RESUMO
We describe the implementation of universal glucose-6-phosphate dehydrogenase (G6PD) screening during the first year of New York State mandated testing, as well as operational challenges and clinical knowledge gained. All infants born at or transferred to our center between June 21, 2022 and June 30, 2023, underwent testing for G6PD enzyme deficiency and were included in the study cohort. Infant blood samples were collected and sent to a reference laboratory for quantitative assay. After initiation of universal screening, a quality improvement initiative was launched to: monitor and improve the suitability of blood sample collection to ensure timely return of results;improve the reliability and validity of the reference laboratory enzyme assay; andestablish accurate reference ranges for G6PD deficiency in newborns.A total of 5601 newborns were included. Within the first year of implementation, the percentage of samples yielding any test result increased from 76% to 85%, and most patients had a G6PD result available within 1 day of discharge. We established a more accurate threshold for G6PD deficiency in newborns of <4.9 U/g Hb and G6PD intermediate of <10.0 U/g Hb. Using the updated reference ranges, 224 patients in our cohort were identified as G6PD deficient or intermediate (4.0%). Through a quality-sensitive process, we identified the importance of a standardized approach, improved sample collection processes, decreased sample turnaround time, and established more accurate reference ranges. We hope our experiences will help others seeking to improve processes and implement similar programs at other institutions.
Assuntos
Deficiência de Glucosefosfato Desidrogenase , Triagem Neonatal , Humanos , Deficiência de Glucosefosfato Desidrogenase/diagnóstico , Deficiência de Glucosefosfato Desidrogenase/sangue , Recém-Nascido , Triagem Neonatal/métodos , Feminino , Masculino , New York , Melhoria de Qualidade , Valores de ReferênciaRESUMO
Glucose-6-phosphate dehydrogenase (G6PD) deficiency is one of the most common enzymopathies worldwide. Patients with G6PD deficiency are usually asymptomatic throughout their life but can develop acute hemolysis after exposure to free radicals or certain medications. Several studies have shown that serum miRNAs can be used as prognostic biomarkers in various types of hemolytic anemias. However, the impact of G6PD deficiency on circulating miRNA profiles is largely unknown. The present study aimed to assess the use of serum miRNAs as biomarkers for detecting hemolysis in the nonacute phase of G6PD deficiency. Patients with severe or moderate G6PD Viangchan (871G > A) deficiency and normal G6PD patients were enrolled in the present study. The biochemical hemolysis indices were normal in the three groups, while the levels of serum miR-451a, miR-16, and miR-155 were significantly increased in patients with severe G6PD deficiency. In addition, 3D analysis of a set of three miRNAs (miR-451a, miR-16, and miR-155) was able to differentiate G6PD-deficient individuals from healthy individuals, suggesting that these three miRNAs may serve as potential biomarkers for patients in the nonhemolytic phase of G6PD deficiency. In conclusion, miRNAs can be utilized as additional biomarkers to detect hemolysis in the nonacute phase of G6PD deficiency.
Assuntos
Biomarcadores , Deficiência de Glucosefosfato Desidrogenase , Hemólise , MicroRNAs , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Biomarcadores/sangue , Estudos de Casos e Controles , Glucosefosfato Desidrogenase/genética , Glucosefosfato Desidrogenase/sangue , Deficiência de Glucosefosfato Desidrogenase/sangue , Deficiência de Glucosefosfato Desidrogenase/diagnóstico , Deficiência de Glucosefosfato Desidrogenase/genética , MicroRNAs/sangueRESUMO
Quantitative diagnosis of glucose-6-phosphate dehydrogenase (G6PD) deficiency is essential for the safe administration of 8-aminoquinoline based radical cure for the treatment of Plasmodium vivax infections. Here, we present the PreQuine Platform (IVDS, USA), a quantitative biosensor that uses a dual-analyte assay for the simultaneous measurement of Hemoglobin (Hgb) levels and G6PD enzyme activity within the same sample. The platform relies on a downloadable mobile application. The device requires 10µl of whole blood and works with a reflectance-based meter. Comparing the G6PD measurement normalized by Hgb of 12 samples from the PreQuine Platform with reference measurements methods (spectrophotometry, Pointe Scientific, USA and hemoglobin meter, HemoCue, Sweden) showed a positive and significant agreement with a slope of 1.0091 and an intercept of -0.0379 under laboratory conditions. Next steps will be to conduct field trials in Bangladesh, Cambodia, and the USA to assess diagnostic performance, user friendliness and acceptance.
