Glucose-6-phosphate Dehydrogenase Status Research Articles

The effect of single low-dose primaquine treatment for uncomplicated Plasmodium falciparum malaria on haemoglobin levels in Ethiopia: a longitudinal cohort study

BackgroundTo interrupt residual malaria transmission and achieve successful elimination of Plasmodium falciparum in low-transmission settings, the World Health Organization (WHO) recommends the administration of a single dose of 0.25 mg/kg (or 15 mg/kg for adults) primaquine (PQ) combined with artemisinin-based combination therapy (ACT), without glucose-6-phosphate dehydrogenase (G6PD) testing. However, due to the risk of haemolysis in patients with G6PD deficiency (G6PDd), PQ use is uncommon. Thus, this study aimed to assess the safety of a single low dose of PQ administered to patients with G6PD deficiency.MethodsAn observational cohort study was conducted with patients treated for uncomplicated P. falciparum malaria with either single-dose PQ (0.25 mg/kg) (SLD PQ) + ACT or ACT alone. Microscopy-confirmed uncomplicated P. falciparum malaria patients visiting public health facilities in Arjo Didessa, Southwest Ethiopia, were enrolled in the study from September 2019 to November 2022. Patients with uncomplicated P. falciparum malaria were followed up for 28 days through clinical and laboratory diagnosis, such as measurements of G6PD levels and haemoglobin (Hb) concentrations. G6PD levels were measured by a quantiative CareSTART™ POCT S1 biosensor machine. Patient interviews were also conducted, and the type and frequency of clinical complaints were recorded. Hb data were taken on days (D) 7, 14, 21, and 28 following treatment with SLD-PQ + ACT or ACT alone.ResultsA total of 249 patients with uncomplicated P. falciparum malaria were enrolled in this study. Of these, 83 (33.3%) patients received ACT alone, and 166 (66.7%) received ACT combined with SLD-PQ treatment. The median age of the patients was 20 (IQR 28–15) years. G6PD deficiency was found in 17 (6.8%) patients, 14 males and 3 females. There were 6 (7.2%) and 11 (6.6%) phenotypic G6PD-deficient patients in the ACT alone and ACT + SLD-PQ arms, respectively. The mean Hb levels in patients treated with ACT + SLD-PQ were reduced by an average of 0.45 g/dl (95% CI = 0.39 to 0.52) in the posttreatment phase (D7) compared to a reduction of 0.30 g/dl (95% CI = 0.14 to − 0.47) in patients treated with ACT alone (P = 0.157). A greater mean Hb reduction was observed on day 7 in the G6PDd ACT + SLD-PQ group (− 0.60 g/dL) than in the G6PDd ACT alone group (− 0.48 g/dL); however, there was no statistically significant difference (P = 0.465). Overall, D14 losses were 0.10 g/dl (95% CI = − 0.00 to 0.20) and 0.05 g/dl (95% CI = − 0.123 to 0.22) in patients with and without SLD-PQ, respectively (P = 0.412).ConclusionsThis study’s findings indicate that using SLD-PQ in combination with ACT is safe for uncomplicated P. falciparum malaria regardless of the patient's G6PD status in Ethiopian settings. Caution should be taken in extrapolating this finding in other settings with diverse G6DP phenotypes.

Glucose-6-Phosphate Dehydrogenase Levels and Oxidative Stress Markers Among Cancer Patients in Jos, Nigeria

Glucose-6-phosphate dehydrogenase (G6PD) is a sensitive cytosolic antioxidant enzyme that could be associated with carcinogenesis. Hence, its plasma levels are a good indicator to monitor cancer-induced cellular stress. This study aimed to determine the correlation between Glucose-6-phosphate dehydrogenase and oxidative stress markers among cancer patients in Jos, Nigeria. This case-control study involved 100 subjects (60 cancer patients and 40 healthy control subjects). Their blood samples were collected to measure the levels of G6PD and oxidative stress markers (malondialdehyde, total plasma peroxide, total antioxidant potential, and oxidative stress indices). Twenty-four (40.0%) of the cancer patients were G6PD deficient. Of this, 13 (54.2%) were females G6PD. Of the G6PD deficient cancer patients, 11(45.8%) were male, conversely, 16 (44.4%) of the cancer subjects who had normal G6PD were males. Of the cancer patients, 26.7%; 13.3%, 11.7 % and 10% had prostate, breast cancer, chronic lymphocytic leukemia (CLL), and hepatocellular carcinoma (HCC), respectively were the most frequent. There was no significant association between G6PD deficiency and cancer (<I>X<sup>2</sup></I>=0.025, <i>p</i>=0.804). Among G6PD deficiency cancer patients, the oxidative stress markers were significantly (<i>p<</i>0.05) higher compared to the control group. These findings showed that relatively more of the cancer patients had normal G6PD status even in increased cellular oxidative stress which could be due to host genetic factors. This suggests the need for further experiments on molecular characterization of mechanisms responsible for the findings.

