Operational effectiveness of tafenoquine and primaquine for the prevention of Plasmodium vivax recurrence in Brazil: a retrospective observational study.

BACKGROUND: Prevention of Plasmodium vivax malaria recurrence is essential for malaria elimination in Brazil. We evaluated the real-world effectiveness of an updated treatment algorithm for P vivax radical cure in the Brazilian Amazon. METHODS: In this non-interventional observational study, we used retrospective data from the implementation of a P vivax treatment algorithm at 43 health facilities in Manaus and Porto Velho, Brazil. The treatment algorithm consisted of chloroquine (25 mg/kg over 3 days) and point-of-care quantitative glucose-6-phosphate dehydrogenase (G6PD) testing followed by single-dose tafenoquine 300 mg (G6PD normal, aged ≥16 years, not pregnant and not breastfeeding), 7-day primaquine 0·5 mg/kg per day (G6PD intermediate or normal, aged ≥6 months, not pregnant, and not breastfeeding or breastfeeding for >1 month), or primaquine 0·75 mg/kg per week for 8 weeks (G6PD deficient, aged ≥6 months, not pregnant, and not breastfeeding or breastfeeding for >1 month). P vivax recurrences were identified from probabilistic linkage of routine patient records from the Brazilian malaria epidemiological surveillance system. Recurrence-free effectiveness at day 90 and day 180 was estimated using Kaplan-Meier analysis and hazard ratios (HRs) by multivariate analysis. This clinical trial is registered with ClinicalTrials.gov, NCT05096702, and is completed. FINDINGS: Records from Sept 9, 2021, to Aug 31, 2022, included 5554 patients with P vivax malaria. In all treated patients of any age and any G6PD status, recurrence-free effectiveness at day 180 was 75·8% (95% CI 74·0-77·6) with tafenoquine, 73·4% (71·9-75·0) with 7-day primaquine, and 82·1% (77·7-86·8) with weekly primaquine. In patients aged at least 16 years who were G6PD normal, recurrence-free effectiveness until day 90 was 88·6% (95% CI 87·2-89·9) in those who were treated with tafenoquine (n=2134) and 83·5% (79·8-87·4) in those treated with 7-day primaquine (n=370); after adjustment for confounding factors, the HR for recurrence following tafenoquine versus 7-day primaquine was 0·65 (95% CI 0·49-0·86; p=0·0031), with similar outcomes between the two treatments at day 180 (log-rank p=0·82). Over 180 days, median time to recurrence in patients aged at least 16 years who were G6PD normal was 92 days (IQR 76-120) in those treated with tafenoquine and 68 days (52-94) in those treated with 7-day primaquine. INTERPRETATION: In this real-world setting, single-dose tafenoquine was more effective at preventing P vivax recurrence in patients aged at least 16 years who were G6PD normal compared with 7-day primaquine at day 90, while overall efficacy at 180 days was similar. The public health benefits of the P vivax radical cure treatment algorithm incorporating G6PD quantitative testing and tafenoquine support its implementation in Brazil and potentially across South America. FUNDING: Brazilian Ministry of Health, Municipal and State Health Secretariats; Fiocruz; Medicines for Malaria Venture; Bill & Melinda Gates Foundation; Newcrest Mining; and the UK Government. TRANSLATION: For the Portuguese translation of the abstract see Supplementary Materials section.

Operational feasibility of Plasmodium vivax radical cure with tafenoquine or primaquine following point-of-care, quantitative glucose-6-phosphate dehydrogenase testing in the Brazilian Amazon: a real-life retrospective analysis.

