Glucose-6-phosphate Dehydrogenase Screening Research Articles

Controversies in our understanding of extreme hyperbilirubinemia in glucose-6-phosphate dehydrogenase-deficient neonates.

Despite declarations that kernicterus should be a "never-event", the condition continues to occur, glucose-6-phosphate dehydrogenase (G6PD)-deficiency being a leading cause. In this paper, we address some controversies regarding the pathophysiology and the potential for extreme hyperbilirubinemia associated with G6PD-deficiency. We present evidence to demonstrate that G6PD-deficiency-associated neonatal hyperbilirubinemia is no longer limited to countries and geographic regions to which the condition was indigenous, but is also encountered in North America and other Western countries with a low inherent G6PD-deficiency frequency. Pathophysiologically, while a diminished bilirubin conjugative component is undoubtedly present, we present evidence that there is a component of increased hemolysis as well, contributing to the extreme, exponential hyperbilirubinemia associated with G6PD-deficiency. Extreme hyperbilirubinemia in G6PD heterozygotes, while less frequent than in male hemizygotes or female deficient homozygotes, has been reported, suggesting previous underestimation of the risks of heterozygosity. Universal neonatal screening for G6PD-deficiency, while not expected to prevent acute, episodic hyperbilirubinemia, should increase awareness, thereby facilitating earlier referral for treatment, prior to the onset of bilirubin encephalopathy. Finally, we speculate as to what the future looks like for babies with G6PD-deficiency, potential therapeutic stratagems, and the effect of G6PD-deficiency on medical conditions beyond the realm of neonatal hyperbilirubinemia. IMPACT STATEMENTS: G6PD-deficiency is encountered in North America and Western countries previously thought to have a low frequency of the condition. Extreme, sudden neonatal hyperbilirubinemia is due, in the main, to increased hemolysis, an independent risk factor for neurotoxicity. Extreme hyperbilirubinemia may follow apparently resolved neonatal hyperbilirubinemia which had been treated by phototherapy. Female G6PD heterozygotes, previously thought to be unaffected clinically by G6PD-deficiency, while at low risk, may, nevertheless, develop extreme hyperbilirubinemia. Universal neonatal G6PD screening should be aimed towards increasing caretaker awareness and facilitating referral for treatment prior to the onset of bilirubin encephalopathy.

Tafenoquine following G6PD screening versus primaquine for the treatment of vivax malaria in Brazil: A cost-effectiveness analysis using a transmission model.

Malaria transmission modelling has demonstrated the potential impact of semiquantitative glucose-6-phosphate dehydrogenase (G6PD) testing and treatment with single-dose tafenoquine for Plasmodium vivax radical cure but has not investigated the associated costs. This study evaluated the cost-effectiveness of P. vivax treatment with tafenoquine after G6PD testing using a transmission model. We explored the cost-effectiveness of using tafenoquine after G6PD screening as compared to usual practice (7-day low-dose primaquine (0.5 mg/kg/day) without G6PD screening) in Brazil using a 10-year time horizon with 5% discounting considering 4 scenarios: (1) tafenoquine for adults only assuming 66.7% primaquine treatment adherence; (2) tafenoquine for adults and children aged >2 years assuming 66.7% primaquine adherence; (3) tafenoquine for adults only assuming 90% primaquine adherence; and (4) tafenoquine for adults only assuming 30% primaquine adherence. The incremental cost-effectiveness ratios (ICERs) were estimated by dividing the incremental costs by the disability-adjusted life years (DALYs) averted. These were compared to a willingness to pay (WTP) threshold of US$7,800 for Brazil, and one-way and probabilistic sensitivity analyses were performed. All 4 scenarios were cost-effective in the base case analysis using this WTP threshold with ICERs ranging from US$154 to US$1,836. One-way sensitivity analyses showed that the results were most sensitive to severity and mortality due to vivax malaria, the lifetime and number of semiquantitative G6PD analysers needed, cost per malaria episode and per G6PD test strips, and life expectancy. All scenarios had a 100% likelihood of being cost-effective at the WTP threshold. The main limitations of this study are due to parameter uncertainty around our cost estimates for low transmission settings, the costs of G6PD screening, and the severity of vivax malaria. In our modelling study that incorporated impact on transmission, tafenoquine prescribed after a semiquantitative G6PD testing was highly likely to be cost-effective in Brazil. These results demonstrate the potential health and economic importance of ensuring safe and effective radical cure.