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

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. 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. 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. 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. Brazilian Ministry of Health, Municipal and State Health Secretariats; Fiocruz; Medicines for Malaria Venture; Bill & Melinda Gates Foundation; Newcrest Mining; and the UK Government. For the Portuguese translation of the abstract see Supplementary Materials section.

Functional effects of an African glucose-6-phosphate dehydrogenase (G6PD) polymorphism (Val68Met) on red blood cell hemolytic propensity and post-transfusion recovery.

Donor genetic variation is associated with red blood cell (RBC) storage integrity and post-transfusion recovery. Our previous large-scale genome-wide association study demonstrated that the African G6PD deficient A- variant (rs1050828, Val68Met) is associated with higher oxidative hemolysis after cold storage. Despite a high prevalence of X-linked G6PD mutation in African American population (>10%), blood donors are not routinely screened for G6PD status and its importance in transfusion medicine is relatively understudied. To further evaluate the functional effects of the G6PD A- mutation, we created a novel mouse model carrying this genetic variant using CRISPR-Cas9. We hypothesize that this humanized G6PD A- variant is associated with reduced G6PD activity with a consequent effect on RBC hemolytic propensity and post-transfusion recovery. G6PD A- RBCs had reduced G6PD protein with ~5% residual enzymatic activity. Significantly increased in vitro hemolysis induced by oxidative stressors was observed in fresh and stored G6PD A- RBCs, along with a lower GSH:GSSG ratio. However, no differences were observed in storage hemolysis, osmotic fragility, mechanical fragility, reticulocytes, and post-transfusion recovery. Interestingly, a 14% reduction of 24-h survival following irradiation was observed in G6PD A- RBCs compared to WT RBCs. Metabolomic assessment of stored G6PD A- RBCs revealed an impaired pentose phosphate pathway (PPP) with increased glycolytic flux, decreasing cellular antioxidant capacity. This novel mouse model of the common G6PD A- variant has impaired antioxidant capacity like humans and low G6PD activity may reduce survival of transfused RBCs when irradiation is performed.

Prevalence and molecular heterogeneity of glucose-6-phosphate dehydrogenase (G6PD) deficiency in the Senoi Malaysian Orang Asli population.

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is an X-linked genetic disorder characterized by reduced G6PD enzyme levels in the blood. This condition is common in populations exposed to malaria; an acute febrile disease caused by Plasmodium parasites. G6PD-deficient individuals may suffer from acute hemolysis following the prescription of Primaquine, an antimalarial treatment. The population at risk for such a condition includes the Senoi group of Orang Asli, a remote indigenous community in Malaysia. This study aimed to elucidate the G6PD molecular heterogeneity in this subethnic group which is important for malaria elimination. A total of 662 blood samples (369 males and 293 females) from the Senoi subethnic group were screened for G6PD deficiency using a quantitative G6PD assay, OSMMR2000-D kit with Hb normalization. After excluding the family members, the overall prevalence of G6PD deficiency in the studied population was 15.2% (95% CI: 11-19%; 56 of 369), with males (30 of 172; 17.4%) outnumbering females (26 of 197; 13.2%). The adjusted male median (AMM), defined as 100% G6PD activity, was 11.8 IU/gHb. A total of 36 participants (9.6%; 26 male and 10 female) were deficient (<30% of AMM) and 20 participants (5.4%; 4 male and 16 female) were G6PD-intermediate (30-70% of AMM). A total of 87 samples were genotyped, of which 18 showed no mutation. Seven mutations were found among 69 genotyped samples; IVS11 T93C (47.1%; n = 41), rs1050757 (3'UTR +357A>G)(39.1%; n = 34), G6PD Viangchan (c.871G>A)(25.3%; n = 22), G6PD Union (c.1360C>T)(21.8%; n = 19), c.1311C>T(20.7%; n = 18), G6PD Kaiping (c.1388G>A)(8.0%; n = 7), and G6PD Coimbra (c.592C>T)(2.3%; n = 2). Our analysis revealed 27 hemizygote males, 18 heterozygote females, 7 homozygote females, and 2 compound heterozygote females. This study confirms the high prevalence of G6PD deficiency among the Senoi Malaysian Orang Asli, with a significant degree of molecular heterogeneity. More emphasis should be placed on screening for G6PD status and proper and safe use of Primaquine in the elimination of malaria among this indigenous population.

