno-infantil nas maternidades. Resultados: A amostra foi realizada por conveniência e contou com a participação de 218 profissionais, os achados revelaram que 98,2% dos profissionais apresentaram sintomatologia positiva ao menos em uma das três dimensões avaliadas, que sugeriram o diagnóstico da SB. Conclusão: a pandemia trouxe forte impacto à saúde emocional às equipes das maternidades estudadas o que resultou em uma alta ocorrência da SB. Com base na presença dos fatores que predispuseram ao surgimento da síndrome pode ser sugerido uma implementação de ações que busquem cuidar do ambiente de trabalho desses profissionais.

Introduction: the challenges of the current pandemic imposed on health professionals the adequacy of the work process, including in maternity hospitals, which was often in direct contradiction with the evidence of humanization of care. This can result in increasing levels of occupational damage. Objective: to analyze the factors associated with burnout syndrome (BS) among health professionals who work in the care of pregnant women, postpartum women and newborns in public maternity hospitals in Aracaju during the coronavirus pandemic. Methodology: this is a descriptive study with a quantitative approach, carried out with health professionals who worked in maternal and child care in maternity hospitals. Results: the sample was carried out for convenience and had the participation of 218 professionals, the findings revealed that 98.2% of professionals had positive symptoms in at least one of the three dimensions evaluated, which suggested the diagnosis of BS. Conclusion: the pandemic had a strong impact on the emotional health of the teams of the maternity hospitals studied, which resulted in a high occurrence of BS. Based on the presence of factors that predisposed to the emergence of the syndrome, an implementation of actions that seek to take care of the work environment of these professionals can be suggested.

Africanized Bee Venom (Apis mellifera Linnaeus): Neuroprotective Effects in a Parkinson's Disease Mouse Model Induced by 6-hydroxydopamine.

This study evaluated the neuroprotective effects of the Africanized bee venom (BV) and its mechanisms of action after 6-hydroxydopamine-(6-OHDA)-induced lesion in a mice model. Prior to BV treatment, mice received intrastriatal microinjections of 6-OHDA (no induced dopaminergic neuronal death) or ascorbate saline (as a control). BV was administered subcutaneously at different dosages (0.01, 0.05 or 0.1 mg·Kg-1) once every two days over a period of 3 weeks. The open field test was carried out, together with the immunohistochemical and histopathological analysis. The chemical composition of BV was also assessed, identifying the highest concentrations of apamin, phospholipase A2 and melittin. In the behavioral evaluation, the BV (0.1 mg·Kg-1) counteracted the 6-OHDA-induced decrease in crossings and rearing. 6-OHDA caused loss of dopaminergic cell bodies in the substantia nigra pars compacta and fibers in striatum (STR). Mice that received 0.01 mg·Kg-1 showed significant increase in the mean survival of dopaminergic cell bodies. Increased astrocytic infiltration occurred in the STR of 6-OHDA injected mice, differently from those of the groups treated with BV. The results suggested that Africanized BV has neuroprotective activity in an animal model of Parkinson's disease.

Soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) and other inflammatory mediators in malaria by Plasmodium vivax during enteroparasites coinfection.

Malaria is a major health issue with more than 200 million cases occurring annually. Moreover, in Malaria endemic area are frequently observed Malaria-enteroparasite co-infections associated with the modulation of inflammatory response. In this aspect, biomarkers play an important role in the disease prognosis. This study aimed to evaluate inflammatory mediators in malaria during coinfection with enteroparasites. A subset of serum samples already collected was analyzed and divided into four groups: Malaria (n = 34), Co-infected (n = 116), Enteroparasite (n = 120) and Control (n = 95). The serum levels of sTREM-1 and IL-6 were measured by ELISA. TNF-α, and IL-10 levels were previously carried out by flow cytometry. Higher serum levels of sTREM-1 and IL-6 were showed in malaria patients compared to healthy controls. In co-infected malarial patients sTREM-1 serum levels were similar to control group. Interestingly, co-infected malaria patients showed IL-6 serum levels decreased compared to individuals only infected with P. vivax. However, in Malaria patients and co-infected there was a positive correlation between the IL-6 and IL-10 levels (P < 0.0001). This is the first report of sTREM-1 levels in P. vivax infected. Moreover, the results revealing a divergent effect of co-infection with the increased balance between pro-and anti-inflammatory cytokines and reduced IL-6 levels but increases the anemia occurrence. The results also highlight the potential use of IL-6 as a biomarker for P. vivax and enteroparasites coinfection.

