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1.
PLoS Negl Trop Dis ; 14(9): e0008697, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32925910

RESUMO

The proportion of Plasmodium vivax malaria among all malarias is increasing worldwide. Treatment with 8-aminoquinolines remain the only radical cure. However, 8-aminoquinolines can cause severe hemolysis in glucose-6-phosphate dehydrogenase (G6PD) deficient patients. The population of the multi-ethnic Chittagong Hill Tracts (CHT) carry the highest malaria burden within Bangladesh. As in many countries the national treatment guidelines recommend 8-aminoquinoline based radical cure without routine G6PD deficiency (G6PDd) testing to guide treatment. Aim of this study was to determine the need for routine testing within a multi-ethnic population by assessing the prevalence of G6PDd among the local population. Participants from 11 ethnicities were randomly selected and malaria status was assessed by microscopy, rapid diagnostic test (RDT) and polymerase chain reaction (PCR). G6PD status was determined by spectrophotometry and G6PD genotyping. The adjusted male median (AMM) was defined as 100% G6PD activity, participants were categorized as G6PD deficient (<30% activity), G6PD intermediate (30% to 70% activity) or G6PD normal (>70% activity). Median G6PD activities between ethnicities were compared and the association between G6PD activity and malaria status was assessed. 1002 participants were enrolled and tested for malaria. G6PD activity was measured by spectrophotometry in 999 participants and host G6PD genotyping undertaken in 323 participants. Seven participants (0.7%) had peripheral parasitaemia detected by microscopy or RDT and 42 by PCR (4.2%). Among 106 participants (32.8%) with confirmed genotype, 99 (93.4%) had the Mahidol variant. The AMM was 7.03U/gHb with 90 (9.0%) G6PD deficient participants and 133 (13.3%) with intermediate G6PD activity. Median G6PD activity differed significantly between ethnicities (p<0.001), proportions of G6PD deficient individuals ranged from 2% to 26% but did not differ between participants with and without malaria. The high G6PDd prevalence and significant variation between ethnicities suggest routine G6PDd testing to guide 8-aminoquinoline based radical in the CHT and comparable settings.


Assuntos
Grupos Étnicos/genética , Deficiência de Glucosefosfato Desidrogenase/epidemiologia , Deficiência de Glucosefosfato Desidrogenase/genética , Glucosefosfato Desidrogenase/genética , Glucosefosfato Desidrogenase/metabolismo , Adulto , Aminoquinolinas/efeitos adversos , Aminoquinolinas/uso terapêutico , Bangladesh/epidemiologia , Testes Diagnósticos de Rotina , Feminino , Deficiência de Glucosefosfato Desidrogenase/complicações , Deficiência de Glucosefosfato Desidrogenase/diagnóstico , Humanos , Malária Vivax/complicações , Malária Vivax/tratamento farmacológico , Malária Vivax/epidemiologia , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , Prevalência , Adulto Jovem
2.
Am J Trop Med Hyg ; 103(1): 394-403, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32372747

RESUMO

Tafenoquine has been licensed for the single-dose radical cure of Plasmodium vivax in adults; however, it is only recommended in patients with > 70% of normal glucose-6-phosphate dehydrogenase (G6PD) activity. Because this may hinder widespread use, we investigated sex-based treatment strategies in which all adult patients are tested with a qualitative G6PD rapid diagnostic test (RDT). Glucose-6-phosphate dehydrogenase normal males are prescribed tafenoquine in all three strategies, whereas G6PD normal females are prescribed either a low-dose 14-day primaquine regimen (PQ14, total dose 3.5 mg/kg) or a high-dose 7-day primaquine regimen (PQ7, total dose 7 mg/kg), or referred to a healthcare facility for quantitative G6PD testing before prescribing tafenoquine. Patients testing G6PD deficient are prescribed a weekly course of primaquine for 8 weeks. We compared the cost-effectiveness of these three strategies to usual care in four countries using a decision tree model. Usual care in Ethiopia does not include radical cure, whereas Afghanistan, Indonesia, and Vietnam prescribe PQ14 without G6PD screening. The cost per disability-adjusted life-year (DALY) averted was expressed through incremental cost-effectiveness ratios (ICERs). Compared with usual care, the ICERs for a sex-based treatment strategy with PQ7 for females from a healthcare provider perspective were $127 per DALY averted in Vietnam, $466 in Ethiopia, $1,089 in Afghanistan, and $4,443 in Indonesia. The PQ14 and referral options cost more while averting fewer DALYs than PQ7. This study provides an alternative cost-effective mode of rolling out tafenoquine in areas where initial testing with only a G6PD RDT is feasible.