Molecular Characterization of Erythrocyte Glucose-6-Phosphate Dehydrogenase Deficiency in Different Ethnic Groups of Blood Donors in Mauritania.

Glucose-6-phosphate-dehydrogenase (G6PD) deficiency is the most frequent enzymopathy worldwide; it is a genetic disorder that affects red blood cells and causes hemolysis. Here, we conducted a study on G6PD-deficient subjects in Mauritania to evaluate the molecular characteristics associated with a deficiency in this enzyme and the frequency of nucleotide polymorphisms in the glucose-6-phosphate dehydrogenase gene. A total of 943 blood samples were collected from blood donors (803 males and 140 females; 364 white Moors; 439 black Moors; 112 Pulaar; 18 Wolof; 10 Soninke). All blood samples were analyzed using a rapid screening test. G6PD status was analyzed quantitatively by the Randox G6PD test. Samples deficient in G6PD were extracted from the whole blood samples and subjected to DNA genotyping. The most frequent G6PD variants were determined by two molecular techniques: restriction fragment length polymorphism (RFLP) and multiplex PCR using the GENESPARK G6PD African kit. A total of six single nucleotide polymorphisms (SNPs) (G202A, A376G, A542T, G680T, C563T, and T968C) were identified. The prevalence of G6PD deficiency in this population sample was 8.1%. The most common mutation was A376G/202A and was characterized by the G6PD A-phenotype, which is more common in the G6PD-deficient black Moors population. The wilaya in Nouakchott was the most affected among the 13 wilayas studied. This study shows, for the first time, the presence of the G680T mutation.

G6PD testing and radical cure for Plasmodium vivax in Cambodia: A mixed methods implementation study.

IntroductionCambodia aims to eliminate malaria by 2025, however tackling Plasmodium vivax (P.v) presents multiple challenges. The prevalence of glucose-6-phosphate dehydrogenase (G6PD) deficiency has prevented the deployment of 8-aminoquinolones for “radical cure”, due to the risk of severe haemolysis. Patients with P. vivax have therefore continued to experience recurrent relapses leading to cumulative health and socioeconomic burden. The recent advent of point of care testing for G6PD deficiency has made radical cure a possibility, however at the time of the study lack of operational experience and guidance meant that they had not been introduced. This study therefore aimed to design, implement and evaluate a new care pathway for the radical cure of P.vivax.MethodsThis implementation study took place in Pursat province, Western Cambodia. The interventions were co-developed with key stakeholders at the national, district, and local level, through a continuous process of consultations as well as formal meetings. Mixed methods were used to evaluate the feasibility of the intervention including its uptake (G6PD testing rate and the initiation of primaquine treatment according to G6PD status); adherence (self-reported); and acceptability, using quantitative analysis of primary and secondary data as well as focus group discussions and key informant interviews.ResultsThe co-development process resulted in the design of a new care pathway with supporting interventions, and a phased approach to their implementation. Patients diagnosed with P.v infection by Village Malaria Workers (VMWs) were referred to local health centres for point-of-care G6PD testing and initiation of radical cure treatment with 14-day or 8-week primaquine regimens depending on G6PD status. VMWs carried out follow-up in the community on days 3, 7 and 14. Supporting interventions included training, community sensitisation, and the development of a smartphone and tablet application to aid referral, follow-up and surveillance. The testing rate was low initially but increased rapidly over time, reflecting the deliberately cautious phased approach to implementation. In total 626 adults received G6PD testing, for a total of 675 episodes. Of these 555 occurred in patients with normal G6PD activity and nearly all (549/555, 98.8%) were initiated on PQ14. Of the 120 with deficient/intermediate G6PD activity 61 (50.8%) were initiated on PQ8W. Self-reported adherence was high (100% and 95.1% respectively). No severe adverse events were reported. The pathway was found to be highly acceptable by both staff and patients. The supporting interventions and gradual introduction were critical to success. Challenges included travel to remote areas and mobility of P.v patients.ConclusionThe new care pathway with supporting interventions was highly feasible with high levels of uptake, adherence and acceptability in this setting where high prevalence of G6PD deficiency is high and there is a well-established network of VMWs. Scaling up of the P.v radical cure programme is currently underway in Cambodia and a decline in reduction in the burden of malaria is being seen, bringing Cambodia a step closer to elimination.

