PO 8609 PREVALENCE AND RISK FACTORS FOR GLUCOSE-6-PHOSPHATE DEHYDROGENASE (G6PD) DEFICIENCY IN TWO P. VIVAX MALARIA-ENDEMIC AREAS IN SUDAN

BackgroundPlasmodium vivax malaria is a major health problem in Sudan and the parasite has become widely distributed in the recent years. The WHO recommends the use of primaquine as radical cure for liver dormant stage, the hypnozoite. However, prior its use, a test for Glucose-6-phosphate Dehydrogenase (G6PD) should be performed. The objective of the current study was to determine prevalence and risk factors for G6PD deficiency in two P. vivax malaria-endemic areas in Sudan.MethodsA cross-sectional study recruiting 557 subjects from two malaria-endemic areas in Sudan was conducted. Demographic data and blood samples were collected. G6PD activity was measured by spectrometry using SPINREACT enzymatic-UV kit.ResultsThe measured G6PD activities for both sites ranged from 0.6 to 37.7 U/g Hb, with a median value of 12.8 U/g Hb. There was a significant difference in enzyme activity by study site (p<0.001), but not by sex (p=0.91). Overall, across the two study sites, 22 (3.9%) is G6PDd (<30%). Prevalence of G6PDd (<30%) in Khartoum is 1.8% (4/230) compared to 4.8% (16/327) in New Hafla. In univariate analysis predictors of G6PDd were study site (odds ratio of G6PD activity <3.8, Khartoum relative to New Halfa=0.22 (95% CI: 0.08 to 0.66), p=0.006), and recent antibiotic use (OR=2.45 (95% CI: 1.1 to 5.5), p=0.027). In multivariate analysis, the only factor that was significant was the individual’s weight in kilograms, with an OR of 0.97 (95% CI 0.95 to 0.99, p=0.014).ConclusionG6PD deficiency is less prevalent among Sudanese population and this indicates that the use of primaquine for radical cure of P. vivax malaria is safe.

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Determining Quantitative Diagnostic Test Cut-off in G6PD Heterozygous Women for Tafenoquine Therapy

10.21203/rs.2.19598/v1 ◽

2019 ◽

Author(s):

Maria Swastika ◽

Alida R Harahap ◽

Lydia V Panggalo ◽

Sri Widia A Jusman ◽

Ari W Satyagraha

Keyword(s):

G6pd Deficiency ◽

Ex Vivo ◽

Strong Association ◽

G6pd Activity ◽

Main Function ◽

Ex Vivo Model ◽

Stress Markers ◽

Oxidative Markers ◽

Significant Difference ◽

Glucose 6 Phosphate Dehydrogenase

Abstract Background Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common enzyme disorder in the world. Its main function is to generate NADPH that is required for anti-oxidative pathway in the cells especially in red blood cells (RBC). G6PD deficiency is X-linked and thus subject to random X-chromosome inactivation in women giving them mosaic expression of G6PD activities in their individual cells. This phenomenon makes it difficult for diagnosis with the currently available G6PD qualitative diagnostic tests. With the rolling out of newly marketed anti-malarial drug tafenoquine which has a long half-life, screening for G6PD deficiency becomes a necessity where those with <70% G6PD activity cannot receive this drug. Thus, evidence for a quantitative cut-off for G6PD activity is needed to ensure safe drug administration.Methods RBC models were developed to analyze the effect of oxidant on RBC oxidative markers namely total glutathione (GSH) and malondialdehyde (MDA). G6PD activity was measured using quantitative assay from Trinity Biotech and was correlated with cytofluorometric assay. RBC from G6PD heterozygous women with different G6PD activities were also analyzed for comparison.Results There was a negative correlation between G6PD activity and CuCl concentration and a strong association between G6PD activities and proportion of G6PD normal RBC in CuCl-treated models and in ex vivo RBC. However, in terms of oxidative stress markers analyses, unlike the hypothesis where the lower G6PD activity, the higher MDA and the lower GSH level, our CuCl RBC model showed that in low G6PD activities (10-30%) cells, the MDA level is lower compared to the rest of the models (p<0.05). Our ex vivo model however were in line with the hypothesis, although the result was not significant (p=0.5). There was a significant difference between RBC with <60% and those with >80% G6PD activities in CuCl RBC model but not in ex vivo RBC (p=0.5). Genotyping heterozygous subjects showed G6PD Viangchan variant with 2.97 U/g Hb (33% activity) and 6.58 U/g Hb (74% activity).Conclusions The MDA and GSH analyses have pointed to the 60% G6PD activity cut-off. This provides an evidence of possible cut-off for tafenoquine administration in G6PD heterozygous women.