Assuntos
Aminoquinolinas/efeitos adversos , Anemia Hemolítica/induzido quimicamente , Antimaláricos/efeitos adversos , Deficiência de Glucosefosfato Desidrogenase/diagnóstico , Malária Vivax/tratamento farmacológico , Primaquina/efeitos adversos , Adulto , Afeganistão , Aminoquinolinas/administração & dosagem , Anemia Hemolítica/etiologia , Antimaláricos/administração & dosagem , Cloroquina/administração & dosagem , Análise Custo-Benefício , Etiópia , Feminino , Deficiência de Glucosefosfato Desidrogenase/complicações , Hemizigoto , Heterozigoto , Homozigoto , Humanos , Indonésia , Masculino , Programas de Rastreamento , Adesão à Medicação , Plasmodium vivax , Primaquina/administração & dosagem , Anos de Vida Ajustados por Qualidade de Vida , Recidiva , Fatores Sexuais , Vietnã
3.
PLoS Med ; 17(5): e1003084, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32407380

RESUMO

BACKGROUND: The radical cure of Plasmodium vivax and P. ovale requires treatment with primaquine or tafenoquine to clear dormant liver stages. Either drug can induce haemolysis in individuals with glucose-6-phosphate dehydrogenase (G6PD) deficiency, necessitating screening. The reference diagnostic method for G6PD activity is ultraviolet (UV) spectrophotometry; however, a universal G6PD activity threshold above which these drugs can be safely administered is not yet defined. Our study aimed to quantify assay-based variation in G6PD spectrophotometry and to explore the diagnostic implications of applying a universal threshold. METHODS AND FINDINGS: Individual-level data were pooled from studies that used G6PD spectrophotometry. Studies were identified via PubMed search (25 April 2018) and unpublished contributions from contacted authors (PROSPERO: CRD42019121414). Studies were excluded if they assessed only individuals with known haematological conditions, were family studies, or had insufficient details. Studies of malaria patients were included but analysed separately. Included studies were assessed for risk of bias using an adapted form of the Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) tool. Repeatability and intra- and interlaboratory variability in G6PD activity measurements were compared between studies and pooled across the dataset. A universal threshold for G6PD deficiency was derived, and its diagnostic performance was compared to site-specific thresholds. Study participants (n = 15,811) were aged between 0 and 86 years, and 44.4% (7,083) were women. Median (range) activity of G6PD normal (G6PDn) control samples was 10.0 U/g Hb (6.3-14.0) for the Trinity assay and 8.3 U/g Hb (6.8-15.6) for the Randox assay. G6PD activity distributions varied significantly between studies. For the 13 studies that used the Trinity assay, the adjusted male median (AMM; a standardised metric of 100% G6PD activity) varied from 5.7 to 12.6 U/g Hb (p < 0.001). Assay precision varied between laboratories, as assessed by variance in control measurements (from 0.1 to 1.5 U/g Hb; p < 0.001) and study-wise mean coefficient of variation (CV) of replicate measures (from 1.6% to 14.9%; p < 0.001). A universal threshold of 100% G6PD activity was defined as 9.4 U/g Hb, yielding diagnostic thresholds of 6.6 U/g Hb (70% activity) and 2.8 U/g Hb (30% activity). These thresholds diagnosed individuals with less than 30% G6PD activity with study-wise sensitivity from 89% (95% CI: 81%-94%) to 100% (95% CI: 96%-100%) and specificity from 96% (95% CI: 89%-99%) to 100% (100%-100%). However, when considering intermediate deficiency (<70% G6PD activity), sensitivity fell to a minimum of 64% (95% CI: 52%-75%) and specificity to 35% (95% CI: 24%-46%). Our ability to identify underlying factors associated with study-level heterogeneity was limited by the lack of availability of covariate data and diverse study contexts and methodologies. CONCLUSIONS: Our findings indicate that there is substantial variation in G6PD measurements by spectrophotometry between sites. This is likely due to variability in laboratory methods, with possible contribution of unmeasured population factors. While an assay-specific, universal quantitative threshold offers robust diagnosis at the 30% level, inter-study variability impedes performance of universal thresholds at the 70% level. Caution is advised in comparing findings based on absolute G6PD activity measurements across studies. Novel handheld quantitative G6PD diagnostics may allow greater standardisation in the future.