Assuntos
Deficiência de Glucosefosfato Desidrogenase , Glucosefosfato Desidrogenase , Hemoglobinas , Humanos , Glucosefosfato Desidrogenase/metabolismo , Glucosefosfato Desidrogenase/sangue , Deficiência de Glucosefosfato Desidrogenase/diagnóstico , Deficiência de Glucosefosfato Desidrogenase/sangue , Hemoglobinas/análise , Hemoglobinas/metabolismo , Técnicas Biossensoriais/métodos , Malária Vivax/diagnóstico , Malária Vivax/sangue , AminoquinolinasRESUMO
BACKGROUND: Transfusion of blood from glucose-6-phosphate dehydrogenase (G6PD) enzyme deficient donors could cause a potentially unfavorable outcome, especially in newborns and those with hemoglobinopathies. AIMS: To determine the prevalence of G6PD deficiency in Thai blood donors, the characteristics of G6PD deficient blood, and the efficacy of fluorescent spot test (FST) to screen for G6PD deficiency in a hospital blood bank setting. METHODS: Blood samples were obtained from 514 Thai blood donors who donated blood at Siriraj Hospital (Bangkok, Thailand) during December 2020-February 2021. G6PD deficiency status was screened using FST, and in vitro hemolysis of red blood cell parameters of G6PD deficient blood units was compared with those of normal control units at different time points during 35 days of refrigerated storage. RESULTS: The prevalence of G6PD deficiency was 7.59% (35 [8.73%] males, 4 [3.54%] females). The sensitivity of FST was 100% (95% confidence interval [CI]: 90.97-100%), and the specificity was 99.58% (95%CI: 98.49-99.95%). In vitro hemolysis was not significantly different between G6PD deficiency and normal controls. CONCLUSION: The prevalence of G6PD deficiency in this study was 7.59%. FST was demonstrated to be an effective and reliable method for G6PD deficiency screening among Thai blood donors in a hospital blood bank setting.
Assuntos
Doadores de Sangue , Deficiência de Glucosefosfato Desidrogenase/diagnóstico , Deficiência de Glucosefosfato Desidrogenase/epidemiologia , Bancos de Sangue , Eritrócitos/patologia , Feminino , Deficiência de Glucosefosfato Desidrogenase/sangue , Hemólise , Humanos , Masculino , Prevalência , Tailândia/epidemiologiaRESUMO
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.
Assuntos
Técnicas Biossensoriais/normas , Deficiência de Glucosefosfato Desidrogenase/diagnóstico , Glucosefosfato Desidrogenase/sangue , Feminino , Liofilização , Deficiência de Glucosefosfato Desidrogenase/sangue , Humanos , Testes Imediatos/normas , Reprodutibilidade dos Testes , EspectrofotometriaAssuntos
Eritrócitos Anormais , Deficiência de Glucosefosfato Desidrogenase , Linfoma Difuso de Grandes Células B , Adulto , Eritrócitos Anormais/metabolismo , Eritrócitos Anormais/patologia , Deficiência de Glucosefosfato Desidrogenase/sangue , Deficiência de Glucosefosfato Desidrogenase/tratamento farmacológico , Deficiência de Glucosefosfato Desidrogenase/patologia , Humanos , Linfoma Difuso de Grandes Células B/sangue , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Linfoma Difuso de Grandes Células B/patologia , MasculinoRESUMO
BACKGROUND/AIMS: Defects in the Glucose-6-Phosphate Dehydrogenase (G6PD) enzyme enhance cellular oxidative damage, thus impairing erythrocytes and radically shortening their lifespan. We aimed to study programmed erythrocyte cell death in G6PD-deficient patients, describe the molecular genetics basis of G6PD and investigate phenotype-genotype correlations. METHODS: We explored eryptosis using the annexin V-binding assay, taken as an indicator of PS exposure at the erythrocyte surface. We assessed reactive oxygen species (ROS) production, intracellular calcium concentrations and ceramide formation at the cell surface. Prior to and following treatments, cells were analyzed by flow cytometry. Finally, we explored G6PD gene mutations through PCR-Sanger sequencing. RESULTS: Before stimulation, PS-exposing erythrocytes were significantly higher in G6PD-deficient patients than in healthy volunteers. This was paralleled by a significant increase in reactive oxygen species production, suggesting that oxidative stress is the main trigger of PS exposure in G6PD-deficient erythrocytes. Five previously described mutations were detected in our patients. Two genotypes correlated with a significantly higher percentage of PS-exposing cells. CONCLUSION: Our study uncovers a novel effect detected in G6PD-deficient erythrocytes which is cell membrane scrambling with PS translocation to the erythrocyte surface. Our findings shed a light on the mechanisms of premature erythrocyte clearance in G6PD deficiency.