BACKGROUND: To achieve malaria elimination, Brazil must implement Plasmodium vivax radical cure. We aimed to investigate the operational feasibility of point-of-care, quantitative, glucose-6-phosphate dehydrogenase (G6PD) testing followed by chloroquine plus tafenoquine or primaquine. METHODS: This non-interventional, observational study was done at 43 health facilities in Manaus (Amazonas State) and Porto Velho (Rondônia State), Brazil, implementing a new P vivax treatment algorithm incorporating point-of-care quantitative G6PD testing to identify G6PD status and single-dose tafenoquine (G6PD normal, aged ≥16 years, and not pregnant or breastfeeding) or primaquine (intermediate or normal G6PD, aged ≥6 months, not pregnant, or breastfeeding >1 month). Following training of health-care providers, we collated routine patient records from the malaria epidemiological surveillance system (SIVEP-Malaria) retrospectively for all consenting patients aged at least 6 months with parasitologically confirmed P vivax malaria mono-infection or P vivax plus P falciparum mixed infection, presenting between Sept 9, 2021, and Aug 31, 2022. The primary endpoint was the proportion of patients aged at least 16 years with P vivax mono-infection treated or not treated appropriately with tafenoquine in accordance with their G6PD status. The trial is registered with ClinicalTrials.gov, NCT05096702, and is completed. FINDINGS: Of 6075 patients enrolled, 6026 (99·2%) had P vivax mono-infection, 2685 (44·6%) of whom were administered tafenoquine. G6PD status was identified in 2685 (100%) of 2685 patients treated with tafenoquine. The proportion of patients aged at least 16 years with P vivax mono-infection who were treated or not treated appropriately with tafenoquine in accordance with their G6PD status was 99·7% (95% CI 99·4-99·8; 4664/4680). INTERPRETATION: Quantitative G6PD testing before tafenoquine administration was operationally feasible, with high adherence to the treatment algorithm, supporting deployment throughout the Brazilian health system. FUNDING: Brazilian Ministry of Health, Municipal and State Health Secretariats; Fiocruz; Medicines for Malaria Venture; Bill & Melinda Gates Foundation; Newcrest Mining; and the UK Government. TRANSLATION: For the Portuguese translation of the abstract see Supplementary Materials section.

Surgical Technique of Central and Over-the-Top Full-Endoscopic Decompression of the Cervical Spine: A Technical Note.

Endoscopic surgery of the cervical spine is constantly evolving and the spectrum of its indications has expanded in recent decades. Full-endoscopic techniques have standardized the procedures for posterior and anterior access. The full-endoscopic approach was developed to treat degenerative diseases with the least possible invasion and without causing instability of the cervical spine. The posterior full-endoscopic approach is indicated for the treatment of diseases of the lateral part of the vertebral segment, such as herniations and stenoses of the lateral recess and vertebral foramen. There has been little discussion of this approach to the treatment of central stenosis of the cervical spine. This technical note describes a step-by-step surgical technique for central and over-the-top full-endoscopic decompression in the cervical spine, using a 3.7 mm working channel endoscope. This technique has already been shown to be effective in a recent case series with a 4.7 mm working channel endoscope, and may represent a new treatment option for central or bilateral lateral recess stenosis. There is also the possibility of a bilateral full-endoscopic approach, but this may be associated with greater muscle damage and a longer operative time. Case series and comparative studies should be encouraged to confirm the safety and utility of this technique.

Clinical performance validation of the STANDARD G6PD test: A multi-country pooled analysis.

INTRODUCTION: Screening for G6PD deficiency can inform disease management including malaria. Treatment with the antimalarial drugs primaquine and tafenoquine can be guided by point-of-care testing for G6PD deficiency. METHODS AND FINDINGS: Data from similar clinical studies evaluating the performance of the STANDARD G6PD Test (SD Biosensor, South Korea) conducted in Bangladesh, Brazil, Ethiopia, India, Thailand, the United Kingdom, and the United States were pooled. Test performance was assessed in a retrospective analysis on capillary and venous specimens. All study sites used spectrophotometry for reference G6PD testing, and either the HemoCue or complete blood count for reference hemoglobin measurement. The sensitivity of the STANDARD G6PD Test using the manufacturer thresholds for G6PD deficient and intermediate cases in capillary specimens from 4212 study participants was 100% (95% Confidence Interval (CI): 97.5%-100%) for G6PD deficient cases with <30% activity and 77% (95% CI 66.8%-85.4%) for females with intermediate activity between 30%-70%. Specificity was 98.1% (95% CI 97.6%-98.5%) and 92.8% (95% CI 91.6%-93.9%) for G6PD deficient individuals and intermediate females, respectively. Out of 20 G6PD intermediate females with false normal results, 12 had activity levels >60% on the reference assay. The negative predictive value for females with G6PD activity >60% was 99.6% (95% CI 99.1%-99.8%) on capillary specimens. Sensitivity among 396 P. vivax malaria cases was 100% (69.2%-100.0%) for both deficient and intermediate cases. Across the full dataset, 37% of those classified as G6PD deficient or intermediate resulted from true normal cases. Despite this, over 95% of cases would receive correct treatment with primaquine, over 87% of cases would receive correct treatment with tafenoquine, and no true G6PD deficient cases would be treated inappropriately based on the result of the STANDARD G6PD Test. CONCLUSIONS: The STANDARD G6PD Test enables safe access to drugs which are contraindicated for individuals with G6PD deficiency. Operational considerations will inform test uptake in specific settings.