Assuntos
Deficiência de Glucosefosfato Desidrogenase/diagnóstico , Deficiência de Glucosefosfato Desidrogenase/metabolismo , Glucosefosfato Desidrogenase/metabolismo , Espectrofotometria , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Antimaláricos/uso terapêutico , Criança , Pré-Escolar , Feminino , Deficiência de Glucosefosfato Desidrogenase/tratamento farmacológico , Humanos , Lactente , Recém-Nascido , Malária/epidemiologia , Masculino , Pessoa de Meia-Idade , Adulto Jovem
4.
Brasília; Brasil. Ministério da Saúde; abr. 2020.
Não convencional em Português | LILACS, Coleciona SUS, BRISA/RedTESA | ID: biblio-1096175

RESUMO

OBJETIVO Esta nota técnica tem por objetivo apresentar uma avaliação técnica sobre a segurança da cloroquina e da hidroxicloroquina em pacientes com deficiência de glicose6-fosfato desidrogenase (G6PD), visando a fornecer subsídios para a recomendação sobre o rastreamento da deficiência de G6PD em pacientes elegíveis para tratamento com cloroquina ou hidroxicloroquina devido à infecção por coronavírus (COVID-19). DOS FATOS Trata-se de despacho emitido pelo Gabinete do Ministro da Saúde (0014309411) em 06 de abril de 2020, anexado ao processo 25000.048031/2020-24. O referido despacho apresenta um e-mail direcionado à Chefia de Gabinete do Ministro da Saúde, encaminhado pela profissional Dra. Silmara Paula Gouvea de Marco, vinculada à Universidade de São Paulo, intitulado "Problema Sério com Cloroquina". Neste, a autora da mensagem relata preocupação com o "efeito colateral de alto nível em pacientes com deficiência de G6PD ­ Anemia Hemolítica", sugerindo que "antes de ministrar o medicamento, laboratórios rastreiem a Def de G6PD, pois tais pacientes podem vir a óbito caso façam uso de tal medicamento", fazendo referência à utilização de cloroquina em pacientes com infecção por coronavírus (COVID-19). O processo foi recebido por esta coordenação em 13 de abril de 2020. DA ANÁLISE: Os medicamentos cloroquina e hidroxicloroquina foram recomendados pelo Ministério da Saúde como possibilidade terapêutica em pacientes com diagnóstico confirmado da COVID-19, hospitalizados e com a forma grave da doença, em caráter off label, ou seja, sem indicação prévia em bula. Ressalta-se que a sugestão do uso pode ser modificada a qualquer tempo, a depender dos resultados das pesquisas científicas em curso A bula da cloroquina informa sua contraindicação para pacientes com deficiência de glicose-6-fosfato desidrogenase e a bula da hidroxicloroquina adverte que seu uso nesses pacientes deve ser feito com cautela. A cloroquina é uma 4-aminoquinolina tradicionalmente recomendada como antimalárico. Quando administrada em combinação com primaquina (8-aminoquinolina), confere cura radical aos pacientes infectados por Plasmodium vivax. Estudos conduzidos com a primaquina na década de 1950 identificaram risco aumentado de anemia hemolítica em pacientes com deficiência de G6PD tratados com primaquina. CONCLUSÕES A cloroquina apresenta contraindicação em bula para pacientes com deficiência de G6PD e a bula da hidroxicloroquina recomenda uso com cautela nesses pacientes. Apesar disso, as evidências atualmente disponíveis não apontam para risco aumentado da utilização desses medicamentos em pacientes com deficiência de G6PD. Dessa forma, não se justifica o rastreamento de deficiência de G6PD em todos os pacientes elegíveis para tratamento com cloroquina ou hidroxicloroquina devido à infecção por coronavírus (COVID-19).


Assuntos
Humanos , Cloroquina/uso terapêutico , Infecções por Coronavirus/tratamento farmacológico , Deficiência de Glucosefosfato Desidrogenase/diagnóstico , Hidroxicloroquina/uso terapêutico , Avaliação da Tecnologia Biomédica
6.
PLoS One ; 15(1): e0228207, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32004348

RESUMO

BACKGROUND: Primaquine is an approved radical cure treatment for Plasmodium vivax malaria but treatment can result in life-threatening hemolysis if given to a glucose-6-phosphate dehydrogenase deficient (G6PDd) patient. There is a need for reliable point-of-care G6PD diagnostic tests. OBJECTIVES: To evaluate the performance of the CareStart™ rapid diagnostic test (RDT) in the hands of healthcare workers (HCWs) and village malaria workers (VMWs) in field settings, and to better understand user perceptions about the risks and benefits of PQ treatment guided by RDT results. METHODS: This study enrolled 105 HCWs and VMWs, herein referred to as trainees, who tested 1,543 healthy adult male volunteers from 84 villages in Cambodia. The trainees were instructed on G6PD screening, primaquine case management, and completed pre and post-training questionnaires. Each trainee tested up to 16 volunteers in the field under observation by the study staff. RESULTS: Out of 1,542 evaluable G6PD volunteers, 251 (16.28%) had quantitative enzymatic activity less than 30% of an adjusted male median (8.30 U/g Hb). There was no significant difference in test sensitivity in detecting G6PDd between trainees (97.21%), expert study staff in the field (98.01%), and in a laboratory setting (95.62%) (p = 0.229); however, test specificity was different for trainees (96.62%), expert study staff in the field (98.14%), and experts in the laboratory (98.99%) (p < 0.001). Negative predictive values were not statistically different for trainees, expert staff, and laboratory testing: 99.44%, 99.61%, and 99.15%, respectively. Knowledge scores increased significantly post-training, with 98.7% willing to prescribe primaquine for P.vivax malaria, an improvement from 40.6% pre-training (p < 0.001). CONCLUSION: This study demonstrated ability of medical staff with different background to accurately use CareStart™ RDT to identify G6PDd in male patients, which may enable safer prescribing of primaquine; however, pharmacovigilance is required to address possible G6PDd misclassifications.