Development of a New Formulation Based on In Situ Photopolymerized Polymer for the Treatment of Spinal Cord Injury.

Spinal Cord Injury (SCI) promotes a cascade of inflammatory events that are responsible for neuronal death and glial scar formation at the site of the injury, hindering tissue neuroregeneration. Among the main approaches for the treatment of SCI, the use of biomaterials, especially gelatin methacryloyl (GelMA), has been proposed because it is biocompatible, has excellent mechanical properties, favoring cell adhesion and proliferation. In addition, it can act as a carrier of anti-inflammatory drugs, preventing the formation of glial scars. The present work presents the development and in situ application of a light-curing formulation based on GelMA containing a natural extract rich in anti-inflammatory, antioxidant and neuroprotective substances (hydroalcoholic extract of red propolis-HERP) in an experimental model of SCI in rats. The formulations were prepared and characterized by time of UV exposition, FTIR, swelling and degradation. The hydrogels containing 1 mg/mL of HERP were obtained by the exposure to UV radiation of 2 µL of the formulation for 60 s. The locomotor evaluation of the animals was performed by the scale (BBB) and demonstrated that after 3 and 7 days of the injury, the GelMA-HERP group (BBB = 5 and 7) presented greater recovery compared to the GelMA group (BBB = 4 and 5). Regarding the inflammatory process, using histomorphological techniques, there was an inflammation reduction in the groups treated with GelMA and GelMA-HERP, with decreases of cavitation in the injury site. Therefore, it is possible to conclude that the use of GelMA and GelMA-HERP hydrogel formulations is a promising strategy for the treatment of SCI when applied in situ, as soon as possible after the injury, improving the clinical and inflammatory conditions of the treated animals.

Contribution of Research in the West Indies and Northeast Amazonia to Knowledge of the 2014-2015 Chikungunya Epidemic in the Americas.

PURPOSE OF REVIEW: Although the chikungunya virus was discovered more than 60 years ago, it has only really been studied since the outbreak in La Reunion in 2005-2006. Ten years later, between 2014 and 2015, the chikungunya virus spread throughout the Americas, affecting millions of people. The objective of this review is to describe the contributions of research on chikungunya virus infection gained from epidemic in the West Indies and the Guiana Shield. RECENT FINDINGS: Prevalence data were similar to those found in the Indian Ocean or Asia during epidemics. Clinically, there is now a better understanding of the typical, atypical, and severe forms. Several studies have insisted on the presence of neurological forms of chikungunya infection, such as encephalitis or Guillain-Barré syndrome. Cases of septic shock due to chikungunya virus as well as thrombotic thrombocytopenic purpura were described for the first time. Given the magnitude of the epidemic and the large number of people affected, this has led to a better description and new classifications of chikungunya virus infections in specific populations such as pregnant women, the elderly, and children. Several studies also described the behavior of populations faced with an emerging disease. SUMMARY: Current epidemiological data from tropical regions highlights the risk of spreading emerging diseases at higher latitudes, especially concerning arboviruses, since the vector Aedes albopictus is already established in many parts of northern countries. A better understanding of the disease and its epidemic dynamics will foster better management, the crucial importance of which was demonstrated during the COVID-19 epidemic.

Effects of Resistance Training on Oxidative Stress Markers and Muscle Damage in Spinal Cord Injured Rats.