Molecular epidemiology of SARS-CoV-2 variants in circulation in the state of Maranhão, Brazil.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a coronavirus belonging to the beta CoV genus, responsible for SARS in humans, which became known as COVID-19. The emergence of variants of this virus is related to the presence of cases of reinfection, reduced vaccine effectiveness and greater transmission of the virus. Objective: In this study, we evaluated the molecular epidemiology of SARS-CoV-2 lineages circulating in the state of Maranhão. This is a cross-sectional and retrospective epidemiological study of genomic surveillance of SARS-CoV-2. The study comprised of 338 genomes sequenced by the Next Generation Sequencing technique on Illumina's Miseq equipment, submitted to Global Initiative on Sharing Avian Influenza Data, 190 (56.2%) are from samples of female and 148 (43.8%) from male patients. Sequencing performed covered samples of patients aged between 1 and 108 years, with emphasis on the age groups from 30 to 39 years with 15.0% of sequenced genomes and 20 to 29 years with 12.4%. As for the distribution of sequenced genomes by health macro-regions, 285 (84.3%) are from cities in the northern macro-region. We evidenced the circulation of 29 lineages and sub-lineages, four of which belonging to the Delta variant (AY.43, AY.99.1, AY.99.2 and AY.101 responsible for 4.5% of the genomes) and the others belonging to the Omicron variant, with emphasis on: BA.1 and sub-lineages (42.8%); BA.4, BA.5 and sub-lineages (5.3% and 41.1%); the sub-lineages DL.1 and BQ.1 (5% and 2%). A strong genomic surveillance system allows the study of the natural history of the disease, when there is a resurgence of SARS-CoV-2 cases.

Quantitative G6PD Deficiency Screening in Routine Malaria Diagnostic Units in the Brazilian Amazon (SAFEPRIM): An Operational Mixed-Methods Study.

BACKGROUND: Glucose-6-phosphate dehydrogenase (G6PD) deficiency testing is not routinely performed before primaquine treatment in most Plasmodium vivax endemic areas, despite the risk of primaquine-associated hemolysis. This is due to the operational challenges associated with pragmatic G6PD testing and as such needs to be addressed. METHODS AND FINDINGS: This mixed-methods operational study was aimed at implementing the quantitative point-of-care StandardTM G6PD (SD Biosensor, Korea) screening test in malaria treatment units (MTUs) in the municipalities of Rio Preto da Eva and Mâncio Lima, in the Brazilian Amazon, between mid-January 2020 and December 2020. In total, 1286 P. vivax cases were treated based on the Standard G6PD test: 1230 had activity equal to or greater than 4.0 U/g Hb, and 56 less than 4.0 U/g Hb. No G6PD deficient (G6PDd) genotypes were found in 96 samples from the 1230, and only 21 of the 56 G6PDd cases had confirmed G6PDd genotypes. Evaluations were conducted on the proficiency of health care professionals (HCPs) training to perform the test, the reliability of testing performed in the field, and the perceptions of HCPs and patients about the implementation. Post-training proficiency was 73.4% after a 4-hour training session. This study revealed that locations with lower malaria caseloads will need regular refresher training. The test was well accepted by both HCPs and patients. Signs and symptoms of hemolysis were not always associated with malaria treatment drugs by HCPs and patients. INTERPRETATION: Point-of-care quantitative G6PD testing can be performed at MTUs in the Brazilian Amazon to inform treatment decisions with primaquine. Limitations related to technical and cultural aspects need to be addressed further when expanding screening to larger areas.