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The impact of using primaquine without prior G6PD testing: a case series describing the obstacles to the medical management of haemolysis

Wellcome Open Research ◽

10.12688/wellcomeopenres.15100.2 ◽

2019 ◽

Vol 4 ◽

pp. 25 ◽

Cited By ~ 2

Author(s):

Cindy S. Chu ◽

Germana Bancone ◽

Nay Lin Soe ◽

Verena I. Carrara ◽

Gornpan Gornsawun ◽

...

Keyword(s):

Health Care Providers ◽

G6pd Deficiency ◽

Case Series ◽

Radical Cure ◽

Care Providers ◽

Medical Treatments ◽

Normal Individuals ◽

High Index Of Suspicion ◽

Glucose 6 Phosphate Dehydrogenase ◽

The Impact

Radical cure of Plasmodium vivax malaria in glucose-6-phosphate dehydrogenase (G6PD) deficient individuals employs weekly primaquine dosing. This is the only recommended regimen for this patient sub-group. If national malaria programs mandate daily primaquine dosing (the recommended regimen for G6PD normal individuals), then G6PD testing before prescription is necessary to avoid iatrogenic haemolysis in G6PD deficient individuals. In this case series, two P. vivax infected patients with unknown G6PD status from two different countries were prescribed primaquine as per national malaria program guidelines. During treatment both patients presented to the clinic with symptoms of anaemia after taking primaquine incorrectly. The clinical management of the iatrogenic severe haemolysis that occurred in these patients demonstrates the various adverse effects primaquine can cause, that other common medical treatments also have haemolytic potential, and how the diagnosis of G6PD deficiency can be elusive during acute haemolysis. Health care providers should provide careful instructions about primaquine dosing, be watchful for haemolysis, and have a high index of suspicion for G6PD deficiency in the presence of haemolysis if the G6PD status is previously unknown.

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Prevalence and associated factors for Pterygium in Han and Mongolian adults: across-sectional study in inner Mongolian, China

10.21203/rs.2.196/v1 ◽

2019 ◽

Author(s):

Yuhan Wang ◽

Guangliang Shan ◽

Linyang Gan ◽

Yonggang Qian ◽

Ting Chen ◽

...

Keyword(s):

Risk Factors ◽

Protective Factors ◽

Rural Areas ◽

Inner Mongolia ◽

Univariate Analysis ◽

Education Level ◽

Study Cohort ◽

Sectional Study ◽

Factors Associated ◽

Significant Difference

Abstract Background: To investigate the prevalence of and factors associated with pterygium in Han and Mongolian adults at four survey sites in Inner Mongolia, China. Methods: A population-based, cross-sectional study was conducted. Using a stratified sampling method, we eventually included 2,651 participants of at least30 years of age from a total of 3,468 eligible residents. Factors associated with pterygium were analysed using univariate analysis and logistic regression models. Results: There were 1,910 Han adults and 741 Mongolian adults included in this study. The mean± standard deviation of age for individuals in the study cohort was 48.93±11.06 years. The overall prevalence of pterygium was 6.4% (n=169), and the prevalences of bilateral and unilateral pterygium were 1.4% (n=38) and 4.8% (n=128), respectively. The most common grade of pterygium was Grade 2. After univariate analysis, eleven factors were considered in a multivariate analysis. The results indicated that age (P<0.001), education level (P<0.001), outdoor occupation (P=0.026), and time spent in rural areas (P<0.001) were significantly associated with pterygium, whereas gender and ethnicity were not risk factors. In subgroup analysis, BMI≥28 was a protective factor for Han individuals (OR 0.42, 95% CI 0.21-0.81, P=0.01), but a risk factor for Mongolian individuals (OR 2.39, 95% CI 1.02-5.58, P=0.044). The BF% in Han and Mongolian individuals had significant difference (P<0.001). Conclusions: Our results indicated that an outdoor occupation, old age and time spent in rural areas are risk factors for pterygium in Inner Mongolia. Living near an urban survey site (Hohhot and Tsining District) and having a higher education level are protective factors for pterygium. Ethnicity, gender, smoking, diabetes and high blood pressure are not associated with pterygium. Different dietary structures in Han and Mongolian adults may lead to different fat content of body and therefore contributes to the prevalence of pterygium. Keywords: Pterygium, prevalence, Han and Mongolian, risk factors, protective factors