BACKGROUND: Spinal cord injury (SCI) is a condition that affects the central nervous system, is characterized by motor and sensory impairments, and impacts individuals' lives. The objective of this study was to evaluate the effects of resistance training on oxidative stress and muscle damage in spinal cord injured rats. METHODOLOGY: Forty Wistar rats were selected and divided equally into five groups: Healthy Control (CON), Sham (SHAM) SCI Untrained group (SCI-U), SCI Trained group (SCI- T), SCI Active Trained group (SCI- AT). Animals in the trained groups were submitted to an incomplete SCI at T9. Thereafter, they performed a protocol of resistance training for four weeks. RESULTS: Significant differences in muscle damage markers and oxidative stress in the trained groups, mainly in SCI- AT, were found. On the other hand, SCI- U group presented higher levels of oxidative stress and biomarkers of LDH and AST. CONCLUSION: The results highlight that resistance training promoted a decrease in oxidative stress and a significative response in muscle damage markers.

Red Propolis and Its Dyslipidemic Regulator Formononetin: Evaluation of Antioxidant Activity and Gastroprotective Effects in Rat Model of Gastric Ulcer.

Propolis has various pharmacological properties of clinical interest, and is also considered a functional food. In particular, hydroalcoholic extracts of red propolis (HERP), together with its isoflavonoid formononetin, have recognized antioxidant and anti-inflammatory properties, with known added value against dyslipidemia. In this study, we report the gastroprotective effects of HERP (50-500 mg/kg, p.o.) and formononetin (10 mg/kg, p.o.) in ethanol and non-steroidal anti-inflammatory drug-induced models of rat ulcer. The volume, pH, and total acidity were the evaluated gastric secretion parameters using the pylorus ligature model, together with the assessment of gastric mucus contents. The anti-Helicobacter pylori activities of HERP were evaluated using the agar-well diffusion method. In our experiments, HERP (250 and 500 mg/kg) and formononetin (10 mg/kg) reduced (p < 0.001) total lesion areas in the ethanol-induced rat ulcer model, and reduced (p < 0.05) ulcer indices in the indomethacin-induced rat ulcer model. Administration of HERP and formononetin to pylorus ligature models significantly decreased (p < 0.01) gastric secretion volumes and increased (p < 0.05) mucus production. We have also shown the antioxidant and anti-Helicobacter pylori activities of HERP. The obtained results indicate that HERP and formononetin are gastroprotective in acute ulcer models, suggesting a prominent role of formononetin in the effects of HERP.

In situ photocrosslinkable formulation of nanocomposites based on multi-walled carbon nanotubes and formononetin for potential application in spinal cord injury treatment.

Carbon nanotubes (CN) have been studied to treat spinal cord injuries because of its electrical properties and nanometric dimensions. This work aims to develop a photopolymerizable hydrogel containing CN functionalized with an anti-inflammatory molecule to be used in situ on spinal cord injuries. The CN functionalization step was done using the drug (formononetin). The nanocomposites were characterized by morphological analysis, FTIR, Raman Spectroscopy, thermal analysis and cytotoxicity assays (MTT and HET-CAM). The nanocomposites were incorporated into gelatin methacryloyl hydrogel and exposed to UV light for photopolymerization. The volume of the formulation and the UV exposition time were also analyzed. The CN characterization showed that formononetin acted as a functionalization agent. The functionalized CN showed safe characteristics and can be incorporated in photocrosslinkable formulation. The UV exposition time for the formulation photopolymerization was compatible with the cell viability and also occurred in the injury site.

Contributing to Elimination of Cross-Border Malaria Through a Standardized Solution for Case Surveillance, Data Sharing, and Data Interpretation: Development of a Cross-Border Monitoring System.

BACKGROUND: Cross-border malaria is a significant obstacle to achieving malaria control and elimination worldwide. OBJECTIVE: This study aimed to build a cross-border surveillance system that can make comparable and qualified data available to all parties involved in malaria control between French Guiana and Brazil. METHODS: Data reconciliation rules based on expert knowledge were defined and applied to the heterogeneous data provided by the existing malaria surveillance systems of both countries. Visualization dashboards were designed to facilitate progressive data exploration, analysis, and interpretation. Dedicated advanced open source and robust software solutions were chosen to facilitate solution sharing and reuse. RESULTS: A database gathering the harmonized data on cross-border malaria epidemiology is updated monthly with new individual malaria cases from both countries. Online dashboards permit a progressive and user-friendly visualization of raw data and epidemiological indicators, in the form of time series, maps, and data quality indexes. The monitoring system was shown to be able to identify changes in time series that are related to control actions, as well as differentiated changes according to space and to population subgroups. CONCLUSIONS: This cross-border monitoring tool could help produce new scientific evidence on cross-border malaria dynamics, implementing cross-border cooperation for malaria control and elimination, and can be quickly adapted to other cross-border contexts.