Assuntos
Testes Diagnósticos de Rotina , Deficiência de Glucosefosfato Desidrogenase/diagnóstico , Primaquina/efeitos adversos , Características de Residência , Adulto , Camboja , Feminino , Glucosefosfato Desidrogenase/metabolismo , Deficiência de Glucosefosfato Desidrogenase/metabolismo , Humanos , Malária Vivax/tratamento farmacológico , Masculino , Sistemas Automatizados de Assistência Junto ao Leito , Primaquina/uso terapêutico , Medição de Risco , Adulto Jovem
7.
Malar J ; 19(1): 40, 2020 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-31969155

RESUMO

BACKGROUND: The Sustainable Development Goals (SDG) call for increased gender equity and reduction in malaria-related mortality and morbidity. Plasmodium vivax infections in pregnancy are associated with maternal anaemia and increased adverse perinatal outcomes. Providing radical cure for women with 8-aminoquinolines (e.g., primaquine) is hindered by gender-specific complexities. CASE PRESENTATION: A symptomatic episode of vivax malaria at 18 weeks of gestation in a primigravid woman was associated with maternal anaemia, a recurrent asymptomatic P. vivax episode, severe intra-uterine growth restriction with no other identifiable cause and induction to reduce the risk of stillbirth. At 5 months postpartum a qualitative glucose-6-phosphate dehydrogenase (G6PD) point-of-care test was normal and radical cure with primaquine was prescribed to the mother. A 33% fractional decrease in haematocrit on day 7 of primaquine led to further testing which showed intermediate phenotypic G6PD activity; the G6PD genotype could not be identified. Her infant daughter was well throughout maternal treatment and found to be heterozygous for Mahidol variant. CONCLUSION: Adverse effects of vivax malaria in pregnancy, ineligibility of radical cure for pregnant and postpartum women, and difficulties in diagnosing intermediate levels of G6PD activity multiplied morbidity in this woman. Steps towards meeting the SDG include prevention of malaria in pregnancy, reducing unnecessary exclusion of women from radical cure, and accessible quantitative G6PD screening in P. vivax-endemic settings.


Assuntos
Equidade em Saúde/estatística & dados numéricos , Malária Vivax/epidemiologia , Complicações Parasitárias na Gravidez/epidemiologia , Adolescente , Aminoquinolinas/uso terapêutico , Anemia/tratamento farmacológico , Anemia/etiologia , Antimaláricos/uso terapêutico , Combinação Arteméter e Lumefantrina/uso terapêutico , Feminino , Retardo do Crescimento Fetal/etiologia , Retardo do Crescimento Fetal/terapia , Deficiência de Glucosefosfato Desidrogenase/diagnóstico , Humanos , Recém-Nascido Pequeno para a Idade Gestacional , Transtornos da Lactação/etiologia , Transtornos da Lactação/parasitologia , Malária Vivax/tratamento farmacológico , Malária Vivax/mortalidade , Gravidez , Complicações Parasitárias na Gravidez/tratamento farmacológico , Complicações Parasitárias na Gravidez/mortalidade , Resultado da Gravidez , Primaquina/uso terapêutico
9.
J Trop Pediatr ; 66(3): 284-289, 2020 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-31821472

RESUMO

PURPOSE: Newborn screening is the need of the hour in a developing country like India as there is paucity of data from studies conducted in government hospitals with large sample size. The purpose of the study is to estimate incidence rate and recall rates for five conditions screened in the neonatal period namely congenital hypothyroidism, congenital adrenal hyperplasia, glucose-6-phosphate dehydrogenase (G6PD) deficiency, galactosemia and phenyl ketonuria (PKU). METHODS: The study was conducted at VaniVilas Hospital attached to Bangalore Medical College and Research Institute. A retrospective analysis of the results of newborn screening programme during a 3-year period between January 2016 and December 2018 was done. There were 47 623 livebirths during this period out of which 41 027 babies were screened (coverage-86% of total livebirths). Heelprick samples after 48 h of life and prior to discharge were analysed by quantitative assessment. Neonates having positive screening results were recalled by telephonic call for repeat screening and confirmatory tests. RESULTS: G6PD deficiency was the most common disorder with an incidence of 1:414, followed by congenital hypothyroidism and Congenital Adrenal Hyperplasia with an incidence of 1:2735 and 1:4102, respectively. Galactosemia and PKU were found to be rare in our population. The overall average recall rate was 0.6% which meant that 24 normal newborns were recalled for testing for one confirmed case. The recall rate was relatively higher for galactosemia and G6PD deficiency which was at 0.25% each compared to the other conditions where it was below 0.05%. CONCLUSION: The results of the study emphasize the need for universal newborn screening especially in all government hospitals with large birth cohorts.