Genotype-phenotype association and biochemical analyses of glucose-6-phosphate dehydrogenase variants: Implications for the hemolytic risk of using 8-aminoquinolines for radical cure.

Background: Plasmodium vivax remains the malaria species posing a major threat to human health worldwide owing to its relapse mechanism. Currently, the only drugs of choice for radical cure are the 8-aminoquinolines (primaquine and tafenoquine), which are capable of killing hypnozoites and thus preventing P. vivax relapse. However, the therapeutic use of primaquine and tafenoquine is restricted because these drugs can cause hemolysis in individuals with glucose-6-phosphate dehydrogenase (G6PD) deficiency. This study aimed to assess and understand the hemolytic risk of using 8-aminoquinolines for radical treatment in a malaria endemic area of Thailand. Methods: The prevalence of G6PD deficiency was determined using a quantitative test in 1,125 individuals. Multiplexed high-resolution meltinging (HRM) assays were developed and applied to detect 12 G6PD mutations. Furthermore, biochemical and structural characterization of G6PD variants was carried out to understand the molecular basis of enzyme deficiency. Results: The prevalence of G6PD deficiency was 6.76% (76/1,125), as assessed by a phenotypic test. Multiplexed HRM assays revealed G6PD Mahidol in 15.04% (77/512) of males and 28.38% (174/613) of females, as well as G6PD Aures in one female. G6PD activity above the 30% cut-off was detected in those carrying G6PD Mahidol, even in hemizygous male individuals. Two variants, G6PD Murcia Oristano and G6PD Songklanagarind + Viangchan, were identified for the first time in Thailand. Biochemical characterization revealed that structural instability is the primary cause of enzyme deficiency in G6PD Aures, G6PD Murcia Oristano, G6PD Songklanagarind + Viangchan, and G6PD Chinese 4 + Viangchan, with double G6PD mutations causing more severe enzyme deficiency. Conclusion: In western Thailand, up to 22% of people may be ineligible for radical cure. Routine qualitative tests may be insufficient for G6PD testing, so quantitative tests should be implemented. G6PD genotyping should also be used to confirm G6PD status, especially in female individuals suspected of having G6PD deficiency. People with double G6PD mutations are more likely to have hemolysis than are those with single G6PD mutations because the double mutations significantly reduce the catalytic activity as well as the structural stability of the protein.

DIAGNOSTIC ACCURACY COMPARISON OF THE QUANTITATIVE POINT-OF-CARE ECO G6PD AND BREWERS TEST FOR ASSESSMENT OF G6PD DEFICIENCY IN INFECTIOUS DISEASES