Resurgence risk for malaria, and the characterization of a recent outbreak in an Amazonian border area between French Guiana and Brazil.

BACKGROUND: In 2017, inhabitants along the border between French Guiana and Brazil were affected by a malaria outbreak primarily due to Plasmodium vivax (Pv). While malaria cases have steadily declined between 2005 and 2016 in this Amazonian region, a resurgence was observed in 2017. METHODS: Two investigations were performed according to different spatial scales and information details: (1) a local study on the French Guiana border, which enabled a thorough investigation of malaria cases treated at a local village health center and the entomological circumstances in the most affected neighborhood, and (2) a regional and cross-border study, which enabled exploration of the regional spatiotemporal epidemic dynamic. Number and location of malaria cases were estimated using French and Brazilian surveillance systems. RESULTS: On the French Guianese side of the border in Saint-Georges de l'Oyapock, the attack rate was 5.5% (n = 4000), reaching 51.4% (n = 175) in one Indigenous neighborhood. Entomological findings suggest a peak of Anopheles darlingi density in August and September. Two female An. darlingi (n = 1104, 0.18%) were found to be Pv-positive during this peak. During the same period, aggregated data from passive surveillance conducted by Brazilian and French Guianese border health centers identified 1566 cases of Pv infection. Temporal distribution during the 2007-2018 period displayed seasonal patterns with a peak in November 2017. Four clusters were identified among epidemic profiles of cross-border area localities. All localities of the first two clusters were Brazilian. The localization of the first cluster suggests an onset of the outbreak in an Indigenous reservation, subsequently expanding to French Indigenous neighborhoods and non-Native communities. CONCLUSIONS: The current findings demonstrate a potential increase in malaria cases in an area with otherwise declining numbers. This is a transborder region where human mobility and remote populations challenge malaria control programs. This investigation illustrates the importance of international border surveillance and collaboration for malaria control, particularly in Indigenous villages and mobile populations.

Malária na fronteira do Brasil com a Guiana Francesa: a influência dos determinantes sociais e ambientais da saúde na permanência da doença / Malaria in the borders between Brazil and French Guiana: social and environmental health determinants and their influence on the permanence of the disease

Resumo O objetivo deste artigo é analisar a influência dos determinantes socioambientais da saúde na incidência de malária por Plasmodium vivax na fronteira franco-brasileira. O estudo foi realizado entre 2011 e 2015, no município de Oiapoque (AP), na Amazônia brasileira. Foram incluídos na amostra 253 indivíduos de ambos os sexos, de 10 a 60 anos de idade. Houve predominância de 63,64% (161/253) de casos de malária em adultos do sexo masculino. A faixa etária mais acometida foi de 20 a 29 anos, com 30% (76/253); 84,6% (214/253) dos pacientes não concluíram o ensino médio, e 29,6% (75/253) não concluíram o ensino primário. No aspecto ambiental, houve correlação negativa entre as precipitações pluviométricas e a incidência da malária por P. vivax (p=0,0026). Em termos de mobilidade, constatou-se considerável proporção de migrantes provenientes dos estados do Pará e do Maranhão (55,73%; 141/253). Por fim, os dados apontaram que 31,23% (79/253) dos casos de malária foram importados da Guiana Francesa. Em síntese, a transmissão da malária na fronteira franco-brasileira envolve fatores ecológico-ambientais, biológicos e sociais que se expressam na elevada vulnerabilidade social da população que vive e circula na zona fronteiriça, favorecendo a ocorrência de surtos e a permanência da enfermidade.