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Protective effect of Mediterranean-type glucose-6-phosphate dehydrogenase deficiency against Plasmodium vivax malaria

eLife ◽

10.7554/elife.62448 ◽

2021 ◽

Vol 10 ◽

Author(s):

Ghulam R Awab ◽

Fahima Aaram ◽

Natsuda Jamornthanyawat ◽

Kanokon Suwannasin ◽

Watcharee Pagornrat ◽

...

Keyword(s):

Protective Effect ◽

Plasmodium Vivax ◽

G6pd Deficiency ◽

Vivax Malaria ◽

Malaria Incidence ◽

Large Population ◽

Credible Interval ◽

Radical Cure ◽

Plasmodium Vivax Malaria ◽

Glucose 6 Phosphate Dehydrogenase

X-linked glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common human enzymopathy. The severe Mediterranean variant (G6PD Med) found across Europe and Asia is thought to confer protection against malaria, but its effect is unclear. We fitted a Bayesian statistical model to observed G6PD Med allele frequencies in 999 Pashtun patients presenting with acute Plasmodium vivax malaria and 1408 population controls. G6PD Med was associated with reductions in symptomatic P. vivax malaria incidence of 76% (95% credible interval [CI], 58–88) in hemizygous males and homozygous females combined and 55% (95% CI, 38–68) in heterozygous females. Unless there is very large population stratification within the Pashtun (confounding these results), the G6PD Med genotype confers a very large and gene-dose proportional protective effect against acute vivax malaria. The proportion of patients with vivax malaria at risk of haemolysis following 8-aminoquinoline radical cure is substantially overestimated by studies measuring G6PD deficiency prevalence in healthy subjects.

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Retrospective analysis of LNM risk factors and the effect of chemotherapy in early colorectal cancer: A Chinese multicenter study

BMC Cancer ◽

10.1186/s12885-020-07363-6 ◽

2020 ◽

Vol 20 (1) ◽

Author(s):

Chunyan Zeng ◽

Dandan Xiong ◽

Fei Cheng ◽

Qingtian Luo ◽

Qiang Wang ◽

...

Keyword(s):

Colorectal Cancer ◽

Risk Factors ◽

Multicenter Study ◽

Tumor Size ◽

Lymphovascular Invasion ◽

Univariate Analysis ◽

Tumor Location ◽

Early Colorectal Cancer ◽

Depth Of Invasion ◽

Significant Difference

Abstract Background Estimating the risk of lymph node metastasis (LNM) is crucial for determining subsequent treatments following curative resection of early colorectal cancer (ECC). This multicenter study analyzed the risk factors of LNM and the effectiveness of postoperative chemotherapy in patients with ECC. Methods We retrospectively analyzed the data of 473 patients with ECC who underwent general surgery in five hospitals between January 2007 and October 2018. The correlations between LNM and sex, age, tumor size, tumor location, endoscopic morphology, pathology, depth of invasion and tumor budding (TB) were directly estimated based on postoperative pathological analysis. We also observed the overall survival (OS) and recurrence in ECC patients with and without LNM after matching according to baseline measures. Results In total, 473 ECC patients were observed, 288 patients were enrolled, and 17 patients had LNM (5.90%). The univariate analysis revealed that tumor size, pathology, and lymphovascular invasion were associated with LNM in ECC (P = 0.026, 0.000, and 0.000, respectively), and the multivariate logistic regression confirmed that tumor size, pathology, and lymphovascular invasion were risk factors for LNM (P = 0.021, 0.023, and 0.001, respectively). There were no significant differences in OS and recurrence between the ECC patients with and without LNM after matching based on baseline measures (P = 0.158 and 0.346, respectively), and no significant difference was observed between chemotherapy and no chemotherapy in ECC patients without LNM after surgery (P = 0.729 and 0.052). Conclusion Tumor size, pathology, and lymphovascular invasion are risk factors for predicting LNM in ECC patients. Adjuvant chemotherapy could improve OS and recurrence in patients with LNM but not always in ECC patients without LNM.