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is an X-linked, hereditary condition caused by mutations in the G6PD gene, that results in protein variants with different enzyme activity levels. G6PD provides reducing power to NADPH (reduced form of nicotinamide adenine dinucleotide phosphate). NADPH effect is critical in red blood cells (RBC) due to the absence of a nucleus. Clinical manifestations are usually mild and are induced by an exogenous agent, such as drugs, infections, or dietary (fava beans). The G6PD deficiency diagnosis is crucial in infectious diseases because both infections and treatment can induce acute hemolysis. Rarely, life-threatening cases can require transfusions of RBC and hemodialysis. The gold standard for the measurement of G6PD activity is a quantitative UV spectrophotometric assay, however, it is inaccessible in most cases. Methemoglobin reduction test (Brewer's test) is a qualitative spot test most used for G6PD deficiency screening, but is imprecise, requires a cold chain, some laboratory infrastructure, trained personnel, and is time-costing. Point-of-care (POC) is a simple and fast semi-quantitative test that is becoming increasingly important when a prompt diagnosis is required and in health care of out-of-reach communities. To compare the diagnostic accuracy of the quantitative POC ECO and Brewers test for assessment of G6PD deficiency. A cross-sectional diagnostic accuracy study was enrolled between May 2020 and December 2021 at the Instituto Nacional de Infectologia Evandro Chagas, Fundação Oswaldo Cruz. Individuals older than 17 years old with a suspicious diagnosis of an infectious disease were eligible. 125 convenience blood samples were tested to compare concordance analysis between Brewers test and POC STANDARD G6PD. The exclusion criteria were hemoglobin concentration < 7.0 g/dL due to technical device limitations. A total of 125 subjects (38 females and 87 males) were recruited. The median age was 42.0 years (range 18–76) in females and 45.0 years (range 19–78) in males. The median of G6PD activity was 7.1 U/g Hb (0.2-17.5). We observed a trend of concordance between the G6PD status (deficient or normal), with low frequencies of discordances in the screenings. The strength of agreement between G6PD tests was classified as almost perfect in all participants (k = 0.82, IC95% = 0.66,0.97) and in subgroups female (k = 0.83, IC95% = 0.59,1.00) and male (k = 0.81, IC95% = 0.59,1.00). The total concordance percentage (number of concordances/total) was 95% in females, 97% in males, and 96% in all participants. Here, we demonstrate POC ECO G6PD test could be performed during medical consultation, guiding the most appropriate therapy almost immediately. In addition to saving time and having comparable results to Brewer's test, it could be performed even in remote areas and with scarce resources, dispensing minimum laboratory requirements. Our findings will be of value to diagnose conditions that could have life-threatening consequences if not timely recognized, such as before initiating primaquine for the treatment of malaria. Therefore, it can improve healthcare in vulnerable isolated communities. We observed a high concordance result between Brewers test and POC STANDARD G6PD, which is becoming the reference test to diagnose G6PD deficiency worldwide.

Safety of single-dose primaquine as a Plasmodium falciparum gametocytocide: a systematic review and meta-analysis of individual patient data

BackgroundIn 2012, the World Health Organization (WHO) recommended single low-dose (SLD, 0.25 mg/kg) primaquine to be added as a Plasmodium (P.) falciparum gametocytocide to artemisinin-based combination therapy (ACT) without glucose-6-phosphate dehydrogenase (G6PD) testing, to accelerate malaria elimination efforts and avoid the spread of artemisinin resistance. Uptake of this recommendation has been relatively slow primarily due to safety concerns.MethodsA systematic review and individual patient data (IPD) meta-analysis of single-dose (SD) primaquine studies for P. falciparum malaria were performed. Absolute and fractional changes in haemoglobin concentration within a week and adverse effects within 28 days of treatment initiation were characterised and compared between primaquine and no primaquine arms using random intercept models.ResultsData comprised 20 studies that enrolled 6406 participants, of whom 5129 (80.1%) had received a single target dose of primaquine ranging between 0.0625 and 0.75 mg/kg. There was no effect of primaquine in G6PD-normal participants on haemoglobin concentrations. However, among 194 G6PD-deficient African participants, a 0.25 mg/kg primaquine target dose resulted in an additional 0.53 g/dL (95% CI 0.17–0.89) reduction in haemoglobin concentration by day 7, with a 0.27 (95% CI 0.19–0.34) g/dL haemoglobin drop estimated for every 0.1 mg/kg increase in primaquine dose. Baseline haemoglobin, young age, and hyperparasitaemia were the main determinants of becoming anaemic (Hb < 10 g/dL), with the nadir observed on ACT day 2 or 3, regardless of G6PD status and exposure to primaquine. Time to recovery from anaemia took longer in young children and those with baseline anaemia or hyperparasitaemia. Serious adverse haematological events after primaquine were few (9/3, 113, 0.3%) and transitory. One blood transfusion was reported in the primaquine arms, and there were no primaquine-related deaths. In controlled studies, the proportions with either haematological or any serious adverse event were similar between primaquine and no primaquine arms.ConclusionsOur results support the WHO recommendation to use 0.25 mg/kg of primaquine as a P. falciparum gametocytocide, including in G6PD-deficient individuals. Although primaquine is associated with a transient reduction in haemoglobin levels in G6PD-deficient individuals, haemoglobin levels at clinical presentation are the major determinants of anaemia in these patients.Trial registrationPROSPERO, CRD42019128185