Assuntos
Hiperplasia Suprarrenal Congênita/diagnóstico , Hipotireoidismo Congênito/diagnóstico , Galactosemias/diagnóstico , Deficiência de Glucosefosfato Desidrogenase/diagnóstico , Cetose/diagnóstico , Triagem Neonatal/métodos , Hiperplasia Suprarrenal Congênita/epidemiologia , Hipotireoidismo Congênito/epidemiologia , Feminino , Galactosemias/epidemiologia , Deficiência de Glucosefosfato Desidrogenase/epidemiologia , Humanos , Incidência , Índia/epidemiologia , Recém-Nascido , Cetose/epidemiologia , Masculino , Avaliação de Programas e Projetos de Saúde
10.
Sports Health ; 12(2): 149-153, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31603370

RESUMO

CONTEXT: Glucose-6-phosphate dehydrogenase (G6PD) deficiency is likely the most prevalent enzyme deficiency on the planet, with an estimated 4.9% of people, or approximately 330 million individuals, across the globe affected by the disease. In the United States, 4% to 7% of the population is likely affected, but each year our nation's major sport leagues become more international. It is important for medical professionals who treat athletes to understand how this genetic condition can affect the athletes we are working with, especially because exercise in itself results in oxidative stress. EVIDENCE ACQUISITION: PubMed was searched for relevant articles published from 1980 to 2018. The search terms G6PD, athletes, military, and sports were used. STUDY DESIGN: Clinical review. LEVEL OF EVIDENCE: Level 4. RESULTS: Though some case reports suggest a potential impact on athlete safety and performance, controlled studies demonstrate limited impact of exercise on oxidative stress in G6PD-deficient individuals. The care of athletes with G6PD deficiency does not drastically differ from the care of athletes without this condition. Most of the medications and supplements that are regularly given to athletes should not negatively affect their health. CONCLUSION: Although the care of athletes with G6PD deficiency is for the most part no different from the care of other athletes, there are certain situations (visiting areas where malaria is endemic) and medications for which it is important to recognize how your management should change. G6PD deficiency is not regularly screened for but could be considered if an athlete has known sickle cell disease or when traveling to areas where malaria is prevalent. Expanding our knowledge of G6PD deficiency will allow for better care of athletes.


Assuntos
Exercício Físico/fisiologia , Deficiência de Glucosefosfato Desidrogenase/tratamento farmacológico , Deficiência de Glucosefosfato Desidrogenase/fisiopatologia , Esportes/fisiologia , Glucosefosfato Desidrogenase/fisiologia , Deficiência de Glucosefosfato Desidrogenase/diagnóstico , Deficiência de Glucosefosfato Desidrogenase/epidemiologia , Humanos , Estresse Oxidativo
11.
J Oncol Pharm Pract ; 26(2): 492-495, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31260379

RESUMO

INTRODUCTION: Glucose 6-phosphate dehydrogenase (G6PD) is a basic antioxidant pathway for erythrocytes, being its deficiency the most common gene mutation worldwide. As breast cancer is one of the most frequent tumors, many of these patients may present with G6PD deficiency prior treatment without notice. CASE REPORT: We present the case of a woman deficient for G6PD with the diagnosis of Stage IIIB (cT4d cN1 cM0) HER2-enriched early breast cancer. MANAGEMENT AND OUTCOME: The patient underwent neoadjuvance with trastuzumab and anthracycline-free chemotherapy, based on docetaxel (75 mg/m2, 120 mg) and carboplatin (AUC 5, 560 mg). She did not present hemolytic crisis and no blood transfusions were needed. She achieved a good pathologic response and completed one-year adjuvant trastuzumab without incidences. DISCUSSION: Although the role of HER2 and trastuzumab in oxidative stress is not yet completely understood, we suggest that trastuzumab may be a suitable agent for treatment in patients with HER2-enriched breast cancer in a non-oxidative chemotherapy scheme, with acceptable responses and no triggering hemolytic crisis.