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The enzymopathy of G6PD deficiency in Jordan: a demographic and biochemical analysis

Asian Journal of Medical Sciences ◽

10.3126/ajms.v10i1.21358 ◽

2018 ◽

Vol 10 (1) ◽

pp. 25-32

Author(s):

Ahmed Al-Imam

Keyword(s):

G6pd Deficiency ◽

Liver Enzymes ◽

Clinical Manifestations ◽

University Hospital ◽

Drug Induced ◽

Mean Values ◽

Significant Difference ◽

Wbc Count ◽

Glucose 6 Phosphate Dehydrogenase ◽

Blood Grouping

Background: G6PD deficiency is an inherited X-linked recessive condition leading to insufficient levels of glucose-6-phosphate dehydrogenase, thus causing hemolytic anaemia under certain circumstances. Materials and Methods: Our study is explorative for cases admitted to Jordan University Hospital. The studied parameters include demographics, clinical manifestations, biochemical markers including Hb level, WBC count, liver enzymes, and blood grouping. Results: Most of the patients were admitted to the emergency unit (53.13%). Individuals who were Rh-positive represented 57.81%, while patients of AB blood group accounted for 75%. The mean values were 4.81 years (age), 29.06 hours (time-to-hospital admission), 38.10 degree Celsius (temperature), 6.11 gm/dl (Hb), 13242.19 (WBC count), 343.20 U/L (S. ALP), and 50.98 IU/L (S. ALT). There was no significant difference between males and females or between favism-induced versus drug-induced hemolytic episodes. AB and Rh positive blood groups are of a protective effect in relation to liver enzymes. Patients who were admitted to the hospital within 24 hours from having clinical manifestations had a better prognosis. Conclusion: This study is the first inferential research on G6PD deficiency from the Middle East to explore cases from one of the largest healthcare centres in Jordan. The role of blood grouping should be investigated prospectively.

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Universal Screening for G6PD Deficiency Detects More Cases Than Selective Testing

Blood ◽

10.1182/blood.v128.22.1261.1261 ◽

2016 ◽

Vol 128 (22) ◽

pp. 1261-1261

Author(s):

Ilan Segal ◽

Shraga Aviner ◽

Ashraf Abu Rmaileh ◽

Ornit Cohen ◽

Avraham Sayag ◽

...

Keyword(s):