Genetic Variants of Glucose-6-Phosphate Dehydrogenase and Their Associated Enzyme Activity: A Systematic Review and Meta-Analysis.

Low glucose-6-phosphate dehydrogenase enzyme (G6PD) activity is a key determinant of drug-induced haemolysis. More than 230 clinically relevant genetic variants have been described. We investigated the variation in G6PD activity within and between different genetic variants. In this systematic review, individual patient data from studies reporting G6PD activity measured by spectrophotometry and corresponding the G6PD genotype were pooled (PROSPERO: CRD42020207448). G6PD activity was converted into percent normal activity applying study-specific definitions of 100%. In total, 4320 individuals from 17 studies across 10 countries were included, where 1738 (40.2%) had one of the 24 confirmed G6PD mutations, and 61 observations (3.5%) were identified as outliers. The median activity of the hemi-/homozygotes with A-(c.202G>A/c.376A>G) was 29.0% (range: 1.7% to 76.6%), 10.2% (range: 0.0% to 32.5%) for Mahidol, 16.9% (range 3.3% to 21.3%) for Mediterranean, 9.0% (range: 2.9% to 23.2%) for Vanua Lava, and 7.5% (range: 0.0% to 18.3%) for Viangchan. The median activity in heterozygotes was 72.1% (range: 16.4% to 127.1%) for A-(c.202G>A/c.376A>G), 54.5% (range: 0.0% to 112.8%) for Mahidol, 37.9% (range: 20.7% to 80.5%) for Mediterranean, 53.8% (range: 10.9% to 82.5%) for Vanua Lava, and 52.3% (range: 4.8% to 78.6%) for Viangchan. A total of 99.5% of hemi/homozygotes with the Mahidol mutation and 100% of those with the Mediterranean, Vanua Lava, and Viangchan mutations had <30% activity. For A-(c.202G>A/c.376A>G), 55% of hemi/homozygotes had <30% activity. The G6PD activity for each variant spanned the current classification thresholds used to define clinically relevant categories of enzymatic deficiency.

Neurologic adverse events of cancer immunotherapy.

Cancer immunotherapy encompasses a wide range of treatment modalities that harness the anti-tumor effects of the immune system and have revolutionized oncological treatment in recent years, with approval for its use in more and more cancers. However, it is not without side effects. Several neurological adverse events have been recognized associated with immune checkpoint inhibitors (ICI) and chimeric antigen receptor (CAR) T-cell therapy, the two main classes of cancer immunotherapy. With the increase in the prevalence of oncological diseases and this type of therapy, it is improbable that neurologists, oncologists, hematologists, and other healthcare professionals who deal with cancer patients will not encounter this type of neurologic complication in their practice in the following years. This article aims to review the epidemiology, clinical manifestations, diagnosis, and management of neurological complications associated with ICI and CAR T-cell therapy.

Neurologic adverse events of cancer immunotherapy / Eventos adversos neurológicos da imunoterapia contra o câncer

ABSTRACT Cancer immunotherapy encompasses a wide range of treatment modalities that harness the anti-tumor effects of the immune system and have revolutionized oncological treatment in recent years, with approval for its use in more and more cancers. However, it is not without side effects. Several neurological adverse events have been recognized associated with immune checkpoint inhibitors (ICI) and chimeric antigen receptor (CAR) T-cell therapy, the two main classes of cancer immunotherapy. With the increase in the prevalence of oncological diseases and this type of therapy, it is improbable that neurologists, oncologists, hematologists, and other healthcare professionals who deal with cancer patients will not encounter this type of neurologic complication in their practice in the following years. This article aims to review the epidemiology, clinical manifestations, diagnosis, and management of neurological complications associated with ICI and CAR T-cell therapy.