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

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

Cut-off values for diagnosis of G6PD deficiency by flow cytometry in Thai population

In heterozygous females, X-inactivation causes a change in glucose-6-phosphate dehydrogenase (G6PD) activity from normal to deficient. Most G6PD screening tests are used to accurately diagnose hemizygous males, but they are less reliable for diagnosing heterozygous females. This study established flow cytometric cut-off values for screening of G6PD deficiency in hemizygous males and heterozygous or homozygous females. We studied 205 (125 females, 80 males) leftover blood samples from quantitative methemoglobin reduction (MR) screening. G6PD gene mutations determined by multiplex amplification refractory mutation system-polymerase chain reaction and direct DNA sequencing were used as the gold standard reference. Accuracy of the test, including the sensitivity, specificity, and positive and negative predictive values, was analyzed using MedCalc software. The optimal cut-off values for classification of %red blood cells with normal G6PD activity or %bright cells into homozygous normal, heterozygous, and homozygous deficiency in females were 85.4–100%, 6.3–85.3%, and 0–6.2%, respectively (sensitivity 93.2%, specificity 100%). The cut-offs for classification into hemizygous normal and hemizygous deficiency in males were 76.5–100% and 0–76.4%, respectively (sensitivity 100%, specificity 96.5%). Flow cytometry can be used to differentiate heterozygous females with intermediate phenotype from homozygous females, but cannot distinguish between heterozygous females with extreme phenotype and homozygous females. By flow cytometry, heterozygous and homozygous deficiency was detected in 29.6% and 3.2% of females, respectively. Among males, hemizygous deficiency was found in 31.3%. Flow cytometry can be used to screen patients with G6PD deficiency, and reliably and efficiently identify heterozygous and homozygous females, and hemizygous males based on cellular G6PD activity.

Nitrofurantoin and glucose-6-phosphate dehydrogenase deficiency: a safety review.

Nitrofurantoin, a broad-spectrum antibiotic available since 1953, is used widely for the treatment of urinary tract infections as it often retains activity against drug-resistant uropathogens. It is contraindicated in pregnant women at term, and in neonates. Like trimethoprim/sulfamethoxazole, nitrofurantoin carries a warning for patients with known sensitivity to oxidant drugs, notably glucose-6-phosphate dehydrogenase (G6PD) deficiency, in whom it may cause haemolytic anaemia. This is a barrier to uptake in tropical regions where there is a high burden of antimicrobial resistance and where G6PD deficiency is common. Early studies of erythrocyte survival following nitrofurantoin suggest it is less likely to cause oxidant haemolysis in individuals with G6PD deficiency than primaquine. Here we review reports of haemolysis associated with nitrofurantoin from the published literature and from USA (FDA Adverse Event Reporting System; FAERS) and European (VigiBase) pharmacovigilance databases. In total, 318 episodes of haemolytic anaemia were reported and 10 deaths, with 42 (13%) in individuals with confirmed or highly probable G6PD deficiency, out of at least 245 million exposures. A causal link between death and exposure was not reported and a precise risk estimation in G6PD-deficient individuals was not possible as there are few reports from regions where this enzymopathy is most prevalent. The evidence suggests a total daily dose of 200 mg nitrofurantoin may be used for short (3–5 day) course urinary tract infection treatment without G6PD screening when accompanied by appropriate advice. Pharmacovigilance in countries with high prevalence of G6PD-deficiency is recommended to monitor for serious adverse events.

Prevalence of Glucose-6-Phosphate Dehydrogenase (G6PD) Deficiency among Malaria Patients in Southern Thailand: 8 Years Retrospective Study

Erythrocytes deficient in glucose-6-phosphate dehydrogenase (G6PD) is more susceptible to oxidative damage from free radical derived compounds. The hemolysis triggered by oxidative agents such as primaquine (PQ) is used for the radical treatment of hypnozoites of P. vivax. Testing of G6PD screening before malaria treatment is not a common practice in Thailand, which poses patients at risk of hemolysis. This retrospective study aimed to investigate the prevalence of G6PD in malaria patients who live in Southern Thailand. Eight hundred eighty-one malaria patients were collected for 8-year from 2012 to 2019, including 785 (89.1%) of P. vivax, 61 (6.9%) of P. falciparum, 27 (3.1%) of P. knowlesi, and 8 (0.9%) of mixed infections. The DiaPlexC genotyping kit (Asian type) and PCR-RFLP were employed to determine the G6PD variants. The result showed that 5 different types of G6PD variants were identified in 26 cases (2.9%); 12/26 (46.2%) had Mahidol (487G>A) and 11/26 (42.3%) had Viangchan (871G>A) variants, while the rest had Kaiping (1388G>A), Union (1360C>T), and Mediterranean (563C>T) variants. G6PD Songklanagarind (196T>A) variant was not found in the study. Our result did not show a significant difference in the malaria parasite densities in patients between G6PD-deficient and G6PD-normal groups. According to our findings, testing G6PD deficiency and monitoring the potential PQ toxicity in patients who receive PQ are highly recommended.