Assuntos
Eriptose , Eritrócitos/metabolismo , Deficiência de Glucosefosfato Desidrogenase/sangue , Estresse Oxidativo , Adolescente , Adulto , Idoso , Anexina A5/sangue , Anexina A5/genética , Criança , Pré-Escolar , Feminino , Deficiência de Glucosefosfato Desidrogenase/genética , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Espécies Reativas de Oxigênio/sangueRESUMO
BACKGROUND: Oxidative Stress, an imbalance in the pro-oxidant/antioxidant homeostasis, occurs in many physiological and non-physiological processes and several human diseases, including diabetes mellitus (DM) and glucose-6-phosphate dehydrogenase (G6PD) deficiency. Since the incidence of G6PD deficiency in Jordan and many parts of the world is high, this study aimed to measure the effect of G6PD deficiency on the oxidative markers and the antioxidant glutathione (GSH) in diabetic and non-diabetic individuals. METHODS: Whole blood G6PD deficiency was screened by the fluorescent spot method, and erythrocyte G6PD activity was determined using a quantitative assay. Since protein carbonyl (PC) and malondialdehyde (MDA) are the most widely measured markers for protein and lipid oxidation, respectively, plasma PC and MDA, in addition to blood GSH were determined by spectrophotometric assays, as biomarkers of oxidative stress. RESULTS: The incidence of G6PD deficiency among the diabetic subjects was 15%. PC level in patients with diabetes and in G6PD-deficient subjects was 5.5 to 6-fold higher than in non-diabetic subjects with sufficient G6PD levels (p<0.001). This fold increase was doubled in diabetic patients with G6PD deficiency (p<0.001). Furthermore, the MDA level was significantly increased by 28-41% in G6PD-deficient, diabetics with sufficient G6PD, and diabetics with G6PD deficiency compared to MDA level in non-diabetic with sufficient G6PD. On the other hand, GSH was significantly reduced to half in G6PD-deficient subjects and in diabetics with G6PD-deficiency. CONCLUSIONS: The results showed that diabetes and G6PD deficiency increased protein oxidation and lipid peroxidation. However, the combination of both disorders has an additive effect only on protein oxidation. On the other hand, GSH level is only reduced in G6PD deficiency. In addition, diabetes and G6PD deficiency appear to be genetically linked since the incidence of G6PD deficiency among people with diabetes is more than the general population.