RESUMO A imunoterapia contra o câncer engloba uma gama de modalidades de tratamento que aumentam os efeitos antitumorais do próprio sistema imunológico do paciente e revolucionaram o tratamento oncológico nos últimos anos, com aprovação para seu uso em cada vez mais neoplasias. No entanto, não é sem efeitos colaterais. Vários eventos adversos neurológicos foram reconhecidos associados aos inibidores de checkpoint imunológico (ICI) e à terapia de células T com receptor de antígeno quimérico (CAR-T), as duas principais classes de imunoterapia contra o câncer. Com o aumento da prevalência de doenças oncológicas e desse tipo de terapia, é improvável que neurologistas, oncologistas, hematologistas e demais profissionais de saúde que lidam com pacientes com câncer não encontrem esse tipo de complicação neurológica em sua prática nos próximos anos. Este artigo tem como objetivo revisar a epidemiologia, as manifestações clínicas, o diagnóstico e o manejo das complicações neurológicas associadas à terapia com ICI e células CAR-T

Repeatability and reproducibility of a handheld quantitative G6PD diagnostic.

BACKGROUND: The introduction of novel short course treatment regimens for the radical cure of Plasmodium vivax requires reliable point-of-care diagnosis that can identify glucose-6-phosphate dehydrogenase (G6PD) deficient individuals. While deficient males can be identified using a qualitative diagnostic test, the genetic make-up of females requires a quantitative measurement. SD Biosensor (Republic of Korea) has developed a handheld quantitative G6PD diagnostic (STANDARD G6PD test), that has approximately 90% accuracy in field studies for identifying individuals with intermediate or severe deficiency. The device can only be considered for routine care if precision of the assay is high. METHODS AND FINDINGS: Commercial lyophilised controls (ACS Analytics, USA) with high, intermediate, and low G6PD activities were assessed 20 times on 10 Biosensor devices and compared to spectrophotometry (Pointe Scientific, USA). Each device was then dispatched to one of 10 different laboratories with a standard set of the controls. Each control was tested 40 times at each laboratory by a single user and compared to spectrophotometry results. When tested at one site, the mean coefficient of variation (CV) was 0.111, 0.172 and 0.260 for high, intermediate, and low controls across all devices respectively; combined G6PD Biosensor readings correlated well with spectrophotometry (rs = 0.859, p<0.001). When tested in different laboratories, correlation was lower (rs = 0.604, p<0.001) and G6PD activity determined by Biosensor for the low and intermediate controls overlapped. The use of lyophilised human blood samples rather than fresh blood may have affected these findings. Biosensor G6PD readings between sites did not differ significantly (p = 0.436), whereas spectrophotometry readings differed markedly between sites (p<0.001). CONCLUSIONS: Repeatability and inter-laboratory reproducibility of the Biosensor were good; though the device did not reliably discriminate between intermediate and low G6PD activities of the lyophilized specimens. Clinical studies are now required to assess the devices performance in practice.

Morphological and Transcriptional Changes in Human Bone Marrow During Natural Plasmodium vivax Malaria Infections.

BACKGROUND: The presence of Plasmodium vivax malaria parasites in the human bone marrow (BM) is still controversial. However, recent data from a clinical case and experimental infections in splenectomized nonhuman primates unequivocally demonstrated the presence of parasites in this tissue. METHODS: In the current study, we analyzed BM aspirates of 7 patients during the acute attack and 42 days after drug treatment. RNA extracted from CD71+ cell suspensions was used for sequencing and transcriptomic analysis. RESULTS: We demonstrated the presence of parasites in all patients during acute infections. To provide further insights, we purified CD71+ BM cells and demonstrated dyserythropoiesis and inefficient erythropoiesis in all patients. In addition, RNA sequencing from 3 patients showed that genes related to erythroid maturation were down-regulated during acute infections, whereas immune response genes were up-regulated. CONCLUSIONS: This study thus shows that during P. vivax infections, parasites are always present in the BM and that such infections induced dyserythropoiesis and ineffective erythropoiesis. Moreover, infections induce transcriptional changes associated with such altered erythropoietic response, thus highlighting the importance of this hidden niche during natural infections.