Prevalence of Glucose-6-phosphate Dehydrogenase Deficiency in Aligarh, India: A Pilot Study

Introduction: Deficiency of glucose-6-phosphate dehydrogenase (G6PD) enzyme in erythrocytes is among the prevalent X-linked recessive genetic disorders and affects approximately 400 million people across the globe. It causes neonatal hyperbilirubinemia, also hemolysis eventually leading to hemolytic anemia when exposed to oxidative stress. Purpose: The purpose of the study was to find out the prevalence of G6PD deficiency in Aligarh (Western Uttar Pradesh) India. Materials and Methods: The data and samples were collected from a total of 106 individuals. All the required information were recorded in a standardized questionnaire, blood was taken with their prior consent. Blood typing test and fluorescent spot test (FST) were performed, spots were arranged accordingly and observed. Results: Out of total 106 individuals surveyed, 10% of them were found to be deficient for G6PD enzyme, 5% were intermediate, and 85% were normal. Significant association was found for G6PD deficiency and gender (P < 0.05) of the individuals while non-significant association were reported for G6PD deficiency and consanguinity (P < 0.8) and for G6PD deficiency and blood groups (P < 0.9). Conclusion: FST is a good method for G6PD screening and detecting the deficiency in fields. This pilot study highlights the prevalence of G6PD enzymopathy in Aligarh and will help government programs of this area to prevent and control the genetic disorder

Global economic costs due to vivax malaria and the potential impact of its radical cure: A modelling study.

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. 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. 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.

A novel point-of-care device for measuring glucose-6-phosphate dehydrogenase enzyme deficiency

Extreme hyperbilirubinemia can cause bilirubin neurotoxicity. Infants with glucose-6-phosphate dehydrogenase (G6PD) deficiency can develop hemolysis and thus are at high risk. We evaluated a device that quantitatively measures G6PD activity kinetically using digital microfluidics (DMF). Intra- and inter-instrument and -day imprecision (CVs) were first assessed. G6PD activity in 86 samples was then measured and compared between DMF and 2 reference methods. Overall DMF reproducibility was 3.8% over 5 days by 2 operators on 2 instruments. Mean intra- and inter-instrument variabilities were 3.6% and 3.9%, respectively (n = 28), with a user variability of 4.3%. Mean G6PD activity was 6.40±4.62 and 6.37±4.62 U/g hemoglobin for DMF and Reference Methods 1 (n = 46) and 12.15±3.86 and 11.48±1.55 for DMF and 2 (n = 40), respectively, and strongly correlated (r = 0.95 and 0.95) with mean biases of +0.04±2.90 and +0.67±1.55 for methods 1 and 2, respectively. The novel device could be used for early newborn G6PD screening.

A Study on the Relevance of Glucose-6-Phosphate Dehydrogenase Level Screening in Patients with Rheumatic Diseases Prior to Initiating Treatment With Hydroxychloroquine.

ObjectiveDrug-induced hemolytic anemia can occur in patients with glucose-6-phosphate-dehydrogenase (G6PD) deficiency. The practice of G6PD-deficiency screening in the rheumatology field has been inconsistent. This study aimed to determine the utility of screening prior to the initiation of hydroxychloroquine and/or sulfasalazine in rheumatology patients in the ambulatory clinics at Stony Brook University Hospital, New York.MethodsWe conducted a retrospective chart review of cases of rheumatic diseases that were screened for G6PD deficiency at Stony Brook University Hospital ambulatory clinics. Demographic details and relevant clinical and laboratory data of the patients were collected. The data from similar studies in the literature were searched for and reviewed.ResultsThis study consisted of 228 patients with systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), and Sjögren’s syndrome. Among those patients, 94.7% received hydroxychloroquine, sulfasalazine, or dapsone; 41% (89/228) of patients were screened for G6PD deficiency, and the majority of them were on treatment with hydroxychloroquine. Of those patients, 7.9% (five Caucasians and two African Americans) were found to have G6PD deficiency, and two of the G6PD-deficient patients received hydroxychloroquine. There was no incidence of hemolytic anemia documented in any of the seven patients with G6PD deficiency. We reviewed the literature and found three similar studies of patients receiving hydroxychloroquine with no reported hemolytic anemia from different medical centers in the US, and the frequency of G6PD deficiency reported in these studies was 1.4%, 4.0%, and 4.2%, respectively.ConclusionsOur study suggests that the frequency of G6PD deficiency in our rheumatic population is similar to that of the general population, and the risk of hemolytic anemia in G6PD deficiency associated with hydroxychloroquine is extremely rare. Hence, G6PD screening may not be recommended prior to starting treatment with hydroxychloroquine.