Assuntos
Diabetes Mellitus/sangue , Deficiência de Glucosefosfato Desidrogenase/sangue , Peroxidação de Lipídeos/fisiologia , Estresse Oxidativo/fisiologia , Comorbidade , Diabetes Mellitus/epidemiologia , Feminino , Deficiência de Glucosefosfato Desidrogenase/epidemiologia , Humanos , Jordânia/epidemiologia , MasculinoRESUMO
Population risks for neonatal hyperbilirubinaemia (NH) vary. Knowledge of local risks permits interventions that may reduce the proportion becoming severe. Between January 2015 and May 2016, in a resource-limited setting on the Thailand-Myanmar border, neonates from 28 weeks' gestation were enrolled into a prospective birth cohort. Each neonate had total serum bilirubin measurements: scheduled (24, 48, 72 and 144 hours of life) and clinically indicated; and weekly follow up until 1 month of age. Risk factors for developing NH were evaluated using Cox proportional hazard mixed model. Of 1710 neonates, 22% (376) developed NH (83% preterm, 19% term). All neonates born <35 weeks, four in five born 35-37 weeks, and three in twenty born ≥38 weeks had NH, giving an overall incidence of 249 per 1000 livebirths [95%CI 225, 403]. Mortality from acute bilirubin encephalopathy was 10% (2/20) amongst the 5.3% (20/376) who reached the severe NH threshold. One-quarter (26.3%) of NH occurred within 24 hours. NH onset varied with gestational age: at a median [IQR] 24 hours [24, 30] for neonates born 37 weeks or prematurely vs 59 hours [48, 84] for neonates born ≥38 weeks. Risk factors for NH in the first week of life independent of gestational age were: neonatal G6PD deficiency, birth bruising, Sgaw Karen ethnicity, primigravidae, pre-eclampsia, and prolonged rupture of membranes. The genetic impact of G6PD deficiency on NH was partially interpreted by using the florescent spot test and further genotyping work is in progress. The risk of NH in Sgaw Karen refugees may be overlooked internationally as they are most likely regarded as Burmese in countries of resettlement. Given high levels of pathological jaundice in the first 24 hours and overall high NH burden, guidelines changes were implemented including preventive PT for all neonates <35 weeks and for those 35-37 weeks with risk factors.
Assuntos
Bilirrubina/sangue , Deficiência de Glucosefosfato Desidrogenase/sangue , Hiperbilirrubinemia Neonatal/sangue , Kernicterus/sangue , Estudos de Coortes , Estudos Epidemiológicos , Etnicidade/genética , Feminino , Genótipo , Deficiência de Glucosefosfato Desidrogenase/complicações , Deficiência de Glucosefosfato Desidrogenase/genética , Deficiência de Glucosefosfato Desidrogenase/mortalidade , Humanos , Hiperbilirrubinemia Neonatal/genética , Hiperbilirrubinemia Neonatal/mortalidade , Hiperbilirrubinemia Neonatal/patologia , Recém-Nascido , Kernicterus/complicações , Kernicterus/genética , Kernicterus/mortalidade , Masculino , Mianmar/epidemiologia , Pré-Eclâmpsia/sangue , Pré-Eclâmpsia/genética , Pré-Eclâmpsia/mortalidade , Gravidez , Modelos de Riscos Proporcionais , Estudos Prospectivos , Fatores de Risco , Tailândia/epidemiologiaRESUMO
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).
Assuntos
Técnicas Biossensoriais , Deficiência de Glucosefosfato Desidrogenase/diagnóstico , Glucosefosfato Desidrogenase/sangue , Testes Imediatos/normas , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Aminoquinolinas/uso terapêutico , Antimaláricos/uso terapêutico , Brasil , Criança , Pré-Escolar , Estudos Transversais , Feminino , Deficiência de Glucosefosfato Desidrogenase/sangue , Hemólise , Humanos , Modelos Lineares , Malária Vivax/complicações , Malária Vivax/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Curva ROC , Adulto JovemRESUMO
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.
Assuntos
Competência Clínica , Deficiência de Glucosefosfato Desidrogenase/diagnóstico , Glucosefosfato Desidrogenase/sangue , Capacitação em Serviço , Malária/diagnóstico , Testes Imediatos , Brasil , Etiópia , Deficiência de Glucosefosfato Desidrogenase/sangue , Humanos , Índia , Malária/sangue , Malária/tratamento farmacológico , Rotulagem de Produtos , Inquéritos e QuestionáriosRESUMO
Deficiency of glucose-6-phosphate dehydrogenase (G6PD) is the single most common enzymopathy, present in approximately 400 million humans (approximately 5%). Its prevalence is hypothesized to be due to conferring resistance to malaria. However, G6PD deficiency also results in hemolytic sequelae from oxidant stress. Moreover, G6PD deficiency is associated with kidney disease, diabetes, pulmonary hypertension, immunological defects, and neurodegenerative diseases. To date, the only available mouse models have decreased levels of WT stable G6PD caused by promoter mutations. However, human G6PD mutations are missense mutations that result in decreased enzymatic stability. As such, this results in very low activity in red blood cells (RBCs) that cannot synthesize new protein. To generate a more accurate model, the human sequence for a severe form of G6PD deficiency, Med(-), was knocked into the murine G6PD locus. As predicted, G6PD levels were extremely low in RBCs, and deficient mice had increased hemolytic sequelae to oxidant stress. Nonerythroid organs had metabolic changes consistent with mild G6PD deficiency, consistent with what has been observed in humans. Juxtaposition of G6PD-deficient and WT mice revealed altered lipid metabolism in multiple organ systems. Together, these findings both establish a mouse model of G6PD deficiency that more accurately reflects human G6PD deficiency and advance our basic understanding of altered metabolism in this setting.