Clinical analysis of the characteristics of patients diagnosed with hemolytic anemia induced by hepatitis E viral infection

The extrahepatic manifestations of hepatitis E virus (HEV) infection include hemolytic anemia. However, the clinical characteristics of HEV-induced hemolytic anemia have been only sporadically reported in case reports, and there is a scarcity of relevant systematic reviews. The aim of the current study was to analyze and summarize the clinical characteristics of patients diagnosed with HEV-induced hemolytic anemia. This study included 1 patient diagnosed with HEV-induced hemolytic anemia who was admitted to our hospital and 19 additional patients identified through the available literature. Of the 20 patients included in this study, the majorities were from China and India (12 and 6 cases, respectively); furthermore, 13 of them were men and 7 were women, with an average age of 35 (16–56) years. The highest total bilirubin level was 646 (452–913) μmol/L, highest alanine aminotransferase level was 1335 (708–2798) IU/L, and lowest hemoglobin level was 6.0 ± 2.0 g/dL. Additionally, 10 patients (50.0%, 10/20) underwent the glucose-6-phosphate dehydrogenase (G6PD) activity test, and all of them were diagnosed with G6PD deficiency (100.0%, 10/10). Finally, 18 patients (90.0%) recovered and 2 died (10.0%) after treatment. Most of the patients with HEV-induced hemolytic anemia recovered with treatment. Acute HEV infection that causes hemolytic anemia is strongly associated with the G6PD status of the patients.

Impact of pre-emptive rapid testing for glucose-6-phosphate dehydrogenase deficiency prior to rasburicase administration at a tertiary care centre: A retrospective study.

Glucose-6-phosphate dehydrogenase (G6PD) deficiency, the most common enzymopathy in humans, can cause acute haemolysis resulting from exposure to certain medications, chemicals, infections and fava beans. Rasburicase, used to manage elevated uric acid levels in the oncologic emergency of tumour lysis syndrome, is one such drug. The US Food and Drug Administration (FDA) recommends testing of G6PD status prior to rasburicase administration for patients at higher risk for G6PD deficiency. We performed a retrospective chart review of all oncology patients for whom a semi-quantitative biochemical test for detecting G6PD deficiency was performed prior to rasburicase administration over a 2.5-year period, in a large academic metropolitan hospital. We identified 16 out of 260 tested individuals as G6PD-deficient (6.1%), including six females. On average, test results were electronically available to health care providers within 4hours of sample collection, with most results available within 2-3hours. Four G6PD-deficient patients developed elevated uric acid levels. Two of the G6PD-deficient patients were treated with rasburicase, and subsequently developed haemolysis, which was appropriately managed. In summary, by providing information about G6PD status with a rapid turnaround time, we have taken a significant step towards personalized medicine in our institution. In spite of the test implementation, two out of four G6PD-deficient patients, who were no longer candidates for rasburicase use, still received the drug, highlighting the need for improved provider education.

Neonatal jaundice in Ghanaian children: Assessing maternal knowledge, attitude, and perceptions.

BackgroundNeonatal jaundice (NNJ) is a major cause of preventable childhood mortality and long-term impairment especially in countries with significant prevalence of the inherited condition, glucose-6-phosphate dehydrogenase (G6PD) defect. In Ghana, routine screening of pregnant women for G6PD defect is standard care. Prevention of poor health outcomes from NNJ is contingent on population health literacy and early diagnosis. As part of a project to evaluate a screening tool for NNJ, we assessed the knowledge, attitude, and perceptions of Ghanaian mothers on NNJ at baseline.MethodsUsing a cross-sectional design, mothers attending antenatal and postnatal clinics at 3 selected health facilities in 2 geographical regions of Ghana were interviewed. Data on mothers’ understanding, perceptions, beliefs, and actions towards NNJ were evaluated. Chi-square test was used to determine the association between selected maternal characteristics and knowledge, attitude, and perception to NNJ.ResultsOf the 504 mothers interviewed, 428(85.4%) had heard about NNJ, 346 (68.7%) said the earliest signs are seen in the eyes, 384(76.2%) knew NNJ may be harmful and 467(92.7%) recommended seeking healthcare for the jaundiced newborn. None of the women knew about G6PD or their G6PD status following antenatal screening. Most did not know the signs/symptoms of severe NNJ. Of the 15 mothers who had had a jaundiced neonate, cost was the most perceived (8 out of 15) barrier to accessing health care. There were significant associations (p-value ≤ 0.05) between maternal age, educational level, and knowledge of NNJ.ConclusionDespite the high level of awareness of NNJ, gaps still exit in the knowledge, attitudes and perceptions of mothers concerning NNJ. Improving education of women about the causes, symptoms/signs, and the role of G6PD in severe NNJ is recommended. Addressing barriers to accessing healthcare for the jaundiced infant may enhance timely management of NNJ and reduce the associated complications and mortality.