Large-scale Degradation of the Tocantins-Araguaia River Basin.

The Tocantins-Araguaia Basin is one of the largest river systems in South America, located entirely within Brazilian territory. In the last decades, capital-concentrating activities such as agribusiness, mining, and hydropower promoted extensive changes in land cover, hydrology, and environmental conditions. These changes are jeopardizing the basin's biodiversity and ecosystem services. Threats are escalating as poor environmental policies continue to be formulated, such as environmentally unsustainable hydropower plants, large-scale agriculture for commodity production, and aquaculture with non-native fish. If the current model persists, it will deepen the environmental crisis in the basin, compromising broad conservation goals and social development in the long term. Better policies will require thought and planning to minimize growing threats and ensure the basin's sustainability for future generations.

Evaluation of a point-of-care diagnostic to identify glucose-6-phosphate dehydrogenase deficiency in Brazil.

BACKGROUND: Glucose-6-phosphate dehydrogenase (G6PD) deficiency is a common enzyme deficiency, prevalent in many malaria-endemic countries. G6PD-deficient individuals are susceptible to hemolysis during oxidative stress, which can occur from exposure to certain medications, including 8-aminoquinolines used to treat Plasmodium vivax malaria. Accordingly, access to point-of-care (POC) G6PD testing in Brazil is critical for safe treatment of P. vivax malaria. METHODOLOGY/PRINCIPAL FINDINGS: This study evaluated the performance of the semi-quantitative, POC STANDARD G6PD Test (SD Biosensor, Republic of Korea). Participants were recruited at clinics and through an enriched sample in Manaus and Porto Velho, Brazil. G6PD and hemoglobin measurements were obtained from capillary samples at the POC using the STANDARD and HemoCue 201+ (HemoCue AB, Sweden) tests. A thick blood slide was prepared for malaria microscopy. At the laboratories, the STANDARD and HemoCue tests were repeated on venous samples and a quantitative spectrophotometric G6PD reference assay was performed (Pointe Scientific, Canton, MI). G6PD was also assessed by fluorescent spot test. In Manaus, a complete blood count was performed. Samples were analyzed from 1,736 participants. In comparison to spectrophotometry, the STANDARD G6PD Test performed equivalently in determining G6PD status in venous and capillary specimens under varied operating temperatures. Using the manufacturer-recommended reference value thresholds, the test's sensitivity at the <30% threshold on both specimen types was 100% (95% confidence interval [CI] venous 93.6%-100.0%; capillary 93.8%-100.0%). Specificity was 98.6% on venous specimens (95% CI 97.9%-99.1%) and 97.8% on capillary (95% CI 97.0%-98.5%). At the 70% threshold, the test's sensitivity was 96.9% on venous specimens (95% CI 83.8%-99.9%) and 94.3% on capillary (95% CI 80.8%-99.3%). Specificity was 96.5% (95% CI 95.0%-97.6%) and 92.3% (95% CI 90.3%-94.0%) on venous and capillary specimens, respectively. CONCLUSION/SIGNIFICANCE: The STANDARD G6PD Test is a promising tool to aid in POC detection of G6PD deficiency in Brazil. TRIAL REGISTRATION: This study was registered with ClinicalTrials.gov (identifier: NCT04033640).

Usability of a point-of-care diagnostic to identify glucose-6-phosphate dehydrogenase deficiency: a multi-country assessment of test label comprehension and results interpretation.