Assuntos
Eritrócitos/metabolismo , Deficiência de Glucosefosfato Desidrogenase/metabolismo , Glucosefosfato Desidrogenase/genética , Hemólise/genética , Animais , Modelos Animais de Doenças , Feminino , Técnicas de Introdução de Genes , Glucosefosfato Desidrogenase/metabolismo , Deficiência de Glucosefosfato Desidrogenase/sangue , Deficiência de Glucosefosfato Desidrogenase/genética , Humanos , Masculino , Camundongos , Mutação , Estresse Oxidativo/genéticaRESUMO
BACKGROUND: In 2017, an estimated 14 million cases of Plasmodium vivax malaria were reported from Asia, Central and South America, and the Horn of Africa. The clinical burden of vivax malaria is largely driven by its ability to form dormant liver stages (hypnozoites) that can reactivate to cause recurrent episodes of malaria. Elimination of both the blood and liver stages of the parasites ("radical cure") is required to achieve a sustained clinical response and prevent ongoing transmission of the parasite. Novel treatment options and point-of-care diagnostics are now available to ensure that radical cure can be administered safely and effectively. We quantified the global economic cost of vivax malaria and estimated the potential cost benefit of a policy of radical cure after testing patients for glucose-6-phosphate dehydrogenase (G6PD) deficiency. METHODS AND FINDINGS: Estimates of the healthcare provider and household costs due to vivax malaria were collated and combined with national case estimates for 44 endemic countries in 2017. These provider and household costs were compared with those that would be incurred under 2 scenarios for radical cure following G6PD screening: (1) complete adherence following daily supervised primaquine therapy and (2) unsupervised treatment with an assumed 40% effectiveness. A probabilistic sensitivity analysis generated credible intervals (CrIs) for the estimates. Globally, the annual cost of vivax malaria was US$359 million (95% CrI: US$222 to 563 million), attributable to 14.2 million cases of vivax malaria in 2017. From a societal perspective, adopting a policy of G6PD deficiency screening and supervision of primaquine to all eligible patients would prevent 6.1 million cases and reduce the global cost of vivax malaria to US$266 million (95% CrI: US$161 to 415 million), although healthcare provider costs would increase by US$39 million. If perfect adherence could be achieved with a single visit, then the global cost would fall further to US$225 million, equivalent to $135 million in cost savings from the baseline global costs. A policy of unsupervised primaquine reduced the cost to US$342 million (95% CrI: US$209 to 532 million) while preventing 2.1 million cases. Limitations of the study include partial availability of country-level cost data and parameter uncertainty for the proportion of patients prescribed primaquine, patient adherence to a full course of primaquine, and effectiveness of primaquine when unsupervised. CONCLUSIONS: Our modelling study highlights a substantial global economic burden of vivax malaria that could be reduced through investment in safe and effective radical cure achieved by routine screening for G6PD deficiency and supervision of treatment. Novel, low-cost interventions for improving adherence to primaquine to ensure effective radical cure and widespread access to screening for G6PD deficiency will be critical to achieving the timely global elimination of P. vivax.