Association between Glucose-6-Phosphate Dehydrogenase Deficiency and Asthma

Background: Among the determinants contributing to the pathogenesis of asthma, antioxidant genetic factors play a leading role. Glucose-6-phosphate dehydrogenase (G6PD) is an enzyme that is competent to detoxify free radicals. Although a relationship between G6PD deficiency and asthma has been previously reported, the literature is still scanty. In this study, we test this hypothesis in a large cohort of patients from Sardinia, Italy. Methods: A retrospective case–control study was performed using data from 11,829 clinical records of outpatients referred to a teaching hospital for a medical visit. In total, 455 cases (asthma-positive) and 11,374 controls (asthma-negative) were compared for G6PD status using multivariable analysis, adjusting for all covariates. Results: Overall, G6PD deficiency was detected in 11.2% of study participants and was associated with an increased risk of asthma (odds ratio (OR) 1.63; 95% confidence interval (CI) 1.27–2.10). Additional variables significantly associated with asthma were female sex (OR 1.66; 95% CI 1.34–2.06), overweight/obesity (OR 1.56; 95% CI 1.27–1.92), smoking (OR 1.44; 95% CI 1.449–3.963), and high socioeconomic status (OR 1.40; 95% CI 1.16–1.70), whereas age was inversely related with asthma (OR 0.49; 95% CI 0.39–0.61). Conclusions: Our study shows that G6PD deficiency is an independent risk for asthma. These findings suggest that G6PD should be assessed in asthmatic patients for better risk stratification.

G6PD diaxBox: Digital image-based quantification of G6PD deficiency

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common enzymopathy in humans. More than 400 million people worldwide are affected by this genetic condition. Testing for G6PD deficiency before drug administration is essential for patient safety. Rapidly ascertaining the G6PD status of a person is desirable for proper treatment. The device described in this study, the G6PD diaxBOX, was developed to quantify G6PD deficiency using paper-based analytical devices (PADs) and a colorimetric assay. The G6PD diaxBOX is a straightforward, affordable, portable, and instrument-free analytical system. The major components of the G6PD diaxBox are a banknote-checking UV fluorescent lamp and camera that are easy to access and analysis software. When NADPH is generated, it absorbs at UV 340 nm and emits colored light that is detected with the camera. The determined Pearson's coefficient shows that the color intensity measured from the G6PD diaxBOX correlated with G6PD activity level. Also, a Bland-Altman analysis indicated that more than 95% of the measurement error was in the upper and lower boundaries (±2 SD) and the error from the severe and moderate deficiency group was less than ± 1 SD. Therefore, the error from G6PD diaxBOX was within the limit boundary and the overall accuracy was more than 80%. The G6PD diaxBOX facilitates the effective and efficient quantification of G6PD deficiency and as such represents a clinically well-suited, rapid point-of-care test.

Cell-Derived Microparticles in Blood Products from Blood Donors Deficient in Glucose-6-Phosphate Dehydrogenase.

To quantitate the microparticles (MPs) in whole blood and blood products obtained from blood donors who are deficient in glucose-6-phosphate dehydrogenase (G6PD). The current study analyzed whole blood and blood components prepared from 49 blood donors with G6PD deficiencies and 98 with G6PD-normal results. Packed red blood cells (PRBCs), platelet concentrate (PC), and plasma were prepared according to transfusion laboratory procedures. MP concentrations were determined using a flow cytometer. Blood components prepared from donors with G6PD deficiency were characterized by higher red blood cell-derived MP (RMP) concentration in PRBCs (25,526 vs 18,738 particles/µL) but lower concentrations of platelet-derived MPs (PMPs; in whole blood and PC), leukocyte-derived MPs (LMP; in whole blood and plasma) and total MP (in PC), compared with those from donors with G6PD-normal test results. These results suggest that differences in G6PD status may account for variation in RMP levels during processing.