Risk Factors ◽

G6pd Deficiency ◽

Universal Screening ◽

Conflicts Of Interest ◽

Fold Increase ◽

Population Based ◽

Multicultural Society ◽

Glucose 6 Phosphate Dehydrogenase ◽

Enzyme Test ◽

Background Testing

Abstract Background: Testing for glucose-6-phosphate dehydrogenase (G6PD) deficiency is traditionally restricted to jaundiced neonates, as well as to those whose risk factors provide sufficient grounds to suspect the deficiency. We assumed that in a multi-ethnic, multicultural society, routine neonatal screening for G6PD deficiency would detect more affected neonates. Methods: An observational, population-based, cohort study was designed to compare the incidence of G6PD deficiency between two groups of neonates using a validated qualitative enzyme test. Incidence of G6PD deficiency was calculated retrospectively for one group of neonates born between January 2005 and July 2012 (i.e., epoch 1), when only "at-risk" newborns were tested for the deficiency (i.e., group 1). Incidence was also calculated for a second, prospective group of neonates, who were all to be born between August 2012 and April 2014 (i.e., epoch 2), and were all screened for the deficiency irrespective of risk factors. Results: A total of 39,268 live-born infants were included in our study. In epoch 1, 6.8% of all newborns were tested for the deficiency, compared to about 87% in epoch 2. The incidence of G6PD deficiency was 0.4% (119/29,332) and 1.6% (156/9,936) in epoch 1 and epoch 2, respectively (p<0.05). Among females, there was a 6.6-fold increase in incidence of G6PD deficiency between epoch 1 (0.08% [12/14,410]) and epoch 2 (0.53% [26/4,881]), while among males there was a 3.4-fold increase in incidence between epoch 1 and epoch 2 (0.72% [107/14,922] and 2.47% [125/5055], respectively). Conclusions: As universal screening for G6PD deficiency detects more affected newborns than the selective, risk-factor-based testing does, we suggest that validation of our study and cost-effectiveness analyses may further the aim of introducing universal screening for G6PD deficiency for neonates born in multi-ethnic, multicultural society setting. Disclosures No relevant conflicts of interest to declare.

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Dietary Patterns and Oxidative Stress in a Population of Women with Breast Cancer in the North-Western Regions of Algeria (Saida and El-Bayadh)

Journal of Drug Delivery and Therapeutics ◽

10.22270/jddt.v10i6.4543 ◽

2020 ◽

Vol 10 (6) ◽

pp. 24-30

Author(s):

Noureddine Halla ◽

Kebir Boucherit ◽

Kadda Hachem ◽

Amouria Asmouni ◽

Hanane Derrab ◽

...

Keyword(s):

Breast Cancer ◽

Oxidative Stress ◽

Risk Factors ◽

Dietary Patterns ◽

Demographic Data ◽

The Body ◽

Cancer Risk Factors ◽

The North ◽

Significant Difference ◽

North Western

Objective: The aim of this work is the study of risk factors for breast cancer in a population of women in the north-western regions of Algeria (Saida and El-Bayadh) Methodology: A case-control study was carried out on 40 women including 20 cancerous women and 20 control women, in order to determine the dietary patterns and general characteristics of the population studied and to compare the hematological and biochemical parameters, and markers of oxidative/antioxidant status between control women and breast cancer women. Results: The results obtained show that there is no significant difference in the average age however the body mass index was significantly increased in cancer women, revealing overweight (p <0.05), compared to control women. The marital status of the target population is predominantly a married woman status and the level of education shows a relatively low level in breast cancer cases compared to women controls. The illiteracy rate is exceptionally high in cancer women compared to controls (35% versus 20%). In addition, the levels of glucose, creatinine, HDL and ALAT are similar between the two groups of women. The contents of urea, cholesterol, triglyceride, LDL, ASAT, malondialdehyde and uric acid are significantly increased in women with breast cancer compared to women controls. But the vitamin C content is significantly reduced in cancer women compared to control women. Conclusion: We conclude from this study that there is an association between breast cancer and lipid alteration, oxidative stress, age, increase in BMI, socio-demographic data, professional situation, age, means of menstruation and menopause, and ultimately the lifestyle. All these factors are risk factors for breast cancer in the region of Saida and El-Bayadh. Keywords: Breast Cancer, Risk Factors, Dietary Patterns, Oxidative Stress.

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The Effect of Tri-Modality Therapy with Bladder Preservation for Selective Muscle-Invasive Bladder Cancer

Technology in Cancer Research & Treatment ◽

10.1177/15330338211062323 ◽

2021 ◽

Vol 20 ◽

pp. 153303382110623

Author(s):

Zhang Zhiyu ◽

Zhou Qi ◽

Song Zhen ◽

Ouyang Jun ◽

Zhang Jianglei

Keyword(s):