BACKGROUND: Point-of-care glucose-6-phosphate dehydrogenase (G6PD) testing has the potential to make the use of radical treatment for vivax malaria safer and more effective. Widespread use of G6PD tests as part of malaria case management has been limited, in part due to due concerns regarding product usability, user training, and supervision. This study seeks to assess how well end users can understand the Standard™ G6PD Test (SD Biosensor, Suwon, South Korea) workflow, result output, and label after training. This will ultimately help inform test registration and introduction. METHODS: Potential G6PD test users who provide malaria case management at three sites in Brazil, Ethiopia, and India were trained on the use of the SD Biosensor Standard G6PD Test and assessed based on their ability to understand the test workflow and interpret results. The assessment was done through a questionnaire, designed to assess product usability against key technical product specifications and fulfill regulatory evidence requirements. Any participant who obtained 85% or above correct responses to the questionnaire was considered to adequately comprehend how to use and interpret the test. RESULTS: Forty-five participants, including malaria microscopists, laboratory staff, nurses, and community health workers took part in the study. Seventy-eight percent of all participants in the study (35/45) obtained passing scores on the assessment with minimal training. Responses to the multiple-choice questions indicate that most participants understood well the test intended use, safety claims, and warnings. The greatest source of error regarding the test was around the correct operating temperature. Most test results were also read and interpreted correctly, with the haemoglobin measurement being a more problematic output to interpret than the G6PD measurement. CONCLUSIONS: These data results show how a standardized tool can be used to assess a user's ability to run a point-of-care diagnostic and interpret results. When applied to the SD Biosensor Standard G6PD Test, this tool demonstrates that a range of users across multiple contexts can use the test and suggests improvements to the test instructions and training that can improve product usability, increase user comprehension, and ultimately contribute to more widespread effective use of point-of-care G6PD tests. TRIAL REGISTRATION: NCT04033640.

Real-life implementation of a G6PD deficiency screening qualitative test into routine vivax malaria diagnostic units in the Brazilian Amazon (SAFEPRIM study).

BACKGROUND: Glucose-6-phosphate dehydrogenase (G6PD) deficiency greatly hinders Plasmodium vivax malaria radical cure and further elimination due to 8-aminoquinolines-associated hemolysis. Although the deleterious health effects of primaquine in G6PD deficient individuals have been known for over 50 years, G6PD testing is not routinely performed before primaquine treatment in most P. vivax endemic areas. METHOD/PRINCIPAL FINDINGS: The qualitative CareStart G6PD screening test was implemented in 12 malaria treatment units (MTUs) in the municipality of Rio Preto da Eva, Western Brazilian Amazon, a malaria endemic area, between February 2019 and early January 2020. Training materials were developed and validated; evaluations were conducted on the effectiveness of training health care professionals (HCPs) to perform the test, the interpretation and reliability of routine testing performed by HCPs, and perceptions of HCPs and patients. Most HCPs were unaware of G6PD deficiency and primaquine-related adverse effects. Most of 110 HCPs trained (86/110, 78%) were able to correctly perform the G6PD test after a single 4-hour training session. The test performed by HCPs during implementation showed 100.0% (4/4) sensitivity and 68.1% (62/91) specificity in identifying G6PD deficient patients as compared to a point-of-care quantitative test (Standard G6PD). CONCLUSIONS/SIGNIFICANCE: G6PD screening using the qualitative CareStart G6PD test performed by HCPs in MTUs of an endemic area showed high sensitivity and concerning low specificity. The amount of false G6PD deficiency detected led to substantial loss of opportunities for radical cure.

Plastic pollution: A focus on freshwater biodiversity.

Plastics are dominant pollutants in freshwater ecosystems worldwide. Scientific studies that investigated the interaction between plastics and freshwater biodiversity are incipient, especially if compared to the marine realm. In this review, we provide a brief overview of plastic pollution in freshwater ecosystems around the world. We found evidence of plastic ingestion by 206 freshwater species, from invertebrates to mammals, in natural or semi-natural ecosystems. In addition, we reported other consequences of synthetic polymers in freshwater ecosystems-including, for instance, the entanglement of animals of different groups (e.g., birds). The problem of plastic pollution is complex and will need coordinated actions, such as recycling programs, correct disposal, stringent legislation, regular inspection, replacement of synthetic polymers with other materials, and ecological restoration. Current information indicates that the situation in freshwater ecosystems may be as detrimental as the pollution found in the ocean, although highly underappreciated.

Methylprednisolone as Adjunctive Therapy for Patients Hospitalized With Coronavirus Disease 2019 (COVID-19; Metcovid): A Randomized, Double-blind, Phase IIb, Placebo-controlled Trial.