Glucose-6-phosphate dehydrogenase deficiency and stroke outcomes.

To assess the risk of glucose-6-phosphate dehydrogenase (G6PD) on stroke prognosis, we compared outcomes between patients with stroke with and without G6PD deficiency. The study recruited 1,251 patients with acute ischemic stroke. Patients were individually categorized into G6PD-deficiency and non-G6PD-deficiency groups according to G6PD activity upon admission. The primary endpoint was poor outcome at 3 months defined by a modified Rankin Scale (mRS) score ≥2 (including disability and death). Secondary outcomes included the overall mRS score at 3 months and in-hospital death and all death within 3 months. Logistic regression and Cox models, adjusted for potential confounders, were fitted to estimate the association of G6PD deficiency with the outcomes. Among 1,251 patients, 150 (12.0%) were G6PD-deficient. Patients with G6PD deficiency had higher proportions of large-artery atherosclerosis (odds ratio [OR] 1.53, 95% confidence interval [CI] 1.09-2.17) and stroke history (OR 1.93, 95% CI 1.26-2.90) compared to the non-G6PD-deficient group. The 2 groups differed significantly in the overall mRS score distribution (adjusted common OR 1.57, 95% CI 1.14-2.17). Patients with G6PD deficiency had higher rates of poor outcome at 3 months (adjusted OR 1.73, 95% CI 1.08-2.76; adjusted absolute risk increase 13.0%, 95% CI 2.4%-23.6%). The hazard ratio of in-hospital death for patients with G6PD-deficiency was 1.46 (95% CI 1.37-1.84). G6PD deficiency is associated with the risk of poor outcome at 3 months after ischemic stroke and may increase the risk of in-hospital death. These findings suggest the rationality of G6PD screening in patients with stroke.

Cost-Effectiveness Analysis of Sex-Stratified Plasmodium vivax Treatment Strategies Using Available G6PD Diagnostics to Accelerate Access to Radical Cure.

.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.

The modified G6PD deficiency screening test

Glucose-6-phosphate dehydrogenase (G6PD) deficiency, which involves the mutation of the G6PD gene on the X chromosome, is the most common enzyme defect in humans. G6PD produces nicotinamide adenine dinucleotide phosphate (NADPH) for red blood cell protection from oxidative stress. Oxidative stress-induced red blood cell hemolysis in G6PD-deficient patients leads to anemia, jaundice, acute renal failure, and kernicterus in newborns. Currently, the fluorescent spot test (FST) is widely used for G6PD deficiency screening. This test detects NADPH production under UV light. This study purposed to modify the G6PD deficiency screening test based on NADPH production and the ability to detect the results of the color change in the color of the reaction. Blood samples of 60 subjects were collected and screened for G6PD deficiency using FST method. All samples were tested with the modified G6PD screening test and the quantitative assay kit. The results from the modified test showed the color red for normal cases, whereas the color brown indicated G6PD deficiency cases. The cutoff value of G6PD activity detected by the quantitative method was less than 2.9 U/gHb for G6PD deficiency. The precision of this study was 100 %. The results of sensitivity, specificity, negative predictive value (NPV), and positive predictive value (PPV) of the modified test were 100 %, 96.7 %, 100 %, and 96.7 %, respectively. The modified G6PD screening test can be used for the screening of G6PD deficiency in newborns, for support through providing more information, and for self-protection from oxidative stress.

Vivax malaria in pregnancy and lactation: a long way to health equity

BackgroundThe 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 presentationA 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.ConclusionAdverse 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.