Assuntos
Antimaláricos/economia , Antimaláricos/uso terapêutico , Custos de Medicamentos , Saúde Global/economia , Malária Vivax/tratamento farmacológico , Malária Vivax/economia , Primaquina/economia , Primaquina/uso terapêutico , Adolescente , Adulto , Antimaláricos/efeitos adversos , Criança , Pré-Escolar , Tomada de Decisão Clínica , Redução de Custos , Análise Custo-Benefício , Terapia Diretamente Observada , Feminino , Testes Genéticos/economia , Deficiência de Glucosefosfato Desidrogenase/sangue , Deficiência de Glucosefosfato Desidrogenase/diagnóstico , Deficiência de Glucosefosfato Desidrogenase/economia , Deficiência de Glucosefosfato Desidrogenase/genética , Gastos em Saúde , Hemólise/efeitos dos fármacos , Humanos , Incidência , Lactente , Recém-Nascido , Malária Vivax/epidemiologia , Masculino , Adesão à Medicação , Modelos Econômicos , Seleção de Pacientes , Primaquina/efeitos adversos , Indução de Remissão , Resultado do Tratamento , Adulto JovemRESUMO
Transfusion-related lung injury (TRALI) is a condition that develops suddenly within the first six hours after a blood transfusion and it is one of the most important causes of blood transfusion-related mortality. There are few data in the literature about TRALI in the neonatal period. We present two newborn patients who developed TRALI after exchange transfusion due to high bilirubin levels. Our first case was a late preterm LGA baby and was on CPAP. The baby was intubated due to sudden deterioration after the exchange transfusion. Our second case was born at term and, an exchange transfusion was performed on the 5th day of life. He developed respiratory distress unexpectedly soon after the exchange transfusion and was intubated. Glucose-6- phosphate dehydrogenase (G6PD) deficiency was detected in both of our cases. We wanted to emphasize that TRALI should be considered in the differential diagnosis of respiratory distress that develops soon after a transfusion in the newborn period and to draw attention to that TRALI may develop more frequently in patients with G6PD deficiency.
Assuntos
Transfusão Total/efeitos adversos , Deficiência de Glucosefosfato Desidrogenase , Deficiência de Glucosefosfato Desidrogenase/sangue , Deficiência de Glucosefosfato Desidrogenase/diagnóstico por imagem , Deficiência de Glucosefosfato Desidrogenase/terapia , Humanos , Recém-Nascido , Masculino , Lesão Pulmonar Aguda Relacionada à Transfusão/sangue , Lesão Pulmonar Aguda Relacionada à Transfusão/diagnóstico por imagem , Lesão Pulmonar Aguda Relacionada à Transfusão/terapiaRESUMO
COVID-19 has become a major public health problem since December, 2019 and no highly effective drug has been found until now. Numbers of infected people and deaths by COVID-19 are increasing every day worldwide, therefore self-isolation and protection are highly recommended to prevent the spread of the virus and especially to protect major risk groups such as the elderly population and people with comorbidities including diabetes, hypertension, cancer, cardiovascular diseases and metabolic syndrome. On the other hand, young people without any secondary disease have died by COVID-19 as well. In this study we compared two male patients infected by COVID-19 at the same age and one of them was diagnosed with G6PD deficiency. Both COVID-19 and G6PD deficiency enhance the risk of hemolysis and thrombosis. Serum biochemistry, hemogram and immunological parameters showed that risk of hemolysis and thrombosis may increase in the G6PD deficient patient infected by COVID-19.
Assuntos
COVID-19/genética , Deficiência de Glucosefosfato Desidrogenase/genética , Glucosefosfato Desidrogenase/genética , Trombose/genética , Adulto , COVID-19/sangue , COVID-19/complicações , COVID-19/virologia , Deficiência de Glucosefosfato Desidrogenase/sangue , Deficiência de Glucosefosfato Desidrogenase/complicações , Deficiência de Glucosefosfato Desidrogenase/patologia , Hemólise/fisiologia , Humanos , Masculino , Fatores de Risco , SARS-CoV-2/genética , SARS-CoV-2/patogenicidade , Trombose/sangue , Trombose/etiologia , Trombose/virologiaRESUMO
Accurate measurement of glucose-6-phosphate dehydrogenase (G6PD) activity is critical for malaria treatment as misclassification of G6PD deficiency could cause serious harm to patients. G6PD activity should be assessed in blood samples on the day of collection. Otherwise, specimens should be stored under suitable conditions to prevent loss of G6PD activity. Here, we assessed stability and integrity of G6PD testing in samples from normal controls, heterozygous females, and G6PD deficient individuals using water-soluble tetrazolium salts (WST-8) assay. Specimens were stored as ethylenediaminetetraacetic acid (EDTA) whole blood and dried blood spots (DBS) at various temperatures (37⯰C, room temperature, 4⯰C and -20⯰C) and under different humidity conditions (with and without desiccant). G6PD normal samples were stable for up to 1 year when stored at -20⯰C under controlled conditions, with 85% and 91% G6PD activity in EDTA whole blood and DBS in the presence of desiccant, respectively. Specimens from heterozygous females showed greater G6PD activity when stored as DBS, with 85% enzyme activity after 1 year of storage at -20⯰C under controlled conditions in the presence of desiccant. G6PD deficient samples rapidly lost enzyme activity in all storage conditions tested. However, the reduction in G6PD enzyme activity in G6PD deficient samples did not interfere with G6PD classification. Samples stored under suitable conditions for G6PD testing will allow accurate measurement of enzyme activity, prevent misclassification of G6PD deficiency and enable safe and effective use of antimalarial drugs such as primaquine and tafenoquine.
