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.

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.

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.

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.

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.

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.

Recurrence of Plasmodium falciparum after treatment with quinine and doxycycline in the Amazon basin.

OBJECTIVE: To investigate whether the recurrence of infection by Plasmodium falciparum in patients from the Brazilian Amazon was caused by an inadequate exposure to quinine. METHODS: A retrospective study was carried out using blood samples from patients with slide-confirmed infection by P. falciparum, classified according to the parasitological response after 28 days of follow-up. Quinine and doxycycline were measured in plasma samples by high-performance liquid chromatography. A statistical model was used to estimate parasite clearance rates. RESULTS: Six of 40 patients who met the criteria for inclusion in the study showed recurrence of parasitaemia within 28 days after the commencement of treatment. A group of six patients with adequate parasitological response was formed to avoid bias when the variables were compared. Parasitaemia at admission was similar in both groups. Plasma quinine concentrations were similar in both groups on days 1, 2 and 3 and ranged from 1.07 to 4.35 µg/ml in cured patients and from 1.1 to 3.2 µg/ml in patients with parasite recurrence. Concentrations of doxycycline were similar in both groups on day 3. The parasite clearance rate constant was 0.131 ± 0.16 h in the cured patients and 0.117 ± 0.02 h in those showing recurrence. The slope half-life in the cured patients was 4.8 h and 5.4 h in recurrence cases. The hillslope of the cured group (14.24) increased sharply compared to the recurrence group (4.13). CONCLUSION: There is evidence of a decreased in vivo sensitivity to quinine of P. falciparum strains in the Brazilian Amazon basin.

Neuroprotective effect of Portulaca oleracea extracts against 6-hydroxydopamine-induced lesion of dopaminergic neurons.

The Portulaca oleracea L. (Portulacaceae) is a cosmopolitan species with a wide range of biological activities, including antioxidant and neuroprotective actions. We investigated the effects of P. oleracea extracts in a 6-hydroxydopamine rat model of Parkinson's disease, a debilitating disorder without effective treatments. Chemical profiles of aqueous and ethanolic extracts of whole plant were analyzed by thin layer chromatography and the antioxidant activity was assessed by 2,2-diphenyl-1-picrilhidrazila method. Male Wistar rats received intrastriatal 6-hydroxydopamine and were treated with vehicle or extracts (oral, 200 and 400 mg/kg) daily for two weeks. The behavioral open field test was conducted at days 1 and 15. Immunohistochemical analysis was performed 4 weeks after surgery to quantify tyrosine-hydroxylase cell counts in the substantia nigra pars compacta. Extracts presented antioxidant activity in concentrations above 300 µg/kg. The chromatographic analysis revealed the presence of Levodopa, alkaloids, flavonoids, saponins, tannins, terpenoids and polysaccharides. Both extracts improved motor recovery 15 days after lesion and protected from tyrosine-hydroxylase cell loss after 4 weeks, but these effects were more evident for the aqueous extract. Because the dopamine precursor is present, in addition to antioxidant compounds and neuroprotective effects, P. oleracea can be considered as potential strategy for treating Parkinson's disease.

Hydroalcoholic extract of red propolis promotes functional recovery and axon repair after sciatic nerve injury in rats.

CONTEXT: Peripheral axon injury and degeneration are often mediated by oxidative stress and inflammation. The hydroalcoholic extract of the red propolis (HERP) has attracted great attention because of its antioxidant and anti-inflammatory activities. OBJECTIVE: The objective of this work is to study the effect of HERP on nerve repair and functional recovery after sciatic nerve injury (SNI) in rats. MATERIALS AND METHODS: The chemical markers in HERP were identified using high-resolution mass spectroscopy. After axonotmesis of sciatic nerve, ibuprofen (IBP) and HERP treatments were orally administered for 28 d. Behavioural tests were performed weekly after SNI. The myelinated axon number was counted using morphometric analysis. RESULTS: The compounds found in HERP were pinocembrin, formononetin, vestitol, and biochanin A. The animals that underwent SNI showed a significant decrease in motor function based on the Basso, Beattie and Bresnahan scale and sciatic functional index compared with sham animals until 7 d after the surgery (p < 0.05). After 14 and 21 d, the SNI groups treated with either HERP or IBP showed significant improvement (p < 0.01), and the SNI group treated with HERP 10 mg/kg showed accelerated motor recovery compared with the other groups (p < 0.01). SNI caused also a reduction in the myelinated axon counts, and treatment with HERP 10 mg/kg induced a significant increase in the number of myelinated fibres compared with all other groups. CONCLUSION: HERP promoted regenerative responses and accelerated functional recovery after sciatic nerve crush. Thus, it can be considered to be a new strategy or complementary therapy for treating nerve injuries.

Efficacy in the treatment of malaria by Plasmodium vivax in Oiapoque, Brazil, on the border with French Guiana: the importance of control over external factors.