Abstract This study analyzes the influence of socio-environmental health determinants on the maintenance of Plasmodium vivax malaria at the borders between French Guiana and Brazil. This study was carried out between 2011 and 2015 in the city of Oiapoque, Amapá, situated in the Brazilian Amazon region. The sample included 253 individuals of both sexes aged between 10 and 60 years. The disease was predominant in 63.64% (161/253) adult males. The most affected age group was 20 to 29 years old, with 30% (76/253). About 84.6% did not complete high school, while 29.6% (75/253) of the cases had not finished the first degree. Concerning the environmental aspect, negative correlation was observed between rainfall and the incidence of P. vivax malaria (p=0.0026). In terms of mobility, there was a considerable influx of migrants from the states of Pará and Maranhão, with 55.73% (141/253). Lastly, the data indicated that 31.23% (79/253) of malaria cases were imported from French Guiana. In summary, the transmission of malaria in these particular borders involved ecological, environmental, biological and social factors, which are expressed in the high social vulnerability of the population living and circulating in the border zone, favoring the occurrence of outbreaks and the maintenance of the disease.

Technological prospection: patents mapping involving compounds for the treatment of L-DOPA-induced dyskinesias.

Introduction: Parkinson's disease (PD), is a disorder debilitant characterized by the reduction of nigrostriatal dopaminergic neurons within the midbrain, specifically in the substantia nigra pars compacta, which results for the dopamine (DA) depletion in the striatum. Dopamine replacement therapies with the 3,4-dihydroxy-L-phenylalanine (Levodopa or L-DOPA) represent the most common strategy to treat PD. However, chronic administration of L-DOPA results in abnormal involuntary movement (AIMs). Thus, the present study aimed to prospect patents of alternative treatment strategies for L-DOPA-induced dyskinesias.Areas covered: This review covers the therapeutic patents published over the 2001-2019 period in the WIPO, INPI, and ESPACENET, which report treatment strategies for L-DOPA induced dyskinesias (LIDs).Expert opinion: In recent years, several pharmaceutical companies, as well as universities and researchers have tested effective compounds for LIDs treatment, showing substances that act on central pathways as antagonists and agonists of the serotonergic system, which may result in the key to onset of LIDs in animal models of PD. Future works aiming to elucidate the L-DOPA, Flibanserin, Eltoprazine, and Pridopidina mechanisms of action on the receptors of the serotonergic system and D2 receptors of the indirect pathway, will allow the development of effective therapies for LIDs.

The haematological consequences of Plasmodium vivax malaria after chloroquine treatment with and without primaquine: a WorldWide Antimalarial Resistance Network systematic review and individual patient data meta-analysis.

BACKGROUND: Malaria causes a reduction in haemoglobin that is compounded by primaquine, particularly in patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency. The aim of this study was to determine the relative contributions to red cell loss of malaria and primaquine in patients with uncomplicated Plasmodium vivax. METHODS: A systematic review identified P. vivax efficacy studies of chloroquine with or without primaquine published between January 2000 and March 2017. Individual patient data were pooled using standardised methodology, and the haematological response versus time was quantified using a multivariable linear mixed effects model with non-linear terms for time. Mean differences in haemoglobin between treatment groups at day of nadir and day 42 were estimated from this model. RESULTS: In total, 3421 patients from 29 studies were included: 1692 (49.5%) with normal G6PD status, 1701 (49.7%) with unknown status and 28 (0.8%) deficient or borderline individuals. Of 1975 patients treated with chloroquine alone, the mean haemoglobin fell from 12.22 g/dL [95% CI 11.93, 12.50] on day 0 to a nadir of 11.64 g/dL [11.36, 11.93] on day 2, before rising to 12.88 g/dL [12.60, 13.17] on day 42. In comparison to chloroquine alone, the mean haemoglobin in 1446 patients treated with chloroquine plus primaquine was - 0.13 g/dL [- 0.27, 0.01] lower at day of nadir (p = 0.072), but 0.49 g/dL [0.28, 0.69] higher by day 42 (p < 0.001). On day 42, patients with recurrent parasitaemia had a mean haemoglobin concentration - 0.72 g/dL [- 0.90, - 0.54] lower than patients without recurrence (p < 0.001). Seven days after starting primaquine, G6PD normal patients had a 0.3% (1/389) risk of clinically significant haemolysis (fall in haemoglobin > 25% to < 7 g/dL) and a 1% (4/389) risk of a fall in haemoglobin > 5 g/dL. CONCLUSIONS: Primaquine has the potential to reduce malaria-related anaemia at day 42 and beyond by preventing recurrent parasitaemia. Its widespread implementation will require accurate diagnosis of G6PD deficiency to reduce the risk of drug-induced haemolysis in vulnerable individuals. TRIAL REGISTRATION: This trial was registered with PROSPERO: CRD42016053312. The date of the first registration was 23 December 2016.