Assuntos
Neoplasias da Mama/tratamento farmacológico , Deficiência de Glucosefosfato Desidrogenase/tratamento farmacológico , Terapia Neoadjuvante/métodos , Pós-Menopausa/efeitos dos fármacos , Receptor ErbB-2 , Trastuzumab/administração & dosagem , Idoso , Antineoplásicos Imunológicos/administração & dosagem , Neoplasias da Mama/complicações , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/genética , Feminino , Deficiência de Glucosefosfato Desidrogenase/complicações , Deficiência de Glucosefosfato Desidrogenase/diagnóstico , Humanos , Pós-Menopausa/genética , Receptor ErbB-2/genética , Resultado do Tratamento
12.
J Formos Med Assoc ; 119(1 Pt 1): 69-74, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30979648

RESUMO

BACKGROUND: Nationwide newborn screening for glucose-6-phosphate dehydrogenase (G6PD) deficiency has been implemented in Taiwan since 1987 and the G6PD enzyme activity levels were applied for diagnosis confirmation. As the reference value of G6PD enzyme activity was not available for infants aged 7-90 days, this study was performed to determine the enzyme level in different genotypes. METHODS: Between January 1, 2016 and June 30, 2017, 410 term infants aged 7-90 days old visiting National Taiwan University Hospital Hsinchu branch were enrolled. The comparisons of G6PD enzyme activities among genotype groups were performed. RESULTS: G6PD enzyme activity was negatively correlated with age (R = -0.212, p = 0.01). For infants under 30 days of age, the G6PD enzyme activity levels were 1.4 ± 0.9 U/g Hb in hemizygotes (n = 76), 6.5 ± 2.0 U/g Hb in heterozygotes (n = 47), and 13.6 ± 3.7 U/g Hb in those without G6PD mutations (n = 70). Among infants more than 30 days old, G6PD enzyme activity levels were 0.9 ± 0.5 U/g Hb in hemizygotes (n = 46), 6.0 ± 2.7 U/g Hb in heterozygotes (n = 23), and 11.7 ± 3.4 U/g Hb in those without G6PD mutations (n = 148). G6PD levels differed significantly among the groups defined by genotypes. CONCLUSION: We determined G6PD enzyme activity levels in infants aged between 7 and 90 days in Taiwan. Completing the reference data and determining the cutoff values for different G6PD deficiency disease statuses will help pediatricians to make accurate diagnoses.


Assuntos
Deficiência de Glucosefosfato Desidrogenase/diagnóstico , Deficiência de Glucosefosfato Desidrogenase/metabolismo , Glucosefosfato Desidrogenase/metabolismo , Triagem Neonatal , Feminino , Genótipo , Glucosefosfato Desidrogenase/genética , Deficiência de Glucosefosfato Desidrogenase/genética , Humanos , Lactente , Recém-Nascido , Masculino , Mutação , Valores de Referência , Taiwan
13.
PLoS One ; 14(12): e0226927, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31860695

RESUMO

Neonatal jaundice is a common and severe disease in premature infants with Glucose-6-Phosphate Dehydrogenase (G-6-PD) deficiency. The World Health Organization (WHO) has recommended screening for G-6-PD deficiency in newborns for early recognition as well as to prevent unwanted outcomes in a timely manner. The present study aimed to assess a point-of-care, careSTARTTM G6PD biosensor as a quantitative method for the diagnosis of G-6-PD deficiency. Factors influencing the evaluation of G-6-PD enzyme activity were examined in 40 adults, including ethylenediaminetetraacetic acid (EDTA) anticoagulant, hematocrit concentration, storage temperature and time. Analytic performance of the careSTARTTM G6PD biosensor was evaluated in 216 newborns and compared with fluorescent spot test (FST) and standard quantitative G-6-PD enzyme activity (SGT) assay. The results of factors affecting the G-6-PD enzyme activity showed that the activity determined from finger-prick was not statistically different from venous blood (p = 0.152). The G-6-PD value was highly dependent on the hematocrit and rose with increasing hematocrit concentration. Its activity was stable at 4°C for 3 days. Reliability analysis between the careSTARTTM G6PD biosensor and SGT assay showed a strong correlation with a Pearson's correlation coefficient of 0.82 and perfect agreement by intraclass correlation coefficient (ICC) of 0.90. Analysis of the area under the Receiver Operating Curve (AUC) illustrated that the careSTARTTM G6PD biosensor had 100% sensitivity, 96% specificity, 73% positive predictive value (PPV), 100% negative predictive value (NPV) and 97% accuracy at 30% of residual activity. While the diagnostic ability for identifying G-6-PD deficiency had 78% sensitivity, 89% specificity, 56% positive predictive value (PPV), 96% negative predictive value (NPV) and 88% accuracy when stratified by gender. The careSTARTTM G6PD biosensor is an attractive option as a point-of-care quantitative method for G-6-PD activity detection. Quantification of G-6-PD enzyme activity in newborns is the most effective approach for the management of G-6-PD deficiency to prevent severe jaundice and acute hemolysis.