Ispitivanje i upoređivanje troškova G6PD enzimskog skrining testa za novorođenu decu u odnosu na troškove lečenja pacijenata sa favizmom hospitalizovanih usled hemolize

Objective. We compared the glucose-6-phosphate dehydrogenase (G6PD) deficiency screening costs in neonates and treatment costs for patients with favism who were referred to the government hospitals of Isfahan with acute hemolysis. Methods. In this retrospective study, 116 patients with favism were selected, and their clinical data and treatment costs were recorded in Iranian Rials (IRR) and United States Dollars (USD). The costs of neonatal G6PD screening tests were estimated based on quantitative and qualitative screening kits by referring to each hospital's laboratories. Approximately 84760 births occurred in Isfahan province from October 2014 to October 2015. Results. Based on our results, 73 patients (62.9%) were males, and 43 of them (37.1%) were females. The causes for hemolysis were the consumption of broad beans in 78.4%, infection in 19.8%, and drugs (erythromycin and sodium cephalothin) in 1.7% of patients. The majority of patients (46.6%) received a single blood transfusion, and 18.9% received two or more transfusions, while 34.5% had received no blood transfusions. The mean and standard deviation of patients' medical expenses were 7,472,005±7,329,847 IRR (276.74±271.47 USD). The total cost of treatment for patients was 869,162,324 IRR (32,191.19 USD). The screening cost for all newborns from October 2014 to October 2015 with qualitative kits was 754,364,000 IRR (27,939.40 USD) and with the quantitative kits was 960,330,800 IRR (35,567.80 USD). Conclusion. The costs of the qualitative screening test for G6PD deficiency are lower than the costs of treatments of favism patients in Isfahan.

Clinical Spectrum of Primaquine-induced Hemolysis in Glucose-6-Phosphate Dehydrogenase Deficiency: A 9-Year Hospitalization-based Study From the Brazilian Amazon.

Despite glucose-6-phosphate dehydrogenase (G6PD) deficiency prevalence of 5% in the Amazon, primaquine is administered without G6PD screening. This is an important cause of hospitalization among Plasmodium vivax-infected individuals, leading to life-threatening anemia and acute renal failure across endemic areas. In Manaus, the frequency of primaquine-induced hemolysis was 85.2 cases per 100 000 primaquine users.

Mutation of glucose-6-phosphate dehydrogenase deficiency in Chinese Han children in eastern Fujian.

We aim to investigate the mutation types of glucose-6-phosphate dehydrogenase (G6PD) deficiency in Chinese Han children in eastern Fujian Province.A total of 904 Chinese Han neonates (male: 733 with positive G6PD deficiency and 28 with weakly positive deficiency; female: 73 with positive G6PD deficiency and 70 with weakly positive deficiency) received G6PD screening in our center from January 2014 to December 2016 were included in this study. Additionally, 904 age-matched normal Chinese Han individuals (male: 761; female: 143) were selected as control. Neonatal G6PD deficiency screening was performed through blood sample collection from the heels, using the commercial kits. Multicolor melting curve analysis (MMCA) method was used to determine the G6PD mutation type in the 904 cases. If it failed to detect mutations in the cases with abnormal enzyme activity, the polymerase chain reaction (PCR) and gene sequencing were used to determine the mutation sites. PCR and gene sequencing were used to determine the mutation sites in the 904 individuals with normal enzyme activity. Three most common mutation types in Chinese population were compared between Fujian and other provinces.Among the 904 neonates with abnormal G6PD enzyme activity, 17 mutation types were detected including 15 single point mutations and 7 complex mutations. Three most common mutation types were c.1376G > T, c.1388G > A, and c.95A > G accounted for 72.6% of the total mutations in eastern Fujian.The proportion of mutational types in G6PD and the degree of enzyme activity change in various mutational types were found in the neonates of Fujian Province. Our study may enrich the molecular diagnosis of G6PD deficiency meaning Fujian Province.