Complex malaria epidemiology in an international border area between Brazil and French Guiana: challenges for elimination.

BACKGROUND: The epidemiological surveillance of malaria is a necessary intervention for eliminating the disease from the planet. The international border zones of the Amazon continue to be highly vulnerable to malaria since population mobility impedes elimination. Although in the past few years, cases of malaria have had an essential reduction in Brazil, this trend was not confirmed in municipalities along the border. This study aimed to establish the epidemiology of the disease during the last 13 years in Oiapoque, a Brazilian municipality at the international border with French Guiana, an overseas department, to develop strategies for the control/elimination of malaria in these areas. RESULTS: Data collected from 2003 to 2015 from the Malaria Epidemiological Surveillance System was used. It was found that, despite the important reduction in cases (68.1%), the annual parasite index remained a high epidemiological risk. The disease is seasonal in that the period of highest transmission occurs between September and December. Between 2003 and 2015, eight outbreaks were identified, with one of these lasting 15 months between August 2006 and October 2007. There were changes in the epidemiological profile, with imported cases representing 67.7% of cases from 2003 to 2007 and representing 32.9% of cases from 2008 to 2015 (p < 0.01). The greatest number of cases was among Brazilians coming from the artisanal gold mines of French Guiana. There were also changes in the profile of autochthonous malaria with an increase in urban cases from 14.3% in 2003 to 32.3% in 2015 (p < 0 .01). The burden of malaria in indigenous areas was also very high (67.3% in rural areas) in 2015. There were changes in the parasite species profile with a significant decrease of cases of Plasmodium falciparum (p = 0.01). Children under 15 years old, representing 9.7% of cases at the onset of the study, accounted for 34.2% of case notifications (p < 0.01) in 2015. Also, 74% of cases in 2003 and 55.9% in 2015 (p < 0.01) were among men. CONCLUSIONS: The fragility of local health services in cross-border areas continues to be an obstacle for malaria elimination.

Pharmacokinetics of mefloquine administered with artesunate in patients with uncomplicated falciparum malaria from the Brazilian Amazon basin.

BACKGROUND: A fixed-dose combination of mefloquine with artesunate was evaluated in cases of falciparum malaria in the Brazilian Amazon basin with acceptable efficacy, safety and tolerability. However, there are no data on the pharmacokinetics of mefloquine in this coformulation in Brazil, which is valuable to evaluate whether Plasmodium is exposed to an effective concentration of the drug. METHODS: A prospective, single-arm study was conducted in male patients with slide-confirmed infection by Plasmodium falciparum using two tablets of a fixed-dose combination of artesunate (100 mg) and mefloquine base (200 mg) once daily and over 3 consecutive days. Serial blood samples were collected at admission and throughout 672 h post-administration of the drugs. Mefloquine was measured in each blood sample by high-performance liquid chromatography. The pharmacokinetic parameters were determined by non-compartmental analysis. RESULTS: A total of 61 patients were enrolled in the study and 450 whole blood samples were collected for mefloquine measurement. The mefloquine half-life was 10.25 days, the maximum concentration (Cmax) was 2.53 µg/ml, the area-under-the-curve (AUC0-∞) was 359 µg/ml h, the observed clearance (Cl/f) was 0.045 l/kg/h and the volume of distribution (V/f) was 14.6 l/kg. Mefloquine concentrations above 0.5 µg/ml were sustained for a mean time of 9.2 days. CONCLUSION: The pharmacokinetic parameters of mefloquine determined in the study suggest an adequate exposure of parasite to mefloquine in the multiple oral dose regimen of the fixed dose combination of mefloquine and artesunate.