472 G6PD deficiency is associated with decreased maternal serum Alpha-fetoprotein levels

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is an inherited X-linked recessive disorder, being the most common enzymatic defect of erythrocytes in humans. Since G6PD deficiency has been associated with metabolic comorbidities and placental dysfunction, we aimed to examine whether this disorder can affect the levels of maternal serum biochemical screening markers. For this retrospective study, we collected data of all pregnant women delivering in our medical center between January 2015 to December 2019. The inclusion criteria were any documentation of maternal serum biochemical screening markers: free beta-human chorionic gonadotropin (HCG), pregnancy-associated plasma protein A (PAPP-A), maternal serum alpha-fetoprotein (AFP), HCG and unconjugated estriol. Overall, 6,186 women with documented maternal serum biochemical screening markers were detected, 63 of these (1.0%) with G6PD deficiency. No difference in demographic or obstetrical characteristics was noted between G6PD-deficient women to the remaining cohort (including maternal age, body mass index, gestational age and birth weight). In G6PD-deficient women, significantly lower levels of maternal AFP were found compared to the remaining cohort (0.87±0.28 vs. 1.05±0.28 multiples of median, respectively, p<0.001, Table 1). In addition, marginally lower second trimester HCG levels were found in G6PD deficiency (1.0±0.58 vs. 1.15±0.69 multiples of median in the remaining cohort, p=0.07). Since the placenta plays a major role in HCG synthesis, as well as in transferring the fetal AFP to maternal circulation, the placental effects of G6PD deficiency may explain lower levels of these markers. As maternal serum AFP measurement serves as a screening tool for neural tube defects, as well as a component of biochemical screening for Down syndrome, G6PD status may affect the screening results. Thus, the findings of our study may be of great importance in prenatal surveillance, and should be further explored.

Assessment of serum aflatoxin B1 levels in neonatal jaundice with glucose-6-phosphate dehydrogenase deficiency: a preliminary study.

Aflatoxin (AF) contamination of food products is still a major health issue globally. Prior studies suggest that exposure to AFs during pregnancy has harmful fetal outcomes. This preliminary study was designed to assess serum AFB1 levels in neonatal jaundice (NNJ) secondary to glucose-6-phosphate dehydrogenase (G6PD) deficiency. Twenty-four full-term neonates with hemolytic jaundice secondary to G6PD deficiency were enrolled in the study. Erythrocyte G6PD status was assessed colorimetrically, and serum aflatoxin B1 (AFB1) concentrations were measured by high-performance liquid chromatography. The results revealed that AFB1 was detected in 58% (14/24) of the studied newborns while detected in 75% (18/24) of their mothers. AFB1 positive cases had a highly significantly lower birthweight and G6PD activity (P=0.001, each). Birthweight (r=-0.574, P=0.032) and G6PD activity (r=-0.585, P=0.028) negatively correlated with serum AFB1 levels while serum alanine aminotransferase activity positively correlated with serum AFB1 levels (r=0.536, P=0.048). Maternal AFB1 exposure is associated with adverse birth outcomes as verified by the low birthweight and the evident decline in the activity of G6PD enzyme with the resultant hemolytic NNJ.

COVID-19 reveals redox vulnerabilities in two minority groups

The COVID-19 pandemic spread rapidly throughout the world, but some populations were more affected than others. For example, compared to other groups, a higher morbidity and mortality was documented in African Americans and individuals of Mediterranean descent. These populations are marked by both increased prevalence of glucose-6-phosphate dehydrogenase (G6PD) deficiency, and lower utilization of angiotensin receptor blockers/angiotensin converting enzyme inhibitors in the treatment of hypertension. In this brief report, we suggest that G6PD status should be assessed in all COVID-19 positive individuals belonging to the two ethnic groups. If detected, N-acetylcysteine should be utilized to lower the oxidative burden and “sartans” should be prescribed as first-line therapy in hypertensive individuals.

Wide range of G6PD activities found among ethnic groups of the Chittagong Hill Tracts, Bangladesh.

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.