Hyperbilirubinemia management in neonates <2000 g screened for glucose-6-phosphate dehydrogenase deficiency in a tertiary neonatal unit

Background: Prematurity and glucose-6-phosphate dehydrogenase (G6PD) deficiency are considered important risk factors in neonatal hyperbilirubinemia. G6PD screening is performed by many neonatal units to identify this risk factor. Few studies evaluated the role of this screening on the management of hyperbilirubinemia in preterm infants during their neonatal hospitalization. This study aims to evaluate effects of G6PD screening on treatment of hyperbilirubinemia in infants <2000 g admitted to Neonatal Intensive Care Unit. Methods: All neonates <2000 g who were admitted to neonatal unit for 3 years (2013–2015) were retrospectively included in the study. Data related to risk factors and management of hyperbilirubinemia were collected and analyzed on these infants. A number of phototherapy units used for treatment, duration phototherapy, and level of bilirubin were compared between G6PD deficient and nondeficient infants and presented. Results: Included in this retrospective study were 621 infants. About half on included infants were < 1500 g. Gestational age groups as follow: ≤28 weeks, 23.3%; 29–32 weeks, 37.5%; 33–36 weeks, 33.6%; and ≥37 weeks, 5.6%. Prevalence of G6PD deficiency was 10.3%. The highest recorded serum bilirubin was significantly higher in G6PD deficient group compared with nondeficient one (161.6 μmol/l ± 57.5 vs. 145.4 μmol/l ± 46.4, P = 0.01). G6PD deficient infants were treated with more phototherapy than nondeficient group (85.9% vs. 64.5%, P < 0.001). G6PD deficient low birth weight neonates were more likely to receive intensive phototherapy. None of the G6PD deficient patients was treated with exchange transfusion. Conclusion: Prevalence of G6PD deficiency among low birth weight infant in the United Arab Emirates is similar to data reported in full-term infants. Screening for G6PD in preterm infant is associated with more treatment using phototherapy and may contribute in preventing severe hyperbilirubinemia.

Expanding the clinical and genetic spectrum of G6PD deficiency: The occurrence of BCGitis and novel missense mutation

Glucose-6-phosphate dehydrogenase (G6PD) is a key enzyme in the pentose phosphate pathway that ensures sufficient production of coenzyme nicotinamide adenine dinucleotide phosphate (NADPH) by catalyzing the reduction of NADP+ to NADPH. Noteworthy, the latter mediates the production of reactive oxygen species (ROS) by phagocytic cells such as neutrophils and monocytes. Therefore, patients with severe forms of G6PD deficiency may present impaired NADPH oxidase activity and become susceptible to recurrent infections. This fact, highlights the importance to characterize the immunopathologic mechanisms underlying the susceptibility to infections in patients with G6PD deficiency. Here we report the first two cases of G6PD deficiency with Bacille Calmette-Guérin (BCG) adverse effect, besides jaundice, hemolytic anemia and recurrent infections caused by Staphylococcus aureus. The qualitative G6PD screening was performed and followed by oxidative burst analysis using flow cytometry. Genetic and in silico analyses were carried out by Sanger sequencing and mutation pathogenicity predicted using bioinformatics tools, respectively. Activated neutrophils and monocytes from patients displayed impaired oxidative burst. The genetic analysis revealed the novel missense mutation c.1157T>A/p.L386Q in G6PD. In addition, in silico analysis indicated that this mutation is pathogenic, thereby hampering the oxidative burst of neutrophils and monocytes from patients. Our data expand the clinical and genetic spectrum of G6PD deficiency, and suggest that impaired oxidative burst in this severe primary immune deficiency is an underlying immunopathologic mechanism that predisposes to mycobacterial infections.

National G6PD neonatal screening program in Gaza Strip of Palestine: rationale, challenges and recommendations.

Congenital genetic disorders affecting neonates or young children can have serious clinical consequences if undiagnosed and left untreated. Early detection and an accurate diagnosis are, therefore, of major importance for preventing negative patient outcomes. Even though the occurrence of each specific metabolic disorder may be rare, their collective impact of preventable complications may be of considerable importance to the public health. Our previous studies showed that glucose-6-phosphate dehydrogenase (G6PD) deficiency is a problem of public health importance that has been shown to be a predominant cause of acute hemolytic anemia requiring hospitalization in Palestinian young children in Gaza Strip. Intriguingly, the majority of these children had one of the three variants, Mediterranean(c.) (563T) , African G6PD A-(c.) (202A) (/c.) (376G) and heretofore unrecognized as a common G6PD-deficient variant G6PD Cairo(c.) (404C) . The high prevalence of G6PD deficiency, as well as dietary factors in the region that precipitate anemia, argues for a need to protect the Palestinian children from a treatable and manageable genetic and metabolic disorder. This work reviews and discusses rationales and challenges of G6PD screening program in Gaza Strip. We advocate adopting a national neonatal G6PD screening program in Gaza Strip to identify children at risk and promote wellness and health for Palestine.