Assuntos
Técnicas Biossensoriais/métodos , Ensaios Enzimáticos Clínicos/métodos , Deficiência de Glucosefosfato Desidrogenase/diagnóstico , Glucosefosfato Desidrogenase/análise , Testes Hematológicos/métodos , Triagem Neonatal/métodos , Sistemas Automatizados de Assistência Junto ao Leito , Adolescente , Doadores de Sangue , Confiabilidade dos Dados , Feminino , Deficiência de Glucosefosfato Desidrogenase/complicações , Humanos , Recém-Nascido , Icterícia Neonatal/etiologia , Masculino , Sensibilidade e Especificidade , Adulto Jovem
14.
PLoS Med ; 16(12): e1002992, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31834890

RESUMO

BACKGROUND: To reduce the risk of drug-induced haemolysis, all patients should be tested for glucose-6-phosphate dehydrogenase (G6PD) deficiency (G6PDd) prior to prescribing primaquine (PQ)-based radical cure for the treatment of vivax malaria. This systematic review and individual patient meta-analysis assessed the utility of a qualitative lateral flow assay from Access Bio/CareStart (Somerset, NJ) (CareStart Screening test for G6PD deficiency) for the diagnosis of G6PDd compared to the gold standard spectrophotometry (International Prospective Register of Systematic Reviews [PROSPERO]: CRD42019110994). METHODS AND FINDINGS: Articles published on PubMed between 1 January 2011 and 27 September 2019 were screened. Articles reporting performance of the standard CSG from venous or capillary blood samples collected prospectively and considering spectrophotometry as gold standard (using kits from Trinity Biotech PLC, Wicklow, Ireland) were included. Authors of articles fulfilling the inclusion criteria were contacted to contribute anonymized individual data. Minimal data requested were sex of the participant, CSG result, spectrophotometry result in U/gHb, and haemoglobin (Hb) reading. The adjusted male median (AMM) was calculated per site and defined as 100% G6PD activity. G6PDd was defined as an enzyme activity of less than 30%. Pooled estimates for sensitivity and specificity, unconditional negative predictive value (NPV), positive likelihood ratio (LR+), and negative likelihood ratio (LR-) were calculated comparing CSG results to spectrophotometry using a random-effects bivariate model. Of 11 eligible published articles, individual data were available from 8 studies, 6 from Southeast Asia, 1 from Africa, and 1 from the Americas. A total of 5,815 individual participant data (IPD) were available, of which 5,777 results (99.3%) were considered for analysis, including data from 3,095 (53.6%) females. Overall, the CSG had a pooled sensitivity of 0.96 (95% CI 0.90-0.99) and a specificity of 0.95 (95% CI 0.92-0.96). When the prevalence of G6PDd was varied from 5% to 30%, the unconditional NPV was 0.99 (95% CI 0.94-1.00), with an LR+ and an LR- of 18.23 (95% CI 13.04-25.48) and 0.05 (95% CI 0.02-0.12), respectively. Performance was significantly better in males compared to females (p = 0.027) but did not differ significantly between samples collected from capillary or venous blood (p = 0.547). Limitations of the study include the lack of wide geographical representation of the included data and that the CSG results were generated under research conditions, and therefore may not reflect performance in routine settings. CONCLUSIONS: The CSG performed well at the 30% threshold. Its high NPV suggests that the test is suitable to guide PQ treatment, and the high LR+ and low LR- render the test suitable to confirm and exclude G6PDd. Further operational studies are needed to confirm the utility of the test in remote endemic settings.


Assuntos
Testes Diagnósticos de Rotina , Deficiência de Glucosefosfato Desidrogenase/diagnóstico , Glucosefosfato Desidrogenase/genética , Primaquina/uso terapêutico , Testes Diagnósticos de Rotina/métodos , Doenças Endêmicas , Feminino , Deficiência de Glucosefosfato Desidrogenase/tratamento farmacológico , Humanos , Malária/tratamento farmacológico , Malária/epidemiologia , Malária Vivax/epidemiologia , Masculino , Sistemas Automatizados de Assistência Junto ao Leito , Primaquina/efeitos adversos , Sensibilidade e Especificidade
17.
BMC Med ; 17(1): 151, 2019 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-31366382

RESUMO

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.