Assuntos
Coleta de Amostras Sanguíneas/métodos , Deficiência de Glucosefosfato Desidrogenase/sangue , Deficiência de Glucosefosfato Desidrogenase/diagnóstico , Programas de Rastreamento/métodos , Sais de Tetrazólio , Feminino , Deficiência de Glucosefosfato Desidrogenase/genética , Heterozigoto , Humanos , Masculino , TemperaturaAssuntos
Acalypha/toxicidade , Deficiência de Glucosefosfato Desidrogenase/diagnóstico , Hemoglobinúria/diagnóstico , Hemólise/efeitos dos fármacos , Metemoglobinemia/induzido quimicamente , Pré-Escolar , Família , Deficiência de Glucosefosfato Desidrogenase/sangue , Humanos , L-Lactato Desidrogenase/sangue , Masculino , Estresse OxidativoRESUMO
The severe pneumonia caused by the human coronavirus (hCoV)-SARS-CoV-2 has inflicted heavy casualties, especially among the elderly and those with co-morbid illnesses irrespective of their age. The high mortality in African-Americans and males, in general, raises the concern for a possible X-linked mediated process that could affect the viral pathogenesis and the immune system. We hypothesized that G6PD, the most common X-linked enzyme deficiency, associated with redox status, may have a role in severity of pneumonia. Retrospective chart review was performed in hospitalized patients with COVID19 pneumonia needing supplemental oxygen. A total of 17 patients were evaluated: six with G6PD deficiency (G6PDd) and 11 with normal levels. The two groups (normal and G6PDd) were comparable in terms of age, sex, co-morbidities, and laboratory parameters-LDH, IL-6, CRP, and ferritin, respectively. Thirteen patients needed ventilatory support ; 8 in the normal group and 5 in the G6PDd group (72% vs.83%). The main differences indicating increasing severity in normal vs. G6PDd groups included G6PD levels (12.2 vs. 5.6, P = 0.0002), PaO2/FiO2 ratio (159 vs. 108, P = 0.05), days on mechanical ventilation (10.25 vs. 21 days P = 0.04), hemoglobin level (10 vs. 8.1 P = 0.03), and hematocrit (32 vs. 26 P = 0.015). Only one patient with G6PDd died; 16 were discharged home. Our clinical series ascribes a possible biological role for G6PDd in SARS-CoV2 viral proliferation. It is imperative that further studies are performed to understand the interplay between the viral and host factors in G6PDd that may lead to disparity in outcomes. KEY POINTS: ⢠COVID19 studies show higher mortality in men, due to severe pneumonia and ARDS, indicating possible X-linked mediated differences ⢠G6PD, the most common X-linked enzymopathy, highly prevalent in African Americans and Italians, maintains redox homeostasis. ⢠Preclinical studies using G6PD deficient (G6PDd) cells infected with human coronavirus (hCoV), show impaired cellular responses, viral proliferation and worsening oxidative damage. ⢠Retrospective chart review in hospitalized patients with COVID19 pneumonia needing supplemental oxygen shows differences between the two groups (Normal and G6PDd) in hematological indices; the G6PDdgroup demonstrated prolonged PaO2/FiO2 ratio, and longer days on mechanical ventilation indicating the severity of the pneumonia.