Risk Factors ◽

Bladder Cancer ◽

Linear Regression Analysis ◽

Univariate Analysis ◽

Tnm Staging ◽

Invasive Bladder Cancer ◽

Muscle Invasive Bladder Cancer ◽

Bladder Preservation ◽

Significant Difference ◽

Muscle Invasive

Objectives: To compare the efficacy of complete transurethral resection of bladder tumor combined with postoperative chemoradiotherapy and radical cystectomy (RC) in the treatment of muscle-invasive bladder cancer (MIBC). Methods: This is a single-center, retrospective study. Clinical data of 125 patients with MIBC admitted to the First Affiliated Hospital of Soochow University from December 2012 to December 2015 were retrospectively analyzed, in which 79 patients (tri-modality therapy [TMT] group) received TMT bladder-sparing treatment, and 41 patients (RC group) received RC. The differences of probabilities for 1-year, 2-year, 5-year, and comprehensive overall survival (OS), progress-free survival (PFS) between 2 groups were calculated using Kaplan–Meier product limited estimates. Univariate and multivariate analyses were performed to detect potential risk factors for OS and PFS. Results: There was no statistical difference between the TMT group and RC group in the 1-year, 2-year, 5-year, comprehensive OS rate, and PFS rate. And survival analysis found no significant difference in OS and PFS between the 2 groups. Univariate analysis showed that age, TNM staging, and prognostic nutritional index (PNI) were associated with OS, while PNI was connected to tumor recurrence. Multiple linear regression analysis indicated that TNM staging and PNI were independent risk factors for OS. Conclusions: TMT can be used as an alternative to RC for MIBC patients under the premise of strict control of indications, rigorous postoperative follow-up, and timely salvage cystectomy. PNI was negatively correlated with OS and PFS, while TNM staging was positively correlated with OS.

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Determining a Critical Threshold for G6PD Activity below which RBC Response to Oxidative Stress is Poor

10.21203/rs.2.19598/v3 ◽

2020 ◽

Author(s):

Maria Swastika ◽

Alida R Harahap ◽

Lydia V Panggalo ◽

Sri Widia A Jusman ◽

Ari W Satyagraha

Keyword(s):

Oxidative Stress ◽

G6pd Deficiency ◽

Ex Vivo ◽

Strong Association ◽

G6pd Activity ◽

World Health ◽

Critical Threshold ◽

Main Function ◽

Oxidative Markers ◽

Significant Difference

Abstract Background Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common enzyme disorder in the world. Its main function is to generate NADPH that is required for anti-oxidative pathway in the cells especially in red blood cells (RBC). G6PD deficiency is X-linked and thus subject to random X-chromosome inactivation in women giving them mosaic expression of G6PD activities in their individual cells. This phenomenon makes it difficult for diagnosis with the currently available G6PD qualitative diagnostic tests. With the rolling out of newly marketed anti-malarial drug tafenoquine, which has a long half-life, screening for G6PD deficiency becomes a necessity where those with <70% G6PD activity cannot receive this drug. Thus, evidence for a quantitative cut-off for G6PD activity is needed to ensure safe drug administration.Methods RBC models were developed to analyse the effect of oxidant on RBC oxidative markers namely total glutathione (GSH)and malondialdehyde (MDA). G6PD activity was measured using quantitative assay from Trinity Biotech and was correlated with cytofluorometric assay. RBC from twoG6PD heterozygous women with different G6PD activities were also analysed for comparison.Results There was a negative correlation between G6PD activity and CuCl concentration and a strong association between G6PD activities and proportion of G6PD normal RBC in CuCl-treated models and in ex vivo RBC. However, in terms of oxidative stress markers analyses, unlike the hypothesis where the lower G6PD activity, the higher MDA and the lower GSH level, the CuCl RBC model showed that in low G6PD activities (10-30%) cells, the MDA level is lower compared to the rest of the models (p<0.05). The ex vivo models however were in line with the hypothesis, although the result was not significant (p=0.5). There was a significant difference between RBC with <60% and those with >80% G6PD activities in CuCl RBC model, but not in ex vivo RBC (p=0.5). Genotyping heterozygous subjects showed G6PDViangchan variant with 2.97U/gHb (33% activity) and 6.58 U/gHb (74% activity). Conclusions The GSH analysis has pointed to the 60% G6PD activity cut-off and this data is supportive of the old World Health Organization threshold for intermediate upper limit of 60% G6PD activity. However, there are significant limitations in using MDA assay with CuCl RBC model because the RBC was already stressed due to the copper treatment and thus present a different result when compared to the ex-vivo model.

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