Assuntos
Anemia Hemolítica/etiologia , Antimaláricos/efeitos adversos , Malária Vivax/complicações , Malária Vivax/tratamento farmacológico , Primaquina/efeitos adversos , Adulto , Cloroquina/uso terapêutico , Feminino , Deficiência de Glucosefosfato Desidrogenase/complicações , Deficiência de Glucosefosfato Desidrogenase/diagnóstico , Hemólise/efeitos dos fármacos , Humanos , Masculino , Pessoa de Meia-Idade , Plasmodium vivax/efeitos dos fármacos
18.
Arch Argent Pediatr ; 117(4): 263-270, 2019 08 01.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-31339274

RESUMO

Glucose-6-phosphate dehydrogenase deficiency is an erythrocyte enzyme disorder caused by mutations in the G6PD gene, which has an X-linked inheritance. Here we analyze the clinical and laboratory characteristics of 24 subjects with G6PD deficiency over 25 years. Their median age at diagnosis was 10.2 years (range: 0.6-56.4). No symptoms were observed in 54.2 % of patients, whereas 25 % had chronic non-spherocytic hemolytic anemia; 12.5 %, neonatal jaundice and postinfectious hemolytic anemia; and 8.3 %, acute hemolytic anemia after ingestion of fava beans. The 24 studied patients had variants that had been previously described in the bibliography. The clinical characteristics observed here were consistent with the variants found. A total of 21 women from the maternal line of affected subjects were identified as deficiency carriers using molecular biology techniques, so they received the corresponding genetic counseling.


Assuntos
Deficiência de Glucosefosfato Desidrogenase/diagnóstico , Deficiência de Glucosefosfato Desidrogenase/genética , Adolescente , Adulto , Argentina , Criança , Pré-Escolar , Feminino , Genótipo , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Fenótipo , Estudos Retrospectivos , Adulto Jovem
19.
Arch Pediatr ; 26(6): 370-373, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31278024

RESUMO

We report the case of a neonate with a new, previously undescribed, glucose-6-phosphate dehydrogenase (G6PD) gene mutation, which was revealed by severe cholestasis, hyperbilirubinemia, and transient liver dysfunction. The severity of the clinical phenotype with ongoing chronic hemolytic anemia suggests that this mutation belongs to class 1 G6PD deficiency. The hemizygous mutation «c.675G>c; p.Trp225Cys¼ was detected by genomic sequencing. Since severe G6PD deficiency can be revealed by cholestasis, it is important to check G6PD enzyme activity when faced with a case of liver dysfunction in the neonatal period.


Assuntos
Colestase/etiologia , Deficiência de Glucosefosfato Desidrogenase/diagnóstico , Glucosefosfato Desidrogenase/genética , Insuficiência Hepática/etiologia , Mutação , Colestase/diagnóstico , Marcadores Genéticos , Deficiência de Glucosefosfato Desidrogenase/complicações , Deficiência de Glucosefosfato Desidrogenase/genética , Insuficiência Hepática/diagnóstico , Humanos , Recém-Nascido , Masculino
20.
Int J Med Sci ; 16(5): 623-629, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31217728

RESUMO

Purpose: Age-related macular degeneration (AMD) is the leading cause of blindness in the elderly in Western Countries. Evidence indicates that Glucose-6-Phosphate Dehydrogenase (G6PD) deficiency, a common genetic abnormality, may protect against ischemic heart and cerebrovascular disease, ocular vascular disorders, and colorectal cancer. This study was undertaken to ascertain whether G6PD deficiency may protect against AMD. Materials and Methods: 79 men with late-stage AMD and 79 male, age-matched cataract controls without AMD were recruited in March-December 2016. Smoking status, clinical history, and drug use were recorded. A blood sample was taken from each participant. Complete blood count, hemoglobin, glucose, creatinine, cholesterol, triglycerides, transaminases, bilirubin, and erythrocyte G6PD activity were measured. Stepwise logistic regression was used to investigate the association between G6PD deficiency and AMD. Results: G6PD deficiency was found in 7 (8.9%) AMD patients and 8 (10.1%) controls, a not statistically significant difference. Stepwise logistic regression disclosed that AMD was significantly associated with increased diastolic blood pressure (OR=1.09, 95% CI=1.03-1.15, P=0.02) and LDL-cholesterol (OR=1.02, 95% CI=1.0001-1.03, P=0.049) and lower values of white blood cell (WBC) count (OR=0.71, 95% CI=0.56-0.88, P=0.02) and aspartate aminotransferase (AST) (OR=0.92, 95% CI=0.85-0.99, P=0.044). Conclusion: Results suggest that G6PD deficiency has no protective effect on nor is a risk factor for AMD. Larger studies are necessary to confirm whether increased diastolic blood pressure and LDL-cholesterol and lower values of WBC count and AST are risk factors for AMD.


Assuntos
Catarata/metabolismo , Deficiência de Glucosefosfato Desidrogenase/epidemiologia , Degeneração Macular/metabolismo , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Catarata/epidemiologia , Catarata/genética , Glucosefosfato Desidrogenase/genética , Glucosefosfato Desidrogenase/metabolismo , Deficiência de Glucosefosfato Desidrogenase/complicações , Deficiência de Glucosefosfato Desidrogenase/diagnóstico , Humanos , Itália/epidemiologia , Degeneração Macular/epidemiologia , Degeneração Macular/genética , Masculino , Pessoa de Meia-Idade , Fatores de Risco
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