BACKGROUND: Steroid use for coronavirus disease 2019 (COVID-19) is based on the possible role of these drugs in mitigating the inflammatory response, mainly in the lungs, triggered by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This study aimed to evaluate the efficacy of methylprednisolone (MP) among hospitalized patients with suspected COVID-19. METHODS: A parallel, double-blind, placebo-controlled, randomized, Phase IIb clinical trial was performed with hospitalized patients aged ≥18 years with clinical, epidemiological, and/or radiological suspected COVID-19 at a tertiary care facility in Manaus, Brazil. Patients were randomly allocated (1:1 ratio) to receive either intravenous MP (0.5 mg/kg) or placebo (saline solution) twice daily for 5 days. A modified intention-to-treat (mITT) analysis was conducted. The primary outcome was 28-day mortality. RESULTS: From 18 April to 16 June 2020, 647 patients were screened, 416 were randomized, and 393 were analyzed as mITT, with 194 individuals assigned to MP and 199 to placebo. SARS-CoV-2 infection was confirmed by reverse transcriptase polymerase chain reaction in 81.3%. The mortality rates at Day 28 were not different between groups. A subgroup analysis showed that patients over 60 years old in the MP group had a lower mortality rate at Day 28. Patients in the MP arm tended to need more insulin therapy, and no difference was seen in virus clearance in respiratory secretion until Day 7. CONCLUSIONS: The findings of this study suggest that a short course of MP in hospitalized patients with COVID-19 did not reduce mortality in the overall population. CLINICAL TRIALS REGISTRATION: NCT04343729.

Negative impacts of mining on Neotropical freshwater fishes

Mining activities have significantly affected the Neotropical freshwater ichthyofauna, the most diverse in the world. However, no study has systematized knowledge on the subject. In this review, we assembled information on the main impacts of mining of crude oil, gold, iron, copper, and bauxite on aquatic ecosystems, emphasizing Neotropical freshwater fishes. The information obtained shows that mining activities generate several different disturbances, mainly via input of crude oil, metals and other pollutants, erosion and siltation, deforestation, and road construction. Mining has resulted in direct and indirect losses of fish diversity in several Neotropical waterbodies. The negative impacts on the ichthyofauna may change the structure of communities, compromise entire food chains, and erode ecosystem services provided by freshwater fishes. Particularly noteworthy is that mining activities (legal and illegal) are widespread in the Neotropics, and often located within or near protected areas. Actions to prevent and mitigate impacts, such as inspection, monitoring, management, and restoration plans, have been cursory or absent. In addition, there is strong political pressure to expand mining; if - or when - this happens, it will increase the potential of the activity to further diminish the diversity of Neotropical freshwater fishes.(AU)

As atividades de mineração têm impactado significativamente a ictiofauna de água doce Neotropical, a mais diversa do mundo. Porém, nenhum estudo sistematizou o conhecimento sobre o assunto. Nesta revisão, reunimos informações sobre os principais impactos da mineração de petróleo, ouro, ferro, cobre, e bauxita sobre os ecossistemas aquáticos, com ênfase nos peixes de água doce Neotropicais. As informações obtidas mostram que as atividades de mineração geram diferentes distúrbios, principalmente por meio de petróleo bruto, metais e outros poluentes, erosão e assoreamento, desmatamento e construção de estradas. A mineração resultou em perda direta e indireta de diversidade de peixes de vários corpos d'água Neotropicais. Os impactos negativos sobre a ictiofauna podem alterar a estrutura das comunidades, comprometer cadeias alimentares inteiras, bem como degradar os serviços ecossistêmicos fornecidos pelos peixes de água doce. Particularmente importante é que as atividades de mineração (legais e ilegais) são generalizadas na região Neotropical, e frequentemente estão localizadas dentro ou perto de áreas protegidas. Ações de prevenção e mitigação de impactos, como planos de fiscalização, monitoramento, manejo e restauração, têm sido precárias ou ausentes. Além disso, há forte pressão política para expandir a mineração; se - ou quando - isso acontecer, aumentará o potencial da atividade em diminuir ainda mais a diversidade de peixes de água doce Neotropicais.(AU)