BACKGROUND: Plasmodium vivax malaria is an important public health issue in the Amazon region, and it accounts for approximately 84 % of cases of the disease. Migration across the border between Brazil and French Guiana contributes to the maintenance of the disease. The aim of this study was to evaluate the therapeutic and parasitological responses of patients with P. vivax malaria treated with chloroquine and primaquine in the socio-environmental context of cross-border interactions between Brazil and French Guiana. The factors controlled were diagnostic agreement, adherence, adjustment of primaquine doses for patient weight, and quality of the drugs used. METHODS: A prospective study was conducted in 2011 with 103 individuals aged 10-60 years with a positive diagnosis of P. vivax treated with chloroquine (10 mg base/kg on the first day, followed by 7.5 mg/kg on the second and third days) and primaquine for 7 days, who were followed for 28 days. The primaquine doses were adjusted for the patients' weight. A number of factors were determined: epidemiological characteristics, origin of patients, signs and symptoms, initial parasitaemia and parasitaemia clearance time, blood concentrations of chloroquine and primaquine, quality of anti-malarial drugs and diagnostic agreement. RESULTS: Ninety-five patients were followed for 28 days. There was a 100 % agreement in microscopic diagnosis between field laboratory and reference centre. The adhesion to the treatment was 100 %. Of these patients, 32.6 % received a weight-adjusted dose of primaquine. The chloroquine and primaquine tablets were consistent with the optimal quality limits for human consumption. The investigated patients achieved optimal blood exposure to anti-malarial drugs. The parasitological and therapeutic response was adequate in 99.0 % of cases. CONCLUSIONS: In the municipality of Oiapoque, the therapeutic regime used for the treatment of P. vivax malaria using chloroquine combined with primaquine remains effective, when external factors are controlled, such as the quality of anti-malarial drugs, the adhesion to the treatment prescribed, the correct diagnostic and the adjustment of primaquine dose for patient body weight.

Malaria on the Guiana Shield: a review of the situation in French Guiana.

In a climate of growing concern that Plasmodium falciparum may be developing a drug resistance to artemisinin derivatives in the Guiana Shield, this review details our current knowledge of malaria and control strategy in one part of the Shield, French Guiana. Local epidemiology, test-treat-track strategy, the state of parasite drug resistance and vector control measures are summarised. Current issues in terms of mobile populations and legislative limitations are also discussed.

Land cover, land use and malaria in the Amazon: a systematic literature review of studies using remotely sensed data.

The nine countries sharing the Amazon forest accounted for 89% of all malaria cases reported in the Americas in 2008. Remote sensing can help identify the environmental determinants of malaria transmission and their temporo-spatial evolution. Seventeen studies characterizing land cover or land use features, and relating them to malaria in the Amazon subregion, were identified. These were reviewed in order to improve the understanding of the land cover/use class roles in malaria transmission. The indicators affecting the transmission risk were summarized in terms of temporal components, landscape fragmentation and anthropic pressure. This review helps to define a framework for future studies aiming to characterize and monitor malaria.

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.

Implementation of basic quality control tests for malaria medicines in Amazon Basin countries: results for the 2005-2010 period.

BACKGROUND: Ensuring the quality of malaria medicines is crucial in working toward malaria control and eventual elimination. Unlike other validated tests that can assess all critical quality attributes, which is the standard for determining the quality of medicines, basic tests are significantly less expensive, faster, and require less skilled labour; yet, these tests provide reproducible data and information on several critical quality attributes, such as identity, purity, content, and disintegration. Visual and physical inspection also provides valuable information about the manufacturing and the labelling of medicines, and in many cases this inspection is sufficient to detect counterfeit medicines. The Promoting the Quality of Medicines (PQM) programme has provided technical assistance to Amazon Malaria Initiative (AMI) countries to implement the use of basic tests as a key screening mechanism to assess the quality of malaria medicines available to patients in decentralized regions. METHODS: Trained personnel from the National Malaria Control Programmes (NMCPs), often in collaboration with country's Official Medicine Control Laboratory (OMCL), developed country- specific protocols that encompassed sampling methods, sample analysis, and data reporting. Sampling sites were selected based on malaria burden, accessibility, and geographical location. Convenience sampling was performed and countries were recommended to store the sampled medicines under conditions that did not compromise their quality. Basic analytical tests, such as disintegration and thin layer chromatography (TLC), were performed utilizing a portable mini-laboratory. RESULTS: Results were originally presented at regional meetings in a non-standardized format that lacked relevant medicines information. However, since 2008 information has been submitted utilizing a template specifically developed by PQM for that purpose. From 2005 to 2010, the quality of 1,663 malaria medicines from seven AMI countries was evaluated, mostly collected from the public sector, 1,445/1,663 (86.9%). Results indicate that 193/1,663 (11.6%) were found not to meet quality specifications. Most failures were reported during visual and physical inspection, 142/1663 (8.5%), and most of these were due to expired medicines, 118/142 (83.1%). Samples failing TLC accounted for 27/1,663 (1.6%) and those failing disintegration accounted for 24/1,663 (1.4%). Medicines quality failures decreased significantly during the last two years. CONCLUSIONS: Basic tests revealed that the quality of medicines in the public sector improved over the years, since the implementation of this type of quality monitoring programme in 2005. However, the lack of consistent confirmatory tests in the quality control (QC) laboratory, utilizing methods that can also evaluate additional quality attributes, could still mask quality issues. In the future, AMI countries should improve coordination with their health authorities and their QC lab consistently, to provide a more complete picture of malaria medicines quality and support the implementation of corrective actions. Facilities in the private and informal sectors also should be included when these sectors constitute an important source of medicines used by malaria patients.

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.

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.

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.

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.